Adenoma ; pathology ; Colonic Neoplasms ; pathology ; Humans ; Intestinal Mucosa ; pathology

The aim of the present study was to determine whether angiotensin-converting enzyme inhibitors (ACEI) could contribute to the protective effects of preconditioning, and to explore its underlying mechanism. The Langendorff model of isolated rat heart was used. Cardiac contractility and lactate dehydrogenase (LDH) in the coronary effluent were measured, and infarct area of hearts after 30 min of ischemia followed by 120 min of reperfusion was analyzed. We found that: (1) The subthreshold preconditioning (2 min of ischemia and 10 min of reperfusion), captopril (an ACEI with sulfhydryl groups) or perindoprilate (an ACEI without sulfhydryl groups) alone did not protect the hearts from being injured by 30 min of ischemia and 120 min of reperfusion. (2) However, the combination of captopril or perindoprilate with subthreshold preconditioning could decrease left ventricular end-diastolic pressure (LVEDP), increase left ventricular developed pressure (LVDP) and coronary flow compared with the subthreshold preconditioned group. The combination treatments also inhibited the release of LDH from ischemia/reperfusion hearts, and reduced the infarct area in ischemic heart after 2 h of reperfusion (P<0.05). (3) By using NOS inhibitor L-NAME (100 mumol/L) before combined administration of ACEI with subthreshold preconditioning, the protection effect triggered by the combination treatment was significantly reduced. Pretreatment of the hearts with mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel inhibitor 5-HD (100 mumol/L) also abolished the protection effect (P<0.05). (4) Subthreshold preconditioning, captopril or perindoprilate alone could enhance the NO content in coronary effluent (P<0.05), but the combination of captopril or perindoprilate with subthreshold preconditioning could further augment the NO content compared with the subthreshold preconditioned group (P<0.05). The results indicate that ACEIs with or without sulfhydryl groups may potentiate the subthreshold preconditioning to trigger cardiac protection effect against the ischemia/reperfusion injury. This protection effect in the heart is possibly mediated by the generation of NO and the activation of mitoK(ATP) channel.

OBJECTIVETo investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake.

METHODSWith a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model.

RESULTSFecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in β diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01).

CONCLUSIONShort-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.

OBJECTIVETo investigate the effect of arctiin on advanced oxidation protein product (AOPP)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells and explore the mechanisms underlying this effect.

METHODSHuman proximal tubular cells (HK-2 cells) were treated with bovine serum albumin (BSA) or AOPPs in the presence or absence of arctiin. The expressions of E-cadherin, vimentin, and GRP78 at the protein and mRNA levels in the cells were examined using Western blotting and quantitative real-time PCR. The level of reactive oxygen species (ROS) was measured by flow cytometry with DCFH-DA as the fluorescent probe.

RESULTSCompared with BSA-treated cells, the cells treated with AOPPs showed decreased expression of epithelial cell marker E-cadherin and overexpression of mesenchymal marker vimentin and endoplasmic reticulum stress marker GRP78 with an increased ROS level. These changes induced by AOPPs were partly inhibited by arctiin.

CONCLUSIONArctiin can ameliorate AOPP-induced EMT in tubular cells by inhibiting endoplasmic reticulum stress, and oxidative stress response may participate in this process.

Advanced Oxidation Protein Products ; adverse effects ; Cadherins ; metabolism ; Cell Line ; Endoplasmic Reticulum Stress ; Epithelial Cells ; cytology ; drug effects ; Epithelial-Mesenchymal Transition ; Furans ; pharmacology ; Glucosides ; pharmacology ; Heat-Shock Proteins ; metabolism ; Humans ; Kidney Tubules ; cytology ; drug effects ; Oxidative Stress ; Reactive Oxygen Species ; metabolism ; Vimentin ; metabolism

OBJECTIVETo determine whether U50488H, a selective agonist of kappa-opioid receptor, could induce biphasic (early and late) cardioprotection against myocardial ischemia/reperfusion injury and to explore the underlying mechanisms.

METHODSIsolated perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion and the cardiac function was evaluated.

RESULTLeft ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) and maximal velocity of contraction and relaxation (+/-dP/dtmax) were improved when U50488H was administered 1 or 24 h before ischemia (P<0.05). Myocardial infarct size, activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent were lower in the U50488H pretreatment group than those in the control group. Administration of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib abolished the late phase of cardioprotection produced by administration of U50488H 24 h before ischemia. Activities of CK and LDH in the coronary effluent were higher in U50488H and celecoxib co-pretreatment group than those in U50488H group. However, administration of celecoxib did not block the early phase of cardioprotection by 1 h treatment of U50488H before ischemia.

CONCLUSIONThe late (but not the early) phase of cardioprotection induced by kappa-opioid receptor agonist might be mediated by COX-2.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Creatine Kinase ; metabolism ; Cyclooxygenase 2 ; physiology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; L-Lactate Dehydrogenase ; metabolism ; Male ; Myocardial Infarction ; enzymology ; pathology ; Myocardial Reperfusion Injury ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, kappa ; agonists

AIM To observe the effects of Tangzhi Kangping Granules (Astragali Radix,Ligustri lucidi Fructus,Schisandrae chinensis Fructus,etc.) on regulating blood sugar and lipid of rats with glucose and lipid metabolism disorders.METHODS Among the seventy rats for the trial,ten rats were randomly assigned to normal control group,the other 60 rats were injected with STZ citric acid-sodium citrate solution (60 mg/kg) combined with high-fat emulsion (10 mL/kg) for 4 weeks to be the models of glucose and lipid metabolism disorders.The model rats were divided into model control group,mefformin + fenofibrate group,Xiaoke Pills + Xuezhikang group,and high,medium and low dose Tangzhi Kangping Granules groups.After 4-week intragastric administration,the rats had their levels of fasting serum glucose (GLU),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipids (LDL-C),insulin (INS),adiponectin (ADP),leptin (Leptin),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) measured.RESULTS Compared with the model control group,the rats in high,medium and low dose Tangzhi Kangping Granules groups displayed significantly decreased serum contents of GLU,TG and TC,lowered levels of LDL-C,ADP,Leptin,IL-6,TNF-α,and yet significantly increased levels of HDL-C and INS.CONCLUSION Tangzhi Kangping Granules,a blood sugar andlipid regulator may adjust the levels of insulin,adiponectin and leptin,and therefore improves the body's inflammatory environment to alleviate insulin resistance.

