Search Results (11,350)

This study evaluated the effects of supplementing Alpinia katsumadai and Wurfbainia vera extracts on the growth performance, antioxidant capacity, intestinal metabolites, and microbiota of Danzhou chickens. Using Danzhou broilers, we examined the individual or combined inclusion of Alpinia katsumadai and Wurfbainia vera extracts in a 2 × 2 factorial layout. Four hundred and eighty female dual-purpose chickens were randomly assigned to four treatments (six replicates of 20 chicks each): control basal diet (CON), basal + 600 mg kg⁻¹Alpinia katsumadai (T1), basal + 600 mg kg⁻¹ Wurfbainia vera (T2), or basal + 600 mg kg⁻¹ Alpinia katsumadai + 600 mg kg⁻¹ Wurfbainia vera (T3). All treatments differed significantly from CON. For intestinal morphology, T1, T2, and T3 increased jejunal villus height and villus-to-crypt ratio while reducing crypt depth. T1 exceeded CON (p < 0.05), and an interaction was detected. T1 raised the abundances of Bacteroidota, Bifidobacterium, Tidjanibacter, and Phocaeicola relative to CON (p < 0.05). T3 exhibited higher activities of glutathione peroxidase and catalase than CON, T2, and T1 (p < 0.05). Metabolomically, T1, T2, and T3 elevated intestinal Menaquinone-9, lecithin, and L-galactono-1,5-lactone versus CON (p < 0.05). T3 lowered 3-(R)-Hydroxyoctadecadienoic acid and 9-(R)-Hydroxyoctadecadienoic acid versus CON and T1, and increased eugenol versus CON (p < 0.05). Overall, T1 and T2, especially in combination, enhance antioxidant capacity, improve gut morphology, promote beneficial microbiota and activate health-related metabolic pathways in Danzhou broilers. Full article

Diabetic cardiomyopathy (DCM) is a distinct myocardial disorder that develops independently of coronary artery disease and hypertension and represents a major contributor to heart failure in patients with diabetes. Beyond hemodynamic alterations, DCM is driven by complex molecular mechanisms involving metabolic dysregulation, mitochondrial dysfunction, inflammation, and fibrotic remodeling. Increasing evidence identifies oxidative stress as a central integrative process linking these pathogenic pathways in the diabetic heart. Chronic hyperglycemia, insulin resistance, and altered substrate utilization promote excessive generation of reactive oxygen species, overwhelming endogenous antioxidant defenses and disrupting myocardial redox homeostasis. Oxidative stress induces direct damage to lipids, proteins, and DNA while simultaneously activating redox-sensitive signaling pathways that amplify inflammation, endothelial dysfunction, cardiomyocyte apoptosis, and fibrosis. In addition, epicardial and visceral adipose tissue have emerged as active contributors to myocardial oxidative stress through paracrine and systemic mechanisms, reinforcing inflammatory and fibrotic crosstalk. This review provides a comprehensive overview of the molecular sources and targets of oxidative damage in DCM, examines the impairment of antioxidant defense systems, and discusses emerging therapeutic strategies aimed at restoring redox balance. Full article

7-ketocholesterol (7-KC) is a bioactive oxysterol generated under oxidative stress and may contribute to bone marrow niche reprogramming in acute myeloid leukemia (AML), thereby promoting stress tolerance and therapeutic resistance Bone marrow mesenchymal stromal cells (MSCs) from healthy donors and AML patients were exposed to subtoxic 7-KC concentrations for 24 h. We evaluated the ABC transporters involved in lipid transport, multidrug resistance and membrane microdomain remodeling; Hedgehog pathway proteins; stress–survival signaling; redox balance by glutathione measurements, and mitochondrial function and dynamics, including membrane potential and gene expression of mitochondrial fission and fusion regulators. Results were integrated using principal component analysis (PCA), heatmaps, and correlation-based networks. Multivariate analyses revealed an integrated, lineage-dependent response. Healthy donor MSCs showed greater plasticity of the efflux and microdomain axis and higher oxidative and mitochondrial vulnerability at high 7-KC doses. AML-MSCs exhibited a basal preconditioned state phenotype and preferentially routed the response toward Hedgehog and stress–survival modules, accompanied by glutathione expansion and adaptive mitochondrial remodeling. 7-KC acts as a broad modulator of several MSC functions, linking sterol homeostasis to Hedgehog signaling, stress–survival pathways, redox balance, and mitochondrial remodeling, potentially supporting a pro-survival, more therapy-tolerant leukemic niche. Full article

