OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) combined with mosapride on gastric emptying rate and gastric motility in the rats with diabetic gastroparesis. METHODS: Using random number table method, 68 male SD rats were divided into a blank group (12 rats) and a model establishment group (56 rats). In the model establishment group, the models of diabetic gastroparesis were established with intraperitoneal injection of streptozotocin combined with high-fat and high-sugar diet. Six weeks later, the successful rat models in the model establishment group were randomized into a model group, an EA group, a mosapride group and a combined treatment group, 12 rats in each one. In the EA group, EA was exerted at "Zusanli" (ST 36) (disperse-dense wave, 2 Hz/15 Hz in frequency, 2 mA in intensity) for 20 min. In the mosapride group, mosapride was intervened with intragastric administration (2 mg/kg). In the combined treatment group, electroacupuncture at "Zusanli" (ST 36) was combined with intragastric administration of mosapride. The intervention was given once daily in each group. There was 1 day at interval after 6-day intervention, consecutively for 5 weeks. At the end of intervention, the random blood glucose, gastric emptying rate and the data of gastric motility (average intra-gastric pressure, amplitude and frequency of gastric motility) were detected. RESULTS: Compared with the blank group, blood glucose was increased in the model group (P<0.001). Blood glucose was reduced in the EA group, the mosapride group and the combined treatment group as compared with the model group separately (P<0.001, P<0.01), whereas, compared with the mosapride group, blood glucose was decreased in the combined treatment group (P<0.05). In comparison with the blank group, the gastric emptying rate, the average intra-gastric pressure and the amplitude of gastric motility were all decreased in the model group (P<0.001) and the frequency of gastric motility was increased (P<0.001). Gastric emptying rate, the average intra-gastric pressure and the amplitude of gastric motility were increased in the EA group, the mosapride group and the combined treatment group (P<0.01, P<0.05, P<0.001) and the frequency of gastric motility was decreased (P<0.001) as compared with the model group respectively. Compared with the EA group, the average intra-gastric pressure and the amplitude of gastric motility were increased in the combined treatment group (P<0.001). In comparison with the mosapride group, the gastric emptying rate, the average intra-gastric pressure, the amplitude and frequency of gastric motility in the combined treatment group, as well as the frequency of gastric motility in the EA group were all increased (P<0.05, P<0.001, P<0.01). CONCLUSION Electroacupuncture at "Zusanli" (ST 36) combined with intragastric administration of mosapride could regulate blood glucose and improve the gastric motility in the rats with diabetic gastroparesis. The effect is better than either simple electroacupuncture or mosapride.
Acupuncture Points ; Animals ; Benzamides ; Diabetes Mellitus/therapy* ; Electroacupuncture ; Gastrointestinal Motility/physiology* ; Gastroparesis/etiology* ; Male ; Morpholines ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation. METHODS: Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema. RESULTS: Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ²=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01). CONCLUSIONS AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.
Animals ; Benzamides ; Graft Rejection/prevention & control* ; Graft Survival ; Liver/pathology* ; Liver Transplantation ; Mechanistic Target of Rapamycin Complex 1 ; Morpholines ; Pyrimidines ; Rats ; Rats, Inbred Lew

This study aims to investigate the efficacy, safety, and cost-effecctiveness of Qizhi Weitong Granules in the treatment of functional dyspepsia. Specifically, two commonly used clinical protocols for the treatment of functional dyspepsia were selected: Qizhi Weitong Granules+Mosapride vs Mosapride alone(control). Meta-analysis of previous clinical studies was performed to examine the efficacy and safety, and pharmacoeconomic evaluation was carried out according to the results of the Meta-analysis. The cost-effectiveness analysis was carried out to elucidated the incremental cost-effectiveness ratio(ICER), and the sensitivity was analyzed with tornado dia-gram and Monte Carlo simulation. The willingness-to-pay threshold of patients for functional dyspepsia was investigated and compared with the ICER to evaluate whether Qizhi Weitong Granules was cost-effective. The result showed that the effective rate of Qizhi Weitong Granules combined with Mosapride in the treatment of functional dyspepsia was 95.49%, which was higher than that of Mosapride alone(73.30%)(OR=8.52, 95%CI[4.36, 16.64])(P<0.000 1). The two groups showed no significant difference in safety. The price of Qizhi Weitong Granules+Mosapride was higher than that of Mosapride alone. The ICER was 640.29 CNY, 1 506.67 CNY lower than the willingness-to-pay threshold. The sensitivity analysis showed that the analysis results were relatively stable. Thus, Qizhi Weitong Granules+Mosapride is safe, effective, and economical in the treatment of functional dyspepsia, which should be further promoted in clinical settings.
Benzamides ; Cost-Benefit Analysis ; Dyspepsia/drug therapy* ; Economics, Pharmaceutical ; Gastrointestinal Agents/therapeutic use* ; Humans ; Morpholines ; Treatment Outcome

