Search Results (851)

Male fertility is declining worldwide, with notable reductions in sperm counts, emphasizing the need for new therapeutic interventions. Atranorin (ATR), a lichen-derived secondary metabolite, exhibits strong antioxidant and anti-inflammatory activities. This study assessed the protective effects of ATR on type 1 diabetes (T1D)-induced reproductive dysfunction in rats. T1D was induced in male Wistar rats via a single intraperitoneal injection of alloxan at 150 mg/kg body weight (bw). ATR significantly ameliorated T1D-related reproductive damage. At 170 mg/kg bw, ATR reduced hyperglycemia by 66% and attenuated seminal inflammation, decreasing leukocyte infiltration (−51%) and myeloperoxidase (MPO) activity (−68%). Oxidative balance improved, as evidenced by increased total antioxidant status (TAS) (+203%) and decreased thiobarbituric acid reactive substances (TBARS) (−73%), hydrogen peroxide (H₂O₂) (−45%), and total oxidant status (TOS) (−70%). Steroidogenesis was restored through enhanced 3β-hydroxysteroid dehydrogenase (3β-HSD) (+65%) and 17β-hydroxysteroid dehydrogenase (17β-HSD) (+102%) activities, resulting in a 90% recovery of testosterone levels. Seminal plasma function improved, with increased fructose levels (+71%), normalized pH (7.4), and enhanced hyaluronidase (HYAL) (+71%), adenosine triphosphatase (ATPase) (+71%), and prostatic acid phosphatase (PAP) (+79%) activities. Fertility biomarkers, such as adenosine deaminase (ADA) (+148%) and lactate dehydrogenase-C4 (LDH-C4) (+62%), increased, and essential minerals Zn²⁺ (+72%), Ca²⁺ (+96%), Mg²⁺ (+84%), and Se (+57%) were restored. Consequently, sperm density (+87%), viability (+69%), and motility (+189%) improved, while abnormalities declined (−46%). Histological findings confirmed the restoration of spermatogenesis and epididymal maturation. ATR effectively counteracts diabetes-induced reproductive dysfunction by reducing oxidative and inflammatory stress while improving hormonal and seminal parameters. Full article

Background: Following the earthquakes that occurred in Turkey in 2023, the resulting demolition dust (DD) negatively impacted air quality and led to an increase in respiratory diseases. Although the harmful effects of crystalline and amorphous silica are known, the effects of hydrated cement dust (HCD), autoclaved aerated concrete dust (AACD), and DD on the lungs have not been sufficiently investigated. This rat study presents the first experimental data on the toxicity of these dusts. Methods: In the study, the structural properties of dust particles smaller than 5 µm were characterized using XRD analysis. Subsequently, 48 female rats were divided into four groups: HCD, AACD, DD, and control. The relevant dust suspensions were administered to the experimental groups, and physiological saline was administered to the control group intranasally a total of five times over a 15-day period, once every 3 days. Subsequently, bronchoalveolar lavage fluid, blood, and lung tissues were analyzed. Results: An increase in emphysema was observed in all exposure groups, and this increase was significant in the AAC and HC groups. Inflammation and alveolar wall thickness increased in the HC and DD groups. Goblet cell hyperplasia was detected only in the HC group; increases in CD68⁺ macrophages and TGF-β, as well as elevated hydroxyproline, were detected only in the DD group and supported the fibrotic response (p < 0.05). Neutrophil increase was specific to the AAC group. In all exposure groups, Akt/NF-κB pathway proteins, caspase-9, and MPO levels increased, while Bcl-xl levels decreased (p < 0.05). The findings indicate that the examined dusts trigger inflammation and apoptosis. Conclusion: Exposure to HCD, AACD, and DD causes lung damage by modulating the Akt/NF-κB signaling cascade; it enhances the apoptotic process through Bcl-xl suppression and caspase-9 increase. DD also induces a marked fibrotic response. Full article

