Targeting muscle-bone crosstalk with hormone-like peptides: Systems approach reveals RGHGP-mediated suppression of LAMB1-MAPK osteoclastogenesis.

DUSP1 interacts with BIP to regulate Staphylococcus aureus-induced apoptosis through the MAPK signaling pathway.

Medicinal-chemistry-driven strategies for the synthesis of antiosteoclastogenic small molecules targeting RANKL and its downstream signaling pathways.

Comparative transcriptomics of adherent and suspension chicken fibroblast cell lines for the optimization of cultivated meat processes.

Gamma-aminobutyric acid (GABA) is a naturally occurring bioactive component in plants. Our previous study demonstrated that ultrasound could increase the activity of glutamate decarboxylase (GAD) and effectively enhance GABA accumulation in coffee leaves. However, the mechanism underlying this action has yet to be explored. In this study, we investigated how ultrasound promotes GABA accumulation in coffee leaves by analyzing the relative contribution of the two GABA synthesis pathways, as well as changes in the key enzymes, signal molecules, and transcriptomes in coffee leaves under ultrasound treatment. The mechanical extraction had a negligible effect on GABA levels in coffee leaves, and the substrate sodium glutamate was essential for GABA accumulation under ultrasound stress. Aminoguanidine pretreatment reduced GABA content by 31.02% under ultrasound treatment. Fluorescent imaging revealed increased intracellular Ca2+ and H+ levels, potentially contributing to enhanced GAD activity in ultrasound-treated leaves. Transcriptomic analysis identified 1053 differentially expressed genes associated with multiple metabolic pathways, including carbohydrates, amino acids, flavonoids, and other primary and secondary metabolite biosynthesis. Further analysis indicated that ultrasound may enhance GABA accumulation by modulating Ca2+, reactive oxygen species, mitogen-activated protein kinase, and phosphatidylinositol signaling pathways, as well as the glyoxylate and dicarboxylate metabolic pathways. This study revealed that ultrasound promoted GABA accumulation mainly through the GABA shunt pathway, with mechanical extraction playing a minimal role. Ultrasound may enhance GAD activity by increasing intracellular Ca2+ levels and lowering pH, while also regulating the expression of genes related to GABA biosynthesis. © 2026 Society of Chemical Industry.

The regulation of gene expression and its connection to the dynamics of plasma membrane signaling hubs (lipid rafts) have largely remained unexplored to date. Ras signaling plays crucial roles in the initiation and progression of colon adenocarcinoma (COAD) by regulation of gene expression, including DNA methyltransferase 1 (DNMT1). Gene-specific hypermethylation and genome-wide hypomethylation are well characterized in various cancers, including COAD. In view of this, we have examined how the signaling pathway orchestrated by plasma membrane-associated lipid rafts coordinates with the epigenetic modifications that precisely modulate a specific group of (hub) genes involved. First, we have identified COAD-specific hub genes (COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2) through extensive bioinformatics analyses, which revealed that increased expression of these hub genes facilitates the onset and progression of COAD. Comprehensive computational analyses of methylation patterns confirmed that atypical hypomethylation at these gene loci elevates their expression in COAD. Thereafter, we have explored how the dynamics of plasma membrane signaling hubs', such as lipid rafts, influence gene-specific promoter methylation dynamics within the nucleus of COAD cells. Our experimental analyses indicated that the transient destabilization (TD) of lipid rafts through ectopic cholesterol efflux activates the epidermal growth factor (EGF)-independent lipid raft-associated epidermal growth factor receptor (EGFR)-rat sarcoma (RAS)-mitogen-activated protein kinase (MAPK) signaling pathway, leading to increased expression of DNMTs and decreased expression of hub genes in COAD cells. These results strongly suggest that the plasma membrane lipid raft-associated EGFR-RAS-MAPK axis, functioning from membrane signaling hubs, can regulate genes located in various chromosomal locations. Ectopic expressions of DNMT1 impose an epigenetic checkpoint at those target loci by methylation of promoter DNA of the respective genes. We conclude that, gene specific hypomethylation of some genes, including COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 drives COAD and would serve as potential markers for COAD screening.

Global research trends and hotspots of rheumatoid arthritis and mitogen-activated protein kinase-a bibliometrics and visualization analysis.

