A Review on Epigenome Editing using CRISPR-based Tools to Rejuvenate Skin Tissues

Genomic activity is controlled by a sophisticated series of cell functions known as the epigenome. The creation of tools capable of directly altering various processes is required to unravel this intricacy. Additionally, by employing tailored DNA-binding platforms connected with effector domains to serve as targeted transcription factors or epigenetic modifiers, it is possible to control the chemical modifiers that regulate the genome's activity. Neoplastic disorders have received the most attention in the study of epigenetics, though the epigenome's significance in a variety of disease processes is now well acknowledged. Researchers are inspired to investigate novel approaches to revert these pathogenic alterations to their normal patterns by considering the fact that the epigenome profile of individuals with aging skin cells or other skin disorders, including atopic dermatitis, differs from that of healthy individuals. Here in this review, we discuss the use of CRISPR/dCas9 as a cutting-edge and flexible tool for fundamental studies on chromatin structure, transcription regulation, and epigenetic landscapes, as well as the potential of this method in these fields. Furthermore, we review on common and recently invented methods to make epigenetic alterations possible in daughter cells after any mitotic differentiations. In the very near future, CRISPR-based epigenomic editing will become a potent tool for comprehending and regulating biological functions

Understanding the prion-like behavior of mutant p53 proteins in triple-negative breast cancer pathogenesis: The current therapeutic strategies and future directions

Breast cancer (BC) is viewed as a significant public health issue and is the primary cause of cancer-related deaths among women worldwide. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype that predominantly affects young premenopausal women. The tumor suppressor p53 playsa vital role in the cellular response to DNA damage, and its loss or mutations are commonly present in many cancers, including BC. Recent evidence suggests that mutant p53 proteins can aggregate and form prion-like structures, which may contribute to the pathogenesis of different types of malignancies, such as BC. This review provides an overview of BC molecular subtypes, the epidemiology of TNBC, and the role of p53 in BC development. We also discuss the potential implications of prion-like aggregation in BC and highlight future research directions. Moreover, a comprehensive analysis of the current therapeutic approaches targeting p53 aggregates in BC treatment is presented. Strategies including small molecules, chaperone inhibitors, immunotherapy, CRISPR-Cas9, and siRNA are discussed, along with their potential benefits and drawbacks. The use of these approaches to inhibit p53 aggregation and degradation represents a promising target for cancer therapy. Future investigations into the efficacy of these approaches against various p53 mutations or binding to non-p53 proteins should be conducted to develop more effective and personalized therapies for BC treatment

The sequence variation of mitochondrial tRNA tyrosine and cysteine among Iranian women with idiopathic recurrent miscarriage: A case-control study

Abstract Background: Recurrent miscarriage is one of the most prevalent reproductive diseases. This phenomenon has several reasons, including maternal, hormonal, immunological, and parental genetic factors. Idiopathic recurrent miscarriage (IRM), with no distinctive etiology, involves about half of the recurrent miscarriage cases. Some mutations in mitochondrial DNA can lead to miscarriage. Mitochondrial tRNA (mt-tRNA) mutations cause nearly half of the mitochondrial disorders. Objective: To identify mt- tRNA C y s & T y r gene mutations in Iranian women with IRM. Materials and Methods: In this case-control study, 100 Iranian women with IRM and 100 women as control without any history of miscarriage were investigated by polymerase chain reaction-single strand conformation polymorphism technique followed by gene sequencing. Bioinformatics analysis were done using human mitochondrial genome database, molecular evolutionary genetics analysis, mammalian mitochondrial-tRNA, etc. Results: Results showed 4 mt-tRNA mutations including 1 cysteine mt-tRNA mutation (5824C > T) and 3 tyrosine mt-tRNA mutations (5868T > A, 5849C > T, and 5836T > C) in our cases. Conclusion: Amongst the 4 mutations found, one was novel that is still not reported. Our bioinformatics analysis revealed that these mutations can be pathogenic. They occurred in tRNA-conserved regions and their secondary structure was changed, which can result in mitochondrial dysfunction. Mutations of these genes may help in the assessment of IRM. Further study of all 22 mt-tRNAs possible mutations is recommended to describe their etiologic role in IRM