Search Results (13,417)

Diarrhea significantly impacts livestock and poultry health, causing growth delays and higher mortality rates. Macleaya cordata extract (MCE) demonstrates strong antioxidant, antibacterial, and anti-inflammatory properties, indicating its potential as a therapeutic agent for diarrhea. This research investigated whether MCE alleviates lipopolysaccharide (LPS)-induced diarrhea in mice through modulation of the gut microbiota. Here, changes in short-chain fatty acids (SCFAs) and gut bacterial structure were analyzed using gas chromatography–mass spectrometry (GC-MS) and 16S rRNA gene sequencing, respectively. The effects of MCE administration (40 mg/kg) on intestinal injury and inflammatory responses were assessed in mice induced with LPS. These results show that MCE-treated mice exhibited significantly lower diarrhea indices, attenuated duodenal villus shortening, and decreased crypt depth compared with LPS-induced mice. MCE treatment substantially reduced the mRNA expression of IL-6, IL-1β and NF-κB in the duodenum, as well as the serum levels of TNF-α and IL-8. Furthermore, MCE significantly increased SCFA levels, particularly acetic acid, and reshaped the gut microbiota composition by increasing the abundance of Lachnospiraceae. Given the close interaction between gut microbiota, microbial metabolites, and host inflammatory responses, these microbial and metabolic alterations are closely associated with the attenuation of intestinal and systemic inflammation. In conclusion, the protective effects of MCE against LPS-induced diarrhea in mice are closely associated with the modulation of gut microbiota structure, suppression of inflammatory responses, and enhancement of acetic acid production. This study provides a mechanistic basis for MCE as a natural alternative to antibiotics for treating inflammatory diarrhea in livestock and poultry. Full article

Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent pollutants that can be sequestered within human adipose tissue due to their lipophilic nature. While this accumulation poses toxicological risks depending on dose and individual susceptibility, the specific morphological impact of chronic PAH storage on tissue architecture remains poorly defined. Here, we performed a histopathological and morphometric analysis on human subcutaneous adipose tissue samples characterized by high pyrene levels. We evaluated tissue organization, collagen distribution, the presence of inflammatory, neural, and vascular alterations and adipocyte morphometry to assess the structural response to PAH sequestration. Despite high pyrene concentrations, PAH-positive tissues maintained preserved overall architecture with normal collagen distribution, absence of lymphocytic infiltration, low macrophages, unaltered nerve fiber patterns, without evidence of vascular remodeling. Morphometry revealed smaller adipocyte area in PAH-positive samples, although not statistically significant. Our experimental data indicate that high PAH accumulation does not necessarily induce subcutaneous adipose tissue remodeling, suggesting that biochemical or metabolic alterations might occur even in the absence of evident histological changes. Further studies, with a broadened cohort, are needed to define the threshold at which PAHs’ presence translates into permanent tissue damage. Full article

Acute kidney injury, a broad term associated with diverse etiologies, is a common pathological condition that develops into chronic disease via mechanisms that have yet to be fully understood. Key processes that promote chronic disease transition include mitochondrial dysfunction and aberrant complement system activation, specifically inducing inflammation and accumulation of pro-fibrotic changes. Although emerging evidence strongly indicates that these two processes are closely intertwined, identification of appropriate therapeutic targets remains limited. Among complement proteins, terminal portions of the cascade, including complement 5 (C5), exert particularly robust effects on mitochondrial function across tissues, including the kidney. Moreover, C5 is the most terminal portion of the cascade to produce a highly pro-inflammatory anaphylatoxin, positioning C5 as an ideal clinical target during kidney injury/disease. In this review, we will hence summarize current knowledge regarding mitochondrial contributions to kidney pathophysiology through the lens of the close relationship between mitochondria and the complement system, particularly C5. Full article