OBJECTIVETo evaluate whether Shenfu injection (SFI) protects against cardiac myocyte injury induced by Fupian injection (FPI) in vitro.

METHODSH9c2 cells were separately treated with FPI, Renshen injection (RSI) and SFI. Cell viability, lactate dehydrogenase (LDH) release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 (CYP2J3) mRNA expression were analyzed.

RESULTSThe viability of H9c2 cells treated with SFI (37 and 75 mg/mL) was significantly higher than that of H9c2 cells treated with FPI (25 and 50 mg/mL) (P<0.05, P<0.01, respectively). LDH activity of H9c2 cells treated with SFI (75 mg/mL) was significantly decreased (P<0.01) compared with that of H9c2 cells treated with FPI (50 mg/mL). SFI (150 mg/mL) significantly attenuated FPI (100 mg/mL)-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI (12 and 25 mg/mL), SFI (18 and 37 mg/mL) treatment could effectively reverse the change of caspase-3/7 activity (P<0.01 and P<0.01, respectively). Compared with FPI (6 and 25 mg/mL), apoptotic cells decreased significantly (P<0.05, P<0.01, respectively) when H9c2 cells were incubated with SFI (9 and 37 mg/mL). The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 (P<0.01), which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment.

CONCLUSIONThese observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.

Animals ; Apoptosis ; drug effects ; Caspases ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Cytochrome P-450 Enzyme System ; genetics ; physiology ; Drugs, Chinese Herbal ; pharmacology ; L-Lactate Dehydrogenase ; secretion ; Myocytes, Cardiac ; drug effects ; enzymology ; Rats

ABSTRACT To consider the cultivation of children's drug clinical research professionals guided by post competence. METHODS The current research status of post competency for clinical research professionals was analyzed, the necessity of constructing a post competency model for children's drug clinical research professionals was discussed, the post competency elements of children's drug clinical research professionals was analyzed, a hierarchical and systematic training goal for children's drug clinical research professionals was set. RESULTS The post competency model for children's drug clinical research professionals needs to be urgently established. CONCLUSION Building a post competency model for children's drug clinical research professionals is an important path for cultivating clinical research professionals in children's drugs.

This study was aimed to investigate the effect of AML1-ETO fusion protein on the anti-apoptotic gene BCL-2 in leukemic cells and to explore its role in leukemogenesis. The apoptotic levels of U937-WT, U937-Mock and U937-A/E1-4 cells were examined by flow cytometry. And cleaved caspase-3 protein expression was detected by Western blot. BCL-2 gene expression both in AML1-ETO-expressing cells or U937 nonexpressing cells and in leukemia cells of AML patients with or without t(8;21) was assessed by quantitative PCR. The chromatin immunoprecipitation (ChIP)-based PCR was used to investigate the direct interaction between the AML1-ETO and BCL-2 promoter in AML1-ETO positive leukemia cell line. The results indicated that in U937-A/E cells but not in U937-WT or U937-Mock cells, apoptotic cells statistically significantly increased, and AML1-ETO expression also significantly enhanced activation of caspase-3. AML1-ETO-expressing cell subclones displayed significantly low levels of BCL-2 mRNA in comparison with the non-transfected U937. In primary bone marrow cells of acute myeloid leukemia containing AML1-ETO, levels of BCL-2 mRNA were markedly lower as compared with other acute myeloid leukemias lacking this translocation. The enriched regions in transfected cells were located within BCL-2 promoter. It is concluded that BCL-2 is the direct target gene of AML1-ETO. AML1-ETO can down-regulate the expression of BCL-2.
Core Binding Factor Alpha 2 Subunit ; genetics ; metabolism ; Gene Expression Regulation, Leukemic ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Oncogene Proteins, Fusion ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RUNX1 Translocation Partner 1 Protein ; U937 Cells

Objective    To understand the status quo of depression and anxiety emotion in perioperative patients with thoracic neoplasms under the concept of enhanced recovery after surgery. Methods    Huaxi emotional-distress index scale (HEI) was adopted to investigate the mental status of 195 patients with thoracic neoplasms in Department of Thoracic Surgery, West China Hospital, and the nursing outpatients between September and November in 2016. There were 118 males and 77 females at age of 17–80 (55.72±12.66) years. Results    There was significant difference in mental health level between the preoperative patients and the postoperative patients (3.70±3.41 vs. 11.01±9.78, P<0.001). The incidence of depression and anxiety emotion in the postoperative patients was significantly higher than that in the preoperative patients (50.00% vs. 9.60%, P<0.001). Besides, there was significant difference of depression and anxiety degree between the preoperative patients and postoperative patients (P<0.001). Moderate to severe depression and anxiety were mostly found in the postoperative patients while mild to moderate depression and anxiety in the preoperative patients. Conclusion    Patients with thoracic neoplasms have much emotional obstacle in perioperative period. The incidence and severity degree of depression and anxiety emotion in postoperative patients are higher than those in preoperative patients.