Search Results (27,764)

Background/Objectives: High-altitude pulmonary edema (HAPE) remains a serious condition with limited preventive options. This study evaluated the prophylactic protective effects of nebulized human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in a rat model of hypobaric hypoxia-induced lung injury and explored potential mechanistic clues, with a focus on oxidative stress and TEK/Tie2 signaling. Methods: Rats were exposed to hypobaric hypoxia (47 kPa; 9.7% O₂) for 72 h and received prophylactic nebulized hUC-MSC-EVs (300 μg/rat). Lung injury was evaluated by histopathology, wet-to-dry ratio, and bronchoalveolar lavage fluid (BALF) protein concentration. Invasive pulmonary function indices were measured using a forced oscillation system. BALF cytokines (TNF-α, IL-6, and IL-10), reactive oxygen species (ROS), and TEK/Tie2 expression in lung tissue were assessed. In addition, transcriptome sequencing (RNA-seq) was performed to characterize global transcriptional changes. N-acetylcysteine (NAC), a classical antioxidant, was included as an auxiliary mechanistic intervention to assess the association of ROS with TEK/Tie2 changes. Results: Compared with hypoxia controls, prophylactic nebulized hUC-MSC-EVs reduced histopathological injury, pulmonary edema, and barrier leakage, and improved pulmonary function indices. hUC-MSC-EV intervention also attenuated inflammatory responses in BALF, with decreased TNF-α and IL-6 and increased IL-10. Hypobaric hypoxia increased ROS accumulation and decreased TEK/Tie2 expression, whereas nebulized hUC-MSC-EVs reduced ROS and partially preserved TEK/Tie2 expression. NAC pretreatment similarly reduced ROS and was accompanied by Tie2 preservation. Conclusions: Prophylactic nebulized hUC-MSC-EVs mitigated hypobaric hypoxia-induced lung injury, accompanied by reduced oxidative stress, improved vascular barrier integrity, and preservation of TEK/Tie2 expression. These findings support nebulized hUC-MSC-EVs as a potential lung-targeted prophylactic strategy for hypobaric hypoxia-induced lung injury and suggest that ROS imbalance may be associated with Tie2 preservation. Full article

A549 cells are widely used as an in vitro model of alveolar type II (ATII) epithelial cells; however, their phenotype and metabolic state are highly sensitive to culture conditions, cell density, and the duration of static, non-passaged cultivation. Here, we examined how prolonged static culture affects lipid metabolism, mitochondrial bioenergetics, and viability in A549 cells. A549 cultures were maintained without passaging for up to 25 days in DMEM or Ham’s F-12 and analyzed using lipid secretion assays, targeted lipidomics, [¹⁴C]-acetate incorporation, Seahorse bioenergetic profiling, and transcriptional analysis of stress-associated markers. Several surfactant-associated readouts were highest during early culture, peaking on day 7, as evidenced by elevated expression of ABCA3 and SP-A and maximal secretion of surfactant-associated phospholipids. With prolonged cultivation and increasing culture density, cellular phosphatidylglycerol levels declined progressively and became nearly undetectable by day 25, accompanied by reduced anabolic lipid metabolism, lower oxygen consumption, and impaired glycolytic activity. These changes coincided with increased reactive oxygen species, elevated intracellular Ca²⁺ levels, and increased expression of stress-associated transcripts, including CASP1, IL1B, and C3. Later stages were also associated with reduced mitochondrial respiration and decreased viability. Collectively, our findings show that prolonged static culture is associated with metabolic remodeling and reduced bioenergetic capacity in A549 cells. Full article

