Biochimie最新文献

{"title":"Inside front cover-EDB","authors":"","doi":"10.1016/S0300-9084(25)00203-2","DOIUrl":"10.1016/S0300-9084(25)00203-2","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Page IFC"},"PeriodicalIF":3.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145044604","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(25)00177-4","DOIUrl":"10.1016/S0300-9084(25)00177-4","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"236 ","pages":"Page IFC"},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865849","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":"Small molecule based targeting of the CssA RNA thermometer: insights from computational and biophysical approaches","authors":"Akanksha Sharma ,&nbsp;Priyanka Gopi ,&nbsp;Rimjhim Trivedi ,&nbsp;Dinesh Kumar ,&nbsp;Janeka Gartia ,&nbsp;Adukamparai Rajukrishnan Suresh Babu ,&nbsp;Prateek Pandya ,&nbsp;Gurpal Singh ,&nbsp;Ravi Pratap Barnwal","doi":"10.1016/j.biochi.2025.07.017","DOIUrl":"10.1016/j.biochi.2025.07.017","url":null,"abstract":"<div><div>The exploration of RNA as a therapeutic target is relatively recent. The field of RNA targeting with small molecules remains elusive despite significant advances via approaches such as the development of bioinformatics tools and strategies facilitating improved modes of action. Non-coding RNAs like RNA thermometers reported in many bacterial pathogens are exciting targets due to the translational control exerted by these RNA elements. The current work involves virtual screening of an <em>in house</em> library of small molecules against CssA RNA thermometer from <em>Neisseria meningitidis</em> via docking and molecular dynamics (MD) simulations followed by <em>in vitro</em> experiments to affirm the binding of small molecules to the target RNA. Fluorescence binding assay and NMR provide evidence for RNA thermometer-small molecule binding. The present study would open new avenues in the domain of small molecule-based targeting of RNA. Interestingly, an RNA thermometer has never been exploited as a drug target. Targeting such RNA elements with small molecules would facilitate structure-based small molecule design with better affinity for the target RNA. From among spiro-pyrrolidine based heterocycles that showed the best binding affinity with the RNAs, a small molecule was identified as the top lead with the potential for targeting the CssA RNA thermometer.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 110-124"},"PeriodicalIF":3.3,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669077","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":"5-(3, 4-methylenedioxyphenyl)-4-ethyl-2E, 4E-pentadienoic acid piperidide as MdeA efflux pump inhibitor of Staphylococcus aureus","authors":"Rahul Bhat ,&nbsp;Neha Jeena ,&nbsp;Samsher Singh ,&nbsp;Nitin Pal Kalia ,&nbsp;Narendra Singh Chauhan ,&nbsp;Surrinder Koul ,&nbsp;Govind Yadav ,&nbsp;Saurabh Saran ,&nbsp;Inshad Ali Khan","doi":"10.1016/j.biochi.2025.07.016","DOIUrl":"10.1016/j.biochi.2025.07.016","url":null,"abstract":"<div><div>The analogue of piperine <strong>5-(3,4-methylenedioxyphenyl)-4-ethyl-2<em>E</em>,4<em>E</em>-pentadienoic acid piperidide</strong> (IIIM-1133), was evaluated in this in combination with pseudomonic acid A, commonly known as mupirocin against of <em>S. aureus</em> including Methicillin Resistant <em>S. aureus</em> (MRSA). Initial screening of compound revealed an increase in the potency of mupirocin, with a reduction in the minimum inhibitory concentration (MIC) values from 0.25 μg/mL to 0.06 μg/mL in case of wild type and MRSA strains of <em>S. aureus</em> and from 256 μg/mL to 32 μg/mL in mup^r-1 strain. The combination decreased the mutation frequency against mupirocin in wild-type <em>S. aureus</em>. The demonstrated ability of IIIM-1133 to suppress ethidium bromide efflux in MdeA-overexpressing <em>S. aureus</em> Mup^r-1 substantiated its effectiveness as an efflux pump inhibitor. Docking studies demonstrated that IIIM-1133 binds strongly in the substrate pocket of the MdeA efflux pump, highlighting its potential as an efflux pump inhibitor. IIIM-1133 alone and in combination with mupirocin was found to be nontoxic when tested on RAW 264.7 cells lines. A topical formulation of 2 % mupirocin with 0.5 % IIIM-1133 showed better efficacy in reducing the bacterial load in the infected site and sterilizing the infected patch. Furthermore, the formulation revealed better tissue healing potential with an anti-inflammatory activity by suppressing Il-6 and TNF-α. This formulation exhibited better efficacy than markedly available 2 % mupirocin.