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Luo Z, Yan X, Liu Y, Nan F, Lei Y, Ren Y, Li L. Prognostic significance of Ki-67 in assessing the risk of progression, relapse or metastasis in pheochromocytomas and paragangliomas. Ann Med 2025; 57:2478312. [PMID: 40079941 DOI: 10.1080/07853890.2025.2478312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 01/15/2025] [Accepted: 01/16/2025] [Indexed: 03/15/2025] Open
Abstract
INTRODUCTION Since the Fourth edition of the WHO classification, PPGLs have been recognized for their metastatic potential, though no clear features can accurately predict this behavior. The prognostic value of Ki-67 in assessing the risk of progression, relapse, or metastasis in PPGLs remains debated. METHODS This cohort study included 501 patients diagnosed with PPGLs at the First Hospital of Jilin University between 2000 and 2022, with clinical data, treatment details, pathological indicators, and germline gene test results collected. Bulk sequencing was performed on formalin-fixed paraffin-embedded (FFPE) primary tumor samples from 87 patients. Progression-free survival (PFS) was analyzed using multivariable Cox regression. RESULTS Among the 119 enrolled patients with PPGLs, the average age was 45.7 ± 14.0 years, and the median follow-up time was 46 months. A significant finding was the high expression of CDK1, a gene known to be significantly associated with the metastatic risk of PPGLs, in samples with Ki-67 ≥ 3% (p < 0.0001). More importantly, patients with PPGLs and a Ki-67 level ≥ 3% had a 3.59-fold higher risk of progression, relapse or metastasis compared to those with Ki-67 < 3% (HR = 4.59, 95% CI: 1.06-11.95), after adjusting for all confounding factors. In the composite model, the addition of Ki-67 enhanced the predictive ability of the combined model of SDHB, primary site, tumor size, and invade neighboring tissue (AUC = 0.888, 95% CI: 0.808-0.967 vs. AUC = 0.874, 95% CI: 0.783-0.965). CONCLUSION A Ki-67 level ≥ 3% is associated with an increased risk of progression, relapse or metastasis in patients with PPGLs.
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Affiliation(s)
- Zilan Luo
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Xu Yan
- Pathology Department, The First Hospital of Jilin University, Changchun, China
| | - Yang Liu
- Tumor Immunotherapy Research Center of Jilin University, Changchun, China
| | - Fengrui Nan
- Tumor Immunotherapy Research Center of Jilin University, Changchun, China
| | - Yuhong Lei
- Tumor Immunotherapy Research Center of Jilin University, Changchun, China
| | - Yuan Ren
- Tumor Immunotherapy Research Center of Jilin University, Changchun, China
| | - Lingyu Li
- Cancer Center, The First Hospital of Jilin University, Changchun, China
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Yang J, Wu J, Xie X, Xia P, Lu J, Liu J, Bai L, Li X, Yu Z, Li H. Perilipin-2 mediates ferroptosis in oligodendrocyte progenitor cells and myelin injury after ischemic stroke. Neural Regen Res 2025; 20:2015-2028. [PMID: 39254564 PMCID: PMC11691472 DOI: 10.4103/nrr.nrr-d-23-01540] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 01/17/2024] [Accepted: 02/27/2024] [Indexed: 09/11/2024] Open
Abstract
JOURNAL/nrgr/04.03/01300535-202507000-00024/figure1/v/2024-09-09T124005Z/r/image-tiff Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination. Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage. Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation, and plays an important role in the pathological process of ischemic stroke. However, there are few studies on oligodendrocyte progenitor cell ferroptosis. We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia. Bioinformatics analysis suggested that perilipin-2 (PLIN2) was involved in oligodendrocyte progenitor cell ferroptosis. PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation. For further investigation, we established a mouse model of cerebral ischemia/reperfusion. We found significant myelin damage after cerebral ischemia, as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area. The ferroptosis inhibitor, ferrostatin-1, rescued oligodendrocyte progenitor cell death and subsequent myelin injury. We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells. Plin2 knockdown rescued demyelination and improved neurological deficits. Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.
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Affiliation(s)
- Jian Yang
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Jiang Wu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Xueshun Xie
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Pengfei Xia
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Jinxin Lu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Jiale Liu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Lei Bai
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Xiang Li
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Zhengquan Yu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
| | - Haiying Li
- Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- Institute of Stroke Research, Soochow University, Suzhou, Jiangsu Province, China
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Shang Q, Wang Z, Wang S, Zhang W, Wang Q, Wang R, Huang D, Pan X. Integrated transcriptomics and metabolomics elucidate how arbuscular mycorrhizal fungi alleviate drought stress in Juglans sigillata. Microbiol Res 2025; 296:128135. [PMID: 40056711 DOI: 10.1016/j.micres.2025.128135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/18/2025] [Accepted: 03/01/2025] [Indexed: 03/10/2025]
Abstract
Walnut (Juglans sigillata), an economically significant ecotype of the Juglans genus in the Juglandaceae family, is cultivated mainly in southwest China, a region prone to seasonal drought. Drought significantly reduced both the yield and quality of walnuts in this area. Arbuscular mycorrhizal fungi (AMF) are symbiotic fungi that colonize plant roots and play crucial roles in enhancing plant drought resistance. This study investigated the effects of AMF on the alleviation of drought stress. Compared to non-inoculated drought-stressed plants, AMF inoculation improved plant growth, increased photosynthetic capacity, enhanced reactive oxygen species (ROS) scavenging ability, and significantly activities of superoxide Dismutase, peroxidase, and catalase were significantly increased by 19.90 %, 18.43 %, and 8.39 %, respectively. malondialdehyde, Superoxide anion, and Hydrogen peroxide levels decreased by 18.39 %, 20.75 %, and 21.44 %, respectively, and soluble sugar and proline concentrations also significantly increased (P < 0.05), helping to maintain the osmotic balance. In addition, transcriptome results showed that ATP-binding cassette transporter related to drought resistance were significantly enriched in plants inoculated with AMF, and genes related to growth, such as IAA and CKT synthesis, transcription factors (BZIP, WRKY, and GTE), and related antioxidant enzymes. The mitogen-activated protein kinases pathway-related genes were upregulated in the inoculated drought treatment group, whereas pinobanksin and homoeriodictyol were upregulated in the inoculated drought treatment group, both of which provide support for drought resistance. In summary, AMF alleviated drought stress and promoted Juglans sigillata growth by modulating key physiological, biochemical, and molecular mechanisms involved in drought resistance. This study offers important theoretical insights that support the application of AMF in sustainable agricultural practices.
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Affiliation(s)
- Qing Shang
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences, Guizhou University, Guiyang, Guizhou 550025, China; Guizhou Engineering Research Center for Fruit Crops, College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China
| | - Zhifan Wang
- Guizhou Engineering Research Center for Fruit Crops, College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China; College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China
| | - Shuyu Wang
- College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China
| | - Wen'e Zhang
- College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China
| | - Qian Wang
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences, Guizhou University, Guiyang, Guizhou 550025, China
| | - Ruipu Wang
- Guizhou Engineering Research Center for Fruit Crops, College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China; College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China
| | - Dong Huang
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), College of Life Sciences, Guizhou University, Guiyang, Guizhou 550025, China; Guizhou Engineering Research Center for Fruit Crops, College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China; College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China.
| | - Xuejun Pan
- Guizhou Engineering Research Center for Fruit Crops, College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China; College of Agriculture, Guizhou University, Guiyang, Guizhou 550025, China.
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San Antonio C, Poynton H, Krick K, Hannigan R. Ocean warming and acidification alter calcification and innate immune system gene expression in juvenile American lobsters, Homarus americanus. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART D, GENOMICS & PROTEOMICS 2025; 54:101404. [PMID: 39708720 DOI: 10.1016/j.cbd.2024.101404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 12/07/2024] [Accepted: 12/15/2024] [Indexed: 12/23/2024]
Abstract
The Gulf of Maine, home to American lobster, Homarus americanus, is experiencing rapid ocean warming (OW) and acidification (OA) due to climate change. While some studies have investigated the effects of either ocean acidification (OA) or warming (OW) on lobsters, few explore the interaction of these stressors, particularly on gene expression. We evaluated the effects of OA and OW on early benthic juvenile lobster transcriptomics using RNA sequencing and RT-qPCR through two distinct aquarium experiments. Lobsters were reared under OW/OA conditions aligned with values predicted for 2100: decrease in pH by 0.3-0.4 units; mean sea surface warming of 2.89 °C. RNA was isolated from carapace hypodermal tissue in both experiments. The multi-stressor treatment in the RNAseq experiment had the greatest differential expression. Genes of interest pertaining to calcification and cuticle development were primarily downregulated under high temperature but upregulated under acidified and multi-stressor conditions. In the RT-qPCR experiment, crustin alone was significantly downregulated and only under the most extreme multi-stressor treatment. This gene along with the prophenoloxidase activating enzyme had expression that trended toward downregulation across all treatments, suggesting a possible correlation to immune suppression. Expression profiles for crustin and the calcification gene, carbonic anhydrase differed across treatments based on molt cycle timing, indicating that stressor impacts may vary depending on the molt cycle phase. Elevated temperature had a greater effect on the expression of calcification and cuticle development genes, though the direction of expression reversed with multiple stressors. These results indicate the impacts of OW and OA on early benthic juvenile lobsters are complex, possibly synergistic, vary with molt cycle, and potentially interfere with normal cuticle development, which may increase susceptibility to injury or disease.
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Affiliation(s)
- Christine San Antonio
- School for the Environment, University of Massachusetts Boston, Boston, MA 02125, USA.
| | - Helen Poynton
- School for the Environment, University of Massachusetts Boston, Boston, MA 02125, USA.
| | - Keegan Krick
- School for the Environment, University of Massachusetts Boston, Boston, MA 02125, USA
| | - Robyn Hannigan
- School for the Environment, University of Massachusetts Boston, Boston, MA 02125, USA; Presidents Office, Ursinus College, Collegeville, PA 19426, USA
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Ren H, Zhi J, Li D, Yue W, Liu L. Transcriptomic analysis of the response of Spodoptera frugiperda (Lepidoptera: Noctuidae) to short-term low-temperature stress. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART D, GENOMICS & PROTEOMICS 2025; 54:101394. [PMID: 39700742 DOI: 10.1016/j.cbd.2024.101394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 12/06/2024] [Accepted: 12/07/2024] [Indexed: 12/21/2024]
Abstract
Spodoptera frugiperda is a major invasive pest that poses a serious threat to crops worldwide. Low temperature is a key factor limiting the survival and reproduction for this pest. To study the responses of S. frugiperda to low-temperature stress, high-throughput sequencing was used to perform transcriptomic analysis on the 6th instar larvae under low-temperature stress at 5 °C and 10 °C, along with 25 °C as a control. As a result, 215 differentially expressed genes (DEGs) were identified under different low-temperature stresses. Upon functional annotation of the DEGs in KEGG and GO databases, the number of DEGs annotated in control vs. LT10 comparison was the largest (n = 150), whereas fewer DEGs (n = 89) were annotated in control vs. LT5 comparison. This discrepancy suggested that S. frugiperda might adopt different strategies to cope with low-temperature stress. The DEGs in the GO database were particularly associated with cell catalytic activity, cell anatomical entity process, cell apoptosis, and cell binding channel. KEGG annotation analysis of the different low-temperature stresses showed that most of the enriched pathways were related to carbon metabolism, oxidative phosphorylation, and lipid metabolism. The results will be the basis for mastering the cold tolerant mechanism of S. frugiperda, and is of great significance for its prevention.
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Affiliation(s)
- Huawei Ren
- Institute of Entomology, Guizhou University/Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Guizhou, Guiyang 550025, China
| | - Junrui Zhi
- Institute of Entomology, Guizhou University/Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Guizhou, Guiyang 550025, China.
| | - Dingyin Li
- Institute of Entomology, Guizhou University/Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Guizhou, Guiyang 550025, China
| | - Wenbo Yue
- Institute of Entomology, Guizhou University/Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Guizhou, Guiyang 550025, China
| | - Li Liu
- Institute of Entomology, Guizhou University/Guizhou Provincial Key Laboratory for Agricultural Pest Management of the Mountainous Region, Guizhou, Guiyang 550025, China
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Naskar S, Sharma S, Kuotsu K, Halder S, Pal G, Saha S, Mondal S, Biswas UK, Jana M, Bhattacharjee S. The biomedical applications of artificial intelligence: an overview of decades of research. J Drug Target 2025; 33:717-748. [PMID: 39744873 DOI: 10.1080/1061186x.2024.2448711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/13/2024] [Accepted: 12/26/2024] [Indexed: 01/11/2025]
Abstract
A significant area of computer science called artificial intelligence (AI) is successfully applied to the analysis of intricate biological data and the extraction of substantial associations from datasets for a variety of biomedical uses. AI has attracted significant interest in biomedical research due to its features: (i) better patient care through early diagnosis and detection; (ii) enhanced workflow; (iii) lowering medical errors; (v) lowering medical costs; (vi) reducing morbidity and mortality; (vii) enhancing performance; (viii) enhancing precision; and (ix) time efficiency. Quantitative metrics are crucial for evaluating AI implementations, providing insights, enabling informed decisions, and measuring the impact of AI-driven initiatives, thereby enhancing transparency, accountability, and overall impact. The implementation of AI in biomedical fields faces challenges such as ethical and privacy concerns, lack of awareness, technology unreliability, and professional liability. A brief discussion is given of the AI techniques, which include Virtual screening (VS), DL, ML, Hidden Markov models (HMMs), Neural networks (NNs), Generative models (GMs), Molecular dynamics (MD), and Structure-activity relationship (SAR) models. The study explores the application of AI in biomedical fields, highlighting its enhanced predictive accuracy, treatment efficacy, diagnostic efficiency, faster decision-making, personalised treatment strategies, and precise medical interventions.
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Affiliation(s)
- Sweet Naskar
- Department of Pharmaceutics, Institute of Pharmacy, Kalyani, West Bengal, India
| | - Suraj Sharma
- Department of Pharmaceutics, Sikkim Professional College of Pharmaceutical Sciences, Sikkim, India
| | - Ketousetuo Kuotsu
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India
| | - Suman Halder
- Medical Department, Department of Indian Railway, Kharagpur Division, Kharagpur, West Bengal, India
| | - Goutam Pal
- Service Dispensary, ESI Hospital, Hoogly, West Bengal, India
| | - Subhankar Saha
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India
| | - Shubhadeep Mondal
- Department of Pharmacology, Momtaz Begum Pharmacy College, Rajarhat, West Bengal, India
| | - Ujjwal Kumar Biswas
- School of Pharmaceutical Science (SPS), Siksha O Anusandhan (SOA) University, Bhubaneswar, Odisha, India
| | - Mayukh Jana
- School of Pharmacy, Centurion University of Technology and Management, Centurion University, Bhubaneswar, Odisha, India
| | - Sunirmal Bhattacharjee
- Department of Pharmaceutics, Bharat Pharmaceutical Technology, Amtali, Agartala, Tripura, India
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Gao C, Nie H. Transcriptome analysis reveals molecular mechanism of Dosinia corrugata in response to acute heat stress. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. PART D, GENOMICS & PROTEOMICS 2025; 54:101426. [PMID: 39879904 DOI: 10.1016/j.cbd.2025.101426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 01/19/2025] [Accepted: 01/22/2025] [Indexed: 01/31/2025]
Abstract
This study seeks to explore the molecular regulatory mechanism within Dosinia corrugata in response to extreme high-temperature conditions, aiming to enhance the sustainable development of the D. corrugata aquaculture industry. To identify heat-responsive genes and elucidate adaptive mechanisms, we conducted transcriptional profiling of D. corrugata gills after 12 h and 24 h of acute heat stress. At 12 h and 24 h under acute heat stress, we detected 6842 and 1112 differentially expressed genes (DEGs), respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis revealed that co-enriched pathways at both time points included Apoptosis-multiple species, Ubiquitin-mediated proteolysis, Tumor Necrosis Factor (TNF) signaling pathway, and Retinoic acid-inducible Gene I (RIG-I)-like receptor signaling pathway in response to acute heat stress. It is noteworthy that at 12 h of acute heat stress, metabolic pathways were significantly enriched, while at 24 h, immune-related pathways showed significant enrichment. Based on the co-enrichment pathways identified at both time points during acute heat stress (12 h and 24 h), we constructed a potential regulatory network for differentially expressed genes under heat stress. This study offers valuable insights into comprehending the potential molecular regulatory mechanisms that underlie D. corrugata's response to elevated temperatures.