Chromatin remodelers play essential roles in modulating nucleosome structure and enabling dynamic transcriptional control. Arabidopsis calmodulin-binding transcription activators CAMTA1/2/3 negatively regulate plant immunity by suppressing the expression of biosynthesis genes of major defence hormones salicylic acid (SA) and N-hydroxy-pipecolic acid (NHP). The autoimmunity of the camta2/3 mutant is partially suppressed by loss of the NHP biosynthesis enzyme SAR deficient 4 (SARD4). During a forward genetic screen with the mildly autoimmune camta2/3 sard4 mutant, we identified chromatin-remodelling factor 5 (chr5) as its partial suppressor. The chr5 single mutants displayed decreased SA biosynthesis and compromised basal immunity. Further RNA-sequencing with chr5 defined immune-related genes that were downregulated in the mutants, including those involved in SA and NHP biosynthesis and signalling, PTI and ETI pathways. Our analysis highlights the roles of CHR5 in immune-specific chromatin remodelling events, contributing to transcriptional reprogramming during plant defence responses. Full article

Vein graft disease remains a significant limitation to the long-term patency of venous conduits following coronary artery bypass grafting. Early oxidative stress, triggered by ischaemia–reperfusion injury and haemodynamic changes following the implantation of veins into the arterial circulation, disrupts endothelial integrity and initiates inflammation, apoptosis, and maladaptive remodelling. The KEAP1-NRF2 axis is a central regulator of cellular antioxidant responses; however, its role in the development of vein graft disease remains poorly defined. This narrative review aimed to summarise what is known about NRF2/KEAP1 signalling in modulating vein graft pathology. Methods: A systematic search of PubMed was conducted to identify original research studies examining the NRF2/KEAP1 pathway in human saphenous vein tissue in vivo or ex vivo. Narrative synthesis was performed due to limited evidential availability and study heterogeneity. Results: Only one study has directly evaluated NRF2 pathway activation directly in human saphenous vein tissue, and it demonstrated that Protandim (a herbal dietary supplement) treatment increased antioxidant enzyme activity and reduced oxidative stress markers, including superoxide and 4-hydroxynonenal, both known activators of MAPK-dependent smooth muscle proliferation. Adjacent studies in other cells and tissues reveal that NRF2 intersects with multiple pathways central to vein graft pathology: it suppresses NFκB-mediated inflammation, modulates eNOS-NO signalling, inhibits NADPH oxidase expression, regulates MAPK activation, and influences angiogenic responses. However, context-dependent activation of NRF2 under arterial cyclic stretch can paradoxically drive proliferation through p62-mediated KEAP1 sequestration and enhanced glutathione synthesis. Conclusions: The NRF2/KEAP1 pathway serves as a central integrator of oxidative stress responses that directly intersect with established mechanisms of intimal hyperplasia and pathological angiogenesis. Post-translational KEAP1 inhibition may offer a targeted intervention point to limit these processes. Critical gaps remain regarding our understanding of the role of NRF2 in human saphenous vein under physiological arterial conditions and sex-specific pathway regulation. Mechanistic studies in vein-specific models are essential for advancing our understanding and any potential therapeutic translation. Full article

Atrioventricular valves prevent the backward flow of blood from the ventricles to the atria and are essential for the efficient pumping of blood throughout the body. Errors in development can lead to congenital atrioventricular valve disease. Atrioventricular valve formation is a multi-step process that involves endocardial cushion formation, valve progenitor cell proliferation, valve sinus formation, valve elongation, and extracellular matrix remodeling. Increasing evidence suggests that hemodynamic cues are required across multiple steps. Here, we compare atrioventricular valve formation in different in vivo models and review how biomechanical forces regulate atrioventricular valve formation. Full article

Cytokines are central regulators of inflammation and immune responses within the tumor microenvironment and have been implicated in cancer progression and prognosis. However, the prognostic value of coordinated cytokine-related transcriptional programs across cancer types has not been systematically explored. Pan-cancer transcriptomic and clinical data were analyzed to construct a cytokine-related prognostic signature using least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were stratified into high-risk and low-risk groups based on the derived risk score. Prognostic performance was evaluated in training and test cohorts, and biological relevance was assessed through survival analyses and pathway-level investigations. A 16-gene cytokine-related signature was established that consistently stratified patients into distinct prognostic groups across multiple cancer types. High cytokine-related risk scores were significantly associated with unfavorable survival outcomes and were linked to enhanced cell cycle activity, epithelial-mesenchymal transition, and extracellular matrix remodeling. Integration of the risk score with clinical variables improved individualized survival prediction. Immunohistochemical analyses further confirmed increased protein expression of representative risk-associated genes, including pannexin 1 (PANX1) and FERM domain containing 8 (FRMD8), in multiple tumor tissues compared with corresponding normal tissues. The cytokine-related prognostic signature captures key inflammatory and immune-related programs underlying tumor aggressiveness and provides a robust tool for pan-cancer risk stratification with potential clinical utility. Full article

