Bioscience Reports最新文献

{"title":"The role of growth hormone in metastasis and angiogenesis of breast cancer.","authors":"Tamanna Alam, Mingyang Hu, Rivka L Isaacson","doi":"10.1042/BSR20253516","DOIUrl":"10.1042/BSR20253516","url":null,"abstract":"<p><p>Breast cancer is a complex disease which has many factors affecting its progression and metastasis. Although steroid hormones, especially oestrogen, are most commonly associated with breast cancer, growth hormone (GH) also plays a substantial role in its development and spread via the activation of downstream signalling pathways and the regulation of growth factors such as insulin-like growth factor-1 (IGF-1) and the vascular endothelial growth factor (VEGF). Breast cancer patients usually have elevated levels of GH and IGF-1 in their circulation. Growth hormone receptor (GHR) signalling enhances migratory ability of tumour cells and excess IGF-1 production promotes angiogenesis. Gaining a full understanding of the mechanisms behind GH and breast cancer will allow researchers to develop more therapeutics to treat this devastating disease.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146211975","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: Apigenin inhibits epithelial-mesenchymal transition of human colon cancer cells through NF-κB/Snail signaling pathway.","authors":"Jiafeng Tong, Ying Shen, Zhenghua Zhang, Ye Hu, Xu Zhang, Li Han","doi":"10.1042/BSR20190452_RET","DOIUrl":"10.1042/BSR20190452_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112203","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":"Mutations affecting the β-sheet at the extracellular opening of the intimin β-barrel domain lead to reduced protein levels and inefficient passenger secretion.","authors":"Sai Priya Sarma Kandanur, Fabian A Renschler, Lara Breuer, Monika S Schütz, Jack C Leo","doi":"10.1042/BSR20253581","DOIUrl":"10.1042/BSR20253581","url":null,"abstract":"<p><p>Attaching and effacing pathogens, such as enteropathogenic and enterohaemorrhagic Escherichia coli, rely on an adhesin, intimin, for attachment to enterocytes and downstream effects leading to actin pedestal formation. Intimin belongs to the inverse autotransporter family (type 5e secretion systems), which secrete the extracellular adhesive domain or passenger via a hairpin intermediate. While many of the next steps in secretion are now understood, how the hairpin initially forms is not known. We sought to investigate this by making point mutations at several positions in the β-barrel domain of intimin, as this domain forms at least part of the secretion pore. We made the mutations in a wild-type background and in a stalled intermediate caught in the hairpin conformation, which allowed us to uncouple passenger secretion from hairpin formation. Surprisingly, most of the point mutations did not have an appreciable effect on hairpin formation or passenger secretion, and larger changes such as replacing the entire linker region with a flexible glycine-serine stretch showed only a modest reduction in passenger secretion. By contrast, mutations affecting a small β-sheet at the extracellular face of the intimin β-barrel between two extracellular loops and the C-terminus of the linker had a more pronounced effect on secretion, and abolishing this β-sheet prevented hairpin formation and led to complete loss of the wild-type protein. Our results show that the intimin β-barrel is remarkably tolerant to changes and that the β-sheet on the extracellular side of this domain plays a central role in passenger secretion and protein levels.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123414","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: Extracellular regulated kinase 5 mediates osteoporosis through modulating viability and apoptosis of osteoblasts in ovariectomized rats.","authors":"Tuan-Mao Guo, Yan-Li Xing, Hai-Yun Zhu, Lan Yang, Guo-Xiong Liu, Xi-Min Qiao","doi":"10.1042/BSR20190432_RET","DOIUrl":"10.1042/BSR20190432_RET","url":null,"abstract":"","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112182","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":"Borrelia BBJ25 is a plasmid-encoded Omp85-family protein associated with a potential export system.","authors":"Abigail Nixon, Evelina Soliman, Jaroslaw Bryk, Martin Carr, Christopher D O Cooper, Richard J Bingham","doi":"10.1042/BSR20254082","DOIUrl":"10.1042/BSR20254082","url":null,"abstract":"<p><p>The Borrelia genome consists of a linear chromosome and numerous linear and circular plasmids. Using a computational framework, we examined the plasmid proteome of Borrelia burgdorferi sensu lato to identify potential outer membrane (OM) β-barrel proteins. Our approach identified BBJ25 on plasmid lp38 as an Omp85 superfamily domain with structural homology to BamA/TamA. Analysis of the surrounding genes reveal a cluster of seven genes. Structure-function analysis (AlphaFold3 and DALI) points towards a role in membrane transport, with two chaperone proteins (BBJ23, BBJ24), the Omp85-family domain BBJ25, a homodimeric MacB-like type-VII ABC transporter with an associated ATP-binding domain (BBJ26, BBJ27), a LolA-like domain (BBJ28), and one protein of unknown function (BBJ29). Taken together, this points towards a role in the ATP-driven extraction of a non-polar ligand, possibly lipoproteins, from the inner membrane and delivery to the OM. Structural homology is detected to Escherichia coli proteins involved in lipoprotein sorting (LolACDE). Wider analysis of the Borrelia genus revealed two major variants of this 7-gene cluster, distributed across multiple different linear elements including lp17, lp28, lp38, and the linear chromosome of Borrelia turcica. Borrelia valaisiana was found to have both allelic variants coexisting in the same genospecies on different linear plasmids (lp28-3 and lp28-8). Previous studies have reported up-regulation of these genes in response to mammalian signals. The conservation of these proteins throughout the Borrelia genus, coupled with the occurrence of multiple copies in some genospecies, point towards a critical function. The identity of the target ligand remains uncertain and requires experimental verification.