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Abnormal aggregation of amyloid-β protein (Aβ) in brain plays a vital role in the occurrence of Alzheimer's disease (AD). Hence, inhibiting Aβ aggregation is one major tactic for therapy of AD. Previous studies have found that tolcapone can inhibit Aβ42 aggregation and reduce the cytotoxicity induced by Aβ42 aggregates, but clinical studies have found that tolcapone has strong liver toxicity. To reduce the liver toxicity of tolcapone, its side chain structure was modified to obtain its derivative phenethyl (E)-2-cyano-3-(3,4 dihydroxy-5-nitrobenzene)-acrylate (PCDNA). Thioflavin T (ThT) and atomic force microscopy (AFM) assays were used to explore the inhibitory effect of PCDNA on Aβ42 fibrillogenesis. The cytotoxicity assays were used to explore the inhibitory effect of PCDNA against the cytotoxicity induced by Aβ42 aggregates. In addition, the depolymerization effect of PCDNA on mature Aβ42 fibrils was also explored. Finally, molecular docking was used to explore the interaction between PCDNA and Aβ42 pentamer. These results lay the foundation for the study of the structural analogues of tolcapone as Aβ inhibitors.
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Aim To investigate the effect of liver X receptor (LXR) activation on the proliferation of hippocampal neural stem cells in global cerebral ischemia/reperfusion (I/R) mice,and its mechanisms.Methods A total of 75 C57BL/6 mice were randomly divided into three groups,namely the sham operation group,the cerebral I/R group and the cerebral I/R with TO901317 treatment (I/R + TO90) group.The I/R mouse model was induced via the bilateral common carotid artery occlusion.HE staining was used to detect the pathological changes in hippocampal CA1 region.Immunohistochemistry was executed to detect hippocampus DCX + cells.Immunofluorescence of BrdU was implemented to detect the proliferation neural stem cell.Morris water maze test was used to assess spatial learning and memory in mice.Western blot was used to detect the expression of hippocampus LXRα,LXRβ,ABCA1,p-ERK1/2,t-ERK1/2,p-CREB,t-CREB,BDNF.Results LXR activation improved cognitive recovery(P ＜0.01),and induced the proliferation of neural stem cells (P ＜ 0.01) in I/R mice.The expressions of hippocampal ABCA1,p-ERK1/2,p-CREB,BDNF in I/R + TO90 group mice also increased (P ＜ 0.01).Conclusions LXR activation can induce the proliferation of hippocampal neural stem cells and facilitate cognitive recovery following global cerebral I/R in mice,which may be related to the activation of hippocampal ERK1/2-CREB-BDNF pathway and then promoting endogenous neurogenesis in the hippocampus DG region of I/R mice.
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Aim To evaluate the effects of salvianolic acid B ( Sal B ) on bone metabolism and its potential mechanism in high fat diet ( HFD) mice.Methods Thirty C57BL/6J male mice were divided into three groups with 10 mice each, namely normal , HFD and HFD+Sal B.HFD and HFD+Sal B mice were treated with HFD, and HFD+Sal B group mice were also with Sal B (125 mg· kg -1· d-1).After 12 weeks' treat-ment, femurs were harvested .The effects of Sal B on biomechanical strength were evaluated by biomechani-cal tests, and the effects of Sal B on bone microstruc-ture were evaluated by Safranin O/fast green staining and hematoxylin and eosin staining .The expression of nuclear factor-kappa B ( NF-κB)-p65 and NADPH ox-idase 4 ( Nox4 ) and cathepsin K in femurs was deter-mined by immunohistochemical staining . Results Maximum load and elastic load significantly decreased ,and the trabeculae became thinner and irregular in the femurs of HFD mice , while Sal B treatment could re-verse the descending biomechanical strength and the disorganized femurs bone micro-structures in HFD mice.In addition, the expressions of Nox4, NF-κB-p65 and cathepsin Kmarkedly increased in HFD mice , and Sal B possessed the ability to down-regulate the ex-pression of Nox4, NF-κB-p65, and cathepsin K in the femurs triggered by HFD .Conclusions Sal B treat-ment improves bone metabolism via regulating Nox 4/NF-κB/cathepsin K signaling pathway in HFD mice . The findings contribute to the understanding and exten-sion of the applications of Salvia miltiorrhiza and its constituents on osteoporosis .
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To investigate the difference in clinical efficacy and safety of different meropenem regimens on patients with serious infection in ICU. Then, 228 patients with serious infection in ICU were divided by random into control group [intermittent administration in 1000mg/30min single dose] and research group [continuous administration in 200mg/10min +800mg/180min], respectively. The blood concentration of meropenem were recorded in two groups at different time points, and difference in treatment effectiveness, iconographic effectiveness, bacterial eradication rate, 28-day survival rate and many other clinical scoring indices [SOFA, APACHEII, CPIS, and SIRS] were compared between two groups. There were 212 patients completing the whole research, including 104 patients in research group and 108 patients in control group. The difference in treatment effectiveness [77.8% vs 53.7%], iconographic effectiveness [51.0% vs 18.5%], and 28-day survival rate [86.5% vs 64.8%] between two groups performed statistical significance [P<0.05]. However, the difference in bacterial eradication rate [48.0% vs 46.3%] performed no statistical significance. Eight hours later, the difference in average blood concentration between two groups [9.61 +/- 3.63 micro g/ml vs 1.5 +/- 0.51 micro g/ml] showed statistical significance. Moreover, the difference in clinical scoring indices except APACHE II score between two groups performed statistical significance. It was helpful to maintain the blood concentration of meropenem by extending the transfusion time. Therefore, it could increase the clinical cure rate and 28-day survival of patients with serious infection in ICU, improve clinical indices, and reduce the usage amount of antibiotics
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OBJECTIVE@#To study the role of microRNA-126 in the development of lung cancer.@*METHODS@#The biological function of microRNA-126 was detected using EdU assay and CCK-8 assay; the target gene of microRNA-126 was analyzed using real time RT-PCR and Western blot assay.@*RESULTS@#In A549 cell line, overexpression of microRNA-126 inhibits the proliferation rate; VEGF is the target gene of microRNA-126; microRNA-126 exerts its function via regulating VEGF protein level.@*CONCLUSIONS@#microRNA-126 inhibits the proliferation in A549 cell line.
