Effects of GLP-1 Receptor Polymorphisms on Adolescent Obesity

Obesity is becoming a concerning disease in developing countries. Like other multifactorial diseases, genetics plays a substantial role in the development of this disease. We tried to investigate genetic variations (mutation/polymorphism) of GLP-1R gene in children diagnosed with obesity and to identify their possible connections with obesity and other conditions. Genomic DNA was extracted from 162 overweight/obese patients and 100 controls. Later, full exon sequencing and association studies were carried out. Three polymorphisms and one mutation were detected in the fourth and fifth exons of the GLP-1R gene. Some variations were detected in three cases from which 1/3 had non-alcoholic fatty liver disease (NAFLD) but none showed insulin resistance (IR). There were also statistically meaningful results for ‘Odds Ratio’ among different genotypes and allele frequencies in groups with NAFLD and/or IR. In addition, there was an increase in risk for NAFLD and a decrease in risk for IR. In the homozygous group, also the prospect of IR was double declined. Patients with the A allele of this polymorphism showed a drop in risk for IR as well. GLP-1R polymorphisms could influence obesity and diabetes and thus the functional analysis of the GLP-1R polymorphisms is benevolent

Regulatory Functions of MicroRNAs in Cancer Pathogenesis

MicroRNAs (miRNAs) are a large family of evolutionary conserved small non-coding RNA molecules that firstly discovered in 1993. They regulate gene expression of about 50% of protein-coding genes at the post-transcriptional level. MiRNAs can target numerous messenger RNAs and subsequent misexpression of them can affect many different signaling pathways. They are playing a pivotal role in cancer development by regulation of the genes expression which involved in the proliferation, survival, differentiation, apoptosis or metastasis of the cancer cells. Several treatment approaches such as inhibition of oncomiRs and restoration of tumor suppressor miRNAs have been established in certain types of cancers and some other miRNA-based strategies are in development for cancer prevention and treatment. Nowadays, cancer is the most important target of miRNA therapeutics and the specific mechanisms by which miRNA mediates cancer pathways needs more research and study

A novel TNFRSF1A gene mutation in a patient with tumor necrosis factor receptor-associated periodic syndrome

© 2016 King Faisal Specialist Hospital & Research CentreTumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a periodic fever syndrome inherited in an autosomal dominant fashion. It stems from mutations in the TNFRSF1A (accession number: NM_001065) gene expressing the receptor for tumor necrosis factor α. A patient with TRAPS may present with prolonged episodes of fever attacks, abdominal pain, severe myalgia, and painful erythema on the trunk or extremities. Here, we report an 8-year-old boy with febrile attacks occurring every 1–2 months and continuing for 3–4 days. The patient experienced 40 °C-fever attacks without chills. Approximately 80% of fever attacks were accompanied by abdominal manifestations. Direct sequencing analysis was used to assess the genomic DNA of the patient, and a heterozygous R426L mutation in exon 10 of the TNFRSF1A gene in an autosomal dominant inheritance fashion was identified. Further genetic analyses were also carried out on his parents. Due to the fact that the mutation was not inherited from the parents, it was likely that R426L was a de novo and novel mutation in the TNFRSF1A gene, which can trigger TRAPS or TRAPS-like symptoms

MicroRNAs as regulators of apoptosis mechanisms in cancer

MicroRNAs or miRNAs are small non-coding RNAs that regulate gene expression. Their discovery has brought new knowledge in biological processes of cancer. Involvement of miRNAs in cancer development includes several major pathways from cell transformation to tumor cell development, metastasis and resistance to treatment. The first part of this review discusses miRNAs function in the intrinsic and extrinsic pathways of apoptosis. Due to the fact that many miRNAs that regulate apoptosis have been shown to play a major role in tumor cell resistance to treatment, in the second part of the review we aim at discussing miRNAs potential in becoming curative molecules

Caffeic acid phenethyl ester activates pro-apoptotic and epithelial-mesenchymal transition-related genes in ovarian cancer cells A2780 and A2780cis

Ovarian cancer is a highly aggressive pathology, displaying a poor prognosis and chemoresistance to classical therapy. The present study was conducted to evaluate the effect of caffeic acid phenethyl ester (CAPE) on survival of ovarian cancer cell lines, A2780 (sensitive to cisplatin) and A2780cis (resistant to cisplatin). MTT assay was used to evaluate cell viability, while the apoptotic processes were examined by flow cytometry and qRT-PCR. A reduction of cell proliferation and activation of the apoptosis was observed in both cell lines. qRT-PCR evaluation demonstrated the activation of the pro-apoptotic genes (BAD, CASP8, FAS, FADD, p53) in both cell lines. The limited therapeutic effect in A2780 cells is explained by the activation of epithelial-mesenchymal transition-related genes (ZEB1, ZEB2, or TGFBB1) as displayed by Ingenuity Network analysis. Overall data suggest that CAPE can be used as an alternative in sensitizing cells to chemotherapy