Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
High-content screening identifies mTORC1-independent TFEB activators that promote protective autophagy.
Miyano T, Suzuki K, Sera T
Biochem Biophys Res Commun · 2026 Aug · PMID 42229171 · Publisher ↗
Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway. It becomes active upon nuclear translocation and induces the expression of genes involved in autophagy and lysosomal function. Mecha...
Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway. It becomes active upon nuclear translocation and induces the expression of genes involved in autophagy and lysosomal function. Mechanistic target of rapamycin complex 1 (mTORC1) inhibition typically triggers this process; however, chronic mTORC1 suppression often induces adverse metabolic and proliferative effects, necessitating the identification of mTORC1-independent mechanisms driving TFEB nuclear translocation. Therefore, this study aimed to identify pharmacological activators of TFEB nuclear translocation that function independently of mTORC1 inhibition. In this study, we developed a high-content screening assay to quantify TFEB nuclear translocation in HeLa cells and screened a library of 560 approved compounds. We identified two compounds, NSC-319726 and ML-SA1, that promoted TFEB nuclear translocation without reducing p70S6K phosphorylation, supporting an mTORC1-independent mechanism. Both compounds significantly increased LC3-II accumulation and the signal intensity of an autolysosomal marker, indicating enhanced autophagic flux. Functionally, these compounds protected the cells against staurosporine-induced apoptosis and hydrogen peroxide-induced oxidative stress. Notably, pre-treatment conferred significantly greater protection than co-treatment, suggesting that TFEB-mediated transcriptional remodeling is necessary for maximal cytoprotection. Overall, these findings highlight the potential of high-content phenotypic screening to identify mTORC1-independent TFEB activators and suggest NSC-319726 and ML-SA1 as pharmacological inducers of protective autophagy in vitro.
Base editing reveals context-dependent regulation of adhesion, anoikis, and motility by BAP1 in renal cell models.
Koo C, Lee D, Lee B … +3 more , Kim S, Lee J, Kwon J
Biochem Biophys Res Commun · 2026 Aug · PMID 42229170 · Publisher ↗
BAP1 is a tumor-suppressive deubiquitinase essential for DNA repair, and missense mutations in BAP1 are common in clear cell renal cell carcinoma (ccRCC). We previously showed that correction of the inactivating Glu31Lys...
BAP1 is a tumor-suppressive deubiquitinase essential for DNA repair, and missense mutations in BAP1 are common in clear cell renal cell carcinoma (ccRCC). We previously showed that correction of the inactivating Glu31Lys mutation in KMRC-20 ccRCC cells using CRISPR/Cas9 base editing restored BAP1 function, reinstated anchorage dependence, and re-sensitized cells to anoikis. Here, we investigated whether disruption of Glu31 is sufficient to induce anchorage-independent growth and anoikis resistance in normal kidney epithelial cells. Using adenine base editing, we introduced an inactivating Glu31Gly mutation into HK-2 cells, generating two independent isogenic BAP1-mutant clones, and established a BAP1-knockout clone by CRISPR/Cas9 as an additional control. Glu31Gly mutants exhibited complete loss of BAP1 deubiquitinase activity and impaired UV-induced DNA damage repair, comparable to knockout cells. Despite the clear functional inactivation of BAP1, the Glu31Gly and knockout HK-2 cells neither acquired anchorage-independent growth nor anoikis resistance; instead, detached cells displayed increased apoptosis. In KMRC-20 cells, restoration of BAP1 enhanced both migration and invasion, whereas BAP1 inactivation or loss in HK-2 cells increased invasion but reduced migration, indicating distinct context-dependent roles for BAP1 in normal versus malignant renal cells. These findings demonstrate that BAP1 inactivation alone is insufficient to confer anchorage-independent survival in normal kidney epithelial cells and suggest that additional oncogenic alterations are required during kidney tumorigenesis. Our study further highlights the utility of precise base editing for dissecting the functional consequences of clinically relevant cancer mutations.
Tepraloxydim metabolite exposure disrupts placental function revealed by single-cell sequencing and metabolomics.
Teng Y, Qi Z, Han J … +7 more , Duan Z, Cheng D, Xia J, Wang A, Yang L, Li H, Zhang T
Biochem Biophys Res Commun · 2026 Aug · PMID 42229169 · Publisher ↗
The impact of pesticide exposure on pregnancy outcomes is of increasing concern, yet the effects of a metabolite of the relatively new herbicide tepraloxydim (DMP) on placental development remain poorly understood. This...
