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Assessment of Immunotoxicity of Dextran Coated Ferrite Nanoparticles in Albino Mice 右旋糖酐包被纳米铁氧体对白化小鼠的免疫毒性评价
Pub Date : 2015-10-20 DOI: 10.1155/2015/518527
S. Syama, V. Gayathri, P. Mohanan
In this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress by in vitro and in vivo methods. Cytotoxicity was performed in vitro using splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNF β) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNF β. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10–20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice.
在本研究中,我们合成了尺寸<25 nm的葡聚糖包被铁氧体纳米颗粒(DFNPs),并通过体外和体内方法对其细胞毒性、免疫毒性和氧化应激进行了表征和评价。体外用不同浓度的DFNPs对脾细胞进行细胞毒性实验。测定脾细胞分泌的选定细胞因子(IL-1、IL-10和TNF β)的基因表达。同时,对18只白化小鼠腹腔注射100 mg DFNPs进行免疫刺激。分别于第7、14、21天处死6只。脾脏免疫毒性反应,分析肝脏抗氧化参数(脂质过氧化、还原性谷胱甘肽、谷胱甘肽过氧化物酶、超氧化物歧化酶和谷胱甘肽还原酶)。结果表明,DFNPs未引起任何免疫反应,抗氧化防御机制无明显改变。此外,细胞因子的mRNA表达显示IL-10表达增加,随后IL-1和TNF β表达降低。最终,肝肌动蛋白基因的DNA测序显示,与对照组相比,所有治疗组的非保守区(10-20个碱基)都发生了碱基改变。因此,可以得出结论,DFNPs在细胞水平上无毒,腹腔内暴露于小鼠时无免疫毒性。
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引用次数: 5
Redox Changes Induced by General Anesthesia in Critically Ill Patients with Multiple Traumas. 全身麻醉对多发创伤危重患者氧化还原变化的影响。
Pub Date : 2015-01-01 DOI: 10.1155/2015/238586
Marius Papurica, Alexandru Florin Rogobete, Dorel Sandesc, Raluca Dumache, Radu Nartita, Mirela Sarandan, Alina Carmen Cradigati, Loredana Luca, Corina Vernic, Ovidiu Horea Bedreag

The critically ill polytrauma patient is a constant challenge for the trauma team due to the complexity of the complications presented. Intense inflammatory response and infections, as well as multiple organ dysfunctions, significantly increase the rate of morbidity and mortality in these patients. Moreover, due to the physiological and biochemical imbalances present in this type of patients, the bioproduction of free radicals is significantly accelerated, thus installing the oxidative stress. In the therapeutic management of such patients, multiple surgical interventions are required and therefore they are being subjected to repeated general anesthesia. In this paper, we want to present the pathophysiological implications of oxidative stress in critically ill patients with multiple traumas and the implications of general anesthesia on the redox mechanisms of the cell. We also want to summarize the antioxidant treatments able to reduce the intensity of oxidative stress by modulating the biochemical activity of some cellular mechanisms.

由于并发症的复杂性,危重多发伤患者对创伤团队来说是一个持续的挑战。强烈的炎症反应和感染,以及多器官功能障碍,显著增加了这些患者的发病率和死亡率。此外,由于这类患者存在生理生化失衡,自由基的生物生成明显加快,从而产生氧化应激。在这类患者的治疗管理中,需要多次手术干预,因此他们要接受反复的全身麻醉。在本文中,我们想介绍氧化应激在多重创伤危重患者中的病理生理意义,以及全身麻醉对细胞氧化还原机制的影响。我们还想总结一些抗氧化处理能够通过调节一些细胞机制的生化活性来降低氧化应激的强度。
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引用次数: 13
Identification of Putative Molecular Markers Associated with Root Traits in Coffea canephora Pierre ex Froehner. 鉴定与 Coffea canephora Pierre ex Froehner 根系特征相关的假定分子标记。
Pub Date : 2015-01-01 Epub Date: 2015-03-03 DOI: 10.1155/2015/532386
Devaraja Achar, Mallikarjuana G Awati, M Udayakumar, T G Prasad

