{"title":"Genetic diversity of the Y-chromosome in domestic animals: from evolutionary insights to functional implications.","authors":"Manjit Panigrahi, Divya Rajawat, Sonali Sonejita Nayak, Surya Kant Verma, Anal Bose, Nishu Bharia, Triveni Dutt","doi":"10.1007/s11033-025-11049-2","DOIUrl":"https://doi.org/10.1007/s11033-025-11049-2","url":null,"abstract":"<p><p>The Y-chromosome, a hallmark of male-specific inheritance, holds immense importance in domestic animal genetics. It harbors the Sex-determining Region Y (SRY) gene, which initiates testis development and male differentiation. Due to its strict paternal inheritance and minimal recombination outside the pseudoautosomal regions (PARs), the Y-chromosome is a stable and reliable marker for studying male lineage, phylogeography, and patrilineal evolution in domestic species. Despite these constraints, advances in sequencing technologies and molecular tools (like Y-STRs and Y-SNPs) have enabled in-depth exploration of Y-chromosomal diversity. A comparative overview of the Y-chromosome architecture is presented for major domestic species, including cattle, sheep, goats, pigs, horses, dogs, and poultry. The genes present on the Y-chromosome are of growing interest in breeding programs to enhance male reproductive performance and disease resistance. Understanding Y-chromosome diversity is also critical for conservation genetics, especially in preserving indigenous breeds and managing genetic bottlenecks. This review also highlights the importance of Y-chromosome analysis in breeding strategies, particularly when combined with advanced tools. Studying Y-chromosome diversity provides valuable insights into male-driven domestication events. With the ongoing development of high-resolution molecular techniques, the scope for Y-chromosome-based research in domestic animals is expanding rapidly, promising to improve both scientific understanding and practical outcomes in animal breeding and conservation.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1031"},"PeriodicalIF":2.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292835","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":"A systematic analysis of various clonal lineages of colistin-resistant Klebsiella pneumoniae with mgrB mutations.","authors":"Santosh Kumar Singh, Minakshi Gupta, Khageshwar Mahato, Shweta Shrivastava, Vijay Kant Pandey, Darshan Kumar, Jasai Mardi, Dipika Priya, Kwang-Hyun Baek, Awdhesh Kumar Mishra","doi":"10.1007/s11033-025-11132-8","DOIUrl":"https://doi.org/10.1007/s11033-025-11132-8","url":null,"abstract":"<p><p>Klebsiella pneumoniae poses a significant health threat due to their pathogenicity and high propensity to acquire resistance to wide range of antimicrobial agents. Colistin, a non-ribosomal secondary cationic amphipathic peptide, exhibits bactericidal activity. Despite its known nephrotoxic and neurotoxic effects, colistin remains in use for treating multidrug-resistant bacterial infections. However, the widespread use of colistin has led to the global emergence of colistin-resistant K. pneumoniae strains. This review investigates the global epidemiology of various clonal lineages of colistin-resistant K. pneumoniae. A comprehensive search was conducted across various databases, including PubMed, ScienceDirect, and Google Scholar. A total of 81 distinct colistin-resistant K. pneumoniae sequence types were identified worldwide, with the highest clonal diversity observed in India and China (n = 16), followed by South Korea (n = 15), Brazil (n = 14), France and Saudi Arabia (n = 12), Nigeria (n = 11), Colombia (n = 9), and Italy and Taiwan (n = 8). eBURST analysis grouped 87 colistin-resistant sequence types into 51 singletons and 9 clonal complexes, forming 5 distinct clonal groups. The findings indicate a broad global distribution of colistin-resistant K. pneumoniae clones, marked by diverse mgrB mutations. This underscores the urgent need for robust monitoring and surveillance to curb the development and dissemination of colistin-resistant K. pneumoniae and to ensure effective infection control measures.