Biochimie最新文献

{"title":"Inside front cover-EDB","authors":"","doi":"10.1016/S0300-9084(25)00306-2","DOIUrl":"10.1016/S0300-9084(25)00306-2","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Page IFC"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 impact of prion protein N- and C-terminal fragments on the pathological transformation of alpha-synuclein","authors":"Sofiya Kudryavtseva ,&nbsp;Yulia Stroylova ,&nbsp;Sviatlana Smolskaya ,&nbsp;Evgeniia Leisi ,&nbsp;Kseniya Barinova ,&nbsp;Vladimir Muronetz","doi":"10.1016/j.biochi.2025.10.004","DOIUrl":"10.1016/j.biochi.2025.10.004","url":null,"abstract":"<div><div>The interaction between different groups of amyloidogenic proteins is certainly involved in the development of neurodegenerative diseases, however, information about the role of such interactions is limited and contradictory. Of particular interest is the prion protein, individual fragments of which are formed in nerve tissues during proteolytic cleavage and can bind to alpha-synuclein, modeling its amyloid transformation <em>in vivo</em>. To investigate the role of individual domains of the prion protein (PrP) in regulating its own amyloid transformation, as well as alpha-synuclein fibrillation, we isolated PrP N- and C-terminal fragments (serine residue +23–124 aa and 103–234 aa, respectively) and studied their properties. The isolated C-terminal fragment formed more beta structures than the full-length protein, but at the same time, the efficiency of the fragment to form amyloid fibrils was reduced probably due to the dimensional issues. The N-terminal fragment of PrP not only did not form fibrillar structures, but also prevented amyloid transformation of full-length PrP. However, the PrP N-terminal fragment as well as prion protein monomers and mature fibrils’ particles had the opposite effect on the transformation of wild-type alpha-synuclein and its mutant form A53T, significantly reducing the lag phase of the aggregation. As a result, the heterogeneous small-sized aggregates were formed instead of large structured fibrils. This study discusses the fundamental possibility of using N-terminal fragments of PrP to prevent amyloidogenic transformation of full-length prion protein, along with the impact of proteolytic cleavage of PrP <em>in vivo</em> on the development of prion diseases and synucleinopathies.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 100-111"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Premature aging in chronic kidney disease: Decoding senescence biomarkers and therapeutic opportunities","authors":"Carlos Eduardo H.V. P.F. Braga ,&nbsp;Jessyca S. de Brito ,&nbsp;Marcia Ribeiro ,&nbsp;Karen Salve Coutinho-Wolino ,&nbsp;Bruna Regis ,&nbsp;Bruna Calixto ,&nbsp;Renata Cristina Bezerra Rodrigues ,&nbsp;Angela Yee-Moon Wang ,&nbsp;Peter Stenvinkel ,&nbsp;Denise Mafra","doi":"10.1016/j.biochi.2025.10.008","DOIUrl":"10.1016/j.biochi.2025.10.008","url":null,"abstract":"<div><div>Chronic kidney disease (CKD) is characterized by a premature aging phenotype. CKD-related stressors, such as inflammation, oxidative stress, the buildup of uremic toxins, hyperphosphatemia, mitochondrial dysfunction, sirtuin inhibition, and klotho deficiency, trigger cell cycle arrest, inducing senescence in tubular epithelial cells, endothelial cells, and podocytes, accelerating CKD progression and leading to the expression of senescence-related genes and the senescence-associated secretory phenotype (SASP). This condition promotes local (e.g., interstitial fibrosis, glomerulosclerosis, endothelial dysfunction) and systemic damage, including micro- and macrovascular dysfunction, early vascular aging, and an increased risk of cardiovascular mortality. Markers such as SA-β-gal, p16^INK4a, p21^CIP1, p53, and SASP components (e.g., IL-6, MCP-1, MMP-3), as well as telomere shortening and mitochondrial DNA accumulation, are frequently used to identify senescence. Despite their predictive potential, the application of these biomarkers for disease progression and cardiovascular complications remains underexplored in patients with CKD. This narrative review explores the complex relationship between senescence and CKD, reviews key senescence biomarkers, emphasizes their importance for diagnosis, and evaluates the potential of senotherapies to reduce complications of premature aging in this population.