Biochimie最新文献

{"title":"Advances in CRISPR-based genetic engineering of Bifidobacterium.","authors":"Xiaotong Lin, Yixin Zhang, Jiayi Cheng, Jialong Chen, Xin Liu","doi":"10.1016/j.biochi.2026.09.003","DOIUrl":"10.1016/j.biochi.2026.09.003","url":null,"abstract":"<p><p>Bifidobacterium plays a vital role in gut health, immunity, and metabolism, yet natural strains show limited native functional capabilities and genetic manipulability. Recent advances in genome editing, especially CRISPR-based systems, have provided novel approaches for engineering Bifidobacterium, though strain-specific variability and restriction-modification barriers remain substantial constraints. This review outlines the evolution from traditional homologous recombination to CRISPR/Cas technologies, highlighting applications of endogenous and exogenous systems, including CRISPRi/a and base editing. In preclinical and food biotechnology contexts, genetically engineered strains have shown potential as targeted delivery vehicles and functional probiotics. Despite these achievements, challenges such as strain variability, restriction-modification barriers, and biosafety concerns persist. Where genetic accessibility can be established, the integration of CRISPR technology with synthetic biology may enable more precise gene regulation and could support the development of next-generation engineered Bifidobacterium-based platforms.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium in aging and longevity.","authors":"William Gerard Pierce, John James Mackrill","doi":"10.1016/j.biochi.2026.09.002","DOIUrl":"10.1016/j.biochi.2026.09.002","url":null,"abstract":"<p><p>Selenium is an essential dietary micronutrient, exerting beneficial effects over a limited range of concentrations. Insufficient dietary intake of selenium increases the risk of type 2 diabetes, infertility, immune dysfunction, prostate cancer, cognitive decline, prostate cancer, colorectal cancer in females, skeletal muscle disorders, overall mortality and an endemic cardiomyopathy known as Keshan disease. Excessive intake of selenium is toxic, leading to a condition termed selenosis, that is associated with damage to the nails, dermatitis, alopecia, central nervous system dysfunction and death. Selenium exerts its biological effects through low-molecular weight molecules, through a small family of selenoproteins which contain the 21st amino acid selenocysteine, and via selenium-binding proteins, in which an atom of selenium is covalently bound to a cysteine residue. In addition to being regulated by body selenium status, the abundance and function of these biomolecules can be controlled by other dietary components (including copper, zinc, folic acid, resveratrol, vitamin A and α-linoleic acid) and other factors, such as exercise and caloric restriction. This review comprehensively surveys the effects of selenium-containing biomolecules on aging and aims to generate rationales underpinning the biphasic effects of this element on life-span, health-span and disease. This will provide a framework for understanding the effects of selenium on mechanisms of aging, as the starting point for development of interventions that will promote longevity and health-span.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erythrocyte trans fatty acid accumulation in elderly sarcopenic patients: biochemical evidence for oxidative stress-driven cis-trans isomerization of membrane lipids.","authors":"Amira Zarrouk, Imen Ghzaiel, Gérard Lizard, Mohammed Hammami, Sonia Hammami","doi":"10.1016/j.biochi.2026.09.001","DOIUrl":"10.1016/j.biochi.2026.09.001","url":null,"abstract":"<p><p>Free radical-mediated cis-trans isomerization of polyunsaturated fatty acids (FA) is well established in food chemistry, yet its occurrence as an endogenous biochemical process in oxidatively stressed human tissues remains poorly characterized. Sarcopenia, a geriatric syndrome defined by progressive loss of skeletal muscle mass and function, is associated with chronic oxidative stress. We hypothesized that this oxidative milieu drives in vivo cis-trans isomerization of erythrocyte membrane FA, generating trans isomers distinguishable from dietary exposure. A cross-sectional study was conducted in 160 subjects aged ≥65 years, classified as sarcopenic (n = 97) or non-sarcopenic (n = 63) by SARC-F questionnaire and handgrip strength. Erythrocyte FA profiles were determined by gas chromatography; plasma oxysterols were quantified by GC-MS. Specific trans isomers were markedly elevated in sarcopenic patients, especially C18:1 trans-11 (3.09-fold; p < 0.001) and the linoleic acid isomer C18:2 trans-9, cis-12 (2.66-fold; p < 0.001). Their cis