Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A.

BACKGROUND: Major depressive disorder (MDD) shows increased coronary artery disease (CAD) risk of unknown mechanism(s). MDD is more common in women than men; CAD diagnosis can be difficult in women. Elevations of the inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) predict increased CAD risk in populations; few data on these markers exist in MDD, particularly in remitted patients. METHODS: We measured fasting am serum CRP (high sensitivity, CRP(hs)) and SAA in 18 unmedicated, remitted women with MDD (mean age 41 +/- (SD)12, body mass index (BMI) 25.2 +/- 4.1 kg/m(2)) and 18 BMI-matched healthy control subjects (age 36 +/- 10, BMI 25.3 +/- 3.8 kg/m(2)) on 2 separate occasions, > or = 6 days apart. RESULTS: Repeat SAA and CRP(hs) measurements strongly correlated across study days (SAA: r = .83, p < .001; CRP(hs): r = .94, p < .001). Both SAA (5.30 +/- 3.39 vs. 2.84 +/- 1.87 mg/L, p < .005) and CRP(hs) (3.23 +/- 3.17 vs. 1.12 +/- 1.45 mg/L; p < .01) were significantly elevated in MDD women versus controls. CONCLUSIONS: Elevated SAA and CRP(hs) in remitted, unmedicated women with MDD indicate a pro-inflammatory state unrelated to current depressive symptoms or pharmacotherapy. These findings suggest that inflammatory mechanisms may in part underlie findings of increased CAD risk in MDD.     

氯丙醇对大鼠的毒性研究

进行氯丙醇对大鼠毒作用研究 ,并进行氯丙醇暴露对健康影响评价的生物效应标志物探讨 ,为进行人群氯丙醇暴露对健康的影响评价提供科学依据。选用健康雄性断乳SD大鼠 1 76只 ,随机分为 8组 ,经口灌胃给予 0、0 2 5、0 5、1 0、2 0、4 0、8 0、1 6 0mg kg的 3 氯 1 ,2 丙二醇 (3 MCDP) 90天 ,进行体重、食物利用率、血液学指标、血生化指标、尿液中N 乙酰 β D 氨基葡萄糖苷酶 (NAG)、γ 谷胺酰转肽酶 (GGT)和总蛋白、精子数目、精子存活率和畸形率、睾丸组织中乳酸脱氢酶 (LDH)和乳酸脱氢酶同工酶 X(LDH X)、脏体比及其病理组织学测定和分析。结果表明 ,不同暴露剂量的氯丙醇对动物体重、食物利用率、血红蛋白、红细胞、白细胞、血丙氨酸氨基转移酶 (AST)、天冬氨酸氨基转移酶 (ALT)、肌酐、尿素氮、血清碱性磷酸酶 (ALP)、乳酸脱氢酶 (LDH)、总蛋白、白蛋白、尿GGT酶和总蛋白及睾丸LDH酶均未见显著影响。在 4 0、8 0和 1 6 0mg kg剂量组 ,动物尿N 乙酰 β D 氨基葡萄糖苷酶 (NAG)活性显著增加 ,肾体比增大 ,并出现肾毒性病理改变 ,精子数目也降低。在 8 0和 1 6 0mg kg剂量组 ,精子存活率和睾丸LDH X显著降低 ,睾丸和附睾出现病理改变 ,3 MCDP无致精子畸变作用。由此可见尿液中NAG酶活性和精子     

Molecular and cellular biomarkers for field cancerization and multistep process in head and neck tumorigenesis

Summary One way to explain the development of head and neck cancer is through the theories of field cancerization, i.e., the exposure of an entire field of tissue to repeated carcinogenic insult, and multistep process, i.e., development of multiple cancers in a predisposed field through a series of recognizable states. Recent molecular genetic studies of histologically normal and prealignant epithelia of high-risk subjects and studies of malignant tumors in aerodigestive tract epithelia have identified a continuum of accumulated specific genetic alterations that possibly occur during the clonal evolution of tumors, namely, during the multistep process. Second primary or multiple primary tumors arise in the same fields as independent clones, with similar but unique molecular genetic and/or cellular alterations. Consequently, the assessment of these genetic and phenotypic alterations has been integrated into clinical chemoprevention trials in an effort to identify biomarkers that are also risk predictors and intermediate end points. This review covers candidate biomarkers of the processes of field cancerization and multistep tumor development in aerodigestive tract epithelia, including general and specific genetic markers, proliferation markers, and squamous differentiation markers.     

Correlation between in vivo and in vitro toxic effects of foreign compounds

Studies in rats in vivo and in isolated hepatocytes from the same species and strain of animal in vitro with the hepatotoxicant hydrazine have shown that despite measuring the same parameters in each system, the effects do not always show a quantitative or qualitative correlation. For example depletion of glutathione and ATP occurred in both systems but required a much higher concentration of hydrazine in vitro. The effects on triglyceride levels, citrulline synthesis and taurine levels in vivo were not observed in vitro and the inhibition of urea synthesis and cytotoxicity in vitro were not observed in vivo.Inhibition of protein synthesis proved to be the marker which showed the best correlation, occurring at a similar hydrazine concentration in vitro and in vivo although not to the same extent.The situation with other toxicants is variable, in some cases correlation is good, in others modification of conditions in vitro are required.     

超声弹性成像技术联合血清学标志物预测2型糖尿病的应用价值

<正>多项研究表明,非酒精性脂肪性肝病患者(NAFLD)发生2型糖尿病(type 2 diabetes mellitus,T2DM)的风险是正常人的5倍^[1-3]。在T2DM患者中,NAFLD的患病率可高达70%^[4]。肝脏瞬时弹性成像技术(tran-sient elastography,TE)是近年来新兴的超声无创检查方法,主要基于超声信号在肝组织中传播受肝细胞中脂滴的影响而出现显著衰减的原理来评估肝脏脂肪性病变,     

老年病人的术后认知功能障碍

术后认知功能障碍（POCD）定义为术后通过反复多次神经心理测试,患者的基本认知功能出现不同程度的损害。而早期术后认知功能及精神障碍更多见于老年患者。虽然POCD多见于心脏手术术后，但非心脏手术后发生POCD亦不少见，老年患者（年龄大于65岁）行心脏手术或非心脏手术，术后1周POCD的发生率分别为50%及26%。POCD的高危因素包括：高龄、术前认知受损以及酗酒等。POCD影响生活质量，加重社会负担并干扰药物治疗效果，延长患者住院周期。有必要深入的研究POCD的病因和神经功能保护的策略。     

Comprehensive analysis of key lncRNAs in HCV-positive hepatocellular carcinoma

IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset {"type":"entrez-geo","attrs":{"text":"GSE17856","term_id":"17856"}}GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.     

The biomolecules of beauty: biochemical pharmacology and immunotoxicology of cosmeceuticals

ABSTRACT

Many ingredients in cosmetic products help to develop complex formulations that improve the quality of life in terms of disease prevention, health maintenance, beauty enhancement, and building self-esteem. The beneficial effects promoted from the use of biomolecule-rich substances into the formulations of various topical application products are considered useful ingredients in cosmetic and therapeutic applications. This review article attempts to understand the various biomolecules found in cosmetic products, particularly macromolecules, which may have an important role in prevention or preservation. Increasing demand of cosmetics all over the world has increased the awareness related to safety issue. Cosmetic products may contain potential contact allergens or precursors that can be oxidized or metabolized to generate contact allergens which can potentially cause allergic reactions or dermatitis. These substances can pose hazards to human health due to their ability to activate T cells that can cause allergic contact dermatitis, an inflammatory skin disease. Finally, the simultaneous on-site measurement of different substances from a single sample, called multiplexed point-of-care testing, has recently become increasingly important for the in vitro quantification of pathological or toxicological samples. Hence, the technological advancements in clinical sciences will be helpful in the identification of ingredients in cosmetic preparations.