Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
Bioenergetic benefits and therapeutic potential of storable mitochondria.
Shibata T, El-Darawish Y, Sakakibara K … +8 more , Takeda M, Hayashi J, Nitta Y, Ohta Y, Yamada Y, Tsai R, Ota H, Suganuma M
Biochem Biophys Res Commun · 2026 Aug · PMID 42284991 · Publisher ↗
Mitochondrial transplantation is an emerging therapeutic strategy for various diseases associated with mitochondria dysfunction; however, conventional isolation methods require fresh tissue due to the fragility of isolat...
Mitochondrial transplantation is an emerging therapeutic strategy for various diseases associated with mitochondria dysfunction; however, conventional isolation methods require fresh tissue due to the fragility of isolated mitochondria, limiting clinical application. We previously developed a novel isolation method to recover high-quality mitochondria (Mitochondria oRganelle Complex; MRC-Q) from cryopreserved cell stocks. In this study, we characterized the biological profiles of MRC-Q and investigated its intracellular behavior and metabolic impact on recipient cells. MRC-Q maintained exceptionally high structural integrity of both outer and inner membranes, respiratory capacity, and high catalase activity even after cryopreservation and thawing. When delivered to human fibroblasts and vascular endothelial cells, RFP-labeled MRC-Q was rapidly internalized as independent puncta without fusing with the endogenous mitochondrial network. MRC-Q treatment significantly enhanced cellular respiration and ATP levels, and upregulated the expression of electron transport chain components and mitochondrial transcription factor A (TFAM). Furthermore, MRC-Q conferred dose-dependent resistance to HO-induced oxidative stress. These results suggest that MRC-Q acts not only as a transient energy source but also as a biological catalyst that triggers endogenous mitochondrial biogenesis. Our findings demonstrated that MRC-Q is a scalable and potent candidate for next-generation mitochondrial replacement therapy.
Dietary fatty acids activate FATP4 and lipid transport via HIF1α and KDM4B in the small intestinal enterocytes.
Xu M, Bian L, Huang L … +2 more , Yin Y, Zhang L
Biochem Biophys Res Commun · 2026 Aug · PMID 42284990 · Publisher ↗
The intestinal lipid metabolism is a vital factor that affects energy homeostasis. However, the regulatory mechanisms of the intestinal lipid transport and absorption, which is the first step of intestinal lipid metaboli...
The intestinal lipid metabolism is a vital factor that affects energy homeostasis. However, the regulatory mechanisms of the intestinal lipid transport and absorption, which is the first step of intestinal lipid metabolism, remain unclear. In this study, we found that high-fat diet increased the expression of fatty acid transporter protein 4 (FATP4) and KDM4B in the small intestines of both male and female mice. In the enterocytes, fatty acids (palmitic acid and oleic acid) increased the expression of KDM4B and FATP4 dose- and time-dependently. Knockdown of KDM4B inhibited the fatty acids induced elevation of FATP4 and lipid absorption in the enterocytes. Meanwhile, our results showed that the HIF1α was increased by fatty acids in the small intestines and enterocytes, and the inhibition of HIF1α blocked the fatty acid-induced increase of KDM4B as well as FATP4 and lipid absorption. In summary, dietary fatty acids regulated FATP4 and lipid absorption in the small intestinal enterocytes via HIF1α and KDM4B. These findings provide insights into the regulatory mechanisms of intestinal lipid absorption and potential therapeutic targets to combat metabolic diseases such as obesity.
State-dependent remodeling of dopamine receptor expression across mushroom body in Drosophila.
Chiang MH, Lu CY, Wu YY … +3 more , Wei HT, Wu T, Wu CL
Biochem Biophys Res Commun · 2026 Aug · PMID 42284989 · Publisher ↗
Internal physiological states profoundly reshape sensory processing and whether distinct internal state modulate the expression of neurotransmitter receptors. Here, using endogenous split-GFP receptor tagging in Drosophi...
Internal physiological states profoundly reshape sensory processing and whether distinct internal state modulate the expression of neurotransmitter receptors. Here, using endogenous split-GFP receptor tagging in Drosophila, we systematically mapped dopamine receptor dynamics across all 15 mushroom body (MB) lobe compartments under hunger and thirst states. We found that hunger selectively increased Dop1R1 expression throughout αβ MB lobe compartments and increased Dop2R expression across α'β' MB lobe compartments. In contrast, thirst broadly upregulated both Dop1R1 and Dop2R in γ MB lobe compartments while simultaneously reducing Dop2R expression in αβ MB lobe. Thirst also induced compartment-specific remodeling within α'β' MB neurons (MBn), including increased Dop1R1 expression in α'3 and decreased expression in β'1 regions. Notably, these receptor dynamics occurred without significant changes in baseline dopamine release from upstream dopaminergic neurons (DAN) during different internal physiological states, suggesting that hunger and thirst states regulate downstream circuit responsiveness primarily through selective remodeling of dopamine receptor expression rather than alterations in presynaptic dopaminergic activity. Together, our findings uncover a previously unrecognized mechanism by which internal physiological states reshape dopaminergic receptor organization to regulate neural circuit functions.