The aim of the study was to assess the microbial composition of bronchial secretions in chronic obstructive pulmonary disease (COPD), focusing on the impact of the exacerbation patterns on the common components of the respiratory flora and their relationship with inflammatory proteins. A total of 72 clinically stable COPD patients provided sputum and blood samples for 16S rRNA gene amplification and peripheral biomarkers. Beta-diversity analyses of the bronchial microbiome showed significant differences between infrequent and frequent (≥2) exacerbators (p = 0.001). Haemophilus was underrepresented in frequent exacerbators (relative abundance [RA] 0.07 [0.003–0.31] vs. 0.24 [0.06–2.36], p = 0.02) while the presence of Pseudomonas was increased (7.70 [0.66–11.68] vs. 1.11 [0.37–2.88], p = 0.01). Eight common taxa, Prevotella, Moryella, Atopobium, Megasphaera, Parvimonas, Veillonella, Bulleidia and Selenomonas, showed significant decreases in their RAs when exacerbations required hospitalization. RAs of Haemophilus and eight common taxa were positively correlated (p < 0.01). Among them, Porphyromonas, Leptotrichia and Selenomonas showed a negative correlation with blood interleukin-8 (IL-8) (p < 0.01) and an equivalent correlation was found for Haemophilus parainfluenzae. Frequent exacerbations cause a decrease in the RA of Haemophilus and have a more extensive impact when hospitalization is required. The RAs of common bronchial bacteria were closely related and some of them were inversely associated with blood IL-8 levels. Full article

Background/Objectives: Inflammatory mediators within the tumor microenvironment contribute to lung cancer progression by enhancing cellular motility and invasive capacity through cytokine-dependent signaling networks. Modulation of these inflammation-associated pathways by dietary bioactive compounds may provide complementary strategies for limiting cancer aggressiveness. Our objective was to examine the inhibitory effects of a cyanidin-3-O-glucoside (C3G)-rich fraction from Kum Akha pigmented black rice (CKAB-P1) on inflammation-stimulated A549 cancer cell progression. Methods: CKAB-P1 was obtained through solvent-partition extraction and chemically characterized using the pH differential method and high-performance liquid chromatography. A549 cells were pretreated with CKAB-P1 or C3G, followed by stimulation with conditioned medium predominantly containing IL-6 and IL-1β derived from LPS-exposed THP-1 macrophages (THP-1-CS). Effects on cancer cell migration and invasion were evaluated using wound-healing, Transwell invasion, gelatin zymography, and Western blot analyses. Results: CKAB-P1 contained 106.62 ± 3.54 mg/g extract of total anthocyanins, with C3G representing the major constituent (59.42 ± 2.54 mg/g extract). Exposure of THP-1-CS stimulated migration and invasion of A549 lung cancer, and neutralization of IL-6 and IL-1β reduced these pro-migratory effects, confirming cytokine involvement. Treatment with CKAB-P1 (10–40 μg/mL) or C3G (2.5–20 μg/mL) markedly attenuated inflammation-enhanced migration and invasion (p < 0.05). A reduction in MMP-2 and MMP-9 activity, along with decreased expression of invasion-associated protein expressions (uPA, uPAR, and MT1-MMP), was observed. Furthermore, both CKAB-P1 and C3G attenuated phosphorylation of JAK1 and STAT3. Conclusions: These findings suggest that anthocyanin-enriched black rice fraction may limit inflammation-driven A549 lung cancer cell aggressiveness through modulation of the cytokine-driven JAK1/STAT3 signaling cascade, indicating its potential relevance as a bioactive dietary component targeting tumor-associated inflammatory signaling. Full article

