Introduction; MS is an inflammatory progressive disease with destruction of myelin sheath of neurons and axons. Among environmental risk factors HHV-6 might plays a role in MS. HHV-6 is a lymphotropic virus causing neurological symptoms. HHV-6 may exist in the PBMCs and CNS in a latent state. Materials and Methods; This case-control study was conducted on 116 new cases of MS whom naive to MS drugs. The control group consist 116 non-MS individuals whose gender, age and their place of residency were matched with the cases. Ten ml of peripheral blood was collected from each participant, their Sera and PBMCs were separated and the DNA was extracted from them separately. After Nested-PCR, the PCR products were sequenced. Statistical analysis of data was performed by V.22 of SPSS software and chi-square and Fisher’s exact tests and Odd‘s ratio were used. The P≤0.05 was considered as statistically significant. Results; considering of existence of HHV-6, there was a significant difference in PBMCs and Sera of case and control group, but among male participants the difference between cases and controls was not significant while this figure for female participants was significant in PBMCs and Sera. Regarding age group, only 21-25 and 31-35 groups were statistically significant. All positive samples were variant 6B of HHV-6. Discussion; HHV-6 can be considered as a MS risk factor mainly in female cases, especially in the age group of 20-35. HHV-6 is in its active state (Sera) in these patients.

Immunocompromised individuals have been shown to mount a reduced response to vaccination, resulting in reduced vaccine effectiveness in this cohort. Therefore, in the post vaccination era, immunocompromised individuals remain at high risk of breakthrough infection and COVID-19 related hospitalisation and death. There has been a marked paucity of systematic review evaluating existing data describing the clinical measures of efficacy of COVID-19 vaccination in protecting immunocompromised individuals, specifically against, breakthrough infections and severe COVID-19. Therefore, we conducted a systematic review which aimed to provide a summary of current clinical evidence of the effectiveness of COVID-19 vaccination in the immunocompromised population. Our findings demonstrated that immunocompromised patients remained at high risk of breakthrough infection and severe COVID-19 outcomes compared to the general population. These groups included those with: cancer, organ transplants, chronic kidney disease, HIV and immunodeficiencies, amongst others. This demonstrated that vaccination does not offer an adequate level of protection in these groups, necessitating further measures such as Evusheld and further boosters.

Introduction:This study focused on investigating the effects of LncRNA DANCR regulation of Keap1-Nrf2/ARE pathway on inflammation and oxidative stress in RA. Methods:The levels of LncRNA DANCR/miR-486-3p/ Keap1 in peripheral blood of 30 RA groups and 30 normal subjects were examined, and the association of LncRNA DANCR with inflammatory indicators of rheumatoid arthritis was investigated. We construct overexpression plasmids and small interfering RNAs of LncRNA DANCR to investigate the relationship between LncRNA DANCR and FLSs viability and migration in rheumatoid arthritis, as well as the effects on cellular oxidative stress factors and Keap1-Nrf2/ARE pathway; molecular biology analysis was used to predict microRNAs that can bind LncRNA DANCR, and luciferase verified the binding sites of LncRNA DANCR with Keap1 and miR-486-3p; to further refine the gene and protein expression results, we used RT- qPCR and immunoblotting assays . Results: In both groups of PBMCs, the expression levels of LncRNA DANCR and Keap1 mRNA were higher in the rheumatoid arthritis group than in the normal control group, and the opposite was true for miR-486-3p; LncRNA DANCR was positively correlated with TAOC, IL6, RF, IL17, anti-CCP, MDA, and SOD, but not with ESR, DAS28, IL11, and SOD, DAS28, IL11, ROS, CRP were negatively correlated; overexpression of lncRNA DANCR stimulated the Keap1-Nrf2/ARE pathway, decreased the expression of IL10, SOD, TAOC, and increased the expression levels of MDA, IL11, IL-17, PD-L1, and silencing of lncRNA DANCR was the opposite, but knockdown of miR- 486-3p or overexpression of keap1 reversed the expression of the above-mentioned inflammatory and oxidative factors. In addition, pcDNA-DANCR clearly showed stronger cell invasion and migration ability and exacerbated its inflammatory response, we verified their targeting relationship using dual luciferase. Conclusion: The low-expressed lncRNA DANCR may regulate the Keap1-Nrf2/ARE pathway and suppress the inflammatory and oxidative responses in RA patients.

