Toxicity of Cry1A toxins from Bacillus thuringiensis to CF1 cells does not involve activation of adenylate cyclase/PKA signaling pathway

Bacillus thuringiensis (Bt) bacteria produce Cry toxins that are able to kill insect pests. Different models explaining the mode of action of these toxins have been proposed. The pore formation model proposes that the toxin creates pores in the membrane of the larval midgut cells after interaction with different receptors such as cadherin, aminopeptidase N and alkaline phosphatase and that this pore formation activity is responsible for the toxicity of these proteins. The alternative model proposes that interaction with cadherin receptor triggers an intracellular cascade response involving protein G, adenylate cyclase (AC) and protein kinase A (PKA). In addition, it was shown that Cry toxins induce a defense response in the larvae involving the activation of mitogen-activated kinases such as MAPK p38 in different insect orders. Here we analyzed the mechanism of action of Cry1Ab and Cry1Ac toxins and a collection of mutants from these toxins in the insect cell line CF1 from Choristoneura fumiferana, that is naturally sensitive to these toxins. Our results show that both toxins induced permeability of K⁺ ions into the cells. The initial response after intoxication with Cry1Ab and Cry1Ac toxins involves the activation of a defense response that involves the phosphorylation of MAPK p38. Analysis of activation of PKA and AC activities indicated that the signal transduction involving PKA, AC and cAMP was not activated during Cry1Ab or Cry1Ac intoxication. In contrast we show that Cry1Ab and Cry1Ac activate apoptosis. These data indicate that Cry toxins can induce an apoptotic death response not related with AC/PKA activation. Since Cry1Ab and Cry1Ac toxins affected K⁺ ion permeability into the cells, and that mutant toxins affected in pore formation are not toxic to CF1, we propose that pore formation activity of the toxins is responsible of triggering cell death response in CF1cells.     

松龄血脉康胶囊联合低剂量厄贝沙坦治疗65岁以上高血压患者疗效观察

目的观察松龄血脉康胶囊联合低剂量厄贝沙坦治疗65岁以上老年高血压病患者的临床疗效。方法将90例65岁以上高血压患者随机分为松龄血脉康胶囊联合低剂量厄贝沙坦治疗组和高剂量厄贝沙坦对照组。治疗组给予松龄血脉康胶囊1.5g,每天3次,同时加厄贝沙坦75mg/d;对照组单纯给予厄贝沙坦150mg/d治疗。两组治疗周期为1个月进行比较血压控制情况及不良反应等指标水平。结果治疗后,两组患者收缩压和舒张压均较治疗前下降,差异有统计学意义(P0.05);治疗后两组患者的收缩压、舒张压比较,差异无统计学意义(P0.05)。结论松龄血脉康联合低剂量厄贝沙坦治疗高血压疗效确切,无明显不良反应,值得临床应用。     

Concentration‐ and flux‐based dose–responses of isoprene emission from poplar leaves and plants exposed to an ozone concentration gradient

Concentration‐ and flux‐based O₃ dose–responses of isoprene emission from single leaves and whole plants were developed. Two poplar clones differing in O₃ sensitivity were exposed to five O₃ levels in open‐top chambers for 97 d: charcoal‐filtered ambient air (CF), non‐filtered ambient air (NF) and NF plus 20 ppb (NF + 20), 40 ppb (NF + 40) and 60 ppb (NF + 60). At both leaf and plant level, isoprene emission was significantly decreased by NF + 40 and NF + 60 for both clones. Although intra‐specific variability was found when the emissions were up‐scaled to the whole plant, both leaf‐ and plant‐level emissions decreased linearly with increasing concentration‐based (AOT40, cumulative exposure to hourly O₃ concentrations >40 ppb) and flux‐based indices (POD_Y, cumulative stomatal uptake of O₃ > Y nmol O₃ m^?2 PLA s^?1). AOT40‐ and POD₇‐based dose–responses performed equally well. The two clones responded differently to AOT40 and similarly to POD_Y (with a slightly higher R² for POD₇) when the emission was expressed as change relative to clean air. We thus recommend POD₇ as a large‐scale risk assessment metric to estimate isoprene emission responses to O₃ in poplar.     