Background: As the body’s first line of defense against environmental stressors, the skin is highly susceptible to UVB-induced damage, which triggers inflammation and impairs barrier function. This study investigates the protective effects of safflower seed oil (SSO) and fermented Artemisia annua oil (FAAO) against UVB-induced skin injury. Methods: The protective effects of SSO and FAO against UVB irradiation was first tested in HaCaT keratinocyte. Subsequently, a UVB-irradiated SKH-1 mouse model was established to evaluate these two oils. RNA-seq analysis was employed to investigate the potential molecular mechanisms by which SSO and FAO repair the skin barrier. Results: In vitro experiments demonstrated that SSO (0.25%) and FAAO (0.1%) significantly enhanced HaCaT keratinocyte viability following UVB exposure while selectively modulating pro-inflammatory cytokine production. In a UVB-irradiated SKH-1 mouse model, standalone SSO or FAAO treatment partially ameliorated epidermal hyperplasia and restored UV-reduced collagen content, while the 1:1 SSO/FAAO combination exhibited superior efficacy in restoring skin architecture, reducing erythema and edema, and suppressing immune cell infiltration. Transcriptomic profiling revealed that the combined treatment promoted structural repair by attenuating inflammatory responses and preserving extracellular matrix homeostasis. Conclusions: Together, these findings underscore the potential of SSO/FAAO as a multifunctional botanical intervention for mitigating UVB-induced cutaneous damage. Full article

Surgical resection remains a cornerstone in the multidisciplinary management of central nervous system (CNS) tumors, particularly diffuse gliomas. Traditionally, the role of surgery has been evaluated primarily through quantitative metrics such as extent of resection and its association with survival outcomes. However, despite maximal and radiologically complete resections, recurrence remains nearly universal in malignant CNS tumors, suggesting that surgical cytoreduction alone does not fully account for post-surgical disease dynamics. Emerging biological and molecular evidence indicates that surgery represents not merely a technical intervention, but a biologically active event that profoundly reshapes tumor evolution and treatment response. In this review, we propose a conceptual framework that redefines surgery as a key biological driver in CNS tumor progression. We synthesize evidence demonstrating that surgical trauma induces inflammation, hypoxia, vascular remodeling, immune modulation, and extracellular matrix reorganization, collectively reprogramming the residual tumor microenvironment. These changes create selective pressures that favor the survival and expansion of adaptive tumor cell subpopulations, including invasive and stem-like phenotypes. From an evolutionary perspective, surgical resection functions as an acute selective bottleneck acting on heterogeneous tumor ecosystems, contributing to clonal selection and molecular divergence at recurrence. We further examine the dissociation between surgical (anatomical) margins and molecular (biological) margins, highlighting how biologically active tumor cells infiltrate beyond radiologically defined boundaries. This discrepancy provides a biological explanation for marginal and distant recurrences and challenges anatomy-based paradigms of surgical completeness. Importantly, we discuss how surgery-induced biological changes influence postoperative radiotherapy and systemic therapies, affecting radiosensitivity, target delineation, and therapeutic vulnerability. Finally, we outline future directions toward surgery-integrated precision neuro-oncology, emphasizing the potential of spatial profiling, liquid biopsy, advanced imaging, and artificial intelligence to capture perioperative tumor evolution. By reframing surgery as a biological inflection point rather than a neutral prelude to adjuvant treatment, this review advocates for a dynamic, biology-driven continuum of care aimed at anticipating tumor adaptation and improving long-term disease control in CNS tumors. Full article

