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A New Insight into Molecular Function of Smads Signalings in Diabetic Nephropathy Smads信号在糖尿病肾病中的分子功能新认识
Pub Date : 2019-01-01 DOI: 10.4172/2379-1764.1000265
Hiroyuki Ono, H. Abe, T. Doi
Diabetic Nephropathy (DN) is the leading cause of end-stage renal failure and is associated with increased morbidity and mortality compared with other causes of renal diseases. Therefore, it is important to elucidate the pathogenesis of DN and establish effective therapies for its treatment. Morphologically, DN is characterized by mesangial matrix expansion caused by the excessive deposition of extracellular matrix proteins such as type IV collagen. Prolonged exposure to hyperglycemia induces Advanced Glycation End Products (AGEs). AGE/RAGE (receptor for AGE) axis induces Bone Morphogenetic Proteins 4 (BMP4) and transforming growth factor-β (TGF-β). Both BMP4/Smad1 and TGF-β/Smad3 signaling pathways are involved in the progression of DN. In particular, Smad1 is the key signaling molecule that is directly involved in the initiation and progression of glomerulosclerosis in DN. BMP4 induces Smad1 and phosphorylation of Smad1 C-terminal domain, its interaction with Smad4, and its translocation into the nucleus, where it regulates the transcription of Col4. However, no study has elucidated the mechanisms underlying the significance of Smad1 linker domain (pSmad1L) in DN. Moreover, the precise role of Smad3 signaling pathway under diabetic conditions is not completely understood, including the correlation between Smad1 and Smad3 signaling. This review article shows that pSmad1L is very important for attenuating DN, and that a new molecular interplay between Smad1 and Smad3 signaling under a diabetic condition might facilitate novel therapeutic agents.
糖尿病肾病(DN)是终末期肾衰竭的主要原因,与其他肾脏疾病原因相比,糖尿病肾病的发病率和死亡率增加。因此,阐明DN的发病机制,建立有效的治疗方法具有重要意义。形态学上,DN的特征是细胞外基质蛋白如IV型胶原的过度沉积导致系膜基质扩张。长期暴露于高血糖诱导晚期糖基化终产物(AGEs)。AGE/RAGE (AGE受体)轴诱导骨形态发生蛋白4 (BMP4)和转化生长因子-β (TGF-β)。BMP4/Smad1和TGF-β/Smad3信号通路均参与DN的进展。特别是,Smad1是直接参与DN肾小球硬化发生和进展的关键信号分子。BMP4诱导Smad1和Smad1 c端结构域的磷酸化,与Smad4相互作用,并易位进入细胞核,在细胞核中调节Col4的转录。然而,没有研究阐明Smad1连接域(pSmad1L)在DN中的作用机制。此外,Smad3信号通路在糖尿病中的确切作用尚不完全清楚,包括Smad1和Smad3信号通路之间的相关性。这篇综述文章表明pSmad1L对DN的衰减非常重要,并且Smad1和Smad3信号传导之间的一种新的分子相互作用可能会促进新的治疗药物的产生。
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引用次数: 0
Comparison of Two Solid-Phase Extraction (SPE) Methods for the Identification and Quantification of Porcine Retinal Protein Markers by LC?MS/MS 两种固相萃取(SPE)法液相色谱法鉴别定量猪视网膜蛋白标记物的比较女士/小姐
Pub Date : 2018-06-20 DOI: 10.4172/2379-1764.1000262
Carsten Schmelter, S. Funke, Jana Treml, Anja Beschnitt, N. Perumal, C. Manicam, N. Pfeiffer, F. Grus
Proper sample preparation protocols represent a critical step for liquid chromatography mass spectrometry (LC-MS)-based proteomic study designs and influence the speed, performance and automation of high-throughput data acquisition. Main objective of this study was to compare two commercial Solid-Phase Extraction (SPE)-based sample preparation protocols (comprising SOLAμTM HRP SPE spin plates from Thermo Fisher Scientific and ZIPTIP® C18 pipette tips from Merck Millipore) for analytical performance, reproducibility and analysis speed. The house swine (Sus scrofa domestica) represents a promising animal model for studying human eye diseases including glaucoma and provides excellent requirements for the qualitative and quantitative MS based comparison in terms of ocular proteomics. In total 6 technical replicates of two protein fractions (extracted with 0.1% dodecyl-s-maltoside (DDM) or 1% trifluoroacetic acid (TFA)) of porcine retinal tissues were subjected to in-gel trypsin digestion and purified with both SPE-based workflows (N=3) prior LC-MS/MS analysis. On average both protein fractions (DDM and TFA) provided the identification of 550 ± 70 and 305 ± 48 proteins after ZIPTIP® purification protocol and SOLAμTM workflow resulted in the detection of 513 ± 55 and 300 ± 33 proteins (FDR0.05) regarding protein recovery between both SPE methods. However, only glaucoma protein marker methyl-CpG-binding protein 2 (MECP2) showed a significant (P=0.02) higher abundance in ZIPTIP®-purified replicates in comparison to SOLAμTM-treated study samples. Nevertheless, this result was not confirmed by in-gel trypsin digestion of recombinant MECP2 (P=0.24). In conclusion, both SPE-based purification methods worked equally well in terms of analytical performance and reproducibility, whereas the analysis speed and the semi‑automation of the SOLAμTM spin plates workflow is much more convenient in comparison to the manual ZIPTIP® C18 pipette tip protocol.
合适的样品制备方案是基于液相色谱-质谱(LC-MS)的蛋白质组学研究设计的关键步骤,并影响高通量数据采集的速度、性能和自动化。本研究的主要目的是比较两种基于固相萃取(SPE)的商业样品制备方案(包括来自Thermo Fisher Scientific的SOLAμTM HRP SPE旋转板和来自Merck Millipore的ZIPTIP®C18移液头)的分析性能、重现性和分析速度。家猪(Sus scrofa domestica)是研究包括青光眼在内的人类眼病的一种有前景的动物模型,在眼蛋白质组学方面为定性和定量的MS比较提供了良好的要求。用0.1%十二烷基-s-麦糖苷(DDM)和1%三氟乙酸(TFA)提取猪视网膜组织的两个蛋白质组分,共6个技术重复,用凝胶胰酶消化,并使用两种基于spe的工作流程(N=3)预先进行LC-MS/MS分析。在ZIPTIP®纯化协议和SOLAμTM工作流程后,两种SPE方法的蛋白质回收率平均为513±55和300±33 (FDR0.05),两种方法的蛋白质回收率分别为550±70和305±48个。然而,与sola μ tm处理的研究样品相比,只有青光眼蛋白标记物甲基cpg结合蛋白2 (MECP2)在ZIPTIP®纯化的重复中显示出显著(P=0.02)高的丰度。然而,重组MECP2的胰酶切法并没有证实这一结果(P=0.24)。总之,两种基于spe的纯化方法在分析性能和重现性方面都同样出色,而与手动ZIPTIP®C18移液头协议相比,SOLAμTM自旋板的分析速度和半自动化工作流程更加方便。
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引用次数: 3
Investigation of Gluthatione S-Transferase Variants in a Healthy Population in Goiânia-Go goiata - go健康人群中谷胱甘肽s转移酶变异的研究
Pub Date : 2018-03-09 DOI: 10.4172/2379-1764.1000256
Lucas Carlos Gomes Pereira, N. A. Bérgamo, A. Reis, C. Anunciação, E. Silveira-Lacerda
Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activities of the enzymes predisposing individuals to a lot of disiases. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various populations. Therefore, the present study was performed to determine the prevalence GSTM1*0/*0, GSTT1*0/*0 and GSTP1 Ile105Val polymorphisms in 100 healthy individuals from Goiânia - GO. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex-PCR approach, whereas GSTP1 polymorphisms were examined by PCR-RFLP. The frequencies of GSTM1 and GSTT1 *0/*0 genotypes are 49% and 31%, respectively. The frequencies of GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes were 40%, 53% and 7%, respectively. The wild-type (Ile) and variant (Val) allele frequencies were 66.5% and 33.5%, respectively. The combined genotypes distribution of GSTM1, GSTT1 and GSTP1 polymorphisms showed 12 possible genotypes present in our population; seven of them have a frequency greater than 5%. The effect of combined genotypes of these GSTs polymorphisms is still unknown. These findings in healthy population, give us such more information for the future epidemiological and clinical studies. Using to examine the effect of these combinations in drugs metabolism and cancer predisposition, further largest group would be needed, since their frequencies are quite low. To our of GSTs polymorphisms, this is the first study indicating the frequencies of genetic polymorphisms of GST superfamily in a health population in a Goiania population.
