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Ultrastructure study of the transgenic REN2 rat aorta – part 2: media, external elastic lamina, and adventitia 转基因REN2大鼠主动脉的超微结构研究——第二部分:中膜、外弹性层和外膜
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6392
M. Hayden, J. Sowers, V. DeMarco
Background The renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of vascular stiffness, hypertension and accelerated atherosclerosis, which are associated with the metabolic syndrome (MetS) and type 2 diabetes mellitus. In addition to the intima, RAAS plays an important role in vascular media and adventitial remodeling. Methods Descending thoracic aortas of young male transgenic heterozygous (mRen2) 27 (Ren2) rats were utilized for ultrastructural study. This lean model of hypertension, insulin resistance, and oxidative stress harbors the mouse renin gene and is known to have increased aortic tissue levels of angiotensin II, angiotensin type 1 receptors, and elevated plasma aldosterone levels. Results Ultrastructural observations substantiate known and novel findings in the tunica media, internal and external elastic lamina, and tunica adventitia, which includes: increased media collagen - proteoglycan matrix expansion, increased secretory and proliferative activity and migration of vascular smooth muscle cells (VSMCs) into a newly developing subendothelial neointima, increased VSMC caveolae, mitochondria degeneration, apoptosis; and lipid retention at the elastin lamellar interface. Openings in the external elastic lamina allow pericyte-to-VSMC contacts. The tunica adventitia exhibits stromal pericyte hyperplasia with actively synthetic phenotype and pericyte-pericyte connections. Conclusion While these studies only represent a single snapshot in time, they provide an evaluation of early abnormal ultrastructural vascular remodeling in Ren-2 models of the conduit-elastic thoracic aorta.
肾素-血管紧张素-醛固酮系统(RAAS)在血管僵硬、高血压和加速动脉粥样硬化的发生和发展中起重要作用,并与代谢综合征(MetS)和2型糖尿病相关。除了内膜外,RAAS在血管介质和外膜重构中也起着重要作用。方法采用转基因杂合雄性(mRen2) 27 (Ren2)年轻大鼠胸降主动脉进行超微结构研究。这种高血压、胰岛素抵抗和氧化应激的瘦模型含有小鼠肾素基因,已知其主动脉组织血管紧张素II、血管紧张素1型受体水平升高,血浆醛固酮水平升高。结果超微结构观察证实了中膜、内外弹性层和外膜中已知的和新的发现,包括:中膜胶原-蛋白聚糖基质扩张增加,血管平滑肌细胞(VSMC)分泌和增殖活性增加,向新形成的内皮下新内膜迁移,血管平滑肌细胞小泡增加,线粒体变性,细胞凋亡;以及弹性蛋白层状界面的脂质保留。外部弹性层的开口允许周细胞与vsmc接触。外膜表现为间质周细胞增生,具有活跃的合成表型和周细胞-周细胞连接。结论虽然这些研究只代表了一个单一的时间快照,但它们提供了对导管弹性胸主动脉Ren-2模型早期异常超微结构血管重构的评估。
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引用次数: 4
Designing an ideal 3D-bioprint conduit for axonal repair and regeneration: a neurosurgical perspective 设计理想的3d生物打印管道用于轴突修复和再生:神经外科的观点
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6382
Caleb E. Stewart, C. Kan, D. Nguyen, O. Sulaiman
Peripheral nerve injuries occur through three mechanisms, specifically, crush, compression or transection. Disruption of communication between the peripheral and central nervous system follows and leads to motor and sensory deficits. Peripheral nerves in humans have a limited capacity to self-regenerate following injury, which makes nerve transfer the current gold-standard for treatment. Functional nerve regeneration is contingent on several factors ranging from span of injury and the age of the patient. Bioprinted nerve guidance conduits are an emerging candidate for treating peripheral nerve injuries. To optimize the performance of nerve guidance conduits, a firm understanding of neurobiology and the pathophysiology following injury is necessary. This article provides an overview of nerve regeneration and the desirable features when designing a nerve conduit from a neurosurgical perspective.
