Search Results (28,538)

Staphylococcus aureus is a major bacterial pathogen that can cause clinical infections and foodborne illnesses through the production of 25 exotoxin types. The most frequently implicated toxins in food poisoning outbreaks are Staphylococcal enterotoxins type A–E (SEA-SEE), which are the first enterotoxins discovered. While in vitro detection methods are available to identify the presence of enterotoxins, they cannot distinguish between biologically active and inactive forms of the toxins. Detection of biologically active enterotoxins currently relies on in vivo testing, using the emetic response in kittens or monkeys. Here, we show the development of an in vitro assay to detect the active forms of SEB, a potential biological warfare agent and leading cause of food poisoning, and SEC1, a frequent cause of staphylococcal food poisoning. The novel assay involves the implementation of a genetically engineered Jurkat T-cell line expressing TCR Vβ3, resulting in a dose response of IL-2 production when exposed to active toxin. We also show that at a concentration of 100 ng/mL, the biological activity of SEB is significantly decreased at temperatures over 70 °C, while pasteurization at 63 °C only slightly reduces the biological activity of the toxin. Our studies provide an alternative method to animal testing to determine the presence of active toxins and provide possible inactivation methods of the toxins. Full article

Background/Objectives: Formulating antibiotics as active pharmaceutical ingredient ionic liquids (API-ILs) has been proposed as a strategy to help overcome antimicrobial resistance. However, the effects of API-ILs on bacterial mutation frequency, an increase of which is associated with a higher risk of resistance development, have not yet been assessed. Here, API-ILs based on the antibiotic ciprofloxacin were synthesized using five structurally different counter ions of varying biological activity - low ([Chol]⁺ and [EMMor]⁺), intermediate ([TMC₁₀A]⁺) and high ([TMC₁₆A]⁺ and [TC₈MA]⁺) - and investigated in terms of their antimicrobial activity and mutation frequency in Escherichia coli MG1655. Methods: API-ILs were synthesized according to the CBILS© route. Conductivities and antimicrobial activity (determined by minimal inhibitory concentrations (MICs) and disk diffusion (DD) assays) of API-ILs as well as of individual API and ILs were measured, followed by mutation frequency assays. Results: Five novel ciprofloxacin-based API-ILs were synthesized. Overall, a lower dissociation of API-ILs compared to the respective ILs was observed, indicating presence of stable ion pairs in aqueous solution. All API-ILs retained the antimicrobial activity of ciprofloxacin. A higher mutation frequency (2.6–6.99-fold increase) was observed for API-ILs than for ciprofloxacin alone (1.71-fold increase), when compared to no treatment control, while ILs alone had no or a moderate impact (0.62–1.65-fold increase). Conclusions: Although it is possible to synthesize novel stable API-IL compounds with a high antimicrobial activity using ciprofloxacin and ILs of different structural classes, this can result in increased bacterial mutation frequencies. It is therefore crucial to improve our understanding of how API-ILs can be designed in a safer way. Full article

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

Major depressive disorder (MDD) is clinically heterogeneous, and peripheral inflammatory biomarkers may help clarify early biological mechanisms before illness chronicity or pharmacologic treatment confound interpretation. This systematic review synthesized evidence on peripheral inflammatory biomarkers in first-episode, drug-naïve major depressive disorder (FEDN-MDD) compared with healthy controls and examined associations with clinical severity. Following PRISMA 2020, searches of PubMed/MEDLINE, Embase, PsycINFO, and Scopus from inception to 19 March 2026 identified 313 records; after screening, 16 publications were included in qualitative synthesis. Studies varied in age group, biological matrix, assay platform, and statistical reporting, precluding meta-analysis. The most frequently assessed biomarkers were IL-1β, TNF-α, IL-6, and CRP/hs-CRP. IL-6 showed the clearest recurrent tendency toward elevation in FEDN-MDD, whereas CRP/hs-CRP findings were partially positive but methodologically limited. TNF-α and IL-1β findings were mixed, and clinical correlations with depressive severity were sparse and inconsistent. Overall, the evidence supports heterogeneous early immune dysregulation in a subset of patients with FEDN-MDD rather than a single reproducible inflammatory signature. Peripheral inflammatory biomarkers should currently be considered research tools for biological stratification and mechanistic hypothesis generation, pending larger standardized longitudinal studies. Full article