The impact of pesticide exposure on pregnancy outcomes is of increasing concern, yet the effects of a metabolite of the relatively new herbicide tepraloxydim (DMP) on placental development remain poorly understood. This study combining single-cell RNA sequencing with metabolomics, to systematically investigate the effects of DMP on placental cellular composition, transcriptional programs, and metabolic homeostasis in a mouse model. We found that DMP crosses the placental barrier and is detected in placental tissue with subcellular distribution patterns suggestive of endoplasmic reticulum association, inducing extensive reprogramming of the placental metabolic network, with the branched-chain amino acid (BCAA) degradation pathway emerging as a central node of metabolic disruption. Single-cell transcriptomic analysis further revealed that DMP exposure altered the differentiation trajectories and functional states of major placental cell types, including fibroblasts, trophoblasts, endothelial cells, and macrophages. Specifically, fibroblasts exhibited a pro-fibrotic phenotypic shift, trophoblast differentiation pathways were redirected, endothelial cells showed reduced metabolic plasticity, and macrophages underwent pro-inflammatory polarization. Key metabolic genes such as Cyb5a, LDHA, and MDH1 were upregulated in their respective cell types, suggesting their potential role in DMP-induced placental dysfunction. This study provides the first systematic evidence of the mechanisms by which DMP disrupts placental structure and function through metabolic reprogramming and altered cell fate, offering important experimental basis for assessing its health risks during pregnancy.
Integrated single-nucleus transcriptomics reveals stage-dependent neuronal and oligodendroglial remodeling in the Alzheimer's disease prefrontal cortex.
Lu C, Wang Y, Zhang Z … +1 more , Zhang X
Biochem Biophys Res Commun · 2026 Aug · PMID 42224827 · Publisher ↗
Alzheimer's disease (AD) progression is accompanied by cell-type-specific vulnerability in the human cortex, but how neuronal and glial subtypes are remodeled across pathological stages remains incompletely understood. H...
Alzheimer's disease (AD) progression is accompanied by cell-type-specific vulnerability in the human cortex, but how neuronal and glial subtypes are remodeled across pathological stages remains incompletely understood. Here, we integrated five publicly available single-nucleus RNA-seq datasets from the human prefrontal cortex, comprising 945,692 high-quality nuclei, to investigate transcriptional and compositional alterations associated with Braak pathological progression. Seven major cell types were identified across cohorts, including excitatory neurons, inhibitory neurons, astrocytes, oligodendrocytes, oligodendrocyte precursor cells, microglia, and vascular cells. Sample-level pseudobulk differential expression analysis revealed stage-dependent transcriptional remodeling, with prominent alterations in excitatory neurons, oligodendrocytes, and oligodendrocyte precursor cells at advanced pathological stages. Subtype-level compositional analysis further identified selective remodeling of excitatory neuronal and oligodendrocyte subtypes. Exc_0 showed a biphasic pattern across Braak stages, whereas Exc_1 decreased and Exc_4 increased at high pathological burden. In oligodendrocytes, Oligo_1 was enriched at high Braak stages. Functional enrichment analysis linked these key subtypes to synaptic organization, cell junction assembly, cytoplasmic translation, oxidative phosphorylation, and electron transport chain-related processes. These findings suggest that AD pathological progression in the prefrontal cortex involves coordinated neuronal and oligodendroglial remodeling associated with synaptic and metabolic dysfunction.
NRAC: an emerging nutrient-responsive regulator of tissue-specific fatty acid metabolism.
Zhang R
Biochem Biophys Res Commun · 2026 Aug · PMID 42224826 · Full text
Fatty acid (FA) uptake is coordinated across tissues to maintain metabolic homeostasis, yet the mechanisms underlying tissue-specific regulation remain incompletely understood. NRAC has emerged as a nutrient-responsive,...
