Biochem Biophys Res Commun
· 2026 Aug · PMID 42263606
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In radiological and nuclear emergency scenarios, it is crucial to quantify the dose of ionizing radiation exposure. The conventional biodosimetry techniques, such as dicentric assays, are time and resource intensive for...In radiological and nuclear emergency scenarios, it is crucial to quantify the dose of ionizing radiation exposure. The conventional biodosimetry techniques, such as dicentric assays, are time and resource intensive for widespread usage. Exosomes being stable extracellular vesicles bearing molecular cargo can offer a promising alternative for minimally invasive, high-throughput biodosimetry. In the current study, plasma-derived exosomes were isolated using ultracentrifugation in Sprague Dawley rats at 24h, 48h, and 72h following gamma irradiation 2, 5 and 8 Gy. Exosomes were characterized using transmission electron microscopy, dynamic light scattering and western blotting. The untargeted LC-MS lipidomic profiling was conducted to detect alterations in lipid species. The lipid analysis revealed dose and time dependent changes characterized by increased levels of polyunsaturated fatty acids, ceramide phosphoethanolamines, fatty esters, phosphatidylcholines, and sterols, alongside depletion of antioxidant plasmalogens and triglycerides. These lipidomic alterations indicate radiation-induced oxidative stress, membrane remodeling, and apoptotic signaling conveyed through exosomes. A candidate panel of lipid biomarkers showing robust responsiveness to dose and time was identified, offering minimally invasive tool for radiation biodosimetry and triage during emergency scenarios thereby facilitating improved assessment and management of radiological exposures.
Yamada A, Hattori K, Kitano S
… +1 more, Matsusaki M
Biochem Biophys Res Commun
· 2026 Aug · PMID 42263605
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Functional anisotropic tissue reconstruction remains a major challenge in tissue engineering because synthetic polymers lack native extracellular matrix (ECM) functionality, whereas conventional collagen spinning methods...Functional anisotropic tissue reconstruction remains a major challenge in tissue engineering because synthetic polymers lack native extracellular matrix (ECM) functionality, whereas conventional collagen spinning methods often require cytotoxic solvents or chemical crosslinkers incompatible with direct cell encapsulation. We previously developed interfacial spinning technology using collagen and poly (acrylic acid) solutions to fabricate uniaxially aligned cell-laden collagen fibers; however, cell viability was limited using acetic acid (AA) as the collagen solvent. In this study, AA was replaced with lactic acid (LA) or citric acid (CA) to improve cytocompatibility. Both LA and CA preserved fiber-forming capability, collagen assembly behavior, and macroscopic mechanical properties. Cell viability significantly increased from approximately 40% with AA to 80% with LA and CA. Furthermore, co-cultured fibers containing endothelial cells and fibroblasts formed uniaxially aligned capillary networks over centimeter-scale lengths. These findings enable the biofabrication platforms of anisotropic centimeter-scale tissues.
Rapiejko AR, Reddy M, Sacchettini JC
… +1 more, Shell SS
Biochem Biophys Res Commun
· 2026 Aug · PMID 42263604
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Regulation of RNA pools allows for adaptation to stress, which is important in pathogenic bacteria such as Mycobacterium tuberculosis (Mtb). RNA degradation is a significant contributor to RNA abundance, and Ribonuclease...Regulation of RNA pools allows for adaptation to stress, which is important in pathogenic bacteria such as Mycobacterium tuberculosis (Mtb). RNA degradation is a significant contributor to RNA abundance, and Ribonuclease (RNase) E has a rate-limiting role in degradation of most mycobacterial transcripts. Many open questions remain about the RNA substrate requirements and specificities for efficient cleavage by mycobacterial RNase E. Here, we demonstrate that RNase E is only active on substrates with a minimum length of approximately 27 nt using both Mtb and Mycolicibacterium smegmatis (Msm) enzyme variants. Furthermore, we show that mycobacterial RNase E prefers substrates with 5' monophosphates to 5' triphosphates. We present that the positions of cleavage events by RNase E within substrates are dictated by both sequence and distance from the RNA ends. Finally, we show that Msm RNase E behaves similarly to Mtb RNase E, validating the use of this model organism for RNA degradation studies.