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Affiliation(s)
- Changsheng Gao
- College of Fisheries and Life Science, Dalian Ocean University, Dalian 116023, China; Engineering and Technology Research Center of Shellfish Breeding in Liaoning Province, Dalian Ocean University, Dalian 116023, China
| | - Hongtao Nie
- College of Fisheries and Life Science, Dalian Ocean University, Dalian 116023, China; Engineering and Technology Research Center of Shellfish Breeding in Liaoning Province, Dalian Ocean University, Dalian 116023, China.
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Aja PM, Agu PC, Ogbu C, Alum EU, Fasogbon IV, Musyoka AM, Ngwueche W, Egwu CO, Tusubira D, Ross K. RNA research for drug discovery: Recent advances and critical insight. Gene 2025; 947:149342. [PMID: 39983851 DOI: 10.1016/j.gene.2025.149342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/12/2025] [Accepted: 02/16/2025] [Indexed: 02/23/2025]
Abstract
The field of RNA research has experienced significant changes and is now at the forefront of contemporary drug development. This narrative overview explores the scientific developments and historical turning points in RNA research, emphasising the field's critical significance in the development of novel therapeutics. Important discoveries like antisense oligonucleotides (ASOs), mRNA therapies, and RNA interference (RNAi) have created novel treatment options that can be targeted, such as the ground-breaking mRNA vaccinations against COVID-19. Advances in high-throughput sequencing, single-cell RNA sequencing, and epitranscriptomics have further unravelled the complexity of RNA biology, shedding light on the intricacies of gene regulation and cellular diversity. The integration of computational tools and bioinformatics has propelled the identification of RNA-based biomarkers and the development of RNA therapeutics. Despite significant progress, challenges such as RNA stability, delivery, and off-target effects persist, necessitating continuous innovation and ethical considerations. This review provides a critical insight into the current state and prospects of RNA research, emphasising its transformative potential in drug discovery. By examining the interplay between technological advancements and therapeutic applications, we underscore the promising horizon for RNA-based interventions in treating a myriad of diseases, marking a new era in precision medicine.
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Affiliation(s)
- Patrick Maduabuchi Aja
- Biochemistry Department, Biomedical Sciences Faculty, Kampala International University, P.O. Box Ishaka, Bushenyi, Uganda; Biochemistry Department, Faculty of Science, Ebonyi State University, P.M.B. 053 Abakaliki, Ebonyi State, Nigeria.
| | - Peter Chinedu Agu
- Biochemistry Department, Faculty of Science, Ebonyi State University, P.M.B. 053 Abakaliki, Ebonyi State, Nigeria; Department of Biochemistry, Faculty of Science, Evangel University, Nigeria
| | - Celestine Ogbu
- Department of Biochemistry, Faculty of Basic Medical Sciences, Federal University of Health Sciences, Otukpo, Nigeria
| | - Esther Ugo Alum
- Publications and Extension Department, Kampala International University, P. O. Box 20000, Uganda; Biochemistry Department, Faculty of Science, Ebonyi State University, P.M.B. 053 Abakaliki, Ebonyi State, Nigeria
| | - Ilemobayo Victor Fasogbon
- Biochemistry Department, Biomedical Sciences Faculty, Kampala International University, P.O. Box Ishaka, Bushenyi, Uganda
| | - Angela Mumbua Musyoka
- Biochemistry Department, Biomedical Sciences Faculty, Kampala International University, P.O. Box Ishaka, Bushenyi, Uganda
| | - Wisdom Ngwueche
- Department of Biochemistry, Faculty of Biological Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
| | - Chinedu Ogbonia Egwu
- Department of Biochemistry, Faculty of Basic Medical Sciences, Alex Ekwueme Federal University, Ndufu-Alike, Ikwo, Ebonyi State, Nigeria
| | - Deusdedit Tusubira
- Department of Biochemistry, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Kehinde Ross
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom; Institute for Health Research, Liverpool John Moores University, Liverpool, United Kingdom
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Chang H, Li C, Zhu T, Cai S, Chen J, Zhan F, Zeng L, Fang Y, Ye G, Li J, Su J. GLR3.6 T807I Mutation of Casuarina equisetifolia Is Associated With a Decreased JA Response to Insect Feeding by Lymantria xylina. PLANT, CELL & ENVIRONMENT 2025; 48:3185-3198. [PMID: 39718115 DOI: 10.1111/pce.15347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 12/09/2024] [Accepted: 12/12/2024] [Indexed: 12/25/2024]
Abstract
Lymantria xylina is the most important defoliator, damaging the effective coastal windbreak tree species Casuarina equisetifolia. However, the underlying genetic mechanisms through which C. equisetifolia responds to L. xylina attacks remain unknown. Here, we compared the transcriptional, phytohormone and metabolic differences between susceptible (S) and resistant (R) C. equisetifolia cultivars in response to L. xylina feeding. The main L. xylina-induced resistance in C. equisetifolia was a jasmonate (JA) response and JA synthesis was highly induced by L. xylina feeding at both the transcriptional and metabolic levels, thus promoting flavonoid accumulation. The JA response was highly activated by L. xylina feeding on the R but not in the S cultivar, although the JA signalling pathway was intact in both cultivars. We found a single amino acid mutation in the homologues of glutamate receptor-like protein 3.6 (CeGLR3.6T807I) in the S cultivar. Compared with the GLR3.6 homologues in the R cultivar, phosphorylation of CeGLR3.6T807I was not induced by insect feeding, leading to a decreased JA response in the S cultivar. Collectively, this study provides new insights into the function of CeGLR3.6 in regulating the JA response of C. equisetifolia to L. xylina feeding.
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Affiliation(s)
- Huan Chang
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, China
| | - Chengli Li
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, China
| | - Tengfei Zhu
- National Key Laboratory of Wheat Improvement, College of Life Sciences, Shandong Agricultural University, Taian, Shandong Province, China
| | - Shouping Cai
- Fujian Academy of Forestry Sciences, Fuzhou, Fujian Province, China
| | - Jie Chen
- Fujian Academy of Forestry Sciences, Fuzhou, Fujian Province, China
| | - Fangfang Zhan
- Fujian Academy of Forestry Sciences, Fuzhou, Fujian Province, China
| | - Liqiong Zeng
- Fujian Academy of Forestry Sciences, Fuzhou, Fujian Province, China
| | - Yu Fang
- Institute of Soil Fertilizer, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian Province, China
| | - Gongfu Ye
- Fujian Academy of Forestry Sciences, Fuzhou, Fujian Province, China
| | - Jian Li
- Key Laboratory of Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, China
| | - Jun Su
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, China
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10
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Li S, He P, Liu J, Zang S, Luo J, Luo Y, Zhu S, Zang L. Ferulic acid protects against stress-induced myocardial injury in mice. Toxicol Appl Pharmacol 2025; 498:117309. [PMID: 40120650 DOI: 10.1016/j.taap.2025.117309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 03/19/2025] [Accepted: 03/19/2025] [Indexed: 03/25/2025]
Abstract
Excessive stress is a known contributor to cardiovascular diseases (CVD), and ferulic acid (FA), a natural phenolic compound, has demonstrated significant antioxidant and anti-inflammatory properties. This study investigates the protective effects of FA against stress-induced myocardial injury (SIMI) and elucidates the underlying mechanisms. An acute SIMI model was established in mice using low-temperature water immersion restraint. Cardiac function was assessed via cardiac index and histopathological analysis. Serum levels of corticosterone (CORT), lactate dehydrogenase (LDH), and brain natriuretic peptide (BNP) were quantified using enzyme-linked immunosorbent assay (ELISA), along with inflammatory markers TNF-α and IL-1β. The oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and reactive oxygen species (ROS), were analyzed using colorimetric methods and fluorescent probes. Immunohistochemistry (IHC) and Western Blot were used to analyze the expression of proteins related to TNF, MAPK, PPAR-α/PGC-1α, and Nrf2 signaling pathways. Results indicated that FA pretreatment improved cardiac index, myocardial structural integrity, and reduced inflammatory cell infiltration. Serum levels of LDH, BNP, CORT, TNF-α, and IL-1β were significantly decreased in FA-treated SIMI mice. Elevated MDA and ROS levels, along with decreased GSH and SOD levels in the SIMI group, were reversed by FA pretreatment, likely through activation of the PPARα/PGC-1α and Nrf2 signaling pathways. Additionally, FA inhibited the TNF-α/TNFR1 and ERK/JNK MAPK pathways, contributing to its protective effects. In conclusion, FA mitigates SIMI by alleviating oxidative stress and inflammatory responses.
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Affiliation(s)
- Siyong Li
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Peiyi He
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Jiahe Liu
- The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China
| | | | - Jiahao Luo
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Yi Luo
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
| | - Shuguang Zhu
- The First Affiliated Hospital cardiothoracic surgery department, Guangdong Pharmaceutical University, Guangzhou 510080, China.
| | - Linquan Zang
- School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
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11
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Rifai S, Rifai A, Shi X, Khan MA, Guang W, Wang L, Tallon L, Hussain A. Genomic and transcriptomic sequencing in prostate cancer. Curr Opin Oncol 2025; 37:240-249. [PMID: 40071471 DOI: 10.1097/cco.0000000000001136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
Abstract
PURPOSE OF REVIEW Genomic and transcriptomic sequencing technologies have revolutionized our ability to characterize prostate cancer at the molecular level. The underlying premise of next-generation sequencing technologies and their current and evolving applications in prostate cancer management are provided in the review. RECENT FINDINGS Improved methodologies are allowing timely sequencing of the coding regions or both the coding and noncoding regions of the genome to help identify potential mutations and structural variations in the prostate cancer genome, some of which are currently also targetable therapeutically. DNA microarray- based differential gene expression has been supplanted by RNA sequencing (RNA-seq), which not only allows for more accurate quantitation but also nucleotide-level resolution to investigate the entire transcriptome, including alternative gene spliced transcripts and noncoding RNA transcripts, whose full clinical implications have yet to be fully understood and realized. Gene classifier platforms that predict risk of recurrence or metastasis are being incorporated into prostate cancer management algorithms. In the appropriate clinical context, not only somatic but also germline mutation testing is being recommended. SUMMARY Continued clinical integration of sequencing technologies and ongoing research will lead to improved understanding of prostate cancer biology and prostate cancer treatment.
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Affiliation(s)
- Safiullah Rifai
- University of Maryland Greenebaum Comprehensive Cancer Center
| | - Azimullah Rifai
- University of Maryland Greenebaum Comprehensive Cancer Center
| | - Xiaolei Shi
- University of Maryland Greenebaum Comprehensive Cancer Center
- Department of Medicine University of Maryland School of Medicine
| | | | - Wei Guang
- University of Maryland Greenebaum Comprehensive Cancer Center
- Department of Medicine University of Maryland School of Medicine
| | - Linbo Wang
- University of Maryland Greenebaum Comprehensive Cancer Center
| | | | - Arif Hussain
- University of Maryland Greenebaum Comprehensive Cancer Center
- Department of Medicine University of Maryland School of Medicine
- Department of Pathology
- Depepartment of Biochemistry and Molecular Biology
- Baltimore VA Medical Center, Baltimore, Maryland USA
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12
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Hara Y, Kumamoto T, Yoshizawa-Sugata N, Hirai K, Song X, Kawaji H, Ohtaka-Maruyama C. The spatial transcriptome of the late-stage embryonic and postnatal mouse brain reveals spatiotemporal molecular markers. Sci Rep 2025; 15:12299. [PMID: 40210990 DOI: 10.1038/s41598-025-95496-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 03/21/2025] [Indexed: 04/12/2025] Open
Abstract
The neocortical development process includes cell proliferation, differentiation, migration, and maturation, supported by precise genetic regulation. To understand these processes at the cellular and molecular levels, it is necessary to characterize the fundamental anatomical structures by gene expression. However, markers established in the adult brain sometimes behave differently in the fetal brain, actively changing during development. The spatial transcriptome is a powerful analytical method that enables sequence analysis while retaining spatial information. However, a deeper understanding of these data requires computational estimation, including integration with single-cell transcriptome data and aggregation of spots at the single-cell cluster level. The application of such analysis to biomarker discovery has only begun recently, and its application to the developing fetal brain is largely unexplored. In this study, we performed a spatial transcriptome analysis of the developing mouse brain to investigate spatio-temporal regulation of gene expression during development. Using these data, we conducted an integrated study with publicly available mouse data sets. Our data-driven analysis identified novel molecular markers of the choroid plexus, piriform cortex, and thalamus. Furthermore, we identified a novel molecular marker that can determine the dorsal endopiriform nucleus (DEn) of the developmental stage in the claustrum/DEn complex.
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Affiliation(s)
- Yuichiro Hara
- Research Center for Genome & Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan
- Kitasato University School of Frontier Engineering, Sagamihara, Kanagawa, Japan
| | - Takuma Kumamoto
- Developmental Neuroscience Project, Department of Brain & Neurosciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan
| | - Naoko Yoshizawa-Sugata
- Research Center for Genome & Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan
| | - Kumiko Hirai
- Developmental Neuroscience Project, Department of Brain & Neurosciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan
| | - Xianghe Song
- Developmental Neuroscience Project, Department of Brain & Neurosciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan
- Department of Biological Science, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo, Japan
| | - Hideya Kawaji
- Research Center for Genome & Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
- Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Bunkyo, Tokyo, Japan.
| | - Chiaki Ohtaka-Maruyama
- Developmental Neuroscience Project, Department of Brain & Neurosciences, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
- Department of Biological Science, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo, Japan.
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13
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Choi EA, Kim HJ, Kim Y, Jang HB, Hwang YI, Kim YY, Yoo KH, Lee HJ. Epigenetic profiles integrated with transcriptomic reveal the difference between COPD and PRISm in KOCOSS-NIH. Funct Integr Genomics 2025; 25:86. [PMID: 40205238 DOI: 10.1007/s10142-025-01593-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 03/14/2025] [Accepted: 03/26/2025] [Indexed: 04/11/2025]
Abstract
In 2023, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) introduced a provision regarding preserved ratio-impaired spirometry (PRISm), a presumed pre-stage of Chronic Obstructive Pulmonary Disease (COPD), into the COPD guidelines. However, further research in this area is needed. Our study aimed to investigate the epigenetic differences between PRISm and COPD. EWAS (n = 572) and RNA-sequencing (n = 60) were performed on blood samples from the COPD registry, and EWAS was replicated in the KoGES cohort data (n = 98). Our findings revealed significant epigenetic differences between patients with PRISm and COPD. 39,980 CpG-sites displayed differential methylation between PRISm and COPD. Seven gene regions-EEF1A2, EMP2, EPCAM, MTSS1L, ARHGEF10, HYDIN, and FADS2 were not only differentially methylated but also exhibited differential expression. The consistency of differential methylation of CpG sites in five genes, excluding ARHGEF10 and MTSS1L, was replicated in the KoGES study, affirming the distinction between COPD and PRISm. Our research identified seven gene regions as critical contributors related to the modulation of gene expression, including CpG sites that differentiate COPD from PRISm. These results highlight the significance of DNA methylation changes in distinguishing PRISm from COPD and shed light on potential mechanisms by which methylation alterations impact lung function.