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 125-137"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669076","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 X Factor: Regional differences in the level of ontogenetic variations in procoagulant venom activity in the Northwestern Neotropical Rattlesnake (Crotalus culminatus)","authors":"Lorenzo Seneci ,&nbsp;Uthpala Chandrasekara ,&nbsp;Abhinandan Chowdhury ,&nbsp;Vanessa Zarzosa ,&nbsp;Alid Guadarrama-Martínez ,&nbsp;Edgar Neri-Castro ,&nbsp;Alejandro Alagón ,&nbsp;Raul Soria ,&nbsp;Bryan G. Fry","doi":"10.1016/j.biochi.2025.07.015","DOIUrl":"10.1016/j.biochi.2025.07.015","url":null,"abstract":"<div><div>Rattlesnakes are among the most widespread and medically significant venomous snakes in the Americas. Mexico boasts the highest diversity of these snakes, making it an ideal setting for research on the biology and medical implications of rattlesnake venom. The Northwestern Neotropical rattlesnake (<em>Crotalus culminatus</em>), endemic to Mexico, has been previously shown to exhibit an ontogenetic loss of strong Factor X activation procoagulant activity. This pathophysiological activity was poorly neutralized by antivenom but was abolished by a metalloproteinase inhibitor. This toxicological study expands on initial findings to assess ontogenetic venom variation across a broader geographic scale, while also testing the efficacy of three antivenoms and three metalloproteinase inhibitors against <em>C. culminatus</em> coagulotoxicity. Our results reveal a potential geographic influence on ontogenetic loss of FX activation-based procoagulant toxicity, which appears more marked in the state of Morelos than in Guerrero and Michoacán (all within Mexico). Possible evolutionary and ecological explanations for this are discussed. Furthermore, none of the tested antivenoms were able to neutralize procoagulant venom activity. In contrast, the metalloproteinase inhibitors marimastat and prinomastat were effective. However, the metalloproteinase inhibitor DMPS (2,3-Dimercapto-1-propanesulfonic acid) was ineffective even at a 5X higher molarity concentration than prinomastat and marimastat. The results of this study have implications across clinical medicine, toxicology, and evolutionary biology. They highlight the need for improvements in antivenom manufacturing while also providing data supporting the utility of enzyme inhibitors as therapeutic options. The data also lays the foundation for exploring the selection pressures leading to this novel rattlesnake venom phenotype.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 138-149"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669078","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 role of mitochondrial DNA in bone/cartilage diseases","authors":"Ying Wang ,&nbsp;Zuping Wu ,&nbsp;Wei Liu,&nbsp;Mingcheng Lu,&nbsp;Jiejun Shi","doi":"10.1016/j.biochi.2025.07.014","DOIUrl":"10.1016/j.biochi.2025.07.014","url":null,"abstract":"<div><div>Skeletons, as a human sports scaffold, provide attachment points for muscle and ligament attachment, and store significant quantities of calcium and phosphate. The aetiology of bone-related diseases is multifactorial, involving a complex interplay between osteoblasts and osteoclasts, as well as immune system abnormalities. These factors can result in impaired motor function and physical discomfort. Recent studies have indicated an association between mitochondrial DNA (mtDNA) abnormalities and the development of bone and cartilage diseases. The level of mtDNA in body fluid is expected to become a potential diagnostic marker to evaluate the degree of bone destruction and the prognosis of complications. The mtDNA copy number abnormalities, mtDNA mutations, and mtDNA leakage contribute to the deterioration of bone and cartilage-related diseases. The increase in mtDNA copy number has been demonstrated to provide more energy for the proliferation of tumour cells. Conversely, a loss of mtDNA copy number gives rise to abnormal mitochondrial function. The coupling efficiency of oxidative phosphorylation and reactive oxygen species production is modulated by different mtDNA haplotypes, thereby impacting the energy supply required for osteoblast proliferation and differentiation. mtDNA leakage induces inflammatory cytokines via interferon-related pathways and delays fracture healing. The restoration of mtDNA copy number through repair of mitochondrial biogenesis, the reduction of mtDNA leakage, or the inhibition of downstream inflammatory pathways is expected to rescue bone and cartilage-related diseases caused by mtDNA abnormalities.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 98-109"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621467","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":"Identification of lipid biomarkers at different stages of breast cancer by rapid evaporative ionization mass spectrometry (REIMS) using syngeneic balb/c mice breast cancer model","authors":"Kizhakkeppurath Kumaran Ajeeshkumar ,&nbsp;Pranamya Chettiarakkal Haridas ,&nbsp;Rajesh Ravichandran ,&nbsp;Niladri Sekhar Chatterjee ,&nbsp;Sankaramthadathil Sivaraman Roshni ,&nbsp;Peruvazhipurath Appu Aneesh ,&nbsp;Sujith Samraj ,&nbsp;Nisha Aynikkattil Ravindran ,&nbsp;Suseela Mathew ,&nbsp;Saurabh Verma","doi":"10.1016/j.biochi.2025.07.010","DOIUrl":"10.1016/j.biochi.2025.07.010","url":null,"abstract":"<div><div>Lipid metabolite profiling of different phases, i.e., early phase (EP) and metastatic phase, was carried out to find out potential lipid biomarkers in breast cancer. Breast cancer was induced using 4T1 cells in a syngeneic mice model using balb/c mice. Rapid Evaporative Ionization Mass Spectrometry (REIMS) was employed to elucidate the lipid biomarker profile. REIMS analysis revealed 25 significant lipid metabolites with biomarker potential for breast cancer. Definite expression variations of different lipid biomarkers highlight the hallmark lipid biomarker, which in turn might be playing a crucial role in breast cancer induction and progression. Different classes of lipids, such as phospholipids, steroids, fatty acids, etc. were observed in the analysis, and they were found to participate in vital pathways including glycerophospholipid metabolism, steroid hormone biosynthesis, fructose and mannose metabolism, either lipid metabolism, glycerolipid metabolism, glycolysis/gluconeogenesis, inositol phosphate metabolism and the biosynthesis of unsaturated fatty acids, respectively, during breast cancer events. Therefore, these lipid metabolites can be considered a potential lipid biomarker for better diagnosis, such as early detection, and to design an effective breast cancer treatment in the future.