Fatty acid (FA) uptake is coordinated across tissues to maintain metabolic homeostasis, yet the mechanisms underlying tissue-specific regulation remain incompletely understood. NRAC has emerged as a nutrient-responsive, tissue-restricted factor enriched in adipose tissue and heart in both mice and humans. Mouse studies show that Nrac is dynamically regulated by feeding, fasting, and obesity in a tissue-specific manner. Recent work further shows that NRAC interacts with CD36 to regulate CD36-dependent FA uptake in adipocytes. Physiological studies support a role for NRAC in adipose lipid handling and systemic FA homeostasis, while human data link adipose NRAC expression to body fat distribution and circulating lipid traits. Together, current evidence identifies NRAC as an emerging regulator of tissue-specific FA metabolism and cardiometabolic health.
Nervous necrosis virus B2 non-structural protein shut off host translation via sequestration of polyadenylate-binding protein.
Bajpai V, Lin IW, Chiang MH … +7 more , Li CH, Chen CW, Chang CC, Cheng CA, Wang YS, Chen SC, Chang CY
Biochem Biophys Res Commun · 2026 Aug · PMID 42218873 · Publisher ↗
Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis disease in piscine larvae worldwide. As a positive-sense RNA virus, NNV performs its replication, transcription, translation and assembly in t...
Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis disease in piscine larvae worldwide. As a positive-sense RNA virus, NNV performs its replication, transcription, translation and assembly in the cytoplasm of host cell. However, the ectopic expression of viral B2 non-structural protein was observed to translocate into nucleus of grouper brain cells. In this study, we found that the nuclear translocation of B2 was accompanied by host translation shutoff which was examined by the surface sensing of translation (SUnSET) puromycin labelling experiment. Furthermore, the ectopically expressed B2 protein was also observed to co-localize with polyadenylate-binding protein (PABP) in cytoplasm and nucleus of transfected cell. The far-Western blotting further confirmed the interaction between B2 and PABP. Finally, the decrease in B2 protein levels at the late stage of infection appears to result from lysosome-mediated degradation facilitated by its interaction with Mx proteins. These results reveal that NNV B2 non-structural protein contributes to host translation shutoff after infection.
Knocking-down testis-specific protein Y-encoded-like 2 alleviates hypertension through down-regulating the transcription of GluN2A/B in hypothalamic paraventricular nucleus.
Xue JH, Yu JY, Bai J … +4 more , Su Q, Li HB, Li Y, Jiang HL
Biochem Biophys Res Commun · 2026 Aug · PMID 42217416 · Publisher ↗
Increased expression of both the nucleosome assembly protein (NAP) superfamily member testis-specific protein Y-encoded-like 2 (TSPYL2) and N-methyl-D-aspartate receptor (NMDAR) in the hypothalamic paraventricular nucleu...
Increased expression of both the nucleosome assembly protein (NAP) superfamily member testis-specific protein Y-encoded-like 2 (TSPYL2) and N-methyl-D-aspartate receptor (NMDAR) in the hypothalamic paraventricular nucleus (PVN) is crucial for the pathogenesis of hypertension, yet how they interact during hypertension is not fully understood. It is highly possible that NMDAR can be regulated by TSPYL2 in the PVN during hypertension. To examine the hypothesis, TSPYL2 is knocked-down or overexpressed in the PVN of spontaneously hypertensive rats (SHRs) and the normotensive control Wistar-Kyoto rats (WKYs), as well as the cultured primary PVN cells of SHRs. The transcription of NMDAR subunits, together with the blood pressure, plasma norepinephrine (NE) and the inflammatory responses and oxidative stress in the PVN were examined. Results suggested that TSPYL2 knockdown reduced blood pressure, downregulated the transcription of GluN2A/B and reduced inflammatory responses and oxidative stress in the PVN; while in the PVN of WKYs, it did not cause such significant changes. In vitro examination further revealed reduced basal cellular Ca concentration after TSPYL2 knockdown, indicating tampered NMDAR function. These results suggest that TSPYL2 is critical for maintaining hypertension via transcriptional regulation of GluN2A/B. Interfering with TSPYL2 can block GluN2A/B expression and suppress the function of NMDARs in the PVN, which reduces the high blood pressure of hypertensive animals.
ABI5 and ABI3 mediate FIS-PRC2 recruitment to IKU2 and modulate endosperm cellularization during seed development.
Gan S
Biochem Biophys Res Commun · 2026 Aug · PMID 42217415 · Publisher ↗
Seed size is tightly associated with endosperm proliferation and the onset of cellularization. The mitotic proliferation rate of the early endosperm and the initiation timing of cellularization act as key developmental n...
