Biochimie最新文献

{"title":"Recent advances in protein synthesis inhibitors","authors":"Alisa P. Chernyshova ,&nbsp;Petr V. Sergiev ,&nbsp;Dmitrii A. Lukianov ,&nbsp;Vera A. Alferova","doi":"10.1016/j.biochi.2026.01.005","DOIUrl":"10.1016/j.biochi.2026.01.005","url":null,"abstract":"<div><div>Antimicrobial resistance threatens the long-standing efficacy of antibiotics and underscores the need to expand, refine, and diversify antimicrobial therapies. Translation is a uniquely druggable process: its machinery is essential, conserved in bacteria, and sufficiently divergent from the eukaryotic counterpart to enable selectivity. This review synthesizes recent progress on inhibitors of initiation, elongation, termination, and recycling. High-resolution structural and biophysical studies have resolved longstanding ambiguities, reassigned ribosomal binding sites, uncovered stage-specific activities in scaffolds previously thought to act elsewhere, and revealed multistage, context-dependent mechanisms. Beyond the canonical stages, quality-control pathways that offer orthogonal points of intervention were observed. Collectively, these advances support structure-guided, context-aware, and hybrid/combination strategies for antibiotic design and therapeutic development.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 21-44"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992151","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":"SUMOylation and anticancer drug resistance","authors":"Hongwei Zhao,&nbsp;Chao Huang","doi":"10.1016/j.biochi.2026.01.007","DOIUrl":"10.1016/j.biochi.2026.01.007","url":null,"abstract":"<div><div>Therapeutic resistance is a major obstacle in cancer treatment, often leading to recurrence and death. SUMOylation is a dynamic and reversible process of post-translational modification through a strict enzyme cascade that regulates the modification of target proteins by SUMO1-5 and SENP family proteins, which are involved in regulating protein stability, function, and localization to influence biological pathways, including cancers. SUMOylation contributes significantly to cancer drug resistance, undermining the efficacy of clinical treatment. Therefore, studying the role of SUMOylation in the development of cancer drug resistance has significant prospects. This review focuses on the important mechanistic role of SUMOylation in promoting or inhibiting cancer drug resistance and summarizes the feasibility of using SUMOylation as a therapeutic target for cancer treatment by combining SUMOylation inhibitors and anticancer drugs, which will provide new insights into overcoming cancer drug resistance and clinical cancer treatment.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"243 ","pages":"Pages 45-58"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013880","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":"Human mitochondrial persulfide dioxygenase is potently and reversibly inhibited by nitric oxide","authors":"Francesca Giordano ,&nbsp;Diogo H.P. Silva ,&nbsp;Elena Forte ,&nbsp;Alessandro Giuffrè ,&nbsp;João B. Vicente","doi":"10.1016/j.biochi.2026.01.001","DOIUrl":"10.1016/j.biochi.2026.01.001","url":null,"abstract":"<div><div>Hydrogen sulfide (H₂S) regulates multiple human physiological processes, its reactivity and range of action being tightly controlled through regulation of H₂S-synthesizing and -detoxifying enzymes. H₂S detoxification is mainly achieved by a mitochondrial sulfide detoxifying pathway including persulfide dioxygenase (PDO). Human PDO (known as ethylmalonic encephalopathy protein 1, ETHE1), a homodimeric enzyme with a mononuclear iron centre active site, catalyzes the conversion of glutathione persulfide (GSSH) and O₂ to reduced glutathione (GSH) and sulfite. Here we report that ETHE1 is potently inhibited by authentic nitric oxide (NO) gas at physiological concentrations, as observed by high resolution respirometry. Inhibition is reversible, occurs via NO binding to the reduced mononuclear iron center and becomes more potent and persistent at lower O₂ levels. Incubation with <span><em>s</em></span>-nitrosoglutathione (GSNO) also appears to partially and transiently inhibit ETHE1, this effect likely resulting from <span><em>s</em></span>-nitrosation of cysteine residues. While ETHE1 is devoid of NO reductase activity, in aerobic conditions it displays low NO degrading activity. These findings unravel a novel layer of cross-regulation between the H₂S and NO gasotransmitters with possible implications on the regulation of numerous physiological and pathophysiological processes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 143-148"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919213","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":"Lmod3 ablation disrupts auditory function without compromising hair cell stereocilia development or MET competence","authors":"Haibo Du ,&nbsp;Xi Huang ,&nbsp;Yixiao Sun ,&nbsp;Hao Zhou","doi":"10.1016/j.biochi.2025.12.005","DOIUrl":"10.1016/j.biochi.2025.12.005","url":null,"abstract":"<div><div>F-actin cytoskeleton plays critical roles in hair cell. This study identifies LMOD3, an F-actin nucleator, as specifically expressed in outer hair cells (OHCs) of mice. <em>Lmod3</em> knockout causes significant hearing loss (about 40 dB elevation in auditory brainstem response (ABR) thresholds, increased distortion product otoacoustic emission (DPOAE) thresholds), while leaving stereocilia morphology and mechanoelectrical transduction (MET) function intact. Phenotypic analyses hint that LMOD3 deficiency likely impairs OHC-based cochlear amplification. Our work establishes LMOD3 as essential for auditory function.