Journal of Biomedical Research最新文献

{"title":"A case of linear and whorled nevoid hypermelanosis.","authors":"Jinxu Qi, Yijia He, Guoqiang Zhang","doi":"10.7555/JBR.39.20250084","DOIUrl":"10.7555/JBR.39.20250084","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"97-98"},"PeriodicalIF":2.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of <i>DDR1</i> contributes to gastric cancer progression by inhibiting the Hippo pathway.","authors":"Haiying Han, Tianqi Shen, Tingting Zhou, Yixuan Yang, Weiyi Toy, Yin Yin Choo, Fan Lin, Yoon Pin Lim","doi":"10.7555/JBR.39.20250198","DOIUrl":"10.7555/JBR.39.20250198","url":null,"abstract":"<p><p>Gastric cancer (GC) is a prevalent and devastating disease with a poor prognosis. The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges. Through isobaric tags for relative and absolute quantitation (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) phosphoproteomic analysis of 14 GC and gastric epithelial cell lines, we discovered the discoidin domain receptor tyrosine kinase 1 (DDR1) as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled. The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with <i>DDR1</i> gene amplification. Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41% and 48% of the intestinal and diffuse types of GC cases, respectively, compared with only 3.5% in normal tissues. Higher <i>DDR1</i> expression was associated with poor prognosis. In cellular models, <i>DDR1</i> overexpression led to accelerated proliferation, invasion, and malignant transformation, putatively <i>via</i> inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression. Notably, <i>DDR1</i>-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors. The present study provides preclinical support for the application of DDR1-selective inhibitors in <i>DDR1</i>-overexpressing GC.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"500-514"},"PeriodicalIF":2.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte to HDL cholesterol ratio predicts obesity-associated cardiac dysfunction.","authors":"Chunsheng Zhao, Jinting Liu, Jiaqi Zhao, Chao Wang, Hui Bai, Qing Yang, Jingjing Ben, Xudong Zhu, Xiaoyu Li, Bin Jiang, Kai Li, Runfeng Sun, Xuexing Ma, Liansheng Wang, Hanwen Zhang, Qi Chen","doi":"10.7555/JBR.38.20240432","DOIUrl":"10.7555/JBR.38.20240432","url":null,"abstract":"<p><p>As the prevalence of obesity increases dramatically, obesity-associated cardiac dysfunction constitutes a considerable challenge to human health. This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction. By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients, we found that both the plasma level of high-density lipoprotein cholesterol (HDL-C) and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction (LVEF). Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio (MHR) was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone. Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function. Collectively, our results demonstrate a superior role of MHR in predicting the risk of an obesity-associated decline in cardiac systolic function among routine metabolic/inflammatory markers.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"32-44"},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic <i>Akkermansia muciniphila</i> alleviates acute kidney injury by protecting the intestinal barrier and modulating gut microbiota and metabolites.","authors":"Juan Ni, Zhan Yang, Xuewei Sun, Qian Cui, Ruonan Zhang, Han Lu, Zihan Wu, Jingfeng Zhu, Huijuan Mao, Kang Liu, Chengliang Tang, Chunhui Wang, Changying Xing, Jin Zhu","doi":"10.7555/JBR.39.20250162","DOIUrl":"10.7555/JBR.39.20250162","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a critical condition with limited effective therapies. <i>Akkermansia muciniphila</i> ( <i>A. muciniphila</i>) is a probiotic with multiple beneficial effects, including the regulation of epithelial cell tight junctions. Since renal pathophysiology is associated with gut barrier integrity, we hypothesized that <i>A. muciniphila</i> may have preventive effects on AKI. We established a lipopolysaccharide (LPS)-induced AKI mouse model to evaluate the effects of <i>A. muciniphila</i>. Our findings showed that pretreatment with <i>A. muciniphila</i> significantly attenuated kidney injury, as evidenced by reduced serum creatinine and urea nitrogen levels, alongside decreased tubular necrosis and apoptosis. <i>A. muciniphila</i> preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome. <i>A. muciniphila</i> notably induced an increase in the relative abundance of the phylum <i>Proteobacteria</i> while decreasing in that of the phylum <i>Bacteroidetes</i>. At the genus level, <i>Prevotella</i>, <i>Faecalibaculum</i>, <i>Moraxella</i>, and <i>Lactobacillus</i> were more abundant in <i>A. muciniphila</i>-pretreated mice. Metabolomic analysis revealed that <i>A. muciniphila</i> altered the gut metabolome, with changes involving pathways such as tyrosine metabolism, alanine/aspartate/glutamate homeostasis, cancer-related carbon flux, and