Search Results (2,131)

Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-κB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), NF-κB, Inhibitor of NF-κB α (IκBα), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the IκBα/NF-κB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism. Full article

Background/Objectives: Exposure to particulate matter (PM) containing bacterial endotoxins triggers inflammation and oxidative stress in the respiratory epithelium. In this study, we investigated chitosan nanoparticle-loaded Cordyceps militaris grown on germinated Rhynchosia nulubilis (GCN) as a potential functional food-derived ingredient against PM- and lipopolysaccharide (LPS)-induced cellular damage in human lung epithelial cells. Methods: This study employed an integrative approach combining GCN analysis with bioinformatics methods using a PM- and LPS-induced pulmonary cellular inflammation model. Gene Expression Omnibus (GEO) transcriptomic datasets and Cytoscape-based network analysis were utilized to identify key hub genes and signaling pathways associated with PM- and LPS-induced pulmonary inflammation, which were subsequently validated by RT-PCR and Western blotting. Results: Nano-encapsulation significantly improved the antioxidant capacity and storage stability of the extract compared with non-encapsulated Cordyceps militaris grown on germinated Rhynchosia nulubilis (GRC). GCN markedly attenuated PM- and LPS-induced cytotoxicity and intracellular reactive oxygen species (ROS) production in a dose-dependent manner, resulting in a therapeutic index approximately 4.5-fold higher than that of GRC under PM and LPS co-exposure. Bioinformatics analysis identified inflammation-related genes and pathways associated with PM- and LPS-induced pulmonary responses, primarily enriched in tumor necrosis factor (TNF)-related inflammatory pathways, Toll-like receptor signaling, and cytokine signaling. Consistent with these findings, GCN suppressed the expression of C-X-C motif chemokine ligand 2 (CXCL-2) and tumor necrosis factor-alpha (TNF-α) mRNA and inhibited mitogen-activated protein kinase (MAPK)-mediated activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) signaling pathways in human type II alveolar epithelial cells (A549). Conclusions: Collectively, nano-encapsulation enhanced the stability and bioactivity of Cordyceps militaris-based extracts, suggesting that GCN may have potential as a functional food-derived candidate ingredient to protect airway epithelial cells against inflammation and oxidative stress induced by PM and LPS. As this study was conducted using an in vitro A549 epithelial cell model, further validation in physiologically relevant systems is needed to confirm its translational applicability. Full article

Background/Objectives: This prospective observational cohort study aimed to evaluate the influence of heated tobacco (HT) and electronic cigarettes (ECs) on bone remodeling markers such as receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), and periodontal status, at baseline and at 3 months after initial periodontal therapy. Methods: The sample comprised 236 participants (130 women, 106 men; mean age 38.96 ± 7.69 years), distributed across non-smokers (n = 72), heated tobacco/HT product users (n = 83), and electronic cigarette/EC users (n = 81). For each patient, the periodontal charting included periodontal probing depth (PPD), bleeding on probing (BOP), and clinical attachment loss (CAL). Unstimulated saliva samples were analyzed for RANKL and OPG levels. All patients underwent nonsurgical periodontal therapy (scaling and root planing). Between-group comparisons were performed using the Kruskal–Wallis test followed by Bonferroni-adjusted pairwise comparisons, while within-group changes over time were assessed using the Wilcoxon signed-rank test. To complement the primary nonparametric analyses, two-way mixed-design ANOVA and ANCOVA models adjusted for baseline values and periodontitis stage were performed as sensitivity analyses. Statistical significance was set at p < 0.05. Results: At baseline, both product user groups exhibited significantly higher PPD (p = 0.005) and CAL (p = 0.001) compared with non-smokers, with no differences between HT and EC users. Salivary RANKL levels were significantly higher in HT and EC users than in non-smokers, and OPG levels did not differ significantly. Following non-surgical periodontal therapy, all parameters improved significantly across groups (p < 0.001). At the 3-month follow-up, both product user groups maintained higher PPD (p = 0.008), CAL (p = 0.001), and salivary RANKL levels, compared with non-smoking individuals (p < 0.001). The RANKL/OPG ratio remained significantly different only for EC users compared with non-smokers (p < 0.001). Conclusions: HT and EC use were associated with differences in periodontal parameters and higher RANKL levels, while differences in the RANKL/OPG ratio were observed in EC users compared with non-smokers. Non-surgical periodontal therapy improved clinical parameters and reduced the RANKL/OPG ratio, highlighting the importance of biofilm control. Full article

