Abstract Cisplatin, an anticancer drug, has limited its clinical application due to its severe nephrotoxicity, such as acute kidney injury (AKI). Damaged or dysfunctional mitochondria caused by cisplatin are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Mitophagy is the mechanism of selective degradation of these damaged mitochondria via autophagy, that is critical to cellular homeostasis and viability. In this study, the protective functions of inorganic nitrate against cisplatin-induced nephrotoxicity are assessed. Our results in vitro show that nitrate significantly reduced the apoptosis of HK2 or NRK52E cells induced by cisplatin treatment. Furthermore, dietary nitrate notably alleviates the tubular and glomerular damages as well as the loss of renal function in cisplatin-induced AKI mice models. These protective effects are closely related to downregulation of cell apoptosis and reduction of reactive oxygen species (ROS) generation. Mechanistically, inorganic nitrate treatment promotes the activation of mitophagy mediated by the PINK1-PRKN/PARK2 pathway, which plays an important role in the maintenance of mitochondrial quality, helping renal tubular cells to survive and recover from cisplatin stress. These novel findings suggest that inorganic nitrate supplementation deserve further exploration as a potential treatment in patients with cisplatin-induced renal injury.
{"title":"Nitrate attenuates cisplatin-induced acute kidney injury by promotion of mitophagy and reduction of oxidative stress","authors":"Haibo Wang, Chunyan Song, Feng Chen, Xiu Liu, Liang Hu, Chunmei Zhang, Songlin Wang, Wenbin Li","doi":"10.1007/s44194-023-00024-3","DOIUrl":"https://doi.org/10.1007/s44194-023-00024-3","url":null,"abstract":"Abstract Cisplatin, an anticancer drug, has limited its clinical application due to its severe nephrotoxicity, such as acute kidney injury (AKI). Damaged or dysfunctional mitochondria caused by cisplatin are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Mitophagy is the mechanism of selective degradation of these damaged mitochondria via autophagy, that is critical to cellular homeostasis and viability. In this study, the protective functions of inorganic nitrate against cisplatin-induced nephrotoxicity are assessed. Our results in vitro show that nitrate significantly reduced the apoptosis of HK2 or NRK52E cells induced by cisplatin treatment. Furthermore, dietary nitrate notably alleviates the tubular and glomerular damages as well as the loss of renal function in cisplatin-induced AKI mice models. These protective effects are closely related to downregulation of cell apoptosis and reduction of reactive oxygen species (ROS) generation. Mechanistically, inorganic nitrate treatment promotes the activation of mitophagy mediated by the PINK1-PRKN/PARK2 pathway, which plays an important role in the maintenance of mitochondrial quality, helping renal tubular cells to survive and recover from cisplatin stress. These novel findings suggest that inorganic nitrate supplementation deserve further exploration as a potential treatment in patients with cisplatin-induced renal injury.","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":"12 3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135992781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Purpose T cell receptor (TCR) usually determines the specificity and unique function of T cells. Recently, the unconventional T cells with a unique TCR have attracted great attentions because of their clinical importance. TCR Vα7.2 + cells, that consist of the CD161 + mucosal associated invariant T (MAIT) cells and CD161 − non-MAIT T cells, have been reported to play crucial roles in immune defenses. However, their characterizations in human blood are still obscure. This study aims to investigate the signatures and functions of circulating TCR Vα7.2 + CD161 + MAIT and TCR Vα7.2 + CD161 − cells under steady state. Methods The TCR Vα7.2 + CD161 + and TCR Vα7.2 + CD161 − cells were separately sorted from healthy donor peripheral blood mononuclear cells (PBMCs) and send for single cell RNA sequencing (scRNA-seq). Flow cytometry analysis was used to verify the findings obtained from scRNA-seq analysis. Results Our findings demonstrated that there are more TCR Vα7.2 + CD161 + cells than TCR Vα7.2 + CD161 − cells in healthy donor PBMCs and revealed the differences between them. Under steady state, 4 TCR Vα7.2 + CD161 + MAIT clusters existed in peripheral blood. Pseudotime analysis further implied the development trajectory of these MAIT cells, which was ordered from CCR7 + resting cluster to LGALS3 + transitional cluster, followed by KLRG1 + cluster and ending with CX3CR1 + terminally differentiated cytotoxic cluster. In addition, our results revealed that TCR Vα7.2 + CD161 − cells consist of different kind of conventional T cells. These TCR Vα7.2 + CD161 − non-MAIT cells showed a higher level of Granzyme B expression and upregulated genes associated with cytotoxicity, which implicated their roles in immune defense. Conclusion Our findings advanced the understandings of the evolution of circulating MAIT cells. We also preliminarily defined the TCR Vα7.2 + CD161 − PBMCs as a combination of versatile CD4 + and CD8 + populations with cytotoxicity.
