Search Results (26,554)

Background/Objectives: Chronic inflammation and oxidative stress are key contributors to colorectal cancer (CRC) development. However, prospective evidence in Asian populations remains limited. This study aimed to investigate the associations between circulating inflammatory cytokines, oxidative markers, and CRC risk in a Korean population. Methods: We conducted a case–cohort study nested within the Korean National Cancer Community (KNCCC) Cohort to investigate associations between inflammatory cytokines, oxidative stress markers, and CRC risk. A total of 128 incident CRC cases and 822 subcohort participants were included. Serum levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, interferon-γ (IFN-γ), IL-10, reactive oxygen species (ROS), and nitric oxide (NO) were measured. Hazard ratios (HRs) were estimated using the Cox proportional hazards models with Barlow’s weighting. Results: Higher serum IL-6 levels were strongly associated with increased CRC risk, with HRs of 6.20 (95% CI: 2.38–16.19), 8.31 (3.24–21.33), and 10.22 (3.95–26.46) for the second through fourth quartiles, compared to the lowest. Detectable levels of IL-1β and IFN-γ were also significantly associated with CRC risk (HRs: 2.16 and 1.53, respectively). Stratified analysis showed that IL-6 and IL-1β were associated with CRC risk in both obese and non-obese participants, while TNF-α, IL-10, and NO were associated with increased risk only among obese individuals. No significant associations were observed for ROS. Conclusions: Elevated levels of inflammatory cytokines (IL-6, IL-1β, IFN-γ) and NO were associated with higher CRC risk, suggesting their potential as early biomarkers. Obesity may modify the associations between certain markers and CRC risk. These findings highlight the role of systemic inflammation and oxidative stress in colorectal carcinogenesis. Full article

Bronchopulmonary dysplasia (BPD) is a chronic lung condition in preterm infants characterized by impaired alveolar development, disrupted vascular growth, and persistent inflammation. These alterations, which often arise from early exposure to mechanical ventilation, oxygen toxicity, and infection, can lead to long-term structural and functional deficits in the developing lung. In adulthood, chronic obstructive pulmonary disease (COPD) represents a major cause of morbidity and mortality and is defined by progressive airflow obstruction, reduced respiratory capacity, and chronic inflammatory responses. Although traditionally considered a disease of adult smokers, growing evidence suggests that early-life respiratory insults play a key role in shaping long-term lung health. Recent studies reveal a biologically plausible link between BPD and later COPD, indicating that premature birth, impaired lung growth, and early inflammatory injury may predispose individuals to earlier or more severe COPD development. This review explores the shared molecular pathways connecting these conditions, focusing on overlapping inflammatory biomarkers such as IL1B, IL6, IL8, TNF, TGFB, and VEGF, which collectively reflect persistent dysregulation of immune and repair mechanisms. Additionally, common genetic variants, including SERPINA1 and HHIP, may contribute to susceptibility across the lifespan. Emerging biomarkers—such as PRMT7, cathelicidin/LL-37, CRISPLD2, and GDF15—offer further insight into disease progression. Identifying these shared markers may ultimately improve early detection and help clinicians pinpoint infants with BPD who face an elevated risk of developing COPD later in life. Full article

The microevolutionary pathways and molecular mechanisms by which the important pathogen Vibrio parahaemolyticus acquires resistance in the aquatic environment under continuous selective pressure from quinolone antibiotic residues are still unknown. Here, the study successfully simulated the long-term pressure of antibiotic residues in aquaculture by susceptible V. parahaemolyticus (VPD14) which was isolated from seafood, to a 30-day in vitro induction with sublethal concentrations of levofloxacin, which yielded the mutants (VPD14M). A phenotypic analysis revealed that VPD14M exhibited resistance to ampicillin, levofloxacin and ciprofloxacin, compared to VPD14. These changes were accompanied by adaptations, including a decreased growth rate and an enhanced biofilm formation capacity. Whole-Genome Sequencing identified that the acquired resistance was primarily attributable to key point mutations in three Quinolone Resistance-Determining Regions (QRDRs). Specifically, a G → T substitution at nucleotide position 248 in the gyrA gene, leading to a serine-to-isoleucine substitution at the 83rd amino acid position (Ser83Ile) of the DNA gyrase subunit A; a C → T substitution at position 254 in the parC gene, resulting in a serine-to-phenylalanine substitution at position 85 (Ser85Phe) of the topoisomerase IV subunit A; and a C → T substitution at position 2242 in the gyrB gene, causing a proline-to-serine substitution at position 748 (Pro748Ser) of the DNA gyrase subunit B. Collectively, the study demonstrated that sublethal antibiotic levels rapidly drive quinolone resistance in V. parahaemolyticus, and the specific mutations identified offer critical support for resistance monitoring and seafood safety alerts. Full article