Coffea canephora exhibit poor root system and are very sensitive to drought stress that affects growth and production. Deeper root system has been largely empirical as better avoidance to soil water limitation in drought condition. The present study aimed to identify molecular markers linked to high root types in Coffea canephora using molecular markers. Contrasting parents, L1 valley with low root and S.3334 with high root type, were crossed, and 134 F1 individuals were phenotyped for root and associated physiological traits (29 traits) and genotyped with 41 of the 320 RAPD and 9 of the 55 SSR polymorphic primers. Single marker analysis was deployed for detecting the association of markers linked to root associated traits by SAS software. There were 13 putative RAPD markers associated with root traits such as root length, secondary roots, root dry weight, and root to shoot ratio, in which root length associated marker OPS1850 showed high phenotypic variance of 6.86%. Two microsatellite markers linked to root length (CPCM13400) and root to shoot ratio (CM211300). Besides, 25 markers were associated with more than one trait and few of the markers were associated with positively related physiological traits and can be used in marker assisted trait selection.

咖啡树的根系较差,对干旱胁迫非常敏感,会影响生长和产量。根系较深在很大程度上被认为能更好地避免干旱条件下的土壤水分限制。本研究旨在利用分子标记鉴定与高根系类型相关的分子标记。将低根型的 L1 山谷和高根型的 S.3334 这对对比亲本杂交,对 134 个 F1 个体进行了根和相关生理性状(29 个性状)的表型分析,并用 320 个 RAPD 引物中的 41 个和 55 个 SSR 多态引物中的 9 个进行了基因分型。利用 SAS 软件对与根相关性状有关的标记进行了单标记分析。有 13 个假定的 RAPD 标记与根长、次生根、根干重和根芽比等根系性状相关,其中与根长相关的标记 OPS1850 表现出 6.86% 的高表型变异。两个微卫星标记与根长(CPCM13400)和根芽比(CM211300)相关。此外,25 个标记与一个以上的性状相关,其中少数标记与正相关的生理性状相关,可用于标记辅助性状选择。
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引用次数: 0
Electrostatic Interactions between Complement Regulator CD46(SCR1-2) and Adenovirus Ad11/Ad21 Fiber Protein Knob. 补体调节因子CD46(SCR1-2)与腺病毒Ad11/Ad21纤维蛋白旋涡的静电相互作用。
Pub Date : 2015-01-01 Epub Date: 2015-08-19 DOI: 10.1155/2015/967465
Carl Z Chen, Ronald D Gorham, Zied Gaieb, Dimitrios Morikis

Adenoviruses bind to a variety of human cells to cause infection. Both the B2 adenovirus 11 and B1 adenovirus 21 use protein knobs to bind to complement regulator CD46(SCR1-2) in order to gain entry into host cells. In each complex, the two proteins are highly negatively charged but bind to each other at an interface with oppositely charged surface patches. We computationally generated single-alanine mutants of charged residues in the complexes CD46(SCR1-2)-Ad11k and CD46(SCR1-2)-Ad21k. We used electrostatic clustering and Poisson-Boltzmann free energy calculations to propose a hypothesis on the role of electrostatics in association. Our results delineate specific interfacial electrostatic interactions that are critical for association in both CD46(SCR1-2)-Ad11k and CD46(SCR1-2)-Ad21k. These results will serve as a predictive tool in the selection of mutants with desired binding affinity in experimental mutagenesis studies. This study will also serve as a foundation for the design of inhibitors to treat adenovirus infections.

腺病毒与多种人体细胞结合引起感染。B2腺病毒11和B1腺病毒21都使用蛋白旋钮与补体调节因子CD46(SCR1-2)结合以进入宿主细胞。在每个复合物中,这两种蛋白质都带高度负电荷,但在带有相反电荷的表面斑块的界面上相互结合。我们通过计算生成了CD46(SCR1-2)-Ad11k和CD46(SCR1-2)-Ad21k复合物中带电残基的单丙氨酸突变体。我们利用静电聚类和泊松-玻尔兹曼自由能计算提出了静电在缔合中的作用假设。我们的研究结果描述了CD46(SCR1-2)-Ad11k和CD46(SCR1-2)-Ad21k中特定的界面静电相互作用,这些相互作用对于CD46(SCR1-2)-Ad11k和CD46(SCR1-2)-Ad21k的结合至关重要。这些结果将作为在实验诱变研究中选择具有所需结合亲和力的突变体的预测工具。本研究也将为设计治疗腺病毒感染的抑制剂提供基础。
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引用次数: 1
Systems Medicine: The Application of Systems Biology Approaches for Modern Medical Research and Drug Development. 系统医学:系统生物学方法在现代医学研究和药物开发中的应用。
Pub Date : 2015-01-01 Epub Date: 2015-08-18 DOI: 10.1155/2015/698169
Duncan Ayers, Philip J Day

