Search Results (28,729)

Background/Objectives: Interleukin-6 (IL-6) is a pro-inflammatory cytokine implicated in the pathogenesis of SLE. Beyond its role in disease activity, IL-6 has also been associated with increased cardiovascular risk, potentially promoting endothelial dysfunction, atherosclerosis, and thromboinflammation. Our study aimed to investigate the associations between IL-6 levels, disease manifestations, organ damage, cardiovascular comorbidities, and treatment regimens in a cohort of SLE patients. Methods: A total of 88 SLE patients were recruited from the Rheumatology Clinic of the Clinical Rehabilitation Hospital, Iași. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI) and irreversible organ damage with the SLICC/ACR Damage Index. Serum IL-6 levels were measured by ELISA. Statistical analyses included Mann–Whitney U tests and Spearman correlation coefficients. Results: Among 88 SLE patients (89.8% female, mean age 51.9 ± 14.8 years), 68.2% presented irreversible organ damage, most frequently cardiovascular (26.1%). Regarding disease manifestations, IL-6 was non-significantly elevated in patients with arthritis, rash, and low complement levels. Serum concentrations also tended to increase with disease severity, being higher in severe compared to moderate activity, and in moderate versus mild activity. Significant associations were found between IL-6 and hypertension (p = 0.027), aortic atherosclerosis (p = 0.034), menopausal status (p = 0.015), and hypercholesterolemia (p = 0.034). No significant differences were observed across treatment subgroups. Conclusions: IL-6 showed limited correlation with SLE clinical activity but was significantly elevated in patients with selected cardiovascular comorbidities. These findings suggest a potential contribution of IL-6 to cardiovascular risk in SLE, warranting further investigation in larger cohorts. Full article

Carrot processing for juice generates substantial pomace residues rich in bioactive compounds, which represent both an environmental challenge and an unexploited resource. This study investigated the protective effects of a polyphenolic extract derived from carrot pomace (CP) against Escherichia coli lipopolysaccharide (LPS)-induced damage. For that, we used IPEC-1 (Intestinal Porcine Epithelial Cells) as an in vitro model of the intestinal epithelium. The total phenolic content of the CP polyphenolic extract (CPE) was 1.017 mg GAE/mL, with flavan-3-ols (epicatechin, catechin, epigallocatechin) accounting for 71.3% of that value. Before being exposed to LPS (10 μg/mL) for 24 h, the cells were pre-treated with CP extract (20.34 µg and 10.17 µg polyphenols/mL of extract corresponding to 1/50 and 1/100 dilution) for 4 h. Epithelial renewal (cell viability, cell proliferation and apoptosis), monolayer/barrier integrity (TEER, FD4 permeability, LDH release), as well as epithelial functionality (synthesis of pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, reactive oxygen species (ROS), nitric oxide (NO) production), MAPK signalling and mitochondrial morphology and function were assessed. The results showed that CP extract had no cytotoxic effects and successfully counteracted LPS-induced loss of cell viability and proliferation. The pre-treatment with CPE at both dilutions significantly reduced LPS-induced apoptosis and cell death. Barrier integrity was preserved with TEER values maintained near baseline: −0.43% and −0.24% for 1/50 and 1/100 dilutions of CPE vs. −53.47% at 72 h for LPS alone, and paracellular FD4 passage was restored to control levels. At the molecular level, CP extract reduced pro-inflammatory cytokine gene expression (IL-6 by 40%, TNF-α by 50–56%) and suppressed LPS-induced MAPK activation by 62.9% and 46.5%, for 1/50 and 1/100 dilutions of CPE, respectively. The pre-treatment of cells with CP extract normalised LPS-induced ROS production and protected mitochondrial morphology and function. These in vitro findings demonstrate that CP extract exerts a protective effect on intestinal epithelial cells, acting through anti-inflammatory, antioxidant and barrier-preserving mechanisms. This supports the hypothesis for valorisation of carrot agro-industrial by-products as functional feed additives for promoting intestinal health. Further in vivo studies are needed to validate this hypothesis and to establish the concentration/rate of inclusion of carrot by-products to achieve the maximal positive effects. Full article