Biochem Biophys Res Commun
· 2026 Aug · PMID 42263603
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BACKGROUND: Ovarian cancer (OC) typically exhibits aggressive growth and is prone to developing cisplatin (DDP) resistance. One of the Kinesin family members KIF11, is a current research hotspot due to its role in cispla...BACKGROUND: Ovarian cancer (OC) typically exhibits aggressive growth and is prone to developing cisplatin (DDP) resistance. One of the Kinesin family members KIF11, is a current research hotspot due to its role in cisplatin resistance, although its underlying mechanisms are not yet fully understood. METHODS: Differentially expressed genes (DEGs) were obtained from TCGA-OV, GSE23391, and GSE29450, from which candidate genes were screened. Applying qRT-PCR and WB, KIF11 expression in OC cell lines was evaluated, followed by loss- and gain-of-function assays. The regulation of cell phenotype by KIF11 knockdown/overexpression was assessed using Transwell assays, CCK-8, flow cytometry, and colony formation assays. LiCl, an activator of the Wnt/β-catenin pathway, and XAV-939, an inhibitor, were applied to examine the regulatory mechanisms. The function related to chemoresistance was studied using a DDP-resistant cell model (SKOV3-DDP). RESULTS: Four candidate genes (BUB1B, CCNB1, KIF11, KIF23) were significantly upregulated in OC samples. In vitro, KIF11 was highly expressed in OC cell lines. KIF11 silencing suppressed cell growth, increased apoptosis, and induced G2/M arrest, effects that were partially rescued by LiCl, supporting a functional link to the Wnt/β-catenin pathway. KIF11 was upregulated in SKOV3-DDP cells compared with parental SKOV3 cells. While KIF11 overexpression had the opposite effects, which XAV-939 mitigated, KIF11 knockdown decreased viability and colony formation and increased apoptosis. CONCLUSION: KIF11 can promote the malignant phenotype and DDP resistance of tumor cells by activating the Wnt/β-catenin signaling pathway in OC. Therefore, KIF11 has the potential to serve as a biomarker for predicting OC progression and the efficacy of DDP treatment.
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259202
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The claustrum is a thin, elongated structure that forms widespread reciprocal connections with most cortical areas and has been proposed to support diverse functions. Recent studies in rats have suggested that the anteri...The claustrum is a thin, elongated structure that forms widespread reciprocal connections with most cortical areas and has been proposed to support diverse functions. Recent studies in rats have suggested that the anterior claustrum, particularly the rostral-to-striatum claustrum (rsCla), may serve as a hub for information integration. However, the connectivity between the rsCla and other brain regions remains poorly understood. In the present study, we examined the connectivity of the rsCla in rats using retrograde tracers. Consistent with previous studies of other claustral regions in rodents, the rsCla exhibited widespread reciprocal connectivity with multiple cortical areas. In contrast, it received relatively strong input from the medial claustrum and showed preferential output to the orbitofrontal cortex. These findings suggest that the rsCla may integrate inputs from the medial claustrum, potentially reflecting more processed signals, together with distributed cortical information, and transmit this integrated representation preferentially to the orbitofrontal cortex, supporting outcome prediction.