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Objective: To study the role of microRNA-126 in the development of lung cancer. Methods: The biological function of microRNA-126 was detected using EdU assay and CCK-8 assay; the target gene of microRNA-126 was analyzed using real time RT-PCR and Western blot assay. Results: In A549 cell line, overexpression of microRNA-126 inhibits the proliferation rate; VEGF is the target gene of microRNA-126; microRNA-126 exerts its function via regulating VEGF protein level. Conclusions: microRNA-126 inhibits the proliferation in A549 cell line.
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Objective: ITS2 barcoding was used to discriminate Zanthoxyli Radix and its adulterants to ensure the quality and clinical safety of this Chinese materia medica. Methods: The internal transcribed spacer 2 (ITS2) regions were amplified and sequenced bi-directionally. Then the obtained sequences were assembled using the CodonCode Aligner. The ITS2 regions were obtained using the hidden Markov model (HMM)-based annotation methods. The genetic distances of the ITS2 regions were computed in accordance with the kimura 2-parameter (K2P) model and Neighbor-joining (NJ) phylogenetic trees were constructed using MEGA5.0. Results: The length of ITS2 sequences of the plants in Zanthoxyli Radix and its adulterants were between 224 and 227 bp. Their mean intraspecific genetic distance (K2P distance) was lower than their mean interspecific genetic distance with the adulterants. The NJ trees showed that the roots of Zanthoxyli Radix could be easily distinguished from its adulterants. Conclusion: ITS2 barcode could be used to identify the roots of Zanthoxyli Radix and its adulterants effectively, and provide the important molecular evidence for the authentication of germplasm resources.
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<p><b>OBJECTIVE</b>To investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC) on TIP30 gene expression and the relationship between TIP30 expression and the sensitivity to 5-fluouracil (5-Fu) in colorectal cancer cells.</p><p><b>METHODS</b>The methylation profile of TIP30 gene in HCT116 colorectal cancer cells was determined by methylation-specific PCR. The levels of TIP30 mRNA and protein were determined by RT-PCR and Western blot after the 5-Aza-dC treatment. MTT assay was used to detect the chemosensitivity of HCT116 cells to 5-Fu.</p><p><b>RESULTS</b>TIP30 gene displayed complete DNA methylation in the HCT116 cells without 5-Aza-dC pretreatment. After the 5-Aza-dC treatment for 3 days, only demethylating PCR amplification product was detected and TIP30 gene showed DNA demethylation. With the prolongation of the time of removal of 5-Aza-dC treatment, methylated and demethylated PCR amplification products were observed and TIP30 gene displayed both DNA methylation and DNA demethylation in the colorectal cancer cells. At the day 10 after removal of 5-Aza-dC, methylating PCR amplification product appeared and TIP30 gene showed DNA methylation. No expressions of TIP30 mRNA and protein were detected in the HCT116 cells untreated with 5-Aza-dC. After the treatment of 5-Aza-dC for 3 d and then removed the 5-Aza-dC, the expressions of TIP30 mRNA and protein were increased obviously. With the prolonged time after 5-Aza-dC removal, the expressions of TIP30 mRNA and protein decreased and reached the lowest level on day 10. The IC50 values of 5-Fu were 41.62, 33.17 and 4.96 µg/ml in the HCT116 cells pretreated with 5-Aza-dC, d0 and d10 with the drug removal after drug treatment for 3 d, respectively.</p><p><b>CONCLUSIONS</b>The results of this study show that the expression of TIP30 gene may be associated with its DNA methylation status and may affect the sensitivity of colorectal cancer cells to 5-Fu.</p>
Subject(s)
Humans , Acetyltransferases , Genetics , Metabolism , Antimetabolites, Antineoplastic , Pharmacology , Azacitidine , Pharmacology , Cell Proliferation , CpG Islands , Genetics , DNA Methylation , Drug Resistance, Neoplasm , Fluorouracil , Pharmacology , Gene Expression Regulation, Neoplastic , HCT116 Cells , Inhibitory Concentration 50 , RNA, Messenger , Metabolism , Transcription Factors , Genetics , MetabolismABSTRACT
<p><b>BACKGROUND</b>Multidrug resistance (MDR) is a main reason for paclitaxel (TAX) treatment failure. Indirubin-3'-monoxime (IRO) and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance.</p><p><b>METHODS</b>In this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 cells using semi-quantitative methods.</p><p><b>RESULTS</b>There was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 µmol/L for IRO and 100 µmol/L for Matrine. So 4 µmol/L of IRO and 100 µmol/L of Matrine were considered as the reversal dosage. When 4 µmol/L of IRO or 100 µmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 (43.56/22.6 nmol/L) and 1.74 (43.56/25.0 nmol/L), respectively. The mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly (P < 0.05) after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone.</p><p><b>CONCLUSION</b>The decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.</p>