564 results on '"Yan Chun Li"'
Search Results
202. The Performance and Mechanism of Waste Tire Crumb Rubber Modified Asphalt
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Pan Zhang, Rui Lv, and Yan Chun Li
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Natural rubber ,Waste management ,Asphalt pavement ,Asphalt ,visual_art ,visual_art.visual_art_medium ,Environmental science ,Crumb rubber ,General Medicine - Abstract
Crumb rubber modified asphalt can not only improve asphalt pavement performance, but also can achieve the waste re-use, further study on the crumb rubber modified asphalt is very important. This paper mainly discusses the action mechanism of waste tire rubber modified asphalt, and analysis the performance improvement of the asphalt when it is mixed with the waste tire rubber. By analyzing the test results of asphalt’s conventional, we find out that mixed the waste tire rubber in asphalt is the resulting in the improvement of asphalt’s performance. Lastly, it discusses waste tire rubber modified asphalt advantages and the prospects of development. Overall, popularize and application the asphalt-rubber mixture is valuable.
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- 2011
203. Molecular Mechanism Underlying 1,25-Dihydroxyvitamin D Regulation of Nephrin Gene Expression
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Zhongyi Zhang, Yunzi Chen, Xueshi Huang, Hongguang Nie, Zhengwei Yuan, Youli Wang, Yan Chun Li, Qun Zhao, and Dilip K. Deb
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Retinoid X receptor ,Biology ,Vitamin D Response Element ,urologic and male genital diseases ,Biochemistry ,Calcitriol receptor ,Histones ,Nephrin ,Mediator Complex Subunit 1 ,Mice ,Calcitriol ,Animals ,Humans ,Gene Regulation ,RNA, Messenger ,Molecular Biology ,Cell Line, Transformed ,Regulation of gene expression ,Bone Density Conservation Agents ,Podocytes ,urogenital system ,Membrane Proteins ,Acetylation ,Cell Biology ,Molecular biology ,female genital diseases and pregnancy complications ,VDRE ,Diabetes Mellitus, Type 1 ,HEK293 Cells ,Retinoid X Receptors ,Diabetes Mellitus, Type 2 ,Gene Expression Regulation ,Nuclear receptor ,Mutation ,Slit diaphragm ,biology.protein ,Receptors, Calcitriol ,RNA Polymerase II - Abstract
Nephrin plays a key role in maintaining the structure of the slit diaphragm in the glomerular filtration barrier. Our previous studies have demonstrated potent renoprotective activity for 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)). Here we showed that in podocytes 1,25(OH)(2)D(3) markedly stimulated nephrin mRNA and protein expression. ChIP scan of the 6-kb 5' upstream region of the mouse nephrin gene identified several putative vitamin D response elements (VDREs), and EMSA confirmed that the VDRE at -312 (a DR4-type VDRE) could be bound by vitamin D receptor (VDR)/retinoid X receptor. Luciferase reporter assays of the proximal nephrin promoter fragment (-427 to +173) showed strong induction of luciferase activity upon 1,25(OH)(2)D(3) treatment, and the induction was abolished by mutations within -312VDRE. ChIP assays showed that, upon 1,25(OH)(2)D(3) activation, VDR bound to this VDRE leading to recruitment of DRIP205 and RNA polymerase II and histone 4 acetylation. Treatment of mice with a vitamin D analog induced nephrin mRNA and protein in the kidney, accompanied by increased VDR binding to the -312VDRE and histone 4 acetylation. 1,25(OH)(2)D(3) reversed high glucose-induced nephrin reduction in podocytes, and vitamin D analogs prevented nephrin decline in both type 1 and 2 diabetic mice. Together these data demonstrate that 1,25(OH)(2)D(3) stimulates nephrin expression in podocytes by acting on a VDRE in the proximal nephrin promoter. Nephrin up-regulation likely accounts for part of the renoprotective activity of vitamin D.