Prolonged exposure to ultraviolet (UV) radiation in sunlight is a major extrinsic factor that impairs skin function and accelerates photoaging. In this study, a murine model of ultraviolet B (UVB)-induced photoaging exhibited characteristic symptoms, including skin roughness, erythema, hyperpigmentation, and increased wrinkle formation. Epicatechin gallate (ECG), a natural flavonoid, has demonstrated potential skin-protective properties. However, its specific effects and mechanisms against UVB-induced photoaging are not fully understood. Here, we investigated the protective role and underlying mechanism of ECG against UVB-induced damage in human epidermal keratinocytes (HaCaT cells). Using network pharmacology, p38 mitogen-activated protein kinase (p38 MAPK), specifically the p38α isoform, was identified as a key potential target of ECG. Our experimental results confirmed that ECG significantly attenuated UVB-induced photoaging. Mechanistically, ECG treatment effectively suppressed UVB-triggered phosphorylation of p38α, promoted autophagic flux (as evidenced by increased LC3B conversion and decreased p62 levels), and substantially reduced intracellular reactive oxygen species (ROS) accumulation. Consequently, ECG mitigated mitochondrial dysfunction, restored normal cell cycle progression, and decreased the expression of senescence-associated markers (p53, p16, p21) and inflammatory cytokines (IL6, TNF-α). In summary, our findings demonstrate that ECG protects against UVB-induced photoaging primarily by inhibiting p38α activation, thereby enhancing autophagy and alleviating oxidative stress. This study positions ECG as a promising therapeutic candidate for preventing and treating skin photoaging. Full article

Background: Obesity-associated inflammation arises from adipose dysfunction and intestinal disturbances, including altered microbiota and short-chain fatty acid (SCFA) metabolism. Beans (Phaseolus vulgaris) are rich in non-digestible carbohydrates and polyphenols, but whether kidney bean varieties differing in seed coat colour exert distinct effects on inflammation in obesity remains unclear. Objective: To determine whether supplementation of an obesogenic high-fat (HF) diet with white or dark red kidney beans modulates gut microbiota, SCFAs, and intestinal, systemic, and neuroinflammatory outcomes. Methods: Male C57Bl/6N mice (n = 12/group) were fed a basal diet (BD; modified AIN-93G), an HF diet (60% kcal from fat), or an HF diet supplemented with 15% cooked white (HF + WK) or dark red kidney beans (HF + DK) for nine weeks. Outcomes included cecal microbiota composition, predicted KEGG pathways with taxon contributors mapped with BURRITO (a tool for linking predicted microbial functions to contributing taxa), and SCFA-related pathways; cecal and fecal SCFA concentrations; colon histomorphometry and expression of gut barrier junction and inflammatory genes; serum cytokines and adipose hormones; and hippocampal inflammatory and barrier genes. Results: Mice consuming bean-supplemented HF diets had higher microbial diversity, enrichment of SCFA-producing taxa (Prevotella, Lactobacillus, Muribaculaceae), and lower obesity-associated genera versus HF alone (Mucispirillum, rc4-4). Bean diets elevated cecal acetate and butyrate concentrations, which aligned with increases in predicted acetate kinase in both bean groups versus HF and BD, and butyrate kinase in HF + DK versus BD. Bean supplementation attenuated HF-induced reduction of goblet cells and systemic interleukin (IL)-10. The HF + DK group had lower colonic tumour necrosis factor (TNF)-α and partially attenuated hippocampal IL-6. SCFAs were inversely associated with systemic and neuroinflammatory markers in HF + DK mice. Conclusions: Kidney bean supplementation mitigated HF diet-induced intestinal, systemic, and neuroinflammatory disturbances in male mice, with microbiota and SCFA modulation. Further, dark red beans exerted stronger anti-inflammatory effects, highlighting the role of seed coat colour in bean-mediated obesity outcomes. Full article

