Jie Zhang, Lei Dai, Chunyan Jiang, Yuxin Zhao, Xiang Ma, Yugui Cui, Jiayin Liu
{"title":"Comparison of Pregnancy Outcomes and Vaginal Microbiota in Endometriosis Patients Undergoing Frozen Embryo Transfer Using Letrozole Combined HMG Versus Hormone Replacement Therapy with GnRH-a Pretreatment.","authors":"Jie Zhang, Lei Dai, Chunyan Jiang, Yuxin Zhao, Xiang Ma, Yugui Cui, Jiayin Liu","doi":"10.7555/JBR.39.20250205","DOIUrl":"https://doi.org/10.7555/JBR.39.20250205","url":null,"abstract":"<p><p>This study investigated differences in reproductive outcomes and vaginal microbiota profiles between two endometrial preparation protocols-letrozole (LE) combined with human menopausal gonadotropin (HMG) and hormone replacement therapy (HRT) with GnRH-a pretreatment-in women with endometriosis (EMs) undergoing frozen embryo transfer (FET). Following 1∶1 propensity score matching, a total of 770 FET cycles were analyzed. No statistically significant differences were observed in live birth rates or clinical pregnancy rates between the two groups. However, the LE + HMG group showed a lower miscarriage trend (13.7% vs. 19.8%, P = 0.070) and significantly fewer cesarean deliveries (64.9% vs. 75.4%, P = 0.020) and hypertensive disorders of pregnancy (4.8% vs. 10.1%, P = 0.039). Recent evidence suggests that GnRH-a treatment may disrupt reproductive tract microbiota. Given ethical constraints on endometrial sampling during FET, vaginal microbiota was used as a surrogate to explore microbial differences between protocols. In the prospective arm, vaginal samples from 55 women in the LE + HMG group and 50 in the GnRH-a HRT group were analyzed using 16S rRNA sequencing and droplet digital PCR. While no significant differences were observed in <i>Lactobacillus</i> or <i>Gardnerella</i> abundance, the GnRH-a HRT group exhibited enrichment of potential pathogens, such as <i>Escherichia-Shigella</i> and <i>Staphylococcus</i>. In conclusion, although both protocols achieved comparable live birth outcomes, the LE + HMG regimen was associated with fewer obstetric complications and a more favorable vaginal microbiota profile compared to GnRH-a HRT.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overexpression of <i>DDR1</i> contributes to gastric cancer progression <i>via</i> inhibition of 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":"https://doi.org/10.7555/JBR.39.20250198","url":null,"abstract":"<p><p>Gastric cancer (GC) is a prevalent and devastating disease with poor prognosis. Lack of biomarkers for early detection and effective targeted therapeutics for GC patients represent two major challenges for this disease. Through iTRAQ-LC-MS/MS phosphoproteomics analysis of 14 GC <i>vs.</i> gastric epithelial cell lines, we discovered Discoidin Domain Receptor tyrosine kinase 1 ( <i>DDR1</i>) as a top potential drug target out of 40 tyrosine kinases detected along with > 1000 phosphoproteins profiled. The DDR1 protein and mRNA levels were found to be upregulated in GC cells concomitant with <i>DDR1</i> gene amplification. IHC staining of more than 200 clinical samples revealed that DDR1 was overexpressed in 41% and 48% of the intestinal and diffuse type of GC cases, respectively, compared to only 3.5% in normal tissues. Higher <i>DDR1</i> expression correlated with poor prognosis. In cellular models, <i>DDR1</i> overexpression led to accelerated proliferation, invasion, and malignant transformation, putatively <i>via</i> Hippo pathway inhibition and consequent activation of the TEAD-YAP targets transcription. Importantly, <i>DDR1</i> overexpressed GC cells exhibited high vulnerability to selective DDR1 inhibitors. Our study provides preclinical supports for the application of DDR1 selective inhibitor for <i>DDR1</i>-overexpressed gastric cancer.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bo Peng, Minghui Jiang, Si Li, Xingyu Chen, Shanshan Cheng, Xingjie Hao
