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Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.
Assuntos
Humanos , Microbioma Gastrointestinal , Medicina Tradicional Chinesa , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Objective: To investigate the effect of modified Lichongtang combined with 5-fluorouracil (5-FU) on epithelial-mesenchymal transition (EMT) of human hepatoma HepG2 cells. Method: The growth of HepG2 cells was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and the effect of Chinese medicine and 5-FU alone or combined use on the growth of HepG2 cells was analyzed by the principle of efficacy. The growth curves of HepG2 cells were plotted to determine the relationship between drug effect and combination index as well as the interaction between drugs. Scratch test was used to detect the effect of modified Lichongtang combined with 5-FU on the migration of HepG2 cells. Cell invasion assay (transwell chamber) was used to detect the effect of modified Lichongtang combined with 5-FU on the invasion ability of HepG2 cells. Real-time quantitative polymerase chain reaction (PCR) was used to detect the effect of modified Lichongtang combined with 5-FU on EMT-related genes E-cadherin, N-cadherin and Zinc finger transcription factors (snail, twist) mRNA expression after 24 hours of treatment on HepG2 cells. The expression levels of E-cadherin, N-cadherin, Snail and Vimentin in HepG2 cells were detected by Western blot after treatment by modified Lichongtang combined with 5-FU for 24 hours. Result: MTT assay showed that with the increase of drug concentration, the inhibitory effect of modified Lichongtang, 5-FU alone or combined use on HepG2 cell growth was also increased. Statistical analysis showed that the combined use of these two drugs at a low dosage could produce better synergistic effect on HepG2 cells after 24 hours of treatment. Therefore, modified Lichongtang and 5-FU were selected to treat HepG2 cells for 24 hours. 25%inhibitory concentration (IC25) was 800 mg·L-1 modified Lichongtang, 3.125 mg·L-15-FU. Blank group, 5-FU group, Lichongtang+5-FU group, and modified Lichongtang group were set for follow-up experiments. Scratch and invasion experiments showed that modified Lichongtang, 5-FU alone and combined use can inhibit HepG2 cell migration and invasion ability (PPPPPPPPPPConclusion: Modified Lichongtang combined with 5-FU can produce a better synergistic effect on HepG2 cells at a low dosage for 24 hours, and can significantly inhibit the migration and invasion of hepatocellular carcinoma cells, up-regulate the expression of E-cadherin, down-regulate the expression of N-cadherin, Snail, Vimentin and Twist in hepatocellular carcinoma cells. Inhibition of tumor cell proliferation, migration, invasion and EMT-related gene expression may be associated with enhancing the efficacy of chemotherapy drugs, and may act as one of the mechanisms for synergistic effect of modified Lichongtang combined with 5-FU.
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Objective:To discuss the effect of Yiqi Jianpi Huayu recipe (YQJPHY) combined with 5-fluorouracil(5-FU) on the growth and immune function of subcutaneous transplanted tumor in MFC tumor bearing 615 mice. Method:Twenty-four mice were inoculated subcutaneously to establish the transplanted tumor model of gastric cancer in mice, and then randomly divided into model control group, YQJPHY (20 g·kg-1)group, 5-FU (25 mg·kg-1) group and (YQJPHY+5-FU) combined group, with 6 rats in each group. After the last administration, the transplanted tumor, spleen and thymus were stripped completely. The tumor inhibition rate, thymus and spleen index were calculated. Flow cytometry was used to determine the content of myeloid-derived suppressor cells (MDSCs) and its subtype polykaryotype cells (PMN-MDSC), single karyotype cells (M-MDSC) in both peripheral blood and tumor tissue, and macrophages and their M1 type, M2 type, T lymphocyte, B lymphocyte, and natural killer cells (NK cells) in peripheral blood. Expressions of arginase-1(Arg-1) and inducible nitric oxide synthesis (iNOS) gene in tumor tissues were detected by Real-time PCR. Result:Compared with model control group, the weight of mice in YQJPHY group increased, whereas the weight of tumor, the weight of tumor, the index of thymus and spleen decreased in 5-FU group(PPPPPPPP+,CD4+,CD8+ T cell group decreased(PPPPPPConclusion:YQJPHY can better inhibit the growth of subcutaneous transplanted tumor when combined with 5-FU, and improve immune status after chemotherapy. The mechanism may be related to the decrease of MDSCs content and the increase of T cell and macrophages content.
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<p><b>OBJECTIVE</b>To explore the inhibitory effect of cinnamaldehyde on invasion capacities of human breast cancer cell line MDA-MB-435S and its relation with regulating the expression of miR-27a.</p><p><b>METHODS</b>The effect of cinnamaldehyde on invasive capacities of MDA-MB-435S was measured by Transwell matrigel invasion assay. The effect of miR-27a expression on invasive capabilities of MDA-MB-435S, the intervention of cinnamaldehyde in the miR-27a expression, and its relation with its effect on invasive capabilities were defected with liposome 2000 transinfection miRNA27a mimics/inhibitors, real time-polymerase chain reaction (Real-time PCR), and Transwell chamber model.</p><p><b>RESULTS</b>Compared with the control group, the number of cells passing through the transwell chamber was more significantly reduced after treated by cinnamaldehyde for 12 h (P < 0.05). The miR-27a expression was 962.07 times and 40% of that of the control group after transinfected by miR-27a mimics and miR-27a inhibitors. After transinfected by miR-27a inhibitors, the number of cells passing through the transwell chamber was more significantly reduced (P < 0.05). The miR-27a expression of MDA-MB-435S was down-regulated by 12-h treatment of cinnamaldehyde (2(-deltaCt) = 0.56, 0.18, 0.18, respectively). The number of miR-27a mimics transinfection pretreated MDA-MB-435S cells passing through the transwell chamber increased more obviously than the number of un-pretreated MDA-MB-435S cells in the control group (P < 0.05).</p><p><b>CONCLUSIONS</b>Cinnamaldehyde could inhibit invasive capabilities of human breast cancer cell line MDA-MB-435S. The over-expression of miR-27a played an important role in the invasive capability of MDA-MB-435S. The inhibition of cinnamaldehyde on invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a.</p>