The gut–mammary axis represents a promising therapeutic target for mastitis. Although plant-derived polysaccharides exhibit immunomodulatory properties, their capacity to modulate this axis—and specifically to ameliorate dysbiosis-induced mastitis—remains unexplored. Here, we investigated the therapeutic potential of Taraxacum kok-saghyz leaf-derived polysaccharides (TKP-L) against mastitis in a murine model of gut dysbiosis, with dysbiosis induced by fecal microbiota transplantation (FMT) from donor cows. Pregnant mice (n = 60) with antibiotic-depleted microbiota received FMT suspensions prepared from the feces of healthy dairy cows or cows with clinical mastitis (based on somatic cell count). Mice were randomly divided into five groups: Control (vehicle), M-FMT (mastitis-cow FMT, disease model), H-FMT (healthy-cow FMT), TKP-L (M-FMT + oral TKP-L, 500 mg/kg/day), and Ciprofloxacin (M-FMT + ciprofloxacin, positive Control). After FMT establishment, TKP-L or ciprofloxacin was administered for 14 days. We assessed histopathology, pro-inflammatory mediators (IL-6, IL-1β, TNF-α, MPO), tight junction proteins (occludin, ZO-1, Claudin-3), and bacterial translocation using GFP-E. coli, and gut/milk microbiota via 16S rRNA sequencing. Compared to the M-FMT group, TKP-L treatment significantly alleviated mammary inflammation and pathology, inhibited pro-inflammatory cytokine expression, and enhanced the expression of tight junction proteins in both intestinal and mammary tissues, correlating with reduced bacterial translocation to the mammary gland. Microbiota analysis showed that TKP-L restored microbial homeostasis in the gut and milk, concurrently increasing the relative abundance of beneficial bacteria such as Limosilactobacillus. TKP-L alleviates gut dysbiosis-induced mastitis in mice by concurrently modulating the gut–mammary axis through microbial remodeling, enhancement of epithelial barriers, and anti-inflammatory actions. These findings highlight TKP-L as a promising gut microbiota-targeting candidate for mastitis intervention. Full article

Metropolitan governance in the U.S. has taken shape over generations and is still evolving. The U.S. territory is literally covered by a myriad of institutions responsible for influencing the country’s physical destiny, cultural identity, and digital representations. Due to their growing complexity, metropolitan areas require adequate institutional mechanisms capable of steering the physical, socio-economic, ecological, and digital transformations within their jurisdictional boundaries. The research question at the core of this article is the following: Where does knowledge concerning land management for metropolitan governance in the U.S.A. come from? This paper aims to review metropolitan governance’s evolution, state of the art, and current challenges in the U.S. at the beginning of the 21st century. The methods consisted mostly of reviews of specialized literature as well as an analysis of two metropolitan archetypal case studies on opposite ends of the country: the sprawling Southwest (Phoenix, Arizona) and the shrinking Northeast Rust Belt (the Albany Capital Region of upstate New York). It is argued that although the Councils of Government (COGs) and metropolitan planning organizations (MPOs) are invaluable in producing land cover and land use change atlases and toolkits of their territories, fragmented units of government within metropolises intensify economic and fiscal disparities and can potentially undermine regional competitiveness and efficiency. The article’s key findings revolve around the current and most pressing challenges and strategies with the potential to move metropolitan governance institutions toward greater regional cooperation and planning. Full article

Zevaquenabant (S-MRI-1867) is a clinical-stage agent that is a peripherally restricted, potent antagonist of CB₁R and an inhibitor of inducible nitric oxide synthase. A novel synthetic route to this highly selective active pharmaceutical agent is described in this paper. This route makes use of rationally installed chiral thio-substituted leaving group derived from a Bunte-salt reaction approach to yield diastereomeric compounds which are further processed to enantiopure compounds. The method will enable a rapid assembly of a variety of chiral sulfonyl amino compounds in this series. Full article