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 42-58"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145314228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HEK293T cells manage overload by the overexpressed full-length Htt variants via proteasome activation","authors":"Nataliia N. Gotmanova ,&nbsp;Tatiana V. Bobik ,&nbsp;Viacheslav A. Kriachkov ,&nbsp;Alexander A. Ezhov ,&nbsp;Anna V. Bacheva","doi":"10.1016/j.biochi.2025.10.014","DOIUrl":"10.1016/j.biochi.2025.10.014","url":null,"abstract":"<div><div>Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a pathological mutation that results in the abnormal expansion of more than 37 consecutive trinucleotide repeats (CAG) in the HTT gene. These repeats encode the polyglutamine tract (polyQ tract) in the huntingtin protein (Htt). Progressive lethal Huntington's chorea is characterized by impaired motor activity and marked cerebral atrophy. The disease affects neurons in specific areas of the central nervous system, mainly GABAergic neurons in the striatum and cortex. It is believed that the neuron-specific proteotoxicity of mutant Htt (mHtt) results from its conformational instability and tendency to aggregate due to elongation of the polyQ-tract. However, recent structural findings challenge these assumptions. To elucidate some key aspects of the molecular mechanisms of HD, we describe the transient expression of full-length normal or mutant huntingtin in HEK293T eukaryotic cells, and options of isolation and purification of huntingtin variants according to the optimized procedure. The short-termed overexpression of Htt/mHtt has been demonstrated to be associated with elevated proteasome and non-proteasome caspase activity, and change in subunit expression. The cellular response to mHtt production manifested primarily as an increase in β1, β5i and in less extent β1i subunits as well as 11Sαβ expression, as observed through both Western blot and RT-qPCR. The microscopy study also revealed an enhancement in the β1i subunit content in HEK293T cells overexpressed Htt and especially mHtt suggesting an immunoproteasome activation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 59-75"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA expression profiling of white adipose tissue in the torpor response of the house mouse (Mus musculus)","authors":"Yuhong Hu ,&nbsp;Stuart R. Green ,&nbsp;Ningmei Wang ,&nbsp;Jing Zhang ,&nbsp;Han Wang ,&nbsp;Ziheng Zhao ,&nbsp;Yue Gao ,&nbsp;Kenneth B. Storey ,&nbsp;Jingze Liu ,&nbsp;Hui Wang","doi":"10.1016/j.biochi.2025.10.012","DOIUrl":"10.1016/j.biochi.2025.10.012","url":null,"abstract":"<div><div>MicroRNAs (miRNAs), a critical class of short non-coding RNAs, regulate metabolic processes associated with mammalian torpor (e.g., <em>Mus musculus</em>), though their precise functional mechanisms remain incompletely characterized. Here, we employ RNA-seq to profile miRNA expression in white adipose tissue (WAT) of active versus torpid C57BL/6 mice. Among 863 detected miRNAs, 12 showed significant differential expression during torpor. <em>In silico</em> prediction of miRNA targets revealed these miRNAs preferentially target cancer-related pathways, indicating their potential role in suppressing cell proliferation during metabolic depression. Intriguingly, steroid biosynthesis genes escaped miRNA-mediated inhibition, suggesting active endocrine modulation by WAT during torpor. Machine learning helped to identify biomarkers for torpor in the mice, specifically a minimum of three miRNAs were sufficient to distinguish adipose samples from control versus torpid conditions. Taken together, this study demonstrates the role of miRNAs as transcriptional regulators of cell signalling pathways within WAT during mouse torpor.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 112-124"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting SmE16, a calcium-binding protein from Schistosoma mansoni with unknown functions","authors":"Thais Rangel Figueiredo ,&nbsp;Miguel Eduardo Salazar Aurich ,&nbsp;Amanda Toledo Machado ,&nbsp;Luis Guilherme Mansor Basso ,&nbsp;Ana Eliza Zeraik","doi":"10.1016/j.biochi.2025.10.005","DOIUrl":"10.1016/j.biochi.2025.10.005","url":null,"abstract":"<div><div><em>Schistosoma mansoni</em> is the causative agent of schistosomiasis, a disease that affects millions of people worldwide. Calcium signaling, essential for various parasite processes, emerges as a potential target. In this study, we focused on the calcium binding protein SmE16, initially identified as an egg-specific antigen