Single dose administration of L-carnitine improves antioxidant activities in healthy subjects.

L-carnitine has been used as a supplement to treat cardiovascular or liver disease. However, there has been little information about the effect of L-carnitine on anti-oxidation capability in healthy human subjects. This study was designed to investigate the correlation between plasma L-carnitine concentration and antioxidant activity. Liquid L-carnitine (2.0 g) was administered orally as a single dose in 12 healthy subjects. Plasma concentration of L-carnitine was detected by HPLC. The baseline concentration of L-carnitine was 39.14 ± 5.65 µmol/L. After single oral administration, the maximum plasma concentration (C(max)) and area under the curve (AUC(0-∞)) were 84.7 ± 25.2 µmol/L and 2,676.4 ± 708.3 µmol/L·h, respectively. The half-life and the time required to reach the C(max) was 60.3 ± 15.0 min and 3.4 ± 0.46 h, respectively. There was a gradual increase in plasma concentrations of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase and total antioxidative capacity (T-AOC) in the first 3.5 h following L-carnitine administration. The plasma concentrations of SOD, GSH-Px, catalase and T-AOC returned to baseline levels within 24 h. A positive correlation was found between L-carnitine concentration and the antioxidant index of SOD (r = 0.992, P < 0.01), GSH-Px (r = 0.932, P < 0.01), catalase (r = 0.972, P < 0.01) or T-AOC (r = 0.934, P < 0.01). In conclusion, L-carnitine increases activities of antioxidant enzymes and the total antioxidant capacity in healthy subjects. It may be useful as a supplementary therapy for chronic illnesses involving excessive oxidative stress.

Long noncoding RNA TUG1 facilitates cell ovarian cancer progression through targeting MiR-29b-3p/MDM2 axis.

Ovarian cancer (OC) is one of the most aggressive female cancers in the world. OC trends to be diagnosed at an advanced stage with abdominal metastasis. Our study explored the biological function and underlying mechanism of lncRNA on OC cell proliferation and migration. The expression of turine up-regulated gene 1 (TUG1) in human OC tissues and cell lines was measured by qRT-PCR. OC cell proliferation, viability, migration, and invasion were measured by MTT assays, colony formation assays, and transwell assays in vitro. Furthermore, the nude mice xenograft model was established to determine the effects of TUG1 in vivo. The relationship between TUG1 and miR-29b-3p, as well as miR-29b-3p and MDM2 were identified using the luciferase reporter assays. We showed that the expression of TUG1 and MDM2 were significantly increased, but the expression of miR-29b-3p was remarkably decreased in OC tissues and cell lines. Knockdown of TUG1 strongly inhibited the ability of cell proliferation, colony formation, migration, and invasion in vitro. The relationship between TUG1 and miR-29b-3p, or miR-29b-3p and MDM2 were predicted by StarBase and miRanda online software. Besides, miR-29b-3p reversed the positive effect of TUG1 on the OC cell proliferation, migration, and invasion through inhibiting MDM2 expression and increasing p53 phosphorylation level. Moreover, knockdown of TUG1 suppressed tumor growth in vivo. Taken all together, this study shows that TUG1 plays a crucial oncogenic role and facilitates cell proliferation, migration, and invasion in OC through regulating miR-29b-3p/MDM2 axis.

Ubenimex Reverses MDR in Gastric Cancer Cells by Activating Caspase-3-Mediated Apoptosis and Suppressing the Expression of Membrane Transport Proteins.

Gastric cancer (GC) is one of the most malignant tumors, accounting for 10% of deaths caused by all cancers. Chemotherapy is often necessary for treatment of GC; the FOLFOX regimen is extensively applied. However, multidrug resistance (MDR) of GC cells prevents wider application of this treatment. Ubenimex, an inhibitor of CD13, is used as an immune adjuvant to treat hematological malignancies. Here, we demonstrate that CD13 expression positively correlates with MDR development in GC cells. Moreover, Ubenimex reverses the MDR of SGC7901/X and MKN45/X cells and enhances their sensitivity to FOLFOX, in part by decreasing CD13 expression, which is accompanied by downregulation of Bcl-xl, Bcl-2, and survivin expression; increased expression of Bax; and activation of the caspase-3-mediated apoptotic cascade. In addition, Ubenimex downregulates expression of membrane transport proteins, such as P-gp and MRP1, by inhibiting phosphorylation in the PI3K/AKT/mTOR pathway to increase intracellular accumulations of 5-fluorouracil and oxaliplatin, a process for which downregulation of CD13 expression is essential. Therefore, the present results reveal a previously uncharacterized function of CD13 in promoting MDR development in GC cells and suggest that Ubenimex is a candidate for reversing the MDR of GC cells.

