👤 Mohammad Hosein Nemati

Apelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR-224, miR-195/miR-195-5p, miR-204-5p, miR-631, miR-4286, miR-637, miR-4493, and miR-214-3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ-NOTCH1, circ-ZNF264, and lncRNA BACE1-AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ₀₀₀₀₀₀₄/miR-1303, miR-15a-5p, and miR-106a-5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy. Show less

Autoimmune disorders (ADs) pose significant health and economic burdens globally, characterized by the body's immune system mistakenly attacking its own tissues. While the precise mechanisms driving their development remain elusive, a combination of genetic predisposition(s) and environmental triggers is implicated. Interleukin-27 (IL-27), among numerous cytokines involved, has emerged as a key regulator, exhibiting dual roles in immune modulation. This review delves into the molecular structure and signaling mechanisms of IL-27, highlighting its diverse effects on various immune cells. Additionally, it explores the involvement of IL-27 in autoimmune diseases, such as multiple sclerosis (MS) and rheumatoid arthritis (RA), offering insights into its potential therapeutic implications. Moreover, its involvement in autoimmune diseases like type 1 diabetes (T1D), inflammatory bowel disease (IBD), myasthenia gravis (MG), Sjögren's syndrome (SS), and Guillain-Barré syndrome (GBS) is multifaceted, with potential diagnostic and therapeutic implications across these conditions. Further research is essential to fully understand IL-27's mechanisms of action and therapeutic potential in autoimmune diseases. Show less

Obesity has become a common global problem. Some obese people can be metabolically healthy. Gene-environment interaction can be important in this context. This study aimed to assess the interaction between dietary fat quality indices and the Melanocortin 4 receptor (MC4R) gene in metabolically healthy and unhealthy overweight and obese women. This cross-sectional study was conducted on 279 women with overweight and obesity. The definition of metabolically healthy and unhealthy phenotypes was done according to Karelis criteria. Dietary assessment was done using a 147-item validated semi-quantitative food frequency questionnaire and dietary fat quality was assessed by cholesterol-saturated fat index (CSI) and the ratio of omega-6/omega-3 (N6/N3) essential fatty acids. MC4R was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. A generalized linear model was used to evaluate the interaction between dietary fat quality indices and the MC4R gene in both crude and adjusted models. Study subjects with higher ratio of N6/N3 had higher homeostatic model assessment for insulin resistance (HOMA IR) index (P = 0.03) and other variables showed no difference according to the tertile of CSI and N6/N3. Participants with the C allele of MC4R rs17782313 had lower height (P < 0.001) and higher HOMA index (P = 0.01). We found that the CC genotype of MC4R interacts with the N6/N3 ratio on the metabolically unhealthy phenotype in the crude model (β = 9.94, CI 2.49-17.39, P = 0.009) and even after adjustment for all confounders (β = 9.002, CI 1.15-16.85, P = 0.02, β =  - 12.12, CI 2.79-21.46, P = 0.01). The data of this study can justify one inconsistency observed in society, regarding dietary recommendations about metabolic health status. Those with CC genotype, are more likely to have an unhealthy phenotype with an increase in N6/N3 as one fat quality indices than those who do not have CC genotype. We found the interaction of dietary fat quality indices such as N6/N3 and the MC4R gene in metabolically unhealthy overweight and obese women. Show less

Infection with the same species of Leishmania (L)donovani causes different manifestations including visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL), indicating that the host-related immunological parameters perform a decisive role in the pathogenesis of diseases. As PKDL is a reservoir of the parasite, a better understanding of the host immune responses is necessary to restrict the L. donovani transmission. The proper local production of Th1 cell-related cytokines (including IFN-γ, TNF-α and IL-12), Th17 cell-derived cytokines (such as IL-17A, IL-17F and IL-22), and CD8 Show less

Allergic airway disorders such as asthma and allergic rhinitis are mainly caused by inhaled allergen-induced improper activation and responses of immune and non-immune cells. One important response is the production of IL-27 by macrophages and dendritic cells (DCs) during the early stage of airway allergies. IL-27 exerts powerful modulatory influences on the cells of innate immunity [eg neutrophils, eosinophils, mast cells, monocytes, macrophages, dendritic cells (DCs), innate lymphoid cells (ILCs), natural killer (NK) cells and NKT cells)] and adaptive immunity (eg Th1, Th2, Th9, Th17, regulatory T, CD8 Show less

IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy. Show less