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Affiliation(s)
- Eun-A Choi
- Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-Eup, Heungdeok-Gu, Cheongju, Republic of Korea
| | - Hyun Jeong Kim
- Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-Eup, Heungdeok-Gu, Cheongju, Republic of Korea.
| | - Youlim Kim
- Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Han Byul Jang
- Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-Eup, Heungdeok-Gu, Cheongju, Republic of Korea
| | - Yong Il Hwang
- Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
| | - Young-Youl Kim
- Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-Eup, Heungdeok-Gu, Cheongju, Republic of Korea
| | - Kwang Ha Yoo
- Division of Pulmonary and Allergy Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea.
| | - Hye-Ja Lee
- Division of Allergy and Respiratory Disease Research, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Osong-Eup, Heungdeok-Gu, Cheongju, Republic of Korea.
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14
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Huang D, Cheng CQ, Zhang HY, Huang Y, Li SY, Huang YT, Huang XL, Pei LL, Luo Z, Zou LG, Yang WD, Zheng XF, Li DW, Li HY. Heat shock transcription factor-mediated thermal tolerance and cell size plasticity in marine diatoms. Nat Commun 2025; 16:3404. [PMID: 40210887 DOI: 10.1038/s41467-025-58547-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/18/2025] [Indexed: 04/12/2025] Open
Abstract
Diatoms are a crucial component of marine ecosystems, recognized for their broad environmental adaptability and wide temperature tolerance. However, the molecular mechanisms underlying their adaptability to diverse temperatures are unknown. In this study, we discover that heat shock transcription factors (HSFs) are potentially important for thermal tolerance in diatoms. Our study focuses on PtHSF2, annotated as HSF2 in Phaeodactylum tricornutum's genome, which is ubiquitous in diatoms. Overexpression of PtHSF2 markedly enhances thermal tolerance and increases cell size; causes significant differential expression of several genes, including cell division cycle protein 45-like (PtCdc45-like), ATM (ataxia telangiectasia mutated), ATR (ataxia telangiectasia and Rad3-related), light-harvesting complex protein 2 (Lhcx2), and fatty acid desaturase. Cleavage Under Targets and Tagmentation (CUT&Tag) and CUT&Tag-qPCR analyses demonstrate that PtHSF2 directly targets and upregulates PtCdc45-like and Lhcx2 while downregulating ATP-binding cassette transporter. Functional validation of PtCdc45-like shows that its overexpression results in larger cell size, enhances antioxidant capacity, and improves cell survival at elevated temperatures. Collectively, our findings elucidate the molecular mechanism by which PtHSF2 mediates high-temperature tolerance in diatoms and validate the functions of its target gene PtCdc45-like. These results highlight the importance of HSFs in diatom temperature adaptation and provide insights into temperature acclimation in microalgae.
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Affiliation(s)
- Dan Huang
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
- Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, Guangzhou, 510630, China
| | - Cai-Qin Cheng
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Hao-Yun Zhang
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Yun Huang
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Si-Ying Li
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Yi-Tong Huang
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Xue-Ling Huang
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Lu-Lu Pei
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Zhaohe Luo
- Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, 361005, China
| | - Li-Gong Zou
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Wei-Dong Yang
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China
| | - Xiao-Fei Zheng
- Department of Sports Medicine, The First Affiliated Hospital, Guangdong Provincial Key Laboratory of Speed Capability, The Guangzhou Key Laboratory of Precision Orthopedics and Regenerative Medicine, Jinan University, Guangzhou, 510630, China
| | - Da-Wei Li
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
| | - Hong-Ye Li
- Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.
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15
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Pan X, Huang C, Bai X, Li F. Causal relationship between breast cancer and acute myeloid leukemia based on two-sample bidirectional Mendelian randomization and transcriptome overlap analysis. Discov Oncol 2025; 16:492. [PMID: 40198525 PMCID: PMC11979033 DOI: 10.1007/s12672-025-02288-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 04/01/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Breast cancer is the most prevalent malignancy and the leading cause of cancer-related deaths among women worldwide. Several case reports have shown that some breast cancer patients subsequently develop acute myeloid leukemia (AML) within a short period. However, the causal relationship and pathogenic mechanisms between breast cancer and AML remain incompletely understood. METHODS Mendelian randomization (MR) analyses were conducted to explore the bidirectional causal relationships between breast cancer and AML. Additionally, we applied the Bayesian Weighted Mendelian Randomization (BWMR) approach to validate the results of the MR analysis. Subsequently, we utilized RNA-seq data from various sources to explore the potential molecular signaling pathways between breast cancer and AML. RESULTS Both IVW method and BWMR approach demonstrated that data from three distinct sources consistently indicated breast cancer as a risk factor for AML, with all sources showing statistically significant results (all P < 0.05, Odds Ratios [ORs] > 1). Bioinformatic analyses suggested that extracellular vesicle functions and p53 signaling pathway may mediate molecular links between breast cancer and AML. Using machine learning, we identified 8 genes with high diagnostic efficacy for predicting the occurrence of AML in breast cancer patients. CONCLUSIONS MR analyses indicated a causal relationship between breast cancer and AML. Additionally, transcriptome analysis offered a theoretical basis for understanding the potential mechanisms and therapeutic targets of AML in breast cancer patients.
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Affiliation(s)
- Xin'an Pan
- Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwai Zheng Street, East Lake District, Nanchang City, 330006, Jiangxi Province, China
| | - Cuihan Huang
- The First Clinical Medical College of Nanchang University, Xuefu Road, Nanchang, 330006, Jiangxi, China
| | - Xinyi Bai
- School of Public, Health of Nanchang University, Xuefu Road, Nanchang, 330006, Jiangxi, China
| | - Fei Li
- Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwai Zheng Street, East Lake District, Nanchang City, 330006, Jiangxi Province, China.
- Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, China.
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16
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Huuki-Myers LA, Montgomery KD, Kwon SH, Cinquemani S, Eagles NJ, Gonzalez-Padilla D, Maden SK, Kleinman JE, Hyde TM, Hicks SC, Maynard KR, Collado-Torres L. Benchmark of cellular deconvolution methods using a multi-assay dataset from postmortem human prefrontal cortex. Genome Biol 2025; 26:88. [PMID: 40197307 PMCID: PMC11978107 DOI: 10.1186/s13059-025-03552-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 03/21/2025] [Indexed: 04/10/2025] Open
Abstract
Cellular deconvolution of bulk RNA-sequencing data using single cell/nuclei RNA-seq reference data is an important strategy for estimating cell type composition in heterogeneous tissues, such as the human brain. Here, we generate a multi-assay dataset in postmortem human dorsolateral prefrontal cortex from 22 tissue blocks, including bulk RNA-seq, reference snRNA-seq, and orthogonal measurement of cell type proportions with RNAScope/ImmunoFluorescence. We use this dataset to evaluate six deconvolution algorithms. Bisque and hspe were the most accurate methods. The dataset, as well as the Mean Ratio gene marker finding method, is made available in the DeconvoBuddies R/Bioconductor package.
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Affiliation(s)
- Louise A Huuki-Myers
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- UK Dementia Research Institute at the University of Cambridge, Cambridge, UK
- Department of Clinical Neurosciences, School of Clinical Medicine, The University of Cambridge, Cambridge, UK
| | - Kelsey D Montgomery
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Sang Ho Kwon
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
| | - Sophia Cinquemani
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Nicholas J Eagles
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | | | - Sean K Maden
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
| | - Joel E Kleinman
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
| | - Thomas M Hyde
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
| | - Stephanie C Hicks
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- Center for Computational Biology, Johns Hopkins University, Baltimore, MD, 21205, USA
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA
- Malone Center for Engineering in Healthcare, Johns Hopkins University, Baltimore, MD, 21218, USA
| | - Kristen R Maynard
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.
- The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
| | - Leonardo Collado-Torres
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
- Center for Computational Biology, Johns Hopkins University, Baltimore, MD, 21205, USA.
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17
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Ivich A, Davidson NR, Grieshober L, Li W, Hicks SC, Doherty JA, Greene CS. Missing cell types in single-cell references impact deconvolution of bulk data but are detectable. Genome Biol 2025; 26:86. [PMID: 40197327 PMCID: PMC11974051 DOI: 10.1186/s13059-025-03506-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 02/12/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Advancements in RNA sequencing have expanded our ability to study gene expression profiles of biological samples in bulk tissue and single cells. Deconvolution of bulk data with single-cell references provides the ability to study relative cell-type proportions, but most methods assume a reference is present for every cell type in bulk data. This is not true in all circumstances-cell types can be missing in single-cell profiles for many reasons. In this study, we examine the impact of missing cell types on deconvolution methods. RESULTS Using paired single-cell and single-nucleus data, we simulate realistic scenarios where cell types are missing since single-nucleus RNA sequencing is able to capture cell types that would otherwise be missing in a single-cell counterpart. Single-nucleus sequencing captures cell types absent in single-cell counterparts, allowing us to study their effects on deconvolution. We evaluate three different methods and find that performance is influenced by both the number and similarity of missing cell types. Additionally, missing cell-type profiles can be recovered from residuals using a simple non-negative matrix factorization strategy. We also analyzed real bulk data of cancerous and non-cancerous samples. We observe results consistent with simulation, namely that expression patterns from cell types likely to be missing appear present in residuals. CONCLUSIONS We expect our results to provide a starting point for those developing new deconvolution methods and help improve their to better account for the presence of missing cell types. Our results suggest that deconvolution methods should consider the possibility of missing cell types.
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Affiliation(s)
- Adriana Ivich
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Natalie R Davidson
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Laurie Grieshober
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Weishan Li
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Stephanie C Hicks
- Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
- Center for Computational Biology, Johns Hopkins University, Baltimore, MD, USA
- Malone Center for Engineering in Healthcare, Johns Hopkins University, Baltimore, MD, USA
| | | | - Casey S Greene
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
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18
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Hua W, Cui R, Yang H, Zhang J, Liu C, Sun J. Uncovering critical transitions and molecule mechanisms in disease progressions using Gaussian graphical optimal transport. Commun Biol 2025; 8:575. [PMID: 40189710 PMCID: PMC11973219 DOI: 10.1038/s42003-025-07995-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 03/25/2025] [Indexed: 04/09/2025] Open
Abstract
Understanding disease progression is crucial for detecting critical transitions and finding trigger molecules, facilitating early diagnosis interventions. However, the high dimensionality of data and the lack of aligned samples across disease stages have posed challenges in addressing these tasks. We present a computational framework, Gaussian Graphical Optimal Transport (GGOT), for analyzing disease progressions. The proposed GGOT uses Gaussian graphical models, incorporating protein interaction networks, to characterize the data distributions at different disease stages. Then we use population-level optimal transport to calculate the Wasserstein distances and transport between stages, enabling us to detect critical transitions. By analyzing the per-molecule transport distance, we quantify the importance of each molecule and identify trigger molecules. Moreover, GGOT predicts the occurrence of critical transitions in unseen samples and visualizes the disease progression process. We apply GGOT to the simulation dataset and six disease datasets with varying disease progression rates to substantiate its effectiveness. Compared to existing methods, our proposed GGOT exhibits superior performance in detecting critical transitions.
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Affiliation(s)
- Wenbo Hua
- School of Mathematics and Statistics, Xi'an Jiaotong University, No.28 Xianning West Rd., Xi'an, 710049, Shaanxi, China
| | - Ruixia Cui
- Key Laboratory of Surgical Critical Care and Life Support (Xi'an Jiaotong University), Ministry of Education, No.28 Xianning West Rd., Xi'an, 710049, Shaanxi, China
- Department of Hepatobiliary Surgery and Liver Transplantation, The Second Affiliated Hospital of Xi'an Jiaotong University, No.154 West 5th Rd., Xi'an, 710004, Shaanxi, China
| | - Heran Yang
- School of Mathematics and Statistics, Xi'an Jiaotong University, No.28 Xianning West Rd., Xi'an, 710049, Shaanxi, China
| | - Jingyao Zhang
- Key Laboratory of Surgical Critical Care and Life Support (Xi'an Jiaotong University), Ministry of Education, No.28 Xianning West Rd., Xi'an, 710049, Shaanxi, China
- Department of SICU, The First Affiliated Hospital of Xi'an Jiaotong University, No.227 Yanta West Rd., Xi'an, 710061, Shaanxi, China
| | - Chang Liu
- Key Laboratory of Surgical Critical Care and Life Support (Xi'an Jiaotong University), Ministry of Education, No.28 Xianning West Rd., Xi'an, 710049, Shaanxi, China.
- Department of Hepatobiliary Surgery and Liver Transplantation, The Second Affiliated Hospital of Xi'an Jiaotong University, No.154 West 5th Rd., Xi'an, 710004, Shaanxi, China.
| | - Jian Sun
- School of Mathematics and Statistics, Xi'an Jiaotong University, No.28 Xianning West Rd., Xi'an, 710049, Shaanxi, China.
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19
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Farajzadeh M, Fathi M, Jalali P, Mahmoudsalehi Kheshti A, Khodayari S, Hojjat-Farsangi M, Jadidi F. Long noncoding RNAs in acute myeloid leukemia: biomarkers, prognostic indicators, and treatment potential. Cancer Cell Int 2025; 25:131. [PMID: 40188050 PMCID: PMC11972515 DOI: 10.1186/s12935-025-03763-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Accepted: 03/20/2025] [Indexed: 04/07/2025] Open
Abstract
Long noncoding RNAs (lncRNAs) have been recognized as significant modulators of gene expression and are essential for various biological functions, even though they don't appear to have the ability to encode proteins. Originally considered dark matter, lncRNAs have been recognized as being dysregulated and contributing to the onset, progression, and resistance to treatment of acute myeloid leukemia (AML). AML is a prevalent type of leukemia characterized by the disruption of myeloid cell differentiation, leading to an increased number of immature myeloid progenitor cells. Currently, the need for novel biomarkers and treatment targets to enhance therapeutic alternatives has led to a focus on lncRNAs as possible indicators for prognostic, therapeutic, and diagnostic systems in various human cancers, including AML. Recent research has recognized a limited set of lncRNAs as possible prognostic biomarkers or diagnoses in AML. This review evaluates the key research that highlights the significance of lncRNAs in AML and discusses their roles and impacts on the disease. Furthermore, we intend to underscore the importance of lncRNAs as new and trustworthy markers for the diagnosis, prediction, drug resistance, and targets for treatment in AML.
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Affiliation(s)
- Maryam Farajzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehrdad Fathi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Pooya Jalali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences,, Tehran, Iran
| | | | - Shahla Khodayari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Farhad Jadidi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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20
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Bainbridge RE, Rosenbaum JC, Sau P, Carlson AE. Genomic Insights into Fertilization: Tracing PLCZ1 Orthologs Across Amphibian Lineages. Genome Biol Evol 2025; 17:evaf052. [PMID: 40106576 PMCID: PMC11965574 DOI: 10.1093/gbe/evaf052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 02/04/2025] [Accepted: 02/26/2025] [Indexed: 03/22/2025] Open
Abstract
Fertilization triggers a cascade of events, including a rise in egg cytosolic calcium that marks the onset of embryonic development. In mammals and birds, this critical process is mediated by the sperm-derived phospholipase C zeta (PLCζ), which is pivotal in releasing calcium from the endoplasmic reticulum in the egg and initiating embryonic activation. Intriguingly, Xenopus laevis, a key model organism in reproductive biology, lacks an annotated PLCZ1 gene, prompting questions about its calcium release mechanism during fertilization. Using bioinformatics and RNA sequencing of adult X. laevis testes, we investigated the presence of a PLCZ1 ortholog in amphibians. While we identified PLCZ1 homologs in 25 amphibian species, including 14 previously uncharacterized orthologs, we found none in X. laevis or its close relative, Xenopus tropicalis. Additionally, we found no compensatory expression of other PLC isoforms in these species. Synteny analysis revealed a PLCZ1 deletion in species within the Pipidae family and another intriguing deletion of potential sperm factor PLCD4 in the mountain slow frog, Nanorana parkeri. Our findings indicate that the calcium release mechanism in frog eggs involves a signaling pathway distinct from the PLCζ-mediated process observed in mammals.