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- 2011
204. D2 receptor overexpression in the striatum leads to a deficit in inhibitory transmission and dopamine sensitivity in mouse prefrontal cortex
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Eleanor H. Simpson, Christoph Kellendonk, Wen-Jun Gao, Yan-Chun Li, and Eric R. Kandel
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Agonist ,Patch-Clamp Techniques ,Genotype ,medicine.drug_class ,Dopamine ,Prefrontal Cortex ,Mice, Transgenic ,Striatum ,Neurotransmission ,Inhibitory postsynaptic potential ,Polymerase Chain Reaction ,Synaptic Transmission ,Mice ,Dopamine receptor D2 ,medicine ,Animals ,Prefrontal cortex ,Multidisciplinary ,Receptors, Dopamine D2 ,Chemistry ,Excitatory Postsynaptic Potentials ,Biological Sciences ,Corpus Striatum ,Electrophysiology ,nervous system ,Schizophrenia ,Excitatory postsynaptic potential ,Neuroscience ,medicine.drug - Abstract
Two distinct defects are thought to be important for the pathophysiology of schizophrenia. One is an increase of D2 receptors (D2Rs) in the striatum and another is a decrease in the GABAergic function in the prefrontal cortex (PFC). Whether these two defects are functionally linked is not known. We previously reported that selective overexpression of D2Rs in the striatum of the mouse causes behavioral abnormality associated with PFC functions. Using patch-clamp recording, we find that overexpression of D2Rs in the striatum affects inhibitory transmission in the PFC and dopamine (DA) sensitivity. The overexpression of D2Rs in the striatum caused an increase in frequency of spontaneous excitatory postsynaptic currents (EPSCs) in layer V pyramidal neurons, whereas their neuronal excitability was unaffected. In contrast, both the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) were significantly decreased in these mice, indicating a reduced inhibitory transmission. Furthermore, in D2R transgenic mice the dopaminergic modulation of evoked IPSCs was shifted, with reduced sensitivity. The change in dopamine sensitivity in the PFC of D2R transgenic mice appears specific for D2Rs because in D2R transgenic mice the effects of D2 agonist but not D1 agonist, on both evoked IPSCs and EPSCs, were reduced. Together, these results indicate that overexpression of D2Rs in the striatum leads to a functional deficit in the GABAergic system. These results provide a functional link between D2R overexpression and GABAergic inhibition in the PFC and suggest that the postulated deficit in GABAergic function in schizophrenia could be secondary to alterations in the striatal dopamine system.
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- 2011
205. Zangia, a new genus of Boletaceae supported by molecular and morphological evidence
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Bang Feng, Zhu L. Yang, and Yan-Chun Li
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Bolete ,Monophyly ,Tylopilus ,Ecology ,Boletaceae ,Boletales ,Botany ,Pileipellis ,Taxonomy (biology) ,Pileus ,Biology ,biology.organism_classification ,Ecology, Evolution, Behavior and Systematics - Abstract
A new distinct genus of Boletales, Zangia, with phenotypic similarities to the genus Tylopilus, is proposed based on molecular and morphological data. The monophyly of Zangia was highly supported using two nuclear and three mitochondrial genes based on Maximum Parsimony, Maximum Likelihood and Bayesian analyses. Morphologically, Zangia is distinguished from other boletoid lineages by its combination of rugose pileus, pinkish to pink hymenophore, pink to pinkish brown spore deposit, pink scabrous squamules on the stipe, chrome yellow to golden yellow stipe base, chrome yellow to golden yellow mycelia on the base of the stipe, ixohyphoepithelium pileipellis, glabrous spores and bluish colour changes in the stipe in some species. Geographically, Zangia is currently only known from southern, southeastern and southwestern China under forests dominated by Fagaceae mixed with Pinaceae. Six species, including 4 new ones and 2 new combinations, are fully documented with taxonomic descriptions and illustrations. A key to the species in Zangia is provided. It is suggested that some of the species might have started diverging from each other relatively recently with the uplifts of the eastern Himalayas and Hengduan Mountains, and both the mycorrhizal host specificity or preference and geographic separation could contribute to their ongoing divergence.
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- 2011
206. Application of Carbon Fiber Composite on Space Camera Frame
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Ke Jun Wang, Ji Hong Dong, Quan Feng Guo, Hai Ping Wang, Wei Guo Zhao, Yan-chun Li, and Wei Li
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Vibration ,Materials science ,Payload (computing) ,Frame (networking) ,General Engineering ,medicine ,Titanium alloy ,Stiffness ,Relative strength ,Composite material ,medicine.symptom ,Space (mathematics) ,Finite element method - Abstract
General materials can satisfy the structure strength requirement of space effective payload easily. But it can hardly satisfy the structure stiffness requirement of space payload. Carbon fiber composite has many excellent properties, such as high relative strength, high relative stiffness, small expansion coefficient, good fatigue resistance and excellent vibration resistance. It can be used to make space products. Firstly, this paper discussed the properties of carbon fiber composite material. Compared with common materials, such as aluminum alloy and titanium alloy, carbon fiber composite material is more suitable for applications of space instruments. Secondly, the metal part embedded technique of carbon fiber composite structure was studied. According to the carbon fiber composite structure of a space camera frame, a few structure forms of embedded part ware studied. A space camera frame of carbon fiber composite was designed and manufactured. Finally, finite element analysis and mechanical tests on the space camera frame was carried out. The results reveal that the characteristic frequency of carbon fiber composite frame is up to 104Hz.The space camera frame is of high stiffness and dimensional stability.
