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1.
Acta Pharmaceutica Sinica B ; (6): 3820-3835, 2021.
Article in English | WPRIM | ID: wpr-922443

ABSTRACT

Pyrrolizidine alkaloids (PAs) are the most common phytotoxins with documented human hepatotoxicity. PAs require metabolic activation by cytochromes P450 to generate toxic intermediates which bind to proteins and form protein adducts, thereby causing cytotoxicity. This study investigated the role of the gut-liver axis in PA intoxication and the underlying mechanisms. We exposed mice to retrorsine (RTS), a representative PA, and for the first time found RTS-induced intestinal epithelium damage and disruption to intestinal barrier function. Using mice with tissue-selective ablation of P450 activity, we found that hepatic P450s, but not intestinal P450s, were essential for PA bioactivation. Besides, in RTS-exposed, bile duct-cannulated rats, we found the liver-derived reactive PA metabolites were transported by bile into the intestine to exert enterotoxicity. The impact of gut-derived pathogenic factors in RTS-induced hepatotoxicity was further studied in mice with dextran sulfate sodium (DSS)-induced chronic colitis. DSS treatment increased the hepatic endotoxin level and depleted hepatic reduced glutathione, thereby suppressing the PA detoxification pathway. Compared to RTS-exposed normal mice, the colitic mice displayed more severe RTS-induced hepatic vasculature damage, fibrosis, and steatosis. Overall, our findings provide the first mode-of-action evidence of PA-induced enterotoxicity and highlight the importance of gut barrier function in PA-induced liver injury.

2.
Article in Chinese | WPRIM | ID: wpr-920740

ABSTRACT

Objective To understand the real prevalence of Clonorchis sinensis infections in the freshwater fish in mainland China, so as to provide insights into clonorchiasis control and detection of freshwater fish. Methods All literatures reporting the prevalence of C. sinensis infections in the freshwater fish, the second intermediate host of the parasite, were jointly retrieved in Chinese and English electronic databases from January 1, 2010 to December 31, 2020, including Wanfang Data, CNKI, PubMed, Web of Science, Embase and Cochrane Library. All studies were screened based on inclusion and exclusion criteria, and the quality of all enrolled literatures was evaluated. The pooled prevalence of C. sinensis infections in freshwater fish and its 95% confidence interval (CI) were estimated using the software Stata version 15.0, and subgroup analyses were performed to investigate the region-, season- and sample source-specific pooled prevalence of C. sinensis infections in freshwater fish. In addition, the sensitivity and publication bias of all included studies were analyzed. Results A total of 40 eligible literatures were included in this study, including 37 Chinese literatures and 3 English literatures, and there were 10 high-quality literatures, 27 moderate-quality literatures and 3 low-quality literatures. A total of 53 species containing 37 959 freshwater fish were reported in these 40 studies, and 73.58% (39/53) of freshwater fish species were identified with C. sinensis infections. Meta-analysis showed 23.5% [95% CI: (0.19, 0.28)] pooled prevalence of C. sinensis infections in freshwater fish in mainland China, and subgroup analyses higher prevalence of C. sinensis infections in freshwater fish in northeastern China [35.7%, 95% CI: (0.22, 0.50)] than in central [25.9%, 95% CI: (0.04, 0.48)] and southern China [20.6%, 95% CI: (0.09, 0.32)], higher prevalence of C. sinensis infections in freshwater fish sampled in spring [44.1%, 95% CI: (0.35, 0.53)] than in autumn [6.7%, 95% CI: (0.05, 0.08)] and summer [3.3%, 95% CI: (−0.01, 0.07)], and higher prevalence of C. sinensis infections in freshwater fish sampled from natural water [25.2%, 95% CI: (0.17, 0.33)] than from retail trades [22.2%, 95% CI: (0.17, 0.28)] and breeding chain [12.3%, 95% CI: (0.03, 0.22)]. However, all included studies had a publication bias with a low sensitivity. Conclusions The prevalence of C. sinensis infections is high in freshwater fish in mainland China, and there are still challenges for clonorchiasis control. Reinforcement of health education, diagnostics development and food safety supervision is recommended in future clonorchiasis control programs.

