Bioscience Reports最新文献

{"title":"Functional characterization of 3β-hydroxysteroid dehydrogenases in Asiatic toad reveals an efficient broad substrate specificity of Bg-3βHSD2.","authors":"Qian Meng, Yaoting Hu, Wenjie Chen, Chuanguang Xiao, Li Yang, Rufeng Wang, Beibei Zhang, Shujuan Zhao, Zhengtao Wang","doi":"10.1042/BSR20260032","DOIUrl":"10.1042/BSR20260032","url":null,"abstract":"<p><p>3β-Hydroxysteroid dehydrogenases (3βHSDs) are key enzymes in steroid metabolism, catalyzing C3 oxidation-reduction and Δ5→Δ4 isomerization reactions that govern metabolic flux across multiple steroidogenic pathways. However, the functional diversity of 3βHSDs involved in bufadienolide metabolism in amphibians remains poorly explored. Here, we systematically characterized the 3βHSD gene family in the Asian toad (Bufo bufo gargarizans) using integrated transcriptomic, biochemical, and metabolomic analyses. Seven Bg-3βHSD genes were identified from multi-tissue transcriptomes generated under control and Pb2+ exposure conditions, and six were heterologously expressed for functional evaluation. In vitro assays revealed pronounced functional divergence among Bg-3βHSD isoforms. Bg-3βHSD1 primarily catalyzed bidirectional C3 redox reactions of C21 steroids and bile acid-related substrates, consistent with canonical steroidogenic roles. In contrast, Bg-3βHSD2 enzyme exhibited broad substrate specificity and high catalytic efficiency toward hormones, bile acids, and bufadienolides. In addition to canonical C3 redox reactions and Δ5→Δ4 isomerization, Bg-3βHSD2 also displayed additional oxidation activity at the C17 position for several steroid substrates. A third homolog, Bg-HSD3B7 (GenBank accession no. XM 044303756.1), selectively converted 7α-hydroxylated sterols, suggesting a potential role in classical bile acid metabolism. Integration of tissue-specific expression profiles with bufadienolide distribution patterns suggests that Bg-3βHSD2 may contribute to connecting classical steroid metabolism with bufadienolide biosynthesis in adrenal tissue. Together, the present study identifies Bg-3βHSD2 as an efficient and versatile steroid-transforming enzyme, expands our knowledge of functional diversity within the amphibian 3βHSD family, and provides insights into the enzymatic basis of steroid and bufadienolide metabolism in B. bufo gargarizans.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolving therapeutic landscape of gut-pancreatic peptide signalling in metabolic disorders: from mono- to multi-agonist therapies.","authors":"Mohan Patil, Federico Piccinini, Elizabeth K M Johnstone, Ilaria Casari, Marco Falasca","doi":"10.1042/BSR20250114","DOIUrl":"10.1042/BSR20250114","url":null,"abstract":"<p><p>The pharmacotherapeutic landscape for the clinical management of type-2 diabetes (T2D), obesity, metabolic dysfunction-associated steatotic liver disease, and steatohepatitis is evolving swiftly in response to the escalating global prevalence and incidence of these interrelated metabolic disorders. Although insulin and metformin formulations have long constituted the foundation of diabetes care, a paradigm shift in T2D management has been observed with the advent of novel pharmacotherapies. Gut peptide analogues are at the forefront of this transformation. The emergence of glucagon-like peptide-1 (GLP-1) receptor agonists represents a watershed moment, fundamentally reshaping the therapeutic landscape for both T2D and obesity due to multifaceted metabolic benefits. The clinical success of GLP-1-based therapies has stimulated pharmaceutical interest in other metabolic peptides. Gut-pancreatic peptides such as glucose-dependent insulinotropic polypeptide, glucagon, amylin, and peptide YY are of particular interest due to their distinct pharmacological benefits and therapeutic promise in metabolic disorders. The present review aims to provide a comprehensive and current overview of non-insulin gut-pancreatic peptide signalling-based therapies that are either clinically approved or under clinical investigation, with a focus on the emerging therapeutic convergence between T2D, obesity, and associated liver disease. The review critically narrates their mechanisms of action, therapeutic efficacy, limitations, current development status, and positioning in the treatment landscape. Furthermore, the review delineates the emerging avenues in the development of novel peptide-based pharmacotherapies, offering insights into their future potential and acquainting the reader with developments in non-insulin gut-pancreatic peptide signalling-based therapies for metabolic disorders.