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Affiliation(s)
- Rachel E Bainbridge
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Joel C Rosenbaum
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Paushaly Sau
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Anne E Carlson
- Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
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21
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Dou F, Ji W, Xie Q, Wang J, Cao Y, Shi J. Transcriptome analysis and temporal expression patterns of wing development-related genes in Lymantria dispar (Lepidoptera: Erebidae). ENVIRONMENTAL ENTOMOLOGY 2025:nvae111. [PMID: 40172523 DOI: 10.1093/ee/nvae111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 10/09/2024] [Accepted: 11/06/2024] [Indexed: 04/04/2025]
Abstract
Spongy moth, Lymantria dispar Linnaeus (Lepidoptera: Erebidae), stands as a pervasive international threat, marked by its designation as one of the "world's 100 worst invasive species" by IUCN, owing to its voracious leaf-eating habits encompassing over 500 plant species. Its strong flight ability facilitates its spread and invasion. The present study aims to uncover differential gene expression, utilizing the Illumina Novaseq6000 sequencing platform for comprehensive transcriptome sequencing and bioinformatic analysis of total RNA extracted from larvae and pupae. Results revealed pivotal processes of protein functional structure conformation, transport, and signal transduction in functional gene annotation during the 2 developmental stages of spongy moth. 18 functional genes, namely, Distal-less (Dll), Wingless (Wg), Decapentaplegic (Dpp), Hedgehog (Hh), Cubitus interruptus (Ci), Patched (Ptc), Apterous (Ap), Serrate (Ser), Fringe (Fng), Achaete (Ac), Engrailed (En), Vestigial (Vg), Scute (Sc), Invected (Inv), Scalloped (Sd), Ultrabithorax (Ubx), Serum Response Factor (SRF), and Spalt-major, associated with wing development were identified, and their expression levels were meticulously assessed through real-time quantitative PCR (RT-qPCR) in 1st-6th instar larvae and male and female pupae wing discs. The results showed that 18 genes exhibited expression. Furthermore, the relative expression values of wing development-related genes were significantly higher in the pupae stage than in the larval stage. The relative expression values of male and female pupae were also significantly different. The RT-qPCR results were in general agreement with the results of transcriptome analysis. This study establishes a foundational understanding of the developmental mechanisms governing the formation of spongy moth wings.
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Affiliation(s)
- Fengrui Dou
- Beijing Key Laboratory for Forest Pest Control and Sino-French Joint Laboratory for Invasive Forest Pests in Eurasia, College of Forestry, Beijing Forestry University, Beijing, People's Republic of China
| | - Wenzhuai Ji
- Beijing Key Laboratory for Forest Pest Control and Sino-French Joint Laboratory for Invasive Forest Pests in Eurasia, College of Forestry, Beijing Forestry University, Beijing, People's Republic of China
| | - Qing Xie
- Beijing Key Laboratory for Forest Pest Control and Sino-French Joint Laboratory for Invasive Forest Pests in Eurasia, College of Forestry, Beijing Forestry University, Beijing, People's Republic of China
| | - Jingyu Wang
- Beijing Key Laboratory for Forest Pest Control and Sino-French Joint Laboratory for Invasive Forest Pests in Eurasia, College of Forestry, Beijing Forestry University, Beijing, People's Republic of China
| | - Yixia Cao
- Biomedical Department, China Certification & Inspection (Group) Inspection Co., Ltd. (CCIC), Beijing, People's Republic of China
| | - Juan Shi
- Beijing Key Laboratory for Forest Pest Control and Sino-French Joint Laboratory for Invasive Forest Pests in Eurasia, College of Forestry, Beijing Forestry University, Beijing, People's Republic of China
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22
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Yang J, Xin B, Wang X, Wan Y. Cancer-associated fibroblasts in breast cancer in the single-cell era: Opportunities and challenges. Biochim Biophys Acta Rev Cancer 2025; 1880:189291. [PMID: 40024607 DOI: 10.1016/j.bbcan.2025.189291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025]
Abstract
Breast cancer is a leading cause of morbidity and mortality in women, and its progression is closely linked to the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), key components of the TME, play a crucial role in promoting tumor growth by driving cancer cell proliferation, invasion, extracellular matrix (ECM) remodeling, inflammation, chemoresistance, and immunosuppression. CAFs exhibit considerable heterogeneity and are classified into subgroups based on different combinations of biomarkers. Single-cell RNA sequencing (scRNA-seq) enables high-throughput and high-resolution analysis of individual cells. Relying on this technology, it is possible to cluster complex CAFs according to different biomarkers to analyze the specific phenotypes and functions of different subpopulations. This review explores CAF clusters in breast cancer and their associated biomarkers, highlighting their roles in disease progression and potential for targeted therapies.
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Affiliation(s)
- Jingtong Yang
- China-Japan Union Hospital of Jilin University, Jilin University, Changchun 130033, Jilin, China
| | - Benkai Xin
- China-Japan Union Hospital of Jilin University, Jilin University, Changchun 130033, Jilin, China
| | - Xiaoyu Wang
- China-Japan Union Hospital of Jilin University, Jilin University, Changchun 130033, Jilin, China
| | - Youzhong Wan
- China-Japan Union Hospital of Jilin University, Jilin University, Changchun 130033, Jilin, China.
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23
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Yang J, Zheng Z, Jiao Y, Yu K, Bhatara S, Yang X, Natarajan S, Zhang J, Pan Q, Easton J, Yan KK, Peng J, Liu K, Yu J. Spotiphy enables single-cell spatial whole transcriptomics across an entire section. Nat Methods 2025; 22:724-736. [PMID: 40074951 PMCID: PMC11978521 DOI: 10.1038/s41592-025-02622-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 01/29/2025] [Indexed: 03/14/2025]
Abstract
Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization of gene expression within whole-tissue sections, but current approaches remain plagued by the challenge of achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. Spotiphy delivers the most precise cellular proportions in extensive benchmarking evaluations. Spotiphy-derived inferred single-cell profiles reveal astrocyte and disease-associated microglia regional specifications in Alzheimer's disease and healthy mouse brains. Spotiphy identifies multiple spatial domains and alterations in tumor-tumor microenvironment interactions in human breast ST data. Spotiphy bridges the information gap and enables visualization of cell localization and transcriptomic profiles throughout entire sections, offering highly informative outputs and an innovative spatial analysis pipeline for exploring complex biological systems.
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Affiliation(s)
- Jiyuan Yang
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Ziqian Zheng
- Department of Industrial & Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA
| | - Yun Jiao
- Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Kaiwen Yu
- Center of Proteomics and Metabolomics, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Sheetal Bhatara
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Xu Yang
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Sivaraman Natarajan
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Jiahui Zhang
- Department of Industrial & Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA
| | - Qingfei Pan
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - John Easton
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Koon-Kiu Yan
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA
| | - Junmin Peng
- Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
| | - Kaibo Liu
- Department of Industrial & Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA.
| | - Jiyang Yu
- Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
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24
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Yang H, Jiang L, Bao X, Liu H, Xu Q, Yao X, Cai S, Fang Y, Su J, Li J. CeJAZ3 suppresses longifolene accumulation in Casuarina equisetifolia, affecting the host preference of Anoplophora chinensis. PEST MANAGEMENT SCIENCE 2025; 81:2202-2214. [PMID: 39723485 DOI: 10.1002/ps.8618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 10/27/2024] [Accepted: 12/08/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Casuarina equisetifolia, a crucial species of coastal windbreaks, is highly susceptible to infestation by Anoplophora chinensis. This stem-boring pest poses a significant threat to the health and sustainability of Casuarina equisetifolia forests. Understanding the molecular mechanisms underlying the host preference of A. chinensis to Casuarina equisetifolia is essential for developing effective pest management strategies. RESULTS Through field surveys, we identified two cultivars of Casuarina equisetifolia that exhibited differing levels of host preference for A. chinensis. Further analysis of multi-omics data (phenomics, transcriptomics, and metabolomics) from these cultivars revealed that longifolene plays a significant role in attracting A. chinensis to Casuarina equisetifolia. Additionally, the jasmonic acid (JA) signaling pathway was found to suppress longifolene accumulation, primarily through the interaction between the jasmonate ZIM-domain (JAZ) proteins and the terpene synthase (TPS) gene. Moreover, we identified a critical JAZ component, CeJAZ3, whose overexpression led to the down-regulation of TPS expression levels and, consequently, a reduced release of longifolene. CONCLUSION We confirmed that the negative regulator of host preference, CeJAZ3, in the JA signaling pathway can suppress the expression of TPSs, thereby down-regulating the accumulation of longifolene in Casuarina equisetifolia and indirectly suppressing the attraction of host plants to A. chinensis, which provides a basis for the integrated management of A. chinensis. © 2024 Society of Chemical Industry.
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Affiliation(s)
- Hua Yang
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- The Higher Educational Key Laboratory for Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Lijuan Jiang
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- The Higher Educational Key Laboratory for Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Xiaochun Bao
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- The Higher Educational Key Laboratory for Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Haolan Liu
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- The Higher Educational Key Laboratory for Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Qianle Xu
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- The Higher Educational Key Laboratory for Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Xingliang Yao
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Shouping Cai
- Fujian Academy of Forestry Sciences, Fuzhou, China
| | - Yu Fang
- Institute of Resources, Environment and Soil Fertilizer, Fujian Academy of Agricultural Sciences, Fuzhou, China
| | - Jun Su
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Jian Li
- College of Forestry, Fujian Agriculture and Forestry University, Fuzhou, China
- The Higher Educational Key Laboratory for Forest Ecosystem Process and Management of Fujian Province, Fujian Agriculture and Forestry University, Fuzhou, China
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25
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Yin R, Gao J, Liu Y, Guo C. Functional analysis of the effects of propofol on tamoxifen‑resistant breast cancer cells: Insights into transcriptional regulation. Oncol Lett 2025; 29:194. [PMID: 40041408 PMCID: PMC11878209 DOI: 10.3892/ol.2025.14940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 02/06/2025] [Indexed: 03/06/2025] Open
Abstract
Although 70% of patients with estrogen receptor-positive breast cancer benefit from tamoxifen (TAM) therapy, the development of resistance to TAM leads to high rates of metastasis and a poor prognosis. Propofol, a commonly used anesthetic, can inhibit the occurrence and progression of breast cancer. In the present study, the effects of propofol on TAM-resistant (TR) breast cancer cells were evaluated. MCF7-TR cells were treated with or without propofol. Subsequently, cell cycle progression and the induction of apoptosis were detected by flow cytometry, whereas cell proliferation was assessed using Cell Counting Kit-8 and colony formation assays. Furthermore, the potential transcriptional regulatory effects of propofol on MCF7-TR cells were investigated using RNA sequencing. The results indicated that propofol significantly promoted cell cycle arrest, induced apoptosis, and inhibited proliferation and colony formation in MCF7-TR cells. Furthermore, transcriptome sequencing analysis revealed 1,065 differentially expressed genes between propofol-treated MCF7-TR and untreated MCF7-TR cells. Gene Ontology annotation enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Set Enrichment Analysis indicated that propofol affected the expression levels of genes located on the 'plasma membrane' and 'cell periphery', while mainly regulating signals involved in cancer biology, immune response and metabolic pathways. These results identified the potential effects of propofol on TR breast cancer cells and provided a theoretical basis for clinical treatment, particularly for individuals with TAM resistance.
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Affiliation(s)
- Runyang Yin
- Department of Anesthesiology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
| | - Jing Gao
- First Clinical Medical College, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
| | - Yang Liu
- Department of Clinical Laboratory, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
| | - Chunyan Guo
- Department of Anesthesiology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia Autonomous Region 010050, P.R. China
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26
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Laghari F, Chang Q, Zhang H, Zhang J, Pan L, Pu Z, Bao J, Zhang R. Potential mechanisms and therapeutic effect of dietary resveratrol supplementation on the spleen organ of chicken in chronic unpredictable mild stress transcriptomic analysis. Poult Sci 2025; 104:104940. [PMID: 40031383 PMCID: PMC11919410 DOI: 10.1016/j.psj.2025.104940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/30/2025] [Accepted: 02/21/2025] [Indexed: 03/05/2025] Open
Abstract
Chronic unpredictable mild stress (CUMS) affects chicken immune system and welfare, causing huge losses of growth performance and welfare. Resveratrol (RSV), an antioxidant and anti-inflammatory natural plant polyphenol, is widely used for the prevention of stress related disease. The aim of this study is to explore the therapeutic effect of RSV on spleen damage in CUMS. We successfully constructed a CUMS model. A total of 288 healthy one-day-old chicks were used in this study and were divided in 3 groups, control, CUMS and CUMS+RSV group. During 42 days of age, spleen tissue samples were collected and analyzed. Transmission electron microscope (TEM), Hematoxylin and eosin (H&E) staining, immunofluorescence, qRT- PCR, Western blots, immunohistochemical staining and RNA- sequencing (RNA-seq) technology was used to determine any changes and analyzed the mRNA and enrichment pathways. Histopathology and ultrastructure showed there was a severe damage of tissues. The results of RNA-seq showed that a total of 206, 267 and 211 DEGs were identified (log2 Fold Change| >1, P < 0.05) in control -vs- CUMS group, CUMS -vs- CUMS+RSV group and control -vs- CUMS+RSV group, respectively. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the SDEGs, two immune/stress- related pathways including PPAR signaling pathway and neuroactive ligand receptor interaction were selected. The genes related to PPAR signaling pathway identified were PLIN1, MMP1, ANGPTL4 and FABP4 and Neuroactive ligand-receptor interaction genes were GRPR, NTSR1, KNG1 and AGT. The PLIN1, MMP1, ANGPTL4, FABP4, GRPR, KNG1 and AGT were up regulated and NTSR1 was down regulated in CUMS group. When compared to CUMS -vs- CUMS+RSV group, PLIN1, FABP4, KNG1 and AGT were down regulated genes and NTSR1 was up regulated gene. Taken together, KEGG pathway analyses of DEGs, verified by qRT-PCR and Western blots, the current study suggested that these data reveal the promising role of RSV in the prevention and therapy of a wide variety of tissue damage and PPAR signaling pathway, neuroactive ligand-receptor interaction in chronic unpredictable mild stress.
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Affiliation(s)
- Farooque Laghari
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China
| | - Qingqing Chang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China
| | - Haoran Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China
| | - Jiaqi Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China
| | - Liying Pan
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China
| | - Zhaohong Pu
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China
| | - Jun Bao
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China; Key Laboratory of Chicken Genetics and Breeding, Ministry of Agriculture and Rural Affairs, Harbin, Heilongjiang 150030, PR China
| | - Runxiang Zhang
- College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, PR China; Key Laboratory of Chicken Genetics and Breeding, Ministry of Agriculture and Rural Affairs, Harbin, Heilongjiang 150030, PR China.