谷胱甘肽s -转移酶(GSTs)基因的遗传多态性可能影响该酶的解毒活性,使个体易患多种疾病。由于这些遗传变异的存在,在不同人群中观察到GSTs解毒能力的个体间和种族差异。因此,本研究旨在确定100例goinia - GO健康个体中GSTM1*0/*0、GSTT1*0/*0和GSTP1 Ile105Val多态性的患病率。采用多重pcr方法分析GSTM1和GSTT1多态性,采用PCR-RFLP方法检测GSTP1多态性。GSTM1和GSTT1 *0/*0基因型的频率分别为49%和31%。GSTP1 Ile/Ile、Ile/Val和Val/Val基因型频率分别为40%、53%和7%。野生型(Ile)和变异型(Val)等位基因频率分别为66.5%和33.5%。GSTM1、GSTT1和GSTP1基因型的组合分布表明,在人群中存在12种可能的基因型;其中7个频率大于5%。这些GSTs多态性的组合基因型的影响尚不清楚。这些在健康人群中的发现,为我们未来的流行病学和临床研究提供了更多的信息。为了检验这些组合对药物代谢和癌症易感性的影响,还需要进一步的大规模研究,因为它们的频率相当低。对于我们的GST多态性,这是第一个研究表明GST超家族遗传多态性在Goiania人群中健康人群的频率。
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引用次数: 0
Biosimilars: A Review of Published Randomized Control Trials Comparing Biosimilars with their Reference Products 生物类似药:已发表的比较生物类似药与其参考产品的随机对照试验综述
Pub Date : 2018-01-05 DOI: 10.4172/2379-1764.1000252
R. Olteanu, M. Constantin, Alexandra Zota
Biosimilars represent a therapeutic revolution for many immune-mediated inflammatory diseases. Biosimilars have different regulatory requirements than those of originators. These regulatory requirements are based on the evidence generated from bioequivalence studies, and in particular from RCTs. The goal of our review was to search for published randomized control trials that investigate biosimilars compared to their reference medicine (infliximab, adalimumab, etanercept, ustekinumab) in chronic inflammatory diseases (psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative cholitis, by using the Medline (PubMed) databases. Nineteen randomized control trials investigating biosimilars compared to their reference drug were included. As of November 2017, five anti-TNF biosimilar agents have been granted approval and are available on the market for patients with as inflammatory disease in the European Union. The Infliximab biosimilars CT-P13 (Remsima, Inflectra) and SB2 (Flixabi), the etanercept biosimilars SB4 (Benepali) and GP2015 (Elrezi) and adalimumb biosimilars ABP501 (Amgevita, Solymbic), SB5 (Imraldi) and BI 695501(Cyltezo). Evidence of equivalence between biosimilars and reference drugs was supported by head-to-head randomized clinical trials: two published randomized clinical trials for SB2, SB4, GP2015, ABP501, SB5, BI695501 and three published randomized control trial in the case of CT-P13 and ABP 501. Although not all randomized clinical trials comparing biosimilar to its reference product have been published, the present situation is satisfactory and provision of further clinical trials awaited.
