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Gdowicz-Kłosok A, Krześniak M, Łasut-Szyszka B, Butkiewicz D, Rusin M. Antibacterial Activity of the p53 Tumor Suppressor Protein-How Strong Is the Evidence? Int J Mol Sci 2025; 26:4416. [PMID: 40362653 PMCID: PMC12072856 DOI: 10.3390/ijms26094416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Revised: 04/28/2025] [Accepted: 05/02/2025] [Indexed: 05/15/2025] Open
Abstract
The p53 tumor suppressor is best known for controlling the cell cycle, apoptosis, DNA repair, and metabolism, but it also regulates immunity and is able to impede the live cycle of viruses. For this reason, these infectious agents encode proteins which inactivate p53. However, what is less known is that p53 can also be inactivated by human pathogenic bacteria. It is probably not due to collateral damage, but specific targeting, because p53 could interfere with their multiplication. The mechanisms of the antibacterial activity of p53 are poorly known. However, they can be inferred from the results of high-throughput studies, which have identified more than a thousand p53-activated genes. As it turns out, many of these genes code proteins which have proven or plausible antibacterial functions like the efficient detection of bacteria by pattern recognition receptors, the induction of pro-inflammatory pyroptosis, the recruitment of immune cells, direct bactericidal activity, and the presentation of bacterial metabolites to lymphocytes. Probably there are more antibacterial, p53-regulated functions which were overlooked because laboratory animals are kept in sterile conditions. In this review, we present the outlines of some intriguing antibacterial mechanisms of p53 which await further exploration. Definitely, this area of research deserves more attention, especially in light of the appearance of antibiotic-resistant bacterial strains.
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Affiliation(s)
| | | | | | | | - Marek Rusin
- Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, 44-101 Gliwice, Poland; (A.G.-K.); (M.K.); (B.Ł.-S.); (D.B.)
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Liao J, Deng S, Shi B, Wang M, Yin Y, Cao Y, Liu R, Huang X, Jiang L, Shi Q. HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer. Virol J 2025; 22:109. [PMID: 40253372 PMCID: PMC12008847 DOI: 10.1186/s12985-025-02731-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/09/2025] [Indexed: 04/21/2025] Open
Abstract
BACKGROUND Recent researches indicated a down-regulation of Human beta-defensin2 (HBD2) expression in cervical cancer cells, but the mechanism and clinical significance is not clear yet. METHODS In this paper, based on the data from the TCGA database, the bioinformatics analysis provided by the UALCAN server was used. The HBD2 mRNA levels were tested with RT-qPCR in cells and protein concentration in cell cultural supernatant was assayed with ELISA. When the gene of Human papillomavirus type 16 E7 oncoprotein (HPV16 E7) overexpression or knockdown, the protein expression of ASK1 and p38 MAPK was detected by Western blot. RESULTS The bioinformatics analysis results implied that mRNA levels of HBD2 in cervical cancer were lower obviously than healthy people. HBD2 mRNA levels and protein in CaSki and SiHa cells increased obviously under the condition of HPV16 E7 gene silence. However, HBD2 mRNA and protein levels decreased significantly in C33A and CaCo2 cells not only under the conditions of treatment with HPV16 E7 gene overexpression, but also the inhibition of ASK1-p38 MAPK pathway by SB-203580 or GS-4997, or shRNA expression plasmid of ASK1 transefction. Moreover, p-ASK1(Thr845), the activity forming protein of ASK1, and p-p38, decreased in C33A and CaCo2 cells accompanied with HPV16 E7 overexpression, while p-ASK1(Ser966) protein, an inhibitory forming protein kept in a same stable levels. The completely opposite patterns of the protein expression in ASK1-p38 MAPK pathway were obtained in CaSki and SiHa cells transfected with HPV16 E7 siRNA sequence. Interestingly, statistical higher levels of phosphorylated p38 and cellular apoptosis rates, were found in SiHa cells exposed in Anisomycin than in DMSO solution. And increased HBD2 protein concentration in cell cultural supernatant and decreased cell survial rates, were confirmed in CaSki and SiHa cells treatment with Anisomycin, at the same time. CONCLUSIONS Our results implied that HPV16 E7 suppresses HBD2 expression via the inhibition of the ASK1-p38 MAPK signaling pathway, and this mechanism might be a key way of anti-tumor effect of Anisomycin. This study provided a novel insight into the expression and regulation mechanism of HBD2 in tumors and offered a possible therapeutic strategy by using defensins for cervical cancer in future.
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Grants
- 30760280, 81760472 National Natural Science Foundation of China
- 30760280, 81760472 National Natural Science Foundation of China
- 202130621 Health Commission Project of Jiangxi Province,China
- 202130621 Health Commission Project of Jiangxi Province,China
- 202130621 Health Commission Project of Jiangxi Province,China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
- 20181BAB205064 Natural Science Funding of Jiangxi province, China
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Affiliation(s)
- Juanjuan Liao
- Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Shanshan Deng
- Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Bowen Shi
- The First Clinical Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Meizhen Wang
- the hospital of Nanchang University, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Yingying Yin
- the hospital of Nanchang University, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Yanli Cao
- Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Renping Liu
- Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Xiaotian Huang
- Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China
| | - Lixia Jiang
- Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, China
| | - Qiaofa Shi
- Department of Medical Microbiology & Immunology, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, 330031, Jiangxi, China.
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Wang L, Yang H, Cao L, Yang Y, Ding R. Integrative genomic pan-cancer analysis reveals the prognostic significance of DEFB1 in tumors. Discov Oncol 2025; 16:552. [PMID: 40244529 PMCID: PMC12006651 DOI: 10.1007/s12672-025-02340-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 04/08/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Defensin beta 1 (DEFB1) is a key immune response gene, but its role in cancer remains unclear. This study aims to explore DEFB1 expression, genetic alterations, immune infiltration, and prognostic significance across various cancer types. METHODS We analyzed DEFB1 expression and its association with cancer prognosis using data from public platforms, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Human Protein Atlas (HPA). Additionally, we examined DEFB1 genetic alterations, immune cell infiltration, and its molecular partners using various bioinformatics tools. RESULTS DEFB1 expression was highest in salivary glands, kidneys, and pancreas. In cancers, DEFB1 was upregulated in cholangiocarcinoma, kidney chromophobe, and melanoma, but downregulated in breast, colon, and rectal cancers. High DEFB1 expression was linked to poorer overall survival in lung adenocarcinoma and pancreatic adenocarcinoma, but better survival in head and neck squamous cell carcinoma. Genetic analysis revealed alterations in liver and gastric cancers. Immune infiltration analysis showed a correlation between DEFB1 and cancer-associated fibroblasts in liver cancer, while neutrophil infiltration was linked to bladder carcinoma, diffuse large B-cell lymphoma, and lung squamous cell carcinoma. Key genes associated with DEFB1 included KLK1, BSND, and CLCNKB. DISCUSSION This study highlights DEFB1's potential as a prognostic biomarker and its influence on the tumor immune microenvironment across different cancers. These findings suggest DEFB1 could be a target for future cancer therapies, although further studies are needed to validate these results.
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Affiliation(s)
- Li Wang
- Department of Breast Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, China.
| | - Hongyu Yang
- Department of Rheumatology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, China
| | - Lu Cao
- Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
| | - Yang Yang
- Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, China
| | - Ran Ding
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.
