Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells.

DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T-test (two-tailed) was used to compare differences between groups, and the significance level was set at P<0.05.

DUSP6 mRNA expression and protein expression were reduced after transfection with DUSP6-siRNA directly and similar trend with transfection with miR-145. The treated group with DUSP6-siRNA or miR-145 suppressed MDA-MB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase.

DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells.

DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells.

To observe the therapeutic effect of folic acid in combination with adult neural stem cells on spinal cord injury and to investigate the possible mechanism.

A total of 120 Wistar rats were randomly assigned to six groups normal, model, sham-surgery, folic acid injection, adult neural stem cell transplantation, and combination (folic acid injection + adult neural stem cells transplantation) groups. Morphology of neural stem cells was observed by inverted microscopy. Expression of CD105, CD45, CD44, and CD29 were detected by flow cytometry; expression of neuron-specific enolase and glial fibrillary acidic protein were determined by immunofluorescence. Motor coordination and integration capabilities were assessed using BBB scores; Morphology of spinal cord tissues was observed by hematoxylin-eosin staining and 5-bromodeoxyuridine immunohistochemistry. GDNF, BDNF and NT-3 expression in spinal cord tissues were determined by ELISA; while expression of the apoptosis-related proteins BCL-2, Bax and caspase-3 was detected using western blotting.

Flow cytometry showed that the isolated cells were positive for CD44 and CD29 and negative for CD105 and CD45. Combination treatment significantly improved the behavior of model rats with spinal cord injury, attenuated inflammatory reaction of spinal cord tissues, restored injured nerve cells, and increased expression of GDNF, BDNF and NT-3 in spinal cord tissues, up regulated BCL-2 expression, and down regulated Bax and caspase-3 expression.

Folic acid in combination with adult neural stem cells significantly improved nerve function and plays a key role in maintaining microenvironment homeostasis in the neurons of rats with spinal cord injury.

Folic acid in combination with adult neural stem cells significantly improved nerve function and plays a key role in maintaining microenvironment homeostasis in the neurons of rats with spinal cord injury.Mesenchymal stem cells (MSCs) are a reliable cell source for tissue regeneration. However, the molecular mechanisms underlying the directed differentiation of MSCs remain unclear; thus, their use is limited. Here, we investigate HOXB7 function in the osteogenic differentiation potentials of MSCs using stem cells from apical papilla (SCAPs) and bone marrow stem cells (BMSCs). The HOXB7 gene is highly expressed in BMSCs compared with dental tissue-derived MSCs. We found that, in vitro, over-expression of HOXB7 in SCAPs enhanced alkaline phosphatase (ALP) activity and mineralization. HOXB7 over-expression affected the mRNA expression of osteonectin (ON), collagen alpha-2(I) chain (COL1A2), bone sialoprotein (BSP), and osteocalcin (OCN), led to the expression of the key transcription factor, runt-related transcription factor 2 (RUNX2), and promoted SCAP osteogenic differentiation in vitro. The knock-down of HOXB7 inhibited ALP activity, mineralization, and the expression of ON, BSP, COL1A2, OCN, and RUNX2 in BMSCs in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis was triggered when HOXB7 was activated. Furthermore, Over-expression of HOXB7 significantly increased the levels of HOXB7 associated with the BSP promoter by ChIP assays. Taken together, these results indicate that HOXB7 enhances SCAP osteogenic differentiation by up-regulating RUNX2 and directly activating transcript of BSP. Thus, the activation of HOXB7 signaling might improve tissue regeneration mediated by MSCs. These results provide insight into the mechanism underlying the directed differentiation of MSCs.Obesity has been reported to be one of the significant contributors to various chronic disease conditions. Childhood obesity has been on an alarming increase over recent years leading to various health complications. Millions of children undergo surgery each year as a part of medical care on various health grounds. In the present study, influence of vitamin C on the effect of obesity and over-weight under anaesthetic exposure was analysed. Separate groups of neonatal mice (C57BL/6) were fed on high-fat diet to induce obesity. The mice were administered with vitamin C at 30 and 60 mg/kg b.wt post natal day 1 (P1) to P21. P7 mice were exposed to equipotent doses of isoflurane or sevoflurane or desflurane. Neuroapoptosis was assessed by measuring activated caspase-3 and TUNEL assay. Plasma S100β levels were detected by ELISA. The mice were assessed for their general behaviour. Morris water maze test was performed to assess the spatial working memory. Anesthesia exposure caused severe neuroapoptosis and also raised the levels of plasma S100β. Neuroapotosis, working memory and learning impairments observed following anesthetics were comparatively more profound on high fat diet fed mice. Desflurane exposure resulted in higher apoptotic counts, learning and memory deficits than equipotent dose of isoflurane and sevoflurane. Vitamin C supplementation offered significant protection against anesthetic induced neurotoxicity and behavioural alterations. Vitamin C administration resulted in marked reduction in neurotoxicity induced by anesthesia and as well improved learning and memory of both normal and high fat diet fed mice.

