Biochemical And Biophysical Research Communications[JOURNAL]
Sun
200 papers
Quercetin suppresses TGF-β1-induced proliferation and migration of vascular smooth muscle cells via the Smad2/3/MMP-9 signaling axis.
Lu Z, Ma M, Lu L … +3 more , Pan K, Chen Z, Cao H
Biochem Biophys Res Commun · 2026 Jul · PMID 42402230 · Publisher ↗
Aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) are central to the pathogenesis of occlusive vascular diseases including atherosclerosis and restenosis. Quercetin, a naturally occurring flavo...
Aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) are central to the pathogenesis of occlusive vascular diseases including atherosclerosis and restenosis. Quercetin, a naturally occurring flavonoid with established cardioprotective properties, has been reported to inhibit VSMC dysfunction, yet the underlying molecular mechanisms remain incompletely defined. Here, we demonstrate that quercetin dose-dependently suppresses TGF-β1-induced proliferation and migration of human aortic VSMCs. Mechanistically, quercetin attenuates TGF-β1-mediated phosphorylation of Smad2/3 and markedly reduces expression of matrix metalloproteinase-9 (MMP-9). Using the selective TGF-β type I receptor inhibitor SB431542, we establish that MMP-9 expression in VSMCs is regulated through the canonical Smad2/3 signaling pathway. Rescue experiments with MMP-9 overexpression reversed the anti-proliferative and anti-migratory effects conferred by TGF-β receptor blockade, confirming MMP-9 as an essential downstream effector. These findings delineate the TGF-β1/Smad2/3/MMP-9 signaling axis as a molecular target of quercetin in VSMCs and provide mechanistic rationale for quercetin-based therapeutic strategies in vascular remodeling diseases.
Biosynthesis, characterization and biological potential of microbe-mediated silver nanoparticles using thermophilic actinomycetes, Streptomyces nigra.
Sekar HS, Shanmugam J, Ravichandran B … +2 more , Ahamed NS, Sundararaj AS
Biochem Biophys Res Commun · 2026 Jul · PMID 42401011 · Publisher ↗
Silver nanoparticles (AgNPs) were synthesized using the cell-free extract of Streptomyces nigra (GenBank Accession: PP565016), a thermophilic actinobacterium isolated from scorched stubble environment, a previously unexp...
Silver nanoparticles (AgNPs) were synthesized using the cell-free extract of Streptomyces nigra (GenBank Accession: PP565016), a thermophilic actinobacterium isolated from scorched stubble environment, a previously unexplored ecological niche. The nanoparticle (NPs) formation was confirmed through the appearance of strong Surface Plasmon Resonance (SPR) peak at 422 nm. The characterization of biogenic AgNPs includes SEM (Scanning Electron Microscope), Zeta potential, XRD (X-ray Diffraction), FT-IR (Fourier Transform Infrared Spectroscopy), along with EDAX (Energy Dispersive X-ray Analysis) which confirms their spherical morphology, crystalline nature and surface functionalization with biological molecules. AgNPs show significant antibacterial activity against both Gram positive and negative bacteria with zone of inhibition ranging from 10 to 18 mm. The particles exhibited notable antioxidant activity indicating their potential to neutralize oxidative stress. Anti-inflammatory activity was confirmed by the denaturation of protein with the IC value of 41.8 ± 0.64 μg/mL. Antidiabetic potential was assessed via α-amylase inhibition assay, which was dose dependent (IC 49.61 ± 0.56 μg/mL). The MTT assay demonstrated dose-dependent cytotoxicity against prostate cancer cell lines (PC3), with significant reduction in cell viability and colony formation. Apoptosis induction was confirmed visually by AO/EtBr dual staining. This study highlights that S. nigra is a promising microbial source for the biosynthesis of multifunctional AgNPs possessing potential biological activity.
COP9 signalosome 8 mediated autophagy drives proliferation, invasion, and metastasis in pancreatic ductal adenocarcinoma.
Guo X, Cheng H, Wang D … +3 more , Wang Z, Hu Q, Zhang Y
Biochem Biophys Res Commun · 2026 Jul · PMID 42401010 · Publisher ↗
The present study aimed to explore the role of COP9 signalosome 8 (COPS8) as a novel molecule in pancreatic ductal adenocarcinoma (PDAC). A total of 9 genes were first identified by intersecting the differential genes of...
