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Substantial evidence suggests that ovarian oxidative stress can result in severe ovarian dysfunction. The purpose of this article is to investigate the potential of SIRT6 in alleviating premature ovarian failure (POF) by inhibiting oxidative stress. To mimic POF, mice were administered daily subcutaneous injections of d-galactose. The levels of E2, FSH, LH, AMH, and progesterone in serum were measured, along with changes in follicles and SIRT6 levels. Mice were treated with the SIRT6 agonist MDL-800, SIRT6 levels, follicles, and aforementioned hormones were reassessed. The effects of MDL-800 on oxidative stress and apoptosis were subsequently identified. Primary granulosa cells were isolated from mice, and the effects of H2O2 and MDL-800 on cell viability, oxidative stress, SIRT6 level, and apoptosis were evaluated. In addition, the regulation of SIRT6 on H3K9AC/p66SHC was verified by examining changes in protein levels, promoter activity, and the reversal effects of p66SHC overexpression. MDL-800 mitigated hormone fluctuations, reduced follicle depletion in ovarian tissue, and attenuated oxidative stress and apoptosis in mice. In vitro experiments demonstrated that MDL-800 enhanced the resilience of primary granulosa cells against H2O2, as evidenced by increased cell viability and reduced oxidative stress and apoptosis. Furthermore, SIRT6 was found to decrease H3K9AC and p66SHC levels, as well as attenuate p66SHC promoter activity. The protective effects of MDL-800 on cells were reversed upon p66SHC overexpression. In summary, this study highlights that activation of SIRT6 can alleviate POF and reduce oxidative stress by degrading H3K9AC and suppressing p66Shc levels in granulosa cells. [ABSTRACT FROM AUTHOR]

To explore the mechanism of inconsistent relationships between plasma lipid profiles and post-traumatic stress disorder (PTSD) reported before, we hypothesized that interplays might exist between PTSD and a variation of rs5925 at low-density lipoprotein receptor (LDLR) gene on plasma lipid profiles. To test our hypothesis, we analyzed the plasma lipid profiles of 709 high school pupils with various genotypes of LDLR rs5925 and with or without PTSD. The results demonstrated that PTSD prevalence in the C allele carriers was higher than that in the TT homozygotes regardless of gender. The C allele carriers had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratios of TC to high-density lipoprotein cholesterol (TC/HDL-C) and LDL-C/HDL-C than the TT homozygotes in the male controls, and only higher TC in the female controls, but no differences in the male or female PTSD subjects. PTSD increased TC in the female TT homozygotes but not in the female C allele carriers. PTSD increased TC/HDL-C in the male TT homozygotes but not in the C allele carriers. These results suggest interactions between PTSD and LDLR rs5925 on plasma lipid profiles, which may be among the explanations for previously reported inconsistent relationships between LDLR rs5925 or PTSD and plasma lipid profiles, and facilitate the development of precision medicine interferences in hypercholesterolemia in individuals with different genetic backgrounds and psychiatric status. Psychiatric care or drug supplement may particularly be needed by female hypercholesterolemic subjects with the TT genotype of LDLR rs5925 in Chinese adolescents. [ABSTRACT FROM AUTHOR]

To explain the inconsistent relationship between proprotein convertase subtilisin/kexin type 9 (PCSK9) rs7552841 and plasma lipids profiles, we hypothesized that interplays might occur among gender, PCSK9 rs7552841 and posttraumatic stress disorder (PTSD) on plasma lipids levels. To test this hypothesis, a population of 704 Chinese Han high school students was used, which had been recruited after the 2008 Wenchuan Earthquake. In this population, the plasma levels of glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) had been measured by routine methods. PTSD had been assessed by the PTSD Checklist Civilian Version (PCL-C). PCSK9 rs7552841 was analyzed by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. The T allele carriers had significantly higher levels of TG, TC, LDL-C, and glucose than the CC homozygotes of PCSK9 rs7552841 after the adjustment for age and BMI in the female students, but not in the male students. When PTSD was taken into consideration, the female T allele carriers had significantly higher TG, TC, LDL-C and glucose than the female CC homozygotes after the adjustment for age and BMI only in the subjects without PTSD, but not in the PTSD patients. No significant differences were observed in the male students regardless of PTSD and the adjustment for age and BMI. These results suggest that PCSK9 rs7552841 is associated with plasma lipids profiles only in female adolescents, but not in male students. This association can be modified and negated by PTSD.