Constitutively active MEK1 expression driven by the myeloid-selective MRP8 promoter induces epithelial hyperplasia and papilloma formation.
Zang Y, Duan R, Miranda MB … +2 more , Rigatti LH, Johnson DE
Biochem Biophys Res Commun · 2026 Aug · PMID 42284988 · Publisher ↗
The mitogen-activated protein kinase kinase (MEK)/extracellular-regulated kinase (ERK) signaling pathway is hyperactivated in myeloid leukemias characterized by differentiation blockade, suggesting a potential role in di...
The mitogen-activated protein kinase kinase (MEK)/extracellular-regulated kinase (ERK) signaling pathway is hyperactivated in myeloid leukemias characterized by differentiation blockade, suggesting a potential role in disruption of myeloid differentiation. However, other reports indicate that MEK/ERK activation is required for normal myeloid differentiation. To investigate the in vivo role of MEK/ERK hyperactivation in myeloid differentiation and leukemia development we generated transgenic mice with doxycycline (DOX)-inducible expression of constitutively active MEK1 (CA-MEK1) under the control of the myeloid-selective MRP8 promoter. Two independent transgenic lines (lines A and B) were generated. Strikingly, both lines developed epithelial abnormalities following DOX induction of CA-MEK1. Line A mice exhibited pervasive skin/epithelial thickening, while line B mice developed papillomas. Prominent induction of CA-MEK1 was detected in epidermis, but not dermis, and was accompanied by epithelial cell hyperplasia. Line B mice also exhibited CA-MEK1 induction and ERK1/2 phosphorylation/activation in bone marrow and blood. Induction of CA-MEK1 over a range of 8-33 weeks, however, failed to alter the frequency of monocytes and granulocytes in the blood of line B mice. Collectively, our findings demonstrate that the MRP8 promoter is active in both myeloid and epithelial tissues. Moreover, we confirm earlier reports that hyperactivation of MEK/ERK signaling in epithelial tissues promotes epithelial hyperplasia. In addition, our findings indicate that hyperactivation of the MEK/ERK pathway alone is insufficient to alter myeloid differentiation and initiate leukemia development. We propose that MEK/ERK hyperactivation likely acts to promote proliferation or cell survival in leukemias where differentiation has been blocked by other genetic or epigenetic events.
Machine learning defines a histone deacetylase-associated transcriptional prognostic signature with single-cell resolution in breast cancer.
Wang Y, Wang Y, Li Y … +5 more , Xu Y, Kong L, Liu L, He L, Dai J
Biochem Biophys Res Commun · 2026 Aug · PMID 42284987 · Publisher ↗
BACKGROUND: Breast cancer (BC) is a highly heterogeneous malignancy, and transcriptional programs associated with histone deacetylases (HDACs) may provide clinically relevant prognostic information. However, the downstre...
BACKGROUND: Breast cancer (BC) is a highly heterogeneous malignancy, and transcriptional programs associated with histone deacetylases (HDACs) may provide clinically relevant prognostic information. However, the downstream prognostic significance of HDAC-associated molecular heterogeneity remains incompletely understood. METHODS: Non-negative matrix factorization (NMF) was performed in the TCGA cohort to identify HDAC-related molecular subtypes, followed by weighted gene co-expression network analysis and differential-expression analysis to derive candidate genes. A prognostic signature was then constructed using multiple machine-learning algorithms and validated across external BC cohorts. Additional analyses included multivariable and continuous-risk Cox regression, correlation analysis between the HDAC-related risk score (HRS) and HDAC family member expression, and single-cell gene-set scoring using Seurat's AddModuleScore function. Key hub genes were further examined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). RESULTS: NMF consensus clustering identified five HDAC-related molecular clusters with distinct survival outcomes and immune-infiltration patterns in TCGA-BRCA. WGCNA further identified subtype-associated co-expression modules, and candidate features were obtained by intersecting HDAC-cluster-associated DEGs with WGCNA-derived hub genes. A 24-gene HRS model based on CoxBoost + SuperPC showed stable prognostic performance across the TCGA training cohort and seven external breast cancer validation cohorts. Multivariable Cox analyses supported the independent prognostic value of HRS in several major cohorts. Single-cell analysis showed cell-type-specific heterogeneity of the model-related signature score, and UTRN, LIMCH1, ARNT2, and PYDC1 showed concordant expression patterns in public datasets and preliminary qRT-PCR/WB validation. CONCLUSION: These findings suggest that the HDAC-associated HRS model may serve as an exploratory prognostic framework for breast cancer, while further mechanistic and prospective validation is required before clinical translation.