Objective: The purpose of this study was to determine the biological association between host-derived HSP47 and fungal-derived HSP90 in the context of vulvovaginal candidiasis (VVC) and to examine their relationships with clinical, inflammatory, and metabolic phenotypes in infected and healthy women. Methods: This study followed a six-month case–control design (February–July 2025) and was conducted at the University of Tabuk Hospital in Tabuk, Saudi Arabia. A total of 84 women aged 18–45 years were recruited, of which 42 were VVC-infected, and 42 were healthy controls. ELISA kits were used to test vaginal swabs for HSP47 and HSP90. Clinical, hematological, cytokine, and metabolic markers were also evaluated. Mann–Whitney U, Spearman correlation, and multiple linear regression tests were performed to analyze the data. Results: The levels of HSP47 and HSP90 were significantly higher among infected patients (2.29 ng/mL and 3341 ng/mL, respectively) when compared with controls (0.58 ng/mL and 1025.7 ng/mL; p < 0.001). Women who were infected were older (p = 0.02), but there were no significant differences in terms of BMI (p = 0.29). The levels of vitamin D and adiponectin were significantly decreased (p < 0.001), while pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ, TGF-β, and IL-8) and WBC counts were higher compared to the control group. The hematology results were characterized by inflammation-related anemia and disturbed protein metabolism. The ROC analysis demonstrated good diagnostic performance, with an AUC of 1.0 in the case of HSP47 and 0.905 in the case of HSP90. In the case of the infected patients, the regression models were found to be weak (HSP90 R² = 0.154; HSP47 R² = 0.273), although HSP47 retained significant connections with IL-8 (p = 0.005) and IFN-γ (p = 0.028). Conclusions: High levels of HSP47 and HSP90 are observed in VVC, reflecting an epithelial stress response and fungal persistence. These HSPs have high diagnostic accuracy, which justifies their potential as biomarkers for the timely detection of VVC; they also have further implications as early biomarkers for prognostic and treatment monitoring support, despite the poor predictive models. This study has some limitations that must be addressed; in particular, the regression analyses failed to provide statistically significant predictive models, likely due to the limited sample size. In addition, the specificity of HSP90 and HSP47 for VVC in comparison with other vaginal infections was not evaluated. Full article

Parathyroid allotransplantation is a promising treatment for hypoparathyroidism, yet immune rejection and fibrosis remain significant barriers. This study evaluates a novel immunoprotective culture system utilizing a moderate-intensity static magnetic field (SMF) to modulate lymphocyte migration without compromising graft functionality. Human parathyroid cells were encapsulated and divided into 10 experimental groups, co-cultured with Jurkat T-lymphocytes, and either exposed to SMF or maintained as controls. Over 72 h, we analyzed parathormone (PTH) secretion, cell viability (via proliferation assays), and molecular expression patterns of key markers (VitDR, PTH, GCM2, and CaSR). Lymphocyte dynamics were monitored through comparative imaging and cytokine profiling (IL-1α, IL-1β, and IL-2). SMF exposure significantly altered Jurkat cell behavior; while lymphocytes in unexposed groups aggregated around microcapsules, they were effectively repelled and migrated away from the graft interface under SMF exposure. Crucially, this biophysical manipulation was safe: no significant differences in PTH secretion or viability were observed across groups. All groups maintained essential genetic markers. Our findings demonstrate that SMF exposure induces lymphocyte migration away from the capsule without compromising parathyroid cell characteristics or functionality. Integrating encapsulation with SMF represents a novel, non-pharmacological, non-invasive immunoprotective strategy for parathyroid allotransplantation, offering a technological alternative to systemic immunosuppression. Full article

Tongue squamous cell carcinoma (TSCC) is clinically heterogeneous, and patients with a similar TNM stage can experience markedly different outcomes. We systematically reviewed omics-driven studies to identify prognostic TSCC biomarkers. Although fundamentally prognostic, we discussed their theoretical translational relevance regarding future clinical decisions—such as treatment stratification or surveillance intensity—while strictly framing them as preliminary, hypothesis-generating targets. PubMed, Scopus, Web of Science, and Cochrane were searched for original human studies published between 2014 and 2024 using high-throughput genomic or transcriptomic profiling. Study selection followed referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), data were extracted with a structured workbook, and risk of bias was assessed using QUIPS and PROBAST, with reporting completeness appraised using REMARK. Seventeen studies were included, identifying 85 distinct biomarkers. Across biomarkers supported by multivariable overall survival analyses, higher-risk associations were reported for NELL2, PDE4D, CTTN, HBEGF, and CA9, whereas lower-risk associations were reported for AC139530.1, LINC01711, CCDC96, CYP2J2, and SPAG16. Recurrent biological themes included IL-17 signaling, ECM-receptor interaction, and focal adhesion. CA9 was the only biomarker reported in more than one included study, supporting its prioritization for validation. Although the evidence remains heterogeneous and largely hypothesis-generating, these markers may support the future validation of response-oriented therapeutic stratification in TSCC. Full article