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Wang Q, Dong J, Jing X, Long Y, Jia H, Li Y, Wang J. Unveiling Ventilator-Associated Pneumonia: S100A8 as a Promising Biomarker Through Integrated RNA-Seq Analysis. J Multidiscip Healthc 2024; 17:6199-6210. [PMID: 39759083 PMCID: PMC11697655 DOI: 10.2147/jmdh.s495121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 12/23/2024] [Indexed: 01/07/2025] Open
Abstract
Background and Objectives Ventilator-associated pneumonia (VAP) was a common and severe complication of invasive mechanical ventilation. The traditional VAP diagnostic model relied on laboratory microbiological cultures. However, VAP had unclear pathogenesis, and its accurate identification was difficult due to the varying levels of pathogen detection in different laboratories. There was an urgent need for new diagnostic biomarkers for VAP. Methods The transcriptome of VAP patients was analyzed and computed using bioinformatics techniques in this study. The screen identified differentially expressed genes (DEGs) from the chemokine CC family, the S-100 family, and the α-defensin family, which are highly associated with immune-related antimicrobial functions. Single-cell landscape data revealed an increase in MTRNR2L12+ cells and a decrease in naïve CD4+ T cells, ciliated cells, and CD8+ T cells in VAP patients, indicating a significant change in the homeostatic profile in patients. Moreover, this paper explored differential gene expression at the single-cell level. Results The study analyzed 46 VAP samples and 48 normal samples to explore VAP pathogenesis and identify potential biomarkers. Both bulk RNA seq and scRNA-seq analysis revealed that S100A8 was highly expressed in the VAP group. This phenomenon was caused by the cellular level differential expression of B cells. In contrast, the reduced FN1 and HLA-DRB5 expressions in the VAP group may be influenced by the expression of T cells, macrophages, and ciliated cells. Western blot experiments detected S100A8 expression in the patient samples. Conclusion In this study, we combine bulk RNA-seq and scRNA-seq analyses to screen and validate the potential of S100A8, a gene with consistent expression, as a biomarker, providing a new perspective for VAP diagnosis.
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Affiliation(s)
- Qixing Wang
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Jiayong Dong
- Department of Liver Surgery and Organ Transplantation, Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China
| | - Xin Jing
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Yanling Long
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Hongyu Jia
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Yingchuan Li
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
| | - Junjie Wang
- Department of Critical Care Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China
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Han M, Wang X, Su L, Pan S, Liu N, Li D, Liu L, Cui J, Zhao H, Yang F. Intestinal microbiome dysbiosis increases Mycobacteria pulmonary colonization in mice by regulating the Nos2-associated pathways. eLife 2024; 13:RP99282. [PMID: 39412514 PMCID: PMC11483126 DOI: 10.7554/elife.99282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2024] Open
Abstract
Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota's effect on Mycobacterium's colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the 'gut-lung axis'. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.
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Affiliation(s)
- MeiQing Han
- Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - Xia Wang
- Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
| | - Lin Su
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - Shiqi Pan
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - Ningning Liu
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - Duan Li
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - Liang Liu
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - JunWei Cui
- Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
| | - Huajie Zhao
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
| | - Fan Yang
- Department of Tuberculosis, The First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
- Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical UniversityXinxiangChina
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Colomina-Alfaro L, Sist P, D'Andrea P, Urbani R, Marchesan S, Stamboulis A, Bandiera A. Materials derived from the human elastin-like polypeptide fusion with an antimicrobial peptide strongly promote cell adhesion. J Mater Chem B 2024; 12:8966-8976. [PMID: 39045800 DOI: 10.1039/d4tb00319e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2024]
Abstract
Protein and peptide materials have attracted great interest in recent years, especially for biological applications, in light of their possibility to easily encode bioactivity whilst maintaining cytocompatibility and biodegradability. Heterologous recombinant expression to produce antimicrobial peptides is increasingly considered a convenient alternative for the transition from conventional methods to more sustainable production systems. The human elastin-like polypeptide (HELP) has proven to be a valuable fusion carrier, and due to its cutting-edge properties, biomimetic materials with antimicrobial capacity have been successfully developed. In this work, we have taken advantage of this platform to produce a difficult-to-synthesise sequence as that of the human β-defensin 1 (hBD1), an amphipathic cationic peptide with structural folding constraints relevant to its bioactivity. In the design of the gene, highly specific endoproteinases recognition sites were introduced to release the active forms of hBD1. After the expression and purification of the new fusion construct, its biological activity was evaluated. It was found that both the fusion biopolymer and the released active forms can inhibit the growth of Escherichia coli in redox environments. Remarkably, 2D and 3D materials derived from the biopolymer showed a strong cell adhesion-promoting activity. These results suggest that HELP represents a multitasking platform that not only facilitates the production of bioactive domains and derived materials but could also pave the way for the development of new approaches to study biological interactions at the molecular level.
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Affiliation(s)
- Laura Colomina-Alfaro
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. abandiera.units.it
| | - Paola Sist
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. abandiera.units.it
| | - Paola D'Andrea
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. abandiera.units.it
| | - Ranieri Urbani
- Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy
| | - Silvia Marchesan
- Department of Chemical and Pharmaceutical Sciences, University of Trieste, 34127 Trieste, Italy
| | - Artemis Stamboulis
- School of Metallurgy and Materials, Biomaterials Research Group, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK
| | - Antonella Bandiera
- Department of Life Sciences, University of Trieste, 34127 Trieste, Italy. abandiera.units.it
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Yu JM, Sun CQ, Xu HH, Jiang YL, Jiang XY, Ni SQ, Zhao TY, Liu LX. Navigating the labyrinth of long non-coding RNAs in colorectal cancer: From chemoresistance to autophagy. World J Gastrointest Oncol 2024; 16:3376-3381. [PMID: 39171173 PMCID: PMC11334040 DOI: 10.4251/wjgo.v16.i8.3376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/03/2024] [Accepted: 05/22/2024] [Indexed: 08/07/2024] Open
Abstract
Long non-coding RNAs (lncRNAs), with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity, have been found to impact colorectal cancer (CRC) through various biological processes. LncRNA expression can regulate autophagy, which plays dual roles in the initiation and progression of cancers, including CRC. Abnormal expression of lncRNAs is associated with the emergence of chemoresistance. Moreover, it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance. Two recent studies titled "Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506" and "Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription" revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC, respectively. In this editorial, we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.
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Affiliation(s)
- Jia-Mei Yu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Chong-Qi Sun
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Huan-Huan Xu
- Department of Hematology and Oncology, Department of Geriatric Lung Cancer Research Laboratory, Jiangsu Province Geriatric Hospital, Nanjing 210009, Jiangsu Province, China
| | - Ya-Li Jiang
- Central Laboratory, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Ili & Jiangsu Joint Institute of Health, Yining 835000, Xinjiang Uyghur Autonomous Region, China
| | - Xing-Yu Jiang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Si-Qi Ni
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Ting-Yu Zhao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Ling-Xiang Liu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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Wu B, Quan C, He Y, Matsika J, Huang J, Liu B, Chen J. Targeting gut and intratumoral microbiota: a novel strategy to improve therapy resistance in cancer with a focus on urologic tumors. Expert Opin Biol Ther 2024; 24:747-759. [PMID: 38910461 DOI: 10.1080/14712598.2024.2371543] [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: 04/07/2024] [Accepted: 06/19/2024] [Indexed: 06/25/2024]
Abstract
INTRODUCTION Growing attention has been drawn to urologic tumors due to their rising incidence and suboptimal clinical treatment outcomes. Cancer therapy resistance poses a significant challenge in clinical oncology, limiting the efficacy of conventional treatments and contributing to disease progression. Recent research has unveiled a complex interplay between the host microbiota and cancer cells, highlighting the role of the microbiota in modulating therapeutic responses. AREAS COVERED We used the PubMed and Web of Science search engines to identify key publications in the fields of tumor progression and urologic tumor treatment, specifically focusing on the role of the microbiota. In this review, we summarize the current literature on how microbiota influence the tumor microenvironment and anti-tumor immunity, as well as their impact on treatments for urinary system malignancies, highlighting promising future applications. EXPERT OPINION We explore how the composition and function of the gut microbiota influence the tumor microenvironment and immune response, ultimately impacting treatment outcomes. Additionally, we discuss emerging strategies targeting the microbiota to enhance therapeutic efficacy and overcome resistance. The application of antibiotics, fecal microbiota transplantation, and oncolytic bacteria has improved tumor treatment outcomes, which provides a novel insight into developing therapeutic strategies for urologic cancer.
