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1.
Article in Chinese | WPRIM | ID: wpr-906293

ABSTRACT

Objective:To compare the therapeutic efficacies of Wujiwan at two different compatibilities (No.1 and No.2) on irritable bowel syndrome (IBS) based on neuro-endocrine-immune network, and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine (TCM). Method:The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty (PTCA) in suckling rats. The animals were randomly divided into a control group, a model group, a dicetel group (0.01 g·kg<sup>-1</sup>), low- (0.335 g·kg<sup>-</sup><bold><sup>1</sup></bold>), medium- (0.67 g·kg<sup>-</sup><bold><sup>1</sup></bold>), and high-dose (1.34 g·kg<sup>-</sup><bold><sup>1</sup></bold>) No. 1 Wujiwan groups, and low- (0.385 g·kg<sup>-</sup><bold><sup>1</sup></bold>), medium- (0.77 g·kg<sup>-</sup><bold><sup>1</sup></bold>), and high-dose (1.54 g·kg<sup>-</sup><bold><sup>1</sup></bold>) No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells (MC) in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine (5-HT), substance P (SP), somatostatin (SS), and vasoactive intestinal peptide (VIP) in the blood/colon tissue were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assay. Result:There was no significant difference in body weight among different groups. Compared with the control group, the model group exhibited decreased thresholds of abdominal elevation and bow back elevation (<italic>P<</italic>0.01), increased density of MCs in the colon tissue (<italic>P<</italic>0.05), up-regulated levels of 5-HT, SP, and SS in the blood and colon tissue (<italic>P<</italic>0.05, <italic>P<</italic>0.01), and elevated VIP level in the colon tissue (<italic>P</italic><0.05). Compared with the model group, Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation (<italic>P</italic><0.01), diminish the count of MC in the colon tissue (<italic>P</italic><0.05), and reduce the levels of 5-HT, SP, SS, and VIP (<italic>P</italic><0.05). As demonstrated by the comparison of No. 1 and No. 2 Wujiwan, No. 1 was superior to No. 2 in reducing the concentrations of 5-HT, SP, and SS in the blood, especially in 5-HT (<italic>P</italic><0.01). No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan, No. 2 significantly reduced SP expression, and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups (<italic>P</italic><0.05). Conclusion:Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect, No. 1 was superior to No. 2, while in terms of local effect, No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics, while No. 2 had an advantageous effect on intestinal sensation over No. 1.

2.
Article in Chinese | WPRIM | ID: wpr-906220

ABSTRACT

Objective:To analyze active components, its targets and signaling pathways of Shenlian formula based on network pharmacology, and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease (ASCVD), in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine (TCMSP), its target proteins were obtained by SymMap and ETCM Databases, and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions (PPI) network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds, 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 (PTGS2), estrogen receptor 1 (ESR1) and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic, nitric oxide biosynthetic process, response to estradiol, angiogenesis, inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway, phosphatidylinositol-3 kinase (PI3K)/ protein kinase B (Akt) signaling pathway, hypoxia induction factor-1 (HIF-1) signaling pathway and apoptosis. Among them, the regulatory effect of Shenlian formula on apoptosis may act on not only TP53, but also different signaling pathways of apoptosis respectively, thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area, improve the myocardial histopathological changes, and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD, and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