The role of histidine metabolism in tumor progression and its clinical significance.
Zhang Y, Lin R, Wang Y … +2 more , Dong J, Liang F
Biochem Biophys Res Commun · 2026 Aug · PMID 42284986 · Publisher ↗
Histidine is a conditionally essential amino acid that links nutritional supply with bioactive function and serves as a precursor for molecules central to tumor metabolic reprogramming. Through histidine decarboxylase (H...
Histidine is a conditionally essential amino acid that links nutritional supply with bioactive function and serves as a precursor for molecules central to tumor metabolic reprogramming. Through histidine decarboxylase (HDC), it is converted to histamine; through histidine ammonia lyase (HAL), it yields urocanic acid and downstream metabolites. It also connects to one-carbon metabolism through catabolic intermediates and participates in protein histidine phosphorylation. The abundance and activity of these metabolic outputs vary markedly across cancer types, sample sources, and tumor regions. Interpreting these patterns therefore necessitates attention to tumor lineage, cellular origin, and local tissue conditions. This review covers current knowledge on histidine metabolism in cancer across four areas: metabolic pathways, regulation of key enzymes, effects on the immune microenvironment, and challenges in clinical translation. We propose that histidine metabolism forms a regulatory network shaped by tumor lineage, cell type, local tissue ecology, and therapeutic pressure. Understanding this network may reconcile discrepancies in the literature and provide a foundation for patient stratification, strategies to overcome drug resistance, and rational design of combination therapies.
Isolation and characterization of a lytic phage targeting carbapenem-resistant Pseudomonas aeruginosa.
Jia P, Wang X, Jian Y … +5 more , Zhao R, Fang Z, Li Y, Wu M, Wang K
Biochem Biophys Res Commun · 2026 Aug · PMID 42284985 · Publisher ↗
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major clinical challenge because of the limited availability of effective treatment options. In this study, we isolated four phages, designated Zpj1-Zpj4, from hosp...
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major clinical challenge because of the limited availability of effective treatment options. In this study, we isolated four phages, designated Zpj1-Zpj4, from hospital sewage samples using the clinical strain CRPA-11d as the host. Genomic analysis showed that these phages were closely related double-stranded DNA phages and lacked identifiable genes associated with lysogeny, virulence, or antibiotic resistance. Taxonomic analysis assigned them to the genus Yuavirus, subfamily Rabinowitzvirinae, family Mesyanzhinovviridae, and class Caudoviricetes. Among them, phage Zpj4 was selected for further characterization. Its biological properties were evaluated by determining genomic features, optimal multiplicity of infection (MOI), one-step growth kinetics, host range, efficiency of plating (EOP), stability, and in vitro antibacterial and anti-biofilm activities. Its therapeutic efficacy was further assessed in a CRPA-11d induced mouse model of acute lung injury by measuring bacterial burdens in the lungs, livers, and spleens, together with lung histopathology. Phage Zpj4 exhibited favorable properties, including a short latent period, a high burst size, and strong stability. It markedly inhibited CRPA-11d growth and biofilm formation in vitro. In the mouse model, phage Zpj4 treatment significantly reduced bacterial burdens in the lungs, livers, and spleens and alleviated lung tissue injury. These findings indicated that phage Zpj4 is a promising candidate for the treatment of CRPA infections.
Ultrasound-triggered self-assembled cascade nanozymes for ROS-mediated synergistic chemodynamic therapy.
Zhao Z, Li L, Qi W … +3 more , Zhou Y, Lu M, Luo Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42275836 · Publisher ↗
Chemodynamic therapy (CDT) is severely limited by insufficient reactive oxygen species (ROS) generation and high glutathione (GSH)-mediated antioxidant defense in the tumor microenvironment. To address these challenges,...