Wang Y, Yu Z, Huang Z
… +3 more, Xu C, Cao Y, Sun Z
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259201
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BACKGROUND: Zinc finger proteins (ZFPs) play important roles following ischemic stroke (IS), but systematic investigations into their potential as biomarkers are still lacking. METHODS: Multi-omics data were integrated w...BACKGROUND: Zinc finger proteins (ZFPs) play important roles following ischemic stroke (IS), but systematic investigations into their potential as biomarkers are still lacking. METHODS: Multi-omics data were integrated with machine learning approaches. Transcriptomic data for IS were obtained from the GEO database. IS-related ZFP genes were identified through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and ZFP gene set screening. Feature genes were selected using LASSO, SVM-RFE, and random forest algorithms. Causal relationships were validated using Mendelian randomization (MR), summary-data-based MR (SMR) and Bayesian colocalization analyses. The diagnostic model was validated in an external dataset. Functional mechanisms were explored via immune infiltration analysis, gene set enrichment analysis (GSEA), and single-cell sequencing (scRNA-seq). Drug screening and safety assessment were performed using deep learning, molecular docking, and phenome-wide association study (PheWAS). RESULTS: A total of 46 IS-related ZFP genes were identified. Six feature genes were selected through machine learning. SMR, TSMR, and colocalization analyses identified ZNF438 and ZNF608 as risk genes and ZNF566 as a protective gene, with colocalization further confirming shared causal variants. A diagnostic model based on these three genes performed well in both the training cohort (AUC = 0.955) and the validation cohort (AUC = 0.897). Immune infiltration analysis revealed that ZNF438 and ZNF608 were positively correlated with neutrophils, while ZNF566 showed a negative correlation. ScRNA-seq revealed their specific expression patterns in cell types. Drug screening identified 2-phenylethynesulfonamide as a compound with stable binding to the three targets, and PheWAS suggested favorable safety profiles for these targets. CONCLUSION: ZNF438, ZNF566, and ZNF608 were identified as IS-related ZFP biomarkers. The constructed model demonstrated good diagnostic performance, providing new candidate targets for molecular diagnosis and targeted therapy of IS.
Olanipekun JT, Ghaisas HD, McQueen C
… +9 more, Ward DG, Stanulović VS, Hoogenkamp M, Hulme CH, Wright KT, Nakajima H, Johnson LDV, Brown G, Johnson WE
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259200
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We generated serum-supplemented and serum-free mouse ST2 mesenchymal stem/stromal cell conditioned medium (MSC CM) to treat mouse E14-Tg2A embryonic stem (ES) cells. Coating tissue culture plates with serum-free MSC CM p...We generated serum-supplemented and serum-free mouse ST2 mesenchymal stem/stromal cell conditioned medium (MSC CM) to treat mouse E14-Tg2A embryonic stem (ES) cells. Coating tissue culture plates with serum-free MSC CM promoted ES cell growth. In 3D ES cultures primed with the Wnt/β catenin agonist, CHIR99201, serum-free MSC CM induced gastruloid formation with axial elongation and TBXT (Brachyury) immunoreactivity localized in the elongation tips. Serum-supplemented MSC CM and control media did not have these effects. Extended gastruloid culture in serum-free MSC CM resulted in pleiomorphic structures that contracted rhythmically. These beating ES gastruloids were immunopositive for cardiac Troponin T. Proteomic analyses of serum-free MSC CM identified multiple target proteins that promote ES cell adhesion, growth, morphogenesis, mesodermal and cardiomyocyte differentiation, notably vascular endothelial growth factor and leukemia inhibitory factor. Hence, this study has utilised a novel model system to interrogate the secretome activity of MSCs and shown that this can generate ES cell-derived cardiomyocytes.