Silicosis, an irreversible occupational lung disease resulting from prolonged exposure to respirable crystalline silica, faces challenges due to limitations in existing mammalian models. This study evaluated whether laboratory-prepared respirable α-quartz silica could induce immune cell–inflammatory–fibrotic initiation related to silicosis in zebrafish embryos as a tool for early toxicity assessment. Zebrafish embryos at 48 h post-fertilization (hpf) were microinjected into hindbrain ventricle with respirable α-quartz silica (test material 3.056 μm vs. standard material 3.217 μm) derived from natural α-quartz ore. The results indicated a significant decrease in zebrafish survival rates and an increase in malformation rates following exposure respirable α-quartz silica materials. Additionally, alterations in midbrain and hindbrain lengths were observed, while body length remained unaffected. Behavioral assessments revealed reduced touch response rates, decreased average speed, and less time spent in the central zone during open field tests in the treatment groups. In vivo imaging demonstrated sequential recruitment of neutrophils (peak at 18 h post-injection) and macrophages (peak at 24 h post-injection). qPCR analysis revealed upregulation of inflammation-related genes (tnf-α, il-6, il-1β) and fibrosis-related genes (tgf-β, acta-2, collagen). Moreover, the hydroxyproline content, a marker for fibrosis, was significantly elevated, although no mature fibrosis was observed histologically. These findings demonstrate that respirable α-quartz silica elicits pathophysiological changes associated with silicosis early initiation in zebrafish embryos. This supports the utility of the zebrafish embryo as a practical tool for early toxicity assessment and mechanistic studies of silica-induced immune–inflammatory–fibrotic initiation, with potential implications for silica exposure early risk warning. Full article

Background/Objectives: Pregnancy is characterized by complex immunological adaptations that may increase susceptibility to infections, including SARS-CoV-2. Interleukin-6 (IL-6), a key pro-inflammatory cytokine, plays a crucial role in the immune response and has been strongly implicated in the pathogenesis of COVID-19. Genetic variations in the IL6 gene, particularly single-nucleotide polymorphisms (SNPs) in the promoter region, can modulate IL-6 expression and potentially influence individual susceptibility to viral infections. This study aimed to evaluate the relationship between promoter region IL6 gene polymorphisms and COVID-19 susceptibility, as well as the inflammatory response, in pregnant women. Methods: We enrolled in this study 204 pregnant women with evidence of SARS-CoV-2 infection in pregnancy and 134 pregnant women with no evidence of SARS-CoV-2 infection in the past. Genotyping was conducted for the two functional SNPs in the IL6 promoter region, rs1800796 and rs1800797, via Sanger sequencing, and for associations with COVID-19 susceptibility and IL-6 levels were analyzed. Results: No significant association was found between IL6 polymorphisms and COVID-19, IL-6 levels, age, or immunization status. IL-6 levels > 5 pg/mL were more frequent in SARS-CoV-2-negative pregnant women than in SARS-CoV-2-positive pregnant women (p = 0.032). Among vaccinated participants, IL-6 levels were significantly higher in SARS-CoV-2-negative pregnant women (p = 0.044), while no difference was observed in the unvaccinated group. Conclusions:IL6 polymorphisms rs1800797 and rs1800796 were not associated with infection susceptibility or IL-6 levels. These results highlight the complex immunological interplay between pregnancy, infection, and genetic background and support the need for further research in larger cohorts. Full article