Chemodynamic therapy (CDT) is severely limited by insufficient reactive oxygen species (ROS) generation and high glutathione (GSH)-mediated antioxidant defense in the tumor microenvironment. To address these challenges, we developed an ultrasound-triggered self-assembled cascade nanozyme (HSA-GOx-CuO) that amplifies ROS production through triple synergy: glucose oxidase (GOx)-mediated glucose depletion (starvation therapy) and hydrogen peroxide self-supply, CuO-driven GSH depletion, and synergistic CDT. In vitro studies using 4T1 breast cancer cells showed that under US stimulation, HSA-GOx-CuO significantly elevated intracellular ROS levels, induced potent apoptosis (late apoptotic rate: 85.1%), and promoted dendritic cell maturation (97.9% CD80CD86 DCs). In vivo, the nanozyme efficiently accumulated in tumors via the enhanced permeability and retention effect, achieving a 92.6% tumor inhibition rate with strong growth suppression. This US-activatable cascade nanoplatform integrates starvation therapy and GSH depletion, offering a safe and novel strategy for precision synergistic CDT of tumors.
Enhanced intracellular uptake of genetic material into suspended cells via light-induced "tornado" condensation without using any transfection reagents.
Chatterjee S, Hayashi K, Tamura M … +3 more , Tokonami S, Iida T, Nakase I
Biochem Biophys Res Commun · 2026 Aug · PMID 42275835 · Publisher ↗
The present research demonstrates the application of light-induced enhancement of cellular uptake of genetic materials (DNA and siRNA) into the living suspension cells. Based on the position of the photothermal conversio...
The present research demonstrates the application of light-induced enhancement of cellular uptake of genetic materials (DNA and siRNA) into the living suspension cells. Based on the position of the photothermal conversion substrate, two distinct experimental setups were evaluated: (1) the bottom surface of a cell culture plate coated with a gold nanofilm functioning as the substrate, and (2) a setup where a cover glass coated with a gold nanofilm functioning as the substrate was placed over the cell culture medium. In both setups, the near-infrared laser was focused onto the gold nanofilm, inducing convection in the extracellular medium through light-induced condensation of cells and genetic material. Despite not using any transfection reagents whatsoever, this experimental technique significantly promoted the cellular uptake, cytosolic release, and expression of the target genetic material. In particular, the setup (2) exhibited lower cytotoxicity after light irradiation compared to setup (1) due to the photothermally controlled Marangoni convection. Additionally, the simulation results also confirmed the superiority of this system. These results demonstrate that the inverted optical condensation with the photothermal source at the top of the reaction container has the potential to enhance the transfection of genetic material into suspension cells avoiding the damage, and such a mechanism would be used for highly efficient transfection of various biochemical substances leading to the unconventional drug delivery.
B cell receptor signaling promotes endogenous retrovirus-associated lymphomagenesis in T-cell-deficient B6-Ly5.1 mice.
Todo K, Hikida M
Biochem Biophys Res Commun · 2026 Aug · PMID 42275834 · Publisher ↗
Endogenous retroviruses (ERVs) are typically epigenetically silenced but can contribute to tumorigenesis upon reactivation under immunodeficient conditions. However, the precise physiological triggers and microenvironmen...
Endogenous retroviruses (ERVs) are typically epigenetically silenced but can contribute to tumorigenesis upon reactivation under immunodeficient conditions. However, the precise physiological triggers and microenvironmental mechanisms driving ERV-mediated oncogenesis in vivo remain poorly understood. Here, we demonstrate that B cell receptor (BCR) signaling triggers ERV (specifically Emv10) reactivation and promotes lymphomagenesis in T cell-deficient B6-Ly5.1 mice. The resulting tumors exhibited a distinct germinal center B cell-like (GCL) phenotype with somatic hypermutations and harbored recurrent eMLV proviral insertions near the Plch2 locus on chromosome 4, associated with aberrant activation of Plch2. In vivo, chronic antigen stimulation with NP-Ficoll significantly accelerated lethal GCL development, accompanied by systemic accumulation of malignant cells. Crucially, in a model where direct BCR stimulation was restricted to a minor subset of λ B cells, the accelerated malignancies arose predominantly from non-stimulated λ B cell clones. These findings suggest that physiological BCR activation may promote lymphomagenesis through a non-cell-autonomous mechanism. Our model highlights a novel, vital role for T cell-mediated immune surveillance in restricting ERV-driven tumor propagation across the host B cell compartment.
Hematopoietic cell kinase activation in skeletal myocytes contributes to local inflammation and pain sensitization in myofascial trigger points.
Jin F, He R, Tang Q … +2 more , Yang S, Qi F
Biochem Biophys Res Commun · 2026 Aug · PMID 42269276 · Publisher ↗
INTRODUCTION: Myofascial trigger points (MTrPs) are key pathological features of myofascial pain syndrome (MPS), and local inflammation is a key driver of their initiation and persistence. Hematopoietic cell kinase (HCK)...
