Simultaneous quantification of cardiovascular disease related metabolic risk factors using liquid chromatography tandem mass spectrometry in human serum.

Recent observations from metabonomic studies have consistently found that branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), glutamine (Gln), glutamic acid (Glu), Gln/Glu ratio, carnitine, and several species of acylcarnitines and lysophosphatidylcholines (LPCs) are possible risk factors for metabolic diseases such as diabetes mellitus (DM) and cardiovascular diseases (CVD). We described here a simple and reliable method for simultaneous quantification of these metabolic risk factors by liquid chromatography tandem mass spectrometry (LC-MS/MS). Serum samples were extracted with isopropanol, and the extracted metabolites were separated by hydrophilic interaction liquid chromatography (HILIC) and detected with electrospary ionization (ESI) inpositive ion mode with multiple reaction monitor (MRM) mode.

Effect of 22 Novel Cytochrome P450 2D6 (CYP2D6) Variants Found in the Chinese Population on Hemangeol Metabolism In Vitro.

Background And Objectives: Hemangeol, approved for the treatment of proliferative infantile hemangiomas requiring systemic therapy, is metabolized by cytochrome P450 2D6 (CYP2D6), which is a highly polymorphic enzyme that metabolizes a large number of drugs. More than 100 CYP2D6 allelic variants have been reported so far, including 22 novel variants that discovered in our lab in the Chinese population. Our study aimed to probe the enzymatic activity of these variants toward hemangeol in vitro with recombinant microsomes that expressed in sf21 insect cells using a baculovirus-mediated expression system.

Cartilage oligomeric matrix protein is a natural inhibitor of thrombin.

Thrombin is an effector enzyme for hemostasis and thrombosis; however, endogenous regulators of thrombin remain elusive. Cartilage oligomeric matrix protein (COMP), a matricellular protein also known as thrombospondin-5, is essential for maintaining vascular homeostasis. Here, we asked whether COMP is involved in the process of blood coagulation.

Age-Based Differences in the Genetic Determinants of Glycemic Control: A Case of FOXO3 Variations.

Background: Glucose homeostasis is a trait of healthy ageing and is crucial to the elderly, but less consideration has been given to the age composition in most studies involving genetics and hyperglycemia.

Methods: Seven variants in FOXO3 were genotyped in three cohorts (n = 2037; LLI, MI_S and MI_N; mean age: 92.5 ± 3.

The effects of energy intake of four different feeding patterns in rats.

Energy intake can affect the metabolism. But it is not very clear that how and to what degree the metabolism can be changed by energy intake quantity and change. Here we applied four feeding patterns in male Sprague-Dawley rats--normal ad libitum diet (NFal), high-fat diet (HFal), caloric restriction (CR) after HFal (HFal-NFcr), and refeeding from CR to ad libitum (HFal-NFcr-NFal).

FOXO3 variants are beneficial for longevity in Southern Chinese living in the Red River Basin: A case-control study and meta-analysis.

Forkhead box class O (FOXO) transcription factors play a crucial role in longevity across species. Several polymorphisms in FOXO3 were previously reported to be associated with human longevity. However, only one Chinese replication study has been performed so far.

CD109 attenuates TGF-β1 signaling and enhances EGF signaling in SK-MG-1 human glioblastoma cells.

CD109 is a glycosylphosphatidylinositol-anchored cell surface protein that is frequently detected in squamous cell carcinomas. CD109 is a negative regulator of TGF-β1 signaling in human keratinocytes, and the N-terminal fragment of CD109 secreted from cells after cleavage by the furin protease is important for modulating TGF-β1 signaling. Previously, we found that CD109 is expressed in human glioblastoma cells; however, the role of CD109 in glioblastoma cells is not established.

Clinical features of diabetes retinopathy in elderly patients with type 2 diabetes in Northern Chinese.

Objective: The objective was to estimate the prevalence and clinical characteristics of diabetes retinopathy (DR) in elderly individuals with type 2 diabetes mellitus in Northern Chinese.

Materials And Methods: 595 eligible subjects (263 men, 332 women) assisted by the community health service center in Beijing, China were involved with averaged 70.6 ΁ 8.

SIRT1 functions as an important regulator of estrogen-mediated cardiomyocyte protection in angiotensin II-induced heart hypertrophy.

Background: Sirtuin 1 (SIRT1) is a member of the sirtuin family, which could activate cell survival machinery and has been shown to be protective in regulation of heart function. Here, we determined the mechanism by which SIRT1 regulates Angiotensin II- (AngII-) induced cardiac hypertrophy and injury in vivo and in vitro.

Methods: We analyzed SIRT1 expression in the hearts of control and AngII-induced mouse hypertrophy.

In vitro and in vivo characterization of 13 CYP2C9 allelic variants found in Chinese Han population.

Our previous study detected totally 35 CYP2C9 allelic variants in 2127 Chinese subjects, of whom 21 novel alleles were reported for the first time in Chinese populations. The aim of the present study was to characterize the 13 CYP2C9 allelic variants both in vitro and in vivo. Different types of CYP2C9 variants were highly expressed in COS-7 cells, and 50 μM tolbutamide was added as the probing substrate to evaluate their metabolic abilities in vitro.

A gain-of-function mutation in Tnni2 impeded bone development through increasing Hif3a expression in DA2B mice.