from <em>S. mansoni</em>. However, our results indicate that SmE16 is a widely expressed protein, present across all developmental stages and tissues, with high expression in the adult worm's esophagus, evidenced by our in situ hybridization experiments. The recombinant protein was expressed in <em>Escherichia coli</em> and purified to assess its conformational change upon calcium binding. Biophysical analyses demonstrated that SmE16 undergoes significant structural alterations in the presence of calcium ions. Furthermore, calcium binding promotes partial oligomerization and significantly enhances the thermal stability of the protein. These structural changes are often associated with proteins recognized as calcium sensors, suggesting that SmE16 might play an active role in calcium-mediated signaling pathways. These findings highlight the importance of SmE16 in potential cellular signaling, paving the way for further research into its biological functions.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 1-10"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deadly innovations: Molecular phylogenetics and evolution of phospholipase A2 toxins in viperid snake venoms","authors":"Lorenzo Seneci ,&nbsp;Vivek Suranse ,&nbsp;Marco Mancuso ,&nbsp;Tobias Senoner ,&nbsp;Bing Xie ,&nbsp;Ivan Koludarov ,&nbsp;Kartik Sunagar ,&nbsp;Bryan G. Fry","doi":"10.1016/j.biochi.2025.10.010","DOIUrl":"10.1016/j.biochi.2025.10.010","url":null,"abstract":"<div><div>Snake venoms have surged as model systems in evolutionary biology thanks to the dynamic diversification and accelerated evolution of many toxin families. Among these, phospholipase A₂ (PLA₂) constitute a prime example as they are ubiquitous across the venomous snake radiation and have evolved a wide variety of pathophysiological activities. This is especially true in vipers (family Viperidae), one of the most successful and medically significant venomous snake lineages worldwide. In this study, we gathered publicly available sequences of viper venom PLA₂s to recreate the molecular phylogeny and toxicological evolution of this toxin family to date. Furthermore, we determined the selection regimes regulating the evolution of these toxins with a comparative approach that combines multiple methodologies of phylogenetic reconstruction and analysis of selection signatures. Our phylogeny confirms the basal position of Asp49 PLA₂s (proteins with Asp at position 49), while derived clades, such as the non-enzymatic Lys49 myotoxins and the poorly characterised Ser49 type, are nested within. Neurotoxicity arose on multiple independent occasions (all within the Asp49 clade), with monomeric and dimeric forms only distantly related to each other. Positive Darwinian selection was widespread across the viper PLA₂ tree, in line with previous research. However, purifying selection was also preponderant (perhaps due to structural constraints imposed by the pathophysiological targets of these toxins) and relatively neutral substitutions were observed in certain clades. Overall, this study provides novel insights into the evolutionary history of viper venom PLA₂s through a comprehensive phylogenetic framework and highlights the need for complementary genomic and functional research into these toxins.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 137-152"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered hemostatic dynamics and its regulation in follicular microenvironment of women with polycystic ovary syndrome","authors":"Roshan Dadachanji ,&nbsp;Snehal Bhingardeve ,&nbsp;Sadhana K. Desai ,&nbsp;Vijay Mangoli ,&nbsp;Srabani Mukherjee","doi":"10.1016/j.biochi.2025.09.015","DOIUrl":"10.1016/j.biochi.2025.09.015","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS), presents with gynecological and metabolic issues such as anovulatory infertility, insulin resistance, hyperandrogenism, and obesity, and long-term cardiometabolic risks. Emerging evidence highlights coagulation–fibrinolysis balance influences essential ovarian functions, including ovulation, corpus luteum function, granulosa cell luteinization, and ECM remodeling. This study explores the relatively understudied coagulation and fibrinolytic factors in the ovarian microenvironment in Indian women. This case-control study examined the hemostatic potential of the follicular microenvironment in PCOS (n = 35) and controls (n = 30) by analyzing coagulation and fibrinolytic profiles in follicular fluid (FF), and