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27
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Kringel D, Lötsch J. Knowledge of the genetics of human pain gained over the last decade from next-generation sequencing. Pharmacol Res 2025; 214:107667. [PMID: 39988004 DOI: 10.1016/j.phrs.2025.107667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/11/2025] [Accepted: 02/18/2025] [Indexed: 02/25/2025]
Abstract
Next-generation sequencing (NGS) technologies have revolutionized pain research by providing comprehensive insights into genetic variation across the genome. Recent studies have expanded the known spectrum of mutations in genes such as SCN9A and NTRK1, which are commonly mutated in hereditary sensory neuropathies. NGS has uncovered critical alternative splicing events and facilitated single-cell transcriptomics, revealing cellular heterogeneity within tissues. An NGS-based classifier predicted extremely high opioid requirements with 80 % accuracy, highlighting the importance of tailoring opioid therapy based on genetic profiles. Key genes such as GDF5, COL11A1, and TRPV1 have been linked to osteoarthritis risk and pain sensitivity, while HLA-DRB1, TNF, and P2X7 play critical roles in inflammation and pain modulation in rheumatoid arthritis. Innovative tools, such as an atlas of the somatosensory system in neuropathic pain, have been developed based on NGS data, focusing on the dorsal root and trigeminal ganglia. This approach allows the analysis of cellular changes during the development of chronic pain. In the study of rare variants, NGS outperforms single nucleotide variant candidate studies and classical genome-wide association approaches. The complex data generated by NGS enables integrated multi-omics approaches, allowing deeper exploration of the molecular and cellular basis of pain perception. In addition, the characterization of non-coding RNAs has opened new therapeutic avenues. NGS-based pain research faces challenges related to complex data analysis and interpretation of rare genetic variants with unknown biological functions. Nevertheless, NGS offers significant potential for improving personalized pain management and highlights the need for interdisciplinary collaboration to translate findings into clinical practice.
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Affiliation(s)
- Dario Kringel
- Goethe - University, Institute of Clinical Pharmacology, Theodor Stern Kai 7, Frankfurt am Main 60590, Germany
| | - Jörn Lötsch
- Goethe - University, Institute of Clinical Pharmacology, Theodor Stern Kai 7, Frankfurt am Main 60590, Germany; University of Helsinki, Faculty of Medicine, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, 00014, Finland; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Theodor-Stern-Kai 7, Frankfurt am Main 60596, Germany.
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28
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Sun R, Wang Y, Zhu R, Li L, Xi Q, Dai Y, Li J, Cao Y, Guo X, Pan X, Wang Q, Zhang B. Genome-wide identification of CA genes in cotton and the functional analysis of GhαCA4-D, GhβCA6-D and GhγCA2-D in response to drought and salt stresses. Int J Biol Macromol 2025; 304:140872. [PMID: 39938833 DOI: 10.1016/j.ijbiomac.2025.140872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 01/25/2025] [Accepted: 02/08/2025] [Indexed: 02/14/2025]
Abstract
Carbonic anhydrases (CAs) are critical metalloenzymes, widely exist in organisms, which involve in many physiological processes, including response to adverse environmental conditions. Although CA genes have been comprehensive identified and analyzed in numerous plants, there are a few of reports in cotton. Therefore, we conducted an exhaustive research for CA genes from two tetraploid cotton species and their ancestral species. A total of 138 CA genes were found, and 45 of them belonged to Gossypium hirsutum. Phylogenetic relationships and sequences analysis showed that CA genes were categorized into three distinct subtypes: α-type, β-type and γ-type. The exon numbers of β-type members were highly variable. Various types of cis-elements, including drought inducibility, were identified in CA genes, suggesting that CA genes might be involved in the regulation of drought stress response. qRT-PCR was applied to assess the gene expression level in various tissues under drought stress. The results indicated that the expression levels of GhαCA4-D, GhβCA1-A, GhβCA1-D, GhβCA3-D and GhβCA6-D were significantly higher in leaves than that in stems and roots. The expression of GhαCA4-A, GhαCA8-A, GhαCA4-D, GhβCA3-D, GhβCA6-D and GhγCAL1-D was significantly upregulated in roots at severe drought treatment. The functions of GhαCA4-D, GhβCA6-D and GhγCA2-D were analyzed using virus-induced gene silencing (VIGS) technology. Compared to the controls, GhγCA2-D-silenced upland cotton seedlings were more sensitive to salt stress. However, the drought tolerance of GhαCA4-D and GhβCA6-D silenced plants was significantly decreased. Stomatal density, width and area were significantly higher in TRV:GhβCA6-D compared to TRV:00 inoculated plants. GhαCA4-D silenced plants were susceptible to oxidative stress, and silencing GhαCA4-D induced leave cell death. Our results will assist to make clear the regulatory mechanism of CA genes under abiotic stress.
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Affiliation(s)
- Runrun Sun
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Yuanyuan Wang
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Ruihao Zhu
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Lijie Li
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China; Department of Biology, East Carolina University, Greenville, NC 27858, USA
| | - Qianhui Xi
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Yunpeng Dai
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Jiahui Li
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Yuanyuan Cao
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Xinlei Guo
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China
| | - Xiaoping Pan
- Department of Biology, East Carolina University, Greenville, NC 27858, USA
| | - Qinglian Wang
- Henan International Joint Laboratory of Functional Genomics and Molecular Breeding of Cotton, Henan Collaborative Innovation Center of Modern Biological Breeding, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China.
| | - Baohong Zhang
- Department of Biology, East Carolina University, Greenville, NC 27858, USA.
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Palliyath GK, Jangam AK, Katneni VK, Kaikkolante N, Panjan Nathamuni S, Jayaraman R, Jagabattula S, Moturi M, Shekhar MS. Meta-analysis to Unravel Core Transcriptomic Responses in Penaeus vannamei Exposed to Biotic and Abiotic Stresses. Biochem Genet 2025; 63:1459-1478. [PMID: 38570440 DOI: 10.1007/s10528-024-10772-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 03/03/2024] [Indexed: 04/05/2024]
Abstract
Shrimp farming, a dominant economic activity in coastal areas, is affected by different abiotic and biotic stress factors. These stressors, under poor management conditions, could affect growth and health of farmed animals. Understanding the common gene expressions in response to stress, regardless of the specific stress factor, holds significant importance in the field of functional genomics. Scope of this study is to identify the core transcriptomic responses in the shrimp species Penaeus vannamei exposed to various abiotic and biotic stress conditions and to decipher their functional importance. To achieve our objective, we gathered and analyzed multiple RNA-seq datasets related to twelve abiotic and nine biotic stress conditions. Through the in silico meta-analysis, we predicted 961 differentially expressed genes (meta-DEGs) for abiotic stress conditions and 517 meta-DEGs for biotic stress conditions, respectively. These meta-DEGs represent genes that are commonly expressed across different stress factors and are indicative of the organism's general response to stress. The annotation of nineteen core up-regulated meta-DEGs revealed their diverse functions in detoxification, cell adhesion, metal ion binding, and oxidative phosphorylation. These genes play a crucial role in stress response and immune defense. For abiotic stress, significant pathways associated with the stress response include tryptophan metabolism, starch and sucrose metabolism, fatty acid degradation, carbohydrate digestion and absorption, phenylalanine metabolism, drug metabolism-other enzymes, arachidonic acid metabolism, and fatty acid elongation. Similarly, for biotic stress, metabolism of xenobiotics by cytochrome P450, pentose and glucuronate interconversions, steroid hormone biosynthesis, and drug metabolism-cytochrome P450 were found to be significant pathway associations. In addition, the study also predicted 17 stress regulatory motifs present in the identified meta-DEGs. These motifs have significance in identifying the stress responses of the organism. The metabolic pathways and regulatory motifs associated with abiotic and biotic stress factors identified through this study could be a valuable resource for developing stress management approaches in shrimp aquaculture.
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Affiliation(s)
| | | | | | | | | | - Roja Jayaraman
- ICAR-Central Institute of Brackishwater Aquaculture, Chennai, India
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30
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Cao X, Ye X, Sattar A. Walnut husk transcriptome dataset of codling moth ( Cydia pomonella) infestation at different times. Data Brief 2025; 59:111366. [PMID: 40027249 PMCID: PMC11870269 DOI: 10.1016/j.dib.2025.111366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 01/13/2025] [Accepted: 01/30/2025] [Indexed: 03/05/2025] Open
Abstract
Walnuts, along with almonds, cashews, and hazelnuts, are renowned as the world's "four famous nuts," with walnuts being the foremost among them. Walnut fruit is rich in nutrients, including proteins, fats, polyphenols, sugars, phospholipids, melatonin, sterols, flavonoids, iron, zinc, manganese, and other trace elements, as well as dietary fiber. However, the codling moth poses a significant threat to walnut fruits as a major pest. Despite its importance, the transcriptomic changes in walnut husk at different times of codling moth infestation have not been fully explored. In this study, we employed the Illumina NovaSeq 6000 platform to sequence the transcriptome of walnut husk at various time points (0, 12, 24, 36, 48, and 72 hours) after codling moth infestation. The RNA-seq libraries yielded between 41,402,492 and 48,358,932 clean reads, resulting in a total of 120.34 Gb of clean data after filtering out low-quality reads. In total, 936 million reads were generated, with approximately 90% aligning uniquely to the reference genome. Differential expression analysis revealed the number of differentially expressed genes (DEGs) at each time point, including 21 genes associated with plant hormone synthesis. The results of this study provide new insights into the transcriptional changes in walnut husk induced by codling moth infestation and lay a foundation for future research on walnut husk defense mechanisms. The raw FASTQ files from this transcriptome experiment are publicly available in the NCBI Sequence Read Archive (SRA) under the BioProject accession number PRJNA1140835.
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Affiliation(s)
- Xiaoyan Cao
- College of Horticulture, Xinjiang Agricultural University, China
| | - Xiaoqin Ye
- College of Forestry and Landscape Architecture, Xinjiang Agricultural University, China
| | - Adil Sattar
- College of Forestry and Landscape Architecture, Xinjiang Agricultural University, China
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31
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Luo S, Wu X, Wang H, Zhang Y, Xie L. Nitrate induced hepatic fibrosis in tadpoles of Bufo gargarizans by mediating alterations in toll-like receptor signaling pathways. ENVIRONMENTAL RESEARCH 2025; 270:120961. [PMID: 39875068 DOI: 10.1016/j.envres.2025.120961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 01/30/2025]
Abstract
The nitrate pollution has become an increasingly serious environmental problem worldwide, and the toxic effects of elevated nitrate levels in the environment on aquatic animals remain to be elucidated. The purpose of the present study was to investigate the mechanisms of liver injury to tadpoles after exposure to nitrate from embryonic to metamorphic climax and to assess the recovery process of liver function after cessation of exposure. In the group with continuous nitrate exposure, the livers and thyroid of tadpoles showed remarkably histological lesions, of this with structural disorganization of the hepatocytes, cellular atrophy, and fibrosis, as well as significant reduction in the follicular and colloidal area of the thyroid. Meanwhile, the expression levels of genes related to inflammatory signaling pathways, such as TLR2, TLR6 and NF-κB, were significant elevated. After termination of exposure at Gs23, liver damage (histologic, ultrastructural, and molecular levels) was almost completely recovered, whereas thyroid gland damage was irreversible. Overall, this study shed light on the harmful effects of nitrate pollution on amphibian health and emphasizes the importance of controlling nitrate emissions in the environment.
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Affiliation(s)
- Shuangyan Luo
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; College of Life Science, Shaanxi Normal University, 710119, Xi'an, China
| | - Xueyi Wu
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China
| | - Hongyuan Wang
- College of Life Science, Shaanxi Normal University, 710119, Xi'an, China
| | - Yongpu Zhang
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, 325003, Wenzhou, China.
| | - Lei Xie
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, 325003, Wenzhou, China.
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32
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Wang G, Zhang J, Li Y, Zhang Y, Dong W, Wu H, Wang J, Liao P, Yuan Z, Liu T, He W. Integrating single-cell RNA sequencing, WGCNA, and machine learning to identify key biomarkers in hepatocellular carcinoma. Sci Rep 2025; 15:11157. [PMID: 40169794 PMCID: PMC11962163 DOI: 10.1038/s41598-025-95493-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 03/21/2025] [Indexed: 04/03/2025] Open
Abstract
The microarray and single-cell RNA-sequencing (scRNA-seq) datasets of hepatocellular carcinoma (HCC) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify HCC-related biomarkers. Based on an analysis of scRNA-seq data, several marker genes expressed on tumor cells have been identified. Three machine-learning algorithms were used to identify shared diagnostic genes. Furthermore, logistic regression analysis was conducted to re-evaluate and identify essential biomarkers, which were then employed to develop a diagnostic prediction model. Additionally, AutoDockTools were used for molecular docking to investigate the association between the most sensitive drug and the core proteins. 44 genes were obtained by intersecting the WGCNA results, marker genes from scRNA-seq data, and up-regulated DEGs. Three machine-learning algorithms refined CDKN3, PPIA, PRC1, GMNN, and CENPW as hub biomarkers. GMNN and PRC1 were further selected by logistic regression analysis to build a nomogram. The molecular docking results showed that the drug NPK76-II-72-1 had a good binding ability with the GMNN and PRC1 proteins. The results highlighted CDKN3, PPIA, PRC1, GMNN, and CENPW as potential detection biomarkers for HCC patients. Our research offers novel insights into the diagnosis and treatment of HCC.
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Affiliation(s)
- Gang Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Jiaxing Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Yirong Li
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Yuyu Zhang
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Weiwei Dong
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Hengquan Wu
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Jinglan Wang
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Peiqing Liao
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Ziqiang Yuan
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China
| | - Tao Liu
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China.
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China.
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China.
| | - Wenting He
- School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu Province, China.
- The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu Province, China.
- Gansu Provincial Key Laboratory of Environmental Oncology, Lanzhou, 730000, Gansu Province, China.
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Li LC, Zhang ZH, Liu L, Chen B, Jin YC, Wang YZ. Protective Effects of Qingre Sanjie Jiaonang on Pulmonary Fibrosis: A Pilot Study. J Inflamm Res 2025; 18:4551-4565. [PMID: 40191096 PMCID: PMC11970429 DOI: 10.2147/jir.s479432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 03/21/2025] [Indexed: 04/09/2025] Open
Abstract
Background Qingre Sanjie Jiaonang (QRSJ) is a single herbal preparation from Senecio scandens Buch.-Ham.ex D. Don which has been proved to have anti-inflammatory and antioxidant effects. QRSJ has been used in treating upper respiratory tract inflammation and acute bronchitis in China for nearly twenty years. Purpose This study aims to explore the potential effects of QRSJ in alleviating pulmonary fibrosis (PF) and its mechanisms. Study Design and Method A mouse model of PF was induced by intratracheal injection of Bleomycin (BLM, 5 mg/kg), followed by different doses of QRSJ administration (0.5 g/kg, 1.0 g/kg) for 28 days. The lung tissues were collected and prepared for Hematoxylin-Eosin (H&E) staining to observe the pathological changes, while Masson staining was for determining collagen production. RNA sequencing (RNA-seq), flow cytometry and immunofluorescence experiments were employed to investigate the impact of QRSJ on the immune microenvironment. The expression levels of IL-1β, IL-6, CXCL15 (mouse homologue of human IL-8), and TNF-α in the bronchoalveolar lavage fluid (BALF) and serum of mice were observed. Besides, the levels of high mobility group protein B1 (HMGB1), an inflammatory and profibrotic mediator, in the BALF, serum and lung tissues of mice were also detected. Results The mouse model of PF was successfully established by checking the pathological examinations. With QRSJ intervention, BLM-induced destruction of alveolar structure and inflammatory cell infiltration were alleviated. H&E results further revealed that the administration of BLM and QRSJ had no impact on kidney histological structure of mice. Meanwhile, QRSJ inhibited the deposition of collagen, decreased the expression of fibronectin and lumican. Next, QRSJ treatment improved immune cell infiltration in the lung, along with the down-regulation of CD45 and Ly6G, and led to a decrease in the immune cell count in BALF. Furthermore, QRSJ alleviated the release of inflammatory factors, including NE, IL-1β, IL-6, CXCL15, and TNF-α. Besides, QRSJ significantly reduced the level of proinflammatory cytokine HMGB1. Conclusion This study demonstrated the benefits of QRSJ in improving the pathological abnormalities in a PF model, revealing the new potential of the old drug. It should be attributed to the regulation of abnormal immune microenvironment and HMGB1 release. Future efforts should focus on its specific pharmacological mechanisms and clinical outcomes.