Modak K, Dey A, Bharti KK
… +4 more, Gautam MK, Mondal S, Dutta PP, Gangwar M
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259199
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Cell signaling pathways regulate essential cellular processes including inflammation, oxidative stress, proliferation, apoptosis, metabolism, and immune homeostasis. Dysregulation of interconnected pathways such as NF-κB...Cell signaling pathways regulate essential cellular processes including inflammation, oxidative stress, proliferation, apoptosis, metabolism, and immune homeostasis. Dysregulation of interconnected pathways such as NF-κB, MAPK, PI3K/Akt, Nrf2/ARE, JAK/STAT, AMPK/mTOR, and Wnt/β-catenin contributes significantly to chronic diseases including cancer, diabetes, cardiovascular disorders, neurodegenerative diseases, and inflammatory conditions. Increasing evidence indicates that plant-derived phytochemicals act as multitarget modulators capable of restoring signaling balance through simultaneous regulation of multiple molecular networks. This review provides an updated and integrative overview of phytochemical-mediated modulation of major signaling pathways involved in chronic diseases, emphasizing mechanistic cross-talk and translational relevance. A comprehensive literature survey was conducted using PubMed, SciFinder, and Google Scholar to collect experimental and clinical evidence on phytochemical regulation of signaling pathways. Major phytochemicals including curcumin, resveratrol, quercetin, berberine, epigallocatechin gallate, apigenin, and ginsenosides suppress NF-κB, PI3K/Akt, MAPK, and JAK/STAT signaling while activating Nrf2-mediated antioxidant defense, AMPK signaling, autophagy, and apoptosis. These compounds also regulate metabolic inflammation, neuroinflammation, mitochondrial dysfunction, and cancer-associated signaling networks. Unlike previous reviews focused on isolated pathways or individual compounds, this review integrates signaling cross-talk and multitarget phytochemical actions across diverse chronic diseases. Despite promising therapeutic potential, clinical translation remains limited by poor bioavailability, pharmacokinetic variability, lack of standardization, and insufficient large-scale clinical validation.
Xu Y, Wang X, Sun Y
… +7 more, Ye X, Gao Y, Li L, Wu Y, Zhou K, Pan Y, Ma S
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259198
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Immunotherapy has revolutionized the treatment of esophageal squamous cell carcinoma (ESCC), but its clinical application is limited by low response rates and acquired resistance. The exploration of underlying is hampere...Immunotherapy has revolutionized the treatment of esophageal squamous cell carcinoma (ESCC), but its clinical application is limited by low response rates and acquired resistance. The exploration of underlying is hampered by the absence of preclinical models that faithfully recapitulate the immune microenvironment and drug-resistant features of ESCC. Here, we established a novel murine ESCC cell line named mESCC-030, which was derived from primary ESCC tumors induced by 4-Nitroquinoline N-oxide (4-NQO) in C57BL/6 mice via consecutive in vivo selection. This cell line was validated by morphological observation and STR identification. Compared with primary parental cells, mESCC-030 exhibits stronger malignant proliferation, invasion and migration capabilities, and achieves 100% subcutaneous tumorigenicity in C57BL/6 mice. Moreover, the syngeneic graft tumors derived from this cell line display prominent resistance to PD-1 antibody therapy. Bulk transcriptomic profiling revealed that this cell line harbors enhanced proliferation-related pathways and diminished immune response pathways. Single-cell RNA sequencing of graft tumors identified a highly proliferative cell cluster in tumor tissues, along with an extremely low proportion of immune infiltrating cells. Taken together, the mESCC-30 cell line and its syngeneic tumors represent a typical immune-cold tumor model, providing a novel platform to uncover immunotherapy resistance mechanisms and develop combination therapeutic strategies.
Su R, Li L, Gu J
… +8 more, Xu R, Long Y, Shi W, Song W, Wang X, Li C, Fei J, Li Y
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259197
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The rapid evolution of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) variants, particularly mutations in the spike protein, has compromised the efficacy of many therapeutics, highlighting the urgent need fo...The rapid evolution of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) variants, particularly mutations in the spike protein, has compromised the efficacy of many therapeutics, highlighting the urgent need for broad-spectrum antiviral strategies. The RNA-dependent RNA polymerase (RdRp), a core enzyme essential for viral replication and transcription, represents an ideal target due to its high sequence conservation across SARS-CoV-2 variants and related coronaviruses, as well as its functional indispensability-mutations in its catalytic core typically incur significant viral fitness costs. In this study, we designed antisense oligonucleotides (ASOs) targeting the highly conserved RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. Using RNAstructure v6.3 and OligoWalk for rational design based on secondary structure and binding thermodynamics, we identified several candidate ASOs. In plasmid-transfected cells, RDRP-5 potently knocked down RdRp mRNA expression. In a SARS-CoV-2 replicon system, it significantly suppressed viral replication. Furthermore, in live virus infection models, RDRP-5 effectively reduced viral RNA load and titers of multiple Variants of Concern, including the SARS-CoV-2 Wuhan-Hu-1, Delta, Omicron, and XBB.1.1.6. These findings establish RDRP-5 as a promising broad-spectrum ASO therapeutic candidate that targets an evolutionarily constrained region of RdRp, thereby overcoming variant-driven resistance. More broadly, this study validates the strategy of targeting conserved viral replication machinery as a potent approach to combat both current and future emerging coronaviruses, offering a potential pathway for rapid deployment against future pandemics.
