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background: Ovarian aging is associated with declining numbers and quality of oocytes and follicles. Oxidative stress by reactive oxygen species (ROS) contributes to somatic aging in general, and also has been implicated in reproductive aging. Telomere shortening is also involved in aging, and telomeres are particularly susceptible to ROS-induced damage. Previously, we have shown that antioxidant N-acetyl-L-cysteine (NAC) effectively rescues oocytes and embryos from ROS-induced telomere shortening and apoptosis in vitro. Using mice as models, we tested the hypothesis that reducing oxidative stress by NAC might prevent or delay ovarian aging in vivo.methods: Initially, young females were treated with NAC in drinking water for 2 months and the quality of fertilized oocytes and early embryo development were evaluated. Next, young mice 1 -1 1 2 months old were treated for 1 year with NAC added in drinking water, and their fertility was analyzed starting at 6 months, as indicated by litter size, oocyte number and quality. The ovaries were also examined for telomere activity and length and the expression of selected genes related to aging and DNA damage.results: Short-term treatment of mice for 2 months with NAC demonstrated that NAC improved the quality of fertilized oocytes and early embryo development. Mice treated with a long-term low concentration (0.1 mM) of NAC had increased litter sizes at the ages of 7-10 months compared with age-matched controls without NAC treatment. NAC also increased the quality of the oocytes from these older mice. Moreover, the expression of sirtuins was increased, telomerase activity was higher and telomere length was longer in the ovaries of mice treated with NAC compared with those of the control group.conclusions: These data suggest that appropriate treatment with the antioxidant NAC postpones the process of oocyte aging in mice.

Structural damages to radiation and associative fibre tracts, caused by brain oedema and WM demyelination, may account for the cognitive deficits in ESRD patients.

MicroRNA-132 (miR‑132) has been reported to play a tumor suppressive role in different human malignancies. However, its role and underling mechanism in hepatocellular carcinoma (HCC) remains poorly defined due to lack of target gene information. In the present study, we demonstrated that the mean level of miR‑132 in hepatocellular carcinoma (HCC) tissues was significantly lower than that in matched tumor-adjacent tissues, and its expression negatively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Similarly, the expression of miR‑132 was obviously reduced in HCC cell lines as compared with a normal hepatic cell line. Ectopic expression of miR‑132 inhibited cell proliferation, colony formation, migration and invasion, and induced apoptosis in HepG2 cells. In vivo studies showed that miR‑132 inhibited tumor growth of HCC and decreased tumor volume and weight. In addition, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR‑132 by a luciferase reporter assay. Western blot and qRT-PCR analysis indicated that PIK3R3 was significantly downregulated by miR‑132 in HCC cells. miR‑132 expression inversely correlated with PIK3R3 mRNA expression in clinical HCC tissues. Investigations into possible mechanisms revealed that miR‑132 inactivated the AKT/mTOR signaling pathway, which may contribute to inhibition of proliferation, migration, and invasion of HCC. These findings suggested that miR‑132 may serve as a potential target in the treatment of human HCC.

Glypican-3 (GPC3) is a heparan sulfate proteoglycan that has an important role in cell growth and differentiation, and its function in tumorigenesis is tissue-dependent. In hepatocellular carcinoma (HCC), the overexpression of GPC3 has been demonstrated to be a reliable diagnostic indicator. However, the mechanisms that regulate the expression and function of GPC3 remain unclear. The oncoprotein c-Myc is a transcription factor that plays a significant role in more than 50% of human tumors. We report here that GPC3 is a transcriptional target of c-Myc and that the expression of c-Myc is also regulated by GPC3, thus forming a positive feedback signaling loop. We found that the overexpression of c-Myc could induce GPC3 promoter-dependent luciferase activity in luciferase reporter experiments. Furthermore, mutational analysis identified c-Myc-binding sites within the GPC3 promoter. The exogenous overexpression of c-Myc increased the endogenous messenger RNA (mRNA) and protein levels of GPC3. Chromatin immunoprecipitation experiments revealed the binding of c-Myc to the endogenous GPC3 promoter, indicating that c-Myc can directly transcriptionally activate GPC3. Interestingly, GPC3 can also elevate c-Myc expression. Overexpression of GPC3 increased c-Myc protein levels, whereas the knockdown of GPC3 reduced c-Myc expression levels. Lastly, the elevated levels of c-Myc correlate with the overexpression of GPC3 in human HCC samples. Conclusion: These data provide new mechanistic insight into the roles of GPC3 and of c-Myc in the development of HCC. (HEPATOLOGY 2012;56:1380-1390 P rimary hepatocellular carcinoma (HCC) is the world's fifth most common cancer, and the third most common cause of cancer deaths. 1 HCC is a common malignant tumor, and causes over 100,000 HCC deaths per year in China. 2 Only 10%-20% of total HCCs can be treated in the early stage by surgery. Most HCCs are diagnosed at late stages, and as a result they progress rapidly, are difficult to treat, and exhibit poor prognosis. Early diagnosis and treatment are critical factors for improving the survival of HCC patients.Recent research has shown that glypican-3 (GPC3) is a specific and sensitive biomarker for the diagnosis of HCC. 3 GPC3 is a proteoglycan that is localized on the cell surface. The abnormal expression of GPC3 in HCC was first reported by Hsu et al. 4 in 1997. In that study, 75% of HCC patients were found to overexpress GPC3 messenger RNA (mRNA), whereas patients with benign liver disease or normal livers exhibited no expression of GPC3 mRNA or protein. Soluble GPC3 protein can be detected in the serum of 50% of HCC patients, demonstrating its value as a diagnostic marker for HCC. 5 The expression of GPC3, its receptor, and of other growth factors coordinate signal transduction pathways that regulate cellular morphology and a variety of cellular behaviors, such as adhesion,

