The enteric nervous system (ENS) is recognized as a second brain because of its complexity and its largely autonomic control of bowel function. Recent progress in studying the interactions between the ENS and the central nervous system (CNS) has implicated alterations of the gut/brain axis as a possible mechanism in the pathophysiology of autism spectrum disorders (ASDs), Parkinson’s disease (PD) and other human CNS disorders, whereas the underlying mechanisms are largely unknown because of the lack of good model systems. Human induced pluripotent stem cells (hiPSCs) have the ability to proliferate indefinitely and differentiate into cells of all three germ layers, thus making iPSCs an ideal source of cells for disease modelling and cell therapy. Here, hiPSCs were induced to differentiate into neural crest stem cells (NCSCs) efficiently. When co-cultured with smooth muscle layers of ganglionic gut tissue, the NCSCs differentiated into different subtypes of mature enteric-like neurons expressing nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP), choline acetyltransferase (ChAT) or calretinin with typical electrophysiological characteristics of functional neurons. Furthermore, when they were transplanted into aneural or aganglionic chick, mouse or human gut tissues in ovo, in vitro or in vivo, hiPSC-derived NCSCs showed extensive migration and neural differentiation capacity, generating neurons and glial cells that expressed phenotypic markers characteristic of the enteric nervous system. Our results indicate that enteric NCSCs derived from hiPSCs supply a powerful tool for studying the pathogenesis of gastrointestinal disorders and brain/gut dysfunction and represent a potentially ideal cell source for enteric neural transplantation treatments.

Nestin is widely expressed in numerous tumors and has become a diagnostic and prognostic indicator. However, the exact mechanism by which nestin contributes to tumor malignancy remains poorly understood. Here, we found marked upregulation of nestin expression in highly proliferative and invasive gastrointestinal stromal tumor (GIST) specimens. Nestin knockdown in GIST cells reduced the proliferative and invasive activity owing to a decrease of mitochondrial intracellular reactive oxygen species (ROS) generation. Furthermore, nestin was co-localized with mitochondria, and knockdown of nestin increased mitochondrial elongation and influenced the mitochondrial function, including oxygen consumption rates, ATP generation and mitochondrial membrane potential and so on. In exploring the underlying mechanism, we demonstrated nestin knockdown inhibited the mitochondrial recruitment of Dynamin-related protein1 and induced the change of mitochondrial dynamics. Thus, nestin may have an important role in GIST malignancy by regulating mitochondrial dynamics and altering intracellular ROS levels. The findings provide new clues to reveal mechanisms by which nestin mediates the proliferation and invasion of GISTs.

No abstract

No abstract

PurposeProliferative vitreoretinopathy (PVR) is the leading cause of failure of surgery for rhegmatogenous retinal detachment. Although indirect evidence suggests that this disease might be autoimmune in nature, direct proof for this hypothesis is lacking. The purpose of this study was to determine in a murine model whether PVR can develop in the absence of T- or B-cell immunity.MethodsFour- to six-week-old Rag-1 gene knockout (KO) and congenic wild-type mice (WT) on the C57.Bl/6 background were studied. PVR was induced by intravitreal injection of 3 μl dispase at the concentration of 0.2 U/μl. PVR development was monitored by electroretinograms, the macroscopic observation of hemorrhage, cataract, retinal folds, and of an uneven iris, as well as the histological detection of epiretinal membranes on haematoxylin–eosin stained tissue. Additionally, immunofluorescence analysis was performed. These manifestations of PVR were assessed 1, 2, 4, 6, and 8 weeks after the intravitreal injection.ResultsThe data showed that the immune-deficient Rag-1 KO mice developed PVR with similar kinetics and severity as did the fully immune competent congenic WT mice. Carboxyfluorescein diacetate succinimidyl ester-labeled T cells that are specific for ovalbumin were detected in the inflamed vitreous and retina showing that T cells that are not specific for autoantigens present in the eye can migrate to PVR lesions. Therefore, the mere presence of T cells in PVR lesions does not imply an autoimmune pathogenesis.ConclusionThis study suggests that T- and B-cell immunity is not essential for the induction of PVR.

Tooth extraction is one of the most common causes of dental anxiety and pain, leading to the elevation of blood pressure (BP) and heart rate (HR). Such effects may be exaggerated and cause life-threatening accidents in patients with hypertension. Therefore, the pain and anxiety management of these patients is imperative. Virtual reality (VR) has been demonstrated to be a distraction method to relieve anxiety and pain in clinical operations. Thus, we hypothesized that VR can control the elevation of BP and HR in patients with hypertension. In this study, 96 eligible patients with controlled hypertension who needed tooth extraction were randomized to the VR or standard care group by stratified randomization of anxiety grade and gender. Their BP and HR were dynamically monitored. The corresponding systolic and diastolic BP and HR values were selected when systolic BP was at the highest point of the process. BP was converted into mean arterial pressure (MAP) for comparison per the following formula: MAP = (systolic BP + 2 × diastolic BP)/3. Statistical analyses were by intention to treat and conducted in SPSS. Nonparametric rank sum tests were used to compare the difference of ΔMAP and ΔHR between the VR and standard care groups. Multivariate linear regression was applied to evaluate the effect of VR on ΔMAP and ΔHR. The results showed that the VR technique significantly decreased the elevation of MAP ( P < 0.001) and HR ( P < 0.001), and this effect was found even after adjusting for baseline characteristics and additional surgical procedures (ΔMAP, P < 0.001, R2 = 0.276; ΔHR, P < 0.001, R2 = 0.152). VR did not increase the incidence of adverse events ( P = 0.677). In conclusion, the VR technique was effective in controlling BP and HR within an acceptable range and can help manage BP and HR during tooth extraction for patients with hypertension (Chinese Clinical Trial Registry: ChiCTR2100042132).