生物仿制药代表了许多免疫介导的炎症性疾病的治疗革命。生物仿制药的监管要求与原研药不同。这些监管要求是基于生物等效性研究,特别是随机对照试验得出的证据。本综述的目的是通过Medline (PubMed)数据库检索已发表的随机对照试验,研究生物仿制药与参考药物(英夫利昔单抗、阿达木单抗、依那西普、乌斯特金单抗)在慢性炎症性疾病(银屑病、银屑病关节炎、类风湿关节炎、强直性脊柱炎、克罗恩病、溃疡性胆道炎)中的疗效。纳入了19项随机对照试验,研究生物仿制药与其参比药物的对比。截至2017年11月,五种抗tnf生物类似药已获得批准,并可在欧盟市场上用于炎症性疾病患者。英夫利昔单抗生物类似药CT-P13 (Remsima, Inflectra)和SB2 (Flixabi),依那西普生物类似药SB4 (Benepali)和GP2015 (Elrezi)以及阿达仑生物类似药ABP501 (Amgevita, Solymbic), SB5 (Imraldi)和BI 695501(Cyltezo)。生物仿制药与参比药等效性的证据得到了头对头随机临床试验的支持:2项已发表的针对SB2、SB4、GP2015、ABP501、SB5、BI695501的随机临床试验和3项针对CT-P13和ABP501的随机对照试验。虽然并不是所有比较生物仿制药与其参比产品的随机临床试验都已发表,但目前的情况令人满意,并等待进一步的临床试验的提供。
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引用次数: 1
Investigation of Markers of Artemisinin Resistance at Selected Intervals during the 72 h Period after Artemisinin based Combination Therapy Dosing in Kisumu Western Kenya 肯尼亚西部基苏木地区以青蒿素为基础的联合治疗给药后72 h内选定时间间隔的青蒿素耐药标志物研究
Pub Date : 2018-01-01 DOI: 10.4172/2379-1764.1000259
Apollo Asenath, L. Chebon, K. Mitei, Benjamin H. Opot, Dennis W. Juma, A. Nyerere, B. Andagalu, H. Akala, Matthew L. Brown
Background: Microscopic parasite detection during the course of treatment or follow-up suggests that a proportion of ACT treated children in Kenya do not completely clear Plasmodium falciparum parasitemia. Plasmodium falciparum mutation in chloroquine resistance transporter gene (Pfcrt76), multidrug resistance gene1 (Pfmdr1), deubiquitinating enzyme gene (Pfcubp-1) and clathrin vesicle associated adapter 2, u subunit encoding gene (Pfap2mu) and multidrug resistant protein 1 gene (Pfmrp1) have been associated with subsequent patent recrudescence after ACT treatment. As there are no validated markers of ACT resistance in Africa to-date, surveillance of changes in these polymorphisms during the course of treatment is useful in establishing their role in ACT treatment outcome. Methods: 118 P. falciparum 2013 to 2015 samples from ACT clinical efficacy studies were genotyped for frequency of drug resistance polymorphisms using sequence analyzers. Each sample was screened at least three to four-time points namely; day zero before start of treatment then days 2 and 3 after initiation of treatment plus the day of subsequent parasitemia by microscopy prior to day 42 for some of the subjects. Sequence analyzers were used to genotype for frequency of drug resistance polymorphisms, Pfmdr1 gene copy number and genetic diversity typing of the 12 microsatellite loci. Genetic diversity of parasite populations across four time-points was determined by analysis of 12 microsatellite loci. Worldwide Antimalarial Resistance Network’s parasite clearance estimator (PCE) was used to determine parasite clearance rates. Results: The new genes Pfap2mu and Pfubp had S145C and E1528D being most polymorphic with prevalence’s of 18% and 19%, respectively Pfmdr1 86,184 and 1246 had significant increase in wild type alleles between day zero and time-points 3 and 4. Microsatellite profile analysis show that the mean number of alleles in all the loci across the 8 populations ranged from 9.250 to 1.000. Poly α was the most polymorphic with 35 alleles. The mean unbiased HE was 0.672 while Shannon diversity index for the 8 populations was ranging between 0.182-0.000, none of the parasite analyzed had matching haplotypes. The mean parasite clearance half-life was 2.63 h (95% confidence interval [CI]) and the median clearance half-life was 2.24 h. The parasite clearance half-life ranged from 1.14-5.05 h. Conclusion: Increased wild-type Pfmdr1 86,184 and 1246 as well as polymorphisms in Pfap2mu and Pfcubp-1 in post day zero suggest that these genes could be responding to ACT dosing and therefore require continued monitoring. Samples with multiple copies of the Pfmdr1 did not indicate show effect on parasite clearance rate. Though there was no correlation between these profiles and clearance rates, further evaluations are needed to determine the potential public health implications of these observations and the utility of these loci as markers of artemisinin sensitivity in populations of
