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关键词： Helicobacter pylori   Gastric epithelial cell   Matrix metalloproteinase-10   Reactive oxygen species   Metformin   Inflammatory response  

摘要： Helicobacter pylori infection is one of the most common factors inducing gastric mucosal inflammation. Upon infecting gastric epithelial cells, H. pylori generates reactive oxygen species (ROS), which act as inducers of matrix metalloproteinases (MMPs). ROS can regulate MMP gene expression and promote their production through the ERK signaling pathway, with MMP-10 being a primary MMP induced during H. pylori infection. By mediating the remodeling of the gastric epithelial and lamina propria layers, MMP-10 enhances H. pylori colonization and its pro-inflammatory effects. As resistance to eradication therapies has significantly increased, H. pylori eradication rates have continued to decline. We investigated the antioxidant effects of metformin on cell viability, migration, and invasion. The in vitro levels of ROS, MMP-10, and the inflammatory factor IL-1 beta in H. pylori-infected gastric epithelial cells were assessed to determine whether metformin could alleviate H. pylori-induced inflammation and elucidate its potential mechanisms of action. These findings may provide novel insights into adjunctive therapeutic strategies for the effective clinical eradication of H. pylori infection. The results indicated that H. pylori infection significantly increased ROS production, activating the ERK pathway and upregulating MMP-10 expression, which enhanced cellular invasion and the inflammatory response. Metformin intervention effectively blocked this pathological cascade, significantly reducing ROS levels, MMP-10 expression, and the release of inflammatory cytokines, exerting an inhibitory effect on H. pylori-induced inflammation and demonstrating the potential application of metformin as a therapeutic agent.

关键词： Rheumatoid arthritis   mesenchymal stem cell   preconditioning   miR-92a   green tea EGCG   mic-ADSCs  

摘要： Background The global prevalence of rheumatoid arthritis (RA) is on the rise. Numerous studies have demonstrated the potential of stem cell-based therapies in RA treatment. Experimental evidence suggests that preconditioning enhances the regenerative capabilities of stem cells compared to their unconditioned *** This study aimed to evaluate whether adipose-derived stem cells (ADSCs) preconditioned with green tea epigallocatechin gallate (EGCG) and miR-92a exhibit superior therapeutic effects in RA compared to unconditioned *** Both in vitro and in vivo models were employed. In the cellular model, ADSCs were preconditioned with EGCG and miR-92a. In the animal model, male Wistar rats were used, and RA was induced using the collagen-induced arthritis (CIA) model. Following RA induction, the animals were divided into six groups: Sham (healthy rats), RA (RA-induced rats), RA+ADSC (RA-induced rats receiving unconditioned ADSCs), RA+E-ADSC (RA-induced rats receiving EGCG-preconditioned ADSCs), RA+mic-ADSC (RA-induced rats receiving miR-92a mimic-preconditioned ADSCs), and RA+inh-ADSC (RA-induced rats receiving miR-92a inhibitor-preconditioned ADSCs).Results In the cellular model, preconditioning with EGCG and miR-92a activated the CXCR4/p-Akt signaling pathway, thereby enhancing ADSC viability. In the animal model, RA induction caused several joint pathologies, including hind paw swelling, disrupted bone metabolism, immune cell infiltration, increased expression of IL-17, KLF4, and IL-6, as well as cartilage degradation. While transplantation of unconditioned ADSCs modestly improved these pathological features, the administration of E-ADSCs and mic-ADSCs significantly ameliorated these conditions in RA rats. Conversely, the therapeutic effects of E-ADSCs and mic-ADSCs were attenuated by the transplantation of *** The therapeutic effects of E-ADSCs and mic-ADSCs in RA were strongly associated with the modulation of the KLF4/IL-1

关键词： STING   acetyl CoA   glycolysis   immunometabolism   interferon  

摘要： Interferon gamma (IFN-γ) is a pleotropic cytokine which is a central mediator of the immune response to pathogen infection, while also playing important roles in tumour suppression and the pathogenesis of various autoimmune diseases. Consequently, there is potential utility in the treatment of a number of pathological conditions via being able to modify IFN-γ secretion. T cells and natural killer (NK) cells are the primary IFN-γ sources, with metabolic rewiring prior to their activation and IFN-γ secretion in both a unifying feature. The mechanisms by which metabolic changes, particularly increased glycolysis, drive enhanced IFN-γ production are multi-faceted, but are likely focused on epigenetic changes via increased acetyl CoA levels which fuels histone acetylation. Herein, we discuss the mechanisms by which metabolic changes drive altered IFN-γ synthesis by immune cells.

