Biochimica et biophysica acta. General subjects最新文献

{"title":"Histidine betaine trimethylammonia-lyase, enzyme coupled with terminal urocanate reductase in Shewanella woodyi grown anaerobically","authors":"Yulia V. Bertsova,&nbsp;Marina V. Serebryakova,&nbsp;Alexander A. Baykov,&nbsp;Alexander V. Bogachev","doi":"10.1016/j.bbagen.2025.130886","DOIUrl":"10.1016/j.bbagen.2025.130886","url":null,"abstract":"<div><div>Bacteria coping with oxygen deficiency can switch to alternative terminal electron acceptors, which can be normal metabolic intermediates or products of dedicated coupled reactions. In the latter case, the genes for the respective terminal reductase and coupling enzyme are expected to cluster in the genome. Here, we determined the roles of two uncharacterized periplasmic proteins encoded by the <em>swoo_3912</em>–<em>swoo_3913</em> gene cluster in the facultatively anaerobic marine bacterium <em>Shewanella woodyi</em>. We confirmed the current database annotation of the former protein as “urocanate reductase” but identified the latter protein as a histidine betaine trimethylammonia-lyase (HBTL). HBTL converts histidine betaine into urocanate and trimethylamine and is remarkably specific for histidine betaine as substrate. HBTL requires Mg²⁺ for activity and undergoes slow reversible inactivation at low Mg²⁺ concentrations. HBTL activity was not evident in <em>S. woodyi</em> cells grown aerobically but was induced in cells grown anaerobically. Both histidine betaine and urocanate supported anaerobic <em>S. woodyi</em> growth and, hence, respiration. Similar gene clusters are found in many anaerobic bacteria, suggesting a wide occurrence of the anaerobic respiration pathway discovered in this work in the bacterial world.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130886"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522421","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":"Receptor binding domain of SARS CoV2 spike protein exhibits in vitro liquid-liquid phase separation due to structural disorderedness that may challenge the vaccine-generated antibody binding","authors":"Manikanta Sodasani ,&nbsp;Abhinav V.K.S. Grandhi ,&nbsp;Niharikha Mukala ,&nbsp;Jahnavi Chintalapati ,&nbsp;Madhuri Vissapragada ,&nbsp;Madhumita Aggunna ,&nbsp;Ravikiran S. Yedidi","doi":"10.1016/j.bbagen.2025.130889","DOIUrl":"10.1016/j.bbagen.2025.130889","url":null,"abstract":"<div><div>In this study we expressed, purified and demonstrated the protein liquid-liquid phase separation (LLPS) formation by the receptor binding domain (RBD) of coronavirus spike protein <em>in vitro</em>.</div><div>Our molecular dynamics simulations revealed multiple structurally disordered regions lacking secondary structural elements within RBD that exhibited high structural flexibility with deviations as high as 6 Å over 500 ns in support of our <em>in vitro</em> findings.</div><div>Additionally these disordered regions overlap with epitopes potentially altering their architecture.</div><div>Based on these results we conclude that the structural disorderedness of RBD causes LLPS formation <em>in vitro</em> and may potentially challenge the COVID-19 vaccine efficacy.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130889"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572886","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":"Pharmacological inhibition of Trypanosoma cruzi aldo-keto reductase (TcAKR) and its effect on benznidazole resistance","authors":"Patricia Andrea Garavaglia ,&nbsp;Sebastián Aduviri ,&nbsp;Pablo Trujillo ,&nbsp;Laura Mónica Tasso ,&nbsp;Joaquín Juan Bautista Cannata ,&nbsp;Monica Pickholz ,&nbsp;Gabriela Andrea García","doi":"10.1016/j.bbagen.2025.130880","DOIUrl":"10.1016/j.bbagen.2025.130880","url":null,"abstract":"<div><div>Chagas disease, caused by the protozoan <em>Trypanosoma cruzi</em>, has become a global health concern due to increased globalization. Several studies suggest that the aldo-keto reductase from <em>T. cruzi</em> (<em>T</em>cAKR) is involved in resistance to benznidazole, the drug commonly used to treat this infection.</div><div>To further support the role of <em>Tc</em>AKR in drug resistance, we evaluated its interaction with four compounds —quercetin, flufenamic acid, phenolphthalein, and menadione—previously reported as inhibitors of other AKRs. Molecular docking was performed to assess affinity and molecular specific interactions, and the inhibitory effects of these compounds on both <em>Tc</em>AKR activities —aldo-keto reductase and quinone-oxidoreductase— were experimentally determined.