Search

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.

Previous research has indicated that higher red blood cell distribution width (RDW) increases the risk of coronary heart disease. However, no studies have established a link between RDW and coronary heart disease in the rheumatoid arthritis population. This research aims to explore the association between RDW and coronary heart disease among individuals with rheumatoid arthritis. We selected demographic data, laboratory data, lifestyle, and medical history from the National Health and Nutrition Examination Survey (NHANES), specifically including age, gender, poverty, RDW, race, BMI, diabetes, education, coronary heart disease, hypertension, cholesterol, smoking, and drinking. RDW and coronary heart disease were found to have a positive association in the rheumatoid arthritis population (OR = 1.145, 95%CI: 1.036–1.266, P = .0098), even after adjusting for factors such as age, gender, race, education level, smoking, and drinking. Subgroup analysis showed a stronger positive association, particularly in individuals aged 55–66 years, males, and the Hispanic White population with diabetes or hypercholesterolemia. There is a significant correlation between RDW and coronary heart disease among individuals with rheumatoid arthritis.

Reducing losses caused by pathogens is an effective strategy for stabilizing crop yields. Daunting challenges remain in cloning and characterizing genes that inhibit stripe rust, a devastating disease of wheat (Triticum aestivum) caused by Puccinia striiformisf. sp. tritici(Pst). We found that suppression of wheat zeaxanthin epoxidase 1 (ZEP1) increased wheat defense against Pst. We isolated the yellow rust slower 1(yrs1) mutant of tetraploid wheat in which a premature stop mutation in ZEP1-Bunderpins the phenotype. Genetic analyses revealed increased H2O2accumulation in zep1mutants and demonstrated a correlation between ZEP1dysfunction and slower Pstgrowth in wheat. Moreover, wheat kinase START 1.1 (WKS1.1, Yr36) bound, phosphorylated, and suppressed the biochemical activity of ZEP1. A rare natural allele in the hexaploid wheat ZEP1-Bpromoter reduced its transcription and Pstgrowth. Our study thus identified a novel suppressor of Pst, characterized its mechanism of action, and revealed beneficial variants for wheat disease control. This work opens the door to stacking wheat ZEP1variants with other known Pstresistance genes in future breeding programs to enhance wheat tolerance to pathogens.