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Liu D, Ding X, Yang Y. Anti-cancer effects of carnosol in DMBA-induced oral experimental carcinogenesis by oncogenic signaling pathways on in vivo and in silico study. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04010-4. [PMID: 40220028 DOI: 10.1007/s00210-025-04010-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/03/2025] [Indexed: 04/14/2025]
Abstract
The most prevalent malignant tumor in the oral cavity, accounting for more than 90% of all oral malignancies, is oral squamous cell carcinoma (OSCC). Therefore, detection or prevention of malignant transformation remains a viable target for the future. Carnosol is a compound derived from rosemary that contains both antioxidant and anti-carcinogens. This study examined the defensive properties of carnosol in DMBA-induced oral carcinogenesis. We have developed the computational based docking analysis to predict the binding affinity and interaction of carnosol with inflammatory and pro-apoptotic proteins. Carnosol was the most potential bioactive compound shows strong binding affinity to low binding energy to bind above the proteins. Following this, we created a hamster model to study buccal pouch carcinogenesis induced by DMBA and assessed buccal tissues using histopathological, biochemical, and western blotting. Carnosol treatment effectively reduced DMBA-induced pathological changes in buccal tissues: Altered detoxification, increased antioxidant levels, and reduced lipid peroxidation enzymes levels. We then examined the impact of carnosol intervention on the modulation of the levels of inflammatory factors and pro-apoptotic markers in oral carcinogenesis. Binding energy was studied between the carnosol between the inflammatory (NF-κB and COX-2) and apoptotic (Bax, caspase-3, and caspase-9) proteins using molecular docking. Our findings suggest that carnosol enhances antioxidant and detoxification levels, potentially prevents oral carcinogenesis by modifying the inflammatory and pro-apoptotic signaling pathways, and acts as an anti-cancer agent.
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Affiliation(s)
- Dengke Liu
- Department of Cardiology and Endodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, No.769 Shengli Road, Xingqing District, Ningxia Hui Autonomous Region, Ningxia, 750003, China.
| | - Xiaoyan Ding
- Department of Cardiology and Endodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, No.769 Shengli Road, Xingqing District, Ningxia Hui Autonomous Region, Ningxia, 750003, China
| | - Yafeng Yang
- Department of Cardiology and Endodontics, Stomatological Hospital, General Hospital of Ningxia Medical University, No.769 Shengli Road, Xingqing District, Ningxia Hui Autonomous Region, Ningxia, 750003, China
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Ahmadirad H, Omrani M, Azmi N, Saeidian AH, Jahromi MK, Mirtavoos-Mahyari H, Akbarzadeh M, Teymoori F, Farhadnejad H, Mirmiran P. Dietary phytochemical index and the risk of cancer: A systematic review and meta-analysis. PLoS One 2025; 20:e0319591. [PMID: 40173150 PMCID: PMC11964270 DOI: 10.1371/journal.pone.0319591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Accepted: 02/04/2025] [Indexed: 04/04/2025] Open
Abstract
BACKGROUND Recently, the association between dietary phytochemical index (DPI) and the risk of cancer has been the focus of researchers, however, this possible association has not been fully understood. The current meta-analysis aimed to assess the relationship between DPI and the risk of cancers. METHODS A literature search by the main keywords such as "dietary phytochemical index", "DPI", and "cancer" was completed using Scopus, PubMed, and Web of Science up to December 2024 and references of retrieved relevant articles. Observational studies examining the association between the DPI and the risk of cancers were included. The reported odds ratio (OR) with a 95% confidence interval (CI) for each study was converted into log OR, and their standard deviation was calculated. Then to compute the pooled OR, the random-effects model with inverse variance weighting method was performed. RESULTS Nine case-control studies were included in the present meta-analysis. The sample size ranged from 120 to 851 with an age range from 18 to 75 years. The pooled results indicate an inverse association between DPI and the risk of all cancers (OR: 0.40; 95% CI: 0.29-0.54, I2 = 0.00%; P-value < 0.001). Also, subgroup analysis indicated that higher a DPI score is related to the decreased risk of breast cancer (OR: 0.38; 95% CI: 0.26-0.55, I2 = 0.00%; P-value < 0.001) and pooled non-breast cancer including glioma, prostate, and colorectal cancers (OR: 0.43; 95% CI: 0.27-0.71, I2 = 0.00%; P-value = 0.001). CONCLUSIONS The results of the current meta-analysis revealed that the higher DPI score is associated with a decreased odds of cancers. Large-scale cohort studies are recommended to validate the findings presented in the current study.
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Affiliation(s)
- Hamid Ahmadirad
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Morteza Omrani
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Nikoo Azmi
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Hesam Saeidian
- Department of Surgery, Rasool-E Akram Hospital School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mitra Kazemi Jahromi
- Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Hanifeh Mirtavoos-Mahyari
- Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Akbarzadeh
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Molecular Biology, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farshad Teymoori
- Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
- Nutritional Sciences Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Hossein Farhadnejad
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sandilya V, El-Gameel D, Atashi M, Nguyen T, Fowowe M, Bhuiyan MMAA, Daramola O, Nwaiwu J, Hamdy NA, Ghanem M, El-Khordagui LK, Abdallah SM, El-Yazbi A, Mechref Y. LC-MS/MS-Profiling of Human Serum Unveils Significant Increase in Neuroinflammation and Carcinogenesis Following Chronic Organophosphate Exposure. J Proteome Res 2025; 24:1342-1355. [PMID: 39905624 DOI: 10.1021/acs.jproteome.4c00995] [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: 02/06/2025]
Abstract
The utilization of organophosphate pesticides (OPs) has escalated in response to the growing global food demand driven by a rapidly increasing population and the environmental disruptions caused by climate change. While acute exposure leads to cholinergic poisoning, chronic OP exposure has been linked to organ dysfunction, inflammation, and carcinogenesis. Serum samples from healthy individuals (n = 11), patients with acute OP exposure (n = 12), and those with chronic OP exposure (n = 31) were analyzed to discern the differentially expressed pathways after acute and chronic OP exposure. Differential expression analysis identified 132 proteins altered in chronic exposure vs control, 86 in acute exposure vs control, and 124 in chronic vs acute exposure. Pathway analysis revealed increased blood coagulation and reduced LXR/RXR activation and DCHR24 signaling in both acute and chronic exposures. Elevated levels of pro-inflammatory proteins, such as S100A8, VWF, and GPIBA, were observed, particularly in chronic exposure, highlighting significant inflammatory effects of OP exposure. These findings provide insights into the pathological mechanisms underlying chronic OP exposure and its contribution to inflammation and long-term health risks.
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Affiliation(s)
- Vishal Sandilya
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Dina El-Gameel
- Department of Pharmacy Practice, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Mojgan Atashi
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Thu Nguyen
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Mojibola Fowowe
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | | | - Oluwatosin Daramola
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Judith Nwaiwu
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
| | - Noha A Hamdy
- Department of Pharmacy Practice, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Maha Ghanem
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Labiba K El-Khordagui
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Salwa M Abdallah
- Center of Excellence for Toxicological Testing, Department of Mammalian and Aquatic Toxicology, Central Agricultural Pesticides Lab (CAPL), Agricultural Research Center (ARC), Giza, Egypt
| | - Ahmed El-Yazbi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria, Egypt
- Faculty of Pharmacy and Research & Innovation Hub, Alamein International University, Alamein, Egypt
| | - Yehia Mechref
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409, United States
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Wang Y, Fang J, Yuan Q, Yu J, Hu J. GPX3 as a Novel and Potential Therapeutic Target in the Shared Molecular Mechanisms of Traumatic Brain Injury and Parkinson's Disease. J Inflamm Res 2025; 18:1911-1928. [PMID: 39935526 PMCID: PMC11812561 DOI: 10.2147/jir.s506891] [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: 11/17/2024] [Accepted: 01/29/2025] [Indexed: 02/13/2025] Open
Abstract
Background Traumatic brain injury (TBI) is a prevalent neurological disorder associated with significant public health burdens and long-term risks, including neurodegenerative diseases such as Parkinson's disease (PD). Emerging evidence suggests a strong link between moderate to severe TBI and an elevated risk of PD, though the underlying mechanisms remain poorly understood. Materials and Methods Common differentially expressed genes (DEGs) were identified in GEO datasets of patients with traumatic brain injury (TBI) and Parkinson's disease (PD). Further analyses, including GO and KEGG pathway enrichment, protein-protein interaction (PPI) network construction, hub gene identification, as well as miRNA and transcription factor prediction and drug candidate screening, were conducted. Subsequently, the expression of hub genes was validated using additional TBI- and PD-related GEO datasets and the Comparative Toxicogenomics Database (CTD). Finally, the expression of hub genes was further validated in a mouse model of TBI induced by controlled cortical impact (CCI). Results Shared transcriptional signatures between TBI and PD were uncovered, highlighting overlapping molecular networks and pathways. The glutathione peroxidase 3 (GPX3) gene emerged as a pivotal hub gene, with its expression significantly altered in both TBI and PD datasets. Conclusion This study underscores the critical role of GPX3 in the molecular intersection of TBI and PD, suggesting it as a novel and potential therapeutic target, offering new insights into potential therapeutic strategies.
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Affiliation(s)
- Yue Wang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Neurosurgical Institute of Fudan University, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Clinical Medical Center of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
| | - Jiang Fang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Neurosurgical Institute of Fudan University, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Clinical Medical Center of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
| | - Qiang Yuan
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Neurosurgical Institute of Fudan University, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Clinical Medical Center of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
| | - Jian Yu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Neurosurgical Institute of Fudan University, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Clinical Medical Center of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
| | - Jin Hu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Neurosurgical Institute of Fudan University, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
- Shanghai Clinical Medical Center of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China
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Malik S, Sureka N, Ahuja S, Aden D, Zaheer S, Zaheer S. Tumor-associated macrophages: A sentinel of innate immune system in tumor microenvironment gone haywire. Cell Biol Int 2024; 48:1406-1449. [PMID: 39054741 DOI: 10.1002/cbin.12226] [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: 12/11/2023] [Revised: 06/10/2024] [Accepted: 07/08/2024] [Indexed: 07/27/2024]
Abstract
The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti-tumorigenic M1-like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR-M cells). While CAR-T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR-M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third-generation CAR-M technology, offering insight into in-vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early-stage TAM-targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes.
