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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]

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.

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.