Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing. Diseases are both varied and complex, and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics. Additionally, this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.

The unique physicochemical characteristics of nanoparticles have recently gained increasing attention in a diverse set of applications, particularly in the biomedical field. However, concerns about the potential toxicological effects of nanoparticles remain, as they have a higher tendency to generate excessive amounts of reactive oxygen species (ROS). Due to the strong oxidation potential, the excess ROS induced by nanoparticles can result in the damage of biomolecules and organelle structures and lead to protein oxidative carbonylation, lipid peroxidation, DNA/RNA breakage, and membrane structure destruction, which further cause necrosis, apoptosis, or even mutagenesis. This review aims to give a summary of the mechanisms and responsible for ROS generation by nanoparticles at the cellular level and provide insights into the mechanics of ROS-mediated biotoxicity. We summarize the literature on nanoparticle toxicity and suggest strategies to optimize nanoparticles for biomedical applications.

FOXO3a is a member of the FOXO subfamily of forkhead transcription factors that mediate a variety of cellular processes including apoptosis, proliferation, cell cycle progression, DNA damage and tumorigenesis. It also responds to several cellular stresses such as UV irradiation and oxidative stress. The function of FOXO3a is regulated by a complex network of processes, including post-transcriptional suppression by microRNAs (miRNAs), post-translational modifications (PTMs) and protein–protein interactions. FOXO3a is widely implicated in a variety of diseases, particularly in malignancy of breast, liver, colon, prostate, bladder, and nasopharyngeal cancers. Emerging evidences indicate that FOXO3a acts as a tumor suppressor in cancer. FOXO3a is frequently inactivated in cancer cell lines by mutation of the FOXO3a gene or cytoplasmic sequestration of FOXO3a protein. And its inactivation is associated with the initiation and progression of cancer. In experimental studies, overexpression of FOXO3a inhibits the proliferation, tumorigenic potential, and invasiveness of cancer cells, while silencing of FOXO3a results in marked attenuation in protection against tumorigenesis. The role of FOXO3a in both normal physiology as well as in cancer development have presented a great challenge to formulating an effective therapeutic strategy for cancer. In this review, we summarize the recent findings and overview of the current understanding of the influence of FOXO3a in cancer development and progression.

Rationale:: Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently. Objective:: The purpose of this study was to test the hypothesis that microRNA-103/107 and H19 can participate in the regulation of RIPK1- and RIPK3-dependent necrosis in fetal cardiomyocyte-derived H9c2 cells and myocardial infarction through targeting FADD. Methods and Results:: Our results show that FADD participates in H ₂ O ₂ -induced necrosis by influencing the formation of RIPK1 and RIPK3 complexes in H9c2 cells. We further demonstrate that miR-103/107 target FADD directly. Knockdown of miR-103/107 antagonizes necrosis in the cellular model and also myocardial infarction in a mouse ischemia/reperfusion model. The miR-103/107-FADD pathway does not participate in tumor necrosis factor-α–induced necrosis. In exploring the molecular mechanism by which miR-103/107 are regulated, we show that long noncoding RNA H19 directly binds to miR-103/107 and regulates FADD expression and necrosis. Conclusions:: Our results reveal a novel myocardial necrosis regulation model, which is composed of H19, miR-103/107, and FADD. Modulation of their levels may provide a new approach for preventing myocardial necrosis.

Huijuan Gao, Xin Li, Xiatian Chen, Deng Hai, Chuang Wei, Lei Zhang, and Peifeng Li. J. Microbiol. Biotechnol. 2022;32:1226-33. https://doi.org/10.4014/jmb.2205.05041

Colorectal cancer (CRC) is one of the most common digestive diseases worldwide. It has steadily ascended to the top three cancers in terms of incidence and mortality. The primary cause is the inability to diagnose it at an early stage. Therefore, early detection and diagnosis are essential for colorectal cancer prevention. Although there are now various methods for CRC early detection, in addition to recent developments in surgical and multimodal therapy, the poor prognosis and late detection of CRC still remain significant. Thus, it is important to investigate novel technologies and biomarkers to improve the sensitization and specification of CRC diagnosis. Here, we present some common methods and biomarkers for early detection and diagnosis of CRC, we hope this review will encourage the adoption of screening programs and the clinical use of these potential molecules as biomarkers for CRC early detection and prognosis.