This study aimed to investigate the ameliorative effects of glucuronolactone (GL) as a dietary additive on high-fat diet (HFD)-induced growth suppression and metabolic disorders in turbot. A 10-week feeding trial was conducted using juvenile turbot (16.7 ± 0.03 g). Two diets with different protein (%)/lipid (%) levels were formulated: PC (54/12) and NC (47/17). Based on the NC diet, three experimental diets were prepared by supplementing 200 (G200), 400 (G400), and 600 (G600) mg/kg of GL. The present results show that compared to the PC group, HFDs significantly inhibited the growth performance of turbot and induced severe metabolic disorders, hepatointestinal damage, and gut microbiota dysbiosis. Dietary GL supplementation effectively reversed these adverse effects. Specifically, compared to the NC group, GL supplementation significantly restored growth performance, enhanced non-specific immunity, and systematically improved metabolic health. In the liver, GL notably ameliorated tissue damage and downregulated key lipogenic genes (SREBP1, ACC, FAS, PPARγ), while upregulating genes involved in lipid oxidation and catabolism (PPARα1, CPT1, ACOX1, HSL, LPL) and lipid transport (ApoB100, MTP), thereby alleviating hepatic lipid deposition. Furthermore, GL activated the Nrf2/Keap1 antioxidant pathway, up-regulating the expression of genes such as SOD, CAT, GPX, and HO-1. It also suppressed the NF-κB-mediated inflammatory response (downregulation of IL-1β, IFN-γ and TNF-α2; upregulation of IL-10 and TGF-β2) and the mitochondrial apoptosis pathway (increased Bcl-2/Bax ratio; downregulation of Caspase3/7/9), collectively mitigating oxidative damage and cellular apoptosis. Moreover, GL restored intestinal morphology, enhanced the expression of tight junction proteins (Claudin-3, Claudin-7, ZO-1, Occludin) and MUC2, and inhibited MLCK signaling. These improvements led to a reduction in serum D-LA levels, indicating strengthened intestinal barrier function. Concurrently, GL reshaped the gut microbiota composition by enriching beneficial bacteria such as Akkermansia and suppressing potential pathogens like Listeria. In summary, GL effectively alleviated HFD-induced growth suppression and metabolic damage in turbot by improving lipid metabolism and alleviating hepatic injury, while concurrently restoring intestinal barrier integrity and microbiota homeostasis. Full article

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is a major complication and leading cause of mortality in SSc. Transforming growth factor-β (TGF-β) has been implicated as a central mediator of fibrosis; however, while TGF-β1 has been extensively studied, the roles of TGF-β2 and TGF-β3 remain incompletely defined. Here, we systematically compared the effects of TGF-β1, TGF-β2, and TGF-β3 in dermal and lung fibroblasts, evaluating extracellular matrix synthesis and contraction, cytokine secretion, proliferation, and myofibroblast differentiation. TGF-β2 and TGF-β3 induced greater profibrotic cytokine release of Interleukin (IL)-6 and IL-11 and increased collagen-I and fibronectin synthesis compared with TGF-β1 in dermal and lung fibroblasts (all p < 0.05). TGF-β2 and TGF-β3 stimulated greater collagen-I contraction in dermal fibroblasts (p < 0.05), but greater myofibroblast differentiation in lung fibroblasts (p < 0.05). The TGF-β isoforms did not affect proliferation. All TGF-β isoforms activated SMAD2/3 signalling; however, TGF-β2 and TGF-β3 reduced expression of TGF-β Receptor II and the inhibitory regulator, SMAD7. In summary, TGF-β2 and TGF-β3 have a more pronounced profibrotic effect than TGF-β1 on dermal and lung fibroblast functions, making them potential targets for treatment for skin and lung fibrosis in diseases such as SSc. Full article