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Affiliation(s)
- Shaivy Malik
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, New Delhi, India
| | - Niti Sureka
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, New Delhi, India
| | - Sana Ahuja
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, New Delhi, India
| | - Durre Aden
- Department of Pathology, Hamdard Institute of Medical Science and Research, Jamia Hamdard, New Delhi, New Delhi, India
| | - Samreen Zaheer
- Department of Radiotherapy, Jawaharlal Nehru Medical College, AMU, Aligarh, India
| | - Sufian Zaheer
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, New Delhi, India
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Tan J, Dong X, Liu H. Mitochondrial DNA is a sensitive surrogate and oxidative stress target in oral cancer cells. PLoS One 2024; 19:e0304939. [PMID: 39226291 PMCID: PMC11371132 DOI: 10.1371/journal.pone.0304939] [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: 05/21/2024] [Accepted: 08/13/2024] [Indexed: 09/05/2024] Open
Abstract
Cellular oxidative stress mediated by intrinsic and/or extrinsic reactive oxygen species (ROS) is associated with disease pathogenesis. Oxidative DNA damage can naturally be substituted by mitochondrial DNA (mtDNA), leading to base lesion/strand break formation, copy number changes, and mutations. In this study, we devised a single test for the sensitive quantification of acute mtDNA damage, repair, and copy number changes using supercoiling-sensitive quantitative PCR (ss-qPCR) and examined how oxidative stress-related mtDNA damage responses occur in oral cancer cells. We observed that exogenous hydrogen peroxide (H2O2) induced dynamic mtDNA damage responses, as reflected by early structural DNA damage, followed by DNA repair if damage did not exceed a particular threshold. However, high oxidative stress levels induced persistent mtDNA damage and caused a 5-30-fold depletion in mtDNA copy numbers over late responses. This dramatic depletion was associated with significant growth arrest and apoptosis, suggesting persistent functional consequences. Moreover, oral cancer cells responded differentially to oxidative injury when compared with normal cells, and different ROS species triggered different biological consequences under stress conditions. In conclusion, we developed a new method for the sensitive detection of mtDNA damage and copy number changes, with exogenous H2O2 inducing dynamic mtDNA damage responses associated with functional changes in stressed cancer cells. Finally, our method can help characterize oxidative DNA damage in cancer and other human diseases.
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Affiliation(s)
- Jingyu Tan
- The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Xinlin Dong
- The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
| | - Haiwen Liu
- The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
- Liaoning Provincial Key Laboratory of Clinical Oncology Metabonomic, Jinzhou, China
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Zheng Q, Xu X, Weng J, Li M, Li B, Cao Y. The elevated expression of serum glutathione reductase in hepatocellular carcinoma and its role in assessing the therapeutic efficacy and prognosis of transarterial chemoembolization. Free Radic Biol Med 2024; 221:225-234. [PMID: 38815771 DOI: 10.1016/j.freeradbiomed.2024.05.043] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/22/2024] [Accepted: 05/26/2024] [Indexed: 06/01/2024]
Abstract
BACKGROUND Currently, there is a scarcity of reliable biomarkers that can accurately forecast the outcome and prognosis of transarterial chemoembolization (TACE). In this study, we assessed the diagnostic efficacy of serum glutathione reductase (GR) as a biomarker for hepatocellular carcinoma (HCC) and its practicality in predicting TACE treatment response. METHODS The baseline positive rate and level of serum GR were analyzed and compared between HCC group and control group. Serum GR levels were assessed at three specific time points in 181 patients with unresectable HCC who underwent TACE (HCC-TACE). The correlation between serum GR levels and clinical pathological factors, tumor reactivity, and prognosis was investigated. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized for assessing the treatment response to TACE. A nomogram for predicting the response to TACE treatment efficacy was developed. RESULTS Serum GR demonstrated superior diagnostic performance in HCC patients. The baseline levels of serum GR were associated with the patient's age, tumor size, BCLC staging, and tumor thrombi of the portal vein (TTPV) (p < 0.05). Elevated baseline levels of serum GR were also identified as independent prognostic factors for predicting lower overall survival (OS) and shorter time to radiological progression (TTP) (p < 0.001). Moreover, it is worth noting that non-responders group exhibited a substantial increase in median GR level in the fourth week following TACE treatment (p < 0.0001), whereas the median GR level of responders group did not display a significant augmentation (p > 0.05). Lastly, the changes in serum GRt1-t3 were negatively correlated with TTP (p < 0.001). The nomogram developed to predict the risk of mRECIST responsiveness in patients with HCC-TACE demonstrated excellent discriminatory ability. CONCLUSION Serum GR can serve as a valuable biomarker for the diagnosis of HCC and for predicting the therapeutic efficacy and prognosis of TACE treatment.
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Affiliation(s)
- Qingzhu Zheng
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Xiaohong Xu
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jiamiao Weng
- Fujian Medical University Provincial Clinical Medical College, Fuzhou, 350001, China
| | - Mingjie Li
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Bin Li
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
| | - Yingping Cao
- Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Milanović Ž. Exploring enzyme inhibition and comprehensive mechanisms of antioxidant/prooxidative activity of natural furanocoumarin derivatives: A comparative kinetic DFT study. Chem Biol Interact 2024; 396:111034. [PMID: 38723799 DOI: 10.1016/j.cbi.2024.111034] [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: 01/31/2024] [Revised: 04/04/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024]
Abstract
This study aimed to explore the antioxidant and prooxidative activity of two natural furanocoumarin derivatives, Bergaptol (4-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, BER) and Xanthotoxol (9-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, XAN). The collected thermodynamic and kinetic data demonstrate that both compounds possess substantial antiradical activity against HO• and CCl3OO• radicals in physiological conditions. BER exhibited better antiradical activity in comparison to XAN, which can be attributed to the enhanced deprotonation caused by the positioning of the -OH group on the psoralen ring. In contrast to highly reactive radical species, newly formed radical species BER• and XAN• exhibited negligible reactivity towards the chosen constitutive elements of macromolecules (fatty acids, amino acids, nucleobases). Furthermore, in the presence of O2•─, the ability to regenerate newly formed radicals BER• and XAN• was observed. Conversely, in physiological conditions in the presence of Cu(II) ions, both compounds exhibit prooxidative activity. Nevertheless, the prooxidative activity of both compounds is less prominent than their antioxidant activity. Furthermore, it has been demonstrated that anionic species can engage in the creation of a chelate complex, which restricts the reduction of metal ions when reducing agents are present (O2•─ and Asc─). Moreover, studies have demonstrated that these chelating complexes can be coupled with other radical species, hence enhancing their ability to inactivate radicals. Both compounds exhibited substantial inhibitory effects against enzymes involved in the direct or indirect generation of ROS: Xanthine Oxidase (XOD), Lipoxygenase (LOX), Myeloperoxidase (MPO), NADPH oxidase (NOX).
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Affiliation(s)
- Žiko Milanović
- University of Kragujevac, Institute for Information Technologies, Department of Science, Jovana Cvijića bb, 34000, Kragujevac, Serbia.
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Nicolson GL, Ferreira de Mattos G. Membrane Lipid Replacement for reconstituting mitochondrial function and moderating cancer-related fatigue, pain and other symptoms while counteracting the adverse effects of cancer cytotoxic therapy. Clin Exp Metastasis 2024; 41:199-217. [PMID: 38879842 DOI: 10.1007/s10585-024-10290-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 04/25/2024] [Indexed: 06/30/2024]
Abstract
Cancer-related fatigue, pain, gastrointestinal and other symptoms are among the most familiar complaints in practically every type and stage of cancer, especially metastatic cancers. Such symptoms are also related to cancer oxidative stress and the damage instigated by cancer cytotoxic therapies to cellular membranes, especially mitochondrial membranes. Cancer cytotoxic therapies (chemotherapy and radiotherapy) often cause adverse symptoms and induce patients to terminate their anti-neoplastic regimens. Cancer-related fatigue, pain and other symptoms and the adverse effects of cancer cytotoxic therapies can be safely moderated with oral Membrane Lipid Replacement (MLR) glycerolphospholipids and mitochondrial cofactors, such as coenzyme Q10. MLR provides essential membrane lipids and precursors to maintain mitochondrial and other cellular membrane functions and reduces fatigue, pain, gastrointestinal, inflammation and other symptoms. In addition, patients with a variety of chronic symptoms benefit from MLR supplements, and MLR also has the ability to enhance the bioavailability of nutrients and slowly remove toxic, hydrophobic molecules from cells and tissues.
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Affiliation(s)
- Garth L Nicolson
- Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA, 92647, USA.
- Department of Molecular Pathology, The Institute for Molecular Medicine, P.O. Box 9355, S. Laguna Beach, CA, 92652, USA.
| | - Gonzalo Ferreira de Mattos
- Laboratory of Ion Channels, Biological Membranes and Cell Signaling, Department of Biophysics, Facultad de Medicina, Universidad de La República, Montevideo, Uruguay
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Jayaraman S, Natarajan SR, Veeraraghavan VP, Jasmine S. Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3). J Oral Biol Craniofac Res 2023; 13:704-713. [PMID: 37731845 PMCID: PMC10507650 DOI: 10.1016/j.jobcr.2023.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/23/2023] [Accepted: 09/09/2023] [Indexed: 09/22/2023] Open
Abstract
Background Calotropin, a cardiac glycoside obtained from the plant Calotropis gigantea, has demonstrated promising potential as an anti-tumorigenesis compound. Objective The main objective of this study was to investigate the potential anti-cancer properties of calotropin against HSC-3 oral squamous cancer cells and to elucidate the underlying mechanisms involved in its action. Material and method Calotropin were treated in HSC-3 to evaluate cell viability by MTT assay. Flow cytometry analysis divulged that calotropin G0/G1 phase cell cycle arrest and apoptosis in HSC-3 cells. Calotropin displayed inhibitory properties against aerobic glycolysis, a metabolic alteration using glucose uptaken, lactose production and LDHA activity assays. Furthermore, migration and invasion assays help that calotropin has ability to reduce the migratory and invasive of HSC-3 cells, using transwell and Matrigel assay. Validation of mRNA expression through RT-PCR. Molecular docking was implemented to validate the binding association of calotropin with apoptosis and metastatic regulating targets. Result The results exemplify that increasing doses of calotropin effectively hold back the HSC-3 cell progression. Migration and invasion assays help that calotropin has ability to reduce the migratory and invasive of HSC-3 cells, indicating its potential to inhibit cancer metastasis. These results imply that calotropin may influence genes linked to metastasis and apoptosis in order to achieve its beneficial effects on cancer. Docking results provided further support, showing a high binding energy between calotropin and metastasis-mediated pathways. Conclusion Overall, our findings shed an experimental evidence on how calotropin inhibits the HSC-3 oral squamous cancer cell growth, highlighting the drug's potential as a treatment for oral cancer. Further, investigation on in-vivo experiment is warranted to explore its potential mechanism of action and to develop a novel drug towards clinical trial.
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Affiliation(s)
- Selvaraj Jayaraman
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Sathan Raj Natarajan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Vishnu Priya Veeraraghavan
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai, 600077, India
| | - Sharmila Jasmine
- Department of Oral Maxillofacial Surgery, Rajas Dental College and Hospital, Kavalkinaru, Tirunelveli, 627105, Tamil Nadu, India
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11
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Peng H, Zhou Q, Liu J, Wang Y, Mu K, Zhang L. Endoplasmic reticulum stress: a vital process and potential therapeutic target in chronic obstructive pulmonary disease. Inflamm Res 2023; 72:1761-1772. [PMID: 37695356 DOI: 10.1007/s00011-023-01786-0] [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: 03/03/2023] [Revised: 05/14/2023] [Accepted: 05/16/2023] [Indexed: 09/12/2023] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD), a chronic and progressive disease characterized by persistent respiratory symptoms and progressive airflow obstruction, has attracted extensive attention due to its high morbidity and mortality. Although the understanding of the pathogenesis of COPD has gradually increased because of increasing evidence, many questions regarding the mechanisms involved in COPD progression and its deleterious effects remain unanswered. Recent advances have shown the potential functions of endoplasmic reticulum (ER) stress in causing airway inflammation, emphasizing the vital role of unfolded protein response (UPR) pathways in the development of COPD. METHODS A comprehensive search of major databases including PubMed, Scopus, and Web of Science was conducted to retrieve original research articles and reviews related to ER stress, UPR, and COPD. RESULTS The common causes of COPD, namely cigarette smoke (CS) and air pollutants, induce ER stress through the generation of reactive oxygen species (ROS). UPR promotes mucus secretion and further plays a dual role in the cell apoptosis-autophagy axis in the development of COPD. Existing drug research has indicated the potential of UPR as a therapeutic target for COPD. CONCLUSIONS ER stress and UPR activation play significant roles in the etiology, pathogenesis, and treatment of COPD and discuss whether related genes can be used as biomarkers and therapeutic targets.