The rising burden of diabetic kidney disease (DKD) and its associated lipid abnormalities underscores the need for new mechanistic insights. Uromodulin, a kidney-enriched protein, has been associated with metabolic disorders in human studies, yet its functional role in systemic lipid metabolism remains elusive. In this study, transcriptomic datasets were analyzed to investigate uromodulin expression and biological function in DKD. Subsequently, a diabetic model was induced in UMOD^+/+ and UMOD^−/− rats using a combination of a high-fat diet, unilateral nephrectomy, and streptozotocin to assess renal and metabolic phenotypes. Public RNA-seq data indicated that uromodulin expression was downregulated in DKD and was enriched in the fatty acid metabolism pathway. At baseline, UMOD^−/− rats resembled UMOD^+/+ rats in terms of growth, routine serum lipids, and major organ function. However, in diabetes, UMOD^−/− rats exhibited higher mortality and pronounced hyperlipidemia. Hyperlipidemia occurred prior to the onset of renal dysfunction. Of note, this exacerbated lipid dysregulation represented a lipodystrophy-like phenotype rather than secondary changes in the pancreas, liver, or circulating cytokines (IL-6, IL-1β, and TNF-α). Moreover, UMOD^−/− rats displayed exacerbated tubular injury and enhanced renal lipid accumulation in DKD relative to UMOD^+/+ rats. Collectively, uromodulin protects diabetic rats from death, prevents epididymal white adipose tissue from browning, and attenuates kidney injury. Our findings identify uromodulin as a novel regulator of the kidney–adipose axis. Full article

Background: Hydrogen breath testing is commonly used to assess intestinal fermentation and diagnose small intestinal bacterial overgrowth (SIBO). However, it remains unclear whether hydrogen production reflects systemic inflammatory or metabolic status. This study evaluated the relationship between hydrogen production dynamics and systemic biomarkers using a data-driven analytical approach. Methods: This cross-sectional study included 162 adults undergoing lactulose hydrogen breath testing. Hydrogen production was characterized using continuous measures, including area under the curve (AUC), early and late hydrogen responses, and unsupervised clustering-derived hydrogen response groups. Associations with serum 25-hydroxyvitamin D, C-reactive protein (CRP), leukocyte count, and interleukin-6 (IL-6) were assessed using multivariable regression models adjusted for age and body mass index (BMI). Results: Hydrogen production showed substantial interindividual variability. Unsupervised analysis identified low-, intermediate-, and high-hydrogen response groups. Differences between groups were driven mainly by overall fermentation intensity rather than distinct temporal response profiles. No significant associations were observed between hydrogen production metrics and systemic biomarkers. Hydrogen-related variables were not independently associated with vitamin D, CRP, leukocyte count, or IL-6 concentrations. In contrast, BMI was consistently associated with inflammatory markers, particularly CRP and IL-6. Correlation analyses demonstrated strong relationships among hydrogen-derived variables but weak associations with systemic parameters. Conclusions: Data-driven analysis revealed marked heterogeneity in intestinal hydrogen production but no detectable association with systemic inflammatory or metabolic markers within the present cohort. These findings suggest that hydrogen breath test metrics primarily reflect local intestinal fermentation rather than systemic physiological status. Hydrogen breath testing remains useful for assessing gastrointestinal function, but no evidence supporting its value as a marker of systemic inflammation was identified in the present cohort. Full article

The efficient capture of carbon dioxide (CO₂) using polymer, supported ionic liquids (ILs) remains challenging due to limited understanding of atomic-scale interaction mechanisms. Here, a polystyrene (PS) oligomer supported by an amidinium chloride-based IL is proposed as a CO₂-absorbing material. Density functional theory (DFT) calculations were employed to investigate the structural, electronic, and intermolecular interaction energy characteristics of the PS oligomer, amidinium chloride ILs, CO₂, and their binary and ternary complexes. Molecular electrostatic potential maps (MEPs), reduced density gradient (RDG) plots with non-covalent interaction (NCI) snapshots, quantum theory of atoms in molecules critical point (CP) analysis, and electron localization function (ELF) analysis reveal pronounced hydrogen bonding and dispersion interactions between PS and IL that modulate the electronic environment of the IL anion, which is the primary CO₂ binding site. Interaction energy calculations show that the ternary PS–IL–CO₂ complex exhibits a significantly enhanced binding energy compared to the isolated IL–CO₂ complex, providing quantitative evidence for the cooperative role of the PS support. The results indicate enhanced CO₂ binding in the presence of PS supported by ILs, driven by cooperative electrostatic and dispersion interactions. These findings provide molecular-level insights into CO₂ capture mechanisms in polymer–IL hybrid systems. Full article

