Journal of Biosciences最新文献

{"title":"Preconditioned umbilical-cord mesenchymal stem-cell exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miRNA signaling rather than HGF signaling.","authors":"Ratna Puspita, Ahmad Aulia Jusuf, Radiana Dhewayani Antarianto, Andri Pramesyanti Pramono","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Biliary atresia (BA) is a prominent cause of liver cirrhosis in pediatric patients with a high pediatric end-stage liver disease (PELD) score and a Laennec score of 4 at the Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia. Bile duct-ligated rat models have been used to mimic the clinical condition of BA partially. This study aims to evaluate the potential miRNAs of preconditioned umbilical-cord mesenchymal stem-cell exosomes (UC-MSC-exosomes) in comparison with the combined exosomes-HGF effect on liver histology, liver function, and hepatocyte-signaling in bile duct-ligated rats. Characterization of preconditioned UC-MSC-exosomes fulfilled the ISEV 2018 criteria. Liver histology showed trends of hepatocytes, inflammatory cells, and oval cell numbers returning to slightly below normal levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination, with no statistically significant difference. A significant difference in bile duct proliferation post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination was observed when compared with the control. Trends towards lower deposition of collagen around the porta area and total area fractions post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination showed no statistically significant difference; however, there was a slightly lower total collagen area fraction in the exosomes-HGF combination group. Functional hepatocyte preservation was indicated by increased albumin expression and partially improved CYP3A4 levels post-preconditioned UC-MSC-exosomes or the exosomes-HGF combination. There was also a different trend in functional hepatocyte biochemical markers, SGOT (AST) and SGPT (ALT), between preconditioned UC-MSC-exosomes and the exosomes-HGF combination. NanoString microarray analysis of liver tissue and bioinformatics analysis were done to investigate in-depth hepatocyte signaling. miRNA profiling of the liver from preconditioned UC-MSC-exosomes identified the upregulation of hsa-miR-1-3p and hsa-miR-372-3p, which inhibit key signaling pathways, e.g., MAPK, PI3K-AKT, and NF-κB, and the downregulation of hsa-miR-520a-3p, which promotes hepatocyte proliferation and survival. miRNA profiles of the liver from the exosomes-HGF combination identified five different miRNA expressions (upregulated hsa-miR-144-3p, hsa-let7-5p, hsa-let7a-5p, hsa-let7e-5p, and hsa-miR-32-5p) and shared only one similar miR with the exosomes-treated liver (downregulated hsa-520a-3p). These miR differences contribute to the hepatocyte signaling in the exosomes-HGF combination group. Preconditioned UC-MSC-exosomes preserve functional hepatocytes in bile duct-ligated rats through alternate miR-mediated signaling rather than HGF signaling.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-sectional associations between plasma copper, zinc and prediabetes among rural Indian adolescent girls: baseline data from the DERVAN cohort (DERVAN-8).","authors":"Suvarna Patil, Netaji Patil, Rohit Bhat, Pallavi Hardikar-Bhat, Sagar Chavan, Ankit Kud, Omkar Dervankar, Charudatta Joglekar","doi":"10.1007/s12038-026-00597-9","DOIUrl":"https://doi.org/10.1007/s12038-026-00597-9","url":null,"abstract":"<p><p>Copper and zinc are essential minerals for proper metabolic function, and their imbalance could potentially cause prediabetic conditions. We investigated associations of copper and zinc with glycaemic parameters in 1473 adolescent girls aged 15-18 years at baseline in the DERVAN cohort study. Anthropometric indices, glucose, insulin and glycated haemoglobin were measured, and prediabetes was diagnosed using American Diabetes Association criteria. Copper was positively associated with fasting glucose, insulin and insulin resistance, and inversely associated with insulin sensitivity. Zinc was positively associated with fasting glucose and inversely associated with beta-cell function. In multivariate analysis, girls in the third and fourth quartiles of plasma copper had significantly higher odds of prediabetes than those in the lowest quartile. Longitudinal follow-up of the cohort will clarify whether these trace minerals contribute to progression toward diabetes.