Growth hormone treatment of premature ovarian failure in a mouse model via stimulation of the Notch-1 signaling pathway.

Premature ovarian failure (POF) is a condition affecting 1% of women in the general population, causing amenorrhea, hypergonadotropism and hypoestrogenism before the age of 40. Currently, POF cannot be reversed and, although treatments are available, there is an urgent need for improved treatment strategies. Growth hormone (GH) is a pleiotropic hormone that affects a broad spectrum of physiological functions, from carbohydrate and lipid metabolism to the immune response. GH has previously been used to treat POF in non-transgenic preclinical trials, but the biochemical mechanism underlying these effects are unclear. In the present study, a mouse model of POF was generated using cyclophosphamide. Treatment of POF mice with recombinant mouse growth hormone (rmGH) was revealed to markedly reduce POF histopathology in ovarian tissue, relieve ovarian granulosa cell injury, reduce the number of atretic follicles and significantly increase the number of mature oocytes. Furthermore, an enzyme-linked immunosorbent assay revealed that plasma estradiol levels increased and plasma follicle stimulating hormone levels decreased with time in a group of mice treated with a medium dose of rmGH (0.8 mg/kg) when compared with the POF model group (P<0.05). In addition, reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis demonstrated elevated levels of Notch-1 signaling pathway factors (Notch1, CBF1, and HES1) in wild-type mice and those treated with medium and high doses of rmGH, but not in those treated with low doses of rmGH. In conclusion, GH may promote ovarian tissue repair, estrogen release and oocyte maturation via activation of the Notch-1 signaling pathway in ovarian tissue.

Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Aß1-42 expression.

Oxidative stress and ageing are important factors contributing to the pathogenesis of Alzheimer's disease (AD), which is associated with neuronal damage and ß-amyloid (Aß) deposition. The p66shc adaptor protein is important for the regulation of oxidative stress and ageing. In the present study, SH-SY5Y human neuroblastoma cells were treated with anisomycin in order to establish a cell model of oxidative stress-induced neuronal damage. The results from quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting demonstrated that anisomycin was able to stimulate the secretion of Aß1-42 from SH-SY5Y cells and upregulate the expression levels of p66shc, which was associated with concomitant damage to SH-SY5Y cells. In addition, the protective effects of various small molecule compounds with antioxidant properties against neuronal damage were evaluated. Notably, treatment of SH-SY5Y cells with gallic acid was associated with significant downregulation of p66shc protein expression levels, reduced anisomycin-induced secretion of Aß1-42, and increased superoxide dismutase activity and acetylcholine secretion levels. The results of the present study suggested that anisomycin is able to promote oxidative neuronal damage by inducing the secretion of Aß1-42 from neurons and increasing the neuronal expression of p66shc, and this damage may be attenuated by treatment with gallic acid. Therefore, gallic acid and similar small molecule compounds may be considered for the alleviation of neuronal oxidative stress injury in patients with AD.

microRNA-182 inhibits the proliferation and migration of glioma cells through the induction of neuritin expression.

Astrocytomas are the most common type of glial tumors and carry a poor prognosis. However, the pathogenesis of astrocytomas remains to be elucidated. Neuritin, a novel member of the neurotrophic factors family, has been shown to be associated with tumor malignancy, via the regulation of apoptosis and proliferation. In the present study, microRNA-182 (miR-182) was cloned and transfected into the U251 human astrocytoma cell line, in order to investigate its regulatory effects on the proliferation and migration of these cells, as well as its association with the expression of neuritin. The results showed that miR-182 specifically targets the gene encoding neuritin, NRN1, as demonstrated by a reduction in the protein and mRNA levels of NRN1. In addition, overexpression of miR-182 affected cell cycle regulation and cell migration capacity in vitro, which may have been associated with the promotion of apoptosis by this molecule. In conclusion, endogenous miR-182 may be involved in the pathogenesis of astrocytoma, which is associated with the miR-182-regulated gene, NRN1.

Tripterygium glycosides induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway.

Premature ovarian failure (POF) is a typical pathological disease of the reproductive system in aging females. Infection, inflammation, immune abnormalities, genetic mutation, radiotherapy and chemotherapy can cause POF. Tripterygium glycosides (TGs) are a component extracted from the Chinese herb Tripterygium wilfordii Hook. f., also known as Huangteng. Although TGs have been used to treat various diseases, drug resistance and toxicity can affect patients. The aim of the present study was to investigate the mechanism of TG-induced POF in rats. The rats were treated with different concentrations of TG, and pathology assays showed that the TG-induced POF was predominantly composed of interstitial cells in a fibrous matrix with a reduced number of follicles at each stage and an increased number of collapsed oocytes. Furthermore, reverse transcription-quantitative polymerase chain reaction (PCR) and immunohistochemistry assays indicated that the expression levels of serine/threonine kinase 11 (Stk11), p53 p21 and activated caspase-3 were elevated significantly in the TG-treated groups. Serine 15 phosphorylation of p53 was also enhanced significantly in the TG-treated groups. In addition, a chromatin immunoprecipitation-PCR assay revealed that the TGs induced p53 activation and enhanced the transcription of p21. In conclusion, TGs induce apoptosis and necrosis in rat ovarian tissues, as well as POF, via p53 phosphorylation and activation of the Stk11-p53-p21 signaling pathway.

Effects of rice bran on sensory and physico-chemical properties of emulsified pork meatballs.

Four kinds of bran, which are milled from important rice cultivators in Taiwan, have high contents of dietary fiber, fat and protein. The use of rice bran in Kung-wan, an emulsified pork meatball, was investigated. It was found that protein and fat contents, and white index of meatballs decreased as the amount of bran increased. A texture profile analysis (TPA) also indicated the hardness, gumminess and chewiness of the Kung-wan decreased. The sensory scores of taste, texture and overall acceptability of meatballs with less than 10% added bran showed no significant difference from those for meatballs without bran. However, the added amount of 15% enriched meatballs resulted in inferior sensory scores. The bran's particle size profoundly affected the sensory and physico-chemical properties of the meat products. Meatballs enriched with smaller bran particles possessed higher TPA indices and sensory scores than those added with larger ones. No significant differences in proximate composition, cooking yield, color and sensory quality were found among emulsified meatballs enriched with four different kinds of bran. Conclusively, the suitable amount of rice bran that should be added to emulsified pork meatballs was less than 10% and a smaller particle size would result in better quality.