The present study aimed to explore the role of COP9 signalosome 8 (COPS8) as a novel molecule in pancreatic ductal adenocarcinoma (PDAC). A total of 9 genes were first identified by intersecting the differential genes of the GSE15471 and GSE62165 datasets with 248 Neddylation genes from the Reactome Pathway Database. The association between disease-free survival and the 9 genes in patients with PDAC was analyzed. Analysis using The Cancer Genome Atlas, Gene Expression Omnibus and Gene Expression Profiling Interactive Analysis databases revealed that COPS8 was highly expressed in patients with PDAC, and PDAC tissues exhibited significantly higher COPS8 expression levels compared to those found in paracancerous tissues. Finally, the above results were verified by cellular experiments, reverse transcription-quantitative PCR, Western blotting and immunohistochemistry. The mRNA expression levels of COPS8 were significantly elevated in the pancreatic cancer cell lines PANC-1and MIA PaCa-2 compared to those in HPNE normal pancreatic cells, and the protein expression levels of COPS8 were also significantly elevated in the pancreatic cancer cells PANC-1 and MIA PaCa-2. COPS8 protein was significantly increased in cancer tissues of patients with pancreatic cancer compared to paracancerous tissues. The proliferative, migratory and invasive abilities of PANC-1 and MIA PaCa-2 cells were significantly reduced after knockdown of COPS8. The results showed that knockdown of COPS8 in PANC-1 and MIA PaCa-2 cells decreased Microtubule-associated proteins 1A/1B light chain 3B (LC3Ⅱ/LC3Ⅰ), while Sequestosome 1 (P62/SQSTM1) expression was elevated. COPS8 may promote the proliferation, invasion, and metastasis of pancreatic cancer cells by regulating autophagy.
Tumor budding in colorectal cancer: partial EMT, microenvironmental remodeling, and metastatic competence.
Wang T, Fei H, Liu X … +4 more , Zhang L, Liang W, Wei X, Fei F
Biochem Biophys Res Commun · 2026 Jul · PMID 42401009 · Publisher ↗
Tumor budding (TB) is a pathological hallmark of malignant invasion at the invasive front of colorectal cancer (CRC) and provides a morphologic window into early dissemination. In the International Tumor Budding Consensu...
Tumor budding (TB) is a pathological hallmark of malignant invasion at the invasive front of colorectal cancer (CRC) and provides a morphologic window into early dissemination. In the International Tumor Budding Consensus Conference (ITBCC) framework, buds are single tumor cells or clusters of up to four cells, graded by hotspot counting to support standardized evaluation. Evidence from histopathology, single-cell profiling, spatially resolved analyses, and functional models links TB to invasion-competent tumor states. TB often tracks partial epithelial-mesenchymal transition, with weakened cell-cell adhesion, E-cadherin loss, altered β-catenin localization, and activation of integrin signaling, cytoskeletal remodeling, and extracellular matrix (ECM) degradation while retaining epithelial features. Spatial/trajectory analyses suggest that budding-rich regions concentrate plastic, stem-like programs biased toward migration and stress tolerance and lie close to intravasation. The TB niche also shows immune and metabolic specialization, with constrained dendritic-cell maturation and antigen presentation, reduced or dysfunctional CD8 T-cell and NK-cell activity, and enrichment of tumor-associated macrophages and other suppressive myeloid programs. Hypoxia-driven glycolysis, lactate-associated acidification, adenosine signaling, and myeloid lipid-metabolic reprogramming can further stabilize invasive phenotypes and raise the threshold for immune control. Digital pathology and AI-enabled whole-slide analysis can improve scoring consistency and add spatial readouts linking TB patterns to immune contexture and stromal organization. Collectively, TB marks an interface between invasive tumor biology and the local microenvironment with direct relevance for risk stratification and therapeutic tailoring in CRC.
Exploring the therapeutic versatility and multitarget pharmacological potential of acyl hydrazone-hydrazide scaffolds.
Rajimon KJ, Gopalsamy RG
Biochem Biophys Res Commun · 2026 Jul · PMID 42401008 · Publisher ↗
Acyl hydrazones and hydrazides are of great interest in medicinal chemistry because their pharmacophoric group (-CO-NH-N=CH-) shows keto-enol tautomerism and E/Z isomerism, which gives them dynamic stereochemical propert...
Acyl hydrazones and hydrazides are of great interest in medicinal chemistry because their pharmacophoric group (-CO-NH-N=CH-) shows keto-enol tautomerism and E/Z isomerism, which gives them dynamic stereochemical properties. They are of particular value to medicinal chemists due to their ability to undergo multiple weak non-covalent interactions and metal chelation. This review systematically studied the various biological activities of acyl hydrazone and hydrazide derivatives, which are therapeutically important compounds. Although several synthetic methods, including microwave-assisted, ultrasound-assisted, aqueous-phase, and enzyme-catalyzedare mentioned, the main emphasis is to gain insight into the pharmacological significance and bioactivity of these derivatives. It also found that the structure-activity relationships (SAR) influence their pharmacologic outcomes. Improved synthetic accessibility, combined with their potential to interact with multiple biological targets, highlights the value of acyl hydrazones as versatile candidates in therapeutic research. These features collectively support their continued investigation as important molecular frameworks for the design and development of novel bioactive agents.
