Frontiers of Medicine最新文献_第9页

Phase separation in cGAS-STING signaling. cGAS STING信号中的相分离。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-10-31 DOI: 10.1007/s11684-023-1026-6

Quanjin Li, Pu Gao

引用次数: 0

Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice. Dynein axonemal 重链 10 缺乏症会导致人类和小鼠出现原发性睫状肌运动障碍。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-06-13 DOI: 10.1007/s11684-023-0988-8

Rongchun Wang, Danhui Yang, Chaofeng Tu, Cheng Lei, Shuizi Ding, Ting Guo, Lin Wang, Ying Liu, Chenyang Lu, Binyi Yang, Shi Ouyang, Ke Gong, Zhiping Tan, Yun Deng, Yueqiu Tan, Jie Qing, Hong Luo

{"title":"Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice.","authors":"Rongchun Wang, Danhui Yang, Chaofeng Tu, Cheng Lei, Shuizi Ding, Ting Guo, Lin Wang, Ying Liu, Chenyang Lu, Binyi Yang, Shi Ouyang, Ke Gong, Zhiping Tan, Yun Deng, Yueqiu Tan, Jie Qing, Hong Luo","doi":"10.1007/s11684-023-0988-8","DOIUrl":"10.1007/s11684-023-0988-8","url":null,"abstract":"Primary ciliary dyskinesia (PCD) is a congenital, motile ciliopathy with pleiotropic symptoms. Although nearly 50 causative genes have been identified, they only account for approximately 70% of definitive PCD cases. Dynein axonemal heavy chain 10 (DNAH10) encodes a subunit of the inner arm dynein heavy chain in motile cilia and sperm flagella. Based on the common axoneme structure of motile cilia and sperm flagella, DNAH10 variants are likely to cause PCD. Using exome sequencing, we identified a novel DNAH10 homozygous variant (c.589C > T, p.R197W) in a patient with PCD from a consanguineous family. The patient manifested sinusitis, bronchiectasis, situs inversus, and asthenoteratozoospermia. Immunostaining analysis showed the absence of DNAH10 and DNALI1 in the respiratory cilia, and transmission electron microscopy revealed strikingly disordered axoneme 9+2 architecture and inner dynein arm defects in the respiratory cilia and sperm flagella. Subsequently, animal models of Dnah10-knockin mice harboring missense variants and Dnah10-knockout mice recapitulated the phenotypes of PCD, including chronic respiratory infection, male infertility, and hydrocephalus. To the best of our knowledge, this study is the first to report DNAH10 deficiency related to PCD in human and mouse models, which suggests that DNAH10 recessive mutation is causative of PCD.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9999725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis. ADT-OH 可改善 DSS 引起的结肠炎的肠道屏障功能并重塑肠道微生物群。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-29 DOI: 10.1007/s11684-023-0990-1

Zhiqian Bi, Jia Chen, Xiaoyao Chang, Dangran Li, Yingying Yao, Fangfang Cai, Huangru Xu, Jian Cheng, Zichun Hua, Hongqin Zhuang

{"title":"ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis.","authors":"Zhiqian Bi, Jia Chen, Xiaoyao Chang, Dangran Li, Yingying Yao, Fangfang Cai, Huangru Xu, Jian Cheng, Zichun Hua, Hongqin Zhuang","doi":"10.1007/s11684-023-0990-1","DOIUrl":"10.1007/s11684-023-0990-1","url":null,"abstract":"Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long noncoding RNA LOC646029 functions as a ceRNA to suppress ovarian cancer progression through the miR-627-3p/SPRED1 axis. 长非编码 RNA LOC646029 作为一种 ceRNA，通过 miR-627-3p/SPRED1 轴抑制卵巢癌的进展。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-12 DOI: 10.1007/s11684-023-1004-z

Pengfei Zhao, Yating Wang, Xiao Yu, Yabing Nan, Shi Liu, Bin Li, Zhumei Cui, Zhihua Liu

引用次数: 0

Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective cohort study. 合并症患者接种灭活疫苗预防 SARS-CoV-2 感染：一项前瞻性队列研究。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-12 DOI: 10.1007/s11684-023-0995-9