Seed size is tightly associated with endosperm proliferation and the onset of cellularization. The mitotic proliferation rate of the early endosperm and the initiation timing of cellularization act as key developmental nodes that determine final seed volume and weight. In Arabidopsis thaliana, the FERTILIZATION-INDEPENDENT SEED Polycomb Repressive Complex 2 (FIS-PRC2) performs crucial functions throughout gametogenesis and seed development. Here, we report that the transcription factors ABSCISIC ACID-INSENSITIVE 5 (ABI5) and ABSCISIC ACID-INSENSITIVE 3 (ABI3) directly bind to the promoter of the core endosperm regulatory gene IKU2 and repress its transcription. Moreover, FIS-PRC2 is recruited to the IKU2 promoter via physical interaction with promoter-bound ABI5. FIS-PRC2 further facilitates the deposition of the repressive H3K27me3 epigenetic mark at the IKU2 locus. Collectively, our results reveal that ABI5 and ABI3 modulate the expression of endosperm developmental genes by recruiting the FIS-PRC2 complex.
Identification of PANoptosis-related gene SIK1 in MASLD by bioinformatics, machine learning and experimental validation.
Zhang H, Liu X, Liu Y … +6 more , Gong D, Lai M, Ge B, Wang D, Tan M, Chen P
Biochem Biophys Res Commun · 2026 Aug · PMID 42217414 · Publisher ↗
OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) constitutes a chronic inflammatory condition within the spectrum of metabolic liver diseases, characterized by the accumulation of hepatic lipid...
OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD) constitutes a chronic inflammatory condition within the spectrum of metabolic liver diseases, characterized by the accumulation of hepatic lipids in the absence of significant alcohol consumption, however, the contribution of PANoptosis to its pathobiology remains largely undefined. METHODS: We retrieved MASLD transcriptomic datasets from the Gene Expression Omnibus (GEO). Shared genes were first defined by intersecting differentially expressed genes (DEGs) with modules identified by weighted gene co-expression network analysis (WGCNA). To identify the PANoptosis-related hub genes, a comprehensive approach was adopted, integrating three distinct machine-learning algorithms: least absolute shrinkage and selection operator (LASSO) regression, random forest (RF), and support-vector machine recursive feature elimination (SVM-RFE). Receiver operating characteristic (ROC) curves were constructed to quantify the diagnostic performance of each candidate gene. Immune-infiltration landscapes were delineated with CIBERSORT. Finally, the expression of the hub gene was corroborated in vitro, in vivo and in human biopsies. RESULTS: The PANoptosis-related gene SIK1 exhibited robust association with MASLD and significant diagnostic value. Immune-infiltration profiling revealed a marked increase in gamma delta T cells and resting mast cells in MASLD tissues relative to controls. Experimental validation further confirmed that SIK1 expression was significantly down-regulated in MASLD samples. CONCLUSION: Our findings illuminate novel aspects of PANoptosis in MASLD, thereby paving the way for future research into its underlying pathogenesis and the development of targeted therapeutic strategies.
RBM46 promotes meiotic initiation during oogenesis.
Li J, Shen J, Ma Y … +1 more , Zhou J
Biochem Biophys Res Commun · 2026 Aug · PMID 42217413 · Publisher ↗
RNA binding protein RBM46, as an integral component of MEIOC-YTHDC2 complex, governs the RNA binding specificity in posttranscriptional regulation of male meiotic initiation. RBM46 is also indispensable for embryonic ooc...
RNA binding protein RBM46, as an integral component of MEIOC-YTHDC2 complex, governs the RNA binding specificity in posttranscriptional regulation of male meiotic initiation. RBM46 is also indispensable for embryonic oocyte development in mice. However, the precise phenotypic consequences and underlying regulatory mechanisms of RBM46 in female germ cells remain largely uncharacterized. Here, we demonstrate that RBM46 deficiency leads to derepression of CCNA2, meiotic arrest at leptotene stage and widespread germ cell apoptosis in embryonic ovaries. Transcriptomic profiling of RBM46-deficient ovaries at embryonic day 16.5 revealed significant upregulation of Stra8 and Lin28a, alongside downregulation of multiple meiotic genes. In HEK293T cells, ectopic co-expression of RBM46, MEIOC and YTHDC2 promoted degradation of reporter mRNAs bearing either Lin28a or Mga 3'UTR. Notably, Deletion of the RBM46-binding motif "AAUCAU" within Lin28a 3'UTR reduced this repressive effect. Collectively, these findings establish an essential role of RBM46 for meiotic initiation in female germ cells and identify Lin28a and Mga transcripts as direct targets subject to RBM46-mediated decay.