The gut–skin axis is increasingly implicated in psoriasis pathogenesis, yet the cross-compartment convergence of molecular programs remains incompletely defined. We constructed a conceptual “Triple-Hit” multi-omics framework by integrating five independent public datasets spanning gut microbial functional remodeling (shotgun metagenomics), systemic immune cell methylomes (PBMC and CD8+ T-cell EPIC 850K), and lesional skin regulatory layers (miRNA and bulk RNA-seq). In the gut compartment, functional profiles exhibited a selective reduction in microbial lipid catabolic potential, including decreased fatty acid degradation and a lowered composite lipid degradation score, alongside heterogeneous shifts across SCFA-associated metabolic pathways. Systemically, PBMC methylomes revealed widespread regional remodeling (45,396 DMRs) enriched for membrane-proximal signaling and cytoskeletal programs, while CD8+ T cells showed specific epigenetic alterations in lipid- and glycosphingolipid-associated loci, suggesting a systemic metabolic–epigenetic alignment. In the skin, we identified a compact miRNA signature (168 DE-miRNAs) and a mechanistically interpretable, directionality-constrained miRNA–mRNA bridge that aligns with an AMP-dominant inflammatory transcriptome, consistent with reduced post-transcriptional restraint. Collectively, these findings support a convergent multi-omics framework linking putative microbial metabolic remodeling, systemic immune priming, and cutaneous effector programs. This study provides a systems-level perspective on psoriasis pathogenesis, highlighting the metabolic–epigenetic–transcriptional convergence as a potential avenue for therapeutic intervention. Full article

Background/Objectives: Acute exercise remodels many interconnected biochemical pathways in metabolically active tissues. This remodeling involves the activation of the energy-sensing AMP-activated protein kinase (AMPK) to maintain cellular energy homeostasis. Critical energy reserves of glycogen, primarily stored in liver and skeletal muscle and known to interact with AMPK, are utilized to help meet increased energy demands with exercise. However, the breadth of metabolic pathways regulated by acute exercise and AMPK’s interactive roles with glycogen remain incompletely understood. This study therefore aimed to map mouse liver and skeletal muscle metabolite responses to continuous acute exercise and disruption of AMPK-glycogen interactions. Methods: Liquid chromatography–mass spectrometry-based untargeted metabolomics was used to measure the relative abundance of liver and gastrocnemius muscle metabolites at rest and following an acute bout of continuous treadmill running in wild type (WT) and AMPK transgenic mice with double knock-in (DKI) mutations in the β subunit carbohydrate binding module that mediates glycogen binding. Results: Over 200 total metabolites were identified/annotated across liver and skeletal muscle, including 45 metabolites responsive to exercise (p < 0.05; FDR < 0.1). Exercise-regulated metabolites included known metabolic pathways and metabolites never associated or with only emerging evidence related to exercise (e.g., ergothioneine) and/or AMPK-glycogen interactions (N6,N6,N6-trimethyl-L-lysine, a precursor of L-carnitine). Conclusions: Liver and skeletal muscle metabolomic profiles displayed shifts between WT and DKI mice at rest, with shifts also detected following a continuous acute exercise bout. An interaction effect was also observed in skeletal muscle, suggesting differential muscle metabolite responses to acute exercise in DKI mice that may contribute to their functional impairments in metabolic control and exercise capacity versus WT. Collectively, these findings expand the molecular landscape of acute exercise and reveal liver and muscle metabolites underlying exercise-induced metabolic responses. Full article

The widespread presence of microplastics (MPs), heavy metals, and herbicide residues in agricultural soil raises concerns about their combined effects on soil microorganisms. This study examined the combined impact of Zn(II)/Cu(II), low-density polyethylene (LDPE), and metolachlor (MET) on Trichoderma harzianum IM 7002, a strain isolated from heavily polluted soil in central Poland. Exposure to LDPE and MET alone reduced fungal growth and induced oxidative stress, whereas Zn(II) at a concentration of 5 mM and Cu(II) at a concentration of 2.5 mM stimulated growth and enhanced MET degradation. HPLC MS/MS analysis identified transformation products, confirming active degradation even under co-exposure to LDPE and metals. Notably, simultaneous exposure to MET, LDPE, and Cu(II) (5 mM) increased antioxidant enzyme activity and decreased lipid peroxidation, suggesting a strengthened antioxidant defense and/or partial utilization of reactive oxygen species during MET biotransformation. Pollutant mixtures also caused quantitative shifts in membrane phospholipid composition and a slight increase in membrane permeability, indicating both toxic effects and adaptive membrane remodeling in response to chemical stress. Overall, T. harzianum IM 7002 exhibited high tolerance to complex pollutant mixtures while maintaining herbicide-degradation capacity, highlighting its potential for remediation of contaminated agricultural soils. Full article