Interleukin-13 receptor α2 (IL-13Rα2) has traditionally been considered a decoy receptor; however, its cellular functions beyond the immune system remain unclear. We aimed to investigate the role of IL-13Rα2 in C2C12 myoblast proliferation and differentiation. IL-13Rα2 expression was knocked down in C2C12 cells using siRNA. Myogenic differentiation was evaluated by myosin heavy chain (MyHC) immunostaining and by quantifying the expression of myogenic regulatory and fusion-related genes. Myoblast proliferation was assessed using BrdU incorporation and cell number analyses, and signaling events induced by IL-13Rα2 knockdown were analyzed via immunoblotting and immunocytochemical analysis. IL-13Rα2 knockdown did not alter myogenic differentiation or the expression of fusion-associated genes. In contrast, IL-13Rα2 knockdown significantly increased BrdU incorporation and cell number, accompanied by increased Akt phosphorylation and decreased ERK phosphorylation. Cyclin D1 and cyclin-dependent kinase 4 (CDK4) levels were also increased. Akt inhibition abolished the enhanced proliferation and normalized Cyclin D1/CDK4 levels, whereas ERK activation did not further modify the knockdown-associated phenotype. These findings demonstrate that IL-13Rα2 negatively regulates myoblast proliferation by modulating the Akt–Cyclin D1–CDK4 signaling pathway, while being dispensable for myogenic differentiation. 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

The exponential increase in photovoltaic panel (PV) waste highlights the urgent need to develop efficient and sustainable recycling processes. It is estimated that by 2030, 8 million tons of PV modules will reach their end-of-life stage, posing a significant environmental challenge and requiring the development of green technologies for resource recovery. This study assessed the performance of imidazolium-based ionic liquids (ILs) as “designer solvents” for the selective leaching of copper and silver from disused PV panels. Specifically, four quaternary imidazolium salts were evaluated: [Bmim]HSO₄, [Emim]HSO₄, [Bmim]Cl, and [Emim]Cl. Leaching tests were conducted on silicon wafers containing 0.28% Ag and 0.19% Cu under varying temperatures (25, 50, and 80 °C), IL concentrations (20% and 60% v/v), and hydrogen peroxide (H₂O₂) dosages (0% and 3% v/v) as an oxidizing agent. The results identified [Bmim]HSO₄ as the most effective leaching agent. The system achieved a maximum copper extraction of 96.70% at 60% v/v concentration and 80 °C. For silver, the highest extraction of 45.13% was obtained using [Bmim]HSO₄ at 20% v/v and 80 °C. The addition of H₂O₂ was crucial, demonstrating a clear synergistic effect with the imidazolium-based ILs by promoting oxidative dissolution. These findings confirm that imidazolium-based ionic liquids represent a promising and environmentally friendly alternative for the recovery of high-value metals in the circular economy of photovoltaic recycling. Full article

Background: The high incidence and severe health threat of Toxoplasma gondii (T. gondii) infection, particularly in immunocompromised patients, underscore the urgent need for the development of a safe and effective vaccine. The aim of this study was to develop a novel multi-epitope vaccine (USM.TOXOII) incorporating the T. gondii GRA14, SAG1, and GRA1 antigens, and to assess its immunogenicity in BALB/c mice. Methods: Using bioinformatics approach, the USM.TOXOII was designed and evaluated. The encoding gene (471 bp) was then constructed and cloned into the pET-30a (+) plasmid before being transformed into E. coli expression system. The recombinant USM.TOXOII protein was subsequently expressed and purified. Finally, an animal study was performed to assess the vaccine’s immunogenicity. Results: The USM.TOXOII protein (17.27 kDa) was soluble and contained a His tag protein. Immunization of BALB/c mice with USM.TOXOII significantly elevated serum levels of total IgG, IgG1, and IgG2a (p < 0.05). Cytokine analysis revealed a significant increase in IFN-γ production, whereas IL-4 levels remained unchanged, suggesting a Th1-biased immune response. Conclusions: Collectively, these findings indicate that USM.TOXOII possesses immunogenic potential and is capable of inducing both humoral and cellular immune responses in BALB/c mice. Future challenge studies with live T. gondii tachyzoites are warranted to evaluate its protective efficacy in vivo. Full article