granulosa cells (GCs). We observed significantly reduced transcript expressions of fibrinolytic factors including serine proteinase inhibitor (SERPINE1), tissue-type plasminogen activator (PLAT), coagulation factor fibrinogen gamma (FGG) in PCOS GCs. Conversely, transcript levels of thrombomodulin (THBD) and urokinase plasminogen activator receptor (PLAUR) were significantly higher in GCs of PCOS women compared to controls. Levels of both plasminogen activators, PLAT and PLAU, along with anticoagulant proteins, tissue factor pathway inhibitor and protein S were markedly declined, while plasminogen, THBD and histidine rich glycoprotein levels were significantly raised in FF of women with PCOS. Further, the construction of miRNA-mRNA regulatory network suggested that miRNAs may also be involved in hemostatic regulation in follicle microenvironment of PCOS. Our study showed that altered profiles of coagulation and fibrinolysis factors within follicular microenvironment of PCOS could contribute to disrupted hemostatic balance, mainly evidenced by compromised fibrinolysis. This may have significant implications for ovulatory dysfunction due to altered rupture, ECM remodeling and cumulus expansion in affected women.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 31-41"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoform switching in the CD44/ESRP1 axis as a driver of EMT and cancer stemness across tumor types","authors":"K. Jankowska ,&nbsp;W. Wójtowicz ,&nbsp;M. Wierzbinka ,&nbsp;K. Raszczok ,&nbsp;K. Bajdak-Rusinek","doi":"10.1016/j.biochi.2025.10.015","DOIUrl":"10.1016/j.biochi.2025.10.015","url":null,"abstract":"<div><div>Alternative splicing of cluster of differentiation 44 (CD44), regulated by epithelial splicing regulatory protein 1 (ESRP1), plays a critical role in cancer progression. The switch between CD44 variant (CD44v) and standard (CD44s) isoforms is tightly linked to epithelial–mesenchymal transition (EMT), metastatic potential and cancer stem cell (CSC) maintenance. This review integrates recent isoform-resolved findings to elucidate the molecular mechanisms underlying CD44/ESRP1-mediated splicing and its involvement in oncogenic signaling pathways promoting invasion, plasticity and therapy resistance. We also examine cancer-specific CD44 isoform expression patterns and assess their prognostic and therapeutic relevance. We propose that isoform-specific profiling of the CD44/ESRP1 axis may serve as a predictive framework for metastasis and therapy response, paving the way for targeted splicing-based therapeutics.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 19-30"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA damage induces p53-dependent activation of the lncRNA TCERG1L-AS1 to regulate cell proliferation","authors":"Madhur Sharma ,&nbsp;Nidhi Chourasia ,&nbsp;Priyanka Priyanka ,&nbsp;Debi Prasad Sarkar ,&nbsp;Alo Nag ,&nbsp;Sandeep Saxena","doi":"10.1016/j.biochi.2025.10.002","DOIUrl":"10.1016/j.biochi.2025.10.002","url":null,"abstract":"<div><div>While long non-coding RNAs (lncRNAs) are increasingly recognized as critical regulators in stress responses, a systematic characterization of those regulated by p53 has remained incomplete. In this study, we adopted an integrative strategy that combined curated p53 ChIP-seq data with publicly available transcriptome profiles to identify lncRNAs potentially regulated by p53. Among these, we identified TCERG1L-AS1, a lncRNA whose promoter region contains canonical p53-binding motifs, as also demonstrated by luciferase reporter assays. TCERG1L-AS1 expression is specifically induced under genotoxic and oxidative stress, but not in response to metabolic stress, and its induction is dependent on functional p53. Functionally, enforced expression of TCERG1L-AS1 triggers G1-phase arrest and inhibits cellular proliferation and migration, as shown by flow cytometry, MTT, wound healing, and transwell migration assays. Transcriptome-wide analyses following TCERG1L-AS1 overexpression or silencing did not identify a consistent downstream effector, supporting emerging models in which certain lncRNAs act through indirect or scaffold-based mechanisms. Collectively, these findings establish TCERG1L-AS1 as a novel p53-regulated lncRNA with functional significance in tumor suppression and cellular stress responses.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"240 ","pages":"Pages 76-87"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}