الملخص
Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
الموضوعات
Animals , Humans , Mice , Apoptosis , Cause of Death , Cell Proliferation , Colon , Colorectal Neoplasms , Fluorouracil , Heterografts , In Vitro Techniques , Repression, Psychology , RNA, Small Interferingالملخص
Objective To investigate the changes of relevant characteristics in the Beagle model of type 2 diabetes mellitus(T2DM) induced by high fat diet and low dose streptozotocin (STZ) injection. Methods Thirty male Beagles were randomly divided into three groups:(1) Control group (n=10), fed with a standard chow. (2) High fat diet group (n=10), fed with high fat diet. (3) Model group (n=10), fed with high fat diet for two months and then given STZ in?jection. Lee index, fasting blood glucose, serum insulin levels, urine glucose and blood biochemical indexes were regularly detected. Oral glucose tolerance test ( OGTT) and histopathological examination were performed. Results After treatment for two months, the insulin resistance and dyslipidemia appeared and Lee index significantly increased in the high fat diet group and model group (P11?1 mmol/ L and were not restored at three hours, showed some pancreatic histological damages and diseases. Conclusions A beagle model of type 2 diabetes mellitus is construc?ted, exhibiting some characteristics of human type 2 diabetes mellitus such as hyperglycemia,hyperinsulinism,dyslipidemia and other typical features.
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Objective:To explore therapeutic effect of intravenous injection of propafenone on patients with paroxys‐mal supraventricular tachycardia (PSVT) and its safety .Methods :A total of 80 PSVT patients ,who were treated in our department of cardiology from Mar 2009 to Feb 2014 ,were selected .According to random number table meth‐od ,they were randomly and equally divided into propafenone group (received propafenone intravenously) and amio‐darone group (received amiodarone intravenously) .Heart rate ,cardioversion time ,clinical total effective rate and incidence rates of adverse reactions were recorded and compared between two groups before and 24h after treat‐ment .Results:There was no significant difference in total effective rate between two groups , P>0.05. Compared with amiodarone group ,there were significant reductions in cardioversion time [ (18.9 ± 3.2) min vs .(7.3 ± 1.0) min] , heart rate after treatment 24 h [ (99.6 ± 8.4) beats/min vs .(81.2 ± 5.9) beats/min] in propafenone group , P<0.05 both .Conclusion:Intravenous injections of propafenone and amiodarone possess similar therapeutic effect on paroxysmal supraventricular tachycardia ,but propafenone can achieve rapid cardioversion and reduce heart rate with satisfying safety ,which is worth further extending .
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Objective: To investigate the predictive value of an early inflammatory response factor, Rho kinase activity for left ventricle remodeling (LVR) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A total of 120 acute STEMI patients treated in our hospital from 2010-10 to 2013-06 were studied, all patients were ifrst time received primary percutaneous coronary intervention (PCI) with stent implantation. Rho kinase activity and B-type natriuretic peptide (BNP) were measured before PCI, echocardiography was conducted at 24 hours and 12 months after STEMI respectively to clarify LVR diagnosis. The patients were divided into 2 groups as LVR group, n=97 and Non-LVR group, n=23, the above indexes were compared between 2 groups. Results: The level of Rho kinase was higher in LVR group than that in Non-LVR group, P Conclusion: High Rho kinase activity could predict LVR in acute STEMI patients with primary PCI and stent implantation.
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The examinations of optical coherence tomography (OCT) images were obtained in 136 patients. Lactated Ringer's solution or physiological saline was used randomly as perfusate. Their electrocardiogram and cardiac enzymes were acquired to compare the safety and image quality of two perfusates.The incidence of ventricular arrhythmia and rise of cardiac enzymes were lower in the lactated Ringer's solution group than those in the physiological saline group.Yet the image quality of OCT had no difference.The use of lactated Ringer's solution as perfusate instead of physiological saline in OCT examination may protect the ischemic myocardium and reduce the incidence of complications.
