Latest ArticlesFree fatty acid receptor 1 (FFAR1), also known as G protein-coupled receptor 40 (GPR40), is a receptor for diverse free fatty acids. This review aims at summarizing effects and mechanisms of FFAR1 on insulin secretion and related blood glucose and lipids metabolism. FFAR1 is involved in the occurrence and development of type 2 diabetes, but its specific mechanism has not been clarified. FFAR1 is expressed in the wide variety of issues, especially β-cells in the pancreatic islets, as well as α-cells in islets, central nervous tissue, subcutaneous fat, skeletal muscle, gastrointestinal tract, etc. FFAR1 can act on islet β-cells to promote the secretion of insulin, promote α-cells on glucagon secretion, and regulate the secretion of endocrine cells in the gastrointestinal tract to balance the level of glucose and lipids. Existing research found that FFAR1 agonists have significant advantages. They promote insulin release, reduce weight and protect pancreatic β-cells, and have no risk of hypoglycemia. To in-depth understand the role of FFAR1 as a drug target in the treatment of diabetes, further pharmacological studies are still needed in order to obtain safer and more effective drugs against type 2 diabetes.
Multidrug resistance (MDR) seriously affects the clinical efficacy of chemotherapeutic drugs. One of the main mechanisms of MDR is the overexpression of P-glycoprotein (P-gp) in tumor cells that reduces the intracellular drug concentrations and limits the effective use of chemotherapeutic drugs. Accordingly, application of P-gp inhibitors that can reverse tumor MDR is an effective strategy to enhance the anti-tumor effect of chemotherapeutic drugs. In recent years, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) has been widely applied as the potential P-gp inhibitor for its excellent P-gp inhibition effect as well as good safety. In this paper, we reviewed the P-gp inhibitors, the mechanisms of TPGS in reversing P-gp-mediated MDR and the application of TPGS-based nano-drug delivery system.
Anthraquinones are not only the main active constituents but also the index components for the quality control of Rhei Radix et Rhizoma. To study the anthraquinone biosynthesis, Rheum palmatum L. seedlings were subjected to a high-throughput transcriptomic sequencing analysis by Illumina HiSeqTM 2000 150PE. The Illumina sequencing generated a total of 11.04 G clean data resulting in 736 309 74 clean reads, deposited in the sequence read archive (SRA accession SRP160030). Trinity do novo assembly yielded 93 646 unigenes, with an average of 1 108 nt. Functional annotation revealed that all unigenes were successfully annotated in the NR, NT, Swiss-port, PFAM, and KOG databases. GO enrichments showed that 57 subgroups were involved in biological process, cellular component, and molecular function. KEGG analysis indicated that 1 107 unigenes were implicated in 19 standard secondary metabolic pathways. 172 unigenes were analyzed to encode 28 key enzymes during the MVA, MEP, shikimic acid, and polyketide pathways related to anthraquinone biosynthesis. 125 CYP450 and 73 UGTs unigenes were related the modification of secondary metabolites in R. palmatum L. Furthermore, seven unigenes with full length cDNAs were successfully verified by RT-PCR and sequencing analyses. Then, MISA prediction produced a number of 18 885 simple sequence repeats (SSRs). Herein, the transcriptomic gene expression profiles of R. palmatum L. and candidate genes during the anthraquinone biosynthesis pathway were obtained for the first time. The results provided basic information for subsequent gene function characterization, secondary metabolic pathway analysis, and anthraquinone biosynthesis and regulation elucidation in R. palmatum L.
Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with high mortality and increased prevalence. The target therapy of pulmonary hypertension is mainly dependent on vasodilation, but how to improve vascular remodeling with stem cell therapy has not been fully understood. Over the past ten years, the researches on endothelial progenitor cells, mesenchymal stem cells and pluripotent cells have brought the hope to patients with pulmonary hypertension. This article mainly introduces the latest progress of stem cell technology in the intervention of pulmonary hypertension, and discusses the problems in the application.
Indoleamine 2, 3-dioxygenase 1 (IDO1) is a key enzyme of L-tryptophan metabolic oxidation pathway, in which the L-tryptophan is transformed into N-formyl kynurenine by oxidative cleavage. IDO1 is considered as a potential target for the development of cancer immunotherapeutic molecules. Up to now, at least 10 drug candidates have been advanced into clinical research. In this review, the binding mode and structure-activity relationships of the representative IDO1 small molecule inhibitors were summarized according the characteristics of chemical structures. Hopefully, this review could provide some insights for further development of novel IDO1 inhibitors.
