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1.
J Ethnopharmacol ; 329: 118001, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38467318

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In 2020, liver cancer contributed to approximately 0.9 million new cases and 0.83 million deaths, making it the third leading cause of mortality worldwide. Andrographis paniculata (Burm.f.) Nees(APN), a traditional Chinese or ethnic medicine extensively utilized in Asia, has been historically employed for treating hepatitis and liver cancer. However, the precise molecular mechanism responsible for its therapeutic efficacy remains unclear. AIM OF THE STUDY: To identify and replace the active components of APN on liver cancer, which is investigate the potential of a Multi-Component Chinese Medicine derived from Andrographis paniculata (Burm.f.) Nees(APN-MCCN) for the treatment of liver cancer. MATERIALS AND METHODS: Firstly, the TCMSP database and two liver cancer disease databases were utilized to optimize the chemical constituents of APN and the disease-related targets of liver cancer. The network was constructed using Cytoscape to visualize the relationships between them. Subsequently, the optimal combination of components in APN-MCCN for the treatment of liver cancer was determined using the contribution index method. HPLC analysis was performed to measure the content of each component. Pathway enrichment and gene annotation were conducted using the ClueGo plugin. In vivo efficacy was evaluated by transplanting S180 and H22 tumor-bearing mouse models. In vitro efficacy was determined through MTT assay, morphological observations, flow cytometry analysis, and scratch tests. Western blotting was used to validate the protein expression. The transfection techniques were employed to knockdown the expressions of key protein in different pathway. RESULTS: We obtained 24 effective compounds, with andrographolide contributing 20.78%, wogonin contributing 41.85%, and oroxylin A contributing 30.26% to the overall composition. Based on the predicted enrichment degree and correlation with liver cancer, we identified a total of 27 pathways, among which the Leptin signaling pathway, AGE-RAGE signaling pathway, and Cell Cycle signaling pathway were selected for further investigation. The content of andrographolide, oroxylin A, and wogonin in APN was found to be 0.104%, 0.0024%, and 0.0052%, respectively. In vivo experiments demonstrated that APN-MCCM significantly reduced tumor weight in S180 tumor-bearing mice and prolonged the survival time of H22 liver cancer-bearing mice. APN-MCCM exhibited inhibitory effects on the proliferation, apoptosis, and migration of liver cancer cells while arresting them in the G2/M phase. Furthermore, APN-MCCM down-regulated the protein expression of NCOA1, PTPN1, and GSK3B in the Leptin signaling pathway, NOS2 and NOS3 in the AGE-RAGE signaling pathway, CCNA2, CDK1, CDK2, and CDK7 in the Cell Cycle signaling pathway. Additionally, it upregulated the protein phosphorylation of p-P38 and p-JUN in the AGE-RAGE signaling pathway. Knockout experiments revealed that the inhibitory effect of APN-MCCM on liver cancer cell migration was prevented when the MAPK or NCOA1 genes were knocked out. Similarly, knocking out the CDK7 gene blocked the G2/M phase arrest induced by APN-MCCM in liver cancer cells. CONCLUSIONS: APN-MCCM, consisting of andrographolide, wogonin, and oroxylin A, exhibits inhibitory effects on the cell proliferation of liver cancer cells by targeting the cell cycle pathway. Additionally, it suppresses the migration of liver cancer cells through the AGE-RAGE and Leptin signaling pathways.


Subject(s)
Andrographis , Carcinoma, Hepatocellular , Cell Cycle , Cell Proliferation , Diterpenes , Flavonoids , Leptin , Liver Neoplasms , Signal Transduction , Animals , Cell Proliferation/drug effects , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/metabolism , Diterpenes/pharmacology , Diterpenes/isolation & purification , Humans , Signal Transduction/drug effects , Andrographis/chemistry , Mice , Cell Cycle/drug effects , Flavonoids/pharmacology , Flavonoids/isolation & purification , Leptin/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Agents, Phytogenic/isolation & purification , Male , Cell Line, Tumor , Hep G2 Cells , Mice, Nude , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Flavanones
2.
Front Oncol ; 12: 887244, 2022.
Article in English | MEDLINE | ID: mdl-35656510