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Affiliation(s)
- Bingquan Wu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chao Quan
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yunbo He
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Juliet Matsika
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jinliang Huang
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Bolong Liu
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Andrology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China
| | - Jinbo Chen
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Li S, Mu R, Guo X. Defensins regulate cell cycle: Insights of defensins on cellular proliferation and division. Life Sci 2024; 349:122740. [PMID: 38777302 DOI: 10.1016/j.lfs.2024.122740] [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: 02/20/2024] [Revised: 05/12/2024] [Accepted: 05/18/2024] [Indexed: 05/25/2024]
Abstract
Defensins are a class of small antimicrobial peptides that play a crucial role against pathogens. However, recent research has highlighted defensins exhibit the ability to influence cell cycle checkpoints, promoting or inhibiting specific phases such as G1 arrest or S/M transition. By regulating the cell cycle, defensins impact the proliferation of normal and cancerous cells, with implications for cancer development and progression. Dysregulation of defensin expression can disrupt the delicate balance of cell cycle regulation, leading to uncontrolled cell growth and an increased risk of tumor formation. Defensins contribute to the resolution of inflammation, stimulate angiogenesis, and enhance the migration and proliferation of cells involved in tissue repair. Furthermore, The ability of defensins to respond to microenvironmental changes further demonstrates the significance of these peptides in host defense mechanisms and immune function. By adjusting their expression, defensins continue to combat pathogens effectively and maintain homeostasis within the body. This review highlights the multifaceted role of defensins in regulating the cell cycle and their broader implications in cancer progression, tissue repair, and microenvironmental response.
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Affiliation(s)
- Shuang Li
- Institute of Wound Prevention and Treatment, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China.
| | - Rongrong Mu
- Affiliated Hospital of Sichuan Nursing Vocational College, The Third People's Hospital of Sichuan Province, China
| | - Xueqin Guo
- Department of Pathology, Gaomi City People's Hospital, Gaomi 261500, China
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Eid N, Davamani F. Human β-defensin-1 activates autophagy in human colon cancer cells via regulation of long non-coding RNA TCONS_00014506. World J Gastrointest Oncol 2024; 16:2894-2901. [PMID: 39072156 PMCID: PMC11271776 DOI: 10.4251/wjgo.v16.i7.2894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 04/26/2024] [Accepted: 05/14/2024] [Indexed: 07/12/2024] Open
Abstract
Macroautophagy (hereafter referred to as autophagy) is a prosurvival mechanism for the clearance of damaged cellular components, specifically related to exposure to various stressors such as starvation, excessive ethanol intake, and chemotherapy. This editorial reviews and comments on an article by Zhao et al, to be published in World J Gastrointestinal Oncology in 2024. Based on various molecular biology methodologies, they found that human β-defensin-1 reduced the proliferation of colon cancer cells, which was associated with the inhibition of the mammalian target of rapamycin, resulting in autophagy activation. The activation of autophagy is evidenced by increased levels of Beclin1 and LC3II/I proteins and mediated by the upregulation of long non-coding RNA TCONS_00014506. Our study discusses the impact of autophagy activation and mechanisms of autophagy, including autophagic flux, on cancer cells. Additionally, we emphasize the importance of describing the detailed methods for isolating long noncoding RNAs TCONS_00014506. Our review will benefit the scientific community and improve the overall clarity of the paper.
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Affiliation(s)
- Nabil Eid
- Anatomy Department, Division of Human Biology, School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Fabian Davamani
- Division of Applied Biomedical Sciences and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia
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Wang L, Su J, Liu Z, Ding S, Li Y, Hou B, Hu Y, Dong Z, Tang J, Liu H, Liu W. Identification of immune-associated biomarkers of diabetes nephropathy tubulointerstitial injury based on machine learning: a bioinformatics multi-chip integrated analysis. BioData Min 2024; 17:20. [PMID: 38951833 PMCID: PMC11218417 DOI: 10.1186/s13040-024-00369-x] [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: 01/17/2024] [Accepted: 06/10/2024] [Indexed: 07/03/2024] Open
Abstract
BACKGROUND Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN. METHODS The gene chip data were retrieved from the GEO database using the search term ' diabetic nephropathy '. The ' limma ' software package was used to identify differentially expressed genes (DEGs) between DN and control samples. Gene set enrichment analysis (GSEA) was performed on genes obtained from the molecular characteristic database (MSigDB. The R package 'WGCNA' was used to identify gene modules associated with tubulointerstitial injury in DN, and it was crossed with immune-related DEGs to identify target genes. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on differentially expressed genes using the 'ClusterProfiler' software package in R. Three methods, least absolute shrinkage and selection operator (LASSO), support vector machine recursive feature elimination (SVM-RFE) and random forest (RF), were used to select immune-related biomarkers for diagnosis. We retrieved the tubulointerstitial dataset from the Nephroseq database to construct an external validation dataset. Unsupervised clustering analysis of the expression levels of immune-related biomarkers was performed using the 'ConsensusClusterPlus 'R software package. The urine of patients who visited Dongzhimen Hospital of Beijing University of Chinese Medicine from September 2021 to March 2023 was collected, and Elisa was used to detect the mRNA expression level of immune-related biomarkers in urine. Pearson correlation analysis was used to detect the effect of immune-related biomarker expression on renal function in DN patients. RESULTS Four microarray datasets from the GEO database are included in the analysis : GSE30122, GSE47185, GSE99340 and GSE104954. These datasets included 63 DN patients and 55 healthy controls. A total of 9415 genes were detected in the data set. We found 153 differentially expressed immune-related genes, of which 112 genes were up-regulated, 41 genes were down-regulated, and 119 overlapping genes were identified. GO analysis showed that they were involved in various biological processes including leukocyte-mediated immunity. KEGG analysis showed that these target genes were mainly involved in the formation of phagosomes in Staphylococcus aureus infection. Among these 119 overlapping genes, machine learning results identified AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1 and FSTL1 as potential tubulointerstitial immune-related biomarkers. External validation suggested that the above markers showed diagnostic efficacy in distinguishing DN patients from healthy controls. Clinical studies have shown that the expression of AGR2, CX3CR1 and FSTL1 in urine samples of DN patients is negatively correlated with GFR, the expression of CX3CR1 and FSTL1 in urine samples of DN is positively correlated with serum creatinine, while the expression of DEFB1 in urine samples of DN is negatively correlated with serum creatinine. In addition, the expression of CX3CR1 in DN urine samples was positively correlated with proteinuria, while the expression of DEFB1 in DN urine samples was negatively correlated with proteinuria. Finally, according to the level of proteinuria, DN patients were divided into nephrotic proteinuria group (n = 24) and subrenal proteinuria group. There were significant differences in urinary AGR2, CCR2 and DEFB1 between the two groups by unpaired t test (P < 0.05). CONCLUSIONS Our study provides new insights into the role of immune-related biomarkers in DN tubulointerstitial injury and provides potential targets for early diagnosis and treatment of DN patients. Seven different genes ( AGR2, CCR2, CEBPD, CISH, CX3CR1, DEFB1, FSTL1 ), as promising sensitive biomarkers, may affect the progression of DN by regulating immune inflammatory response. However, further comprehensive studies are needed to fully understand their exact molecular mechanisms and functional pathways in DN.
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Affiliation(s)
- Lin Wang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Jiaming Su
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Zhongjie Liu
- Beijing University of Chinese Medicine, Beijing, China
| | - Shaowei Ding
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yaotan Li
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Baoluo Hou
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yuxin Hu
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Zhaoxi Dong
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Jingyi Tang
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Hongfang Liu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China.
| | - Weijing Liu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
- Renal Research Institution of Beijing University of Chinese Medicine, Dongzhimen Hospital, Affiliated to Beijing University of Chinese Medicine, Beijing, China.
- Beijing University of Chinese Medicine, Beijing, China.
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12
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Peła Z, Gałecka M, Murgrabia A, Kondratowicz A, Gałecki P. Depressive Disorder and Dermatological Autoimmune Diseases. J Clin Med 2024; 13:3224. [PMID: 38892934 PMCID: PMC11172791 DOI: 10.3390/jcm13113224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/22/2024] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases.
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Affiliation(s)
| | | | | | | | - Piotr Gałecki
- Department of Adult Psychiatry, Medical University of Lodz, 92-213 Lodz, Poland; (Z.P.); (M.G.); (A.M.); (A.K.)
