Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
Hyperglycemia promotes O-GlcNAcylation-dependent vulnerability and modulates temozolomide response in glioblastoma.
Vergueiro A, Menezes A, Rocha N … +3 more , Moura-Neto V, Todeschini A, Dias WB
Biochem Biophys Res Commun · 2026 Aug · PMID 42247812 · Publisher ↗
Glioblastoma (GB) exhibits metabolic reprogramming influenced by systemic conditions such as hyperglycemia. Here, we investigated whether glycemic status modulates glycosylation pathways and therapeutic response in patie...
Glioblastoma (GB) exhibits metabolic reprogramming influenced by systemic conditions such as hyperglycemia. Here, we investigated whether glycemic status modulates glycosylation pathways and therapeutic response in patient-derived GB cells. Hyperglycemia was associated with increased expression of hexosamine biosynthetic pathway (HBP) enzymes (GFAT1/2) and O-GlcNAcylation machinery (OGT/OGA), correlating with blood glucose levels and defining distinct metabolic profiles. In contrast, N-glycosylation-related enzymes showed heterogeneous regulation. Functionally, inhibition of O-GlcNAcylation reduced cell viability and enhanced sensitivity to temozolomide (TMZ), particularly in cells derived from hyperglycemic patients. These findings indicate that hyperglycemia promotes a glycosylation-dependent metabolic adaptation while creating a targetable vulnerability. Targeting O-GlcNAcylation may improve therapeutic response in hyperglycemia-associated glioblastoma.
Posterior ligamentous injury induces progressive ankylosis-like structural remodeling in rhesus macaques.
Chen Y, Sun X, Su D … +4 more , Luo F, Zhang M, Xu Y, Yang J
Biochem Biophys Res Commun · 2026 Aug · PMID 42247811 · Publisher ↗
Structural progression in ankylosing spondylitis (AS) is difficult to model in species with human-relevant spinal anatomy and long-term imaging readouts. Here, we established a rhesus macaque model of AS-like structural...
Structural progression in ankylosing spondylitis (AS) is difficult to model in species with human-relevant spinal anatomy and long-term imaging readouts. Here, we established a rhesus macaque model of AS-like structural remodeling by standardized posterior L2-L6 musculoligamentous injury, with sham-operated animals serving as negative controls. Longitudinal CT/MRI assessment was performed for up to 50 months, supplemented by ex vivo micro-CT and whole-section histology. Model animals developed cumulative structural changes that progressed from early focal entheseal/subchondral remodeling to posterior ossification, segmental bridging, sacroiliac joint structural involvement, and late ankylosis-like remodeling, whereas sham animals showed no typical AS-like structural lesions. CT-based semiquantitative assessment demonstrated a progressive increase in structural burden over time and indicated that posterior elements were the dominant anatomical domain contributing to the terminal ankylosis-like phenotype. Whole-section histology further supported a tissue-level continuum from posterior and peri-discal fibrotic remodeling to late fibro-osseous change, consistent with the imaging-defined progression from focal remodeling to bridging and structural fixation. These findings show that posterior musculoligamentous injury in rhesus macaques can drive long-term, quantifiable, AS-like structural remodeling and nominate the posterior musculoligamentous complex as a potential anatomical and histological hub linking local injury repair, fibrosis, fibro-osseous transition, and ankylosis-like progression.
Biological mechanisms and social determinants of antimicrobial resistance.
Bajpai M, Saraf T, Bajpai U
Biochem Biophys Res Commun · 2026 Aug · PMID 42247810 · Publisher ↗
Bacterial antimicrobial resistance (AMR) is a defining global health crisis, projected to cause 1.91 million annual deaths globally by 2050. These alarming statistics call for a holistic, dual-lens approach that examines...
Bacterial antimicrobial resistance (AMR) is a defining global health crisis, projected to cause 1.91 million annual deaths globally by 2050. These alarming statistics call for a holistic, dual-lens approach that examines the molecular strategies bacteria use to develop antibiotic resistance, as well as the socio-economic drivers and structural inequities that remain critically overlooked in AMR governance. This review delves into two seemingly unrelated but critical aspects of bacterial AMR: biological mechanisms of bacterial resistance and the social norms and structural inequities that play significant roles in the development and spread of antibiotic resistance. Bacterial resistance mechanisms operate at the genotypic and phenotypic levels, inducing inheritable changes or temporary structural adaptations. A deeper understanding of these diverse mechanisms can help identify new drug targets and develop new antibiotics. We advocate that while discovering new classes of antibiotics and averting resistance mechanisms is paramount, prioritising technical solutions without a socially informed framework cannot yield the results required. Examining how occupational exposures, economic equities and gendered roles drive informal antibiotic usage and increase exposure to resistant pathogens is equally crucial. Hence, by combining the biological mechanisms of resistance with the social norms that facilitate its occurrence and spread, a comprehensive roadmap for socially grounded interventions should be developed.
