Biochimie最新文献

{"title":"Expression and purification of the second homeodomain of the transcriptional regulator Zinc-finger homeobox 2.","authors":"María Gabriela Álvarez-Rodríguez, José L Neira, Felipe Hornos, Jesús M Torres, Sergio Martínez-Rodríguez","doi":"10.1016/j.biochi.2026.10.022","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.022","url":null,"abstract":"<p><p>Zinc finger homeobox 2 (ZFHX2) is a 2572-residue-long, multidomain protein involved in the rare inherited congenital hypoalgesia. This pain insensitive phenotype is associated with a missense mutation (arginine to lysine at R1913) at the C-terminus of the second homeodomain (HDo2), comprising residues 1857-1916 of ZFHX2. In this work, we expressed and purified wild-type HDo2 and the mutant R1913K by using Ni²⁺-IMAC and a polishing gel filtration chromatography step. The isolated wild-type HDo2 was a monomeric, well-folded, stable polypeptide, with a high percentage of α-helix-like structure, as judged from the far-ultraviolet (UV) circular dichroism (CD), fluorescence and 1D-¹H-NMR spectra. Similar conformational properties were observed for the R1913K mutant. Thermal denaturations for both species, followed by fluorescence and far-UV CD, yielded similar apparent thermal denaturation midpoints. Therefore, the development of hypoalgesia does not seem to be related to global conformational changes in the structure of the domain, as monitored by those macroscopic probes.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217066","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":"A non-enzymatic C-type lectin from bullhead shark Heterodontus japonicus skin amplifies coagulation via common-pathway downstream of factor Xa.","authors":"Shintaro Matsui, Osamu Nakamura, Miki Nakao, Takanori Oyoshi, Shigeyuki Tsutsui","doi":"10.1016/j.biochi.2026.10.023","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.023","url":null,"abstract":"<p><p>The rapid arrest of bleeding after injury is essential for survival, and blood coagulation is the central mechanism of hemostasis. We previously reported that a C-type lectin (HjCL) present in the skin mucus of the bullhead shark (Heterodontus japonicus) exhibits procoagulant activity; however, its underlying molecular mechanism remains unclear. In this study, we evaluated the effects of HjCL on pathway-specific clotting reactions using prothrombin time (PT) and activated partial thromboplastin time (aPTT) assays. HjCL accelerated aPTT reagent-triggered clotting, as indicated by the shortened time to reach 50% of maximal fibrin formation (t50). In contrast, no procoagulant effect was observed in the reactions initiated by the PT reagent. We performed synthetic substrate assays for the factors Xa and thrombin to further assess the activation of common-pathway enzymes at the plasma level. HjCL enhanced thrombin generation in the aPTT assay but did not increase factor Xa generation. Together, these results suggest that HjCL does not act as an initiator of coagulation but rather promotes coagulation at a stage downstream of factor Xa formation, consistent with its role in the amplification phase of the common pathway. Our findings suggest a previously unrecognized mechanism by which a non-enzymatic protein modulates blood coagulation in cartilaginous fish, providing new insights into hemostatic regulation in early-diverging vertebrates.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208243","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":"Sterol metabolism in Caenorhabditis elegans-insights into nematode biology and potential control targets.","authors":"Tamirat Kaba Tona, Camilla M Donnelly, Doaa M Hanafy, Shokoofeh Shamsi, David J Leaver","doi":"10.1016/j.biochi.2026.10.020","DOIUrl":"10.1016/j.biochi.2026.10.020","url":null,"abstract":"<p><p>Parasitic nematodes inflict billion-dollar losses globally each year as they infect humans, livestock and plants. Exploiting fundamental biochemical differences between these parasites and their hosts could accelerate the discovery of improved control measures. One key area of biochemical difference between nematodes and their hosts is sterol biosynthesis as nematodes, unlike vertebrates, are unable to synthesise sterols de novo and therefore depend on exogenous sterols obtained from their diet or environment. However, they can extensively modify these sterols through specialised metabolic pathways, producing metabolites including C4-methylated sterols and dafachronic acids that have important roles in nematode development and physiology. This mini review focuses on sterol biochemistry and metabolism of nematodes, in particular, sterol metabolism in the model worm Caenorhabditis elegans.