3.
Acta Pharmaceutica Sinica B ; (6): 1885-1902, 2021.
Article in English | WPRIM | ID: wpr-888840

ABSTRACT

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of

4.
Article in Chinese | WPRIM | ID: wpr-706998

ABSTRACT

Objective To study the effects of five different kinds of Chinese medicine materials on dissolution of pills; To evaluate their in vitro - in vivo correlation.Methods Five different types of traditional Chinese medicine materials, such as starch, fiber, protein, grease and polysaccharide materials, were selected by uniform design to the proposed 8 model formulation and preparation of pills, and the cumulative release rate and in vivo plasma concentration of berberine hydrochloride were determined by HPLC. The effects of Chinese medicine materials on the drug release behavior of pills in vitro - in vivo were investigated. And the in vitro - in vivo correlation of the pills was evaluated.Results Starch and fiber materials could promote the release of the pills, and protein and grease materials has a blocking effect on the pills dissolution. Polysaccharide materials have no significant effect on the dissolution of the pills. Pills in vitro - in vivo correlation was significant.Conclusion Chinese medicine materials have the characteristics of medicine-assisted unity, which can control the dissolution and bioavailability of pills by adjusting the proportion of powder in the prescription. And the pills have good correlation in vitro - in vivo.

5.
Chinese Circulation Journal ; (12): 355-359, 2018.
Article in Chinese | WPRIM | ID: wpr-703864

ABSTRACT

Objectives: To analyze the relationship between lung ultrasound B line and NT-proBNP, E/e' in order to explore the accuracy of B lines for diagnosing pulmonary edema in patients with acute heart failure (AHF). Methods: A total of 124 AHF patients admitted in out hospital from 2016-02 to 2017-02 were enrolled. According to the number of B line, patients were divided into 3 groups: Mild pulmonary edema group, patients with B line<15, Moderate pulmonary edema group, 15≤B line<30 and Severe pulmonary edema group, B line≥30. Basic clinical condition and echocardiography parameters were compared among 3 groups; relationships between B line and NT-proBNP, E/e', EF, pulmonary artery pressure were analyzed respectively; the sensitivity and specificity for B-line diagnosing NT-proBNP≥5000 pg/ml and E/e'≥14 were evaluated by ROC curve analysis. Results: Compared with Mild and Moderate pulmonary edema groups, Severe pulmonary edema group had the severer NYHA grade, more wet rale, higher NT-proBNP level and more chest X-ray of pulmonary congestion, P<0.05. Compared with Mild pulmonary edema group, Moderate and Severe pulmonary edema groups had decreased LVEF, P<0.05; Severe pulmonary edema group showed increased diastolic function such as elevated E/A, pulmonary artery pressure and E/e',P<0.05.B line was positively related to NT-proBNP,E/e'and pulmonary artery pressure,negatively related to EF.B line had the best correlation to NT-proBNP (r=0.803, P<0.001), the next was E/e'(r=0.794, P<0.001) and the worst was pulmonary artery pressure (r=0.330, P<0.001). The cutoff values of B line for diagnosing NT-proBNP≥5000pg/ml and E/e'≥14 were both 30, the AUC of ROC=0.823 and 0.768 respectively. Conclusions: Lung ultrasound B line had good correlation to NT-proBNP and E/e', which could accurately assess the pulmonary edema in AHF patients.