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 77-84"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145758710","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":"ANGPTL4 regulates the adipogenic–osteogenic differentiation balance of bone marrow mesenchymal stem cells: A novel mechanism of osteoporosis from the perspective of lipid metabolism","authors":"Fuhao Huang ,&nbsp;Zhu Zhu ,&nbsp;Qiqiang Xing ,&nbsp;Ming Li","doi":"10.1016/j.biochi.2025.12.014","DOIUrl":"10.1016/j.biochi.2025.12.014","url":null,"abstract":"<div><div>To investigate the role of lipid metabolism abnormalities in the progression of osteoporosis (OP), clarify the impact of the key regulator angiopoietin-like protein 4 (ANGPTL4) on the adipogenic–osteogenic differentiation balance of bone marrow mesenchymal stem cells (BMSCs), and provide new insights into the molecular mechanisms and targeted therapy of OP, single-cell and multi-omics transcriptomic datasets were integrated with lipid metabolism–related gene sets. Potential key genes were identified through AUCell scoring, enrichment analysis, and machine learning algorithms validated by 5-fold cross-validation. CellChat was applied to analyze intercellular communication, while GSVA revealed associated signaling pathways. Furthermore, functional validation was performed by knocking down ANGPTL4 in BMSCs using two independent siRNA sequences. The effects on differentiation were assessed by lipid accumulation and osteogenic mineralization assays, biochemical assays, recombinant protein rescue experiments, time-course Western blot, and qPCR analysis of clinical bone marrow samples. Analysis revealed that OP-BMSCs exhibited significantly enhanced lipid metabolism activity. ANGPTL4 was identified as a core candidate gene, demonstrating robust discriminative power with a mean AUC of 0.777 in 5-fold cross-validation. Functional assays confirmed that ANGPTL4 knockdown significantly inhibited adipogenesis while enhancing osteogenic differentiation independent of cell proliferation. Importantly, treatment with recombinant ANGPTL4 protein effectively reversed these phenotypic changes. Mechanistically, ANGPTL4 silencing specifically upregulated BMP2, BMP4, and BMPR1A, leading to the activation of p-Smad1/5/9 and the accelerated expression of Runx2 and Ocn in a time-dependent manner. Consistent with these findings, <em>ANGPTL4</em> mRNA levels were significantly elevated in bone marrow samples from OP patients. In conclusion, ANGPTL4 serves as a critical checkpoint connecting lipid metabolism and OP pathology. It inhibits osteogenesis by suppressing the BMP2/4-BMPR1A-Smad signaling axis. Targeting ANGPTL4 effectively restores the adipo-osteogenic balance of BMSCs, suggesting it is a promising candidate target for OP therapy, pending further <em>in vivo</em> validation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 118-133"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893483","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":"A comprehensive review on the advanced glycation end products detection: From conventional to advanced approaches","authors":"Subhrajeet Sahoo ,&nbsp;Michael Howsam ,&nbsp;Frédéric J. Tessier ,&nbsp;Rashmi S. Tupe","doi":"10.1016/j.biochi.2025.12.004","DOIUrl":"10.1016/j.biochi.2025.12.004","url":null,"abstract":"<div><div>The glycation process ultimately generates advanced glycation end products (AGEs) either exogenously or endogenously. With unique structural and functional properties, AGEs contribute to diabetic complications and other glycation-mediated disorders. Owing to the variety of conglomerations, AGEs quantification demands the development of specific and feasible techniques. This article summarizes the molecular mechanism of AGEs formation, along with classifications based on origin, chemical nature, and cellular localization. Moreover, the scope and limitations of existing quantification techniques for both exogenous and endogenous AGEs are discussed. Currently, spectroscopy, chromatography, and immunoassays are widely used methods for measuring AGEs. LC-MS/MS remains the most reliable and specific method, while ELISA and fluorescence spectroscopy offer practical alternatives for specific applications. Non-invasive detection techniques, such as AGEs readers and the facial glycation system, have paved the way; however, associated costs and controversies restrict their feasibility. Hence, future studies with a focus on established and emerging detection techniques for AGEs are crucial to understand the comprehensive role of AGEs in disease progression.