</div><div>Binding affinities, in decreasing order, were: quercetin &gt; flufenamic acid &gt; phenolphthalein &gt; menadione. Both quercetin and flufenamic acid interacted with amino acid residues located outside the enzyme's active site. Quercetin completely inhibited both <em>Tc</em>AKR activities, while flufenamic acid inhibited approximately 50 %. Phenolphthalein and menadione showed low levels of inhibition. The inhibition profiles of quercetin and flufenamic acid were consistent with a noncompetitive mechanism.</div><div>The effect of quercetin on benznidazole resistance was evaluated in transfected parasites overexpressing <em>Tc</em>AKR, which are 1.8-fold more resistant to this drug. Quercetin treatment restored benznidazole sensitivity in these parasites, reducing the IC₅₀ to levels comparable to those of control parasites. These results provide further evidence of <em>Tc</em>AKR's involvement in benznidazole resistance and suggest that its inhibition can enhance treatment efficacy.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130880"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464715","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":"Decoding chromatin nanoscale plasticity in situ: Insights from native AFM imaging","authors":"Hongfeng Cui,&nbsp;Yu Zhang,&nbsp;Tianyu Chen,&nbsp;Mengzhu Guo,&nbsp;Qi Wen,&nbsp;Jiawei Peng,&nbsp;Yifei Yang,&nbsp;Xian Hao","doi":"10.1016/j.bbagen.2025.130887","DOIUrl":"10.1016/j.bbagen.2025.130887","url":null,"abstract":"<div><div>Chromatin structure and its plasticity are central to gene regulation and DNA-associated processes, yet their nanoscale architecture and dynamic assembly remain elusive. Here, we propose a novel <em>in situ</em> approach—combining hypotonic treatment with high-drop spreading—to obtain native, naked chromosomes and visualize chromatin fine structure using atomic force microscopy (AFM). This strategy enables minimally invasive observation of chromatin under near-physiological conditions. We reveal that chromatin is composed of ∼10 nm DNA–histone particles as its fundamental units. Strikingly, these particles exhibit remarkable structural plasticity, dynamically assembling into heterogeneous nucleosome-beaded chains through stacking and partial melting. This challenges the classical “beads-on-a-string” model by demonstrating that chromatin is neither uniform nor static, but structurally versatile at the nanoscale. In addition, we investigated how histone acetylation and ATP modulate chromatin plasticity. Our findings highlight the coexistence of core particle stability and spatial-temporal variability, providing a revised molecular framework for chromatin's functional adaptability. These insights offer a fresh perspective on how chromatin structural diversity underpins its complex regulatory capacity.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130887"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562483","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":"Hepatic response to ethanol feeding in a hepatocyte-specific fatty acid binding protein-4 knock out mouse model","authors":"Neha Attal ,&nbsp;Trenton A. Pritt ,&nbsp;Melissa Stair ,&nbsp;Tony E. Reeves ,&nbsp;Iain H. McKillop","doi":"10.1016/j.bbagen.2025.130885","DOIUrl":"10.1016/j.bbagen.2025.130885","url":null,"abstract":"<div><h3>Background</h3><div>Early alcohol-dependent liver disease (ALD) is characterized by increased hepatic fat storage (hepatosteatosis). Fatty acid binding protein 4 (FABP4), a protein not normally expressed in liver, becomes highly expressed in ALD. This study developed a hepatocyte-specific FABP4 mouse knockout (HS-<em>Fabp4</em>^−/−) to study liver responses to alcohol.</div></div><div><h3>Methods</h3><div>An HS-<em>Fabp4</em>^−/− mouse was created using a Cre/loxP embryonic stem cell approach. Male and female HS-<em>Fabp4</em>^−/− and wildtype (WT; C57Bl/6) mice were maintained on ethanol-drinking water (EtOH-DW) for 4-weeks. Liver damage, triglyceride content and pathology were assessed. Hepatic FABP1–9 mRNA and FABP4 and FABP5 protein were measured. Human hepatoma cell proliferation in response to exogenous FABP4 or FABP5 was analyzed.