INTRODUCTION: Myofascial trigger points (MTrPs) are key pathological features of myofascial pain syndrome (MPS), and local inflammation is a key driver of their initiation and persistence. Hematopoietic cell kinase (HCK) is critical for the regulation of inflammation; however, its role in MTrPs remains unreported. The study was designed to characterize the expression profile, cellular localization and functional significance of HCK in MTrPs. METHODS: MTrPs tissues were obtained from the trapezius muscles of patients with MPS via needle biopsy for RNA sequencing and phosphorylation antibody microarray analysis to characterize the gene expression profiles and HCK activation. A rat MTrPs model was employed to explore the role of HCK. The HCK inhibitor A419259 was locally injected into MTrPs to evaluate its analgesic effects. Pain-like behaviors were assessed using the Randall-Selitto and nest-building tests. The effects of the HCK inhibitor on local inflammation were evaluated via RT-qPCR. RESULTS: Differentially expressed mRNAs in human MTrPs were predominantly enriched in the inflammation-related pathways. Phosphorylated HCK concentrations were significantly elevated in both human and rat MTrPs model. Immunolocalization demonstrated that phosphorylated HCK was mainly expressed in the skeletal myocytes rather than in the infiltrating immune cells. Local injection of A419259 markedly inhibited cytokine expressions in MTrPs and ameliorated pain-like behaviors (increased mechanical withdrawal threshold, improved nest-building ability, and reduced anxiety-like behaviors) in MTrPs rat models. CONCLUSION: HCK activation in skeletal myocytes contributes to local inflammation and peripheral sensitization of MTrPs. HCK is a promising therapeutic target for local injection therapy for MPS.
Fingolimod induces cytotoxic stress and apoptosis-like cell death in drug-sensitive and P-glycoprotein-overexpressing acute myeloid leukemia cells.
Štefík P, Ďurišová K, Špaldová J … +4 more , Šofranková L, Nechajová D, Breier A, Lakatoš B
Biochem Biophys Res Commun · 2026 Aug · PMID 42269275 · Publisher ↗
Over the last several years, sphingolipids have been shown to regulate numerous cellular processes, including cell adhesion, migration, proliferation, senescence, death, or differentiation. Dysregulation of sphingolipid...
Over the last several years, sphingolipids have been shown to regulate numerous cellular processes, including cell adhesion, migration, proliferation, senescence, death, or differentiation. Dysregulation of sphingolipid metabolism or sphingolipid mediated signaling is usually found in malignant cells, supporting uncontrolled tumor growth, suppression of immune responses, or drug resistance of cancer cells. Hence, novel drugs targeting sphingolipid metabolism or signaling are investigated as promising anticancer agents. Fingolimod is a synthetic analogue of sphingosine and employed for the treatment of relapse-remitting multiple sclerosis. Furthermore, fingolimod has been also studied as a potential antineoplastic drug owing to its ability to modulate metabolism and signaling pathways of cancer cells to promote inhibition of the cell cycle progression or induction of apoptosis. In our work, acute myeloid leukemia cell lines SKM-1 and MOLM-13 were employed together with their sublines displaying a multi-drug resistant phenotype due to P-glycoprotein overexpression. Our results indicate that fingolimod acts as a potent inducer of apoptosis-like cell death with the maximum effect observed after 8 h. This is also accompanied by a decrease in mitochondrial membrane potential, the generation of reactive oxygen species, an increase in intracellular calcium concentration, and the activity of stress-activated kinases JNK and p38. Fingolimod applied in sublethal concentrations can also induce accumulation of cells in the G0/G1 phase; however, this effect is not accompanied by the differentiation of leukemia cells. Although fingolimod treatment led to a decrease in the expression of P-glycoprotein on mRNA level, the same concentration of fingolimod had virtually no effect on its activity.
Engineering and characterization of a novel PD-L1/VEGF bispecific antibody with enhanced VEGF-neutralizing capacity.
Chen Q, Hang T, Mao D … +18 more , Zhou A, Xu J, Liu T, Zheng C, Zhang X, Guo Q, Ji L, Qian W, Hou S, Li J, Han F, Wang X, Zhang X, Guo Y, Zhang D, Li J, Guo H, Sun Z
Biochem Biophys Res Commun · 2026 Aug · PMID 42269274 · Publisher ↗
Combined blockade of PD-L1 and VEGF represents a promising therapeutic strategy for cancer, yet enhancing anti-VEGF efficacy remains challenging. Here, we engineered a novel bispecific antibody, PLVBP, by fusing a novel...
