Apelin and Apelin Receptor in Follicular Granulosa Cells of Buffalo Ovaries: Expression and Regulation of Steroidogenesis.

Apelin (APLN), as a ligand for APJ (an orphan G-protein-coupled receptor), is an adipokine with pleiotropic effects in many physiological processes of the body. It has an important role in the control of reproduction particularly in females (mainly in control of ovarian function). This study was carried out to investigate the mRNA and protein amounts of APLN/APJ in granulose cells (GCs) of ovarian follicles with small (SF), medium (MF), and large (LF) sizes of buffalo (Bubalus bubalis) and the effect of IGF1 and follicle-stimulating hormone (FSH) on the expression levels of APLN/APJ. In addition, we evaluated the effect of various doses of APLN (isoforms -13 and -17) singly or in combination with IGF1 and FSH on estradiol (E2) and progesterone (P4) secretion in GCs. The mRNA and protein abundance of APLN was the highest in GCs of LF while the APJ expression enhanced with follicle enlargement in GCs (p-value <0.01). IGF1 and FSH elevated the mRNA and protein amounts of APLN and FSH, and IGF1 increased the expression of APJ in buffalo GCs (p-value <0.01). Both isoforms of APLN (-13/-17) singly or in the presence of IGF1 or FSH increased the secretion of E2 and P4 with or without preincubation of cells with APJ antagonist (ML221 10 µM), although we had some variation in the effects. Concurrently, APLN-13/-17 significantly increased the mRNA and protein expression of CYP19A1 and StAR (p-value <0.01). ML221 substantially diminished the secretion of E2 and P4 and also the expression of CY19A1 and StAR in buffalo GCs (p-value <0.01). We also revealed that APLN-13/-17 (10-9 M), singly or in response to IGF1 and FSH, increased the production of E2 and P4 in different times of stimulation. In conclusion, APLN may play a crucial role in steroidogenesis and follicular development in ovarian GCs of buffalo.

Resveratrol induces SIRT1-Dependent autophagy to prevent H2O2-Induced oxidative stress and apoptosis in HTR8/SVneo cells.

INTRODUCTION: Pre-eclampsia (PE) is a serious complication of pregnancy, and the likely pathogenic basis of early onset PE are placental dysfunction and increased oxidative stress. Resveratrol (RES) is a potent antioxidant which has shown beneficial effects in many diseases. The aim of this study was to investigate the protective effects of RES against oxidative stress-induced damage in trophoblasts, and elucidate the potential mechanisms. METHODS: We established an in vitro model of oxidative stress by exposing the human first-trimester extravillous trophoblast cell line HTR8/SVneo to H2O2. The level of oxidative stress was reflected by ROS, MDA and SOD. The viability of cells was determined by the MTS assay. Apoptosis was detected using Annexin V-FITC staining and flow cytometry. Levels of SIRT1(sirtuin 1) and autophagy-related proteins (LC3, Beclin-1, p62) were detected by western blot. Autophagosomes were observed by transmission electron microscopy (TEM). RESULTS: Pre-treatment with RES significantly ameliorated H2O2-induced cytotoxicity, morphological damage, oxidative stress and apoptosis. Mechanistically, RES restored the levels of SIRT1 and autophagy-related proteins including LC3-II, Beclin-1 and p62 that were dysregulated by H2O2. Blocking autophagy by 3-methyladenine (3-MA) completely abolished the protective effects of RES, as did knocking down SIRT1. CONCLUSION: RES may protect human trophoblasts against H2O2-induced oxidative stress by activating SIRT1-dependent autophagy, and therefore has therapeutic potential in PE.

Magnetically Recyclable Fe3O4@Zn xCd1- xS Core-Shell Microspheres for Visible Light-Mediated Photocatalysis.

