Glioblastoma is the most malignant and common intrinsic brain tumor, but the molecular mechanism of glioma pathophysiology is poorly understood. Recent data have shown that microRNAs regulate the expression of several genes associated with human cancer. In the present study, the function of miR-34c in glioma cells was analyzed. It was demonstrated that miR-34c-3p and miR-34c-5p were downregulated in gliomas, by performing qPCR on tumor tissues from glioma patients and glioma cell lines, compared with normal brain tissues and a normal glial cell line. Furthermore, the miR-34c expression was found to be inversely correlated with glioma WHO grades. Overexpression of miR-34c-3p inhibited U251 and U87 cell proliferation; however, miR-34c-5p only had an effect on U251 cells. Transfection with miR-34c-3p or miR-34c-5p in U251 cells and with miR-34c-3p in U87 cells produced S-phase arrest with G0/G1 reduction and induced cell apoptosis, but no significant changes were observed with miR-34c-5p transfection in U87 cells, normal or negative control groups. However, significant inhibition of glioma cell invasion was observed following transfection with miR-34c-3p and miR-34c-5p. Moreover, it was identified that miR-34c-3p overexpression reduced the expression of Notch pathway members, but miR-34c-5p overexpression did not. Therefore, these results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights into the role of miR-34c in glioma, which includes tumor-suppressing effects on proliferation, apoptosis and invasiveness.
Numerous studies have demonstrated the antioxidant effects of grape seed proanthocyanidin extract (GSPE). The generation of free radicals and the ensuing apoptosis may contribute to the pathogenesis of epilepsy; therefore, in the present study, we examined the effects of GSPE on cognitive impairment and neuronal damage induced by chronic seizures in rats. Seizures were induced by a daily intraperitoneal (i.p.) injection of pentylenetetrazole (PTZ; 35 mg/kg/day, 36 days). Two other groups were treated with GSPE (100 or 200 mg/kg/day, orally) for 24 days and then for 36 days prior to each PTZ injection. After the final PTZ injection, hippocampus-dependent spatial learning was assessed using the Morris water maze (MWM). The rats were then sacrificed for the measurement of hippocampal malondialdehyde (MDA, a measure of lipid peroxidation) and glutathione (GSH, a measure of endogenous antioxidant capacity) levels, and for the expression of pro-apoptotic factors [cytochrome c (Cyt c), caspase-9 and caspase-3]. The mitochondrial generation of reactive oxygen species (ROS), degree of mitochondrial swelling, neuronal damage and mitochondrial ultrastructure were also examined. Performance in the MWM was markedly impaired by PTZ-induced seizures, as evidenced by longer escape latencies during training and fewer platform crossings during the probe trial. This cognitive decline was accompanied by oxidative stress (MDA accumulation, ROS generation, reduced GSH activity), an increased expression of pro-apoptotic proteins, as well as damage to CA1 pyramidal neurons and the mitochondria. Pre-treatment with GSPE dose-dependently reversed PTZ-induced impaired performance in the MWM, oxidative stress, mitochondrial ROS generation, the expression of pro-apoptotic proteins and neuronal and mitochondrial damage. Thus, GSPE may reverse the hippocampal dysfunction induced by chronic seizures, by reducing oxidative stress and preserving mitochondrial function.