Combined blockade of PD-L1 and VEGF represents a promising therapeutic strategy for cancer, yet enhancing anti-VEGF efficacy remains challenging. Here, we engineered a novel bispecific antibody, PLVBP, by fusing a novel high-affinity anti-PD-L1 antibody (T0004) with four VEGF binding domains derived from VEGFR1 D2 (domain II). PLVBP was efficiently expressed in mammalian cells and purified via a three-step chromatography process, achieving over 98% purity. Comprehensive structural characterization confirmed its homogeneity, stability, and preserved secondary structure. Surface plasmon resonance (SPR) analysis revealed that PLVBP binds to PD-L1 and VEGF165 with sub-nanomolar affinities. Functional assays demonstrated that PLVBP maintained potent PD-L1 binding while exhibiting significantly enhanced VEGF binding affinity and capacity compared to bevacizumab. Furthermore, in cell-based assays, PLVBP effectively suppressed VEGF-induced HUVEC proliferation and migration, confirming its VEGF-neutralizing activity. Furthermore, PLVBP simultaneously engaged both PD-L1 and VEGF, validating its dual-targeting capability. Preliminary stability assessments indicated that PLVBP largely maintained its physicochemical and functional integrity during long-term storage in non-optimized buffer. These findings highlight PLVBP as a promising bispecific therapeutic candidate with enhanced avidity-driven VEGF capture, providing a strong foundation for further preclinical development.
Activated B lymphocytes induce hepatocyte injury in autologous co-culture system.
Guan W, Lv Z, Peng H … +2 more , Gao H, Zhang H
Biochem Biophys Res Commun · 2026 Aug · PMID 42269273 · Publisher ↗
Hepatic B cells are increasingly implicated in liver inflammation and fibrosis, but whether activated hepatic B cells aggravate primary hepatocyte injury remains insufficiently defined. We established a paired same-donor...
Hepatic B cells are increasingly implicated in liver inflammation and fibrosis, but whether activated hepatic B cells aggravate primary hepatocyte injury remains insufficiently defined. We established a paired same-donor co-culture system using primary hepatocytes and hepatic B cells isolated from the same mouse liver. Primary hepatocytes were obtained from perfused liver lobes by blood clearance, collagenase I digestion, filtration, and Percoll gradient purification. Hepatic B cells were isolated from paired liver lobes after rapid cold phosphate-buffered saline (PBS)-based washing to remove residual blood, tissue mincing, collagenase IV digestion, red blood cell lysis, Percoll gradient purification, and negative magnetic B-cell enrichment. The workflow yielded viable primary hepatocytes and hepatic B cells with CD19-positive purity above 90% after magnetic sorting and 72-h culture. Under optimized co-culture conditions, lipopolysaccharide (LPS)-activated hepatic B cells secreted TNF-α, IL-6, and IL-1β in culture supernatants and induced hepatocyte morphological damage, increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity, and upregulation of cleaved caspase-3. These findings support activated hepatic B cells as inflammatory amplifier cells that can promote hepatocyte injury and apoptosis through soluble inflammatory mediators in a same-donor primary-cell system.
OGT-mediated O-GlcNAcylation of STAT1 impairs its Ser727 phosphorylation and weakens antitumor immunity of tumor-associated macrophages in cervical cancer.
Wu C, Huang L, Xu J … +2 more , Liu G, Shen Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42269272 · Publisher ↗
The immunosuppressive tumor microenvironment (TME), shaped significantly by tumor-associated macrophages (TAMs), facilitates immune escape in cervical cancer. The dynamic post-translational modification O-GlcNAcylation,...
The immunosuppressive tumor microenvironment (TME), shaped significantly by tumor-associated macrophages (TAMs), facilitates immune escape in cervical cancer. The dynamic post-translational modification O-GlcNAcylation, regulated by O-GlcNAc transferase (OGT), has been implicated in cancer progression, but its specific role in modulating TAM function within the TME remains largely unknown. This study aimed to investigate the impact and mechanism of tumor cell OGT-mediated O-GlcNAcylation on the functional polarization of TAMs and anti-tumor immunity in cervical cancer. We employed a co-culture system of THP-1-derived macrophages and cervical cancer CaSki cells with OGT gain- or loss-of-function manipulation. Macrophage polarization was assessed via flow cytometry (CD86/M1, CD206/M2) and phagocytosis assays. Cytokine secretion profiles were measured by ELISA. The molecular mechanism was explored using co-immunoprecipitation, Western blot, and site-directed mutagenesis of STAT1. OGT overexpression in CaSki cells reprogrammed co-cultured macrophages towards an M2-like phenotype, suppressed their phagocytic capacity, and altered cytokine secretion towards a pro-tumorigenic profile. Mechanistically, OGT directly O-GlcNAcylated STAT1 at serine 727 (Ser727), which competitively inhibited its phosphorylation. Crucially, the immunomodulatory effects of OGT were completely abolished in STAT1-knockout or STAT1 Ser727-mutant CaSki cells. Conversely, pharmacological inhibition of OGT promoted an M1-like macrophage phenotype and enhanced phagocytosis. Our findings reveal a novel immune evasion mechanism in cervical cancer whereby tumor cell OGT, via O-GlcNAcylating and inactivating STAT1 at Ser727, drives TAMs into an immunosuppressive M2-like state. Targeting the OGT/STAT1 axis may represent a promising strategy to reprogram the TME and restore anti-tumor immunity.