In hemodialysis patients, Body Mass Index is insufficient in assessing their nutritional status due to the ‘obesity paradox’ and the association between body composition and inflammation. This study assessed the relationship between body composition, traditional inflammatory markers, the new NETosis indicators (neutrophil extracellular traps), and their association with 12-month mortality. The study included 99 maintenance hemodialysis (HD) patients. Their body composition was assessed using bioelectrical impedance analysis. Blood serum was tested for inflammatory markers (hs-CRP-high sensitive c-reactive protein, IL-6 interleukin-6, TNF-α tumor necrosis factor alfa, IL-1β interleukin-1 beta), NETosis markers (citrullinated histone CH3, myeloperoxidase -MPO, elastase), and nutritional status parameters (albumin, transferrin). No correlation between BMI -body mas index and inflammation was demonstrated. Higher adipose tissue, particularly visceral, was significantly positively correlated with IL-6 and hs-CRP levels, while muscle mass was negatively correlated with inflammation. Dialysis catheter use was associated with higher CH3 levels (NETosis indicator) and lower albumin concentrations. Low albumin levels and high TNF-α levels were independent predictors of death. Body composition, rather than BMI, is associated with the severity of inflammation. Visceral obesity is positively correlated with increased inflammation, while muscle mass shows an inverse association. Dialysis catheters are linked to higher NETosis markers and lower albumin levels, which are associated with a poorer prognosis. Full article

Background. Hematological inflammatory indices from the complete blood count have been proposed as inexpensive prognostic markers in sepsis. The systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) are the most studied, but the performance of monocyte-containing alternatives (SIRI, AISI) in the elderly, in whom immunosenescence may alter the leukocyte phenotype, remains poorly characterized. Methods. In a single-center retrospective cohort of patients aged ≥65 years admitted to a tertiary ICU with Sepsis-3-defined sepsis (n = 127, 33 deaths), we compared the discrimination of six indices (NLR, PLR, MLR, SII, SIRI, AISI) for 30-day all-cause mortality using AUROC with bootstrap confidence intervals and pairwise DeLong tests. Independent associations were assessed by logistic regression adjusted for APACHE II and age; incremental value over APACHE II was explored using IDI, cNRI, calibration and decision curve analysis, with bootstrap optimism correction. Results. Thirty-day mortality was 26.0%. The monocyte-containing indices (AISI, SIRI, MLR) discriminated better than SII and NLR, and AISI was significantly superior to SII, NLR and PLR on DeLong testing, though not to SIRI, MLR or APACHE II. After adjustment for APACHE II and age, AISI, SIRI and MLR remained independently associated with mortality, whereas SII and PLR did not. Adding AISI to APACHE II improved reclassification and calibration and yielded higher net clinical benefit across clinically relevant thresholds. Conclusions. In this exploratory, single-center analysis, monocyte-containing indices, particularly AISI, were more strongly associated with 30-day mortality in elderly ICU sepsis than SII or NLR. AISI, SIRI and MLR were strongly intercorrelated and near-equivalent, and AISI did not significantly exceed APACHE II in discrimination. These hypothesis-generating findings require prospective external validation before clinical use. Full article

Hypobaric hypoxia poses a serious threat to growth and development and can induce pronounced inflammatory responses. These effects are closely associated with the gut microbiota. However, the underlying mechanisms, particularly the role of gut microbiota in regulating hepatic metabolism under chronic hypoxic conditions, remain poorly understood. In this study, SD rats were used as recipients and assigned to three groups: a hypobaric hypoxia group (H), an antibiotic-treated group (HA), and an antibiotic-treated group receiving fecal microbiota transplantation from plateau zokors (HAM). All rats were maintained in a hypobaric hypoxia chamber simulating an altitude of 6000 m for 30 days. Subsequently, growth performance, routine hematological parameters, and multi-omics profiles were evaluated. Compared with the H group, both the HAM and HA groups showed significantly increased average daily gain (ADG) (p < 0.05), while the ADG/ADFI ratio was significantly higher in the HAM group than in the H group (p < 0.05). Monocyte count (Mon#) and monocyte percentage (Mon%) were significantly higher in the HA group than in both the H and HAM groups (p < 0.05). Microbiota analysis revealed significant enrichment of Lachnospiraceae_NK4A136_group in the HAM group, whereas Desulfovibrio was significantly enriched in the HA group (p < 0.05). Fecal metabolomics showed that ursodeoxycholic acid (UDCA) was significantly increased in the HAM group (p < 0.05). In the liver metabolome, the anti-inflammatory lipid FAHFA 18:1/20:3 was significantly elevated in the HAM group, whereas pro-inflammatory factors, including uric acid and leukotriene D4, were significantly reduced (p < 0.05). Correlation analysis further demonstrated that the abundance of Lachnospiraceae was positively correlated with FAHFA 18:1/20:3 and negatively correlated with uric acid and creatinine (p < 0.05). Collectively, these findings indicate that the gut microbiota can modulate gut–liver metabolism, alleviate inflammatory responses, and enhance the adaptation of rats to hypoxic environments. This study provides valuable insights into potential strategies for promoting sustainable animal health and adaptation under hypoxic conditions. Full article