{"title":"Cross-phenotype genome-wide association study supports shared genetic etiology between skin and gastrointestinal tract diseases.","authors":"Bo Peng, Minghui Jiang, Si Li, Xingyu Chen, Shanshan Cheng, Xingjie Hao","doi":"10.7555/JBR.39.20250166","DOIUrl":"https://doi.org/10.7555/JBR.39.20250166","url":null,"abstract":"<p><p>The comorbidity of skin and gastrointestinal tract (GIT) diseases, primarily driven by the gut-skin axis (GSA), is well-known. However, the genetic contribution to the GSA remains unclear. Here, using genome-wide association study (GWAS) summary statistics from European populations, we performed genome-wide pleiotropic analysis to investigate the shared genetic basis and causal associations between skin and GIT diseases. We observed extensive genetic correlations and overlaps between skin and GIT diseases. A total of 298 pleiotropic loci were identified, 75 of which were colocalized, and 61 exhibited pleiotropic effects across multiple trait pairs, including 2p16.1 ( <i>PUS10</i>), 6p21.32 ( <i>HLA-DRB1</i>), 10q21.2 ( <i>ZNF365</i>), and 19q13.11 ( <i>SLC7A10</i>). Additionally, five novel loci were identified based on the pleiotropic analysis, with <i>RORA</i> at 15q22.2 validated by the latest inflammatory bowel disease GWAS. Gene-based analysis found 394 unique pleiotropic genes, which were enriched in GSA-associated tissues and immune system, whereas protein-protein interaction analysis further revealed the GPCR-cAMP, chromatin remodeling, JAK-STAT, and HLA-mediated immunity pathways coregulate GSA comorbidity. Notably, the JAK-STAT pathway showed strong potential in drug repurposing, with Adalimumab targeting <i>TNF</i> and Ustekinumab targeting <i>IL-12B</i> already used to treat both skin and GIT diseases. Finally, Mendelian randomization analysis suggested five significant causal associations, and subsequent mediation analysis introduced three potential microbiota-GIT-skin pathways. Taken together, our study suggested that the shared genetic factors between skin and GIT diseases are widely distributed across the genome. These findings will improve our understanding of the genetic basis of GSA and offer significant implications for simultaneously treating skin and GIT diseases.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuebin Zhao, Jian Zheng, Weimin Zheng, Jinrong Lin, Guangshuo Ding, Xinhui Yu, Jun Cao, Yun Chen, Bo Shen, Gaoqian Feng
{"title":"Mechanisms and targets of harnessing <i>Culex pipiens</i>-specific antibodies as a novel vector control strategy.","authors":"Xuebin Zhao, Jian Zheng, Weimin Zheng, Jinrong Lin, Guangshuo Ding, Xinhui Yu, Jun Cao, Yun Chen, Bo Shen, Gaoqian Feng","doi":"10.7555/JBR.39.20250135","DOIUrl":"https://doi.org/10.7555/JBR.39.20250135","url":null,"abstract":"<p><p>Mosquito-borne diseases pose a significant global health threat, necessitating novel vector control strategies. This study explores the potential of harnessing the host immunity against mosquitoes through vaccination. Using <i>Culex pipiens</i> ( <i>C. pipiens</i>) as the study model, we found polyclonal antibodies against <i>C. pipiens</i> abdomen significantly compromised the mosquito oviposition and increased mosquito mortality, primarily through the classical complement activation pathway. However, repeated exposure led to resistance, indicating potential adaptation. Proteomic analysis identified metabolic proteins as key targets, with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighting their roles in carboxylic acid metabolism, tyrosine degradation, and proteasome pathways. Intriguingly, cross-species reactivity was confirmed <i>via</i> Western blot, showing strong binding of <i>Culex</i>-specific antibodies to <i>Anopheles</i> and <i>Aedes</i> abdominal proteins. This study provides mechanistic insights into antibody-based mosquito suppression, highlighting its feasibility as a novel vector control strategy while underscoring the need for further research on resistance management and ecological impacts.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lijuan Zong, Chong Liu, Li Zhang, Xueyou Tao, Qingyan Tian, Xiaokai Zhou, Yu Wang, Na Shen, Jiaming Gong, Qingyuan Zhuang, Tong Wang, Wentao Liu, Ying Shen, Liang Hu
{"title":"Remote neuromuscular electrical stimulation upregulates MDK to enhance macrophage efferocytosis <i>via</i> LRP1 in wound healing.","authors":"Lijuan Zong, Chong Liu, Li Zhang, Xueyou Tao, Qingyan Tian, Xiaokai Zhou, Yu Wang, Na Shen, Jiaming Gong, Qingyuan Zhuang, Tong Wang, Wentao Liu, Ying Shen, Liang Hu","doi":"10.7555/JBR.38.20240375","DOIUrl":"https://doi.org/10.7555/JBR.38.20240375","url":null,"abstract":"<p><p>Neuromuscular electrical stimulation (NMES) is a well-established therapeutic approach for chronic wounds. Conventionally, NMES involves direct electrode contact with wounds or adjacent healthy skin; however, it is limited by the need for wound exposure and increased pain. Our preliminary study demonstrated the innovative application of remote NMES (rNMES) to the skeletal muscle of the distal calf, demonstrating the potential to accelerate wound healing in remote areas. rNMES is effective in human clinical trials in our previous work, although the underlying mechanisms remain unclear. As rNMES is often used to stimulate muscle contraction in long-term bedridden patients, we analyzed GEO database data and found that exercise promotes midkine (MDK) expression in muscle, a small secreted heparin-binding protein that interacts with multiple cell surface receptors to promote growth. MDK significantly enhanced macrophage efferocytosis in a low-density lipoprotein receptor-related protein 1 (LRP1)-dependent manner. Our findings demonstrate that rNMES upregulates MDK expression in skeletal muscles through the AMPK-ERK axis, facilitating its delivery to wounds through the circulatory system and promoting LRP1-mediated efferocytosis of apoptotic cells, thereby expediting wound healing.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-14"},"PeriodicalIF":2.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":"https://doi.org/10.7555/JBR.38.20240432","url":null,"abstract":"<p><p>As prevalence of obesity increases dramatically, obesity-associated cardiac dysfunction constitutes a huge challenge to human health. This study aims to find more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction. By retrospectively analyzing the clinical characteristics of 5,648 disease patients, we find that both plasma level of high-density lipoprotein (HDL-C) and blood monocyte count have significant associations with left ventricular ejection fraction (LVEF) impairment. Univariate and multivariate regression analyses reveal that monocyte to HDL-C ratio (MHR) is stronger in predicting risk of LVEF decline than both HDL-C and monocyte. Mediation analysis further indicates a mediative effect of high MHR on the obesity-associated cardiac systolic function decline. As such, our results demonstrate a superior role of MHR in predicting risk of obesity-associated decline in cardiac systolic function among the routine metabolic/inflammatory markers.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"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":"https://doi.org/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":2.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/10.7555/JBR.39.20250114","url":null,"abstract":"<p><p>V-raf-leukemia viral oncogene 1(RAF1), a serine/threonine protein kinase, is universally acknowledged 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 (NCD) feeding, over-expression of <i>Raf1</i> in AgRP neurons leads to obesity in mice characterized by increased body weight, fat mass, and impaired glucose tolerance. Conversely, knock-out of the <i>Raf1</i> gene in AgRP neurons protects against DIO, reducing fat mass and improving glucose tolerance. Mechanistically, <i>Raf1</i> activates the MAPK signaling pathway, culminating in cAMP response element-binding protein (CREB) phosphorylation, which enhances transcription of <i>Agrp</i> and <i>Npy</i>. Insulin stimulation further potentiates 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 the 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":"1-19"},"PeriodicalIF":2.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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
{"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":"https://doi.org/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 epithelial cell tight junctions regulation. Since renal pathophysiology is associated with gut barrier integrity, we hypothesized that <i>A. muciniphila</i> may have potential 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 diminished tubular necrosis and apoptosis. <i>A. muciniphila</i> preserved the intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome. <i>A. muciniphila</i> induced notably an increase in the relative abundance of phylum <i>Proteobacteria</i> while a decrease of <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 affecting modulation of pathways, including tyrosine metabolism, alanine/aspartate/glutamate homeostasis, cancer-related carbon flux, and GABAergic synaptic signaling. In conclusion, our findings demonstrate <i>A. muciniphila</i>'s renoprotective effects through gut-kidney axis modulation, laying the foundation for subsequent studies to verify the connection between gut microbiota and AKI.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}