Escherichia coli O157:H7 is a pathogenic bacterium that causes severe intestinal infections characterized by inflammation and disruption of the intestinal barrier. Probiotic lactic acid bacteria (LAB) from milk can support intestinal health and combat enteric pathogens; however, the potential of feline milk-derived LAB against E. coli O157:H7 infection remains unclear. In this study, Pediococcus acidilactici (P. acidilactici) M22, isolated from feline milk, was evaluated for probiotic activity in vitro and in vivo in a C57BL/6 mouse model of Escherichia coli O157:H7 infection. In vitro assays demonstrated that M22 significantly inhibited the adhesion of Escherichia coli O157:H7 to intestinal epithelial cells. For in vivo assessment, C57BL/6 mice were orally administered M22 prior to infection with E. coli O157:H7. Protective effects were evaluated by monitoring body weight loss, colon length, disease activity index (DAI), myeloperoxidase (MPO) activity, cytokine levels, tight junction protein expression, oxidative stress markers, and gut microbiota composition. M22-treated mice exhibited significantly less body weight loss and lower DAI scores than infected controls. M22 also prevented colon shortening, indicating reduced colonic damage. Probiotic treatment attenuated neutrophil infiltration and mucosal inflammation, as evidenced by decreased colonic MPO activity, reduced levels of pro-inflammatory cytokines, and elevated anti-inflammatory IL-10. Additionally, M22 preserved intestinal barrier function by upregulating tight junction proteins and mitigating infection-induced histopathological changes. M22 supplementation enhanced antioxidant defenses in colonic tissue (lower malondialdehyde, higher superoxide dismutase and glutathione), indicating reduced oxidative stress. Furthermore, gut microbiota analysis (16S rRNA sequencing) revealed that M22 counteracted infection-induced dysbiosis, restoring microbial diversity and a healthy composition (enrichment of beneficial commensals and suppression of harmful bacteria). By safeguarding intestinal integrity and homeostasis, M22 emerges as a promising next-generation probiotic for improving intestinal health in companion animals. Full article

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with poor prognosis, frequent relapse, and treatment-related toxicity. The discovery of novel anti-leukemic agents with improved selectivity remains an urgent clinical need. In this study, rhizomes of Angiopteris evecta, a medicinal plant used in Thai traditional medicine, were collected from twelve locations in Thailand and extracted using solvents of increasing polarity. Among thirty-six crude fractional extracts, the ethyl acetate crude fractional extract from source No. 003 (AE EtOAc No. 003) exhibited the strongest cytotoxic activity against KG-1a and EoL-1 leukemic cell lines, with low toxicity toward normal peripheral blood mononuclear cells. Bioactivity-guided fractionation yielded the ternary mixture, a furanone-rich mixture dominated by 5-(1-hydroxyethyl)-dihydro-2-furanone. The ternary mixture inhibited leukemic cell proliferation by inducing apoptosis, causing cell cycle arrest, and downregulating WT1 expression in EoL-1 cells. Network pharmacology and molecular docking analyses implicated AKT1, MAPK signaling, apoptosis-related pathways, and WT1 as key molecular targets. In addition, AE EtOAc No. 003 and the ternary mixture suppressed TNF-α and IL-6 production in LPS-stimulated macrophages. Collectively, A. evecta-derived furanone compounds represent promising lead candidates for anti-leukemic drug development. Full article

Background/Objectives: Interleukin-6 (IL-6), a pleiotropic cytokine involved in immune regulation, is consistently detected in human semen, even in the absence of overt infection. Its contribution to sperm dysfunction, oxidative stress, and inflammation remains incompletely understood. This study evaluated the associations between seminal IL-6 concentrations and markers of semen quality, oxidative stress, nuclear integrity, and genital tract inflammation in infertile men. Methods: A cohort of 204 infertile men was assessed. Seminal IL-6 was quantified by electrochemiluminescence immunoassay. Semen parameters, malondialdehyde (MDA), catalase (CAT) activity, sperm DNA fragmentation index (DFI), sperm chromatin decondensation index (SDI), leukocytospermia, and bacteriospermia were measured. Analyses included correlation testing, IL-6 threshold stratification (<30, 30–60, 60–100, ≥100 pg/mL), and multivariate regression. Results: IL-6 was detectable in all samples (median: 31.52 pg/mL; range: 1.5–5000 pg/mL). Higher IL-6 levels were significantly associated with reduced sperm concentration, progressive motility, and vitality, and with increased DFI, SDI, MDA, leukocyte counts, and bacteriospermia (p < 0.001). In multivariate models, IL-6 independently predicted reduced progressive motility (β = −0.005; p = 0.032) and elevated leukocyte count (β = 0.0018; p < 0.0001). Logistic regression further showed that IL-6 increased the odds of DFI ≥ 30%, SDI ≥ 30%, and bacteriospermia (p < 0.05). Conclusions: Seminal IL-6 emerges as a sensitive biomarker of immuno-oxidative stress and sperm dysfunction in infertile men. Its integration into clinical evaluation may improve the assessment of inflammatory and oxidative contributors to male infertility. Full article

