Synthesis of 5-(1-Alkoxyalkylidene)tetronates by Direct Condensation Reactions of Tetronates with Thionolactones and Thionoesters.

We report a two-step approach to bicyclic and monocyclic 5-(1-alkoxyalkylidene)tetronates starting from lactones/esters. The method features the use of thionolactones and thionoesters as activated forms of lactones/esters that allows the direct condensation with tetronates via one-pot enolate formation, nucleophilic addition, S-methylation, and DBU-promoted elimination. The value of the method was demonstrated by the stereoselective syntheses of two natural products: 5,6-Z-fadyenolide (Z/E ratio = 6:1) and 9,10-methylenedioxy-5,6-Z-fadyenolide (Z/E ratio = 9:1).

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT­qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP­N2/XPD plasmid was transfected into human ESCC cell lines (EC9706 and EC109). The proliferation, apoptosis, migration and invasion of EC9706 or EC109 cells were assessed following transfection with the XPD overexpression plasmid. The chemosensitivity of EC9706 or EC109 cells to cisplatin or fluorouracil was evaluated by CCK­8 assay. The expression levels of phosphoinositide 3­kinase (PI3K)/AKT, nuclear factor (NF)­κB, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen­activated protein kinase (MAPK) signaling pathway­related genes were detected by RT­qPCR and western blot analysis. The results demonstrated that the expression level of XPD was markedly lower in ESCC tissue samples than in adjacent normal esophageal tissue samples. The pEGFP­N2/XPD plasmid was successfully transfected into EC9706 or EC109 cells, inducing XPD overexpression. A High XPD expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of EC9706 and EC109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p­AKT, c­Myc, Cyclin D1, Bcl­2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)­9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPD inhibits the growth and invasion of EC9706 and EC109 cells, whilst also enhancing the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for ESCC treatment and drug resistance.

Aberrant Interhemispheric Connectivity in Obstructive Sleep Apnea-Hypopnea Syndrome.

OBJECTIVE: To determine the changes in interhemispheric functional coordination in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) relative to controls, using a recently introduced method of analysis: voxel-mirrored homotopic connectivity (VMHC). METHODS: Twenty-nine patients with OSAHS and twenty-six normal sex-, age-, and education-matched controls were recruited and resting-state functional magnetic resonance imaging data were obtained. We employed VMHC to analyze the interhemispheric functional connectivity differences between groups. The z-values of alterations in VMHC in brain region were correlated with clinical characteristics. RESULTS: Compared with controls, patients with OSAHS had significantly higher scores for body mass index (t = 5.749, P < 0.001), apnea-hypopnea index (AHI; t = 7.706, P < 0.001), oxygen desaturation index (t = 6.041, P < 0.001), and Epworth sleepiness scale (t = 3.711, P < 0.001), but significantly lower scores on the Rey-Osterrieth complex figure test-immediate recall (t = -3.727, P < 0.05). On the same basis, the VMHC showed significant increases in bilateral calcarine cortex and precuneus. Moreover, significant, positive correlations were found in only these areas between the AHI and the VMHC change coefficients (r = 0.399, P = 0.032; r = 0.378, P = 0.043). CONCLUSION: We found a memory defect in patients with OSAHS. The correlation between the abnormal VMHC and the AHI in patients with OSAHS suggested that AHI might be a key factor in cognitive dysfunction, which might offer new insights into the neural pathophysiology underlying OSAHS-related cognitive deficits.

A network meta-analysis of eight chemotherapy regimens for treatment of advanced ovarian cancer.

This study compared the short-term efficacies of different chemotherapy regimens in the treatment of advanced ovarian cancer (AOC) through pair-wise and network meta-analyses (NMA). Randomized controlled trials (RCTs) identified in a comprehensive online literature search met our inclusion criteria. Direct and indirect evidence was combined to compare odds ratios (OR) and surfaces under the cumulative ranking curves (SUCRA) across the different treatment regimens. Twelve eligible RCTs were finally included, involving eight regimens (Paclitaxel + Carboplatin [PC], Gemcitabine + Carboplatin [GC], Carboplatin, Pegylated Liposomal Doxorubicin + Carboplatin [PLD + Carboplatin], Paclitaxel, Paclitaxel + Carboplatin + Topotecan [PC + Topotecan], Paclitaxel + Carboplatin + Epirubicin [PC + Epirubicin] and Docetaxel + Carboplatin [DC]). The NMA results revealed that in terms of overall response rate (ORR) and disease control rate (DCR), PC (ORR: OR=2.59, 95%CI=1.20-6.22; DCR: OR=2.58, 95%CI=1.05-6.82) and GC (ORR: OR=2.08, 95%CI=1.08-4.37; DCR: OR=2.43, 95%CI=1.07-5.80) were more effective against AOC than Carboplatin alone. Similarly, PC (OR=0.21, 95%CI=0.05-0.69), GC (OR=0.31, 95%CI=0.09-0.90) and PLD + Carboplatin (OR=0.22, 95%CI=0.04-0.92) slowed disease progression better than Carboplatin alone. We also found that PC was more efficacious against AOC than Carboplatin or Paclitaxel single-agent chemotherapy. Combination chemotherapy is thus recommended for AOC, and should guide subsequent drug development and treatment strategies.