Background: Sarcopenia and frailty are highly prevalent extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD) and are strongly associated with reduced exercise tolerance, exacerbation risk, hospitalizations, and mortality. Beyond inflammation, oxidative stress, and physical inactivity, emerging evidence highlights nutrition as a major modifiable driver of muscle deterioration in COPD. Nutritional deficits impair anabolic signaling, exacerbate proteolysis, worsen mitochondrial dysfunction, and contribute to frailty progression. Methods: This narrative review synthesizes evidence from PubMed, Embase, Scopus, and Web of Science up to 2025, integrating mechanistic, metabolic, nutritional, and biomarker-related pathways underlying muscle dysfunction in COPD. Studies examining inflammation, hypoxemia, oxidative stress, hormonal imbalance, nutrition, and emerging biomarkers were included. Results: COPD-related sarcopenia results from converging inflammatory (TNF-α, IL-6), catabolic (FOXO, UPS), metabolic, and vascular mechanisms, compounded by energy deficiency, protein insufficiency, and micronutrient deficits. Inadequate intake of protein, vitamin D, antioxidants, and omega-3 fatty acids increase anabolic resistance, enhance muscle catabolism, and worsen frailty. Nutritional interventions, particularly high-protein supplementation, leucine-enriched formulas, vitamin D repletion, omega-3 fatty acids, and multimodal nutrition–exercise programs, demonstrate benefits in muscle mass, strength, and physical performance. Biomarkers such as GDF-15, CAF22, and specific microRNAs reflect nutritional status and correlate with muscle health in COPD. Conclusions: Sarcopenia and frailty in COPD arise from a complex interplay of inflammatory, metabolic, nutritional, and lifestyle-related factors. Integrating nutritional assessment and targeted dietary interventions with exercise and pulmonary rehabilitation is essential to counteract anabolic resistance and improve functional outcomes. Advances in biomarker research may support earlier diagnosis and personalized nutrition-based therapeutic strategies. Full article

Chronic rhinosinusitis (CRS) constitutes a multicausal inflammatory disease of the nose and paranasal sinuses, often associated with olfactory dysfunction (OD), a symptom that significantly impacts patients’ quality of life. OD in CRS was traditionally thought to be related to mechanical obstruction of the olfactory cleft, but is now considered to be multifactorial, involving conductive, inflammatory, and sensorineural mechanisms as well. Type-2 inflammatory response (high interleukins IL-4, IL-5, IL-13), eosinophilia, and increased IgE are involved in epithelial damage, impaired neurogenesis, and persistent olfactory loss, especially in chronic rhinosinusitis with nasal polyps (CRSwNP). In addition, peripheral chronic inflammation may also play a role in central neural remodeling, which may potentially affect olfactory function. Objective psychophysical testing is necessary to accurately assess olfactory function because self-reports may lack reliability. Management strategies aim at reducing inflammation and restoring sinonasal ventilation. First-line therapy with intranasal corticosteroids and short courses of systemic corticosteroids may be useful for symptomatic relief. Biologic agents directed against type-2 inflammation have demonstrated significant benefits in selected cases. Functional Endoscopic Sinus Surgery (FESS) plays an important role in the treatment of refractory CRS to restore the airflow and to improve the delivery of topical drugs. Olfactory outcomes following surgery, however, are variable and often incomplete, reflecting underlying inflammation and neuroepithelial damage. Disease recurrence, especially in type-2–driven CRS, affects long-term outcomes, underscoring the necessity to incorporate surgery in an individualized, endotype-informed treatment strategy. Full article

