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1.
Preprint in English | medRxiv | ID: ppmedrxiv-22279933

ABSTRACT

ObjectivesTo prospectively investigate the associations of habitual fish oil use with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large-scale cohort. DesignProspective population-based cohort study. SettingUK Biobank. ParticipantsA total of 110 440 participants aged 37 -73 years who completed a questionnaire on supplement use, which included fish oil at baseline were enrolled between 2006 and 2010 and followed up until 2022. Main exposureAll participants filled out questionnaires about the habitual use of supplements, including fish oil. Main outcome measuresSARS-CoV-2 infection, COVID-19 hospital admission and COVID-19 mortality. ResultsAt baseline, 29 424 (26.6%) of the 110 440 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.95 (0.93 to 0.98) for SARS-CoV-2 infection among participants with follow-up time less than 12.1 years but no significant associations were observed for participants with follow-up time more than 12.1 years. For COVID-19-related outcomes, the hazard ratios were 0.79 (95% confidence interval 0.71 to 0.88) for COVID-19 hospital admission and 0.72 (0.60 to 0.87) for COVID-19 mortality. For COVID-19-related outcomes, the association seemed to be stronger among those with longstanding illness. The Cox proportional hazard analysis after propensity-score matching yielded consistent results. ConclusionsHabitual fish oil supplement is associated with a lower risk of hospital admission and mortality with COVID-19, but not associated with SARS-CoV-2 infection in the population with more than 12.1 years of follow-up.

2.
Preprint in English | medRxiv | ID: ppmedrxiv-22279047

ABSTRACT

ObjectiveConcerns have been raised about the widespread use of proton pump inhibitors (PPIs), and current findings linking the regular use of PPIs to respiratory infections remain inconsistent. Our study aims to evaluate whether PPI use increases the risk of pneumonia, influenza, and COVID-19. MethodThe presented study included 160,923 eligible participants from the UK Biobank (mean age 56.5 years, 53% women). Cox proportional hazards regression and propensity score-matching analyses were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Effect modifications by stratifications, including indications and CYP2C19 phenotypes were tested. ResultsThe regular use of PPIs was associated with increased risks of developing pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26-1.59) and influenza (HR 1.31, 95% CI 1.11-1.55). However, the risk of COVID-19 infection among regular PPI users was not significantly increased (HR 1.05, 95% CI 0.95-1.16). The burden was more notably observed in patients without indications of PPI use (HR 1.52, 95% CI 1.33-1.73 for pneumonia; HR 1.36, 95% CI 1.12-1.64 for influenza). The risk for pneumonia was higher among the CYP2C19 rapid and ultrarapid metabolizers (HR 1.45, 95% CI 1.22-1.73, P for interaction < 0.001). The propensity score-matching analyses yielded similar trends. ConclusionsThe regular use of PPIs is associated with increased susceptibility to pneumonia and influenza, but not COVID-19 infection. The risks are even higher among recipients without main indications. Our study highlights the appropriate use and de-prescribing of PPIs according to indications and CYP2C19 phenotypes for patients and clinical practitioners. What is already known on this topicO_LIProton pump inhibitors (PPIs) have been extensively used in clinical practice, while emerging studies suggest the adverse effects associated with their long-term use. C_LIO_LIThe linkage between PPIs and respiratory infections has been indicated, whereas controversy remains. C_LI What this study addsO_LIIn the large cohort involving 160,923 individuals, regular use of PPIs was associated with 42% and 31% increased risks of pneumonia and influenza, respectively, but not COVID-19 infection. C_LIO_LIThe burdens were more evident among PPI users without main indications, and CYP2C19 rapid and ultrarapid metabolizers. C_LI How this study might affect research, practice or policyO_LIConsidering the potential risk of respiratory infections, appropriate use following indications and metabolic phenotypes, as well as de-prescribing of PPIs are highlighted. C_LI