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1029"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286579","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":"Modulation of inflammatory and cuproptotic crosstalk by Ethyl and propyl gallate: a multi-targeted strategy against experimental colitis.","authors":"Priyanka Raju Chougule, Sukesh Narayan Sinha, Sudip Ghosh, Sangaraju Rajendra, Saikanth Varma, Suresh Challa, Manjula Bhanoori","doi":"10.1007/s11033-025-11098-7","DOIUrl":"https://doi.org/10.1007/s11033-025-11098-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by oxidative stress, immune dysregulation, and epithelial barrier dysfunction. This study investigated the protective effects of two phenolic antioxidants derived from food sources, ethyl gallate (EG) and propyl gallate (PG), in conjunction with copper-enriched water, against dextran sulfate sodium (DSS)-induced colonic injury in mice. The focus was on the modulation of inflammation, oxidative stress, apoptosis, and the novel regulatory pathway of cuproptosis.</p><p><strong>Method: </strong>The experimental protocol entailed the induction of colitis through the administration of 2.5% DSS in drinking water over a period of seven days, along with oral administration of EG, PG, or their combination at a dosage of 50 mg/kg for 21 days. Cytokine levels were quantified using ELISA, while qPCR and western blotting were employed to analyze inflammatory markers (NF-κB, JAK2-STAT3), oxidative markers (Nrf2/HO-1), apoptotic markers (Bcl2/Bax), and cuproptotic markers (FDX1/DLAT). The TUNEL assay was used to evaluate apoptotic cell death.</p><p><strong>Results: </strong>EG and PG significantly reduced the levels of TNF-α, IL-1β, and IL-6 by inhibiting the NF-κB and JAK-STAT signalling pathways while concurrently increasing the levels of IL-37. Oxidative stress is alleviated through activation of the Nrf2/HO-1 pathway. Apoptosis was suppressed via upregulation of Bcl-2/Bcl-XL and downregulation of BAX, as corroborated by the TUNEL assay results. Additionally, EG and PG mitigated cuproptosis by decreasing the expression of FDX1, DLAT, and LIAS, thereby maintaining intestinal barrier integrity.</p><p><strong>Conclusion: </strong>The observations presented herein offer significant mechanistic insights into the role of ethyl gallate (EG) and propyl gallate (PG), in conjunction with copper-enriched water, in the management of ulcerative colitis through the modulation of inflammatory, oxidative, apoptotic, and cuproptotic pathways. Notably, this study is the first to document the effects of EG and PG on cuproptosis-related proteins and their potential role in alleviating DSS-induced colonic toxicity, thereby supporting further investigation of their application as food-based therapeutic agents for intestinal disorders.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1030"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286555","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":"Major genic factors influencing nitrogen response in rice revealed through in-silico characterization and expression dynamics of a set of novel candidate genes.","authors":"Jeet Roy, Ankur Poudel, Sagnik Chanda, Antara Das, Amitha Mithra Sevanthi, Jayanthi Madhavan, Viswanathan Chinnusamy, Pranab Kumar Mandal","doi":"10.1007/s11033-025-11139-1","DOIUrl":"https://doi.org/10.1007/s11033-025-11139-1","url":null,"abstract":"<p><strong>Background: </strong>Rice is a primary cereal and staple food worldwide. Although rice cultivation requires a large amount of nitrogenous fertilizer, its nitrogen use efficiency (NUE) is only 20-50%. Therefore, in addition to soil and fertilizer management, it is crucial to improve the genetic potential of nitrogen use efficiency (NUE) in rice for this complex polygenic trait, which remains largely unexplored.</p><p><strong>Methods and results: </strong>In the present study, 20 promising novel genes identified earlier were first characterized in silico, followed by expression analysis in different tissues and growth stages under N-optimal and N-stress conditions in the contrasting rice genotypes N22 (poor NUE) and IR64 (superior NUE). We observed some special features in different genes, like the absence of essential coding sequences (ATG or stop codons), untranslated transcripts (lncRNAs), overlapping gene sequences, and genes with antisense transcripts. Due to this complexity, the functions of these genes are yet to be determined. Expression profiling under nitrogen stress showed upregulation in both vegetative and reproductive stages in N22, while in IR64, upregulation was observed at the seedling stage and downregulation during the reproductive stage.</p><p><strong>Conclusion: </strong>Apart from functional proteins, nitrogen stress-responsive genes in rice also transcribe into lncRNAs, some of them showing allelic variation across genotypes. These genes are regulated by light and hormone-responsive promoter elements under nitrogen stress. This study improves the understanding of important N-stress responsive genes and alleles in the two contrasting genotypes. The present study aims to identify promising genes with unique features for their functional validation, and for supporting the molecular breeding programs to develop rice lines with improved NUE.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1025"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286595","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}