This study was conducted to determine whether quantitative trait loci (QTL) controlling traits of agronomic importance detected in recombinant inbred lines (RILs) are also expressed in testcross (TC) hybrids of rice. A genetic map was constructed using an RIL population derived from a cross between B5 and Minghui 63, a parent of the most widely grown hybrid rice cultivar in China. Four TC hybrid populations were produced by crossing the RILs with three maintaining lines for the widely used cytoplasmic male-sterile (CMS) lines and the genic male-sterile line Peiai64s. The mean values of the RILs for the seven traits investigated were significantly correlated to those of the F 1 hybrids in the four TC populations. Twenty-seven main-effect QTL were identified in the RILs. Of these, the QTL that had the strongest effect on each of the seven traits in the RILs was detected in two or more of the TC populations, and six other QTL were detected in one TC population. Epistatic analysis revealed that the effect of epistatic QTL was relatively weak and cross combination specific. Searching publicly available QTL data in rice revealed the positional convergence of the QTL with the strongest effect in a wide range of populations and under different environments. Since the main-effect QTL is expressed across different testers, and in different genetic backgrounds and environments, it is a valuable target for gene manipulation and for further application in rice breeding. When a restorer line that expresses main-effect QTL is bred, it could be used in a number of cross combinations. H ETEROSIS has been very successfully exploited in diverse plants and animals. In agriculture, hybrid varieties contribute strongly worldwide to the production of many crop species, including the most important food crops, such as maize and rice (Stuber 1994;Yuan 1998;Khush 2001). Hybrid rice has a yield advantage of 15-20% over the best commercial rice varieties. The area planted to hybrid rice in China accounts for .50% of the total rice area of the country at present. The cultivation of hybrid rice has started on a large scale in many Asian countries.Several hypotheses have been proposed to explain the genetic basis of heterosis. The dominance hypothesis (Bruce 1910) proposes that dominant factors from either parent mask deleterious recessive mutations from the other parent in the heterozygous F 1 population. In contrast, the overdominance hypothesis (Shull 1908) holds that heterozygosity at single loci confers properties that are superior to either homozygote. The two hypotheses have been verified with molecular biology experiments (Stuber et al. 1992;Xiao et al. 1995). A third hypothesis suggests that heterosis may arise from epistasis between alleles at different loci (Yu et al. 1997;Goodnight 1999). More recently, further results have suggested that epistasis is the primary genetic basis of heterosis. It is suggested that separate efforts should be taken for breeding high-yielding inbred and hybrid cultivars in rice Luo et al. 2001)....

Icariin is a flavonoid isolated from the traditional Chinese herbal medicine Epimedium brevicornum Maxim and has been reported to be effective for the treatment of a variety of cardiovascular diseases. The aim of the present study was to investigate the effect and mechanism of icariin on atherosclerosis (AS) using a high-cholesterol diet (HCD)-induced rat model. Seventy male Wistar rats were divided into five groups: 20 in the control group, 20 in the AS group, 10 in the simvastatin group, 10 in the low-dose icariin group, and 10 in the high-dose icariin group. A HCD and vitamin D3 were administered to establish AS rat model. The five groups of rats received daily intragastric administration of normal saline, simvastatin, or icariin (30 mg/kg/d, 60 mg/kg/d) for 4 weeks. The levels of blood lipids, superoxide dismutase (SOD), and malonaldehyde (MDA) were measured. The mRNA levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were analyzed by real-time RT-PCR, and the serum levels of IL-6 and TNF-α were measured using ELISA kit. In addition, the expression of phosphorylated p38 (p-p38) MAPK was detected by Western blot analysis. The results indicated that AS rat models were successfully constructed. In the AS group, the levels of blood lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), and MDA were significantly increased, while high-density lipoprotein-cholesterol (HDL-C) and SOD were significantly decreased, compared with those in the control group. However, icariin succeeded in improving these biochemical parameters towards the normal values in the control group. In the simvastatin group and the icariin groups, the serum levels of IL-6 and TNF-α and the related tissue mRNA levels, as well as the expression of p-p38 MAPK, were markedly reduced compared with the AS group. In conclusion, the present study indicated that icariin inhibited the HCD-induced dyslipidemia in rats, the mechanisms may be associated with the anti-inflammation, anti-oxidative stress, and downregulation of p-p38 MAPK by icariin.

Abstract. The miR-222 cluster has been demonstrated to function as oncomiR in human hepatocellular carcinoma (HCC). miR-222 confers chemotherapy drug resistance in various cancers, including HCC. However, the effects and mechanisms by which miR-222 regulates liver tumorigenicity and confers sorafenib (SOR) resistance remain unclear. Here we first investigated the miR-222 effect on proliferation, cell cycle, apoptosis, migration and invasion of HCC. Our results demonstrated that miRNA inhibitors specially targeting miR-222 significantly suppressed cellular proliferation, migration, invasion and G1/S transition of the cell cycle, and induced cell apoptosis in HepG2 cells. In addition, we investigated whether miR-222 confers SOR resistance in HepG2 cells to explore it roles in acquisition of drug resistance. The results showed that miR-222 inhibitors induced sensitivity to the antitumor effect of sorafenib in human HepG2 cells. Importantly, our study also showed that miR-222 could regulate the expression of phosphorylation PI3K and AKT, which might contribute to miR-222 conferred SOR resistance in HepG2 cells. In conclusion, this study demonstrates that miR-222 can promote cell proliferation, migration and invasion, and decrease cell apoptosis, as well as enhance the resistance of HCC cells to sorafenib miR-222 through activating the PI3K/AKT signaling pathway.