Notes

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Diabetes, one of the most common chronic diseases in the modern world, has pancreatic β cell deficiency as a major part of its pathophysiological mechanism. Pancreatic regeneration is a potential therapeutic strategy for the recovery of β cell loss. However, endocrine islets have limited regenerative capacity, especially in adult humans. Almost all hypoglycemic drugs can protect β cells by inhibiting β cell apoptosis and dedifferentiation via correction of hyperglycemia and amelioration of the consequent inflammation and oxidative stress. Several agents, including glucagon-like peptide-1 and γ-aminobutyric acid, have been shown to promote β cell proliferation, which is considered the main source of the regenerated β cells in adult rodents, but with less clarity in humans. Pancreatic progenitor cells might exist and be activated under particular circumstances. Artemisinins and γ-aminobutyric acid can induce α-to-β cell conversion, although some disputes exist. Intestinal endocrine progenitors can transdeterminate into insulin-producing cells in the gut after FoxO1 deletion, and pharmacological research into FoxO1 inhibition is ongoing. Other cells, including pancreatic acinar cells, can transdifferentiate into β cells, and clinical and preclinical strategies are currently underway. In this review, we summarize the clinical and preclinical agents used in different approaches for β cell regeneration and make some suggestions regarding future perspectives for clinical application.Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells that could differentiate into multiple tissues. MSC-based therapy has become an attractive and promising strategy for treating human diseases through immune regulation and tissue repair. However, accumulating data have indicated that MSC-based therapeutic effects are mainly attributed to the properties of the MSC-sourced secretome, especially small extracellular vesicles (sEVs). sEVs are signaling vehicles in intercellular communication in normal or pathological conditions. sEVs contain natural contents, such as proteins, mRNA, and microRNAs, and transfer these functional contents to adjacent cells or distant cells through the circulatory system. MSC-sEVs have drawn much attention as attractive agents for treating multiple diseases. The properties of MSC-sEVs include stability in circulation, good biocompatibility, and low toxicity and immunogenicity. Moreover, emerging evidence has shown that MSC-sEVs have equal or even better treatment efficacies than MSCs in many kinds of disease. This review summarizes the current research efforts on the use of MSC-sEVs in the treatment of human diseases and the existing challenges in their application from lab to clinical practice that need to be considered.Adipose-derived stem cells (ADSCs) residing in the stromal vascular fraction (SVF) of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis (SSc), a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions. Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous manifestations of SSc patients. Subasumstat However, currently available data indicate that ADSCs may represent a double-edged sword in SSc, as they may exhibit a pro-fibrotic and anti-adipogenic phenotype, possibly behaving as an additional pathogenic source of pro-fibrotic myofibroblasts through the adipocyte-to-myofibroblast transition process. Thus, in the perspective of a larger employ of SSc-ADSCs for further therapeutic applications, it is important to definitely unravel whether these cells present a comparable phenotype and similar immunosuppressive, anti-inflammatory, anti-fibrotic and pro-angiogenic properties in respect to healthy ADSCs. In light of the dual role that ADSCs seem to play in SSc, this review will provide a summary of the most recent insights into the preclinical and clinical studies employing SVF and ADSCs for the treatment of the disease and, at the same time, will focus on the main findings highlighting the possible involvement of these stem cells in SSc-related fibrosis pathogenesis.The recent progress in derivation of pluripotent stem cells (PSCs) from farm animals opens new approaches not only for reproduction, genetic engineering, treatment and conservation of these species, but also for screening novel drugs for their efficacy and toxicity, and modelling of human diseases. Initial attempts to derive PSCs from the inner cell mass of blastocyst stages in farm animals were largely unsuccessful as either the cells survived for only a few passages, or lost their cellular potency; indicating that the protocols which allowed the derivation of murine or human embryonic stem (ES) cells were not sufficient to support the maintenance of ES cells from farm animals. This scenario changed by the innovation of induced pluripotency and by the development of the 3 inhibitor culture conditions to support naïve pluripotency in ES cells from livestock species. However, the long-term culture of livestock PSCs while maintaining the full pluripotency is still challenging, and requires further refinements. Here, we review the current achievements in the derivation of PSCs from farm animals, and discuss the potential application areas.We introduce a fast model based deep learning approach for calibrationless parallel MRI reconstruction. The proposed scheme is a non-linear generalization of structured low rank (SLR) methods that self learn linear annihilation filters from the same subject. It pre-learns non-linear annihilation relations in the Fourier domain from exemplar data. The pre-learning strategy significantly reduces the computational complexity, making the proposed scheme three orders of magnitude faster than SLR schemes. The proposed framework also allows the use of a complementary spatial domain prior; the hybrid regularization scheme offers improved performance over calibrated image domain MoDL approach. The calibrationless strategy minimizes potential mismatches between calibration data and the main scan, while eliminating the need for a fully sampled calibration region.
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