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A series of novel 1,3,4-oxadiazole-artemisinin hybrids have been designed and synthesized. An MTT assay revealed that most of tested hybrids showed more enhanced anti-proliferative activities than artemisinin, among which A8 had the superior potency with IC50 values ranging from 4.07 μM to 9.71 μM against five tested cancer cell lines. Cell colony formation assays showed that A8 could inhibit significantly more cell proliferation than artemisinin and 5-fluorouracil. Further mechanism studies reveal that A8 induces apoptosis and ferroptosis in MCF-7 cells in a dose-dependent manner, and CYPs inhibition assays reveal that A8 has a moderate inhibitory effect on CYP1A2 and CYP3A4 in the human body at 10 μM. The present work indicates that hybrid A8 may merit further investigation as a potential therapeutic agent. [ABSTRACT FROM AUTHOR]

Time-of-Use (TOU) electricity pricing provides an opportunity for industrial users to cut electricity costs. Although many methods for Economic Load Dispatch (ELD) under TOU pricing in continuous industrial processing have been proposed, there are still difficulties in batch-type processing, since power load units are not directly adjustable and nonlinearly depend on production planning and scheduling. In this paper, for hot rolling, a typical batch-type and energy intensive process in steel industry, a production scheduling optimization model for ELD is proposed under TOU pricing, in which the objective is to minimize electricity costs while considering penalties caused by jumps between adjacent slabs. A NSGA-II based multiobjective production scheduling algorithm is developed to obtain Pareto optimal solutions, and then TOPSIS based multicriteria decision-making is performed to recommend an optimal solution to facilitate field operation. Experimental results and analyses show that the proposed method cuts electricity costs in production, especially in case of allowance for penalty score increase in a certain range. Further analyses show that the proposed method has effect on peak load regulation of power grid. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Annona muricata L. is used to treat cancer in some countries. Extracts of Annona muricata have been shown to cause apoptosis of various cancer cells in vitro , and inhibit tumor growth in vivo in animal models. However, the molecular mechanisms underlying its anti-cancer and apoptotic effects of the herb remain to be explored. Aim of study The study investigated the molecular mechanisms underlying liver cancer cell apoptosis triggered by the ethanol extract of leaves of Annona muricata L. Materials and methods Liver cancer HepG2 cells were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry and TUNEL assays were performed to confirm apoptosis. We employed functional proteomic analysis to delineate molecular pathways underlying apoptosis triggered by the herbal extract. Results We showed that the extract was able to reduce viability and trigger apoptosis of the cancer cells. Proteomic analysis identified 14 proteins associated with the extract-elicited apoptosis, which included the increased expression levels of HSP70, GRP94 and DPI-related protein 5. Western blot analysis confirmed that the extract did up-regulated the protein levels of HSP70 and GRP94. Results from bioinformatic annotation pulled out two molecular pathways for the extract, which, notably, included endoplasmic reticulum (ER) stress which was evidenced by the up-regulation of HSP70, GRP94 and PDI-related protein 5. Further examinations of typical protein signaling events in ER stress using western blot analysis have shown that the extract up-regulated the phorsphorelation of PERK and eIF2α as well as the expression level of Bip and CHOP. Conclusion Our results indicate that the ethanol extract of leaves of Annona muricata L. causes apoptosis of liver cancer cells through ER stress pathway, which supports the ethnomedicinal use of this herb as an alternative or complementary therapy for cancer. [ABSTRACT FROM AUTHOR]

Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1) in vitro studies using cell line models; (2) serum pharmacology; (3) in vivo studies using animal models; and (4) clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance. [ABSTRACT FROM AUTHOR]

Aim: To investigate the prevalence and risk factors of polypoid lesions of gallbladder (PLG) among the health examinees in the Shanghai region, China., Methods: A total of 11,816 subjects who underwent health examinations in our hospital between August 2010 and February 2011 were analyzed retrospectively. Among them, there were 7174 men and 4642 women. PLG was diagnosed by the real-time ultrasonography. Those with the body mass index (BMI) ≥ 28 were considered to be obese. Blood biochemical indices were detected with the fully automatic biochemical analyzer and hepatitis B surface antigen (HBsAg) was tested by the automated enzyme immunoassay. The correlations between the prevalence of PLG and age, sex, BMI, serum cholesterol (T-Cho), triglycerides (TG), blood sugar, HBsAg, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), gallstone and fatty liver were investigated. After univariate analysis of 11 variables, stepwise logistic regression analysis was performed to explore the risk factors of PLG., Results: There was a significant difference in sex, T-Cho, HBsAg, HDL-C, LDL-C and fatty liver between the PLG-positive group and the PLG-negative group (332/163 vs 6842/4479, P = 0.003; 22/473 vs 295/11,026, P =0.013; 92/403 vs 993/10,328, P = 0.001; 47/448 vs 332/10,989, P = 0.001; 32/463 vs 381/10,940, P = 0.001; 83/412 vs 3260/8061, P = 0.001). No significant difference was found in the age, BMI, TG, blood sugar and gallstone between the two groups (47.3 ± 26 vs 45.1 ± 33, P = 0.173; 59/436 vs 1097/10,224, P = 0.102; 52/443 vs 982/10,339, P = 0.158; 17/478 vs 295/11,026, P = 0.26; 24/471 vs 395/10,926, P = 0.109). Logistic regression analysis showed that the sex, HBsAg and HDL-C were independent risk factors for the development of PLG in a descending order of HDL-C > HBsAg > sex., Conclusion: In healthy people, the male gender, positive HBsAg, and low HDL-C confer higher risks of PLG development.