The exponential development of highly advanced scientific and medical research technologies throughout the past 30 years has arrived to the point where the high number of characterized molecular agents related to pathogenesis cannot be readily integrated or processed by conventional analytical approaches. Indeed, the realization that several moieties are signatures of disease has partly led to the increment of complex diseases being characterized. Scientists and clinicians can now investigate and analyse any individual dysregulations occurring within the genomic, transcriptomic, miRnomic, proteomic, and metabolomic levels thanks to currently available advanced technologies. However, there are drawbacks within this scientific brave new age in that only isolated molecular levels are individually investigated for their influence in affecting any particular health condition. Since their conception in 1992, systems biology/medicine focuses mainly on the perturbations of overall pathway kinetics for the consequent onset and/or deterioration of the investigated condition/s. Systems medicine approaches can therefore be employed for shedding light in multiple research scenarios, ultimately leading to the practical result of uncovering novel dynamic interaction networks that are critical for influencing the course of medical conditions. Consequently, systems medicine also serves to identify clinically important molecular targets for diagnostic and therapeutic measures against such a condition.

在过去的30年里,高度先进的科学和医学研究技术的指数级发展已经达到了这样一种程度,即与发病机制有关的大量特征分子制剂不能轻易地通过传统的分析方法进行整合或处理。事实上,认识到一些部分是疾病的特征,部分地导致了复杂疾病特征的增加。由于目前可用的先进技术,科学家和临床医生现在可以调查和分析在基因组、转录组、微分子组、蛋白质组和代谢组水平上发生的任何个体失调。然而,在这个科学勇敢的新时代,也有一些缺点,因为只有孤立的分子水平才能单独研究它们对任何特定健康状况的影响。自1992年提出以来,系统生物学/医学主要关注整体途径动力学的扰动,从而导致所研究条件的发生和/或恶化。因此,系统医学方法可以用于揭示多种研究场景,最终导致发现新的动态相互作用网络的实际结果,这些网络对影响医疗条件的过程至关重要。因此,系统医学也用于确定临床上重要的分子靶点,用于针对这种疾病的诊断和治疗措施。
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引用次数: 56
Primer Based Approach for PCR Amplification of High GC Content Gene: Mycobacterium Gene as a Model. 基于引物的高GC含量基因PCR扩增方法——以分枝杆菌基因为模型。
Pub Date : 2014-01-01 Epub Date: 2014-03-24 DOI: 10.1155/2014/937308
Arbind Kumar, Jagdeep Kaur

The genome of Mycobacterium is rich in GC content and poses problem in amplification of some genes, especially those rich in the GC content in terminal regions, by standard/routine PCR procedures. Attempts have been made to amplify three GC rich genes of Mycobacterium sp. (Rv0519c and Rv0774c from M. tuberculosis and ML0314c from M. leprae). Out of these three genes, Rv0774c gene was amplified with normal primers under standard PCR conditions, while no amplification was observed in case of Rv0519c and ML0314c genes. In the present investigation a modified primer based approach was successfully used for amplification of GC rich sequence of Rv0519c through codon optimization without changing the native amino acid sequence. The strategy was successfully confirmed by redesigning the standard primers with similar modifications followed by amplification of ML0314c gene.