counterparts were not significantly elevated. By contrast, two trans species that retain the cis-9 configuration, the ruminant dietary marker C18:2 cis-9, trans-11 (CLA) and the geometric isomer C18:2 cis-9, trans-12, were both paradoxically reduced (p = 0.007 and p < 0.001, respectively). Total trans FA correlated with non-enzymatic oxysterols 7-ketocholesterol (ρ = 0.49, p < 0.001),7α-hydroxycholesterol (ρ = 0.43, p = 0.003), and 7β-hydroxycholesterol (ρ = 0.49, p < 0.001), but not with enzymatically formed 24S-hydroxycholesterol. On multivariate analysis, total trans fatty acids remained independently associated with sarcopenia (OR 1.28; p = 0.018). These findings provide the first biochemical evidence that chronic oxidative stress in sarcopenic elderly patients drives endogenous cis-trans isomerization of membrane FA, challenging the notion that elevated trans FA represent a purely dietary phenomenon.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiometabolic disease risk: the joint role of the UCP1, UCP2, UCP3, and FTO gene variants.","authors":"Anna E Pravednikova, Antonina Nikitich, Anna Andrzejczak, Anna Tomkiewicz, Lidia Karabon, Damian Skrypnik, Pawel Bogdanski, Eugene S Grebenshchikov, Boris Shulgin, Yulii V Shidlovskii","doi":"10.1016/j.biochi.2026.08.020","DOIUrl":"10.1016/j.biochi.2026.08.020","url":null,"abstract":"<p><p>Cardiometabolic diseases (CMDs) impose a significant global health burden. Although CMDs rarely occur in isolation, most genetic studies have examined individual conditions separately, overlooking shared pathogenic pathways that link them into a continuous cardiometabolic continuum. Moreover, population-specific data for Eastern and Central Europe are scarce, and combined effects of variants in key metabolism-related genes, such as UCP1-UCP3 and FTO, have not been studied within cardiometabolic continuum. In this study, we investigated individual and combinatorial effects of UCP1-UCP3, and FTO variants on risk of CMDs as a continuum in Central Russian and Polish populations. We identified novel risk-increasing combinations: minor alleles of UCP2 c.-866G > A and UCP3 c.-55C > T; and minor alleles of UCP3 c.-55C > T and FTO c.46_23525T > A with wild alleles of four UCP1 and two UCP2 variants. Protective effects were observed for two novel combinations: minor allele of FTO c.46_23525T > A with wild alleles of all studied UCPs variants; and minor allele of UCP2 c.-866G > A with wild allele of UCP2 p.Ala55Val. The FTO variant showed context-dependent effects, shifting from risk to protection depending on genetic background. Increased age, BMI, WtHR, and BF% were also significant predictors, with sex-specific differences. Predictive quality of models integrating genetic and non-genetic factors (AUC up to 0.97) further underscore the potential value of this approach. In silico analysis suggested these variants exhibit regulatory functions across various tissues, which potentially involved in CMD pathogenesis. This is the first study to demonstrate combinatorial UCP1-UCP3 and FTO effects on risk of CMDs as a continuum in Central Russian and Polish populations.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osmolytes suppress liquid‒liquid phase separation and the aggregation of Tau.","authors":"Jingye Lin, Zongbao Wang, Chenxi Liu, Yiwen Hua, Sen Li","doi":"10.1016/j.biochi.2026.08.019","DOIUrl":"10.1016/j.biochi.2026.08.019","url":null,"abstract":"<p><p>Tau liquid-liquid phase separation (LLPS) is increasingly recognized as an early event that promotes pathological aggregation in Alzheimer's disease and other tauopathies. Osmolytes are natural chemical chaperones that stabilize protein conformations, yet their effects on Tau phase behavior remain poorly understood. Here, we show that sucrose, trehalose, glucose, maltose, and betaine suppress Tau LLPS and dissolve preformed Tau droplets, shifting the equilibrium toward soluble monomers in vitro. Among the five osmolytes, trehalose and glucose exhibited the strongest inhibitory effects on Tau LLPS. They also suppressed the liquid-to-solid phase transition of Tau droplets, as evidenced by reduced Thioflavin T (ThT) fluorescence, inhibition of fibril formation observed by transmission electron microscopy (TEM), and improved condensate dynamics in fluorescence recovery after photobleaching (FRAP) assays performed in okadaic acid-treated cells. These results indicate that osmolytes interfere with multiple stages of Tau phase transition-from initial condensate formation to pathological maturation and fibrillization. Our findings establish osmolytes as effective modulators of Tau phase behavior and provide mechanistic insights into the physicochemical regulation of Tau phase transitions.