二氮嗪对自发性高血压大鼠心功能及心肌ERK和JNK表达的影响

目的:探讨二氮嗪对离体自发性高血压大鼠心脏缺血/再灌注心功能及心肌组织ERK和JNK表达的影响及可能机制。方法:雄性自发性高血压大鼠取心行Langendorff灌流。实验分为5组(n=6/组):对照组(Con)在平衡后继续灌流40min,全心缺血25min,复灌30min。其余各组除全心缺血前处理不同外,余均同对照组。缺血预处理组(IP)2次给予5min缺血+10min复灌,二氮嗪预处理组(DP)给予2次含50μmol·L-1二氮嗪的K-H液10min后给不含二氮嗪的K-H液5min,5-HD、5-HD+DP组则在平衡后给予10min150μmol·L-1线粒体KATP阻断剂5-HD,余同Con及DP组。结果:IP组及DP组复灌末左室发展压、+dP/dtmax和-dP/dtmax的恢复率均高于Con组(P<0.01),但两组左室舒张末期压恢复率低于Con组(P<0.01);5-HD能拮抗二氮嗪引起的心功能指标的改善。复灌末IP、DP及5-HD+DP组ERK表达增加。IP组及DP组心肌的JNK表达低于Con组(P<0.05),5-HD+DP组JNK表达显著高于DP组。结论:二氮嗪预处理对离体自发性高血压大鼠心肌缺血/再灌注损伤有保护作用,此保护作用可能与ERK的表达增加及JNK表达减少有关。     

Association between cyclooxygenase-2 gene polymorphisms and risk of periodontitis: a meta-analysis involving 5653 individuals

There ?765G > C, ?1195G > A, and 8473T > C polymorphisms in cyclooxygenase-2 (COX-2) gene polymorphisms and periodontitis risk were investigated based on published studies; however, their results could not give a conclusive result. Hence, we performed this meta-analysis of six published studies with eight case–control studies including these three polymorphisms which searched from PubMed and Web of Science up to October 15th, 2013. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between the three polymorphisms of COX-2 and periodontitis risk. The results from 2,580 periodontitis patients and 3,073 healthy controls showed that none of ?765G > C, ?1195G > A, or 8473T > C polymorphism was not associated with periodontitis susceptibility [Take ?765G > C for example: OR = 0.94, 95 % CI = (0.57–1.53) for C vs. G; OR = 2.34, 95 % CI = (0.72–7.62) for CC vs. GG; OR = 0.68, 95 % CI = (0.46–1.01) for CG vs. GG; OR = 0.81, 95 % CI = (0.52–1.27) for (CG+GG) vs. GG; OR = 2.57, 95 % CI = (0.80–8.29) for CC vs. (GG+CG)]. In subgroup analyses according to the type of periodontitis and ethnicity for ?765G > C and ?1195G > A, and deviations in Hardy–Weinberg equilibrium for ?765G > C, we only observe a boundary association between ?1195G > A polymorphism and Asian population. However, due to limitations of this meta-analysis, the results should treat with caution and we suggest the further researches should be carried out to verify our results.     

Anti-IL-33 antibody treatment inhibits airway inflammation in a murine model of allergic asthma

Interleukin (IL)-33 is a recently described member of the IL-1 family and has been shown to induce production of T helper type 2 cytokines. In this study, an anti-IL-33 antibody was evaluated against pulmonary inflammation in mice sensitized and challenged with ovalbumin. The anti-IL-33 or a control antibody (150 μg/mouse) was given intraperitoneally as five doses before the sensitization and antigen challenge. Treatment with anti-IL-33 significantly reduced serum IgE secretion, the numbers of eosinophils and lymphocytes, and concentrations of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid compared with administration of a control antibody. Histological examination of lung tissue demonstrated that anti-IL-33 significantly inhibited allergen-induced lung eosinophilic inflammation and mucus hypersecretion. Our data demonstrate for the first time that anti-IL-33 antibody can prevent the development of asthma in a mouse model and indicate that blockade of IL-33 may be a new therapeutic strategy for allergic asthma.     

Aristolochic acid I induced autophagy extenuates cell apoptosis via ERK 1/2 pathway in renal tubular epithelial cells

Autophagy is a lysosomal degradation pathway that is essential for cell survival and tissue homeostasis. However, limited information is available about autophagy in aristolochic acid (AA) nephropathy. In this study, we investigated the role of autophagy and related signaling pathway during progression of AAI-induced injury to renal tubular epithelial cells (NRK52E cells). The results showed that autophagy in NRK52E cells was detected as early as 3-6 hrs after low dose of AAI (10 μM) exposure as indicated by an up-regulated expression of LC3-II and Beclin 1 proteins. The appearance of AAI-induced punctated staining of autophagosome-associated LC3-II upon GFP-LC3 transfection in NRK52E cells provided further evidence for autophagy. However, cell apoptosis was not detected until 12 hrs after AAI treatment. Blockade of autophagy with Wortmannin or 3-Methyladenine (two inhibitors of phosphoinositede 3-kinases) or small-interfering RNA knockdown of Beclin 1 or Atg7 sensitized the tubular cells to apoptosis. Treatment of NRK52E cells with AAI caused a time-dependent increase in extracellular signal-regulated kinase 1 and 2 (ERK1/2) activity, but not c-Jun N-terminal kinase (JNK) and p38. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased AAI-induced autophagy that was accompanied by an increased apoptosis. Taken together, our study demonstrated for the first time that autophagy occurred earlier than apoptosis during AAI-induced tubular epithelial cell injury. Autophagy induced by AAI via ERK1/2 pathway might attenuate apoptosis, which may provide a protective mechanism for cell survival under AAI-induced pathological condition.     