</div></div><div><h3>Results</h3><div>Hepatocyte-specific FABP4 deletion was confirmed in HS-<em>Fabp4</em>^−/− mice. No gross phenotypic differences were observed between HS-<em>Fabp4</em>^−/− and WT. Maintenance on EtOH-DW resulted in microsteatosis, increased hepatic triglycerides, and elevated aspartate and alanine transaminases, with no differences detected between pair-matched HS-<em>Fabp4</em>^−/− and WT mice. Hepatic FABP1–9 mRNA analysis revealed increased FABP4 and FABP5 mRNA expression in WT mice, and elevated FABP5 mRNA in HS-<em>Fabp4</em>^−/− mice in response to EtOH-DW, effects that were mirrored in serum FABP4/5 protein. Exposure of hepatoma cells to FABP4 or FABP5 revealed FABP4, but not FABP5, stimulated cell proliferation.</div></div><div><h3>Conclusions</h3><div>Hepatocyte-specific FABP4 deletion does not alter hepatic fat accumulation in response to EtOH feeding. Hepatic FABP4 protein produced in response to EtOH is released from hepatocytes and exogenous FABP4 promotes hepatoma cell proliferation <em>in vitro</em>, an effect not observed for FABP5.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130885"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511575","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 vesicles from hypoxia-preconditioned mesenchymal stem cells preserve mitochondrial functions and redox homeostasis in ischemia–reperfusion-induced acute kidney injury","authors":"Marcela Andrade-Soares ,&nbsp;Mayra Alves ,&nbsp;Clara Rodrigues-Ferreira ,&nbsp;Jarlene A. Lopes ,&nbsp;Thuany Crisóstomo ,&nbsp;Gloria Costa-Sarmento ,&nbsp;Christina M. Takiya ,&nbsp;Amaury Pereira-Acácio ,&nbsp;Adalberto Vieyra","doi":"10.1016/j.bbagen.2025.130874","DOIUrl":"10.1016/j.bbagen.2025.130874","url":null,"abstract":"<div><div>Acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) remains a significant clinical challenge due to its rapid progression, limited therapeutic options, and high morbidity. Mitochondrial dysfunction is a critical component of AKI pathogenesis, contributing to oxidative stress, impaired bioenergetics, and tissue injury. Extracellular vesicles (EV) derived from mesenchymal stem cells (MSC) have emerged as potential candidates for organ protection through the modulation of inflammatory and oxidative pathways. This study evaluated the effects of EV secreted by hypoxia-preconditioned adipose-derived MSC on mitochondrial function in a rat model of I/R-induced AKI. Wistar rats were assigned to four groups: SHAM, I/R, SHAM + EV, and I/R + EV. Hypoxia-preconditioned EV (2 × 10⁹) or vehicle were administered subcapsularly 1 h prior to bilateral renal artery clamping (45 min ischemia, 1 h reperfusion). Histological analyses demonstrated that EV treatment effectively prevented tubular injury, inflammatory infiltration, and preserved renal architecture. EV enhanced Nrf2 nuclear translocation, upregulated HO-1 expression, and stabilized antioxidant defenses. Furthermore, EV preserved mitochondrial membrane potential, respiratory control ratio, ATP synthesis, and the abundance of electron transport chain complexes I, III, and IV, although complex II remained vulnerable. Proton leak responses were unaffected. These results demonstrate that hypoxia-preconditioned MSC-derived EV exert rapid protective effects on renal mitochondria and redox homeostasis during early reperfusion, offering a promising therapeutic strategy for AKI prevention in clinical scenarios such as transplantation and major cardiovascular surgeries. Further studies are needed to characterize the cargo of EV and their long-term outcomes.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130874"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420862","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 effect of gold nanoparticle size and shape on the structure and activity of Domain 3 of an alternative sigma factor of Staphylococcus aureus","authors":"Tanaya Chatterjee,&nbsp;Debasmita Sinha","doi":"10.1016/j.bbagen.2025.130888","DOIUrl":"10.1016/j.bbagen.2025.130888","url":null,"abstract":"<div><h3>Background</h3><div>The modern era has witnessed the vast applications of nanoparticles (NPs) ranging from drug delivery to biomedical usages. Herein we report for the first time the effect of gold nanoparticles (AuNPs) of different sizes and shapes on a stress response protein <em>σ</em>^<em>B</em> from <em>Staphylococcus aureus,</em> the pathogen causing infection. Among the three conserved domains of <em>σ</em>^<em>B</em>, we focused on Domain 3 which binds to an anti-sigma factor RsbW of <em>S. aureus</em>.</div></div><div><h3>Methods</h3><div>We explored the interaction of recombinant <em>σ</em>^<em>B3</em> (r<em>σ</em>^<em>B3</em>) with three types of AuNPs; spherical with 10 nm (AuNS10) and 100 nm (AuNS100) diameter and rod shaped (AuNR10). Structural modulations of r<em>σ</em>^<em>B3</em> by AuNPs <em>were</em> studied using different biophysical techniques. Native-PAGE was run for r<em>σ</em>^<em>B3</em>-cRsbW binding assay using AuNR10.</div></div><div><h3>Results</h3><div>Isothermal titration calorimetry revealed exothermic and endothermic heat changes for r<em>σ</em>^<em>B3</em>-AuNSs and r<em>σ</em>^<em>B3</em>-AuNR, respectively. Far-UV CD of r<em>σ</em>^<em>B3</em> showed loss of α-helical content with AuNR10 using higher molar ratios of 1:5 and 1:10. Binding to 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid (bis-ANS) indicated enhanced fluorescence intensity for r<em>σ</em>^<em>B3</em>-AuNR10 conjugate, implying unfolding of r<em>σ</em>^<em>B3</em> thereby exposing hydrophobic regions. Binding assay of r<em>σ</em>^<em>B3</em> with cRsbW displayed impaired protein-protein interaction using r<em>σ</em>^<em>B3</em>-AuNR10 molar ratio of 1:10. The efficacy of AuNR10 was also observed for the biofilm inhibition by <em>S. aureus.</em></div></div><div><h3>Conclusions</h3><div>We show how the size and shape of AuNPs modulate the structure/function of r<em>σ</em>^<em>B3</em> of <em>S. aureus</em>.</div></div><div><h3>General significance</h3><div>Because of the involvement of r<em>σ</em>^<em>B3</em> in <em>S. aureus</em> pathogenesis, the structural/functional modulation by AuNR10 could be of therapeutic relevance for nanoparticle-based antibacterial strategies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130888"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562553","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":"Copper transporter 1 contributes to the progression of cholangiocarcinoma","authors":"Yanpeng Ma ,&nbsp;Longlong Liu ,&nbsp;Jiayue Duan ,&nbsp;Xiaojian Wang","doi":"10.1016/j.bbagen.2025.130876","DOIUrl":"10.1016/j.bbagen.2025.130876","url":null,"abstract":"<div><h3>Background</h3><div>Cholangiocarcinoma (CCA) is characterized by poor prognosis and a lack of effective biomarkers and therapeutic targets. Although copper dysregulation has been implicated in CCA, the role of the copper transporter SLC31A1 (CTR1) in its progression remains poorly understood.</div></div><div><h3>Methods</h3><div>The mRNA and protein levels of SLC31A1 in tumor and adjacent non-tumor tissues was evaluated by RT-PCR and enzyme-linked immunosorbent assay, respectively. Tissue copper concentrations were determined using a colorimetric complexation assay. Correlations between SLC31A1 expression, copper accumulation, and clinicopathological parameters were evaluated using Pearson's analysis. Cell proliferation and colony formation were assessed by the cell counting kit 8 and colony formation assays, respectively. Mitochondrial function was assessed by measuring intracellular ATP levels, reactive oxygen species (ROS) production, and the glutathione redox ratio.</div></div><div><h3>Results</h3><div>Elevated SLC31A1 expression was significantly associated with microvascular invasion, larger tumor size (≥5 cm), and advanced AJCC stage (III–IV). Both SLC31A1 mRNA and protein levels were significantly upregulated in CCA tissues compared with adjacent non-tumor tissues and correlated with copper accumulation. In vitro, SLC31A1 was highly expressed across multiple CCA cell lines. Silencing SLC31A1 in RBE cells impaired cell proliferation and colony formation. Mechanistically, depletion of SLC31A1 increased intracellular ROS, reduced the GSH/GSSG ratio, and decreased ATP production, indicating disruption of mitochondrial function and redox homeostasis.</div></div><div><h3>Conclusions</h3><div>SLC31A1 promotes cholangiocarcinoma progression by maintaining copper homeostasis, mitochondrial integrity, and redox balance. These findings suggest that SLC31A1 may serve as a potential prognostic biomarker and a candidate therapeutic target.