Soluble signal inhibitory receptor on leukocytes-1 reflects disease activity and assists diagnosis of patients with rheumatoid arthritis.

BACKGROUND: SIRL-1, an immunosuppressive receptor encoded by the VSTM1 gene, has recently been linked to rheumatoid arthritis (RA) due to its association with activated polymorphonuclear neutrophils (PMNs). Considering that the activated PMNs play a crucial role in the pathogenesis of rheumatoid arthritis (RA), we aimed to measure the levels of soluble SIRL-1, investigating whether they add value to RA in the clinical diagnosis. METHODS: Utilizing an enzyme-linked immunosorbent assay, the concentration of sSIRL-1 was measured in serum samples from cohort 1 diagnosed with RA (n = 96), gout (n = 54), osteoarthritis (n = 47), healthy controls (n = 86) and synovial fluid samples from OA (n = 8) and RA (n = 8) patients, respectively. Additionally, an external validation in cohort 2 (n = 156) comprising various inflammatory diseases was employed. RESULTS: The study revealed a distinctive upregulation of sSIRL-1 in the serum of RA compared to HC and other arthralgia diseases (p < 0.0001), which also displayed a significant elevation in synovial fluid from RA compared to OA (p < 0.05). Notably, sSIRL-1 levels exhibited a significant decrease in patients who achieved disease remission (p < 0.05). Furthermore, the diagnostic accuracy of RA was enhanced when sSIRL-1 was combined with anti-CCP and RF, yielding an impressive AUC value of 0.950. CONCLUSION: The expression pattern of sSIRL-1 in RA, coupled with its correlation with disease activity, underscores its potential clinical utility for both diagnosis and disease monitoring in RA patients. This study offers valuable insights into the evolving diagnostic landscape of RA.

Effective Neutralizing Antibody Produced in Mice Directly Immunized with Integrated Pichia pastoris Expressing HPV16L1 Protein.

The human papillomavirus (HPV) vaccine has not been widely used in developing countries because of its high cost and multiple subtype restrictions. The present study aimed to develop an economical, convenient, and effective vaccine to produce neutralizing antibodies. Using late protein 1 (L1) from the HPV16 subtype as the target antigen (HPV16L1) and Pichia pastoris as the antigen release system, integrated P. pastoris expressing HPV16L1 (named yeast-HPV16L1) was prepared and vaccinated directly into mice by subcutaneous multipoint injection. After immunization was performed thrice, high titers (greater than 1:40,960) of specific anti-HPV16L1 antibodies were obtained in immune serum and were observed to continuously rise over time. The indirect hemagglutination test and indirect hemagglutination inhibition test were used to detect neutralizing antibody activity in vitro, and the results demonstrated the hemagglutination ability of the immune serum and the reduction in or loss of the hemagglutination ability if preneutralized antigen was added to the immune serum. The protection conferred by immune serum to tumor-bearing mice at the early stages was confirmed, but the neutralizing activity disappeared when the tumor reached a size of 1 mm3. The neutralization activity of the immune serum was confirmed both in vitro and in vivo.

Acute Exercise-Induced Mitochondrial Stress Triggers an Inflammatory Response in the Myocardium via NLRP3 Inflammasome Activation with Mitophagy.

Increasing evidence has indicated that acute strenuous exercise can induce a range of adverse reactions including oxidative stress and tissue inflammation. However, little is currently known regarding the mechanisms that underlie the regulation of the inflammatory response in the myocardium during acute heavy exercise. This study evaluated the mitochondrial function, NLRP3 inflammasome activation, and mitochondrial autophagy-related proteins to investigate the regulation and mechanism of mitochondrial stress regarding the inflammatory response of the rat myocardium during acute heavy exercise. The results indicated that the mitochondrial function of the myocardium was adaptively regulated to meet the challenge of stress during acute exercise. The exercise-induced mitochondrial stress also enhanced ROS generation and triggered an inflammatory reaction via the NLRP3 inflammasome activation. Moreover, the mitochondrial autophagy-related proteins including Beclin1, LC3, and Bnip3 were all significantly upregulated during acute exercise, which suggests that mitophagy was stimulated in response to the oxidative stress and inflammatory response in the myocardium. Taken together, our data suggest that, during acute exercise, mitochondrial stress triggers the rat myocardial inflammatory response via NLRP3 inflammasome activation and activates mitophagy to minimize myocardial injury.

Expression changes of thrombospondin-1 and neuropeptide Y in myocardium of STZ-induced rats.

Diabetic cardiomyopathy was the most dangerous diabetic complication facing diabetics, with its exact mechanisms remaining obscure. Our study was conducted to investigate the expression of thrombospondin-1 (TSP-1) and neuropeptide Y (NPY) in myocardium of streptozotocin (STZ)-induced diabetic rats. We employed streptozotocin (STZ)-induced diabetic rats to study the alteration of the TSP-1 and NPY expression in the left ventricle myocardium in diabetic and normal group by immunohistochemistry and immunofluorescence. The data of weight, blood sugar and urine sugar indicated no significant difference between the two groups before the animal model was induced. Four weeks after the induction of diabetes the weight of the diabeteic animals was 189.1+/-18.4 g, plasma glucose was 23.7+/-3.25 mmol/L and urine glucose was (++) to (+++); whereas the weight of the control animals was 260.5+/-32.1 g, plasma glucose was 4.9+/-0.5 mmol/L and urine glucose undetectable (-). The differences between the control and the diabetes group were distinct. A significant increase of the TSP-1 and NPY expression was also observed in the diabetic rat's heart. The number of the NPY positive myocardium and the light density of the positive myocardium in the left ventricle of the diabetic model were 17.3+/-2.1 and 102.5+/-9.3/mm(2), respectively, which were considered as increased when compared with the control that were 10.1+/-2.6 and 61.2+/-6.7, respectively. Our results support the view that high glucose conditions can induce an increased synthesis of TSP-1 through the PKC-TGF-beta-TSP-1 pathway, which in turn facilitate TGF-beta activation. Additionally, the activation of PKC may further lead to the over-expression of NPY. This may be involved in diabetic cardiomyopathy.