分枝杆菌基因组中GC含量丰富,对某些基因,特别是末端GC含量丰富的基因,采用标准/常规PCR方法扩增存在问题。对结核分枝杆菌的3个GC富集基因(结核分枝杆菌的Rv0519c和Rv0774c,麻风分枝杆菌的ML0314c)进行了扩增。其中,Rv0774c基因在标准PCR条件下用正常引物扩增,而Rv0519c和ML0314c基因未扩增。本研究在不改变Rv0519c天然氨基酸序列的情况下,利用改良引物优化方法,成功扩增了Rv0519c的GC富序列。通过重新设计具有类似修饰的标准引物,并扩增ML0314c基因,成功地证实了该策略。
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引用次数: 24
An Improved Method for Soil DNA Extraction to Study the Microbial Assortment within Rhizospheric Region. 一种改进的土壤DNA提取方法研究根际微生物分类。
Pub Date : 2014-01-01 Epub Date: 2014-09-15 DOI: 10.1155/2014/518960
Faria Fatima, Neelam Pathak, Smita Rastogi Verma

The need for identification of soil microbial community mainly depends on direct extraction of DNA from soil, a multifaceted environment that is a major pool for microbial genetic diversity. The soil DNA extraction procedures usually suffer from two major problems, namely, inappropriate rupturing of cells and contamination with humic substances. In the present study, five protocols for single type of rhizospheric soil were investigated and their comparison indicated that the inclusion of 120 mM phosphate buffered saline (PBS) for washing and mannitol in the lysis buffer allowed the processing of soil sample in minimal time with no specific equipment requirement. Furthermore, DNA purity and yield were also improved, which allowed the exploitation of genetic potential of soil microbes within soil sample thereby facilitating the amplification of metagenomic DNA. The effectiveness of methods was analyzed using random amplification of polymorphic DNA. The banding patterns revealed that both the abundance and the composition of indigenous microbial community depend on the DNA recovery method.

土壤微生物群落鉴定的需要主要依赖于直接从土壤中提取DNA,土壤是一个多方面的环境,是微生物遗传多样性的主要来源。土壤DNA提取过程通常存在两个主要问题,即细胞破裂不当和腐殖质污染。在本研究中,对单一类型根际土壤的五种方案进行了研究,它们的比较表明,在裂解缓冲液中加入120 mM磷酸盐缓冲盐水(PBS)进行洗涤和甘露醇,可以在最短的时间内处理土壤样品,而不需要特定的设备。此外,DNA的纯度和产量也得到了提高,从而可以利用土壤样品中土壤微生物的遗传潜力,从而促进宏基因组DNA的扩增。通过随机扩增多态DNA分析方法的有效性。结果表明,微生物群落的丰度和组成与DNA恢复方法有关。
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引用次数: 32
Interleukin-6 c.-174G>C Polymorphism and Periodontitis in a Brazilian Population. 白细胞介素- 6c - 174g >C多态性与巴西人群牙周炎的关系
Pub Date : 2014-01-01 Epub Date: 2014-12-04 DOI: 10.1155/2014/490308
Fernanda Gabriela Teixeira, Samir Andrade Mendonça, Kamilla Menezes Oliveira, Djanilson Barbosa Dos Santos, Lucas Miranda Marques, Maise Mendonça Amorim, Raquel de Souza Gestinari

Aim. Periodontitis is an inflammatory disease that affects the teeth supporting structures, triggered by periodontal pathogens, and is influenced by environmental and genetic factors. Genes encoding molecules related to the immune response, such as cytokine, are the main candidates for polymorphisms analysis and may be possibly associated with this pathology. A G/C promoter polymorphism on the IL6 gene has been shown to affect basal IL-6 levels. The aim of this study was to investigate the association between the IL6 c.-174G>C polymorphism and periodontitis in individuals from Vitória da Conquista, Bahia, Brazil. Material and Methods. Three hundred and thirty individuals (134 cases, 196 controls) were genotyped for the IL6 c.-174G>C by MS-PCR technique. Concentrations of salivary IL-6 were determined by ELISA method. Results. The IL6 c.-174G>C polymorphism was associated with periodontitis when comparing the distribution of genotypes between patients with periodontitis and control subjects. The GC genotype appeared as a protective factor for periodontitis. Results showed increased levels of salivary IL-6 in periodontitis patients. Nevertheless, there was no relationship between the concentrations of IL-6 and genotypes when comparing the case and control groups. Conclusions. Our data indicate an association between IL6 c.-174G>C polymorphism and periodontitis and showed that IL-6 may be considered an important marker for periodontitis.