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder characterized by high mortality and limited therapeutic options. Alginate oligosaccharide (AOS), a marine-derived bioactive polysaccharide, exhibits prebiotic, anti-inflammatory and antioxidant properties that are effective against various inflammatory diseases. In this study, a mouse model of SAP was established by intraperitoneal injection of cerulein (100 μg/kg) and lipopolysaccharide (5 mg/kg), and the mice were pretreated with AOS (200 mg/kg) by gavage for 4 consecutive weeks to explore the potential protective efficacy and underlying mechanisms. The results shown that AOS attenuated the severity of SAP, as evidenced by reduced serum amylase and lipase levels, as well as alleviated histopathological injury in both pancreatic and ileal tissues. AOS suppressed the overproduction of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in serum, pancreas, and ileum at protein or mRNA levels. Moreover, AOS effectively diminished pancreatic and ileal inflammatory infiltration and oxidative stress in SAP mice, accompanied by inhibited the TLR4/MyD88/NF-κB pathway and activated the Nrf2/HO-1 antioxidant axis. Furthermore, AOS restored intestinal barrier integrity, as manifested by upregulated expression of tight junction proteins (claudin-1, occludin, ZO-1), reduced serum diamine oxidase, and decreased bacterial translocation from the gut to the pancreas. It was revealed by 16S rRNA sequencing that AOS ameliorated SAP-induced gut dysbiosis by restoring microbial diversity, normalizing the Firmicutes/Bacteroidetes ratio, enriching beneficial genera (Lactobacillus, Blautia), and enhancing cecal short-chain fatty acid (acetic, propionic, butyric acid) production. Collectively, our findings demonstrate that AOS exerts comprehensive protective effects against SAP through suppression of inflammatory signaling and oxidative stress, as well as restoring gut homeostasis. These results suggest that AOS may serve as a promising prebiotic-based nutritional strategy for the management of SAP. Full article

This study investigated the effects of dietary standardized ileal digestible (SID) lysine levels and amylose to amylopectin ratios on the intestinal health of broilers fed an 18.5% crude protein diet from 22 to 42 days of age. A total of 540 healthy male Ross 308 broilers were randomly assigned to nine treatments in a 3 × 3 factorial design consisting of three SID lysine levels (1.00%, 1.20%, and 1.40%) and three AM/AP ratios (0.19, 0.29, and 0.41), with six replicates of 10 birds each. Ileal morphology, intestinal barrier function and inflammation-related gene expression, and the composition of cecal microbiota were evaluated. Significant interactions between lysine level and AM/AP ratio were observed for Occludin, ZO-1, Claudin-1, and TNF-α expression, with the highest expression in the 1.40% lysine + 0.41 AM/AP group and the lowest in the 1.00% lysine + 0.19 AM/AP group. The VH/CD ratio showed a significant interaction, with the highest value in the 1.20% lysine + 0.19 AM/AP group and the lowest in the 1.40% lysine + 0.41 AM/AP group. IL-18 and IL-10 were primarily affected by the main effects of lysine and AM/AP ratio. The expression levels of both IL-10 and IL-18 increased with increasing lysine level and increasing starch AM/AP ratio. Dietary SID lysine level and AM/AP ratio interactively regulate the expression of barrier-related genes, inflammatory status, intestinal morphology, and cecal microbiota, potentially contributing to enhanced intestinal health in broilers. However, because microbial metabolites were not measured, the functional significance of the observed microbiota alterations remains speculative. In broilers fed an 18.5% CP diet, a combination of 1.20% SID lysine with an AM/AP ratio of 0.19 was identified as the optimal strategy for maintaining intestinal morphology from 22 to 42 days of age. 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