ABSTRACT

Background: Transcription factors (TFs) play a crucial role in tumorigenesis and anti-tumor immunity. However, the potential role of large-scale transcription factor regulation patterns in the progression in gastric cancer (GC) is unknown. Methods: We comprehensively assessed the relevance of immune-related TF (IRTF) regulation patterns in anti-tumor immunity and immunotherapy in 1,136 gastric cancer (GC) patients, and evaluated the IRTF score based on IRTF regulation patterns using random forests. Results: Two distinct IRTF regulation patterns were identified, which demonstrating the distinct characteristics in clinical phenotypes, tumor immune microenvironment (TIME), immunogenicity and prognosis in GC. Subsequently, the IRTF score was established to quantify the IRTF regulation pattern for each GC patient. Analysis of large conventional therapy cohorts showed low IRTF score was associated with a better prognosis. In addition, analysis of multiple immunotherapy cohorts showed low IRTF score was also linked to enhanced response to immunotherapy. Conclusion: TF regulation patterns were found to play an important role in the complex immune regulatory relationships in GC. Evaluation of the IRTF regulation patterns in patients will enhance our understanding of immune specificities, and thus, provide effective strategies for personalized therapy.

3.
BMC Cancer ; 21(1): 791, 2021 Jul 08.
Article in English | MEDLINE | ID: mdl-34238253

ABSTRACT

BACKGROUND: Liver cancer is the sixth most commonly diagnosed cancer and the fourth most common cause of cancer death. The purpose of this work is to find new diagnostic biomarkers or prognostic biomarkers and explore the biological functions related to the prognosis of liver cancer. METHODS: GSE25097 datasets were firstly obtained and compared with TCGA LICA datasets and an analysis of the overlapping differentially expressed genes (DEGs) was conducted. Cytoscape was used to screen out the Hub Genes among the DEGs. ROC curve analysis was used to screen the Hub Genes to determine the genes that could be used as diagnostic biomarkers. Kaplan-Meier analysis and Cox proportional hazards model screened genes associated with prognosis biomarkers, and further Gene Set Enrichment Analysis was performed on the prognosis genes to explore the mechanism affecting the survival and prognosis of liver cancer patients. RESULTS: 790 DEGs and 2162 DEGs were obtained respectively from the GSE25097 and TCGA LIHC data sets, and 102 Common DEGs were identified by overlapping the two DEGs. Further screening identified 22 Hub Genes from 102 Common DEGs. ROC and survival curves were used to analyze these 22 Hub Genes and it was found that there were 16 genes with a value of AUC > 90%. Among these, the expression levels of ESR1,SPP1 and FOSB genes were closely related to the survival time of liver cancer patients. Three common pathways of ESR1, FOBS and SPP1 genes were identified along with seven common pathways of ESR1 and SPP1 genes and four common pathways of ESR1 and FOSB genes. CONCLUSIONS: SPP1, AURKA, NUSAP1, TOP2A, UBE2C, AFP, GMNN, PTTG1, RRM2, SPARCL1, CXCL12, FOS, DCN, SOCS3, FOSB and PCK1 can be used as diagnostic biomarkers for liver cancer, among which FOBS and SPP1 genes can also be used as prognostic biomarkers. Activation of the cell cycle-related pathway, pancreas beta cells pathway, and the estrogen signaling pathway, while on the other hand inhibition of the hallmark heme metabolism pathway, hallmark coagulation pathway, and the fat metabolism pathway may promote prognosis in liver cancer patients.


Subject(s)
Biomarkers, Tumor/metabolism , Liver Neoplasms/genetics , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Prognosis , Survival Analysis
4.
Org Biomol Chem ; 19(17): 3911-3924, 2021 05 05.
Article in English | MEDLINE | ID: mdl-33949415

ABSTRACT

The regioselective direct C3-esterification of indoles with OXA is developed in an efficient reaction with carboxylic acids using the catalyst CuBr2 and oxidants Ag2CO3 and K2S2O8. The simple experimental procedure is proved to be broadly applicable to a range of substrates, including aromatic and aliphatic acids, and the corresponding products were obtained in good yields up to 87%. At the same time, it provides a valuable approach to produce C3-benzyl derivatives of indoles through reaction with benzyl carboxylic acid under the same reaction conditions.

