Targeting T Cell Metabolism as a Novel Approach for Treatment of MS: With a Focus on PFKFB3 Inhibitors.

Multiple sclerosis (MS) is one of the organ-specific autoimmune diseases in which immune cells invade the neurons in the central nervous system (CNS) due to loss of tolerance to self-antigens. Consequently, inflammation and demyelination occur in the central nervous system. The pathogenesis of MS is not completely understood. However, it seems that T cells, especially Th17 cells, have an important role in disease development. In recent years, studies on the manipulation of metabolic pathways with therapeutic targets have received increasing attention and have had promising results in some diseases, such as cancers. Glycolysis is a central metabolic pathway and plays an important role in the differentiation of T CD4+ cells to their subsets, especially Th17 cells. This suggests that manipulation of glycolysis, for example, using appropriate safe inhibitors of this pathway can represent a means to affect the differentiation of T CD4+, thus reducing inflammation and disease activity in MS patients. Hence, in this study, we aimed to discuss evidence showing that using inhibitors of 6-phosphofructo-2- kinase/fructose-2,6-biphosphatase 3(PFKFB3) as the main regulator of glycolysis may exert beneficial therapeutic effects on MS patients.

Lower frequency of T stem cell memory (TSCM) cells in hepatitis B vaccine nonresponders.

Despite the availability of an effective vaccine and antiviral treatments, hepatitis B is still a global public health problem. Hepatitis B vaccination can prevent the disease. Vaccination induces long-lasting protective immune memory, and the identification of memory cell subsets can indicate the effectiveness of vaccines. Here, we compared the frequency of CD4+ memory T cell subsets between responders and nonresponders to HB vaccination. Besides, the frequency of IFN-γ+ memory T cells was compared between studied groups. Study participants were grouped according to their anti-HBsAb titer. For restimulation of CD4+ memory T cells, peripheral blood mononuclear cells (PBMCs) were cultured in the presence of HBsAg and PHA for 48 h. Besides, PMA, ionomycin, and brefeldin were added during the last 5 h of incubation to induce IFN-γ production. Flow cytometry was used for analysis. There was a statistically significant difference in the frequency of CD4+CD95+, CD4+CD95Hi, and CD4+CD95low/med T stem cell memory (TSCM) cells between responder and nonresponder groups. However, the comparison of the frequency of memory T cells producing IFN-γ showed no differences. Our results identified a possible defect of immunological CD4+ memory T cell formation in nonresponders due to their lower frequency of CD4+ TSCM cells.

Targeting Citrate Carrier (CIC) in Inflammatory Macrophages as a Novel Metabolic Approach in COVID-19 Patients: A Perspective.

Coronavirus disease-19 (COVID-19) can be a fatal disease and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). SARS-CoV2 is an enveloped virus that belongs to the Beta coronavirus subfamily. After entering into the target cells, this virus replicates rapidly and leads to cellular damage and uncontrolled pulmonary inflammation. Huge amounts of inflammatory cytokines and chemokines are produced by infected lung cells and are associated with monocyte recruitment and accumulation of inflammatory macrophages at the site of infection. Mitochondrial citrate carrier (CIC) expression increases in these macrophages, which results in elevated levels of cytosolic citrate and the production of inflammatory mediators. In this perspective article, we discuss the role of mitochondrial CIC in the metabolism of inflammatory macrophages and we propose that inhibition of this carrier might be a novel therapeutic approach for COVID-19 patients.

Prevalence of Enterobius vermicularis amongst kindergartens and preschool children in Mazandaran Province, North of Iran.

Enterobiasis (oxyuriasis) is probably the most common helminth, which infects humans. Amongst different age groups, prevalence of Enterobius vermicularis in children is high compared to adults. Oxyuriasis is one of the most significant parasitic diseases of children. This nematode in children can result in loss of appetite, insomnia, grinding of the teeth, restlessness, endometritis, abdominal cramps, diarrhea and etc. Due to important complications of this parasite, the objective of the current study was to determine the prevalence of enterobiasis in kindergarten and preschool children of Amol, Mazandaran Province, North of Iran. A total number of 462 children from 32 kindergartens of Amol were examined for the prevalence of E. vermicularis infection, 2013. Adhesive cello-tape anal swab method was trained to parents for sampling. In addition, a questionnaire was designed and filled out to collect demographic information for each individual. Data were analyzed using Chi square test and multivariate logistic regression for each risk factor. The overall prevalence of E. vermicularis infection was 7.1 % (33). Although infection with E. vermicularis in girls 7.9 % was higher compared to boys 6.3 %, there was no significant difference between gender and age (p > 0.05) whereas binary logistic regression showed significant difference between enterobiasis and age (p < 0.05). The findings indicated that the prevalence of E. vermicularis in kindergarten and preschool children is relatively high and still is an important health problem and should not be underestimated due to being highly contagious infection. Therefore, educational programs and mass treatment should be carried out in order to reduce infection incidence in this area and regular parasitological test and attention to personal hygiene in kindergarten and preschool is of great importance.