周围神经损伤主要有三种机制,即挤压、压迫或横断。外周神经系统和中枢神经系统之间的交流中断导致运动和感觉缺陷。人类周围神经在受伤后自我再生的能力有限,这使得神经移植成为目前治疗的金标准。功能性神经再生取决于几个因素,包括损伤范围和患者的年龄。生物打印神经引导导管是治疗周围神经损伤的新兴候选材料。为了优化神经引导导管的功能,对损伤后的神经生物学和病理生理学有深入的了解是必要的。本文从神经外科的角度概述了神经再生和设计神经导管时的理想特征。
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引用次数: 0
Morphological and neurochemical plasticity of rat mesencephalic trigeminal neurons 大鼠中脑三叉神经的形态学和神经化学可塑性
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6388
A. Dandov, D. Atanasova, N. Lazarov
The mesencephalic trigeminal nucleus (Me5) is a unique structure in the central nervous system (CNS), made up of pseudounipolar sensory neurons. It is also a suitable paradigm for studying the plastic alterations in neurons. It is known that the Me5 neurons utilize various neurotransmitters under normal conditions, though little information is available about the morphological and chemical events taking place in the nucleus after injury. This review provides concise description of the structural adaptive changes in Me5 neurons following peripheral axotomy of the masseteric nerve. Furthermore, it validates NADPH-diaphorase activity in them, and using immunohistochemistry for glutamate (Glu), substance P (SP), calcitonin-gene related protein (CGRP), neuropeptide tyrosine (NPY) and galanin (GAL), it deals with the altered neurochemical phenotype of the injured neurons. Our results distinctly show that the Me5 neurons in the rat are extremely sensitive to peripheral injury and we demonstrate their distinct structural and neurochemical plasticity. The adaptive morphological alterations comprise of both qualitative and quantitative alterations in the axotomized Me5 population which are statistically significant when compared with the number and phenotype of the neurons on the contralateral intact side. Besides, the axotomy-induced alterations in the neurochemical character of Me5 are best signified by the down-regulation of the classical neurotransmitters under normal conditions, and the up-regulation of nitric oxide synthase and de novo synthesis of certain neuroactive substances such as NPY, SP, GAL and VIP. It can be inferred that the described phenomena only occur in the nucleus in cases of injury and changes in the environmental cues, and serve as adaptive mechanisms and powerful trophic factors for the neuronal survival in the Me5. There is, undoubtedly, still a long way to go in order to clarify the dynamic and plastic alterations occurring in the CNS in health and disease, and also explain their role in such important functions as pain, perception, learning, cognition and memory.
中脑三叉神经核(Me5)是中枢神经系统(CNS)中一个独特的结构,由伪单极感觉神经元组成。这也是研究神经元可塑性变化的一个合适范例。众所周知,在正常情况下,Me5神经元利用各种神经递质,但关于损伤后核内发生的形态学和化学事件的信息很少。本文简要介绍了咬肌神经外周轴切开术后Me5神经元的结构适应性变化。进一步验证了NADPH-diaphorase的活性,并利用谷氨酸(Glu)、P物质(SP)、降钙素基因相关蛋白(CGRP)、神经肽酪氨酸(NPY)和甘丙氨酸(GAL)的免疫组化,研究了损伤神经元的神经化学表型改变。我们的研究结果清楚地表明,大鼠Me5神经元对外周损伤非常敏感,我们证明了其独特的结构和神经化学可塑性。与对侧完整侧神经元的数量和表型相比,自适应形态学改变包括定性和定量的改变。另外,在正常情况下,典型的神经递质下调,一氧化氮合酶的上调以及NPY、SP、GAL、VIP等神经活性物质的重新合成,最能体现axtomy诱导的Me5神经化学特性的改变。由此可以推断,上述现象仅在受到损伤和环境信号改变的情况下才会发生在细胞核内,是Me5神经元存活的适应性机制和强大的营养因子。毫无疑问,要弄清中枢神经系统在健康和疾病中发生的动态和可塑性变化,并解释它们在疼痛、感知、学习、认知和记忆等重要功能中的作用,还有很长的路要走。
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引用次数: 0
The fibrous cap: a promising target in the pharmacotherapy of atherosclerosis 纤维帽:动脉粥样硬化药物治疗的一个有希望的靶点
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6394
S. Yanev, M. Zhelyazkova-Savova, G. Chaldakov