Objective: To evaluate the efficacy of NADPH oxidase 4 and miR-146a-5p in current treatment planning for ascending aortic aneurysms, independent of aortic diameter, and to develop protocols that will ensure the treatment of ascending aortic aneurysms, which pose a risk for aortic dissection, without complications. Methods: Patients who met the inclusion criteria and underwent surgery at Dr. Siyami Ersek Chest, Heart, and Vascular Surgery Training and Research Hospital for ascending aortic aneurysms and coronary artery disease between 2023 and 2024 were included in the study. This study was designed as a prospective study. Demographic, biochemical, radiological, and echocardiographic data were collected, and NOX4 mRNA and miR-146a-5p expressions were examined and compared in tissue samples. Results: The study was conducted on a total of 50 patients, with 25 patients in the aneurysm group and 25 patients in the control group. miR-146a-5p expression levels were found to be significantly decreased in the patient group compared to the control group (p = 0.001). When NOX4 mRNA expression levels were examined, no significant difference was found between the control and aneurysm groups. No correlation was found between NOX4 mRNA and miR-146a-5p levels (p = 0.764). When the relationship between ascending aorta diameter and both NOX4 mRNA and miR-146a-5p was examined, it was found that miR-146a-5p expression was negatively correlated with ascending aorta diameter (p = 0.036) and did not show a significant correlation with NOX4 mRNA levels (p = 0.318). A similar correlation was also found with ascending aorta length. The correlation of NOX4 mRNA and miR-146a-5p expression levels with age, gender, and ejection fraction was investigated separately. No significant correlation was found for all three variables. The optimum cut-off value to be used to separate the patient group from the control group using miR-146a-5p expression levels, as well as the sensitivity and specificity of miR-146a-5p expression levels when this cut-off value was used, was calculated using an ROC curve. Specificity for miR-146a-5p expression was found to be 88%, and sensitivity was found to be 66%. Conclusions: The study found promising results indicating that NOX4, shown to be a determinant of vascular oxidative stress, is not involved in the development of ascending aortic aneurysms; however, miR-146a-5p, which functions in the regulation of many inflammatory responses, including the regulation of NOX4 expression, may help prevent the development of ascending aortic aneurysms. Further studies aimed at elucidating the genetic and biochemical processes involved in aneurysm development suggest that miR-146a-5p could be a therapeutic target for preventing aneurysms. Full article

Musculoskeletal pain is a major cause of disability and long-term analgesic use, increasing interest in safe non-pharmacological interventions. This focused narrative review examines light-emitting diode (LED)-based photobiomodulation (PBM) for musculoskeletal pain, integrating molecular, mechanistic, clinical, and translational evidence. Red and near-infrared LED-PBM may act through mitochondrial and non-mitochondrial photoacceptors, modulation of ATP production, reactive oxygen species, nitric oxide, calcium signaling, inflammatory pathways, oxidative stress responses, and extracellular matrix repair. Clinical evidence suggests a potential benefit in selected conditions, particularly temporomandibular disorders, fibromyalgia, cervical and myofascial pain, tendon and plantar fascia disorders, knee osteoarthritis, and mild-to-moderate peripheral nerve compression, while findings for non-specific low back pain remain inconsistent. The reviewed literature indicates that therapeutic response depends less on emitter identity alone than on wavelength, irradiance, radiant exposure, treatment geometry, target depth, timing, disease phenotype, and protocol quality. LED-based PBM appears generally well tolerated and clinically promising as an adjunct to rehabilitation, but current evidence is limited by heterogeneous devices, incomplete dosimetry, variable comparators, and short follow-up. Future studies should prioritize standardized reporting, depth-aware dosing, phenotype-based recruitment, biomarker-linked outcomes, and direct laser–LED comparisons under dosimetrically matched conditions. Full article

