Rheumatoid arthritis (RA) is an autoimmune disease with chronic and excessive inflammation. Upregulation of interleukin (IL)-17 is involved in the pathogenesis of RA. STX0119 is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) as a potential target for the treatment of RA. STAT3 is a member of DNA-binding molecules that regulates the expression of proinflammatory cytokines involved in the pathogenesis of RA. The objective of this study was to determine whether STX0119 could inhibit STAT3 and IL-17. We demonstrated that STX0119 decreased T helper (Th) 17 differentiation and IL-17 expression in vitro. STX0119 also improved the severity of zymosan induced arthritis and reduced joint inflammation. STX0119 reduced the proliferation of Th17 and phosphorylated STAT3 expression while increasing Treg differentiation and phosphorylated STAT5 expression. Moreover, STX0119 decreased the expression of IL-6 and -17 but not IL-10. These findings suggest that STX0119 can be used to treat autoimmune RA through inhibiting the activation of STAT3.
Animals ; Arthritis* ; Arthritis, Rheumatoid ; Autoimmune Diseases ; Cytokines ; In Vitro Techniques ; Inflammation ; Interleukin-10 ; Interleukin-17 ; Interleukin-6 ; Interleukins ; Joints ; Mice* ; STAT3 Transcription Factor ; Up-Regulation ; Zymosan

Aim: We designed this study to compare the presence of depressive symptoms pre and 6 months post-MI and to identify the association of various biological and non-biological risk factors with the development of depressive symptoms post-MI. Objective: Coronary artery disease and depressive illness are the largest contributors to global mortality and disability. These disorders frequently occur together and have major health implications. We conducted this study to determine the frequency of increased depressive symptoms following Myocardial Infarction (MI) and analyze associated baseline risk factors. Study Design: Descriptive case series. Place and duration of study: Tertiary care cardiology hospital from Sept 2019 to Jan 2021. Patients and Methods: Patients presenting with a recent episode of myocardial infarction at the out-patient department of cardiology were recruited for this study. Demographic variables and baseline health status were recorded. Hospital Anxiety and Depression Scale (HADS) was applied in two instances, at first contact for depressive symptoms pre-MI and at the second instance 6 months post-MI. An increase in HADS score of 4 or more points after 6 months of MI was considered significant. Association of age, gender, smoking status, employment status, previous MI episode, depression and history of stressful life event with an increase in depression was analyzed. Results: The sample consisted of 140 patients, 88 males and 52 females. The mean age was 51.22 years (SD= ± 12.35). 60.7% (n=85) of patients had an increase in depressive symptoms scores as measured by HADS. Younger age (30 to 50 years), being a smoker and having a previous history of myocardial infarction were associated with a significant increase in depressive symptoms. Conclusion 60.7% of patients have increased depressive symptoms after myocardial infarction. Patients should be regularly screened for emerging depressive symptoms and special attention should be paid to younger patients, smokers and those who have a previous history of coronary artery disease.