Recent advances have shed light on the relationship between smooth muscle cell (SMC) phenotypic modulation, resolution of inflammation and atherosclerotic plaque stability. The thick fibrous cap covering the lipid core of plaques is composed of bundles of SMC and collagen fibers and few macrophages and lymphocytes, all of which make the plaque resistant to rupture. The thin fibrous cap contains many macrophages and lymphocytes, few SMC and less collagen fibers, all of which may weaken the cap, leaving the plaque vulnerable to rupture. In the present Dance Round, we, at a pharmacotherapeutic level, address the possibility of how the control over the activity of the essential cellular components of the plaque, particularly its fibrous cap, could be implicated in plaque stabilization, focusing on (i) the modulation of SMC from contractile to secretory (fibrogenic) phenotype, (ii) the control on plaque inflammation-resolution processes, and (iii) the reduction of plaque lipid content. Further studies on both unstable plaque and aortic aneurysm, which share a similar, matrix-based vulnerability, may bring new insights for pharmacotherapy of vascular injuries.
最近的研究进展揭示了平滑肌细胞(SMC)表型调节、炎症消退和动脉粥样硬化斑块稳定性之间的关系。覆盖斑块脂质核心的厚纤维帽由成束的SMC和胶原纤维以及少量的巨噬细胞和淋巴细胞组成,这些都使斑块具有抗破裂性。薄纤维帽含有大量的巨噬细胞和淋巴细胞,少量的SMC和较少的胶原纤维,这些都可能削弱纤维帽,使斑块容易破裂。在当前的Dance Round中,我们在药物治疗水平上解决了控制斑块基本细胞成分活性的可能性,特别是其纤维帽,可能与斑块稳定有关,重点关注(i) SMC从收缩到分泌(纤维原性)表型的调节,(ii)对斑块炎症消退过程的控制,以及(iii)斑块脂质含量的减少。不稳定斑块和主动脉瘤具有相似的基质易感性,对它们的进一步研究可能会为血管损伤的药物治疗带来新的见解。
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引用次数: 4
Motivational enhancement therapy versus cognitive behavioral therapy in a cohort of men and women with alcohol use disorder 动机增强疗法与认知行为疗法在酒精使用障碍男性和女性队列中的比较
Pub Date : 2019-05-01 DOI: 10.14748/BMR.V30.6393
G. Coriale, F. Rosa, G. Battagliese, S. Gencarelli, M. Fiore, G. Ferraguti, M. Vitali, C. Rotondo, M. Messina, M. L. Attilia
The clinical manifestations of alcohol dependence are not homogeneous. Many studies described both cognitive impairments and psychiatric disorders among people with Alcohol use disorder (AUD). However, AUD can be present without comorbid psychiatric disorders or severe cognitive deficits, namely, “pure alcoholics”. Until now, knowledge about effective treatments for this typology of AUD patients remains unknown. The aim of the present study was to assess two psychological methods of intervention: Cognitive-behavioral treatment (CBT) in the short format and the Motivational enhancement therapy (MET). We then opted to compare the efficacy of methods in treating AUD in both men and women pure alcoholics. We performed a controlled and randomized study consisting of 325 people affected by AUD (244 men, 81 women). 72.3% (n=235; 181 men 54 women) were excluded according to selection criteria. The major percentage of exclusion (38.7%; n=91; 63 men 28 women) regarded patients with comorbid psychiatric disorders. Only the 90 remaining test subjects (27.7% of the sample population; 63 men and 27 women) classified as pure alcoholics were eligible for this study. The test subjects were divided into two groups. One group underwent MET (n=47; 35 men and 12 women) and the other underwent CBT (n=43; 28 men and 15 women). We found a significant adherence to the treatment in the CBT group (19 men and 9 women) compared to the MET group (3 men and 1 woman). At the end of treatment, the dropout rates for the CBT and MET therapy groups were 34.9% and 91.5%, respectively. Moreover, we found no differences in the percentage of abstinent days between CBT and MET groups at three months (CBT: n=36; mean 91.40±15.34; MET: n=18; mean 93.90±11.95; t(52)= 0.605, p=0.550), at six months (CBT: N=30; mean 85.00±30.71; MET: n=9; mean 87.78±33.08; t(37)=-0.234, p=0.820) and at twelve months from the beginning of treatment (CBT: n=28; mean 90.14±22.06; MET: n=4; mean 100±0; t(30)=-0.881, p=0.838). In conclusion, we disclose that CBT in the short format could be an effective treatment strategy for pure alcoholics without psychiatric disorders or severe cognitive deficits.