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198178","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":"A Rapid and Specific RAA-CRISPR/Cas13a Assay for Detecting Streptococcus mutans.","authors":"Xingdong Zhang, Shengjun Bu, He Sun, Shixing Xue, Chuanna Xu, Lijun Liu, Sha Qiu, Qingshuang Wang, Jiayu Wan, Anling Zhang","doi":"10.1016/j.biochi.2026.10.006","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.006","url":null,"abstract":"<p><p>Streptococcus mutans is recognized as a major etiological agent of dental caries, a highly prevalent chronic global health issue. The early identification of such cariogenic pathogens is therefore critical for implementing effective preventive strategies. To address this need, we established an integrated detection platform coupling recombinase-aided amplification (RAA) with CRISPR-Cas13a for S. mutans detection and evaluated its performance against conventional polymerase chain reaction (PCR). The proposed RAA-CRISPR-Cas13a assay exhibited superior sensitivity and faster turnaround time compared to PCR. A distinctive feature of the assay design was the inclusion of a T7 promoter sequence within the forward primer, thereby facilitating direct in vitro transcription without requiring an additional oligonucleotide. The assay demonstrated a broad quantitative detection range from 10¹ to 10⁹ CFU/mL, with a limit of detection (LOD) reaching 3.2 CFU/mL. A strong linear relationship (R² > 0.98) was established between the fluorescence response and the logarithmic bacterial concentration, underscoring the assay's accuracy and robustness. This sensitive and rapid detection system shows considerable promise for screening high-risk populations, allowing not only early detection but also potential evaluation of caries severity and progression. Its simplicity and minimal instrumentation requirements make it particularly suitable for low-resource healthcare environments.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198522","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":"The Evolving Paradigm of Autism: Folate Receptor Autoimmunity deranging Epigenetic Programming in fetal and postnatal Brain Development.","authors":"Vincent Th Ramaekers, Edward V Quadros","doi":"10.1016/j.biochi.2026.10.019","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.019","url":null,"abstract":"<p><p>This review on autism provides a summary of the multiple genetic, epigenetic and environmental changes setting the stage for disturbed brain development due to aberrant synaptogenesis and corticogenesis during the prenatal and post-natal periods. The emphasis is placed on nonmendelian transmission driven by epigenetics. Folate deficiency appears to play a critical role in influencing many of the structural changes contributing to developmental deficits. Impaired passage of folate across the placental and the blood-brain barriers to the fetal and postnatal brain because of folate receptor autoantibodies (FRAb) emerges as the major cause. Cerebral folate deficiency with or without autism has been associated with FOLR1 gene defects, a rare disorder. On the other hand, FRAb in association with low CSF folate is present in most children diagnosed with autism. These autoantibodies are present in more than 1/3 of asymptomatic parents of children with autism or are acquired by the child during the first two years of life. Early detection of FRAb amongst autistic children is necessary to enable high dose folinic acid treatment. The use of folinic acid before conception and during pregnancy among mothers or both parents with FRAb, represents a promising strategy to reduce the risk of autism in future offspring. Interventational treatments in parents prior to pregnancy and optimal therapeutic approaches in infants are needed to prevent disordered development of the pre- or post-natal brain.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186784","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":"Molecular Mechanisms of Plant Secondary Metabolites in Modulation of ROS-mediated Microglial Activation and Neuroinflammation: Special Emphasize to Quercetin.","authors":"Naira Sahakyan, Alvard Minasyan, Mustapha Cherkaoui-Malki, Pierre Andreoletti","doi":"10.1016/j.biochi.2026.10.018","DOIUrl":"https://doi.org/10.1016/j.biochi.2026.10.018","url":null,"abstract":"<p><p>Neuroinflammation is a central pathogenic mechanism in numerous neurological disorders, with microglia playing a pivotal role in coordinating immune responses through tightly regulated redox, metabolic, and inflammatory signaling pathways. While transient microglial activation supports tissue homeostasis and repair, persistent activation promotes excessive production of reactive oxygen and nitrogen species (ROS/RNS), pro-inflammatory mediators, and lipid-derived inflammatory signals, driving chronic neuroinflammation and neurodegeneration. Accordingly, modulation of microglial