3.
Article in Chinese | WPRIM | ID: wpr-905997

ABSTRACT

Objective:To establish an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration, and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome (CVH-IBS). Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty (PTCA) balloon stimulation method. After intragastric administration of Wujiwan (0.245 g·kg<sup>-1</sup>), blood was collected from the jugular vein at different time points, and the plasma concentrations of 10 active ingredients (berberine hydrochloride, palmatine hydrochloride, coptisine hydrochloride, jatrorrhizine hydrochloride, epiberberine, dihydroberberine, evodiamine, evodine, paeoniflorin, albiflorin) in Wujiwan was detected simultaneously by UPLC-MS/MS, the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group, the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent, and the peak time (<italic>t</italic><sub>max</sub>) was prolonged. Among them, the <italic>t</italic><sub>max</sub> of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute, respectively (<italic>P</italic><0.05, <italic>P</italic><0.01). Area under the plasma concentration-time curve (AUC<sub>0-</sub><italic><sub>t</sub></italic>) of each component increased, and evodiamine and paeoniflorin were significantly different (<italic>P</italic><0.05,<italic> P</italic><0.01). The clearance rates (CL/<italic>F</italic>) of these 10 active ingredients were all decreased, among which berberine hydrochloride, palmatine hydrochloride and evodiamine had significant differences (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats, which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.

4.
Article in Chinese | WPRIM | ID: wpr-887991

ABSTRACT

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.


Subject(s)
Apoptosis , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Plant Extracts , Signal Transduction , Tumor Necrosis Factor-alpha/genetics
5.
Article in Chinese | WPRIM | ID: wpr-878869

ABSTRACT

Corona virus disease 2019(COVID-19) has brought untold human sufferings and economic tragedy worldwide. It causes acute myocardial injury and chronic damage of cardiovascular system, which has attracted much attention from researchers. For the immediate strategy for COVID-19, "drug repurposing" is a new opportunity for developing drugs to fight COVID-19. Artemisinin and its derivatives have a wide range of pharmacological activities. Recent studies have shown that artemisinin has clear cardiovascular protective effects. This paper summarizes the research progress on the pathogenesis the pathogenesis of COVID-19 in cardiovascular damage by 2019 novel coronavirus(2019-nCoV) virus from myocardial cell injury directly by 2019-nCoV virus,viral ligands competitively bind to ACE2 and then reduce the protective effect of ACE2 on cardiovascular disease, "cytokine storm" related myocardial damage, arrhythmia and sudden cardiac death induced by the infection and stress, myocardial injury by hypoxemia, heart damage side effects from COVID-19 drugs and summarizing the cardiovascular protective effects of artemisinin and its derivatives have activities of anti-arrhythmia, anti-myocardial ischemia, anti-atherosclerosis and plaque stabilization. Then analyzed the possible multi-pathway intervention effects of artemisinin-based drugs on multiple complications of COVID-19 based on its specific immunomodulatory effects, protective effects of tissue and organ damage and broad-spectrum antiviral effect, to provide clues for the treatment of cardiovascular complications of COVID-19, and give a new basis for the therapy of COVID-19 through "drug repurposing".


Subject(s)
Artemisinins , COVID-19 , Cardiovascular Diseases , Heart Diseases , Humans , SARS-CoV-2
6.
Article in Chinese | WPRIM | ID: wpr-873014

ABSTRACT

Objective:To study the protective effect and mechanism of artemisinin on systemic inflammatory response syndrome (SIRS)mice using endotoxin (LPS)-induced SIRS mouse model. Method:Male BALB/c mice aged 5-7 weeks were randomly divided into normal group, LPS model group, low, medium and high-dose artemisinin groups (25, 50, 100 mg·kg-1) and ibuprofen group (39 mg·kg-1). LPS (10 mg·kg-1) was intraperitoneally injected at the 7th day after the prophylaxis. According to the SIRS clinical diagnostic criteria, the respiratory rate, rectal temperature, lung index, spleen index, glycolipid metabolism, brain tissue inflammatory factors, and phosphorylation of lung tissue inflammation-related proteins were measured. Result:Intraperitoneal injection of LPS significantly reduced the respiratory rate of mice (P<0.05), body temperature decreased significantly (P<0.01), spleen index increased significantly (P<0.01), peripheral blood neutrophil percentage increased significantly (P<0.05), percentage of monocytes decreased significantly (P<0.01), thrombocyte decreased (P<0.01), platelet specific ratio decreased (P<0.01), total cholesterol content in plasma decreased (P<0.01), plasma glucose content decreased (P<0.01). The expression of interleukin-1β increased in hippocampus and cortex of brain tissue (P<0.01), and the secretion of tumor necrosis factor-α increased in hippocampus and cortex of brain tissue (P<0.01). The expression of phosphorylated protein STAT1 was increased (P<0.01), and the expression of phosphorylated protein c-Jun was increased (P<0.01). After the administration of artemisinin, the body temperature and the respiratory rate of mice induced by LPS were significantly increased, the pathological changes of various organs induced by LPS were alleviated, the hypoglycemia induced by LPS was significantly increased (P<0.05), the levels of inflammatory factors in hippocampus and cortex was significantly reduced, and the expressions of phosphorylated proteins STAT1 and c-Jun in lung tissue were significantly reduced (P<0.05, P<0.01). Conclusion:Artemisinin has a significantly protective effect on SIRS mice induced by intraperitoneal injection of LPS possibly by reducing the secretion of inflammatory factors TNF-α and IL-1β.

