Transplanted neural lineage cells derived from dental pulp stem cells promote peripheral nerve regeneration.

Cell therapy for peripheral nerve injury is a promising strategy as regenerative medicine that restores neurological function. However, challenges remain in producing suitable and sufficient amounts of autologous cells for promoting nerve regeneration. This study aimed to identify the characteristics of neural lineage cells (NLCs) differentiated from dental pulp stem cells (DPSCs) and reveal their effect on functional recovery and nerve regeneration after cell transplantation into an immunodeficient rat using a nerve guide conduit. Here we report a protocol of neural induction in monolayer culture and characterize NLCs in vitro. Furthermore, NLCs were transplanted into an immunodeficient rat model with a 10-mm sciatic nerve defect, and cell survival and differentiation were investigated in vivo. Outcomes of nerve regeneration were also assessed using the remyelinated axon numbers, myelin sheath thickness, electrophysiological activities, and gastrocnemius muscle mass. NLCs comprised neuronal, astrocyte, oligodendrocyte, and neural crest lineage cells. NLCs enhanced the activities of endothelial cells, Schwann cells, and neurons in a paracrine-dependent manner in vitro. At 2 weeks post-transplantation, numerous transplanted NLCs differentiated into platelet-derived growth factor receptor alpha (PDGFRα) + oligodendrocyte progenitor cells (OPCs) and a few PDGFRα + /p75 neurotrophin receptor + Schwann cell-like cells derived from OPCs were observed. At 12 weeks post-transplantation, human Schwann cell-like cells survived, and axon growth, remyelination, electrophysiological activities, and muscle atrophy were improved. This study demonstrates the broad application of our protocol of neural induction of DPSCs and portrays the efficacy of transplantation of NLCs derived from human DPSCs as a promising strategy for peripheral nerve regeneration.

MicroRNA 142-5p promotes tumor growth in oral squamous cell carcinoma via the PI3K/AKT pathway by regulating PTEN.

MicroRNAs (miRNAs) play an important role in carcinogenesis and cancer progression. The purpose of this study was to identify miRNAs associated with carcinoma function in OSCC and to investigate the potential role of the specific miRNAs. First, a comprehensive microarray analysis was performed, and miR-142-5p was identified as a candidate miRNA involved in OSCC. miR-142-5p has been reported to show high expression levels in cancer patients and to be involved in tumor growth and metastasis. However, the expression and function of miR-142-5p in oral squamous cell carcinoma (OSCC) are not fully characterized. We evaluated miR-142-5p expression in both OSCC-derived cell lines and primary OSCC tissues and performed functional analysis of miR-142-5p in OSCC-derived cell lines using mimics and inhibitors. miR-142-5p expression was up-regulated in OSCC tissues and OSCC cell lines. Overexpression of miR-142-5p significantly promoted the proliferation and invasion of OSCC cells. Bioinformatics analysis was performed using TargetScan to predict potential target sites that match the seed region of miR-142-5p. Phosphatase and tensin homolog deleted on chromo-some 10 (PTEN) was identified as a potential target and selected for further analysis. PTEN expression levels were down-regulated and AKT expression levels were up-regulated in miR-142-5p-overexpressing cells. We have shown that miR-142-5p targets the PTEN gene and is involved in cancer progression. Our results suggest that miR-142-5p is involved in the progression of OSCC by controlling the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by targeting the PTEN gene. Our findings suggest that miR-142-5p may be a new target for the treatment of OSCC.

Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD.

BACKGROUND & AIMS: A weight-loss-independent beneficial effect of exercise on non-alcoholic fatty liver disease (NAFLD) management has been reported, but the underlying mechanism is unknown. To help determine this mechanism, the effects of exercise on individual tissues (liver, adipose tissue, and skeletal muscle) were retrospectively studied. METHODS: Data from Japanese obese men with NAFLD in a 3-month exercise regimen were analysed and compared with those in a 3-month dietary restriction program designed to achieve weight loss. The underlying mechanism was studied in a smaller subcohort. RESULTS: Independent of the effect of weight loss, the exercise regimen reduced liver steatosis by 9.5% and liver stiffness by 6.8% per 1% weight loss, and resulted in a 16.4% reduction in FibroScan-AST score. Improvements in these hepatic parameters were closely associated with anthropometric changes (reduction in adipose tissue and preservation of muscle mass), increases in muscle strength (+11.6%), reductions in inflammation and oxidative stress (ferritin: -22.3% and thiobarbituric acid: -12.3%), and changes in organokine concentrations (selenoprotein-P: -11.2%, follistatin: +17.1%, adiponectin: +8.9%, and myostatin: -21.6%) during the exercise regimen. Moreover, the expression of target genes of the transcription factor Nrf2, an oxidative stress sensor, was higher in monocytes, suggesting that Nrf2 is activated. Large amounts of high-intensity exercise were effective at further reducing liver steatosis and potentiating improvements in pathophysiological parameters (liver enzyme activities and organokine profiles). CONCLUSIONS: The weight-loss-independent benefits of exercise include anti-steatotic and anti-stiffness effects in the livers of patients with NAFLD. These benefits seem to be acquired through the modification of inter-organ crosstalk, which is characterised by improvements in organokine imbalance and reductions in inflammation and oxidative stress. LAY SUMMARY: We investigated the effects of exercise on non-alcoholic fatty liver disease (NAFLD) that were not related to weight loss. We found that exercise had considerable weight-loss-independent benefits for the liver through a number of mechanisms. This suggests that exercise is important for NAFLD patients, regardless of whether they lose weight.