activation has emerged as an attractive therapeutic strategy. Plant-derived extracts and phytochemicals represent a remarkable source of bioactive molecules such as quercetin, which are able to concomitantly modulate multiple pathways involved in microglial activation. Over the past two decades, numerous studies have investigated their effects using immortalized murine BV-2 cells and, to a lesser extent, primary microglia. Despite differences between these experimental models, current evidence reveals a striking convergence of molecular mechanisms. Plant-derived metabolites consistently attenuate microglial activation through inhibition of the NF-κB and MAPK signaling pathways, activation of the Nrf2/HO-1 antioxidant axis, suppression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokine production, while limiting oxidative stress and lipid peroxidation. Emerging evidence further indicates that these compounds regulate microglial phenotypic plasticity, mitochondrial function, immunometabolic reprogramming, and, potentially, peroxisomal metabolism and mitochondria-peroxisome crosstalk, thereby extending their actions well beyond conventional antioxidant activity. This review critically examines the molecular mechanisms by which plant-derived extracts and phytochemicals regulate microglial function, with particular emphasis on the interconnected networks linking redox homeostasis, inflammatory signaling, lipid metabolism, and organelle communication.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186739","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":"Thermostable fibrinolytic enzymes from Bacillus subtilis and Bacillus thuringiensis: Optimized production, partial purification, and enzymatic characterization of thrombolytic activity.","authors":"Sheela Kumari Sahoo, Poonam Das, Rout George Kerry, Smruti Malinee Sahoo, Atala Bihari Jena, Asim K Duttaroy, Sanatan Majhi","doi":"10.1016/j.biochi.2026.10.017","DOIUrl":"10.1016/j.biochi.2026.10.017","url":null,"abstract":"<p><p>Fibrinolytic enzymes of microbial origin are gaining attention as safer alternatives to conventional thrombolytic drugs. In this study, fibrinolytic enzymes were isolated and characterized from Bacillus subtilis and Bacillus thuringiensis derived from soil samples. Process optimization revealed maximum enzyme production at 37°C and pH 7.0 after 24 h of incubation, with inoculum sizes of 1.5% (B. subtilis) and 1% (B. thuringiensis) in media supplemented with glucose/sucrose and yeast extract. Partial purification yielded specific activities of 191.15 U/mg (B. subtilis) and 218.24 U/mg (B. thuringiensis) with recovery yields of 14.39% and 13.89%, respectively. Both enzymes exhibited stability over broad ranges of pH (5.0-9.0) and temperature (10-60°C). Enzyme activity was enhanced by Mg²⁺ and Ca²⁺ but completely inhibited by EDTA and PMSF, suggestive of serine metalloproteases classification. Amidolytic assays demonstrated high activity with a chymotrypsin substrate, while hemolytic activity remained below 5%, indicating the possibility of initial therapeutic safety. SDS-PAGE revealed molecular masses of 35 kDa (B. subtilis) and 33 kDa (B. thuringiensis). Kinetic analysis showed K_m values of 3.488 mg/mL and 3.125 mg/mL with V_max values of 232.56 U/mL and 178.57 U/mL, respectively. These findings suggest that fibrinolytic enzymes from both strains exhibit promising activity and stability profiles and provide a basis for future studies to determine their potential role in thrombolytic drug development..</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186762","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":"Inhibition of glycan sialylation reduces amyloid-β secretion via suppression of amyloid-β exocytosis.","authors":"Yasuomi Urano, Wakana Maeda, Noriko Noguchi","doi":"10.1016/j.biochi.2026.10.016","DOIUrl":"10.1016/j.biochi.2026.10.016","url":null,"abstract":"<p><p>Among nutrient-sensitive regulatory mechanisms, protein glycosylation is a key post-translational modification that links metabolism to protein function. Amyloid-β (Aβ) peptides play a crucial role in the pathogenesis of Alzheimer's disease (AD). Because excessive accumulation of Aβ is believed to drive AD progression, approaches that reduce Aβ production and secretion remain of considerable therapeutic interest. Accumulating evidence suggests that protein glycosylation influences the processing and trafficking of amyloid-β precursor protein (APP) and other proteins involved in Aβ metabolism. However, while N-linked protein glycosylation has been shown to affect Aβ production, the specific contribution of protein terminal glycan sialylation remains incompletely understood. In this study, we investigated the effects of inhibiting glycan sialylation on Aβ production using CHO cells stably