Sahar Mostajeran, Mohsen Ehsan, Mahla Lashkari, Hajar Mardani Valandani, Ahmad Fatemi, Ali Bazi, Mahdieh Mirzaie, Muhammad Hossein Ashoub, Roohollah Mirzaee Khalilabadi
{"title":"Zataria multiflora extract enhances imatinib-induced cytotoxicity in chronic myeloid leukemia and multiple myeloma cells.","authors":"Sahar Mostajeran, Mohsen Ehsan, Mahla Lashkari, Hajar Mardani Valandani, Ahmad Fatemi, Ali Bazi, Mahdieh Mirzaie, Muhammad Hossein Ashoub, Roohollah Mirzaee Khalilabadi","doi":"10.1007/s11033-025-11106-w","DOIUrl":"https://doi.org/10.1007/s11033-025-11106-w","url":null,"abstract":"<p><strong>Background: </strong>Zataria multiflora (ZM) is a medicinal plant with widespread antitumor effects. Tyrosine kinase inhibitors (TKIs) are considered the mainstay treatment in blood cancers; however, eventual resistance to TKIs poses a significant challenge in this area. The present study aimed to assess the synergistic effects of ZM extract (ZME) along with imatinib, a TKI, against K-562 and U-266 leukemic cell lines.</p><p><strong>Methods: </strong>Cell viability was evaluated using the MTT assay, and apoptosis assessment was also conducted through Annexin-V/PI staining. Additionally, Real-Time PCR was used to assess the expression levels of BCR-ABL, P-TEN, c-MYC, Bax, and Bcl-2 genes. Molecular docking was carried out as an in-silico technique for both BCL-2 and ABL proteins.</p><p><strong>Results: </strong>The results showed that both ZME and imatinib promoted apoptosis in K562 and U266 cells, with combination treatment significantly enhancing apoptotic cell death (e.g., 18.4% apoptosis in K562 cells with ZME + imatinib vs. 8.5% untreated; 46.9% in U266 cells vs. 11.6% untreated, P < 0.05). Combined treatment with imatinib and ZME upregulated the expression of Bax (5-fold in K562, 3-fold in U266) and P-TEN (2-fold in K562, 2.8-fold in U266) genes and downregulated the expression of Bcl-2 (0.3-fold in K562, 0.3-fold in U266), BCR-ABL (0.5-fold in K562), and c-MYC (0.4-fold in K562, 0.2-fold in U266) genes (P < 0.05). Molecular docking showed strong binding affinities between ZME constituents (carvacrol and thymol) and BCL-2 and ABL proteins.</p><p><strong>Conclusions: </strong>ZME shows potential as a complementary agent in vitro, warranting further investigation.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1027"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286584","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}
Herman Irawan, Apon Zaenal Mustopa, Ramadhika Pra Suryadinata, Andi Baso Manguntungi, Joko Pebrianto Trinugroho, Feraliana, Wike Zahra Mustafawi, Mochamad Untung Kurnia Agung, Agus Budiawan Naro Putra, Kartika Dyah Palupi
{"title":"Genome mining identifies Micrococcus yunnanensis strain AZMABM 17 as a potential source of Antioxidant, Anti-Inflammatory, Antidiabetic, and Antiproliferative compounds.","authors":"Herman Irawan, Apon Zaenal Mustopa, Ramadhika Pra Suryadinata, Andi Baso Manguntungi, Joko Pebrianto Trinugroho, Feraliana, Wike Zahra Mustafawi, Mochamad Untung Kurnia Agung, Agus Budiawan Naro Putra, Kartika Dyah Palupi","doi":"10.1007/s11033-025-11104-y","DOIUrl":"https://doi.org/10.1007/s11033-025-11104-y","url":null,"abstract":"<p><strong>Background: </strong>The discovery and characterization of novel microbial strains are critical for advancing our understanding of microbial diversity and their potential applications in biotechnology and medicine.</p><p><strong>Methods: </strong>In this study, we identified and characterized Micrococcus yunnanensis strain AZMABM 17 using 16 S rRNA sequencing and Average Nucleotide Identity (ANI) analysis. Whole-genome sequencing was performed to determine the genomic structure and functional potential of the strain. Functional annotation and predictive analysis of secondary metabolite biosynthesis gene clusters (BGCs) were also conducted. The bioactivity of the isolate was evaluated through antidiabetic, antioxidant, and anti-inflammatory assays by measuring inhibition using a spectrophotometer. Antiproliferative activity was assessed using MTT assays against the MCF-7 breast cancer cell line.