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13
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Monyók Á, Mansour B, Vadnay I, Makra N, Dunai ZA, Nemes-Nikodém É, Stercz B, Szabó D, Ostorházi E. Change in Tissue Microbiome and Related Human Beta Defensin Levels Induced by Antibiotic Use in Bladder Carcinoma. Int J Mol Sci 2024; 25:4562. [PMID: 38674148 PMCID: PMC11050017 DOI: 10.3390/ijms25084562] [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: 03/15/2024] [Revised: 04/12/2024] [Accepted: 04/21/2024] [Indexed: 04/28/2024] Open
Abstract
It is now generally accepted that the success of antitumor therapy can be impaired by concurrent antibiotic therapy, the presence of certain bacteria, and elevated defensin levels around the tumor tissue. The aim of our current investigation was to identify the underlying changes in microbiome and defensin levels in the tumor tissue induced by different antibiotics, as well as the duration of this modification. The microbiome of the tumor tissues was significantly different from that of healthy volunteers. Comparing only the tumor samples, no significant difference was confirmed between the untreated group and the group treated with antibiotics more than 3 months earlier. However, antibiotic treatment within 3 months of analysis resulted in a significantly modified microbiome composition. Irrespective of whether Fosfomycin, Fluoroquinolone or Beta-lactam treatment was used, the abundance of Bacteroides decreased, and Staphylococcus abundance increased. Large amounts of the genus Acinetobacter were observed in the Fluoroquinolone-treated group. Regardless of the antibiotic treatment, hBD1 expression of the tumor cells consistently doubled. The increase in hBD2 and hBD3 expression was the highest in the Beta-lactam treated group. Apparently, antibiotic treatment within 3 months of sample analysis induced microbiome changes and defensin expression levels, depending on the identity of the applied antibiotic.
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Affiliation(s)
- Ádám Monyók
- Department of Urology, Markhot Ferenc University Teaching Hospital, 3300 Eger, Hungary; (Á.M.); (B.M.)
| | - Bassel Mansour
- Department of Urology, Markhot Ferenc University Teaching Hospital, 3300 Eger, Hungary; (Á.M.); (B.M.)
| | - István Vadnay
- Department of Pathology, Markhot Ferenc University Teaching Hospital, 3300 Eger, Hungary; (I.V.); (D.S.)
| | - Nóra Makra
- Department of Medical Microbiology, Semmelweis University, 1085 Budapest, Hungary; (N.M.); (Z.A.D.); (É.N.-N.); (B.S.)
| | - Zsuzsanna A. Dunai
- Department of Medical Microbiology, Semmelweis University, 1085 Budapest, Hungary; (N.M.); (Z.A.D.); (É.N.-N.); (B.S.)
| | - Éva Nemes-Nikodém
- Department of Medical Microbiology, Semmelweis University, 1085 Budapest, Hungary; (N.M.); (Z.A.D.); (É.N.-N.); (B.S.)
| | - Balázs Stercz
- Department of Medical Microbiology, Semmelweis University, 1085 Budapest, Hungary; (N.M.); (Z.A.D.); (É.N.-N.); (B.S.)
| | - Dóra Szabó
- Department of Pathology, Markhot Ferenc University Teaching Hospital, 3300 Eger, Hungary; (I.V.); (D.S.)
- Neurosurgery and Neurointervention Clinic, Semmelweis University, 1085 Budapest, Hungary
| | - Eszter Ostorházi
- Department of Pathology, Markhot Ferenc University Teaching Hospital, 3300 Eger, Hungary; (I.V.); (D.S.)
- Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary
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14
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Gao X, Feng J, Wei L, Dong P, Chen J, Zhang L, Yang Y, Xu L, Wang H, Luo J, Qin M. Defensins: A novel weapon against Mycobacterium tuberculosis? Int Immunopharmacol 2024; 127:111383. [PMID: 38118315 DOI: 10.1016/j.intimp.2023.111383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 12/04/2023] [Accepted: 12/12/2023] [Indexed: 12/22/2023]
Abstract
Tuberculosis (TB) is a serious airborne communicable disease caused by organisms of the Mycobacterium tuberculosis (Mtb) complex. Although the standard treatment antimicrobials, including isoniazid, rifampicin, pyrazinamide, and ethambutol, have made great progress in the treatment of TB, problems including the rising incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the severe toxicity and side effects of antimicrobials, and the low immunity of TB patients have become the bottlenecks of the current TB treatments. Therefore, both safe and effective new strategies to prevent and treat TB have become a top priority. As a subfamily of cationic antimicrobial peptides, defensins are rich in cysteine and play a vital role in resisting the invasion of microorganisms and regulating the immune response. Inspired by studies on the roles of defensins in host defence, we describe their research history and then review their structural features and antimicrobial mechanisms, specifically for fighting Mtb in detail. Finally, we discuss the clinical relevance, therapeutic potential, and potential challenges of defensins in anti-TB therapy. We further debate the possible solutions of the current application of defensins to provide new insights for eliminating Mtb.
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Affiliation(s)
- Xuehan Gao
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Jihong Feng
- Department of Oncology, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People's Hospital, Lishui 323000, China
| | - Linna Wei
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Pinzhi Dong
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Jin Chen
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Langlang Zhang
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Yuhan Yang
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Lin Xu
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Haiyan Wang
- Department of Epidemiology and Health Statistics, Zunyi Medical University, Zunyi, Guizhou 563000, China
| | - Junmin Luo
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China.
| | - Ming Qin
- Department of Immunology, Center of Immunomolecular Engineering, Innovation & Practice Base for Graduate Students Education, Special Key Laboratory of Gene Detection & Therapy, Zunyi Medical University, Zunyi, Guizhou 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, China.
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15
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Scavello F, Amiche M, Ghia JE. The Editorial Position on 'Recent Advances in Multifunctional Antimicrobial Peptides as Preclinical Therapeutic Studies and Clinical Future Applications'. Pharmaceutics 2023; 15:2383. [PMID: 37896143 PMCID: PMC10609690 DOI: 10.3390/pharmaceutics15102383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 09/16/2023] [Indexed: 10/29/2023] Open
Abstract
Antibiotic resistance has recently been recognized as an alarming issue and one of the leading causes of death worldwide [...].
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Affiliation(s)
| | - Mohamed Amiche
- Laboratoire de Biogenèse des Signaux Peptidiques (BioSiPe), Institut de Biologie Paris-Seine, Sorbonne Université-CNRS, 75252 Paris, France
| | - Jean-Eric Ghia
- Department of Immunology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
- Section of Gastroenterology, Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
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16
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Fu J, Zong X, Jin M, Min J, Wang F, Wang Y. Mechanisms and regulation of defensins in host defense. Signal Transduct Target Ther 2023; 8:300. [PMID: 37574471 PMCID: PMC10423725 DOI: 10.1038/s41392-023-01553-x] [Citation(s) in RCA: 55] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 04/11/2023] [Accepted: 06/26/2023] [Indexed: 08/15/2023] Open
Abstract
As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.
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Affiliation(s)
- Jie Fu
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China
| | - Xin Zong
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China
| | - Mingliang Jin
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China
| | - Junxia Min
- The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China
| | - Fudi Wang
- The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China.
- The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China.
| | - Yizhen Wang
- Key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China.
- Key Laboratory of Animal Nutrition and Feed Science in Eastern China, Ministry of Agriculture, Hangzhou, Zhejiang Province, China.
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17
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Teng F, Wei H, Dong X. An immune related signature inhibits the occurrence and development of serous ovarian cancer by affecting the abundance of dendritic cells. Discov Oncol 2023; 14:101. [PMID: 37318692 DOI: 10.1007/s12672-023-00717-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 06/05/2023] [Indexed: 06/16/2023] Open
Abstract
Serous ovarian cancer is one of the major causes of cancer related death among women worldwide. The advanced diagnosis worsens the prognosis of patients with serous ovarian cancer. The immune system has an important impact on the progression of ovarian cancer. Herein, we aimed to establish an immune related prognostic signature to assist in the early diagnosis, treatment, and prognostic evaluation of patients with serous ovarian cancer. Multiple public data sets and immune related genes were obtained from various online public databases, and immune related prognostic signatures were developed through differential expression analysis, univariate Cox proportional hazard regression analysis, and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. The nomogram model, Kaplan-Meier survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis showed that this signature had a good prediction potential. In conclusion, an immune related signature with good prediction efficiency was established through systematic bioinformatics analysis, which may play a tumor inhibition role by affecting the abundance of activated dendritic cells.