The plasma membrane H-ATPase OSA2 negatively regulates salt tolerance in rice seedlings.
Dong M, Xie Z, Lian L … +5 more , Shi L, Zhang J, Liu Q, Jiang Z, Wu C
Biochem Biophys Res Commun · 2026 Jul · PMID 42398405 · Publisher ↗
Plasma membrane (PM) H-ATPases are pivotal for plant adaptation to abiotic stresses; however, the specific function of the rice (Oryza sativa L.) PM H-ATPase isoform OSA2 in salt stress responses remains elusive. In this...
Plasma membrane (PM) H-ATPases are pivotal for plant adaptation to abiotic stresses; however, the specific function of the rice (Oryza sativa L.) PM H-ATPase isoform OSA2 in salt stress responses remains elusive. In this study, using the Zhonghua 11 (ZH11) cultivar, we created an OSA2 knockout mutant (osa2-9) via CRISPR/Cas9 technology and generated OSA2 overexpression lines (OSA2OE). Subcellular localization assays confirmed that OSA2 protein is specifically localized to the cell plasma membrane. Physiological and biochemical analyses under 150 mM NaCl revealed that the survival rate of osa2-9 was significantly higher than that of OSA2OE, albeit slightly lower than the wild type (WT). Salt stress induced a marked elevation in catalase (CAT) and peroxidase (POD) activities in WT plants, effectively mitigating malondialdehyde (MDA) accumulation. Conversely, OSA2OE plants exhibited suppressed CAT activity, excessive MDA accumulation, and exacerbated oxidative damage. Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that OSA2 overexpression significantly repressed the transcription of salt tolerance- and reactive oxygen species (ROS) metabolism-related genes, such as OsHKT1 and OsodCc1, in the roots. Collectively, our findings identify OSA2 as a negative regulator that compromises salt tolerance in rice seedlings, likely by perturbing PM H transport and disrupting antioxidant homeostasis. This study provides a theoretical framework for elucidating the molecular mechanisms underlying rice salt tolerance and for the breeding of salt-resilient cultivars.
MiR-425-5p modulation of CREB1 affects inflammatory response and motor recovery after spinal cord injury.
Qi S, Wang D, Wu Y … +6 more , Wang W, Wang S, Meng H, Zhang Z, Luo Y, Wang X
Biochem Biophys Res Commun · 2026 Jun · PMID 42398338 · Publisher ↗
OBJECTIVE: This study aimed to investigate whether miR-425-5p contributes to post-spinal cord injury (SCI) inflammation and motor dysfunction by targeting CREB1. METHODS: SCI rat models and HO-treated C8-D1A/C8-B4 cellul...
OBJECTIVE: This study aimed to investigate whether miR-425-5p contributes to post-spinal cord injury (SCI) inflammation and motor dysfunction by targeting CREB1. METHODS: SCI rat models and HO-treated C8-D1A/C8-B4 cellular models were established. miR-425-5p and CREB1 were manipulated using inhibitors/antagomirs and siRNAs. Expression levels of miR-425-5p, IL-6, IL-1β, TNF-α, CREB1, and caspase-3 were measured using RT-qPCR. Cell apoptosis was evaluated by flow cytometry. Western blot analysis was performed to assess total CREB1 (t-CREB1) and phosphorylated CREB1 (p-CREB1) levels. Bioinformatics predictions were used to determine the targeting relationship between miR-425-5p and CREB1. BBB locomotor rating scale was employed to quantify motor function recovery in rats. RESULTS: miR-425-5p expression was markedly up-regulated in the HO-induced cell model, whereas CREB1 was down-regulated. CREB1 is a target of miR-425-5p. Inhibition of miR-425-5p significantly reduced apoptosis, suppressed pro-inflammatory cytokine expression, thereby promoting motor recovery; these effects were partially reversed by CREB1 knockdown. In SCI rats, miR-425-5p antagomir treatment alleviated inflammation and promoted motor function recovery; these beneficial effects were partially suppressed by co-administration of si-CREB1 to knockdown CREB1. CONCLUSION: MiR-425-5p upregulation in SCI directly suppresses CREB1 expression, subsequently exacerbating neuroinflammation, which in turn impairs functional recovery.
Xanthoangelol, a chalcone from Angelica keiskei, induces apoptosis in cervical cancer cell lines via the oxidative stress-mediated activation of caspase-8 and caspase-9.
Horiuchi Y, Noguchi H, Taniguchi AY … +1 more , Kazami M
Biochem Biophys Res Commun · 2026 Jun · PMID 42398337 · Publisher ↗
Xanthoangelol (XAG), a chalcone isolated from Angelica keiskei, exhibits various biological activities. Evidence supports its anti-cancer effects, including its ability to promote apoptosis in multiple cancer cell types....
