ObjectiveTo investigate the effect of intraventricular injection of human dental pulp stem cells (DPSCs) on hypoxic-ischemic brain damage (HIBD) in neonatal rats.MethodsThirty-six neonatal rats (postnatal day 7) were assigned to control, HIBD, or HIBD+DPSC groups (n = 12 each group). For induction of HIBD, rats underwent left carotid artery ligation and were exposed to 8% to 10% oxygen for 2 h. Hoechst 33324-labeled human DPSCs were injected into the left lateral ventricle 3 days after HIBD. Behavioral assays were performed to assess hypoxic-ischemic encephalopathy (HIE), and on postnatal day 45, DPSC survival was assessed and expression of neural and glial markers was evaluated by immunohistochemistry and Western blot.ResultsThe HIBD group showed significant deficiencies compared to control on T-maze, radial water maze, and postural reflex tests, and the HIBD+DPSC group showed significant improvement on all behavioral tests. On postnatal day 45, Hoechst 33324-labeled DPSC nuclei were visible in the injected region and left cortex. Subsets of DPSCs showed immunostaining for neuronal (neuron-specific enolase [NSE], Nestin) and glial markers (glial fibrillary acidic protein [GFAP], O4). Significantly decreased staining/expression for NSE, GFAP, and O4 was found in the HBID group compared to control, and this was significantly increased in the HBID+DPSC group.ConclusionIntraventricular injection of human DPSCs improves HIBD in neonatal rats.

Previous studies have investigated the role of microRNAs (miRs) in heart development to reveal the miRNA mechanism of action in congenital heart disease (CHD) in children. The present study aimed to investigate the role of miR‑1 in heart development in P19 cells. The mRNA level for miR‑1 in P19 cells was detected before or after cardiomyocyte differentiation, using reverse transcription‑quantitative polymerase chain reaction analysis. Expression of cardiomyocyte differentiation markers was also analyzed. The effect of miR‑1 overexpression on the viability and apoptosis of differentiated P19 cells was assessed using MTT and Annexin V‑FITC assays, respectively. Furthermore, the effects of miR-1 on expression of markers of cell proliferation and apoptosis were also analyzed in differentiated P19 cells using western blotting. The results demonstrated that P19 cells were successfully differentiated into cardiomyocytes, and that endogenous miR‑1 expression was significantly decreased in differentiated P19 cells compared with undifferentiated P19 cells. Overexpression of miR‑1 resulted in increased viability in differentiated P19 cells and decreased apoptosis, compared with the normal control. In addition, expression of heart and neural crest derivatives expressed transcript 2 (Hand2) was increased in differentiated cells with miR‑1 overexpressed compared with normal cells, while caspase‑3 cleavage was decreased by miR‑1 overexpression. In conclusion, the present study suggested that miR-1 upregulation may be important in regulating cell proliferation and apoptosis in P19 differentiated cardiomyocytes by increasing Hand2 expression and suppressing caspase‑3 cleavage. The present study aimed to provide a theoretical basis for the explanation of the mechanism of CHD and investigate miR‑1 as a potential therapeutic target for its clinical treatment.

Multidrug resistance (MDR) is an important issue in current cancer treatments. In human cancer, drug resistance is primarily associated with the overexpression of multidrug resistance gene 1 (MDR1). Therefore, the human MDR1 gene promoter may be a target for anti‑MDR drug screening. Numerous methods to prevent MDR have been investigated. However, they have been proven to be clinically ineffective. Therefore, the aim of the present study was to investigate whether downregulation of nucleophosmin (NPM) demonstrates any effects on the reversal of MDR in hepatocellular carcinoma (HCC) cells. In the present study, two in vitro MDR HCC cell lines, HepG2/Adriamycin (ADM) and SMMC7721/ADM, were established and the level of MDR was measured. The results demonstrated that NPM downregulation markedly reversed the effects of MDR in the model used. In addition, NPM downregulation reduced P-glycoprotein expression, as well as MDR1 expression. These results suggested that downregulation of NPM may be a novel and effective method of reversing the effects of MDR, and may be a potential adjuvant for tumor chemotherapy.

The upregulation of miR-16-1 expression and heat shock protein 70 (HSP70) and inflammatory reaction mechanism in astrocytes of mice with epilepsy induced by encephalitis B virus infection were studied. Six-to-eight-week-old healthy male C57BL/6 mice received intraperitoneal injection of pilocarpine (320–340 mg/kg, 40 mg/ml) to induce status epilepsy. After 7 days, mice were inoculated with 100 µl Dulbecco's modified Eagle's medium (DMEM) in the neck, including 6.25×23 PFU Japanese encephalitis virus P3 wild strain. The experiment was divided into 4 groups, including, the healthy control group, the epilepsy model group, the model group + negative inoculation group and the virus infection group with 10 mice in each group. The healthy control group received intraperitoneal injection of the same amount of normal saline; the model group + negative inoculation group was injected with the same amount of DMEM without P3. One and three days after infection, 5 mice from each group were sacrificed, hippocampus tissues were obtained and astrocytes were isolated. After purification, glial fibrillary acidic protein was identified by immunohistochemical staining. Infected glial cells were detected by P3 antigen of immunofluorescence staining. RT-PCR method was used to detect the expression of miR-16-1 mRNA in astrocytes. Western blot analysis was used to detect the expression of HSP70. ELISA method was used to detect the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and nuclear factor-κB (NF-κB) inflammatory factors in tail vein blood. Level of expression of miR-16-1 mRNA, HSP70 as well as IL-6, TNF-α and NF-κB inflammatory factor levels of virus infected mice of 1 and 3 days were significantly higher (P<0.05) than those of model group and negative inoculation group and lowest in control group. In conclusion, the level of expression of miR-16-1 and HSP70 can be increased by the infection of Japanese encephalitis virus on the astrocytes of mice with epilepsy, to promote the expression of IL-6, TNF-α and NF-κB of inflammatory factors.

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