Background/Objectives: Parkinson’s disease (PD) exhibits marked sexual dimorphism, with a higher incidence and earlier onset in men than in women. However, the impact of biological sex on systemic molecular alterations in PD remains poorly understood. This pilot study aimed to identify sex-specific circulating signatures associated with PD. Methods: Serum samples from a selected cohort of PD patients and healthy controls (HC) of both sexes were analyzed using an integrated biochemical and ¹H NMR-based metabolomic approach. Oxidative stress markers, antioxidant proteins, inflammatory mediators, matrix metalloproteinases, α-synuclein species, and circulating antibodies were evaluated. Results: This analysis indicated that, while global oxidative stress markers were unchanged, sex-related differences in antioxidant pathways were observed as suggested by the reduced Nrf2 expression observed in PD females and increased IL-6 levels, above all in male PD patients. MMP3 levels were significantly higher in female PD patients compared with males. Male patients showed higher levels of 52 kDa protease-resistant α-synuclein species, while females exhibited increased antibody titers against both monomeric and aggregated forms. Metabolomic profiling suggested a disease-associated metabolic remodeling in PD, with distinct sex-related metabolic signatures and a more pronounced and widespread metabolic dysregulation in males. Conclusions: These findings suggest that biological sex may contribute to systemic molecular heterogeneity in PD, with trends indicating more pronounced inflammatory and metabolic alterations in males and distinct immune-related responses in females. Given the exploratory nature of the study and the limited sample size, these observations should be interpreted cautiously and require validation in larger, independent cohorts. Nevertheless, the results support the importance of considering sex-related molecular differences in future biomarker studies and precision medicine approaches for PD. Full article

Arthritis is a chronic inflammatory disease characterized by progressive joint damage, in which oxidative stress and exacerbated immune responses play a critical role. Synbiotics, defined as a combination of probiotics and prebiotics, may enhance these beneficial effects; however, their efficacy depends on maintaining microbial viability throughout gastrointestinal transit. In this study, we evaluated the anti-inflammatory and antioxidant effects of Levilactobacillus brevis LBH1070. Lacticaseibacillus paracasei ATCC 334 and phenylbutazone (PBZ) were used as probiotic and allopathic drug controls, respectively. Both probiotic strains significantly reduced paw edema by 46%, comparable to PBZ (45%), and decreased lipid oxidation (33–36%) and protein oxidation (40–45%), thereby preserving the integrity of the popliteal lymph node, the lymph node closest to the edema site. Furthermore, L. paracasei ATCC 334 and L. brevis LBH1070 reduced total T helper CD4+ lymphocyte infiltration in the popliteal lymph node by 44–54% and decreased IL-1β-producing T helper lymphocytes by 77–78%, surpassing the effect of PBZ (49%). TNF-α-producing T lymphocytes were also reduced by 60–62%, compared to PBZ (53%). These findings highlight the potential of L. brevis LBH1070, its synbiotic formulation, and L. paracasei ATCC 334 as complementary treatments to modulate immune responses and oxidative stress during arthritis. Full article