Examination of the quality of various force fields and solvation models for the equilibrium simulations of GA88 and GB88

Elucidating the relationship between sequence and conformation is essential for the understanding of functions of proteins. While sharing 88 % sequence identity and differing by only seven residues, GA88 and GB88 have completely different structures and serve as ideal systems for investigating the relationship between sequence and function. Benefiting from the continuous advancement of the computational ability of modern computers, molecular dynamics (MD) simulation is now playing an increasingly important role in the study of proteins. However, the reliability of MD simulations is limited by the accuracy of the force fields and solvent model approximations. In this work, several AMBER force fields (AMBER03, AMBER99SB, AMBER12SB, AMBER14SB, AMBER96) and solvent models (TIP3P, IGB5, IGB7, IGB8) have been employed in the simulations of GA88 and GB88. The statistical results from 19 simulations show that GA88 and GB88 both adopt more compact structures than the native structures. GB88 is more stable than GA88 regardless of the force fields and solvent models utilized. Most of the simulations overestimated the salt bridge interaction. The combination of AMBER14SB force field and IGB8 solvent model shows the best overall performance in the simulations of both GA88 and GB88. AMBER03 and AMBER12SB also yield reasonable results but only in the TIP3P explicit solvent model.     

Digestion-Promoting Effects and Mechanisms of Dashanzha Pill Based on Raw and Charred Crataegi Fructus

Emerging evidence suggests that a high-fat diet (HFD) can influence endoplasmic reticulum (ER) stress and gut microbiota. Crataegi Fructus is a traditional Chinese herb widely used in formulas for dyspepsia, with Dashanzha Pill composed of raw Crataegi Fructus (DR) being a representative drug. Processing products of Crataegi Fructus, however, have a stronger pro-digestive effect, and we hypothesized that Dashanzha Pill composed of charred Crataegi Fructus (DC) is more effective. We found that the contents of glucose 1-phosphate and luteolin in DR and DC were substantially different via ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry. DC outperformed DR in improving histopathological changes, increasing gastrin and motilin, and decreasing vasoactive intestinal peptides in rats with HFD induced dyspepsia. Fecal microbiota analysis revealed that DC could restore the disturbed intestinal microbiota composition, including that of Bacteroides, Akkermansia, and Intestinimonas to normal levels. Furthermore, DC significantly reduced the mRNA and protein levels of glucose-regulated protein 78, protein kinase R-like ER kinase, and eukaryotic initiation factor 2α. Taken together, DC outperformed DR in relieving dyspepsia by regulating gut microbiota and alleviating ER stress.     

Isolation,Identification and Characteristics of an Endophytic Quinclorac Degrading Bacterium Bacillus megaterium Q3

In this study, we isolated an endophytic quinclorac-degrading bacterium strain Q3 from the root of tobacco grown in quinclorac contaminated soil. Based on morphological characteristics, Biolog identification, and 16S rDNA sequence analysis, we identified strain Q3 as Bacillus megaterium. We investigated the effects of temperature, pH, inoculation size, and initial quinclorac concentration on growth and degrading efficiency of Q3. Under the optimal degrading condition, Q3 could degrade 93% of quinclorac from the initial concentration of 20 mg/L in seven days. We analyzed the degradation products of quinclorac using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The major degradation products by Q3 were different from those of previously identified quinclorac degrading strains, which suggests that Q3 may employ new pathways for quinclorac degradation. Our indoor pot experiments demonstrated that Q3 can effectively alleviate the quinclorac phytotoxicity in tobacco. As the first endophytic microbial that is capable of degrading quinclorac, Q3 can be a good bioremediation bacterium for quinclorac phytotoxicity.     

大鼠实验性脾虚证胰腺组织化学研究

用成年雄性Ｗｉｓｔａｒ大鼠３０只,分为（１）正常对照组,喂饲自来水。（２）脾虚组,用苦降破气中药和饮食失节法致成脾虚模型。（３）自然恢复组,动物致虚后,喂饲自来水。（４）中药治疗组。取四组动物胰腺进行ＲＮＡ,琥珀酸脱氢酶（ＳＤＨ）,乳酸脱氢酶（ＬＤＨ）,三磷酸腺苷酶（ＡＴＰａｓｅ）,葡萄糖－６－磷酸酶（Ｇ－６－Ｐａｓｅ）和硫胺素焦磷酸酶（ＴＰＰａｓｅ）组织化学反应和观察,并对ＳＤＨ,ＬＤＨ,ＲＮＡ进行了显微分光光度计定量测定。本研究结果表明,脾虚组胰腺泡细胞的ＲＮＡ,ＳＤＨ,ＡＴＰａｓｅ,Ｇ－６－Ｐａｓｅ,ＴＰＰａｓｅ含量和活性都低于对照组,而ＬＤＨ活性高于对照组。治疗组与自然恢复组相比,治疗组胰腺泡细胞以上指标接近对照组。定量测定与定性的结果一致。本研究表明,脾虚证时胰腺泡细胞上述几种酶活性和ＲＮＡ明显下降,可能在脾虚证发病中起主要作用,中药治疗有显著改善