In addition to their well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells (MSCs) also possess potent immunomodulatory functions both in vitro and in vivo, which render them a potential novel immunotherapeutic tool for a variety of autoimmune and inflammation-related diseases. The major mechanisms may involve (1) the secretion of an array of soluble factors such as prostaglandin E2 (PGE2 ), indoleamine 2, 3-dioxygenase (IDO), transforming growth factor-β (TGF-β), and human leukocyte antigen G5 (HLA-G5); (2) interactions between MSCs and immune cells such as T cells, B cells, macrophages, and dendritic cells. Recently, increasing evidence has supported that MSCs derived from dental tissues are promising alternative sources of multipotent MSCs. We here provide a thorough and extensive review about new findings in the immunomodulatory functions of MSCs derived from several dental tissues, including dental pulp, periodontal ligament, gingiva, exfoliated deciduous teeth, apical papilla, and dental follicle, respectively. The immunomodulatory properties of dental MSCs place them as a more accessible cell source than bone marrow-derived MSCs for cell-based therapy of immune and inflammation-related diseases.
Epidemiological studies have shown that estrogens have protective effects in cardiovascular diseases, even though the results from human clinical trials remain controversial, while most of the animal experiments confirmed this effect, but the detailed mechanism remains unclear. In this study, we found that estradiol (E2) treatment significantly increases the expression of mitochondrial superoxide dismutase (SOD2) in mice and in vitro in human aorta endothelial cells. Further investigation shows that E2 up-regulates SOD2 through tethering of estrogen receptor (ER) to Sp1 and the increased binding of Sp1 to GC-box on the SOD2 promoter, where ERα responses E2-mediated gene activation, and ERβ maintains basal gene expression level. The E2/ER-mediated SOD2 up-regulation results in minimized ROS generation, which highly favors healthy cardiovascular function. Gene therapy through lentivirus-carried endothelium-specific delivery to the vascular wall in high-fat diet (HFT) mice shows that the SOD2 expression in endothelial cells normalizes E2 deficiency-induced ROS generation with ameliorated mitochondrial dysfunction and vascular damage, while SOD2 knockdown worsens the problem despite the presence of E2, indicating that E2-induced SOD2 expression plays an important vasculoprotective role. To our knowledge, this is the first report for the mechanism by which E2 improves cardiovascular function through up-regulation of SOD2 in endothelial cells. In turn, this suggests a novel gene therapy through lentivirus-carried gene delivery to vascular wall for E2 deficiency-induced cardiovascular damage in postmenopausal women.
BackgroundConventional video‐assisted minimally invasive esophagectomy (MIE) is safe and associated with low rates of morbidity and mortality, but the two‐dimensional monitor reduces eye‐hand harmony and viewing yield. Robotic‐assisted minimally invasive esophagectomy (RAMIE) with its virtual reality simulators offers a realistic three‐dimensional environment that facilitates dissection in the narrow working space, but it is expensive and requires longer operative time. Therefore, the aim of this meta‐analysis was to assess the safety and feasibility of RAMIE versus MIE in patients with esophageal cancer.Material and MethodsPubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature databases were systematically searched up to 21 September 2018 for case‐controlled studies that compared RAMIE with MIE.ResultEight case‐controlled studies involving 1862 patients (931 under RAMIE and 931 under MIE) were considered. No statistically significant difference between the two techniques was observed regarding R0 resection rate (OR = 1.1174, P = 0.8647), conversion to open (OR = 0.7095, P = 0.7519), 30‐day mortality rate (OR = 0.8341, P = 0.7696), 90‐day mortality rate (OR = 0.3224, P = 0.3329), in‐hospital mortality rate (OR = 0.3733, P = 0.3895), postoperative complications, number of harvested lymph nodes (mean difference [MD] = 0.8216, P = 0.2039), operation time (MD = 24.3655 min, P = 0.2402), and length of stay in hospitals (LOS) (MD = −5.0228 day, P = 0.1342). The meta‐analysis showed that RAMIE was associated with a significantly fewer estimated blood loss (EBL) (MD = −33.2268 mL, P = 0.0075). And the vocal cord palsy rate was higher in the MIE group compared with RAMIE, and the difference was significant (OR = 0.5696, P = 0.0447).ConclusionThis meta‐analysis indicated that RAMIE and MIE display similar feasibility and safety when used in esophagectomy. However, randomized controlled studies with larger sample sizes are needed to evaluate the benefit and harm in patients with esophageal cancer undergoing RAMIE.
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