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: The effects of the M2a macrophage-induced axonal regeneration of neurons by arginase 1.","authors":"Jieyuan Zhang, Yue Li, Zhaoxia Duan, Jianyi Kang, Kuijun Chen, Guanhua Li, Changmei Weng, Dongdong Zhang, Lu Zhang, Jianmin Wang, Bingcang Li","doi":"10.1042/BSR20193031_RET","DOIUrl":"10.1042/BSR20193031_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 8","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-125b-5p promotes pemphigus vulgaris pathogenesis by modulating desmosome structures.","authors":"Wenxiu He, Tingning Xiao, Hong Hua, Yixiao Xing, Panpan Shang, Jingya Fu, Li Wu Zheng, Pan Wei","doi":"10.1042/BSR20260220","DOIUrl":"10.1042/BSR20260220","url":null,"abstract":"<p><p>Pemphigus vulgaris (PV) is a life-threatening autoimmune bullous disease with an unclear pathogenesis. Our previous study indicated that the expression of miR-125b-5p was significantly elevated in PV patients. MiR-125b-5p has been reported to target P63 mRNA and inhibit the expression of P63, while p53-apoptosis-effector-related-to-PMP-22 (PERP) is a downstream protein regulated by P63. However, the role and underlying molecular mechanisms of miR-125b-5p in PV remain unclear. Here, we explored the roles of miR-125b-5p, P63, and PERP in regulating desmosome integrity and their contribution to PV pathogenesis. The dual-luciferase reporter assay showed that miR-125b-5p inhibited P63 expression by directly binding to the 3' UTR of P63 mRNA. Mouse tongue tissues were cultured in vitro and treated with desmoglein (Dsg) 3-monoclonal antibody (mAb) or with miR-125b-5p overexpression before Dsg3-mAb treatment. Overexpression of miR-125b-5p significantly reduced the mRNA and protein levels of P63 and PERP in Dsg3-mAb-treated tongue tissue. Transmission electron microscopy analysis of the structure of desmosomes revealed that, in tongue tissue with miR-125b-5p overexpression and Dsg3-mAb treatment, the interdesmosal width was significantly increased, the thickness of keratin insertion into the membrane was markedly reduced, and the desmosome structures exhibited evident damage. Together, these findings indicate that miR-125b-5p reduced the expression of both P63 and PERP by targeting P63, thereby contributing to the disruption of desmosome integrity.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connexin 31.9 is expressed in human pancreatic endocrine beta cells, as well as in exocrine ductal epithelial and vascular endothelial cells.","authors":"Elia Martha Pérez-Armendariz, Oscar J Zacarías-Lara, Cristina Revilla-Monsalve, Enrique R Page-Pérez, Beatriz Hernández-Téllez, Ángel Zarain-Herzberg, César A Flores-García, Rocío Arreola-Rosales, Marco E Gudiño-Zayas","doi":"10.1042/BSR20250223","DOIUrl":"10.1042/BSR20250223","url":null,"abstract":"<p><p>Connexin 36 (Cx36)-deficient mice exhibit deregulation of insulin secretion and glucose homeostasis. Mouse islet beta cells express Cx36 and connexin 30.2 (Cx30.2). Human beta cells express Cx36; however, it remains unknown whether they express Cx31.9 protein, the ortholog of Cx30.2. To address this question, sections of 23 human pancreatic autopsy samples from both sexes were analyzed by real-time qRT-PCR with oligonucleotides against Cx31.9 and by immunohistochemistry (IHC) with a specific antibody against this connexin. Mean levels of Cx31.9 mRNA were similar to those of Cx36 mRNA, used as a control gene, in all human samples analyzed (n = 7). IHC studies showed that Cx31.9-positive staining was localized to most islet cells in donor samples (15 of 16). The density of Cx31.9 staining per μm2 was calculated from 31 islet images from 10 donor samples. Pancreatic serial sections revealed that the spatial distribution of anti-Cx31.9-labeled cells is similar to that of anti-Cx36- and anti-insulin-positive cells. Moreover, anti-Cx31.9 staining was also localized in anti-CK19-positive epithelial ductal cells and in the endothelial cells of small, medium, and large-diameter vessels. Cx31.9 protein is expressed in endocrine islet beta cells as well as in exocrine ductal epithelial and vascular endothelial cells. In addition, there is a balance of Cx31.9 and Cx36 mRNA levels in the human pancreas.