[Effect of danhong injection on cerebral injury in patients undergoing coronary artery bypass graft operation with extracorporeal circulation].

OBJECTIVE: To investigate the effect and its possible mechanisms of Danhong Injection (DHI) on cerebral injury during coronary artery bypass graft (CABG) operation with hypothermic cardiopulmonary bypass (CPB). METHODS: Fifty patients went to CABG with CPB were randomly assigned equally to two groups, the control group and the tested group. DHI 1.5 mL/kg was pumped to where the tested group at the times of aortic pre-charging and unclamping respectively, but to the control group, equal volume of normal saline was given instead. Blood samples were taken from jugular bulb at different time points, i. e. before operation (T1, baseline), re-warming to 36 degrees C (T2 ), 30 min (T3 ) and 6 h (T4) after terminating CPB, for determination levels of superoxide dismutase (SOD) activity using xanthine oxidase method, malondialdehyde (MDA) concentration using thiobarbituric method, tumor necrosis factor alpha (TNF-alpha), as well as interleukin-6, -8 using radioimmunoassay and -10 (IL-6, IL-8 and IL-10) using ELISA. RESULTS: Level of SOD activity significantly decreased during (T2) and after CPB (T3 and T4) in the control group, as compared to the T1 (P < 0.01), but it was unchanged in the tested group; level of MDA increased during and after CPB in both groups (P < 0.01), but more significantly in the control group (P < 0.05), so comparison after CPB between the two groups showed a higher SOD and lower MDA level in the tested group. Plasma levels of TNF-alpha, IL-6, IL-8 and IL-10 significantly increased in both groups after CPB (T3 and T4, P < 0.01) as compared to the T1, but the comparison between groups showed lower plasma TNF-alpha, IL-6 and IL-8 levels at T3 and T4, and higher IL-10 level at T4 in the test group (P < 0.01). All patients had stable life signs with no occurrence of adverse reaction. CONCLUSION: DHI has obvious protective effect on cerebral injury in patients undergoing CABG with CPB, the mechanisms may be associated with the actions of anti-oxidation, anti-inflammation and regulation on immune factors.

Antimicrobial aflatoxins from the marine-derived fungus Aspergillus flavus 092008.

A new aflatoxin, aflatoxin B(2b) (1), together with six known compounds, were isolated from the marine-derived fungus Aspergillus flavus 092008 endogenous with the mangrove plant Hibiscus tiliaceus (Malvaceae). The structure of 1 was determined by the spectroscopic and chemical methods. Compound 1 exhibited a moderate antimicrobial activity against Escherichia coli, Bacillus subtilis and Enterobacter aerogenes, with MIC values of 22.5, 1.7 and 1.1 M, respectively. Compound 1 also showed a weak cytotoxicity against A549, K562 and L-02 cell lines, with IC(50) values of 8.1, 2.0 and 4.2 M, respectively. The results showed that hydration and hydrogenation of (8)-double bond significantly reduces the cytotoxicity of aflatoxins, while the esterification at C-8 increases the cytotoxicity.

A new cytotoxic indole-3-ethenamide from the halotolerant fungus Aspergillus sclerotiorum PT06-1.

A new cytotoxic indole-3-ethenamide (1) and two known compounds, 7-(3-methylbut-2-enyl)-1H-indole-3-carbaldehyde (2) and emodin (3) were isolated and identified from the ethyl acetate extract of Aspergillus sclerotiorum PT06-1 in a hypersaline nutrient-rich medium. On the basis of spectroscopic analysis and amino-acid analysis, the new structure of 1 was determined to be (S,E)-3-methyl-2-(N- methylacetamido)-N-(2-(7-(3-methylbut-2-enyl)-1H-indol-3-yl)vinyl)butanamide within 3:1 ratio of rotamers along the acetamido single bond in DMSO-d(6) at room temperature. Compound 1 showed moderate cytotoxicity against A-549 cells and weak cytotoxicity against HL-60 cells with the IC(50) values of 3.0 and 27 µM, respectively. Compound 2 has been separated as natural product for the first time, and its NMR data were also reported for the first time in this study.