Influence of cancer-directed surgery on the prognosis of liver metastases from gastric cancer.

There are controversial about the application of cancer-directed surgery (CDS) in patients with liver metastases from gastric cancer, with improved responses to chemotherapy and targeted treatments, the role of CDS in metastatic gastric cancer to the liver needs to be revisited. This study aimed to evaluate the effect of CDS on patients with liver metastases from gastric cancer. Data for patients with liver metastases from gastric cancer were extracted from the population-based Surveillance, Epidemiology, and End Results (SEER) database. A total of 958 individuals were enrolled, 285 in the CDS group and 673 in the non-cancer guided surgery (Non-CDS) group. Following propensity score matching (PSM) analysis at 1:1 in the two groups,285 were included in the survival analysis for each group. Kaplan-Meier values and Cox proportional risk models were used to estimate the effect of CDS on patients' prognoses. Compared with the Non-CDS group, the CDS group significantly prolonged the median overall survival from 4 months (95% confidence interval [CI] 3-5) to 11 months (95% CI 8-12), p value < 0.001. Overall survival (OS) at 1 year was higher in the CDS group than in the Non-CDS group, at 44% (95 CI 38-50) and 25% (95 CI 20-30), respectively. OS at 3 years was also higher in the CDS group than in the Non-CDS group, at 24% (95 CI 19-29) and 6% (95 CI 3-9), respectively. Multivariate analysis showed that Non-CDS (hazard ratio[HR] = 2.26, 95% CI 1.88-2.72, p value < 0.001) was an adverse independent prognostic factor for patients. This study concludes that CDS prolonged survival in patients with gastric cancer with liver metastases. Due to the lack of information on the quality of life, biomarkers, targeted therapies, and immunotherapy in the SEER database, the observed improved survival rates following CDS of hepatic metastasis from gastric cancer requires prospective studies that take these factors into account to properly address the survival advantages and impact on quality of life of such a method.

Clinical value of combined plasma brain natriuretic peptide and serum cystatin C measurement on the prediction of heart failure in patients after acute myocardial infarction.

This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.

Clinical value of combined plasma brain natriuretic peptide and serum cystatin C measurement on the prediction of heart failure in patients after acute myocardial infarction

This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.

Red-jambo peel extract shows antiproliferative activity against HepG2 human hepatoma cells.

The peel of the red-jambo concentrates the majority of the bioactive compounds and antioxidant capacity of the fruit. Minor phenolic compounds in this part of the fruit are still unknown, as well as the effect of its extracts in in vitro and in vivo studies. In an ethanolic extract of red-jambo, a wider range of phenolic compounds was investigated and the antioxidant cellular antioxidant activity and inhibition of HepG2 cell proliferation were evaluated for the first time. Using HPLC-FLD/DAD for phenolic compounds determination, gallic acid, chlorogenic acid and (-)-epigallocatechin gallate were found for the first time in the peel of the red-jambo fruit. The anthocyanins found (cyanidin 3,5-diglucoside, cyanidin 3-glucoside and peonidin 3-glucoside) were the flavonoid class strongly correlated with the antioxidant capacity methods used in this study (cellular antioxidant activity and oxygen radical absorbance capacity). The ethanolic extract of the peel showed significant effect on reducing the tumoral cell growth and proliferation. Antiproliferative activity of phytochemicals showed no significant correlative relations with total phenolic compounds, flavonoids and anthocyanins, demonstrating which the antiproliferative effect of the extract could be due to the synergic action among the compounds in red-jambo peel.

Potent CYP3A4 Inhibitors Derived from Dillapiol and Sesamol.

Synthesis of 50 analogues of the natural insecticide synergists, dillapiol and sesamol, is reported. These were evaluated as potential insecticide synergists based on their inhibition of human CYP3A4. The most potent inhibitors have a relatively large hydrophobic substituent at either position 5 or 6 of these molecules. For example, 5-(benzyloxy)-6-(3-phenylsulfonyl)propyl)benzo[d][1,3]dioxole (18) and the diphenyl acetate of (6,7-dimethoxybenzo[d][1,3]dioxol-5-yl)propan-1-ol (5n) show inhibitory concentrations for 50% activity IC50 values of 0.086 and 0.2 µM, respectively. These compounds are 106 and 46 times more potent than dillapiol whose IC50 for the inhibition of CYP3A4 is 9.2 µM. The ortho-chloro analogue (8f), whose activity is 86 times the activity of dillapiol, is the most potent of the fourteen 5-(benzyloxy-6-(2 propenyl)benzo[d][1,3]dioxoles prepared for this study.