7.
Article in Chinese | WPRIM | ID: wpr-872933

ABSTRACT

Objective:By means of network pharmacology, the active ingredients, targets and molecular pathways of Shengmaiyin (Dangshen prescription) in the treatment of atherosclerotic cardiovascular disease (ASCVD) were studied, in order to reveal the molecular mechanism of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD, and provide the rational explanation of the compatibility of the combination. Method:The main chemical components of Shengmaiyin (Dangshen prescription) were obtained by means of SymMap database, traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)platform and BATMAN-TCM platform. Compound targets were retrieved by SymMap and the Encyclopedia of Traditional Chinese Medicine (ETCM), and disease targets were retrieved by DisGeNET and GeneCards databases. The intersections of compound targets and disease targets were used to obtain the predicted targets of song-decoction on ASCVD. The Protein-Protein Interaction (PPI) network diagram was constructed through STRING database, and key compounds and targets of Shengmaiyin (Dangshen prescription) acting on ASCVD were obtained through Cytoscape. Finally, the enriched key targets were put for Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis through the Database for Annotation,Visualization and Integrated Discovery(DAVID). Result:There were 33 key compounds and 25 key targets of Shengmaiyin (Dangshen prescription) for ASCVD. The GO analysis showed that the biological functions of Shengmaiyin (Dangshen prescription) in the treatment of key ASCVD targets mainly involved biological processes, such as the regulation of apoptosis, inflammatory response, regulation of nitric oxide synthesis and regulation of insulin secretion. The KEGG pathway was mainly enriched in 20 signaling pathways, including tumor necrosis factor(TNF) signaling pathway, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway, apoptosis signaling pathway and estrogen signaling pathway. Conclusion:Through network pharmacology, this study explored active ingredients and potential targets of Shengmaiyin (Dangshen prescription) in the treatment of ASCVD at the molecular level, preliminarily verified the mechanism of action of Shengmaiyin (Dangshen prescription), and laid a theoretical foundation for further study on the mechanism of action.

8.
Article in Chinese | WPRIM | ID: wpr-872907

ABSTRACT

The normal immune system has the ability to distinguish between "self" and "non-self". Because of its dynamic balance of "immune activity-immune tolerance", it will produce immune response to the non-self antigen, but with no response or weak response to the self-antigen. However, if the balance was broken, T cell in the abnormal immune activation state will respond continually to the self-antigen, with an abnormal immune response, which caused autoimmune disease. Pathologically, "invalid" immune recognition and immune response become the main causes for autoimmune diseases. Co-stimulatory molecule is an important link between Attach antigen presenting cells(APC) and immune cells (T cell and B cell). Studies have proved that excessive co-stimulation and/or insufficient co-inhibition could cause detect of self-tolerance and induce autoimmunity. Although co-stimulatory and co-inhibitory pathways have a significant impact on all ADS, this paper focuses on their effect on two systemic autoimmune diseases [systemic lupus erythematosus (SLE) and rheumatoid arthritis(RA)] and two organ-specific autoimmune diseases [multiple sclerosis (MS) and type 1 diabetes (T1DM)], in order to discuss the pathogenesis and relationship between co-stimulatory molecules and autoimmune diseases.