Tropomyosin-related kinase receptor B (TrkB) has been observed to be a common player in posttraumatic stress disorder (PTSD) and the regulation of serum lipids levels. However, interplays of PTSD with TrkB on serum lipids levels have not been explored yet. This study was to investigate the interplays of PTSD and TrkB rs1187327 on serum lipid profiles. Variants of TrkB rs1187327 of 709 high school students were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses and verified by DNA sequencing. The PTSD Checklist Civilian Version (PCL-C) was used to assess PTSD. Colorimetric methods were used to determine the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and glucose. The results show that the GG homozygotes had a significantly higher level of HDL-C than the A allele carriers of TrkB rs1187327 after the adjustment for gender, age and body mass index (BMI) (1.44 ± 0.299 mmol/L vs. 1.39 ± 0.266 mmol/L, p = 0.036). When PTSD was taken into account, the higher than the A allele carriers level of HDL-C of the GG homozygotes was observed significant after the adjustment for gender, age and BMI only in the subjects without PTSD (1.44 ± 0.293 mmol/ L vs. 1.39 ± 0.267 mmol/L, p = 0.030), but not in the subjects with PTSD. These results suggest that the A allele of TrkB rs1187327 may be associated with decreased levels of serum HDL-C in general healthy adolescents, but not in adolescents with PTSD.

In colorectal cancer, no study has been carried out discovering the relationship among p53, mitochondrial transcription factor A (TFAM) expression and change of mitochondrial DNA (mtDNA) copy number. In our study, co-expression of p53 and TFAM was observed in colon adenocarcinoma tissues, paracancerous tissues and 9 colorectal cancer cell lines. Then, a significant linear correlation was established between either p53 or TFAM expression and advanced TNM stage, positive lymph nodes and low 5-year survival rate in patients with colon adenocarcinoma. Additionally, advanced TNM stage, large tumor burden, presence of distant metastasis, and high TFAM expression were significantly related to poor overall 5-years survival. Moreover, alteration of p53 expression could change TFAM expression but TFAM could not influence p53 expression, and p53 could enhance TFAM expression via binding to TFAM promoter. While, both of p53 and TFAM expression could incrase mtDNA copy number in vitro. In conclusions, p53 might incrase mtDNA copy number through its regulation on TFAM expression via TFAMpromoter.

Different diets consumed by individuals of different ethnicities, gender, and age may cause changes in blood pressure. The current study sought to investigate changes in blood pressures after consumption of a high-carbohydrate (high-CHO) diet by healthy Chinese adolescents. As a population, the Chinese consume a diet with a high carbohydrate content and they have a low incidence of hypertension and coronary artery disease. Dietary data were collected using a 3-day diet diary. Subjects were 672 high school students who were divided into a high-CHO diet group (≥ 55% carbohydrates) and a non-high-CHO diet group (< 55% carbohydrates, < 40% fats). Plasma glucose levels, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Body mass index (BMI), waist-to-hip ratio (WHR), pulse pressure (PP), and mean arterial pressure (MAP) were calculated. Results indicated that males had a higher BMI, glucose level, SBP, DBP, PP, and MAP than females. When diet was taken into account, males in the non-high-CHO diet group had a higher SBP and PP than females. Males in the high-CHO diet group had a higher glucose level than females. Males in the high-CHO diet group had a lower SBP (p = 0.004) and PP (p = 0.002) than males in the non-high-CHO diet group and females in the high-CHO diet group had a lower glucose level (p = 0.003) than females in the non-high-CHO diet group. After adjusting for age, BMI, WHR, heart rate, the total daily energy intake, and the intake of vitamin C, calcium, sodium, potassium and magnesium, significant differences in SBP and PP were noted in males. These results indicate that male adolescents consuming a high-CHO diet had a lower SBP and PP than males consuming a non-high-CHO diet.