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Affiliation(s)
- Fei Teng
- In-Patient Ultrasound Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
- Ultrasound Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hong Wei
- In-Patient Ultrasound Department, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiaoqiu Dong
- Ultrasound Department, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
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18
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Pita López ML, Ruiz Ramírez AV, Alcázar Ríos JA, Santos Hernández C, Guerrero Velázquez C, Prado Montes de Oca E. Cytomegalovirus seropositivity correlates with both human β-defensin 1 and IFN-γ downregulation in women with obesity. Cytokine 2023; 168:156230. [PMID: 37235888 DOI: 10.1016/j.cyto.2023.156230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/24/2023] [Accepted: 05/05/2023] [Indexed: 05/28/2023]
Abstract
Human β-defensin 1 (hBD-1) is a constitutively expressed antimicrobial peptide with antiviral properties. CMV seropositivity has been associated with obesity. It is unknown if hBD-1 levels of are altered in women with obesity and/or CMV seropositivity. In a pilot project of 31 adult women with CMV seropositivity, we calculated the correlation among hBD-1 serum levels (ELISA) and IgG anti-CMV-Index with anthropometric measurements, lipid profiles and glucose levels. hBD-1 showed negative correlation with triglycerides (TG) (r = -0.617; p = 0.033,) and hip circumference (r = -0.596; p = 0.041,). IgG anti-CMV index was negatively correlated with hBD-1 levels and positively correlated with TG (r = 0.702; p = 0.011,) and HC (r = 0.583; p = 0.047,) in women with obesity. As expected, hBD-1 levels correlates with IFN-γ (an antimicrobial peptide elicitor) in the three analyzed groups.These results shows that CMV seropositivity correlates with both IFN-γ levels and hBD-1 levels which in contrast with non-CMV seropositivity scenario, is commonly found an IFN-γ upregulation in individuals with obesity. Further research is encouraged to test if CMV is causing the observed downregulation of the antiviral immune responses of both hBD-1 and IFN-γ as well as their involved mechanisms.
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Affiliation(s)
- María Luisa Pita López
- Research Center in Molecular Biology of Chronic Diseases (CIBIMEC), Southern Campus (CUSUR), Guadalajara University, Av. Enrique Arreola Silva 883, CP 49000 Ciudad Guzmán, Mexico.
| | - Andrea Virginia Ruiz Ramírez
- Graduate Program in Human Genetics, Health Sciences Campus (CUCS), Guadalajara University, Sierra Mojada 950, Col. Independencia, CP 44340 Guadalajara, Jalisco, Mexico; Genetics Department, Western Biomedical Research Center (CIBO), Mexican Institute of Social Security (IMSS), Sierra Mojada 800, Col. Independencia, CP 44340 Guadalajara, Jalisco, Mexico; Laboratory of Regulatory SNPs, Personalized Medicine National Laboratory (LAMPER), Medical and Pharmaceutical Biotechnology, Guadalajara Unit, Research Center in Technology and Design Assistance of Jalisco State (CIATEJ AC), National Council of Science and Technology (CONACYT), Av. Normalistas 800, Colinas de la Normal, CP44270 Guadalajara, Jalisco, Mexico
| | - José Alberto Alcázar Ríos
- Research Center in Molecular Biology of Chronic Diseases (CIBIMEC), Southern Campus (CUSUR), Guadalajara University, Av. Enrique Arreola Silva 883, CP 49000 Ciudad Guzmán, Mexico
| | - Carmen Santos Hernández
- Escuela Nacional de Salud Pública, Universidad de La Habana, Calle 100 #10132 e/ Perla y E. Boyeros, CP 10800 La Habana, Cuba
| | - Celia Guerrero Velázquez
- Research Institute of Odontology, Department of Clinical and Integral Odontology, CUCS, Guadalajara University, Sierra Mojada 950, Col. Independencia, CP 44340 Guadalajara, Jalisco, Mexico
| | - Ernesto Prado Montes de Oca
- Laboratory of Regulatory SNPs, Personalized Medicine National Laboratory (LAMPER), Medical and Pharmaceutical Biotechnology, Guadalajara Unit, Research Center in Technology and Design Assistance of Jalisco State (CIATEJ AC), National Council of Science and Technology (CONACYT), Av. Normalistas 800, Colinas de la Normal, CP44270 Guadalajara, Jalisco, Mexico.
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19
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Wang G, Cui Y, Liu H, Tian Y, Li S, Fan Y, Sun S, Wu D, Peng C. Antibacterial peptides-loaded bioactive materials for the treatment of bone infection. Colloids Surf B Biointerfaces 2023; 225:113255. [PMID: 36924650 DOI: 10.1016/j.colsurfb.2023.113255] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 02/20/2023] [Accepted: 03/06/2023] [Indexed: 03/13/2023]
Abstract
Bacterial bone infection in open fractures is an urgent problem to solve in orthopedics. Antimicrobial peptides (AMPs), as a part of innate immune defense, have good biocompatibility. Their antibacterial mechanism and therapeutic application against bacteria have been widely studied. Compared with traditional antibiotics, AMPs do not easily cause bacterial resistance and can be a reliable substitute for antibiotics in the future. Therefore, various physical and chemical strategies have been developed for the combined application of AMPs and bioactive materials to infected sites, which are conducive to maintaining the local stability of AMPs, reducing many complications, and facilitating bone infection resolution. This review explored the molecular structure, function, and direct and indirect antibacterial mechanisms of AMPs, introduced two important AMPs (LL-37 and β-defensins) in bone tissues, and reviewed advanced AMP loading strategies and different bioactive materials. Finally, the latest progress and future development of AMPs-loaded bioactive materials for the promotion of bone infection repair were discussed. This study provided a theoretical basis and application strategy for the treatment of bone infection with AMP-loaded bioactive materials.
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Affiliation(s)
- Gan Wang
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Yutao Cui
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - He Liu
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Yuhang Tian
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Shaorong Li
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Yi Fan
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Shouye Sun
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China
| | - Dankai Wu
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China.
| | - Chuangang Peng
- Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, PR China.
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20
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Bladder Tissue Microbiome Composition in Patients of Bladder Cancer or Benign Prostatic Hyperplasia and Related Human Beta Defensin Levels. Biomedicines 2022; 10:biomedicines10071758. [PMID: 35885062 PMCID: PMC9313236 DOI: 10.3390/biomedicines10071758] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/13/2022] [Accepted: 07/19/2022] [Indexed: 12/25/2022] Open
Abstract
Balance between the microbiome associated with bladder mucosa and human beta defensin (HBD) levels in urine is a dynamic, sensitive and host-specific relationship. HBD1—possessing both antitumor and antibacterial activity—is produced constitutively, while the inducible production of antibacterial HBD2 and HBD3 is affected by bacteria. Elevated levels of HBD2 were shown to cause treatment failure in anticancer immunotherapy. Our aim was to assess the relationship between microbiome composition characteristic of tumor tissue, defensin expression and HBD levels measured in urine. Tissue samples for analyses were removed during transurethral resection from 55 bladder carcinoma and 12 prostatic hyperplasia patients. Microbiome analyses were carried out with 16S rRNS sequencing. Levels of HBD mRNA expression were measured with qPCR from the same samples, and urinary amounts of HBD1, 2 and 3 were detected with ELISA in these patients, in addition to 34 healthy volunteers. Mann–Whitney U test, Wilcoxon rank sum test (alpha diversity) and PERMANOVA analysis (beta diversity) were performed. Defensin-levels expressed in the tumor did not clearly determine the amount of defensin measurable in the urine. The antibacterial and antitumor defensin (HBD1) showed decreased levels in cancer patients, while others (HBD2 and 3) were considerably increased. Abundance of Staphylococcus, Corynebacterium and Oxyphotobacteria genera was significantly higher, the abundance of Faecalibacterium and Bacteroides genera were significantly lower in tumor samples compared to non-tumor samples. Bacteroides, Parabacteroides and Faecalibacterium abundance gradually decreased with the combined increase in HBD2 and HBD3. Higher Corynebacterium and Staphylococcus abundances were measured together with higher HBD2 and HBD3 urinary levels. Among other factors, defensins and microorganisms also affect the development, progression and treatment options for bladder cancer. To enhance the success of immunotherapies and to develop adjuvant antitumor therapies, it is important to gain insight into the interactions between defensins and the tumor-associated microbiome.