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 66-76"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621464","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":"Sometimes size does matter: Anticoagulant pathophysiological effects of Southwestern Speckled Rattlesnake (Crotalus pyrrhus) venoms are dichotomous by body size","authors":"Zichen Qiao ,&nbsp;Chip Cochran ,&nbsp;Abhinandan Chowdhury ,&nbsp;Lachlan A. Bourke ,&nbsp;Lorenzo Seneci ,&nbsp;Bryan G. Fry","doi":"10.1016/j.biochi.2025.07.012","DOIUrl":"10.1016/j.biochi.2025.07.012","url":null,"abstract":"<div><div>The Southwestern Speckled Rattlesnake (<em>Crotalus pyrrhus</em>) is a medically significant pit viper with envenomation effects that include depletion of fibrinogen levels. Despite this the venom has been poorly studied. To fill this knowledge gap, we 57 venom samples obtained from 19 geographic localities, including both juvenile and adult venoms, for their effect upon human plasma and purified fibrinogen. For most localities, we were able to include both female and male specimens of varying sizes to test possible sexual venom variation and size-related shifts. We found that instead of a geographical variation in coagulotoxicity, <em>C. pyrrhus</em> venoms exhibit a consistent size-related trend, whereby small snakes and adult snakes were both anticoagulant, but differed sharply in the underly biochemistry. Smaller snakes deplete fibrinogen levels through a pseudo-procoagulant (thrombin-like) mechanism whereby fibrinogen is cleaved by kallikrein-scaffold serine proteases to produce weak, transient clots that rapidly break down. In contrast, larger snakes are classically anticoagulant through the inhibition of the blood clotting factors VIIa, FIXa, FXIa and thrombin, while also depleting fibrinogen levels through destructive (non-clotting) cleavage. Antivenom testing on pseudo-procoagulant venoms for three regionally available antivenoms showed an efficacy pattern of Antivipmyn® &gt; BIRMEX® &gt; CroFab®. As such, this study revealed a dramatic ontogenetic change in the venom biochemistry that was conserved across the vast range of this medically important rattlesnake species. In turn, this variation in venom biochemistry may produce differential pathophysiological effects during a human envenomation.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 40-53"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621466","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 promise of cell-based therapies in diabetes: A review of mesenchymal stem cell applications and trials","authors":"Cong Li ,&nbsp;Shaobo Wang ,&nbsp;Jie Jiang ,&nbsp;Wenjin Fu ,&nbsp;Jincheng Zeng","doi":"10.1016/j.biochi.2025.07.011","DOIUrl":"10.1016/j.biochi.2025.07.011","url":null,"abstract":"<div><div>Diabetes mellitus, characterized by chronic hyperglycemia, presents a major global health burden with rising incidence worldwide. Current therapies often fail to achieve sustained glycemic control or halt disease progression, necessitating innovative strategies that target both metabolic dysfunction and autoimmune mechanisms in diabetes. Mesenchymal stem cells (MSCs) have garnered significant attention as a multifaceted therapeutic option, owing to their unique dual capabilities: tissue repair (via differentiation potential and paracrine effects) and immunomodulation (through cytokine secretion and immune cell regulation). This review comprehensively examines the therapeutic potential of MSCs in diabetes, covering: (1) mechanistic insights into how MSCs restore pancreatic β-cell function and mitigate insulin resistance; (2) preclinical evidence supporting their efficacy in both type 1 and type 2 diabetes models; and (3) critical analysis of ongoing clinical trials, including routes of administration, safety profiles, and metabolic outcomes. While promising results have been demonstrated in early-phase trials, we also discuss key challenges such as cell survival, standardization of protocols, and long-term therapeutic durability. By bridging current knowledge gaps with clinical translation needs, this review aims to provide a balanced perspective on MSC-based therapies for diabetes.</div></div>","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"237 ","pages":"Pages 54-65"},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610600","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(25)00131-2","DOIUrl":"10.1016/S0300-9084(25)00131-2","url":null,"abstract":"","PeriodicalId":251,"journal":{"name":"Biochimie","volume":"235 ","pages":"Page IFC"},"PeriodicalIF":3.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571990","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}