Inflammatory Bowel Disease (IBD) is a chronic, recurrent intestinal inflammatory disorder with an unclear etiology. Current pharmaceutical therapies for IBD still have several side effects, necessitating safer and more effective strategies. Edible insects are novel nutritional and bioactive resources with potential anti-inflammatory properties, but the effects of Zophobas morio larvae (ZML) and Tenebrio molitor larvae (TML) on IBD remain insufficiently explored. A 3% dextran sodium sulfate (DSS)-induced mouse colitis model was established to evaluate ZML protein powder (ZMLpp) and TML protein powder (TMLpp). Disease Activity Index (DAI), colon length, spleen weight, histopathology, inflammatory cell infiltration (LCA/MPO staining), inflammatory cytokines (Ccl2, Cxcl1, Ptgs2, Nf-κb), and intestinal microbiota (16S rRNA sequencing) were determined. The result showed that compared with the DSS group, both ZMLpp and TMLpp significantly reduced DAI, mitigated weight loss and hematochezia/diarrhea, restored colon length, attenuated mucosal damage, and preserved goblet cells and crypts, inflammatory cell infiltration, downregulated cytokine expression, improved fecal microbiota dysbiosis, such as increased abundance of beneficial bacteria like Akkermansia. These findings demonstrate that both ZMLpp and TMLpp alleviate DSS-induced colitis by inhibiting inflammation and modulating the microbiota, supporting their application in IBD therapy and the development of anti-colitis functional foods or pharmaceuticals. 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

Osteosarcoma (OS), a highly aggressive bone malignancy, is hard to treat due to complex molecular mechanisms. This study aimed to identify key bioactive compounds from medicine–food homologous (MFH) substances for OS intervention. We analyzed GEO transcriptomic data to get 317 differentially expressed genes (DEGs), screened bioactive compounds from 106 MFH via dual databases, predicted compound–DEG protein interactions with GraphBAN, and filtered 11 core compounds through drug-likeness/toxicity evaluations. Regulatory networks identified 5 key target genes (SOST, ACACB, TACR1, GRIN2B, MPO), 10 key compounds (e.g., ellagic acid dihydrate) and 8 MFHs (e.g., Daidaihua). Molecular docking/MD confirmed stable complexes. GSEA/GSVA revealed pathway dysregulation (e.g., upregulated WNT signaling), and immune analysis showed altered infiltration of 5 cell subsets. 143B cell experiments and qRT-PCR validated findings. MFH-derived compounds, especially ellagic acid dihydrate, have multi-target anti-OS potential, laying a foundation for novel OS therapeutics. Full article

Exercise training has demonstrated potential benefits in addressing the adverse effects of cardiovascular diseases, particularly myocardial infarction (MI). This study analyzed the cardioprotective effects of moderate exercise before and after MI in rats subjected to isoproterenol (ISO)-induced heart damage. Wistar rats were assigned to five groups: controls (CTRL), isoproterenol-treated (ISO), swimming before ISO (PRE + ISO), swimming after ISO (ISO + POST), and swimming both before and after ISO (PRE + ISO + POST). Cardiac function was assessed through echocardiography, while oxidative stress markers, Heme Oxygenase-1 (HO-1) and Myeloperoxidase (MPO), were quantified using biochemical assays and enzyme-linked immunosorbent assay (ELISA). Statistical analyses were conducted by one-way analysis of variance (ANOVA), accompanied by Tukey’s post hoc test. Exercise performed post-MI and both pre- and post-MI significantly reduced ISO-induced infarct size and improved left ventricular function (stroke volume (SV), ejection fraction (EF), and Tei index). HO-1 protein concentration and HO enzyme activity were restored, while swim training reduced the activity of MPO compared to the ISO group. Moderate exercise training, when appropriately timed, provides cardioprotection against ISO-induced myocardial damage by reducing oxidative stress and cardiac dysfunction. Full article