Fabrication of docetaxel-loaded copper oxide-polydopamine-nanosystem for improved chemo/photothermal/photodynamic therapy in laryngeal cancer.
Yu T, Liu J, Zhao J … +5 more , Wang Q, Wang X, Wang H, Jiang R, Xiao H
Biochem Biophys Res Commun · 2026 Aug · PMID 42217412 · Publisher ↗
The integration of near-infrared (NIR) laser phototherapy with chemotherapy in a synergistic multimodal approach holds significant potential for future nanomedicine applications across various tumors, owing to its lower...
The integration of near-infrared (NIR) laser phototherapy with chemotherapy in a synergistic multimodal approach holds significant potential for future nanomedicine applications across various tumors, owing to its lower invasiveness, diminished adverse effects, and enhanced antitumor efficacy. In this study, copper oxide nanoparticles (CO NPs) were functionalized with the chlorin e6 (C6) photosensitizer and coated with polydopamine (PD) to develop a nanosystem (CO@C6-PD) for photodynamic and photothermal therapy (PDT/PTT). Subsequently, the chemotherapeutic agent docetaxel (DT) was incorporated, with folic acid (FA) utilized as a targeted material for laryngeal cancer. The developed FA@CO@C6-PD/DT NPs exhibited a nanoscale diameter, excellent surface charge, efficient DT loading, colloidal stability, cytocompatibility, and regulated DT release. Investigations on TU212 laryngeal cancer cells demonstrated that the FA@CO@C6-PD/DT exhibited significant synergistic antitumor effects via chemo/PDT/PTT, with an IC of 49 μg/mL, markedly less than the 225 μg/mL observed without NIR laser exposure. Furthermore, FA@CO@C6-PD/DT generated elevated reactive oxygen species (ROS) levels upon exposure to a 660 nm laser (2 W/cm for 6 min), leading to alterations in mitochondrial membrane potential and facilitating tumor cell death in TU212 cells. Collectively, the results suggest that FA@CO@C6-PD/DT may serve as a compelling nanoplatform for combination therapy involving chemotherapy, PTT, and PDT in laryngeal cancer.
Metabolic reprogramming in hepatic ischemia-reperfusion injury: crosstalk between mitochondria, lipid metabolism, and ferroptosis.
Pan J, Feng J, Ding Z … +5 more , Fang M, Yu W, Yang L, Zhang X, Wang X
Biochem Biophys Res Commun · 2026 Aug · PMID 42217411 · Publisher ↗
Hepatic ischemia-reperfusion injury is a clinically important complication of liver surgery, transplantation, and trauma, involving oxidative stress, inflammation, immune signaling, microcirculatory dysfunction, metaboli...
Hepatic ischemia-reperfusion injury is a clinically important complication of liver surgery, transplantation, and trauma, involving oxidative stress, inflammation, immune signaling, microcirculatory dysfunction, metabolic disturbance, and regulated cell death. This review does not aim to provide an exhaustive overview of all hepatic ischemia-reperfusion injury mechanisms, but instead focuses on metabolic reprogramming as an integrative framework linking mitochondrial dysfunction, lipid metabolic remodeling, and ferroptosis. During ischemia, oxygen deprivation and adenosine triphosphate depletion may suppress CPT1A-related fatty acid oxidation, promoting lipid accumulation and metabolic stress. During reperfusion, mitochondrial reactive oxygen species generation, Ca dysregulation, and mitochondrial quality-control imbalance may interact with phospholipid remodeling to increase lipid peroxidation susceptibility. Ferroptosis is discussed as a regulated process driven not only by iron overload, but also by impaired GPX4-dependent lipid peroxide detoxification and dysregulated antioxidant pathways such as the Nrf2/SLC7A11/HO-1 axis. The key message of this review is that hepatic ischemia-reperfusion injury progression may reflect a context-dependent mitochondria-lipid metabolism-ferroptosis network rather than isolated or linear injury pathways. This framework may help identify shared therapeutic nodes while recognizing that several mechanisms remain model-dependent and require further validation.