OBJECTIVE: To study the effect of the focal adhesion kinase inhibitor TAE226 on epithelial-mesenchymal transition (EMT) in human oral squamous cell carcinoma (OSCC) cell line. METHODS: HSC-3 and HSC-4 cells were cultured with TAE226 under different concentrations (0, 1, 5, and 10 μmol·L⁻¹) for 24, 48, and 72 h. Real-time quantitative polymerase chain reaction was performed to detect the mRNA expressions of E-cadherin and Vimentin. The protein expressions of E-cadherin and Vimentin were determined by Western blot assay after 48 h of TAE226 treatment. RESULTS: Real-time quantitative polymerase chain reaction showed that increasing the TAE226 dose and reaction time resulted in increased and decreased E-cadherin and Vimentin mRNA expressions, respectively (P<0.05). Western blot assays showed that increasing the TAE226 dose resulted in increased and decreased E-cadherin and Vimentin protein expressions, respectively (P<0.05). CONCLUSIONS TAE226, which is expected to be an effective drug for OSCC treatment, can effectively inhibit the EMT of the OSCC cell line.
Cadherins ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Focal Adhesion Protein-Tyrosine Kinases ; Humans ; Morpholines ; Mouth Neoplasms ; Vimentin

OBJECTIVE: To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms. METHODS: We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor). RESULTS: In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis. CONCLUSIONS ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.
Acetates ; pharmacology ; Apoptosis ; drug effects ; genetics ; Autophagy ; drug effects ; Autophagy-Related Proteins ; metabolism ; Benzopyrans ; pharmacology ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Female ; Gene Expression Regulation ; Humans ; MCF-7 Cells ; Morpholines ; pharmacology ; Proto-Oncogene Proteins c-akt ; antagonists & inhibitors ; metabolism ; Pyrans ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; metabolism ; Triazines ; pharmacology ; Ubiquitin-Conjugating Enzymes ; metabolism

The aim of this paper was to explore the mechanism of Shenxiong Glucose Injection antagonizing apoptosis of H9 c2 cells induced by H_2O_2. H9 c2 cells were pretreated with 1. 7%,3. 4% and 6. 8% Shenxiong Glucose Injection,and then H_2O_2 was introduced to induce apoptosis in vitro. Cell viability was detected by MTS assay,morphological changes of apoptosis were observed by AO/EB fluorescence staining,apoptosis rate was detected by Annexin/PI method,cell expression profile was detected by gene chip technology,the mRNA of PIK3 CA,Bcl-2,Bax,caspase-3 and GAPDH were detected by qRT-PCR,the protein expression levels of PIK3 CA,AKT,P-AKT,Bcl-2,Bax and caspase-3 were detected by Western blot,and the contents of LDH and MDA were detected by kit. The results showed that Shenxiong Glucose Injection of different concentrations significantly increased the viability of H9 c2 cells treated with H_2O_2( P<0. 01),and reversed H_2O_2-induced apoptosis( P< 0. 01). The microarray experiments showed that 138 genes were altered in H9 c2 cells after treatment with Shenxiong Glucose Injection. The differential expression fold of PIK3 CA associated with PI3 K/AKT pathway was 3. 59. The results of qRT-PCR and Western blot showed that Shenxiong Glucose Injection could down-regulate the mRNA and protein expression levels of caspase-3( P<0. 01),up-regulate the mRNA and protein expression level of PIK3 CA and Bcl-2( P<0. 01),and up-regulate the phosphorylation levels of AKT( P<0. 01) in H_2O_2-treated H9 c2 cells. The protective effect of Shenxiong Glucose Injection on H_2O_2 cells injury was significantly inhibited by LY294002,a PI3 K/AKT pathway inhibitor. The results suggested that Shenxiong Glucose Injection may inhibit H_2O_2-induced H9 c2 cells apoptosis by regulating PI3 K/AKT signaling pathway.
Animals ; Apoptosis ; Cell Line ; Chromones ; Drugs, Chinese Herbal ; pharmacology ; Glucose ; Morpholines ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction

OBJECTIVE: To investigate the anti-apoptotic effect of Angelica polysaccharide (APS) on cryopreservated platelets and its mechanism. METHODS: The platelets were divided into 4 group: control group(4 ℃ stored platelets),APS group (APS-treated platelets stored at 4 ℃), LY294002 group (LY294002-treated platelets stored at 4 ℃) and LY294002+APS group(LY294002+APS treated platelets stored at 4 ℃ ). The expression of platelet membrane glycoprotein CD41 and CD61, as well as the platelet apoptotic rate, Caspase 3 expression and mitochondrial membrane potential (MMP) were detected by flow cytometry; the anti-apoptotic mechanism of APS by PI3K /AKT signaling pathway was analyzed by Western blot assay. RESULTS: The apoptosis rate of platelets in LY294002 group obviously increased, the activity of CD41 and CD61 expression gradually decreased along with the enhancement of LY294002 concentrations (r=-0.953)； compared with control group, the apoptosis rate of platelets in LY294002 group was enhanced significantly(P<0.05)，while the apoptosis rate of platelets in LY294002+APS group significantly was reduced(P<0.05) as compare with LY294002 group, which suggest that APS has an anti-apoptotic effect on the cryopreserved platelets. APS decreased the expression of Caspase-3 and inhibited the reduction of mitochondrial membrane potential induced by LY294002, moreover, APS could increase the activation of PI3K /AKT pathway in Plt. CONCLUSION APS has an anti-apoptotic effect on the cryopreserved platelets through activating the PI3K /AKT pathway, decreasing the expression of apoptosis protease Caspase-3 and inhibiting the reduction of MMP.
Angelica ; Apoptosis ; Blood Platelets ; Chromones ; Morpholines ; Phosphatidylinositol 3-Kinases ; Polysaccharides ; Proto-Oncogene Proteins c-akt

Prostaglandin (PG) E plays critical roles during pregnancy and parturition. Emerging evidence indicates that human labour is an inflammatory event. We sought to investigate the effect of PGE on the output of proinflammatory cytokines in cultured human uterine smooth muscle cells (HUSMCs) from term pregnant women and elucidate the role of subtypes of PGE receptors (EP, EP, EP and EP). After drug treatment and/or transfection of each receptor siRNA, the concentrations of inflammatory secreting factors in HUSMCs culture medium were detected by the corresponding ELISA kits. The results showed that, PGE increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) output, decreased chemokine (c-x-c motif) ligand 8 (CXCL8) output in a dose-dependent manner, but had no effect on IL-1β and chemokine (c-c motif) ligand 2 (CCL-2) secretion of HUSMCs. EP/EP agonist 17-phenyl-trinor-PGE stimulated IL-6 and TNFα whilst suppressing IL-1β and CXCL8 output. The effects of 17-phenyl-trinor-PGE on IL-1β and CXCL8 secretion were remained whereas its effect on IL-6 and TNFα output did not occur in the cells with EP knockdown. The stimulatory effects of 17-phenyl-trinor-PGE on IL-6 and TNFα were remained whereas the inhibitory effects of 17-phenyl-trinor-PGE on IL-1β secretion was blocked in the cells with EP knockdown. Either of EP and EP agonists stimulated IL-1β and TNFα output, which was reversed by EP and EP siRNA, respectively. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked EP/EP modulation of TNFα and CXCL8 output. PI3K inhibitor LY294002 and P38 inhibitor SB202190 blocked 17-phenyl-trinor-PGE-induced IL-1β and IL-6 output, respectively. The inhibitors of adenylyl cyclase and PKA prevented EP and EP stimulation of IL-1β and TNFα output, whereas PLC and PKC inhibitors blocked EP- and EP-induced TNFα output but not IL-1β output. Our data suggest that PGE receptors exhibit different effects on the output of various cytokines in myometrium, which can subtly modulate the inflammatory microenvironment in myometrium during pregnancy.
Cells, Cultured ; Chromones ; pharmacology ; Cytokines ; metabolism ; Female ; Humans ; Imidazoles ; pharmacology ; Inflammation ; Morpholines ; pharmacology ; Myocytes, Smooth Muscle ; cytology ; Myometrium ; cytology ; Phosphatidylinositol 3-Kinases ; Pregnancy ; Pyridines ; pharmacology ; Receptors, Prostaglandin E ; physiology