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13481748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: Exosomes derived from circRNA Rtn4-modified BMSCs attenuate TNF-α-induced cytotoxicity and apoptosis in murine MC3T3-E1 cells by sponging miR-146a.","authors":"Guijun Cao, Xianqing Meng, Xiaodong Han, Jinhua Li","doi":"10.1042/BSR20193436_EOC","DOIUrl":"10.1042/BSR20193436_EOC","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into the role of PEDF-R (PNPLA2) in photoreceptors.","authors":"S Patricia Becerra","doi":"10.1042/BSR20250121","DOIUrl":"10.1042/BSR20250121","url":null,"abstract":"<p><p>Photoreceptors are highly specialized neurons that depend on continuous membrane renewal and tightly regulated lipid homeostasis to maintain their visual function. Age-associated disruptions of these processes increase cellular stress and contribute to photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a potent neuroprotective factor in the retina, and the identification of its receptor, PEDF-R (PNPLA2), has provided key mechanistic insight into how PEDF signaling is coupled to lipid metabolism. The present review examines the molecular and cellular mechanisms underlying PEDF-R function in photoreceptors and the retinal pigment epithelium (RPE). PEDF-R acts as a multifunctional enzyme with phospholipase and lipase activities that link extracellular PEDF binding to intracellular lipid remodeling. Through these activities, PEDF-R has been associated with processes essential for photoreceptor survival such as membrane phospholipid turnover, mitochondrial integrity, calcium homeostasis, and redox balance. In addition, PEDF-R contributes to retinoid metabolism and lipid processing associated with outer-segment renewal in the RPE. We further discuss how disruption of the PEDF-PEDF-R pathway impairs lipid homeostasis, promotes oxidative and inflammatory stress, and increases susceptibility to age-related retinal degeneration. These insights position PEDF-R as a key contributor to photoreceptor homeostasis and a potential therapeutic target for preserving retinal function in aging and disease.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13358795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MCM2-7 proteins promote NF-κB transcriptional activity through cooperative promoter recruitment.","authors":"Xian Hong, Ming Sui, Qiang Li, Yan-Ji Lu, Yong-Hong Nie, Yong-Pei Li, Wen-Long Li, Xin-Xin Yue, Jing Xu, Daniel Billadeau, Tao Wang, Zhi-Hui Deng","doi":"10.1042/BSR20260337","DOIUrl":"10.1042/BSR20260337","url":null,"abstract":"<p><p>The minichromosome maintenance 2-7 (MCM2-7) proteins form a hexameric protein complex that is the structural core of replicative helicase, which is essential for accurate DNA replication. While their role in replication is well-established, the biological functions of excess chromatin-bound MCM2-7 proteins remain unclear. Here, we identify a transcriptional regulatory function of MCM2-7 through its interaction with nuclear factor κB (NF-κB) p65. We demonstrate that MCM2-7 proteins and NF-κB p65 reciprocally recruit each other to target gene promoters. Consequently, MCM2-7 proteins facilitate the localization of RNA Pol II to NF-κB target gene promoters and along the gene body, thereby promoting transcription of NF-κB target genes. These findings reveal MCM2-7 proteins promote NF-κB target gene transcription by facilitating p65 and RNA Pol II recruitment, offering a potential avenue for fine-tuning NF-κB target gene transcription.