O-GlcNAcylation of NSD2 promotes lung metastasis of triple-negative breast cancer through extracellular matrix remodeling.
Fu S, Yang C, Liang Z … +7 more , Zhong L, Ji S, Wang Y, Wang J, Kang Z, Bu J, Wang H
Biochem Biophys Res Commun · 2026 Aug · PMID 42217410 · Publisher ↗
Metastasis is the leading cause of treatment failure and poor prognosis in triple-negative breast cancer (TNBC), underscoring the urgent need for effective therapeutic strategies. In this study, we show that O-GlcNAcylat...
Metastasis is the leading cause of treatment failure and poor prognosis in triple-negative breast cancer (TNBC), underscoring the urgent need for effective therapeutic strategies. In this study, we show that O-GlcNAcylation catalyzed by O-GlcNAc transferase (OGT) increases NSD2 stability and thereby promotes TNBC metastasis. Mechanistically, OGT directly interacts with NSD2 and facilitates its O-GlcNAcylation, which impedes ubiquitin-mediated degradation and enhances NSD2 protein stability. OGT knockdown reduces NSD2 protein levels, downregulates extracellular matrix (ECM)-related signaling pathways, decreases collagen production and cell-matrix adhesion, and ultimately inhibits TNBC cell invasion and tumor metastasis. Importantly, disruption of the OGT-NSD2 axis markedly suppresses metastasis in TNBC xenograft models. Together, these findings reveal a novel mechanism by which OGT drives tumor metastasis through modulation of NSD2 O-GlcNAcylation, and identify the OGT-NSD2 axis as a potential therapeutic target for advanced TNBC.
Dantrolene attenuates steatohepatitis and liver fibrosis by suppressing Ca dysregulation.
Sakamoto J, Yamamoto T, Sato M … +7 more , Sasakura A, Nakamura Y, Tominaga N, Inamitsu M, Yamamoto N, Takami T, Sano M
Biochem Biophys Res Commun · 2026 Aug · PMID 42217409 · Publisher ↗
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by steatosis, inflammation, and fibrosis; however, effective pharmacological therapies targeting fibrogenesis remain li...
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by steatosis, inflammation, and fibrosis; however, effective pharmacological therapies targeting fibrogenesis remain limited. Increasing evidence suggests that dysregulation of intracellular calcium (Ca) signaling contributes to hepatic injury and stellate cell activation. In this study, we investigated whether pharmacological suppression of Ca dysregulation by dantrolene, a ryanodine receptor inhibitor, ameliorates steatohepatitis and liver fibrosis. A choline-deficient l-amino acid-defined (CDAA) diet-induced MASH rat model was used to evaluate the in vivo effects of dantrolene. Dantrolene treatment did not affect liver enlargement but partially improved serum markers of hepatocellular injury. Histological analyses revealed marked attenuation of hepatic fibrosis and a significant reduction in glutathione S-transferase π-positive preneoplastic lesions. At the cellular level, dantrolene suppressed free fatty acid-induced lipid accumulation in primary hepatocytes. Furthermore, in human hepatic stellate cells (LX-2), dantrolene markedly inhibited transforming growth factor-β-induced collagen type I expression. Live-cell Ca imaging demonstrated that dantrolene significantly attenuated pathological intracellular Ca elevation associated with stellate cell activation. These findings indicate that Ca dysregulation plays a central role in the pathogenesis of MASH and that targeting intracellular Ca signaling with dantrolene effectively suppresses steatohepatitis and liver fibrosis. Pharmacological modulation of Ca homeostasis may represent a promising and translatable therapeutic strategy for MASH.
Candidate metabolites in sepsis-associated encephalopathy: Network analysis and in vitro validation of glycitein.
Hong Y, Ye M, Huang B … +2 more , Li X, Huang L
Biochem Biophys Res Commun · 2026 Aug · PMID 42217408 · Publisher ↗
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a severe neurological complication of sepsis. Cerebrovascular endothelial injury serves as a key contributor to its pathogenesis, and metabolite-mediated inflammatory...