Yao W, Qu M, Deng C
… +9 more, Zhang C, Zhang X, Hu X, Zhang J, Yang T, Liu F, Wang T, Li D, Wang X
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259196
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Alzheimer's disease (AD) is the leading cause of dementia with no effective disease-modifying treatments. Here, we found that Escherichia coli (E. coli) DH5α relieved learning defects and paralysis, and prolonged lifespa...Alzheimer's disease (AD) is the leading cause of dementia with no effective disease-modifying treatments. Here, we found that Escherichia coli (E. coli) DH5α relieved learning defects and paralysis, and prolonged lifespan in amyloid-β (Aβ)-expressing C. elegans. DH5α inhibited Aβ aggregation via activating the PEK-1-dependent endoplasmic reticulum unfolded protein response (UPRer). We further identified equol from DH5α metabolites, which alleviated AD-related phenotypes through the same PEK-1/UPRer pathway.
Ghzaiel I, Moreau M, Ali S
… +5 more, Quoniou R, Baron S, Perisse F, Lobaccaro JM, Menecier S
Biochem Biophys Res Commun
· 2026 Aug · PMID 42259195
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Cold atmospheric plasma (CAP) is an ionized gas generated at atmospheric pressure in which the temperature of heavy particles (ions, molecules, atoms) remains close to room temperature. CAP produces a complex mixture of...Cold atmospheric plasma (CAP) is an ionized gas generated at atmospheric pressure in which the temperature of heavy particles (ions, molecules, atoms) remains close to room temperature. CAP produces a complex mixture of reactive oxygen and nitrogen species (RONS). Recent studies have demonstrated its ability to induce cell death in various cancer cell lines, both in vitro and in vivo. Interestingly, non-tumoral cells appear to be relatively less affected by CAP treatments, this phenomenon is referred to as CAP selectivity. This study aimed to investigate the differential selectivity of a CAP jet generated by dielectric barrier discharge (DBD) in human prostate cells, comparing prostate cancer PC3 cells with non-tumoral RWPE-1 cells. Cells were exposed to a CAP treatment for 5-60 s and cell viability (MTS assay), plasma membrane integrity (Propidium iodide, PI staining), morphology (phase-contrast microscopy), intracellular ROS production (DHE staining), and antioxidant enzyme activities (SOD (superoxide dismutase), catalase, GPx (glutathione peroxidase)) were assessed 4 h and 24 h post-treatment. CAP exposure induced a time-dependent decrease in PC3 cell viability, with significant effect on viability observed at exposures ≥30 s, whereas RWPE-1 cells showed relative resistance. PI staining confirmed greater plasma membrane damage in PC3 compared to RWPE-1 cells. Morphological alterations such as cell rounding and detachment were more pronounced in PC3 cells than RWPE-1. CAP markedly increased intracellular ROS levels in PC3 cells (up to 73% DHE-positive after 60 s), accompanied by SOD upregulation and reduced catalase and GPx activities. In contrast, RWPE-1 cells exhibited a less pronounced oxidative response and preserved antioxidant enzyme activities. In summary, these results demonstrate differential sensitivity to CAP treatment between prostate cancer cells and non-tumoral cells under the tested conditions, associated with alterations in cellular redox status. These findings suggest that DBD-generated CAP may represent a promising targeted therapeutic approach for prostate cancer treatment.