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Affiliation(s)
- Hao Peng
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Qing Zhou
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Jing Liu
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Yi Wang
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China
| | - Ketao Mu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Avenue 1095, Wuhan, 430030, China.
| | - Lei Zhang
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
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12
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Alaouna M, Penny C, Hull R, Molefi T, Chauke-Malinga N, Khanyile R, Makgoka M, Bida M, Dlamini Z. Overcoming the Challenges of Phytochemicals in Triple Negative Breast Cancer Therapy: The Path Forward. PLANTS (BASEL, SWITZERLAND) 2023; 12:2350. [PMID: 37375975 DOI: 10.3390/plants12122350] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 06/02/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023]
Abstract
Triple negative breast cancer (TNBC) is a very aggressive subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. TNBC is thought to be produced by Wnt, Notch, TGF-beta, and VEGF pathway activation, which leads to cell invasion and metastasis. To address this, the use of phytochemicals as a therapeutic option for TNBC has been researched. Plants contain natural compounds known as phytochemicals. Curcumin, resveratrol, and EGCG are phytochemicals that have been found to inhibit the pathways that cause TNBC, but their limited bioavailability and lack of clinical evidence for their use as single therapies pose challenges to the use of these phytochemical therapies. More research is required to better understand the role of phytochemicals in TNBC therapy, or to advance the development of more effective delivery mechanisms for these phytochemicals to the site where they are required. This review will discuss the promise shown by phytochemicals as a treatment option for TNBC.
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Affiliation(s)
- Mohammed Alaouna
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa
| | - Clement Penny
- Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Parktown 2193, South Africa
| | - Rodney Hull
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
| | - Thulo Molefi
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
- Department of Medical Oncology, Steve Biko Academic Hospital and University of Pretoria, Pretoria 0001, South Africa
| | - Nkhensani Chauke-Malinga
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
- Department of Plastic and Reconstructive Surgery, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Pretoria 0001, South Africa
| | - Richard Khanyile
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
- Department of Medical Oncology, Steve Biko Academic Hospital and University of Pretoria, Pretoria 0001, South Africa
| | - Malose Makgoka
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
- Department of Surgery, Faculty of Health Sciences, Steve Biko Academic Hospital, University of Pretoria, Pretoria 0001, South Africa
| | - Meshack Bida
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
- Department of Anatomical Pathology, National Health Laboratory Service (NHLS), University of Pretoria, Pretoria 0001, South Africa
| | - Zodwa Dlamini
- SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0001, South Africa
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13
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Aydın PK, Turkyılmaz IB, Gul IB, Bulan OK, Yanardag R. Drug repurposing: Metformin's effect against liver tissue damage in diabetes and prostate cancer model. J Diabetes Metab Disord 2023; 22:225-236. [PMID: 37255805 PMCID: PMC10225428 DOI: 10.1007/s40200-022-01109-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 08/08/2022] [Indexed: 06/01/2023]
Abstract
Background There are evidences linking diabetes to the pathogenesis and progression of various cancers. Metformin is a well-known antidiabetic drug that reduces the levels of circulating glucose and insulin in patients with both insulin resistance and hyperinsulinemia. Aim of the present study was to evaluate the effect of metformin on the liver of rats bearing prostate cancer, diabetes and prostate cancer + diabetes via histopathological and biochemical methods. Methods Male Copenhagen rats were divided into six groups. Control group, diabetic group, cancer group, diabetic + cancer group, diabetic + cancer + metformin group, cancer + metformin group. Diabetes was induced by injecting single dose of streptozotocin (65 mg/kg) to Copenhagen rats, cancer induced 2 × 104 Mat-LyLu cells. Metformin treatment was administered daily by gavage following inocculation of the Mat- Lylu cells to fifth and sixth group. The experiment was terminated on the 14th day following Mat-LyLu cell injection. At the end of the experimental period, the rats were sacrificed, and liver tissue was taken. Liver damage was scored. Biochemically, serum prostate-specific antigen level was determined by employing Enzyme Linked Immuno Sorbent Assay method. In addition, the activities of different enzyme and biochemical parameters were determined spectrophotometrically inform the hepatic tissue specimens. Results The findings of this study reveal that histopathological and biochemical damage in cancer and diabetic + cancer groups decreased significantly in the metformin treated groups. Conclusion These highlights that the antidiabetic drug metformin can be repositioned for attenuating liver tissue damage associated with prostate cancer and diabetes.
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Affiliation(s)
- Pınar Koroglu Aydın
- Faculty of Medicine, Department of Histology and Embryology, Halic University, Istanbul, Turkey
| | - Ismet Burcu Turkyılmaz
- Faculty of Engineering, Department of Chemistry, Istanbul University- Cerrahpasa, Istanbul, Turkey
| | - Ilknur Bugan Gul
- Faculty of Science, Department of Biology, Istanbul University, Vezneciler, Istanbul, Turkey
| | - Omur Karabulut Bulan
- Faculty of Science, Department of Biology, Istanbul University, Vezneciler, Istanbul, Turkey
| | - Refiye Yanardag
- Faculty of Engineering, Department of Chemistry, Istanbul University- Cerrahpasa, Istanbul, Turkey
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Wagner S, Gómez de Cedrón M, Navarro Del Hierro J, Martín-Hernández D, Siles MDLN, Santoyo S, Jaime L, Martín D, Fornari T, Ramírez de Molina A. Biological Activities of Miracle Berry Supercritical Extracts as Metabolic Regulators in Chronic Diseases. Int J Mol Sci 2023; 24:ijms24086957. [PMID: 37108121 PMCID: PMC10138767 DOI: 10.3390/ijms24086957] [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: 03/11/2023] [Revised: 04/01/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Synsepalum dulcificum (Richardella dulcifica) is a berry fruit from West Africa with the ability to convert the sour taste into a sweet taste, and for this reason, the fruit is also known as the "miracle berry" (MB). The red and bright berry is rich in terpenoids. The fruit's pulp and skin contain mainly phenolic compounds and flavonoids, which correlate with their antioxidant activity. Different polar extracts have been described to inhibit cell proliferation and transformation of cancer cell lines in vitro. In addition, MB has been shown to ameliorate insulin resistance in a preclinical model of diabetes induced by a chow diet enriched in fructose. Herein, we have compared the biological activities of three supercritical extracts obtained from the seed-a subproduct of the fruit-and one supercritical extract obtained from the pulp and the skin of MB. The four extracts have been characterized in terms of total polyphenols content. Moreover, the antioxidant, anti-inflammatory, hypo-lipidemic, and inhibition of colorectal cancer cell bioenergetics have been compared. Non-polar supercritical extracts from the seed are the ones with the highest effects on the inhibition of bioenergetic of colorectal (CRC) cancer cells. At the molecular level, the effects on cell bioenergetics seems to be related to the inhibition of main drivers of the de novo lipogenesis, such as the sterol regulatory element binding transcription factor (SREBF1) and downstream molecular targets fatty acid synthase (FASN) and stearoyl coenzyme desaturase 1 (SCD1). As metabolic reprograming is considered as one of the hallmarks of cancer, natural extracts from plants may provide complementary approaches in the treatment of cancer. Herein, for the first time, supercritical extracts from MB have been obtained, where the seed, a by-product of the fruit, seems to be rich in antitumor bioactive compounds. Based on these results, supercritical extracts from the seed merit further research to be proposed as co-adjuvants in the treatment of cancer.
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Affiliation(s)
- Sonia Wagner
- Precision Nutrition and Cancer Program, Molecular Oncology Group, IMDEA Food Institute, Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
- Medicinal Gardens SL, Marqués de Urquijo 47, 28008 Madrid, Spain
| | - Marta Gómez de Cedrón
- Precision Nutrition and Cancer Program, Molecular Oncology Group, IMDEA Food Institute, Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - Joaquín Navarro Del Hierro
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
- Facultad de Veterinaria, Sección Departamental de Tecnología Alimentaria, Universidad Complutense de Madrid (ROR 02p0gd045), 28040 Madrid, Spain
| | - Diego Martín-Hernández
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - María de Las Nieves Siles
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - Susana Santoyo
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - Laura Jaime
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - Diana Martín
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - Tiziana Fornari
- Institute of Food Science and Research (CIAL), Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
| | - Ana Ramírez de Molina
- Precision Nutrition and Cancer Program, Molecular Oncology Group, IMDEA Food Institute, Universidad Autónoma de Madrid (CEI UAM + CSIC), 28049 Madrid, Spain
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15
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Berdiaki A, Neagu M, Spyridaki I, Kuskov A, Perez S, Nikitovic D. Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix? Antioxidants (Basel) 2023; 12:antiox12040824. [PMID: 37107200 PMCID: PMC10135151 DOI: 10.3390/antiox12040824] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/22/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.
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16
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Moon J, Kitty I, Renata K, Qin S, Zhao F, Kim W. DNA Damage and Its Role in Cancer Therapeutics. Int J Mol Sci 2023; 24:4741. [PMID: 36902170 PMCID: PMC10003233 DOI: 10.3390/ijms24054741] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/22/2023] [Accepted: 02/23/2023] [Indexed: 03/05/2023] Open
Abstract
DNA damage is a double-edged sword in cancer cells. On the one hand, DNA damage exacerbates gene mutation frequency and cancer risk. Mutations in key DNA repair genes, such as breast cancer 1 (BRCA1) and/or breast cancer 2 (BRCA2), induce genomic instability and promote tumorigenesis. On the other hand, the induction of DNA damage using chemical reagents or radiation kills cancer cells effectively. Cancer-burdening mutations in key DNA repair-related genes imply relatively high sensitivity to chemotherapy or radiotherapy because of reduced DNA repair efficiency. Therefore, designing specific inhibitors targeting key enzymes in the DNA repair pathway is an effective way to induce synthetic lethality with chemotherapy or radiotherapy in cancer therapeutics. This study reviews the general pathways involved in DNA repair in cancer cells and the potential proteins that could be targeted for cancer therapeutics.