Biochemical characterization and structural insights of trehalose-6-phosphate phosphatases from Stenotrophomonas maltophilia and Xanthomonas axonopodis.
Kim S, Lee S, Park SY … +1 more , Kim JS
Biochem Biophys Res Commun · 2026 Aug · PMID 42241980 · Publisher ↗
The trehalose-6-phosphate phosphatase (TPP) of the OtsA-OtsB pathway is essential for bacterial osmoregulation and survival. Crucially, this pathway is absent in eukaryotic organisms, providing a strategic advantage for...
The trehalose-6-phosphate phosphatase (TPP) of the OtsA-OtsB pathway is essential for bacterial osmoregulation and survival. Crucially, this pathway is absent in eukaryotic organisms, providing a strategic advantage for developing selective antimicrobials with minimal host toxicity. In this study, we characterized two Group 3 TPPs-Smal-TPP from the opportunistic human pathogen Stenotrophomonas maltophilia and Xaxo-TPP from the phytopathogen Xanthomonas axonopodis. Both enzymes exhibit the canonical features of the HAD superfamily, including a strict requirement for divalent metal ions (Mg or Mn) at a pH optimum of 7.5. Kinetic analysis revealed specific turnover rates (kcat) of 0.009 s for Smal-TPP and 0.003 s for Xaxo-TPP, contrasting with the higher velocities reported for other bacterial orthologs. Structural modeling suggests that histidine-driven displacement of the hinge loop increases the energetic barrier for domain apposition. Furthermore, we identify an acidic cluster that likely serves as an electrostatic filter and a bulky phenylalanine residue that introduces steric hindrance; together, these features rationalize the observed substrate affinities and slow turnover. We conclude that Group 3 TPPs prioritize biochemical resilience over maximal catalytic velocity. These findings establish a structural framework for designing selective inhibitors that exploit the unique architectural traits of these pathogenic enzymes.
Eco-friendly fabrication of ZnO nanoparticles from Syzygium cumini seeds for potential anticancer and respiratory antimicrobial applications.
Lathika K, Vijayakumar S, Devadharshini D … +1 more , Sneha P
Biochem Biophys Res Commun · 2026 Aug · PMID 42241979 · Publisher ↗
Nanotechnology has advanced a wide range of biomedical research areas, including antimicrobial and anticancer investigations. Among nanomaterials, zinc oxide nanoparticles (ZnO NPs) have gained attention due to their phy...
Nanotechnology has advanced a wide range of biomedical research areas, including antimicrobial and anticancer investigations. Among nanomaterials, zinc oxide nanoparticles (ZnO NPs) have gained attention due to their physicochemical properties and biological activity. In this study, crystalline (wurtzite) ZnO NPs were synthesized via an eco-friendly green approach using Syzygium cumini seed extract. The use of seed extract, compared to commonly reported plant parts, provides a distinct phytochemical environment that may influence nanoparticle formation and functionality. The synthesized ZnO NPs were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS), confirming their crystalline structure, morphology, vibrational features, and surface chemical composition. The average crystallite size was estimated to be ∼17 nm. UV-visible spectroscopy showed an absorption peak around ∼270 nm, which is attributed to phytochemical constituents of the extract rather than the intrinsic band-edge absorption of ZnO. Fourier-transform infrared (FT-IR) analysis indicated the involvement of biofunctional groups in nanoparticle synthesis and stabilization. The antibacterial activity, evaluated using the agar well diffusion method, showed inhibition against Streptococcus pneumoniae, Staphylococcus aureus, Veillonella parvula, and Fusobacterium nucleatum. Quantitative assays, including minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), confirmed effective bactericidal activity, particularly against S. pneumoniae. In addition, the ZnO NPs exhibited dose-dependent cytotoxicity against the A549 human lung cancer cell line, with an IC value of ∼62.5 μg/mL. Overall, the results demonstrate that green-synthesized ZnO NPs exhibit notable in vitro antibacterial and cytotoxic activity. However, further studies involving detailed mechanistic evaluation and in vivo validation are required to establish their broader applicability.
An antibody targeting the proximal extracellular domain of OSMRβ inhibits IL-31 signaling: mechanism and structural insights.
Zhang C, Guo T, Zheng Y … +5 more , Pang X, Wang L, Li Y, Gao F, Xiao H
Biochem Biophys Res Commun · 2026 Aug · PMID 42241978 · Publisher ↗
Oncostatin M receptor beta (OSMRβ) is an essential signal-transducing subunit in the IL-31/IL-31 receptor alpha (IL-31RA)/OSMRβ complex and is implicated in inflammatory and pruritic diseases. We previously developed a h...
