RESUMO
BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and fibrosis. We showed an elevated interferon γ response in patients with primary sclerosing cholangitis and in multidrug resistance protein 2-deficient ( Mdr2-/- ) mice developing sclerosing cholangitis. Interferon γ induced expression of the cytotoxic molecules granzyme B (GzmB) and TRAIL in hepatic lymphocytes and mediated liver fibrosis in sclerosing cholangitis. APPROACH AND RESULTS: In patient samples and Mdr2-/- mice, we identified lymphocyte clusters with a cytotoxic gene expression profile using single-cell RNA-seq and cellular indexing of transcriptomes and epitopes by sequencing analyses combined with multi-parameter flow cytometry. CD8 + T cells and NK cells showed increased expression of GzmB and TRAIL in sclerosing cholangitis. Depletion of CD8 + T cells ameliorated disease severity in Mdr2-/- mice. By using Mdr2-/- × Gzmb-/- and Mdr2-/- × Tnfsf10-/- mice, we investigated the significance of GzmB and TRAIL for disease progression in sclerosing cholangitis. Interestingly, the lack of GzmB resulted in reduced cholangiocyte apoptosis, liver injury, and fibrosis. In contrast, sclerosing cholangitis was aggravated in the absence of TRAIL. This correlated with elevated GzmB and interferon γ expression by CD8 + T cells and NK cells enhanced T-cell survival, and increased apoptosis and expansion of cholangiocytes. CONCLUSIONS: GzmB induces apoptosis and fibrosis in sclerosing cholangitis, whereas TRAIL regulates inflammatory and cytotoxic immune responses, subsequently leading to reduced liver injury and fibrosis.
RESUMO
The versatile uses of Copper(II) Fluoride (CuF2) are well known; these include its usage as a precursor in chemical synthesis as well as its contribution to the creation of sophisticated materials and electronics. There are interesting opportunities to study the interactions between these elements because of their unique crystal structure, which contains copper ions and fluoride anions. Its potential in optoelectronic devices and conductive qualities also make it a viable material for next-generation technologies. To better understand the structural properties of CuF2 and how they affect its entropy, we present new Zagreb indices in this study and use them to calculate entropy measures. We also build a regression model to clarify the relationship between the calculated indices and entropy levels. The findings of our investigation offer significant understanding regarding the ability of the suggested Zagreb indices to extract meaningful content and their correlation with entropy in the context of CuF2. This information is important for understanding CuF2 alloys and for exploring related complex materials.
Assuntos
Cobre , Fluoretos , Cobre/química , EntropiaRESUMO
An effective anticoagulation therapy is required for patients with atrial fibrillation because it presents a significant risk of stroke. The current study evaluates the relative safety as well as efficacy of rivaroxaban in patients who are diagnosed with atrial fibrillation. A thorough literature review of relevant databases was conducted, focusing on academic and clinical studies that were published from 2017 onward. Inclusion criteria comprised randomized controlled trials and other observational studies comparing the incidence of stroke and the safety index of rivaroxaban in atrial fibrillation. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) for data overview reporting and overview. A total of 21 studies were selected based on the inclusion criteria. A total of 19/21 studies advocated the adoption of rivaroxaban for minimizing stroke incidence. Rivaroxaban also showed superiority in achieving the therapeutic objectives, i.e., reduction in the incidence of stroke. The results for rivaroxaban against warfarin showed an improved safety index and effectiveness of rivaroxaban. The total effect size for the analysis was calculated to be Z=2.62 (p-value=0.009). The individual effect of all studies favored the "rivaroxaban" group. The heterogeneity in the study was as follows: tau2=0.10; chi2=110.10, df=6; I2=95%. The second analysis for risk reduction and incidence of stroke after rivaroxaban therapy also showed a bias towards rivaroxaban therapy. The combined effect for the analysis was found to be as follows: HR=0.73 ((95% CI: 0.50, 1.07). The total effect was calculated to be Z=1.61 (p-value= 0.10). The heterogeneity was found to be as follows: tau2= 0.20, chi2=89.97, df=6, I2=93%. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines.