Isoliquiritigenin prevents hyperglycemia-induced renal injuries by inhibiting inflammation and oxidative stress via SIRT1-dependent mechanism

Diabetic nephropathy (DN) as a global health concern is closely related to inflammation and oxidation. Isoliquiritigenin (ISL), a natural flavonoid compound, has been demonstrated to inhibit inflammation in macrophages. Herein, we investigated the effect of ISL in protecting against the injury in STZ-induced type 1 DN and in high glucose-induced NRK-52E cells. In this study, it was revealed that the administration of ISL not only ameliorated renal fibrosis and apoptosis, but also induced the deterioration of renal function in diabetic mice. Mediated by MAPKs and Nrf-2 signaling pathways, respectively, upstream inflammatory response and oxidative stress were neutralized by ISL in vitro and in vivo. Moreover, as further revealed by the results of molecular docking, sirtuin 1 (SIRT1) binds to ISL directly, and the involvement of SIRT1 in ISL-mediated renoprotective effects was confirmed by studies using in vitro models of SIRT1 overexpression and knockdown. In summary, by reducing inflammation and oxidative stress, ISL has a significant pharmacological effect on the deterioration of DN. The benefits of ISL are associated with the direct binding to SIRT1, the inhibition of MAPK activation, and the induction of Nrf-2 signaling, suggesting the potential of ISL for DN treatment.Subject terms: Pharmacology, Molecular biology     

Cardiac Fibroblasts Contribute to Myocardial Dysfunction in Mice with Sepsis: The Role of NLRP3 Inflammasome Activation

Myocardial contractile dysfunction in sepsis is associated with the increased morbidity and mortality. Although the underlying mechanisms of the cardiac depression have not been fully elucidated, an exaggerated inflammatory response is believed to be responsible. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome is an intracellular platform that is involved in the maturation and release of interleukin (IL)-1β. The aim of the present study is to evaluate whether sepsis activates NLRP3 inflammasome/caspase-1/IL-1β pathway in cardiac fibroblasts (CFs) and whether this cytokine can subsequently impact the function of cardiomyocytes (cardiac fibroblast-myocyte cross-talk). We show that treatment of CFs with lipopolysaccharide (LPS) induces upregulation of NLRP3, activation of caspase-1, as well as the maturation (activation) and release of IL-1β. In addition, the genetic (small interfering ribonucleic acid [siRNA]) and pharmacological (glyburide) inhibition of the NLRP3 inflammasome in CFs can block this signaling pathway. Furthermore, the inhibition of the NLRP3 inflammasome in cardiac fibroblasts ameliorated the ability of LPS-chalenged CFs to impact cardiomyocyte function as assessed by intracellular cyclic adenosine monophosphate (cAMP) responses in cardiomyocytes. Salient features of this the NLP3 inflammasome/ caspase-1 pathway were confirmed in in vivo models of endotoxemia/sepsis. We found that inhibition of the NLRP3 inflammasome attenuated myocardial dysfunction in mice with LPS and increased the survival rate in mice with feces-induced peritonitis. Our results indicate that the activation of the NLRP3 inflammasome in cardiac fibroblasts is pivotal in the induction of myocardial dysfunction in sepsis.     

武汉东湖桡足类的生态学演变

根据１９６２－１９６３,１９７４－１９７５,１９７９－１９９１年在武汉东湖进行的调查资料,考察了过去三十年内在东湖两个代表性采样站桡足类的种类组成及现存量的变化。结果表明：桡足类种类数由６０年代的１４种减少为９０年代的７种,Ｉ、Ⅱ站在种类组成的差别趋于消失。统计结果表明,东湖桡足类现存量以８０年代初、中期较高。但在水平分布格局上却发生了根本变化,由１９８７年前的Ｉ站现存量高于Ⅱ站,至１９８７年后Ⅱ站高于Ｉ站。本文还就影响东湖桡足类演变的生态因子进行了讨论。     

TaTPP-7A positively feedback regulates grain filling and wheat grain yield through T6P-SnRK1 signalling pathway and sugar–ABA interaction

Grain size and filling are two key determinants of grain thousand-kernel weight (TKW) and crop yield, therefore they have undergone strong selection since cereal was domesticated. Genetic dissection of the two traits will improve yield potential in crops. A quantitative trait locus significantly associated with wheat grain TKW was detected on chromosome 7AS flanked by a simple sequence repeat marker of Wmc17 in Chinese wheat 262 mini-core collection by genome-wide association study. Combined with the bulked segregant RNA-sequencing (BSR-seq) analysis of an F₂ genetic segregation population with extremely different TKW traits, a candidate trehalose-6-phosphate phosphatase gene located at 135.0 Mb (CS V1.0), designated as TaTPP-7A, was identified. This gene was specifically expressed in developing grains and strongly influenced grain filling and size. Overexpression (OE) of TaTPP-7A in wheat enhanced grain TKW and wheat yield greatly. Detailed analysis revealed that OE of TaTPP-7A significantly increased the expression levels of starch synthesis- and senescence-related genes involved in abscisic acid (ABA) and ethylene pathways. Moreover, most of the sucrose metabolism and starch regulation-related genes were potentially regulated by SnRK1. In addition, TaTPP-7A is a crucial domestication- and breeding-targeted gene and it feedback regulates sucrose lysis, flux, and utilization in the grain endosperm mainly through the T6P-SnRK1 pathway and sugar–ABA interaction. Thus, we confirmed the T6P signalling pathway as the central regulatory system for sucrose allocation and source–sink interactions in wheat grains and propose that the trehalose pathway components have great potential to increase yields in cereal crops.     

