CD4+T-cells facilitate wound healing post-myocardial infarction (MI) but promote left-ventricular (LV) remodeling during ischemic heart failure (HF; 8 weeks post-MI). Therefore, it is critical to understand if sustained CD4+T-cell activation leads to this pathological response, or if phenotypically different T-cells are activated during MI vs. HF. Using flow cytometry, we found that cardiac CD4+T-cells exhibit two distinct patterns of transmigration. First pattern consisted of a rapid CD4+T-cell response with maximal levels seen at 3 days post-MI which return to baseline by 14 days. However, during HF we observed a 2nd phase of activation and CD4+T-cells were ∼20-fold higher in HF as compared to sham-operated mice. Importantly, these biphasic kinetics were observed with all major T-cell subsets such as Th1, Th2, Th17, and regulatory T-cells suggesting a global change. To determine the role of this 2nd peak of T-cell activation, CD4-iDTR mice were generated and treated with DT every 10 from 28 days post-MI to deplete CD4+T-cells during chronic HF. While littermate control mice showed increased end-systolic and end-diastolic volumes (ESV and EDV) and decreased ejection fraction (EF) from 4 to 8 weeks post-MI, depletion of CD4+T-cells in Cre + mice significantly blunted LV remodeling and inhibited progressive increases in the EDV and ESV, and reduction in EF. This suggests that CD4+T-cell responses occurring during HF are different than those occurring during MI and promote LV remodeling and progressive cardiac dysfunction. Temporal immunomodulation of CD4+T-cells could be a translatable modality for ischemic HF.
25 June 2025 in World Journal of Microbiology and Biotechnology
Food security and crop production are challenged worldwide due to overpopulation, changing environmental conditions, crop establishment failure, and various kinds of post-harvest losses. The demand for high-quality foods with improved nutritional quality is also growing day by day. Therefore, production of high-quality produce and reducing post-harvest losses of produce, particularly of perishable fruits and vegetables, are vital. For many decades, attempts have been made to improve the post-harvest quality traits of horticultural crops. Recently, modern genetic tools such as genome editing emerged as a new approach to manage and overcome post-harvest effectively and efficiently. The different genome editing tools including ZFNs, TALENs, and CRISPR/Cas9 system effectively introduce mutations (In Dels) in many horticultural crops to address and resolve the issues associated with post-harvest storage quality. Henceforth, we provide a broad review of genome editing applications in horticulture crops to improve post-harvest stability traits such as shelf life, texture, and resistance to pathogens without compromising nutritional value. Moreover, major roadblocks, challenges, and their possible solutions for employing genome editing tools are also discussed.