Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.

BACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD. METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model. RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables. CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

[Correlation of betel nut chewing and clinicopathologic factors of oral squamous cell carcinoma].

PURPOSE: To investigate the correlation of clinicopathologic factors and immunophenotypic features with betel nut chewing in oral squamous cell carcinoma(OSCC). METHODS: The data of 88 patients with OSCC were collected. According to the habit of betel nut chewing, the clinicopathologic factors and immunohistochemical parameters were analyzed. The relationship between clinicopathologic factors of OSCC and betel nut chewing was analyzed with univariate analysis and multivariate analysis using SPSS 17.0 software package. RESULTS: 46.6% of patients had the habit of betel nut chewing and 67.0% of patients had tongue cancer and buccal cancer. The pathological stages were mainly T2 (40.9%). From univariate analysis of the results, differentiation degree, ki-67, p53 was significantly correlated with the habit of betel nut chewing(P<0.05); while gender, age, location, pathological T stage and cervical lymph node metastasis were not significantly correlated with habit of betel nut chewing (P>0.05). From multivariate analysis of the results, location and differentiation degree were significantly correlated with the habit of betel nut chewing (P<0.05). CONCLUSIONS: ki-67 and p53 protein are lowly expressed in OSCC patients with the habit of betel nut chewing, suggesting that clinicopathologic factors such as the proliferation activity, malignancy, differentiation and prognosis of tumor are much better. Differentiation degree are relatively good in OSCC patients with the habit of betel nut chewing. Cheek and tongue are the most common site of OSCC.

Anti-hepatitis B virus activity and hepatoprotective effect of des(rhamnosyl) verbascoside from Lindernia ruellioides in vitro.

Although clinically approved hepatitis B virus (HBV) polymerase inhibitors (lamivudine-3TC, entecavir, etc.) serve as effective therapeutics, the virus can easily generate resistance to them. Therefore, the treatment of HBV infection remains a public health problem. Numerous studies have shown that natural products have prospective anti-HBV activity. The purpose of this study was to isolate and extract des(rhamnosyl) verbascoside from Lindernia ruellioides (Colsm.) Pennell and explore its anti-HBV and hepatoprotective effects. Anti-HBV activity was evaluated in HepG2.2.15 cells, a human hepatocellular carcinoma cell line with HBV-stable infection, and its protective effect was evaluated in HL-7702 cells, a normal human liver cell line. HepG2.2.15 cells maintained normal growth morphology within the selected concentration range of des(rhamnosyl) verbascoside. It also inhibited the expression of HBV antigens and HBV DNA in a dose- and time-dependent manner in vitro. Further, western blot experiments showed that it could downregulate HBV X protein (HBx) expression in a dose-dependent manner. In the H2 O2 -induced hepatocyte injury model, the cell-survival rate of the HL-7702 cells with the highest drug dose reached 85.25%, which was significantly improved compared with that of the model group. Most of the cells returned to normal morphology, showing polygonal or fusiform structures. Thus, it may be stated that des(rhamnosyl) verbascoside exhibits anti-HBV activity and hepatoprotective effects in vitro and may exert an anti-HBV effect via antigen inhibition, HBV DNA secretion, and HBx protein expression.

Fabrication and Cytotoxicity of Fucoidan-Cisplatin Nanoparticles for Macrophage and Tumor Cells.

Fucoidan, an anionic, sulfated polysaccharide from brown seaweed, is known to exhibit antitumor and immunomodulatory functions. To develop an immune protection and chemotherapeutic agent, fucoidan-cisplatin nanoparticles (FCNPs) were designed. FCNPs were prepared by mixing cisplatin with fucoidan solution or fucoidan with cisplatin solution, followed by dialysis to remove trace elements. The nanoparticles, comprising 10 mg of fucoidan and 2 mg of cisplatin, which exhibited the highest cisplatin content and loading efficiency during the production process, were named as Fu100Cis20. The cisplatin content, cisplatin loading efficiency, nanoparticle size, and zeta potential of Fu100Cis20 were 18.9% ± 2.7%, 93.3% ± 7.8%, 181.2 ± 21.0 nm, and -67.4 ± 2.3 mV, respectively. Immune protection assay revealed that Fu100Cis20-treated RAW264.7 cells were protected from the cytotoxicity of cisplatin. Furthermore, antitumor assay indicated that Fu100Cis20-treated HCT-8 cells showed stronger cytotoxicity than those treated with cisplatin alone. These results suggested that fucoidan-based nanoparticles exhibited suitable particle size and high drug encapsulation, and that Fu100Cis20 has potential application in both immunotherapy and chemotherapy.