Introduction: Understanding superficial epigastric vessel anatomy is crucial for abdominal surgeries like laparoscopy, especially in neonates, to prevent injury. While standard courses are described, variations occur. This case report highlights a unique anatomical variation in the superficial epigastric artery found during the dissection of a stillborn neonatal cadaver. Case Report: In contrast to the usual origin from the femoral artery, this variation features the inferior epigastric artery penetrating the anterior abdominal wall near the umbilicus and branching superiorly to supply the superficial abdominal wall. Conclusions: This distinctive vascular configuration, which to the best of our knowledge has not been previously described in neonatal anatomical literature, diverges from the typical symmetrical arrangement and previously reported variations. The study stresses the clinical importance of this finding, especially for laparoscopic procedures in neonates. During trocar placement, surgeons should be cognizant of such variations to reduce the risk of iatrogenic injuries, including rectus sheath hematoma. The report highlights the need for further investigation to establish the prevalence of this variation and its potential effects on surgical safety and outcomes in a broader neonatal population, which may also reflect the dynamic vascular remodeling that occurs during early developmental stages. Full article

Right ventricular pressure overloading [RVPO] with secondary maladaptive RV remodeling and progressive myocardial dysfunction in patients with pulmonary hypertension associated with left-sided heart diseases [PH-LHDs] and in those with pulmonary arterial hypertension [PAH] still remains one of the most complex challenges in cardio-pulmonary medicine. Despite the advances in the optimization of diagnostic tools and the expansion of treatment options, there is still a great need for further research to gain a better understanding of the major pathophysiological mechanisms involved in both the RV responses to PO and to find new possibilities to stop the progression of the alterations inside the pulmonary arterial circulation [PAC]. This article summarizes current knowledge about the particularities of the RV structural and functional responses to abnormal PO and also provides an overview of the benefits and limitations of the currently available tools for clinical evaluations of the RV adaptability to high afterload. A major focus of this review relates to the possibilities for obtaining evidence about the existence of a still remaining adaptability to a normal afterload in an over-burdened RV, in case of abolition of the pathological PO and, in this regard, to also evaluate the clinical usefulness of the RV adaptability estimation for certain critical therapeutic decisions. Among the most important conclusions of this updated overview are: 1. Whereas single parameters are insufficiently reliable for the evaluation of RV dysfunction and for predictions of its prognostic relevance across the whole spectrum of RVPO, properly selected and integrated multiparametric approaches had meanwhile unequivocally proved that they can usually become sufficiently reliable. 2. Multiparametric approaches can substantially improve the prediction of a preserved RV responsiveness to the abolition of its steady PO by reversal of RV maladaptive remodeling and by the normalization of RV pump function. Such a prediction, which can be decisive for therapeutic decision-making especially in candidates for ventricular assist device [LVAD] implantation or thoracic organ transplantation, can have a crucial impact on patient survival. 3. The complex and temporally highly variable interactions between certain structural and functional changes in both the PAC and in the hemodynamic overloaded right-sided heart, as well as between the two ventricles, can often hamper the interpretation of certain changes in the measured parameters and even relevantly alter their reliability. Additionally, the progressive aggravation of a secondary tricuspid regurgitation [TR] has a particularly high negative (often also misleading) impact on the diagnostic and prognostic relevance of RVPO evaluations. Full article

Osteoarthritis (OA) is a multifactorial disease characterized by inflammation, extracellular matrix remodeling, and joint degeneration, and it still lacks disease-modifying treatments. Here, we applied an ex vivo OA model based on transwell co-cultures of cartilage and synovial membrane explants harvested from OA patients to compare the effects of adipose-derived stem/stromal cell (ASC) conditioned medium (CM) with dexamethasone (DEX), a clinically used corticosteroid. Explants were treated for 48 h with 100 nM DEX, CM derived from 5 × 10⁵ ASCs, or left untreated. Outcomes included gene and protein expression of key mediators, metalloprotease and aggrecanase activities, and nitric oxide release. DEX significantly reduced inflammatory markers (e.g., PTGS, IL-1β, and IDO) and VEGF expression in both tissues, while CM did not elicit consistent anti-inflammatory effects. Regarding matrix remodeling, both treatments reduced metalloprotease activity, with DEX modulating MMP3 and MMP13 expression in both tissues and CM reducing only MMP3 expression in cartilage while presenting high levels of TIMP-1. These results confirm the robustness of the model, demonstrated by reproducible responses to DEX and its high-throughput potential, and underscore the need for mechanistic studies to optimize novel biotherapeutics. Full article