Latest ArticlesCalcium-activated chloride channel (CaCC) is an anion channel, widely distributed in the human body, taking a part in cell functions including secretion, heart muscle repolarization, nerve signal transmission and several physiological activities. The anoctamin 1 (ANO1) protein is the molecular basis of CaCC and the modification of ANO1 protein will produce a variety of pharmacological effects, such as analgesia, treating dysentery and asthma, even tumor proliferation and migration inhibition. In the past decade, many methods in screening of ANO1 regulators have been developed. Although a series of the ANO1-based CaCC regulatory molecules have been identified, the pharmacological effects of these molecules are not consistent. In this review, we introduce ANO1 protein regulators from many aspects including bio-test methods, structure-activity relationships, and the potential applications.
Using a UHPLC-TOF/MS method combined with software of Masslynx V4.1 and database in the literatures, a total of 20 polygala oligosaccharide esters (POEs) were identified in 60% ethanol extract of Kai Xin San (KXS-60%E). Furthermore, 14 POEs as well as 4 POE-metabolites were identified in rat plasma. The results revealed that POEs and POE-metabolites which were identified in rat plasma, were key components in KXS-60%E and the potential bioactive compounds for KXS action in the treatment of AD.
Bromodomain-containing proteins (BCPs) can specifically recognize acetylated lysine (KAc) in histones and other substrate proteins. Recently, several kinase inhibitors were found to inhibit bromodomains, such as the PLK1 inhibitor BI-2536 and the JAK2 inhibitor TG101209, which bind to BRD4 with IC50 values of 25 nmol·L-1 and 130 nmol·L-1, respectively. To obtain potent BRD4 inhibitors from inhibitor BI-2536, we used dihydroquinoxalin-2(1H)-one to replace the 7, 8-dihydropteridin-6(5H)-one in BI2536. By exploring the structure-activity relationships of the new dihydroquinoxalin-2(1H)-one structures, we obtained a novel phenyl side chain series of BRD4 inhibitors. We identified several potent BRD4 inhibitors, especially compounds 16, 22, 28 and 29, which had IC50 values below 100 nmol·L-1 in fluorescence anisotropy (FA) assays, indicating this series of compounds are worth to fruther investigation.
Anthocyanins has a high health benefits and biological activity, which can make the solution easily absorbed and has a bright color, beautiful appearance in oral liquid. However, due to its particularity antioxidant activity, it is easy to be affected by the external physical and chemical factors, and then oxidation, polymerization, degradation and other unstable phenomena occurs that seriously affect the stability of products and shelf life. The traditional methods of pH regulation, deoxygenation and light avoidance could not meet the demand of stable anthocyanins. Addition of stabilizer to anthocyanins is a new effective way to improve the stability of anthocyanins. This paper is prepared to summarize systematically the principle and application methods of anthocyanins stabilizers to explore the key technology of clarification and stabilization of traditional Chinese medicine in the natural oral liquid, which may provide theoretical support and technical reference for the development and utilization of anthocyanins stabilizer.
The flavin-containing monooxygenase (FMOs) is recognized as an important complimentary enzyme system next to the cytochrome P450 (CYP450), which catalyzes the metabolism of many xenobiotics (nucleophilic heteroatom-containing chemicals) and several endobiotics. This article provides a comprehensive introduction of FMOs including the biological characteristics, catalytic mechanism, substrate specificity, genetic polymorphisms. The effect of FMOs on drug metabolism and individual differences and relation with diseases are also mentioned. It is valuable for the discovery of therapeutic targets and design of new drug candidate.
Hepatocellular carcinoma (HCC) is the most common liver cancer, which is also the second leading cause of death in cancer. With the development of molecular biology and technology, gene therapy has become a new potential method to treat the cancer. As a viral gene-delivery system, the adeno-associated virus (AAV) is the most promising delivery vehicle for its high efficiency of infection, low pathogenicity and low immunogenicity. However, AAV has a wide range of host that may lead to side effects. Targeted gene therapy can achieve site-specific and high efficient gene expression, which avoids toxicity of systemic and non-targeted gene expression to improve the safety and efficacy of gene therapy. In this review, we provide an overview of the pathogenesis of HCC and the characteristics of AAV. Moreover, we discuss the targeting strategies currently employed in the gene therapy for HCC with a focus on targeting the transductional, transcriptional and posttranscriptional levels. New strategies are proposed for improving the quality of life and survival rate of patients with HCC.
Soluble resistance-related calcium-binding protein, SORCIN, is a 22 kDa calcium binding protein with "penta-EF hand", which participates in the regulation of intracellular calcium homeostasis in cells. SORCIN is highly expressed in many tissues such as hearts and brains. It is overexpressed in some of cancer tissues as well. Recently, a large amount of clinical data showed that SORCIN was closely related to drug resistance in cancer. Meanwhile, basic research found that SORCIN participates in the formation of multidrug resistance (MDR) and is related to severity and poor prognosis of tumors. Moreover, it may also regulate MDR induced by ATP-binding cassette transporters. Therefore, SORCIN is expected to become a new target for diagnosis and treatment of MDR. The present review summarizes recent progress in SORCIN study and its effect on MDR.
Fragments of the human indoleamine 2, 3-dioxygenase 1 (IDO1) gene 5'-UTR (untranslated 1 245 bp region) promoters were amplified by PCR and cloned into pGL4.20 vector in the construction of reporter vector pGL4-IDO1-luc. A549 cells were transfected with the constructed plasmid and IDO1 inhibitor screening model was established with dual-luciferase reporter assay. Based on the model, we screened natural small molecules which could down-regulate the expression of IDO1 on tumor cells. The anti-tumor activities were examined by MTT, Western blotting and lactic dehydrogenase (LDH) release assays. Toosendanin (NS-180) down regulated the IDO1 expression and inhibited IFN-γ-induced STAT1 and STAT3 phosphorylation in A549 cells. Moreover, NS-180 significantly increased the cytotoxicity of co-cultured NK cells on A549 cells in LDH release assays. In summary, NS-180 is a novel and potent IDO1 inhibitor, which has an antitumor activity for cancer immunotherapies.
The present study was aimed to investigate the role and mechanisms of kallistatin in protection against oxidative stress-induced hepatic stellate cell damage. The effects of kallistatin on the viability, the intracellular superoxide level and Akt, eNOS molecules were investigated in human hepatic stellate cell line LX-2 and the incompletely activated primary rat hepatic stellate cells. Two different oxidative-stress related models, the hydrogen peroxide model and the iron-overload model were used in the experiments. The results show that kallistatin protected the hepatic stellate cells from oxidative damage and repaired the cell damage by oxidative stress. The main mechanism is antioxidant activity of kallistatin, which can remove the oxidized substances inside the cells. On the other way, kallistatin activates Akt and eNOS molecules to generate the antioxidant effect. Our results help to explore new anti-fibrotic targets.
Ellipticine is an alkaloid isolated from natural product with cytotoxicity, which has antitumor and anti-aids activity. Since it was first identified in 1959, a great deal of effort has been devoted to the development of various approaches for synthesis of ellipticine. This review provides a summary for synthesis approaches of ellipticine from different starting materials. The antitumor mechanism and structure-activity relationship are also discussed.
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