Mineralocorticoid receptor antagonist-mediated cognitive improvement in a mouse model of Alzheimer's type: possible involvement of BDNF-H2S-Nrf2 signaling

The present study explored the role and mechanisms of mineralocorticoid receptor antagonists in β-amyloid (Aβ)-induced cognitive impairment. A single intracerebroventricular injection of Aβ_1-42 was given to mice, and after 14 days of injection, memory was evaluated using the Morris water maze test. Spironolactone (25 and 50 mg/kg) and eplerenone (50 and 100 mg/kg) were administered for two days before and for 14 days after Aβ injection. Mineralocorticoid receptor blockers attenuated Aβ-induced cognitive impairment assessed in terms of decrease in day 4 escape latency time (ELT) in comparison to day 1 ELT (suggesting an increase in learning) along with an increase in time spent in target quadrant on day 5 (suggesting the retrieval of learned things). These drugs also increased the expression of BDNF, H₂S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α in the frontal cortex and hippocampus. Co-administration of ANA-12, BDNF receptor antagonist (0.25 and 0.5 mg/kg) abolished cognitive improving functions of mineralocorticoid receptor blockers, attenuated H₂S, Nrf2, reduced glutathione, and decreased β-amyloid and TNF-α. It is concluded that spironolactone and eplerenone attenuate cognitive decline of Alzheimer's type, possibly through upregulation of BDNF levels in the frontal cortex and hippocampus, which may increase H₂S, decrease Aβ, activate Nrf2-dependent antioxidant system, and decrease neuroinflammation.     

大蒜多糖预处理对缺氧缺糖/复氧复糖大鼠心肌细胞的拮抗作用

目的:研究大蒜多糖(GP)预处理对缺氧缺糖/复氧复糖损伤大鼠心肌细胞的拮抗作用研究,并初步探讨其作用机制。方法:采用连二亚硫酸钠(Na2S2O4)建立乳鼠心肌细胞糖氧剥离的A/R损伤模型,不同剂量GP(10、30和100mg/L)预处理24h后,比色法测定细胞培养液中iNOS和NO含量,测定细胞内SOD活性及MDA含量。结果:与A/R模型组比较,GP预处理可增加胞内SOD活性和培养液中iNOS活力,降低NO释放量和胞内MDA含量。结论:GP预处理对A/R损伤心肌细胞具有明显的抗氧化作用,可能与清除自由基的产生有关。     

Isolation,Characterization, and Genome Analysis of a Novel Bacteriophage,Escherichia Phage vB_EcoM-4HA13, Representing a New Phage Genus in the Novel Phage Family Chaseviridae

Shiga toxin-producing Escherichia coli (STEC) is one of the leading causes of foodborne illnesses in North America and can lead to severe symptoms, with increased fatality risk for young children. While E. coli O157:H7 remains the dominant STEC serotype associated with foodborne outbreaks, there has been an increasing number of non-O157 STEC outbreaks in recent years. For the food industry, lytic bacteriophages offer an organic, self-limiting alternative to pathogen reduction—one that could replace or reduce the use of chemical and physical food processing methods. From EHEC-enriched sewage, we isolated a novel bacteriophage, vB_EcoM-4HA13 (4HA13). Phenotypic characterizations revealed 4HA13 to possess a myoviral morphotype, with a high specificity to non-motile O111 serotype, and a long latent period (90 min). Through genomic analyses, this 52,401-bp dsDNA phage was found to contain 81 CDS, but no detectable presence of antibiotic resistance, integrase, or virulence genes. A BLASTn search for each of the identified 81 CDS yielded homologues with low levels of similarity. Comparison of RNA polymerase and terminase large subunit amino acid sequences led to the proposal and acceptance of a new bacteriophage family, Chaseviridae, with 4HA13 representing a new species and genus. The discovery of this phage has broadened our current knowledge of bacteriophage diversity.     

Grafting antibiofilm polymer hydrogel film onto catheter by SARA SI-ATRP

Abstract

Catheters are widely used and play an important role in medicine. However, catheter-associated infection is prevalent even under stringent sterile conditions. Biofilms are formed when bacteria populate the surfaces of catheters. This makes the biofilm resistant to antibiotics. Hence, it is imperative for there to be an inherently antifouling and anti-bacterial catheter to mitigate the formation of biofilm. This paper aims to outline the synthesis of non-leachable anti-biofilm and anti-bacterial cationic film coatings through direct polymerization using supplemental activator and reducing agent surface initiated atom transfer radical polymerization (SARA SI-ATRP). Three crosslinked cationic coatings comprising of Diallyl dimethyl ammonium chloride (DADMAC), or ε-poly-L-lysine HCl methacrylic acid (EPL-MA) together with a crosslinker (polyethylene glycol dimethacrylate, PEGDMA) were investigated. These non-leachable covalently linked coatings with DADMAC can achieve more than 2 log reduction (99.0%) with Methicillin-resistant Staphylococcus aureus (MRSA) and 1.25 log reduction (94.4%) with Vancomycin resistant Enterococcus (VRE) in in vitro studies.     