Green tea and liver cancer risk: A meta-analysis of prospective cohort studies in Asian populations.

OBJECTIVES: The aim of this meta-analysis was to investigate whether an association existed between green tea consumption and the risk for liver cancer in prospective cohort studies in Asian populations. METHODS: Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science, and the Chinese Bio-medicine Database published before April 2015. Study-specific risk estimates for the highest versus non- or lowest and increment of daily cup of green tea consumption levels were combined based on fixed- or random-effects models. STATA 11.0 (Stata Corporation, College Station, TX, USA) software was used for statistical analysis. RESULTS: Nine prospective cohort articles involving 465,274 participants and 3694 cases of liver cancer from China, Japan, and Singapore were included. The summary relative risk (RR) indicated a significant association between the highest green tea consumption and reduced risk for liver cancer (summary RR, 0.88; 95% confidence interval [CI], 0.81-0.97). However, no statistically significant association was observed when analyzing daily consumption of one cup (summary RR, 0.97; 95% CI, 0.95-1.00). When stratified by sex, the protective effect of green tea consumption on risk for liver cancer was observed only in the group of women (summary RR, 0.78; 95% CI, 0.64-0.96), but not in men (summary RR, 0.89; 95% CI, 0.79-1.00). CONCLUSIONS: The present analysis indicated the preventive effects of green tea intake on the risk for liver cancer in female Asian populations. However, additional studies are needed to make a convincing case for this association.

[Effect of cadmium on estrogen receptor from rat uterus in vitro.].

OBJECTIVE: To investigate the effect of cadmium (Cd) on estrogen receptor and to assess its endocrine disrupting action. METHODS: The estrogen receptor rich supernatant was prepared from the ovariectomized Sprague-Dawley rats. The effects of cadmium on estrogen binding were performed using a sing-dose ligand-binding assay. Extract from uterus were treated with various concentrations of cadmium (0, 10(-3), 10(-5) or 10(-7) mol/L) for various pre-incubation time (0, 30, 60, 90 min) by means of orthogonal experimental design with orthogonal layout of L16(4(5)) (the experiment was repeated for 5 times). In addition to the radioinert competitor, each assay included a zero tube and a DES standard curve for quality control purpose. Data for cadmium and the DES standard curve were plotted as percent [3H]-E2 bound versus log (molar concentration), and the IC50 for cadmium was determined. The RBA for cadmium was calculated by dividing the IC50 of DES in terms of the IC50 of cadmium. RESULTS: Cadmium could not block the binding of estradiol to the receptor because hormone binding did not change with increasing cadmium concentration or increasing preincubation time. The results showed that the binding of [3H]-estradiol to uterine cytosols was not significant (P > 0.05). The Bmax (its unit is pmol/mg protein) of various concentrations of cadmium (0, 10(-3), 10(-5) or 10(-7) mol/L) for pre-incubating 0 min is 203.15 +/- 75.16, 203.41 +/- 22.78, 220.82 +/- 45.35, 209.10 +/- 49.66 respectively; The Bmax of them for pre-incubating 30 min is 215.67 +/- 92.97, 139.79 +/- 53.78, 205.27 +/- 23.60, 172.63 +/- 55.09 respectively. The Bmax of them for pre-incubating 60 min is 197.11 +/- 50.68, 203.24 +/- 66.33, 183.92 +/- 31.89, 183.33 +/- 32.70, respectively. The Bmax of them for pre-incubating 90 min is 229.69 +/- 76.88, 175.70 +/- 70.28, 164.26 +/- 24.46, 150.78 +/- 65.97 respectively. Mean IC50 for cadmium is 10(-4) - 10(-3) M. If the affinities of DES binding to estrogen receptors was taken to be 100%, the relative binding affinities of cadmium was 10(-6) - 10(-7). The results indicated that cadmium had only a very poor affinity with estrogen receptor. CONCLUSION: In vitro assay cadmium did not have distinct disrupting effect on binding of estradiol to estrogen receptors from rat uterine.