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21
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Colombo F, Illescas O, Noci S, Minnai F, Pintarelli G, Pettinicchio A, Vannelli A, Sorrentino L, Battaglia L, Cosimelli M, Dragani TA, Gariboldi M. Gut microbiota composition in colorectal cancer patients is genetically regulated. Sci Rep 2022; 12:11424. [PMID: 35794137 PMCID: PMC9259655 DOI: 10.1038/s41598-022-15230-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 06/21/2022] [Indexed: 12/21/2022] Open
Abstract
AbstractThe risk of colorectal cancer (CRC) depends on environmental and genetic factors. Among environmental factors, an imbalance in the gut microbiota can increase CRC risk. Also, microbiota is influenced by host genetics. However, it is not known if germline variants influence CRC development by modulating microbiota composition. We investigated germline variants associated with the abundance of bacterial populations in the normal (non-involved) colorectal mucosa of 93 CRC patients and evaluated their possible role in disease. Using a multivariable linear regression, we assessed the association between germline variants identified by genome wide genotyping and bacteria abundances determined by 16S rRNA gene sequencing. We identified 37 germline variants associated with the abundance of the genera Bacteroides, Ruminococcus, Akkermansia, Faecalibacterium and Gemmiger and with alpha diversity. These variants are correlated with the expression of 58 genes involved in inflammatory responses, cell adhesion, apoptosis and barrier integrity. Genes and bacteria appear to be involved in the same processes. In fact, expression of the pro-inflammatory genes GAL, GSDMD and LY6H was correlated with the abundance of Bacteroides, which has pro-inflammatory properties; abundance of the anti-inflammatory genus Faecalibacterium correlated with expression of KAZN, with barrier-enhancing functions. Both the microbiota composition and local inflammation are regulated, at least partially, by the same germline variants. These variants may regulate the microenvironment in which bacteria grow and predispose to the development of cancer. Identification of these variants is the first step to identifying higher-risk individuals and proposing tailored preventive treatments that increase beneficial bacterial populations.
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22
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Zaher H, Shawky N, Rashed LA, Elmasry MF. Estimation of tissue level of human beta-defensin 1 in vitiligo before and after narrowband ultraviolet B phototherapy: A case-control study. PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2022; 38:397-400. [PMID: 34907609 DOI: 10.1111/phpp.12760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Revised: 12/07/2021] [Accepted: 12/12/2021] [Indexed: 06/14/2023]
Affiliation(s)
- Hesham Zaher
- Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Nevine Shawky
- Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Laila Ahmed Rashed
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Maha Fathy Elmasry
- Dermatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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23
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Wang Y, Wang X, Zhu M, Ge L, Liu X, Su K, Chen Z, Zhao W. The Interplay Between Cervicovaginal Microbial Dysbiosis and Cervicovaginal Immunity. Front Immunol 2022; 13:857299. [PMID: 35359942 PMCID: PMC8960256 DOI: 10.3389/fimmu.2022.857299] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 02/21/2022] [Indexed: 12/02/2022] Open
Abstract
The cervicovaginal microbiota plays a key role in the health and reproductive outcomes of women. In reality epidemiological studies have demonstrated that there is an association between the structure of cervicovaginal microbiota and reproductive health, although key mechanistic questions regarding these effects remain unanswered and understanding the interplay between the immune system and the structure of the cervicovaginal microbiota. Here, we review existing literature relating to the potential mechanisms underlying the interaction between vaginal microbes and the immune system; we also describe the composition and function of the microbiome and explain the mechanisms underlying the interactions between these microbial communities and various aspects of the immune system. Finally, we also discuss the diseases that are caused by disorders of the reproductive tract and how the immune system is involved. Finally, based on the data presented in this review, the future perspectives in research directions and therapeutic opportunities are explored.
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Affiliation(s)
- Ya Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Xiaoli Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Meiling Zhu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Li Ge
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Xiaochen Liu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Kaikai Su
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Zhengzheng Chen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
| | - Weidong Zhao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China
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Wu J, Zhang T, Xiong H, Zeng L, Wang Z, Peng Y, Chen W, Hu X, Su T. Tumor-Infiltrating CD4 + Central Memory T Cells Correlated with Favorable Prognosis in Oral Squamous Cell Carcinoma. J Inflamm Res 2022; 15:141-152. [PMID: 35035226 PMCID: PMC8754505 DOI: 10.2147/jir.s343432] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/16/2021] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy with a poor prognosis, in which tumor-infiltrating immune cells may play a critical role. Therefore, our study aims to screen potential immune cells and immune-related genes for predicting OSCC prognosis. METHODS A total of 310 OSCC patients with full transcriptional data and clinical characteristics were extracted from the TCGA database. Then, we obtained their abundance of tumor-infiltrating immune cells on TIMER 2.0 and analyzed them using xCell method. Univariate and multivariate Cox regressions were applied successively to identify the immune cells associated with overall survival of OSCC patients. Furthermore, we screened the prognostic genes that related to the identified immune cells and validated their expressions by immunohistochemistry. RESULTS CD4+ central memory T (TCM) cell was recognized as the sole independent immune cell correlated with OSCC prognosis (p = 0.0085). A novel nomogram based on CD4+ TCM cell abundance was established for predicting the prognosis of OSCC patients, with calibration plots showing good performance for 1-, 3-, 5-year overall survival. Thirty-four related prognostic genes were screened according to the differential abundance of CD4+ TCM cell infiltration. In immunohistochemistry analysis, DEFB1 showed a significant positive relationship with the density of CD4+ TCM cells (p = 0.0075). CONCLUSION CD4+ central memory T cell was proposed as an independent prognostic biomarker for OSCC patients. DEFB1 might positively regulate the abundance of tumor-infiltrating CD4+ TCM cells, thus improving OSCC prognosis. Our findings may provide a new insight into better prognosis prediction and precise medicine for OSCC.
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Affiliation(s)
- Jin Wu
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Tianyi Zhang
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Haofeng Xiong
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Liujun Zeng
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Zijia Wang
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Ying Peng
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Weijun Chen
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Xin Hu
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
| | - Tong Su
- Department of Oral and Maxillofacial Surgery, Center of Stomatology, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China
- Institute of Oral Cancer and Precancerous Lesions, Central South University, Changsha, Hunan, 410008, People’s Republic of China
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25
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Qiao Q, Bai R, Song W, Gao H, Zhang M, Lu J, Hong M, Zhang X, Sun P, Zhang Q, Zhao P. Human α-defensin 5 suppressed colon cancer growth by targeting PI3K pathway. Exp Cell Res 2021; 407:112809. [PMID: 34487729 DOI: 10.1016/j.yexcr.2021.112809] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 08/23/2021] [Accepted: 09/01/2021] [Indexed: 01/06/2023]
Abstract
Defensins are highly conserved antimicrobial peptides, which ubiquitously expressed in different species. In addition to the functions in host defense, their aberrant expression have also been documented in cancerous tissue including breast cancer, lung caner and renal carcinoma etc. Whereas, roles of Defensin Alpha 5 (DEFA5) in colon cancer has not been explored. Bioinformatic analysis was used to study the expression of DEFA5 and its correlation with clinical outcomes; Western blot, qPCR, Co-immunoprecipitation, xenograft models were used to the study the molecular mechanism. Decreased expression of DEFA5 at protein level was observed in colon tissues. Colon cancer cell lines proliferation and colony formation capacity were significantly suppressed by DEFA5 overexpression. Moreover, in vivo tumor growth in nude mice was also suppressed by DEFA5 overexpression, suggesting a tumor suppressor role of DEFA5 in colon cancer. Mechanistically, DEFA5 directly binds to the subunits of PI3K complex, thus attenuates the downstream signaling transduction, leads to delayed cell growth and metastasis. Collectively, we concluded that DEFA5 showed an inhibitory effect in colon cancer cell growth and may serve as a potential tumor suppressor in colon cancer.
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Affiliation(s)
- Qiao Qiao
- Department of Obstetrics and Gynecology, Affiliated Hospital of Inner Mongolia Medical University, No.1, Tongdao North Street, Huimin District, Hohhot, 010050, PR China.
| | - Ruixia Bai
- Department of Clinical Laboratory, Inner Mongolia People's Hospital, Zhaowuda Road, Hohhot, 010018, PR China.
| | - Wanying Song
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Haining Gao
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Minyu Zhang
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Jingkun Lu
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Mei Hong
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Xuan Zhang
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Peng Sun
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
| | - Qian Zhang
- Pediatric Intensive Care Unit, Affiliated Hospital of Inner Mongolia Medical University, 1#, Xinhua Street, Hohhot, 010050, PR China.
| | - Pengwei Zhao
- Laboratory of Microbiology and Immunology, School of Basic Medical Science, Inner Mongolia Medical University, Xinhua Street, Hohhot, 010059, PR China.
