Inflammation and immunological disarrays are associated with acute exercise in type 2 diabetes.

Objective: Type 2 diabetes (T2D) is the most common metabolic disorder that is associated with insulin resistance. The aim of the present study is to discover details of the molecular mechanism of exercise on control or progress of diabetic condition in patients via network analysis. Methods: Gene expression profiles of patients with T2D before and after doing exercise are retrieved from Gene Expression Omnibus (GEO) and are pre-evaluated by the GEO2R program. Data are studied based on expression values, regulatory relationships between the differentially expressed genes (DEGs), gene ontology analyses, and protein-protein interaction PPI network analysis. Results: A number of 118 significant DEGs were identified and classified based on fold change (FC) values as most dysregulated genes and dysregulated individuals. Action map analysis revealed that 18 DEGs appeared as the critical genes. Gene ontology analysis showed that 24 DEGs are connected to at least four pathways. JUN, IL6, IL1B, PTGS2, FOS, MYC, ATF3, CXCL8, EGR1, EGR2, NR4A1, PLK3, TTN, and UCP3 were identified as central DEGs. Conclusion: Finally; JUN, IL6, IL1B, PTGS2, FOS, ATF3, CXCL8, EGR1, and EGR2 were introduced as the critical targeted genes by exercise. Since the critical genes after exercise are upregulated and mostly are known as the risk factors of T2D, it can be concluded that unsuitable exercise can develop diabetic conditions in patients. Acute exercise-induced inflammation and immune disturbances seem to be associated with the development of T2D in patients.

A Contemporary Review on the Critical Role of Nonsteroidal Anti-inflammatory Agents in Colorectal Cancer Therapy.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are widely recognized as effective pain relievers and function by inhibiting the cyclooxygenase enzyme (COXs). Moreover, they have been found to participate in various cellular processes through different signaling pathways, such as WNT, MAPK, NF-κB, and PI3K/AKT/mTOR. This makes them potential candidates for chemoprevention of several malignancies, particularly colorectal cancer (CRC). However, the use of NSAIDs in cancer prevention and treatment is a complex issue due to their adverse effects and gastrointestinal toxicity. Therefore, it is crucial to explore combination therapies that can minimize side effects while maximizing synergistic effects with other agents and to evaluate the success rate of such approaches in both pre-clinical and clinical studies. In this review, we aim to provide an overview of the effects of NSAIDs in the prevention and treatment of CRC. We will focus on elucidating the possible mechanisms of action of these drugs, the signaling pathways involved in CRC, and the potential synergistic effects when combined with other therapeutic agents.

The role of miRNAs as a big master regulator of signaling pathways involved in lymphoblastic leukemia.

MicroRNAs (miRNAs) belong to small noncoding RNAs, which have long attracted researchers' attention because of their potency in acting either as oncogenes or tumor-suppressors in cancers. acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) are two known types of leukemia with high mortality rates in adults and children. On a molecular basis, various signaling pathways are active in both types, making researchers consider the potential role of miRNAs in activating or suppressing these pathways to further hinder cancer development. In this review, we summarized the potential miRNAs, especially circulating ones, involved in essential signaling pathways in the ALL and CLL patients which serve as biomarkers and valuable targets in the treatment fields.

Interaction between non-coding RNAs and Toll-like receptors.

Toll-like receptors (TLRs) are a large group of pattern recognition receptors which are involved in the regulation of innate immune responses. Based on the interplay between TLRs and adapter molecules, two distinctive signaling cascades, namely the MyD88-dependent and TRIF-dependent pathways have been recognized. TLRs are involved in the development of a wide variety of diseases including cancer and autoimmune disorders. A large body of evidence has shown interaction between two classes of non-coding RNAs, namely microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). These interactions have prominent roles in the pathogenesis of several disorders including infectious disorders, autoimmune conditions and neoplastic disorders. This review aims at description of the interaction between these non-coding RNAs and TLRs.

Therapeutics strategies against cancer stem cell in breast cancer.

Breast cancer is known as a most prevalent cancer and second deadly cancer, among women worldwide. Due to the high incidence rate of breast cancer and limitations of conventional therapy it seemed essential to look for new targets in cancer cells and directly target them such as target therapy on breast cancer stem cells. In this review we indicate some of therapeutic uses of cancer stem cells in breast cancer. Some strategies are targeting surface specific markers and activated signaling pathways in their microenvironment such as Notch, Hedgehog, Wnt/b-catenin, PI3K/Akt, NF-kB, BMP and TGF-ß and their maintenance and drug resistance, using various miRNAs, enhancement of CSCs apoptosis, differentiation therapy, blocking epithelial to mesenchymal transition and using different natural compounds. Recent studies have shown that cancer stem cells play major roles in target therapy on breast cancer. The new manipulation approaches of cancer stem cells can be used as target therapy of breast cancer that were highlighted for immunotherapy of cancer.

Meta-analysis of GABRB3 Gene Polymorphisms and Susceptibility to Autism Spectrum Disorder.

Several lines of evidence have suggested that the GABA receptor subunit ß3 (GABRB3) gene is a genetic contributor in the autism spectrum disorder (ASD). The aberrant expression of GABRB3 is reported in ASD patients which may be a consequence of the presence of certain genetic variants in the promoter region of the gene. The associations between single-nucleotide polymorphisms (SNPs) within this gene and ASD have been analyzed in previous studies. However, the results are conflicting. In the present study, we performed a meta-analysis on association between two SNPs located in the promoter region of GABRB3 gene (rs4906902 and rs20317) and ASD. The literature search was performed based on criteria provided by the meta-analysis of observational studies in epidemiology (MOOSE). The association between mentioned SNPs and ASD was calculated using pooled odd ratios (ORs) and 95% confidence intervals. The result of the present meta-analysis indicates that neither rs4906902 nor rs20317 are significantly associated with the risk of ASD. The underlying mechanism of the aberrant expression of GABRB3 gene in ASD patients should be investigated in other biological levels.