9.
Chinese Medical Journal ; (24): 1639-1648, 2020.
Article in English | WPRIM | ID: wpr-827570

ABSTRACT

BACKGROUND@#The efficacy of entecavir (ETV) add-on peg-interferon therapy compared with ETV monotherapy in treatment-naïve hepatitis B virus (HBV) patients remains controversial. We investigated whether adding peg-interferon to ongoing ETV treatment leads to a better curative effect or not.@*METHODS@#All patients have been recruited between August 2013 and January 2015 from the Shanghai Public Health Clinical Center and Zhongshan Hospital (China). Eligible HBV patients (n = 144) were randomly divided (1:1) to receive either ETV monotherapy (n = 70) or peg-interferon add-on therapy from week 26 to 52 (n = 74). Patients were followed-up for at least 2 years. Indexes including hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) seroconversion rate, sustained virologic response, transient elastography value, and histological scores were evaluated every 3 months until the end of the study. The rate of patients with HBsAg loss was defined as the primary endpoint criteria.@*RESULTS@#At week 26, no patient achieved HBsAg seroconversion in either group. At week 52, one patient in the monotherapy group was HBsAg-negative but there was none in the combination therapy group. The monotherapy group showed significantly better liver function recovery results than the combination therapy group. At week 78, one patient in the combination group had HBsAg seroconverted. At week 104, only three patients in the combination therapy group were HBsAg-negative compared with one patient in monotherapy. The mean alanine aminotransferase and aspartate aminotransferase levels and transient elastography values decreased significantly compared with baseline. Both groups showed a favorable decrease in alpha-fetoprotein (monotherapy: 4.5 [2.8, 7.1] vs. 2.2 [1.8, 3.1] ng/mL, P < 0.001; combination therapy: 5.7 [3.0, 18.8] vs. 3.2 [2.0, 4.3] ng/mL, P < 0.001) and an improved result of liver biopsy examination scores. The combination group showed a better improvement in histology compared with the monotherapy group (mean transient elastography value 6.6 [4.9, 9.8] vs. 7.8 [5.4, 11.1] kPa, P = 0.028). But there was no significant difference in HBsAg conversion rate (1.8% [1/56] vs. 4.1% [3/73], P = 0.809) and HBeAg conversion rate (12.5% [7/56] vs. 11.0% [8/73], P = 0.787), as well as HBV-DNA, sustained virologic response (93.2% vs. 98.5%, P = 0.150) between the two groups.@*CONCLUSIONS@#Both therapies supported liver function recovery and histology improvement. Combination therapy did not show better anti-viral efficacy in HBsAg or HBeAg seroconversion compared with monotherapy. However, combination therapy played a more positive role in reversing hepatic fibrosis compared with monotherapy.@*TRIAL REGISTRATION@#ClinicalTrials.gov: NCT02849132; https://clinicaltrials.gov/ct2/show/NCT02849132.

10.
Journal of Medical Postgraduates ; (12): 732-736, 2020.
Article in Chinese | WPRIM | ID: wpr-822592

ABSTRACT

ObjectiveTo explore the value of MSCT for differentiating the hypovascular pancreatic neuroendocrine tumors (Hypo-PNETs) from mass-forming pancreatitis.Methods21 patients with histological-confirmed MPFs and 19 patients with Hypo-PNETs who underwent preoperative dynamic contrast-enhanced CT were included. The CT images were analyzed including tumor size,density, border, CT values in each phase, dilatation of pancreatic duct and bile duct and metastases. The clinical data included age, sex and clinical symptoms.ResultsMFPs often occurred in male patient compared with Hypo-PNETs (85.7% vs 52.6%, P<0.05), and the difference is statistically significant; Metastases only occurred in Hypo-PNETs (P<0.05), and the difference is drastically significant. The well-defined margin often occurred in Hypo-PNETs (52.4% vs 47.6%, P=0.032). Solid tumor more happened in MFPs(95.2% vs 47.4%, P<0.05). The CT values in the portal of MFPs were higher than Hypo-PNETs(P<0.05). The combined features showed accepted diagnostic performance for differentiating Hypo-PNETs from MFPs (89.5% of sensitivity and 95.2% of specificity).ConclusionMFPs often occurred in male patient, and CT values of portal phase, density, border and metastases may be valuable for differentiating Hypo-PNETs from MFPs.