背景:在治疗或随访过程中,显微镜下的寄生虫检测表明,肯尼亚一部分接受ACT治疗的儿童没有完全清除恶性疟原虫。恶性疟原虫氯喹耐药转运蛋白基因(Pfcrt76)、多药耐药基因1 (Pfmdr1)、去泛素化酶基因(Pfcubp-1)和网格蛋白囊泡相关受体2、u亚基编码基因(Pfap2mu)和多药耐药蛋白1基因(Pfmrp1)突变与ACT治疗后的专利复发有关。由于迄今为止非洲还没有证实的ACT耐药标记物,因此在治疗过程中监测这些多态性的变化有助于确定它们在ACT治疗结果中的作用。方法:采用序列分析仪对2013 ~ 2015年ACT临床疗效研究中118份恶性疟原虫耐药多态性频率进行基因分型。每个样本至少筛选三到四个时间点,即;治疗开始前的第0天,治疗开始后的第2天和第3天,以及在第42天之前显微镜下观察到的一些受试者随后的寄生虫病。利用序列分析仪对12个微卫星位点的耐药多态性频率、Pfmdr1基因拷贝数和遗传多样性分型进行基因型分析。通过对12个微卫星位点的分析,确定了4个时间点上寄生虫种群的遗传多样性。使用世界抗疟药网络的寄生虫清除率估计器(PCE)来确定寄生虫清除率。结果:新基因Pfap2mu和Pfubp的S145C和E1528D多态性最多,患病率分别为18%和19%,Pfmdr1 86,184和1246的野生型等位基因在第0天至时间点3和4之间显著增加。微卫星分析结果表明,8个群体中所有等位基因位点的平均等位基因数在9.250 ~ 1.000之间。Poly α多态性最高,共有35个等位基因。8个群体的平均无偏HE为0.672,Shannon多样性指数在0.182 ~ 0.000之间,单倍型均不匹配。平均半衰期为2.63 h(95%可信区间[CI]),中位半衰期为2.24 h。寄生虫半衰期范围为1.14-5.05 h。结论:野生型Pfmdr1 86,184和1246的增加以及Pfap2mu和Pfcubp-1的多态性在第0天后增加,表明这些基因可能对ACT剂量有反应,因此需要继续监测。含有多个Pfmdr1拷贝的样本没有显示出对寄生虫清除率的影响。虽然这些特征与清除率之间没有相关性,但需要进一步评估,以确定这些观察结果对公共卫生的潜在影响,以及这些基因座作为全球恶性疟原虫种群中青蒿素敏感性标记物的效用。
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引用次数: 1
Refining Fertilizer Rate Recommendation for Maize Production Systems in Assosa, North Western Ethiopia 埃塞俄比亚西北部阿索萨玉米生产系统精炼肥料用量建议
Pub Date : 2018-01-01 DOI: 10.4172/2379-1764.1000253
Dessalegn Tamene, Bekele Anbessa, Tigist Adisu Legesse, G. Dereje
Maize growers need balanced crop nutrition to maximize its yield potential and get the most out of their fertilizer investment. In practice, this requires making all of the required nutrients available to the maize crop by the right amount or rate. The objectives of this study was to determine optimum N, P, K and S response curve under balanced fertilization and to establish economic mixes blended fertilizers and determine soil, crop specific optimum N, P, K and S fertilizers rates for maize crop grown in Assosa areas. The experiment was conducted using randomized complete block design (RCBD) with three replications consisting of a total of 8 treatments for N, P, K and 10 treatments for S. Therefore; the result revised that the N level was highly significant (P<0.05) on grain yield. The highest grain yield (7292.5 kg ha-1) was obtained at the lowest nitrogen rate with balanced fertilizer of 46 kg N ha-1+PKSZnB while significantly the lowest grain yield (3298.6 kg ha-1) was records from control. The application of 69 kg ha-1 P resulted in grain yield increases, aboveground biomass yield was also affected in the same amount of P with balanced fertilizers having increased biomass yield with P application. Even if the ANOVA results shows significant difference on that of treated with K fertilizer, there was slight variation within treatments except the highest rates of K fertilizer. Across the S rate studies, all S rates with balanced fertilizers had a statistically significant yield increment from the control and Recommended NP. From the across-treatment yield increase, treatment 10 Kg S ha-1+NPKZnB gives maximum yield (6717.7 kg ha-1). Analyzed across S rate, the economic optimum S rate was also 10 Kg S ha-1 for the clay textured soils of Assosa.