Distal arthrogryposis type 2B (DA2B) is an important genetic disorder in humans. However, the mechanisms governing this disease are not clearly understood. In this study, we generated knock-in mice carrying a DA2B mutation (K175del) in troponin I type 2 (skeletal, fast) (TNNI2), which encodes a fast-twitch skeletal muscle protein.

8q24 rs4242382 polymorphism is a risk factor for prostate cancer among multi-ethnic populations: evidence from clinical detection in China and a meta-analysis.

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations.

Materials And Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically- confirmed PCa (n=335) and from age-matched normal controls (n=347).

Age-dependent tissue expression patterns of Sirt1 in senescence-accelerated mice.

Sirtuin 1 (Sirt1) has a range of molecular functions and has emerged as an important protein in aging and metabolic regulations. Studies have reported a correlation between disturbance of Sirt1 activity and the onset of aging‑ or obesity‑associated diseases, including diabetes, cardiovascular disease and neurodegenerative disorders. However, a systematic investigation to examine the changes of Sirt1 expression in a wide range of ages and to what degree it changes has yet to be performed.

[Effect of type 2 diabetes with hypertension on cognitive function-a study on elderly living in the communities of Beijing].

Objective: To study the effects of type 2 diabetes (T2DM) with hypertension on cognitive function in those community-based elderly who were aged 60 and over, in Beijing.

Methods: 82 patients with T2DM, 142 patients with both T2DM and hypertension and 277 normal controls were investigated in this study. Both methods as: the Montreal Cognitive Assessment (MoCA) and Mini-Mental Status Examination (MMSE)were used to determine cognitive change.

Effects of cytochrome P450 2C9 polymorphism on bosentan metabolism.

Cytochrome P450 (P450) 2C9 is an important member of the P450 enzyme superfamily, with 58 CYP2C9 allelic variants previously reported. Genetic polymorphisms of CYP2C9 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The aim of this study was to assess the catalytic activities of 38 human CYP2C9 alleles, including 24 novel alleles (*36-*60) found in the Han Chinese population, toward bosentan (BOS) in vitro.

Regulation of cargo-selective endocytosis by dynamin 2 GTPase-activating protein girdin.

In clathrin-mediated endocytosis (CME), specificity and selectivity for cargoes are thought to be tightly regulated by cargo-specific adaptors for distinct cellular functions. Here, we show that the actin-binding protein girdin is a regulator of cargo-selective CME. Girdin interacts with dynamin 2, a GTPase that excises endocytic vesicles from the plasma membrane, and functions as its GTPase-activating protein.

Protein phosphatase 4 promotes hepatic lipogenesis through dephosphorylating acetyl‑CoA carboxylase 1 on serine 79.

Reversible phosphorylation has a critical role in the regulation of the activity of acetyl‑CoA carboxylase 1 (ACC1), which is associated with de novo lipogenesis. It has been shown that AMP‑activated protein kinase (AMPK) phosphorylates ACC1 on serine 79 and inhibits its activity; however, the mechanism of ACC1 dephosphorylation remains elusive. Protein phosphatase 4 (PP4), a ubiquitous serine/threonine phosphatase, regulates a variety of cellular functions; however, whether PP4 is involved in lipid metabolism has yet to be elucidated.

[Screening of variation in the promoter of PPARGC1A gene and study of its association with the risk of type 2 diabetes in ethnic Hans from Beijing].

Objective: To study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM).

Methods: A 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814).

Gender-specific DNA methylome analysis of a Han Chinese longevity population.

Human longevity is always a biological hotspot and so much effort has been devoted to identifying genes and genetic variations associated with longer lives. Most of the demographic studies have highlighted that females have a longer life span than males. The reasons for this are not entirely clear.

KNDC1 knockdown protects human umbilical vein endothelial cells from senescence.

KNDC1 (kinase noncatalytic C-lobe domain containing 1), a brain-specific Ras guanine nucleotide exchange factor, controls the negative regulation of neuronal dendrite growth. However, the effect of KNDC1 on cellular senescence remains to be elucidated. The present study investigated the impact of KNDC1 knockdown on human endothelial cell senescence and the mechanisms underlying this effect.

Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women.

The knowledge of dyslipidemia and its genetic contributors in oldest-old subjects is limited; in addition, the majority of oldest-old subjects are females. Evidence has accumulated that multiple genetic factors play important roles in determining susceptibility to dyslipidemia and extended life span. Cholesterol ester transfer protein (CETP) and apolipoprotein E (APOE) are two plausible candidate genes for human longevity owing to their functionally related modulation of circulating lipid homeostasis; however, few studies have considered their interplay.

Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling.

Background: Recently, evidence indicated that the rapamycin-eluting stent which was used worldwide may contribute to an increased risk for thrombosis. On the contrary, other researchers found it was safe. Thus, it is necessary to clarify the effect of rapamycin on thrombosis and the corresponding mechanisms.

Clinical significance of Girdin expression detected by immunohistochemistry in non-small cell lung cancer.

Girdin protein has been implicated in cell migration and proliferation control. Previous evidence has confirmed that Girdin is a pivotal protein during cancer progression. To date, no evidence has been identified for the clinical significance of Girdin expression in non-small cell lung cancer (NSCLC).