Anemia represents one of the most frequent systemic complications of inflammatory bowel disease (IBD), with a consistently higher prevalence reported in patients with Crohn’s disease (CD) compared with ulcerative colitis (UC). While chronic inflammation, impaired iron absorption, and intestinal blood loss are recognized contributors, microbiome-mediated mechanisms influencing host iron availability remain insufficiently explored. Emerging evidence indicates that CD-associated dysbiosis is characterized by an increased abundance of siderophore-producing bacteria, particularly members of the Enterobacteriaceae family. Because siderophores are high-affinity iron-chelating molecules capable of competing with host iron acquisition systems and partially escaping lipocalin-2-mediated sequestration, their expansion may contribute to reduced luminal iron bioavailability. In this systematic review, we analyzed comparative microbiome studies published between 2016 and 2026 that directly evaluated microbial differences between CD and UC. CD microbiota consistently demonstrated enrichment in siderophore-associated taxa relative to UC. Based on these findings, we propose that microbiome-driven iron competition may represent an additional mechanistic contributor to the increased prevalence and persistence of anemia observed in CD. Although direct in vivo quantification of siderophore activity in IBD remains limited, the convergence of ecological, functional, and strain-level microbiome evidence supports a biologically plausible interaction between microbial iron-scavenging strategies and host iron metabolism. Full article

Background/Objectives: Tordylium trachycarpum Boiss. (Apiaceae) is traditionally used in Kurdish ethnomedicine for the management of gastrointestinal disorders; however, its pharmacological efficacy and safety profile remain insufficiently investigated. This study evaluated, for the first time, the gastroprotective activity and associated antioxidant, inflammatory, and apoptotic responses of the methanolic extract of T. trachycarpum using an ethanol-induced gastric ulcer model in Sprague–Dawley rats. Methods: Preliminary phytochemical screening revealed the presence of phenolics, flavonoids, terpenoids, tannins, coumarins, and glycosides. Acute oral toxicity testing demonstrated no signs of toxicity at doses up to 5 g/kg. Gastric ulceration was induced by absolute ethanol, and animals were pretreated with the extract (250 and 500 mg/kg) or omeprazole (20 mg/kg). Results: The extract significantly decreased the gastric lesion area from 258.50 ± 6.38 mm² in the ulcer control group to 143.70 ± 0.76 mm² and 115.50 ± 0.76 mm², corresponding to ulcer inhibition rates of 44.41% and 55.31%. Additionally, the extract increased mucus production, maintained mucosal structure, and raised stomach pH. Biochemical analysis showed a significant increase in antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)] and a reduction in malondialdehyde (MDA) levels, indicating attenuation of oxidative stress. In addition, the extract modulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-10). Blood-based ELISA analysis demonstrated increased expression of heat shock protein 70 (HSP70) and reduced Bax levels, suggesting anti-apoptotic activity. Conclusions: These findings indicate that T. trachycarpum exerts significant gastroprotective activity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms, supporting its traditional use and highlighting its potential as a natural therapeutic candidate for the management of gastric ulcers. Full article