BACKGROUND: Sepsis-associated encephalopathy (SAE) is a severe neurological complication of sepsis. Cerebrovascular endothelial injury serves as a key contributor to its pathogenesis, and metabolite-mediated inflammatory regulation may be involved in this process. However, the specific candidate metabolites and their underlying pathways remain poorly characterized. This study aimed to identify candidate metabolites related to SAE through network pharmacology and to provide preliminary in vitro validation. MATERIALS AND METHODS: A "microbiota-substrate-metabolite-target-signal pathway" (MMTS) network was constructed by integrating metabolite databases, target prediction resources, and sepsis-related encephalopathy gene databases. Candidate metabolites were screened through protein-protein interaction analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, drug-likeness assessment, toxicology screening, and molecular docking. Glycitein was selected as a representative candidate for preliminary validation in a lipopolysaccharide (LPS)-induced human brain microvascular endothelial cell (hCMEC/D3) injury model. Cell activity, migration, tube formation, inflammatory factor release, intracellular reactive oxygen species levels, and NF-κB-related molecule expression were assessed. RESULTS: A total of 206 gut microbiota-related metabolites and 1518 potential targets were identified. Network analysis predicted 20 key targets related to SAE. PPI network analysis indicated TNF, IL6, CXCL8, NFKB1, and TLR4 as central nodes. KEGG analysis was particularly enriched in the Toll-like receptor, NOD-like receptor, and NF-κB signaling. 14 candidate metabolites were retained after integrated screening. In LPS-treated hCMEC/D3 cells, glycitein partially restored cell viability, migration, and tube formation, reduced IL-6 and TNF-α levels, alleviated intracellular ROS accumulation, and was associated with downregulation of NFKB1, CXCL8, and IL-6 expression, together with reduced phosphorylation of NF-κB p65 and IκBα. CONCLUSIONS: This study prioritized candidate metabolites associated with SAE through database-supported network analysis. Preliminary in vitro validation suggested that glycitein was associated with attenuation of inflammatory endothelial injury-related phenotypes, providing a basis for further mechanistic studies.
Aloe-emodin ameliorates non-alcoholic fatty liver disease by regulating the ZNRF3/Wnt/β-catenin axis and suppressing hepatic lipogenesis.
Li W, Pan M, Tang J
Biochem Biophys Res Commun · 2026 Aug · PMID 42214922 · Publisher ↗
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with limited approved pharmacological treatment options, creating an urgent need for novel therapeutic agents. This study investigated th...
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with limited approved pharmacological treatment options, creating an urgent need for novel therapeutic agents. This study investigated the efficacy and underlying molecular mechanism of aloe-emodin, a natural anthraquinone from Rhei Radix et Rhizoma, in treating NAFLD. In a high-fat diet (HFD)-induced mouse model, aloe-emodin administration significantly reduced body and liver weight, ameliorated hepatic steatosis, lowered serum ALT and hepatic lipid levels, and suppressed the expression of key lipogenic genes. These protective effects were recapitulated in an in vitro model using free fatty acid (FFA)-treated hepatocytes, where aloe-emodin reduced intracellular lipid accumulation without affecting cell viability. Mechanistic investigation revealed that aloe-emodin restored AMPK activation, increased PPARα-associated fatty acid oxidation markers, and suppressed Wnt/β-catenin signaling. Functional rescue experiments further supported the involvement of the ZNRF3-Wnt/β-catenin axis in the anti-lipogenic effects of aloe-emodin. Molecular docking identified ZNRF3, a critical negative regulator of the Wnt pathway, as the top potential binding target for aloe-emodin. We confirmed that ZNRF3 expression, which was downregulated in NAFLD models, was significantly restored by aloe-emodin treatment. Crucially, rescue experiments demonstrated that the therapeutic and anti-lipogenic effects of aloe-emodin were abolished both in vivo and in vitro when ZNRF3 was genetically knocked down or when the Wnt pathway was pharmacologically activated. These findings suggest that aloe-emodin ameliorates NAFLD, at least in part, by restoring ZNRF3 expression and suppressing Wnt/β-catenin pathway-associated lipogenic activation.
Activation of PIEZO1 impairs tissue expansion by inducing fibroblast apoptosis.
Guo Y, Wen Z, Bai R … +6 more , Liu W, Liang B, Song Y, Zhang Y, Ma X, Yu Z
Biochem Biophys Res Commun · 2026 Aug · PMID 42214921 · Publisher ↗
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TXNDC15 suppresses lung adenocarcinoma progression by inducing NEK4-dependent G2/M entry blockade.