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130876"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443536","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":"Structural characterization of a L-dehydroascorbic acid–L-homocysteine thiolactone reaction product: Intracellular formation in neuronal cells","authors":"Ghizlane Loubane ,&nbsp;Gabriel Robert ,&nbsp;Syed Benazir Firdaus ,&nbsp;Raphaël Robidas ,&nbsp;Christian Comeau ,&nbsp;Pierre-Luc Boudreault ,&nbsp;Jeampy E. Komba ,&nbsp;Hugo Gagnon ,&nbsp;J Richard Wagner ,&nbsp;Stephen Naylor ,&nbsp;Klaus Klarskov","doi":"10.1016/j.bbagen.2025.130882","DOIUrl":"10.1016/j.bbagen.2025.130882","url":null,"abstract":"<div><div>Homocysteine thiolactone (HTL) has been implicated in cardiovascular and neurological pathologies. While homocysteine can S-homocysteinylate thiol groups in proteins, the chemical properties of HTL facilitates covalent binding to protein ε-amino groups on lysine residues, which can initiate protein aggregation. Ascorbate plays an important role in the prevention of oxidative stress. Ascorbate is easily oxidized by the loss of two electrons to dehydroascorbate (DHA), which can be reduced back to ascorbate by thiol-containing smaller and larger molecules. In the present study, reaction products between two aldehydes, formaldehyde and propionaldehyde as well as DHA with the physiological relevant isomer of homocysteine thiolactone i.e. L-HTL were purified, and their structure was determined by 1D and 2D-nuclear magnetic resonance. In all three cases the reaction products are likely formed by initial imine condensation, subsequent formation of a hemiaminal product followed by HTL ring opening and intramolecular nucleophilic attack of the resulting thiol anion to form a six-member thiazinane ring with a carboxylic acid group. The structure of the DHA, L-HTL reaction product was confirmed by high resolution accurate ESIMS/MS in negative mode. Formation of the reaction product between DHA and HTL prevented N-homocysteinylation of cytochrome <em>c</em> by HTL, confirming earlier observations. The reaction product is formed in human neuroblastoma cells (SH-SY5Y) when exposed to HTL and DHA or ascorbate, potentially preventing protein aggregation. The consequences associated with formation of a reaction product between DHA and HTL suggest that DHA could protect against protein N-homocysteinylation.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130882"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464716","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":"Nanobody-based imaging: Advancing precision in molecular diagnostics","authors":"Zohre Eftekhari,&nbsp;Fatemeh Kazemi-Lomedasht","doi":"10.1016/j.bbagen.2025.130884","DOIUrl":"10.1016/j.bbagen.2025.130884","url":null,"abstract":"<div><div>Molecular imaging is a cornerstone of modern medicine, enabling non-invasive visualization of biological processes at the molecular level. The emergence of nanobodies (Nbs), small single-domain antibody fragments derived from camelids, has transformed this field due to their superior tissue penetration, rapid clearance, and high target specificity compared to conventional antibodies. This review focuses on the integration of Nbs with positron emission tomography (PET) and single-photon emission computed tomography (SPECT) two complementary molecular imaging modalities known for their high sensitivity, quantitative potential, and clinical relevance. Nb-based PET and SPECT imaging probes are emerging as powerful tools for detecting disease-associated molecular targets with exceptional precision. Their unique properties, including high affinity, specificity, and stability, make them ideal candidates for developing advanced radiotracers that enable early disease detection, monitoring of therapeutic responses, and evaluation of novel treatment strategies. Despite these advantages, several challenges remain, such as scalable Nb production, reduction of immunogenicity in clinical applications, and optimization of radiolabeling methods that preserve Nb integrity and function. This review highlights recent advances in Nb engineering, radiolabeling strategies, and preclinical and clinical applications of Nb-based PET and SPECT imaging, while outlining critical directions for future research. By addressing current limitations, Nb-based molecular imaging holds great promise for improving diagnostic accuracy, advancing personalized medicine, and expanding its clinical impact across diverse disease areas.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 1","pages":"Article 130884"},"PeriodicalIF":2.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145487720","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}