"Hyperglycemic Memory": Observational Evidence to Experimental Inference.

Several epidemiological studies have appreciated the impact of "duration" and "level" of hyperglycemia on the initiation and development of chronic complications of diabetes. However, glycemic profiles could not fully explain the presence/absence and severity of diabetic complications. Genetic issues and concepts of "hyperglycemic memory" have been introduced as additional influential factors involved in the pathobiology of late complications of diabetes. In the extended phase of significant diabetes randomized, controlled clinical trials, including DCCT/EDIC and UKPDS, studies have concluded that the quality of glycemic or metabolic control at the early time around the diabetes onset could maintain its protective or detrimental impact throughout the following diabetes course. There is no reliable indication of the mechanism by which the transient exposure to a given glucose concentration level could evoke a consistent cellular response at target tissues at the molecular levels. Some biological phenomena, such as the production and the concentration of advanced glycation end products (AGEs), reactive oxygen species (ROS) and protein kinase C (PKC) pathway activations, epigenetic changes, and finally, the miRNAs-mediated pathways, may be accountable for the development of hyperglycemic memory. This work summarizes evidence from previous experiments that may substantiate the hyperglycemic memory soundness by its justification in molecular terms.

An Update on the Application of CRISPR Technology in Clinical Practice.

The CRISPR/Cas system, an innovative gene-editing tool, is emerging as a promising technique for genome modifications. This straightforward technique was created based on the prokaryotic adaptive immune defense mechanism and employed in the studies on human diseases that proved enormous therapeutic potential. A genetically unique patient mutation in the process of gene therapy can be corrected by the CRISPR method to treat diseases that traditional methods were unable to cure. However, introduction of CRISPR/Cas9 into the clinic will be challenging because we still need to improve the technology's effectiveness, precision, and applications. In this review, we first describe the function and applications of the CRISPR-Cas9 system. We next delineate how this technology could be utilized for gene therapy of various human disorders, including cancer and infectious diseases and highlight the promising examples in the field. Finally, we document current challenges and the potential solutions to overcome these obstacles for the effective use of CRISPR-Cas9 in clinical practice.

The hsa-miR-3613-5p, a potential oncogene correlated with diagnostic and prognostic merits in kidney renal clear cell carcinoma.

MicroRNA-3613 (hsa-miR-3613-5p), a biomarker with a dual role as an oncogenic or tumor suppressor, is associated with different types of cancer. This study aimed to determine the correlation between the hsa-miR-3613-5p gene expression and Kidney renal clear cell carcinoma (KIRC). Utilizing several bioinformatics tools, we examined the expression level and clinicopathological value of hsa-miR-3613-5p in patients with KIRC compared to normal tissues. Other bioinformatic measures, including survival analysis, diagnostic merit of hsa-miR-3613-5p, downstream target prediction, potential upstream lncRNAs, network construction, and functional enrichment analysis of hsa-miR-3613-5p, were performed. We observed that overexpression of hsa-miR-3613-5p in KIRC tissues had valuable diagnostic merit and was significantly correlated with the poor overall survival of KIRC patients. We also realized a correlation between abnormal expression of hsa-miR-3613-5p and several clinical parameters such as pathological stage, race, age, and histological grades in patients with KIRC. Moreover, we constructed the most potential regulatory network of hsa-miR-3613-5p in KIRC with 17 different axes, including four pseudogenes, two lncRNAs, and three mRNAs. Besides, we uncovered six variants in the mature form of hsa-miR-3613-5p. Finally, pathway enrichment analysis demonstrated that the top-ranked pathways for hsa-miR-3613-5p are cell cycle, cell adhesion molecules (CAMs), and hepatocellular carcinoma pathways. The present report suggests that the higher expression of hsa-miR-3613-5p is associated with the progression of KIRC. Therefore, it may be considered a valuable indicator for the early detection, risk stratification, and targeted treatment of patients with KIRC.

Circadian Oscillation of Natural Antisense Transcripts Related to Human Core Clock Genes.

BACKGROUND: Circadian clocks are autonomous intracellular oscillators that synchronize metabolic and physiological processes with the external signals. So, misalignment of environmental and endogenous circadian rhythms leads to disruption of biological activities in living organisms. Noncoding transcripts including antisense RNAs are an important component of the molecular clocks. Commonly, the antisense transcripts are involved in the regulation of gene expression. PER2AS and CRY1AS are the only known Natural Antisense Transcripts (NAT) among the core clock genes, which overlap with the PER2 and CRY1 genes, respectively. In this study, we hypothesized that PER2AS and CRY1AS like the other clock genes, exhibit the oscillatory behavior in a 24-hour period and affect the expression of PER2 and CRY1. METHODS: First, the A549 cell line was cultured under standard conditions. After horse serum shock, RNA extraction and cDNA synthesis was performed; then the expression fluctuations of PER2AS, CRY1AS, PER2, and CRY1 were measured with Real-time PCR. RESULTS: Our result showed that PER2AS and CRY1AS had similar oscillation patterns with their sense strand during 24-hour period. CONCLUSION: Therefore, we suggested that PER2AS and CRY1AS transcripts probably by preventing the interaction of miRNAs with PER2 and CRY1 mRNAs, influence the expression of them, positively.