GABAergic synaptic signaling. In conclusion, our findings indicate that <i>A. muciniphila</i> exerts renoprotective effects by modulating the gut-kidney axis, thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"76-88"},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A healthy lifestyle pattern and mortality risk in patients of type 2 diabetes mellitus: a prospective cohort study in China.","authors":"Hao Yu, Xinyi Liu, Xueni Cheng, Xikang Fan, Yuefan Shen, Ke Liu, Yanan Wan, Jian Su, Yu Qin, Zhongming Sun, Yan Lu, Shujun Gu, Chong Shen, Dong Hang, Jinyi Zhou","doi":"10.7555/JBR.39.20250107","DOIUrl":"10.7555/JBR.39.20250107","url":null,"abstract":"<p><p>This study aimed to evaluate the association of a healthy lifestyle pattern with mortality risk among patients with type 2 diabetes mellitus (T2DM). Data were derived from a prospective cohort enrolling 13,776 Chinese patients with T2DM. A healthy lifestyle pattern was constructed based on six lifestyle factors, including smoking, alcohol consumption, dietary habit, physical activity, sedentary time, and sleep duration. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. During a median follow-up of 9.0 years, 2,497 deaths were recorded. Compared to T2DM patients with the lifestyle pattern scoring 0-2, those scoring 5-6 had a 40% lower risk for all-cause mortality (HR = 0.60, 95% CI: 0.52-0.69), 33% lower risk for CVD mortality (HR = 0.67, 95% CI: 0.52-0.69), and 25% lower risk for cancer mortality (HR = 0.75, 95% CI: 0.58-0.97). In addition, we found that the association between the lifestyle pattern and all-cause mortality risk was stronger in females than in males ( <i>P</i> for interaction < 0.05). In conclusion, adherence to a healthy lifestyle pattern is associated with a decreased risk of all-cause, CVD, and cancer mortality, which has important implications for reducing premature mortality in patients with T2DM.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-9"},"PeriodicalIF":3.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12683505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAF1 in AgRP neurons involved in the regulation of energy metabolism <i>via</i> the MAPK signaling pathway.","authors":"Yuqian Chen, Lianci Ren, Xinyi Xu, Zhenning Sun, Mingxi Dai, Yin Li, Xiang Ma, Juxue Li","doi":"10.7555/JBR.39.20250114","DOIUrl":"10.7555/JBR.39.20250114","url":null,"abstract":"<p><p>V-raf-leukemia viral oncogene 1 (RAF1), a serine/threonine protein kinase, is well established to play a crucial role in tumorigenesis and cell development. However, the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown. In this study, we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity (DIO) mice. Under normal chow diet feeding, overexpression of <i>Raf1</i> in AgRP neurons led to obesity in mice characterized by increased body weight, fat mass, and impaired glucose tolerance. Conversely, <i>Raf1</i> knockout in AgRP neurons protected against diet-induced obesity, reducing fat mass and improving glucose tolerance. Mechanistically, <i>Raf1</i> activated the MAPK signaling pathway, culminating in the phosphorylation of cAMP response element-binding protein (CREB), which enhanced transcription of <i>Agrp</i> and <i>Npy</i>. Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis, highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance. Collectively, these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis, positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"45-62"},"PeriodicalIF":2.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LAG3 facilitates MHC Ⅱ trogocytosis with assistance of the ER-PM junction.","authors":"Zibin Wang, Jing Wang, Wene Zhao, Wen Liu","doi":"10.7555/JBR.39.20250144","DOIUrl":"10.7555/JBR.39.20250144","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"89-92"},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects and toxicity profiles of consolidative and salvage thoracic radiotherapy following chemoimmunotherapy in patients with extensive-stage small cell lung cancer.","authors":"Ruozhou Sun, Dan Zong, Xin Chen, Yizhi Ge, Ning Jiang, Lijun Zhao, Xue Song, Xia He, Xiangzhi Zhu","doi":"10.7555/JBR.39.20250067","DOIUrl":"10.7555/JBR.39.20250067","url":null,"abstract":"<p><p>The present study assessed the efficacy and safety of thoracic radiotherapy (TRT) following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC), focusing on the influence of different TRT timing strategies (consolidative <i>vs.</i> salvage) on survival rates. We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022. Patients receiving consolidative TRT (cTRT) within three months after completion of first-line treatment were compared with those receiving salvage TRT (sTRT) after disease progression. The primary endpoints were overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS); the secondary endpoint included safety. The cTRT group ( <i>n</i> = 41) showed significantly longer median OS (26.6 <i>vs.</i> 14.8 months, <i>P</i> = 0.048), PFS (12.9 <i>vs.</i> 3.5 months, <i>P</i> < 0.0001), and DMFS (10.7 <i>vs.