Search Results (10,022)

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article

(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article

Background: Bimekizumab, secukinumab, and ixekizumab are IL-17-targeting biologics approved for the treatment of moderate-to-severe plaque psoriasis. While secukinumab and ixekizumab selectively inhibit IL-17A, bimekizumab targets both IL-17A and IL-17F, potentially providing greater anti-inflammatory efficacy. This study aimed to compare the real-world effectiveness, safety, and tolerability of these agents in a Polish dermatology center between 2019 and 2024. Methods: We conducted a retrospective analysis of 98 patients meeting at least one of the following criteria: PASI ≥ 10, BSA ≥ 10, DLQI ≥ 10, or involvement of special areas with inadequate response or contraindications to ≥2 systemic therapies. Patients with prior exposure only to IL-17 inhibitors were excluded. PASI, BSA, and DLQI scores were recorded at baseline, week 4, and week 12. Due to differences in dosing schedules, outcomes were aligned using standardized timepoints and exponential modeling of continuous response trajectories. Mixed-effects ANOVA was used to assess the influence of baseline factors (age, BMI, PsA status) on treatment outcomes. Adverse events were documented at each monthly follow-up visit. Results: Bimekizumab showed the greatest effect size for PASI reduction (Hedges’ g = 3.662), followed by secukinumab (2.813) and ixekizumab (1.986). Exponential modeling revealed a steeper response trajectory with bimekizumab (intercept = 0.289), suggesting a more rapid PASI improvement. The efficacy of bimekizumab was particularly notable in patients who were previously treated with IL-23 inhibitors. All three agents demonstrated favorable safety profiles, with no serious adverse events or discontinuations. The most frequent adverse events were mild and included upper respiratory tract infections and oral candidiasis. Conclusions: This real-world analysis confirmed that IL-17 inhibitors effectively improved PASI, BSA, and DLQI scores in moderate-to-severe psoriasis. Bimekizumab demonstrated the most rapid early improvements and a higher modeled likelihood of complete clearance, without significant differences at week 12. All agents were well tolerated, underscoring the need for further individualized, large-scale studies. Full article

Background: Septic arthritis is an orthopedic emergency. However, optimal biomarkers and diagnostic criteria remain unclear. The study aimed to evaluate the diagnostic performance of routinely used and novel biomarkers, including serum C-reactive protein (CRP), synovial white blood cells (WBC), pentraxin-3 (PTX3), interleukin-6 (IL-6), and presepsin, in distinguishing septic from non-septic arthritis. Methods: Thirty-one patients undergoing arthrocentesis were included. Patients were categorized into septic and non-septic arthritis groups. Synovial fluid and serum samples were analyzed for five biomarkers. Diagnostic performance was assessed by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Synovial WBC demonstrated the highest diagnostic performance among single biomarkers (AUC = 0.837, p = 0.012). Among novel biomarkers, PTX3 showed the highest accuracy and sensitivity. The serum CRP and synovial WBC combination yielded an AUC of 0.853, with 100% sensitivity, 68.0% specificity, 42.9% PPV, and 100% NPV. Adding all three novel biomarkers to this combination increased the AUC to 0.887 (p = 0.004), maintaining 100% sensitivity and NPV. When individually added, PTX3 achieved 100% sensitivity and NPV, while presepsin showed the highest specificity (96.0%), PPV (75.0%), and accuracy (87.1%). Conclusions: Serum CRP and synovial WBC remain essential biomarkers for diagnosing septic arthritis; however, combining them with PTX3, IL-6, and presepsin improved diagnostic accuracy. PTX3 is best suited for ruling out septic arthritis due to its high sensitivity and NPV, whereas presepsin is more useful for confirmation, given its specificity and PPV. These results support a tailored biomarker approach aligned with diagnostic intent. Full article

