Abstract Conotoxins belong to the large families of disulfide-rich peptide toxins from cone snail venom, and can act on a broad spectrum of ion channels and receptors. They are classified into different subtypes based...Abstract Conotoxins belong to the large families of disulfide-rich peptide toxins from cone snail venom, and can act on a broad spectrum of ion channels and receptors. They are classified into different subtypes based on their targets. The a-conotoxins selectively inhibit the current of the nicotinic acetylcholine receptors. Because of their unique selectivity towards distinct nAChR subtypes, a-conotoxins become valuable tools in nAChR study. In addition to the X-ray structures of a-conotoxins in complex with acetyleholine-binding protein, a homolog of the nAChR ligand-binding domain, the high-resolution crystal structures of the extracellular domain of the al and a9 subunits are also obtained. Such structures not only revealed the details of the configuration of nAChR, but also provided higher sequence identity templates for modeling the binding modes of a-conotoxins to nAChR. This mini-review summarizes recent modeling studies for the determination of the binding modes of a-conotoxins to nAChR. As there are not crystal structures of the nAChR in complex with conotoxins, computational modeling in combination of mutagenesis data is expected to reveal the molecular recognition mechanisms that govern the interactions between a-conotoxins and nAChR at molecular level. An accurate determination of the binding modes of a-conotoxins on AChRs allows rational design of a-conotoxin analogues with improved potency or selectivity to nAChRs.展开更多
<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for in...<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects.<strong> Subjects and Methods:</strong> This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. <strong>Results:</strong> Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. <strong>Conclusions:</strong> Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.展开更多
In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function...In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function in neurotransmission since the astrocyte activated by neurotransmitters produces gliotransmitters that negatively feedback to the presynapse. It is hypothesized that in schizophrenia nonfunctional astrocytic receptors cannot be activated, thus losing their modulating function. This causes a generalization of information processing in the neuronal networks such that the brain is unable to distinguish between subjects and objects in the environment. Delusions, hallucinations and cognitive impairment occur on the behavioral level. In a model of a cholinergic tripartite synapse, it is shown that glial binding proteins modify neurotransmission by occupancy with cognate neurotransmitters temporarily turning off neurotransmission on the presynapse. Most recently, glial binding proteins have been engineered. It is proposed that the substitution of glial binding proteins may balance synaptic information processing in schizophrenia since these proteins exert a modulatory function comparable to functional astrocytic receptors. Rap- id technical developments may enable this novel treatment approach in schizophrenia.展开更多
目的探究GATA结合蛋白3(GATA binding protein 3,GATA3)对乳腺癌细胞迁移能力的影响。方法在MCF7细胞中利用慢病毒载体介导的基因干涉技术敲低GATA3基因,使用实时定量荧光PCR(qRT-PCR)和蛋白质印迹检测GATA3和LIFR的mRNA和蛋白表达水平,...目的探究GATA结合蛋白3(GATA binding protein 3,GATA3)对乳腺癌细胞迁移能力的影响。方法在MCF7细胞中利用慢病毒载体介导的基因干涉技术敲低GATA3基因,使用实时定量荧光PCR(qRT-PCR)和蛋白质印迹检测GATA3和LIFR的mRNA和蛋白表达水平,Transwell实验检测MCF7细胞的迁移能力。在MCF7和T47D细胞中用染色质免疫沉淀(ChIP-qPCR)实验检测GATA3在LIFR的启动子区的结合位点。在敲低GATA3基因的MCF7细胞中回补LIFR,通过细胞划痕实验和Transwell实验检测MCF7细胞的迁移能力。结果与对照组相比,敲低GATA3基因的MCF7细胞的迁移能力增强(P_(均)<0.05)。与对照组相比,敲低GATA3基因的MCF7细胞的LIFR表达水平降低(P_(均)<0.05)。乳腺癌细胞MCF7与T47D中GATA3在LIFR的启动子区有结合(P_(均)<0.05)。在敲低GATA3基因的MCF7细胞中稳定过表达LIFR可以部分挽救GATA3基因敲低引起的细胞迁移能力的增强(P_(均)<0.05)。结论GATA3通过转录激活LIFR抑制乳腺癌细胞MCF7的迁移。展开更多
基金supported by the National Natural Science Foundation of China (81502977 to Dr. Yu R. and 81373322 to Dr. Jiang T.)China Postdoctoral Science Foundation funded project (No.861505020050 for Dr. Yu R.)+1 种基金Special Foundation for Qingdao Basic Research Program (15-9-1-85-jch)Fundamental Research Funds for the Central Universities (No.841512007 for Dr. Yu R.)
文摘Abstract Conotoxins belong to the large families of disulfide-rich peptide toxins from cone snail venom, and can act on a broad spectrum of ion channels and receptors. They are classified into different subtypes based on their targets. The a-conotoxins selectively inhibit the current of the nicotinic acetylcholine receptors. Because of their unique selectivity towards distinct nAChR subtypes, a-conotoxins become valuable tools in nAChR study. In addition to the X-ray structures of a-conotoxins in complex with acetyleholine-binding protein, a homolog of the nAChR ligand-binding domain, the high-resolution crystal structures of the extracellular domain of the al and a9 subunits are also obtained. Such structures not only revealed the details of the configuration of nAChR, but also provided higher sequence identity templates for modeling the binding modes of a-conotoxins to nAChR. This mini-review summarizes recent modeling studies for the determination of the binding modes of a-conotoxins to nAChR. As there are not crystal structures of the nAChR in complex with conotoxins, computational modeling in combination of mutagenesis data is expected to reveal the molecular recognition mechanisms that govern the interactions between a-conotoxins and nAChR at molecular level. An accurate determination of the binding modes of a-conotoxins on AChRs allows rational design of a-conotoxin analogues with improved potency or selectivity to nAChRs.
文摘<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects.<strong> Subjects and Methods:</strong> This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. <strong>Results:</strong> Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. <strong>Conclusions:</strong> Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.
文摘In chronic schizophrenia, synaptic information processing is unbalanced, as shown in a model of glial-neuronal synaptic units, called tripartite synapses. The glial component of the synapse exerts a modifying function in neurotransmission since the astrocyte activated by neurotransmitters produces gliotransmitters that negatively feedback to the presynapse. It is hypothesized that in schizophrenia nonfunctional astrocytic receptors cannot be activated, thus losing their modulating function. This causes a generalization of information processing in the neuronal networks such that the brain is unable to distinguish between subjects and objects in the environment. Delusions, hallucinations and cognitive impairment occur on the behavioral level. In a model of a cholinergic tripartite synapse, it is shown that glial binding proteins modify neurotransmission by occupancy with cognate neurotransmitters temporarily turning off neurotransmission on the presynapse. Most recently, glial binding proteins have been engineered. It is proposed that the substitution of glial binding proteins may balance synaptic information processing in schizophrenia since these proteins exert a modulatory function comparable to functional astrocytic receptors. Rap- id technical developments may enable this novel treatment approach in schizophrenia.
文摘目的探究GATA结合蛋白3(GATA binding protein 3,GATA3)对乳腺癌细胞迁移能力的影响。方法在MCF7细胞中利用慢病毒载体介导的基因干涉技术敲低GATA3基因,使用实时定量荧光PCR(qRT-PCR)和蛋白质印迹检测GATA3和LIFR的mRNA和蛋白表达水平,Transwell实验检测MCF7细胞的迁移能力。在MCF7和T47D细胞中用染色质免疫沉淀(ChIP-qPCR)实验检测GATA3在LIFR的启动子区的结合位点。在敲低GATA3基因的MCF7细胞中回补LIFR,通过细胞划痕实验和Transwell实验检测MCF7细胞的迁移能力。结果与对照组相比,敲低GATA3基因的MCF7细胞的迁移能力增强(P_(均)<0.05)。与对照组相比,敲低GATA3基因的MCF7细胞的LIFR表达水平降低(P_(均)<0.05)。乳腺癌细胞MCF7与T47D中GATA3在LIFR的启动子区有结合(P_(均)<0.05)。在敲低GATA3基因的MCF7细胞中稳定过表达LIFR可以部分挽救GATA3基因敲低引起的细胞迁移能力的增强(P_(均)<0.05)。结论GATA3通过转录激活LIFR抑制乳腺癌细胞MCF7的迁移。