3.
Preprint in English | bioRxiv | ID: ppbiorxiv-473326

ABSTRACT

As an essential enzyme to SARS-CoV-2, main protease (MPro) is a viable target to develop antivirals for the treatment of COVID-19. By varying chemical compositions at both P2 and P3 sites and the N-terminal protection group, we synthesized a series of MPro inhibitors that contain {beta}-(S-2-oxopyrrolidin-3-yl)-alaninal at the P1 site. These inhibitors have a large variation of determined IC50 values that range from 4.8 to 650 nM. The determined IC50 values reveal that relatively small side chains at both P2 and P3 sites are favorable for achieving high in vitro MPro inhibition potency, the P3 site is tolerable toward unnatural amino acids with two alkyl substituents on the -carbon, and the inhibition potency is sensitive toward the N-terminal protection group. X-ray crystal structures of MPro bound with 16 inhibitors were determined. All structures show similar binding patterns of inhibitors at the MPro active site. A covalent interaction between the active site cysteine and a bound inhibitor was observed in all structures. In MPro, large structural variations were observed on residues N142 and Q189. All inhibitors were also characterized on their inhibition of MPro in 293T cells, which revealed their in cellulo potency that is drastically different from their in vitro enzyme inhibition potency. Inhibitors that showed high in cellulo potency all contain O-tert-butyl-threonine at the P3 site. Based on the current and a previous study, we conclude that O-tert-butyl-threonine at the P3 site is a key component to achieve high cellular and antiviral potency for peptidyl aldehyde inhibitors of MPro. This finding will be critical to the development of novel antivirals to address the current global emergency of concerning the COVID-19 pandemic.

4.
Preprint in English | bioRxiv | ID: ppbiorxiv-473330

ABSTRACT

Boceprevir is an HCV NSP3 inhibitor that has been explored as a repurposed drug for COVID-19. It inhibits the SARS-CoV-2 main protease (MPro) and contains an -ketoamide warhead, a P1 {beta}-cyclobutylalanyl moiety, a P2 dimethylcyclopropylproline, a P3 tert-butyl-glycine, and a P4 N-terminal tert-butylcarbamide. By introducing modifications at all four positions, we synthesized 20 boceprevir-based MPro inhibitors including PF-07321332 and characterized their MPro inhibition potency in test tubes (in vitro) and human host cells (in cellulo). Crystal structures of MPro bound with 10 inhibitors and antiviral potency of 4 inhibitors were characterized as well. Replacing the P1 site with a {beta}-(S-2-oxopyrrolidin-3-yl)-alanyl (opal) residue and the warhead with an aldehyde leads to high in vitro potency. The original moieties at P2, P3 and the P4 N-terminal cap positions in boceprevir are better than other tested chemical moieties for high in vitro potency. In crystal structures, all inhibitors form a covalent adduct with the MPro active site cysteine. The P1 opal residue, P2 dimethylcyclopropylproline and P4 N-terminal tert-butylcarbamide make strong hydrophobic interactions with MPro, explaining high in vitro potency of inhibitors that contain these moieties. A unique observation was made with an inhibitor that contains an P4 N-terminal isovaleramide. In its MPro complex structure, the P4 N-terminal isovaleramide is tucked deep in a small pocket of MPro that originally recognizes a P4 alanine side chain in a substrate. Although all inhibitors show high in vitro potency, they have drastically different in cellulo potency in inhibiting ectopically expressed MPro in human 293T cells. All inhibitors including PF-07321332 with a P4 N-terminal carbamide or amide have low in cellulo potency. This trend is reversed when the P4 N-terminal cap is changed to a carbamate. The installation of a P3 O-tert-butyl-threonine improves in cellulo potency. Three molecules that contain a P4 N-terminal carbamate were advanced to antiviral tests on three SARS-CoV-2 variants. They all have high potency with EC50 values around 1 M. A control compound with a nitrile warhead and a P4 N-terminal amide has undetectable antiviral potency. Based on all observations, we conclude that a P4 N-terminal carbamate in a boceprevir derivative is key for high antiviral potency against SARS-CoV-2.