Background Extracellular matrix (ECM) degradation, chondrocyte inflammation, and cellular senescence contribute to the pathology of osteoarthritis (OA). Empagliflozin, a selective inhibitor of sodium-glucose cotransporter-2 (SGLT2), has been reported to show the anti-inflammatory properties in several conditions. However, whether empagliflozin can be used to improve OA is still unknown. Methods The protective effects and underlying mechanism of empagliflozin in OA were investigated in vitro and in vivo. Cell viability, catabolic markers, inflammatory mediators, cellular senescence level, cartilage degeneration were evaluated by CCK-8 assay, safranine O staining, ELISA, real-time PCR, western blot, β-galactosidase Staining, and histological analysis. Results We found that empagliflozin significantly downregulated the expression of catabolic enzymes (MMP9 and MMP13), and decreased the expression of inflammatory mediators (NO, PGE2, IL-6, COX2, and INOS), and reduced the cellular senescence level in IL-1β-treated chondrocytes by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. What’s more, empagliflozin prevented cartilage degeneration in DMM-induced OA mice model with significant lower OARSI grade. Conclusion Our findings reveal that empagliflozin inhibited chondrocytes ECM degradation, inflammation and cellular senescence in vitro and prevented cartilage degeneration in vivo by suppressing NF-κB signal pathway, indicating a therapeutic potential in OA treatment.

Background: Here we conducted this study to find the changes in the hematological parameters of healthy individuals that can predict their immune status, also this study aims to find out whether herd immunity against COVID-19 is developing or not in the Pakistani population. Methods: A comparative cross-sectional study of 210 healthy individuals was conducted. All individuals were divided into three groups i.e IgG positive, IgG negative, and IgG and IgM both positive based on ELISA results. Data analysis was done by SPSS version 25 for windows. Results: A statistically significant effect was found among the three groups in terms of mean hemoglobin level, mean hematocrit, mean corpuscular hemoglobin concentration, mean red blood cells count, RDW-CV, mean lymphocyte, mean neutrophil, mean eosinophils, and mean basophil. The study also showed that 52.8% (n=74) had neither taken vaccination nor had any history of previous covid infection but still their antibodies were positive. Conclusion: There was a statistically significant difference among hematological parameters between immune and nonimmune groups and can predict the covid immune status also the study predicted that herd immunity against COVID-19 is developing in Pakistan.

Abstract Introduction Severe COVID-19 management is still challenging. Having a laboratory factor to predict the severity of a patient’s condition can be very useful in how to approach each patient. There have been studies concentrating on the correlation between serum C-reactive protein (CRP) level and COVID-19 severity but we aim to reach a threshold for CRP in disease severity determination. Methods We conducted a thorough search on PubMed, Web of Science and Google Scholar databases, and 323 studies were assessed for eligibility in three phases. The T-test was applied for the CRP level cutoffs. Results Eventually, 11 articles and 1615 patients were included in this systematic review. Our analysis evaluated combined mean, median, and standard deviation of severe patients’ CRP to be respectively 73.37, 53.80 and 47.936. Based on the combined mean, 75mg/dl was suggested as an initial threshold for baseline CRP in hospitalized patients for developing severe conditions. Conclusion This study recommends that COVID-19 patients with on-admission serum CRP levels of 75 mg/dl and more are likely associated with severe conditions. Thus, anti-inflammatory agents and further following may be helpful in these patients.

At present, the effect of exogenous interleukin (IL) -17A in septic mice is still controversial. This study further explored the effect of exogenous IL-17A on multiple organ function and prognosis in septic mice. Mice model of sepsis was established by cecal ligation and puncture (CLP) method, and the mice were randomly divided into 8 groups according to different intervention measures: Sham+PBS, CLP+PBS, CLP+0.25μg IL-17A, CLP+0.5μg IL-17A, CLP+1μg IL-17A, CLP+2μg IL-17A, CLP+4μg IL-17A and CLP+Anti-IL-17A. Survival rates were monitored and recorded at 12-hour intervals, and the expression changes of blood routine, related inflammatory cytokines, liver and kidney function indexes of mice. Pathological injuries of lung, liver and kidney of mice in each group were detected by H&E staining, and the evaluation of bacterial translocation in vitro was performed by inoculation medium. The results showed that except for the sham-operated group, the 7-day survival rate of the mice in the CLP+1μg IL-17A group was the highest (75%). And exogenous administration of appropriate dose of IL-17A was beneficial to reduce alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cre) in septic mice. The pathological damage of lung, liver and kidney tissue also can be alleviated, and the colony count of peripheral blood and spleen tissue of mice were also significantly decreased. From this, we concluded that exogenous administration of appropriate dose of IL-17A can improve the bacterial clearance ability of septic mice, and improve the multiple organ dysfunction and 7-day survival rate of the septic mice.