Periodontitis represents a primary etiological factor in tooth mobility, with oxidative stress contributing critically to periodontal tissue destruction. Evodiamine (EVO), a quinazolinocarboline alkaloid, exhibits multiple biological activities; however, its antioxidant effects and mechanism in periodontitis have not been elucidated. The aim of this study was to investigate the regulatory effect of EVO on oxidative stress in periodontitis and to explore the associated molecular mechanism. The results indicate that EVO exhibits potent antimicrobial activity against key periodontal pathogens and suppresses pathogen-induced ROS generation as well as the release of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) under periodontitis conditions. EVO binds specifically to the Kelch domain of KEAP1 with a strong binding energy (−11.67 kcal/mol), inhibits KEAP1–NRF2 interaction, and consequently upregulates the expression of antioxidant enzymes (HO-1, NQO1, GCLC, and SOD2), while downregulating the expression of iNOS, COX2, and NOX2. Furthermore, EVO inhibits the pro-apoptotic effect of the JAK2/STAT3 signaling axis and mitigates inflammation, alleviates cell cycle arrest, and promotes the migration and repair of periodontal ligament cells. Collectively, these findings suggest that EVO acts as a potential binder of KEAP1 that alleviates periodontal inflammation through modulation of oxidative stress and regulation of the JAK2/STAT3 pathway. Full article

Background: Patients with type 2 diabetes mellitus (T2DM) undergoing cardiac surgery represent a high-risk population characterized by substantial cardiometabolic stress and increased susceptibility to postoperative heart failure, renal dysfunction, and unplanned rehospitalization. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors provide established cardiorenal protection in ambulatory populations, their perioperative impact in cardiac surgery cohorts remains insufficiently defined. Methods: In a single-center retrospective cohort of 620 T2DM patients, inverse probability of treatment weighting and time-dependent Cox regression were applied to account for perioperative treatment interruption and delayed postoperative reinitiation when evaluating the association between chronic SGLT2 inhibitor therapy and 12-month rehospitalization risk. To provide biological context for the observed clinical associations, target-driven systems pharmacology, molecular docking against SGLT2, NHE1, AMPK, and NLRP3, and protein–protein interaction (PPI) network analysis were performed. Hub proteins were identified using Maximal Clique Centrality, followed by functional enrichment (GO/KEGG) analysis. Results: Chronic SGLT2 inhibitor therapy was associated with reduced first rehospitalization (HR 0.64; 95% CI 0.48–0.85; p = 0.002) and a lower cumulative rehospitalization burden (IRR 0.61; 95% CI 0.46–0.82; p = 0.001), primarily driven by heart failure-related and metabolic phenotypes. Molecular docking analyses identified favorable binding with SGLT2 and additional cardiometabolic and inflammatory targets, including NHE1, AMPK, NLRP3, IKKβ, IL-6Rα, and PPAR isoforms, suggesting modulation of myocardial ion homeostasis, metabolic resilience, and inflammatory signaling. PPI analysis identified eight hub proteins (AKT1, MTOR, STAT3, EGFR, PIK3CA, SRC, MAPK1, and MAPK3) significantly enriched in PI3K/AKT, MAPK/ERK, and ErbB signaling pathways. Conclusions: Chronic SGLT2 inhibitor therapy was independently associated with reduced postoperative rehospitalization and cumulative event burden in T2DM patients undergoing cardiac surgery. Integrated in silico analyses offer mechanistic hypotheses consistent with the observed clinical associations. These findings suggest that structured perioperative SGLT2 inhibitor management may contribute to improved postoperative outcomes, while prospective validation in future studies would strengthen these findings. However, given the retrospective observational design, these findings should be interpreted as associative rather than causal. Full article