Immune checkpoint inhibitors (ICIs) show promise in cancer but have limited efficacy in ovarian cancer. This study compared combinations of the PD-1/PD-L1 inhibitor with anti-LAG-3, anti-TIM-3, or anti-CTLA-4 to identify the most effective regimen by assessing T-cell CD8/CD4 ratios and cytokine production. T cells isolated from ovarian cancer tissues (mean 3.8 × 10⁸ cells) were stimulated and treated with the PD-1/PD-L1 inhibitor alone or combined with anti-LAG-3, anti-TIM-3, or anti-CTLA-4. Flow cytometry measured CD8/CD4 expression; ELISAs quantified TNF-α, IL-6, and IFN-γ. Anti-PD-1 monotherapy produced no significant change in CD8/CD4 ratio (1.36 ± 0.43 vs. 1.41 ± 0.36) or cytokine levels. Combination therapy with PD-1/PD-L1 inhibitor + anti-CTLA-4 induced the largest increase in CD8/CD4 ratio (3.69 ± 1.33, p < 0.001) compared with PD-1/PD-L1 inhibitor alone; increases were smaller for PD-1/PD-L1 inhibitor + anti-LAG-3 (2.11 ± 0.63, p = 0.009) and PD-1/PD-L1 inhibitor + anti-TIM-3 (1.87 ± 0.48, p = 0.026). TNF-α rose significantly only with PD-1/PD-L1 inhibitor + anti-CTLA-4 (106.69 ± 45.42 pg/mL, p = 0.008), not with PD-1/PD-L1 inhibitor + anti-LAG-3 (72.46 ± 31.79 pg/mL, p = 0.231) or PD-1/PD-L1 inhibitor + anti-TIM-3 (82.06 ± 33.63 pg/mL, p = 0.074). IFN-γ increase was greater with PD-1/PD-L1 inhibitor + anti-CTLA-4 than with PD-1/PD-L1 inhibitor + anti-LAG-3 (p = 0.026). In conclusion, dual PD-1/PD-L1 and CTLA-4 blockade induced concomitant increases in T-cell CD8/CD4 proportions and cytokine levels compared to monotherapy or alternative ICI pairings. These descriptive ex vivo observations offer preliminary evidence of altered immune profiles, highlighting this combination as a candidate for further functional validation. Full article

The failure of therapy in muscle invasive bladder cancer (MIBC) is primarily attributed to tumor heterogeneity and therapy resistance. We propose a novel approach targeting interleukin-13 receptor subunit alpha 2 (IL-13Rα2), which is expressed on bladder cancer (BC) cells but absent in normal urothelial cells. We investigated the therapeutic effects of WPD101a immunotoxin (IL-13-DT390) on IL-13Rα2-expressing BC cells in relation to BC cell phenotype and functional characteristics in vitro using both 2-dimensional (2D) and 3-dimensional (3D) models. Cell phenotype and IL-13Rα2 expression were assessed using flow cytometry, immunofluorescence, and Western blot analysis. The biological effects of WPD101a were evaluated by measuring cell viability and proliferation using the MTT, sulforhodamine B (SRB), CellTiter-Glo and Live/Dead assays. Apoptosis was assessed using Annexin V/propidium iodide (PI) staining, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of CASP genes expression. We found that the reference BC cell lines TCC-SUP, JMSU-1 and UM-UC-3 express IL-13Rα2 at various level in contrast to RT-4, HCV-29 and 5637 cells. Cells expressing IL-13Rα2 were sensitive to WPD101a at lower concentrations in the 2D model (0.1 ng/mL) compared to the 3D model (1.0 ng/mL). IL-13Rα2-negative cells remain resistant to the immunotoxin. WPD101a induces apoptosis in BC cells expressing IL-13Rα2 as confirmed by the presence of apoptotic cells, increase the proportion of cells in the subG1 phase, and by the effector CASP3, CASP7, and initiator CASP8, CASP9 genes expression. This study confirmed receptor-dependent cytotoxic effects of WPD101a and the ability and specificity to inhibit growth and apoptosis induction in MIBC cells expressing IL-13Rα2. Full article