Altered translation efficiency of specific mRNAs in a zebrafish model of Diamond-Blackfan anemia syndrome.
Uechi T, Nagatomo M, Nakajima Y … +2 more , Suzuki Y, Kenmochi N
Biochem Biophys Res Commun · 2026 Aug · PMID 42269271 · Publisher ↗
Diamond-Blackfan anemia syndrome (DBAS) is a congenital pure red-cell aplasia that is often accompanied by physical deformities. Heterozygous mutations in more than 20 ribosomal protein (RP) genes have been linked to the...
Diamond-Blackfan anemia syndrome (DBAS) is a congenital pure red-cell aplasia that is often accompanied by physical deformities. Heterozygous mutations in more than 20 ribosomal protein (RP) genes have been linked to the disease. The most frequently mutated gene is RPS19, which accounts for 25% of the patients. Haploinsufficiency of the RP genes may affect translation of specific mRNAs that could be related to the anemia. However, the underlying mechanisms are still unclear. To evaluate the impacts of RP depletion on translation, using a zebrafish model of DBAS with knockdown of the RPS19 ortholog (rps19), we compared changes in polysomal mRNAs with those in total mRNAs in the DBAS model to examine the translation efficiency of individual transcripts. As a result, we calculated the translation efficiency of 5464 transcripts. Among them, the transcripts from 75 genes exhibited translational repression to less than half compared to the controls. Erythropoiesis-related genes were enriched among the repressed genes. Unexpectedly, some genes related to glycan biosynthesis were also translationally repressed. One of these was the pigq gene, which participates in a glycosylphosphatidylinositol-anchor biosynthesis. We injected synthesized pigq mRNA into embryos with rps19 knockdown (the DBAS model), and found that the anemia phenotype was rescued, but morphological defects were not, indicating its role in erythropoiesis in zebrafish. These results suggest that impaired translation of erythropoiesis-related and glycan biosynthesis-related genes is implicated in the pathogenesis of DBAS.
Nicotinic acetylcholine receptors and their role in ghrelin-producing cells.
Ensho T, Saito H, Kamimura Y … +3 more , Ueda Y, Doi A, Iwakura H
Biochem Biophys Res Commun · 2026 Aug · PMID 42269270 · Publisher ↗
Gastric orexigenic peptide ghrelin has been implicated in tobacco addiction, but there are conflicting results regarding the effects of acute smoke on the plasma ghrelin levels. In this study, we screened the effects of...
Gastric orexigenic peptide ghrelin has been implicated in tobacco addiction, but there are conflicting results regarding the effects of acute smoke on the plasma ghrelin levels. In this study, we screened the effects of tobacco-related chemicals, especially focusing on the effects of nicotine on ghrelin regulation at cellular level. Nicotine alone modestly stimulated ghrelin secretion, and enhanced the stimulatory effects of isoproterenol and oxytocin on ghrelin secretion from ghrelin-producing MGN3-1 cells evaluated by a newly developed ghrelin-HiBiT assay system. MGN3-1 cells expressed high levels of α4β2 nicotinic acetylcholine receptor, and α4β2 selective agonist, epibatidine evoked substantial intracellular Ca elevation. These results indicate that nAChR has a potential role in ghrelin secretion and ghrelin-mediated tobacco addiction.
Silver-based compounds in dentistry: Multifaceted applications, cellular antibacterial mechanisms, and safety considerations.
Xu M, Yu X, Guo X
Biochem Biophys Res Commun · 2026 Aug · PMID 42269269 · Publisher ↗
Silver-based compounds represent a promising strategy against oral biofilm-related diseases. This review systematically examines their evolution from simple salts to advanced delivery platforms, including silver diamine...