BACKGROUND: Chemotherapy is the most important method for cancer treatment. However, chemotherapy induced nausea and vomiting (CINV) has a profound effect on patients. In recent years, there have been new antiemetic drugs, such as aprepitant. We review the curative effect of aprepitant with tropisetron and dexamethasone for prevention of nausea and vomiting in patients receiving Cisplatin chemotherapy. METHODS: Observation is divided into three stages. Whole study phase (0-120 h after chemotherapy administration), acute phases (0-24 h), and delayed phase (24 h-120 h). The primary endpoints were complete response (CR) and complete prevention (CP) during the three different study phase. RESULTS: In the whole study phase, 86.02% of patients achieved CR; in acute phases and delayed phases were 89.25%, 87.1%, respectively. CP were 46.22%, 83.87%, 45.16%, respectively. Anti-CINV effect was significantly associated with age distribution (P=0.008). CONCLUSIONS Aprepitant with tropisetron and dexamethasone prevented effectively CNIV for patients receiving Cisplatin chemotherapy. This combination could improve the quality of life and the compliance of patient with chemotherapy.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; adverse effects ; Aprepitant ; Cisplatin ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Morpholines ; pharmacology ; Nausea ; chemically induced ; prevention & control ; Quality of Life ; Vomiting ; chemically induced ; prevention & control

OBJECTIVE: : To investigate the effect of nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 on the migration of human non-small cell cancer A549 cells and related mechanism. METHODS: : The inhibition effect of FK866 on A549 cells was tested by MTT assay. A549 cells were treated with 1.0 and 10.0 nmol/L FK866, and the cell migration was evaluated by modified wound scratch assay. The mRNA expression of E-cadherin and vimentin was detected by real-time RT-PCR, and the expression of ERK1/2 and pERK1/2 was determined by Western blotting. RESULTS: : FK866 inhibited the proliferation of A549 cells in a time-and concentration-dependent manner; after treatment for 72 h, the IC of FK866 was 9.55 nmol/L. When 1.0 nmol/L or 10.0 nmol/L FK866 was continuously applied 48 h before and 48 h after a scratch was made in wound scratch assay, the migration of A549 cells was significantly inhibited. However, when the FK866 was applied only 48 h after the scratch, the migration of A549 cells was inhibited by 10.0 nmol/L but not by 1.0 nmol/L FK866. The mRNA expression of E-cadherin and vimentin, and the activated ERK1/2 were significantly increased after 1.0 nmol/L FK866 treatment for 72 h. The pretreatment with nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide(1.0 mmol/L) or ERK1/2 inhibitor U0126 (10.0 μmol/L) reversed the up-regulation of E-cadherin and vimentin expression induced by FK866. CONCLUSIONS s: Low concentration of FK866 decreases the migration of A549 cells through the inhibition of NAD level, activation of ERK1/2 and up-regulation of E-cadherin expression. However, it also up-regulates the expression of vimentin, indicating that it may have dual effects on the migration of tumor cells.
A549 Cells ; Cadherins ; genetics ; Cell Movement ; drug effects ; Gene Expression Regulation ; drug effects ; Humans ; Morpholines ; pharmacology ; Neurokinin-1 Receptor Antagonists ; pharmacology ; Nicotinamide Phosphoribosyltransferase ; antagonists & inhibitors ; Piperazines ; pharmacology ; Vimentin ; genetics