A One-Step, Monolayer Culture and Chemical-Based Approach to Generate Insulin-Producing Cells From Human Adipose-Derived Stem Cells to Mitigate Hyperglycemia in STZ-Induced Diabetic Rats.

The global population of individuals afflicted with diabetes mellitus has been increasing year by year, and this disease poses a serious threat to human health as well as the economies worldwide. Pancreatic or islet transplantations provide one of the most effective and long-term therapies available to treat diabetes, but the scarcity and quality of pancreatic islets limit their use in treatments. Here, we report the development of a one-step, monolayer culture, and chemical-based protocol that efficiently mediates the differentiation of human adipose-derived stem cells (hADSCs) into insulin-producing cells (IPCs). Our data indicate that hADSCs in monolayer culture that are allowed to differentiate into IPCs are superior to those in suspension cultures with respect to insulin secretion capacity (213-fold increase), cell viability (93.5 ± 3.27% vs. 41.67 ± 13.17%), and response to glucose stimulation. Moreover, the expression of genes associated with pancreatic lineage specification, such as PDX1, ISL1, and INS (encoding insulin), were expressed at significantly higher levels during our differentiation protocol (6-fold for PDX1 and ISL1, 11.5-fold for INS). Importantly, in vivo studies demonstrated that transplantation with IPCs significantly mitigated hyperglycemia in streptozotocin-induced diabetic rats. Our results indicate that this one-step, rapid protocol increases the efficiency of IPC generation and that the chemical-based approach for IPC induction may reduce safety concerns associated with the use of IPCs for clinical applications, thereby providing a safe and effective cell-based treatment for diabetes.

State of the art of tertiary treatment technologies for controlling antibiotic resistance in wastewater treatment plants.

Antibiotic resistance genes (ARGs) have been considered as emerging contaminants of concern nowadays. There are no special technologies designed to directly remove ARGs in wastewater treatment plants (WWTPs). In order to reduce the risk of ARGs, it is vital to understand the efficiency of advanced treatment technologies in removing antibiotic resistance genes in WWTPs. This review highlights the application and efficiency of tertiary treatment technologies on the elimination of ARGs, s, based on an understanding of their occurrence and fate in WWTPs. These technologies include chemical-based processes such as chlorination, ozonation, ultraviolet, and advanced oxidation technology, as well as physical separation processes, biological processes such as constructed wetland and membrane bioreactor, and soil aquifer treatment. The merits, limitations and ameliorative measures of these processes are discussed, with the view to optimizing future treatment strategies and identifying new research directions.

Chemical induced conversion of mouse fibroblasts and human adipose-derived stem cells into skeletal muscle-like cells.

Use of stem cells in regenerative medicine holds great promise in treating people suffering from various otherwise incurable ailments. Direct conversion of somatic cells to other lineages thereby bypassing the intermediate pluripotent state has enormous applicability with respect to time requirement for conversion as well as safety issues. Among various approaches, chemical induced cell conversion is safe yet effective, and the use of small molecules has thus increased greatly in recent years in regenerative fields due to easy applicability, efficient scalability, and consistent reproducibility. Here we report a combination of small molecules capable of converting mouse fibroblasts into skeletal muscle-like cells (SMLCs) without requiring ectopic transcription factor expression. We observed that a combination of chemicals is necessary and sufficient to convert mouse fibroblast to SMLCs that have functional similarity to skeletal muscles. In addition, we also found that cytokines responsible for modulating several key signaling pathways enhance the maturation of converted SMLCs into multinucleated myocytes. Epigenetic analysis revealed that this conversion is accomplished by an epigenetic overhaul, followed by activation of key signal pathways responsible for activating skeletal specific loci. We further observed that human adipocyte-derived stem cells can be converted into SMLCs under conditions similar to that of fibroblasts. This study not only provides an example of chemical induced direct conversion, but also underlines the key signaling pathways that are needed to induce mesodermal lineages and muscles from pleotropic type cells.

Advances in the Generation of Functional ß-cells from Induced Pluripotent Stem Cells As a Cure for Diabetes Mellitus.

Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic ß-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional ß-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into ß- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and ß-cells via different reprogramming strategies and growth factor supplementation. However, these generated ß-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional ß-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature ß-cells by reprogramming stem cells into iPSCs that are further programmed to ß-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature ß-cells.

Phenolic compounds and antioxidant properties of arabinoxylan hydrolysates from defatted rice bran.

BACKGROUND: The water unextractable arabinoxylans (WUAX) contain beneficial phenolic compounds that can be used for food rather than for animal feed. The antioxidant activities of defatted rice bran obtained by xylanase-aided extraction is reported herein. The chemical and molecular characteristics of extracted fractions were investigated. RESULTS: The WUAX hydrolysate precipitated by 0-60% ethanol (F60), 60-90% ethanol (F6090), and more than 90% ethanol (F90) had decreased molar masses with increasing ethanol concentration. The fractions of interest, F60 and F6090, contained 75% arabinoxylans with ferulic acid as the major bound phenolic acid, followed by p-coumaric acid. According to chemical-based antioxidant assays F60 and F6090 exhibited higher diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and ferric iron reducing ability than F90 which contained minor contents of small sugars and free phenolic acids. In cell-based antioxidant assays, using the fluorescent 2',7'-dichlorofluorescein diacetate probe, all three fractions were potent intracellular scavengers. CONCLUSION: The high molar mass of WUAX hydrolysates with high amount of bound phenolics contributes to the chemical-based antioxidant activity. All fractions of WUAX hydrolysates showed high potent intracellular scavenging activity regardless of molar mass, content and the component of bound phenolics. © 2017 Society of Chemical Industry.