6.
Article in Chinese | WPRIM | ID: wpr-699479

ABSTRACT

Objective To explore the effect of adenosine preconditioning on vascular endothelial growth factor(VEGF)and angiopoietin-1 (Ang-1) in oxygen-glucose deprivation and reoxygenation astrocytes.Methods Astrocytes of pallium in Sprague Dawley rats were cultured in vitro,and the third generation of astrocytes were passaged to 96 pore plate.The astrocytes were divided into normal control group,oxygen-glucose deprivation group and adenosine preconditioning group randomly when the astrocytes adhered to the wall and grew the evection.The cells in the normal control group did not received oxygen glucose deprivation;the cells in the oxygen-glucose deprivation group received oxygen-glucose deprivation 8 h and reoxygenation 24 h;the cells in the adenosine preconditioning group were given adenosine 100 μmol · L-1 at 24 hours before received oxygen-glucose deprivation 8 h and reoxygenation 24 h.The shape of astrocytes were observed after reoxygenation 24 h.The cytoactivity of astrocytes in each group was detected by methyl thiazolyl tetrazolium assay;the concentration of VEGF and Ang-1 in supernatant of astrocytes in each group was detected by enzyme linked immunosorbent assay.Results The astrocytes in the normal control group grew well.The edema of astrocytes in the oxygen-glucose deprivation group was obvious,and the cell body became round;the cell morphology changed from irregular to spindle shape;and the neurites became shorter or even disappeared.Compared with the oxygen-glucose deprivation group,the astrocytes in the adenosine preconditioning group had a mildly edema,and the cells were arranged orderly.The vitality of astrocytes in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was 0.698 ± 0.059,0.196 ± 0.062,0.412 ± 0.009 respectively;the vitality of astrocytes in the oxygen-glucose deprivation group was obviously lower than that in the normal control group(q =3.561,P <0.05);the vitality of astrocytes in the adenosine preconditioning group was obviously higher than that in the oxygen-glucose deprivation group (q =2.102,P < 0.05).The concentration of VEGF in supemate in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was (0.038 ± 0.005),(0.053 ± 0.007),(0.084 ± 0.006) μg · L-1 respectively;the concentration of Ang-1 in supemate in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was (0.030 ± 0.007),(0.049 ± 0.008),(0.080 ± 0.004) μg · L-1 respectively.The concentration of VEGF and Ang-1 in the oxygen-glucose deprivation group were obviously higher than those in the normal control group(q =1.394,1.633;P < 0.05);the concentration of VEGF and Ang-1 in the adenosine preconditioning group were obviously higher than those in the oxygen-glucose deprivation group (q =1.584,1.632;P < 0.05).Conclusion The adenosine preconditioning can increase the expression of VEGF and Ang-1 in astrocytes after oxygen-glucose deprivation.It can enhance the tolerance of brain to ischemia-reperfusion injury and produce neural protection effect.

7.
Article in Chinese | WPRIM | ID: wpr-690509

ABSTRACT

Steaming method is a traditional processing method for Gastrodiae Rhizoma(GR). The current studies on the steaming method's mechanism of GR are mainly focused on facilitating softening slice, destroying the β-glycosidic bond enzymes to reduce the decomposition of gastrodia glycosides (killing enzyme and protecting glycosides). The researches on the processing mechanism are still incomplete, while revealing and analyzing the active components in the body's metabolic process are important channels and new models to clarify the mechanism of traditional medicine processing. In order to provides a reference for the in-depth study of the processing mechanism of GR, we have reviewed the relevant literature at home and abroad in recent years and briefly summarized the processing, composition analysis and in vivo metabolism of GR in this study.

8.
Article in Chinese | WPRIM | ID: wpr-852200

ABSTRACT

There is abundant processing theory in the system of traditional Chinese medicine. The deep excavation and research of that is conducive to promoting the development of science of Chinese materia medica (CMM), ensuring the quality of CMM prepared in ready-to-use forms and promoting the clinical rational use of drugs. Based on the current research status of CMM processing theory, using the representative drugs as the object, modern pharmacological research as a guide, the contents of the relevant studies of “raw and cooked different use” theory, “carbonic herbs for hemostasis” theory and theory of auxiliary material action were elaborated. The review provided reference for the further research on traditional processing theory and also provided a scientific basis for the clinical rational use of processed products of CMM.