5.
Preprint in English | bioRxiv | ID: ppbiorxiv-447950

ABSTRACT

A number of inhibitors have been developed for the SARS-CoV-2 main protease (MPro) as potential COVID-19 medications but little is known about their selectivity. Using enzymatic assays, we characterized inhibition of TMPRSS2, furin, and cathepsins B/K/L by more than a dozen of previously developed MPro inhibitors including MPI1-9, GC376, 11a, 10-1, 10-2, and 10- 3. MPI1-9, GC376 and 11a all contain an aldehyde for the formation of a reversible covalent hemiacetal adduct with the MPro active site cysteine and 10-1, 10-2 and 10-3 contain a labile ester to exchange with the MPro active site cysteine for the formation of a thioester. Our data revealed that all these inhibitors are inert toward TMPRSS2 and furin. Diaryl esters also showed low inhibition of cathepsins. However, all aldehyde inhibitors displayed high potency in inhibiting three cathepsins. Their determined IC50 values vary from 4.1 to 380 nM for cathepsin B, 0.079 to 2.3 nM for cathepsin L, and 0.35 to 180 nM for cathepsin K. All aldehyde inhibitors showed similar inhibition levels toward cathepsin L. A cellular analysis indicated high potency of MPI5 and MPI8 in inhibiting lysosomal activity, which is probably attributed to their inhibition of cathepsins. Among all aldehyde inhibitors, MPI8 shows the best selectivity toward cathepsin L. With respect to cathepsins B and K, the selective indices are 192 and 150, respectively. MPI8 is the most potent compound among all aldehyde inhibitors in cellular MPro inhibition potency and anti-SARS-CoV-2 activity in Vero E6 cells. Cathepsin L has been demonstrated to play a critical role in the SARS-CoV-2 cell entry. By selectively inhibiting both SARS-CoV-2 MPro and the host cathepsin L, MPI8 potentiates dual inhibition effects to synergize its overall antiviral potency and efficacy. Due to its high selectivity toward cathepsin L that reduces potential toxicity toward host cells and high cellular and antiviral potency, we urge serious consideration of MPI8 for preclinical and clinical investigations for treating COVID-19.

6.
Preprint in English | bioRxiv | ID: ppbiorxiv-447613

ABSTRACT

As an essential enzyme of SARS-CoV-2, the pathogen of COVID-19, main protease (MPro) triggers acute toxicity to its human cell host, an effect that can be alleviated by an MPro inhibitor with cellular potency. By coupling this toxicity alleviation with the expression of an MPro-eGFP fusion protein in a human cell host for straightforward characterization with fluorescent flow cytometry, we developed an effective method that allows bulk analysis of cellular potency of MPro inhibitors. In comparison to an antiviral assay in which MPro inhibitors may target host proteases or other processes in the SARS-CoV-2 life cycle to convene strong antiviral effects, this novel assay is more advantageous in providing precise cellular MPro inhibition information for assessment and optimization of MPro inhibitors. We used this assay to analyze 30 literature reported MPro inhibitors including MPI1-9 that were newly developed aldehyde-based reversible covalent inhibitors of MPro, GC376 and 11a that are two investigational drugs undergoing clinical trials for the treatment of COVID-19 patients in United States, boceprevir, calpain inhibitor II, calpain inhibitor XII, ebselen, bepridil that is an antianginal drug with potent anti-SARS-CoV-2 activity, and chloroquine and hydroxychloroquine that were previously shown to inhibit MPro. Our results showed that most inhibitors displayed cellular potency much weaker than their potency in direct inhibition of the enzyme. Many inhibitors exhibited weak or undetectable cellular potency up to 10 M. On contrary to their strong antiviral effects, 11a, calpain inhibitor II, calpain XII, ebselen, and bepridil showed relatively weak to undetectable cellular MPro inhibition potency implicating their roles in interfering with key steps other than just the MPro catalysis in the SARS-CoV-2 life cycle to convene potent antiviral effects. characterization of these molecules on their antiviral mechanisms will likely reveal novel drug targets for COVID-19. Chloroquine and hydroxychloroquine showed close to undetectable cellular potency to inhibit MPro. Kinetic recharacterization of these two compounds rules out their possibility as MPro inhibitors. Our results also revealed that MPI5, 6, 7, and 8 have high cellular and antiviral potency with both IC50 and EC50 values respectively below 1 M. As the one with the highest cellular and antiviral potency among all tested compounds, MPI8 has a remarkable cellular MPro inhibition IC50 value of 31 nM that matches closely to its strong antiviral effect with an EC50 value of 30 nM. Given its strong cellular and antiviral potency, we cautiously suggest that MPI8 is ready for preclinical and clinical investigations for the treatment of COVID-19.