Oncostatin M receptor beta (OSMRβ) is an essential signal-transducing subunit in the IL-31/IL-31 receptor alpha (IL-31RA)/OSMRβ complex and is implicated in inflammatory and pruritic diseases. We previously developed a high-affinity monoclonal antibody (2O2) that targets the proximal extracellular domain (amino acids 619-734) of canine OSMRβ (cOSMRβ) and shows no cross-reactivity with human OSMRβ (hOSMRβ). Here, we elucidate its functional mechanism of action and determine the co-crystal structure of the 2O2 Fab fragment in complex with this domain at a resolution of 2.76 Å. Consistent with the epitope location far away from the cytokine-binding domain (CBD) of cOSMRβ, 2O2 does not compete with canine IL-31 (cIL-31) for cOSMRβ binding. However, the in vitro functional assay demonstrated that 2O2 inhibits cIL-31-induced phosphorylation of STAT5 in DH-82 cells. Mechanistically, this inhibition is achieved through antibody-induced internalization of cOSMRβ from the cell surface. Structural analysis reveals that 2O2 binds at an oblique angle relative to the membrane, creating steric hindrance that induces localized lipid bilayer invagination. The bivalent IgG exhibits ∼34-fold higher potency than its monovalent Fab, reflecting not only avidity but also mechanical consequences of dual receptor engagement: crosslinking two receptor complexes exerts a stretching force that amplifies membrane invagination and promotes efficient endocytic uptake. This mechanism enables clearance of the entire signaling complex, including the cytokine, from the cell surface-a functional advantage over conventional cytokine-blocking antibodies. These findings establish 2O2 as a novel canine therapeutic candidate with a distinct internalization-driven mechanism of action.
Artesunate attenuates sepsis-induced myocardial injury: A preliminary investigation into the JAK2/STAT3 pathway via integrated network pharmacology and experimental validation.
Li T, Lv Y, Zhang J … +13 more , Rui H, Ma X, Wang J, Jiang Y, Yuan Y, Meng Y, Ma X, Zheng X, Yan X, Li M, Zhang B, Dong X, Ma L
Biochem Biophys Res Commun · 2026 Aug · PMID 42241977 · Publisher ↗
BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, frequently induces myocardial injury, which stands as one of its most common and severe complications and a ke...
BACKGROUND: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, frequently induces myocardial injury, which stands as one of its most common and severe complications and a key factor contributing to poor patient prognosis. This study aims to investigate the protective effect of Artesunate (AS) on sepsis-induced myocardial injury (SIMI) and to elucidate the underlying molecular mechanisms by integrating network pharmacology prediction with experimental validation. METHODS: Sepsis was induced in male Wistar rats using the cecal ligation and puncture (CLP) method, and the rats were randomly divided into five groups (n = 6/group): Ctrl, Sham, CLP, AS + CLP, and vehicle + CLP. To assess the cardioprotective effect of AS, serum levels of myocardial injury markers (BNP, LDH, CK-MB, hs-cTnI) were measured by ELISA, and myocardial histopathology was evaluated by H&E staining. The potential targets and pathways of AS against SIMI were then predicted using network pharmacology. Serum inflammatory cytokines (IL-6, TNF-α) and oxidative stress markers (SOD, MDA) were further examined by ELISA, and cardiomyocyte apoptosis was assessed by TUNEL staining. Finally, the expression of key proteins in the JAK2/STAT3 signaling pathway in myocardial tissue was determined by Western blotting to explore the underlying mechanism. RESULTS: AS significantly ameliorated pathological damage and reduced serum myocardial enzyme levels in septic rats compared to the CLP group. Network pharmacology identified 68 potential targets of AS. GO analysis revealed their primary enrichment in molecular functions such as kinase regulator activity, while KEGG enrichment analysis showed their significant association with pathways including inflammatory response. Molecular docking demonstrated favorable binding affinities between AS and core targets such as STAT3. Experimental validation further showed that AS treatment significantly decreased serum concentrations of IL-6 and TNF-α, increased SOD activity while reducing MDA content, and lowered the myocardial cell apoptosis index. Moreover, AS administration notably downregulated the protein expression levels of p-JAK2 and p-STAT3 in myocardial tissue. CONCLUSION: Based on network pharmacology prediction and experimental validation, it was demonstrated that AS protects against SIMI by inhibiting the JAK2/STAT3 signaling pathway, thereby alleviating inflammation, oxidative stress, and cardiomyocyte apoptosis. These findings provide compelling pharmacological evidence for the drug repurposing of Artesunate.