The skin of Bufo bufo gargarizans Cantor has long been used for the treatment of hepatitis B in China and supercritical carbon dioxide extraction (SC-CO₂) is widely used in extracting active ingredients from natural products. The aim of present study was to assess the anti-hepatitis B virus (HBV) effect of the supercritical CO₂ extract from the skin of Bufo bufo gargarizans Cantor (SCE-BC). Cytotoxicity of SCE-BC was analyzed using an MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] assay in HepG2.2.15 cells. The hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core-related antigen (HBcrAg) concentrations in cell culture medium were determined by chemiluminescent enzyme immunoassay. HBV mRNA in cells was determined using real-time polymerase chain reaction. SCE-BC concentrations below 10(-2) μg/mL had no significant toxicity to HepG2.2.15 cells. SCE-BC at 10(-4) μg/mL effectively inhibited the secretion of HBeAg by 23.36% on day 6. It was more potent than the positive control lamivudine (100 μg/mL) in terms of the inhibition of HBeAg and HBcrAg secretion on day 6. Consistent with the HBV antigen reduction, HBV mRNA expression was markedly inhibited in comparison to the control when HepG2.2.15 cells were treated with SCE-BC. Moreover, SCE-BC had greater inhibitory activity with respect to HBeAg than to HBsAg. Since HBeAg promotes immune tolerance and persistent infection during HBV infection, the present results suggest that immune tolerance induced by HBeAg might be overcome by SCE-BC. Therefore, SCE-BC warrants further investigation.

A high-carbohydrate low-fat (HC/LF) diet and lipoprotein lipase gene (LPL) Ser447Stop and Hind III polymorphisms have separately been found to be associated with triacylglycerol (TG) and high density lipoprotein cholesterol (HDL-C). This study sought to test the effects of LPL polymorphisms and an HC/LF diet on the serum lipid profile of Chinese with a lower incidence of coronary artery disease (CAD) consuming a diet with less fat and more carbohydrates. Fifty-six healthy subjects (22.89 ± 1.80 years) were given a control diet of 30.1% fat and 54.1% carbohydrates for 7 days, followed by an HC/LF diet of 13.8% fat and 70.1% carbohydrate for 6 days; there were no changes in the fatty acid composition or restrictions on total energy. Serum lipid profiles at baseline, before and after the HC/LF diet, and LPL polymorphisms were analyzed. After 6 days of the HC/LF diet, TG and the homeostasis model assessment of insulin resistance (HOMAIR) index were found to increase only in females with S447S. No decrease in HDL-C was noted. In subjects with Hind III polymorphism, increased TG was found in all females but not in males. Increased HDL-C, together with apolipoprotein (apo) AI, was found in male H- carriers but not in males with H+/H+ and females. In conclusion, LPL Ser447Stop and Hind III polymorphisms modified the effects of an HC/LF diet on the serum lipid profiles of a young Chinese population in different ways. Effective strategies for dietary interventions targeted at younger populations should take into account the interplay between genetic polymorphisms, diet, and gender.

An abundance of candidate genes have been reported as susceptibility factors for the risk of nasopharyngeal carcinoma (NPC). Vitamin D receptor (VDR) plays an important role in cellular differentiation and the control of proliferation in a variety of cell types. To our knowledge, however, no study has reported the relationship between the VDR and NPC. The purpose of this study is to explore the potential correlation between single-nucleotide polymorphisms of the VDR gene (VDR) Fok I and Bsm I and NPC. A total of 171 patients with NPC and 176 age- and sex-matched controls were involved in this study. Genotypes were determined by using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. There were no significant differences in the genotype and allele frequencies of VDR Fok I and Bsm I polymorphisms between the group of patients with NPC and the control group in a Chinese Han population (for VDR Fok I: adjusted OR 1.03, 95% CI: 0.76-1.41; for VDR Bsm I: adjusted OR 0.80, 95% CI: 0.48-1.33). Further studies will be needed to explore the complicated gene-gene interaction and gene-environmental interactions in the susceptibility to NPC, especially in ethnically disparate populations in cohort study samples.

The investigation of novel genes involved in the derangement of glucose and lipid metabolism is of particular importance in understanding the development of metabolic syndrome (MS). In the present study, bioinformatic analyses were carried out to explore the structures and roles of the proteins encoded by the four cDNA sequences identified in our previous studies as associated with MS. Homology analyses demonstrated that the proteins encoded by Sequence 1, Sequence 2, Sequence 3, and Sequence 4 were homologous with fibrinogen gamma polypeptide, liver fibrinogen-like 1, chromosome 10 open reading frame 104, and an unnamed protein product, respectively. Because the structures were well-known for fibrinogen gamma polypeptide and liver fibrinogen-like 1, further analyses were performed only for Sequence 3 and Sequence 4. Analyses of functional domains showed that the predicted proteins encoded by Sequence 3 and Sequence 4 had multiple phosphorylation and myristoylation sites. These results indicated that the two predicted proteins might be intermediate proteins in some signaling pathways. In order to explore the possible association of Sequence 3 with MS, HepG2 cells, a human hepatoma cell line, were treated with different concentrations of glucose (mannitol as osmotic control) for 48 h. Glucose at concentrations of 22 and 33.3 mM significantly increased the mRNA expression of Sequence 3 compared to glucose at 5.6 mM while mannitol had no significant effect on the mRNA expression of Sequence 3. These results indicated that the mRNA expression of Sequence 3 was positively associated with glucose higher than physiological concentrations.