Copper sulphate pentahydrate is widely used in agriculture to control bacterial and fungal diseases in various crops. Despite its extensive application, limited data exist regarding its potential toxic effects on juvenile rats following early-life exposure. In addition to oxidative stress and inflammation, copper overload may also trigger cuproptosis, a recently identified copper-dependent form of regulated cell death. This study aimed to investigate the histopathological, biochemical, and molecular effects of copper sulphate exposure on major organs in juvenile rats and to elucidate the associated inflammatory and oxidative stress-related mechanisms. Male and female Sprague–Dawley rats (30–40 days old, 50–70 g) were randomly assigned to control and experimental groups. Following copper sulphate exposure, histopathological examinations were performed on major organs, including the liver, kidney, heart, lung, and reproductive tissues (testis in males and ovary in females). Immunohistochemical analyses of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB) were conducted. Oxidative stress parameters, including malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS), were measured using ELISA. Gene expression levels of TNF-α and NF-κB were evaluated by quantitative real-time PCR (qRT-PCR). Copper sulphate exposure induced significant histopathological alterations in all examined tissues of both male and female juvenile rats. Biochemical findings revealed increased oxidative stress, evidenced by elevated MDA and TOS levels along with altered TAS values. Furthermore, immunohistochemical and gene expression analyses demonstrated upregulation of TNF-α and NF-κB, indicating activation of inflammatory pathways. Copper sulphate exposure leads to widespread morphological changes in juvenile rats, potentially mediated by oxidative stress and inflammation. These findings provide insight into the biological impact of early-life pesticide exposure. Further studies are warranted to clarify the underlying molecular mechanisms and to develop effective preventive or therapeutic approaches. Full article

Inflammaging is defined as chronic low-grade inflammation associated with aging and is increasingly recognized as a dynamic and mechanistically driven biological process rather than a state adequately described by circulating biomarkers alone. Traditional inflammatory markers alone, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive Protein (CRP), fail to capture the complexity, tissue specificity, and causal architecture of inflammaging. Recent experimental evidence has demonstrated that diverse upstream drivers, including immunosenescence, gut microbiome dysbiosis, metabolic dysfunction, and cellular senescence, converge on a limited number of central inflammatory hubs, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, GMP–AMP synthase–stimulator of interferon genes (cGAS–STING), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and p38 mitogen-activated protein kinase (p38 MAPK) signaling. These mechanistic nodes represent promising therapeutic targets, potentially modifiable biological processes, and support the emerging concept of ‘druggable inflammaging’, whereby senotherapeutics, inflammasome inhibitors, innate immune modulators, and metabolic interventions may actively modify aging-associated inflammatory biology rather than simply monitor it through biomarkers. This review highlights a paradigm shift from biomarker-based assessment toward mechanism-based intervention, where inflammaging can be characterized as a modifiable biological process and a central target for precision pharmacological strategies in aging-related diseases. Full article

The influenza A virus (IAV) has been responsible for multiple seasonal epidemics and poses a pandemic threat, and the growing number of variant strains constitutes a persistent threat to humanity. This study aimed to identify anti-influenza compounds from a traditional Chinese medicine (TCM) monomer library using a machine learning approach, with calmodulin as a hypothesis-driven target. The antiviral efficacy of the compounds with the highest predicted binding scores from virtual screening was evaluated using integrated computational and experimental approaches. A pre-trained protein language model (ConPLex) was employed for virtual screening. Molecular docking was used to predict binding characteristics, and network pharmacology was applied to generate hypotheses on multi-target mechanisms. The cytotoxicity and anti-H1N1 activity of the selected compounds were assessed in vitro, followed by in vivo evaluation of survival, lung pathology, viral load, and inflammatory mediators in a lethal mouse infection model. Sodium deoxycholate (NaDC) and deoxycholic acid (DCA) were identified as promising lead compounds. Both exhibited dose-dependent inhibition of viral replication in vitro with low cytotoxicity. Treatment with NaDC and DCA significantly improved survival rates and reduced lung pathology in H1N1-infected mice. Treatment was associated with suppression of nuclear factor kappa-B (NF-κB) activation, reduced pro-inflammatory cytokines, and elevated interleukin-10 (IL-10) levels. Molecular docking predictions indicated that NaDC and DCA exhibit moderate binding affinity for calmodulin, with binding energies of −8.38 kcal/mol and −7.61 kcal/mol, respectively. Furthermore, network pharmacology analysis suggested that these compounds may modulate pathways related to viral infection, inflammation, and immune regulation. NaDC and DCA demonstrate anti-influenza activity both in vitro and in vivo, reducing viral replication and alleviating inflammatory lung injury. These findings position NaDC and DCA as promising lead compounds for anti-influenza drug development and provide a foundation for further mechanistic validation. Full article

Juvenile intestinal ischemia–reperfusion (JII/R) is a pediatric surgical emergency caused by mesenteric vessel occlusion and has a high mortality rate. Malrotation can cause intestinal ischemia in infants due to midgut volvulus. It affects not only the intestine itself but also other organs, such as cardiac tissue. Therefore, searching for more effective therapeutic solutions is an essential critical need. This directed our thoughts to evaluate the role of ambrisentan (AMB) in a rat model of induced JII/R by clamping the superior mesenteric artery. Forty juvenile male Wistar albino rats (3–4 weeks old) were randomly divided into four experimental groups: control (CON) group, JII/R group, and AMB-treated groups (30, 60 mg/kg) with JII/R. Induction of JII/R results in significant changes in cardiac enzymes, oxidative stress, inflammatory, and apoptotic parameters with high expression of endothelin receptor A (ERA). Also, histopathological changes revealed extensive mucosal damage, loss of intestinal villi, dysregulated and degenerated cardiac fibers with inflammatory cell infiltration, and tissue necrosis. In contrast, AMB administration significantly reduced the elevated levels of cardiac enzymes, malondialdehyde (MDA), nuclear factor kappa B (NF-κB), ERA, and caspase-3 expression. However, AMB treatment increased immune expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), Ki-67, and mammalian target of rapamycin (mTOR) and showed remarkable improvement in the histopathological changes. AMB could be considered as an adjuvant medical treatment for cases of JII/R. Full article

Chronic low-grade inflammation is a hallmark of aging and a major driver of metabolic and degenerative diseases. While systemic immune dysfunction has been widely investigated, the contribution of barrier tissues to persistent inflammatory signaling remains incompletely defined. The oral mucosa represents a uniquely exposed barrier, continuously challenged by microbial, mechanical, and metabolic stressors and characterized by a specialized immune architecture. Here, we synthesize current evidence supporting the oral barrier as an active immunometabolic interface linking local immune activation to systemic inflammatory tone. Spatially organized epithelial, neutrophil, and antigen-presenting cell (APC) compartments coordinate immune responses tightly coupled to metabolic reprogramming, including hypoxia-inducible factor-1α (HIF-1α)-dependent glycolysis and mitochondrial reactive oxygen species (mtROS) production. In parallel, the oral microbiota provides ligands and metabolites such as lipopolysaccharide (LPS), short-chain fatty acids (SCFAs), and succinate, which activate pattern-recognition receptors (PRRs), including toll-like receptors (TLRs) and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, thereby sustaining nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-mediated inflammatory signaling. Barrier disruption and dysbiosis promote microbial translocation and persistent innate immune activation, while saliva and gingival crevicular fluid facilitate systemic dissemination of inflammatory mediators. Overall, sustained immunometabolic engagement at the oral barrier emerges as a key driver of chronic low-grade systemic inflammation and a potential therapeutic target in inflammaging. Full article