Exosomes derived from M2-polarized tumor-associated macrophages contribute to immune escape in cervical cancer.
Weng X, Zeng C, Lv J … +5 more , Huang F, You Z, Hu A, Liang J, Fu J
Biochem Biophys Res Commun · 2026 Aug · PMID 42241976 · Publisher ↗
BACKGROUND: Tumor-associated macrophages (TAMs), particularly those polarized toward an M2-like phenotype, are major contributors to the immunosuppressive microenvironment in cervical cancer. Although soluble mediators s...
BACKGROUND: Tumor-associated macrophages (TAMs), particularly those polarized toward an M2-like phenotype, are major contributors to the immunosuppressive microenvironment in cervical cancer. Although soluble mediators such as IL-10 and TGF-β have been well characterized, the role of macrophage-derived exosomes in regulating immune checkpoint expression on tumor cells remains unclear. METHODS: Exosomes were isolated from IL-4-polarized RAW264.7 macrophages and applied to HPV-positive TC-1 murine cervical cancer cells. PD-L1 expression was evaluated by quantitative PCR and flow cytometry. Functional impacts on antigen-specific CD8 T cells were assessed using co-culture cytotoxicity assays and measurement of effector cytokines. The dependency on PD-L1 was determined through Cd274 knockdown. In vivo experiments were performed in a syngeneic TC-1 tumor model with intratumoral exosome administration and anti-PD-1 treatment. RESULTS: TAM-derived exosomes were efficiently internalized by tumor cells and induced significant upregulation of PD-L1 at both mRNA and protein levels without affecting cell viability. This led to impaired CD8 T cell-mediated killing and reduced secretion of IFN-γ, CXCL9, and CXCL10. The immunosuppressive effect was abolished in Cd274-deficient tumor cells and reversed by anti-PD-1 only in the presence of PD-L1. In mice, TAM exosomes promoted tumor growth, decreased CD8 T cell infiltration, and attenuated the efficacy of anti-PD-1 therapy. CONCLUSION: TAM-derived exosomes drive PD-L1-dependent immune evasion in cervical cancer. Targeting this myeloid exosome-tumor signaling axis represents a promising strategy to overcome resistance to immune checkpoint blockade.
Ethanol antagonizes human olfactory receptors through receptor-dependent competitive and noncompetitive mechanisms.
Kasahara C, Terada Y, Ojiro I … +5 more , Kobayashi R, Takeuchi M, Negoro H, Ishida H, Ito K
Biochem Biophys Res Commun · 2026 Aug · PMID 42241975 · Publisher ↗
Mechanisms of ligand-receptor interactions at olfactory receptors (ORs), particularly those of antagonists, remain largely unclear. Here, we investigated how ethanol-empirically known to suppress human olfactory percepti...
Mechanisms of ligand-receptor interactions at olfactory receptors (ORs), particularly those of antagonists, remain largely unclear. Here, we investigated how ethanol-empirically known to suppress human olfactory perception-modulates OR activity using a heterologous assay system. Ethanol did not activate OR1A1 or OR2W1 but significantly suppressed agonist-induced responses in a concentration-dependent manner. Pharmacological analyses revealed that ethanol acts as a competitive antagonist for OR1A1 and a noncompetitive antagonist for OR2W1, demonstrating receptor-dependent modes of inhibition. Washout experiments showed that ethanol-induced suppression was rapid and reversible, supporting direct receptor antagonism. Structural modeling using AlphaFold3 suggested distinct ethanol binding positions in OR1A1 and OR2W1, providing a structural basis for their different inhibition mechanisms. Furthermore, analyses of primary alcohols (C1-C6) revealed a chain-length-dependent shift in receptor pharmacology, with shorter alcohols acting as antagonists and longer alcohols exhibiting partial or full agonist activity. These findings identify ethanol as a novel OR antagonist and demonstrate receptor-dependent antagonism by a single ligand, offering new insights into olfactory receptor-ligand interactions.
Precision targeting of SRC signaling in glioblastoma: Mechanistic insights and bilosome nanotechnology.
Madalageri M, Sadashivanavar V, Kinnal R … +2 more , Atchou K, Sreedhara Ranganath Pai K
Biochem Biophys Res Commun · 2026 Aug · PMID 42241974 · Publisher ↗
The most aggressive and treatment-resistant primary brain malignancy is glioblastoma (GBM). It spreads widely throughout the brain, grows rapidly, and often does not respond to conventional therapies. The aberrant activa...