Metabolic reprogramming is a hallmark of psoriasis, yet the contribution of lactate metabolism to keratinocyte-mediated immune dysregulation remains undefined. Through integrated bulk and single-cell RNA sequencing, validated by immunofluorescence and metabolic assays, we identified the mitochondrial protein SCO2 as a key pathogenic hub gene upregulated in psoriatic lesions. Functionally, SCO2 overexpression promoted keratinocyte migration and triggered a metabolic shift characterized by mitochondrial pyruvate accumulation and intracellular lactate retention. Single-cell analysis further revealed that SCO2-high keratinocytes establish pathogenic crosstalk with CCR7⁺ dendritic cells via MIF-(CD74 + CD44) interactions, wherein these CCR7⁺ dendritic cells serve as the primary source of IL-23 and co-stimulatory signals (CD80/CD86) to drive robust T cell priming. Our findings highlight SCO2 as a pivotal immunometabolic switch linking keratinocyte metabolism to adaptive immunity. Targeting SCO2 offers a novel strategy to disrupt the keratinocyte-driven recruitment of CCR7⁺ DCs, thereby attenuating the IL-23-mediated inflammatory cascade. Furthermore, SCO2 may serve as a potential biomarker for metabolic dysregulation in psoriatic lesions. Full article

Background: The tumor microenvironment (TME) plays a central role in pancreatic ductal adenocarcinoma (PDAC) progression, yet how mechanical cues shape stromal cell behavior remains poorly defined. Here, we investigate how dimensional priming of adipose-derived stromal cells (ADSCs) alters their immunomodulatory functions and subsequent impact on PDAC growth. Methods: ADSCs were cultured under two-dimensional (2D) or three-dimensional (3D) conditions and evaluated using in vitro co-culture systems with PDAC organoids and in vivo xenograft models. Stromal phenotype, cytokine secretion, tumor growth, invasion, and immune cell infiltration were assessed. Results: ADSCs cultured in three-dimensional (3D) hydrogels exhibited reduced Caveolin-1 (CAV-1) expression and reprogramming toward a stress-adapted, CAF-like phenotype compared with two-dimensional (2D) cultures. In vitro, 2D-primed ADSCs constrained PDAC organoid growth, increased MMP-2 activity, and required direct cell–cell contact to suppress tumor viability. By contrast, 3D-primed ADSCs preserved organoid structure but markedly enhanced tumor cell migration through soluble factors, accompanied by increased IL-6 and TNF-α and reduced IL-10 secretion during co-culture. In vivo, 3D-primed ADSCs promoted the largest tumors with aggressive invasion and loss of Col-Tgel containment associated with tumor expansion, whereas 2D-primed ADSCs suppressed tumor growth and maintained gel boundaries. Immunohistochemistry confirmed elevated Ki-67 in tumors containing 3D-primed ADSCs, while macrophage infiltration (F4/80⁺) was highest in 2D-primed tumors and lowest in 3D-primed tumors. Conclusions: Dimensional priming fundamentally reprograms ADSC phenotype and alters their stromal–immune interactions, generating a tumor-permissive state that accelerates PDAC progression. These findings identify mechanical cues as critical regulators of stromal plasticity and highlight dimensional priming as a potentially targetable axis within the PDAC microenvironment. Full article