酒精依赖的临床表现不尽相同。许多研究描述了酒精使用障碍(AUD)患者的认知障碍和精神障碍。然而,AUD可以在没有共病精神障碍或严重认知缺陷的情况下出现,即“纯粹的酗酒者”。到目前为止,关于这种类型AUD患者的有效治疗方法仍然未知。本研究的目的是评估两种心理干预方法:短格式的认知行为治疗(CBT)和动机增强治疗(MET)。然后,我们选择比较治疗男性和女性纯酗酒者AUD的方法的疗效。我们进行了一项对照和随机研究,包括325名AUD患者(244名男性,81名女性)。72.3% (n = 235;根据选择标准,181名男性(54名女性)被排除在外。主要排除率(38.7%;n = 91;63名男性28名女性)共病精神障碍患者。只剩下90名测试对象(占样本总人数的27.7%;63名男性和27名女性)被归类为纯酗酒者,符合这项研究的条件。测试对象被分成两组。一组行MET治疗(n=47;35名男性和12名女性),另一名接受CBT治疗(n=43;男性28人,女性15人)。我们发现CBT组(19名男性和9名女性)与MET组(3名男性和1名女性)相比有显著的治疗依从性。治疗结束时,CBT组和MET组的辍学率分别为34.9%和91.5%。此外,我们发现CBT组和MET组在三个月时的戒断天数百分比没有差异(CBT: n=36;平均91.40±15.34;遇见:n = 18;平均93.90±11.95;t(52)= 0.605, p=0.550), 6个月时(CBT: N=30;平均85.00±30.71;遇见:n = 9;平均87.78±33.08;t(37)=-0.234, p=0.820)和治疗开始后12个月(CBT: n=28;平均90.14±22.06;遇见:n = 4;意思是100±0;t (30) = -0.881, p = 0.838)。综上所述,我们揭示了简短形式的CBT对于没有精神疾病或严重认知缺陷的纯酗酒者可能是一种有效的治疗策略。
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引用次数: 1
Modeling traumatic brain injury: mechanisms of early neuronal and axon degeneration in the infant rodent brain 创伤性脑损伤模型:幼鼠大脑早期神经元和轴突变性的机制
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6385
K. Dikranian
Traumatic brain injury (TBI) remains a major health challenge and affects the young disproportionately. Accidental and non-accidental TBI in children is a major contributor to morbidity, disability, and death. TBI in this critical period leads to profound neuronal and axonal degeneration followed by cognitive, psychological and memory impairment, altered processing speed, impaired executive functions, emotional liability as well as word finding difficulties. Cognitive and behavioral changes may remain unrecognized for periods even after sustaining mild injury. Although accidental and non-accidental inflicted injury (blunt force or violent shaking-inflicting brain injury or “Shaken baby” syndrome) posits a major clinical and sociological problem, mechanisms of tissue degeneration might be largely similar. The scope of this review will be the experimental research related to modeling blunt (concussive) head trauma specifically to the infant rodent brain resulting in acute (early) and protracted (late) degenerative changes such as axonal degeneration and apoptotic neuronal cell death. Similarly, discussion will be limited to therapeutic windows and potentials for ameliorating the development of early brain injury.