expressing human APP. Treatment with the sialyltransferase inhibitor P-3Fax-Neu5Ac (P-3Fax) significantly reduced extracellular Aβ levels, while intracellular Aβ levels were increased. Importantly, P-3Fax treatment did not alter β-secretase- or γ-secretase-mediated cleavage of their substrates, indicating that changes in secretase activity do not account for the reduction in extracellular Aβ. In addition, P-3Fax treatment markedly reduced plasma membrane levels of lysosome-associated membrane protein 1 (LAMP1), consistent with impaired lysosomal exocytosis. Taken together, these results indicate that inhibition of sialylation by P-3Fax reduces extracellular Aβ levels independently of secretase activity, potentially through impaired lysosomal exocytotic pathways. Our findings identify glycan sialylation as a key regulatory factor in Aβ trafficking and provide new insight into the cellular mechanisms controlling Aβ homeostasis.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169319","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":"Organelle localization and trafficking of ether lipids: Current evidence and open questions.","authors":"Denise Kummer, Katrin Watschinger","doi":"10.1016/j.biochi.2026.10.004","DOIUrl":"10.1016/j.biochi.2026.10.004","url":null,"abstract":"<p><p>Ether glycerophospholipids are abundant and functionally versatile membrane lipids whose defining sn-1 ether (plasmanyl), or vinyl ether (plasmenyl, plasmalogen) linkage, and polyunsaturated sn-2 chains provide membranes with unique biophysical and signaling properties. Biogenesis is partitioned between two organelles: peroxisomes establish the sn-1 ether linkage and deliver 1-O-alkyl intermediates to the endoplasmic reticulum, where headgroup addition and remodeling occur. Introduction of the vinyl ether double bond by plasmanylethanolamine desaturase then yields plasmalogens. Emerging evidence indicates that ether lipids are unevenly distributed across cellular membranes, reflecting both local metabolic control and selective trafficking. Biosynthetic intermediates are delivered from peroxisomes to the endoplasmic reticulum via ACBD4/5-VAPA/B membrane contact sites, which also couple ether lipid-flux to cholesterol homeostasis. At the plasma membrane, ATP8B2 flippase enforces inner leaflet enrichment of plasmalogens, linking their molecular shape to membrane curvature, raft organization, and signaling. Beyond these core sites, additional pools of ether lipids are detected in the Golgi, mitochondria, endolysosomal system, lipid droplets, and the nucleus, where they are proposed to support membrane organization, and trafficking, yet their organelle-specific functions and transport mechanisms remain poorly defined. In this review we summarize the current knowledge about cellular and subcellular distribution of ether lipids, their biosynthesis, remodeling, degradation, and intracellular trafficking. We also highlight recent methodological advances enabling organelle-resolved lipidomics and live-cell tracking of ether lipids and outline open questions regarding contact-site identity and regulation, transport specificity between plasmanyl and plasmenyl species, and pathophysiological mislocalization mechanisms.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170628","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":"Probing phospholipid bilayer structure and interaction using ATR-FTIR spectroscopy.","authors":"Merve Örer, Thomas Bürgi","doi":"10.1016/j.biochi.2026.10.013","DOIUrl":"10.1016/j.biochi.2026.10.013","url":null,"abstract":"<p><p>The cell membrane plays a critical role in maintaining cellular integrity and regulating interactions between the cell and its environment. The understanding of many biological processes relies on obtaining molecular level information on the structure and dynamic behaviour of membranes, interactions between molecules within the membrane, as well as interactions between membrane and external compounds. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy has emerged as a powerful analytical technique for investigating biological membranes due to its surface sensitivity and minimal sample preparation requirements. The technique enables the characterization of lipid bilayers, protein secondary structures, and membrane interactions with external molecules such as drugs or antimicrobial peptides. This mini-review summarizes the principles of ATR spectroscopy and highlights its applications in the study of lipid bilayers, including lipid organization, protein-lipid interactions, and membrane structural changes. The advantages, limitations, and future perspectives of ATR-based approaches in membrane research are also discussed.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170887","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}