| 1 | Transl Psychiatry 2011 -1 1: e36 |
|---|---|
| PMID | 22832610 |
| Title | 增强peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype. |
| 抽象的 | 精神病患者通常存在低级外周炎症。Toll样受体（TLR）是启动炎症的模式识别分子。我们的目标是研究精神病中的周围TLR活性。四十精神分裂症患者,20双相患者和forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24?h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1?, IL-6, IL-8 and tumour necrosis factor-? (TNF?). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1?, IL-6, IL-8 and TNF?) release is enhanced in stimulated whole blood from精神分裂症与HC相比，双极患者和双极患者。IL-1？，IL-6和TNF的夸张释放？在用TLR2激动剂HKLM治疗后，与对照组相比，两种疾病都检测到。增强TLR4-induced increases in IL-1? for both disorders coupled with TNF? increases for bipolar patients were observed. TLR8-induced increases in IL-1? for both disorders as well as IL-6 and TNF? increases for bipolar patients were detected. TLR9-induced increases in IL-8 for精神分裂症patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNF? levels were significantly elevated in精神分裂症patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders. |
| SCZ Keywords | 精神分裂症 |
| 2 | BMC Res Notes 2012 -1 5：69 |
| PMID | 22280494 |
| Title | 快速多重高分辨率熔化方法分析早产中炎症相关的SNP。 |
| 抽象的 | Complex traits like cancer, diabetes, obesity or精神分裂症arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs) from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM) analysis is a new method in which polymerase chain reaction (PCR) and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB) is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB. 在这里，我们使用实时PCR，然后使用HRM分析来同时识别早产疗法炎症途径涉及的几种基因变异。SNP来自TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism. We were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB. Several gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing their association to PTB. It can easily be used for simultaneously analyze any set of SNPs, either as the first choice for new association studies or as a complement to large-scale genotyping analysis. Given that inflammatory pathway is in the base of several diseases, it is potentially useful to analyze a broad range of disorders. |
| SCZ Keywords | 精神分裂症 |
| 3 | 摩尔。神经生物醇。2013年8月48日：190-204 |
| PMID | 23436141 |
| Title | Role of the Toll Like receptor (TLR) radical cycle in chronic inflammation: possible treatments targeting the TLR4 pathway. |
| 抽象的 | Activation of the Toll-like receptor 4 (TLR4) complex, a receptor of the innate immune system, may underpin the pathophysiology of many human diseases, including asthma, cardiovascular disorder, diabetes, obesity, metabolic syndrome, autoimmune disorders, neuroinflammatory disorders,精神分裂症，躁郁症，自闭症，临床抑郁症，慢性疲劳综合征，酗酒和甲苯吸入。TLR是识别损伤相关的分子模式和与病原体相关的分子模式的模式识别受体，包括革兰氏阴性细菌的脂多糖（LPS）。在这里，我们专注于环境因素，这些因素已知会触发TLR4,如臭氧、大气颗粒物,长-lived reactive oxygen intermediate, pentachlorophenol, ionizing radiation, and toluene. Activation of theTLR4pathways may cause chronic inflammation and increased production of reactive oxygen and nitrogen species (ROS/RNS) and oxidative and nitrosative stress and therefore TLR-related diseases. This implies that drugs or substances that modify these pathways may prevent or improve the abovementioned diseases. Here we review some of the most promising drugs and agents that have the potential to attenuate TLR-mediated inflammation, e.g., anti-LPS strategies that aim to neutralize LPS (synthetic anti-LPS peptides and recombinant factor C) andTLR4/MYD88拮抗剂，包括Eritoran，CYP，EM-163，Epigallocatechin-3-Gallate，6-Shogaol，Cinnamon提取物，N-乙酰半胱氨酸，褪黑激素和分子氢。作者认为，TLR自由基（ROS/RNS）周期的激活是基于许多“文明”疾病的常见途径，而靶向TLR自由基循环可能是治疗许多炎症性疾病的有效方法。 |
| SCZ Keywords | 精神分裂症 |
| 4 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Jul 44: 301-11 |
| PMID | 23587629 |
| Title | The TRIPS (Toll-like receptors in immuno-inflammatory pathogenesis) Hypothesis: a novel postulate to understand schizophrenia. |