创伤性脑损伤(TBI)仍然是一个主要的健康挑战,对年轻人的影响尤为严重。儿童偶然性和非偶然性脑外伤是发病、残疾和死亡的主要原因。这一关键时期的创伤性脑损伤会导致严重的神经元和轴突退化,随之而来的是认知、心理和记忆障碍,处理速度改变,执行功能受损,情绪不稳定以及找词困难。认知和行为的改变可能在一段时间内不被发现,即使是在遭受轻微伤害之后。虽然意外和非意外造成的伤害(钝器或剧烈摇晃造成的脑损伤或“摇晃婴儿”综合征)提出了一个主要的临床和社会学问题,但组织变性的机制可能在很大程度上是相似的。本综述的范围将是与模拟钝性(震荡)头部创伤有关的实验研究,特别是对幼鼠大脑造成急性(早期)和延续性(晚期)退行性改变,如轴突变性和神经元细胞凋亡。同样,讨论将仅限于治疗窗口和改善早期脑损伤发展的潜力。
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引用次数: 1
Acute stimulation of vagus nerve modulates brain neurotrophins, and stimulates neuronal plasticity in the hippocampus of adult male rats 迷走神经急性刺激可调节脑营养因子,刺激成年雄性大鼠海马神经元可塑性
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6391
Pamela Rosso, M. Fiore, E. Fico, A. Iannitelli, P. Tirassa
The present study was aimed at evaluating whether single intermittent acute cervical vagus nerve stimulation (ACVS), pro-vided at a frequency which exhibits a clinical efficacy, may influence brain neurotrophins and hippocampal plasticity. With this purpose, the brain of adult male rats undergoing ACVS was used to analyze the expression of Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF) in brain areas known to synthetize these growth factors, and the expression the neural cell adhesion molecule (NCAM), the synaptophysin (SYP) and biosynthetic GABA (GAD67) in the hippocampus. The effects of ACVS on NGF and BDNF protein and mRNA in hippocampus, hypothalamus and cortex two hours after stimulation were shown to be dependent on the frequencies of ACVS stimulation. Prolonged (three days post stimulation) modifications of NGF and BDNF were also observed in the hippocampus of ACVS rats. An early enhancement of the plasticity markers NCAM, SYP and GAD67 was also found in ACVS hippocampus. Three days after stimulation, NCAM and GAD67 levels were still higher than controls. Immunohistochemistry confirms the stimulatory effects of ACVS on GABA showing an increase in GAD67-positive cells in the dentate gyrus and CA3 hippocampal areas. This study shows that ACVS affects brain NGF and BDNF synthesis in a frequency-dependent manner. Neurotrophins changes are associated with increased hippocampal plasticity, as demonstrated by the observed molecular and morphological modifications. These findings support the role of brain neurotrophins in the ACVS mechanism of action.