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- 2011
207. Podocytes as Target of Vitamin D
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Yan Chun Li
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Vitamin ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Models, Biological ,vitamin D deficiency ,Podocyte ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,medicine ,Vitamin D and neurology ,Animals ,Humans ,Diabetic Nephropathies ,Vitamin D ,Podocytes ,business.industry ,Wnt signaling pathway ,Vitamin D Deficiency ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Glomerular Filtration Barrier ,Slit diaphragm ,Kidney Failure, Chronic ,business ,Kidney disease - Abstract
Vitamin D deficiency is a prominent feature of chronic kidney disease (CKD) even in its early stages. While vitamin D deficiency leads to mineral imbalance and bone problems in CDK patients, it also accelerates the progression of kidney disease. Ever since the observation that vitamin D analogs reduce proteinuria in CKD patients, it has been postulated that podocytes are major target of the reno-protective action of vitamin D. Recent large randomized clinical trials have confirmed the potent anti-proteinuric activity of vitamin D therapy. Studies from various animal models of kidney disease have demonstrated that vitamin D prevents podocyte injury and cell loss, promotes the expression of slit diaphragm proteins and maintains the integrity of the glomerular filtration barrier. Emerging experimental data suggest that vitamin D may protect podocytes by targeting multiple pathways, including the renin-angiotensin system, Wnt/β-catenin pathway and pro-apoptotic pathway.
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- 2011
208. A Combination of Phase Transfer Catalyst and Ultrasonic Irradiation Promotes Synthesis of Mandelic Aci
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Yu-Quan Zhang, Xu-Dong Zheng, Ke Gai, Yan-Chun Li, and Dong-Ping Cheng
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General Chemistry - Published
- 2014
209. Microwave-Assisted Acetylation of Phenols without Catalyst Under Solvent Free Condition
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Yu-Quan Zhang, Yan-Chun Li, Ji-Hua Zhu, Zhi-Feng Li, Guo-Zhe Guo, and Dong-Ping Chen
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General Chemistry - Published
- 2014
210. Cover Feature: Solvent-Controlled α-Monobromination, α,α-Dibromination or Imidation of 1,3-Diketones with N -Bromosuccinimide (Eur. J. Org. Chem. 41/2018)
- Author
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Jing Zhou, Zhimeng Wu, Yan-Chun Li, Liang-Hua Zou, and Ping-Gui Li
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Solvent ,chemistry.chemical_compound ,chemistry ,Feature (computer vision) ,Organic Chemistry ,Cover (algebra) ,Physical and Theoretical Chemistry ,N-Bromosuccinimide ,Medicinal chemistry - Published
- 2018
211. A novel differential multiuser detection algorithm for multiuser MIMO-OFDM systems
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Zhengmin Kong, Qiao-ling Tong, Yan-chun Li, and Guang-xi Zhu
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Minimum mean square error ,Computational complexity theory ,Orthogonal frequency-division multiplexing ,MIMO ,General Engineering ,Context (language use) ,MIMO-OFDM ,Multiuser detection ,Computer Science::Performance ,Reduction (complexity) ,Astrophysics::Solar and Stellar Astrophysics ,Algorithm ,Computer Science::Information Theory ,Mathematics - Abstract
We propose an efficient low bit error rate (BER) and low complexity multiple-input multiple-output (MIMO) multiuser detection (MUD) method for use with multiuser MIMO orthogonal frequency division multiplexing (OFDM) systems. It is a hybrid method combining a multiuser-interference-cancellation-based decision feedback equalizer using error feedback filter (MIMO MIC DFE-EFF) and a differential algorithm. The proposed method, termed ‘MIMO MIC DFE-EFF with a differential algorithm’ for short, has a multiuser feedback structure. We describe the schemes of MIMO MIC DFE-EFF and MIMO MIC DFE-EFF with a differential algorithm, and compare their minimum mean square error (MMSE) performance and computational complexity. Simulation results show that a significant performance gain can be achieved by employing the MIMO MIC DFE-EFF detection algorithm in the context of a multiuser MIMO-OFDM system over frequency selective Rayleigh channel. MIMO MIC DFE-EFF with the differential algorithm improves both computational efficiency and BER performance in a multistage structure relative to conventional DFE-EFF, though there is a small reduction in system performance compared with MIMO MIC DFE-EFF without the differential algorithm.