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has revealed a complex interplay between respiratory and neurological manifestations. This study utilized K18-hACE2 transgenic mice to investigate the morphological, ultrastructural, and transcriptomic changes induced by SARS-CoV-2 infection in both lungs and brain tissues. Histopathological analysis at seven days post-infection revealed significant pulmonary damage characterized by interstitial pneumonia, alveolar septal thickening, with a marked inflammatory infiltrate predominantly consisting of neutrophils and lymphocytes, and an abnormal profile of type II pneumocytes. Concurrently, in the brain, we observed vasculitis, gliosis, and edema, indicating an inflammatory response and vascular compromise that can disturb the blood–brain barrier. In addition, gene expression in lung tissue presented increased CCL2, IL10, and GDDA45D in infected mice and the downregulation of proinflammatory genes. However, in brain tissue, the increased expression of CCL2, CASP1, IL6, IFNB1, and GDDA45G inflammatory genes was observed in infected K18-hACE2 mice. Full article

A diverse range of 4-dimethylaminopyridinium (DMAP) bis(trifluoromethylsulfonyl)-amide ionic liquids with specific functionalities (alkyl, alkoxy, hydroxyalkyl and benzyl) were designed, characterized and compared with their pyridinium analogs in terms of their physical and radiolytic properties. The influence of the dimethylamino group on ionic liquid structure was investigated by X-ray diffraction and molecular dynamics simulations. The influence of the electron-donating ability of the dimethylamino-substituted cation is evident in the differences in the electronic density of states between the DMAP and pyridinium ILs. This leads to substantial changes in the radical transients observed in pulse radiolysis of the neat ILs. It was found that the DMAP salts were higher melting, more viscous and less conducting than their pyridinium analogs. However, the DMAP salts exhibited higher thermal stabilities and could therefore be useful for high-temperature applications. Full article

Background/Objectives: The IUCN endangered spotted pond turtle (Geoclemys hamiltonii) demonstrates markedly reduced resistance to Aeromonas hydrophila-induced infections compared to the red-eared slider (Trachemys scripta). This study investigates the immunological basis for this disparity by analyzing infection outcomes and splenic transcriptomes of both species post-pathogen challenge. Methods: In a preliminary experiment, 32 turtles (16 G. hamiltonii and 16 T. scripta) were exposed to A. hydrophila. Results: G. hamiltonii developed skin ulcer syndrome at a significantly higher incidence (81.25%) than T. scripta (12.5%) (p < 0.05). Comparative transcriptomic analysis identified 19 differentially expressed immune-related genes, with qPCR validation across five tissues (heart, liver, spleen, intestine, blood) revealing pronounced interspecies differences in IL18, STAT1, IFIH1, and CD28 expression. Notably, IL18 and its downstream effector STAT1 were robustly upregulated in T. scripta but were considerably lower in G. hamiltonii, correlating with delayed IFN-γ pathway activation and impaired epidermal barrier repair. Concurrently, CD28 upregulation in T. scripta facilitated rapid T-cell-mediated pathogen clearance, whereas its delayed induction in G. hamiltonii hindered adaptive immunity. These findings implicate dysregulated innate (IL18/STAT1) and adaptive (CD28) immune pathways as key determinants of G. hamiltonii’s susceptibility to bacterial infection. Conclusions: Despite the critical conservation status of G. hamiltonii, the immunological basis underlying its heightened susceptibility to bacterial infections remains largely unexplored; this study addresses this gap by comparing the splenic transcriptomes of G. hamiltonii and T. scripta following A. hydrophila challenge, identifying the dysregulated IL18-STAT1 Immune Axis and CD28-mediated adaptive immunity as key determinants, thereby providing actionable immune targets for conservation breeding and susceptibility screening in this endangered species. Full article