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26
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Silva-Carvalho AÉ, Cardoso MH, Alencar-Silva T, Bogéa GMR, Carvalho JL, Franco OL, Saldanha-Araujo F. Dissecting the relationship between antimicrobial peptides and mesenchymal stem cells. Pharmacol Ther 2021; 233:108021. [PMID: 34637839 DOI: 10.1016/j.pharmthera.2021.108021] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 10/02/2021] [Accepted: 10/06/2021] [Indexed: 02/06/2023]
Abstract
Among the various biological properties presented by Mesenchymal Stem Cells (MSCs), their ability to control the immune response and fight pathogen infection through the production of antimicrobial peptides (AMPs) have been the subject of intense research in recent years. AMPs secreted by MSCs exhibit activity against a wide range of microorganisms, including bacteria, fungi, yeasts, and viruses. The main AMPs produced by these cells are hepcidin, cathelicidin LL-37, and β-defensin-2. In addition to acting against pathogens, those AMPs have also been shown to interact with MSCs to modulate MSC proliferation, migration, and regeneration, indicating that such peptides exert a more diverse biological effect than initially thought. In the present review, we discuss the production of AMPs by MSCs, revise the multiple functions of these peptides, including their influence over MSCs, and present an overview of clinical situations in which the antimicrobial properties of MSCs may be explored for therapy. Finally, we discuss possibilities of combining MSCs and AMPs to generate improved therapeutic strategies.
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Affiliation(s)
- Amandda Évelin Silva-Carvalho
- Laboratório de Hematologia e Células-Tronco, Departamento de Ciências da Saúde, Universidade de Brasília, Brasília, DF, Brazil
| | - Marlon Henrique Cardoso
- S-Inova Biotech, Universidade Católica Dom Bosco, Programa de Pós-Graduação em Biotecnologia, Campo Grande, MS, Brazil
| | - Thuany Alencar-Silva
- Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil
| | - Gabriela Muller Reche Bogéa
- Laboratório de Hematologia e Células-Tronco, Departamento de Ciências da Saúde, Universidade de Brasília, Brasília, DF, Brazil
| | - Juliana Lott Carvalho
- Programa de Pós-graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil; Faculty of Medicine, University of Brasilia, Brasilia, DF, Brazil
| | - Octávio Luiz Franco
- S-Inova Biotech, Universidade Católica Dom Bosco, Programa de Pós-Graduação em Biotecnologia, Campo Grande, MS, Brazil; Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de Brasília, Brasília, DF, Brazil
| | - Felipe Saldanha-Araujo
- Laboratório de Hematologia e Células-Tronco, Departamento de Ciências da Saúde, Universidade de Brasília, Brasília, DF, Brazil.
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27
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Sanegre S, Eritja N, de Andrea C, Diaz-Martin J, Diaz-Lagares Á, Jácome MA, Salguero-Aranda C, García Ros D, Davidson B, Lopez R, Melero I, Navarro S, Ramon Y Cajal S, de Alava E, Matias-Guiu X, Noguera R. Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma. Front Cell Dev Biol 2021; 9:670185. [PMID: 34150764 PMCID: PMC8209546 DOI: 10.3389/fcell.2021.670185] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Accepted: 04/12/2021] [Indexed: 12/22/2022] Open
Abstract
The invasive tumor front (the tumor–host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors.
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Affiliation(s)
- Sabina Sanegre
- Cancer CIBER (CIBERONC), Madrid, Spain.,Department of Pathology, School of Medical, University of Valencia-INCLIVA, Valencia, Spain
| | - Núria Eritja
- Cancer CIBER (CIBERONC), Madrid, Spain.,Institut de Recerca Biomèdica de LLeida (IRBLLEIDA), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, University of Lleida - University of Barcelona, Barcelona, Spain
| | - Carlos de Andrea
- Cancer CIBER (CIBERONC), Madrid, Spain.,Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain
| | - Juan Diaz-Martin
- Cancer CIBER (CIBERONC), Madrid, Spain.,Institute of Biomedicine of Sevilla, Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
| | - Ángel Diaz-Lagares
- Cancer CIBER (CIBERONC), Madrid, Spain.,Cancer Epigenomics, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain
| | - María Amalia Jácome
- Department of Mathematics, MODES Group, CITIC, Faculty of Science, Universidade da Coruña, A Coruña, Spain
| | - Carmen Salguero-Aranda
- Cancer CIBER (CIBERONC), Madrid, Spain.,Institute of Biomedicine of Sevilla, Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
| | - David García Ros
- Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain
| | - Ben Davidson
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.,Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Rafel Lopez
- Cancer CIBER (CIBERONC), Madrid, Spain.,Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.,Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Ignacio Melero
- Cancer CIBER (CIBERONC), Madrid, Spain.,Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain
| | - Samuel Navarro
- Cancer CIBER (CIBERONC), Madrid, Spain.,Department of Pathology, School of Medical, University of Valencia-INCLIVA, Valencia, Spain
| | - Santiago Ramon Y Cajal
- Cancer CIBER (CIBERONC), Madrid, Spain.,Department of Pathology, Vall d'Hebron University Hospital, Autonomous University of Barcelona, Barcelona, Spain
| | - Enrique de Alava
- Cancer CIBER (CIBERONC), Madrid, Spain.,Institute of Biomedicine of Sevilla, Virgen del Rocio University Hospital/CSIC/University of Sevilla/CIBERONC, Seville, Spain
| | - Xavier Matias-Guiu
- Cancer CIBER (CIBERONC), Madrid, Spain.,Institut de Recerca Biomèdica de LLeida (IRBLLEIDA), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge, University of Lleida - University of Barcelona, Barcelona, Spain
| | - Rosa Noguera
- Cancer CIBER (CIBERONC), Madrid, Spain.,Department of Pathology, School of Medical, University of Valencia-INCLIVA, Valencia, Spain
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28
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Stieglitz S, Frohnhofen H. [Aging of the lungs and immune system as hellmark in the pathogenesis of idiopathic pulmonary fibrosis and COVID-19]. DER PNEUMOLOGE 2021; 18:162-173. [PMID: 33519332 PMCID: PMC7829037 DOI: 10.1007/s10405-020-00374-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 12/17/2020] [Indexed: 06/12/2023]
Abstract
Idiopathic pulmonary fibrosis (IPF) does not occur in younger persons. Therefore, it is not surprising that the nine hallmarks of biological aging can all be found in the pathomechanism of IPF. In this respect the homeostasis of cellular protein synthesis, degradation and recycling becomes unbalanced, which causes a dysregulation of repair mechanisms in the case of lung damage. Severve acute respiratory syndrome coronarvius type 2 (SARS-CoV-2) infections may also predominantyl seen in aged persons. In this situation cellular aging of the lungs also plays a role but additionally, the aging of the immune system is also of great importance. Immunosenescence is associated with a loss of naïve T‑cells. Moreover, there are gender-specific differences with a loss of B‑cells only in men but not in women, which partly explains the more severe course of COVID-19 pneumonia in older men.
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Affiliation(s)
- Sven Stieglitz
- Klinik für Pneumologie, Allergologie, Schlaf- und Intensivmedizin, Petrus Krankenhaus Wuppertal, Carnaper Str. 48, 42283 Wuppertal, Deutschland
- Fakultät für Gesundheit, Department Humanmedizin, Lehrstuhl für Geriatrie, Universität Witten-Herdecke, Witten, Deutschland
| | - Helmut Frohnhofen
- Fakultät für Gesundheit, Department Humanmedizin, Lehrstuhl für Geriatrie, Universität Witten-Herdecke, Witten, Deutschland
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29
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Casciaro B, Cappiello F, Verrusio W, Cacciafesta M, Mangoni ML. Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations. Curr Top Med Chem 2021; 20:1264-1273. [PMID: 32338221 DOI: 10.2174/1568026620666200427090912] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 03/06/2020] [Accepted: 03/16/2020] [Indexed: 01/10/2023]
Abstract
The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.