{"title":"Single cell transcriptomics reveal the heterogeneities of TCR Vα7.2+CD161+ and TCR Vα7.2+CD161− T cells in human peripheral blood","authors":"Mingyang Li, Hua Jin, Ling Wei, Tianzhen Zhang, Shiyang Huang, Guangyong Sun, Jian Zhang, Jidong Jia, Chunquan Li, Dong Zhang, Dan Tian","doi":"10.1007/s44194-023-00026-1","DOIUrl":"https://doi.org/10.1007/s44194-023-00026-1","url":null,"abstract":"Abstract Purpose T cell receptor (TCR) usually determines the specificity and unique function of T cells. Recently, the unconventional T cells with a unique TCR have attracted great attentions because of their clinical importance. TCR Vα7.2 + cells, that consist of the CD161 + mucosal associated invariant T (MAIT) cells and CD161 − non-MAIT T cells, have been reported to play crucial roles in immune defenses. However, their characterizations in human blood are still obscure. This study aims to investigate the signatures and functions of circulating TCR Vα7.2 + CD161 + MAIT and TCR Vα7.2 + CD161 − cells under steady state. Methods The TCR Vα7.2 + CD161 + and TCR Vα7.2 + CD161 − cells were separately sorted from healthy donor peripheral blood mononuclear cells (PBMCs) and send for single cell RNA sequencing (scRNA-seq). Flow cytometry analysis was used to verify the findings obtained from scRNA-seq analysis. Results Our findings demonstrated that there are more TCR Vα7.2 + CD161 + cells than TCR Vα7.2 + CD161 − cells in healthy donor PBMCs and revealed the differences between them. Under steady state, 4 TCR Vα7.2 + CD161 + MAIT clusters existed in peripheral blood. Pseudotime analysis further implied the development trajectory of these MAIT cells, which was ordered from CCR7 + resting cluster to LGALS3 + transitional cluster, followed by KLRG1 + cluster and ending with CX3CR1 + terminally differentiated cytotoxic cluster. In addition, our results revealed that TCR Vα7.2 + CD161 − cells consist of different kind of conventional T cells. These TCR Vα7.2 + CD161 − non-MAIT cells showed a higher level of Granzyme B expression and upregulated genes associated with cytotoxicity, which implicated their roles in immune defense. Conclusion Our findings advanced the understandings of the evolution of circulating MAIT cells. We also preliminarily defined the TCR Vα7.2 + CD161 − PBMCs as a combination of versatile CD4 + and CD8 + populations with cytotoxicity.","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135853718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-16DOI: 10.1007/s44194-023-00023-4
Weining Hu, Yin Zhang, J. Mei, X. Fang
{"title":"Spatial transcriptomics in human biomedical research and clinical application","authors":"Weining Hu, Yin Zhang, J. Mei, X. Fang","doi":"10.1007/s44194-023-00023-4","DOIUrl":"https://doi.org/10.1007/s44194-023-00023-4","url":null,"abstract":"","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45221439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-25DOI: 10.1007/s44194-023-00022-5
Chang Liu, Yinghua Yuan, Rong-Rong Xie, Lin Zhang, Hao Wang, Jin-Kui Yang
{"title":"The role of the HERG channel in the secretion of glucagon-like peptide-1 (GLP-1) from murine intestinal L-cells","authors":"Chang Liu, Yinghua Yuan, Rong-Rong Xie, Lin Zhang, Hao Wang, Jin-Kui Yang","doi":"10.1007/s44194-023-00022-5","DOIUrl":"https://doi.org/10.1007/s44194-023-00022-5","url":null,"abstract":"","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42884266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-06DOI: 10.1007/s44194-023-00021-6
Chang-Jun Zhang, Zidan Jin
{"title":"Homeostasis and dyshomeostasis of the retina","authors":"Chang-Jun Zhang, Zidan Jin","doi":"10.1007/s44194-023-00021-6","DOIUrl":"https://doi.org/10.1007/s44194-023-00021-6","url":null,"abstract":"","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42221146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-06DOI: 10.1007/s44194-022-00017-8
X. Yang, Parker Li, Z. Kang, Wenbin Li
{"title":"Targeted therapy, immunotherapy, and chemotherapy for chordoma","authors":"X. Yang, Parker Li, Z. Kang, Wenbin Li","doi":"10.1007/s44194-022-00017-8","DOIUrl":"https://doi.org/10.1007/s44194-022-00017-8","url":null,"abstract":"","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41903955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1007/s44194-022-00018-7
Jingjing Zhou, Jinjie Xu, Rui Liu, Han Qi, Jian Yang, Tong Guo, Jia Zhou, Xuequan Zhu, Ling Zhang, Xiongying Chen, Nan Lyu, Zizhao Feng, Guofu Zhang, Min Liu, Weiwei Wang, Yun Wang, Zhifang Zhang, Le Xiao, Yuan Feng, Gang Wang
Background: Major depressive disorder (MDD) imposes a heavy global disease burden. However, current etiology, diagnosis and treatment remain unsatisfactory and no previous study has resolved this problem. Building on the strengths and limitations of previous cohort studies of MDD, the prospective cohort study of depression (PROUD) is a 3-year large-scale cohort study designed to collect multidimensional data with a flexible follow-up schedule and strategy. The goal is to establish a nationally representative, high-quality, standardized depression cohort to support precise diagnosis and treatment of MDD and address the gap in current research.