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Affiliation(s)
- Jaeyoung Moon
- Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Republic of Korea
| | - Ichiwa Kitty
- Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Republic of Korea
| | - Kusuma Renata
- Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Republic of Korea
- Magister of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia
| | - Sisi Qin
- Department of Pathology, University of Chicago, Chicago, IL 60637, USA
| | - Fei Zhao
- College of Biology, Hunan University, Changsha 410082, China
| | - Wootae Kim
- Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan 31151, Chungcheongnam-do, Republic of Korea
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Recent Overview of Potent Antioxidant Activity of Coordination Compounds. Antioxidants (Basel) 2023; 12:antiox12020213. [PMID: 36829772 PMCID: PMC9952845 DOI: 10.3390/antiox12020213] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/06/2023] [Accepted: 01/16/2023] [Indexed: 01/18/2023] Open
Abstract
During recent decades, the complexation of organic ligands toward several metal ions of s-p and d-block has been applied as a plan to enhance its antioxidant performance. Due to their wide range of beneficial impacts, coordination compounds are widely used in industries, specifically in the medicinal and pharmaceutical fields. The activity is generally improved by chelation consequently knowing that the characteristics of both ligands and metals can lead to the development of greatly active compounds. Chelation compounds are a substitute for using the traditional synthetic antioxidants, because metal chelates present benefits, including a variety in geometry, oxidation states, and coordination number, that assist and favor the redox methods associated with antioxidant action. As well as understanding the best studied anti-oxidative assets of these compounds, coordination compounds are involved in the free radical scavenging process and protecting human organisms from the opposing effects of these radicals. The antioxidant ability can be assessed by various interrelated systems. The methodological modification offers the most knowledge on the antioxidant property of metal chelates. Colorimetric techniques are the most used, though electron paramagnetic resonance (EPR) is an alternative for metallic compounds, since color does not affect the results. Information about systems, with their benefits, and restrictions, permits a dependable valuation of the antioxidant performance of coordination compounds, as well as assisting application in various states wherever antioxidant drugs are required, such as in food protection, appropriate good-packaged foods, dietary supplements, and others. Because of the new exhaustive analysis of organic ligands, it has become a separate field of research in chemistry. The present investigation will be respected for providing a foundation for the antioxidant properties of organic ligands, future tests on organic ligands, and building high-quality antioxidative compounds.
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Sadiq IZ. Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation. Curr Mol Med 2023; 23:13-35. [PMID: 34951363 DOI: 10.2174/1566524022666211222161637] [Citation(s) in RCA: 65] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 11/03/2021] [Accepted: 11/08/2021] [Indexed: 12/16/2022]
Abstract
Free radicals contain one or more unpaired electrons in their valence shell, thus making them unstable, short-lived, and highly reactive species. Excessive generation of these free radicals ultimately leads to oxidative stress causing oxidation and damage to significant macromolecules in the living system and essentially disrupting signal transduction pathways and antioxidants equilibrium. At lower concentrations, ROS serves as "second messengers," influencing many physiological processes in the cell. However, higher concentrations beyond cell capacity cause oxidative stress, contributing to human pathologies such as diabetes, cancer, Parkinson's disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis, and Alzheimer's disease. Signaling pathways such as NF-κB, MAPKs, PI3K/Akt/ mTOR, and Keap1-Nrf2- ARE modulate the detrimental effects of oxidative stress by increasing the expression of cellular antioxidant defenses, phase II detoxification enzymes, and decreased production of ROS. Free radicals such as H2O2 are indeed needed for the advancement of the cell cycle as these molecules influence DNA, proteins, and enzymes in the cell cycle pathway. In the course of cell cycle progression, the cellular redox environment becomes more oxidized, moving from the G1 phase, becoming higher in G2/M and moderate in the S phase. Signals in the form of an increase in cellular pro-oxidant levels are required, and these signals are often terminated by a rise in the amount of antioxidants and MnSOD with a decrease in the level of cyclin D1 proteins. Therefore, understanding the mechanism of cell cycle redox regulation will help in the therapy of many diseases.
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Affiliation(s)
- Idris Zubairu Sadiq
- Department of Biochemistry, Faculty of life Sciences, Ahmadu Bello University, Zaria-Nigeria
- Department of Biochemistry, Faculty of Sciences, Maryam Abacha American University of Niger, ADS Avenue, Roi Muhammad VI Du Maroc Maradi, Republique Du Niger
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Zhang Y, Xu L, Ren Z, Liu X, Song J, Zhang P, Zhang C, Gong S, Wu N, Zhang X, Xie C, Lu Z, Ma M, Zhang Y, Chen Y, Lin C. LINC01615 maintains cell survival in adaptation to nutrient starvation through the pentose phosphate pathway and modulates chemosensitivity in colorectal cancer. Cell Mol Life Sci 2022; 80:20. [PMID: 36576581 PMCID: PMC11071770 DOI: 10.1007/s00018-022-04675-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/29/2022] [Accepted: 12/15/2022] [Indexed: 12/29/2022]
Abstract
Numerous mechanisms involved in promoting cancer cell survival under nutrient starvation have been described. Long noncoding RNAs (lncRNAs) have emerged as critical players in colorectal cancer (CRC) progression, but the role of lncRNAs in the progression of CRC under nutrient starvation has not been well clarified. Here, we identified a lncRNA, LINC01615, that was significantly upregulated in response to serum starvation. LINC01615 can contribute to the adaptation of CRC cells to serum-deprived conditions and enhance cell survival under similar conditions. LINC01615 activated the pentose phosphate pathway (PPP) under serum starvation, manifested as decreased ROS production and enhanced nucleotide and lipid synthesis. Glucose-6-phosphate dehydrogenase (G6PD) is a key rate-limiting enzyme of the PPP, and LINC01615 promoted G6PD expression by competitively binding with hnRNPA1 and facilitating G6PD pre-mRNA splicing. Moreover, we also found that serum starvation led to METTL3 degradation by inducing autophagy, which further increased the stability and level of LINC01615 in a m6A-dependent manner. LINC01615 knockdown combined with oxaliplatin achieved remarkable antitumor effects in PDO and PDX models. Collectively, our results demonstrated a novel adaptive survival mechanism permitting tumor cells to survive under limiting nutrient supplies and provided a potential therapeutic target for CRC.
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Affiliation(s)
- Yi Zhang
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
- Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221000, China
| | - Lei Xu
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
- Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, 221000, China
| | - Zeqiang Ren
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Xin Liu
- Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Jun Song
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Pengbo Zhang
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Chong Zhang
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Shuai Gong
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Nai Wu
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Xiuzhong Zhang
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China
| | - Chanbin Xie
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, 410013, Hunan, China
| | - Zhixing Lu
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, 410013, Hunan, China
| | - Min Ma
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, 410013, Hunan, China
| | - Yi Zhang
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, 410013, Hunan, China
| | - Yifei Chen
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, 410013, Hunan, China
- Department of Otolaryngology and Head Neck Surgery, Affiliated Changsha Hospital of Hunan Normal University, Changsha, China
| | - Changwei Lin
- Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, China.
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Central South University, Changsha, 410013, Hunan, China.
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20
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Raman Spectroscopy and Imaging Studies of Human Digestive Tract Cells and Tissues-Impact of Vitamin C and E Supplementation. Molecules 2022; 28:molecules28010137. [PMID: 36615330 PMCID: PMC9822473 DOI: 10.3390/molecules28010137] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 11/17/2022] [Accepted: 12/04/2022] [Indexed: 12/28/2022] Open
Abstract
Cancers of digestive tract such as colorectal cancer (CRC) and gastric cancer (GC) are the most commonly detected types of cancer worldwide and their origin can be associated with oxidative stress conditions. Commonly known and followed antioxidants, such as vitamin C and E, are widely considered as potential anti-cancer agents. Raman spectra have great potential in the biochemical characterization of matter based on the fact that each molecule has its own unique vibrational properties. Raman spectroscopy allows to precisely characterize components (proteins, lipids, nucleic acids). The paper presents the application of the Raman spectroscopy technique for the analysis of tissue samples and cells of the human colon and stomach. The main goal of this study is to show the differences between healthy and cancerous tissues from the human digestive tract and human normal and cancer colon and gastric cell lines. The paper presents the spectroscopic characterization of normal colon cells, CCD-18 Co, in physiological and oxidative conditions and effect of oxidative injury of normal colon cells upon supplementation with vitamin C at various concentrations based on Raman spectra. The obtained results were related to the Raman spectra recorded for human colon cancer cells-CaCo-2. In addition, the effect of the antioxidant in the form of vitamin E on gastric cancer cells, HTB-135, is presented and compared with normal gastric cells-CRL-7869. All measured gastric samples were biochemically and structurally characterized by means of Raman spectroscopy and imaging. Statistically assisted analysis has shown that normal, ROS injured and cancerous human gastrointestinal cells can be distinguished based on their unique vibrational properties. ANOVA tests, PCA (Principal Component Analysis) and PLSDA (Partial Least Squares Discriminant Analysis) have confirmed the main role of nucleic acids, proteins and lipids in differentiation of human colon and stomach normal and cancer tissues and cells. The conducted research based on Raman spectra proved that antioxidants in the form of vitamin C and E exhibit anti-cancer properties. In consequence, conducted studies proved that label-free Raman spectroscopy may play an important role in clinical diagnostic differentiation of human normal and cancerous gastrointestinal tissues and may be a source of intraoperative information supporting histopathological analysis.
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21
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Christodoulou MC, Orellana Palacios JC, Hesami G, Jafarzadeh S, Lorenzo JM, Domínguez R, Moreno A, Hadidi M. Spectrophotometric Methods for Measurement of Antioxidant Activity in Food and Pharmaceuticals. Antioxidants (Basel) 2022; 11:2213. [PMID: 36358583 PMCID: PMC9686769 DOI: 10.3390/antiox11112213] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 07/30/2023] Open
Abstract
In recent years, there has been a growing interest in the application of antioxidants in food and pharmaceuticals due to their association with beneficial health effects against numerous oxidative-related human diseases. The antioxidant potential can be measured by various assays with specific mechanisms of action, including hydrogen atom transfer, single electron transfer, and targeted scavenging activities. Understanding the chemistry of mechanisms, advantages, and limitations of the methods is critical for the proper selection of techniques for the valid assessment of antioxidant activity in specific samples or conditions. There are various analytical techniques available for determining the antioxidant activity of biological samples, including food and plant extracts. The different methods are categorized into three main groups, such as spectrometry, chromatography, and electrochemistry techniques. Among these assays, spectrophotometric methods are considered the most common analytical technique for the determination of the antioxidant potential due to their sensitivity, rapidness, low cost, and reproducibility. This review covers the mechanism of actions and color changes that occur in each method. Furthermore, the advantages and limitations of spectrophotometric methods are described and discussed in this review.
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Affiliation(s)
| | - Jose C. Orellana Palacios
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
| | - Golnaz Hesami
- Department of Food Science and Technology, Sanandaj Branch, Islamic Azad University, Pasdaran St., Sanandaj P.O. Box 618, Iran
| | - Shima Jafarzadeh
- School of Engineering, Edith Cowan University, Joondalup, WA 6027, Australia
| | - José M. Lorenzo
- Centro Tecnológico de la Carne de Galicia, Avd. Galicia N° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain
- Área de Tecnología de los Alimentos, Facultad de Ciencias de Ourense, Universidade de Vigo, 32004 Ourense, Spain
| | - Rubén Domínguez
- Centro Tecnológico de la Carne de Galicia, Avd. Galicia N° 4, Parque Tecnológico de Galicia, San Cibrao das Viñas, 32900 Ourense, Spain
| | - Andres Moreno
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
| | - Milad Hadidi
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain
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22
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Zhang J, Gao J, Cui J, Wang Y, Jin Y, Zhang D, Lin D, Lin J. Tumor-associated macrophages in tumor progression and the role of traditional Chinese medicine in regulating TAMs to enhance antitumor effects. Front Immunol 2022; 13:1026898. [PMID: 36311793 PMCID: PMC9611775 DOI: 10.3389/fimmu.2022.1026898] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 09/27/2022] [Indexed: 11/24/2022] Open
Abstract
Purpose To emphasize the importance of tumor-associated macrophages (TAMs) in tumor immunity and to describe the ways in which extracts from Traditional Chinese Medicine (TCM) achieve tumor therapy by modulating macrophages. Significance By summarizing these available data, this review focused on TAMs and TCM and can build the foundation for future research on antitumor therapeutics. Methods In this review, we summarized the key functions of TAMs in cancer development and overviewed literature on TCM targeting TAMs together with other immune cells aiming to enhance antitumor immunity. Conclusions With an indispensable role in antitumor immunity, TAMs contribute to tumor progression, migration, invasion, angiogenesis, lymphangiogenesis, and immunosuppressive microenvironment. In recent years, TCM has gradually gained attention as a potential antitumor adjunctive therapy in preclinical and clinical trials. TCM is also a regulator of cytokine secretion and cell surface molecule expression in balancing the tumor microenvironment (TME), especially macrophage activation and polarization. Therefore, it is believed that TCM could serve as modifiers with immunomodulatory capability.