11.
Article in Chinese | WPRIM | ID: wpr-777448

ABSTRACT

In the background of the high incidence and high mortality of cardiovascular diseases,atherosclerosis is the main pathological feature of cardiovascular diseases and the core pathological basis for disease progression. In the evolution of atherosclerotic plaques,the rupture of unstable plaques,plaque shedding and formation of thrombosis are the most dangerous parts. In this process,the formation of plaque fibrosis is the core mechanism regulating plaque stability. Additionally,fibrosis reflects dynamic changes in the inflammatory processes and pathological changes. In view of the inflammation regulation and fibrosis regulation,this paper clarified the process of atherosclerotic plaque,explained the roles of relevant inflammatory cells and cytokines in plaque stability,and summed up drug researches related with stable plaque in recent years. In the future,improving the fibrosis will be a new idea for stabilizing plaque in atherosclerosis drug development.


Subject(s)
Atherosclerosis , Drug Therapy , Pathology , Cytokines , Fibrosis , Humans , Inflammation , Plaque, Atherosclerotic , Drug Therapy , Pathology , Thrombosis , Drug Therapy , Pathology
12.
Article in Chinese | WPRIM | ID: wpr-773100

ABSTRACT

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.


Subject(s)
Animals , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Docetaxel , Pharmacology , Drug Carriers , Lung Neoplasms , Drug Therapy , Pathology , Mice , Micelles , Nanoparticles , Particle Size , Taxoids
13.
Article in Chinese | WPRIM | ID: wpr-773092

ABSTRACT

This paper was mainly to discuss the potential role and mechanism of Lianhua Qingwen Capsules(LHQW) in inhibiting pathological inflammation in the model of acute lung injury caused by bacterial infection. For in vitro study, the mRNA expression of MCP-1 in RAW264.7 cells and THP-1 cells, the content of MCP-1 in cell supernatant, as well as the effect of LHQW on chemotaxis of macrophages were detected. For in vivo study, mice were randomly divided into 7 groups, including normal group, model group(LPS 5 mg·kg~(-1)), LHQW 300, 600 and 1 200 mg·kg~(-1)(low, middle and high dose) groups, dexamethasone 5 mg·kg~(-1) group and penicillin-streptomycin group. Then, the anal temperature was detected two hours later. Dry weight and wet weight of lung tissues in mice were determined; TNF-α and MCP-1 levels in alveolar lavage fluid and MCP-1 in serum were detected. In addition, the infiltration of alveolar macrophages was also observed and the infiltration count of alveolar macrophages was measured by CCK-8 method. HE staining was also used to observe the inflammatory infiltration of lung tissues in mice. Both of the in vitro and in vivo data consistently have confirmed that: by down-regulating the expression of MCP-1, LHWQ could efficiently decrease the chemotaxis of monocytes toward the pulmonary infection foci, thus blocking the disease development in ALI animal model.