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 22-41"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746225","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":"Functional characterization of Cr-CATHs: Novel antimicrobial peptides from the coastal bird Chroicocephalus ridibundus","authors":"Haoran Dou ,&nbsp;Shuangyu Li ,&nbsp;Pingchuan Zhang ,&nbsp;Zifan Ye ,&nbsp;Lili Li ,&nbsp;Yipeng Wang ,&nbsp;Xudong Jiao","doi":"10.1016/j.biochi.2025.12.008","DOIUrl":"10.1016/j.biochi.2025.12.008","url":null,"abstract":"<div><div>The escalating global threat of antimicrobial resistance (AMR) and chronic biofilm-associated infections underscores the urgent need for novel therapeutic agents. Antimicrobial peptides (AMPs) offer a promising alternative due to their potent activity, broad-spectrum efficacy, and low resistance induction. In this study, we identified three novel cathelicidin-like peptides—Cr-CATH-1 (Cr1), Cr-CATH-2 (Cr2), and Cr-CATH-3 (Cr3)—from <em>Chroicocephalus ridibundus</em>. These peptides were systematically evaluated for their physicochemical properties, antimicrobial activity, bactericidal kinetics, and effects on biofilm formation and persister cells. Cr1 exhibited the most potent and broad-spectrum antimicrobial activity, particularly against Gram-negative and aquatic pathogens. Although Cr2 and Cr3 displayed relatively weaker antimicrobial effects, both peptides were effective in biofilm eradication and persister cell killing. Cr1 also demonstrated strong bactericidal activity, low cytotoxicity, and minimal hemolysis, suggesting a favorable safety profile. Its stability under physiological salt conditions, along with its ability to disrupt bacterial membranes, bind to DNA, and induce reactive oxygen species (ROS) production, highlights its therapeutic potential. <em>In vivo</em>, Cr1 significantly reduced bacterial load and improved survival in a murine peritonitis model, further supporting its potential for clinical and aquaculture applications. Our results suggest that Cr1 is a promising candidate for further development, while Cr2 and Cr3 may provide valuable insights for targeted therapeutic strategies, warranting additional investigation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 59-76"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800867","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 CYP134 family in Gram-positive bacteria: From Bacillus to beyond, an orphan P450 lineage awaiting functional discovery","authors":"Yiru Wang ,&nbsp;Ying Li","doi":"10.1016/j.biochi.2025.12.001","DOIUrl":"10.1016/j.biochi.2025.12.001","url":null,"abstract":"<div><div>Cytochrome P450 monooxygenases (CYPs) are pivotal enzymes in microbial metabolism, catalyzing a broad spectrum of oxidative reactions with ecological, physiological, and biotechnological significance. Within this superfamily, numerous <em>Bacillus</em> CYPs have been experimentally characterized, yet the CYP134 lineage remains poorly understood and is generally considered an orphan family. Although limited in vitro activities have been observed, a clear physiological substrate or function has not been defined. Despite this uncertainty, CYP134 members are widely distributed across Gram-positive bacteria, particularly within the Firmicutes, and exhibit the conserved structural motifs that safeguard P450 catalytic competence. Their expression is often responsive to environmental cues such as iron limitation and stress, pointing toward potential roles in specialized metabolic circuits and microbial competition. The evolutionary conservation, structural stability, and ecological responsiveness of these enzymes underscore their relevance as emerging candidates for functional discovery. This review integrates current structural, genomic, and ecological perspectives on CYP134 proteins, highlights unresolved questions, and proposes future avenues for exploring their biochemical activities and biotechnological applications.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 9-21"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688958","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":"Inside front cover-EDB","authors":"","doi":"10.1016/S0300-9084(26)00037-4","DOIUrl":"10.1016/S0300-9084(26)00037-4","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Page IFC"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147396675","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":"Extracellular mitochondria: a potential player involved in exercise health benefits","authors":"Mafalda Barbosa Pedrosa ,&nbsp;Lúcio Lara Santos ,&nbsp;Rita Ferreira ,&nbsp;José Magalhães","doi":"10.1016/j.biochi.2025.12.011","DOIUrl":"10.1016/j.biochi.2025.12.011","url":null,"abstract":"<div><div>Exercise is widely recognized as an effective nonpharmacological therapy for noncommunicable diseases, with its health benefits mediated in part by exerkines. Recently, extracellular mitochondria (ex-Mito) have been suggested as a player in mediating intercellular communication. While it is known that the health benefits of exercise involve the remodeling of mitochondria in multiple organs, the impact of exercise on circulating ex-Mito is poorly understood. Most existing studies have focused on cell-free circulating mitochondrial DNA, skeletal muscle-derived extracellular vesicles, or platelet-derived mitochondria, without focusing on other types of ex-Mito. The cellular origin of exercise-induced circulating ex-Mito and the role of each form (vesicle-enclosed, free, or as mitochondrial components) in mediating exercise's therapeutic effects are yet to be elucidated. This review aims to delve into the role of ex-Mito as potential players in exercise-related health benefits, paving the way for future research aimed at uncovering the molecular culprits of this nonpharmacological therapy, including mitochondrial transfer and transplantation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"242 ","pages":"Pages 97-107"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851877","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}