7.
China Pharmacy ; (12): 1249-1252, 2018.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-704775

ABSTRACT

OBJECTIVE:To establish a method for content determination of total saponins and platycodin D in Platycodon grandiflorum from Sichuan and investigate the difference of 2 indexes in P. grandiflorum from Sichuan of different cultivated years. METHODS:The content of total saponins in P. grandiflorum from Sichuan was determined by UV spectrophotometry. The content of platycodin D was determined by HPLC. The contents of total saponins and platycodin D were compared among each 10 samples of annual,biennial and triennial P. grandiflorum from Sichuan. RESULTS:Average contents of total saponins in annual,biennial and triennial P. grandiflorum from Sichuan were 2.47% ,3.01% ,2.47% ,respectively;average contents of platycodin D were 0.23%,0.27%,0.33%,respectively. The contents of 2 indexes in annual P. grandiflorum from Sichuan were in relative low level, while the content total saponins in biennial P. grandiflorum from Sichuan was the highest;the content of platycodin D in triennial P. grandiflorum was the highest. CONCLUSIONS:The contents of indexes are different among P. grandiflorum from Sichuan of different cultivated years. But there is no correlation between them. It is suggested to select biennial and triennial P. grandiflorum from Sichuan.

8.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-482023

ABSTRACT

A sensitive and selective method based on gas chromatography hyphenated to mass spectrometry (GC-MS) was developed and validated for the determination of atractylon in rat plasma. Plasma samples were processed by liquid-liquid extraction with ethyl acetate-n-hexane (1:1, v/v) using acetophenone as an internal standard (IS). Analytes were determined in selective ion monitoring (SIM) mode using target ions at m/z 108.1 for atractylon and m/z 105.1 for acetophenone. The calibration curve was linear over the concentration range of 10-1000 ng/mL with lower limit of quantification of 10 ng/mL. The intra- and inter-day precision variations were not more than 10.4% and 9.6%, respectively, whilst accuracy values ranged from -6.5% to 4.9%. Extraction recovery of the assay was satisfactory. This method was suc-cessfully applied to quantification and pharmacokinetic study of atractylon in rat plasma after in-tragastric administration of Atractylodis extract.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-478592

ABSTRACT

This article was aimed to survey the use of Chinese minority medicine, in order to provide differences and similarities among different Chinese minority medicine, and to analyze the relations among species resources, using range, functions and indications. It provided a basic scientific platform for the development, research and use of minority medicine. The books and journals published since the late 1970s (the country after the reform and opening up) had been collected, classified. And reference books on current Chinese minority medicine had been compiled. The results showed that the first draft of the book had been completed and delivered to the press. The dictionary had cited 53 traditional medicine used by minority groups. The total number of minority medicine was 7 734. The total characters amount in the book was 1 700 000 words. It was concluded that the species of minority medicine were various. There was rich information on their harvest, medicinal parts, functions and indications with prominent features. The existing major problems were to clarify the standard of the species as well as their major functions and indications.

10.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-447822

ABSTRACT

Objective To study the cardiac function effect of allopurinol for hypemricemia combined with dilated cardiomyopathy patients.Methods One hundred and twenty hypemricemia combined with dilated cardiomyopathy patients were divided into allopurinol group and control group according to the treatment method with 60 cases each.All the patients were given conventional treatment,the control group was added the nitroprusside treatment,and the allopurinol group was added the allopurinol and nitroprusside treatment.The treatment period was 3 months.Results The total effective rate in allopurinol group was significantly higher than that in control group [90.0% (54/60) vs.75.0% (45/60)],there was statistical difference (P < 0.05).After treatment,the left ventricular ejection fraction and left ventricular posterior wall thickness at end-systole in allopurinol group were significantly higher than those in control group [(67.85 ± 7.12)% vs.(30.78 ±7.00)% and (1.40 ±0.20) mm vs.(1.16 ±0.18) mm[,but the left ventricular internal diameter at end-systole,left ventricular internal diameter at end-diastole and left ventricular posterior wall thickness at end-diastole were significantly lower than those in control group [(4.72 ± 0.41) mm vs.(6.48 ± 0.47) mm,(2.93 ± 0.32) mm vs.(5.56 ± 0.62) mm and (0.77 ± 0.13) mm vs.(0.92 ± 0.18) mm],there were statistical differences (P < 0.05).After treatment,The uric acid,urea nitrogen and creatinine were significantly lower than those in control group [(45.43 ± 11.24) μ mol/L vs.(167.23 ± 19.22) μ mol/L,(10.23 ± 7.12)mmol/L vs.(40.93 ± 8.09)mmol/L and (32.01 ± 8.34) mmol/L vs.(78.09 ±9.11) mmol/L],there were statistical differences (P < 0.05).Conclusion Allopurinol used for treating hyperuricemia combined with dilated cardiomyopathy patients can reduce uric acid,early reversal the atherosclerosis and improve heart function,it should be widely applied research.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-453328