Xanthoangelol (XAG), a chalcone isolated from Angelica keiskei, exhibits various biological activities. Evidence supports its anti-cancer effects, including its ability to promote apoptosis in multiple cancer cell types. However, its impact on cervical cancer cells and its underlying mechanisms remain unclear. In this study, we investigated the cytotoxic, and pro-apoptotic effects of XAG in human cervical cancer cell lines (HeLa, and CaSki). XAG significantly reduced cell viability in a concentration-dependent manner and induced apoptosis, as evidenced by DNA fragmentation, caspase-3 activation, and PARP cleavage. Time-course analyses revealed that XAG rapidly disrupted intracellular redox balance, characterized by an early increase in the GSSG/GSH ratio, prior to the execution phase of apoptosis. Western blot analyses demonstrated activation of both extrinsic and intrinsic apoptotic pathways, including cleavage of caspase-8 and caspase-9, as well as an increased Bax/Bcl-2 ratio. Pharmacological inhibition of caspase-8, but not caspase-9, effectively suppressed XAG-induced PARP cleavage, indicating a predominant contribution of the extrinsic pathway in apoptosis induction. Collectively, XAG induces apoptosis in cervical cancer cells via early redox imbalance followed by caspase-dependent signaling, with caspase-8 playing a critical role.
Suchilactone ameliorates podocyte injury in membranous nephropathy by modulating the JNK/p38 MAPK pathway in vitro.
Mo Y, Xu Y, Lai X … +5 more , Li Y, Huang Q, Zhao Y, Zhao C, Xu Y
Biochem Biophys Res Commun · 2026 Jul · PMID 42398336 · Publisher ↗
Membranous nephropathy (MN) represents an autoimmune glomerular condition fundamentally marked by immune complex accumulation and complement initiation. About 20 to 30 percent of patients go on to develop chronic kidney...
Membranous nephropathy (MN) represents an autoimmune glomerular condition fundamentally marked by immune complex accumulation and complement initiation. About 20 to 30 percent of patients go on to develop chronic kidney disease. Current immunosuppressive treatment regimens frequently possess considerable potential toxicity, necessitating the development of more effective and safer therapeutic alternatives. Suchilactone (Suc) is a newly found compound with potential effects against inflammation, but its function in MN remains unreported. The MN model in podocytes utilizing serum activated by zymosan A was established. The impact of Suc on cell viability was confirmed through the CCK8 assay. A transcriptomic analysis was performed to clarify the mechanism of action of Suc in MN. Pharmacological experiments utilizing Western blot, quantitative real-time PCR, and immunofluorescence were performed to corroborate transcriptomic results. We assessed the abundance of key podocyte proteins, inflammatory markers, and components of intracellular signaling pathways. To further elucidate the connection between MAPK and Suc in MN, we employed specific inhibitors in our experimental approach. It was demonstrated that Suc markedly protected podocytes by suppressing the expression of inflammatory cytokines TNF-α and IL-1β, inhibiting the inflammatory pathway protein p65, reversing the decline of nephrin and podocin-critical podocyte proteins-and reducing C5b-9 release. This process fixed damage to podocytes to keep the glomerular filtration barrier integrity. Experiments on transcriptomics and intracellular pathways showed that the JNK/p38 MAPK pathway contribute to these effects. In conclusion, Suc can protect podocytes from complement-mediated injury and reduce inflammation through the JNK/p38 MAPK pathway to ameliorates complement-mediated podocyte injury in MN.
Palmitic acid-induced metabolic stress alters differentiation-associated gene expression in human ameloblast-like cells.
Nakagawa M, Iwawaki Y, Iwata T … +5 more , Tanaka E, Yoshida K, Kudo Y, Miyoshi K, Mizusawa N
Biochem Biophys Res Commun · 2026 Jun · PMID 42398335 · Publisher ↗
Metabolic stress during enamel development may influence ameloblast differentiation and enamel formation, although the underlying mechanisms remain poorly understood. In this study, we investigated transcriptional and ce...
Metabolic stress during enamel development may influence ameloblast differentiation and enamel formation, although the underlying mechanisms remain poorly understood. In this study, we investigated transcriptional and cellular responses to palmitic acid (PA) in the human ameloblast-like cell line HAM3 using a custom quantitative reverse transcription polymerase chain reaction panel based on amelogenesis imperfecta-related genes. PA exposure under both sustained low-dose conditions (50 μM for 24 h) and acute high-dose conditions (500 μM for 4 h) induced coordinated transcriptional changes associated with enamel maturation and cellular stress responses. Expression of the maturation-associated gene AMTN was detectable at baseline and consistently upregulated following PA exposure, whereas that of the epithelial transcription factor gene BCL11B was selectively suppressed under acute high-dose conditions. PA also induced expression of stress-responsive genes including GDF15 and HMOX1. In parallel, immunoblotting demonstrated increased levels of cleaved caspase-3 and LC3-II, while immunofluorescence analysis revealed accumulation of p62-positive structures, consistent with stress-associated apoptosis and altered autophagy-related processes. These findings suggest that PA-induced metabolic stress promotes a stress-associated pseudo-maturation-like transcriptional state in ameloblast-like cells while activating coordinated cellular stress responses. This study provides a potential framework linking metabolic stress environments to altered enamel development.