The most aggressive and treatment-resistant primary brain malignancy is glioblastoma (GBM). It spreads widely throughout the brain, grows rapidly, and often does not respond to conventional therapies. The aberrant activation of SRC, a non-receptor tyrosine kinase, is a major factor in GBM development. The SRC Paradox, a sharp divergence in which strong molecular suppression in vitro fails to translate into clinical efficacy because of the blood-brain barrier's (BBB) restrictive kinetics, has historically hampered the translational trajectory of SRC inhibitors in GBM. This paper reassesses the SRC tyrosine kinase as a crucial orchestrator of GBM invasiveness, whose therapeutic potential remains constrained by physiological barriers rather than merely acting as a redundant signaling node. To overcome this translational impasse, we propose the crucial integration of bilosomes, which are bile-salt-stabilized vesicular nanocarriers. In contrast to conventional liposomal systems, bilosomes' distinct amphiphilic structure and greater membrane flexibility may enhance BBB permeation and cellular uptake while protecting SRC inhibitors from metabolic breakdown and systemic sequestration. We also analyze the molecular interactions between the glioma microenvironment and bilosomal surface functionalization. This review lays a rigorous foundation for the next generation of CNS-specific nanomedicines by integrating current advances in bilosomal pharmacokinetics with the basic biology of SRC-mediated oncogenic signaling, turning the "SRC Paradox" into a solid clinical reality.
Multiple comprehensive analyses identify that upregulation of Myomesin 2 suppresses cardiomyocyte proliferation.
Suzuki S, Tanaka S, Wada Y … +7 more , Kametani Y, Sakai H, Nishinaka K, Egawa K, Okada Y, Obana M, Fujio Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42241973 · Publisher ↗
Mammalian cardiomyocytes lose their proliferative capacity shortly after birth; however, molecular mechanisms that regulate cardiomyocyte proliferation remain to be fully elucidated. This study aimed to identify genes th...
Mammalian cardiomyocytes lose their proliferative capacity shortly after birth; however, molecular mechanisms that regulate cardiomyocyte proliferation remain to be fully elucidated. This study aimed to identify genes that regulate cardiomyocyte proliferation through multiple comprehensive analyses. RNA-sequencing analysis was performed using proliferating neonatal rat cardiomyocytes. We also retrieved and analyzed publicly available single-cell RNA-sequencing datasets from rat hearts on postnatal days 1 and 7. Pseudotime trajectory analysis identified a cardiomyocyte cluster undergoing cell cycle exit at postnatal day 7. Comparative gene expression analysis of this cluster between postnatal day 1 and day 7 identified Myomesin 2 (Myom2) as a candidate for regulation of cardiomyocyte proliferation. Real time qRT-PCR analysis demonstrated that Myom2 expression increased during cardiac maturation. Further, we investigated the effect of Myom2 expression on cardiomyocyte proliferation. Immunofluorescence microscopic analysis revealed that adenoviral overexpression of Myom2 significantly reduced the proportion of proliferating cardiomyocytes and promoted cardiomyocyte binucleation. Collectively, these findings indicate that postnatal induction of Myom2 suppresses cardiomyocyte proliferation and promotes binucleation.
Computational discovery and molecular modelling of small-molecule modulators of GDNF.
Vankadoth UN, Pandi S, Pakala S … +3 more , Koteswara Rao M, Krishnan B, Amineni U
Biochem Biophys Res Commun · 2026 Aug · PMID 42241930 · Publisher ↗
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and motor dysfunction. Glial cell line-derived neurotrophic factor (GDNF) is essential for neuronal mainten...
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and motor dysfunction. Glial cell line-derived neurotrophic factor (GDNF) is essential for neuronal maintenance; however, its pathological overexpression has been linked to neuroinflammation and PD progression. This study presents an integrative in silico strategy to identify novel small-molecule inhibitors targeting GDNF to mitigate its pro-inflammatory effects. A structure-based virtual screening workflow in Maestro v13.4 evaluated 28.5 million compounds using HTVS, SP, and XP docking protocols. Five lead molecules displayed stronger binding affinities than the reference inhibitor SOS (-6.678 kcal/mol), forming stable hydrogen-bond and hydrophobic interactions with key GDNF residues. Molecular dynamics simulations over 300 ns confirmed the structural stability of the GDNF-ligand complexes, supported by consistent RMSD/RMSF profiles and favourable MMGB/PBSA binding free energies. Additionally, DFT and PCA/FEL analyses indicated optimal electronic properties and stable conformational dynamics of the identified compounds. Among them, GDNF000064 emerged as the most promising inhibitor capable of modulating GDNF overexpression, suggesting its potential to reduce neuroinflammation and protect dopaminergic neurons. Overall, this computational framework provides valuable insights for the rational design of GDNF-targeted therapeutics for PD.