Human health risks of metals and metalloids in muscle tissue of Synodontis zambezensis Peters, 1852 from Flag Boshielo Dam,South Africa

Muscle tissue from 63 Synodontis zambezensis collected bimonthly in 2013 at Flag Boshielo Dam were analysed for metals and metalloids in a desktop human health risk assessment. The Hazard Quotient, based on a weekly meal of 67 g of fish muscle, exceeded the maximum acceptable level of one for lead, cobalt, cadmium, mercury, arsenic and selenium. The concentrations of these elements were higher in 2013 than those recorded in 2009 and 2012 in other fish species from Flag Boshielo Dam and these may pose a long-term health risk if consumed regularly by impoverished rural communities reliant on fish as a source of protein.     

氟比洛芬酯复合小剂量芬太尼对腹腔镜胆囊切除术患者镇痛效果及凝血功能的影响

目的:探讨氟比洛芬酯复合小剂量芬太尼在腹腔镜胆囊切除术后静脉自控镇痛中的应用及对患者凝血功能的影响。方法:选择2015年11月~2016年11月于我院行腹腔镜胆囊切除术的患者102例,随机分为对照组和研究组,每组51例。对照组患者术后采用小剂量芬太尼静脉自控镇痛,研究组患者术后采用氟比洛芬酯复合小剂量芬太尼静脉自控镇痛。观察并比较两组患者手术前后血清纤维蛋白原(Fg),活化部分凝血酶原时间(APTT),凝血酶原时间(PT),血小板计数(PLT),P物质,5-烃色胺(5-HT),白细胞介素-6、8(IL-6、IL-8)水平以及术后并发症的发生情况。结果:术前,比较两组Fg、APTT、PT、PLT、P物质、5-HT、IL-6、IL-8无差异(P0.05);术后,两组Fg、APTT、PT、PLT、P物质、5-HT、IL-6、IL-8均较术前上升,研究组低于对照组,差异均有统计学意义(P0.05)。研究组术后并发症率低于对照组(P0.05)。结论:氟比洛芬酯复合小剂量芬太尼能够提高腹腔镜胆囊切除术患者静脉自控镇痛的效果,改善凝血功能,降低炎症因子水平。     

Sunflower germination and growth behavior under various gamma radiation absorbed doses

Gamma radiation, various absorbed doses (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 krad) effects were evaluated on sunflower (Helianthus annus. L.) germination and growth characteristics. Sunflower healthy seeds were exposed to gamma radiation source Co⁶⁰ at nuclear institute for food and agriculture and exposed seeds were grown under controlled laboratory conditions. In comparison to control, gamma radiation absorbed doses affected the measured response positively i.e., radical length, plumule length, number of roots, seedling fresh weight, seedling dry weight, germination percentage, time of germination and diameter of hypocotyl of sunflower enhanced up to 83.15%, 70.32%, 73.03%, 4.80%, 3.26%, 72.0%, ? 18.88% and 12.58%, respectively. The time of germination, fresh weight and percent moisture contents enhanced insignificantly, however, the response was higher than control. All gamma radiation absorbed doses showed a stimulatory effect on sunflower germination and seedling growth characteristics. The low gamma radiation absorbed doses were found to be more effective versus higher doses for enhancing the germination and growth characteristics of sunflower. In view of positive effect of gamma radiation of sunflower germination and growth characteristics, it is concluded that this techniques could possibly be used for the enhancement of germination, growth and ultimately yield in sunflower in areas where germination is low due to unfavorable conditions.     