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Affiliation(s)
- Jiatong Zhang
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jiafeng Gao
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Jingwen Cui
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yongqiang Wang
- The Preventive Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Yipeng Jin
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Di Zhang
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Degui Lin
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
- *Correspondence: Degui Lin, ; Jiahao Lin,
| | - Jiahao Lin
- The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, China
- Center of Research and Innovation of Chinese Traditional Veterinary Medicine, China Agricultural University, Beijing, China
- *Correspondence: Degui Lin, ; Jiahao Lin,
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23
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Chemical structure, antioxidant and anti-inflammatory activities of two novel pectin polysaccharides from purple passion fruit (Passiflora edulia Sims) peel. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133309] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Khaksar S, Kiarostami K, Alinaghi S. The Effects of Methanol Extracts of Hyssopus officinalis on Model of Induced Glioblastoma Multiforme (GBM) in Rats. J Mol Neurosci 2022; 72:2045-2066. [PMID: 35963984 DOI: 10.1007/s12031-022-02058-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: 02/24/2022] [Accepted: 08/04/2022] [Indexed: 11/27/2022]
Abstract
Given the complexity of pathophysiological processes of brain tumors, ineffective therapies, and high mortality rate, new therapeutic options with less toxicity are necessary. Hyssopus officinalis (hyssop) is an aromatic plant with important biological activities. The aim of this study is to assess the anti-cancer effect of hyssop extract on damages of glioblastoma multiforme. In this study, total flavonoids, phenolic content, and quantification of phenolic compound of hyssop extracts were analyzed. In vitro antioxidant properties of hyssop extract were also examined. In addition, cell viability, apoptosis, and cell cycle were evaluated in C6 glioma cell culture. In vivo, the rats were divided randomly into four main groups: intact, control, vehicle, and treatment groups. 1 × 106 C6 rat glioma cells were implanted into the right caudate nucleus of the rat's brain. The treatment group received the methanol extract of hyssop (100 mg/kg) for 7 days. Evolution of locomotor activity, tumor volume, survival rate, activities of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), vascular endothelial growth factor (VEGF) expression, TUNEL-positive cells, p53 and p21 mRNA expression, and histological alterations were performed. The results showed that the methanol extract of hyssop increased the apoptosis and reduced the cell division of C6 glioma cells in cell culture. Moreover, methanol extract decreased the tumor volume and prolonged survival. Also, the activity of SOD and CAT enzymes was reduced in tumor tissue and enhanced in surrounding tissue. TUNEL-positive cells were increased in methanol extract of hyssop group. The expression of p53 and p21 mRNA was upregulated in the treatment group. Moreover, the histological analysis indicated a considerable decrease in invasion of tumor cells and inflammation in the hyssop-treated rats. According to the achieved results, it can be stated that hyssop has sufficient potential to inhibit damage of brain tumors, at least in part, by affecting the oxidative stress and cell proliferation pathways.
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Affiliation(s)
- Sepideh Khaksar
- Department of Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
| | - Khadijeh Kiarostami
- Department of Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Shahrzad Alinaghi
- Department of Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
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25
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Molnar R, Szabo L, Tomesz A, Deutsch A, Darago R, Raposa BL, Ghodratollah N, Varjas T, Nemeth B, Orsos Z, Pozsgai E, Szentpeteri JL, Budan F, Kiss I. The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers. Cells 2022; 11:cells11081300. [PMID: 35455979 PMCID: PMC9029301 DOI: 10.3390/cells11081300] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 04/08/2022] [Accepted: 04/10/2022] [Indexed: 12/11/2022] Open
Abstract
Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.
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Affiliation(s)
- Richard Molnar
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7624 Pécs, Hungary; (L.S.); (A.T.); (A.D.); (R.D.); (B.L.R.)
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
- Correspondence: (R.M.); (J.L.S.); (F.B.)
| | - Laszlo Szabo
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7624 Pécs, Hungary; (L.S.); (A.T.); (A.D.); (R.D.); (B.L.R.)
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Andras Tomesz
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7624 Pécs, Hungary; (L.S.); (A.T.); (A.D.); (R.D.); (B.L.R.)
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Arpad Deutsch
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7624 Pécs, Hungary; (L.S.); (A.T.); (A.D.); (R.D.); (B.L.R.)
| | - Richard Darago
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7624 Pécs, Hungary; (L.S.); (A.T.); (A.D.); (R.D.); (B.L.R.)
| | - Bence L. Raposa
- Doctoral School of Health Sciences, Faculty of Health Sciences, University of Pécs, 7624 Pécs, Hungary; (L.S.); (A.T.); (A.D.); (R.D.); (B.L.R.)
| | - Nowrasteh Ghodratollah
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Timea Varjas
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Balazs Nemeth
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Zsuzsanna Orsos
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Eva Pozsgai
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
| | - Jozsef L. Szentpeteri
- Institute of Transdisciplinary Discoveries, Medical School, University of Pécs, 7624 Pécs, Hungary
- Correspondence: (R.M.); (J.L.S.); (F.B.)
| | - Ferenc Budan
- Institute of Transdisciplinary Discoveries, Medical School, University of Pécs, 7624 Pécs, Hungary
- Institute of Physiology, Medical School, University of Pécs, 7624 Pécs, Hungary
- Correspondence: (R.M.); (J.L.S.); (F.B.)
| | - Istvan Kiss
- Department of Public Health Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary; (N.G.); (T.V.); (B.N.); (Z.O.); (E.P.); (I.K.)
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Hoti G, Matencio A, Rubin Pedrazzo A, Cecone C, Appleton SL, Khazaei Monfared Y, Caldera F, Trotta F. Nutraceutical Concepts and Dextrin-Based Delivery Systems. Int J Mol Sci 2022; 23:4102. [PMID: 35456919 PMCID: PMC9031143 DOI: 10.3390/ijms23084102] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/26/2022] [Accepted: 04/02/2022] [Indexed: 12/12/2022] Open
Abstract
Nutraceuticals are bioactive or chemical compounds acclaimed for their valuable biological activities and health-promoting effects. The global community is faced with many health concerns such as cancers, cardiovascular and neurodegenerative diseases, diabetes, arthritis, osteoporosis, etc. The effect of nutraceuticals is similar to pharmaceuticals, even though the term nutraceutical has no regulatory definition. The usage of nutraceuticals, to prevent and treat the aforementioned diseases, is limited by several features such as poor water solubility, low bioavailability, low stability, low permeability, low efficacy, etc. These downsides can be overcome by the application of the field of nanotechnology manipulating the properties and structures of materials at the nanometer scale. In this review, the linear and cyclic dextrin, formed during the enzymatic degradation of starch, are highlighted as highly promising nanomaterials- based drug delivery systems. The modified cyclic dextrin, cyclodextrin (CD)-based nanosponges (NSs), are well-known delivery systems of several nutraceuticals such as quercetin, curcumin, resveratrol, thyme essential oil, melatonin, and appear as a more advanced drug delivery system than modified linear dextrin. CD-based NSs prolong and control the nutraceuticals release, and display higher biocompatibility, stability, and solubility of poorly water-soluble nutraceuticals than the CD-inclusion complexes, or uncomplexed nutraceuticals. In addition, the well-explored CD-based NSs pathways, as drug delivery systems, are described. Although important progress is made in drug delivery, all the findings will serve as a source for the use of CD-based nanosystems for nutraceutical delivery. To sum up, our review introduces the extensive literature about the nutraceutical concepts, synthesis, characterization, and applications of the CD-based nano delivery systems that will further contribute to the nutraceutical delivery with more potent nanosystems based on linear dextrins.
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Affiliation(s)
| | | | | | | | | | | | | | - Francesco Trotta
- Department of Chemistry, University of Torino, Via P. Giuria 7, 10125 Torino, Italy; (G.H.); (A.M.); (A.R.P.); (C.C.); (S.L.A.); (Y.K.M.); (F.C.)
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27
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Schuster C, Wolpert N, Moustaid-Moussa N, Gollahon LS. Combinatorial Effects of the Natural Products Arctigenin, Chlorogenic Acid, and Cinnamaldehyde Commit Oxidation Assassination on Breast Cancer Cells. Antioxidants (Basel) 2022; 11:591. [PMID: 35326241 PMCID: PMC8945099 DOI: 10.3390/antiox11030591] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/12/2022] [Accepted: 03/17/2022] [Indexed: 02/06/2023] Open
Abstract
Major obstacles in current breast cancer treatment efficacy include the ability of breast cancer cells to develop resistance to chemotherapeutic drugs and the off-target cytotoxicity of these drugs on normal cells, leading to debilitating side effects. One major difference between cancer and normal cells is their metabolism, as cancer cells acquire glycolytic and mitochondrial metabolism alterations throughout tumorigenesis. In this study, we sought to exploit this metabolic difference by investigating alternative breast cancer treatment options based on the application of phytochemicals. Herein, we investigated three phytochemicals, namely cinnamaldehyde (CA), chlorogenic acid (CGA), and arctigenin (Arc), regarding their anti-breast-cancer properties. These phytochemicals were administered alone or in combination to MCF-7, MDA-MB-231, and HCC1419 breast cancer or normal MCF-10A and MCF-12F breast cells. Overall, our results indicated that the combination treatments showed stronger inhibitory effects on breast cancer cells versus single treatments. However, only treatments with CA (35 μM), CGA (250 μg/mL), and the combination of CA + CGA (35 μM + 250 μg/mL) showed no significant cytotoxic effects on normal mammary epithelial cells, suggesting that Arc was the driver of normal cell cytotoxicity in all other treatments. CA + CGA and, to a lesser extent, CGA alone effectively induced breast cancer cell death accompanied by decreases in mitochondrial membrane potential, increased mitochondrial superoxide, reduced mitochondrial and glycolytic ATP production, and led to significant changes in cellular and mitochondrial morphology. Altogether, the combination of CA + CGA was determined as the best anti-breast-cancer treatment strategy due to its strong anti-breast-cancer effects without strong adverse effects on normal mammary epithelial cells. This study provides evidence that targeting the mitochondria may be an effective anticancer treatment, and that using phytochemicals or combinations thereof offers new approaches in treating breast cancer that significantly reduce off-target effects on normal cells.
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Affiliation(s)
- Caroline Schuster
- Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.S.); (N.W.)
| | - Nicholas Wolpert
- Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.S.); (N.W.)
| | - Naima Moustaid-Moussa
- Nutritional Sciences Department, Texas Tech University, Lubbock, TX 79409, USA;
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
| | - Lauren S. Gollahon
- Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA; (C.S.); (N.W.)