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Affiliation(s)
- Liu-Cheng Li
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China
| | - Zhi-Hui Zhang
- Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, People’s Republic of China
| | - Lei Liu
- Department of Orthopaedics, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, 312000, People’s Republic of China
| | - Bo Chen
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China
| | - Ye-Cheng Jin
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China
| | - Yu-Zhen Wang
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China
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Braun BC, Hryciuk MM, Meneghini D. Transcriptome analysis of corpora lutea in domestic cats (Felis catus) reveals strong differences in gene expression of various hormones, hormone receptors and regulators across different developmental stages. BMC Genomics 2025; 26:325. [PMID: 40165054 PMCID: PMC11959938 DOI: 10.1186/s12864-025-11510-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 03/20/2025] [Indexed: 04/02/2025] Open
Abstract
In the domestic cat (Felis catus), the corpus luteum (CL) is the main source of progestogen during pregnancy. Here, we studied gene expression changes in different life cycle stages of the CL of pseudopregnant cats to identify potential regulatory factors. Results revealed no support for different regression substages, which were previously defined on the basis of morphological examination analysis and intraluteal hormone content, as only a very low number of differentially expressed genes and no subclusters in PCA plot were detected. By comparing the regression stage with the developmental/maintenance stage, we detected a total of 6174 differentially expressed genes in the sample set, of which 2882 were upregulated and 3292 were downregulated. The large changes in the expression levels of some genes indicate that the endocrine function of the CL may not be restricted to progesterone (P4) secretion. The findings suggest that domestic cat CLs could also be a source of adipokines such as adiponectin or APELA. The expression of these genes is highly variable and reversed between stages. The life cycle and activity of CLs seem to be regulated by different factors, as genes encoding for the hormone receptors LHCGR and PAQR5 were more highly expressed in the development/maintenance stage, in contrast to this encoding for LEPR, which is higher expressed in regression stage. For regression stage, we identified different potential ways to modulate the cholesterol level and/or P4 concentration. Furthermore, we found differences from previous studies in other species for many genes that were studied in more detail, as well as when analysing functions and pathways. Our findings support the hypothesis that different stages of the CL life cycle in domestic cats can be characterized by changes in gene regulation and that CL life cycles are partly differentially regulated between species.
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Affiliation(s)
- Beate C Braun
- Department of Reproduction Biology, Leibniz Institute for Zoo and Wildlife Research, 10315, Berlin, Germany.
| | - Michał M Hryciuk
- Department of Reproduction Biology, Leibniz Institute for Zoo and Wildlife Research, 10315, Berlin, Germany
| | - Dorina Meneghini
- Department for Evolutionary Genetics, Leibniz Institute for Zoo and Wildlife Research, 10315, Berlin, Germany
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Wu S, Luo Y, Wei F, Li Y, Fan J, Chen Y, Zhang W, Li X, Xu Y, Chen Z, Xia C, Hu M, Li P, Gu Q. Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation. Food Funct 2025. [PMID: 40152095 DOI: 10.1039/d4fo06308b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.
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Affiliation(s)
- Shiying Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yuenuo Luo
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Fangtong Wei
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yanan Li
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, China
| | - Jiayi Fan
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yongqiang Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Wenjie Zhang
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Xuelong Li
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Yang Xu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ziqi Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Chenlan Xia
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Mingyang Hu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
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Cai ZX, Zeng ZH, Chen WZ, Guo ZJ, Lu YP, Liao JH, Zeng H, Chen MY. Transcriptomic and metabolomic insights into flavor variations in wild and cultivated Agaricus bisporus. Sci Rep 2025; 15:10798. [PMID: 40155773 PMCID: PMC11953371 DOI: 10.1038/s41598-025-95714-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 03/24/2025] [Indexed: 04/01/2025] Open
Abstract
Agaricus bisporus is a widely cultivated edible fungus globally. However, the mechanisms underlying the differences in flavor and nutritional traits between wild-type (W) and cultivated-type (C) strains remain unclear, which hinders the artificial breeding of high-quality varieties. This study systematically revealed, for the first time, the molecular and metabolic basis of flavor divergence between wild and cultivated A. bisporus by integrating transcriptomics and metabolomics. A total of 43 strains (23 wild-type and 20 cultivated-type) were analyzed using high-throughput sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to dissect differences in gene expression and metabolite profiles. Results showed that although total protein and amino acid contents exhibited no significant differences, transcriptomic analysis identified significant upregulation of AGABI2DRAFT_188981 and AGABI2DRAFT_191000 (genes associated with high-affinity methionine permease MUP1) in cultivated strains, suggesting their indirect regulation of flavor formation via methionine metabolism. Metabolomic analysis further revealed a marked increase in uridine levels in cultivated strains (3.2-fold higher than wild-type, p < 0.01), indicating potential medicinal value, while wild strains were enriched with flavor precursors such as fumaric acid and isoleucine (fold change ≥ 2.5). In contrast, cultivated strains accumulated metabolites like 2-hydroxybutyric acid and α-ketoglutarate (VIP > 1.5). This study pioneered the construction of a gene-metabolite correlation network, identifying a strong positive correlation between AGABI2DRAFT_191352 (6-phosphofructokinase) and 2-hydroxybutyric acid (r = 0.82), highlighting the regulatory role of glycolytic flux in flavor metabolism. These findings not only elucidate the impact of artificial cultivation on metabolic reprogramming in A. bisporus but also provide critical molecular targets for targeted breeding of strains with enhanced flavor and nutritional value, offering practical significance for advancing the edible fungi industry.
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Affiliation(s)
- Zhi-Xin Cai
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Zhi-Heng Zeng
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Wen-Zhi Chen
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Zhong-Jie Guo
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Yuan-Ping Lu
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Jian-Hua Liao
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Hui Zeng
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China
| | - Mei-Yuan Chen
- Institute of Edible Mushroom, Fujian Academy of Agricultural Sciences, Fuzhou, Fujian, China.
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Tian X, Wang Z, Yi C, Shi Y, Jia C, Li X, Jiang F, Wang Z. Effects of basal division of posterior pallial amygdala on the motor behaviors in pigeons based on transcriptome analysis. Brain Res Bull 2025; 224:111322. [PMID: 40154927 DOI: 10.1016/j.brainresbull.2025.111322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Revised: 03/13/2025] [Accepted: 03/24/2025] [Indexed: 04/01/2025]
Abstract
The basal division of posterior pallial amygdala (PoAb) was one important part of the amygdala in birds. PoAb mainly mediated turning behavior. However, the regulating neuromechanisms of PoAb in motor behavior was not clear yet. In this study, we selected septalis lateralis (SL) as the stimulated nucleus because it was closely associated with PoAb and had clear neuroregulatory functions, and we also used unrelated nuclei (entopallium) and unstimulated blank treatment (CK) as controls. We aim to study the neuroregulatory mechanisms of PoAb by investigating the differences of transcriptome level in different groups. A total of 622 differentially expressed genes (DEGs) were obtained from PoAb after comparing the SL stimulating group with the CK control group. GO functional annotation and KEGG pathway enrichment analysis showed that the upregulated 608 DEGs mainly involved energy supply and fluid balance. A total of 345 DEGs were obtained from the PoAb when comparing SL stimulation group and entopallium stimulation group. The upregulated 187 DEGs were mainly involved in cell communication and signal transductions. The study indicated that PoAb may modulate motor behaviour mainly by increasing ATP production and facilitating synaptic transmission, in which genes such as SMAD3, TMED3, GRIA2, HTR1B and SNCG play an important role. We revealed the mechanisms of brain regulation behaviour from gene level, and provided the theoretical foundation for understanding the avian brain.
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Affiliation(s)
- Xinmao Tian
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China; School of Medicine and Health, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China; Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, Henan 450000, China.
| | - Zishi Wang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
| | - Chunzhi Yi
- School of Medicine and Health, Harbin Institute of Technology, Harbin, Heilongjiang, 150001, China; Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, Henan 450000, China.
| | - Yuhua Shi
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
| | - Chongchong Jia
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China; School of Electrical and Information Engineering, Zhengzhou University, Zhengzhou, Henan 450001, China.
| | - Xiujuan Li
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
| | - Feng Jiang
- School of Artificial Intelligence (School of Future Technology), Nanjing University of Information Science & Technology, Nanjing, Jiangsu, 210000, China.
| | - Zhenlong Wang
- School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
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Islam MSU, Shing P, Ahmed M, Zohra FT, Rownaq A, Paul SK, Rahman SM, Sarkar MAR. Genome-wide identification and characterization of NCED gene family in soybean (Glycine max L.) and their expression profiles in response to various abiotic stress treatments. PLoS One 2025; 20:e0319952. [PMID: 40131870 PMCID: PMC11936224 DOI: 10.1371/journal.pone.0319952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 02/11/2025] [Indexed: 03/27/2025] Open
Abstract
The NCED (9-cis-epoxy carotenoid dioxygenase) enzyme regulates the biosynthesis of abscisic acid (ABA), which is responsible for plant growth, development, and response to various environmental challenges. However, no genome-wide identification, characterization, functional regulatory element analysis, and expression profiles in response to different abiotic stresses of the NCED gene family have yet to be investigated in an economically important legume plant species, soybean (Glycine max L.). Through comprehensive analysis, 16 NCED genes (named GmNCED1 to GmNCED16) belonging to the RPE65 domain were identified in the soybean genome and found to be unequally distributed over 9 distinct chromosomes. The distinct intron-exon structures of GmNCED genes were categorized into six groups and shared a close relationship with the grapevine. Segmental gene duplication events and the purifying selection process were evident in GmNCED genes, according to evolutionary studies. Cis-acting regulatory element analysis revealed that GmNCED genes were largely associated with light response as well as stress response. ERF, MYB, bZIP, and LBD emerged as the major transcription factors in GmNCED genes. The protein-protein interactions demonstrated the close relationship between GmNCED and Arabidopsis thaliana proteins, while micro-RNA analysis revealed the involvement of GmNCED genes in plant growth and development as well as in the regulation of abiotic stress. The expression profiles of GmNCED2, GmNCED11, and GmNCED12 provided evidence of their engagement in dehydration and sodium salt stress, whereas GmNCED14 and GmNCED15 were up-regulated in drought stress. Moreover, the up-regulation of GmNCED13 and GmNCED14 genes in heat tolerant germinated seed stages at high temperature delta region. More specifically, GmNCED14 might be used as a novel candidate gene under drought stress, and influencing seed germination at high temperature. Overall, this study identified the crucial role of GmNCED in conferring resistance against abiotic stress such as dehydration, salt, and drought, and also uncovering the detailed regulatory mechanism of ABA biosynthesis during seed germination.
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Affiliation(s)
- Md Shohel Ul Islam
- Laboratory of Functional Genomics and Proteomics, Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Pollob Shing
- Laboratory of Functional Genomics and Proteomics, Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Mahin Ahmed
- Laboratory of Functional Genomics and Proteomics, Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Fatema Tuz Zohra
- Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University of Rajshahi, Rajshahi, Bangladesh
| | - Amina Rownaq
- Institute of Biological Sciences, University of Rajshahi, Rajshahi, Bangladesh
| | - Suronjeet Kumar Paul
- Laboratory of Functional Genomics and Proteomics, Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Shaikh Mizanur Rahman
- Laboratory of Functional Genomics and Proteomics, Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh
| | - Md. Abdur Rauf Sarkar
- Laboratory of Functional Genomics and Proteomics, Department of Genetic Engineering and Biotechnology, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Bangladesh
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Davies JWA, Bredy TW, Marshall PR. Cutting-edge RNA technologies to advance the understanding of learning and memory. Neurobiol Learn Mem 2025; 219:108050. [PMID: 40147812 DOI: 10.1016/j.nlm.2025.108050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 02/13/2025] [Accepted: 03/24/2025] [Indexed: 03/29/2025]
Abstract
Following the recent emergence of RNA as a therapeutic tool, and coupled with an explosion in the development of new RNA technologies, it is rapidly becoming clear that the 21st century is the era of RNA. Neuroscience as a discipline has a long history of embracing new technology to advance the understanding of brain function, particularly in the context of learning and memory. In this short review, we highlight four broad categories of emerging RNA technologies, namely: imaging, isolation, identification and manipulation, and discuss their potential to advance the fundamental understanding of how RNA impacts experience-dependent plasticity, learning, and memory.
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Affiliation(s)
- Joshua William Ashley Davies
- UQ Centre for RNA in Neuroscience, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia; Genomic Plasticity Laboratory, Genome Sciences and Cancer Division & Eccles Institute of Neuroscience, John Curtain School of Medical Research, Australian National University, Canberra 2601, Australia.
| | - Timothy William Bredy
- UQ Centre for RNA in Neuroscience, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.
| | - Paul Robert Marshall
- Genomic Plasticity Laboratory, Genome Sciences and Cancer Division & Eccles Institute of Neuroscience, John Curtain School of Medical Research, Australian National University, Canberra 2601, Australia.
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Oh HR, Park YH, Hong HR, Kim HJ, Park J, Han Y, Ko SG, Shin EC, Kim TG, Cho HT, Pan JH, Shin HR, Shim YY, Reaney MJT, Cho TJ, Hong JY, Kim YJ, Han BK, Lee GJ, Lee K, Do SG, Kim JK. Tetragonia tetragonioides extract prevented high-fat-diet-induced obesity and changed hepatic and adipose transcriptomic signatures in C57BL/6J male mice. Biosci Biotechnol Biochem 2025; 89:599-611. [PMID: 39799382 DOI: 10.1093/bbb/zbaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 01/08/2025] [Indexed: 01/15/2025]
Abstract
Obesity, often driven by high-fat diets (HFDs), is a major global health issue, necessitating effective preventive measures. Tetragonia tetragonoides, a plant with known medicinal properties, has not been extensively studied for its effects on HFD-induced obesity and related genetic changes in mice. This study explores the impact of T. tetragonoides extract (TTE; 300 mg/kg) on obesity-related traits in C57BL/6J male mice, with a focus on transcriptomic changes in the liver and white adipose tissue (WAT). Over 8 weeks, TTE supplementation led to significant reductions in obesity-related phenotypes and modulated gene expression altered by HFD. Key genes like Cd180 and MUPs, linked to immune responses and lipid metabolism, were notably influenced by TTE. The study highlighted TTE's effects on lipid metabolism pathways in the liver and immune processes in WAT, underscoring its potential as an anti-obesity agent, while advocating for further research into its bioactive components.