Subject(s)
Acute Lung Injury , Microbiology , Animals , Bacterial Infections , Drug Therapy , Bronchoalveolar Lavage Fluid , Capsules , Chemokine CCL2 , Metabolism , Chemotaxis , Drugs, Chinese Herbal , Pharmacology , Humans , Lipopolysaccharides , Lung , Macrophages , Mice , Random Allocation , THP-1 Cells , Tumor Necrosis Factor-alpha , Metabolism
14.
Article in Chinese | WPRIM | ID: wpr-771523

ABSTRACT

Human health has been severely threatened by malignant tumors continuously.Rational and effective drug use provides an effective means for the treatment of malignant tumors,and is expected to become an important way to solve the problem of tumor treatment in the future.In recent years,with the escalation of new cancer theories and the emergence of clinical drug resistance,innovative research and development of anti-cancer drugs has always been a hot spot and focus in cancer research.Among them,the discovery of novel anti-cancer drugs from natural compound is of top priority due to its strong anti-cancer efficacy and the abundant drug resources.Therefore,it is imperative to systematically summarize the cutting-edge advancements of the natural products and their potential pharmacological mechanisms according to the characteristics of tumor progression,and put forward the new directions and trends for further development of anti-cancer natural products in the future.Specifically,the research advancements on anti-cancer effect of natural products were reviewed,focusing on both the traditional and innovative application.We hope this review could bring the light on the research path of the natural anti-cancer products clearly and comprehensively,and also provide inspirations for innovative,safer and more effective anti-cancer drug development and exploration.


Subject(s)
Antineoplastic Agents , Pharmacology , Biological Products , Pharmacology , Humans , Neoplasms , Drug Therapy , Research
15.
Article in Chinese | WPRIM | ID: wpr-802162

ABSTRACT

Objective:To study the effect of Shenlian extract (SL extract) on macrophage function and inflammatory resolution in lipid peroxidation inflammatory injury models. Method:The effects of different concentrations of SL extract (2.5, 5.0, 10.0, 20.0 mg·L-1) on the polarization type, foam formation and chemotactic function of macrophages were detected with RAW264.7 cells induced by oxidized low-density lipoprotein(ox-LDL). Western blot was used to detect pro-inflammatory resolution factor arachidonate 5-lipoxygenase(ALOX5) and inducible inducible nitric oxide synthase(iNOS), and phosphorylated p65 (p-p65) and phosphorylated IκK (p-IκK) in nuclear factor(NF)-κB related signaling pathways. Result:Compared with the control group, ox-LDL enhanced the expressions of M1 macrophage markers TNF-α, IL-1β, iNOS (PPPα, IL-1β, and iNOS (PPPPκK was inhibited significantly (PConclusion:In the inflammatory damage model of lipid peroxidation, SL extract can regulate the polarization of macrophage, inhibit the chemotaxis and foaming of ox-LDL, increase the inflammatory resolution molecular expression, and improve the state of lipid peroxidation, which may be related to the inhibition of NF-κB signaling pathway.

16.
Article in Chinese | WPRIM | ID: wpr-802132

ABSTRACT

Objective: To investigate the protective effect of phenolic compounds 4-hydroxybenzylideneacetone and (HBAc)3,4-dihydroxybenzylideneacetone (DHBAc) of Osmundae Rhizoma on the systemic inflammatory response syndrome (SIRS) in mice by establishing the mice model of SIRS.Method: BALB/c mice were randomly divided into the normal group,the SIRS model group and the different doses of HBAC and DHBAc group (25,50,100 μg·kg-3).Lipopolysaccharides (LPS) was injected intraperitoneally after 7 days of prophylactic administration.After 5 hours of modeling,the anus temperature,respiratory rate,the number of white blood cell (WBC) and platelets (PLT),WBC classification,glycolipid metabolism,inflammatory factor and signal transducing phosphorylated protein of lung were measured.Result: Intraperitoneal injection with LPS (6 mg·kg-1) in mice can significantly reduce the respiratory rate (PPPPPβ(PPPPPPPPPβ(PConclusion: The SIRS model can be established through intraperitoneal injection of LPS.HBAc and DHBAc have protective effects on endotoxin-induced SIRS in mice,and may exert anti-inflammatory effects through IκB and c-JUN pathways.

17.
Article in Chinese | WPRIM | ID: wpr-802078

ABSTRACT

Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.