Magnetically recyclable photocatalyst has drawn considerable research interest because of its importance in practical applications. Herein, we demonstrate a facile hydrothermal process to fabricate magnetic core-shell microspheres of Fe3O4@Zn xCd1- xS, successfully using Fe3O4@ZnS core-shell microspheres as sacrificed templates. The as-prepared magnetically recyclable photocatalysts show efficient photochemical reduction of Cr(VI) under irradiation of visible light. The photochemical reduction mechanism has been studied to illustrate the reduction-oxidation ability of the photogenerated electrons (e-) and holes (h+), which play an important role in the reduction of Cr(VI) to Cr(III) and oxidation of organic dyes. The as-prepared Fe3O4@Zn0.55Cd0.45S core-shell microspheres show good chemical stability and only a slight decrease in the photocatalytic activity after four recycles. In particular, the as-prepared photocatalysts could be easily recycled and reused by an external magnetic field. Therefore, this work would provide a facile chemical approach for controlled synthesis of magnetic nanostructures combined with alloyed semiconductor photocatalysts for wastewater treatment.

Discovery of [1,2,3]Triazolo[4,5-d]pyrimidine Derivatives as Novel LSD1 Inhibitors.

Lysine specific demethylase 1 (LSD1) plays a pivotal role in regulating the lysine methylation. The aberrant overexpression of LSD1 has been reported to be involved in the progression of certain human malignant tumors. Abrogation of LSD1 with RNAi or small molecule inhibitors may lead to the inhibition of cancer proliferation and migration. Herein, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives were synthesized and evaluated for their LSD1 inhibitory effects. The structure-activity relationship studies (SARs) were conducted by exploring three regions of this scaffold, leading to the discovery of compound 27 as potent LSD1 inhibitor (IC50 = 0.564 µM). Compound 27 was identified as a reversible LSD1 inhibitor and showed certain selectivity to LSD1 over monoamine oxidase A/B (MAO-A/B). When MGC-803 cells were treated with compound 27, the activity of LSD1 can be significantly inhibited, and the cell migration ability was also suppressed. Docking studies indicated that the hydrogen interaction between the nitrogen atom in the pyridine ring and Met332 could be responsible for the improved activity of 2-thiopyridine series. The [1,2,3]triazolo[4,5-d]pyrimidine scaffold can be used as the template for designing new LSD1 inhibitors.

Controlled synthesis of upconverting nanoparticles/CuS yolk-shell nanoparticles for in vitro synergistic photothermal and photodynamic therapy of cancer cells.

Synergistic photodynamic and photothermal therapy of cancer cells is of considerable scientific and technological interest. In this work, we demonstrate a sacrificial template strategy to fabricate yolk-shell nanoparticles combining upconversion nanoparticles (UCNPs) and CuS nanoparticles. Lanthanide-doped upconversion nanoparticles of NaYF4:30% Yb,1% Nd,0.5% Er@NaYF4:20% Nd (also denoted as UCNPs) have been prepared as 808 nm light excited remote-controlled nanotransducers for in vitro cancer cell treatment. The upconversion fluorescence of the as-prepared UCNPs@CuS yolk-shell nanoparticles is completely quenched under the excitation of an 808 nm laser, which demonstrates that the energy transfer between the UCNPs and CuS is very efficient. In addition, the as-prepared UCNPs@CuS nanoparticles show higher production ability for hydroxyl radicals (˙OH) and singlet oxygen (1O2) compared to CuS hollow nanospheres of similar size. In particular, the excited shell layer (CuS) showed an enhanced photothermal effect while producing reactive oxygen species (ROS) including singlet oxygen (1O2) and hydroxyl radicals (˙OH) after being exposed to near infrared (NIR) light. Thus, the as-prepared UCNPs@CuS yolk-shell nanoparticles exhibited the synergistic effect of photothermal and photodynamic therapy of cancer cells, which resulted in significant cell death after exposure to an 808 nm laser. The synthetic strategy will provide an alternative method to fabricate other UCNP based core-shell nanoparticles for potential and important applications in bionanotechnology including theranostics, multimodal treatment, magnetic resonance imaging-guided photodynamic therapy, etc.

[The incidence and mortality of lung cancer among residents in Yangpu district of Shanghai from 2002 to 2010].