Wang X, Yang H, Ma S
… +3 more, Shi L, Li T, Yang N
Biochem Biophys Res Commun
· 2026 Aug · PMID 42251821
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Homologous recombination (HR) is a high-fidelity pathway for repairing DNA double-strand breaks, with the replication protein A (RPA)-Rad51 exchange representing a critical step. We previously reported that phosphorylate...Homologous recombination (HR) is a high-fidelity pathway for repairing DNA double-strand breaks, with the replication protein A (RPA)-Rad51 exchange representing a critical step. We previously reported that phosphorylated HIV-1 transactivator of transcription specific factor 1 (HTATSF1) interacts directly with DNA topoisomerase 2-binding protein 1 (TopBP1) and recruits it to DNA damage sites to promote RPA-Rad51 exchange and HR repair. Here, we demonstrate that TopBP1 cooperatively binds phosphorylated HTATSF1 through its BRCT1 and BRCT2 domains. We present the crystal structure of TopBP1 BRCT0-2 in complex with the phosphorylated extreme C terminus (ECT) peptide of HTATSF1, identifying key residues in BRCT1 involved in recognition. Notably, the N-terminal segment of the ECT peptide adopts a unique conformation, enabling specific hydrophobic interactions with V158 in BRCT1. Mutagenesis and binding assays confirm V158 as a key determinant allowing TopBP1 BRCT1 to discriminate HTATSF1 from other phosphorylated ligands. Furthermore, AlphaFold3 modeling combined with biochemical validation indicates that the ECT peptide also engages BRCT2 domain via its conserved phospho-binding pocket. Our work provides a structural basis for the specific TopBP1-HTATSF1 interaction and advances the mechanistic understanding for HR regulation.
Kumar A, Das S, Koirala N
… +3 more, Khatua D, Kshatriya R, Jyoti A
Biochem Biophys Res Commun
· 2026 Aug · PMID 42251820
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BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by persistent inflammation and oxidative stress-mediated pathogenesis. Identifying patient-specific drug targeting oxidati...BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by persistent inflammation and oxidative stress-mediated pathogenesis. Identifying patient-specific drug targeting oxidative damage is of paramount importance. Resveratrol has emerged as a promising therapeutic candidate owing to its antioxidant and anti-inflammatory properties. This study aims to identify its targets and evaluate its therapeutic efficacy in neutrophil-driven oxidative stress in COPD. METHODS: Bioinformatic analyses were performed using the GSE11952 and GSE232805 datasets. Top-ranked hub genes were identified for candidate drug screening and validated through molecular docking. Human peripheral blood neutrophils from healthy volunteers as well as COPD patients were isolated and challenged with bacteria or PMA, with or without resveratrol, under ex-vivo cigarette smoke exposure (CSE) followed by Python-based statistical and exploratory data analyses. We further assessed the effects of resveratrol on reactive oxygen species (ROS) generation and neutrophil extracellular traps (NETs) formation. RESULTS: The top-ranked identified hub genes common across the three centrality algorithms were FN1, CD44, ITGA5, and THBS1, having roles in extracellular matrix-receptor interaction, advanced glycation end-products-receptor, hypoxia-inducible factor 1, cytokine signalling, and ferroptosis pathways. Molecular docking results demonstrated the highest binding affinity between resveratrol and ITGA5 (-7.4 kcal/mol). Ex-vivo quantitative analysis revealed that resveratrol significantly attenuated bacterial-induced ROS in healthy and CSE neutrophils. Additionally, it showed significant efficacy in reducing ROS and NET formation in PMA-stimulated neutrophils of COPD patients. CONCLUSION: Resveratrol exerted a significant antioxidant effect in modulating oxidative stress in COPD. Integrated bioinformatics and ex-vivo experiments suggest that ITGA5 may be a candidate target through which Resveratrol suppressed ROS generation and NETs formation in COPD.