9.
Article in English | WPRIM | ID: wpr-812095

ABSTRACT

Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. However, PMR-associated hepatotoxicity is becoming a safety issue. In our previous in vivo study, an interaction between stilbenes and anthraquinones has been discovered and a hypothesis is proposed that the interaction between stilbene glucoside-enriching fraction and emodin may contribute to the side effects of PMR. To further support our previous in vivo results in rats, the present in vitro study was designed to evaluate the effects of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-β-D-glucopyranoside (TSG) on the cellular absorption and human liver microsome metabolism of emodin. The obtained results indicated that the absorption of emodin in Caco-2 cells was enhanced and the metabolism of emodin in human liver microsomes was inhibited after TSG treatment. The effects of the transport inhibitors on the cellular emodin accumulation were also examined. Western blot assay suggested that the depressed metabolism of emodin could be attributed to the down-regulation of UDP-glucuronosyltransferases (UGTs) 1A8, 1A10, and 2B7. These findings definitively demonstrated the existence of interaction between TSG and emodin, which provide a basis for a better understanding of the underlying mechanism for PMR-induced liver injury.


Subject(s)
Caco-2 Cells , Chemical and Drug Induced Liver Injury , Emodin , Metabolism , Fallopia multiflora , Glucosides , Toxicity , Glucuronosyltransferase , Humans , Plant Roots , Stilbenes , Toxicity
10.
China Pharmacy ; (12): 5049-5052, 2017.
Article in Chinese | WPRIM | ID: wpr-704471

ABSTRACT

OBJECTIVE:To provide theoretical reference for clinical research and application of TCM Mahuang decoction.METHODS:TCM components of Mahuang decoction were analyzed by literature searching and data analysis,and TCM component database was established.The active compounds were selected through computer simulation prediction,and the related targets were predicted.Molecular pharmacology mechanism of TCM Mahuang decoction in the treatment of typhoid syndrome was investigated.RESULTS:Mahuang decoction contained about 723 compounds,among which E.sinica contained 236 compounds,Cinnamomum cassia contained 115 compounds,Glycyrrhiza uralensis contained 287 compounds,and Amygdalus Communis contained 85 compounds.43 active compounds were screened through computer simulation prediction,and 18 related targets were mainly related to vasodilation effect,adrenergic action and the effect of promoting smooth muscle contraction.CONCLUSIONS:By combining oral bioavailability prediction by computer,drug-like analysis and target prediction,the study determines the effect of active compounds in Mahuang decoction on typhoid syndrome by the means of vasodilation,adrenergic action and promoting smooth muscle contraction.

11.
Acta Pharmaceutica Sinica ; (12): 966-972, 2015.
Article in Chinese | WPRIM | ID: wpr-257040

ABSTRACT

Ribavirin is a broad-spectrum antiviral agent and glycyrrhizin has activities of anti-inflammation, immunoregulation and anti-viral infections. To enhance antiviral efficacy and weaken side-effects of ribavirin, antiviral effects of the combination of glycyrrhizin and ribavirin were studied in the present study. Firstly, a mouse model of viral pneumonia was established by inoculation of influenza H1N1 virus. Protective effects of glycyrrhizin and ribavirin used alone or in combination against H1N1 virus infection in mice were evaluated based on the survival rate, lung index and virus titer in lungs of mice. Results showed that the combination of glycyrrhizin and ribavirin significantly inhibited the lung consolidation with a 36% inhibition ratio on the lung swell of infected mice. The combination of the two drugs exhibited synergetic effects on survival of infected mice. The combination of 50 mg · kg(-1) · d(-1) glycyrrhizin and 40 mg · kg(-1) · d(-1) ribavirin resulted a 100% protection for infected mice with a synergetic value of 36, which was significantly higher than the control group and each drug alone. This combination also resulted a significant drop of lung virus titer (P < 0.01), as well as inhibition on the production of proinflammatory cytokines IL-6 (P < 0.01), TNF-α (P < 0.01) and IL-1β (P < 0.05) induced by virus infection compared to the control. The treatment of ribavirin plus glycyrrhizin was more effective in influenza A infection in mice than either compound used alone, which suggested a potential clinical value of the combination of the two agents.