5.
J Org Chem ; 86(2): 1789-1801, 2021 01 15.
Article in English | MEDLINE | ID: mdl-33393296

ABSTRACT

The regioselective arylation of inert C3-H bonds in indoles reacting with arylboronates via effective copper-mediated catalysis with the aid of a facile and removable 2-pyridinylisopropyl (PIP) group without ligand participation is reported. This newly established method features high compatibility with diverse functional groups between coupling partners, including both indole substrates and arylboron reagents, consequentially leading to operational simplicity and providing access to generate the desired arylated products in good to excellent yields of up to 97%. Synthetically, the PIP-derived amide moiety could subsequently be readily removed under mild reaction conditions to produce useful indole carboxylic acids for further transformation.

6.
BMC Anesthesiol ; 20(1): 204, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32799814

ABSTRACT

BACKGROUND: Postoperative pain in ambulatory surgery is a multifactorial issue affecting patient satisfaction, time of discharge, and rehospitalization. This study evaluated the efficacy and safety of nalbuphine for the treatment of postoperative pain after ambulatory surgery, relative to tramadol. METHODS: This multi-center, randomized, double blind, and controlled study was conducted at 10 centers. In accordance with the inclusion criteria, 492 ambulatory surgery patients were recruited. These patients had moderate to severe pain after ambulatory surgery, with a visual analogue scale (VAS) score > 3 cm. They were randomly divided into an experimental (n = 248) or control (n = 244) group and treated for analgesia with 0.2 mg/kg of nalbuphine or 2 mg/kg of tramadol, respectively. VAS scores, adverse events, and vital signs of the patients were recorded before administration (baseline; T1); and 30 min (T2), 2 h (T3), 4 h (T4), and 6 h (T5) after administration of analgesia. A decrease in pain intensity of more than 25% compared with the baseline was used as an indicator of analgesic efficacy. The experimental and control groups were compared with regard to this indicator of efficacy at each timepoint. RESULTS: The VAS scores of the experimental and control groups were statistically comparable at timepoints T1-T4. At T5, the VAS scores of the experimental group were significantly lower than that of the control. The pain intensity was significantly higher in the experimental group compared with the control at T2 and T3. Adverse events and vital signs were similar for the two groups at each timepoint. CONCLUSIONS: Nalbuphine can provide effective and safe pain relief in patients after ambulatory surgery. TRIAL REGISTRATION: The registration number is ChiCTR-IOR-16010032 , the date of registration was 2016-11-28.


Subject(s)
Ambulatory Surgical Procedures/methods , Analgesics, Opioid/administration & dosage , Nalbuphine/administration & dosage , Pain Management/methods , Pain, Postoperative/drug therapy , Tramadol/administration & dosage , Adult , Ambulatory Surgical Procedures/adverse effects , Analgesics, Opioid/adverse effects , Double-Blind Method , Female , Humans , Male , Middle Aged , Nalbuphine/adverse effects , Pain, Postoperative/diagnosis , Postoperative Nausea and Vomiting/chemically induced , Postoperative Nausea and Vomiting/diagnosis , Prospective Studies , Tramadol/adverse effects
7.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-817705

ABSTRACT

@#【Objective】To investigate the effect of dexmedetomidine on the phagocytosis of macrophages.【Methods】 RAW264.7 cells were divided into control group,DEX group,and BRL44408 + DEX group. Expression of α2A adrenergic receptor,p-Akt and Akt were detected by Western Blotting;Phagocytosis Assay Kit(IgG PE)was used to measure the phagocytosis of macrophages. 【Results】 α2A adrenergic receptor was detected in RAW264.7 cells;Dexmedetomidine could enhance the phagocytosis of macrophages(P < 0.001),and BRL44408 reversed the enhancement of phagocytic ability of macrophages(P < 0.001);Dexmedetomidine upregulated the expression of Akt in RAW264.7 cells,while the use of BRL44408 inhibited the activation of the Akt pathway(P < 0.01).【Conclusion】Dexmedetomidine could enhance phagocytosis of RAW264.7 by activating the Akt pathway through the α2A adrenergic receptor.

8.
Org Biomol Chem ; 17(38): 8749-8755, 2019 10 14.
Article in English | MEDLINE | ID: mdl-31549131

ABSTRACT

A direct coupling of 2H-indazoles' C3 position and acyl groups has been achieved to produce 3-acyl-2H-indazoles. The Ni(ii)-catalyzed acylation might proceed through a radical pathway for the reaction of 2H-indazoles with either aryl or alkyl aldehydes in the presence of the free radical initiator TBHP and additive PivOH. This method provided a superior approach to fulfil the direct C3-acylation of 2H-indazoles with yields up to 91%. And various substituted 2H-indazoles were well tolerated with this method, enriching the diversity of 2H-indazole derivatives. In comparison with previously reported approaches for the C3-acylation of 2H-indazoles, the developed reaction represents a more convenient and economical method directly using aldehydes as the acylation agents.