Metabolic syndrome (MetS) is characterised by cardiometabolic risk factors and is closely associated with increased oxidative stress and chronic low-grade inflammation. MetS is largely driven by adverse lifestyle behaviours, particularly physical inactivity, and regular physical activity is recognised as a central strategy for its prevention and management. This study aimed to assess the long-term impact of a five-year follow-up period of physical activity on oxidative stress, inflammatory biomarkers, and cardiometabolic health in adults with MetS. Forty participants diagnosed with MetS (50% men, aged 55–75 years) were selected and stratified into two groups: those who increased their physical activity and those who reduced it during the intervention. Physical activity was assessed using metabolic equivalent task minutes per week (MET·min/week), and evaluations were performed at baseline, 3 years, and 5 years. Participants who increased physical activity showed a progressive reduction in reactive oxygen species (ROS) produced by peripheral blood mononuclear cells (PBMCs), together with a decrease in plasma malondialdehyde (MDA). Antioxidant enzyme activities, including catalase and superoxide dismutase, exhibited a favourable long-term profile, with recovery or maintenance of higher activity levels by the end of follow-up, reflecting enhanced endogenous antioxidant defence. Inflammatory status improved and was characterised by a reduction in myeloperoxidase (MPO) activity and a sustained increase in plasma interleukin-15 (IL-15). These participants also showed reductions in body weight, body mass index (BMI), waist circumference, fasting glucose, and glycosylated haemoglobin A1c (HbA1c), consistent with improved insulin sensitivity and metabolic control. Participants who reduced physical activity tended to show unfavourable trajectories in several biomarkers. Increasing physical activity over time is associated with substantial improvements in redox balance, inflammatory status, and cardiometabolic health in adults with MetS. These findings reinforce the central role of physical activity as a fundamental therapeutic component within lifestyle interventions aimed at mitigating metabolic dysfunction and preventing MetS progression. Full article

To date, neutrophil-derived myeloperoxidase (MPO), a key mediator of inflammation and oxidative stress, has predominantly been assessed in peripheral fluids by protein concentration rather than enzymatic activity, mainly due to methodological limitations. However, MPO activity directly reflects the enzyme’s cytotoxic potential and pathogenic role in inflammatory diseases. To address this gap, we employed an optimized immunocapture assay to evaluate MPO activity, specific activity, and protein concentration in females with type 2 diabetes mellitus (T2DM), a condition tightly linked to chronic low-grade inflammation and obesity. Our findings revealed that females with T2DM exhibited nearly three-fold higher serum MPO activity and more than two-fold greater specific activity compared to controls with no differences in MPO protein concentration. Notably, MPO-specific activity remained significantly associated with T2DM (p < 0.01 to p < 0.001 across multivariate models), even after adjusting for age and dual-energy X-ray absorptiometry-derived measures of total and regional fat mass. Only android/gynoid fat distribution retained marginal significance in these models. This study is the first demonstration that MPO enzymatic activity, rather than protein concentration, is independently linked to T2DM in females. These findings underscore the importance of assessing functional MPO activity in the context of metabolic disease and support its potential role as a pathophysiological marker. Full article

Background/Objectives: Diabetes mellitus impairs skin wound healing by promoting a chronic inflammatory response and increased oxidative stress. This study aimed to investigate the healing potential of menthol in skin wounds of diabetic rats. Methods: A single dose of streptozotocin (50 mg/kg, i.p.) induced type 1 diabetes mellitus in male Wistar rats. After nine days, a skin wound was made on the rats’ back and treated with vehicle, insulin-based cream (0.5 U/g), or menthol-based cream (0.5%) for 14 days. After the euthanasia, the wound area was destined for assays of anti-inflammatory and antioxidant activity, protein expression levels by Western blotting, measurement of MPO activity, and quantitative mRNA expression. Nitrite levels were measured in blood plasma. Results: The group treated with menthol-based cream decreased the wound area by 94%. Also, menthol reduced the levels of TNF-α and IL-6 and increased IL-10 levels, besides stimulating the activity of antioxidant enzymes SOD, GPx, and GR, and enhancement in GSH and nitrite levels. Menthol downregulated the expression of Nfκb and upregulated the Il10 and Ki67 gene expression and the eNOS protein expression. Conclusions: Topically applied menthol accelerated the skin wound healing in diabetic rats through anti-inflammatory and antioxidant activities and increased cell proliferation, supporting its potential as a therapeutic strategy for diabetic wound management. Full article