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Affiliation(s)
- Hea Ry Oh
- Department of Regulatory Science, Korea University, Sejong, Republic of Korea
- Naturetech, Jincheon, Republic of Korea
| | - Yong Hyun Park
- Department of Regulatory Science, Korea University, Sejong, Republic of Korea
- Naturetech, Jincheon, Republic of Korea
| | | | - Hyun Jin Kim
- Department of Regulatory Science, Korea University, Sejong, Republic of Korea
- Naturetech, Jincheon, Republic of Korea
| | - Jinbong Park
- Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Yohan Han
- Department of Microbiology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Seong-Gyu Ko
- Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| | - Eui Cheol Shin
- Department of GreenBio Science, Gyeongsang National University, Jinju, Republic of Korea
| | - Tae Gyun Kim
- The Bioinformatix, Gwangmyeong, Republic of Korea
| | | | - Jeong Hoon Pan
- Department of Food and Nutrition, Chosun University, Gwangju, Republic of Korea
- The Basic Science Institute of Chosun University, Chosun University, Gwangju, Republic of Korea
| | - Hyo Ri Shin
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
| | - Youn Young Shim
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
- Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK, Canada
| | - Martin J T Reaney
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
- Department of Food and Bioproduct Sciences, University of Saskatchewan, Saskatoon, SK, Canada
| | - Tae Jin Cho
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
| | - Ji Youn Hong
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
| | - Young Jun Kim
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
| | - Bok Kyung Han
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
| | - Geung-Joo Lee
- Department of Horticulture, Chungnam National University, Daejeon, Republic of Korea
| | - Kangwook Lee
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
| | | | - Jae Kyeom Kim
- Department of Food and Biotechnology, Korea University, Sejong, Republic of Korea
- Department of Behavioral Health and Nutrition, University of Delaware, Newark, DE, USA
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Comendul A, Ruf-Zamojski F, Ford CT, Agarwal P, Zaslavsky E, Nudelman G, Hariharan M, Rubenstein A, Pincas H, Nair VD, Michaleas AM, Fremont-Smith PD, Ricke DO, Sealfon SC, Woods CW, Claypool KT, Jaimes R. Comprehensive guide for epigenetics and transcriptomics data quality control. STAR Protoc 2025; 6:103607. [PMID: 39869481 PMCID: PMC11799959 DOI: 10.1016/j.xpro.2025.103607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 09/27/2024] [Accepted: 01/07/2025] [Indexed: 01/29/2025] Open
Abstract
Host response to environmental exposures such as pathogens and chemicals can include modifications to the epigenome and transcriptome. Improved signature discovery, including the identification of the agent and timing of exposure, has been enabled by advancements in assaying techniques to detect RNA expression, DNA base modifications, histone modifications, and chromatin accessibility. The interrogation of the epigenome and transcriptome cascade requires analyzing disparate datasets from multiple assay types, often at single-cell resolution, derived from the same biospecimen. However, there remains a paucity of rigorous quality control standards of those datasets that reflect quality assurance of the underlying assay. This guide outlines a comprehensive suite of metrics that can be used to ensure quality from 11 different epigenetics and transcriptomics assays. Recommended mitigative actions to address failed metrics are provided. The workflow presented aims to improve benchwork protocols and dataset quality to enable accurate discovery of exposure signatures.
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Affiliation(s)
- Arianna Comendul
- Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA, USA
| | - Frederique Ruf-Zamojski
- Cedars-Sinai Medical Center, Department of Medicine, Los Angeles, CA, USA; Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Colby T Ford
- Tuple LLC, Charlotte, NC, USA; University of North Carolina at Charlotte, Department of Bioinformatics and Genomics, Charlotte, NC, USA; University of North Carolina at Charlotte, Center for Computational Intelligence to Predict Health and Environmental Risks (CIPHER), Charlotte, NC, USA
| | | | | | | | - Manoj Hariharan
- Genomic Analysis Laboratory, Salk Institute, La Jolla, CA, USA
| | | | - Hanna Pincas
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Adam M Michaleas
- Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA, USA
| | | | - Darrell O Ricke
- Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA, USA
| | | | | | - Kajal T Claypool
- Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA, USA
| | - Rafael Jaimes
- Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA, USA.
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42
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Pradeepkiran JA, Islam MA, Sehar U, Reddy AP, Vijayan M, Reddy PH. Impact of diet and exercise on mitochondrial quality and mitophagy in Alzheimer's disease. Ageing Res Rev 2025; 108:102734. [PMID: 40120948 DOI: 10.1016/j.arr.2025.102734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/26/2024] [Accepted: 03/15/2025] [Indexed: 03/25/2025]
Abstract
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions of people worldwide. It is characterized by the accumulation of beta-amyloid and phosphorylated tau, synaptic damage, and mitochondrial abnormalities in the brain, leading to the progressive loss of cognitive function and memory. In AD, emerging research suggests that lifestyle factors such as a healthy diet and regular exercise may play a significant role in delaying the onset and progression of the disease. Mitochondria are often referred to as the powerhouse of the cell, as they are responsible for producing the energy to cells, including neurons to maintain cognitive function. Our article elaborates on how mitochondrial quality and function decline with age and AD, leading to an increase in oxidative stress and a decrease in ATP production. Decline in mitochondrial quality can impair cellular functions contributing to the development and progression of disease with the loss of neuronal functions in AD. This article also covered mitophagy, the process by which damaged or dysfunctional mitochondria are selectively removed from the cell to maintain cellular homeostasis. Impaired mitophagy has been implicated in the progression and pathogenesis of AD. We also discussed the impact of impaired mitophagy implicated in AD, as the accumulation of damaged mitochondria can lead to increased oxidative stress. We expounded how dietary interventions and exercise can help to improve mitochondrial quality, and mitochondrial function and enhance mitophagy in AD. A diet rich in antioxidants, polyphenols, and mitochondria-targeted small molecules has been shown to enhance mitochondrial function and protect against oxidative stress, particularly in neurons with aged and mild cognitively impaired subjects and AD patients. Promoting a healthy lifestyle, mainly balanced diet and regular exercise that support mitochondrial health, in an individual can potentially delay the onset and progression of AD. In conclusion, a healthy diet and regular exercise play a crucial role in maintaining mitochondrial quality and mitochondrial function, in turn, enhancing mitophagy and synaptic activities that delay AD in the elderly populations.
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Affiliation(s)
| | - Md Ariful Islam
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Ujala Sehar
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Arubala P Reddy
- Nutritional Sciences Department, College Human Sciences, Texas Tech University, Lubbock, TX, USA
| | - Murali Vijayan
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - P Hemachandra Reddy
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Nutritional Sciences Department, College Human Sciences, Texas Tech University, Lubbock, TX, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
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43
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Wu T, Zhan F, Zeng L, Sun Y, Fu S, Fang Y, Lin X, Lin H, Su J, Cai S. Arginine accumulation suppresses heat production during fermentation of the biocontrol fungus Beauveria bassiana. Appl Environ Microbiol 2025; 91:e0213424. [PMID: 39907454 PMCID: PMC11921393 DOI: 10.1128/aem.02134-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 01/15/2025] [Indexed: 02/06/2025] Open
Abstract
Beauveria bassiana (Bb) is one of the most widely used biocontrol agents, and its products constitute more than one-third of the global market share of fungal insecticides. Solid-state fermentation (SSF) is widely used in the production of Beauveria bassiana (Bb) because of its economic practicality and high production efficiency. However, the heat generated during fermentation can sharply reduce both the yield and quality of Bb, and current industrial methods to mitigate high temperatures during fermentation are inadequate, leading to increased production costs. Thus, exploring the underlying mechanism of how heat is produced by Bb is crucial for improving the SSF procedure and yield. This study employed multiomics data analysis of Bb during SSF to explore the relationships between fungal fermentation and environmental factors. We found that the heat production period for SSF was 12 hours to 48 hours post-inoculation. To further explore the underlying mechanism during this heating period, we identified 454 temperature-correlated metabolites (TCMs) and 1,994 temperature-correlated genes (TCGs). Annotations of the above TCMs and TCGs revealed significant enrichment in the arginine biosynthesis pathway; specifically, the expression level of glutamine synthetase, a TCG, decreased with fermentation time, whereas the expression levels of the TCGs L-arginine and L-glutamine increased with fermentation time, and glutamine synthetase and L-glutamine in the arginine biosynthesis pathway cycle produced the end product L-arginine. Furthermore, when the substrates of the SSF were treated with exogenous arginine, the temperature peak of the SSF significantly decreased with increasing concentration of exogenously added arginine.IMPORTANCEA large amount of experimental evidence from the field has shown that Bb is an irreplaceable mature product that protects the health of our agriculture and ecosystem. In addition to high efficiency and host extensiveness, low cost is a critical merit that makes Bb products frequently used in the field. However, the growing cost of power and labor in the Bb industry, especially the SSF procedure, has significantly increased the price of its products, thus restricting the use of Bb in the field. This study not only fills the theoretical knowledge gaps concerning the molecular basis of the interrelationship between Bb and the fermentation environment during SSF but also provides an economical and applicable strategy (the addition of arginine to the fermentation media) to further lower the cost and increase the yield of Bb during SSF at the industrial level.
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Affiliation(s)
- Tong Wu
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, China
- Fujian Academy of Forestry, Key Laboratory of National Forestry and Grassland Administration on Timber Forest Breeding and Cultivation for Mountainous Areas in Southern China, Fuzhou, China
| | - Fangfang Zhan
- Fujian Academy of Forestry, Key Laboratory of National Forestry and Grassland Administration on Timber Forest Breeding and Cultivation for Mountainous Areas in Southern China, Fuzhou, China
| | - Liqiong Zeng
- Fujian Academy of Forestry, Key Laboratory of National Forestry and Grassland Administration on Timber Forest Breeding and Cultivation for Mountainous Areas in Southern China, Fuzhou, China
| | - Yanli Sun
- Forestry Development Center of Lanshan District in Linyi, Shandong, China
| | - Shihui Fu
- Liancheng Forestry Bureau, Liancheng, China
| | - Yu Fang
- Institute of Resources, Environment and Soil Fertilizer, Fujian Academy of Agricultural Sciences, Fuzhou, China
| | | | - Haoyu Lin
- Fujian Academy of Forestry, Key Laboratory of National Forestry and Grassland Administration on Timber Forest Breeding and Cultivation for Mountainous Areas in Southern China, Fuzhou, China
| | - Jun Su
- Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Shouping Cai
- Fujian Academy of Forestry, Key Laboratory of National Forestry and Grassland Administration on Timber Forest Breeding and Cultivation for Mountainous Areas in Southern China, Fuzhou, China
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Ling Z, Niego B, Li Q, Villa VS, Bhattaram D, Hu M, Gong Z, Smith LM, Frey BL, Ren X. Chemoselective Characterization of New Extracellular Matrix Deposition in Bioengineered Tumor Tissues. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.03.18.643336. [PMID: 40166338 PMCID: PMC11956949 DOI: 10.1101/2025.03.18.643336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/02/2025]
Abstract
The extracellular matrix (ECM), present in nearly all tissues, provides extensive support to resident cells through structural, biomechanical, and biochemical means, and in return the ECM undergoes constant remodeling from interacting cells to adapt to the evolving tissue states. Bioengineered 3D tissues, commonly known as cell-ECM composites, are robust model systems to recapitulate and investigate native pathophysiology. Key to this engineered morphogenesis process are the intricate cell-ECM interactions reflected by how cells respond to and thereby modulate their surrounding microenvironments through their ongoing ECM secretome. However, investigating ECM-regulated new ECM production has been challenging due to the proteomic background from the pre-existing biomaterial ECM. To address this hindrance, here we present a chemoselective strategy to label, enrich, and characterize newly synthesized ECM (newsECM) proteins produced by resident cells, allowing distinction from the pre-existing ECM background. Applying our analytical pipeline to bioengineered tumor tissues, either built upon decellularized ECM (dECM-tumors) or as ECM-free tumor spheroids (tumoroids), we observed distinct ECM synthesis patterns that were linked to their extracellular environments. Tumor cells responded to the dECM presence with elevated ECM remodeling activities, mediated by augmented digestion of pre-existing ECM coupled with upregulated synthesis of tumor-associated ECM. Our findings highlight the sensitivity of newsECM profiling to capture remodeling events that are otherwise under-represented by bulk proteomics and underscore the significance of dECM support for enabling native-like tumor cell behaviors. We anticipate the described newsECM analytical pipeline to be broadly applicable to other tissue-engineered systems to probe ECM-regulated ECM synthesis and remodeling, both fundamental aspects of cell-ECM crosstalk in engineered tissue morphogenesis.
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Affiliation(s)
- Zihan Ling
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
| | - Burke Niego
- Department of Chemistry, University of Wisconsin, Madison, Wisconsin, United States
| | - Qingyang Li
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
| | - Vanessa Serna Villa
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
| | - Dhruv Bhattaram
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
| | - Michael Hu
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
| | - Zhuowei Gong
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
| | - Lloyd M. Smith
- Department of Chemistry, University of Wisconsin, Madison, Wisconsin, United States
| | - Brian L. Frey
- Department of Chemistry, University of Wisconsin, Madison, Wisconsin, United States
| | - Xi Ren
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States
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45
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PANG GUANTING, LI YAOHAN, SHI QIWEN, TIAN JINGKUI, LOU HANMEI, FENG YUE. Omics sciences for cervical cancer precision medicine from the perspective of the tumor immune microenvironment. Oncol Res 2025; 33:821-836. [PMID: 40191729 PMCID: PMC11964870 DOI: 10.32604/or.2024.053772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 08/01/2024] [Indexed: 04/09/2025] Open
Abstract
Immunotherapies have demonstrated notable clinical benefits in the treatment of cervical cancer (CC). However, the development of therapeutic resistance and diverse adverse effects in immunotherapy stem from complex interactions among biological processes and factors within the tumor immune microenvironment (TIME). Advanced omic technologies offer novel insights into a more expansive and thorough layer of the TIME. Furthermore, integrating multidimensional omics within the frameworks of systems biology and computational methodologies facilitates the generation of interpretable data outputs to characterize the clinical and biological trajectories of tumor behavior. In this review, we present advanced omics technologies that utilize various clinical samples to address scientific inquiries related to immunotherapies for CC, highlighting their utility in identifying metastasis dissemination, recurrence risk, and therapeutic resistance in patients treated with immunotherapeutic approaches. This review elaborates on the strategy for integrating multi-omics data through artificial intelligence algorithms. Additionally, an analysis of the obstacles encountered in the multi-omics analysis process and potential avenues for future research in this domain are presented.
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Affiliation(s)
- GUANTING PANG
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
| | - YAOHAN LI
- College of Artificial Intelligence and Big Data for Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
| | - QIWEN SHI
- Collaborative Innovation Center for Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, China
| | - JINGKUI TIAN
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
| | - HANMEI LOU
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - YUE FENG
- Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China
- Department of Gynecological Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
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Zhou R, Xie Y, Wang Z, Liu Z, Lu W, Li X, Wei C, Li X, Wang F. Single-cell transcriptomic analysis reveals CD8 + T cell heterogeneity and identifies a prognostic signature in cervical cancer. BMC Cancer 2025; 25:498. [PMID: 40102789 PMCID: PMC11916872 DOI: 10.1186/s12885-025-13901-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Accepted: 03/10/2025] [Indexed: 03/20/2025] Open
Abstract
BACKGROUND In recent years, immunotherapy has made significant progress. However, the understanding of the heterogeneity and function of T cells, particularly CD8 + T cells, in cervical cancer (CESC) microenvironment remains insufficient. We aim to characterize the heterogeneity, developmental trajectory, regulatory network, and intercellular communication of CD8 + T cells in cervical squamous cell carcinoma and to construct a prognostic risk model based on the transcriptomic characteristics of CD8 + T cells. METHODS We integrated single-cell RNA sequencing data from CESC tumor samples with bulk transcriptome data from TCGA and GEO databases. We identified CD8 + T cell subsets in the CESC microenvironment, revealing significant interactions between CD8 + T cells and other cell types through intercellular communication analysis. Pseudotime trajectory analysis revealed dynamic transcriptional regulation during CD8 + T cell differentiation and functional acquisition processes. We constructed a transcriptional regulatory network for CESC CD8 + T cells, identifying key transcription factors. Based on CD8 + T cell-related genes, a prognostic risk model comprising eight core genes was developed and validated using machine learning. RESULTS We identified four distinct CD8 + T cell subsets, namely progenitor, intermediate, proliferative, and terminally differentiated, each exhibiting unique transcriptomic characteristics and functional properties. CD8 + T cell subsets interact with macrophages through different ligand-receptor networks, including the CCL-CCR signaling pathway and costimulatory molecules. Sorafenib was identified as a potential immunotherapeutic drug through drug screening. Experimental validation demonstrated that sorafenib enhances the cytotoxicity of CD8 + T cells by increasing the secretion of IFN-γ and TNF-α, thereby significantly inhibiting the invasiveness and survival of CESC cells. CONCLUSIONS Our study provides valuable insights into the heterogeneity and functional diversity of CD8 + T cells in CESC. We demonstrate that a CD8 + T cell-related prognostic signature may serve as a potential tool for risk stratification in patients with CESC. Additionally, our finding suggests that sorafenib could be a promising therapeutic candidate for improving antitumor immunity in this patient population.
