N6-methyladenosine-modified TRIM37 augments sunitinib resistance by promoting the ubiquitin-degradation of SmARCC2 and activating the Wnt signaling pathway in renal cell carcinoma.

Tripartite motif-containing 37 (TRIM37) is reportedly a key member of the superfamily of TRIM proteins. Emerging evidence underscores the close association between dysregulated TRIM37 expression and the progression of various human malignancies. However, the precise biological functions and regulatory mechanisms of TRIM37 remain elusive. This study aimed to elucidate the impact of TRIM37 on the chemotherapy sensitivity of renal cell carcinoma (RCC) and uncover its specific molecular regulatory role. Using RT-qPCR and western blot assays, we assessed TRIM37 expression in both RCC patients and RCC cells. Through in vitro and in vivo experiments, we investigated the effects of TRIM37 silencing and overexpression on RCC cell proliferation, stemness capacity, and chemotherapy sensitivity using colony formation and sphere formation assays. Additionally, a co-immunoprecipitation (Co-IP) experiment was conducted to explore putative interacting proteins. Our results revealed elevated TRIM37 expression in both RCC patient tumor tissues and RCC cells. Functional experiments consistently demonstrated that TRIM37 silencing reduced proliferation and stemness capacity while enhancing chemotherapy sensitivity in RCC cells. Furthermore, we discovered that TRIM37 mediates the degradation of SMARCC2 via ubiquitin-proteasome pathways, thereby further activating the Wnt signaling pathway. In conclusion, this study not only sheds light on the biological role of TRIM37 in RCC progression but also identifies a potential molecular target for therapeutic intervention in RCC patients.

The value of bronchodilator response in FEV1 and FeNO for differentiating between chronic respiratory diseases: an observational study.

BACKGROUND: There is no uniform standard for a strongly positive bronchodilation test (BDT) result. In addition, the role of bronchodilator response in differentiating between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) in patients with a positive BDT result is unclear. We explored a simplified standard of a strongly positive BDT result and whether bronchodilator response combined with fractional exhaled nitric oxide (FeNO) can differentiate between asthma, COPD, and ACO in patients with a positive BDT result. METHODS: Three standards of a strongly positive BDT result, which were, respectively, defined as post-bronchodilator forced expiratory volume in 1-s responses (ΔFEV1) increasing by at least 400 mL + 15% (standard I), 400 mL (standard II), or 15% (standard III), were analyzed in asthma, COPD, and ACO patients with a positive BDT result. Receiver operating characteristic curves were used to determine the optimal values of ΔFEV1 and FeNO. Finally, the accuracy of prediction was verified by a validation study. RESULTS: The rates of a strongly positive BDT result and the characteristics between standards I and II were consistent; however, those for standard III was different. ΔFEV1 ≥ 345 mL could predict ACO diagnosis in COPD patients with a positive BDT result (area under the curve [AUC]: 0.881; 95% confidence interval [CI] 0.83-0.94), with a sensitivity and specificity of 90.0% and 91.2%, respectively, in the validation study. When ΔFEV1 was < 315 mL combined with FeNO < 28.5 parts per billion, patients with a positive BDT result were more likely to have pure COPD (AUC: 0.774; 95% CI 0.72-0.83). CONCLUSION: The simplified standard II can replace standard I. ΔFEV1 and FeNO are helpful in differentiating between asthma, COPD, and ACO in patients with a positive BDT result.

Immune effect of a Newcastle disease virus DNA vaccine with IL-12 as a molecular adjuvant delivered by electroporation.

Newcastle disease (ND), caused by virulent Newcastle disease virus (NDV) strains, has been one of the most problematic diseases affecting the poultry industry worldwide. Conventional vaccines provide effective protection for birds to survive ND outbreaks, but they may not completely suppress NDV shedding. NDV strains circulate on farms for a long time after the initial infection and cause potential risks. A new vaccine with fast clearance ability and low viral shedding is needed. In this study, we used interleukin-12 (IL-12) as an adjuvant and electroporation (EP) as an advanced delivery system to improve a DNA vaccine candidate. The fusion (F) protein gene from an NDV strain of the prevalent genotype VII.1.1 was cloned to prepare the vaccine. Chickens immunized with the F gene DNA vaccine co-delivered with an IL-12-expressing plasmid DNA showed higher neutralizing antibody levels and stronger concanavalin-A-induced lymphocyte proliferation than those treated with the F gene DNA vaccine alone. The co-delivered vaccine provided 100% protection, and less viral shedding and a shorter release time were observed in challenged chickens than when the F gene DNA vaccine was administered alone. The use of F gene DNA combined with IL-12 delivered by electroporation is a promising approach for vaccination against ND.

Immune responses of mature chicken bone-marrow-derived dendritic cells infected with Newcastle disease virus strains with differing pathogenicity.

Infection of chickens with virulent Newcastle disease virus (NDV) is associated with severe pathology and increased morbidity and mortality. The innate immune response contributes to the pathogenicity of NDV. As professional antigen-presenting cells, dendritic cells (DCs) play a unique role in innate immunity. However, the contribution of DCs to NDV infection has not been investigated in chickens. In this study, we selected two representative NDV strains, i.e., the velogenic NDV strain Chicken/Guangdong/GM/2014 (GM) and the lentogenic NDV strain La Sota, to investigate whether NDVs could infect LPS-activated chicken bone-derived marrow DCs (mature chicken BM-DCs). We compared the viral titres and innate immune responses in mature chicken BM-DCs following infection with those strains. Both NDV strains could infect mature chicken BM-DC, but the GM strain showed stronger replication capacity than the La Sota strain in mature chicken BM-DCs. Gene expression profiling showed that MDA5, LGP2, TLR3, TLR7, IFN-α, IFN-ß, IFN-γ, IL-1ß, IL-6, IL-18, IL-8, CCL5, IL-10, IL-12, MHC-I, and MHC-II levels were altered in mature DCs after infection with NDVs at all evaluated times postinfection. Notably, the GM strain triggered stronger innate immune responses than the La Sota strain in chicken BM-DCs. However, both strains were able to suppress the expression of some cytokines, such as IL-6 and IFN-α, in mature chicken DCs at 24 hpi. These data provide a foundation for further investigation of the role of chicken DCs in NDV infection.