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- 2010
212. Relationship of Serum ADMA With pulmonary hypertension in patients on hemodialysis
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Chen Xu, Juan Meng, Jing Huang, Qian Mei Sun, Zhong Xin Li, Yan Chun Li, and Wei Jiang
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Transplantation ,medicine.medical_specialty ,Cardiac output ,medicine.diagnostic_test ,Vascular disease ,business.industry ,medicine.medical_treatment ,Doppler echocardiography ,medicine.disease ,Pulmonary hypertension ,Blood pressure ,Nephrology ,medicine.artery ,Internal medicine ,Pulmonary artery ,medicine ,Cardiology ,Hemodialysis ,Endothelial dysfunction ,business - Abstract
BACKGROUND Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide (NO) inhibitor. Increased con-centrations of serum ADMA may also contribute to endothelial dysfunction in patients with pulmonary vascular dis-ease. Pulmonary hypertension in patients with end-stage renal disease (ESRD) on hemodialysis is a newly described entity. The pathogenesis of pulmonary hypertension (PH) is considered to be ESRD-related endothelial dysfunction. The aim of our study was to elucidate the possible relationship between serum ADMA and PH in patients undergo-ing hemodialysis (HD). METHODS The incidence of PH was prospectively estimated by Doppler echocardiography in 69 patients with ESRD undergoing long-term HD (2 hrs of completion of HD). Serum ADMA levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Pulmonary hypertension was defined as pulmonary artery systolic pressure (sPAP) >35 mmHg as determined by Doppler echocardiography using the modified Bernouli equation. Then, the relationship between ADMA and pulmonary arterial pressure (PAP) was analyzed. RESULTS Pulmonary hypertension was detected in 31.9% of patients receiving HD. Pulmonary artery systolic pressure was significantly higher in patients with PH compared with patients without PH (40.79 ± 12.32 versus 24.81 ± 4.54 mmHg; p
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- 2010
213. Combined vitamin D analog and AT1 receptor antagonist synergistically block the development of kidney disease in a model of type 2 diabetes
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Zhongyi Zhang, Anthony Chang, Yan Zhang, Yan Chun Li, Kari E. Wong, Helen Shi, Tao Sun, Gang Ning, Juan Kong, and Dilip K. Deb
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Paricalcitol ,Male ,medicine.medical_specialty ,Time Factors ,Kidney Glomerulus ,Losartan ,Blood Urea Nitrogen ,Diabetic nephropathy ,Renin-Angiotensin System ,Mice ,Internal medicine ,medicine ,Albuminuria ,Animals ,Diabetic Nephropathies ,RNA, Messenger ,renin–angiotensin system ,Extracellular Matrix Proteins ,business.industry ,diabetic nephropathy ,Glomerulosclerosis ,Drug Synergism ,Vitamins ,medicine.disease ,Mice, Inbred C57BL ,compensatory renin increase ,Disease Models, Animal ,Endocrinology ,Diabetes Mellitus, Type 2 ,Gene Expression Regulation ,Nephrology ,Creatinine ,Ergocalciferols ,Slit diaphragm ,Glomerular Filtration Barrier ,Disease Progression ,Receptors, Leptin ,Drug Therapy, Combination ,medicine.symptom ,Inflammation Mediators ,business ,vitamin D analogs ,Angiotensin II Type 1 Receptor Blockers ,glomerulosclerosis ,Biomarkers ,medicine.drug ,Kidney disease - Abstract
We recently showed that losartan and paricalcitol are synergistic in the treatment of diabetic nephropathy in a model of type 1 diabetes. To test this strategy in a model of type 2 diabetes, we treated 2-month-old diabetic Lprdb/db mice with losartan, paricalcitol, or a combination of losartan and paricalcitol for 3 months. Vehicle-treated diabetic mice developed progressive albuminuria and glomerular abnormalities with mesangial expansion and glomerulosclerosis compared to their non-diabetic littermate control mice. Accompanying damage of the glomerular filtration barrier was a marked reduction in podocyte number as well as reduced expression of slit diaphragm proteins. Further, there was increased glomerular expression of extracellular matrix proteins, monocyte chemoattractant protein-1 and transforming growth factor-beta. Losartan or paricalcitol each alone moderately ameliorated albuminuria and glomerular damage. However, their combined use showed a dramatic therapeutic synergism, manifested by prevention of progressive albuminuria, restoration of the glomerular filtration barrier, reversal of the decline in slit diaphragm proteins, reduced synthesis of extracellular matrix proteins, and reduction of glomerulosclerosis. These effects were accompanied by blockade of the compensatory increase of renin production and angiotensin I/II accumulation in the kidney. Thus, our study further shows that vitamin D analogs can increase the efficacy of AT1 receptor blockade, leading to a more effective prevention of kidney disease in type 2 diabetes.
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- 2010
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214. Vitamin D Receptor Attenuates Renal Fibrosis by Suppressing the Renin-Angiotensin System
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Dilip K. Deb, Yan Zhang, Yan Chun Li, Anthony Chang, and Juan Kong
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medicine.medical_specialty ,Biology ,Kidney ,urologic and male genital diseases ,Calcitriol receptor ,Collagen Type I ,Losartan ,Renin-Angiotensin System ,Mice ,Transforming Growth Factor beta ,Fibrosis ,Internal medicine ,Renin–angiotensin system ,medicine ,Renal fibrosis ,Animals ,Cells, Cultured ,Chemokine CCL2 ,Mice, Knockout ,Connective Tissue Growth Factor ,General Medicine ,medicine.disease ,Angiotensin II ,Fibronectins ,Mice, Inbred C57BL ,Disease Models, Animal ,Basic Research ,medicine.anatomical_structure ,Endocrinology ,Nephrology ,Receptors, Calcitriol ,Kidney Diseases ,Angiotensin I ,medicine.drug ,Kidney disease - Abstract
Analogs of vitamin D attenuate renal injury in several models of kidney disease, but the mechanism underlying this renoprotective effect is unknown. To address the role of the vitamin D receptor (VDR) in renal fibrogenesis, we subjected VDR-null mice to unilateral ureteral obstruction for 7 days. Compared with wild-type mice, VDR-null mice developed more severe renal damage in the obstructed kidney, with marked tubular atrophy and interstitial fibrosis. Significant induction of extracellular matrix proteins (fibronectin and collagen I), profibrogenic and proinflammatory factors (TGF-beta, connective tissue growth factor, and monocyte chemoattractant protein 1), and epithelial-to-mesenchymal transition accompanied this histologic damage. Because VDR ablation activates the renin-angiotensin system and leads to accumulation of angiotensin II (AngII) in the kidney, we assessed whether elevated AngII in the VDR-null kidney promotes injury. Treatment with the angiotensin type 1 antagonist losartan eliminated the difference in obstruction-induced interstitial fibrosis between wild-type and VDR-null mice, suggesting that AngII contributes to the enhanced renal fibrosis observed in obstructed VDR-null kidneys. Taken together, these results suggest that the VDR attenuates obstructive renal injury at least in part by suppressing the renin-angiotensin system.
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- 2010
215. The Design and Applied Research of Robot Performance Testing Platform
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Yan Chun Li and Yu Chai
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Engineering ,Data processing ,Software ,Data acquisition ,Robot calibration ,business.industry ,Robot ,Applied research ,General Medicine ,business ,Track (rail transport) ,Simulation ,Humanoid robot - Abstract
A robot performance testing platform is designed and implemented to aid the production and study of the competition robot. The underlying design principle, the mechanical structure, hardware and the data acquisition system software, as well as the PC data processing and display software which make up the testing platform are introduced. The applications of the platform in robot performance testing, track race and the gait planning of humanoid robot are stated, and the future research direction and difficulties of the platform are identified. Practice shows that the research of the platform has significant practical application and theoretical value.
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- 2010
216. Activation of Glycogen Synthase Kinase-3β Is Required for Hyperdopamine and D2Receptor-Mediated Inhibition of Synaptic NMDA Receptor Function in the Rat Prefrontal Cortex
- Author
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Yan-Chun Li, Wen-Jun Gao, Yue Qiao Huang, Dong Xi, and Joy Roman
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medicine.medical_specialty ,General Neuroscience ,Dopaminergic ,Dopamine reuptake inhibitor ,Biology ,Cell biology ,Dopamine receptor D1 ,Endocrinology ,nervous system ,Dopamine receptor D3 ,Dopamine ,Internal medicine ,Dopamine receptor D2 ,medicine ,NMDA receptor ,Long-term depression ,medicine.drug - Abstract
The interactions between dopamine and glutamate systems play an essential role in normal brain functions and neuropsychiatric disorders. The mechanism of NMDA receptor regulation through high concentrations of dopamine, however, remains unclear. Here, we show the signaling pathways involved in hyperdopaminergic regulation of NMDA receptor functions in the prefrontal cortex by incubating cortical slices with high concentration of dopamine or administering dopamine reuptake inhibitor 1-(2-[bis-(4-fluorophenyl)methoxy]ethyl)- 4-(3-phenylpropyl)piperazine (GBR12909)in vivo. We found that, under both conditions, the synaptic NMDA receptor-mediated currents were significantly attenuated by excessive dopamine stimulation through activation of D2receptors. Furthermore, high dose of dopamine failed to affect NMDA receptor-mediated currents after blockade of NR2B subunits but triggered a dynamin-dependent endocytosis of NMDA receptors. The high-dose dopamine/D2receptor-mediated suppression of NMDA receptors was involved in the increase of glycogen synthase kinase-3β (GSK-3β) activity, which in turn phosphorylates β-catenin and disrupts β-catenin–NR2B interaction, but was dependent on neither Gq11 nor PLC (phospholipase C). Moreover, the hyperdopamine induced by GBR12909 significantly decreased the expression of both surface and intracellular NR2B proteins, as well as NR2B mRNA levels, suggesting an inhibition of protein synthesis. These effects were, however, completely reversed by administration of either GSK-3β inhibitor or D2receptor antagonist. These results therefore suggest that GSK-3β is required for the hyperdopamine/D2receptor-mediated inhibition of NMDA receptors in the prefrontal neurons and these actions may underlie D2receptor-mediated psychostimulant effects and hyperdopamine-dependent behaviors in the brain.