Diabetic Neuropathy (DN) is a long-term persistent neuro impairment associated with Type 2 Diabetes Mellitus (T2DM). DN develops when chronic hyperglycaemia damages peripheral and autonomic nerves, giving rise to a broad spectrum of clinical symptoms. The mechanism of DN is elaborate and multicomponent, mediated by persistent hyperglycaemia, lipid metabolic dysfunction, oxidative imbalance, impaired mitochondrial activity, and neuroinflammation, together giving rise to progressive peripheral nerve injury. Persistently raised glucose levels promote the accumulation of glycotoxins, leading to alteration in protein synthesis and function. Inflammatory mediators such as Interleukin-6 (IL-6), C-Reactive Protein (CRP), IL-18, IL-8, and Tumour Necrosis Factor alpha (TNF-α) further amplify nerve damage by activating Nuclear Factor kappa B (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways. Modern strategies for managing DN focus on glycaemic control, lifestyle modifications, and emerging treatments namely Sodium-Glucose Cotransporter 2 (SGLT2) targeting drugs and Glucagon-Like Peptide-1 (GLP-1) mimetic. Further the identification of biochemical markers and molecular targets may facilitate early diagnosis and enable more personalised interventions. Continued collaboration between basic science scientists and clinicians will be essential in translating biochemical insights into tangible benefits for individuals. Despite our growing knowledge of the complexity of DN has sustainably improved in prior years, yet such knowledge of biochemical aspects and earlier predictor of neuropathy associated with diabetes are not entirely clear. Hence, the present review tends to describe the present comprehension about biochemical aspects, mechanism of neurological progression, and interconnected pathways involved in DN.

ATF2-LPCAT1-mediated PKM2 acetylation links cholesterol stress to macrophage metabolic reprogramming and functional remodeling.

Exosomal miR-10b derived from protocatechuic acid-treated efferocytic macrophages inhibits endothelial inflammation by targeting MAP3K7/β-TrCP/NF-κB signaling pathway.

Targeting the SIN1 mediated TTK/LDHA-H3K18la-GLUT3 axis disrupts metabolic-epigenetic crosstalk and suppresses progression in hyperglycolytic breast cancer.

Retraction notice to "p38 Mitogen-activated protein kinase modulates cisplatin resistance in head and neck squamous cell carcinoma cells" [Archives of Oral Biology 122 (2021)104981

Gastric cancer is among the deadliest cancers worldwide, and gastric intestinal metaplasia is a key precancerous phase. Understanding the molecular drivers of abnormal proliferation in intestinal metaplasia (IM) is vital for identifying biomarkers and therapeutic targets. Using single-cell RNA sequencing, we characterized the cellular and molecular dynamics of gastric epithelial tissues across disease stages: control, chronic superficial gastritis, and IM. We identified nine cell types, predominantly epithelial cells, that exhibited increased proliferation with disease progression, suggesting their role in early gastric carcinogenesis. Notably, the regulatory gene TFF3 was significantly upregulated in IM-associated goblet cells (log2FC>1.5, adjusted p-value <0.001) and correlated strongly with disease advancement. Kyoto Encyclopedia of Genes and Genomes analysis revealed the role of the mitogen-activated protein kinase signaling pathway in early gastric cancer, and copy number variation analysis showed a rise in copy number variations, especially in epithelial cells within the chronic superficial gastritis and IM groups. These findings suggest that TFF3 may drive the early stages of gastric cancer, although the precise regulatory mechanisms involved remain to be fully elucidated. Additionally, this research may provide valuable insights into the mechanisms underlying other precancerous lesions and related malignancies.

Steamed garlic attenuates ulcerative colitis in mice by modulating the MAPK signaling pathway and improving intestinal homeostasis.

Leaf color is an important trait for the quality and ornamental value of turfgrass. As an essential component of chlorophyll molecules and related pigments, nitrogen is pivotal for leaf coloration. However, the mechanisms underlying nitrogen-mediated leaf color regulation in perennial turfgrass species remain unclear. In this study, we demonstrate that mitogen-activated protein kinase 6 (LpMPK6) regulates leaf color in perennial ryegrass by phosphorylating LpMYBR1. LpMPK6 overexpression (OE) plants showed leaf chlorosis under soil conditions without nutrient supplementation or in low-nitrogen hydroponic cultivation, accompanied by reduced chlorophyll and nitrogen content. Conversely, LpMPK6 RNAi lines maintained less chlorotic leaves and higher levels of chlorophyll and nitrogen under nitrogen-deficient conditions. Yeast two-hybrid, pull-down, co-immunoprecipitation, and luciferase complementation imaging indicated that LpMPK6 interacted with transcription factor LpMYBR1. Phenotypic analysis revealed that LpMYBR1 functionally antagonized LpMPK6, with more chlorotic leaves and lower levels of chlorophyll and nitrogen in LpMYBR1 RNAi lines, whereas LpMYBR1 OE plants retained more green leaves under nitrogen-deficient conditions. DNA affinity purification, yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase assays demonstrated that LpMYBR1 bound to the promoter of LpNRT1.5 and activated its transcription. Furthermore, LpNRT1.5 regulated leaf color by mediating NO3 - root-to-shoot transport. Notably, LpMPK6 negatively regulated this transport process by phosphorylating LpMYBR1 and suppressing its transactivation of LpNRT1.5. Taken together, our results revealed a mechanism whereby LpMPK6 suppresses LpMYBR1-mediated transcriptional activation of LpNRT1.5 via phosphorylation, thereby regulating NO3 - transport and leaf coloration in perennial ryegrass. These findings provide insights and offer candidate genes for turfgrass quality improvement.