BackgroundChinese medicine Wuzi Yanzong pill (WZYZP) was firstly documented in ancient Chinese medical works “She Sheng Zhong Miao Fang” by Shi-Che Zhang in 1550 AD. The traditional herbal formula is widely used in treating nephrasthenia lumbago, prospermia, erectile dysfunction and male sterility. The present study was to explore the effects of WZYZP on ionizing irradiation-induced testicular damage in mice.MethodsThe pelvic region of male mice was exposed to X-rays for inducing testicular damage. The effects of WZYZP on testicular damage were evaluated in terms of testes weight, sperm quantity and motility, testes oxidative status and serum hormone levels. The alterations in testicular structure were examined by hematoxylin-eosin staining. Additionally, changes in proliferating cell nuclear antigen (PCNA) expression of testes were explored by western blot.ResultsPelvic exposure to x-ray induced reduction in testes weight and sperm quality, along with oxidative stress and abnormal testicular architecture in testes. Oral administration of WZYZP for 3 weeks markedly increased testes weight, sperm quantity and motility, and attenuated testicular architecture damage. Meanwhile, WZYZP treatment significantly reversed the reduction of serum testosterone, and decreased testes malondialdehyde (MDA) and Oxidative stress index (OSI) relative to the radiated mice. Additionally, WZYZP effectively prevented the downregulation of PCNA expression in testes induced by x-ray irradiation.ConclusionThese findings suggest WZYZP exhibits ameliorating effects against ionizing irradiation-induced testicular damage in mice, which may be related to its antioxidation.
This study aims to perform gene diagnosis for nine patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and their parents with multiplex ligation-dependent probe amplification (MLPA), and to carry out prenatal gene diagnosis for one of them. Genomic DNA of the peripheral blood and fetal amniotic fluid cell was extracted from the pedigrees' members with DMD/BMD. Gene diagnosis was performed for theses pedigrees' members using a SALSA KIT. Short tandem repeats (STR) genotyping and X-linkage analysis were performed for the pedigree members of the fetus, which was used in the prenatal diagnosis. MLPA analysis results show that five of nine patients (DMD-1, DMD-2, DMD-4, DMD-8, and DMD-9) with DMD/BMD were found to have several hemizygous exon deletions in the dystrophin gene. The other patients and the fetus did not have any hemizygous deletion or duplication of any exons. The genomic DNA of the fetus was not contaminated by his mother's DNA as identified by STR genotyping. In addition, X-linkage analysis results show that the only X chromosome of the fetus comes from one of his mother's normal X chromosomes. Combined with STR genotyping and X-linkage analysis, MLPA is a convenient, highly effective and reliable gene diagnosis technique for congenital genetic disease.
Background We invented a new antireflux anastomosis method for use in proximal gastrectomy for adenocarcinoma of the esophagogastric junction (AEG) and named it semi-embedded valve anastomosis (SEV). This study was conducted to compare and analyze the short-term efficacy and long-term prognosis of this anastomosis reconstruction method versus laparoscopic total gastrectomy (LTG). Methods We retrospectively analyzed the general data and surgical outcomes of patients with AEG who underwent three united laparoscopic proximal gastrectomy plus semi-embedded valve anastomosis (TULPG-SEV, N = 20) and LTG (N = 20) at our hospital from January 2015 to September 2017 and investigated the incidence of postoperative reflux esophagitis and postoperative nutritional status between the two groups. Survival analysis was also performed. Results The operative time (178.25 ± 15.41 vs 196.5 ± 21.16 min) and the gastrointestinal reconstruction time (19.3 ± 2.53 vs 34.65 ± 4.88 min) of the TULPG-SEV group were significantly less than that of the LTG group. There was no difference in intraoperative blood loss, length of hospital stay, and postoperative complications. There was no difference in the scores on the postoperative reflux disease questionnaires (RDQs) conducted 1 month (P = 0.501), 3 months (P = 0.238), and 6 months (P = 0.655) after surgery between the TULPG-SEV group and LTG group. Gastroscopy revealed 2 cases of reflux esophagitis (grade B or higher) in each group. The postoperative hemoglobin level was better in the TULPG-SEV group than in the LTG group, and the difference was most noticeable at 1 month after surgery (P = 0.024) and 3 months after surgery (P = 0.029). The levels of albumin and total protein were not significantly different between the groups. There were more patients with weight loss over 5 kg after surgery in the LTG group than in the TULPG-SEV group (P = 0.043). There was no significant difference in the 3-year overall survival rate between the two groups (P = 0.356). Conclusion SEV has a certain antireflux effect and can reduce the anastomosis time. Proximal gastrectomy may be better than total gastrectomy for maintaining postoperative hemoglobin levels and reducing weight loss.
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