</i> 3.4 months, <i>P</i> = 0.0044) than the sTRT group ( <i>n</i> = 13). Multivariate analysis revealed that cTRT was an independent, favorable prognostic factor. No significant differences in OS or LRFS were observed between high-dose (≥ 50 Gy) and low-dose (< 50 Gy) TRT. Hematologic and respiratory toxicities were the most frequently reported adverse events, with acceptable tolerability. In conclusion, cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients, and low-dose TRT may be a suitable option.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"467-477"},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative omics and multi-cohort identify <i>IRF1</i> and biological targets related to sepsis-associated acute respiratory distress syndrome.","authors":"Jiajin Chen, Ruili Hou, Xiaowen Xu, Ning Xie, Jiaqi Tang, Yi Li, Xiaoqing Nie, Nuala J Meyer, Li Su, David C Christiani, Feng Chen, Ruyang Zhang","doi":"10.7555/JBR.39.20250066","DOIUrl":"10.7555/JBR.39.20250066","url":null,"abstract":"<p><p>Interferon-related genes are involved in antiviral responses, inflammation, and immunity, which are closely related to sepsis-associated acute respiratory distress syndrome (ARDS). We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS (MEARDS), the Molecular Epidemiology of Sepsis in the ICU (MESSI), and the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls. First, we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression (GReX). Second, we examined the association of the confirmed gene (interferon regulatory factor 1, <i>IRF1</i>) with ARDS risk and survival and conducted a mediation analysis. Through discovery and validation, we found that the GReX of <i>IRF1</i> was associated with ARDS risk (odds ratio [OR _MEARDS] = 0.84, <i>P</i> = 0.008; OR _MESSI = 0.83, <i>P</i> = 0.034). Furthermore, individual-level measured <i>IRF1</i> expression was associated with reduced ARDS risk (OR = 0.58, <i>P</i> = 8.67 × 10 ^-4), and improved overall survival in ARDS patients (hazard ratio [HR _28-day] = 0.49, <i>P</i> = 0.009) and sepsis patients (HR _28-day = 0.76, <i>P</i> = 0.008). Mediation analysis revealed that <i>IRF1</i> may enhance immune function by regulating the major histocompatibility complex, including <i>HLA-F</i>, which mediated more than 70% of protective effects of <i>IRF1</i> on ARDS. The findings were validated by <i>in vitro</i> biological experiments including time-series infection dynamics, overexpression, knockout, and chromatin immunoprecipitation sequencing. Early prophylactic interventions to activate <i>IRF1</i> in sepsis patients, thereby regulating <i>HLA-F</i>, may reduce the risk of ARDS and mortality, especially in severely ill patients.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"11-22"},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12794184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEC1 promotes breast cancer bone metastasis through transcriptional activation of CXCR4.","authors":"Ying Huo, Kaiao Chen, Zhiyi Qiang, Lan Lin, Wei Liu, Jian Yang","doi":"10.7555/JBR.39.20250031","DOIUrl":"10.7555/JBR.39.20250031","url":null,"abstract":"<p><p>Bone metastasis is the primary cause of mortality in breast cancer (BC) patients. The present study elucidates the functional role of the differentiated embryonic chondrocyte-expressed gene 1 (DEC1) in promoting BC-related bone metastasis. Analysis of patient-derived samples and public databases revealed a significant upregulation of DEC1 and CXCR4 in breast tumors compared with adjacent normal tissues, with elevated levels correlating with increased metastatic potential, suggesting their synergistic involvement in BC progression. Intracardiac injection experiments demonstrated that <i>Dec1</i>-WT 4T1 cells induced more severe osteolysis and larger metastatic lesions than <i>Dec1</i>-KD 4T1 cells. In MDA-MB-231 cells, <i>DEC1</i> overexpression (OE) upregulated CXCR4 and proliferation/migration-related genes, whereas <i>DEC1</i> knockdown reversed these effects. Notably, AMD3100, a specific CXCR4 antagonist, partially reversed the <i>DEC1</i>-OE-induced upregulation of CXCR4 and associated pro-metastatic genes. Mechanistically, DEC1 bound to the CXCR4 promoter region (-230 to -326) and activated its transcription, corroborated by ChIP-seq data. Furthermore, pharmacological inhibition of AKT (LY294002) or JAK2 (AZD1480), but not ERK (PD98059), attenuated DEC1-mediated CXCR4 upregulation, although all three inhibitors mitigated DEC1-driven migration-related gene expression. Additionally, DEC1 enhanced CXCL12 secretion from mesenchymal stromal cells and osteoblasts, amplifying the CXCR4/CXCL12 axis within the bone microenvironment. Collectively, our findings demonstrate that DEC1 promotes BC bone metastasis by directly transactivating CXCR4 expression, providing a molecular basis for targeting DEC1 to prevent and treat BC bone metastasis.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"478-499"},"PeriodicalIF":2.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}