Background: The aim of this study was to comprehensively analyze the relationships within a multimodal biomarker panel, including endothelial function indicators, markers of systemic inflammation and myocardial stress, metabolic homeostasis parameters, and an indicator of microstructural damage to nerve tissue in CAD patients with or without type D personality. Methods: This exploratory, cross-sectional, observational study included 72 patients with coronary artery disease. All patients underwent psychological testing (evaluation of type D personality and determination of depression and anxiety levels) and biomarker measurements. The multimodal biomarker panel included measurements of metabolic homeostasis parameters (glucose, total cholesterol, creatinine, insulin, 1,5-anhydroglucitol), markers of systemic inflammation (CRP, IL-6), myocardial stress (NTproBNP), endothelial function parameters (eNOS, EDN1, ADMA, VEGF), and an indicator of microstructural damage to nerve tissue (S100B protein). Results: Biomarker levels revealed no statistically significant differences between the groups with and without personality type D. In personality type D, a direct correlation was found between the level of the brain tissue damage marker S100B and eNOS concentration (R = 0.578; p = 0.006), which was not observed in non-type D. In patients with personality type D, a significant inverse correlation was confirmed between ADMA and creatinine levels (R = −0.524; p = 0.015). In individuals with non-type D personality, a direct correlation was established between total cholesterol levels and VEGF (R = 0.342; p = 0.014). Conclusions: In patients with coronary heart disease, psychological distress (type D) is associated not with an isolated change in biomarker concentrations but with a transformation of the entire structure of their relationships. Personality type D is characterized by a transition from the physiological autonomy of systems to the formation of pathogenetic relationships between them, indicating a decrease in adaptive reserve. Full article

Inflammatory bowel disease (IBD) represents a growing global health threat that markedly increases colorectal cancer risk, yet conventional immunosuppressive agents achieve mucosal healing in only a limited subset of patients. M2-polarized macrophages have been recognized as crucial regulators of mucosal repair through their ability to maintain intestinal microenvironment homeostasis. Here, we investigated the potential effects and mechanisms of macrophage-derived exosomes (Exos) on epithelial barrier function in a murine model of IBD. Murine colitis was induced by intrarectal administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by treatment with Exos isolated from IL-33-treated macrophages (IL-33-Exos) or untreated macrophages (PBS-Exos). Our findings showed that IL-33-Exos markedly ameliorated inflammatory intestinal mucosal injury and improved intestinal barrier dysfunction. Concurrently, IL-33-Exos mitigated intestinal epithelial cell damage, thereby preserving intestinal mucosal integrity. Mechanistic studies revealed that the beneficial effects of IL-33-Exos were implicated in upregulation of Wnt/β-catenin signaling in intestinal epithelial cells. Translationally, these findings suggest that IL-33-Exos may promote epithelial repair in experimental colitis, offering a novel therapeutic avenue for clinical management of inflammatory bowel disease. Full article

Epilepsy is a common chronic neurological disorder characterized by recurrent seizures. Gastrodia elata, the dried tuber of G. elata Bl. (Orchidaceae), is a valuable medicinal and edible botanical resource. This study optimized the preparation of Yellow Rice Wine-Processed G. elata (YPGE) and investigated its antiepileptic effects and underlying mechanisms in a pentylenetetrazol (PTZ)-kindled rat model. Processing parameters were optimized using single-factor experiments combined with an analytic hierarchy process (AHP)-entropy weight method (EWM) weighting strategy and Box–Behnken design–response surface methodology. The optimal parameters were determined as 18% alcohol by volume, 72 °C drying temperature, and 32 h drying time. Compared with unprocessed G. elata (GE), YPGE exhibited 0.54-, 0.13-, 1.87-, and 3.58-fold increases in the contents of gastrodin (GAS), G. elata polysaccharides (GEPs), p-hydroxybenzyl alcohol (p-HBA), and total parishins (TP), respectively, and demonstrated significantly enhanced in vitro antioxidant activity (IC50 values of 2.604, 2.719, and 4.046 mg/mL for DPPH, ABTS, and hydroxyl radicals). In vivo, both GE and YPGE significantly reduced seizure severity, decreased inflammatory cytokines (TNF-α, IL-1β), alleviated oxidative stress (increased SOD and GSH-Px, decreased MDA), and modulated neurotransmitter balance (reduced Glu, increased GABA) in brain tissues. YPGE also upregulated P-glycoprotein expression and reduced neuronal apoptosis in the hippocampal CA1 region by upregulating Bcl-2 and downregulating Bax. These findings suggest that YPGE exerts multi-target antiepileptic effects through synergistic anti-inflammatory, antioxidant, and anti-apoptotic actions, providing experimental evidence for the development of novel antiepileptic therapies based on processed G. elata. Full article