Antioxidant aryl-prenylcoumarin, flavan-3-ols and flavonoids from Eysenhardtia subcoriacea

Antioxidant activity (AOA) assay-guided chemical analysis, using a rat pancreas homogenate model, of aerial parts from Eysenhardtia subcoriacea, led to isolation of the new compound subcoriacin (3-(2'-hydroxy-4',5'-methylendioxyphenyl)-6-(3'-hydroxymethyl-4'-hydroxybut-2'-enyl)-7-hydroxycoumarin) together with the known substances: (+)-catechin, (-)-epicatechin, (+)-afzelechin, eriodictyol, (+)-catechin 3-O-beta-D-galactopyranoside and quercetin 3-O-beta-D-galactopyranoside as bioactive constituents. The structure of the compound was determined from 1D and 2D NMR spectroscopic analyses. Additional known constituents were characterized. The bioactive compounds showed also moderate to strong radical scavenging properties against diphenylpicrylhydrazyl radical (DPPH). In addition, subcoriacin, (+)-catechin, (-)-epicatechin and (+)-afzelechin improved the reduced glutathione levels in rat pancreatic homogenate.     

H2O2应激条件下的活性酵母细胞衍生物的研究

对过氧化氢（H2O2）应激条件下产生的活性酵母衍生物（Live Yeast Cell Derivative,LYCD）进行了研究,结果表明：LYCD对细胞具有明显的促呼吸作用,其作用大小与制备LYCD过程中所加入的H2O2的刺激强度有关。另外,对LYCD中两种重要的抗氧剂-还原型谷胶甘肽（GSH）和超氧化物歧化酶（SOD）的测定分析结果显示：在H2O2的作用下,应激反应发生15min时,LY-CD中SOD的比活力最强,发生30min时,GSH的含量最高,不同的应激产物有各自产生的最佳时间。     

Leptin Response to Glucocorticoid Occurs at Physiological Doses and Is Abolished by Fasting

Objective: To examine the effects of graded doses of hydrocortisone (HC) on leptin secretion, and determine the effect of fasting. Research Methods and Procedures: This was a randomized, placebo‐controlled, crossover study, with a 1‐week “washout” period between interventions. Eight healthy subjects [age = 36 ± 2.3 years (±SE), body mass index = 31.5 ± 1.6 kg/m²] completed the dose‐response study in which an intravenous infusion of saline (placebo) or HC (30 or 100 mg) was administered for 24 hours. Four healthy subjects (age = 35.2 ± 3.0 years, body mass index = 27.1 ± 2.1 kg/m²) completed the fasting study, which entailed continuous infusion of saline, HC (300 mg/24 hours) in the fed state, or HC (300 mg/24 hours) with total caloric deprivation for 24 hours. Blood sampling was performed every 1 to 2 hours for measurement of leptin, cortisol, insulin, and glucose levels. Results: Peak hyperleptinemia occurred after 16 hours of HC infusion; peak/baseline leptin levels were 129% (placebo), 140% (30 mg of HC for 24 hours, p = 0.05), and 185% (100 mg of HC for 24 hours, p < 0.01). During infusion of HC (300 mg/24 hours or placebo), the peak/baseline plasma leptin levels were 16.1 ± 5.8/12.8 ± 5.9 ng/mL (placebo with food, 126%), 14.6 ± 6.0/12.5 ± 6.5 ng/mL (HC fasting, 117%), and 32.5 ± 12.5/12.0 ± 8.4 ng/mL (HC with food, 271%, p < 0.001). Discussion: Leptin secretory responses occur at physiological doses of HC, are obliterated by fasting, and thus may be of metabolic significance.     

A latent contingency table approach to dose finding for combinations of two agents

Summary .  Two-agent combination trials have recently attracted enormous attention in oncology research. There are several strong motivations for combining different agents in a treatment: to induce the synergistic treatment effect, to increase the dose intensity with nonoverlapping toxicities, and to target different tumor cell susceptibilities. To accommodate this growing trend in clinical trials, we propose a Bayesian adaptive design for dose finding based on latent 2 × 2 tables. In the search for the maximum tolerated dose combination, we continuously update the posterior estimates for the unknown parameters associated with marginal probabilities and the correlation parameter based on the data from successive patients. By reordering the dose toxicity probabilities in the two-dimensional space, we assign each coming cohort of patients to the most appropriate dose combination. We conduct extensive simulation studies to examine the operating characteristics of the proposed method under various practical scenarios. Finally, we illustrate our dose-finding procedure with a clinical trial of agent combinations at M. D. Anderson Cancer Center.