A transferrin receptor-based vector enables robust Type-II membrane protein display on mammalian cells.
Sedgwick AJ, Roest J, Zhang G … +4 more , Wright GJ, Langendorf C, Barrow AD, Vivian JP
Biochem Biophys Res Commun · 2026 Jul · PMID 42391659 · Publisher ↗
Cell surface protein display is widely used in biotechnology as a platform for interrogating and engineering protein function in mammalian systems. Current display systems, including pDisplay™, are based on type-I membra...
Cell surface protein display is widely used in biotechnology as a platform for interrogating and engineering protein function in mammalian systems. Current display systems, including pDisplay™, are based on type-I membrane topology and enforce an extracellular N-terminus and cytosolic C-terminus. While suitable for secreted proteins and antibody fragments, they are incompatible with type-II membrane proteins, which instead possess an inverted topology. Despite encompassing an important class of proteins, type-II proteins lack robust and generalisable surface display tools. Here, we report a transferrin receptor 1 (TfR1)-based vector for type-II membrane protein display in mammalian cells. By leveraging the native cytoplasmic and transmembrane architecture of TfR1, the system enforces a correct type-II topology and enables efficient trafficking to the plasma membrane. Using TMEM106b as a representative type-II protein, we show that TfR1 fusion drives robust cell-surface localisation, confirmed by fluorescence-activated cell sorting and confocal microscopy.
NAT10-mediated RNA N4-acetylation promotes intestinal fibroblast senescence via DHRS2.
Zhong J, Zhu J, Xue M … +1 more , Chen J
Biochem Biophys Res Commun · 2026 Jun · PMID 42385484 · Publisher ↗
Intestinal fibroblast senescence contributes to gut aging and the development of related diseases, yet the regulatory mechanisms governing this process remain largely elusive. In this study, we identify the RNA N4-acetyl...
Intestinal fibroblast senescence contributes to gut aging and the development of related diseases, yet the regulatory mechanisms governing this process remain largely elusive. In this study, we identify the RNA N4-acetylcytidine (acC) modification and its cognate writer, N-acetyltransferase 10 (NAT10), as key modulators of human colonic fibroblast senescence. Through a series of loss- and gain-of-function assays, we demonstrate that NAT10-mediated mRNA acC modification is functionally involved in controlling intestinal fibroblast senescence. Suppression of this modification diminishes senescence-associated markers and attenuates replicative, oxidative (HO), and DNA damage-induced (doxorubicin) senescence in intestinal fibroblasts. Mechanistically, NAT10-driven acC deposition enhances DHRS2 mRNA stability, thereby promoting fibroblast senescence. Collectively, our findings establish the NAT10/acC/DHRS2 regulatory axis as a critical player in intestinal fibroblast senescence and suggest its potential as a therapeutic target for age-related intestinal disorders.
Deciphering potent MPL activation by the fucose-binding lectin thrombocorticin.
Watari H, Kageyama H, Okabe M … +3 more , Yokoyama T, Sakai R, Tanaka Y
Biochem Biophys Res Commun · 2026 Jun · PMID 42385483 · Publisher ↗
Thrombocorticin (ThC) is a marine sponge-derived L-fucose-binding lectin that acts as an agonist of the thrombopoietin (TPO) receptor through glycan-mediated receptor crosslinking. We previously identified the bacterial...
Thrombocorticin (ThC) is a marine sponge-derived L-fucose-binding lectin that acts as an agonist of the thrombopoietin (TPO) receptor through glycan-mediated receptor crosslinking. We previously identified the bacterial lectin PA-IIL from Pseudomonas aeruginosa as a structurally related MPL agonist; however, its potency is approximately 70-fold lower than that of ThC. To investigate the structural basis underlying this difference, we performed structure-function analyses using ThC and PA-IIL mutants as well as engineered oligomeric variants. These studies demonstrated that MPL activation could not be explained solely by sugar-binding activity or the apparent oligomeric state. In particular, lectins with similar sugar-binding properties displayed markedly different agonist activities, while alterations in oligomeric organization did not consistently correlate with MPL activation potency. These findings suggest that additional structural features are required for productive receptor activation. To further explore these determinants, we performed genome mining of bacterial proteins whose sequences were similar to those of ThC. Four candidate lectins were heterologously expressed and evaluated for MPL agonist activity. Three exhibited partial agonist activity, reaching approximately 20% of the maximal response induced by ThC. Comparative analyses of amino acid sequences, structural models, and biological activities revealed that neither the ability to bind sugars nor the oligomeric state alone predict MPL agonist potency. Collectively, these findings indicate that productive MPL activation requires structural features beyond the ability to bind sugars and the oligomeric state.