9.
Org Lett ; 21(6): 1740-1743, 2019 03 15.
Article in English | MEDLINE | ID: mdl-30802072

ABSTRACT

Here we reported a method for Cu2+-catalyzed ortho-acyloxylation of either the C(sp2)-H or C(sp2)-X (X = Cl, Br) bond of aromatic amides with carboxylic acid, especially olefine acids, to obtain corresponding products in good yields up to 91%. The catalyst CuBr2 is cheap and stable to conserve in comparison with other metals, like Rh, Pd, Ru, and Cu+. This simple procedure is applicable for wide substrate scope and various functional groups to produce carboxylic esters without any additives or ligands.

10.
Perfusion ; 34(3): 203-210, 2019 04.
Article in English | MEDLINE | ID: mdl-30336744

ABSTRACT

BACKGROUND AND OBJECTIVE: A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. METHOD: A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. RESULTS: As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CONCLUSION: CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.


Subject(s)
Cardiopulmonary Bypass/education , Cardiopulmonary Bypass/methods , Simulation Training/methods , Cardiopulmonary Bypass/instrumentation , China , Humans , Perfusion/instrumentation , Perfusion/methods
11.
Eur J Med Chem ; 137: 598-611, 2017 Sep 08.
Article in English | MEDLINE | ID: mdl-28651225

ABSTRACT

Herein, we described the design and synthesis of a series of pyridazine-3-carboxamides to be CB2-selective agonists via a combination of scaffold hopping and bioisosterism strategies. The compounds were subjected to assessment of their potential activities through calcium mobilization assays. Among the tested derivatives, more than half of these compounds exhibited moderate to potent CB2 agonist activity. Six compounds showed EC50 values below 35 nM, and several derivatives also exhibited significantly enhanced potency and high selectivity at the CB2 receptor over the CB1 receptor. Specifically, compound 26 showed the highest CB2 agonist activity (EC50 = 3.665 ± 0.553 nM) and remarkable selectivity (Selectivity Index > 2729) against CB1. In addition, logPs of some representative compounds were measured to display significantly decreased values in comparison with GW842166X. Furthermore, docking simulations were conducted to explain the interaction mode of this series.


Subject(s)
Pyridazines/pharmacology , Receptor, Cannabinoid, CB2/agonists , Animals , CHO Cells , Cricetulus , Dose-Response Relationship, Drug , Humans , Molecular Docking Simulation , Molecular Structure , Pyridazines/chemical synthesis , Pyridazines/chemistry , Structure-Activity Relationship
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-663976

ABSTRACT

Objective:To explore therapeutic effect of spironolactone combined benazepril on patients with acute ante-rior myocardial infarction(AAMI)and its influence on left ventricular remodeling.Methods:A total of 100 AAMI patients treated in our hospital were regard as study object.According to therapeutic method,they were divided into benazepril group(n=50)and combined treatment group(n=50,received spironolactone combined benazepril),both groups were treated for six months.Therapeutic effect,left ventricular remodeling condition and incidence of adverse reactions were compared between two groups.Results:Compared with before treatment,after six-month treatment,there were significant rise in all indexes of heart rate variability(HRV)and left ventricular ejection fraction(LVEF),and significant reductions in left ventricular end-systolic dimension(LVESd)and left ventricular end-diastolic dimension(LVEDd)in two groups,P<0.05 or <0.01;compared with benazepril group after treatment,there were significant rise in all HRV indexes and LVEF[(52.45 ± 8.65)% vs.(57.85 ± 9.70)%],and significant reductions in LVESd[(36.25 ± 2.13)mm vs.(30.10 ± 2.06)mm]and LVEDd[(58.60 ± 6.41)mm vs.(51.29 ± 6.20)mm]in combined treatment group,P<0.01 all;there was no significant difference in total adverse reaction rate between two groups,P=1.000. Conclusion:Spironolactone combined benazepril can significantly improve HRV and heart function,inhibit left ventricular remodeling in patients with acute anterior myocardial infarction.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-667812