- Obesity Research Institute, Texas Tech University, Lubbock, TX 79409, USA
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28
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In Vitro Neurotoxicity of Flumethrin Pyrethroid on SH-SY5Y Neuroblastoma Cells: Apoptosis Associated with Oxidative Stress. TOXICS 2022; 10:toxics10030131. [PMID: 35324756 PMCID: PMC8955675 DOI: 10.3390/toxics10030131] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/22/2022] [Accepted: 03/01/2022] [Indexed: 11/26/2022]
Abstract
Pyrethroids are neurotoxicants for animals, showing a pattern of toxic action on the nervous system. Flumethrin, a synthetic pyrethroid, is used against ectoparasites in domestic animals, plants, and for public health. This compound has been shown to be highly toxic to bees, while its effects on other animals have been less investigated. However, in vitro studies to evaluate cytotoxicity are scarce, and the mechanisms associated with this effect at the molecular level are still unknown. This study aimed to investigate the oxidative stress and cell death induction in SH-SY5Y neuroblastoma cells in response to flumethrin exposure (1–1000 µM). Flumethrin induced a significant cytotoxic effect, as evaluated by MTT and LDH leakage assays, and produced an increase in the biomarkers of oxidative stress as reactive oxygen species and nitric oxide (ROS and NO) generation, malondialdehyde (MDA) concentration, and caspase-3 activity. In addition, flumethrin significantly increased apoptosis-related gene expressions (Bax, Casp-3, BNIP3, APAF1, and AKT1) and oxidative stress and antioxidative (NFκB and SOD2) mediators. The results demonstrated, by biochemical and gene expression assays, that flumethrin induces oxidative stress and apoptosis, which could cause DNA damage. Detailed knowledge obtained about these molecular changes could provide the basis for elucidating the molecular mechanisms of flumethrin-induced neurotoxicity.
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29
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Porro C, La Torre ME, Tartaglia N, Benameur T, Santini M, Ambrosi A, Messina G, Cibelli G, Fiorelli A, Polito R, Messina G. The Potential Role of Nutrition in Lung Cancer Establishment and Progression. Life (Basel) 2022; 12:270. [PMID: 35207557 PMCID: PMC8877211 DOI: 10.3390/life12020270] [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: 01/16/2022] [Revised: 02/01/2022] [Accepted: 02/08/2022] [Indexed: 11/16/2022] Open
Abstract
Lung cancer is a devastating disease with a high incidence and low survival rates, so recent studies have focused on analyzing the risk factors that might prevent this disease from developing or have protective/therapeutic effects. Nutrition is an important key factor in the prevention and treatment of lung cancer. Various factors appear to be involved in the development of the latter, such as cigarette smoking or certain external environmental factors. The increase in oxidative stress is therefore an integral part of the carcinogenesis process. The biological role of bioactive factors derived from adipose tissue, mainly adipokines, is implicated in various cancers, and an increasing body of evidence has shown that certain adipocytokines contribute to the development, progression and prognosis of lung cancer. Not all adipokines stimulate tumor growth; in fact, adiponectin inhibits carcinogenesis by regulating both cell growth and the levels of inflammatory cytokines. Adiponectin expression is deregulated in several cancer types. Many nutritional factors have been shown to increase adiponectin levels and therefore could be used as a new therapeutic strategy for combating lung cancer. In addition, foods with antioxidant and anti-inflammatory properties play a key role in the prevention of many human diseases, including lung cancer. The purpose of this review is to analyze the role of diet in lung cancer in order to recommend dietary habit and lifestyle changes to prevent or treat this pathology.
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Affiliation(s)
- Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Maria Ester La Torre
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Nicola Tartaglia
- Department of Medical Additionally, Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (N.T.); (A.A.)
| | - Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Mario Santini
- Department of Translational Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.S.); (G.M.)
| | - Antonio Ambrosi
- Department of Medical Additionally, Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (N.T.); (A.A.)
| | - Giovanni Messina
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Giuseppe Cibelli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Alfonso Fiorelli
- Department of Translational Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.S.); (G.M.)
| | - Rita Polito
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Gaetana Messina
- Department of Translational Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.S.); (G.M.)
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Ferrocene-functionalized anilines as potent anticancer and antidiabetic agents: Synthesis, spectroscopic elucidation, and DFT calculations. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.131632] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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31
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Anu D, Naveen P, Devendhiran T, Shyamsivappan S, Kumarasamy K, Lin MC, Frampton CS, Kaveri MV. Synthesis, spectral characterization, X-ray crystallography and biological evaluations of Pd(II) complexes containing 4(N)-substituted thiosemicarbazone. J COORD CHEM 2022. [DOI: 10.1080/00958972.2021.2025222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- D. Anu
- Department of Chemistry, Bharathiar University, Coimbatore, India
| | - P. Naveen
- Department of Chemistry, Dr. NGP Arts and Science College, Bharathiar University, Coimbatore, India
| | - Tamiloli Devendhiran
- Department and Graduate Institute of Applied Chemistry, Chaoyang University of Technology, Taichung City, Taiwan
| | - S. Shyamsivappan
- Department of Chemistry, Dr. NGP Arts and Science College, Bharathiar University, Coimbatore, India
| | - Keerthika Kumarasamy
- Department and Graduate Institute of Applied Chemistry, Chaoyang University of Technology, Taichung City, Taiwan
| | - Mei Ching Lin
- Department and Graduate Institute of Applied Chemistry, Chaoyang University of Technology, Taichung City, Taiwan
| | | | - M. V. Kaveri
- Department of Chemistry, Bharathiar University, Coimbatore, India
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32
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Marchi RC, Campos IA, Santana VT, Carlos RM. Chemical implications and considerations on techniques used to assess the in vitro antioxidant activity of coordination compounds. Coord Chem Rev 2022. [DOI: 10.1016/j.ccr.2021.214275] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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The association of Edaravone with shunt surgery improves behavioral performance, reduces astrocyte reaction and apoptosis, and promotes neuroprotection in young hydrocephalic rats. J Chem Neuroanat 2021; 119:102059. [PMID: 34896559 DOI: 10.1016/j.jchemneu.2021.102059] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/24/2021] [Accepted: 12/06/2021] [Indexed: 11/22/2022]
Abstract
The neuroprotective effect of Edaravone in young hydrocephalic rats associated with a CSF derivation system was evaluated. The drug has already been shown to be beneficial in experimental hydrocephalus, but the combination of this drug with shunt surgery has not yet been investigated. Fifty-seven-day-old Wistar rats submitted to hydrocephalus by injection of kaolin in the cisterna magna were used and divided into five groups: control (n = 10), hydrocephalic (n = 10), hydrocephalic treated with Edaravone (20 mg/kg/day) (n = 10), hydrocephalic treated with shunt (n = 10) and hydrocephalic treated with shunt and Edaravone (n = 10). Administration of the Edaravone was started 24 h after hydrocephalus induction (P1) and continued until the experimental endpoint (P21). The CSF shunt surgery was performed seven days after hydrocephalus induction (P7). Open-field tests, histological evaluation by hematoxylin and eosin, immunohistochemistry by Caspase-3 and GFAP, and ELISA biochemistry by GFAP were performed. Edaravone reduced reactive astrogliosis in the corpus callosum and germinal matrix (p < 0.05). When used alone or associated with CSF shunt surgery, the drug decreased the cell death process (p < 0.0001) and improved the morphological aspect of the astroglia (p < 0.05). The results showed that Edaravone associated with CSF bypass surgery promotes neuroprotection in young hydrocephalic rats by reducing reactive astrogliosis and decreasing cell death.
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34
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Teh SS, Mah SH, Lau HLN, Teng KT, Loganathan R. Antioxidant Potential of Red Palm-Pressed Mesocarp Olein. J Oleo Sci 2021; 70:1719-1729. [PMID: 34759109 DOI: 10.5650/jos.ess21147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Oxidative stress occurs due to the imbalance amount of the free radicals and antioxidants in human body which often associated with numerous chronic diseases. The antioxidant properties of red palm-pressed mesocarp olein (PPMO) have not been widely studied. Therefore, antioxidant properties of PPMO relative to commercially available edible oils, namely red palm olein (RPO), palm olein (PO), extra virgin olive oil (OO) and extra virgin coconut oil (CNO) were studied. PPMO exhibited significant higher phytonutrients which more than 2-fold compared to the edible oils. Overall, antioxidant screening indicated that PPMO has significantly higher antioxidant activities than RPO, PO and CNO in term of DPPH, H2O2, NO scavenging and FIC; and significantly higher H2O2 and FIC than OO. The outcomes of this study reveal that PPMO is as good as commercially available edible oil, also a good source for food applications and dietary nutritional supplements. More importantly, the utilization of PPMO could mitigate oil palm waste problem and results in positive environmental impact.
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Affiliation(s)
- Soek Sin Teh
- Energy and Environment Unit, Engineering and Processing Division, Malaysian Palm Oil Board, 6, Persiaran Institusi
| | - Siau Hui Mah
- School of Biosciences, Taylor's University, Lakeside Campus
| | - Harrison Lik Nang Lau
- Energy and Environment Unit, Engineering and Processing Division, Malaysian Palm Oil Board, 6, Persiaran Institusi
| | - Kim Tiu Teng
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board
| | - Radhika Loganathan
- Nutrition Unit, Product Development and Advisory Services Division, Malaysian Palm Oil Board
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35
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Waldeck-Weiermair M, Yadav S, Spyropoulos F, Krüger C, Pandey AK, Michel T. Dissecting in vivo and in vitro redox responses using chemogenetics. Free Radic Biol Med 2021; 177:360-369. [PMID: 34752919 PMCID: PMC8639655 DOI: 10.1016/j.freeradbiomed.2021.11.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/08/2021] [Accepted: 11/04/2021] [Indexed: 02/03/2023]
Abstract
Hydrogen peroxide (H2O2) is the most abundant reactive oxygen species (ROS) within mammalian cells. At low concentrations, H2O2 serves as a versatile cell signaling molecule that mediates vital physiological functions. Yet at higher concentrations, H2O2 can be a toxic molecule by promoting pathological oxidative stress in cells and tissues. Within normal cells, H2O2 is differentially distributed in a variety of subcellular locales. Moreover, many redox-active enzymes and their substrates are themselves differentially distributed within cells. Numerous reports have described the biological and biochemical consequences of adding exogenous H2O2 to cultured cells and tissues, but many of these observations are difficult to interpret: the effects of exogenous H2O2 do not necessarily replicate the cellular responses to endogenous H2O2. In recent years, chemogenetic approaches have been developed to dynamically regulate the abundance of H2O2 in specific subcellular locales. Chemogenetic approaches have been applied in multiple experimental systems, ranging from in vitro studies on the intracellular transport and metabolism of H2O2, all the way to in vivo studies that generate oxidative stress in specific organs in living animals. These chemogenetic approaches have exploited a yeast-derived d-amino acid oxidase (DAAO) that synthesizes H2O2 only in the presence of its d-amino acid substrate. DAAO can be targeted to various subcellular locales, and can be dynamically activated by the addition or withdrawal of its d-amino acid substrate. In addition, recent advances in the development of highly sensitive genetically encoded H2O2 biosensors are providing a better understanding of both physiological and pathological oxidative pathways. This review highlights several applications of DAAO as a chemogenetic tool across a wide range of biological systems, from analyses of subcellular H2O2 metabolism in cells to the development of new disease models caused by oxidative stress in vivo.