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 28","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Nischarin increases with postnatal hippocampal maturation and regulates cofilin phosphorylation.","authors":"Aiwu Huang, Changfen Xu, Wanghuan Chen, Jiaqi Zhang, Xiong Zhang, Yuemin Ding","doi":"10.1007/s12038-026-00598-8","DOIUrl":"https://doi.org/10.1007/s12038-026-00598-8","url":null,"abstract":"<p><p>The hippocampus, critical for memory integration and synaptic plasticity, undergoes cytoskeletal reorganization during development and maturation, a process regulated by cofilin phosphorylation dynamics. Nischarin is a tumor-suppressive scaffold protein, yet its role in neurodevelopment remains unexplored. This study investigated the spatiotemporal expression of Nischarin and its effect on cofilin during postnatal hippocampal maturation in rats. Using western blot, quantitative reverse transcription-polymerase chain reaction, and shRNA-mediated knockdown in adult rat hippocampal neurons and Neuro-2a cells, we demonstrated that Nischarin expression progressively increased from postnatal day 7 to P28, inversely correlating with declining phosphorylated cofilin levels. Mechanistically, Nischarin reduced phosphorylated cofilin levels by suppressing PAK1/LIMK1 activity. Immunofluorescence revealed that Nischarin knockdown disrupted the subcellular distribution of phosphorylated cofilin by impeding its translocation from the cytoplasm to the nucleus. These findings indicate Nischarin regulates cofilin activity via dual mechanisms: inhibiting phosphorylation through the PAK1/LIMK1 pathway and modulating phosphorylated cofilin nuclear translocation. The study highlights the role of Nischarin in hippocampal neuronal maturation by orchestrating cytoskeletal remodeling and suggests its therapeutic potential in neurodegenerative diseases linked to cofilin dysregulation.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 27","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effects of sorafenib and cilostazol in HepG2 cells.","authors":"Heba Effat, Omnia Mohamed, Marwa Sharaky, Sally Heikal, Shrouk Elshahawy, Eman Gayad","doi":"10.1007/s12038-026-00607-w","DOIUrl":"10.1007/s12038-026-00607-w","url":null,"abstract":"<p><p>Sorafenib, an established multi-kinase inhibitor, is a cornerstone treatment for advanced hepatocellular carcinoma (HCC). This study evaluated the efficacy of combining sorafenib with cilostazol, a phosphodiesterase-3 inhibitor with emerging anticancer properties, in HepG2 cells. Cell proliferation, apoptosis, and expression of VEGF, SMAD4, Bcl-2, TGF-beta, Bax, and caspase-3 were assessed. Combination treatment significantly reduced the IC50 of sorafenib and markedly decreased colony formation compared with either monotherapy. Enhanced apoptosis was observed through increased Bax and caspase-3 levels and reduced Bcl-2 expression. In addition, combined treatment produced potent anti-angiogenic effects through suppression of VEGF and TGF-beta. These findings demonstrate a synergistic interaction between sorafenib and cilostazol and suggest that this combination may represent a promising therapeutic strategy for hepatocellular carcinoma management.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 35","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of calcium responses by K_IR current inactivation in medium spiny neurons.","authors":"John Eric Steephen, Mithun Padmakumar, Rohit Manchanda","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Synaptic plasticity within cortico-striatal circuits critically influences learning and behavior, with the nucleus accumbens (NAc) serving as a key mediating structure. Within the NAc, medium spiny neurons (MSNs) are known to mediate input integration, whose dendritic calcium levels are thought to influence cortico-striatal plasticity. Calcium responses have been observed to correlate with firing frequency and earlier firing onset. Inward rectifying potassium (K_IR) currents inactivate significantly in ~40% of NAc MSNs. Studies have shown that this inactivation enhances firing frequency and advances firing onset. On the basis of these findings, we hypothesized that K_IR inactivation may enhance intracellular calcium levels in MSNs, with implications for synaptic plasticity. Using an 189-compartment computational model of the MSN, the influence of K_IR inactivation on calcium dynamics was investigated. We found that the amplitude of calcium influx was more than twice as large in the tertiary dendrite and at least 9% higher for higher input currents in response to K_IR inactivation. Additionally, the average calcium concentration increased by up to 26.1% in the soma, with enhancements of 4.3-21.4% in the dendrites. Our findings suggest that K_IR inactivation may significantly modulate synaptic plasticity, thereby impacting the learning mediated by the NAc core.