Background/Objectives: Gastro-oesophageal reflux disease (GERD) refers to a disease in which stomach acid rises into the oesophagus. Currently, proton pump inhibitors (PPIs) are the most commonly used medications to treat GERD. However, long-term use of PPIs is not free from side effects, and new treatment strategies are needed. The present study was conducted to evaluate the gastroprotective potential of four different formulations containing both antiacids and medicinal plants considered useful for the treatment of GERD. Methods: The protective effects of the formulations on gastric ulcers in pyloric ligation-induced gastric mucosal lesions in mice were evaluated by measuring gastric emptying, the ulcer index, gastric content, total acidity, and the pH of the gastric fluid. Gastric damage was also assessed by measuring myeloperoxidase (MPO) activity. Results: Formulations containing Glycyrrhiza glabra L. or Glycyrrhiza glabra L. plus Opuntia ficus-indica Mill. and Olea europaea L. (formulations 3 and 4, respectively) increased gastric emptying. All formulations decreased gastro-oesophageal damage (ulceration and MPO activity) and gastric contents and had no effects on total acidity or gastric fluid pH in the pyloric ligation ulcer model. Conclusions: Our results show that all formulations are able to exert cytoprotective and anti-ulcerative effects. However, among the formulations, formulation 4 seems to be the most promising because of its better effects on gastric injury and gastric emptying. These results support the hypothesis of the possible use of medicinal plants in combination with antacid agents in the treatment of GERD. Full article

Background: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation, oxidative stress, and disruption of intestinal metabolic homeostasis. Immunomodulatory nutrients such as arginine, glutamine, and β-hydroxy β-methylbutyrate (HMB) have shown potential benefits; however, their combined molecular effects on UC remain insufficiently defined. Objective: To investigate the individual and combined effects of arginine, glutamine, and HMB on inflammatory and metabolic gene expression, oxidative stress markers, and histopathological outcomes in a dextran sulfate sodium (DSS)-induced colitis model. Methods: Female Sprague Dawley rats were assigned to six groups: control, DSS, DSS + arginine, DSS + glutamine, DSS + HMB, and DSS + mixture. Colitis was induced using 3% DSS. Colon tissues were examined histologically, serum MDA, MPO, and GSH levels were quantified, and mRNA expression of IL6, IL10, COX2, NOS2, ARG2, CCR1, and ALDH4A1 was measured by RT-qPCR. Pathway enrichment analyses were performed to interpret cytokine and metabolic network regulation. Results: DSS induced severe mucosal injury, elevated MDA and MPO, reduced GSH, and significantly increased IL6, COX2, NOS2, ARG2, and CCR1 expression. Glutamine demonstrated the strongest anti-inflammatory and antioxidant effects by decreasing IL6 and COX2 and restoring GSH. Arginine primarily modulated nitric oxide–related pathways, whereas HMB increased ALDH4A1 expression and metabolic adaptation. The combination treatment produced more balanced modulation across inflammatory, chemokine, and metabolic pathways, consistent with enrichment results highlighting cytokine signaling and amino acid metabolism. Histopathological improvement was greatest in the mixture group. Conclusions: Arginine, glutamine, and HMB ameliorate DSS-induced colitis through coordinated regulation of cytokine networks, oxidative stress responses, and metabolic pathways. Their combined use yields broader and more harmonized therapeutic effects than individual administration, supporting their potential as targeted immunonutritional strategies for UC. Rather than targeting a single inflammatory mediator, this study was designed to test whether combined immunonutrient supplementation could promote coordinated regulation of cytokine signaling, oxidative stress responses, and metabolic adaptation, thereby facilitating mucosal repair in experimental colitis. Full article

Oxidative stress (OS) has gained substantial relevance due to its involvement in the pathogenesis of numerous systemic diseases. It is characterized by an imbalance between the production of reactive oxygen species (ROS) and the capacity of endogenous antioxidant systems to neutralize them. Various factors, including trauma, immunological alterations, and psychological stress, may contribute to this condition. The aim of this narrative review was to analyze OS markers and total antioxidant capacity (TAC) in asymptomatic and pericoronitis-associated impacted mandibular third molars (ITMs). This review examines the relationship between OS and impacted ITMs, highlighting the importance of timely clinical management to prevent chronic tissue damage. Current evidence indicates that OS biomarkers such as myeloperoxidase (MPO), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO) are elevated in patients with ITMs, including those classified as asymptomatic, and that a reduction in total antioxidant capacity (TAC) has been observed. The surgical removal of ITMs can effectively reduce OS levels. Following the procedure, oxidative markers typically return to normal within a relatively short period of time, and there is often a significant improvement in TAC. Full article