18.
Article in Chinese | WPRIM | ID: wpr-690938

ABSTRACT

The chimeric antigen receptor (CAR) T cell therapy has gradually became a new trend in the treatment of refractory and relapsed hematologic malignancies by developing for 30 years. With the exciting development of genetic engineering, CAR-T technology has subjected to 4 generations of innovation. Structure of CAR-T started from a single signal molecule to 2 or more than 2 co-stimulatory molecules, and then coding the CAR gene or promoter. CAR-T can specifically recognize tumor antigens, and does not be restricted by major histocompatibility complex (MHC), thus making a breakthrough in clinical treatment. In this review, the history, structure and mechanism of action of CAR-T, as well as the current status and challenges of CAR-T immunotherapy in acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia and multiple myeloma are summarized.


Subject(s)
Antigens, CD19 , Hematologic Neoplasms , Therapeutics , Humans , Immunotherapy , Immunotherapy, Adoptive , Receptors, Antigen, T-Cell , T-Lymphocytes
19.
Article in Chinese | WPRIM | ID: wpr-698794

ABSTRACT

BACKGROUND: Oxidative stress is one of the important mechanisms of postoperative abdominal adhesion. The nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signal pathway is an important endogenous anti-oxidation stress pathway. Our previous study found that ligustrazine nano-spray can inhibit the formation of postoperative abdominal adhesion in rats, and moreover, ligustrazine has an anti-oxidation effect. OBJECTIVE: To observe the effect of ligustrazine nano-spray on the expression of mRNAs and proteins related to the Nrf2-ARE signal pathway in rats with abdominal adhesion, and to investigate the mechanism by which ligustrazine nano-spray inhibits abdominal adhesion via regulating the Nrf2-ARE signal pathway. METHODS: Sprague-Dawley rats were randomly divided into sham group, model group, ligustrazine group and sodium hyaluronate group. In the sham group, only laparotomy was performed without modeling. In the model group, an abdominal adhesion model was created but no drug was used. In the ligustrazine group, ligustrazine nano-spray was used on the wound before incision suturing. In the sodium hyaluronate group, sodium hyaluronate was applied on the wound before incision suturing. RESULTS AND CONCLUSION: Compared with the model group, ligustrazine nano-spray reduced the levels of reactive oxygen species, tissue inhibitor of matrix metalloproteinase 1, but increased the level of matrix metalloproteinase 9 in the rat serum. The expression of Nrf2 and HO-1 mRNA and proteins was also up-regulated in the ligustrazine group relative to the model group. Therefore, ligustrazine nano-sprays can inhibit abdominal adhesions in rats, and its mechanism may be related to the regulation of Nrf2 and heme oxygenase 1 mRNA and proteins expression and the activation of Nrf2-ARE signaling pathway.

20.
Article in Chinese | WPRIM | ID: wpr-689874

ABSTRACT

In view of the fact that the antimalarial effects of artemisinins are significant but the mechanism has not yet been clarified and there are many different opinions, it is possible that artemisinins can produce high anti-malarial efficacy through various mechanisms and multiple pathways. In addition, the researches on the pathogenesis of malaria "erythrocyte membrane plasmodial surface anion channel (PSAC)" in the past few years have provided more positive findings, which may confirm and discover the new antimalarial mechanism of artemisinins. This paper was as to study the effect of dihydroartemisinin (DHA) in vitro on erythrocyte membrane permeability of HB3 plasmodium infection, with using the mechanism of 5% sorbitol can be used to kill the Plasmodium falciparum in red blood cell membrane selectively, the effectual difference of sorbitol on the killing of P. falciparum with adding DHA or not was detected, so as to investigate whether DHA can affect the permeability of the erythrocyte membrane. Result showed that, Pre-stimulation with 10 nmol·L⁻¹ DHA (the final concentration of plasmodium in vitro culture system) for 30 min could significantly decrease the killing effect of sorbitol on the HB3 plasmodium in the P. falciparum erythrocytic cycle, and DHA may inhibit the permeability of the erythrocyte membrane for preventing sorbitol through the red blood cell membrane, thereby reducing the killing effect of sorbitol on the P. falciparum.

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