Retraction notice to "Adenosine A2A receptor inhibition restores the normal transport of endothelial glutamate transporters in the brain" [Biochem. Biophys. Res. Commun. 498 (2018) 795-802].
Bai W, Li P, Ning YL … +5 more , Peng Y, Xiong RP, Yang N, Chen X, Zhou YG
Biochem Biophys Res Commun · 2026 Aug · PMID 42236401 · Publisher ↗
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Platelet lipid rafts: Disease regulatory hubs and precision therapeutic targets in membrane microdomains.
Zhao A, Liu Q, Wang X … +3 more , Wang Y, Wang Z, Liu Z
Biochem Biophys Res Commun · 2026 Aug · PMID 42235332 · Publisher ↗
Lipid rafts are dynamic membrane microdomains enriched in cholesterol and sphingolipids. Platelets, with their unique anucleate nature and a high cholesterol-to-phospholipid ratio, serve as an optimal model for studying...
Lipid rafts are dynamic membrane microdomains enriched in cholesterol and sphingolipids. Platelets, with their unique anucleate nature and a high cholesterol-to-phospholipid ratio, serve as an optimal model for studying lipid raft functionality. These microdomains regulate key platelet processes-including adhesion, aggregation, phosphatidylserine exposure, and the release of inflammatory mediators-by recruiting receptors such as GPIb-IX-V and GPVI, and downstream signalling molecules like Syk and Src family kinases. Consequently, platelet lipid rafts modulate a spectrum of physiological and pathological events, from thrombosis and immune regulation to tumour metastasis. This review delineates the pathogenic roles of platelet lipid rafts in atherosclerosis, sepsis, antiphospholipid syndrome, Alzheimer's disease, and cancer, elucidating underlying mechanisms such as aberrant signal activation, procoagulant microvesicle release, and intercellular crosstalk. Furthermore, we explore emerging therapeutic strategies that target the cholesterol content, protein composition, or dynamic architecture of lipid rafts, offering novel perspectives for personalised antithrombotic regimens.
Electrostatic control of membrane disruption and amorphous coaggregation by dynorphin A variants.
Habibnia M, Catalina-Hernandez E, Barnadas-Rodríguez R … +1 more , Peralvarez-Marin A
Biochem Biophys Res Commun · 2026 Aug · PMID 42235331 · Publisher ↗
Dynorphin A is a highly cationic neuropeptide that exhibits membrane activity beyond its canonical opioid receptor signaling. Here, we investigate how sequence variants of Dynorphin A associated with spinocerebellar atax...
Dynorphin A is a highly cationic neuropeptide that exhibits membrane activity beyond its canonical opioid receptor signaling. Here, we investigate how sequence variants of Dynorphin A associated with spinocerebellar ataxia type 23 modulate membrane disruption and aggregation behavior. Using computational electrophysiology simulations combined with liposome leakage and fluorescence-based aggregation assays, we show that Dynorphin A variants interact with lipid bilayers primarily via electrostatic recruitment, followed by mutation-dependent insertion and transient pore formation. Anionic lipids promote bilayer disruption, while cholesterol attenuates peptide activity in a variant-specific manner. Although Dynorphin A variants do not spontaneously form ordered aggregates, they markedly alter amyloid-β co-assembly by enhancing hydrophobic surface exposure without proportionally increasing fibrillization. These results demonstrate that subtle sequence changes fine-tune the balance between membrane perturbation and amorphous co-aggregation, and highlight electrostatic membrane recruitment as a key determinant of DynA bioactivity.
Neonatal low-bacterial-load during lactation impairs peak bone mass via a gut-liver-bone axis.
Zhao Y, Luo W, Chen T … +3 more , Xu J, Liu W, Liu Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42235330 · Publisher ↗
Peak bone mass (PBM) is a primary determinant of adult osteoporosis susceptibility and fracture risk. The gut microbiota is closely associated with bone homeostasis and PBM. Early-life establishment of the gut microbiota...