- Published
- 2009
217. 1,25-Dihydroxyvitamin D3suppresses high glucose-induced angiotensinogen expression in kidney cells by blocking the NF-κB pathway
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Frances L. Szeto, Dilip K. Deb, Yunzi Chen, Zhongyi Zhang, Yan Chun Li, Yan Zhang, Juan Kong, and Kari E. Wong
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medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Angiotensinogen ,Gene Expression ,Biology ,Calcitriol receptor ,Cell Line ,Renin-Angiotensin System ,Diabetic nephropathy ,Mice ,chemistry.chemical_compound ,Mediator ,Calcitriol ,Internal medicine ,parasitic diseases ,Renin–angiotensin system ,medicine ,Animals ,Diabetic Nephropathies ,Drug Interactions ,Kidney ,NF-kappa B ,NF-κB ,Articles ,Vitamins ,medicine.disease ,Steroid hormone ,Glucose ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Hyperglycemia ,Mesangial Cells ,Signal Transduction ,Kidney disease - Abstract
The renin-angiotensin system (RAS) is a major mediator of renal injury in diabetic nephropathy. Our previous studies demonstrated that 1,25-dihydroxyvitamin D3[1,25(OH)2D3] plays a renoprotective role by suppressing the RAS, with renin and angiotensinogen (AGT) as the main targets. The mechanism whereby 1,25(OH)2D3transcriptionally suppresses renin gene expression has been elucidated; however, how vitamin D regulates AGT remains unknown. Exposure of mesangial cells or podocytes to high glucose (HG; 30 mM) markedly stimulated AGT expression. In mesangial cells, the stimulation was inhibited by 1,25(OH)2D3(20 nM) or NF-κB inhibitor BAY 11–7082, suggesting the involvement of NF- κB in HG-induced AGT expression and the interaction between 1,25(OH)2D3and NF-κB in the regulation. Plasmid pNF-κB-Luc luciferase reporter assays showed that 1,25(OH)2D3blocked HG-induced NF-κB activity. EMSA and ChIP assays demonstrated increased p65/p50 binding to a NF-κB binding site at −1734 in the AGT gene promoter upon high glucose stimulation, and the binding was disrupted by 1,25(OH)2D3treatment. Overexpression of p65/p50 overcame 1,25(OH)2D3suppression, and mutation of this NF-κB binding site blunted 1,25(OH)2D3suppression of the promoter activity. In mice lacking the vitamin D receptor, AGT mRNA expression in the kidney was markedly increased compared with wild-type mice, and AGT induction in diabetic mice was suppressed by treatment with a vitamin D analog. These data indicate that 1,25(OH)2D3suppresses hyperglycemia-induced AGT expression by blocking NF-κB-mediated pathway.
- Published
- 2009
218. Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins
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Xiao Jian Sun, Zhongyi Zhang, Frances L. Szeto, Kari E. Wong, Yan Chun Li, Honggang Ye, Wenshuo Zhang, and Juan Kong
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Male ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,White adipose tissue ,Biology ,Calcitriol receptor ,Ion Channels ,Mitochondrial Proteins ,Mice ,chemistry.chemical_compound ,Oxygen Consumption ,Physiology (medical) ,Adipocyte ,Internal medicine ,Adipocytes ,medicine ,Vitamin D and neurology ,Animals ,Uncoupling Protein 3 ,Uncoupling protein ,Uncoupling Protein 2 ,Vitamin D ,Cells, Cultured ,Uncoupling Protein 1 ,Mice, Knockout ,Lipid metabolism ,Articles ,Lipid Metabolism ,Thermogenin ,Mice, Inbred C57BL ,Endocrinology ,Gene Expression Regulation ,chemistry ,Receptors, Calcitriol ,Female ,Energy Metabolism ,Oxidation-Reduction - Abstract
Recent studies have established that vitamin D plays multiple biological roles beyond calcium metabolism; however, whether vitamin D is involved in energy metabolism is unknown. To address this question, we characterized the metabolic phenotypes of vitamin D receptor (VDR)-null mutant mice. Under a normocalcemic condition, VDR-null mice displayed less body fat mass and lower plasma triglyceride and cholesterol levels compared with wild-type (WT) mice; when placed on a high-fat diet, VDR-null mice showed a slower growth rate and accumulated less fat mass globally than WT mice, even though their food intake and intestinal lipid transport capacity were the same as WT mice. Consistent with the lower adipose mass, plasma leptin levels were lower and white adipocytes were histologically smaller in VDR-null mice than WT mice. The rate of fatty acid β-oxidation in the white adipose tissue was higher, and the expression of uncoupling protein (UCP) 1, UCP2 and UCP3 was markedly upregulated in VDR-null mice, suggesting a higher energy expenditure in the mutant mice. Experiments using primary brown fat culture confirmed that 1,25-dihydroxyvitamin D3directly suppressed the expression of the UCPs. Consistently, the energy expenditure, oxygen consumption, and CO2production in VDR-null mice were markedly higher than in WT mice. These data indicate that vitamin D is involved in energy metabolism and adipocyte biology in vivo in part through regulation of β-oxidation and UCP expression.