ABSTRACT

Objective To compare the influence of propofol combined with sufentanil or remifentanil on the quality of wake-up during scoliosis surgery by wake-up test.Methods Fifty pa-tients undergoing scoliosis surgery were randomized into two groups.During the surgery,propofol combined with sufentanily 0.3-0.6 μg·kg-1·h-1 (group SF)or remifentanil 0.2-0.3 μg·kg-1·min-1 (group RF)were continuously infused to maintain anesthesia,and BIS was maintained at 40-60.In wake-up test,the infusion of sufentanyl in group SF was paused and,the infusion rate of remifentanil in group RF was adjusted to 0.05 μg·kg-1·min-1 until the patient completed the wake-up test under instruction.The time that spontaneous breathing occurred,body movement was detected and the capa-bility to follow instructions in both two groups were recorded.MAP,HR,PET CO2 were measured at the time 10 min after medication adjustment (T1 ),waking up(T2 )and 10 min after waking up (T3 ), respectively,in both two groups.Wake-up quality was also recorded.Results The time that sponta-neous breathing occurred,body movement was detected and the capability to follow instructions in group RF were significantly shorter than those in group SF (P <0.05).At T2 the incidence of agita-tion in group RF was significantly higher than that in group SF(P <0.05).And the hemodynamics of group SF were more stable than those of group RF (P <0.05).Conclusion Propofol combined with sufentanil can improve wake-up quality during scoliosis surgery,but the wake-up time is relatively lon-ger.

12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-356056

ABSTRACT

<p><b>OBJECTIVE</b>To identify comparatively several commercial Chinese herbal medicines and their counterfeits.</p><p><b>METHOD</b>The micromorphological characters were identified. The shape, surface, section and other characters of the medicinal materials were identified by using anatomical lens and scanning apparatus. Pictures were taken and saved.</p><p><b>RESULT</b>Main micromorphological differences between several Chinese herbal medicine including Lonicera macranthoides, L. similis, Cuminum cyminum, Plantago asiatica, Cuscuta chinensis, Sinapis alba, Salvia miltiorrhiza and their counterfeits were identified.</p><p><b>CONCLUSION</b>The reference for the authenticity identification of Chinese herbal medicine and helpful experiences for the research of the same subject were provided.</p>


Subject(s)
Cuminum , Classification , Cuscuta , Classification , Drugs, Chinese Herbal , Plants, Medicinal , Classification , Quality Control , Salvia miltiorrhiza , Classification , Sinapis , Classification
13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-427757

ABSTRACT

ObjectiveTo evaluate therapeutic effect and the possible mechanism of smecta on paraqual plasma concentrations and multiorgans injury induced by paraquat intoxication in rats. Methods A total of 76 healthy adult SD rats were randomly ( random number) divided into group A (control group n =6),group B ( poisoned group n =30 ),group C (smecta-treated group n=30).Rats in groups B and C were treated intragastrically with PQ at 50 mg/kg,the rats in the group C were given with smecta at 50 mg/kg,while the rats in the other two groups were only intragastrically adminstered with saline.Live rats in groups B and C were sacrificed at 2,6,24,48,72 h after administration of PQ for the determination of paraquat plasma concentrations and for HE staining of lung,stomach and jejunum.The rats were executed at the end of trial by the same way in group A.All measurement data were expressed as means + standard deviation ((x) ±s).The data of pathological score were compared with Independent-samples T test and the data of PQ concentration compared with analysis of variance (ANOVA) followed by LSD-t multiple comparison test.P-values of less than 0.05 were considered statistically significant.ResultsThe paraquat plasma concentration ( ng/ml ) was 440.314 ± 49.776 to 4320.6150 ± 413.947.There were different pathological changes of lung,stomach and jejunum in group B. Lung injuries gradually deteriorated,congestion,edema,leukocyte infiltration,incrassated septa and lung consolidation were observed.The pathological changes were obvious such as abruption of mucosa,hyperemic gastric mucosa and leukocyte infiltration in stomach.Haemorrhage of jejunum mucosa,abruption of villus,gland damage and inflammatory cell infiltration were found. Compared with group B,all the pathological changes mentioned above were obviously alleviated in group C ( P < 0.05 ),and the concentrations reduced ( P < 0.01 ).Conclusions Smecta reduced paraquat plasma concentrations and alleviated pathologic injury of rats with PQ poisoning.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-298449