ABSTRACT

Objective To establish a simple and specific method for the determination of rhaponticin in Rhei Radix et Rhizoma. Methods A comparison of the methods of polyamide, silica gel TLC and HPLC in the determination of rhaponticin was studied to investigate the optimum way to identify authentic Rhei Radix et Rhizoma. Results The durability of polyamide and silica gel TLC method for the determination of rhaponticin in Rhei Radix et Rhizoma was poor. HPLC method was more suitable for the detection of rhaponticin. Conclusion HPLC method is accurate and reliable, and can be used for the quality control of Rhei Radix et Rhizoma and provide references for the authenticity of Rhei Radix et Rhizoma.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-663468

ABSTRACT

Objective To develop a new mPCR method for rapid diagnosis of six types of encephalitis causing viruses of HS-VI,HSVII,VZV,EBV,EV71 and CMV.Methods Six pairs of specific primers for CMV,EV71,HSV I,VZV,EBV and HSV II were designed.The mPCR detection method was established and the sensitivity was detected.In order to verify the clinical application value of their multiplex PCR system,fifteen cerebrospinal fluid specimens of clinically suspected VE from the First Affiliated Hospital of Soochow University from 2014 to 2015 were examined by the mPCR method.Results The 6 pairs of primers did not interfere with each other,and the sensitivity of the mPCR system was over 103copies/μl.Among 15 cerebrospinal fluid specimens from patients with suspected viral encephalitis,six specimens(6/15,40%)were tested positive by the mPCR.Among them,HSV I was 5 and CMV was 1.Conclusion The mPCR method for detecting six types of en-cephalitis-associated virus at same time was established with high specificity,sensitivity and stability.

15.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-659936

ABSTRACT

Objective To study clinical effects of the fexofenadine hydrochloride Tablets and BCG-PSN in the treatment of chronic urticaria. Methods 122 patients with chronic urticaria treated in Yiwu skin disease hospital from January 2016 to March 2017 were selected and randomly divided into the control group and the experimental group, 61 patients for each group. The control group was given Fexofenadine Hydrochloride Tablets treatment, the experimental group was given BCG-PSN on the basic treatment of the control group. The patients in the experimental group and the control group were treated for 3 months. The treatment effect and adverse reactions were compared between two groups. Results After the corresponding treatment, the number of invalid cases in the experimental group was 10. In the control group, 21 cases were ineffective. The effective rate of the experimental group was 63.93%, which was significantly higher than 32.97% of the control group with statistical significance (P<0.05). There were no obvious adverse reactions in the two groups, and there was no significant difference in the incidence of adverse reactions. After treatment, the integral score of the experimental group was (3.20±0.42), significantly lower than that of the control group (3.98±0.37), with statistical significance (P<0.05). Conclusion fexofenadine hydrochloride Tablets combined with BCG-PSN for the treatment of chronic urticaria could significantly improve clinical symptoms of patients with good efficacy, high safety and clinical application significance.

16.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-657644

ABSTRACT

Objective To study clinical effects of the fexofenadine hydrochloride Tablets and BCG-PSN in the treatment of chronic urticaria. Methods 122 patients with chronic urticaria treated in Yiwu skin disease hospital from January 2016 to March 2017 were selected and randomly divided into the control group and the experimental group, 61 patients for each group. The control group was given Fexofenadine Hydrochloride Tablets treatment, the experimental group was given BCG-PSN on the basic treatment of the control group. The patients in the experimental group and the control group were treated for 3 months. The treatment effect and adverse reactions were compared between two groups. Results After the corresponding treatment, the number of invalid cases in the experimental group was 10. In the control group, 21 cases were ineffective. The effective rate of the experimental group was 63.93%, which was significantly higher than 32.97% of the control group with statistical significance (P<0.05). There were no obvious adverse reactions in the two groups, and there was no significant difference in the incidence of adverse reactions. After treatment, the integral score of the experimental group was (3.20±0.42), significantly lower than that of the control group (3.98±0.37), with statistical significance (P<0.05). Conclusion fexofenadine hydrochloride Tablets combined with BCG-PSN for the treatment of chronic urticaria could significantly improve clinical symptoms of patients with good efficacy, high safety and clinical application significance.