- Published
- 2009
219. Russula griseocarnosa sp. nov. (Russulaceae, Russulales), a commercially important edible mushroom in tropical China: mycorrhiza, phylogenetic position, and taxonomy
- Author
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Zhu-Liang Yang, Yan-Chun Li, Pei-Gui Liu, Henning Knudsen, and Xiang-Hua Wang
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Taxon ,biology ,Botany ,Spore print ,Pileipellis ,Taxonomy (biology) ,Pileus ,Plant Science ,Russulaceae ,biology.organism_classification ,Ecology, Evolution, Behavior and Systematics ,Russulales ,Russula - Abstract
A new species, Russula griseocarnosa, which was popularly commercially collected as food and medicine and misnamed as European R. vinosa for a long time, is described from tropical China. The dark red sticky pileus, initially greyish context, white spore print, subglobose to ellipsoid basidiospores with high and acute warts, and the pileipellis without dermatocystidia make this new taxon well defined. It resembles R. vinosa in the greyish tinge of the context and the pileipellis structure, but differs from the latter in its white spore print, significantly higher spines on basidiospores, and growing in forests with Fagaceae rather than in coniferous forests. The molecular analysis, based on a combined ITS - nLSU-rDNA sequence data get, showed that R. griseocarnosa clustered with R. vinosa but is clearly distinct from the latter. The phylogenetic placement is further supported by its ectomycorrhizal morphology.
- Published
- 2009
220. Targeted vitamin D receptor expression in juxtaglomerular cells suppresses renin expression independent of parathyroid hormone and calcium
- Author
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Zhongyi Zhang, Yan Chun Li, Shu Q. Liu, Guilin Qiao, and Juan Kong
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medicine.medical_specialty ,Calcitriol ,Parathyroid hormone ,vitamin D ,Mice, Transgenic ,transgenic mice ,030204 cardiovascular system & hematology ,Biology ,Calcitriol receptor ,Plasma renin activity ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,Humans ,RNA, Messenger ,VDR ,030304 developmental biology ,Calcium metabolism ,0303 health sciences ,Juxtaglomerular apparatus ,Juxtaglomerular Apparatus ,Endocrinology ,medicine.anatomical_structure ,Gene Expression Regulation ,Parathyroid Hormone ,Nephrology ,Receptors, Calcitriol ,Calcium ,Calcium-sensing receptor ,PTH ,medicine.drug - Abstract
Previously, we showed that vitamin D receptor gene knockout leads to hyperreninemia independent of calcium metabolism; however, the contribution of parathyroid hormone to renin upregulation remained unclear. Here we separated the role of vitamin D and parathyroid hormone in the regulation of renin expression in vivo by generating transgenic mice that overexpressed the human vitamin D receptor in renin-producing cells using the 4.1 kb Ren-1c gene promoter. Targeting of human vitamin D receptor to the juxtaglomerular cells of the mice was confirmed by immunohistochemistry. Renal renin mRNA levels and plasma renin activity were decreased in these transgenic mice by about 50% and 30%, respectively, with no significant change in blood pressure, calcium, or parathyroid hormone levels. Moreover using vitamin D receptor knockout mice, we found that expression of the human receptor in their juxtaglomerular cells reduced renin expression in these mice without affecting calcium or parathyroid hormone status. Our study shows that suppression of renin expression by 1,25-dihydroxyvitamin D in vivo is independent of parathyroid hormone and calcium.