ABSTRACT

<p><b>OBJECTIVE</b>To study the effects of continuous dry-stress and full-water treatments in different periods of spring on the water condition, permeability of plasma membrane and protective enzymes activities in leaves of Ligusticum chuanxiong.</p><p><b>METHOD</b>Pot cultivation method was applied and physical and biochemical indexes were measured.</p><p><b>RESULT</b>Under dry-stress treatment the soil relative water content (SRWC) and the relative water content (RWC) in leaves decreased gradually with the days of treatment increased, the content of malondialdephyde (MDA) and permeability of plasma membrane increased significantly. The activities of superoxide dismutase (SOD) and catalase (CAT) increased at first and then decreased while the activity of peroxidase (POD) increased. The influence of full-water treatment to all above indexes was the same trend with that of dry-stress treatment approximately but was not significant.</p><p><b>CONCLUSION</b>In this experiment, the suitable soil relative water content for growth of Chuanxiong is about 60%.</p>


Subject(s)
Catalase , Metabolism , Cell Membrane , Metabolism , Cell Membrane Permeability , Drugs, Chinese Herbal , Metabolism , Lipid Peroxidation , Malondialdehyde , Metabolism , Peroxidase , Metabolism , Plant Leaves , Cell Biology , Metabolism , Regression Analysis , Seasons , Stress, Physiological , Superoxide Dismutase , Metabolism , Water , Pharmacology
15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-449272

ABSTRACT

OBJECTIVE: To observe the therapeutic effects of Yiqi Sanju Formula (YQSJF), a compound traditional Chinese herbal medicine, in treatment of non-alcoholic fatty liver disease (NAFLD). METHODS: Sixty-seven patients diagnosed with NAFLD were randomly divided into two groups: YQSJF-treated group (39 cases) and placebo group (28 cases). The NAFLD patients in the two groups were treated with YQSJF and placebo respectively for 3 months. Clinical symptoms, the CT ratio of liver-spleen, body mass index (BMI), waist circumference, homeostatic model assessment for insulin resistance (HOMA2-IR) and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-alpha (TNF-alpha), high sensitivity C-reactive protein (hs-CRP), triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were evaluated before and after treatment. RESULTS: After treatment, the clinical symptoms were improved and the levels of BMI, waist circumference, HOMA2-IR, ALT, AST, TG and TC were decreased significantly in the YQSJF-treated group (P<0.05). The CT ratio of liver-spleen in the YQSJF-treated group was increased significantly as compared with the placebo group (P<0.01).