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Birds and bees do not express RAGE: comparative physiology and non-conventional model organisms hold the key to hyperglycemia tolerance.","authors":"Renee M Borges","doi":"10.1007/s12038-026-00595-x","DOIUrl":"10.1007/s12038-026-00595-x","url":null,"abstract":"<p><p>Much of the diversity of life is fueled by sugar. The Maillard reaction and subsequent formation of advanced glycated end products (AGEs) are key contributors to hyperglycemia-associated pathologies. Interestingly, birds maintain glucose levels higher than mammals yet avoid diabetic complications. This resistance is attributed to adaptations such as reduced glycation susceptibility of serum proteins, efficient glucose transport mechanisms, and metabolic routing of excess glucose into fat rather than glycogen. Birds possess physiological traits including insulin resistance, constitutive glucose transporter expression, and enhanced antioxidant responses mediated by Nrf2 pathways, enabling them to tolerate high metabolic rates and oxidative stress. Nectar-feeding birds show genetic adaptations such as positive selection in MLXIPL, facilitating high sugar metabolism. Similarly, insects like bees rely on trehalose, a non-reducing sugar, as their primary circulating carbohydrate, which protects against glycation damage. Comparative physiology of birds, insects, and other non-conventional organisms highlights alternative metabolic strategies that avoid hyperglycemia-induced damage. These insights suggest that studying diverse biological systems can provide valuable understanding of metabolic regulation and potential therapeutic strategies for human diseases such as diabetes. Comparative approaches may uncover evolutionary mechanisms that mitigate glycation and oxidative damage while sustaining high energy demands.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolomic signatures and gut microbiota dynamics in perinatally undernourished F₁ offspring: Decoding the metabolic footprint.","authors":"Anu V Ranade, Pramukh Subrahmanya Hegde, Megha Bhat Agni, Praveen Rai, Shubham Sukerndeo Upadhyay, Anjana Aravind, Thottethodi Subrahmanya Keshava Prasad, K M Damodara Gowda","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The Developmental Origins of Health and Disease (DOHaD) hypothesis asserts that detrimental prenatal conditions, such as dietary deficiencies, may lead to enduring health consequences. Perinatal undernutrition, an important concern during fetal development, may affect growth and metabolic programming, resulting in lasting health implications. Maternal nutrition is crucial in modulating fetal endocrine systems and metabolic functions, influencing the development, blood circulation, and nutrient absorption. The present study examines the impact of perinatal undernutrition on the composition of gut microbiota and metabolite levels in offspring of undernourished dams, using an Albino Wistar rat model. Furthermore, we investigated the combined impact of astaxanthin (AsX) and docosahexaenoic acid (DHA) supplementation on cardiometabolic outcomes in these progenies. Astaxanthin, a powerful antioxidant, and DHA, an omega-3 fatty acid, have shown the ability to favorably alter the gut flora and metabolic pathways. The direct influence of AsX on gut microbiota remains unexplored, whereas DHA's role in fostering beneficial microbes and regulating metabolite production is well documented. The current study used metabolomics and metagenomics to investigate the intricate relationship between metabolites and gut microbiota in health and disease, offering insights into fetal programming and possible strategies to improve offspring health. The results highlight the need to address perinatal undernutrition and enhance gut health through targeted dietary interventions to improve long-term health outcomes.