Antileishmanial effects of Crotalaria spectabilis Roth aqueous extracts on Leishmania amazonensis

Abstract Fifteen polar extracts from leaf, seed, pod, stem, flower and root of Crotalaria spectabilis were prepared using aqueous systems, based on the principles of green chemistry, and showed different protease inhibitor (PI) activities on trypsin, papain, pepsin and the extracellular L. amazonensis serine protease (LSPIII). The most pronounced inhibitory effect on LSPIII was observed in leaf (CS-P), root, stem, flower (CS-FPVPP) and pod (CS-VA) extracts. Crotalaria extracts exhibited low cytotoxicity on macrophages; however, they decreased the viability of L. amazonensis promastigotes and amastigotes, as observed in leaf (CS-AE, CS-P, CS-T and CS-PVPP), seed (CS-ST), flower and root (CS-RA) extracts. CS-P was chosen to study PI and secondary metabolites and a 10-12 kDa protein, analyzed by mass spectrometry, was identified as a serine PI homologous with papaya latex serine PI. Glycosylated flavonoids, such as quercetins, vitexin and tricin were the major secondary metabolites of CS-P. The presence of PIs in C. spectabilis is a new finding, especially in other organs than seeds since PIs have been reported only in seed legumes. Besides, this is the first report of antileishmanial activity of C. spectabilis extracts and the identification of serine polypeptide PI and glycosylated flavonoids from leaf

An shRNA-Based Screen of Splicing Regulators Identifies SFRS3 as a Negative Regulator of IL-1β Secretion

The generation of diversity and plasticity of transcriptional programs are key components of effective vertebrate immune responses. The role of Alternative Splicing has been recognized, but it is underappreciated and poorly understood as a critical mechanism for the regulation and fine-tuning of physiological immune responses. Here we report the generation of loss-of-function phenotypes for a large collection of genes known or predicted to be involved in the splicing reaction and the identification of 19 novel regulators of IL-1β secretion in response to E. coli challenge of THP-1 cells. Twelve of these genes are required for IL-1β secretion, while seven are negative regulators of this process. Silencing of SFRS3 increased IL-1β secretion due to elevation of IL-1β and caspase-1 mRNA in addition to active caspase-1 levels. This study points to the relevance of splicing in the regulation of auto-inflammatory diseases

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Gender Differences in COVID-19 Among Liver Transplant Recipients: Results from a Multicenter Brazilian Cohort

Introduction: Existing literature presents varying perspectives on the impact of COVID-19 on liver transplant recipients.However, no research has specifically investigated the role of gender differences in the manifestation of COVID-19 among liver transplant recipients. This study aims to examine the effects of COVID-19 on liver transplant recipients, with a focus on gender differences in disease presentation and progression. Methods: Conducted as a multicenter historical cohort study, this research collected patient records through an online questionnaire. Assessing COVID-related mortality was the main objective. Additionally, demographic, clinical, and laboratory data pertaining to disease presentation and progression werecollected. Results: The study included a total of 283 patients, of whom 76 were female and 206 were male. The median follow-up period for males was 99 days (IQR 38-283), while for females, it was 126 days (IQR 44-291). A higher prevalence of cardiovascular disease was observed in males (p=0.002). Females frequently experienced a loss of smell (p=0.021), whereas males commonly exhibited fever (p=0.031). Levels of ALT and gamma-glutamyl transferase were significantly elevated in males (p=0.008 and 0.004, respectively). Although there was a trend towards increased mortality in males, it did not reach statistical significance. Conclusion: This study is the first attempt to investigate gender differences in COVID-19 among liver transplant recipients. Our findings highlight the need for a comprehensive and personalised approach to treating this patient population and underscore the importance of further elucidating the disease presentation in these individuals