排序方式: 共有21条查询结果,搜索用时 16 毫秒
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Chia-Yu Hung Chih-Han Chang Tzu-Jung Lin Hsin-Hui Yi Nian-Zhen Tsai Yu-Ru Chen Yng-Tay Chen 《Molecules (Basel, Switzerland)》2022,27(3)
Acrylamide (ACR) is present in high-temperature-processed high-carbohydrate foods, cigarette smoke, and industrial pollution. Chronic exposure to ACR may induce neurotoxicity from reactive oxygen species (ROS); however, the mechanisms underlying ACR-induced neurotoxicity remain unclear. We studied 28-day subacute ACR toxicity by repeatedly feeding ACR (0, 15, or 30 mg/kg) to rats. We conducted RNA sequencing and Western blot analyses to identify differences in mRNA expression in the blood and in protein expression in the brain tissues, respectively, of the rats. AQP4 transient transfection was performed to identify potential associations with protein regulation. The rats treated with 30 mg/kg ACR exhibited hind-limb muscle weakness. Matrix metalloproteinase (MMP9) expression was higher in the ACR-treated group than in the control group. ACR induced MMP-9 and AQP4 protein expression in the brain tissues of the rats, which subsequently presented with neurotoxicity. In the in vitro study, Neuro-2a cells were transiently transfected with AQP4, which inhibited MMP-9 and TNF receptor-associated factor 6 (TRAF6) expression, and inhibited ACR induced expression of TRAF6, IκBα, and nuclear factor κB (NFκB). Using a combination of in vivo and in vitro experiments, this study revealed that depressive symptoms associated with ACR-induced neurotoxicity are associated with downregulation of AQP4 and induction of the TRAF6 pathway. 相似文献
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Haynes RK Fugmann B Stetter J Rieckmann K Heilmann HD Chan HW Cheung MK Lam WL Wong HN Croft SL Vivas L Rattray L Stewart L Peters W Robinson BL Edstein MD Kotecka B Kyle DE Beckermann B Gerisch M Radtke M Schmuck G Steinke W Wollborn U Schmeer K Römer A 《Angewandte Chemie (International ed. in English)》2006,45(13):2082-2088
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Richard K. Haynes Burkhard Fugmann Jrg Stetter Karl Rieckmann Hans‐Dietrich Heilmann Ho‐Wai Chan Man‐Ki Cheung Wai‐Lun Lam Ho‐Ning Wong Simon L. Croft Livia Vivas Lauren Rattray Lindsay Stewart Wallace Peters Brian L. Robinson Michael D. Edstein Barbara Kotecka Dennis E. Kyle Bernhard Beckermann Michael Gerisch Martin Radtke Gabriele Schmuck Wolfram Steinke Ute Wollborn Karl Schmeer Axel Rmer 《Angewandte Chemie (International ed. in English)》2006,45(13):1989-1989
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Sindhu E. R. Binitha P. P. Saritha S. Nair Balu Maliakel Ramadasan Kuttan 《Natural product research》2020,34(10):1456-1460
AbstractToxicity of the pesticide carbofuran (CF) can be alleviated by curcumin, if not for its poor bioavailability. Hence, we investigated the effect of a bioavailable curcumin-galactomannan complex (CGM) on CF-induced neurotoxicity in rats in comparison to that of unformulated standard curcumin (CS). The CF (5?mg/kg b.wt/day) treatment for 90?days produced chronicity model which were treated with either CS or CGM (100?mg/kg b.wt and 250?mg/kg b.wt/day) for another 30?days. Improvement in CF-induced behaviour was evident in endurance, motor co-ordination and pain response on both CS (p?<?0.01) and CGM (p?<?0.001) supplementation. Amelioration of CF-induced toxicity parameters, oxidative stress, and mitochondrial dysfunction on CS (p?<?0.01) and CGM (p?<?0.001) supplementation was further confirmed by histopathology of brain and liver tissues. But, CGM was more effective in mitigating CF toxicity, with results comparable to that of normal. Hence, CGM might be superior in toxicity management against CF. 相似文献
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Dr. Christofer Lendel Dr. Morten Bjerring Dr. Anatoly Dubnovitsky Robert T. Kelly Dr. Andrei Filippov Prof. Dr. Oleg N. Antzutkin Prof. Dr. Niels Chr. Nielsen Prof. Dr. Torleif Härd 《Angewandte Chemie (International ed. in English)》2014,53(47):12756-12760
Oligomeric and protofibrillar aggregates formed by the amyloid‐β peptide (Aβ) are believed to be involved in the pathology of Alzheimer’s disease. Central to Alzheimer pathology is also the fact that the longer Aβ42 peptide is more prone to aggregation than the more prevalent Aβ40. Detailed structural studies of Aβ oligomers and protofibrils have been impeded by aggregate heterogeneity and instability. We previously engineered a variant of Aβ that forms stable protofibrils and here we use solid‐state NMR spectroscopy and molecular modeling to derive a structural model of these. NMR data are consistent with packing of residues 16 to 42 of Aβ protomers into hexameric barrel‐like oligomers within the protofibril. The core of the oligomers consists of all residues of the central and C‐terminal hydrophobic regions of Aβ, and hairpin loops extend from the core. The model accounts for why Aβ42 forms oligomers and protofibrils more easily than Aβ40. 相似文献
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大气细颗粒物(Atmospheric fine particulate matters,PMs)对人体健康产生的潜在危害已得到广泛关注。越来越多的研究表明,PMs暴露可产生呼吸、心血管系统等损伤影响,然而PMs是否可以进入大脑并产生神经毒性,一直是近年来大气雾霾健康效应的重要研究方向。本文通过梳理现有流行病学研究证据以及体内外实验相关结果,讨论了PMs调控脑神经毒理学效应的潜在途径、不同生理阶段脑神经组织的损伤效应及其内在分子机理。据报道,大气PMs可通过血脑屏障途径和嗅觉神经途径和微生物群肠脑轴等影响神经系统。氧化应激、线粒体损伤、炎症、DNA损伤、表观遗传调节、血液稳态以及几个关键的信号通路被发现与大气PMs暴露引起的神经毒性有关。本文提出了进一步研究PMs神经毒理学效应,特别是针对特殊人群如儿童等神经发育的影响等方面研究的需求。在此基础上,本文指出了今后该领域的研究方向,为大气PMs的神经毒性和公共卫生危害的评价提供了理论依据。 相似文献
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Carbon tetrachloride (CCL4) induces oxidative stress by free radical toxicities, inflammation, and neurotoxicity. Quercetin (Q), on the other hand, has a role as anti-inflammatory, antioxidant, antibacterial, and free radical-scavenging. This study explored protection given by quercetin against CCL4 induced neurotoxicity in rats at given concentrations. Male Wistar rats were divided into four groups Group C: control group; Group CCL4: given a single oral dose of 1 mL/kg bw CCL4; Group Q: given a single i.p injection of 100 mg/kg bw quercetin; and Group Q + CCL4: given a single i.p injection of 100 mg/kg bw quercetin before two hours of a single oral dose of 1 mL/kg bw CCL4. The results from brain-to-body weight ratio, morphology, lipid peroxidation, brain urea, ascorbic acid, reduced glutathione, sodium, and enzyme alterations (aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase, and superoxide dismutase) suggested alterations by CCL4 and a significant reversal of these parameters by quercetin. In silico analysis of quercetin with various proteins was conducted to understand the molecular mechanism of its protection. The results identified by BzScore4 D showed moderate binding between quercetin and the following receptors: glucocorticoids, estrogen beta, and androgens and weak binding between quercetin and the following proteins: estrogen alpha, Peroxisome proliferator-activated receptors (PPARγ), Herg k+ channel, Liver x, mineralocorticoid, progesterone, Thyroid α, and Thyroid β. Three-dimensional/four-dimensional visualization of binding modes of quercetin with glucocorticoids, estrogen beta, and androgen receptors was performed. Based on the results, a possible mechanism is hypothesized for quercetin protection against CCL4 toxicity in the rat brain. 相似文献
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Antibiotics as antibacterial drugs have saved many lives, but have also become a victim of their own success. Their widespread abuse reduces their anti-infective effectiveness and causes the development of bacterial resistance. Moreover, irrational antibiotic therapy contributes to gastrointestinal dysbiosis, that increases the risk of the development of many diseases, including neurological and psychiatric. One of the potential options for restoring homeostasis is the use of oral antibiotics that are poorly absorbed from the gastrointestinal tract (e.g., rifaximin alfa). Thus, antibiotic therapy may exert neurological or psychiatric adverse drug reactions which are often considered to be overlooked and undervalued issues. Drug-induced neurotoxicity is mostly observed after beta-lactams and quinolones. Penicillin may produce a wide range of neurological dysfunctions, including encephalopathy, behavioral changes, myoclonus or seizures. Their pathomechanism results from the disturbances of gamma-aminobutyric acid-GABA transmission (due to the molecular similarities between the structure of the β-lactam ring and GABA molecule) and impairment of the functioning of benzodiazepine receptors (BZD). However, on the other hand, antibiotics have also been studied for their neuroprotective properties in the treatment of neurodegenerative and neuroinflammatory processes (e.g., Alzheimer’s or Parkinson’s diseases). Antibiotics may, therefore, become promising elements of multi-targeted therapy for these entities. 相似文献
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Inside Cover: Introduction of d‐Glutamate at a Critical Residue of Aβ42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity (Chem. Eur. J. 34/2016) 下载免费PDF全文