Mitochondrial genome alterations in cancer: From mutations and epigenetics to targeted therapiesack.
Shetty S, Padmasali NM, Adiga D … +1 more , Kabekkodu SP
Biochem Biophys Res Commun · 2026 Jun · PMID 42385482 · Publisher ↗
Mitochondria play a central role in cellular energetics, metabolism, and apoptosis, and their dysfunction is increasingly recognized as a hallmark of cancer. The mitochondrial genome encodes essential subunits of oxidati...
Mitochondria play a central role in cellular energetics, metabolism, and apoptosis, and their dysfunction is increasingly recognized as a hallmark of cancer. The mitochondrial genome encodes essential subunits of oxidative phosphorylation (OXPHOS) complexes, tRNAs, and rRNAs, which are critical for mitochondrial functions. However, mitochondrial DNA (mtDNA) lacks protective histones and efficient repair mechanisms, rendering it highly susceptible to mutations and epigenetic changes. This review examines the role of mitochondrial-encoded genes (MEGs) in cancer progression, emphasizing the molecular mechanisms through which alterations in these genes contribute to tumorigenesis. We discuss how microsatellite instability, somatic mutations, and epigenetic modifications, such as methylation and non-coding RNA interactions, disrupt mitochondrial function, leading to defective OXPHOS, metabolic reprogramming (including the Warburg effect), elevated reactive oxygen species (ROS) production, and evasion of apoptosis. Furthermore, we highlight the tissue-specific and stage-dependent alterations in MEGs across various cancers, including breast, colorectal, lung, and ovarian malignancies, and explore their potential as diagnostic, prognostic, and therapeutic biomarkers. Finally, we evaluate emerging therapeutic strategies targeting MEGs, including mitochondrial gene editing, allotopic expression, and nanocarrier-based delivery systems, offering insights into future directions in precision oncology. We also discuss how MEG alterations contribute to the Warburg effect, chemoresistance, and tumor metastasis, which are critical barriers to effective cancer treatment. This synthesis highlights the pivotal role of mitochondrial genetics in cancer biology and positions MEGs as promising targets for innovative anticancer therapies.
GPC3 chimeric antigen receptor (CAR)-NK cells combined with Enoblituzumab enhance the anti-tumor efficacy against hepatocellular carcinoma.
Zhuang W, Xiao G, Zhang M … +3 more , Wang J, Tang W, Liang Y
Biochem Biophys Res Commun · 2026 Jun · PMID 42378857 · Publisher ↗
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Although CAR-NK cell therapies have shown promise in hematologic malignancies, their efficacy in solid tumors like HCC is often limited by...
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Although CAR-NK cell therapies have shown promise in hematologic malignancies, their efficacy in solid tumors like HCC is often limited by antigen escape. Here, we investigated a dual-targeting strategy combining GPC3 CAR-NK cells with the B7H3-blocking monoclonal antibody Enoblituzumab. We confirmed GPC3 and B7H3 co-expression in HCC tissues and cell lines via database analysis and flow cytometry. GPC3 CAR-NK cells were generated from expanded human PBMC-derived NK cells. In vitro cytotoxicity against HCC cells was assessed by LDH release and real-time cell analysis, while IFN-γ secretion and CD107a degranulation were measured by ELISA and flow cytometry. In vivo antitumor efficacy was evaluated in NCG mice bearing subcutaneous Huh7 tumors. High GPC3 and B7H3 co-expression correlated with poor patient prognosis. GPC3 CAR-NK cells exhibited potent cytotoxicity against HCC cells in vitro. Enoblituzumab triggered strong killing effects against B7H3-positive tumors. Notably, the combination synergistically enhanced cytotoxicity, IFN-γ production, and CD107a degranulation compared to either monotherapy. In vivo, combination treatment significantly suppressed tumor growth without inducing weight loss or splenomegaly, demonstrating favorable efficacy and safety. Our findings demonstrate that dual targeting of GPC3 and B7H3 effectively enhances NK cell-mediated antitumor activity. This strategy leverages both CAR-mediated specificity and NK cell-intrinsic mechanisms, providing a strong rationale for developing dual-target immunotherapies to improve outcomes in HCC patients.
A miR-382-5p-PORCN axis modulates endogenous Wnt signaling during palatal development.