本研究旨在评估单次间歇性急性颈迷走神经刺激(ACVS)是否会影响脑神经营养因子和海马的可塑性。为此,我们利用ACVS成年雄性大鼠的大脑,分析神经生长因子(NGF)和脑源性神经营养因子(BDNF)在已知合成这些生长因子的脑区表达情况,以及海马区神经细胞粘附分子(NCAM)、突触素(SYP)和生物合成GABA (GAD67)的表达情况。刺激2小时后,ACVS对海马、下丘脑和皮层中NGF和BDNF蛋白及mRNA的影响与ACVS刺激频率有关。ACVS大鼠海马中也观察到长时间(刺激后3天)NGF和BDNF的改变。在ACVS海马中,可塑性标志物NCAM、SYP和GAD67也有早期增强。刺激3天后,NCAM和GAD67水平仍高于对照组。免疫组化证实了ACVS对GABA的刺激作用,显示齿状回和海马CA3区gad67阳性细胞增加。本研究表明,ACVS以频率依赖的方式影响脑NGF和BDNF的合成。神经营养物质的改变与海马可塑性的增加有关,正如观察到的分子和形态改变所证明的那样。这些发现支持了脑神经营养因子在ACVS作用机制中的作用。
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引用次数: 2
Cell-cell communication predicts aging, senescence and death: an integrated, predictive evolutionary approach 细胞-细胞通讯预测衰老、衰老和死亡:一种综合的、可预测的进化方法
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6383
J. Torday
None of the extant theories of aging have proven to be effective in advancing our knowledge of senescence or mortality. In contrast to the gene-centric focus on evolution, the mechanism of cell-cell interactions as the driving force for evolution as the logic of biology is proposed. Since the distribution of  bioenergy over the course of the life cycle is skewed towards the reproductive phase, bioenergy flags in the post-reproductive stage of life, causing failure of cell-cell signaling, loss of homeostatic control, senescence and death. In the interim, the phenotype acts as the ‘agent’ for epigenetic inheritance, obtaining ‘marks’ that inform the organism of changes in the environment. Such marks are inherited by the offspring, providing it with foreknowledge of the environment to come. The organism appears to ‘return’ to the unicellular state over the course of the life cycle, but in reality meiosis is the mechanism of epigenetic inheritance, the adult phenotype being the means for transmitting the epigenetic marks obtained from the environment back to the organism.
没有一种现存的衰老理论被证明能有效地提高我们对衰老或死亡的认识。相对于以基因为中心的进化,细胞-细胞相互作用的机制作为进化的驱动力作为生物学的逻辑被提出。由于生物能源在整个生命周期中的分布向生殖阶段倾斜,生物能源在生命的后生殖阶段消失,导致细胞-细胞信号传导失败,失去稳态控制,衰老和死亡。在此期间,表现型充当表观遗传的“代理人”,获得“标记”,通知生物体环境的变化。这些标记由后代遗传,使其对未来的环境有预知能力。生物体在整个生命周期中似乎“回归”到单细胞状态,但实际上减数分裂是表观遗传的机制,成年表型是将从环境中获得的表观遗传标记传递回生物体的手段。
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引用次数: 2
The role of selenium and zinc in allergic hypersensitization in children 硒和锌在儿童过敏性超敏反应中的作用
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6387
Halyna Pavlyshyn, Viktoriia Sliiva
The prevalence of allergy has increased rapidly over recent years, especially among pediatric patients and it is detected approximately in 2–3% of the world population. Worldwide, respiratory allergic diseases affect nearly 700 million subjects. The pathogenesis of allergy is still poorly understood and is a matter of worldwide concern. It is thought that it results from the interactions between genetic predisposition and excessive and inappropriate immune responses to a large spectrum of environmental risk factors. Recent clinical observations and epidemiological studies have identified associations between nutritional elements (e.g., zinc, and selenium) and allergy prevalence. It is suggested that micronutrients influence the immune system and may play a major role in the development of asthma and in the progression of other allergic diseases. This link is based on the hypothesized benefits of antioxidant functions of certain micronutrients, which may modulate the amount of oxidants in the body. As a result, decrease in oxidative stress may be an important factor in the etiology of childhood asthma. Our aim was to analyze the current literature and to assess whether trace elements level is a risk factor for allergic symptoms in childhood. In this review article, we aimed to describe the properties and biological importance and to define the possible relationship between atopic sensitization and serum levels of zinc and selenium in children. Biomed Rev 2019;30:49-61