的目标。牙周炎是一种影响牙齿支撑结构的炎症性疾病,由牙周病原体引发,并受环境和遗传因素的影响。编码与免疫反应相关的分子的基因,如细胞因子,是多态性分析的主要候选者,可能与这种病理有关。IL-6基因上的G/C启动子多态性已被证明影响基础IL-6水平。本研究的目的是研究IL6 C .- 174g >C多态性与巴西巴伊亚州Vitória da Conquista个体牙周炎之间的关系。材料和方法。采用MS-PCR技术对330例(134例,196例对照)进行il - 6 C - 174g >C基因分型。ELISA法测定唾液IL-6浓度。结果。比较牙周炎患者与对照组的基因型分布,il - 6 C - 174g >C多态性与牙周炎相关。GC基因型是牙周炎的保护因子。结果显示牙周炎患者唾液IL-6水平升高。然而,当比较病例组和对照组时,IL-6的浓度与基因型之间没有关系。结论。我们的数据表明IL-6 C - 174g >C多态性与牙周炎之间存在关联,并表明IL-6可能被认为是牙周炎的重要标志物。
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引用次数: 23
mTOR Signaling in Protein Translation Regulation: Implications in Cancer Genesis and Therapeutic Interventions. 蛋白翻译调控中的mTOR信号:在癌症发生和治疗干预中的意义。
Pub Date : 2014-01-01 Epub Date: 2014-11-20 DOI: 10.1155/2014/686984
Mehvish Showkat, Mushtaq A Beigh, Khurshid I Andrabi

mTOR is a central nutrient sensor that signals a cell to grow and proliferate. Through distinct protein complexes it regulates different levels of available cellular energy substrates required for cell growth. One of the important functions of the complex is to maintain available amino acid pool by regulating protein translation. Dysregulation of mTOR pathway leads to aberrant protein translation which manifests into various pathological states. Our review focuses on the role mTOR signaling plays in protein translation and its physiological role. It also throws some light on available data that show translation dysregulation as a cause of pathological complexities like cancer and the available drugs that target the pathway for cancer treatment.

mTOR是一种中心营养传感器,它向细胞发出生长和增殖的信号。它通过不同的蛋白质复合物调节细胞生长所需的不同水平的可用细胞能量底物。该复合物的一个重要功能是通过调节蛋白质翻译来维持可用的氨基酸库。mTOR通路失调导致蛋白翻译异常,表现为多种病理状态。本文就mTOR信号在蛋白质翻译中的作用及其生理作用作一综述。它还揭示了一些现有数据,表明翻译失调是癌症等病理复杂性的原因,以及针对癌症治疗途径的现有药物。
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引用次数: 173
Regulatory Variants and Disease: The E-Cadherin -160C/A SNP as an Example. 调控变异体与疾病:以E-Cadherin -160C/A SNP为例
Pub Date : 2014-01-01 Epub Date: 2014-09-02 DOI: 10.1155/2014/967565
Gongcheng Li, Tiejun Pan, Dan Guo, Long-Cheng Li

Single nucleotide polymorphisms (SNPs) occurring in noncoding sequences have largely been ignored in genome-wide association studies (GWAS). Yet, amounting evidence suggests that many noncoding SNPs especially those that are in the vicinity of protein coding genes play important roles in shaping chromatin structure and regulate gene expression and, as such, are implicated in a wide variety of diseases. One of such regulatory SNPs (rSNPs) is the E-cadherin (CDH1) promoter -160C/A SNP (rs16260) which is known to affect E-cadherin promoter transcription by displacing transcription factor binding and has been extensively scrutinized for its association with several diseases especially malignancies. Findings from studying this SNP highlight important clinical relevance of rSNPs and justify their inclusion in future GWAS to identify novel disease causing SNPs.

非编码序列中的单核苷酸多态性(SNPs)在全基因组关联研究(GWAS)中一直被忽视。然而,越来越多的证据表明,许多非编码snp,特别是那些位于蛋白质编码基因附近的snp,在形成染色质结构和调节基因表达方面发挥着重要作用,因此,与多种疾病有关。其中一种调节性SNP (rsnp)是E-cadherin (CDH1)启动子-160C/A SNP (rs16260),已知它通过取代转录因子结合来影响E-cadherin启动子转录,并因其与几种疾病特别是恶性肿瘤的关联而被广泛研究。研究该SNP的发现强调了rsnp的重要临床相关性,并证明将其纳入未来的GWAS以鉴定新的致病SNP是合理的。
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引用次数: 38
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