</p><p><strong>Results: </strong>The 16 S rRNA sequencing revealed a 98.28% identity with Micrococcus sp. 3455 and Micrococcus sp. GS57, while ANI analysis showed a 98.30% similarity with Micrococcus yunnanensis DSM 21,948, confirming AZMABM 17 as a novel strain. Whole-genome sequencing revealed a circular chromosome of 2,435,094 base pairs with a GC content of 73%, encoding 2,183 protein-coding genes, including 949 assigned to Gene Ontology (GO) and 1,367 to KEGG Orthology (KO). Functional annotation identified genes involved in amino acid transport, carbohydrate metabolism, and secondary metabolite biosynthesis, including terpenoids and carotenoids. The strain exhibited significant antioxidant, antidiabetic, anti-inflammatory, and antiproliferative activities, with higher metabolite concentrations correlating with increased bioactivities. Predictive analysis identified six putative secondary metabolite biosynthesis gene clusters (BGCs), including terpene and NI-siderophore clusters, suggesting the potential to produce novel bioactive compounds.</p><p><strong>Conclusions: </strong>These findings underscore the biotechnological potential of Micrococcus yunnanensis strain AZMABM 17, particularly in pharmaceutical and environmental applications.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1028"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286607","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}
Fatima Al Nemer, Mohammad Fayyad-Kazan, Bassam Badran, Nada Borghol
{"title":"Spatiotemporal and demographic patterns of SARS-CoV-2 entry gene expression in a Lebanese cohort.","authors":"Fatima Al Nemer, Mohammad Fayyad-Kazan, Bassam Badran, Nada Borghol","doi":"10.1007/s11033-025-11100-2","DOIUrl":"https://doi.org/10.1007/s11033-025-11100-2","url":null,"abstract":"<p><strong>Background: </strong>SARS-CoV-2 infection relies on host entry factors, including ACE2, TMPRSS2, FURIN, and CTSL, which are expressed in the nasal epithelium. Characterizing variations in their expression according to demographic factors and infection stage can offer valuable insights into differential susceptibility and disease progression.</p><p><strong>Objectives: </strong>The aim was to evaluate the baseline nasopharyngeal expression of SARS-CoV-2 host entry genes in a healthy Lebanese population, stratified by age, sex, and smoking status. We also investigated their dynamic regulation throughout the course of mild COVID-19 infection.</p><p><strong>Methods: </strong>We assessed nasopharyngeal expression of ACE2, TMPRSS2, FURIN, and CTSL in 173 COVID-19-negative individuals stratified by age, sex, and smoking. In 84 mild COVID-19 cases, a longitudinal design was applied to evaluate gene expression at four infection stages using RT-qPCR and promoter analysis.</p><p><strong>Results: </strong>Baseline expression of ACE2, FURIN, and CTSL decreased significantly with age, especially after adolescence, while TMPRSS2 showed a biphasic pattern. Females exhibited higher expression of ACE2, FURIN, and CTSL than males; smokers showed a trend toward upregulation without statistical significance. During infection, ACE2, TMPRSS2, and FURIN showed a bell-shaped expression pattern-upregulated in early infection, followed by downregulation during late infection and return to baseline post-infection. CTSL expression remained unchanged. Promoter analysis identified binding sites for immune- and hormone-regulated transcription factors (IRFs, STATs, and ESRs) explaining the observed expression differences.</p><p><strong>Conclusions: </strong>Entry gene expression differs across age, sex, and infection stage; elevated baseline levels in children and females may promote early immune activation and protection, highlighting their complex role in COVID-19 pathogenesis.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1024"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286534","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}
Shu-Yan Xiao, Ya-Hui Lv, Yin-Min Ji, Yi Dong, Mei-Cen Liu, Tao Li, Xiao-Ran Cui, Yi Hu