Peak bone mass (PBM) is a primary determinant of adult osteoporosis susceptibility and fracture risk. The gut microbiota is closely associated with bone homeostasis and PBM. Early-life establishment of the gut microbiota during lactation is crucial for gut microbiota developmental, however, its long-term impact on PBM remains unclear. In this study, we established a neonatal antibiotic exporsure (NeoATB) mouse model to mimic low-bacterial load during lactation period and investigated skeletal outcomes in adulthood. NeoATB mice exhibited significantly reduced femoral PBM and increased osteoclast activity at 24 weeks of age. Persistent alterations of gut microbiota was analyzed by longitudinal 16S rRNA sequencing, accompanied by fecal metabolomic profiling. These changes were associated with hepatic lipid accumulation and upregulation of fatty acid synthase (Fasn), resulting in increased circulating levels of liver-derived fatty acids, particularly palmitic acid (PA). Functional assays demonstrated that PA directly promoted osteoclast differentiation from bone marrow-derived monocytes. Our study showed that low-bacterial load during lactation induces gut microbial dysregulation, hepatic lipid metabolism reprogramming, and subsequent serum fatty acid-mediated excessive osteoclast differentiation, resulting in reduced PBM. Collectively, these findings demonstrated that low-bacterial load during lactation impairs adulthood PBM acquisition by promoting osteoclast differentiation through gut-liver-bone axis.
C-C motif chemokine 3 interferes with oligodendrocyte maturation in the brain.
Nishimura S, Okino H, Ishihara N … +5 more , Nakane T, Vogel CFA, Itoh K, Tominaga T, Ishihara Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42235329 · Publisher ↗
White matter alteration caused by abnormal myelination is a major contribution to the pathophysiology of autism spectrum disorder (ASD). We previously reported that mice prenatally exposed to valproic acid (VPA) showed i...
White matter alteration caused by abnormal myelination is a major contribution to the pathophysiology of autism spectrum disorder (ASD). We previously reported that mice prenatally exposed to valproic acid (VPA) showed increased expression of C-C motif chemokine ligand 3 (CCL3) in the developing hippocampus, and that antagonizing C-C chemokine receptor type 5 (CCR5), a CCL3 receptor, recovered neural circuit dysfunction. Therefore, we investigated the effects of CCL3 on oligodendrocyte differentiation. Treatment of the rat oligodendrocyte precursor cell (OPC) line CG4 and mouse primary OPC with CCL3 promoted CG4 migration. Conditioned media from BV-2 and primary microglia also promoted CG4 migration, and this promotion was cancelled by the CCR5 antagonist, maraviroc. CCL3 inhibited the differentiation of primary OPCs into mature oligodendrocytes. Therefore, microglia-derived CCL3 acts directly on OPCs by promoting their migration and inhibiting their differentiation. In organotypic whole-brain slice cultures, the expression of mature oligodendrocyte markers and the stained area of myelin basic protein (MBP) increased in a time-dependent manner. Treatment of slices with CCL3 reduced the expression of mature oligodendrocyte markers and the area of MBP staining. These changes were reversed by maraviroc pretreatment. In mice prenatally exposed to VPA, the expression of mature oligodendrocyte markers was reduced, myelin was thinner at 10 days of age, and axonal diameter was reduced at 8 weeks of age compared with control mice. These abnormalities were ameliorated by maraviroc treatment. Collectively, CCL3 interferes with oligodendrocyte maturation, thereby delaying axonal myelination and resulting in neural circuit dysfunction mediated by VPA.
Hepatic Senp2 deletion resolves the angiogenic switch in fibrosis via β-catenin/LECT2.
Dou X, Peng Y, Chen F … +7 more , Liu T, Pan B, Wang B, Guo W, Zhu D, Zhao Y, Chang D
Biochem Biophys Res Commun · 2026 Aug · PMID 42235328 · Publisher ↗
Liver fibrosis can arise from diverse etiologies, including metabolic stress and nutritional deficiencies. The methionine- and choline-deficient (MCD) diet induces liver fibrosis independent of metabolic syndrome, offeri...
Liver fibrosis can arise from diverse etiologies, including metabolic stress and nutritional deficiencies. The methionine- and choline-deficient (MCD) diet induces liver fibrosis independent of metabolic syndrome, offering a model to study non-metabolic drivers of hepatic fibrogenesis. SUMO-specific protease 2 (SENP2) has been implicated in metabolic liver disease, but its role in nutritionally induced fibrosis remains unknown. Here, we investigated how hepatic Senp2 regulates MCD-induced liver fibrosis, with a focus on vascular remodeling. Liver-specific Senp2 knockout mice and wild-type littermates were fed an MCD diet to establish fibrosis. Liver injury, fibrosis, inflammation, and angiogenesis were assessed. Hepatic Senp2 deficiency markedly attenuated MCD-induced liver injury, fibrosis, and inflammation. Notably, Senp2 loss triggered a distinct hepatic vascular remodeling pattern: it promoted portal angiogenesis while suppressing hepatic sinusoidal capillarization, as evidenced by altered Cd31 expression and vascular architecture. Mechanistically, Senp2 ablation significantly reduced leukocyte cell-derived chemotaxin 2 (LEC2) expression and secretion, alongside downregulation of both active non-phospho-β-catenin and total β-catenin. In the MCD-induced fibrosis model, hepatic Senp2 drives pathological vascular remodeling through a β-catenin/Lect2 axis. Loss of Senp2 restrains this pathway, rebalances hepatic angiogenesis, and ultimately mitigates fibrosis progression. This reveals a nutrition-specific, pro-fibrotic mechanism of Senp2 centered on vascular regulation, highlighting a potential therapeutic target for non-metabolic fibrotic liver diseases.