Ionic liquids (ILs) are widely used chemical compounds that may pose potential risks to the environment. In the present study, the effects of 1-ethyl-3-methylimidazolium chloride (EMIMCl) on growth, photosynthetic performance, and oxidative stress in maize (Zea mays L.) seedlings were evaluated, and the role of exogenous L-ascorbic acid (AsA) in modulating plant responses to this stress was investigated. Plants were cultivated in soil contaminated with EMIMCl at concentrations ranging from 1 to 1000 mg·kg⁻¹ of soil dry weight (DW) and treated with AsA at concentrations of 0.5–2 mM. EMIMCl significantly inhibited plant growth, reduced photosynthetic pigment content, and impaired chlorophyll fluorescence parameters, accompanied by increased hydrogen peroxide (H₂O₂) and malondialdehyde equivalents (MDA) levels, indicating the induction of oxidative stress. Moderate doses of AsA partially alleviated EMIMCl-induced toxicity, whereas higher AsA concentrations under severe EMIMCl contamination intensified stress symptoms. These findings demonstrate a dose-dependent and biphasic role of AsA in maize responses to EMIMCl-induced stress. Full article

Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection remain a world health problem leading to fibrosis and cirrhosis. Liver damage is primarily mediated by the innate and adaptive immune responses since HBV and HCV are not directly cytotoxic. Kupffer cells and liver-recruited macrophages are heavily implicated in both viral elimination and progression of the disease. HBV and HCV proteins polarize macrophages into either an M1 pro-inflammatory phenotype, promoting hepatocyte damage or into an M2 immunosuppressive phenotype, leading to viral persistence and fibrogenesis via cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β). In this review a brief overview of the heterogeneity of liver macrophages in health and during chronic viral infection is presented. Recognition of viruses by macrophages and the modulation of macrophages by viral proteins in the pathogenesis of liver inflammation and injury are discussed in detail. Most importantly, the mechanisms that HBV and HCV are using to manipulate macrophages and escape elimination are also presented. The role of macrophages in the evolution of acute-on-chronic liver failure is analyzed. Finally, a concise presentation of the emerging, but not yet clinically used, therapeutic strategies targeting macrophages to control chronic HBV infection and restore the dysregulated immune response is discussed. In conclusion, this integrated review of liver macrophage implication summarizes the pathophysiology and pathogenesis of HBV and HCV including acute-on-chronic- liver failure and viral cirrhosis. Full article

Background: Bladder dysfunction is a complicated condition that substantially impairs quality of life for both men and women. Due to the adverse effects and limited efficacy of current therapies, new strategies must be rapidly developed. Female bladder dysfunction arises from multifaceted etiologies distinct from the predominantly male benign prostatic hyperplasia (BPH) that is the focus of existing drug development. In this study, we investigated the therapeutic potential of Quisqualis indica extract (QIE), a traditional medicinal herb that attenuates BPH-induced lower urinary symptoms (LUTS), to elucidate its underlying mechanisms in a female bladder dysfunction model. Methods and Results: A bladder dysfunction model was established by inducing partial bladder outlet obstruction (pBOO) in female Sprague Dawley rats, followed by the oral administration of QIE for 7 weeks. Voiding pattern analysis and cystometry were conducted to evaluate indicators such as voiding frequency, voiding volume, and intravesical pressure. Histological analysis of excised bladder tissue quantified smooth muscle hypertrophy and collagen deposition. Gene expression profiling of inflammatory cytokines and fibrosis-related markers within the bladder tissue was performed to assess tissue remodeling. Furthermore, pharmacological contraction studies examined the direct effects of QIE on detrusor muscle responsiveness to muscarinic and purinergic agonists. QIE administration significantly improved the elevated voiding pressure and abnormal inter-contraction intervals observed in the pBOO rats, restoring normal voiding patterns. Histological examination revealed a marked decrease in muscle hypertrophy and collagen deposition. Expression levels of pro-inflammatory cytokines (TNFα, IL-1β) and fibrosis-associated genes (TGF-β, α-SMA) were downregulated. Pharmacological contraction assays demonstrated that QIE attenuated the hypercontractile response of bladder smooth muscle to a muscarinic agonist, with concurrent reduced expression of muscarinic receptors (M₂, M₃) at the mRNA level. Conclusions:QIE ameliorates key aspects of bladder dysfunction, voiding abnormalities, inflammation, fibrosis, and hypercontractility by modulating muscarinic receptor signaling and fibrotic pathways. This study suggests that QIE warrants further investigation as a natural product-based therapeutic candidate for female bladder dysfunction. Full article