Per- and polyfluoroalkyl substances (PFAS) are persistent, chemically stable compounds widely used in daily life. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were identified as the most relevant PFAS due to their prevalence and toxicity. This study aimed to investigate the immunotoxic mechanisms of a mixture of these PFAS using an in silico approach. Comparative Toxicogenomic Database (CTD), GeneMANIA, CytoHubba (Cytoscape), ToppGene Suite, and Metascape were used for the analysis. A total of 65 immune-related genes were identified as common to all four PFAS, with IFNG, TNF, IL1B, IL6, TYK2, CD3E, CASP8, VAV1, ARHGAP4, and CARD11 emerging as key hub genes. CTD phenotype analysis indicated immune dysregulation, with decreased humoral and adaptive immune responses in humans and tissue-specific modulation of B- and T-cell activity in mice, while no immune-related phenotypes were observed for PFNA. Network analysis identified functional modules associated with apoptotic and immune signaling, endothelial cell migration and angiogenesis, and shared inflammatory and viral response pathways. Disease enrichment analysis associated PFAS with autoimmune disorders (rheumatoid arthritis, asthma), metabolic conditions, and cardiovascular diseases (experimental diabetes, hypertensive disease). These results highlight PFAS involvement in immune modulation, cytokine signaling, and disease susceptibility. Full article

Background: Increasing evidence suggests that schizophrenia may be associated with peripheral immune–inflammatory alterations, although the distributional characteristics and heterogeneity of routinely available complete blood count (CBC)-derived inflammatory indices in real-world psychiatric inpatient settings remain insufficiently characterized. The present study aimed to descriptively evaluate the distributional properties of CBC-derived inflammatory markers in hospitalized patients with schizophrenia using an exploratory panel-based analytical framework. Methods: We conducted a retrospective cross-sectional analysis using anonymized CBC laboratory panels obtained from hospitalized patients with schizophrenia at a tertiary psychiatric center. Following panel reconstruction and quality control procedures, 858 structurally valid CBC panels were included in the analyses. Primary inflammatory indices included neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune–inflammation index (SII). Descriptive distributional analyses, threshold-based prevalence estimation, Spearman correlation analyses, and exploratory unsupervised clustering procedures were performed to evaluate inflammatory variability and internal distributional patterns within the dataset. Results: Median NLR was 2.51 (IQR: 1.95–3.55), median MLR was 0.25 (IQR: 0.19–0.31), median PLR was 124.10 (IQR: 100.40–163.94), and median SII was 686.96 (IQR: 484.81–1045.85). Threshold-based analyses demonstrated substantial variability in inflammatory burden distributions, with 35.9% of panels showing NLR > 3 and 27.0% demonstrating SII > 1000. Correlation analyses revealed strong positive associations among NLR, PLR, and SII, whereas RDW-CV and MPV demonstrated weaker and more heterogeneous relationships with the principal inflammatory indices. Exploratory clustering analyses generated two distributional clusters, including a smaller cluster exhibiting relatively higher NLR, MLR, PLR, SII, WBC, and platelet values than the remaining panels. Female panels demonstrated significantly higher PLR and SII distributions following false discovery rate (FDR) correction. Conclusions: The present findings suggest that CBC-derived inflammatory indices demonstrate substantial distributional variability within this panel-based schizophrenia dataset. Although the exploratory design, absence of patient-level linkage, and lack of clinical confounder adjustment substantially limit biological interpretation, routinely available hematological inflammatory markers may still provide a pragmatic framework for descriptive characterization of inflammatory variability patterns in real-world psychiatric populations. Future patient-level longitudinal studies integrating clinical, pharmacological, and molecular variables will be necessary to determine the potential clinical relevance of inflammatory heterogeneity in schizophrenia. Full article

CXCL12 is a chemokine acting via CXCR4 that plays a key role in inflammatory processes by regulating leukocyte migration and immune responses, making it an important focus of research in neuroinfections. In this study, the CXCL12 chemokine was evaluated as a potential diagnostic marker of different neuroinfections with particular emphasis on tick-borne encephalitis (TBE). A group of 214 patients with confirmed meningitis and/or encephalitis was included and divided according to etiology into TBE, aseptic meningitis, neuroborreliosis, and purulent meningitis. CXCL12 concentration and other inflammatory parameters were measured in cerebrospinal fluid (CSF). CXCL12 levels were compared with those of controls (N = 25) and analyzed statistically. In addition, serum was used to determine albumin concentrations. CXCL12 concentrations were significantly higher in patients with neuroinfections compared to controls and showed good diagnostic performance in the overall study group (AUC = 0.791), with a more moderate diagnostic performance observed in individual etiological groups, except in the purulent meningitis group, where the effect was not statistically significant, likely due to the small sample size. CXCL12 also demonstrated some utility in differentiating between specific etiologies; however, this effect was limited. Better diagnostic performance was observed when CXCL12 was combined with pleocytosis in a composite model differentiating between the TBE group and aseptic meningitis (AUC = 0.761). The presented results indicate the role of CXCL12 in neuroinflammation while simultaneously highlighting its potential in the development of novel diagnostic approaches for viral neuroinfections. Despite higher levels in TBE, its standalone diagnostic value is limited; however, it may enhance diagnostic accuracy when combined with other markers such as pleocytosis. Full article