Subject(s)
Animals , Antiviral Agents , Pharmacology , Disease Models, Animal , Drug Synergism , Drug Therapy, Combination , Glycyrrhizic Acid , Pharmacology , Inflammation , Allergy and Immunology , Influenza A Virus, H1N1 Subtype , Interleukin-1beta , Allergy and Immunology , Interleukin-6 , Allergy and Immunology , Lung , Allergy and Immunology , Virology , Mice , Orthomyxoviridae Infections , Drug Therapy , Pneumonia, Viral , Drug Therapy , Ribavirin , Pharmacology , Tumor Necrosis Factor-alpha , Allergy and Immunology
12.
Article in Chinese | WPRIM | ID: wpr-305080

ABSTRACT

<p><b>OBJECTIVE</b>To explore the brain natriuretic peptide (BNP) on prognostic value in patients with viral myocarditis.</p><p><b>METHODS</b>A total of 48 patients with viral myocarditis and 42 healthy people were enrolled and followed up for two years. The NYHA class and LVEF were recorded and the concentration of BNP were measured.</p><p><b>RESULTS</b>The concentration of BNP were higher and EF were lower in patients with viral myocarditis (P < 0.01) than contrast people. Higher levels of plasma BNP were related to higher mortality.</p><p><b>CONCLUSION</b>Levels of brain natriuretic peptide measured in the plasma could be a useful biochemical marker for the myocarditis, and high concentration of BNP may correlate with poor prognosis in patients with myocarditis.</p>


Subject(s)
Adolescent , Adult , Biomarkers , Blood , Child , Female , Humans , Male , Middle Aged , Myocarditis , Blood , Mortality , Natriuretic Peptide, Brain , Blood , Prognosis , Ventricular Function, Left , Virus Diseases , Blood , Mortality
13.
Chinese Medical Journal ; (24): 939-942, 2011.
Article in English | WPRIM | ID: wpr-239920

ABSTRACT

<p><b>BACKGROUND</b>StentBoost (SB) is a novel angiographic technique which can enhance stent visualization and improve detection of inadequate stent expansion. Studies of SB that compare it with intravascular ultrasound (IVUS), which is the current gold standard for detection of stent underexpansion, remain inadequate. This study aimed to test the correlation of IVUS and SB, and to evaluate the effect of SB guiding the stent postdilatation.</p><p><b>METHODS</b>From March 2009 to June 2010, 52 patients were analyzed using quantitative coronary angiography (QCA), IVUS, and SB. They included 37 patients (54 stents) with postdilatation and 15 patients (21 stents) without postdilatation. Correlations of stent diameter between the three modalities were determined.</p><p><b>RESULTS</b>The minimum diameter, maximum diameter and average diameter of postdilatation obtained by QCA, IVUS, SB were significantly larger than that of poststenting, and the ratio (maximum stent diameter (MaxLD)-minimum stent diameter (MinLD))/MaxLD of postdilatation was smaller. Correlations of MinLD were the highest between IVUS and SB (r = 0.979, P < 0.0001) when compared with QCA and SB (r = 0.973, P < 0.0001), and QCA and IVUS (r = 0.964, P < 0.0001).</p><p><b>CONCLUSIONS</b>SB has superior correlations for stent expansion measured by IVUS when compared with QCA. In addition, there is an important advantage for SB in guiding the stent postdilatation.</p>


Subject(s)
Aged , Coronary Angiography , Methods , Coronary Disease , Therapeutics , Female , Humans , Male , Middle Aged , Stents , Ultrasonography, Interventional , Methods
14.
Article in Chinese | WPRIM | ID: wpr-310377