Kanchana Ngaosuwan, Kamonwan Soonklang, Chawin Warakul, Chirayu Auewarakul, Nithi Mahanonda

{"title":"Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective cohort study.","authors":"Kanchana Ngaosuwan, Kamonwan Soonklang, Chawin Warakul, Chirayu Auewarakul, Nithi Mahanonda","doi":"10.1007/s11684-023-0995-9","DOIUrl":"10.1007/s11684-023-0995-9","url":null,"abstract":"Protection against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection of inactivated vaccines is not well characterized in people with comorbidities, who are at high risk of severe infection. We compared the risk of SARS-CoV-2 infection after complete vaccination with Sinopharm/BBIBP in people with comorbidities (e.g., autoimmune diseases, cardiovascular disease, chronic lung disease, and diabetes) with healthy individuals using a Cox-proportional hazard model. In July-September 2021, a total of 10 548 people (comorbidities, 2143; healthy, 8405) receiving the complete primary series of vaccination with Sinopharm/BBIBP in Bangkok, Thailand were prospectively followed for SARS-CoV-2 infection through text messaging and telephone interviewing for 6 months. A total of 295 infections from 284 participants were found. HRs (95% CI) of individuals with any comorbidities did not increase (unadjusted, 1.02 (0.77-1.36), P = 0.89; adjusted, 1.04 (0.78-1.38), P = 0.81). HRs significantly increased in the subgroup of autoimmune diseases (unadjusted, 2.64 (1.09-6.38), P = 0.032; adjusted, 4.45 (1.83-10.83), P = 0.001) but not in cardiovascular disease, chronic lung disease, or diabetes. The protection against SARS-CoV-2 infection of the Sinopharm vaccine was similar in participants with any comorbidities vs. healthy individuals. However, the protection appeared lower in the subgroup of autoimmune diseases, which may reflect suboptimal immune responses among these people.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9767526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of the mechanisms of acupuncture in the treatment of migraine based on functional magnetic resonance imaging and omics. 基于功能磁共振成像和 omics 发现针灸治疗偏头痛的机制。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-06-30 DOI: 10.1007/s11684-023-0989-7

Chong Li, Xinyi Li, Ke He, Yang Wu, Xiaoming Xie, Jiju Yang, Fan Zhang, Yang Yue, Huifeng Hao, Shaokun Zhao, Xin Li, Guihua Tian

{"title":"Discovery of the mechanisms of acupuncture in the treatment of migraine based on functional magnetic resonance imaging and omics.","authors":"Chong Li, Xinyi Li, Ke He, Yang Wu, Xiaoming Xie, Jiju Yang, Fan Zhang, Yang Yue, Huifeng Hao, Shaokun Zhao, Xin Li, Guihua Tian","doi":"10.1007/s11684-023-0989-7","DOIUrl":"10.1007/s11684-023-0989-7","url":null,"abstract":"Migraine is one of the most prevalent and disabling neurological disease, but the current pharmacotherapies show limited efficacy and often accompanied by adverse effects. Acupuncture is a promising complementary therapy, but further clinical evidence is needed. The influence of acupuncture on migraine is not an immediate effect, and its mechanism remains unclear. This study aims to provide further clinical evidence for the anti-migraine effects of acupuncture and explore the mechanism involved. A randomized controlled trial was performed among 10 normal controls and 38 migraineurs. The migraineurs were divided into blank control, sham acupuncture, and acupuncture groups. Patients were subjected to two courses of treatment, and each treatment lasted for 5 days, with an interval of 1 day between the two courses. The effectiveness of treatment was evaluated using pain questionnaire. The functional magnetic resonance imaging (fMRI) data were analyzed for investigating brain changes induced by treatments. Blood plasma was collected for metabolomics and proteomics studies. Correlation and mediation analyses were performed to investigate the interaction between clinical, fMRI and omics changes. Results showed that acupuncture effectively relieved migraine symptoms in a way different from sham acupuncture in terms of curative effect, affected brain regions, and signaling pathways. The anti-migraine mechanism involves a complex network related to the regulation of the response to hypoxic stress, reversal of brain energy imbalance, and regulation of inflammation. The brain regions of migraineurs affected by acupuncture include the lingual gyrus, default mode network, and cerebellum. The effect of acupuncture on patients' metabolites/proteins may precede that of the brain.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9752245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Discovery of small molecule degraders for modulating cell cycle. 发现用于调节细胞周期的小分子降解剂。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-11-08 DOI: 10.1007/s11684-023-1027-5