{"title":"The NLRP3 inflammasome: a pivotal orchestrator of multisystem diseases-from molecular mechanisms to therapeutic innovation.","authors":"Shu-Yan Xiao, Ya-Hui Lv, Yin-Min Ji, Yi Dong, Mei-Cen Liu, Tao Li, Xiao-Ran Cui, Yi Hu","doi":"10.1007/s11033-025-11116-8","DOIUrl":"https://doi.org/10.1007/s11033-025-11116-8","url":null,"abstract":"<p><p>The NLRP3 inflammasome, a key regulatory component in the innate immune system, bridges pathogen recognition to chronic disease pathogenesis by modulating pyroptosis, inflammatory factor release, and metabolic homeostasis. Its central role in inflammatory cascades has positioned it as a prime therapeutic target. This review delineates the NLRP3 inflammasome's pathological contributions to multisystem disorders-spanning neurological, cardiovascular, respiratory, gastrointestinal, urological, endocrine, and rheumatological immune diseases-while systematically evaluating associated therapeutic strategies. Furthermore, we consolidate the classical activation pathways of this molecular complex and discuss targeted inhibition approaches against both the NLRP3 inflammasome and its downstream effectors. Collectively, this work establishes a critical framework for understanding disease mechanisms and advancing translational interventions.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1026"},"PeriodicalIF":2.8,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286543","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":"Emerging roles of Midnolin in Cancer, Parkinson's Disease, and Metabolic dysfunction.","authors":"Madhur Kalyan, Pankaj Kumar Singh, Arpana Verma","doi":"10.1007/s11033-025-11120-y","DOIUrl":"https://doi.org/10.1007/s11033-025-11120-y","url":null,"abstract":"<p><p>Midnolin has emerged as a versatile protein involved in gene regulation, metabolism and disease. It controls Early Response Genes by promoting their ubiquitin-independent proteasomal degradation. It also affects glucose metabolism by interacting with glucokinase in pancreatic beta cells. Recent studies have highlighted the significant role of Midnolin in various human diseases, including non-alcoholic fatty liver disease, Parkinson's disease, and several malignancies such as liver cancer, breast cancer, gastric cancer, multiple myeloma and B-cell leukemias and lymphomas. Moreover, it has also been linked to lipid metabolism, mitochondrial function and tumor growth. However, its exact role is still not fully understood. This review summarizes current knowledge about Midnolin functions and highlights its potential target for future research in health and disease.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1022"},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280720","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":"Microglial NLRP3 inflammasome activation leads to perineuronal net loss in cocultured neurons.","authors":"Emre Tarakcioglu, Kemal Ugur Tufekci, Sermin Genc","doi":"10.1007/s11033-025-11145-3","DOIUrl":"10.1007/s11033-025-11145-3","url":null,"abstract":"<p><strong>Background: </strong>Microglia play a crucial role in maintaining the health of the central nervous system (CNS) through synaptic pruning, debris clearance, and pathogen elimination; however, sustained microglial inflammation can lead to neuronal damage. The NLRP3 inflammasome, a key regulator of inflammatory responses, has been implicated in various CNS diseases. Perineuronal nets (PNNs) are specialized structures that encase neuron somas, protect neurons from oxidative stress, and stabilize synaptic connections. While inflammatory microglia can degrade PNNs, the specific role of inflammasomes in this degradation process remains unclear.</p><p><strong>Methods and results: </strong>To investigate the role of inflammasomes in degradation of PNNs, neurons were derived from the murine Neuro-2a cell line using retinoic acid. Subsequently, we induced the NLRP3 inflammasome in the murine N9 microglial cell line via exposure to lipopolysaccharide and ATP. The effect of NLRP3 activation on degradation of PNNs was examined by coculturing neurons and microglia with and without NLRP3 inhibition for 24 h. PNNs were quantified using immunofluorescence staining with Wisteria floribunda agglutinin and neurocan antibodies, both of which bind to PNNs. Our findings demonstrate that coculture with NLRP3-activated microglia reduces the percentage of WFA- and neurocan-positive neurons whereas the inhibition of NLRP3 reverses this effect.</p><p><strong>Conclusions: </strong>Our findings highlight the significant role of the NLRP3 inflammasome in the degradation of PNNs in inflammatory states. Moreover, our research suggests that targeting the NLRP3 inflammasome could protect PNN-positive neurons from the damaging effects of inflammation. These findings might provide insight into the inflammatory mechanisms underlying loss of PNNs.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":"52 1","pages":"1023"},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280673","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}