| 抽象的 | Mounting evidence indicates that immune activation and/or immuno-inflammatory reactions during neurodevelopment apparently contribute to the pathogenesis and progression of精神分裂症。妊娠早期期间引发免疫激活/炎症反应已知的重要环境因素之一是产前感染。动物研究的最新理解表明，与氧化/硝化应激的一致性，产前感染引起的母体免疫激活（MIA）/炎症会导致后代的神经发育损害和行为异常。尽管MIA/炎症的基本精确机理过程尚未完全阐明，但越来越多地认识到，构成针对入侵微生物的第一道防线的收费受体（TLR）可能会参与产前感染引起的免疫损伤。有趣的是，一些TLR，尤其是TLR3和TLR4that modulate neurodevelopment, neuronal survival and neuronal plasticity by regulating the neuro-immune cross-talk in the developing and adult brain could also be affected by prenatal infection. Importantly, sustained activation of TLR3/TLR4due to environmental factors including infection and stress has been found to generate excessive reactive oxygen species (ROS)/reactive nitrogen species (RNS) as well as pro-inflammatory mediators during embryogenesis, which result into neuronal damage by necrosis/apoptosis. In recent times, ROS/RNS and immuno-inflammatory mediators are being increasingly linked to progressive brain changes in精神分裂症。Although a significant role of TLR3/TLR4在神经退行性方面，它们在确定性方面，在建立产前感染与免疫炎症，氧化和硝化应激（IO＆ns）反应之间的因果关系中的重要性以及对成人表现的影响精神分裂症is yet to be ascertained. We review here the current knowledge generated from the animal and human studies on the role of TLRs in精神分裂症and finally propose the "TRIPS Hypothesis" (Toll-like receptors in immuno-inflammatory pathogenesis) to elucidate the underlying mechanism(s) of TLR-mediated risk of精神分裂症。Considering the established role of TLR3 andTLR4in antiviral and antibacterial responses respectively, we believe that in some cases of精神分裂症在IO和NS反应很明显的地方，产前感染可能会导致TLR3/TLR4-dependent way. |
| SCZ Keywords | 精神分裂症 |
| 5 | Korean J. Physiol. Pharmacol. 2015 Jul 19: 365-72 |
| PMID | 26170741 |
| Title | Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies. |
| 抽象的 | Aripiprazole（ARI）是一种常用的药物，用于治疗精神分裂症and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4），TLR2和TLR3途径。在肝脏中，ARPGCB和GCB3004均产生相似的毒性曲线。特别是，这两个公式表现出p65/核因子（NF） - ？b，c-jun/激活蛋白（AP）-1，ERK，JNK，p38，caspase 3和Bcl-2中的p65/核因子（NF） - b，c-jun/活化剂蛋白（AP）和BBCl-2中的类似磷酸蛋白分析。脑。相反，这些磷酸蛋白质的模式在其他组织中是可变的。此外，这两个配方在C6神经胶质瘤细胞中没有表现出任何细胞毒性。最后，在可用体内浓度处的两个配方未阻止用LPS，PAM3CSK或Poly（I：C）刺激激活的巨噬细胞样RAW264.7细胞的一氧化氮（NO）产生，也没有改变它们的形态变化。活化的巨噬细胞。综上所述，我们目前的工作是对两种不同公式的阿立哌唑公式的比较研究，这表明这两个公式可用于实现与细胞存活，凋亡以及巨噬细胞的免疫毒性活性相关的脑蛋白的相似功能激活。 |
| SCZ Keywords | 精神分裂症 |
| 6 | J Psychiatry Neurosci 2016 Apr 41：E46-55 |
| PMID | 27070349 |
| Title | Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia. |
| 抽象的 | 先天免疫/炎症系统的改变可能是基于精神分裂症, but we do not understand the mechanisms involved. The main agents of innate immunity are the Toll-like receptors (TLRs), which detect molecular patterns associated with damage and pathogens. The TLR first reported wasTLR4，它仍然是研究最多的一个。 We aimed to describe putative modifications to theTLR4在2例患者中使用2种不同策略的促炎途径精神分裂症and matched controls: 1) quantification of protein and mRNA expression in postmortem prefrontal cortex samples from 30 patients with精神分裂症and 30 controls, and 2) identification of single nucleotide polymorphisms associated with the risk of精神分裂症使用来自214例患者的全血样本精神分裂症and 216 controls. 我们发现证据表明在表达的最初要素的表达改变TLR4信号通路（TLR4, Myeloid differentiation primary response gene 88 [MyD88] and nuclear factor-? B [NF-?B]) in the PFC of patients with精神分裂症。这些改变似乎取决于死亡时的抗精神病药物治疗。此外，MyD88基因内的多态性与精神分裂症risk. 我们研究的主要局限性是在2种不同的队列中使用两种不同方法，缺乏互补的神经精神群，抗精神病药物治疗和自杀的混杂作用是我们研究的主要局限性。 The evidence from this dual approach suggests there is an altered innate immune response in patients with chronic精神分裂症在其中TLR4proinflammatory pathway could be affected. Improved understanding of the stimuli and mechanisms responsible for this response could lead to improved精神分裂症treatment and better control of the side effects of current antipsychotics. |
| SCZ Keywords | 精神分裂症 |