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<p><b>OBJECTIVE</b>To investigate allergic reactions of traditional Chinese medicine (TCM) injections, and to determine the contents of serum IgE and histamine in sensitized animal. The correlation between the preceding contents in serum and allergic reactions may be found, thus offering experimental evidences for advancing the accuracy of anticipation by type I allergy.</p><p><b>METHOD</b>We carried out passive cutaneous anaphylaxis (PCA) tests,active systemic anaphylaxis (ASA) tests and anaphylactoid reactions using three TCM injections, and determined the contents of serum OVA-sIgE, total serum IgE and histamine in sensitized animals by ELISA method.</p><p><b>RESULT</b>The results of PCA test were negative, and there was no significant difference for total serum IgE level between experimental group and normal saline group. In the study of adjuvant effect in TCM injections + OVA (at the dose level that doesn't cause allergic reactions), the PCA results of SHL and YXC were positive and there was a increase in content of serum OVA-sIgE, while the PCA result of QKL was negative with a unobvious increase in the content of serum OVA-sIgE. The content of total serum IgE wasn't remarkably increased in each group and the results of ASA test were all positive. Three injections all caused anaphylactoid symptoms in guinea pigs in different doses or injection speed and the response intensity was found to be dosage and injection speed dependant. Furthermore, there was no significant difference for the content of total serum IgE in each group, whereas serum histamine concentration in every experimental group was markedly higher than normal saline group.</p><p><b>CONCLUSION</b>SHL and YXC increase the sensitivity of guinea pigs on OVA, and three TCM injections can cause allergic reactions in guinea pig. Allergic reactions of three TCM injections are correlated with specific IgE antibodies and histamine contents.</p>
الموضوعات
Animals , Female , Male , Guinea Pigs , Histamine , Blood , Hypersensitivity , Drug Therapy , Immunoglobulin E , Blood , Injections , Medicine, Chinese Traditional , Ovalbumin , Allergy and Immunology , Passive Cutaneous Anaphylaxisالملخص
<p><b>OBJECTIVE</b>To investigate the effect of total anthraquinone in Cassiae Semen on lipid peroxidation and peroxisome proliferator activated receptors gamma (PPAR-gamma) expression in liver tissues of rats with alcoholic fatty liver.</p><p><b>METHOD</b>Referring to literature, it was established animal models of fatty liver feeding with alcohol. Rats were randomized into 6 groups, except the normal group, the other 5 groups of rats had been administered alcohol two times a day for 3 months. Rats were killed at the end of this experiment. It were respectively measured that the contents of ALT, AST, AKP, TG, TC, HDL-C, LDL-C, MDA, SOD, FFA in the serum and TG, TC, MDA, SOD, HL, LPL, FFA in the liver. The left leaf of liver was observed by histopathological staining, the immunohistochemical staining and RT-PCR were used to observe the effects on the expressions of PPAR-gamma mRNA.</p><p><b>RESULT</b>Compared with the model group, total anthraquinone in Cassiae Semen could remarkably decrease the content of ALT, AST, TC, TG, MDA and increase the content of SOD in the serum of the experimental fatty liver induced by alcohol; remarkably decrease the content of TC, TG, FFA and increase the content of HL, LPL, SOD in the liver of the experimental fatty liver with induced by alcohol. Total anthraquinone in Cassiae Semen group was the similar the model group, but remarkably lighten inflammatory cell intiltration and fibrosis increasing. The RT-PCR and immunohistochemical staining results showed that: compared with the normal group,the model group could remarkably decrease the expression of PPAR-gamma mRNA in the liver (P < 0.01). Compared with the model group, total anthraquinone in Cassiae Semen could remarkably increase the expression of PPAR-gamma mRNA in the liver of the experimental fatty liver (P < 0.01).</p><p><b>CONCLUSION</b>The results showed that total anthraquinone in Cassiae Semen has good effects on the treatment of hepatic fat induced by alcohol diet in rats. the possible action mechanism of total anthraquinone in Cassiae Semen possess obvious effect of regulating the disorder of lipid metabolism, ameliorating hepatic function, as well as anti-lipidperoxidation, increasing the expression of PPAR-gamma in hepatic cells of rats.</p>
الموضوعات