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of small interfering RNA (siRNA) targeting human vascular endothelial growth factor (hVEGF) on A549 cell growth in nude mice and angiogenesis on chorioallantoic membrane (CAM) assay.</p><p><b>METHODS</b>Three pairs of hVEGF siRNA-plasmid and non-silencing-plasmid were constructed, and transfected into A549 cells through lipofectamine 2000, respectively. The most effective pair of hVEGF siRNA-plasmid was selected by ELISA and real-time RT-PCR. A549 cells transfected with selected hVEGF siRNA- plasmid, A549 cells transfected with non-silencing-plasmid and A549 cells without transfection were inoculated into nude mice, respectively. Chick embryos were randomly divided into four groups and CAM was treated by different solutions for 48 h: culture media DMEM as negative control group,un-transfected A549 cell culture supernatants as positive control group, hVEGF siRNA A549 cell culture supernatants as hVEGF siRNA group and nonsilencing siRNA A549 cell culture supernatants as non-silencing siRNA group. The CAMs were harvested on d12 for microscopic assays.</p><p><b>RESULT</b>Compared with control group, hVEGF siRNA-plasmid induced 48% reduction in hVEGF secretion by A549 cells accompanied by 70% reduction in hVEGF mRNA. Compared with non-silencing siRNA group, the mean tumor volume of murine xenograft was reduced by 58% in hVEGF siRNA group; time for xenografts growing to 50 mm(3)was delayed by 5.4 d. hVEGF contents in xenograft were reduced by 54%; but mean doubling time of tumors and the growth rate of tumors were not significantly reduced. In CAM assays, hVEGF content was zero in negative group, and in hVEGF siRNA group that was 40%-44% of non-silencing siRNA group or positive group; vessels branch points of CAM in hVEGF siRNA group or non-silencing siRNA group or positive group were increased by 45%-55% compared with negative group; total vessel length of CAM in hVEGF siRNA group was increased by 53% compared with negative group, while in non-silencing siRNA group or positive group that was increased by 97% or 99%. Compared with negative control group, the proliferation of microvessels was increased when cell culture supernatant with hVEGF was added in hVEGF siRNA group, significant proliferated vessels were observed in non-silencing siRNA group or positive group.</p><p><b>CONCLUSION</b>A plasmid-mediated hVEGF siRNA has been constructed and verified, which can effectively downregulate the expression of hVEGF in human A549 cells, resulting in the inhibition of angiogenesis. hVEGF siRNA can delay initial growth of A549 tumor xenograft but not reduce the growth rate.</p>


Subject(s)
Adenocarcinoma , Pathology , Animals , Cell Line, Tumor , Cell Proliferation , Chick Embryo , Chorioallantoic Membrane , Metabolism , Female , Humans , Lung Neoplasms , Pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Neovascularization, Physiologic , RNA Interference , RNA, Messenger , Genetics , RNA, Small Interfering , Genetics , Vascular Endothelial Growth Factor A , Genetics
15.
Article in Chinese | WPRIM | ID: wpr-249554

ABSTRACT

In order to improve the mechanical properties of alpha-tricalcium phosphate (alpha-TCP), we prepared surface-modified carbon fibers (CF) reinforced alpha-TCP composite bone cement. Bone cement was soaked in Ringer's body solution to test its capacity of fast formation of hydroxyapatite crystals and self-solidification. Scan electronic microscope (SEM) observation and compressive strength measurement were taken to analyze the mechanical properties and the micro- morphological structure of CF reinforced alpha-TCP bone cement. The results showed that the bone cement was transferred into hydroxyapatite plates after being soaked in Ringer's simulated body fluid for 5 days. Suitable amount of carbon fibers could well spread in and bond with the matrix of the bone cement. The mechanical properties of the bone cement have been improved by CF reinforcing; the compressive strength reaches 46.7 MPa when the amount of carbon fibers is 0.5% in weight percent, which is 22% higher than that of the non-reinforced alpha-TCP bone cement.


Subject(s)
Bone Cements , Chemistry , Calcium Phosphates , Chemistry , Carbon , Chemistry , Durapatite , Chemistry , Materials Testing
16.
Article in Chinese | WPRIM | ID: wpr-684944

ABSTRACT

Adipose-tissue mesenchymal stem cells, is one kind of multipotent stem cells, can differentiate into adipogenic, osteogenic, chondrogenic, myogenic cells and so on in vitro and in vivo. Human adipose tissue is plentiful, easily harvested in large quantity with little patient discomfort. Adipose-tissue derived mesenchymal stem cells may be an alternative stem cell source for mesenchymal tissue regeneration and engineering without ethical consideration of embryonic stem cells and severe pain resulted by bone marrow procurement. The research work on adipose-tissue mesenchymal stem cells and future clinical perspectives were reviewed.

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