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Affiliation(s)
- Bruno Casciaro
- Center For Life Nano Science @ Sapienza, Italian Institute of Technology, Rome 00161, Italy
| | - Floriana Cappiello
- Laboratory affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro 5, Rome 00185, Italy
| | - Walter Verrusio
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Mauro Cacciafesta
- Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome 00185, Italy
| | - Maria Luisa Mangoni
- Laboratory affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, P.le Aldo Moro 5, Rome 00185, Italy
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30
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Qin Z, Yang X, Chen G, Park C, Liu Z. Crosstalks Between Gut Microbiota and Vibrio Cholerae. Front Cell Infect Microbiol 2020; 10:582554. [PMID: 33194819 PMCID: PMC7644805 DOI: 10.3389/fcimb.2020.582554] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 09/17/2020] [Indexed: 12/11/2022] Open
Abstract
Vibrio cholerae, the causative agent of cholera, could proliferate in aquatic environment and infect humans through contaminated food and water. Enormous microorganisms residing in human gastrointestinal tract establish a special microecological system, which immediately responds to the invasion of V. cholerae, through “colonization resistance” mechanisms, such as antimicrobial peptide production, nutrients competition, and intestinal barrier maintenances. Meanwhile, V. cholerae could quickly sense those signals and modulate the expression of relevant genes to circumvent those stresses during infection, leading to successful colonization on the surface of small intestinal epithelial cells. In this review, we summarized the crosstalks profiles between gut microbiota and V. cholerae in the terms of Type VI Secretion System (T6SS), Quorum Sensing (QS), Reactive Oxygen Species (ROS)/pH stress, and Bioactive metabolites. These mechanisms can also be applied to molecular bacterial pathogenesis of other pathogens in host.
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Affiliation(s)
- Zixin Qin
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoman Yang
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Guozhong Chen
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Chaiwoo Park
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
| | - Zhi Liu
- Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
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31
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Liao M, Zeng F, Li Y, Gao Q, Yin M, Deng G, Chen X. A novel predictive model incorporating immune-related gene signatures for overall survival in melanoma patients. Sci Rep 2020; 10:12462. [PMID: 32719391 PMCID: PMC7385638 DOI: 10.1038/s41598-020-69330-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 07/09/2020] [Indexed: 12/15/2022] Open
Abstract
Melanoma is the most invasive type of skin cancer, in which the immune system plays a vital role. In this study, we aimed to establish a prognostic prediction nomogram for melanoma patients that incorporates immune-related genes (IRGs). Ninety-seven differentially expressed IRGs between melanoma and normal skin were screened using gene expression omnibus database (GEO). Among these IRGs, a two-gene signature consisting of CCL8 and DEFB1 was found to be closely associated with patient prognosis using the cancer genome atlas (TCGA) database. Survival analysis verified that the IRGs score based on the signature gene expressions efficiently distinguished between high- and low-risk patients, and was identified to be an independent prognostic factor. A nomogram integrating the IRGs score, age and TNM stage was established to predict individual prognosis for melanoma. The prognostic performance was validated by the TCGA/GEO-based concordance indices and calibration plots. The area under the curve demonstrated that the nomogram was superior than the conventional staging system, which was confirmed by the decision curve analysis. Overall, we developed and validated a nomogram for prognosis prediction in melanoma based on IRGs signatures and clinical parameters, which could be valuable for decision making in the clinic.
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Affiliation(s)
- Mengting Liao
- Health Management Center, Xiangya Hospital, Central South University, Changsha, 410008, China.,Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China
| | - Furong Zeng
- Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China
| | - Yao Li
- Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China
| | - Qian Gao
- Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China
| | - Mingzhu Yin
- Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China.,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China
| | - Guangtong Deng
- Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China. .,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China. .,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China.
| | - Xiang Chen
- Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, 410008, China. .,Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, China. .,Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, China.
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Cruz Díaz LA, Gutiérrez Ortega A, Chávez Álvarez RDC, Velarde Félix JS, Prado Montes de Oca E. Regulatory SNP rs5743417 impairs constitutive expression of human β-defensin 1 and has high frequency in Africans and Afro-Americans. Int J Immunogenet 2020; 47:332-341. [PMID: 31994826 DOI: 10.1111/iji.12475] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 11/26/2019] [Accepted: 01/02/2020] [Indexed: 01/01/2023]
Abstract
The prediction of regulatory single nucleotide polymorphisms (rSNPs) in proximal promoters of disease-related genes could be a useful tool for personalized medicine in both patient stratification and customized therapy. Using our previously reported method of rSNPs prediction (currently a software called SNPClinic v.1.0) as well as with PredictSNP tool, we performed in silico prediction of regulatory SNPs in the antimicrobial peptide human β-defensin 1 gene in three human cell lines from 1,000 Genomes Project (1kGP), namely A549 (epithelial cell line), HL-60 (neutrophils) and TH 1 (lymphocytes). These predictions were run in a proximal pseudo-promoter comprising all common alleles on each polymorphic site according to the 1,000 Genomes Project data (1kGP: ALL). Plasmid vectors containing either the major or the minor allele of a putative rSNP rs5743417 (categorized as regulatory by SNPClinic and confirmed by PredictSNP) and a non-rSNP negative control were transfected to lung A549 human epithelial cell line. We assessed functionality of rSNPs by qPCR using the Pfaffl method. In A549 cells, minor allele of the SNP rs5743417 G→A showed a significant reduction in gene expression, diminishing DEFB1 transcription by 33% when compared with the G major allele (p-value = .03). SNP rs5743417 minor allele has high frequency in Gambians (8%, 1kGP population: GWD) and Afro-Americans (3.3%, 1kGP population: ASW). This SNP alters three transcription factors binding sites (TFBSs) comprising SREBP2 (sterols and haematopoietic pathways), CREB1 (cAMP, insulin and TNF pathways) and JUND (apoptosis, senescence and stress pathways) in the proximal promoter of DEFB1. Further in silico analysis reveals that this SNP also overlaps with GS1-24F4.2, a lincRNA gene complementary to the X Kell blood group related 5 (XKR5) mRNA. The potential clinical impact of the altered constitutive expression of DEFB1 caused by rSNP rs5743417 in DEFB1-associated diseases as tuberculosis, COPD, asthma, cystic fibrosis and cancer in African and Afro-American populations deserves further research.
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Affiliation(s)
- Luis Antonio Cruz Díaz
- Interinstitutional Posgrade in Science and Technology (PICYT), Research Center of Technology and Design Assistance of Jalisco State, (CIATEJ A.C.), Guadalajara, Mexico.,Laboratory of Regulatory SNPs, Personalized Medicine National Laboratory (LAMPER), Pharmaceutical and Medical Biotechnology, Central Unit, CIATEJ A.C., National Council of Science and Technology (CONACYT), Guadalajara, Mexico
| | - Abel Gutiérrez Ortega
- Laboratory of Regulatory SNPs, Personalized Medicine National Laboratory (LAMPER), Pharmaceutical and Medical Biotechnology, Central Unit, CIATEJ A.C., National Council of Science and Technology (CONACYT), Guadalajara, Mexico
| | - Rocío Del Carmen Chávez Álvarez
- Laboratory of Regulatory SNPs, Personalized Medicine National Laboratory (LAMPER), Pharmaceutical and Medical Biotechnology, Central Unit, CIATEJ A.C., National Council of Science and Technology (CONACYT), Guadalajara, Mexico
| | - Jesús Salvador Velarde Félix
- Faculty of Chemical and Biological Sciences, Autonomous University of Sinaloa, Culiacan, Mexico.,Faculty of Biology, Autonomous University of Sinaloa, Culiacan, Mexico.,Genomic Medicine Center, Dr. Bernardo J. Gastélum Primary Care Hospital, Sinaloa Health Ministry, Culiacan, Mexico
| | - Ernesto Prado Montes de Oca
- Laboratory of Regulatory SNPs, Personalized Medicine National Laboratory (LAMPER), Pharmaceutical and Medical Biotechnology, Central Unit, CIATEJ A.C., National Council of Science and Technology (CONACYT), Guadalajara, Mexico.,Laboratory of Pharmacogenomics and Preventive Medicine, Personalized Medicine National Laboratory (LAMPER), Pharmaceutical and Medical Biotechnology, Central Unit, CIATEJ A.C., CONACYT, Guadalajara, Mexico.,Scripps Research Translational Institute, La Jolla, CA, USA.,Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, USA
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