ABSTRACT
Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3' untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.
ABSTRACT
Objective:To investigate the effect of degassing and peroxidation on metal-ceramic bonding strength of Pd-Ag alloy. Methods:The metal-ceramic interface of group A (peroxidation)and B (degassing)was investigated under scanning electronic micro-scope(SEM)and energy dispersive spectrum (EDS).The bond strength between metal and ceramics was measured using a three-point bend test according to ISO9693.Results:The formation of nodules on the surface of alloy specimens was observed in both groups by SEM.The nodules on the specimens of group A were more densely than those of group B.The diameter of nodules in group B was 1 .5μm approximately.The interface of the metal-ceramic specimens had a clear transition porcelain layer and no hole or slit was present. The mean bonding strength of group A and B was (45.97 ±3.92)MPa and (49.1 1 ±6.42)MPa respectively(P=0.031 ).Conclu-sion:Degassing can improve metal-ceramic bonding strength of Pd-Ag alloy significantly.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the inhibitory effect of ampelopsin (AMP) combined with adriamycin (ADR) on growth of human leukemia multidrug resistant cell line K562/ADR.</p><p><b>METHOD</b>MTT assay was used to detect the effect of AMP on the cytotoxicity of ADR. Jin's formula was used to analyze the effect of combined drug therapy. The expression of P-glycoprotein (P-gp) on cell membrane of K562/ADR was detected using PE-labeled antibody. Flow cytometry was used to determine the influence of AMP on the intracellular accumulation of ADR.</p><p><b>RESULT</b>AMP at the concentration of 1.25 to 5 mg x L(-1) could significantly reverse the multidrug resistance (MDR) to ADR in K562/ADR cells. Co-administration of 1.25 mg x L(-1) AMP and low concentrations of ADR showed an antagonistic effect, while there was an additional to synergistic effect when the concentration of AMP was above 2.5 mg x L(-1). AMP could decrease the expression of P-gp in a concentration-dependent manner and increase the intracellular accumulation of ADR in K562/ADR cells.</p><p><b>CONCLUSION</b>AMP could increased the cytotoxicity and the intracellular accumulation of chemotherapeutic drugs in MDR associated tumor cells through inhibiting the efflux of drugs by P-gp. AMP may be a promising MDR modulator.</p>
Subject(s)
Animals , Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Antineoplastic Agents , Metabolism , Pharmacology , Cell Line, Tumor , Cell Proliferation , Doxorubicin , Metabolism , Pharmacology , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Flavonoids , Pharmacology , Gene Expression Regulation, Neoplastic , Intracellular Space , MetabolismABSTRACT
Aim To investigate the release feature of ginsenoside Rd solid lipid nanoparticles (Rd-SLN) in vitro,and to clarify the difference in absorption of Rd-SLN from varied rat intestinal segments and pharmacokinetic properties in vivo. Methods Dialysis method was used to determine ginsenoside Rd release rate from nanoparticles in vitro. Perfusion method was used to study the intestinal absorption of Rd-SLN in rat. HPLC assay was established to determine the concentration of ginsenoside Rd in plasma. After intragastric administration,the concentrations of drug in rat blood at different time points were recorded to investigate the absorption and pharmacokinetics of Rd-SLN. Results The release of ginsenoside Rd from Rd-SLN was slowed down and presented the property of sustained release. There was no significant difference between the absorption rate of Rd-SLN and control solution in duodenum and jejunum. However,it was obviously different in ileum and colon. Comparing with other intestinal segments,significantly higher percentage of Rd-SLN was absorbed in colon. In Rd-SLN group,the concentration of ginsenoside Rd in blood was maintained,and the Cmax,MRT,AUMC,and AUC were all increased. Conclusions Rd-SLN possesses sustained-release effect. The colon is the preferable absorption site for Rd-SLN in intestinal tract. Rd-SLN can enhance the oral bioavailability of ginsenoside Rd.
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Objective: To determine the content of sanguinarine and chelerythrine in Macleaya microcarpa(Maxim) Fedde. Methods: RP-HPLC was adopted, kromasil C 18 column (150mm?4.6mm.5?m) with a mobile phase acetonitrile-0.1%(V/V) phosphoric acid solution(25∶75) by UV detector at 270nm. Results: The average recoveries of chelerythrine and sanguinarine were 90.2%,92.8%,RSD were 1.5%,2.4% respectively. Conclusion: A simple, rapid and sensitive method with good precision was established.