ABSTRACT
High salt (HS) consumption is a risk factor for multiple autoimmune disorders via disturbing immune homeostasis. Nevertheless, the exact mechanisms by which HS exacerbates rheumatoid arthritis (RA) pathogenesis remain poorly defined. Herein, we found that heightened phosphorylation of PDPK1 and SGK1 upon HS exposure attenuated FoxO1 expression to enhance the glycolytic capacity of CD4 T cells, resulting in strengthened Th17 but compromised Treg program. GSK2334470 (GSK), a dual PDPK1/SGK1 inhibitor, effectively mitigated the HS-induced enhancement in glycolytic capacity and the overproduction of IL-17A. Therefore, administration of GSK markedly alleviated HS-exacerbated RA progression in collagen-induced arthritis (CIA) model. Collectively, our data indicate that HS consumption subverts Th17/Treg homeostasis through the PDPK1-SGK1-FoxO1 signaling, while GSK could be a viable drug against RA progression in clinical settings.
ABSTRACT
INTRODUCTION: Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are two cutaneous conditions with morphological resemblance, which can complicate the diagnosis in some cases. Using immunohistochemistry staining of biomarkers could be beneficial in resolving this obstacle. OBJECTIVES: We investigated a variety of biomarkers assessed in different studies in order to find the most important and helpful biomarkers for differentiation between SCC and lesions capable of spontaneous regression. METHODS: MEDLINE via PubMed and Google Scholar database were used to identify relevant literature up to 15 June 2022. The aim of our analyses was to determine the capability of biomarkers to distinguish between SCC and lesions capable of spontaneous regression using calculated individual and pooled odds ratios (OR) and 95% confidence intervals (CI) and I2 tests. RESULTS: Six potential biomarkers were CD10 with pooled OR= 0.006 (95% CI: 0.001-0.057) and I2=0%; COX-2 with pooled OR=0.089 (95% CI: 0.029-0.269) and I2=17.1%; elastic fibers with pooled OR= 6.69 (95% CI: 2.928-15.281) and I2=0%; IMP-3 with pooled OR=0.145 (95% CI: 0.021-1.001) and I2=44.5%; P53 with pooled OR=0.371 (95% CI: 0.188-0.733) and I2=55.9%; AT1R with OR=0.026 (95% CI: 0.006-0.107). CONCLUSIONS: We suggest the utilization of the following IHC biomarkers for discrimination between lesions with spontaneous regression such as KA and SCC: CD10, COX-2, and elastic fibers.
ABSTRACT
Objective: An experiment was conducted to define the principle of the conventional tube technique, gel card technology, and solid-phase technology of blood transfusion. The study also highlights the test reactions and various methods of grading reactions for each technology. It further discusses the automated equipment available for each technology and compares the equipment, tests reactions, procedures, and sensitivity of these techniques. Material and methods: This cross-sectional study was conducted on blood samples of 40 patients with positive indirect antiglobulin test at the Padmashree Diagnostics Center and the Bangalore Medical Services Trust, India. Tube and gel card method and solid-phase red cell adherence assay (SPRCA) were evaluated. Results: The results revealed SRPCA of 1+ in nine samples, 2+ in 15 samples, 3+ in 13 samples and 4+ in three samples, while the manual method yielded 1+ in 14 samples, 2+ in 13 samples, 3+ in 13 samples and 4+ in one sample. Conclusion: Solid-phase red cell adherence assay is more precise and capable of detecting red cell adherence assay than tube method and indirect Coombs test gel technology.