摘要： BACKGROUND:Interleukin-33 may have a role in COPD pathobiology. FRONTIER-4 (NCT04631016) investigated tozorakimab (an anti-IL-33 monoclonal antibody) in moderate-to-severe COPD patients with chronic bronchitis receiving dual or triple inhaled therapy. METHODS:FRONTIER-4 was a phase 2a, randomized, double-blind, placebo-controlled study. Patients received tozorakimab 600 mg or placebo subcutaneously every 4 weeks for 24 weeks. The primary endpoint was change in pre-bronchodilator (BD) FEV from baseline to week 12. Secondary outcomes included post-BD FEV, time-to-first COPDCompEx event and safety. RESULTS:The intent-to-treat population included 135 patients (tozorakimab, n=67; placebo, n=68). At week 12 in the intent-to-treat population, tozorakimab showed a greater increase from baseline in pre-BD FEV (least-squares mean [LSM]: 24 mL [80% confidence interval (CI): -15,63]; p=0.216) that was not statistically significant, and in post-BD FEV (LSM: 67 mL [80% CI: 17,116]; p=0.044), when compared with placebo. Tozorakimab showed improvements placebo (LSM [80% CI]) in change from baseline in pre-BD FEV (69 mL [9,130]; p=0.072) and post-BD FEV (124 mL [47,201]; p=0.020) at week 12 in a pre-specified subgroup of patients with ≥2 prior exacerbations. Tozorakimab did not significantly reduce the risk of COPDCompEx events (HR: 0.79 [80% CI: 0.57,1.11]; p=0.186) in the intent-to-treat population, although there were greater effects in patients with ≥2 prior exacerbations (hazard ratio: 0.61 [80% CI: 0.37,1.00]). Results were similar in former and current smokers. Tozorakimab was well tolerated. CONCLUSION:Although the primary endpoint was not met in the intent-to-treat population, tozorakimab showed positive efficacy signals placebo in a subgroup of patients with COPD with a high risk of exacerbations.

关键词： Guselkumab   interleukin   IL23   mirikizumab   risankizumab   Th17   ulcerative colitis   ustekinumab  

摘要： IntroductionUlcerative colitis (UC) is a chronic, relapsing and remitting, inflammatory bowel disease. Monoclonal antibodies targeting interleukin (IL)-23p19 have been developed to treat chronic inflammatory diseases mediated by aberrant IL23/Th17 responses, including psoriasis, psoriatic arthritis, and Crohn's disease. More recently, these agents have been evaluated for the treatment of moderately-to-severely active *** coveredIn this review, we summarize and discuss phase 2 and pivotal phase 3 clinical trials informing the efficacy and safety of mirikizumab (AMAC, LUCENT, and SHINE), risankizumab (INSPIRE, COMMAND), and guselkumab (QUASAR, VEGA). The literature search included original research publications, secondary publications, and preliminary data from conference abstracts presented at international gastroenterology meetings from the past 5 *** opinionThe approval of IL23p19 antagonists expands the armamentarium of effective and safe therapies for patients living with moderately-to-severely active UC. These agents demonstrate potent efficacy for both inducing and maintaining symptomatic and objective disease endpoints, including endoscopic, histologic, and biomarker remission. These well-tolerated agents are effective in both advanced treatment-na & iuml;ve and experienced patients. Accordingly, IL23p19 antagonists have the potential to be used in a diverse population of patients with UC, and as potential platform therapies for future combinations with other targeted immunomodulatory agents.

关键词： Anchusa officinalis   wound-healing   antioxidants   immunohistochemical   inflammatory cytokines  

摘要： Wound healing is an intricate, complicated process that needs special attention because of its related complications that may occur if not treated properly or because of therapeutic insufficiency. Common bugloss (Anchusa officinalis L.) is a deep-rooted, hairy perennial herb used in folk medicine for numerous human issues, including wound recovery. To delineate its safety and healing potentials, we investigated the acute toxicity and wound-healing effects of Anchusa officinalis L. (APEAO) aerial part extracts on excisional neck injury in rats. A uniform dorsal neck cut was formed in twenty-four albino rats, which were arbitrarily divided into 4 groups and treated daily with a topical 0.2 ml dose of the following: group A, rats received 10% tween 20;group B, rats received intrasite gel;groups C and D, rats had 250 and 500 mg/kg of APEAO, respectively. The APEAO treatment did not cause toxic damage in rats administered with up to 5 g/kg APEAO. In the wound experiment, APEAO-treated skin exhibited significantly higher deposition of tissue collagen and fibroblast cells. In contrast, inflammatory cells were significantly lower in the recovered tissues of than positve control rats. Topical application of APEAO caused positive modulation of Transforming Growth Factor Beta 1 (angiogenesis) in recovered skin, indicating elevated tissue growth and faster wound-healing action. Moreover, APEAO treatment caused a significant elevation in tissue antioxidants (Superoxide dismutase, glutathione peroxidase, and catalyze) and hydroxyproline (collagen) content, lowering Malondialdehyde levels compared to vehicle rats. Serum inflammatory chemicals (Transforming growth factor alpha, Interlukin-6, and Interlukin-10) were significantly modulated following APEAO application. The outcomes revealed significant tissue regeneration potentials of APEAO exhibited by its modulatory actions on several cellular processes, which could serve as scientific evidence for future investigation regarding t

关键词： HLA-B27   season   uveitis  

关键词： celiac disease   screening   children   transglutaminase antibody   HLA   quality of life   costeffectiveness   population  

摘要： Comprehensive screening of the general population is the only approach capable of identifying the majority of cases with celiac disease. In 2023, the Italian Parliament enacted a law to implement nationwide screening for celiac disease and type 1 diabetes. However, critical decisions regarding the target population, optimal timing, and screening methods remain unresolved. Previous observational studies on birth cohorts of children with genetic risk for these conditions have demonstrated that the incidence peaks early in life and is influenced by HLA risk genotypes. This mini-review explores different aspects of screening for celiac disease, presenting the advantages and challenges of identifying children before onset of symptoms. In addition, we summarize the current knowledge and gaps in understanding related to screening programs for celiac disease in children and adolescents and discuss health benefits, psychosocial aspects and cost-effectiveness, and their potential implications for future public health strategies.