This study is aimed to investigate the potential mechanisms of herceptin-acquired resistance and curcumin to reverse resistance in NCI N87/R gastric cancer cells. Western blot was used to evaluate the effect of curcumin on the expression of IκBα, NF-κBp65, HER-2, caspase-3, Bcl-2 and Bax in herceptin resistant cells; Annexin V-FITC/PI was exploited to analyze the effect of curcumin on cell apoptosis; Caspase kit was used to evaluate the effect of curcumin on the enzymatic activity of caspase-3, 8 and 9. The results showed a low expression of IκBα in the cytoplasm and a high expression of NF-κBp65 in the nucleus of NCI N87/R cells. Correspondingly, inhibition of NF-κB pathway by EVP4593, a specific NF-κB inhibitor, preferentially reduced cell viability of NCI N87/R cells, indicating the activation of NF-κB pathway in NCI N87/R cells. Curcumin preferentially reduced cell proliferation and inhibited NF-κB signaling pathway of NCI N87/R cells, downregulated the expression of HER-2 and Bcl-2, upregulated the expression of Bax, increased the activity of caspase-3, 8 and 9. Taken together, our study demonstrates the correlation between herceptin resistance acquirement of NCI N87 cells and the activation of NF-κB pathway. Moreover, curcumin reverses herceptin resistance of NCI N87 cells possibly by inhibiting NF-κB pathway and inducing cell apoptosis.
Rabdosia japonica(Burm.f.) Hara var.glaucocalyx(Maxim.) Hara is a traditional Chinese medicine, and is known to have anti-tumor effects. This study aims to investigate the effect of glaucocalyxin A (GLA), a diterpenoids extracted from Glaucocalyx Hara, on apoptosis of glioma cells and its mechanism. This study investigated the molecular signaling mechanism of GLA-induced glioma cell apoptosis by analyzing survival rate of C6 rat glioma cells, cell morphology, colony formation ability, interference ribonucleic acid, polymerase chain reaction, and Western blot. The result showed that in the presentce of GLA, the survival rate of C6 rat glioma cells decreased significantly, while the expression of guanine nucleotide-exchange factor-H1 was up-regulated, causing phosphorylation of extracellular regulated protein kinases proteins and apoptosis. Hence, the mechanism of GLA-induced glioma cell apoptosis was the GEF-H1/ERK pathway.
Forsythia suspensa is a herbal medicine that widely used for heat-clearing and detoxification in clinical practice. However, the molecular mechanism of its heat-clearing and detoxifying effect is still unclear. Based on the theory and methods of network pharmacology, the efficacy of the heat-clearing and detoxification of Forsythia suspensa was analyzed in this study. A total of 114 of compounds in Forsythia suspensa were collected, and 15 of effective compounds were obtained by analyzing the bioavailability (OB) and drug-like properties (DL). Then 26 corresponding targets were obtained using reverse pharmacophore-docking method. Using the BioGPS database, the organ location of the target initially was revealed. The compound-targetdisease network model of Forsythia suspensa was constructed by using the Cytoscape, which showed that the material basis of the heat-clearing and detoxification of Forsythia suspensa was to synthesize and synergize the effects by combining various active ingredients of multiple targets, simultaneously. This study explains the scientific mechanism of the heat-clearing and detoxification of Forsythia suspensa, and provides a theoretical foundation for clinical rational usage of Forsythia suspensa.
In this study, twenty containing ethylenediamine groups derivatives of oleanolic acid (OA) were synthesized, their structures were determined by 1H NMR, 13C NMR and HR-MS. The anti-tumor activities in HepG2 and SGC7901 cells were evaluated by MTT assay. The results showed that all compounds exhibited anti-tumor activity, compounds Ⅰ6, Ⅰ8 and Ⅰ9 exhibited significant anti-tumor activities with IC50 values of 16.7, 9.8 and 6.3 μmol·L-1, respectively. Molecular docking studies showed that compounds Ⅰ6-Ⅰ9 produce higher combining ability with VEGFR. Compound Ⅰ6-Ⅰ9 were further evaluated for the inhibitory activity against VEGFR-2, the result showed Ⅰ9 had a strong inhibitory effect on VEGFR with IC50 values of 0.56 μmol·L-1.
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