Baicalein reduces β‐amyloid and promotes nonamyloidogenic amyloid precursor protein processing in an Alzheimer's disease transgenic mouse model

Baicalein, a flavonoid isolated from the roots of Scutellaria baicalensis, is known to modulate γ‐aminobutyric acid (GABA) type A receptors. Given prior reports demonstrating benefits of GABA_A modulation for Alzheimer's disease (AD) treatment, we wished to determine whether this agent might be beneficial for AD. CHO cells engineered to overexpress wild‐type amyloid precursor protein (APP), primary culture neuronal cells from AD mice (Tg2576) and AD mice were treated with baicalein. In the cell cultures, baicalein significantly reduced the production of β‐amyloid (Aβ) by increasing APP α‐processing. These effects were blocked by the GABA_A antagonist bicuculline. Likewise, AD mice treated daily with i.p. baicalein for 8 weeks showed enhanced APP α‐secretase processing, reduced Aβ production, and reduced AD‐like pathology together with improved cognitive performance. Our findings suggest that baicalein promotes nonamyloidogenic processing of APP, thereby reducing Aβ production and improving cognitive performance, by activating GABA_A receptors. © 2013 Wiley Periodicals, Inc.     

病情严重程度及预后评分系统对脓毒症患者的临床应用价值

目的比较急性生理学与慢性健康状况评分Ⅱ（APACHEⅡ）及脓毒症相关性器官功能衰竭评分（SOFA）在脓毒症患者的病情严重程度判断及死亡预后评估的价值。方法收集解放军总医院52例脓毒症患者入院24h内及第3、5、7、10、14d的相关指标,比较APACHEⅡ评分及SOFA评分。结果 52例中有16例死亡,病死率30.8%。脓毒症（Sepsis）、严重脓毒症（Severe Sepsis）及脓毒性休克（Septic Shock）组的APACHEⅡ评分分别为12.0±6.9、16.8±6.8、23.1±5.6（P=0.002）,SOFA评分分别为2.9±2.1、5.9±3.1、11.6±2.9（P〈0.001）。以28d生存期分为生存组（≥28d）和死亡组（〈28d）。死亡组（n=16）第1天的APACHEⅡ评分及SOFA评分均高于生存组（n=36）（分别为14.9±7.1 vs 19.7±7.3,P=0.03;4.6±3.2 vs 8.8±4.0,P〈0.001）,且随病程时间推移,生存组SOFA评分渐降,死亡组呈增高趋势。SOFA评分评估脓毒症者死亡预后的受试者工作特征曲线下面积（AUCROC）为0.795（95%CI,0.662-0.929）,高于APACHEⅡ评分的0.670（95%CI,0.514-0.826）。结论 SOFA评分及其动态变化能更好地评估脓毒症患者病情严重程度及死亡预后。     

Sequences and replication of genomes of the archaeal rudiviruses SIRV1 and SIRV2: relationships to the archaeal lipothrixvirus SIFV and some eukaryal viruses

The double-stranded DNA genomes of the viruses SIRV1 and SIRV2, which infect the extremely thermophilic archaeon Sulfolobus and belong to the family Rudiviridae, were sequenced. They are linear, covalently closed at the ends, and 32,312 and 35,502 bp long, respectively, with an A+T content of 75%. The genomes of SIRV1 and SIRV2 carry inverted terminal repeats of 2029 and 1628 bp, respectively, which contain multiple direct repeats. SIRV1 and SIRV2 genomes contain 45 and 54 ORFs, respectively, of which 44 are homologous to one another. Their predicted functions include a DNA polymerase, a Holliday junction resolvase, and a dUTPase. The genomes consist of blocks with well-conserved sequences separated by nonconserved sequences. Recombination, gene duplication, horizontal gene transfer, and substitution of viral genes by homologous host genes have contributed to their evolution. The finding of head-to-head and tail-to-tail linked replicative intermediates suggests that the linear genomes replicate by the same mechanism as the similarly organized linear genomes of the eukaryal poxviruses, African swine fever virus and Chlorella viruses. SIRV1 and SIRV2 both contain motifs that resemble the binding sites for Holliday junction resolvases of eukaryal viruses and may use common mechanisms for resolution of replicative intermediates. The results suggest a common origin of the replication machineries of the archaeal rudiviruses and the above-mentioned eukaryal viruses. About 1/3 of the ORFs of each rudivirus have homologs in the Sulfolobus virus SIFV of the family Lipothrixviridae, indicating that the two viral families form a superfamily. The finding of inverted repeats of at least 0.8 kb at the termini of the linear genome of SIFV supports this inference.     

南水北调东线工程源头地区钉螺监测

目的了解南水北调东线工程源头地区钉螺分布及其对调水安全的影响。方法每年春季采取系统抽样结合环境抽查法对东线工程源头地区进行钉螺分布调查,同时选择江都水利枢纽泵站消力池滩地定点监测钉螺扩散。结果2006-2009年东线工程源头地区查出钉螺面积分别为256.11、184.55、164.92hm2和121.16hm^2;感染性钉螺面积分别为8.3、1.0、1.0hm^2和0hm^2;活螺密度也呈逐年下降趋势。GoogleEarth地图显示东线工程源头地区钉螺主要分布在夹江和芒稻河。对江都泵站消力池滩地定点监测发现局限性低密度扩散钉螺,分析原因为引河疏浚工程建筑垃圾携带所致。结论南水北调东线源头地区存在钉螺扩散的风险,因此有必要长期开展监测和控制。     

钛合金重建钢板治疗肩胛骨骨折

目的探讨钛合金重建钢板治疗肩胛骨骨折疗效。方法对2007-2009年的17例移位较为明显的肩胛骨骨折采用手术切开复位及钛合金重建钢板内固定治疗,术后均进行早期功能锻炼。结论所有病例均在术后进行10-24个月随访,骨折均已完全愈合,功能恢复按照Hardegger功能评定标准,优10例,良5例,可2例,优良率为88%。结论在严格手术指征下切开复位钛合金重建钢板内固定手术可以取得良好的手术效果,既可以缓解患者症状,也为患者早日进行功能锻炼提供有力的支持。