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123461","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":"Overcoming divalent cation sensitivity is not the only challenge for functional study of ABC transporters within polymer lipid particles.","authors":"Olivia P Hawkins, Thomas J Potter, Luke M Broadbent, Philip Kitchen, Alan D Goddard, Alice J Rothnie","doi":"10.1042/BSR20250256","DOIUrl":"10.1042/BSR20250256","url":null,"abstract":"<p><p>Proteins of the ATP-binding cassette (ABC) transporter superfamily are involved in diverse biological processes including multidrug resistance. As membrane proteins, they exist within a complex lipid environment, and often it is necessary to isolate them from the other membrane components to study their structure, function, and dynamics. Traditionally, detergents have been used to isolate the transporters into micelles but this can strip away lipids that may be essential for function. Polymers such as styrene maleic acid (SMA) offer attractive alternatives to detergents as they retain the protein and lipids in a nanoscale disc. However, to date, no demonstration of full ABC transporter activity in these discs has been achieved, possibly due to the inherent divalent cation sensitivity of the SMA polymers; magnesium is essential for ATP binding to ABC transporters. Novel polymers such as those based on acrylic acid styrene (AASTY) show decreased sensitivity to divalent cations and, as such, may be well placed to probe ABC transporter activity. We have demonstrated that a range of commercially available AASTY polymers solubilise biological membranes efficiently, albeit with slightly different kinetics. ABC transporters can be solubilised and purified using AASTY polymers into discs of a comparable size to those formed by SMA2000. These discs show increased magnesium tolerance but, as for SMA2000, lipids within them do not seem to undergo a full phase transition. We were unable to detect ATPase activity of ABC transporters in AASTY polymer lipid particles, suggesting that magnesium tolerance alone is not sufficient to overcome the challenges.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112226","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":"From fitness to fate: Hippo-YAP-mediated cell competition influence on stem cells activity.","authors":"Apapist Panichewa, Chanchao Lorthongpanich","doi":"10.1042/BSR20253960","DOIUrl":"10.1042/BSR20253960","url":null,"abstract":"<p><p>Cell competition is a fundamental quality-control mechanism where fitter 'winner' cells eliminate less-fit 'loser' counterparts, thereby fine-tuning cell populations during development and maintaining adult tissue integrity. This highly conserved, natural cellular process is absolutely crucial for organogenesis, but once dysfunctional, can instead be exploited by 'super-fit' cancer cells to promote tumourigenesis. This review aims to provide an overview of how heterogeneity is the root cause of cell competition, the factors which influence its emergence, the various modes of cell competition, and finally, the mechanisms by which loser cells are eliminated. We are particularly interested in YAP, a major effector of the Hippo signalling cascade, as a driver of heterogeneity and perpetrator of human pluripotent stem cell (hPSCs) competition. We discuss how differential YAP/TEAD activity, influenced by mechanical stress, defines winner and loser cell identities within stem cell populations. Finally, we discuss the potential of cell competition for advancing regenerative medicine and cancer therapy.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200026","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, purification, and in vitro characterization of the carboxylesterase CEST-9.2 from Caenorhabditis elegans.","authors":"Weijie Xu, Subhradeep Bhar, Steven D Bruner, Rebecca A Butcher","doi":"10.1042/BSR20253840","DOIUrl":"10.1042/BSR20253840","url":null,"abstract":"<p><p>The nematode Caenorhabditis elegans biosynthesizes the ascarosides, a large, modular family of pheromones that are used in chemical communication. A number of carboxylesterase domain-containing (CEST) enzymes are responsible for decorating the glycolipid core of the ascarosides with a variety of modifications. However, these enzymes, which are homologous to human carboxylesterases and acetylcholinesterase, have not been characterized biochemically, and thus the mechanism whereby they attach different modifications to the ascarosides is unknown. Here, we report the expression, purification, and biochemical characterization of a soluble CEST enzyme for the first time. In this study, we focused on CEST-9.2, which is responsible for making (E)-2-methyl-2-butenoyl (MB)-modified ascarosides. We identified candidate substrates for the enzyme, and we successfully expressed a truncated version of CEST-9.2, which is lacking the transmembrane domain, in several expression systems, including Escherichia coli, Pichia pastoris, and Spodoptera frugiperda Sf9 cells. The purified CEST-9.2 from each of these systems was tested against candidate substrates, including ascarosides and either MB-coenzyme A (CoA), MB-choline, or MB-carnitine. No enzymatic activity was detected using these substrates, suggesting that either the transmembrane domain is necessary for activity or that the correct substrates have not yet been identified. We showed that the purified CEST-9.2 from Sf9 cells is well-folded and dimeric, offering a potential starting point for future structural and mechanistic studies.