Silver-based compounds represent a promising strategy against oral biofilm-related diseases. This review systematically examines their evolution from simple salts to advanced delivery platforms, including silver diamine fluoride (SDF), nano-silver fluoride (NSF), silver nanoparticles (AgNPs), and emerging silver-organic complexes. The antibacterial action, common to all forms, stems from bioavailable Ag ions that attack multiple bacterial targets, disrupting cell membranes, metabolic pathways, and DNA, while inducing oxidative stress. Clinically, SDF and NSF effectively arrest caries, whereas AgNPs are primarily integrated into restorative materials, endodontic systems, and periodontal delivery platforms to inhibit dysbiotic biofilm formation. However, therapeutic success is highly formulation-dependent, facing challenges such as rapid Ag inactivation in saliva, esthetic concerns, and nanoparticle agglomeration. Safety profiles reveal a narrow therapeutic window, with risks of argyria from chronic accumulation, highlighting the critical importance of controlled release kinetics. Future translation hinges on the rational design of smart delivery systems, particularly ligand-engineered silver-organic complexes, which offer precise control over Ag release for sustained, localized efficacy with improved safety. Advancing these compounds from broad-spectrum antimicrobials to precision therapeutic platforms holds significant potential for improving outcomes in caries management, periodontal therapy, endodontics, and restorative dentistry.
Wnt11 negatively regulates early chondrogenesis in a cell-type-dependent manner in embryonic mouse mesenchymal cells.
Al Akel D, Terao F, Qi H … +1 more , Takahashi I
Biochem Biophys Res Commun · 2026 Aug · PMID 42263608 · Publisher ↗
Wnt signaling is a key regulator of skeletal development. The ligand-specific roles of Wnt signaling during early chondrogenesis remain incompletely understood. WNT11, a non-canonical Wnt ligand, has established function...
Wnt signaling is a key regulator of skeletal development. The ligand-specific roles of Wnt signaling during early chondrogenesis remain incompletely understood. WNT11, a non-canonical Wnt ligand, has established functions in embryonic morphogenesis, but its contribution to primary chondrogenesis and whether this differs across distinct mesenchymal lineages is unknown. Using embryonic mouse mandibular processes and limb bud micromass cultures, we investigated Wnt11 function through siRNA-mediated knockdown, recombinant WNT11 treatment, and pharmacological Wnt inhibition with the IWP-2. Both cell types underwent spontaneous chondrogenic differentiation, with limb bud cells showing higher baseline output. IWP-2 inhibitor enhanced chondrogenesis in both cell types, more strongly in mandibular process cells, and rapidly suppressed JNK phosphorylation while accelerating SOX9 activation. Knockdown of Wnt11 increased cartilage nodule formation and upregulated chondrogenic markers, while exogenous recombinant WNT11 treatment inhibited differentiation in a cell-specific manner in mandibular process cultures. Rescue experiments indicated that recombinant WNT11 could significantly rescue the pro-chondrogenic effects of IWP-2 inhibition in mandibular processes but not limb bud cultures. These data identify Wnt11 as a cell-type-dependent negative regulator of early chondrogenesis. This is the first direct comparison of Wnt11 function in craniofacial and appendicular embryonic mesenchymal cells, showing lineage-dependent differences with possible implications for craniofacial skeletal development.
Condition-dependent role of VDAC1 oligomerization in doxorubicin-induced mitochondrial iron dysregulation.
Miura S, Sekine T, Misaka T … +6 more , Okochi S, Ogawara R, Yokokawa T, Oikawa M, Ishida T, Takeishi Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42263607 · Publisher ↗
Doxorubicin (DOX)-induced cardiotoxicity is closely associated with mitochondrial iron overload and oxidative stress. Although voltage-dependent anion channel 1 (VDAC1) oligomerization is generally considered a pro-apopt...
Doxorubicin (DOX)-induced cardiotoxicity is closely associated with mitochondrial iron overload and oxidative stress. Although voltage-dependent anion channel 1 (VDAC1) oligomerization is generally considered a pro-apoptotic event, its role in iron-driven mitochondrial stress remains unclear. We herein investigated the effects of pharmacological and genetic regulation of VDAC1 oligomerization in models of DOX-induced cardiotoxicity. DOX increased mitochondrial Fe accumulation, reactive oxygen species (ROS) production, and mitochondrial respiratory impairment, accompanied by augmented VDAC1 oligomerization. Pharmacological inhibition of VDAC1 oligomerization using VBIT-4 unexpectedly exacerbated mitochondrial iron accumulation, oxidative stress, and respiratory dysfunction. In contrast, the ubiquitination-resistant VDAC1 mutant (K53R/K274R) significantly attenuated mitochondrial Fe accumulation, ROS production, and mitochondrial respiratory impairment despite exhibiting increased oligomerization. These findings indicate that oligomer abundance alone does not determine mitochondrial dysfunction, demonstrating the importance of the qualitative state of VDAC1 remodeling under iron-driven oxidative stress. Our study suggests a condition-dependent role of VDAC1 oligomerization in DOX cardiotoxicity and highlights outer mitochondrial membrane remodeling as a potential therapeutic target.
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