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Dyslipidemia, an imbalance in blood lipid levels, is a frequent complication of type 2 diabetes mellitus (DM2) and heightens the risk of cardiovascular diseases (CVDs). Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, are potent competitive inhibitors that reduce plasma cholesterol levels. However, individual responses to statins can vary markedly, possibly due to genetic variations in the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) gene. This study aimed to investigate the pharmacogenetic relationship between the HMGCR gene and hypercholesterolemia in type 2 diabetes mellitus patients who respond differently to atorvastatin, as well as in healthy individuals. Ninety participants were involved, including sixty with type 2 diabetes mellitus and hypercholesterolemia, and thirty healthy individuals. They were randomly assigned to three groups: responsive (received atorvastatin 40 mg), non-responsive (also received atorvastatin 40 mg), and control. Both responsive and non-responsive groups underwent fasting. Biochemical tests were conducted, followed by genetic analysis to identify mutations in the HMGCR gene. The effects of statins in each group were assessed using analysis of variance (ANOVA) and post hoc Tukey's Honestly Significant Difference (HSD) analysis. Atorvastatin 40 mg was administered to assess its efficacy in reducing cholesterol levels in patients with hypercholesterolemia and type 2 diabetes mellitus. The control group exhibited similar cholesterol levels to the responsive group (cholesterol < 200 mg/dl). However, both control and responsive groups significantly differed from the non-responsive group, which had markedly elevated cholesterol levels (> 240 mg/dl). Genetic analysis revealed a cytosine nucleotide insertion in the catalytic domain of the HMGCR gene in only two non-responsive participants to atorvastatin 40 mg therapy. These two patients showed non-responsiveness to atorvastatin 40 mg due to a genetic mutation in the HMGCR gene. This mutation altered the amino acid sequence in the flap domain, replacing isoleucine with a stop codon. As a result, translation was prematurely terminated, leading to the production of truncated proteins. [ABSTRACT FROM AUTHOR]

The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are diseases in which the regulatory mechanisms of the immune response are disturbed. As a result, the body loses self‐tolerance. Since one of the main regulatory mechanisms of the immune response is the CTLA4–CD80/86 axis, this hypothesis suggests that autoimmune diseases potentially share a similar molecular basis of pathogenesis. Hence, investigating the CTLA4–CD80/86 axis may be helpful in finding an appropriate treatment strategy. Therefore, this study aims to investigate the molecular basis of the CTLA4–CD80/86 axis in the regulation of the immune response, and then its role in developing some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. As well, the main therapeutic strategies affecting the CTLA4–CD80/86 axis have been summarized to highlight the importance of this axis in management of autoimmune diseases. Significance statement: The CTLA4–CD80/86 axis as a major regulatory pathway in autoimmune diseases plays an important role in the pathogenesis of these diseases. Therefore, to find an appropriate treatment strategy, knowledge of the CTLA4–CD80/86 axis is helpful. Molecular basis and therapeutic strategies of the CTLA4–CD80/86 axis may help to treat autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. [ABSTRACT FROM AUTHOR]

The COVID-19 infection is a worldwide disease that causes numerous immune-inflammatory disorders, tissue damage, and lung dysfunction. COVID-19 vaccines, including those from Pfizer, AstraZeneca, and Sinopharm, are available globally as effective interventions for combating the disease. The severity of COVID-19 can be most effectively reduced by mesenchymal stromal cells (MSCs) because they possess anti-inflammatory activity and can reverse lung dysfunction. MSCs can be harvested from various sources, such as adipose tissue, bone marrow, peripheral blood, inner organs, and neonatal tissues. The regulation of inflammatory cytokines is crucial in inhibiting inflammatory diseases and promoting the presence of anti-inflammatory cytokines for infectious diseases. MSCs have been employed as therapeutic agents for tissue damage, diabetes, autoimmune diseases, and COVID-19 patients. Our research aimed to determine whether live or dead MSCs are more suitable for the treatment of COVID-19 patients. Our findings concluded that dead MSCs, when directly administered to the patient, offer advantages over viable MSCs due to their extended presence and higher levels of immune regulation, such as T-reg, B-reg, and IL-10, compared to live MSCs. Additionally, dead and apoptotic MSCs are likely to be more readily captured by monocytes and macrophages, prolonging their presence compared to live MSCs. [ABSTRACT FROM AUTHOR]

Cancer, the most deadly disease, is known as a recent dilemma worldwide. Presently different treatments are used for curing cancers, especially solid cancers. Because of the immune-enhancing functions of cytokine, IL-21 as a cytokine may have new possibilities to manipulate the immune system in disease conditions, as it stimulates NK and CTL functions and drives IgG antibody production. Indeed, IL-21 has been revealed to elicit antitumor-immune responses in several tumor models. Combining IL-21 with other agents, which target tumor cells, immune-regulatory circuits, or other immune-enhancing molecules enhances this activity. The exciting breakthrough in the results obtained in pre-clinical situations has led to the early outset of present developing clinical trials in cancer patients. In the paper, we have reviewed the function of IL-21 in solid tumor immunotherapy. [ABSTRACT FROM AUTHOR]

NK cells are defined as the major components of the immunological network which exerts defense against tumors and viral infections as well as regulation of innate and adaptive immunity, shaped through interaction with other cells like T cells. According to the surface markers, NK cells can be divided into CD56dim NK and CD56bright NK subsets. CD56bright NK cells usually are known as regulatory NK cells. Once the immune system loses its self-tolerance, autoimmune diseases develop. NK cells and their subsets can be altered during autoimmune diseases, indicative of their prominent regulatory roles and even pathological and protective functions in autoimmune disorders. In this regard, activation of CD56bright NK cells can suppress activated autologous CD4+ T cells and subsequently prevent the initiation of autoimmunity. In this review article, we summarize the roles of regulatory NK cells in autoimmune disease occurrence which needs more research to uncover their exact related mechanism. It seems that targeting NK cells can be a promising therapeutic platform against autoimmune diseases. [ABSTRACT FROM AUTHOR]