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Affiliation(s)
- Markus Waldeck-Weiermair
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA; Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Neue Stiftingtalstraße 6/6, 8010, Graz, Austria
| | - Shambhu Yadav
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Fotios Spyropoulos
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA; Department of Pediatric Newborn Medicine, Harvard Medical School, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA
| | - Christina Krüger
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Arvind K Pandey
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA
| | - Thomas Michel
- Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
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36
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Gad MF, Mossa ATH, Refaie AA, Ibrahim NE, Mohafrash SMM. Benchmark dose and the adverse effects of exposure to pendimethalin at low dose in female rats. Basic Clin Pharmacol Toxicol 2021; 130:301-319. [PMID: 34738321 DOI: 10.1111/bcpt.13683] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 10/29/2021] [Accepted: 11/01/2021] [Indexed: 11/29/2022]
Abstract
Pendimethalin (PND) is a dinitroaniline herbicide widely used to control broadleaf and annual grasses. Although the acute oral toxicity of PND is >5 g/kg b.wt. in humans (LD50 for rats >5000 g/kg b.wt.), it has been classified as a possible human carcinogen. It is still used in agriculture so, agricultural workers and their families, as well as consumers, can be exposed to this herbicide. The present study is the first report investigating the dose-response effect using the benchmark dose (BMD) and the adverse effects of exposure to PND at low dose via apoptosis responses linked to the expression of tumor necrosis factor-α (TNF-α), FAS, and BAX proteins; oxidative stress; and DNA and liver damage in female rats. The rats were exposed to PND via drinking water at doses equivalent to no-observed-adverse-effect level (NOAEL = 100 mg/kg b.wt.), 200, and 400 mg/kg b.wt. for 28 days. PND caused the overexpression of Tnf-α, Fas, and Bax; increased the levels of serum liver biomarkers; and increased oxidative stress in the liver and erythrocytes. Furthermore, it induced DNA and liver damage in a dose-dependent manner. The BMD showed that serum alkaline phosphatase (ALP) and total antioxidant capacity (78.4 and 30.1 mg/kg b.wt./day, respectively), lipid peroxidation in liver tissue (30.9 mg/kg b.wt./day), catalase in erythrocytes (14.0 mg/kg b.wt./day), and FAS expression in liver tissue (6.89 mg/kg b.wt./day) were highly sensitive biomarkers of PND toxicity. Our findings suggest the generation of reactive oxygen species as a possible mechanism of PND-induced gene overexpression of tumor necrosis factor-α (TNF-α), FAS, and BAX proteins, oxidative stress, and DNA and liver damage in female rats.
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Affiliation(s)
- Marwa F Gad
- Pesticide Chemistry Department, National Research Centre (NRC), Giza, Egypt
| | | | - Amel A Refaie
- Pesticide Chemistry Department, National Research Centre (NRC), Giza, Egypt
| | - Noha E Ibrahim
- Department of Microbial Biotechnology, Genetic Engineering and Biotechnology Division, National Research Centre (NRC), Giza, Egypt
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Abdel Aziz MS, Salama HE. Developing multifunctional edible coatings based on alginate for active food packaging. Int J Biol Macromol 2021; 190:837-844. [PMID: 34517032 DOI: 10.1016/j.ijbiomac.2021.09.031] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 07/25/2021] [Accepted: 09/06/2021] [Indexed: 10/20/2022]
Abstract
The applications of edible coatings stemmed exclusively from alginate in food packaging are restricted due to their inherent deficient antimicrobial, barrier, and UV-barrier properties. In this work, we aimed to design smart alginate-based coatings for active food packaging through the addition of both aloe vera (AV) and garlic oil (GO). The interactions between the film components were verified by FTIR and XRD. Thermal and mechanical properties were improved by the presence of AV and GO. The presence of AV and GO did not significantly influence the transparency of alginate films. The films exhibited a significant UV-shielding to all UV regions. Water vapor permeability was significantly (p < 0.05) reduced either through the incorporation of AV or GO. The antimicrobial properties of the prepared films were considerably improved by the presence of AV and GO. The shelf-life of tomatoes (Solanum lycopersicum L.) was extended when coated with the alginate film incorporated with AV and GO. Owing to the outstanding UV-shielding, mechanical, thermal, and antimicrobial properties, the alginate/AV/GO active coatings could potentially be implemented in the food packaging industry.
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Affiliation(s)
| | - Hend E Salama
- Chemistry Department, Faculty of Science, Cairo University, Giza 12613, Egypt
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38
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Zare‐Bidaki M, Mohammadparast‐Tabas P, Peyghambari Y, Chamani E, Siami‐Aliabad M, Mortazavi‐Derazkola S. Photochemical synthesis of metallic silver nanoparticles using
Pistacia khinjuk
leaves extract (
PKL
@AgNPs) and their applications as an alternative catalytic, antioxidant, antibacterial, and anticancer agents. Appl Organomet Chem 2021. [DOI: 10.1002/aoc.6478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Majid Zare‐Bidaki
- Infectious Diseases Research Center Birjand University of Medical Sciences Birjand Iran
| | | | - Yasaman Peyghambari
- Student Research Committee Birjand University of Medical Sciences Birjand Iran
| | - Elham Chamani
- Department of Clinical Biochemistry, Faculty of Medicine Birjand University of Medical Sciences Birjand Iran
| | - Mahin Siami‐Aliabad
- Student Research Committee Birjand University of Medical Sciences Birjand Iran
- Department of Clinical Biochemistry, Faculty of Medicine Birjand University of Medical Sciences Birjand Iran
| | - Sobhan Mortazavi‐Derazkola
- Medical Toxicology and Drug Abuse Research Center (MTDRC) Birjand University of Medical Sciences Birjand Iran
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39
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Liu M, Wen C, Pan S. Modulator effect of mangiferin on biochemical characterization in 7,12-dimethylbenz[a]anthracene induced oral cancer in experimental hamsters. Vet Med Sci 2021; 7:2015-2025. [PMID: 33949808 PMCID: PMC8464247 DOI: 10.1002/vms3.500] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 04/07/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Newly, chemo-preventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural based constituents. Malignancy urges to augment effectual chemo-preventive agents that are look forward to suppress the tumours which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related with the high prevalence of human oral cancer (OC) patients. METHODS In the present research, we examined to assess antioxidants, lipid peroxidation (LPO) and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7.12-dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma (HCPC). OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks. RESULTS 100% well defined OC establishment with body weight (bw), tumour burden (TB), antioxidant, LPO and liver marker enzymes and also histological changes were observed on DMBA-challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg bw, to DMBA painted hamsters were significantly averted the body weight, succession of tumour, the biochemical as well as histopathological changes. CONCLUSION Findings of this work clearly suggest that the anti-carcinoma effect of mangiferin possesses the modulator effects on potent antioxidant, anti-LPO and detoxification agents to expel the metabolites of malignant cells, on DMBA-provoked BPC in hamsters.
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Affiliation(s)
- Min Liu
- Department of PharmacyQingdao Municipal HospitalQingdaoChina
| | - Chengquan Wen
- Department of PharmacyQingdao Municipal HospitalQingdaoChina
| | - Shengqi Pan
- Department of Intensive Care MedicineQingdao Municipal HospitalQingdaoChina
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40
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Punetha VD, Dhali S, Rana A, Karki N, Tiwari H, Negi P, Basak S, Sahoo NG. Recent Advancements in Green Synthesis of Nanoparticles for improvement of bioactivities: a Review. Curr Pharm Biotechnol 2021; 23:904-919. [PMID: 34387160 DOI: 10.2174/1389201022666210812115233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 04/09/2021] [Accepted: 05/31/2021] [Indexed: 11/22/2022]
Abstract
Natural products have widely been used in applications ranging from antibacterial, antiviral, antifungal and various other medicinal applications. Use of these natural products was recognized way before the establishment of basic chemistry behind the disease and the chemistry of plant metabolites. After the establishment of plant chemistry various new horizons evolved, and application of the natural products breached the orthodox limitations. In one such interdisciplinary area, use of plant materials in the synthesis of nano particles (NPs) has exponentially emerged. This advancement has offered various environment friendly methods where hazardous chemicals are completely replaced by natural products in the sophisticated and hectic synthesis processes. This review is an attempt to understand the mechanism of metal nano particles synthesis using plant materials. It includes details on the role of plant's secondary metabolites in the synthesis of nano particles including the mechanism of action. In addition, use of these nano materials has widely been discussed along with the possible mechanism behind their antimicrobial and catalytic action.
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Affiliation(s)
- Vinay Deep Punetha
- Prof. Rajendra Singh Nanoscience and Nanotechnology Centre, Department of Chemistry, DSB Campus, Kumaun University, Nainital, Uttarakhand. India
| | - Sunil Dhali
- Prof. Rajendra Singh Nanoscience and Nanotechnology Centre, Department of Chemistry, DSB Campus, Kumaun University, Nainital, Uttarakhand. India
| | - Anita Rana
- Prof. Rajendra Singh Nanoscience and Nanotechnology Centre, Department of Chemistry, DSB Campus, Kumaun University, Nainital, Uttarakhand. India
| | - Neha Karki
- Prof. Rajendra Singh Nanoscience and Nanotechnology Centre, Department of Chemistry, DSB Campus, Kumaun University, Nainital, Uttarakhand. India
| | - Himani Tiwari
- Prof. Rajendra Singh Nanoscience and Nanotechnology Centre, Department of Chemistry, DSB Campus, Kumaun University, Nainital, Uttarakhand. India
| | - Pushpa Negi
- Department of Chemistry, Graphic Era Hill University, Bhimtal Campus, Nainital, Uttarakhand. India
| | - Souvik Basak
- Dr. B.C. Roy College of Pharmacy & Allied Health Sciences, Durgapur, WB. India
| | - Nanda Gopal Sahoo
- Prof. Rajendra Singh Nanoscience and Nanotechnology Centre, Department of Chemistry, DSB Campus, Kumaun University, Nainital, Uttarakhand. India
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Archangelidi O, Cullinan P, Simmonds NJ, Mentzakis E, Peckham D, Bilton D, Carr SB. Incidence and risk factors of cancer in individuals with cystic fibrosis in the UK; a case-control study. J Cyst Fibros 2021; 21:302-308. [PMID: 34348871 DOI: 10.1016/j.jcf.2021.07.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 06/08/2021] [Accepted: 07/05/2021] [Indexed: 01/29/2023]
Abstract
To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV1%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.
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Affiliation(s)
- Olga Archangelidi
- National Heart and Lung Institute, Imperial College, London; Amgem Ltd
| | - Paul Cullinan
- National Heart and Lung Institute, Imperial College, London; Royal Brompton Hospital, London
| | - Nicholas J Simmonds
- National Heart and Lung Institute, Imperial College, London; Royal Brompton Hospital, London
| | | | | | - Diana Bilton
- National Heart and Lung Institute, Imperial College, London; Royal Brompton Hospital, London
| | - Siobhán B Carr
- National Heart and Lung Institute, Imperial College, London; Royal Brompton Hospital, London.