OBJECTIVE: To analyze the incidence and mortality of lung cancer patients among residents in Yangpu District of Shanghai from 2002 to 2010. METHODS: The data of lung cancer cases in permanent residents of Yangpu district were collected from the database of the registration and management system in Shanghai city. Temporal trend in the incidence of lung cancer was analyzed by using annual percent change (APC) mode1. The survivals were calculated using SPSS 16.0 and Joinpoint Regression Program 3.5.1 software. RESULTS: A total of 5726 cases of lung cancer were diagnosed from January 2002 to December 2010. Of those, 3865 were males with an average age of onset 70.08 years, and 1861 were females with an average age of onset 70.88 years. The crude incidence rate was 77.36/10(5) in men, significantly higher than 39.31/10(5) in women (U = 24.84, P < 0.01). The standardized incidence rate was 25.23/10(5) in men, significantly higher than 13.47/10(5) in women (U = 13.24, P < 0.01). A total of 5248 cases died of the disease in this period. Of those, 3586 were men. The crude mortality was 71.77/10(5) in men, significantly higher than 35.11/10(5) in women (U = 24.67, P < 0.01). The standardized mortality was 21.72/10(5) in men, significantly higher than 11.08/10(5) in women (U = 13.01, P < 0.01). Both the incidence and mortality rates increased apparently in those older than 45 years. The 1- to 5-year survival rates in all cases were 37.42%, 22.71%, 15.73%, 12.32%, and 10.53%, respectively. The 1- to 5-year survival rates in male cases were significantly lower than those in female cases (P < 0.05 for each comparison). The 1- to 5-year survival rates of the patients whose tumor had been surgically removed were significantly higher than those in the patients without surgery (P < 0.05 for each comparison). CONCLUSIONS: The incidence of lung cancer is close to the mortality in the residents of Yangpu District of Shanghai city. Surgical resection treatment improves the prognosis of lung cancer.

[The occurrence and survival condition of primary liver cancer among residents in Yangpu district of Shanghai between year 2002 and 2010].

OBJECTIVE: To analyze the incidence and survival rates of primary liver cancer (PLC) among residents in Yangpu district of Shanghai. METHODS: A total of 9 730 736 permanent residents (male 4 996 390 and female 4 734 346) of Yangpu district in Shanghai were recruited in the study between year 2002 and 2010; among whom 2726 PLC cases were diagnosed and 2427 death cases were certified. The incidence and mortality of PLC were calculated under the analysis of the new PLC cases and death cases between year 2002 and 2010. The rates were standardized by the demographic composition developed in the Fifth Nationwide Census in year 2000, in order to analyze the survival condition of PLC patients and explore the prognosis of surgical excision treatment. RESULTS: Among the new PLC cases between year 2002 and 2010, 1966 cases were male, whose average age of onset was 59.81; while 760 cases were female, whose average age of onset was 68.93. The crude incidence rate was 39.35/100 000 in male, which was higher than it in female, as 16.05/100 000. The difference showed statistical significance (U = 7.32, P < 0.01). The standardized incidence rates were 21.98/100 000 and 6.96/100 000 in male and female, respectively. The difference showed statistical significance (U = 221.76, P < 0.01). There were 2427 PLC death cases in total, including 1734 male death cases and 693 female death cases. The crude mortality rate was 34.71/100 000 in male and 14.64/100 000 in female, whose difference were statistically significant (U = 6.68, P < 0.01). The standardized mortality rate was 19.16/100 000 in male and 6.06/100 000 in female, whose difference were statistically significant (U = 207.18, P < 0.01). The incidence and mortality rates both increased apparently since males aging over 35 and females over 45. The 1 - 5 year survival rates of PLC patients were 33.95%, 23.11%, 17.04%, 14.42% and 12.29%, respectively. In the surgical excision treatment group (321 cases), the 1 - 5 year survival rates were separately 66.78%, 52.87%, 41.88%, 33.57% and 32.64%; while in the non-surgical treatment group (2405 cases), the 1 - 5 year survival rates were separately 29.04%, 18.58%, 13.30%, 11.16% and 9.01%. The differences in 1 - 5 year survival rates between surgical and non-surgical groups all showed statistical significance (U = 12.78, 10.52, 8.28, 5.56 and 5.12, respectively, P < 0.01). CONCLUSION: The incidence of PLC was close to its mortality in Yangpu district of Shanghai. The male incidence and mortality rates were significantly higher than female corresponding rates. The surgical excision treatment could improve the prognosis of PLC.