The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.

Mycobacterium tuberculosis is a hard-to-eradicate intracellular pathogen that infects one-third of the global population. It can live within macrophages owning to its ability to arrest phagolysosome biogenesis. Autophagy has recently been identified as an effective way to control the intracellular mycobacteria by enhancing phagosome maturation. In the present study, we demonstrate a novel role of miR-155 in regulating the autophagy-mediated anti-mycobacterial response. Both in vivo and in vitro studies showed that miR-155 expression was significantly enhanced after mycobacterial infection. Forced expression of miR-155 accelerated the autophagic response in macrophages, thus promoting the maturation of mycobacterial phagosomes and decreasing the survival rate of intracellular mycobacteria, while transfection with miR-155 inhibitor increased mycobacterial survival. However, macrophage-mediated mycobacterial phagocytosis was not affected after miR-155 overexpression or inhibition. Furthermore, blocking autophagy with specific inhibitor 3-methyladenine or silencing of autophagy related gene 7 (Atg7) reduced the ability of miR-155 to promote autophagy and mycobacterial elimination. More importantly, our study demonstrated that miR-155 bound to the 3′-untranslated region of Ras homologue enriched in brain (Rheb), a negative regulator of autophagy, accelerated the process of autophagy and sequential killing of intracellular mycobacteria by suppressing Rheb expression. Our results reveal a novel role of miR-155 in regulating autophagy-mediated mycobacterial elimination by targeting Rheb, and provide potential targets for clinical treatment.

Previous studies have demonstrated that rodent stem Leydig cell (SLC) transplantation can partially restore testosterone production in Leydig cell (LC)-disrupted or senescent animal models, which provides a promising approach for the treatment of hypogonadism. Here, we isolated human SLCs prospectively and explored the potential therapeutic benefits of human SLC transplantation for hypogonadism treatment. In adult human testes, p75 neurotrophin receptor positive (p75+) cells expressed the known SLC marker nestin, but not the LC lineage marker hydroxysteroid dehydrogenase-3β (HSD3β). The p75+ cells which were sorted by flow cytometry from human adult testes could expand in vitro and exhibited clonogenic self-renewal capacity. The p75+ cells had multi-lineage differentiation potential into multiple mesodermal cell lineages and testosterone-producing LCs in vitro. After transplantation into the testes of ethane dimethane sulfonate (EDS)-treated LC-disrupted rat models, the p75+ cells differentiated into LCs in vivo and secreted testosterone in a physiological pattern. Moreover, p75+ cell transplantation accelerated the recovery of serum testosterone levels, spermatogenesis and reproductive organ weights. Taken together, we reported a method for the identification and isolation of human SLCs on the basis of p75 expression, and demonstrated that transplanted human p75+ SLCs could replace disrupted LCs for testosterone production. These findings provide the groundwork for further clinical application of human SLCs for hypogonadism.

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.