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Yadav SA, Faruck LH, Subramanium R, Surendren LK, Bakshi H. Screening and assessment of molecular mechanistic actions of 5-hydroxy-1-methylpiperidin-2-one against free radicals, lung cancer cell line (A549), and binding properties on bovine serum albumin. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2021. [DOI: 10.1186/s43094-021-00277-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Natural products play a key role in treating different ailment including diabetes, asthma, skin diseases, and cancer. It is well known that synthetic drugs elicit significant toxicity when used in the clinic. A higher drug affinity towards carrier protein Bovine Serum Albumin (BSA) would enhance a higher drug bioavailability which in turn leads to a higher therapeutic efficacy. The focus of the present study was to investigate antioxidant and anti-cancer potential of 5-hyrdoxy1-methylpiperidin-2-one (5-HMP) isolated from leaves of Tragia involucrata.
Methods and material
In vitro free radical scavenging assays and MTT assay were employed to assess the antioxidant activity of 5-HMP and cytotoxicity of 5-HMP on lung cancer cell line, A549, respectively. In addition, attempts were made to investigate 5-HMP binding capacity on BSA by spectral studies and molecular docking.
Results
The antioxidant data revealed that 5-HMP inhibited the radicals with an IC50 value of 49.55 ± 0.75 μg/ml which was comparable with the IC50 values afforded by l-ascorbic acid. 5-HMP exhibited a dose-dependent cytotoxicity on A549 cells with an IC50 value of 30.00 ± 0.55 μg/ml. further 5-HMP induced a cell cycle arrest in A549 at S and G2/M phase. The fluorescence quenching was observed when an increasing concentration of 5-HMP, reacts with a fixed concentration of BSA (1.0 μM). The fluorescence quenching of BSA by 5-HMP indicated a binding constant of K5-HMP = 2.8 ± 1.4 × 104M−1 with corresponding binding free energy (ΔG)−6.06 K.cal/mole.
Conclusions
This paper concluded that 5-HMP possesses antioxidant properties, cytotoxic effects and also it possesses good drug binding properties on bovine serum albumin.
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Development of active edible coating of alginate and aloe vera enriched with frankincense oil for retarding the senescence of green capsicums. Lebensm Wiss Technol 2021. [DOI: 10.1016/j.lwt.2021.111341] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
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Murthy A, Kornel E, Neubardt S. Strategy to reduce radiation exposure in postoperative spinal computed tomography scans. Surg Neurol Int 2021; 12:159. [PMID: 33948329 PMCID: PMC8088488 DOI: 10.25259/sni_289_2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/28/2020] [Indexed: 12/14/2022] Open
Abstract
Background: When diagnosing and treating spinal disorders, spine surgeons commonly utilize computed tomography (CT) scans preoperatively, intraoperatively, and postoperatively. Methods: This article reviews the literature regarding the potentially harmful effects of X-rays, specifically from CT scans. Results: The risk for damaging DNA and developing cancer increases with increasing scan length (e.g., increasing amount of radiation received). Conclusion: When assessing postoperative status, CT scans should be directed only through the area of specific interest to limit the total dose of radiation received by the patient.
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Affiliation(s)
- Anirudh Murthy
- Department of Biology, Stony Brook University, Stony Brook
| | | | - Seth Neubardt
- Department of Orthopedic Surgery, Brain and Spine Surgeons of New York, West Harrison, New York, United States
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Ma S, Li X, Sun Y, Mi R, Li Y, Wen Z, Meng N, Yi L, Du X, Li S. Enzymatic Hydrolysis of Defatted Antheraea pernyi (Lepidoptera: Saturniidae) Pupa Protein by Combined Neutral Protease Yield Peptides With Antioxidant Activity. JOURNAL OF INSECT SCIENCE (ONLINE) 2021; 21:5. [PMID: 33693805 PMCID: PMC7947994 DOI: 10.1093/jisesa/ieab013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Indexed: 06/12/2023]
Abstract
In this study, peptides were prepared from defatted Antheraea pernyi (Lepidoptera: Saturniidae) pupa protein via hydrolysis with combined neutral proteases. Single-factor tests and response surface methodology (RSM) were used to determine the optimal hydrolysis condition suitable for industrial application. Optimal hydrolysis of the defatted pupa protein was found to occur at an enzyme concentration of 4.85 g/liter, a substrate concentration of 41 g/liter, a hydrolysis temperature of 55°C, and a hydrolysis time of 10 h and 40 min. Under these conditions, the predicted and actual rates of hydrolysis were 45.82% and 45.75%, respectively. Peptides with a molecular weight of less than 2,000 Da accounted for 90.5% of the total peptides generated. Some of the peptides were antioxidant peptides as revealed by sequencing and functional analysis. The antioxidant activity of the mixed peptides was subsequently confirmed by an antioxidant activity assay. The results showed that peptides with high antioxidant activity could be obtained from the hydrolysis of A. pernyi pupa protein.
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Affiliation(s)
- Shuhui Ma
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Xuejun Li
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Yongxin Sun
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Rui Mi
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Yajie Li
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Zhixin Wen
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Nan Meng
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Li Yi
- Shanghai Jianqiao University, Shanghai, China
| | - Xingfan Du
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
| | - Shuying Li
- Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China
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Shashni B, Nagasaki Y. Newly Developed Self-Assembling Antioxidants as Potential Therapeutics for the Cancers. J Pers Med 2021; 11:jpm11020092. [PMID: 33540693 PMCID: PMC7912983 DOI: 10.3390/jpm11020092] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/19/2021] [Accepted: 01/28/2021] [Indexed: 02/07/2023] Open
Abstract
Elevated reactive oxygen species (ROS) have been implicated as significant for cancer survival by functioning as oncogene activators and secondary messengers. Hence, the attenuation of ROS-signaling pathways in cancer by antioxidants seems a suitable therapeutic regime for targeting cancers. Low molecular weight (LMW) antioxidants such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO), although they are catalytically effective in vitro, exerts off-target effects in vivo due to their size, thus, limiting their clinical use. Here, we discuss the superior impacts of our TEMPO radical-conjugated self-assembling antioxidant nanoparticle (RNP) compared to the LMW counterpart in terms of pharmacokinetics, therapeutic effect, and adverse effects in various cancer models.
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Affiliation(s)
- Babita Shashni
- Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan;
| | - Yukio Nagasaki
- Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan;
- Master’s School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan
- Center for Research in Isotopes and Environmental Dynamics (CRiED), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan
- Correspondence: ; Fax: +81-(0)29-853-5750
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Aoiadni N, Ayadi H, Jdidi H, Naifar M, Maalej S, Makni FA, El Feki A, Fetoui H, Koubaa FG. Flavonoid-rich fraction attenuates permethrin-induced toxicity by modulating ROS-mediated hepatic oxidative stress and mitochondrial dysfunction ex vivo and in vivo in rat. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:9290-9312. [PMID: 33136269 DOI: 10.1007/s11356-020-11250-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 10/13/2020] [Indexed: 06/11/2023]
Abstract
The present study explores the antioxidant, anti-microbial, and hepatoprotective potentials of flavonoid-rich fractions from Fumaria officinalis against permethrin-induced liver damage ex vivo/in vivo in rat. However, HPLC-DAD analysis revealed the richness of 6 components in ethyl acetate fraction (EAF) where ferulic acid, rosmarinic acid, and myricetin are the most abundant. The in vitro assays showed that EAFs have impressive antioxidant and anti-microbial properties. Ex vivo, permethrin (PER) (100 μM) induced a decrease of hepatic AST and ALT activities and 25-OH vitamin D and vitamin C levels and an increase of ALP and LDH activities, TBARS, and ϒ-GT levels with a disturbance of oxidative status. The hepatoprotective effect of EAF (1 mg/mL) against PER was confirmed by the amelioration of oxidative stress profile. In vivo, permethrin was found to increase absolute and relative liver weights, plasma transaminase activities, lactate-to-pyruvate ratio, hepatic and mitochondrial lipid peroxidation, and protein oxidation levels. This pesticide triggered a decrease of Ca2+ and Mg2+-ATPases and mitochondrial enzyme activities. The co-treatment with EAF reestablished the hepatic and mitochondrial function, which could be attributed to its richness in phenolic compounds.
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Affiliation(s)
- Nissaf Aoiadni
- Laboratory of Animal Eco-Physiology, Faculty of Sciences of Sfax, Street of Soukra Km 3.5, BP 1171, CP 3000, Sfax, Tunisia.
| | - Houda Ayadi
- Laboratory of Biodiversity and Aquatic Ecosystems, Ecology and Planktonology, Sciences Faculty of Sfax, Street of Soukra Km 3.5, BP 1171, CP 3000, Sfax, Tunisia
| | - Hajer Jdidi
- Laboratory of Animal Eco-Physiology, Faculty of Sciences of Sfax, Street of Soukra Km 3.5, BP 1171, CP 3000, Sfax, Tunisia
| | - Manel Naifar
- Laboratory of Biochemistry, CHU Habib Bourguiba, Sfax, Tunisia
| | - Sami Maalej
- Laboratory of Biodiversity and Aquatic Ecosystems, Ecology and Planktonology, Sciences Faculty of Sfax, Street of Soukra Km 3.5, BP 1171, CP 3000, Sfax, Tunisia
| | | | - Abdelfattah El Feki
- Laboratory of Animal Eco-Physiology, Faculty of Sciences of Sfax, Street of Soukra Km 3.5, BP 1171, CP 3000, Sfax, Tunisia
| | - Hamadi Fetoui
- Laboratory of Toxicology and Environmental Health.LR17ES06, Sciences Faculty of Sfax, University of Sfax, BP1171, 3000, Sfax, Tunisia
| | - Fatma Ghorbel Koubaa
- Laboratory of Animal Eco-Physiology, Faculty of Sciences of Sfax, Street of Soukra Km 3.5, BP 1171, CP 3000, Sfax, Tunisia
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Prostate cancer and food-based antioxidants in India as plausible therapeutics. Cancer 2021. [DOI: 10.1016/b978-0-12-819547-5.00019-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Ortiz‐Escarza JM, Medina ME, Trigos A. On the peroxyl radical scavenging ability of β‐sitosterol in lipid media: A theoretical study. J PHYS ORG CHEM 2021. [DOI: 10.1002/poc.4123] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
| | - Manuel E. Medina
- Centro de Investigación en Micología Aplicada Universidad Veracruzana Xalapa Mexico
| | - Angel Trigos
- Centro de Investigación en Micología Aplicada Universidad Veracruzana Xalapa Mexico
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Nirgude S, Choudhary B. Insights into the role of GPX3, a highly efficient plasma antioxidant, in cancer. Biochem Pharmacol 2020; 184:114365. [PMID: 33310051 DOI: 10.1016/j.bcp.2020.114365] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 12/08/2020] [Indexed: 12/20/2022]
Abstract
Glutathione peroxidases are well known antioxidant enzymes. They catalyze the reduction of hydrogen peroxide or organic hydroperoxides using glutathione. Among the reported 8 GPxs, GPx3, a highly conserved protein and a major ROS scavenger in plasma, has been well studied and confirmed to play a vital role as a tumor suppressor in most cancers. Additionally, this gene is known to be epigenetically regulated. It is downregulated either by hypermethylation or genomic deletion. In this review, we summarized the role of GPX3 in various cancers, its use as a prognostic biomarker, and a potential target for clinical intervention.
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Affiliation(s)
- Snehal Nirgude
- Institute of Bioinformatics and Applied Biotechnology, Electronic City Phase 1, Bangalore 560100, India; Registered as graduate student under Manipal Academy of Higher Education, Manipal 576104, India
| | - Bibha Choudhary
- Institute of Bioinformatics and Applied Biotechnology, Electronic City Phase 1, Bangalore 560100, India.
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