Coordinated responses of intestinal epithelial and immune cells are essential for maintaining barrier integrity and immune homeostasis in dogs, yet our mechanistic understanding of probiotic-derived metabolites remains limited due to reliance on non-canine experimental models, highlighting the need for studies in canine-derived systems. Here, we investigated the effects of metabolites derived from Limosilactobacillus reuteri strain ATCC PTA6127 (Lr6127), delivered as a cell-free supernatant (CFS), on canine epithelial MCA-B1 cells and macrophage-like DH82 cells subjected to lipopolysaccharide (LPS)-induced inflammatory stress. Lr6127 CFS significantly reduced epithelial permeability, decreasing FITC–dextran leakage to 94.9 ± 1.9% (normalized relative to LPS-treated control, which was set as 100%) (p < 0.001), despite no detectable transcriptional changes in tight junction, adherens junction, or mucin genes. Barrier effects were instead associated with changes in markers of cellular stress responses, with heme oxygenase expression decreasing from 0.9 ± 0.1 to 0.7 ± 0.1 (p < 0.05). In DH82 immune cells, Lr6127-derived metabolites altered LPS-induced stress- and inflammation-related gene expression patterns; enhanced anti-apoptotic responses, as reflected by the increased BCL2 expression (1.4 ± 0.1 vs. 1.0 ± 0.0; p < 0.01) and elevated BCL2/BAX ratios (p < 0.01); and reduced expression of pro-inflammatory mediators including IL-6 and CCL2 (p < 0.05–0.001). Proteomic analysis corroborated that Lr6127-derived metabolites reduced the abundance of inflammatory and STAT-associated signaling proteins under LPS challenge, while indicating context-dependent changes in immune-related protein profiles under resting condition. Collectively, these results suggest that Lr6127-derived metabolites improved epithelial barrier function, which was accompanied by coordinated changes in cellular stress-related and inflammatory pathways, highlighting their potential to positively influence host responses. Full article

Background/Objectives: Glucocorticoids, including dexamethasone (DEX), are known to demonstrate anti-inflammatory activity, suppress steroidogenesis, and mitigate the adverse effects of chemotherapy. They are therefore widely employed for managing solid malignancies. Emerging evidence indicates that DEX modulates both systemic and local renin–angiotensin system (RAS) activity, including genomic signaling via the glucocorticoid receptor (GR). Methods: DEX-dependent transcriptional responses for the angiotensin receptor genes (AGTR1, AGTR2, MAS1, and LNPEP) were evaluated in ovarian (SKOV3, KURAMOCHI) and prostate (DU-145, PC3) cancer cell lines. The cells were cultured under different serum conditions to determine the influence of nutrient availability on tumor progression. Results: DEX demonstrated distinct mechanisms of action between the ovarian and prostate cancer models. It was found to promote cancer cell survival through tissue-specific modulation of metabolic activity, clonogenic capacity, cell cycle distribution, and apoptotic responses. These effects were accompanied by condition-dependent alterations in angiotensin receptor gene expression. Hence, DEX may mediate the remodeling of local RAS signaling, which may be significant in overall survival and disease-free survival. The findings also indicate a previously-unreported NR3C1–LNPEP correlation, which was consistently observed across in vitro systems and patient datasets, in both ovarian- and prostate-derived cancer models. Conclusions: DEX appears to exert context-dependent regulation of RAS-associated gene networks in ovarian and prostate cancer, suggesting a role in tumor adaptive responses and potentially in therapeutic contexts. Full article