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the functional roles of secondary metabolites in Brassica defense networks.","authors":"Neha Singh, Shubhra Barwa, Neelam Prabha Negi, Geeta Prakash, Khushbu Lamba, Anjana Rustagi","doi":"10.1007/s12038-026-00600-3","DOIUrl":"10.1007/s12038-026-00600-3","url":null,"abstract":"<p><p>Plants produce a diverse array of secondary metabolites (SMs) that play critical roles in adaptation to environmental challenges and defense against pathogens and herbivores. Brassica species accumulate a wide range of SMs, including glucosinolates and their hydrolysis products (isothiocyanates, nitriles, thiocyanates, epithionitriles, and oxazolidinethiones), phenolics, tannins, cyanogenic glycosides, alkaloids, flavonoids, and terpenoids. These compounds function as defense molecules, antioxidants, signaling mediators, and regulators of plant growth and stress responses. This review summarizes current knowledge on the biosynthesis, regulation, and functional roles of Brassica secondary metabolites in plant defense networks. The review highlights the glucosinolate-myrosinase system as a central defense mechanism against insect pests, herbivores, and phytopathogens. The roles of phenolics, tannins, alkaloids, and other nitrogen-containing metabolites in mitigating biotic stress and enhancing resilience are also discussed. Particular emphasis is placed on the molecular regulation of SM biosynthesis by transcription factors including MYBs, MYCs, WRKYs, ERFs, and NAC proteins, as well as by phytohormones such as jasmonic acid, salicylic acid, and brassinosteroids. These signaling pathways coordinate defense responses through activation of genes involved in secondary metabolism, antioxidant activity, and pathogen resistance. Advances in molecular breeding, transgenic approaches, genome editing, metabolomics, and bioinformatics provide opportunities to manipulate secondary metabolite pathways for the development of disease-resistant, stress-tolerant, and nutritionally improved Brassica cultivars. Enhanced understanding of the interaction between secondary metabolites, transcriptional regulators, and phytohormone networks will facilitate sustainable crop improvement strategies while reducing dependence on chemical pesticides and promoting environmentally friendly agriculture.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 31","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypercholesterolemia-induced impairment in sorafenib functionality is overcome by avasimibe co-treatment.","authors":"Dipti Athavale, Himanshi Yaduvanshi, Firoz Khan Bhati, Shyamananda Singh Mayengbam, Tushar H More, Srikanth Rapole, Manoj Kumar Bhat","doi":"10.1007/s12038-026-00593-z","DOIUrl":"https://doi.org/10.1007/s12038-026-00593-z","url":null,"abstract":"<p><p>Avasimibe, a cholesterol-lowering drug with proven safety in clinical trials, has also been repositioned as an anticancer agent in various preclinical investigations. A study from our group reported that hypercholesterolemia promotes hepatocellular carcinoma (HCC) cell survival and impairs the cytotoxic effect of sorafenib, a kinase inhibitor. In the present study, we demonstrate that under hypercholesterolemic conditions, the anticancer efficacy of sorafenib in HCC is enhanced by co-treatment with avasimibe. To elucidate the role of hypercholesterolemia in sorafenib efficacy, both in vitro and in vivo models of HCC were used. In vitro, co-treatment with both drugs synergistically inhibited HCC cell viability and induced cell death under both normal and hypercholesterolemic conditions. At the molecular level, the downregulation of extracellular signal-regulated kinase signaling and the induction of endoplasmic reticulum stress are likely to contribute to the combinatorial cytotoxic effect of sorafenib and avasimibe in vitro. In mice fed on a high-cholesterol diet, the efficacy of sorafenib was restored by co-administration of avasimibe. Collectively, these findings suggest that the reduction in sorafenib efficacy is due to a hypercholesterolemic phenotype that can be restored by avasimibe co-treatment, with implications for treatment strategy.</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 24","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148317120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re-imagining T-cell receptor signaling: parallel paths may be key to discriminatory power.","authors":"Akshay Tiwari, Narendra M Dixit","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>T-cells are important arms of our immune system and are central to our fight against pathogens and cancers (Baral <i>et al.</i> 2019a; Waldman <i>et al.</i> 2020). They recognize infected and cancerous cells and help destroy them while leaving uninfected/normal cells intact. They accomplish this tricky task with exquisite precision. How they do so has been an enigma and the subject of intense investigation for decades (Chakraborty and Weiss 2014; Courtney <i>et al.</i> 2018).</p>","PeriodicalId":15171,"journal":{"name":"Journal of Biosciences","volume":"51 ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}