Hepatitis B induced by hepatitis B virus (HBV) remains a major public health problem worldwide. Although several antiviral drugs have been approved for hepatitis B, they cause significant dose-dependent side-effects (interferon-alpha) and drug resistance (lamivudine, etc.). Safe and potent new anti-HBV drugs are urgently needed. Traditional Chinese medicine (TCM) is an established segment of the health care system in China and widely used for hepatitis B in China and many parts of the world. Many TCMs and related active compounds have been reported that have promising and potent anti-HBV activities, including Phyllanthus, Salvia miltiorrhiza, Rheum palmatum L., Radix Astragali, oxymatrine, artemisinin and artesunate, and wogonin. Thus, TCM is a potential candidate for anti-HBV drugs. More information is needed regarding TCMs, including preparation, standardization, identification of active ingredients, and toxicological evaluation. Therefore, TCM development needs to apply advanced and interdisciplinary methodology and technology and perform further rigorously designed experimental and clinical investigations.

Cinobufacini (Huachansu) is a Chinese medicine prepared from the skin of Bufo bufo gargarizans Cantor (Bufonidae), which has long been used in traditional Chinese medicine (TCM). The aim of present study was to examine the anti-hepatitis B virus (HBV) activities of cinobufacini and its active components bufalin and cinobufagin in the human HBV-transfected cell line HepG2.2.15. The hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core-related antigen (HBcrAg) concentrations in cell culture medium were determined by chemiluminescent enzyme immunoassay after HepG2.2.15 cells were respectively treated with different concentrations of cinobufacini, bufalin, and cinobufagin for 3 or 6 d. HBV DNA and mRNA were determined using transcription-mediated amplification and real-time polymerase chain reaction (PCR), respectively. On d 3, cinobufacini at a concentration of 1 µg/ml had no activity against HBV virological markers. However, on d 6, cinobufacini at 1 µg/ml effectively inhibited the secretion of HBsAg, HBeAg, and HBcrAg by 29.58, 32.87, and 42.52%. It was more potent than the positive control lamivudine (100 µg/ml). Bufalin and cinobufagin slightly inhibited HBV antigen secretion. Treatment with cinobufacini, bufalin, or cinobufagin had no anti-HBV effect on DNA in cell culture medium. Consistent with the HBV antigen reduction, HBV mRNA expression was markedly inhibited in comparison to the control when HepG2.2.15 cells were treated with cinobufacini, bufalin, or cinobufagin. Results suggested that cinobufacini had more potent activity against HBV antigen secretion than its components bufalin and cinobufagin and this inhibitory role was attributed to the specific inhibition of HBV mRNA expression.

Objective: To explore apolipoprotein(apo) E polymorphism and its relationship with plasma apoE genotypes lipids and apolipoproteins in Chinese patients with type 2 diabetes mellitus (2DM)., Methods: were assayed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) ,serum lipids were determined by enzyme method and apolipoproteins were measured by radial immunodiffusion assay in 74 patients with 2DM and 191 healthy subjects without diabetes family history from a population of Chinese Han nationality in Chengdu area., Results: Compared with the control group, the serum TG, TC, LDLC, nHDLC, apoB100, apoCII , apoCIII and apoE levels and TG/HDLC ratio in patients with 2DM were significantly increased (P < 0.001) and the serum HDLC level and apoE/apoC II ratio were significantly decreased (P < 0.001). There was no significant difference in apoE polymorphism between 2DM group and the control group (P > 0.05). In 2DM group, the genotype apoE2 was found to have lower TG/HDLC ratio, compared with the genotypes apoE3 and apoE4; the genotype apoE4 was found to have higher serum apoA I level, compared with the genotypes E3 and E2 (P < 0.001)., Conclusion: The apoE gene polymorphism is associated with serum TG/HDLC ratio and apoA I level to some extent in type 2 diabetes mellitus.