17.
Int J Oncol ; 48(6): 2453-60, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27082253

ABSTRACT

Oridonin is one of the most important antitumor active ingredients of Rabdosia rubescens. Recently published studies from our laboratory have demonstrated that oridonin was able to arrest human gastric cancer SGC-7901 cells at G2/M phase. However, little is known about inducing apoptosis in gastric cancer. The aim of this study was to investigate the effect of oridonin on antineoplastic capability of SGC-7901 cells and the detailed molecular mechanism of oridonin-mediated intrinsic pathway of apoptosis. Cell proliferation was assessed by MTT assay while apoptosis induced by oridonin was determined by Hoechst 33342 staining assay and Annexin V/PI double staining assay. Early apoptotic rate was stained by Annexin V/PI and detected by flow cytometry. Apoptosis pathway was analyzed by western blot analysis of Bcl-2, Bax, cytochrome c and caspase-3 expression. The results showed that oridonin was able to inhibit the SGC-7901 cell proliferation, the 50% growth inhibition (IC50) was 22.74 µM. Oridonin could induce cell apoptosis of SGC-7901 cells and the early apoptotic rates induced by 0, 20, 40, 80 µmol/l oridonin were 1.53±0.67, 3.33±0.29, 84.80±0.82 and 96.43±0.51%, respectively. Western blot analysis revealed that oridonin downregulated Bcl-2 protein (the anti-apoptotic factor) and upregulated Bax protein (pro-apoptotic factor), eventually leading to a reduction in the ratio of Bcl-2/Bax proteins. Furthermore, oridonin induced the release of cytochrome c from the mitochondria to the cytosol and the activation of caspase-3. Taken together, the current study suggested that oridonin induced apoptosis in SGC-7901 cells via the mitochondrial signal pathway, which may represent one of the major mechanisms of oridonin-mediated apoptosis in SGC-7901 cells.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes, Kaurane/pharmacology , Mitochondria/drug effects , Stomach Neoplasms/metabolism , Apoptosis , Caspase 3/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytochromes c/metabolism , Dose-Response Relationship, Drug , Gene Expression Regulation, Neoplastic , Humans , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , Stomach Neoplasms/drug therapy , bcl-2-Associated X Protein/metabolism
18.
J Surg Res ; 201(2): 258-65, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27020805

ABSTRACT

BACKGROUND: Intestinal ischemia-reperfusion (IIR) could lead to acute lung injury, associated with severe alveolar epithelial cells inflammatory and oxidative injury. Alpha7 nicotinic acetylcholine receptor (α7nAChR) is an essential component of the cholinergic anti-inflammatory pathway. The aim of this study was to investigate the important role of α7nAChR on the lung subjected to IIR. METHODS: Thirty-two Sprague-Dawley rats were randomly divided into four groups (n = 8 in each): sham group (group S), model group (group M), α7nAChR agonist PNU-282987-treated group (group PNU), and specific α7nAChR antagonist methyllycaconitine-treated group (group MLA). Intestinal IR damage was induced by clamping the superior mesenteric artery for 75 min, followed by a 120-min reperfusion. All rats were killed at 2 h after release of the clamps. The histologic examination of lungs was made, and lung water content was detected. Expression levels of malondialdehyde, tumor necrosis factor alpha, interleukin-6, and superoxide dismutase activity of the lungs were detected. Additionally, expression level of toll-like receptor (TLR)4 and nuclear factor-kappaB (NF-κB p65) in the nucleus of lung tissue and apoptosis-related protein (Bax, Bcl-2, and cleaved-caspase3) were detected using Western blot. RESULTS: Lungs were damaged after intestine IR, manifested by higher lung water content, histologic score, concentrations of interleukin-6, tumor necrosis factor alpha, and malondialdehyde of group M than those of group S, accompanied with decreased superoxide dismutase activity (P < 0.05). PNU treatment could significantly improve the pulmonary function of rats subjected to IIR. These effects of activation of α7nAChR were associated with suppression of TLR4/NF-κB pathway and subsequent reduction of apoptosis-related protein. However, MLA treatment aggravated lung injury. CONCLUSIONS: α7nAChR plays a role in acute lung injury induced by IIR via attenuating lung oxidative stress and inflammation through suppression of TLR4/NF-κB pathway, resulting in reduction of apoptosis in the lung.