玉米种植者需要均衡的作物营养,以最大限度地提高产量潜力,并从肥料投资中获得最大收益。在实践中,这需要以适当的量或速率为玉米作物提供所有必需的营养。本研究的目的是确定平衡施肥条件下最优氮、磷、钾、硫响应曲线,建立经济的混合肥料,确定阿索萨地区玉米作物土壤、作物特定最优氮、磷、钾、硫施肥量。试验采用随机完全区组设计(RCBD), 3个重复,共8个氮、磷、钾处理和10个硫处理。结果表明,施氮水平对籽粒产量影响极显著(P<0.05)。最低施氮量为46 kg N ha-1+PKSZnB时,籽粒产量最高(7292.5 kg ha-1),而对照的籽粒产量最低(3298.6 kg ha-1)。69 kg hm -1施磷可提高籽粒产量,同等施磷量的平衡肥对地上生物量产量也有影响,生物量产量随施磷量的增加而增加。单因素方差分析结果显示,除施钾率最高外,各处理间差异不大。在S率研究中,平衡肥料的所有S率比对照和推荐NP的产量增加具有统计学显著性。从产量增加情况看,10 Kg S ha-1+NPKZnB处理产量最高(6717.7 Kg ha-1)。综合S速率分析,亚索沙粘土质地土的经济最佳S速率为10 Kg S ha-1。
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引用次数: 13
Murine Model of Neuroschistosomiasis Mansoni: Clinical, Histological and Magnetic Resonance Imaging Studies 曼氏神经血吸虫病小鼠模型:临床、组织学和磁共振成像研究
Pub Date : 2018-01-01 DOI: 10.4172/2379-1764.1000263
T. Fidelis, P. Parreiras, F. T. Moll, F. Meireles, G. B. Filho, P. Coelho, J. Lambertucci
The schistosomiasis mansoni infection is responsible for 3.6% of the worldwide estimated causes of death and the central nervous system can be affected. In humans, the eggs of this helminth have been found in the leptomeninges, cerebral cortex, basal ganglia, choroid plexus, cerebellum and spinal cord. Neurological manifestations, histhology and magnetic resonance imaging of neuroschistosomiasis mansoni in humans serve as our chief reference points for the examination of the experimental infections in murine model. In this study, experimental infection of S. mansoni cercariae in mice aims to demonstrate the presence of granulomas in the brain and correlate to the clinical, histologic, and magnetic resonance findings. Twenty five Swiss-webster mice were infected subcutaneously, and followed for 160 days post-infection. Another group of twenty five mice were not infected and kept as controls. Images were obtained in the different planes by magnetic resonance. Histological samples were stained by Hematoxilin and Eosin (HE) to examine S. mansoni eggs, granulomas and inflammatory lesions. The results showed neurological manifestations as head and chest tilt (to the left or right side), hemiparesis, ataxia, body contortion, loss of balance and spinning, induced by granulomas in several regions of the central nervous system, and vascular changes associated with haemorrages. The MRI indicated multiple irregular nodules dispersed associated with oedema. These findings indicate that the murine model subcutaneously infected by S. mansoni cercarie may be used for studying mechanisms leading to human neuroschistosomiasis.