Based on the limited hepatic hydroxylation efficiency of dietary VD3 in teleosts and the superior bioavailability of its metabolite, 25(OH)D3, this study investigated the regulatory mechanisms of dietary 25(OH)D3 supplementation in yellow catfish—an economically significant species lacking prior nutritional data on this metabolite. A total of 360 fish were divided into three groups—control (basal diet), VD3 (2500 IU/kg VD3), and 25(OH)D3 (2500 IU/kg 25(OH)D3)—and fed for 8 weeks. Compared to the control, both supplemented groups showed elevated superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), and transforming growth factor-β (TGF-β) activities, alongside reduced malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels. The 25(OH)D3 group exhibited higher T-AOC and CAT activities and lower TNF-α than the VD3 group. Metabolomic and transcriptomic analyses identified 65 differentially expressed metabolites (DEMs) and 3515 differentially expressed genes (DEGs). Enrichment analysis indicated that the DEMs (e.g., indole compounds, organic acids, aldosterone, L-kynurenine) and DEGs (pgd, mthfr, nsdhl, nox5, prdx2, mpx, itih2, itih3, eprs1) that were highly and significantly expressed in the 25(OH)D3 group were primarily associated with antioxidant defense and inflammatory responses. Dietary 25(OH)D3 was more effective than VD3 in promoting antioxidant capacity and modulating inflammation in yellow catfish. Full article

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Objectives: To assess the clinical and inflammatory outcomes of patients with calcified coronary arteries treated with rotational atherectomy (RA), compared to those with other intervention procedures. Methods: We conducted a systematic search of PubMed (Medline) and Embase. This review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and applied the PICO criteria. Results: A total of 110 articles were analyzed, comprising 2,328,417 patients with moderate to severe coronary calcified lesions treated with RA, conventional percutaneous coronary intervention (PCI), or other advanced interventions. The pooled incidence of short- to mid-term major adverse cardiovascular events (MACEs) was 6% (95% CI 4–7%), increasing to 17% (95% CI 15–21%) at 6 months. Mortality was 2% (95% CI 1–3%) within 6 months, rising to 7% (95% CI 6–9%) thereafter. RA significantly increased the risk of long-term MACEs, mortality, total lesion revascularization (TLR), bleeding, and fluoroscopy time, and was borderline associated with an increased risk of short-term myocardial infarction and a reduced risk of coronary dissection. RA and other invasive procedures showed similar risks for short-term MACEs, mortality, total vascular revascularization (TVR), stent thrombosis, heart failure, stroke, and inflammation. Conclusions: RA is linked to higher long-term risks of MACEs, mortality, TLR, bleeding, and fluoroscopy time compared to other interventions. While RA shows comparable outcomes for short-term MACEs and mortality with other procedures, it may slightly reduce the risk of coronary dissection. These findings underscore the importance of careful patient selection and weighing long-term risks when considering RA for calcified coronary lesions. Full article

Clonal hematopoiesis of intermediate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell because of a mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. Interestingly, CHIP is associated with a two-fold increase in cardiovascular risk, independently of traditional risk factors. Recent studies using deep-targeted sequencing have revealed that CHIP mutations, primarily TET2 and DNMT3A, present a higher incidence in patients with AF compared to healthy controls. Moreover, the presence of the aforementioned mutations is positively correlated with the progression and the severity of the AF clinical course. Regarding the predisposition of AF, it has been proven that TET2 and ASXL1 mutations, and not DNMT3A mutation, are associated with higher interleukin-6 (IL-6) levels. IL-6 levels, being indices of cardiac remodeling, predispose to an elevated risk for AF in healthy subjects. Currently conducted research has focused on elaborating the mechanisms driving the association between AF and CHIP and on the evaluation of potential interventions to reduce the risk of AF development. The aims of our review are (i) to summarize published evidence regarding the presence of CHIP mutations as a contributor to AF severity and predisposition, and (ii) to highlight the potential benefits of investigating the correlations between CHIP and AF for AF-diagnosed patients. Full article