16.
Journal of Integrative Medicine ; (12): 387-91, 2008.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-449216

ABSTRACT

OBJECTIVE: To explore the possible mechanism of Huoxue Qianyang Formula (HXQYF), a compound traditional Chinese herbal medicine, in reversing the left ventricular hypertrophy (LVH) of spontaneous hypertensive rats (SHRs) by analyzing the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle. METHODS: The experimental study was carried out in SHRs, the sex- and age-matched Wistar-Kyoto (WKY) rats were served as normal control (n=5, normal saline 10 ml/kg daily). Twenty-five SHRs were randomly divided into five groups: untreated group (n=5, normal saline 10 ml/kg daily), high-dose HXQYF-treated group (n=5, 0.84 g/ml HXQYF, 10 ml/kg daily), medium-dose HXQYF-treated group (n=5, 0.42 g/ml HXQYF, 10 ml/kg daily), low-dose HXQYF-treated group (n=5, 0.21 g/ml HXQYF, 10 ml/kg daily) and cilazapril-treated group (n=5, 1 mg/ml cilazapril, 10 ml/kg daily). The drugs were intragastrically administered once daily for 14 weeks. The expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were detected separately by in situ hybridization histochemical method and immunohistochemical method. RESULTS: Compared with the normal control group, the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were significantly increased in untreated group (P<0.01). After treatment, the expressions of c-fos and c-myc mRNAs in left ventricular muscle in HXQYF-treated groups were significantly down-regulated as compared with those of the untreated group (P<0.05). The expressions of c-myc protein were also significantly decreased in high- and medium-dose HXQYF-treated groups as compared with the untreated group (P<0.05), but it had no significant effects in protein expression of c-fos in the three HXQYF-treated groups. CONCLUSION: HXQYF can inhibit the expression of c-myc in ventricular hypertrophy tissue, which may be the mechanism in treating LVH of hypertension.

17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-449884

ABSTRACT

DNA microarray technology is a high throughout method that can analyze the expression of thousands of genes at the same time to form a complete cellular gene expression profile. It has been applied in immunological researches such as the development, maturation, activation and differentiation of immune cells, the regulation of immune responses, the molecular mechanism of allergy, the relation between phenotype and gene expression, and immunological pharmacology, etc. It has deepened our perception of the immune system. It will as well be helpful in the research of the regulative mechanism of traditional Chinese medicine (TCM) toward immune cells and immune responses, the therapeutic mechanisms of TCM toward allergy, the standardization of differentiation of syndrome and herbal pharmacology, etc. The data analysis of the results of DNA microarray experiments is aimed to compare the difference of gene expression levels of different samples and obtain diagnostic gene expression profiles. But there are controversies about the number of samples and choices of statistical methods. Researchers are striving in setting standards of DNA microarray experiments.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-682547

ABSTRACT

0.05). Conclusion The lesions of left and right hemisphere can both cause cognitive impairment, which is significantly correlated with the severity of motor dysfunction in acute stroke patients with subcortical lesion.Great attention should be paid to the evaluation and treatment of cognitive dysfunction in patients with serious hemiplegia.

19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-528562

ABSTRACT

AIM: To study the expression of endostatin in ischemic myocardium of myocardial infarction(MI) rats in various periods and the correlation with VEGF expression and microvascular density(MVD).METHODS: Thirty-two male Sprague-Dawley rats after myocardial infarction were randomly divided into 7,14,21 and 28 days group.The sham group was normal control group(eight rats in each group).The expression of endostatin,VEGF and MVD in ischemic myocardium were observed by immunohistochemistry.RESULTS: The expression of endostatin significantly increased in the ischemic myocardium after MI,peaked at 7 days,then gradually decreased at 14,21 and 28 days.The endostatin level at 28 days was the same as the shams.The changing trends of expression of endostatin in ischemic myocardium after MI were similar to that of VEGF and were significantly correlated with the MVD.CONCLUSION: The expression of endostatin increased in ischemic myocardium of myocardial infarction rats.The changing trends of endostatin were similar to that of VEGF and positively correlated with the MVD.These data suggest that endostatin may modulate ischemic myocardium angiogenesis after myocardial infarction.

20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-580112

ABSTRACT

AIM: To establish a method of fingerprint analysis of Toufengyu Dropping Pill(Radix angelicae dahuricae,Rhizoma chuanxiong and green tea) by HPLC. METHODS: Hypersil ODS2 C_18(4.6 mm?250 mm,5 ?m) column was used,with mixtures of 0.1%TFA solution and acetonitrile as mobile phase in a gradient mode.The flow rate was 1.0 mL/min,the column temperature was at 30 ℃,detection wavelength was at 254 nm. RESULTS: HPLC fingerprint determination with 22 common peaks gained from 10 batches of self-made Tonfengyu Dropping Pill,there were 9 components identified,including caffeine,EGCG,ferulic acid,oxypeucedanin,imperatorin,phellopterin,cnidilin,isoimperatorin and oxypeucedanin hydrate. CONCLUSION: This method is accurate,reliable and can provide more information for the quality control of Toufengyu Dropping Pills.

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