Wang Y, Feng X, Yuan L … +1 more , Xiao W
Biochem Biophys Res Commun · 2026 Aug · PMID 42214920 · Publisher ↗
Lung adenocarcinoma (LUAD) is characterized by high heterogeneity and insidious early-stage progression, leading to a dismal clinical prognosis and posing a formidable challenge in current oncological research. Although...
Lung adenocarcinoma (LUAD) is characterized by high heterogeneity and insidious early-stage progression, leading to a dismal clinical prognosis and posing a formidable challenge in current oncological research. Although the Thioredoxin domain-containing (TXNDC) family is involved in various cancers, the role of TXNDC15 in LUAD remains unclear. Here, we show that TXNDC15 is downregulated in LUAD and predicts better survival. Functional assays reveal that TXNDC15 suppresses proliferation by inducing G2/M phase arrest. Mechanistically, TXNDC15 interacts with the mitotic kinase NEK4, thereby orchestrating the G2/M checkpoint circuitry to restrict malignant progression. These findings highlight the TXNDC15-NEK4 factor as a pivotal regulatory node in LUAD progression.
Employing network toxicology, molecular docking, machine learning, and single-cell analysis to analyze BPA exposure-induced ccRCC.
Chen J, Wu L, Jin H … +1 more , Li Y
Biochem Biophys Res Commun · 2026 Aug · PMID 42214919 · Publisher ↗
This study investigates the molecular mechanisms underlying bisphenol A (BPA)-induced clear cell renal cell carcinoma (ccRCC). We integrated transcriptomic data from multiple GEO datasets and performed differential expre...
This study investigates the molecular mechanisms underlying bisphenol A (BPA)-induced clear cell renal cell carcinoma (ccRCC). We integrated transcriptomic data from multiple GEO datasets and performed differential expression analysis and WGCNA to identify BPA-associated candidate genes. Enrichment analyses implicated pathways including cell adhesion, lipid metabolism, arachidonic acid signaling, and innate immune response. Using twelve machine learning algorithms, we identified four core genes (ITGB2, TBXAS1, LIPA, and CLEC7A), all upregulated in ccRCC. Molecular docking suggested stable BPA-protein interactions with favorable binding energies. Single-cell analysis showed predominant expression of these genes in monocytes and macrophages. LIPA was elevated in kidney cancer tissues and associated with clinical outcomes. In vitro experiments confirmed that BPA exposure promoted ccRCC cell progression by regulating core gene expression. This integrated approach offers new insights into the molecular mechanisms of BPA-induced ccRCC and identifies potential biomarkers for environmental risk assessment.
Staphylococcus aureus activates dendrite elongation in dendritic cells.
Kobata K, Furuta K, Ikeya Y … +3 more , Chishaki Y, Ishikawa K, Kaito C
Biochem Biophys Res Commun · 2026 Aug · PMID 42214918 · Publisher ↗
Dendritic cells (DCs) are thought to extend dendrites to enhance the efficiency of antigen uptake and presentation. We previously reported that short-chain fatty acids (SCFAs), such as butyrate and valerate, promote dend...
Dendritic cells (DCs) are thought to extend dendrites to enhance the efficiency of antigen uptake and presentation. We previously reported that short-chain fatty acids (SCFAs), such as butyrate and valerate, promote dendrite extension in DCs. In this study, we found that the human pathogen Staphylococcus aureus also induces dendrite extension in DCs and investigated the underlying mechanisms. Dendrite extension in DC2.4 cells was induced not only by live S. aureus but also by heat-killed bacteria and purified peptidoglycan (PGN). DC2.4 cells lacking TLR2 or its adaptor protein MyD88 extend dendrites in response to SCFAs, but failed to extend dendrites in response to S. aureus. Furthermore, inhibitors of ERK, PI3K, and Cdc42 suppressed dendrite extension triggered by S. aureus. Co-stimulation with S. aureus and butyrate enhanced dendrite extension beyond either stimulus alone. DC2.4 cells co-stimulated with S. aureus and butyrate also showed increased uptake of insoluble beads and, upon co-culture with T cells, induced elevated production of IL-17 and IL-10 by T cells. Collectively, these findings suggest that S. aureus activates ERK/PI3K/Cdc42 signaling through TLR2 recognition of PGN to drive dendrite extension in DCs. In addition, S. aureus promotes dendrite extension in DCs via a pathway distinct from that of SCFAs, thereby acting cooperatively with SCFAs to enhance immune responses.
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