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.

Autonomic dysfunction is implicated in prehypertension, and previous studies have suggested that therapies that improve modulation of sympathovagal balance, such as biofeedback and slow abdominal breathing, are effective in patients with prehypertension at rest. However, considering that psychophysiological stressors may be associated with greater cardiovascular risk in prehypertensives, it is important to investigate whether heart rate variability biofeedback (HRV-BF) results in equivalent effects on autonomic cardiovascular responses control during stressful conditions in prehypertensives. A total of 32 college students with prehypertension were enrolled and randomly assigned to HRV-BF (n=12), slow abdominal breathing (SAB, n=10) or no treatment (control, n=10) groups. Then, a training experiment consisting of 15 sessions was employed to compare the effect of each intervention on the following cardiovascular response indicators before and after intervention: heart rate (HR); heart rate variability (HRV) components; blood volume pulse amplitude (BVPamp); galvanic skin response; respiration rate (RSP); and blood pressure. In addition, the cold pressor test and the mental arithmetic challenge test were also performed over two successive days before and after the invention as well as after 3 months of follow-up. A significant decrease in HR and RSP and a significant increase in BVPamp were observed after the HRV-BF intervention (P<0.001). For the HRV analysis, HRV-BF significantly reduced the ratio of low-frequency power to high-frequency power (the LF/HF ratio, P<0.001) and increased the normalized high-frequency power (HFnm) (P<0.001) during the stress tests, and an added benefit over SAB by improving HRV was also observed. In the 3-month follow-up study, similar effects on RSP, BVPamp, LF/HF and HFnm were observed in the HRV-BF group compared with the SAB group. HRV-BF training contributes to the beneficial effect of reducing the stress-related cardiovascular response in prehypertensives by improving autonomic sympathovagal modulation.

Colorectal cancer (CRC) is one of the top three most prevalent and deadly cancers. A cancer stem cell (CSC) sub-population that is characterized by the abilities of tumor initiation, self-renewal, metastasis and resistance to chemotherapy can suggest new therapeutic targets. However, no such sub-population has been conclusively identified for CRC, and we lack any marker to identify cells with all of the above characteristics. Here, we report that CD51 CRC cells displayed greater sphere-forming and tumorigenic capacities, increased migratory and invasive potentials, and enhanced chemoresistance compared with CD51 CRC cells. CD51 knockdown reduced the side population, sphere formation, cell motility and inhibited tumor incidence and metastasis in an in vivo tumor model. Furthermore, CD51 could bind transforming growth factor beta (TGF-β) receptors, and that it upregulated TGF-β/Smad signaling. These results indicate that CD51 is a novel functional marker for colorectal CSCs which may provide an therapeutic target for the efficient elimination of colorectal CSCs.

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.