曼氏血吸虫病感染占全世界估计死亡原因的3.6%,可影响中枢神经系统。在人类中,这种蠕虫的卵被发现存在于脑膜、大脑皮层、基底神经节、脉络膜丛、小脑和脊髓中。人类曼氏神经血吸虫病的神经学表现、组织学和磁共振成像是我们检查小鼠模型实验感染的主要参考点。在这项研究中,曼氏尾蚴在小鼠体内的实验感染旨在证明肉芽肿在大脑中的存在,并与临床、组织学和磁共振结果相关。25只瑞士韦氏小鼠皮下感染,感染后随访160天。另一组25只未感染的老鼠作为对照。在不同平面上进行磁共振成像。组织标本采用苏木素和伊红(HE)染色,检查曼氏梭菌卵、肉芽肿和炎性病变。结果显示神经系统表现为头部和胸部倾斜(向左或向右),偏瘫,共济失调,身体扭曲,失去平衡和旋转,由中枢神经系统几个区域的肉芽肿引起,以及与出血相关的血管改变。MRI示多发不规则结节,分散伴水肿。这些结果表明,皮下感染曼氏梭形虫的小鼠模型可用于研究导致人类神经血吸虫病的机制。
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引用次数: 2
Perception Towards Patient Safety Practice and Associated Factors among Health Care Providers of Jimma Zone Public Hospitals 吉马区公立医院医护人员对病人安全行为的认知及相关因素分析
Pub Date : 2018-01-01 DOI: 10.4172/2379-1764.1000261
A. Gizaw, Fikadu Balcha Hailu, Desalegn Tamiru Negese
Patient safety practice is a process, or structure which can reduces the probability of adverse events resulting from exposure to the health care system across a range of diseases and procedures [1]. It is the cornerstone of high-quality health care. An effort defining patient safety practices includes prevention of harmful events and negative health care outcomes, such as mortality and morbidity [2].
患者安全实践是一种过程或结构,可以减少因暴露于卫生保健系统中的一系列疾病和程序而导致的不良事件的可能性[1]。它是高质量卫生保健的基石。定义患者安全实践的努力包括预防有害事件和负面卫生保健结果,如死亡率和发病率[2]。
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引用次数: 9
The Fluctuations in Homocysteine Level Caused by Various Combinations of Folic Acid Cycle Genes Snp Alleles as a Factor in the Course of Pregnancy Violation 叶酸循环基因Snp等位基因不同组合引起的同型半胱氨酸水平波动是妊娠违规过程中的一个因素
Pub Date : 2018-01-01 DOI: 10.4172/2379-1764.1000254
E. Komlichenko, Y. Fedotov, M. A. Uvarova, A. Ivanov
The presence of pathological alleles of single nucleotide polymorphisms (SNP) of the folic acid cycle genes is one of the female reproductive system violation factors including habitual miscarriage and pre-eclampsia. The realizing mechanism for this genetic predisposition is hyperhomocysteinemia-homocysteine level increasing in the blood. This study presenting an attempt to find the relationship between the genotype for the four SNPs of the three folate cycle genes - C677T and A1298C of the MTHFR gene, A2756G of the MTR gene and the A66G of the MTRR gene and the homocysteine level in the blood of women with impaired pregnancy. As a result no direct correlation was found but it was found a statistically significant interlation between the presence of pathological alleles of the studied SNP and the mean square deviation (σ) of the homocysteine level fluctuations over time. For the polymorphism C677T of the MTHFR gene σ of the homocysteine blood level fluctuation is increased up to four times in women with a homozygous pathological state TT compared with the normal homozygotes CC. The clinical importance of monitoring the homocysteine blood level has been shown especially for women with folate cycle genes pathological alleles’ presence.
