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1.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
2.
《Saudi Pharmaceutical Journal》2022,30(6):669-678
BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction. 相似文献
3.
目的:通过逆行神经追踪法研究大鼠骶髂关节的传入神经通路。方法:30只雄性Sprague-Dawley大鼠随机分成非交感神经切除组(A组)和交感神经切除组(B组),每组15只,交感神经切除组切除左侧L1以下椎旁交感干。两组左侧骶髂关节注入30%的辣根过氧化物酶(HRP)20μl,72h后取出双侧的L1-S1背根神经节(DRG),TMB法染色后在光学显微镜下观察HRP阳性神经元细胞并计数。结果:两组左侧L1、L2背根神经节内HRP阳性神经元差异有显著性意义(P<0·05),B组HRP阳性神经元明显减少;左侧L3-S1背根神经节内HRP阳性神经元差异无显著性意义(P>0·05)。结论:L1-S1神经节含有支配同侧骶髂关节的传入神经元,同侧椎旁交感干可能是骶髂关节到L1-L2神经节重要的传入神经旁路,而不是到L3-L5神经节的传入旁路或重要的传入旁路。 相似文献
4.
Graham M. O'Hanlon Margaret B. Lowrie 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1995,103(2):243-250
Disruption of neuromuscular contact by nerve-crush during the early postnatal period causes increased activity and abnormal reflex responses in affected motoneurons, but such changes are not found after nerve-crush in adult animals. We found previously that neonatally lesioned cells develop an abnormal dendritic field, which may explain the functional changes. Here we have studied the dendritic morphology of the same motoneuron pool after nerve-crush at maturity in order to correlate the observed alterations in morphology with physiological findings. One to two months after sciatic nerve-crush in adult animals, motoneurons supplying the extensor hallucis longus muscles of the rat were retrogradely labelled with cholera toxin subunit-B conjugated to horseradish peroxidase. The dendritic tree of labelled cells was then analysed. Following adult nerve-crush, the dendritic tree of the motoneurons was smaller but did not display the localised increase in dendritic density seen after neonatal nerve-crush. These findings support the view that such specific morphological changes contribute to the physiological abnormalities seen only after neonatal nerve injury. 相似文献
5.
本文对17例肾病综合征(NS)患儿和15例健康对照组儿童血红细胞磷脂过氧化氢谷胱甘肽过氧化物酶(PHGPx)活力,脂溶性荧光色素(LSFP)含量进行了研究。结果表明,NS急性期PHGPx活力明显降低.LSFP含量增加;恢复期PHGPx活力较急性期明显提高,但仍低于正常对照组,LSFP虽较急性期下降,但仍高于正常对照组。说明NS存在PHGPx和LSFP的改变,但可逐渐恢复。 相似文献
6.
Reiji Kishida Hideki Onishi Hideo Nishizawa Tetsuo Kadota Richard C. Goris Toyokazu Kusunoki 《Brain research》1986,385(2):263-272
We studied the trigeminal and facial motor nuclei of the hagfish by the retrograde HRP method. We distinguished 4 components in a single column of the motor nuclei of the trigeminal nerve and the facial nerve, viz., the pars magnocellularis of the trigeminal motor nucleus (mVm), the anterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp1), the posterior part of the pars parvocellularis of the trigeminal motor nucleus (mVp2) and the facial motor nucleus (mVII). Although in Nissl preparations only the mVm could be distinguished from the rest of the nucleus, the boundaries of the other 3 components were clearly demarcated in HRP preparations. Intramuscular injections into two representative antagonistic jaw muscles revealed that there was no apparent topological organization of the neurons pertaining to the opening and closing muscles in the mVm and mVp1, but both antagonistic muscles were innervated bilaterally. Although the hagfish does possess a cartilaginous jaw, the organization pattern of the motor nuclei of the jaw muscles seems to be the most primitive of all living vertebrates. 相似文献
7.
用辣根过氧化物酶(HRP)微电泳技术研究大鼠前脑和脑干向中央上核(CS)的纤维投射。将HRP输入CS后,观察到缰核、脚间核和被盖背核区有较多的标记细胞,斜角带核、下丘脑核和乳头体核有少量标记细胞。在外侧缰核、脚间核和被盖背核区可见丰富的顺行标记终末。结果表明,前脑的缰核和脑干的脚间核和被盖背核区是CS的主要传入来源,它们之间存在往返的纤维联系。 相似文献
8.
用辣根过氧化物酶标记的AcLDL2培养小白鼠腹腔巨噬细胞,直观地显示了巨噬细胞表面AcLDL受体的存在,此受体只特异性的识别修饰的LDL,其识别作用与配体分子荷大量负电荷有关。 相似文献
9.
Several neurons from different nuclei give rise to descending spinal tracts and project to various levels in the spinal cord of goldfish, Carassius auratus. These were visualized by retrograde transport of horseradish peroxidase (HRP) administered to the bilaterally transected spinal cord at 6 levels, corresponding to 1st, 5th, 10th, 15th, 20th and 25gh segments of the vertebral column. As many as 16 brain nuclei or neuronal aggregations and the Mauthner cells project posteriorly up to the 20th spinal segment. Restricted neurons of the dorsolateral area in the nucleus preopticus magnocellularis and those of the ventromedial nucleus of the thalamus projected up to the 20th and 25th segments respectively. In the mesencephalon, the nucleus ruber and the nucleus of the medial longitudinal fasciculus revealed retrogradely labeled somata; the former extended up to the 20th segment, while the latter projected up to the 25th segment. The remaining descending projected neurons of the brain belonged to the rhombencephalon. The nucleus of the lateral lemniscus; anterior, magnocellular, descending and posterior divisions of the octaval nucleus: raphe nucleus; Mauthner cell and the neurons located adjacent to the trigeminal tract and those in the vicinity of the secondary gustatory tract sent their processes up to 20th segmental level. However, somata of the superior, medial and inferior divisions of the reticular nucleus and restricted neurons of the facial lobe extended up to 25th segmental level. The pattern of neuronal projections into the spinal cord suggests a topographic organization. 相似文献
10.
H. J. Maragkowitsch E. Irle 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1981,41(3-4):233-246
Summary Thirty-three cat brains with injections of horseradish peroxidase in various regions of the cerebral cortex were screened for afferent projections from the ventral tegmental area, the locus ceruleus, and the parabrachial nuclei. All three structures were found to project to rather divergent parts of the cortex, including regions in the posterior half of the hemisphere. These results, especially for the ventral tegmental area and, to a lesser degree, for the parabrachial neurons, disagree with most of the target loci of established cortical afferents in the rat. Though our results might be attributed to species differences in the cortical innervation of brain stem structures, we prefer explanations which emphasize different densities in the distribution of brain stem afferents to the cortex, and/or which suggest different cortical targets of catecholaminergic and noncatecholaminergic neurons.Supported in part by grant Ma 795 from the Deutsche Forschungsgemeinschaft (DFG) 相似文献