A Mechanism Study of NMDAR1 in A Rat Alzheimer Disease (AD) Model

ABSTRACT This study aimed to investigate the expression and mechanism of N- methyl -D- aspartate receptor 1 (NMDAR1) in the pathogenesis of Alzheimer disease (AD). Eighty adult Wistar rats were randomly divided into 4 groups (n=20 each) to receive an injection of 0, 5, 7 and 10 μl of 1 μg/μl amyloid-β 42 (Aβ1-42) in the hippocampus. Twenty rats in normal control group were injected with equal volume of saline. After 10 days, the hippocampus was isolated from 5 randomly selected rats in each group. The NMDAR1 protein and mRNA expression was determined by immunohistochemical staining and qRT-PCR. The aquaporin-1 (AQP-1) mRNA expression was also measured by qRT-PCR. We found that both NMDAR1 and AQP-1 expression in Aβ1-42 groups was increased in a dose-dependent manner. NMDAR1 and AQP-1 expression in 7 and 10 μl Aβ1-42 groups was significantly higher compared with 0 μl Aβ1-42 group (P <0.01). Further, the 10 μl Aβ1-42 group was randomly divided into 3 subgroups: AD-NMDA, AD-MK-801, and AD-Ctrl subgroup, which was given an intraperitoneal injection of NMDAR agonist NMDA, NMDAR antagonist MK-801 and saline, respectively. The relative APQ-1 expression in each subgroup was determined by qRT-PCR and Western blot analysis after 24 h. The AQP-1 expression was significantly decreased in AD-MK-801 group (P < 0.05), but was markedly increased in AD-NMDA group when compared with AD-Ctrl group (P <0.01). Our study suggested that expression abnormity of NMDAR1 is involved in the pathogenesis of AD. NMDAR1 might regulate the pathogenic process through stimulating the expression of AQP-1.

Sox2 function as a negative regulator to control HAMP expression.

BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore, it is an important goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.

Sox2 function as a negative regulator to control HAMP expression

BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.

Expanding Sca-1(+) mammary stem cell in the presence of oestrogen and growth hormone.

BACKGROUND: Sca-1 is controversial as a mammary stem cell marker in the literature, which may be due to the different isolation protocols and culture media used in different laboratories. The object of our study is to establish the Medium to promote the proliferation of mammary stem cell and explore the possibility of Sca-1 as mammary stem cell marker. METHODS: We used BM medium supplemented with different concentration of 17Β-oestradiol and GH to find out MaECM medium which promoted the proliferation of mouse mammary epithelial cells and inhibited the growth of fibroblasts. Flow cytometry was used to isolate Sca-1(+) and Sca-1(-) cell populations from cultured mammary epithelial cells. Mammary fat pad transplantation and Mammosphere- forming assay were done to confirm the stem cell potential of Sca-1(+) cells. Differentiating culture was used to detect the differentiation potential of Sca-1(+) cells. Real-time PCR was carried out to analyse the expression of mammary stem cell-related genes in Sca-1(+) cells. RESULTS: We first selected the medium suitable for mammary stem cell growth. Stem cell medium BM was used to culture mammary organoids, which generated many fibroblasts. We established MaECM medium supplemented with oestrogen and growth hormone (GH), in which oestrogen promoted mammary epithelial cell proliferation and inhibited fibroblast growth, and GH obviously enhanced the effect of oestrogen on mammary epithelial cell proliferation. Flow cytometry showed that 50% of cells were Sca-1(+) under the culture of MaECM medium. We confirmed that Sca-1(+) cells regenerated mammary outgrowths when transplanted in vivo, formed mammospheres in vitro and differentiated into luminal epithelial cells with milk-secreting function and myoepithelial cells under Matrigel culture. Furthermore, gene expression analysis by Real-time PCR revealed that Sca-1(+) cells expressed markedly higher levels of mammary stem cell-related genes in comparison to Sca-1(-) cells. CONCLUSION: Our research demonstrates that Sca-1(+) mammary stem cells can be more easily isolated when cultured in the presence of oestrogen and GH.

Cellular antioxidant activity of feijoada whole meal coupled with an in vitro digestion.

Consumption of plant food rich meals, such as feijoada, a traditional meal in Brazil, is associated with the reduction of chronic disease. The objectives of this study were to determine phytochemical content and antioxidant activity by chemical and cellular antioxidant assays (CAA) of feijoada with or without in vitro digestion. Feijoada showed no difference in phenolics and flavonoids after digestion. Bound and residue contributions to total phenolics were 20.9% and 32.2%, respectively, suggesting that phenolics reach the colon after intake. Flavonoids in residue and bound fractions represented 50% of total flavonoids. Antioxidant activity of feijoada without digestion was higher than that with digestion; however, it showed lower antiproliferative activity and CAA. Feijoada with in vitro digestion also yielded phenolics with higher CAA. Analyses of whole meals should be used to evaluate phytochemicals present in food mixtures consumed, especially with digestion models coupled with CAA resulting in information similar to those in physiological conditions.

Effect of processing on the phytochemical profiles and antioxidant activity of corn for production of masa, tortillas, and tortilla chips.

The phytochemical profiles (total phenolics, anthocyanins, ferulic acid, carotenoids) and antioxidant activities of five types of corn (white, yellow, high carotenoid, blue, and red) processed into masa, tortillas, and tortilla chips were studied. The nixtamalization process significantly (p < 0.05) reduced total phenolics and antioxidant activities when compared to raw grains. Nixtamalized grains exhibited higher concentration of free phenolics and soluble conjugated ferulic acid and had lower concentrations of bound phenolics and ferulic acid than unprocessed grains. Among processed products, there was little difference in the phytochemical contents and antioxidant activities. Among types of corn, the highest concentrations of total phenolics, ferulic acid, and antioxidant activity were observed in the high-carotenoid genotype followed by the regular yellow counterpart. The white corn contained the lowest amount of total phenolics and antioxidant activity. The pigmented blue corn had the highest anthocyanin concentration followed by the red counterpart. These findings suggest that lime-cooking significantly reduced the phytochemical content of nixtamalized products but released phenolics and ferulic acid.