叶酸循环基因单核苷酸多态性病理性等位基因的存在是习惯性流产、先兆子痫等女性生殖系统侵害因素之一。这种遗传易感性的实现机制是高同型半胱氨酸血症-血液中同型半胱氨酸水平升高。本研究旨在探讨MTHFR基因的C677T和A1298C、MTR基因的A2756G和MTRR基因的A66G这3个叶酸循环基因的4个snp基因型与妊娠受损妇女血液中同型半胱氨酸水平的关系。结果没有发现直接相关,但发现所研究的SNP的病理等位基因的存在与同型半胱氨酸水平随时间波动的均方差(σ)之间存在统计学上显著的相关性。由于MTHFR基因C677T多态性,病理状态为纯合子的TT女性同型半胱氨酸血水平波动σ值比正常纯合子的CC女性高4倍,尤其对存在叶酸周期基因病理等位基因的女性监测同型半胱氨酸血水平具有重要的临床意义。
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引用次数: 1
Strategy for Determination of β 1-Adrenergic Receptor Phosphorylation State In Vivo 体内β 1-肾上腺素能受体磷酸化状态的测定策略
Pub Date : 2018-01-01 DOI: 10.4172/2379-1764.1000258
K. Hayashi, Hiroyuki Kobayashi
β1-adrenergic receptor (Adrb1), a member of the G-protein coupled receptor (GPCR) superfamily, is a critical regulator of heart function. All GPCRs are phosphorylated at multiple sites and the specific pattern of phosphorylation acts as a “barcode” to regulate receptor function and downstream physiological processes in a tissue-specific manner. However, little is known about the location and function of Adrb1 phosphorylation sites in vivo due to the lack of specific antibodies. As a first step to identify the phosphorylation states of Adrb1 and associated functions in the in vivo mouse heart, we developed the following experimental strategy: 1) identification of agonist-dependent Adrb1 phosphorylation sites in isolated perfused mouse heart using advanced phosphoproteomics techniques; 2) definitive assignment of these phosphorylation sites by high-quality mass spectrometry (MS) data obtained from Adrb1- overexpressing HEK 293T cells; 3) generation of knock-in (KI) Mice expressing Adrb1 fused with FLAG-tag at the N-terminus for immunoaffinity purification to reveal phosphorylation status within the living organism; 4) elucidation of phosphorylation levels at specific sites of Adrb1 in KI mouse heart by MS measures of phosphorylated peptide to corresponding unphosphorylated peptide ion intensity ratios. Using this strategy, we identified Ser462 at the C-terminus of Adrb1 as an agonist-dependent phosphorylation site in the perfused mouse heart. We also revealed the basal phosphorylation ratios at Ser274 (0.25), Ser417 (0.55) and Ser462 (0.0023) in KI Mice. These findings provide novel insights into the regulatory mechanisms of Adrb1 function mediated by site-specific phosphorylation.
β1-肾上腺素能受体(Adrb1)是g蛋白偶联受体(GPCR)超家族的成员,是心脏功能的重要调节因子。所有gpcr都在多个位点磷酸化,磷酸化的特定模式作为“条形码”,以组织特异性的方式调节受体功能和下游生理过程。然而,由于缺乏特异性抗体,人们对Adrb1磷酸化位点在体内的位置和功能知之甚少。作为鉴定Adrb1磷酸化状态和在体内小鼠心脏中相关功能的第一步,我们制定了以下实验策略:1)使用先进的磷酸化蛋白质组学技术鉴定离体灌注小鼠心脏中激动剂依赖的Adrb1磷酸化位点;2)通过从Adrb1-过表达HEK 293T细胞获得的高质量质谱(MS)数据确定这些磷酸化位点;3)代表达Adrb1的敲入(KI)小鼠在n端融合FLAG-tag进行免疫亲和纯化,以揭示活体内的磷酸化状态;4)通过质谱测量磷酸化肽与相应的未磷酸化肽离子强度比,阐明KI小鼠心脏中Adrb1特定位点的磷酸化水平。使用这种策略,我们确定了Adrb1 c端Ser462是灌注小鼠心脏中激动剂依赖的磷酸化位点。我们还揭示了KI小鼠中Ser274(0.25)、Ser417(0.55)和Ser462(0.0023)的基础磷酸化比率。这些发现为研究位点特异性磷酸化介导的Adrb1功能调控机制提供了新的见解。
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引用次数: 0
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Advanced techniques in biology & medicine
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