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: This narrative review aims to provide a comprehensive and critical synthesis of current evidence on the role of key interleukins in T1D and T2D, highlighting their immunological functions, genetic associations, clinical correlations, and translational potential. Methods: A targeted literature search was conducted in PubMed, Google Scholar, and ScienceDirect up to January 2025, focusing on English-language clinical and experimental studies involving interleukins and their relevance to T1D and T2D. Reference lists were manually screened for additional sources. Interleukins (ILs) were reviewed individually to assess their immunobiology, disease specificity, and biomarker or therapeutic value. Findings: Pro-inflammatory cytokines such as IL-1β, IL-6, and IL-17 contribute to islet inflammation, insulin resistance, and microvascular damage in both T1D and T2D. Anti-inflammatory mediators including IL-4, IL-10, and IL-13 exhibit protective effects but vary in expression across disease stages. Less-characterized interleukins such as IL-3, IL-5, IL-9, and IL-27 demonstrate dual or context-dependent roles, particularly in shaping immune tolerance and tissue-specific complications such as nephropathy and neuropathy. Polymorphisms in IL-10 and IL-6 genes further suggest genetic contributions to interleukin dysregulation and metabolic dysfunction. Despite promising insights, translational gaps persist due to overreliance on preclinical models and limited longitudinal clinical data. Conclusions: Interleukins represent a mechanistic bridge linking immune dysregulation to metabolic derangements in both T1D and T2D. While their diagnostic and therapeutic potential is increasingly recognized, future research must address current limitations through isoform-specific targeting, context-aware interventions, and validation in large-scale, human cohorts. A unified interleukin-based framework may ultimately advance personalized strategies for diabetes prevention and treatment. Full article

Drug resistance in Candida may result in either a fitness cost or a fitness advantage. Candida auris, whose intrinsic drug resistance remains unclear, has emerged as a significant human pathogen. We aimed to investigate whether Candida fitness, including early interaction with the host innate immune system, depends on the antifungal susceptibility phenotype and putative-associated resistance mutations. We compared interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor α production by human colorectal adenocarcinoma cells stimulated by fluconazole-susceptible and fluconazole-resistant strains of Candida albicans, C. parapsilosis, C. tropicalis, and C. glabrata, as well as fluconazole-resistant C. auris strains. Sensitive Candida strains induced lower cytokine levels compared with C. auris and resistant strains, except for TNF a. Resistant strains induced cytokine levels like C. auris, except for higher IL-1β and lower TNF-α. Susceptible strains exhibited cytokine profiles distinct from those of resistant strains. C. auris induced cytokine levels comparable to resistant strains but displayed profiles resembling those of susceptible strains. This study highlights the relationship among antifungal susceptibility, fungal fitness and host early immunity. C. auris behavior appears to be between fluconazole-sensitive and fluconazole-resistant strains. Understanding these dynamics may enhance the knowledge of the survival and reproduction of resistant Candida and the epidemiology of fungal infections. Full article

Background/Objectives: After diagnosis, it is common for women with breast cancer to gain weight, which is associated with worse clinical outcomes. However, traditional measures such as body weight, BMI, and waist circumference do not detect key changes in body composition, such as fat redistribution or muscle loss. The objective of this exploratory study was to assess the evolution of body composition and muscle strength after one year of treatment, and their relationship with metabolic biomarkers. Methods: Prospective observational study in newly diagnosed breast cancer patients. Body composition was assessed using bioelectrical impedance analysis (BIA) and ultrasound (US); muscle strength was measured by handgrip dynamometry. Biomarkers analyzed included glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glycosylated hemoglobin (HbA1c), total cholesterol (and its fractions), triglycerides, C-reactive protein (CRP), 6-interleukin (IL-6), vitamin D, myostatin, and fibroblast growth factor 21 (FGF-21). Results: Sixty-one women (mean age 58 years) were included. After one year, fat mass and related parameters significantly increased, while skeletal muscle mass and muscle strength decreased. Sarcopenic obesity prevalence rose from 1.16% to 4.9%. No significant changes were found in biomarkers, but positive correlations were observed between fat parameters and insulin, HOMA-IR, and triglycerides, and negative correlations with HDL-cholesterol. Conclusions: BIA and US can detect unfavorable changes in body composition that are not reflected in conventional measurements. At one year post-diagnosis, women showed increased fat accumulation, muscle loss, and reduced strength, even without significant metabolic biomarker changes. Further research is warranted to elucidate the long-term clinical implications of these findings and the external validity in larger cohorts. Full article

Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article