Neoadjuvant chemoimmunotherapy has emerged as a promising treatment strategy for head and neck squamous cell carcinoma (HNSCC). There is an urgent need to improve patient responses to this approach. In this study, we aim to elucidate the mechanisms underlying poor response to neoadjuvant chemoimmunotherapy and to identify strategies to enhance therapeutic efficacy in HNSCC. We identified a cancer stem-like cell (CSC) population enriched in patients with partial response (PR) to neoadjuvant chemoimmunotherapy, characterized by high CD80 expression. CD80 was likewise highly expressed in ALDH^highCD44⁺ and BMI1⁺ populations. Functionally, CD80 knockdown attenuated tumor-sphere-forming capacity and reduced the migration and invasion of tumor cells, whereas CD80 overexpression potentiated these pro-tumorigenic activities. Moreover, CD80 inhibition activated signaling pathways of Th1 immune responses and IL-2 production. CD80 blockade enhanced T cell cytotoxicity. In preclinical HNSCC models, inhibition of CD80 significantly decreased tumor burden, accumulated CD8⁺ T cells, and increased the production of cytotoxic effector molecules. Our data demonstrated that CD80 modulated tumor-cell stemness and malignant phenotype while restraining antitumor T cell immunity. Targeting CD80 augments antitumor immunity and provides a compelling strategy to enhance treatment responses to neoadjuvant chemoimmunotherapy in HNSCC. Full article

The Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by profound immune dysregulation where interleukins play a central role in determining disease severity and response to interventions. This review summarizes the role of interleukins in the immunopathogenesis of COVID-19, with particular emphasis on differences observed across major SARS-CoV-2 variants. Pro-inflammatory interleukins like IL-1β, IL-6, IL-2, IL-17 and IL-18 are critically involved in cytokine storm, hyperinflammation, and acute respiratory distress syndrome, whereas anti-inflammatory cytokines like IL-10 contribute to immune regulation and resolution of inflammation. Elevated levels of IL-1α, IL-1β, IL-4, IL-8, IL-9, IL-16, IL-18 have been documented in the Delta variant as compared with the Omicron variant, with IL-6 being the most frequent interleukin reported to be increased across all SARS-CoV-2 variants relative to the ancestral Wuhan strain. Elevated IL-2, IL-4, IL-6, and IL-10 levels have been associated with Omicron sub-variants. The review encompasses interleukin-based therapeutic strategies, where several IL-1 and IL-6 inhibitors were studied across clinical trials, but only tocilizumab has shown some promise against severe COVID-19. IL-2, IL-6, IL-15 and IL-21 levels were positively correlated with IgG and neutralizing antibody activity after vaccination with longevity of post-vaccination immunity being determined by IL-2 and IL-7. Full article

Developing molecular methods for assessing the effectiveness of physical rehabilitation remains a pressing task. Our pilot study aimed to assess the utility of the transcriptome analysis of muscle biopsies in evaluating the efficacy of the isometric exercises (IEs) added to the standard protocol in the early rehabilitation of older patients during the initial two weeks post total hip arthroplasty (THA). Blood concentrations of total leukocytes, neutrophils, IL6, IL8, IL1β, myoglobin, etc. were measured, and transcriptome analysis of rectus femoris biopsies from the operated leg was performed before and after (1 and 12 days) THA in women aged 73–77 years. The additional IEs in the experimental rehabilitation group led to a significant acceleration in the recovery of IL6, IL8, and IL1β blood levels to the normal ranges compared to the control group, as confirmed by a Fisher’s exact test for this cytokine combination. The results of Gene Set Enrichment Analysis and Differentially Expressed Gene Analyses for the muscle biopsies point to accelerated resolution of inflammation, along with enhanced activation of genes associated with angiogenesis, lymphangiogenesis, vasodilation, and vasoconstriction in the experimental rehabilitation group compared to the control group. Thus, IL6, IL8, and IL1β blood levels can serve in combination as molecular indicators of the efficacy of early rehabilitation after THA, and transcriptome analysis of the rectus femoris biopsies of the operated leg allows for the revelation of the molecular indicators of regenerative processes in muscle tissue near the surgery area after THA. Full article