Associated with high morbidity and mortality, cisplatin-induced acute kidney injury (AKI) is a common clinical complication characterized by oxidative stress, inflammation, and mitochondria-associated signaling. Although multiple signaling pathways have been implicated in AKI progression, effective interventions targeting these complex mechanisms are still lacking. As a medicinal fungus with antioxidant and anti-inflammatory properties, Schizophyllum commune (SC) has shown potential biological activities; however, its renoprotective effects in cisplatin-induced AKI remain unclear. Therefore, this study aimed to investigate SC’s protective effects and underlying mechanisms in a cisplatin-induced AKI mouse model. SC treatment improved renal function and attenuated histopathological damage. It reduced oxidative stress and inflammatory responses, as evidenced by the modulation of malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), and pro-inflammatory cytokines. Mechanistically, SC regulated multiple signaling pathways, including mitogen-activated protein kinase (MAPK), toll-like receptor 4/nuclear factor kappa B (TLR4/ NF-κB), PI3K/AKT, nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), and the calcium/calmodulin-dependent protein kinase kinase–AMP-activated protein kinase–sirtuin 1 (CaMKK–AMPK–Sirt1) axis. In addition, SC modulated apoptosis, autophagy, and PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy, suggesting improved mitochondrial homeostasis. These findings indicate that SC exerts renoprotective effects and may contribute to cisplatin-induced nephrotoxicity mitigation strategies. Full article

Background: Progesterone (P4) is used as an antiseizure medication (ASM) to treat catamenial epilepsy, refractory to first-line drugs. P4 and other neurosteroids (NSs) are important regulators of multiple nervous system functions, including neuronal excitability and synaptic plasticity. In addition to their antiseizure properties, P4 and other NSs are also anti-inflammatory agents. Neuroinflammation is an important pathophysiological mechanism of epilepsy refractory to ASMs. Accordingly, we evaluated the ability of P4 to modulate neuroinflammation, using human microglia activated by lipopolysaccharide (LPS). Methods: Human microglia (HMC3) were stimulated for 3 h with LPS in the absence or presence of various concentrations of P4. Thereafter, levels of (i) toll-like receptor 4 (TLR4), (ii) the NLRP3 inflammasome, and (iii) pro-inflammatory cytokines were quantitated by real-time PCR and Western blot analyses. Phagocytic activity was also assessed using a phagocytosis assay employing fluorescent beads. Results: P4 treatment significantly reduced the microglial inflammatory state induced by LPS, which was mediated by upregulation of the TLR4- and NLRP3-axes. The protective effects of P4 were mediated by inhibition of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NFκB) phosphorylation and reduced activation of Mitogen-Activated Protein Kinases (MAPK). The effects of P4 included a significant reduction in mRNA levels of the main pro-inflammatory cytokines and a reduction in phagocytic activity of HMC3. Conclusions: P4 is endowed with significant anti-inflammatory properties, which may be involved in the beneficial effects reported for drug-resistant catamenial epilepsy. Further research is required to clarify P4 post-receptor mechanisms of action and to explore the roles of other P4-derived NSs. Full article

GLP-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes and obesity and are increasingly relevant in periodontal and implant practice. This review covers mechanisms, preclinical and early human evidence, and practical periodontal considerations; the structured database search is conducted in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) and the International Committee of Medical Journal Editors (ICMJE) principles. Two pathways explain GLP-1RAs’ relevance: indirect effects from better glycemic control, weight loss, and reduced inflammation; and direct tissue effects involving GLP-1R signaling and the GLP-1/dipeptidyl peptidase-4 (DPP-4) axis. Preclinical studies show reduced inflammation, osteoclast activity, and alveolar bone loss, along with improved periodontal stem cell function under hyperglycemia or inflammation via Nuclear Factor-kappaB (NF-kappaB), Wingless-related integration site (Wnt)/beta-catenin, and Mitogen-Activated Protein Kinase (MAPK) pathways. Animal studies on implants and local delivery, including exendin-4 platforms, suggest osteometabolic benefits. Human data are limited and mostly observational, and confounders include metabolic status, smoking, medication, and nutrition. Oral side effects such as xerostomia and dehydration are also noted. At present, GLP-1RA therapy should be regarded as a contextual modifier of periodontal risk and healing capacity rather than as a stand-alone periodontal therapy. Full article

