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
Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is a common signaling pathway used to transduce signals from the extracellular to the intracellular (nucleus) upon the binding of cytokines and growth factors to the extracellular domain of specific cell surface receptors. This signaling pathway is tightly regulated and has a multitude of biological functions such as cell proliferation, differentiation, and apoptosis. Besides, the regulated JAK2/STAT3 signaling plays a crucial role in embryonic development, hemopoiesis, and controlling the immune system. Conversely, aberrantly activated JAK2/STAT3 is frequently detected in varieties of tumors and involved in oncogenesis, angiogenesis, and metastasis of many cancer diseases that are usually refractory to the standard chemotherapy. However, the JAK3/STAT3 pathway recently emerged interestingly as a new site for the development of novel anti-tumor agents and becomes a promising therapeutic target in the treatment of many solid malignancies. Herein, this review aimed to provide insight into the JAK2/STAT3 pathway, in the hope to gain an understanding of its potential role in the pathogenesis, progression, chemotherapy resistance, and cancer therapy of solid tumors.
