Downregulation of miR-599 predicts poor outcome in cervical cancer patients and promotes the progression of cervical cancer.

OBJECTIVE: Cervical cancer remains a leading cause of gynecological cancer-related death. In this study, we aimed to investigate the expression pattern of miR-599 and its prognostic significance in cervical cancer. MATERIALS AND METHODS: The RT-qPCR analysis was used to detect the expression levels of miR-599 in cervical cancer tissues and cell lines. The association between miR-599 expression and clinical characteristics of cervical cancer patients was analyzed using the χ2 test. The Kaplan-Meier analysis and multivariate Cox proportional hazards model were used to explore the prognostic significance of miR-599. Then, CCK-8 assays, transwell migration, and invasion assays were used to assess the effects of miR-599 on tumor cell proliferation, migration, and invasion of cervical cancer cells, respectively. RESULTS: miR-599 expression was significantly downregulated in cervical cancer tissues and cells compared with non-cancerous tissues and HaCaT cells, respectively. Statistical analysis revealed that miR-599 expression was associated with lymph node metastasis and FIGO stage. The miR-599 expression was an independent prognostic factor for overall survival. Functionally, overexpression of miR-599 suppressed cell proliferation, migration, and invasion of cervical cancer cells, while downregulation of miR-599 had opposite effects. CONCLUSION: miR-599 acts as a tumor suppressor in cervical cancer that inhibiting cell proliferation, migration, and invasion of cervical cancer cells, suggesting that miR-599 may be a potential prognostic biomarker and novel targeted strategy for cervical cancer.

A preliminary report: genistein attenuates cerebral ischemia injury in ovariectomized rats via regulation of the PI3K-Akt-mTOR pathway.

Stroke is a leading cause of disability and death in the worldwide. Therefore, prevention of stroke is critically important. Genistein, a natural phytoestrogen extracted from soybeans, has been found to be a potential neuroprotective agent for stroke prevention. However, the role of genistein and its underlying mechanism in ovariectomized rats has been rarely evaluated. In this study, ovariectomized rats were treated with genistein (10 mg/kg) or vehicle daily for two weeks before they received middle cerebral artery occlusion (MCAO) and reperfusion. Seventy-two hours after reperfusion, the neurological function was evaluated by Garcia test, infarct volumes were detected by 2,3,5-triphenyltetrazolium chloride staining; and neuronal damage and cell apoptosis were detected by Nissl and Tunel staining in the ischemic penumbra, respectively. In addition, Western blotting was used to detect the activity of PI3K-Akt-mTOR signal pathway in the ischemic penumbra in different groups. And we found that genistein treatment in ovariectomized rats significantly improved neurological outcomes, reduced infarct volumes, decreased neuronal damage and cell apoptosis, and increased the activity of PI3K-Akt-mTOR signal pathway. Our findings indicated that treatment genistein could alleviate neuronal apoptosis induced by cerebral ischemia in ovariectomized rats via promoting the activity of PI3K-Akt-mTOR signal pathway, which provides a new molecular mechanism for the neuroprotective effects of genistein against stroke.

Comparative pharmacokinetic study on three formulations of Astragali Radix by an LC-MS/MS method for determination of formononetin in human plasma.

Astragali Radix (AR) is a widely used traditional Chinese medicine for healing the cardiovascular, liver and immune systems. Recently, superfine pulverizing technology has been applied to developing novel formulations to improve bioavailability of the active constituents in herbs, such as ultrafine granular powder of AR. In this study, a universal and sensitive quantitative method based on LC-MS/MS was employed for determining formononetin, the main flavonoid in AR, in human plasma for comparative pharmacokinetics of three oral formulations of AR. Formononetin and IS (quercetin) were extracted by ethyl acetate from human plasma and were separated on a C18 column with a mobile phase consisting of acetonitrile and 0.1% formic acid. Positive-ion electrospray-ionization mode was applied in mass spectrometric detection. The quantitative method was validated with regards to selectivity, linearity, accuracy and precision, matrix effect, extraction recovery and stability, and was applied to comparing the pharmacokinetics of ultrafine granular powder (UGP), ultrafine powder (UP) and traditional decoction pieces (TDP) of AR after oral administration. The peak concentration and areas under the concentration-time curve of formononetin in UGP and UP were significantly higher than those of TDP. UGP and UP could significantly improve the bioavailability of AR in human compared with TDP after oral administration.

Comparison of Cr(VI) removal by activated sludge and dissolved organic matter (DOM): importance of UV light.

Removal of toxic Cr(VI) by activated sludge and DOM derived from activated sludge was investigated in this study. A rapid increase in TOC concentration from 50.93 to 127.40 mg L(-1) is observed during the Cr(VI) removal process by activated sludge in the pH range of 2-9. Removal efficiencies of Cr(VI) by either activated sludge or DOM greatly decreased with the increasing initial pH. Kinetics of Cr(VI) removal by activated sludge indicate that both biosorption and bioreduction are involved in the Cr(VI) removal. Cr(VI) removal by DOM is slow in dark, but it is greatly enhanced when UV light is applied. The first-order constant increases from 0.0033 (in dark) to 0.079 min(-1) (UV illumination) at pH 2.0 and 1068 mg L(-1) DOM. The enhancement of Cr(VI) reduction is due to the generation of the reactive intermediates such as O2(●-) and DOM* as DOM absorbed light energy, which plays important roles in the reduction of Cr(VI).

Cr(III) removal by a microalgal isolate, Chlorella miniata: effects of nitrate, chloride and sulfate.

In the present study, nitrate, chloride and sulfate anion systems were used to investigate the presence of anions on the removal of Cr(III) by Chlorella miniata. Kinetic studies suggested that the equilibrium time of Cr(III) biosorption was not affected by the presence of different sodium salts, even at the concentration of 1.0 M, and all reached equilibrium after 24 h. Equilibrium experiments showed that the effects of different anions on Cr(III) biosorption varied, and the inhibitory order was SO4 (2-) > Cl(-) > NO3 (-). Langmuir isotherm indicated that the maximum sorption capacity of C. miniata increased with the increase of pH under different anion systems. The strongest inhibition effect of the sulfate system was attributed to the formation of Cr(OH)SO4 aq. and the decrease of Cr(OH)(2+) and Cr(3+) in solution, while the difference of inhibitory effect in the other two anion systems could be accounted by the formation of the inner-sphere surface complex in the nitrate system and the outer-sphere surface complex in the chloride system. The present study suggested that the presence of anions greatly affected the removal of Cr(III) on C. miniata and thereby their transport in the environment.