Biochem Biophys Res Commun
· 2026 Aug · PMID 42251819
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BACKGROUND: Atrial fibrillation (AF) represents a highly common form of cardiac dysrhythmia, and its development is closely linked to atrial remodeling. The significance of immune cells in the context of AF has garnered...BACKGROUND: Atrial fibrillation (AF) represents a highly common form of cardiac dysrhythmia, and its development is closely linked to atrial remodeling. The significance of immune cells in the context of AF has garnered considerable attention, but the specific mechanism remains unclear. METHODS: Single-cell RNA sequencing database (GSE224959) was analyzed to characterize immune cell populations in atrial tissues from AF patients and non-AF controls. Neutrophil polarization was assessed in vitro, and the effects of N1 neutrophils on cardiomyocyte PANoptosis were evaluated. Cell experiments were performed to unravel the underlying molecular mechanisms. RESULTS: We found that the number of N1 neutrophils in the atrial tissue of AF patients was significantly increased. Functionally, N1 neutrophils promoted cardiomyocyte PANoptosis, as evidenced by enhanced cell death rates, elevated LDH release, decreased ATP levels, upregulated p-MLKL, cleaved caspase-3, and GSDMD-N expression, along with elevated pro-inflammatory cytokine secretion. SOCS2 was revealed to be a crucial modulator of neutrophil N1 polarization. Overexpression of SOCS2 inhibited neutrophil N1 polarization, thereby suppressing cardiomyocyte PANoptosis. Mechanistically, SOCS2 directly interacted with HSPA8, promoted its ubiquitination, and reduced its protein stability. Importantly, HSPA8 overexpression partially counteracted the suppressive effects of SOCS2 on neutrophil N1 polarization. CONCLUSION: SOCS2-mediated ubiquitination of HSPA8 reduced its protein stability, thereby suppressing neutrophil N1 polarization and ultimately attenuating cardiomyocyte PANoptosis, highlighting SOCS2 as a hopeful therapeutic target for AF.
Biochem Biophys Res Commun
· 2026 Aug · PMID 42250342
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The integrin family mediates interactions between cells and the extracellular matrix, and plays a pivotal role in the tumor microenvironment. Integrin α2β1, a ubiquitously expressed collagen receptor, is frequently overe...The integrin family mediates interactions between cells and the extracellular matrix, and plays a pivotal role in the tumor microenvironment. Integrin α2β1, a ubiquitously expressed collagen receptor, is frequently overexpressed in various solid tumors, such as glioblastoma, pancreatic cancer and lung cancer, and plays a critical role in tumor progression. Studies have demonstrated that α2β1 promotes cancer progression by regulating a complex pro-tumorigenic network through multiple mechanisms, including tumor cell proliferation, local invasion and distant metastatic colonization. Recent research has also revealed the role of α2β1 in inducing tumor stem cell phenotypes, as well as its potential as a diagnostic, prognostic biomarker and therapeutic target. In this review, we will examine the diverse functions of α2β1 in cancer progression and explore how these insights can inform the development of therapeutic strategies to overcome drug resistance and metastasis.
Abiskaroon B, Arriaza RH, Chouhan V
… +8 more, Barr MG, Watkins M, Hopkins J, Borowski T, Van Leeuwen T, Grbic M, Grbic V, Chruszcz M
Biochem Biophys Res Commun
· 2026 Aug · PMID 42250341
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In the environment, aromatic compounds are commonly introduced artificially or as natural plant secondary metabolites. A major agricultural pest, Tetranychus urticae, has acquired genes encoding for intradiol ring-cleava...In the environment, aromatic compounds are commonly introduced artificially or as natural plant secondary metabolites. A major agricultural pest, Tetranychus urticae, has acquired genes encoding for intradiol ring-cleavage dioxygenases (IDRCDs) that can detoxify such compounds. Studies of one such IDRCD, TuIDRCD930 (encoded by gene tetur07g05930), revealed a dimerization not seen before in enzymes of this class in T. urticae, including a different oligomerization mechanism observed in fungal and bacterial homologs. Through SEC-SAXS and gel filtration experiments, TuIDRCD930 was found to dimerize by utilizing two different interactions in the N-termini: changes in protonation states and the formation of a disulfide bond. Additionally, in vitro studies demonstrate catalytic efficiency of TuIDRCD930 towards polycyclic aromatic compounds, which represents an evolutionary advantage for T. urticae. It was shown that the dimerization process does not obscure access of relatively large substrates to the enzyme active site. We further displayed that the recombinant version of TuIDRCD930 is active in both monomeric and dimeric states. Overall, this work determines oligomerization and activity not previously described in IDRCDs from T. urticae and provides further evidence of how evolution has provided this pest with novel tools to overcome plant defenses.