Liguo Wang, Zhouli Yang, Guangchen Li, Yongbo Liu, Chao Ai, Yu Rao

引用次数: 0

Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies. 代谢干预结合CTLA-4和PD-1/PD-L1阻断治疗肿瘤：机制和策略。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-10-28 DOI: 10.1007/s11684-023-1025-7

Liming Liao, Huilin Xu, Yuhan Zhao, Xiaofeng Zheng

{"title":"Metabolic interventions combined with CTLA-4 and PD-1/PD-L1 blockade for the treatment of tumors: mechanisms and strategies.","authors":"Liming Liao, Huilin Xu, Yuhan Zhao, Xiaofeng Zheng","doi":"10.1007/s11684-023-1025-7","DOIUrl":"10.1007/s11684-023-1025-7","url":null,"abstract":"Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66783807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart. 在胚胎和成年哺乳动物心脏中持续存在细胞间交流极少的独特单核二倍体心脏亚群。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-06-09 DOI: 10.1007/s11684-023-0987-9

Miaomiao Zhu, Huamin Liang, Zhe Zhang, Hao Jiang, Jingwen Pu, Xiaoyi Hang, Qian Zhou, Jiacheng Xiang, Ximiao He

{"title":"Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart.","authors":"Miaomiao Zhu, Huamin Liang, Zhe Zhang, Hao Jiang, Jingwen Pu, Xiaoyi Hang, Qian Zhou, Jiacheng Xiang, Ximiao He","doi":"10.1007/s11684-023-0987-9","DOIUrl":"10.1007/s11684-023-0987-9","url":null,"abstract":"A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9587273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial. 肝脏导向治疗与转移性葡萄膜黑色素瘤生存率的提高和免疫检查点阻断反应的增加有关：一项回顾性多中心试验的结果。

IF 8.1 3区医学

Frontiers of Medicine Pub Date : 2023-10-01 Epub Date: 2023-07-04 DOI: 10.1007/s11684-023-0993-y

Elias A T Koch, Anne Petzold, Anja Wessely, Edgar Dippel, Markus Eckstein, Anja Gesierich, Ralf Gutzmer, Jessica C Hassel, Harald Knorr, Nicole Kreuzberg, Ulrike Leiter, Carmen Loquai, Friedegund Meier, Markus Meissner, Peter Mohr, Claudia Pföhler, Farnaz Rahimi, Dirk Schadendorf, Max Schlaak, Kai-Martin Thoms, Selma Ugurel, Jochen Utikal, Michael Weichenthal, Beatrice Schuler-Thurner, Carola Berking, Markus V Heppt

{"title":"Liver-directed treatment is associated with improved survival and increased response to immune checkpoint blockade in metastatic uveal melanoma: results from a retrospective multicenter trial.","authors":"Elias A T Koch, Anne Petzold, Anja Wessely, Edgar Dippel, Markus Eckstein, Anja Gesierich, Ralf Gutzmer, Jessica C Hassel, Harald Knorr, Nicole Kreuzberg, Ulrike Leiter, Carmen Loquai, Friedegund Meier, Markus Meissner, Peter Mohr, Claudia Pföhler, Farnaz Rahimi, Dirk Schadendorf, Max Schlaak, Kai-Martin Thoms, Selma Ugurel, Jochen Utikal, Michael Weichenthal, Beatrice Schuler-Thurner, Carola Berking, Markus V Heppt","doi":"10.1007/s11684-023-0993-y","DOIUrl":"10.1007/s11684-023-0993-y","url":null,"abstract":"Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM.","PeriodicalId":12558,"journal":{"name":"Frontiers of Medicine","volume":null,"pages":null},"PeriodicalIF":8.1,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0