The interstitial cells of Cajal (ICCs) interact morphologically and functionally with the elements of the enteric nervous system in the digestive tract. However, direct evidence that ICCs participate in the differentiation of the enteric nervous system is lacking. In this work, we examined in co-culture experiments whether ICCs could stimulate the differentiation of neuroepithelial stem cells (NESCs) to neurons.

NESCs were harvested from the neural tube of embryonic (E11.5) rats, and ICCs were isolated from the colons of newborn rats. Various cell types were identified immunohistochemically.

NESCs reacted with antibodies to the stem-cell marker nest in; ICCs reacted with c-kit antibodies. NESCs, when differentiated into astrocytes, were identified with a marker GFAP, and neurons with marker MAP2. NESCs co-cultured with ICCs, compared with NESCs cultured alone, yielded a significantly greater number of cells positive for the neuronal markers PGP9.5 and nNOS. The co-cultured NESCs also produced more PGP9.5 and nNOS proteins, as measured by Western blotting. In addition, co-cultured ICCs connected morphologically with differentiated NESCs.

These in vitro findings demonstrated that ICCs could induce the neuronal differentiation of NESCs, which connected with differentiated neurons into a network morphologically. The findings provide an experimental basis for in vivo application of the simultaneous transplantation of NESCs and ICCs.

These in vitro findings demonstrated that ICCs could induce the neuronal differentiation of NESCs, which connected with differentiated neurons into a network morphologically. The findings provide an experimental basis for in vivo application of the simultaneous transplantation of NESCs and ICCs.

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with Breast cancer (BC) risk in Asians, but the results have been inconsistent. We therefore performed the present meta-analysis to explore the relationship in detail.

Reported studies were searched from 1990 to October 15, 2014 in PubMed and Wan fang Med Online. We performed a meta-analysis of 13 published case-control studies fitting our eligibility criteria. These studies involved XRCC1 Arg399Gln polymorphisms in 4984 BC cases and 5744 controls in dominant (ArgArg vs. GlnGln+ArgGln), recessive (ArgGln+ArgArg vs. GlnGln), and co-dominant (ArgArg vs. GlnGln) inheritance models. The total odds Ratio (OR) and 95% CI were calculated and analyzed by Review Manager 5.2 and STATE 12.

Overall, significantly increased BC risk was observed in any genetic model (dominant model odds ration [OR] = 1.31, 95% confidence interval [CI] = [1.08, 1.58]; recessive model OR = 0.63, 95% CI = [0.50, 0.81]; codominant model OR = 2.52, 95% CI [1.38, 4.60]) when all eligible studies were pooled into the meta-analysis. In further stratified analyses, no association was found between Arg399Gln polymorphism and BC risk in Chinese fewer than three hereditary models.

Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with increased Breast cancer risk among Asians, except Chinese population.

Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with increased Breast cancer risk among Asians, except Chinese population.The protective role of resveratrol in myocardial ischemia/reperfusion is not well understood. The aim of this study was to investigate whether resveratrol modulates inflammation and oxidative stress and the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, and MI/R + resveratrol. The results demonstrated that compared to MI/R, resveratrol improved cardiac function, reduced myocardial infarction area, myocardial myeloperoxidase (MPO) levels, serum creatinine kinase (CK) and lactate dehydrogenase (LDH) levels. Resveratrol also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reduced the level of malondialdehyde (MDA) in MI/R rats. Resveratrol also enhanced levels of Nrf2 and heme oxygenase-1. In summary, these results demonstrated that resveratrol exerted significant antioxidant and cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/ARE signaling pathway.