RESUMO
The CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)) and the associated protein (Cas9) system, a young but well-studied genome-editing tool, holds plausible solutions to a wide range of genetic disorders. The single-guide RNA (sgRNA) with a 20-base user-defined spacer sequence and the Cas9 endonuclease form the core of the CRISPR-Cas9 system. This sgRNA can direct the Cas9 nuclease to any genomic region that includes a protospacer adjacent motif (PAM) just downstream and matches the spacer sequence. The current challenge in the clinical applications of CRISPR-Cas9 genome-editing technology is the potential off-target effects that can cause DNA cleavage at the incorrect sites. Off-target genome editing confuses and diminishes the therapeutic potential of CRISPR-Cas9 in addition to potentially casting doubt on scientific findings regarding the activities of genes. In this review, we summarize the recent technological advancements in reducing the off-target effect of CRISPR-Cas9 genome editing.
RESUMO
Diabetes is a common metabolic illness characterized by hyperglycemia and is linked to long-term vascular problems that can impair the kidney, eyes, nerves, and blood vessels. By increasing protein glycation and gradually accumulating advanced glycation end products in the tissues, hyperglycemia plays a significant role in the pathogenesis of diabetic complications. Advanced glycation end products are heterogeneous molecules generated from non-enzymatic interactions of sugars with proteins, lipids, or nucleic acids via the glycation process. Protein glycation and the buildup of advanced glycation end products are important in the etiology of diabetes sequelae such as retinopathy, nephropathy, neuropathy, and atherosclerosis. Their contribution to diabetes complications occurs via a receptor-mediated signaling cascade or direct extracellular matrix destruction. According to recent research, the interaction of advanced glycation end products with their transmembrane receptor results in intracellular signaling, gene expression, the release of pro-inflammatory molecules, and the production of free radicals, all of which contribute to the pathology of diabetes complications. The primary aim of this paper was to discuss the chemical reactions and formation of advanced glycation end products, the interaction of advanced glycation end products with their receptor and downstream signaling cascade, and molecular mechanisms triggered by advanced glycation end products in the pathogenesis of both micro and macrovascular complications of diabetes mellitus.
RESUMO
Fetuin-A is a heterodimeric plasma glycoprotein containing an A-chain of 282 amino acids and a B-chain of 27 amino acid residues linked by a single inter-disulfide bond. It is predominantly expressed in embryonic cells and adult hepatocytes, and to a lesser extent in adipocytes and monocytes. Fetuin-A binds with a plethora of receptors and exhibits multifaceted physiological and pathological functions. It is involved in the regulation of calcium metabolism, osteogenesis, and the insulin signaling pathway. It also acts as an ectopic calcification inhibitor, protease inhibitor, inflammatory mediator, anti-inflammatory partner, atherogenic factor, and adipogenic factor, among other several moonlighting functions. Fetuin-A has also been demonstrated to play a crucial role in the pathogenesis of several disorders. This review mainly focuses on the structure, synthesis, and biological roles of fetuin-A. Information was gathered manually from various journals via electronic searches using PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. Studies written in English and cohort, case-control, cross-sectional, or experimental studies were considered in the review, otherwise excluded.
RESUMO
Fetuin-A is a plasma glycoprotein exhibiting multifaceted physiological and pathological functions. It has been determined to be involved in various essential biological functions, such as regulation of calcium metabolism, osteogenesis, and insulin signaling pathway. It also plays a crucial role in the pathogenesis of several disorders, including psoriasis. Psoriasis is a chronic systemic inflammatory disorder caused by a constellation of environmental, immunogenic, and genetic factors. It has been shown that dysregulation of cytokines mediated immune response is responsible for the development of psoriasis. Several recent publications suggest that dysregulation of fetuin-A correlates with psoriasis disease activities, revealing its putative role in the development of psoriasis. Furthermore, clinical application of fetuin-A as a diagnostic marker, prognostic predictor, and therapeutic target for different clinical conditions is in progress, and some are showing promising outcomes. This review primarily focuses on the current understanding of the role of fetuin-A in the pathogenesis of psoriasis and its potential clinical applications, with a brief highlight of psoriasis epidemiology and burden. The information was gathered systematically from various journals via electronic searches using various search engines: PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. The studies involved were restricted to English language. Conversely, articles written in other languages, studies done on fetuin B, or studies conducted on other dermatological diseases were excluded from the review article.