Subject(s)
Acute Lung Injury/prevention & control , Benzamides/therapeutic use , Bridged Bicyclo Compounds/therapeutic use , Intestines/blood supply , Reperfusion Injury/complications , alpha7 Nicotinic Acetylcholine Receptor/agonists , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Animals , Apoptosis/drug effects , Benzamides/pharmacology , Bridged Bicyclo Compounds/pharmacology , Drug Evaluation, Preclinical , Lung/drug effects , Lung/metabolism , NF-kappa B/metabolism , Random Allocation , Rats, Sprague-Dawley , Signal Transduction/drug effects , Toll-Like Receptor 4/metabolism
19.
Article in Chinese | MEDLINE | ID: mdl-26672216

ABSTRACT

OBJECTIVE: To understand the status of echinococcosis in Maqing County of Qinghai Province in order to facilitate echinococcosis control in this region. METHODS: Ultrasonic scanning and indirect hemagglutination assay were used to detect echinococcosis infection in residents >1 year old, according to the People's Republic of China Health Industry Standard--Diagnostic Criteria for Hydatid Disease (WS257-2006). Meanwhile, ELISA was used o detect the Echinococcus antigen in dog's feces collected in Youyun, Dangluo and Xiadawu townships. RESULTS: Ultrasonic scanning showed that the prevalence of hydatid disease in the residents was 7.4% (116/1 561), cystic hydatid disease 5.3% (82/1 561), alveolar hydatid disease 2.2% (34/1 561). The serum positive rate in human population was 23.8%(307/1 288). Of the 82 cases of cystic hydatid disease, 23 cases (28.1%) had the hydatid cyst with a diameter of >10 cm. The prevalence in males and females in the county was 5.3% (40/753) and 9.4% (76/808), respectively (P<0.05). Among populations with different occupations, the highest prevalence of hydatid disease fell into houseworkers (11/61, 18.0%), monks (5/41, 12.2%) and herdsmen (84/758, 11.1%). Among the age groups, the groups of >60 years (24/132, 18.2%) and 30-40 years (31/302, 10.3%) had higher prevalence of hydatid disease. The three townships with the higher prevalence were Youyun (29/247, 11.7%), Changmahe (6/63, 9.5%) and Dangluo (54/645, 8.4%). Of the 199 samples of dog's feces, 54 were positive for Echinococcus antigens (27.1%), with a positive rate of 40.4% (23/57) in Youyun towship, being significantly higher than in the other two (P<0.05). CONCLUSION: Maqin county is a co-endemic area of cystic echinococcosis and alveolar echinococcosis. The prevalence is higher in females and those over 60 years-old.


Subject(s)
Echinococcosis , Echinococcus , Animals , China , Dogs , Enzyme-Linked Immunosorbent Assay , Feces , Female , Hemagglutination Tests , Humans , Infant , Male , Prevalence
20.
Mediators Inflamm ; 2015: 726243, 2015.
Article in English | MEDLINE | ID: mdl-26273142

ABSTRACT

Acute kidney injury associated with renal hypoperfusion is a frequent and severe complication during sepsis. Fluid resuscitation is the main therapy. However, heart failure is usually lethal for those patients receiving large volumes of fluids. We compared the effects of small-volume resuscitation using four different treatment regimens, involving saline, hypertonic saline (HTS), hydroxyethyl starch (HES), or hypertonic saline hydroxyethyl starch (HSH), on the kidneys of rats treated with lipopolysaccharide (LPS) to induce endotoxemia. LPS injection caused reduced and progressively deteriorated systemic (arterial blood pressure) and renal hemodynamics (renal blood flow and renal vascular resistance index) over time. This deterioration was accompanied by marked renal functional and pathological injury, as well as an oxidative and inflammatory response, manifesting as increased levels of tumor necrosis factor-α, nitric oxide, and malondialdehyde and decreased activity of superoxide dismutase. Small-volume perfusion with saline failed to improve renal and systemic circulation. However, small-volume perfusion with HES and HSH greatly improved the above parameters, while HTS only transiently improved systemic and renal hemodynamics with obvious renal injury. Therefore, single small-volume resuscitation with HES and HSH could be valid therapeutic approaches to ameliorate kidney injury induced by endotoxemia, while HTS transiently delays injury and saline shows no protective effects.


Subject(s)
Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Endotoxemia/complications , Fluid Therapy/methods , Hydroxyethyl Starch Derivatives/therapeutic use , Animals , Endotoxemia/chemically induced , Lipopolysaccharides/toxicity , Male , Rats , Rats, Sprague-Dawley , Saline Solution, Hypertonic/therapeutic use
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