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Affiliation(s)
- Rongbin Zhou
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Yuli Xie
- Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Zuheng Wang
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, 530021, China
| | - Zige Liu
- Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, 530021, China
| | - Wenhao Lu
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Xiao Li
- School of Life Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Chunmeng Wei
- Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, 530021, China
| | - Xing Li
- Department of Obstetrics and Gynecology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, No. 85, Wujin Road, Hongkou District, Shanghai, 200080, China.
| | - Fubo Wang
- Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, 530021, China.
- School of Life Sciences, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- Department of Urology, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, China.
- , No. 22, Shuangyong Road, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China.
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Martínez A, Bonaglia S, Di Domenico M, Fonseca G, Ingels J, Jörger KM, Laumer C, Leasi F, Zeppilli D, Baldrighi E, Bik H, Cepeda D, Curini-Galletti M, Cutter AD, Dos Santos G, Fattorini S, Frisch D, Gollner S, Jondelius U, Kerbl A, Kocot KM, Majdi N, Mammola S, Martín-Durán JM, Menegotto A, Montagna PA, Nascimento FJA, Puillandre N, Rognant A, Sánchez N, Santos IR, Schmidt-Rhaesa A, Schratzberger M, Semprucci F, Shimabukuro M, Sommerfield PJ, Struck TH, Sørensen MV, Wallberg A, Worsaae K, Yamasaki H, Fontaneto D. Fundamental questions in meiofauna research highlight how small but ubiquitous animals can improve our understanding of Nature. Commun Biol 2025; 8:449. [PMID: 40097602 PMCID: PMC11914145 DOI: 10.1038/s42003-025-07888-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 03/05/2025] [Indexed: 03/19/2025] Open
Affiliation(s)
- Alejandro Martínez
- Molecular Ecology Group (MEG), Water Research Institute (CNR-IRSA), National Research Council, 28922, Verbania Pallanza, Italy.
| | - Stefano Bonaglia
- Department of Marine Sciences, University of Gothenburg, Gothenburg, Sweden
| | - Maikon Di Domenico
- Center for Marine Studies (CEM), Federal University of Paraná (UFPR), Pontal do Paraná, Paraná, Brazil
| | - Gustavo Fonseca
- Marine Science Institute, Federal University of São Paulo, Santos, Brazil
| | - Jeroen Ingels
- National Institute of Water and Atmospheric Research, 301 Evans Bay Parade, Hataitai, 6021, Wellington, New Zealand
| | | | | | - Francesca Leasi
- Department of Biology, Geology, and Environmental Science, University of Tennessee at Chattanooga, Chattanooga, TN, USA
| | - Daniela Zeppilli
- UMR6197 Biologie et Écologie des Ecosystèmes Marins Profonds, University Brest, CNRS, Ifremer, 29280, Plouzané, France
| | - Elisa Baldrighi
- Department of Biology, The University of Nevada, Reno, NV, USA
| | - Holly Bik
- Department of Marine Science & Institute of Bioinformatics, University of Georgia, Athens, GA, USA
| | - Diego Cepeda
- Department of Life Sciences, University of Alcalá (UAH), Ctra. Madrid-Barcelona Km.33, 600. 28805 Alcalá de Henares, Madrid, Spain
| | - Marco Curini-Galletti
- Department of Veterinary Medicine, University of Sassari, Sassari, Italy
- National Biodiversity Future Center (NBFC), Palermo, Italy
| | - Asher D Cutter
- Department of Ecology & Evolutionary Biology. University of Toronto, Toronto, ON, M5S3B2, Canada
| | - Giovanni Dos Santos
- Zoology Department, Federal University of Pernambuco, 50670-901, Recife-PE, Brazil
| | - Simone Fattorini
- Department of Life, Health & Environmental Sciences, University of L'Aquila, Via Vetoio - Coppito, 67100, L'Aquila, Italy
| | - Dagmar Frisch
- Department of Evolutionary and Integrative Ecology, IGB Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany
| | - Sabine Gollner
- Department of Ocean Systems (OCS), Royal Netherlands Institute for Sea Research (NIOZ), Landsdiep 4, 1797 SZ 't Horntje, Texel, The Netherlands
| | - Ulf Jondelius
- Swedish Museum of Natural History, Department of Zoology, POB 50007, SE-104 05, Stockholm, Sweden
| | - Alexandra Kerbl
- Department for Evolutionary Neurobiology, Centre for Organismal Studies, University Heidelberg. Im Neuenheimer Feld 230, 69120, Heidelberg, Germany
| | - Kevin M Kocot
- Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, USA
| | - Nabil Majdi
- Réserve Naturelle Nationale de la Forêt de la Massane, Sorbonne Université, UPMC Université Paris 06, Observatoire Océanologique de Banyuls, 66650, Banyuls-sur-Mer, France
| | - Stefano Mammola
- Molecular Ecology Group (MEG), Water Research Institute (CNR-IRSA), National Research Council, 28922, Verbania Pallanza, Italy
- National Biodiversity Future Center (NBFC), Palermo, Italy
- Laboratory for Integrative Biodiversity Research (LIBRe), Finnish Museum of Natural History (LUOMUS), University of Helsinki, Helsinki, Finland
| | - José M Martín-Durán
- School of Biological and Behavioural Sciences. Queen Mary University of London. Mile End Road, E1 4NS, London, UK
| | - André Menegotto
- Department of Ecology, Research Centre for Biodiversity and Global Change, Autonomous University of Madrid (CIBC-UAM), C/ Darwin 2, 28049, Madrid, Spain
- Terrestrial Ecology Group (TEG-UAM), Department of Ecology, Autonomous University of Madrid, 28049, Madrid, Spain
- Department of Ecology, ICB, Federal University of Goiás, Goiânia, 74690-900, Brazil
| | - Paul A Montagna
- Harte Research Institute, Texas A&M University-Corpus Christi, Corpus Christi, TX, USA
| | | | - Nicolas Puillandre
- Institut Systématique Evolution Biodiversité (ISYEB), Muséum national d'Histoire naturelle, CNRS, Sorbonne Université, EPHE, Université des Antilles, 57 rue Cuvier, CP51, Paris, France
| | - Anne Rognant
- Océanopolis. Port de Plaisance du Moulin blanc. B.P. 91039. Brest Cedex 1, Brest, 29210, France
| | - Nuria Sánchez
- Facultad de Ciencias Biológicas, Departamento de Biodiversidad, Ecología y Evolución José Antonio Novais, 12. Planta 10. 28040 Madrid, Spain. Universidad Complutense de Madrid, Madrid, Spain
| | - Isaac R Santos
- Department of Marine Sciences, University of Gothenburg, Gothenburg, Sweden
| | | | | | - Federica Semprucci
- Dipartimento di Scienze Biomolecolari., Università degli Studi di Urbino Carlo Bo, Marche, Italy
| | - Mauricio Shimabukuro
- Universidade Federal do Rio Grande (FURG) - Instituto de Oceanografia, Rio Grande, Brazil
| | | | - Torsten H Struck
- Natural History Museum, University of Oslo, 1172, Blindern, 0318, Oslo, Norway
| | - Martin V Sørensen
- Natural History Museum of Denmark, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Wallberg
- Department of Medical Biochemistry and Microbiology, Uppsala University; Husargatan 3, 751 23, Uppsala, Sweden
| | - Katrine Worsaae
- Marine Biological Section, Department of Biology, University of Copenhagen, Universitetsparken 4, 2100, Copenhagen, Denmark
| | | | - Diego Fontaneto
- Molecular Ecology Group (MEG), Water Research Institute (CNR-IRSA), National Research Council, 28922, Verbania Pallanza, Italy
- National Biodiversity Future Center (NBFC), Palermo, Italy
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Razalli II, Abdullah-Zawawi MR, Tamizi AA, Harun S, Zainal-Abidin RA, Jalal MIA, Ullah MA, Zainal Z. Accelerating crop improvement via integration of transcriptome-based network biology and genome editing. PLANTA 2025; 261:92. [PMID: 40095140 DOI: 10.1007/s00425-025-04666-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 03/03/2025] [Indexed: 03/19/2025]
Abstract
MAIN CONCLUSION Big data and network biology infer functional coupling between genes. In combination with machine learning, network biology can dramatically accelerate the pace of gene discovery using modern transcriptomics approaches and be validated via genome editing technology for improving crops to stresses. Unlike other living things, plants are sessile and frequently face various environmental challenges due to climate change. The cumulative effects of combined stresses can significantly influence both plant growth and yields. In navigating the complexities of climate change, ensuring the nourishment of our growing population hinges on implementing precise agricultural systems. Conventional breeding methods have been commonly employed; however, their efficacy has been impeded by limitations in terms of time, cost, and infrastructure. Cutting-edge tools focussing on big data are being championed to usher in a new era in stress biology, aiming to cultivate crops that exhibit enhanced resilience to multifactorial stresses. Transcriptomics, combined with network biology and machine learning, is proving to be a powerful approach for identifying potential genes to target for gene editing, specifically to enhance stress tolerance. The integration of transcriptomic data with genome editing can yield significant benefits, such as gaining insights into gene function by modifying or manipulating of specific genes in the target plant. This review provides valuable insights into the use of transcriptomics platforms and the application of biological network analysis and machine learning in the discovery of novel genes, thereby enhancing the understanding of plant responses to combined or sequential stress. The transcriptomics as a forefront omics platform and how it is employed through biological networks and machine learning that lead to novel gene discoveries for producing multi-stress-tolerant crops, limitations, and future directions have also been discussed.
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Affiliation(s)
- Izreen Izzati Razalli
- Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia
| | - Muhammad-Redha Abdullah-Zawawi
- UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Jalan Ya'acob Latiff, Bandar Tun Razak, 56000, Cheras, Kuala Lumpur, Malaysia
| | - Amin-Asyraf Tamizi
- Malaysian Agricultural Research and Development Institute (MARDI), 43400, Serdang, Selangor, Malaysia
| | - Sarahani Harun
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia
| | | | - Muhammad Irfan Abdul Jalal
- UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Jalan Ya'acob Latiff, Bandar Tun Razak, 56000, Cheras, Kuala Lumpur, Malaysia
| | - Mohammad Asad Ullah
- Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia
- Bangladesh Institute of Nuclear Agriculture (BINA), BAU Campus, Mymensingh, 2202, Bangladesh
| | - Zamri Zainal
- Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia.
- Institute of Systems Biology, Universiti Kebangsaan Malaysia, UKM, 43600, Bangi, Selangor, Malaysia.
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49
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Stojchevski R, Sutanto EA, Sutanto R, Hadzi-Petrushev N, Mladenov M, Singh SR, Sinha JK, Ghosh S, Yarlagadda B, Singh KK, Verma P, Sengupta S, Bhaskar R, Avtanski D. Translational Advances in Oncogene and Tumor-Suppressor Gene Research. Cancers (Basel) 2025; 17:1008. [PMID: 40149342 PMCID: PMC11940485 DOI: 10.3390/cancers17061008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/10/2025] [Accepted: 03/15/2025] [Indexed: 03/29/2025] Open
Abstract
Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to understand the genomic causes behind tumorigenesis, leading to more personalized approaches to diagnosis and treatment. Aberration of tumor suppressors, which undergo two-hit and loss-of-function mutations, and oncogenes, activated forms of proto-oncogenes that experience one-hit and gain-of-function mutations, are responsible for the dysregulation of key signaling pathways that regulate cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, and Wnt/β-catenin. Modern breakthroughs in genomics research, like next-generation sequencing, have provided efficient strategies for mapping unique genomic changes that contribute to tumor heterogeneity. Novel therapeutic approaches have enabled personalized medicine, helping address genetic variability in tumor suppressors and oncogenes. This comprehensive review examines the molecular mechanisms behind tumor-suppressor genes and oncogenes, the key signaling pathways they regulate, epigenetic modifications, tumor heterogeneity, and the drug resistance mechanisms that drive carcinogenesis. Moreover, the review explores the clinical application of sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, and personalized treatment and prevention options, discussing future directions for emerging technologies.
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Affiliation(s)
- Radoslav Stojchevski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA;
- Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
| | - Edward Agus Sutanto
- CUNY School of Medicine, The City College of New York, 160 Convent Avenue, New York, NY 10031, USA;
| | - Rinni Sutanto
- New York Institute of Technology College of Osteopathic Medicine, Glen Head, NY 11545, USA;
| | - Nikola Hadzi-Petrushev
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia; (N.H.-P.)
| | - Mitko Mladenov
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia; (N.H.-P.)
| | - Sajal Raj Singh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, Uttar Pradesh, India (J.K.S.)
| | - Jitendra Kumar Sinha
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, Uttar Pradesh, India (J.K.S.)
| | - Shampa Ghosh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, Uttar Pradesh, India (J.K.S.)
| | | | - Krishna Kumar Singh
- Symbiosis Centre for Information Technology (SCIT), Rajiv Gandhi InfoTech Park, Hinjawadi, Pune 411057, Maharashtra, India;
| | - Prashant Verma
- School of Management, BML Munjal University, NH8, Sidhrawali, Gurugram 122413, Haryana, India
| | - Sonali Sengupta
- Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
| | - Rakesh Bhaskar
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Republic of Korea
| | - Dimiter Avtanski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA;
- Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
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50
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Vo K, Shila S, Sharma Y, Pei GJ, Rosales CY, Dahiya V, Fields PE, Rumi MAK. Detection of mRNA Transcript Variants. Genes (Basel) 2025; 16:343. [PMID: 40149494 PMCID: PMC11942493 DOI: 10.3390/genes16030343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Revised: 03/13/2025] [Accepted: 03/15/2025] [Indexed: 03/29/2025] Open
Abstract
Most eukaryotic genes express more than one mature mRNA, defined as transcript variants. This complex phenomenon arises from various mechanisms, such as using alternative transcription start sites and alternative post-transcriptional processing events. The resulting transcript variants can lead to synthesizing proteins that possess distinct functional domains or may even generate noncoding RNAs, each with unique roles in cellular processes. The generation of these transcript variants is not merely a random occurrence; it is cell-type specific and varies with developmental stages, aging processes, or pathogenesis of diseases. This highlights the biological significance of transcript variants in regulating gene expression and their potential impact on cellular functionality. Despite the biological importance, investigating transcript variants has been hampered by challenges associated with detecting their expression. This review article addresses the advancements in molecular techniques in detecting transcript variants. Traditional methods such as RT-PCR and RT-qPCR can easily detect known transcript variants using primers that target unique exons associated with the variants. Other techniques like RACE-PCR and hybridization-based methods, including Northern blotting, RNase protection assays, and microarrays, have also been utilized to detect transcript variants. Nevertheless, RNA sequencing (RNA-Seq) has emerged as a powerful technique for identifying transcript variants, especially those with previously unknown sequences. The effectiveness of RNA sequencing in transcript variant detection depends on the specific sequencing approach and the precision of data analysis. By understanding the strengths and weaknesses of each laboratory technique, researchers can develop more effective strategies for detecting mRNA transcript variants. This ability will be crucial for our comprehensive understanding of gene regulation and the implications of transcript diversity in various biological contexts.
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Affiliation(s)
| | | | | | | | | | | | | | - M. A. Karim Rumi
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA; (K.V.); (S.S.); (Y.S.); (G.J.P.); (C.Y.R.); (V.D.); (P.E.F.)
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