Journal of Biomedical Research & Environmental Sciences最新文献

{"title":"FAM40A Deficiency Activates the Hippo Pathway to Promote Podocyte Apoptosis and Contribute to FSGS","authors":"Chen Z, Guo Z","doi":"10.37871/jbres2240","DOIUrl":"https://doi.org/10.37871/jbres2240","url":null,"abstract":"Background: Focal Segmental Glomerulosclerosis (FSGS), a major cause of end-stage renal disease, is characterized by podocyte loss via apoptosis and cytoskeletal disruption. Although dysregulation of the Hippo-YAP pathway is implicated in podocyte injury, upstream regulators of this pathway in FSGS pathogenesis remain elusive. Methods: To determine whether FAM40A deficiency precipitates FSGS, we generated heterozygous FAM40A+/− mice by CRISPR/Cas9-mediated deletion of exons 3-8 (Δex3-8 allele). At specified time points, kidneys were collected for histological examination (PAS, TEM), immunofluorescence, and Western blotting to quantify podocyte apoptosis and Hippo pathway activation. Finally, FAM40A+/− mice were randomly assigned to receive treatment with the MST1/2 inhibitor XMU-MP-1 (1 mg/kg/day) via intraperitoneal injection or vehicle treatment for 10 days. Endpoints included urinary Albumin-to-Creatinine Ratio (ACR), renal histology, podocyte density, and podocyte apoptosis markers. Results: We identified FAM40A as a novel negative regulator of the Hippo pathway in podocytes. FAM40A directly suppressed the kinase activity of Mst1/2, thereby preventing phosphorylation and inactivation of the downstream effector YAP. FAM40A deficiency triggered Mst1/2 activation, leading to YAP phosphorylation, nuclear exclusion, and transcriptional repression. This cascade resulted in podocyte apoptosis and exacerbated FSGS phenotypes In vivo. Conclusion: Our study defines the FAM40A-Mst1/2-YAP axis as a critical signalling pathway governing podocyte survival. Loss of FAM40A activates Hippo signalling to promote podocyte apoptosis and FSGS progression. While short-term MST1/2 inhibition ameliorates disease features in mice, further evaluation of safety and feasibility is required. These findings highlight FAM40A as a potential therapeutic target for FSGS.","PeriodicalId":15162,"journal":{"name":"Journal of Biomedical Research & Environmental Sciences","volume":"6 12","pages":"1911-1928"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.37871/jbres2240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147896211","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}

{"title":"The Abiwaijiwuli-Mufasili Attenuates Cartilage Damage and Ameliorates Osteoarthritis In vivo and In vitro By Regulating Serpina3-Mediated Wnt/b-Catenin Pathway","authors":"Qin Ma, Xinyi Liu, Xiaomin Wang, Rui Liu, Jingjing Li, Jialin Wu, Zhe Xu, Peipei Wang, Wei Chen","doi":"10.37871/jbres2132","DOIUrl":"https://doi.org/10.37871/jbres2132","url":null,"abstract":"Introduction: Aibiwajiwuli-Mufasili (ABYJ), an ancient classic formula of Uyghur medicine, is used to treat osteoarthritis (OA) in clinical practice in China, yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic effect of ABYJ on the MIA-induced OA model and ATDC5 cell inflammatory model, and further demonstrated the cartilage renovation of OA through the Serpina3-mediated Wnt/β-catenin pathway. Methods: In this study, the chemical composition of ABYJ were elucidated using optimized ultrahigh-performance liquid chromatography coupled with quadrupole exactive-orbitrap mass spectrometry (UPLC-Q-Exactive-orbitrap-MS). In an in vivo experiment, rats were randomly divided into 6 groups, the OA model in rats were induced by intraarticular injection with sodium iodoacetate (MIA) solution (60mg·mL-1), behavior of model animals were evaluated by Lequesne MG, and Micro-CT imaging was used for morphological evaluation, Hematoxylin-Eosin (HE) and Safranin O-fast green (SF) staining were used for histology assessment. In addition, 4D Label-free quantification proteomics analysis was used to further explore proteins differentially expressed after different treatment. The expression of Serpina3 and proteins on the Wnt/β-catenin signaling pathway in the rats OA models were determined by Western blot. In vitro, a LPS-induced ATDC5 cells inflammation model was used to validate the possible active ingredients and signaling pathway. Result: Our studies had shown that a total of 75 active ingredients of ABYJ formula were identified by UPLC-Q-Exactive-orbitrap-MS, Ten marker compounds were identified using orthogonal partial least-squares discrimination analysis, which indicated colchicine and aloin may be the material basis for ABYJ. ABYJ reversed MIA-induced behavioral characteristics, articular inflammatory lesions, the pathological changes and micro structure of knee joint tissue, balance conversion of cartilage cell in rat and reduced the protein expression level of wnt5a, β-catenin and MMP13, while increased Serpina3. A similar rule was demonstrated, the result in vitro suggested ABYJ could inhibit LPS-induced overproduction of pro-inflammatory mediators in ATDC5 cells, including IL-1β, TNF-α and increased the expression level of Serpina3, the increasing expression of Serpina3 would induce [Ca2+] i influx, accordingly, chondrocyte apoptosis was inhibited. Conclusion: These findings suggest that ABYJ exerts therapeutic effects on joint inflammation and cartilage damage by regulating the wnt5a/β-catenin signaling pathway and modulating the expression of key proteins such as Serpina3, highlighting its potential as a promising candidate for the treatment of joint-related diseases.","PeriodicalId":15162,"journal":{"name":"Journal of Biomedical Research & Environmental Sciences","volume":"6 6","pages":"792-807"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.37871/jbres2132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879361","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}

{"title":"Synergy of Ergothioneine and Tyrosine-Arginine Peptide to boost β-Endorphin Generation to Alleviate Stress-Induced Dermatological Disorders","authors":"Fangru Jiang, Zhe Liu","doi":"10.37871/jbres2086","DOIUrl":"https://doi.org/10.37871/jbres2086","url":null,"abstract":"Objective: This study aimed to investigate the synergistic effects of Ergothioneine (EGT) and Tyrosine-Arginine Peptide (TAP) in promoting β-endorphin production in the skin, aiming to alleviate stress-induced dermatological disorders. Method: An optimal ratio between EGT and TAP for β-endorphin stimulation was ascertained through cell experiments using human dermal fibroblasts and immortalized human keratinocytes. These cells were treated with cortisol to induce stress-related conditions. β-endorphin content was measured following treatment with various EGT-TAP ratios. Additional gene expression analysis was conducted to observe the regulatory effects of the combination on key skin health indicators, using specific primers and qPCR methods. Results: The combination of EGT and TAP displayed a significant synergistic effect on β-endorphin production, with the optimal ratio identified as 9:1. This ratio resulted in a 175.75% and 190.20% increase in β-endorphin generation compared to individual EGT and TAP treatments, respectively. The EGT-TAP combination also mitigated cortisol-induced disruptions in gene expression, positively affecting the expression of extracellular matrix proteins and mitigating the negative effects of stress on skin cell models. Conclusion: The combined administration of EGT and TAP at a 9:1 ratio significantly boosts β-endorphin levels and beneficially regulates gene expression under stress-induced conditions in skin cells. This synergy presents a novel and effective approach to enhance skin health and counteract the detrimental impacts of stress, offering a promising avenue for the development of advanced dermatological treatments.","PeriodicalId":15162,"journal":{"name":"Journal of Biomedical Research & Environmental Sciences","volume":"6 4","pages":"312-319"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.37871/jbres2086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147888878","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}

{"title":"The Effects of Vernalization and Photoperiod Genes Composition on Heading Date in Wheat","authors":"Shaoguang Sun, Yifei Xue, Kui Zhang","doi":"10.37871/jbres1893","DOIUrl":"https://doi.org/10.37871/jbres1893","url":null,"abstract":"The vernalization characteristics of wheat are mainly controlled by vernalization and photoperiod genes, which determine the winter-spring habit and heading-flowering of wheat, and affect its environmental adaptability. In order to understand the effects of vernalization and photoperiod genes on heading date, 12 common wheat varieties widely cultivated in the Huang-Huai region were used as experimental materials, and the effects of different low-temperature vernalization treatments on wheat heading date were studied. Using molecular markers from previous studies, the allelic variations and genotypes of vernalization genes (VRN-A1, VRN-B1, VRN-D1 and VRN-B3) and photoperiod genes (Ppd-A1, Ppd-B1, Ppd-D1) were detected. By identifying the heading date in a controlled greenhouse, the relationship between the vernalization and photoperiod genes composition and the heading date phenotype was analyzed. The experimental results showed that different wheat varieties had different phenotypes after different vernalization treatments. Tian min 198 carried a dominant vernalization gene, and its vernalization characteristics were expressed as spring wheat varieties, with low requirements for low-temperature vernalization. Wheat without a dominant vernalization gene had winter wheat characteristics, with high requirements for low-temperature vernalization. Wheat varieties carrying a dominant vernalization gene can be used to improve late-maturing wheat varieties, and serve as valuable germ plasma resources for variety improvement and introduction. Exploring the effects of different wheat vernalization and photoperiod genes composition on heading date is beneficial to provide a scientific basis for the rational use of wheat varieties, and studying the vernalization and photoperiod genes composition has guiding significance for wheat introduction and ecological breeding.","PeriodicalId":15162,"journal":{"name":"Journal of Biomedical Research & Environmental Sciences","volume":"5 3","pages":"279-289"},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://doi.org/10.37871/jbres1893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147878385","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}

{"title":"<i>Vernonia amygdalina</i> Delile Induces Apoptotic Effects of PC3 Cells: Implication in the Prevention of Prostate Cancer.","authors":"Clement G Yedjou,&nbsp;William Johnson,&nbsp;Solange S Tchounwou,&nbsp;Shaloam Dasari,&nbsp;Sylvianne Njiki,&nbsp;Paul B Tchounwou","doi":"10.37871/jbres1564","DOIUrl":"https://doi.org/10.37871/jbres1564","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) is one of the common cancers in males and its incidence keeps increasing globally. Approximately 81% of PCa is diagnosed during the early stage of the disease. The treatment options for prostate care include surgery, radiotherapy, and chemotherapy, but these treatments often have side effects that may lead to issues such as impotence or decreased bowel function. Our central goal is to test the apoptotic effects of <i>Vernonia amygdalina</i> Delile (an edible medicinal plant that is relatively inexpensive, nontoxic, and virtually without side effects) for the prevention of PCa using human adenocarcinoma (PC-3) cells as a test model.</p><p><strong>Methods: </strong>To address our central goal, PC-3 cells were treated with <i>Vernonia amygdalina</i> Delile (VAD). Cell cycle arrest and cell apoptosis were evaluated by Flow Cytometry assessment. Nucleosomal DNA fragmentation was detected by agarose gel electrophoresis.</p><p><strong>Results: </strong>Flow cytometry data showed that VAD induced cell cycle arrest at the G0/G1 checkpoint and significantly upregulated caspase-3 in treated cells compared to the control cells. Agarose gel electrophoresis resulted in the formation of DNA ladders in VAD-treated cells.</p><p><strong>Conclusions: </strong>These results suggest that inhibition of cancer cell growth, induction of cell cycle arrest, and apoptosis through caspase-3 activation and nucleosomal DNA fragmentation are involved in the therapeutic mechanisms of VAD as a candidate drug towards the prevention and/or treatment of PCa.</p>","PeriodicalId":15162,"journal":{"name":"Journal of Biomedical Research & Environmental Sciences","volume":"3 9","pages":"1118-1124"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9793873/pdf/nihms-1841700.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10800170","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}

{"title":"Improving Invasive Breast Cancer Care Using Machine Learning Technology.","authors":"Clement G Yedjou, Solange S Tchounwou, Jameka Grigsby, Kearra Johnson, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Breast cancer (BC) is the most common malignancy in women worldwide. In the United States, the lifetime risk of developing an invasive form of breast cancer is 12.5% among women. BC arises in the lining cells (epithelium) of the ducts or lobules in the glandular tissue of the breast. The goal of the present study was to use machine learning (ML) as a novel technology to assess and compare the invasive forms of BC including, infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mucinous carcinoma. To achieve this goal, we used ML algorithms and collected a dataset of 334 BC patients available at https://www.kaggle.com/amandam1/breastcancerdataset and interpreted this dataset based on the form of BC, age, sex, tumor stages, surgery type, and survival rate. Among the 334 patients, 70% were diagnosed with infiltrating ductal carcinoma, 27% with infiltrating lobular carcinoma, and 3% with mucinous carcinoma. Overall, out of 334 BC patients: 64 (19.16%) were in stage I, 189 (56.59%) in stage II, and 81 (24.25%) in stage III. Sixty-six, 67, 96, and 105 patients underwent lumpectomy, simple mastectomy, modified radical mastectomy, and other types of surgery, respectively. The survival rates were 83.4% for stage I, 79.1% for stage II, and 77% for stage III. Findings from the present study demonstrated that ML provides an important tool to curate large amount of BC data, as well as a scientific means to improve BC outcomes.</p>","PeriodicalId":15162,"journal":{"name":"Journal of Biomedical Research & Environmental Sciences","volume":"3 8","pages":"980-984"},"PeriodicalIF":0.0,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520759/pdf/nihms-1837289.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40389963","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}