Fentanyl is an extremely potent and highly lipophilic synthetic opioid, whose toxicity is marked by significant respiratory depression and central nervous system impairment. Naloxone is the primary antidote for opioid overdose; however, there is an increasing interest in intravenous lipid emulsion (ILE) as a supplementary therapeutic approach for poisoning with lipophilic agents. This study aimed to assess the antidotal effect of ILE in cases of experimental fentanyl toxicity and to compare its effectiveness with that of naloxone, both when administered alone and in combination. The research was performed on male Wistar rats. Various parameters were monitored, including heart rate, respiratory rate, nociceptive response (Hot Plate test), motor coordination (Rota-rod test), and behavioral metrics (Open Field test). Fentanyl induced significant cardiorespiratory depression and analgesia. Naloxone successfully counteracted the respiratory and nociceptive effects. ILE demonstrated positive effects on specific cardiorespiratory parameters, especially in the initial recovery phase, although its influence on analgesia was less pronounced and occurred later. The combination of naloxone and ILE appeared to promote earlier cardiorespiratory enhancement compared to naloxone used alone; nevertheless, these variations must be viewed with caution due to the brief duration of fentanyl’s effects and the absence of evidence supporting an increased maximal therapeutic benefit. These findings endorse the potential role of ILE as an adjunctive, rather than a standalone, antidotal treatment for acute fentanyl poisoning. Full article

Redox homeostasis is the balance between oxidative processes and antioxidant defenses and is fundamental to cellular integrity. This review critically synthesizes current evidence on the phytochemical composition, redox-modulating mechanisms, and therapeutic bioactivities of Fagonia cretica L. (F. cretica), with the aim of evaluating its translational potential as a natural antioxidant and anticancer agent. F. cretica has emerged as a phytochemically rich candidate containing highly bioactive secondary metabolite for redox-targeted therapeutic applications. Its diverse secondary metabolite profile, including alkaloids, flavonoids, tannins, saponins, terpenoids, glycosides, and phenolic compounds, confers broad biological activity. Bioactive constituents, particularly kaempferol, catechin, quercetin, and arbutin, directly neutralize reactive oxygen species (ROS) and modulate inflammatory pathways through inhibition of COX-1, COX-2, and nitric oxide production. These compounds influence important major ROS-sensitive redox signaling pathways: activation of the Keap1/Nrf2/ARE axis to upregulate cytoprotective genes such as HO-1, NQO1, and GCL, suppression of the NF-κB pathway to attenuate pro-inflammatory cytokine transcription, including TNF-α, IL-1β, and IL-6, and interference with the MAPK-PI3K/Akt cascade to disrupt aberrant cancer cell survival and proliferation. Bioactive compound-rich extracts of F. cretica exhibit anticancer activity in MCF-7 breast cancer cells by inducing DNA damage, cell cycle arrest, and apoptotic signaling through the FOXO3a/p53 pathways. Similar effects have been reported in colorectal (HCT-116) and prostate (PC-3) cancer cells through DNA (cytosine-5)-methyltransferase 1 (DNMT1) downregulation, oxidative stress induction, and ER-β activation. Moreover, these extracts demonstrate cytotoxic effects in HepG2 and Caco-2 intestinal cancer cells, often associated with topoisomerase inhibition and caspase activation. Despite encouraging preclinical evidence, systematic studies encompassing pharmacokinetic profiling, toxicological characterization, and human clinical trials remain essential to translate these findings into safe, evidence-based therapeutic applications. Full article