Biochem Biophys Res Commun
· 2026 Aug · PMID 42250340
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Flowering is a critical developmental event for plants. Here, we identify that the nitrate efflux channel SLOW ANION CHANNEL HOMOLOG 3 (SLAH3) regulates flowering time in Arabidopsis thaliana. The slah3-4 mutant exhibite...Flowering is a critical developmental event for plants. Here, we identify that the nitrate efflux channel SLOW ANION CHANNEL HOMOLOG 3 (SLAH3) regulates flowering time in Arabidopsis thaliana. The slah3-4 mutant exhibited early flowering and reduced rosette leaf number under both long-day and short-day conditions, while SLAH3 overexpression plants exhibited delayed flowering. This regulatory role of SLAH3 was independent of nitrate supply, as the early-flowering phenotype persisted across a range of KNO concentrations in hydroponic culture. Molecular analyses revealed that the expression of the floral repressor FLOWERING LOCUS C (FLC) was downregulated, whereas floral promoters including CONSTANS (CO), FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and LEAFY (LFY) were upregulated in slah3-4. SLAH3 exhibited rhythmic oscillatory expression, and the circadian clock gene TIMING OF CAB EXPRESSION 1 (TOC1) exhibited altered expression in the mutant, while CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY) remained unchanged. RNA situ hybridization further confirmed that SLAH3 modulates flowering time through regulating LFY expression. In summary, our results demonstrate that SLAH3 plays an important biological role in regulating floral transition in Arabidopsis.
Sahu S, Upadhyay A, Kamei S
… +2 more, Vishwakarma C, Pratap JV
Biochem Biophys Res Commun
· 2026 Aug · PMID 42247813
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Quinone oxidoreductases (QORs) play an essential protective role in cellular detoxification by reducing quinones to their less reactive hydroxyquinones. In Leishmania donovani, QOR (LdQOR) constitutes an important compon...Quinone oxidoreductases (QORs) play an essential protective role in cellular detoxification by reducing quinones to their less reactive hydroxyquinones. In Leishmania donovani, QOR (LdQOR) constitutes an important component of the parasite's antioxidant defence machinery, however, its enzymatic characteristics and catalytic mechanism remain poorly understood. Mutant constructs of LdQOR key active site residues (Y48A, Y54A, R268A, T270A and R320A) were generated, expressed, purified and kinetic analyses carried out. The wild-type enzyme exhibited a catalytic efficiency of 0.327 μM min, in comparison, most of the mutant constructs Y48A, Y54A, R268A and R320A (except T270A) showed reduced enzymatic activity and catalytic efficiency. Among these, mutation of arginine residue R320 significantly disrupted catalytic performance, indicating its critical role in maintaining structural integrity and facilitating catalysis. Simultaneously, LdQOR was co-crystallized with its cofactor and a substrate and preliminary structure analysis reveal electron densities consistent with probable cofactor and substrate occupancy within the active site pocket. Interestingly, electron density near Cys127 suggests the possible formation of Cys-NADPH adduct that may contribute to catalysis through active site modulation. The pronounced impact on R320 highlights its relevance in therapeutic intervention and suggests they may serve as a promising target for selective inhibitor design against LdQOR. Collectively, these significant findings of key catalytic residues provide new avenue for future structural and functional studies.