Zearalenone (ZEA), a mycotoxin produced in moldy feed, induces oxidative damage in testicular cells of male animals. These cells are crucial for androgen secretion and male reproductive health. Consequently, identifying effective and safe treatments to maintain testicular redox balance and ensure male animal fertility is imperative. Crocin, a natural compound with recognized antioxidant properties, shows promise; however, its mechanism for mitigating ZEA-induced testicular oxidative injury remains unclear. To elucidate crocin's action on oxidative stress and apoptosis in swine testicular (ST) cells, we treated cells with crocin after establishing a ZEA-induced oxidative stress model. Compared to ZEA treatment alone, crocin significantly ameliorated oxidative stress by inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) elevation, while promoting the activity/levels of catalase (CAT), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD). Furthermore, crocin effectively alleviated ZEA-induced apoptosis by attenuating mitochondrial membrane potential (MMP) depolarization, reducing the apoptosis rate, suppressing the expression of key apoptotic genes caspase 3 (CASP3) and caspase 9 (CASP9), and improving ZEA-induced G1 phase cell cycle arrest. Mechanistically, crocin mitigated oxidative damage at both mRNA and protein levels by restoring the homeostasis of the nuclear factor erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinase (MAPK) signaling pathways, which were dysregulated by ZEA. In conclusion, crocin protects ST cells against ZEA-induced oxidative damage by reducing oxidative stress markers, alleviating ZEA-induced dysregulation of the Nrf2 and MAPK pathways, preventing apoptotic damage, and enhancing cellular antioxidant capacity. This study provides theoretical support for developing crocin as a potential feed additive to prevent oxidative damage to the boar reproductive system.

The family with sequence similarity (FAM) gene family links pathological mechanisms of male infertility and oncogenesis. This review focuses on five key FAM members (FAM71D, FAM46C, FAM170A, FAM83D, and FAM172A), which were selected based on: clinical relevance (FAM83D as a breast cancer prognostic biomarker, hazard ratio, 1.29, p<0.05; FAM71D homozygous mutation c.440G>A associated with asthenoteratospermia); adequate experimental validation (in vitro assays, in vivo models, and clinical samples-for example, FAM170A knockout mice exhibit male infertility, with reduced transcription observed in patients); and recent impact (≥30 PubMed-indexed studies within 5 years and clearly defined mechanisms). In reproduction, FAM71D maintains sperm motility via calmodulin- plasma membrane Ca2+-ATPase (PMCA)- Ca2+ signaling, FAM46C anchors the sperm head-flagellum junction, and FAM170A regulates chromatin remodeling through ubiquitin- specific protease 7 (USP7)-mediated H2B deubiquitination. In oncology, FAM83D activates mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling to drive hepatocellular carcinoma, whereas FAM172A dysregulates p38 mitogen-activated protein kinase in thyroid cancer. Translational advances include FAM83B nanodetection, the Fam20C inhibitor FL-1607 (IC50=2.1 μM), and clustered regularly interspaced short palindromic repeats (CRISPR)-corrected FAM170A. Cross-species functional divergence remains a challenge. FAM genes enable novel diagnostics and targeted therapies for reproductive and oncological care, with near-term clinical applications in personalized assisted reproductive technology and cancer precision medicine.

Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly recognized as a major global contributor to cirrhosis and hepatocellular carcinoma (HCC). However, the key regulatory molecules governing lipid metabolism dysregulation, remains incompletely understood. Clinical sample analyses, cellular models, animal models (HFHC and HFD/CCL4-induced MASH mice), and molecular biology techniques (transcriptomics, LC-MS/MS, etc.) were employed to elucidate the mechanistic of UBQLN1-mediated regulation of hepatocyte lipid accumulation in MASH and evaluates the therapeutic potential of UBQLN1-targeted interventions. The results indicated that UBQLN1 was significantly upregulated in both patients with MASH and in MASH mouse models, demonstrating a positive correlation with hepatic lipid deposition. Genetic knockdown of UBQLN1 markedly reduced hepatic steatosis, inflammatory cell infiltration, and fibrosis progression in MASH mice. Mechanistically, UBQLN1 initiated the p38 mitogen-activated protein kinase (p38 MAPK) pathway via the ubiquitin-mediated degradation of the suppressor of IKKε (SIKE) to promote lipid accumulation in hepatocytes. Furthermore, red blood cell-derived extracellular vesicles loaded with UBQLN1 siRNA (RBC-EVs@siUBQLN1) effectively mitigated lipid accumulation in hepatocytes and improved the progression of MASH in vivo. These findings establish the UBQLN1-SIKE-p38 MAPK axis as a critical regulatory pathway in MASH pathogenesis and develop an RBC-EVs-targeted delivery system for MASH therapy.

Protein 4.1R regulates CCDC26 and impacts myeloid leukemia progression.

Neuroendocrine tumour morphology and platelet derived growth factor receptor alpha expression.