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A peripheral blood-based approach involving vimentin along with AURKA enabled efficient tracking of elusive Oct4/Sox2-expressing disseminated breast cancer stem cells.","authors":"Debomita Sengupta, Debanjan Thakur, Elizabeth Mahapatra, Salini Das, Jayanta Chakrabarti, Sagar Sen, Sutapa Mukherjee","doi":"10.1042/BSR20253828","DOIUrl":"10.1042/BSR20253828","url":null,"abstract":"<p><p>A major impediment in the therapeutic success of breast cancer (BC) arises from the persistence of clinically undetectable breast cancer stem cells (BCSCs) that need addressal by targeting translationally relevant markers to restrain relapse. Aurora kinase A (AURKA), due to its negative prognostic effect, was considered in clinical trials yet showed an unappreciable response, highlighting the need for additional markers. The present study tried exploring AURKA as a tool of relevance to detect the abundance of Oct4/Sox2(octamer-binding transcription factor 4/sex-determining region Y-box 2)-expressing BCSCs. The purpose was to understand the underlying intricacies governing the limited success of AURKA inhibition and to seek an improved relevant marker profile for detecting disseminated BCSCs. Flow cytometry and chromatin immunoprecipitation assay findings correlated Oct4/Sox2/AURKA expression, proposing an Oct4/Sox2 threshold-dependent AURKA induction. Surprisingly, in BC patient blood, Oct4/Sox2+ve cells were apparently lacking AURKA, emphasizing marker profile dynamicity in disseminating BCSCs with transient cell fate alterations. Immunoprecipitation/immunofluorescence results highlighted an interaction of pAURKA with fate-determinant pNUMB, hinting toward the existence of an AURKA/pNUMB axis for mesenchymal fate induction in breast cancer cells. Oct4/Sox2/AURKA+ve cells further expressed vimentin, highlighting a mesenchymal fate in BCSCs as evident from correlated Oct4/Sox2 and vimentin expression in patient blood. Hence, our study indicated an existing Oct4/Sox2/AURKA/pNUMB axis during transient mesenchymal differentiation of BCSCs and subsequently advocated for a peripheral blood-based approach using AURKA and vimentin for tracking BCSCs, thus supporting a co-targeting strategy. Preliminary in vitro intervention using combinatorial targeting of AURKA and vimentin reduced stemness propensities. Based on these interesting observations, further in-depth studies are warranted for clinical validation.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13305960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diacylglycerol enantiomer selectivity of diacylglycerol acyltransferases highlights metabolic specialization in triacylglycerol synthesis across the tree of life.","authors":"Prasad Parchuri, Jay Shockey, Timothy P Durrett, Philip D Bates","doi":"10.1042/BSR20260190","DOIUrl":"10.1042/BSR20260190","url":null,"abstract":"<p><p>Triacylglycerols are the major energy storage lipids in plants, animals, and microorganisms, and are predominantly produced by acyl-CoA:diacylglycerol (DAG) acyltransferases (DGATs). Two enantiomers of the DAG substrate, sn-1,2 and sn-2,3, can be produced by different biological mechanisms; however, little is known about which species produce each enantiomer, the selectivity of DGAT isoforms for either enantiomer, or whether DGAT enantiomer selectivity varies across organisms. Here, DAG enantiomer selectivity of DGAT1 and DGAT2 was measured from eight seed plants, two mammals, one oleaginous yeast, and one photosynthetic microalga using enantiomer-specific in vitro DGAT assays. Across most plants, DGAT1 favored sn-1,2-DAG, whereas DGAT2 preferentially utilized sn-2,3-DAG. However, there were several exceptions. Mammalian DGAT1, DGAT2, and microbial DGAT1s efficiently used both DAG enantiomers, while microbial DGAT2s had unique selectivity. The selectivity of several DGATs for combined acyl-CoA and DAG enantiomer molecular species were also evaluated for biotechnical applications. Therefore, DGAT DAG enantiomer selectivity is common yet strongly dependent on lineage and isoform and likely shaped in part by species-specific metabolic context of triacylglycerol synthesis, turnover, and remodeling. This work expands our understanding of DGAT function and establishes a foundation for leveraging enantiomer-selective acyltransferases in metabolic engineering of tailored lipid products.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13286882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}