转移及非转移肿瘤移植后615小鼠血液流变学变化的研究

血道高转移瘤株FC、淋巴合并血道高转移瘤株U14、淋巴道高转移瘤株H22、非转移瘤株P615分别接种于336只纯系近交615小鼠.不同时间取血并处死动物,进行组织学及血液流变学检查.将转移瘤发展过程分为潜伏期、侵袭期、转移早、中、晚期,非转移瘤发展过程分为潜优期、增殖期、囊腔形成期及中心坏死期.本实验结果显示,不同转移能力及途径肿瘤发展的不同时期血液流变学变化规律不同,因而表明肿瘤侵袭、转移与血液流变学变化之间存在互为因果的紧密关系.其临床诊断及治疗意义被讨论.     

采伐对红松种群结构与动态的影响

红松是我国长白山阔叶红松林的主要建群种,受森林采伐的影响,种群数量急剧下降,现已被列为国家二级保护植物。通过绘制种群静态生命表、生存函数、存活曲线和径级分布图,研究原始林,15%择伐、40%择伐和皆伐后恢复的天然次生林内,红松种群结构和动态的变化规律。结果表明:(1)采伐干扰对红松种群的波动周期影响不大,15%的择伐强度可以提高红松种群的生存期望。(2)原始林和15%择伐林内红松种群存活曲线均为DeeveyⅡ型,种群处于稳定期;40%择伐林内存活曲线介于DeeveyⅡ型和DeeveyⅢ型之间,种群由稳定期向成熟期过渡;皆伐林内存活曲线为DeeveyⅠ型,种群处在增长期。(3)原始阔叶红松林林、15%择伐林和40%择伐林内,红松种群径级结构均呈稳定的倒J型,且在幼树阶段均存在生长更新的停滞现象;与原始林相比,15%择伐林内幼树比例略有下降;40%择伐林和皆伐迹地,随采伐强度的增加,幼树比例明显增大。(4)方差分析表明,4个种群的生存过程差异较大,采伐干扰对红松种群生存过程的影响达到显著水平。     

B(a)P暴露干扰细胞周期调控蛋白影响孕早期小鼠卵巢黄体功能

该研究旨在探讨苯并(a)芘[Benzo(a)pyrene,B(a)P]对孕早期小鼠卵巢黄体功能的影响及机制.体内模型:将昆明小鼠每晚按雌雄3∶1的比例合笼,次晨查得阴栓记为孕第1天(d1);将其随机分为对照组和B(a)P处理组,每日早晨称重后以0.1 mL/10 g动物体质量灌胃给予0.2 mg/(kg·d)的B(a)...     

不同方式处理牛粪对大豆生长和品质的影响

大型养殖场粪便堆积造成严重的环境污染,对这类废弃物开展资源化利用研究具有重要生态学和经济学意义。以不施肥料处理(CK)为对照,研究了生态养殖场牛粪经腐熟(DD)和蚯蚓处理(RD)后对大豆生长与品质的影响。研究表明:生态养殖场牛粪经过两种处理后,在一定施用量范围(DD≤30 t/hm2,RD≤45 t/hm2)内,可显著增加大豆株高、分株数、干物质积累,促进植株生长,增加单株荚数、籽粒数、籽粒重,提高大豆产量(P<0.01)。施入腐熟牛粪30 t/hm2株高和单株结荚数比CK分别增加24.2 cm、63%;经蚯蚓处理后,可以提高牛粪施用量的上限,施入蚯蚓处理过的牛粪45 t/hm2时产量最高、单株结荚数最多,比CK分别增加72%和75%(P<0.01);施入蚯蚓处理过的牛粪15 t/hm2时,粗蛋白含量、蛋脂总量最高,比CK分别增加7%和6%(P<0.01)。本研究可为大型养殖场牛粪资源化利用提供科学依据。     

肺炎链球菌cps操纵子的启动子序列点突变可导致细菌荚膜缺失

摘要:【目的】明确肺炎链球菌荚膜多糖合成操纵子的启动子序列出现的点突变313713 T→C是否可导致细菌荚膜缺失。【方法】Western blot检测肺炎链球菌突变株SPY1 (NC_008533.1 313713 T→C)荚膜多糖含量;实时定量荧光PCR分析荚膜多糖合成基因cps2A、cps2B、cps2C以及cps2D的表达量;构建重组质粒pEVP3-cps promoterD39和pEVP3-cps promoterSPY1,分别转化D39和SPY1菌株,通过β-半乳糖苷酶活性检测来验证转入的启动子序列对细菌荚膜合成的影响,并通过电镜观察荚膜结构和荚膜肿胀试验进一步验证。【结果】肺炎链球菌SPY1 的荚膜多糖含量较野生型显著下降,其相关基因cps2A、cps2B、cps2C以及cps2D的表达量较野生型D39均显著降低;与D39-pEVP3-cps promoterD39对比,D39-pEVP3-cps promoterSPY1的β-半乳糖苷酶活性下降了76%,与SPY1-pEVP3-cps promoterD39相比,SPY1-pEVP3-cps promoterSPY1的β-半乳糖苷酶活性下降了约79%;电镜结果显示,重组SPY1-pEVP3-cps promoterD39荚膜可恢复至野生型水平,并且重组D39-pEVP3-cps promoterSPY1 (NC_008533.1 313713 T→C)荚膜肿胀试验呈阴性。【结论】荚膜多糖合成操纵子的启动子序列点突变313713 T→C可导致荚膜多糖合成基因表达显著下调,从而引起菌株SPY1的荚膜显著减少甚至缺失。