Structural insights into flexible pyruvate binding in an (S)-selective ω-transaminase.
Wu D, Zhang K, Luo Q … +6 more , Zhao K, Xu H, Feng D, Liang B, Ma H, Lu X
Biochem Biophys Res Commun · 2026 Aug · PMID 42229173 · Publisher ↗
(S)-selective ω-transaminases (S-ωTAs) are PLP-dependent enzymes widely employed in biocatalysis for the stereoselective amination of prochiral ketones, yielding enantiopure (S)-amines. Although their stereochemical pref...
(S)-selective ω-transaminases (S-ωTAs) are PLP-dependent enzymes widely employed in biocatalysis for the stereoselective amination of prochiral ketones, yielding enantiopure (S)-amines. Although their stereochemical preference is well established, the structural basis of keto-acceptor recognition and active-site flexibility remains poorly understood. Here, we present a 1.96 Å crystal structure of a marine S-ωTA OM-S25 in complex with PLP and pyruvate (PYR). The enzyme exhibits four protomer in one asymmetric unit, yet electron density reveals pronounced conformational heterogeneity in PYR binding across protomers, channel-proximal transitional states (chain C), deeply buried productive poses (chains A, B, D), and a channel-entrance pose salt-bridged to Lys166. These conformations may represent a potential substrate binding route for acidic acceptors. Molecular docking corroborates the final PYR position, and a conserved flipping arginine, which usual refer to an arginine switch, stabilizes the carboxylate moiety of PYR-like substrates. We propose a stepwise entry pathway for the acceptor PYR in the second half-reaction of S-ωTAs. This pathway involves initial capture of PYR by Lys166 within the access channel, followed by an ∼180° rotation facilitated by Phe22, Tyr153, and Tyr168, progressive relocation through positions C→ D→A→B, and ultimate in the position of chain B for further reaction. Supporting evidence includes activity assays with PYR derivatives, thermal shift assays revealing modest stability perturbations, and gate-region mutagenesis experiments that confirm the proposed entry route. Although PMP-bound structures are essential to fully resolve the second half-reaction, this study provides the most comprehensive structural framework to date for acceptor recognition and the overall transamination mechanism in S-ωTAs. These findings lay a strong foundation for future mechanistic studies and rational enzyme engineering to advance biocatalytic applications.
Dietary monoalkyldiacylglycerol enhances muscle regeneration and induces type Ⅱb myofiber formation in cardiotoxin-injury mice.
Imamura K, Takatani N, Hosokawa M … +1 more , Beppu F
Biochem Biophys Res Commun · 2026 Aug · PMID 42229172 · Publisher ↗
Monoalkyldiacylglycerols (MADG), ether-type glycerolipids found in deep-sea fish animals, promote myotube formation in C2C12 myoblasts. In this study, we investigated the effects of MADG on skeletal muscle regeneration i...
Monoalkyldiacylglycerols (MADG), ether-type glycerolipids found in deep-sea fish animals, promote myotube formation in C2C12 myoblasts. In this study, we investigated the effects of MADG on skeletal muscle regeneration in a mouse model of cardiotoxin-induced muscle injury. Male C57BL/6J mice were fed a diet supplemented with 0.5% MADG for 2 weeks, followed by cardiotoxin injection into the tibialis anterior muscle, and maintained on the experimental diets for up to an additional 2 weeks. The MADG diet increased the number and total area of myofibers 7 and 14 days post-injury compared with the normal diet group. mRNA levels of the myogenic regulatory factors MyoD and Myogenin increased, whereas those of inflammatory factors and satellite cell marker, remained unchanged. Immunohistochemical staining for myofiber type markers showed that dietary MADG promoted a shift toward a more fast-type phenotype, characterized by an increase in the number and proportion of MHC4-positive type Ⅱb fibers. In C2C12 myoblasts and mouse satellite cells, treatment with batyl alcohol, a MADG metabolite, increased Myh4 mRNA expression and decreased Myh2 mRNA expression. Overall, MADG promotes skeletal muscle regeneration and has the potential to induce a fast-twitch shift, accompanied by an increased proportion of type IIb myofibers during muscle repair. These results contribute to a better understanding of the regulation of myofiber types underlying skeletal muscle function and homeostasis.
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