Yu J, Wang Y, Chen Y … +8 more , Yang L, Li F, Li J, Tan Z, Yan J, Jin L, Qiu M, Huang H
Biochem Biophys Res Commun · 2026 Jun · PMID 42378856 · Publisher ↗
Precise temporal regulation of Wnt signaling is required for normal palate development, but the mechanisms controlling endogenous Wnt ligand availability during palatogenesis remain poorly understood. Here, temporal micr...
Precise temporal regulation of Wnt signaling is required for normal palate development, but the mechanisms controlling endogenous Wnt ligand availability during palatogenesis remain poorly understood. Here, temporal microRNA profiling of mouse palatal shelves from embryonic day (E) 13.5 to E15.0 identified miR-382-5p as a dynamically regulated microRNA exhibiting a pronounced but transient decrease at E14.5, a critical stage of palatal shelf apposition. Bioinformatic analysis identified Porcn, an essential regulator of Wnt ligand maturation and secretion, as a candidate target of miR-382-5p. Direct targeting was confirmed by dual-luciferase reporter assays. Overexpression of miR-382-5p reduced PORCN protein abundance without affecting Porcn mRNA levels, indicating post-transcriptional repression. Consistent with reduced PORCN activity, miR-382-5p attenuated endogenous Wnt signaling, as evidenced by decreased Axin2 and Ccnd1 expression and reduced TOP/FOP reporter activity. Importantly, responsiveness to exogenous Wnt3a remained intact, and restoration of PORCN expression using a miRNA-insensitive Porcn coding sequence significantly rescued Wnt signaling activity. Together, these findings identify Porcn as a direct target of miR-382-5p and establish a previously unrecognized miR-382-5p-PORCN-Wnt regulatory axis. The transient decrease of miR-382-5p at E14.5 suggests that developmental relief of Porcn repression may contribute to stage-specific enhancement of endogenous Wnt signaling during palatogenesis.
Development of a vitamin-related gene signature to predict the immune characteristics and prognosis of glioma.
Wu L, Lu J, Zhang Q … +4 more , Huang T, Chen Y, Shi H, Cai J
Biochem Biophys Res Commun · 2026 Jun · PMID 42378855 · Publisher ↗
OBJECTIVES: To establish and validate a vitamin-related gene signature for predicting glioma prognosis and immune characteristics, and to explore the functional relevance of EEF2. METHODS: Survival-related vitamin-associ...
OBJECTIVES: To establish and validate a vitamin-related gene signature for predicting glioma prognosis and immune characteristics, and to explore the functional relevance of EEF2. METHODS: Survival-related vitamin-associated genes were identified from public glioma cohorts to build a prognostic signature. Its clinical relevance, immune associations, and predictive performance were validated. EEF2 function was tested in glioma cells, and its relationship with YPEL1 was explored. RESULTS: A six-gene signature (POSTN, IRX5, EEF2, RAB27A, MDM2, ENO1) independently predicted overall survival and distinguished glioma grade and molecular subtype across cohorts. High-risk gliomas showed elevated immune and stromal scores, reduced tumor purity, enriched immune-cell infiltration, C4 immune-subtype dominance, and pronounced immunosuppressive features comprising upregulated Cancer-Immunity Cycle inhibitors and immune checkpoints. A nomogram integrating the signature with clinicopathological factors accurately predicted 1-, 3-, and 5-year survival. Functionally, EEF2 knockdown promoted glioma cell proliferation, migration, and invasion, and positively regulated YPEL1, supporting its protective role. CONCLUSIONS: This vitamin-related signature links vitamin biology with glioma immunity and prognosis, and EEF2 represents a promising direction for future mechanistic and therapeutic research.
Cyclo(Ser-Tyr) L/D spatial isomerism exerts opposing effects on benign prostatic hyperplasia.
Xun L, Rulan T, Tianyan W … +3 more , Wenting G, Caiyun S, Qiqi S
Biochem Biophys Res Commun · 2026 Jun · PMID 42378854 · Publisher ↗
OBJECTIVE: To investigate the role of two isomers Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) in benign prostatic hyperplasia. Additionally, it seeks to elucidate their mechanisms of action through both in vitro and in v...