近年来,过敏的患病率迅速增加,特别是在儿科患者中,大约占世界人口的2-3%。在世界范围内,呼吸道过敏性疾病影响了近7亿人。过敏的发病机制仍然知之甚少,是全世界关注的问题。据认为,这是遗传易感性与对大量环境危险因素的过度和不适当的免疫反应之间相互作用的结果。最近的临床观察和流行病学研究已经确定了营养元素(如锌和硒)与过敏患病率之间的关联。这表明微量营养素影响免疫系统,并可能在哮喘的发展和其他过敏性疾病的进展中发挥重要作用。这种联系是基于某些微量营养素的抗氧化功能的假设,它们可以调节体内氧化剂的数量。因此,氧化应激降低可能是儿童哮喘发病的一个重要因素。我们的目的是分析目前的文献,并评估微量元素水平是否是儿童过敏症状的危险因素。在这篇综述文章中,我们的目的是描述的性质和生物学重要性,并确定特应性致敏与儿童血清锌和硒水平之间可能的关系。生物医学学报,2019;30:49-61
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引用次数: 0
Immunity and resistance to cryptosporidiosis: the intricate ways of an enigmatic parasitosis 对隐孢子虫病的免疫和抵抗:一种神秘寄生虫病的复杂方式
Pub Date : 2019-05-01 DOI: 10.14748/bmr.v30.6386
K. Stoyanova, S. Pavlov
Genus Cryptosporidium includes around 30 known apicomplexan parasitic species which infect the gastrointestinal tract and rarely the respiratory system of more than 300 vertebrate animals. The immune response against infection by Cryptosporidium spp. includes all strata of innate and adaptive immunity with differences in their significance. The mucosal immunity, expressed predominantly by the “sentinel” role of epitheliocytes, is fundamental to the resistance against an infection (mainly via activation of the TLR4/NF-κB signalling axis). The vast array of epithelial chemokines and cytokines initiate the local inflammatory processes, attract effector cells and may directly suppress the parasite adhesion. The second line of defence includes IFN-γ-production by the NK cells in combination with their innate cytotoxicity against the parasite and the infected epitheliocytes. The adaptive immunity against the parasite depends predominantly on cytotoxic CD4+ Th1-lymphocytes, which makes IFN-γ central to the acquired response too. CD8+ cells aid to some extent the activity of Th1-cells but their involvement is not decisive. While Cryptosporidium infection elicits the synthesis of specific serum and mucosal antibodies, the humoral immunity is of minor importance. In immunocompromised hosts, infants and malnourished children, the mild and usually self-limiting infection can become life-threatening or take a chronic course. It is the second leading cause of fatal diarrhoea in children and one of the major opportunistic pathogens in the continually expanding group of patients with immunodeficiencies and systemic chronic diseases. Unravelling the mechanisms of resistance against Cryptosporidium infection is fundamental for the successful prevention of the disease. Biomed Rev 2019;30:37-48
隐孢子虫属包括大约30种已知的顶复合体寄生物种,它们感染胃肠道,很少感染300多种脊椎动物的呼吸系统。对隐孢子虫感染的免疫反应包括先天免疫和适应性免疫的各个层次,但其意义不同。粘膜免疫主要由上皮细胞的“哨兵”作用表达,是抵抗感染的基础(主要通过激活TLR4/NF-κB信号轴)。大量的上皮趋化因子和细胞因子启动局部炎症过程,吸引效应细胞,并可能直接抑制寄生虫的粘附。第二道防线包括NK细胞产生IFN-γ,结合它们对寄生虫和被感染的上皮细胞的先天细胞毒性。针对寄生虫的适应性免疫主要依赖于细胞毒性CD4+ th1淋巴细胞,这使得IFN-γ也成为获得性反应的中心。CD8+细胞在一定程度上帮助th1细胞的活性,但它们的参与不是决定性的。虽然隐孢子虫感染引起特异性血清和粘膜抗体的合成,但体液免疫的重要性较小。在免疫功能低下的宿主、婴儿和营养不良的儿童中,这种通常为自限性的轻微感染可危及生命或呈慢性病程。它是儿童致命腹泻的第二大原因,也是免疫缺陷和全身性慢性疾病患者群体不断扩大的主要机会性病原体之一。揭示对隐孢子虫感染的抗性机制是成功预防该疾病的基础。生物医学学报,2019;30:37-48
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