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It remains a challenge to differentiate human induced pluripotent stem cells (iPSCs) or embryonic stem (ES) cells to Purkinje cells. In this study, we derived iPSCs from human fibroblasts and directed the specification of iPSCs first to Purkinje progenitors, by adding Fgf2 and insulin to the embryoid bodies (EBs) in a time-sensitive manner, which activates the endogenous production of Wnt1 and Fgf8 from EBs that further patterned the cells towards a midbrain-hindbrain-boundary tissue identity. Neph3-positive human Purkinje progenitors were sorted out by using flow cytometry and cultured either alone or with granule cell precursors, in a 2-dimensional or 3-dimensional environment. However, Purkinje progenitors failed to mature further under above conditions. By co-culturing human Purkinje progenitors with rat cerebellar slices, we observed mature Purkinje-like cells with right morphology and marker expression patterns, which yet showed no appropriate membrane properties. Co-culture with human fetal cerebellar slices drove the progenitors to not only morphologically correct but also electrophysiologically functional Purkinje neurons. Neph3-posotive human cells could also survive transplantation into the cerebellum of newborn immunodeficient mice and differentiate to L7- and Calbindin-positive neurons. Obtaining mature human Purkinje cells in vitro has significant implications in studying the mechanisms of spinocerebellar ataxias and other cerebellar diseases.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in the world, after Alzheimer's disease (AD), affecting approximately 1% of people over 65 years of age. Exosomes were once considered to be cellular waste and functionless. However, our understanding about exosome function has increased, and exosomes have been found to carry specific proteins, lipids, functional messenger RNAs (mRNAs), high amounts of non-coding RNAs (including microRNAs, lncRNAs, and circRNAs) and other bioactive substances. Exosomes have been shown to be involved in many physiological processes in vivo, including intercellular communication, cell migration, angiogenesis, and anti-tumor immunity. Moreover, exosomes may be pivotal in the occurrence and progression of various diseases. Therefore, exosomes have several diverse potential applications due to their unique structure and function. For instance, exosomes may be used as biological markers for the diagnosis and prognosis of various diseases, or as a natural carrier of drugs for clinical treatment. Here, we review the potential roles of exosomes in the pathogenesis, diagnosis, treatment, and prognosis of PD.

Bee venom and its main constituent melittin (MEL) have been extensively studied in the treatment of tumors. However, the non-specific cytotoxicity and hemolytic activity have hampered the clinical application. Currently, a number of research groups have reported a series of optimization strategies, including gene therapy, recombinant immunotoxin incorporating MEL or MEL nanoparticles, targeting tumor cells to attenuate the cytotoxicity and improve its antitumor efficiency and therapeutic capabilities, which have shown very promising in overcoming some of these obstacles. In this review, we summarize the current knowledge regarding anticancer effects of bee venom and its main compound MEL on different kinds of tumor cells as well as elucidate their possible anticancer mechanisms. It could be concluded that MEL exerts multiple effects on cellular functions of cancerous cells such as proliferation, apoptosis, metastasis, angiogenesis as well as cell cycle, and the anticancer processes involve diverse signal molecules and regulatory pathways. We also highlight the recent research progress for efficient delivery of MEL peptide, thus providing new ideas and hopeful strategies for the in vivo application of MEL.

Background: While substance use disorder is one of the overarching health and social issues that might seriously disrupt individuals’ self-control and self-efficacy, most previous studies have been conducted among university students or other groups, and little is known about how the underlying mechanisms between self-control and self-efficacy might impact patients with substance use disorders. Objectives: The purpose of this study is to investigate how resilience and self-esteem mediate the relationships between self-control and self-efficacy among patients with substance use disorders. Methods: We conducted a cross-sectional study of 298 patients with substance use disorder from Shifosi rehab in China. Diagnostic and Statistical Manual of Mental Disorders (5th Edition)-based diagnostic questionnaires were used to collect demographic information and assess addiction severity. The Dual-Modes of Self-Control Scale (DMSC-S) was implemented to measure self-control, while self-esteem was measured using the Self-esteem Scale (SES). The Connor-Davidson Resilience Scale (CD-RISC) was used to measure resilience, and self-efficacy was measured by the regulatory emotional self-efficacy scale (RESE). Results: The correlations between all the dimensions and total scores on the self-control, resilience, self-esteem, and self-efficacy were significantly positive (p < 0.01), indicating that they could predict patients’ self-efficacy. Bootstrap testing indicated that resilience and self-esteem fully mediated the relationship between self-control and self-efficacy, relationships between self-control and self-esteem were partially mediated by resilience, and resilience partially mediated the relationship between self-esteem and self-efficacy. Finally, the multiple-group analysis indicated that the relationships among self-control, resilience, self-esteem, and self-efficiency did not differ with respect to gender. Conclusions: The path from self-control through resilience and self-esteem and on to self-efficacy is significant among patients with substance use disorders, suggesting that increasing self-control, resilience, and self-esteem can improve self-efficacy among patients with substance use disorders.

Autologous dopamine (DA) neurons are a new cell source for replacement therapy of Parkinson’s disease (PD). In this study, we tested the safety and efficacy of autologous induced pluripotent stem cell (iPSC)-derived DA cells for treatment of a cynomolgus monkey PD model. Monkey bone marrow mesenchymal cells were isolated and induced to iPSCs, followed by differentiation into DA cells using a method with high efficiency. Autologous DA cells were introduced into the brain of a cynomolgus monkey PD model without immunosuppression; three PD monkeys that had received no grafts served as controls. The PD monkey that had received autologous grafts experienced behavioral improvement compared with that of controls. Histological analysis revealed no overgrowth of grafts and a significant number of surviving A9 region-specific graft-derived DA neurons. The study provided a proof-of-principle to employ iPSC-derived autologous DA cells for PD treatment using a nonhuman primate PD model.

The gradual deterioration following central nervous system (CNS) injuries or neurodegenerative disorders is usually accompanied by infiltration of degenerated and apoptotic neural tissue debris. A rapid and efficient clearance of these deteriorated cell products is of pivotal importance in creating a permissive environment for regeneration of those damaged neurons. Our recent report revealed that the phagocytic activity of olfactory ensheathing cells (OECs) can make a substantial contribution to neuronal growth in such a hostile environment. However, little is known about how to further increase the ability of OECs in phagocytosing deleterious products. Here, we used an in vitro model of primary cells to investigate the effects of lipopolysaccharide (LPS) and curcumin (CCM) co-stimulation on phagocytic activity of OECs and the possible underlying mechanisms. Our results showed that co-stimulation using LPS and CCM can significantly enhance the activation of OECs, displaying a remarkable up-regulation in chemokine (C-X-C motif) ligand 1, chemokine (C-X-C motif) ligand 2, tumor necrosis factor-α, and Toll-like receptor 4, increased OEC proliferative activity, and improved phagocytic capacity compared with normal and LPS- or CCM-treated OECs. More importantly, this potentiated phagocytosis activity greatly facilitated neuronal growth under hostile culture conditions. Moreover, the up-regulation of transglutaminase-2 and phosphatidylserine receptor in OECs activated by LPS and CCM co-stimulation are likely responsible for mechanisms underlying the observed cellular events, because cystamine (a specific inhibitor of transglutaminase-2) and neutrophil elastase (a cleavage enzyme of phosphatidylserine receptor) can effectively abrogate all the positive effects of OECs, including phagocytic capacity and promotive effects on neuronal growth. This study provides an alternative strategy for the repair of traumatic nerve injury and neurologic diseases with the application of OECs in combination with LPS and CCM.