Methods: PROUD is a patient-based, nationally representative multicenter prospective cohort study with baseline and 3-year follow-up assessments. It will be carried out from January 2022 to December 2026 in 52 qualified tertiary hospitals in China. A total of 14,000 patients diagnosed with MDD, according to the DSM-5 criteria, and aged ≥ 16 years, will be recruited to PROUD. Participants aged 18-65 years who have not received any treatment during a depressive episode will be included in the precision medicine cohort (PMC) of PROUD (n=4,000). Patients who meet the general eligibility criteria but not the PMC criteria will be included in the naturalistic observation cohort (NOC) of PROUD (n=10,000). A multiple follow-up strategy, including scheduled, remote, telephone, external visits and patient self-reports, will be implemented to collect comprehensive sociodemographic, clinical information, biospecimens, neuroimaging, cognitive function and electrophysiology data and digital phenotypes according to strict standard operating procedures implemented across centers. Trial registration: ChiCTR2200059053, registered on 23 April 2022, http://www.chictr.org.cn/showproj.aspx?proj=165790.
Conclusions: PROUD is a prospective cohort study of MDD patients in China. It will provide a comprehensive database facilitating further analyses and aiding the development of homeostatic and precision medicine in China.
{"title":"A prospective cohort study of depression (PROUD) in China: rationale and design.","authors":"Jingjing Zhou, Jinjie Xu, Rui Liu, Han Qi, Jian Yang, Tong Guo, Jia Zhou, Xuequan Zhu, Ling Zhang, Xiongying Chen, Nan Lyu, Zizhao Feng, Guofu Zhang, Min Liu, Weiwei Wang, Yun Wang, Zhifang Zhang, Le Xiao, Yuan Feng, Gang Wang","doi":"10.1007/s44194-022-00018-7","DOIUrl":"https://doi.org/10.1007/s44194-022-00018-7","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) imposes a heavy global disease burden. However, current etiology, diagnosis and treatment remain unsatisfactory and no previous study has resolved this problem. Building on the strengths and limitations of previous cohort studies of MDD, the prospective cohort study of depression (PROUD) is a 3-year large-scale cohort study designed to collect multidimensional data with a flexible follow-up schedule and strategy. The goal is to establish a nationally representative, high-quality, standardized depression cohort to support precise diagnosis and treatment of MDD and address the gap in current research.</p><p><strong>Methods: </strong>PROUD is a patient-based, nationally representative multicenter prospective cohort study with baseline and 3-year follow-up assessments. It will be carried out from January 2022 to December 2026 in 52 qualified tertiary hospitals in China. A total of 14,000 patients diagnosed with MDD, according to the DSM-5 criteria, and aged ≥ 16 years, will be recruited to PROUD. Participants aged 18-65 years who have not received any treatment during a depressive episode will be included in the precision medicine cohort (PMC) of PROUD (<i>n</i>=4,000). Patients who meet the general eligibility criteria but not the PMC criteria will be included in the naturalistic observation cohort (NOC) of PROUD (<i>n</i>=10,000). A multiple follow-up strategy, including scheduled, remote, telephone, external visits and patient self-reports, will be implemented to collect comprehensive sociodemographic, clinical information, biospecimens, neuroimaging, cognitive function and electrophysiology data and digital phenotypes according to strict standard operating procedures implemented across centers. Trial registration: ChiCTR2200059053, registered on 23 April 2022, http://www.chictr.org.cn/showproj.aspx?proj=165790.</p><p><strong>Conclusions: </strong>PROUD is a prospective cohort study of MDD patients in China. It will provide a comprehensive database facilitating further analyses and aiding the development of homeostatic and precision medicine in China.</p>","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":"2 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10535840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1007/s44194-022-00019-6
Lei Lin, Yong-ping Chen, Yuxiang Liao, L. Yuan, Xiao-kai Huang, Ji-Chen Ruan, Meng Li, Huiran Lin, Lei Miao
{"title":"HOTAIR gene polymorphisms and risk of glioma in Chinese children","authors":"Lei Lin, Yong-ping Chen, Yuxiang Liao, L. Yuan, Xiao-kai Huang, Ji-Chen Ruan, Meng Li, Huiran Lin, Lei Miao","doi":"10.1007/s44194-022-00019-6","DOIUrl":"https://doi.org/10.1007/s44194-022-00019-6","url":null,"abstract":"","PeriodicalId":72735,"journal":{"name":"Current medicine (Cham, Switzerland)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49476546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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