Animals , Male , Rats , Anthraquinones , Chemistry , Therapeutic Uses , Cassia , Chemistry , Fatty Liver, Alcoholic , Drug Therapy , Metabolism , Immunohistochemistry , Lipid Peroxidation , Liver , Metabolism , Pathology , PPAR gamma , Genetics , Metabolism , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reactionالملخص
<p><b>OBJECTIVE</b>To investigate the effects and mechanism of Tripterygium hypoglaucum (THH) on serum IL-1, IL-6, and TNF-alpha in chronic, nephritis rats.</p><p><b>METHOD</b>The rabbit serum of anti-rat kidney was initially prepared, and then injected into normal rats to induce the formation of chronic glomerulonephritis. In this model, THH was administrated for 4 weeks, while saline and prednisone were respectively used as negative and positive controls. Some of laboratory parameters were observed from the rats above.</p><p><b>RESULT</b>THH not only significantly decreased urine protein, reduced serum urea nitrogen, but also decreased the releases of inflammatory mediators (such as IL-1, IL-6 and TNF-alpha).</p><p><b>CONCLUSION</b>THH is effective in treating rat nephrotoxic serum glormerulonephritis, its mechanism probably related to decreasing inflammatory mediator levels.</p>
الموضوعات
Animals , Female , Male , Rats , Chronic Disease , Drug Therapy , Interleukin-1 , Blood , Interleukin-6 , Blood , Kidney , Pathology , Nephritis , Blood , Drug Therapy , Pathology , Plant Extracts , Pharmacology , Therapeutic Uses , Rats, Sprague-Dawley , Time Factors , Tripterygium , Chemistry , Tumor Necrosis Factor-alpha , Bloodالملخص
Objective To compare the effect of percutaneons coronary interventions (PCI) combined with polydanshinolate on myocardial reperfusion with PCI combined with regular medicine in patients with acute myocardi-al infrarction ,and whether polydanshinolate would decrease no-reflow,improve the myocardial micro-circulation and the ventricular remodeling and clinical end-point events at the sixth month. Methods Random,parallel control and prospective clinical design was used in the current study. Sixty eligible patients for PCI, who were diagnosed as first-time acute myocardial infrarction with ST stage increasing,were recruited in the study with informed consent. All par-ticipants were divided into two groups randomly. Group A was treated with PCI combined with polydanshinolate, group B was treated with PCI combined with regular medicine. The participants were followed up for six months. The resolution of the sum of ST segment elevation (sum STR) ,corrected TIMI frame count (CTFC) and myocardial con-trast echocardiography (MCE) were used to assess myocardial perfusion. Bleeding events, heart function and major adverse cardiac events (MACE) were observed during hospitalization and follow-up visit. Results No significant difference was observed between two groups on the clinical condition and the results of emergency CAG and PCI. Compared to group B,the incidence of TIMI grade 3 was significantly higher in group A (90.0% vs 63.3% ,χ~2 = 4.565, P=0.0326). Sum STR one hour after PCI in group A was siguificanfly higher than that in group B (80.0% vs 50.0%, χ~2=4.689, P=0.0304). CTFC after PCI also differed significantly between the two groups (24.1±8.3 vs 33.4±15.9 respectively,P=0.0062). Localized myocardial blood flow 48 hours after PCI showed no significant difference between the two groups (P>0.05), whereas both increased at the 7th day after PCI (5.85±1.26 vs 2.09±1.85,t=9.2008,P<0.0001 ;3.95±1.35 vs 1.95±1.29,t=5.8666,P<0.0001) ,and there were signifi-cant difference between the two groups (P<0.05). No significant difference of LVEF, LVEDV, LVESV were found between the two groups during the hospitalization and follow-up visit after 6 months (P>0.05). The incidences of cardiovascular events and severe heart failure during hospitalization and follow-up visit in group A were significantly lower than that in group B (P<0.05 ). Conclusions Polydanshinolate addition to PCI could reduce no reflow phe-nomenan in patients of acute myocardial infrarction, improve myocardial reperfusion, and furthermore, decrease cardi-ovascular events and ameliorate prognosis.
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Objective To screen out the effective constituents with estrogenic action in Fructus psoraleae. Methods Fructus psoraleae was separated by using systemic solvent distillation method, and the effective fraction was screened out by the experiment of increasing the uterine weight in mice. Then the petroleum fraction was separated by sil; ca gel chromatrography and the effective constituent was screened by the experiment of increasing the uterine weight in mice. Results High-dose(5g/kg) of the petroleum fraction showed obvious estrogenic action (P