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145586218","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":"Homocysteine thiolactone affects paraoxonase 1 activity via altered paraoxonase 1 distribution on high-density lipoprotein particles.","authors":"Rina Kawaguchi, Tsunehiro Miyakoshi, Akira Yoshimoto, Shoichi Hosoya, Yuki Kugii, Takehiko Sasaki, Nobuharu Suzuki, Ryunosuke Ohkawa","doi":"10.1042/BSR20253768","DOIUrl":"10.1042/BSR20253768","url":null,"abstract":"<p><p>Hyperhomocysteinemia is a risk factor of cardiovascular disease (CVD). High-density lipoprotein (HDL) plays an important role in anti-atherosclerosis, with its anti-atherogenic function attributed to HDL-associated proteins such as apolipoprotein A-I (apoA-I) and paraoxonase 1 (PON1). Homocysteine (Hcy) thiolactone modifies lysine residues in proteins, thereby altering their function. Although dysfunction of apoA-I and PON1 has been reported, the precise modification sites and underlying mechanisms have remained unclear. In this study, we aimed to identify Hcy-thiolactone modification sites on apoA-I and PON1. In addition, we sought to clarify the effects of Hcy-thiolactone on PON1 activity and its distribution. Modification sites were analyzed using MALDI-TOF MS. The effects of Hcy-thiolactone on various specimens, including purified proteins, reconstituted HDL (rHDL), HDL collected by ultracentrifugation, and serum samples, were characterized using enzymatic assays measuring three major PON1 activities (arylesterase, paraoxonase, and lactonase) and Western blotting. Our results demonstrated that while some Hcy-thiolactone modification sites were detected on apoA-I, PON1 itself was not directly modified by Hcy-thiolactone. Thiolactonase activity was reduced by Hcy-thiolactone in large HDL particles. Furthermore, a general reduction of PON1 activity and changes in HDL remodeling and distribution were observed in serum samples treated with Hcy-thiolactone. These findings suggest that PON1 dysfunction induced by Hcy-thiolactone is influenced by alterations in HDL remodeling and the enzyme's distribution on HDL particles. Analysis of PON1's distribution dynamics under pathological conditions may provide crucial insights into the mechanism of HDL function decline in CVD.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12905485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910249","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":"Serum proteomics mirrors the histopathological changes underlying different etiologies of primary mitral valve disease.","authors":"Amaia Garcia-Peña, Jaime Ibarrola, Marina Segur, Adela Navarro, Alba Sádaba, Carolina Tiraplegui, Mattie Garaikoetxea, Ernesto Martín-Núñez, Amaya Fernández-Celis, Rafael Sádaba, Virginia Alvarez, Eva Jover, Natalia López-Andrés","doi":"10.1042/BSR20253900","DOIUrl":"10.1042/BSR20253900","url":null,"abstract":"<p><p>Mitral valve disease (MVD) is the most common valvulopathy and a frequent cause of heart failure and death. However, data regarding the molecular basis are scarce. We aimed to thoroughly explore and compare the circulating, molecular, and histopathological profiles in the main subtypes of primary chronic MVD. In total, 300 patients with chronic primary MVD undergoing mitral valve (MV) replacement were enrolled and classified in the four main etiologic subtypes: calcific mitral valve disease (CMVD, n = 81), rheumatic disease (RHVD, n = 114), Barlow's disease (BD, n = 70), and fibroelastic deficiency (FED, n = 35). Discovery studies were performed using Olink Proteomics® technology in 80 serums from MVD patients (n = 20/etiology). Histopathologic study, ELISA, and zymography were performed on resected MVs to analyze extracellular matrix (ECM) composition and remodeling, inflammation, and calcification. Serum proteomics identified markers exclusively overexpressed in each MVD etiologic subtype. Further enrichment analyses revealed specific etiology-dependent pathways involving calcification, inflammation, or ECM remodeling. Such etiology-dependent differences were mirrored in the excised MVs both architecturally and compositionally. CMVD and RHVD valves had a marked ECM disorganization with increased collagen deposition and presence of nodular and diffuse calcification, respectively. Moreover, RHVD valves exhibited high levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and matrix degradation enzymes. BD valves showed enhanced inflammatory markers and infiltrates. Moreover, BD and FED valves presented marked proteoglycans deposition. Our study identified circulating markers involved in calcification, inflammation, and ECM remodeling, which may be associated with specific MVD etiologies. The differences in serum markers seem to mirror histopathologic and molecular alterations in the MVs with potential applications into the clinic as diagnosis biomarkers. Identification of underlying molecular mechanisms of each etiology is essential to discover new specific therapeutic targets.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12863031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809336","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}