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant phospholipases D: functions, structures, and enzymatic activities.","authors":"Loris Malcles, Assia Mouhand, Abdelkarim Abousalham, Alexandre Noiriel","doi":"10.1016/j.biochi.2026.08.016","DOIUrl":"10.1016/j.biochi.2026.08.016","url":null,"abstract":"<p><p>Phospholipases D (PLDs) (EC 3.1.4.4) are enzymes capable of hydrolyzing the distal phosphodiester bond of phospholipid (PL) substrates. PLD reaction frees phosphatidic acid (PA), a key intermediate in lipid metabolism and an important signaling molecule involved in multiple cellular and physiological processes. Widely distributed across prokaryotes and eukaryotes, PLDs have diversified considerably and fulfill distinct biological functions depending on the organism and physiological context. In plants, increasing evidence highlights their central roles in adaptation to abiotic and biotic stresses, reproductive processes, and developmental regulation, making them particularly relevant in the context of current agronomic and environmental challenges. This review examines the phylogenetic diversity of plant PLDs, with particular emphasis on cereal species, and summarizes recent advances in the characterization of their biological functions. Recent structural data obtained from plant PLDs also provide new insights into structure-function relationships within the PLD superfamily and help refine our understanding of the structural organization and enzymatic properties of plant PLDs.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electronegativity-based subfractionation of intermediate-density lipoproteins: Comparison with main lipoprotein classes.","authors":"Omer Akyol, Huan-Hsing Chiang, Frances W Ouyang, Jody V Vykoukal, Johannes F Fahrmann, Alan R Burns, Munenori Ishibashi, Chao-Yuh Yang, Chu Huang Chen","doi":"10.1016/j.biochi.2026.08.013","DOIUrl":"10.1016/j.biochi.2026.08.013","url":null,"abstract":"<p><p>Studying the chemical characteristics of intermediate-density lipoprotein (IDL), a transient metabolite and direct precursor to LDL, is crucial for understanding LDL heterogeneity and atherogenic potential. This study aimed to characterize the physicochemical properties and lipidomic composition of distinct IDL subfractions and evaluate their proatherogenic effects. Using ultracentrifugation and anion-exchange chromatography, we fractionated IDL into five increasingly electronegative subpopulations (I1-I5), analogous to LDL, VLDL, and HDL subclasses with high resolution. We then comprehensively characterized these overlooked remnants using TEM, electrophoresis, and exploratory LC-MS lipidomics. Our analysis showed I1 (49.6%) was the least and I5 (6.3%) the most electronegative subfraction. TEM revealed a significant size difference, with I5 particles (averaged 37.9 ± 11.2 nm) being larger than I1 particles (averaged 25.1 ± 4.6 nm; p < 0.05). Furthermore, electrophoretic protein fingerprinting suggested complex remodeling of the putative surface apolipoprotein cargo in highly electronegative particles. Exploratory lipidomic profiling indicated that I5 was enriched in lipid species associated with proatherogenic pathways, including triacylglycerides, lysophosphatidylcholines, and lysophosphatidylethanolamines, whereas I1 particles were enriched in structural phospholipids. These patterns highlight IDL's profound lipidomic heterogeneity. Similarities among V5, I5, and L5 strongly support a shared metabolic continuum, with I5 potentially representing an intermediate transition stage. Crucially, functional assays revealed that the electronegative I5 subfraction possessed potent cytotoxicity in endothelial and monocytic cell models compared to other lipoprotein subfractions and oxLDL, significantly reducing viability and increasing cell death. Given IDL's limited circulation time, the presence of the highly electronegative and lipotoxic I5 subfraction may substantially enhance the overall proatherogenic potential of electronegative lipoproteins.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WITHDRAWN: The hybrid energy metabolism profile of human colorectal cancer cells.","authors":"Rafael Moreno-Sánchez, Emma Verónica Moreno-Saavedra, Emma Saavedra, Jorge Luis Vargas-Navarro, Sara Rodríguez-Enríquez","doi":"10.1016/j.biochi.2026.08.014","DOIUrl":"10.1016/j.biochi.2026.08.014","url":null,"abstract":"<p><p>This article has been withdrawn at the request of the authors, the Editor-in-Chief and publisher for the following reason: subsequently to the pre-proof publication, it came to our attention that the manuscript may contain material or data for which publication was not authorized and that authorship cannot be verified. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the surface: plasmalogens are dispensable for retinal integrity and fertility in the mouse.","authors":"Ilaria Dorigatti, Viktorija Juric, Michael J Blumer, Denise Kummer, Janik Kokot, Georg Golderer, Fabian Dorninger, Johannes Berger, Markus A Keller, Katrin Watschinger","doi":"10.1016/j.biochi.2026.08.010","DOIUrl":"10.1016/j.biochi.2026.08.010","url":null,"abstract":"<p><p>Ether lipids and their subclass, the plasmalogens, are critical regulators of membrane organization, signaling, and stress responses in multiple tissues. Inborn errors in their anabolism cause severe multi-organ diseases such as Rhizomelic Chondrodysplasia Punctata and related peroxisomal disorders. The Gnpat knockout mouse model, characterized by total ether lipid deficiency, recapitulates key features of this disorder, including dense bilateral cataracts, microphthalmia, and infertility, but the specific contribution of different subclasses, particularly plasmalogens, remains elusive. The recent identification of the Peds1 gene allows dissecting the impact of selective plasmalogen deficiency with retention of plasmanyl lipids, another ether lipid subgroup. Here, we performed the first side-by-side comparison of Gnpat and Peds1 knockout in mice on a matched genetic background (C57BL/6 x CD1). Additionally, we assessed Peds1 knockout on a pure C57BL/6N genetic background. Plasmanyl lipids in Peds1 knockout mice were sufficient to prevent cataract formation on both genetic backgrounds, despite marked shifts in the ocular phospholipidome. Also, fertility and reproductive function were found to be preserved in Peds1 knockout mice. Our data demonstrate that plasmanyl lipids can partially protect against the severe phenotypes observed in mouse models of total ether lipid deficiency; notably, the ocular and reproductive phenotypes were plasmalogen-independent, indicating that loss of the vinyl ether double bond is not the key determinant of all symptoms in human and murine ether lipid deficiency and can at least partly be compensated by plasmanyl lipids.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into the neuroprotective effects of monoterpene-rich Eucalyptus citriodora essential oil: integrated in silico and in vitro analysis in 6-OHDA-treated N2a neuronal cells.","authors":"Amel Abidi, Enxhi Shaba, Lorenza Vantaggiato, Oumayma Kouki, Olfa Masmoudi-Kouki, Luca Bini, Cristina Ulivieri, Claudia Landi, Taoufik Ghrairi","doi":"10.1016/j.biochi.2026.08.005","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.08.005","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss driven by mitochondrial dysfunction, oxidative stress, and proteostasis collapse, for which current therapies remain symptomatic. This study investigated the neuroprotective effects of Eucalyptus citriodora essential oil (ECEO) on 6-hydroxydopamine (6-OHDA)-induced toxicity in N2a neuroblastoma cells. GC-MS analysis showed that ECEO was dominated by oxygenated monoterpenes, mainly citronellal (60.7%), isopulegol (16%), and citronellol (5.7%). In silico analysis of these constituents showed favorable ADMET profiles, predicted blood-brain barrier permeability, and non-overlapping multitarget engagement across enzymes, GPCRs and nuclear receptors. At the cellular level, ECEO pretreatment significantly restored cell viability (86.7% of control), reduced LDH release, attenuated ROS and NO, and limited mitochondrial depolarization. Quantitative 2D-gel/MALDI-TOF/TOF proteomics identified 94 differentially abundant proteins, of which 20 showed validated PD-related associations (KEGG, Gene4PD, and DisGeNET databases). ECEO pretreatment modulated 12 of these proteins across mechanistically coherent pathways: (i) reversal of 6-OHDA-induced reprogramming of energy metabolism, by normalizing the glycolytic enzymes PKM and PGK1 and restoring the TCA enzyme SUCLG2; (ii) reinforcement of proteostasis through PSMB4 and PSMA3 induction, VCP upregulation and attenuation of ER stress marker HSPA5/BiP; (iii) preservation of mitochondrial and cytoskeletal integrity through PHB1 induction and bilateral TUBB5 restoration. Overall, our results suggest that ECEO exerts significant neuroprotective effects in a cellular PD model by coordinately modulating energy metabolism, proteostasis, antioxidant defense, and structural integrity. Given its predominance in oxygenated monoterpenes the neuroprotective activity of ECEO may result from the combined contribution of the major constituents supporting further investigation in age-related neurodegeneration.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}