Osteoarthritis (OA) is a highly prevalent joint disorder traditionally considered a consequence of mechanical cartilage wear; however, it is now recognized as a complex, multifactorial disease driven by interconnected molecular and cellular mechanisms. This narrative review synthesizes current knowledge on key pathogenic pathways underlying OA progression, with a focus on inflammatory signaling, subchondral bone remodeling, and dysregulation of mineral metabolism. Chronic low-grade inflammation promotes catabolic responses in chondrocytes and contributes to cartilage degradation. In addition, obesity influences OA pathogenesis through both biomechanical loading and adipokine-mediated inflammatory mechanisms. Alterations in the receptor activator of nuclear factor kappa-B/receptor activator of nuclear factor kappa-B ligand/osteoprotegerin (RANK/RANKL/OPG) axis disrupt bone homeostasis and promote pathological subchondral remodeling, while imbalances in inorganic phosphate metabolism contribute to crystal deposition and further joint damage. These processes interact synergistically, driving disease progression. Current therapeutic strategies remain largely symptomatic and do not adequately target underlying molecular drivers. A deeper understanding of these mechanisms may facilitate the development of disease-modifying therapies. Full article

Background: Polygonum cuspidatum (Hu Zhang) is a polyphenol-rich botanical in which resveratrol occurs at low levels mainly as polydatin. In this study, we generated a microbially converted P. cuspidatum extract (CPE) with markedly enriched resveratrol content from the unconverted P. cuspidatum extract (PE), and evaluated its anticancer efficacy and safety in comparison with those of the unconverted extract. Methods: High-performance liquid chromatography (HPLC), A549 cell-based assays, an A549 xenograft model, and a 28-day repeated-dose rat study were performed. Results: HPLC showed near-complete depletion of polydatin, marked enrichment of resveratrol, and a modest reduction in emodin. CPE more effectively inhibited A549 cell proliferation and migration than PE, suppressed NLRP3 inflammasome and nuclear factor kappa B (NFκB) signaling, and promoted reactive oxygen species (ROS) accumulation and mitochondrial apoptosis. Oral CPE also significantly reduced tumor growth in an A549 xenograft model. In a 28-day repeated-dose rat study, no treatment-related abnormalities were observed in blood biochemistry or histopathology. Conclusions: These findings support CPE as a promising functional food ingredient. Full article

Food-derived bioactive peptides have become a research hotspot in diabetes nutritional intervention due to their high safety, wide availability, and multi-target activities. This review addresses this by proposing a systems biology integration framework that defines these peptides as pleiotropic regulators of the gut microbiota-immune inflammation-metabolic signaling network, offering a novel systems-level perspective beyond previous reviews focused on single enzymes or pathways. The framework consists of three synergistic tiers. Tier 1 inhibits α-amylase, α-glucosidase or dipeptidyl peptidase-IV (DPP-IV) to control postprandial blood glucose. Tier 2 corrects insulin resistance by modulating phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), activating nuclear factor erythroid 2-related factor 2 (Nrf2), and suppressing nuclear factor kappa-B (NF-κB). Tier 3 uses the gut as a hub to remotely coordinate metabolism via the gut–liver and gut–pancreas axes. The review also systematically summarizes the major sources and preparation methods of food-derived antidiabetic peptides, analyzes their advantages including multi-target network regulation, safety, and sustainability, as well as challenges such as oral bioavailability, insufficient clinical evidence, processing stability, and regulatory hurdles. Finally, it outlines future directions focusing on three actionable priorities: AI-assisted design, oral delivery systems, and high-quality clinical studies. This framework offers a new perspective for applying food-derived peptides in precision nutrition intervention for diabetes. Full article

Dendrobium officinale has attracted increasing attention as a functional food because of its diverse biological activities; however, the photoprotective potential of its protein-derived peptides remains poorly understood. In this study, D. officinale protein hydrolysates were fractionated by ultrafiltration according to molecular weight, and their protective effects against ultraviolet B (UVB)-induced photoaging were systematically evaluated in HaCaT keratinocytes. Among the tested fractions, low-molecular-weight peptide fractions exhibited relatively stronger antioxidant activity and effectively reduced intracellular reactive oxygen species (ROS) accumulation in UVB-irradiated cells. In addition, the peptide fractions alleviated UVB-induced inflammatory responses and decreased matrix metalloproteinase (MMP) expression, which was associated with modulation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Higher-molecular-weight fractions showed relatively stronger effects on maintaining skin barrier-related functions and were associated with regulation of transforming growth factor-β/Smad (TGF-β/Smad) signaling and collagen-related protein expression. Overall, these findings demonstrate functional differences among Dendrobium officinale peptide fractions and suggest their potential application as natural photoprotective ingredients in functional foods and cosmeceutical products. Full article