The silent information regulator protein 2 (Sir2) and its homologues play an important role in the regulation of cellular physiological processes such as survival, apoptosis, and aging. SIRT1, the mammalian Sir 2 homologue, has been shown to deacetylate a wide range of non-histone substrates and histone substrates. It has been constantly reported that SIRT1 may be associated with the occurrence of metabolic syndrome, genomic homeostasis, tumors, and neurodegenerative diseases. Calorie restriction may mitigate many major diseases in rodent models by SIRT1-mediated deacetylase activity and prolong the life expectancies in these animals. Therefore, SIRT1 may be emphasized as a new therapy target for many different diseases.
Animals ; Caloric Restriction ; Humans ; Longevity ; Sirtuin 1 ; genetics ; physiology ; Substrate Specificity

OBJECTIVETo verify the regulation of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT 2), which is associated with cholesterol metabolism, by saturated fatty acids (SFAs).

METHODSPalmitic acid (PA), the most abundant saturated fatty acid in plasma, and oleic acid (OA), a widely distributed unsaturated fatty acid, were used to treat hepatic cells HepG2, HuH7, and mouse primary hepatocytes. In addition, PA at different concentrations and PA treatment at different durations were applied in HepG2 cells. In in vivo experiment, three-month male C57/BL6 mice were fed with control diet and SFA diet containing hydrogenated coconut oil rich of SFAs. The mRNA level of ACAT2 in those hepatic cells and the mouse livers was detected with real-time polymerase chain reaction (PCR).

RESULTSIn the three types of hepatic cells treated with PA, that SFA induced significant increase of ACAT2 expression (Pü0.01), whereas treatment with OA showed no significant effect. That effect of PA was noticed gradually rising along with the increase of PA concentration and the extension of PA treatment duration (both Pü0.05). SFA diet feeding in mice resulted in a short-term and transient increase of ACAT2 expression in vivo, with a peak level appearing in the mice fed with SFA diet for two days (Pü0.05).

CONCLUSIONSFA may regulate ACAT2 expression in human and mouse hepatic cells and in mouse livers.

Animals ; Base Sequence ; Cell Line, Tumor ; DNA Primers ; Dose-Response Relationship, Drug ; Fatty Acids ; pharmacology ; Humans ; Liver ; enzymology ; Male ; Mice ; Mice, Inbred C57BL ; Sterol O-Acyltransferase ; metabolism

The process of drug in vivo is influenced by the circadian rhythm, which may cause circadian variation in drug efficacy and toxici-ty.This study mainly reviewed the circadian rhythm of drug kinetic processes such as absorption, distribution, metabolism and excretion of drug.Moreover, Authors also described the application of circadian rhythm in the treatment of disease.

OBJECTIVETo study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation during vascular lesion formation and to elucidate the potential mechanisms.

METHODSSIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell (VSMC) lysate. Smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) C57BL/6 mice and their littermate wild-type (WT) controls underwent complete carotid artery ligation (ligation groups) or the ligation-excluded operation (sham groups). The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 (SIRT1H363Y), and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis.

RESULTSSIRT1 was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation (P<0.001) and VSMCs treated with serum (P<0.05 at the transcriptional level, P<0.001 at the protein level). No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL (P<0.001). The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 (P<0.001), while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 (P<0.001).

CONCLUSIONSOverexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT1.

Animals ; Apoptosis ; Carotid Arteries ; physiology ; Fas Ligand Protein ; genetics ; GATA6 Transcription Factor ; physiology ; Male ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1 ; physiology ; Up-Regulation

Abetalipoproteinemia ; Cilia ; Humans ; Kartagener Syndrome

To provide the ancient literary evidence support for the clinical application and development of classical prescription based on systematical collection and analysis of the ancient Chinese medical literature containing Jinshui Liujun Jian, including its origin and development. Bibliometric analysis was used and information of Jinshui Liujun Jian in ancient Chinese medical literature was then collected for statistical analysis of formula compositions, main indications, dosage, preparation methods, etc. A total of 151 valid items of data were obtained from 48 ancient Chinese medicine books. Jinshui Liujun Jian was first recorded in Jingyue Quanshu written by ZHANG Jiebin. This prescription consisted of Rehmanniae Radix Praeparata, Angelicae Sinensis Radix, Pinelliae Rhizome, Citri Reticulatae Pericarpium, Poria and Glycyrrhizae Radix et Rhizome Praeparata cum Melle, and it was mainly used to treat the deficiency of lung and kidney, edema and excess production of phlegm, or Yin deficiency in the old, insufficient blood-qi, wind-cold evil, cough and disgusting, asthma and excessive phlegm. Doctors in later dynasties mostly followed the prescription compositions, dosages and indications in Jingyue Quanshu, and extended the clinical application of this prescription.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Prescriptions ; Rhizome