OBJECTIVE: To investigate the role of two isomers Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) in benign prostatic hyperplasia. Additionally, it seeks to elucidate their mechanisms of action through both in vitro and in vivo experiments. METHODS: Benign prostatic hyperplasia (BPH) was induced using testosterone propionate. The pharmacological effects of Cyclo (L-Ser-L-Tyr) and Cyclo (D-Ser-L-Tyr) were evaluated. Efficacy and safety were assessed by measuring prostate weight, calculating the prostate index, and conducting histopathological and biochemical analyses. Mechanistic studies incorporated transcriptomics, immunohistochemistry, CCK-8 assays, siRNAs transfection, Western blotting, molecular docking, and molecular dynamics simulations. RESULTS: Cyclo (L-Ser-L-Tyr) reduced prostate index, attenuated prostatic epithelial hyperplasia and interstitial fibrosis, lowered TNF-α and IL-1β levels, and suppressed inflammation. In contrast, finasteride fails to alleviate prostate fibrosis, while Cyclo (D-Ser-L-Tyr) showed no therapeutic effect and significantly increased serum ALT and AST, indicating potential hepatotoxicity. Transcriptomic analysis showed that Cyclo (L-Ser-L-Tyr) reversed elevated expression of BPH-associated genes and affected pathways including cancer, apoptosis, p53, and MAPK signaling. In prostate tissues and cells, Cyclo (L-Ser-L-Tyr) reduced protein levels of AR and BCL-2. In BPH-1 cells, AR knockout markedly decreased BCL-2 expression. Molecular dynamics simulations showed that Cyclo (L-Ser-L-Tyr) forms a stable complex with AR. CONCLUSION: Cyclo (L-Ser-L-Tyr) ameliorates BPH by modulating the AR/BCL-2 axis and inflammatory mediators, whereas Cyclo (D-Ser-L-Tyr) is ineffective and may be hepatotoxic. These results support the clinical potential of Cyclo (L-Ser-L-Tyr).
Necrotic tumor cells contribute to pro-tumoral responses and inflammatory mediator production via NF-κB activation in oral squamous cell carcinoma.
Yamazaki M, Abé T, Maruyama S … +3 more , Tomihara K, Izumi K, Tanuma JI
Biochem Biophys Res Commun · 2026 Jun · PMID 42372655 · Publisher ↗
Although tumor necrosis has traditionally been regarded as a passive consequence of rapid tumor growth, current evidence suggests that necrotic tumor cells actively modulate the behavior of surrounding viable cancer cell...
Although tumor necrosis has traditionally been regarded as a passive consequence of rapid tumor growth, current evidence suggests that necrotic tumor cells actively modulate the behavior of surrounding viable cancer cells. In this study, we investigated whether necrotic tumor cells promote pro-tumoral activation of oral squamous cell carcinoma (OSCC) cells and aimed to elucidate its underlying mechanisms. Human OSCC cell lines were exposed to necrotic tumor cells under both direct and indirect co-culture conditions. Necrotic cells significantly enhanced proliferation, migration, and invasion of viable OSCC cells independent of direct cell-cell contact, which indicates the involvement of soluble factors. Necrotic cell stimulation induced the nuclear accumulation of NF-κB p65 and increased the expression of downstream inflammatory mediators, including CXCL8. Pharmacological inhibition of NF-κB signaling attenuated necrotic cell-induced pro-tumoral phenotypes and reduced CXCL8 secretion. These findings suggest that necrotic tumor cells induce pro-tumoral phenotypic changes in OSCC cells by activating canonical NF-κB signaling and subsequent pro-inflammatory responses. Additionally, this study provides a mechanistic insight into the role of tumor necrosis in establishing a tumor-favorable microenvironment.
GPR4 promotes ferroptosis in nucleus pulposus cells via MAPK-dependent mitophagy suppression.
Zhao J, Xu Z, Niu J … +5 more , Du H, Zhang Y, Zhao Y, Gao C, Wu D
Biochem Biophys Res Commun · 2026 Jun · PMID 42372654 · Publisher ↗
Inflammatory diseases are known to lower the pH value of the extracellular microenvironment. However, the role of proton-activated G protein-coupled receptors (GPCRs) in the progression of intervertebral disc degeneratio...
Inflammatory diseases are known to lower the pH value of the extracellular microenvironment. However, the role of proton-activated G protein-coupled receptors (GPCRs) in the progression of intervertebral disc degeneration (IVDD) remains largely unexplored. In this study, we identified GPR4 as a key regulator of IVDD progression. Our analysis revealed a significant upregulation of GPR4 in degenerative human intervertebral discs. The expression of GPR4 was assessed using immunohistochemistry (IHC). Functional assays, including flow cytometry, immunofluorescence and WB, were performed to evaluate the impact of GPR4 on ferroptosis. We observed that GPR4 expression was significantly elevated in tert-butyl hydroperoxide (TBHP)-treated degenerative nucleus pulposus cells. Proteomic sequencing further demonstrated that GPR4 overexpression altered gene expression related to the mitochondrial energy metabolism and ferritin homeostasis. Notably, knockdown of GPR4 via shRNA (shGPR4) enhanced the MAPK-mediated mitophagy while suppressing ferroptosis in TBHP-exposed NP cells. These findings suggested that GPR4 played a critical role in IVDD pathogenesis and may serve as a potential therapeutic target for mitigating disc degeneration.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe