Chen Li, Kerui Wang, Xingfeng Mao, Xiuxiu Liu, Yingmei Lu
{"title":"Upregulated inwardly rectifying K <sup>+</sup> current-mediated hypoactivity of parvalbumin interneuron underlies autism-like deficits in <i>Bod1</i>-deficient mice.","authors":"Chen Li, Kerui Wang, Xingfeng Mao, Xiuxiu Liu, Yingmei Lu","doi":"10.7555/JBR.38.20240394","DOIUrl":"https://doi.org/10.7555/JBR.38.20240394","url":null,"abstract":"<p><p>Parvalbumin-positive (PV <sup>+</sup>) interneuron dysfunction is believed to be linked to autism spectrum disorder (ASD), a neurodevelopmental disorder, characterized by social deficits and stereotypical behaviors. However, the underlying mechanisms of PV <sup>+</sup> interneuron dysfunction remain largely unclear. Here, we found that a deficiency of biorientation defective 1 ( <i>Bod1</i>) in PV <sup>+</sup> interneuron led to an ASD-like phenotype in <i>Pvalb-Cre</i>; <i>Bod1</i> <sup><i>f/f</i></sup> mice. Mechanistically, we identified that <i>Bod1</i> deficiency induced hypoactivity of PV <sup>+</sup> interneuron and hyperactivity of calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) neurons in the medial prefrontal cortex (mPFC), as determined by whole-cell patch-clamp recording. Additionally, it concurrently decreased the power of high gamma oscillation, as assessed by <i>in vivo</i> multi-channel electrophysiological recording. Furthermore, we found that <i>Bod1</i> deficiency enhanced inwardly rectifying K <sup>+</sup> current, leading to an increase in the resting membrane potential of PV <sup>+</sup> interneurons. Importantly, the gain-of-function of <i>Bod1</i> improved social deficits and stereotypical behaviors in <i>Pvalb-Cre</i>; <i>Bod1</i> <sup><i>f/f</i></sup> mice. These findings provide mechanistic insights into the PV <sup>+</sup> interneuron dysfunction and suggest new strategies for developing PV <sup>+</sup> interneuron therapies for ASD.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752769","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}
Izzatullo Ziyoyiddin O G Li Abdullaev, Ulugbek Gapparjanovich Gayibov, Sirojiddin Zoirovich Omonturdiev, Sobirova Fotima Azamjonovna, Sabina Narimanovna Gayibova, Takhir Fatikhovich Aripov
{"title":"Molecular pathways in cardiovascular disease under hypoxia: Mechanisms, biomarkers, and therapeutic targets.","authors":"Izzatullo Ziyoyiddin O G Li Abdullaev, Ulugbek Gapparjanovich Gayibov, Sirojiddin Zoirovich Omonturdiev, Sobirova Fotima Azamjonovna, Sabina Narimanovna Gayibova, Takhir Fatikhovich Aripov","doi":"10.7555/JBR.38.20240387","DOIUrl":"https://doi.org/10.7555/JBR.38.20240387","url":null,"abstract":"<p><p>Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases, including ischemia, heart failure, and hypertension. Under hypoxic conditions, oxygen deficiency disrupts oxidative phosphorylation in mitochondria, impairing ATP production and generating reactive oxygen species (ROS). These reactive species induce mitochondrial dysfunction, leading to oxidative stress, calcium imbalance, and activation of apoptosis pathways. Mitochondrial K-ATP (mitoK-ATP) and mitochondrial permeability transition pore (mPTP) channels are particularly affected, contributing to membrane potential loss, cytochrome C release, and cell death. This review explores the molecular mechanisms underlying hypoxia-induced cardiovascular diseases, with a focus on mitochondrial impairment, ion channel dysfunction, and ROS overproduction. Additionally, we examine hypoxia-inducible factor 1-alpha (HIF-1α) as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress. Antioxidants and compounds modulating key ion channels, such as K-ATP and mPTP, are highlighted as promising interventions for mitigating hypoxia-induced damage. Furthermore, we emphasize the potential of integrating <i>in vitro</i>, <i>in vivo</i>, and <i>in silico</i> studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-16"},"PeriodicalIF":2.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692233","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}
Xiang Wang, Xuan Wang, Mengsheng Zhao, Lijuan Lin, Yi Li, Ning Xie, Yanru Wang, Aoxuan Wang, Xiaowen Xu, Can Ju, Qiuyuan Chen, Jiajin Chen, Ruili Hou, Zhongwen Zhang, David C Christiani, Feng Chen, Yongyue Wei, Ruyang Zhang
{"title":"Bidirectional Mendelian randomization and mediation analysis of million-scale data reveal causal relationships between thyroid-related phenotypes, smoking, and lung cancer.","authors":"Xiang Wang, Xuan Wang, Mengsheng Zhao, Lijuan Lin, Yi Li, Ning Xie, Yanru Wang, Aoxuan Wang, Xiaowen Xu, Can Ju, Qiuyuan Chen, Jiajin Chen, Ruili Hou, Zhongwen Zhang, David C Christiani, Feng Chen, Yongyue Wei, Ruyang Zhang","doi":"10.7555/JBR.38.20240421","DOIUrl":"https://doi.org/10.7555/JBR.38.20240421","url":null,"abstract":"<p><p>Emerging evidence highlights the role of thyroid hormones in cancer, though findings are controversial. Research on thyroid-related traits in lung carcinogenesis is limited. Using UK Biobank data, we conducted bidirectional Mendelian randomization (MR) to assess causal links between lung cancer risk and thyroid dysfunction (hypothyroidism/hyperthyroidism) or function traits (free thyroxine [FT4], normal-range TSH). Furthermore, in the smoking-behavior stratified MR analysis, we evaluated the mediating effect of thyroid-related phenotypes on the association between smoking phenotype and lung cancer. We confirmed significant associations between lung cancer risk and hypothyroidism (hazards ratio [HR] = 1.14, 95% confidence interval [CI] = 1.03-1.26, <i>P</i> = 0.009) as well as hyperthyroidism (HR = 1.55, 95% CI = 1.29-1.87, <i>P</i> = 1.90×10 <sup>-6</sup>) in the UKB. Moreover, the MR analysis indicated a causal effect of thyroid dysfunction on lung cancer risk (OR <sub>inverse variance weighted [IVW]</sub> = 1.09, 95% CI = 1.05-1.13, <i>P</i> = 3.12×10 <sup>-6</sup> for hypothyroidism; OR <sub>IVW</sub> = 1.08, 95% CI = 1.04-1.12, <i>P</i> = 8.14×10 <sup>-5</sup> for hyperthyroidism). We found that FT4 levels were protective against lung cancer risk (OR <sub>IVW</sub> = 0.93, 95% CI = 0.87-0.99, <i>P</i> = 0.030). Additionally, the stratified MR analysis demonstrated the distinct causal effect of thyroid dysfunction on lung cancer risk among smokers. Hyperthyroidism mediated the effect of smoking behavior, especially the age of smoking initiation (17.66% mediated), on lung cancer risk. Thus, thyroid dysfunction phenotypes play causal roles in lung cancer development exclusively among smokers and act as mediators in the causal pathway from smoking to lung cancer.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596977","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":"Intermediate filaments and their associated molecules.","authors":"Jing Gao, Fumihiko Nakamura","doi":"10.7555/JBR.38.20240193","DOIUrl":"https://doi.org/10.7555/JBR.38.20240193","url":null,"abstract":"<p><p>Intermediate filaments (IFs) in human cells are the products of six distinct gene families, all sharing homology in a core rod domain. These IFs assemble into non-polar polymers, providing cytoplasmic and nuclear mechanical support. Recent research has revealed the active and dynamic properties of IFs and their binding partners. This regulation extends beyond cell mechanics to include migration, mechanotransduction, and tumor growth. This comprehensive review will catalog all human IF genes and IF-associated proteins (IFAPs), detailing their names, sizes, functions, associated human diseases, relevant literature, and links to resources like Uniprot and the Protein Atlas database. These links provide access to additional information such as protein structure, subcellular localization, disease-causing mutations, and pathology. Using this catalog, we will overview the current understanding of the biological functions of IFs and IFAPs. This overview is crucial for identifying gaps in their characterization and understanding IF-mediated mechanotransduction. Additionally, we will consider potential future research directions.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390892","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":"Letter to the Editor The presence of glutathione S-transferase in recombinant S100A9 alters its effect on human sperm function.","authors":"Estefania Massa, Gastón Prez, Sergio Ghersevich","doi":"10.7555/JBR.38.20240155","DOIUrl":"https://doi.org/10.7555/JBR.38.20240155","url":null,"abstract":"","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-4"},"PeriodicalIF":2.2,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390973","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":"Hepatic SIRT6 protects against cholestatic liver disease primarily <i>via</i> inhibiting bile acid synthesis.","authors":"Wen Zhang, Jiahui Wang, Luyao Yang, Yuyun Shao, Hongjun Peng, Longfeng Jiang, Liang Sheng","doi":"10.7555/JBR.38.20240172","DOIUrl":"https://doi.org/10.7555/JBR.38.20240172","url":null,"abstract":"<p><p>Cholestatic liver disease, caused by the accumulation of hazardous bile acids in the liver, may result in cirrhosis, fibrosis, or liver failure. Activation of SIRT6 prevents cholestasis-associated pathological events, such as oxidative stress and mitochondrial biogenesis disorders, and inhibits bile acid synthesis to alleviate cholestatic liver injury. However, it is still uncertain which pathway is responsible for the therapeutic effect of SIRT6 in reducing cholestasis. Therefore, we treated liver-specific <i>Sirt6</i> knockout mice with N-Acetylcysteine, Keap1-Nrf2-IN-1, or acadesine to remove oxidative stress and/or trigger mitochondrial biogenesis after cholestatic liver disease modeling, but these measures did not significantly improve cholestatic symptoms. However, MDL801, a SIRT6 agonist that downregulating CYP7A1, the key enzyme in bile acid synthesis, exhibited favorable therapeutic effects. In addition, the hepatic knockdown of <i>Cyp7A1</i> further confirmed that inhibition of hepatic bile acid synthesis might be the main pathway by which SIRT6 alleviates cholestatic liver disease. These findings provide a solid basis for the potential application of SIRT6 agonists in the treatment of cholestatic liver disease.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"1-17"},"PeriodicalIF":2.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769215","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}