- Published
- 2008
221. Suppression of renin–angiotensin gene expression in the kidney by paricalcitol
- Author
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Bernardo Rodriguez-Iturbe, Michael Freundlich, Yan Zhang, Zhongyi Zhang, Yasmir Quiroz, Yan Chun Li, José R. Weisinger, and Yanauri Bravo
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Male ,Paricalcitol ,medicine.medical_specialty ,medicine.medical_treatment ,Down-Regulation ,Renal function ,vitamin D ,urologic and male genital diseases ,Calcitriol receptor ,renal insufficiency ,Rats, Sprague-Dawley ,Renin-Angiotensin System ,chemistry.chemical_compound ,Internal medicine ,Renin–angiotensin system ,medicine ,Vitamin D and neurology ,Animals ,vitamin D receptor activators ,renin–angiotensin system ,Kidney ,business.industry ,Nephrectomy ,Rats ,Vascular endothelial growth factor ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,chemistry ,Nephrology ,Ergocalciferols ,paricalcitol ,Kidney Failure, Chronic ,Receptors, Calcitriol ,progression ,business ,medicine.drug - Abstract
The renal renin-angiotensin system plays a major role in determining the rate of chronic renal disease progression. Treatment with activators of the vitamin D receptor retards the progression of experimental chronic renal disease, and vitamin D is known to suppress the renin-angiotensin system in other organs. Here we determined if the beneficial effects of paricalcitol (19-nor 1,25-dihydroxyvitamin D(2)) were associated with suppression of renin-angiotensin gene expression in the kidney. Rats with the remnant kidney model of chronic renal failure (5/6 nephrectomy) were given two different doses of paricalcitol thrice weekly for 8 weeks. Paricalcitol was found to decrease angiotensinogen, renin, renin receptor, and vascular endothelial growth factor mRNA levels in the remnant kidney by 30-50 percent compared to untreated animals. Similarly, the protein expression of renin, renin receptor, the angiotensin type 1 receptor, and vascular endothelial growth factor were all significantly decreased. Glomerular and tubulointerstitial damage, hypertension, proteinuria, and the deterioration of renal function resulting from renal ablation were all similarly and significantly improved with both treatment doses. These studies suggest that the beneficial effects of vitamin D receptor activators in experimental chronic renal failure are due, at least in part, to down-regulation of the renal renin-angiotensin system.
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- 2008
222. Loss of Vitamin D Receptor Produces Polyuria by Increasing Thirst
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Mark W. Musch, Yan Chun Li, Yan Zhang, Frances L. Szeto, Kari E. Wong, Zhongyi Zhang, Juan Kong, and Dongdong Li
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medicine.medical_specialty ,Vasopressin ,Sodium-Hydrogen Exchangers ,Calcitriol receptor ,Losartan ,Thirst ,Mice ,Polyuria ,Internal medicine ,Renin ,medicine ,Animals ,Kidney ,Reverse Transcriptase Polymerase Chain Reaction ,Sodium-Hydrogen Exchanger 3 ,Chemistry ,Angiotensin II ,General Medicine ,Subfornical organ ,Up-Regulation ,Mice, Inbred C57BL ,Basic Research ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Nephrology ,Receptors, Calcitriol ,Salts ,medicine.symptom ,Proto-Oncogene Proteins c-fos ,medicine.drug - Abstract
Vitamin D receptor (VDR)-null mice develop polyuria, but the underlying mechanism remains unknown. In this study, we investigated the relationship between vitamin D and homeostasis of water and electrolytes. VDR-null mice had polyuria, but the urine osmolarity was normal as a result of high salt excretion. The urinary responses to water restriction and to vasopressin were similar between wild-type and VDR-null mice, suggesting intact fluid-handling capacity in VDR-null mice. Compared with wild-type mice, however, renin and angiotensin II were dramatically upregulated in the kidney and brain of VDR-null mice, leading to a marked increase in water intake and salt appetite. Angiotensin II–mediated upregulation of intestinal NHE3 expression partially explained the increased salt absorption and excretion in VDR-null mice. In the brain of VDR-null mice, expression of c-Fos, which is known to associate with increased water intake, was increased in the hypothalamic paraventricular nucleus and the subfornical organ. Treatment with an angiotensin II type 1 receptor antagonist normalized water intake, urinary volume, and c-Fos expression in VDR-null mice. Furthermore, despite a salt-deficient diet to reduce intestinal salt absorption, VDR-null mice still maintained the increased water intake and urinary output. Together, these data indicate that the polyuria observed in VDR-null mice is not caused by impaired renal fluid handling or increased intestinal salt absorption but rather is the result of increased water intake induced by the increase in systemic and brain angiotensin II.
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- 2008
223. Vitamin D and diabetic nephropathy
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Yan Chun Li
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Ras Inhibitor ,medicine.medical_specialty ,Combination therapy ,business.industry ,Endocrinology, Diabetes and Metabolism ,Vitamins ,medicine.disease ,Blockade ,Renin-Angiotensin System ,Diabetic nephropathy ,Endocrinology ,Mediator ,Internal medicine ,Diabetes mellitus ,Renin–angiotensin system ,Internal Medicine ,Vitamin D and neurology ,Animals ,Humans ,Medicine ,Diabetic Nephropathies ,Kidney Diseases ,Vitamin D ,business - Abstract
Diabetic nephropathy (DN) is the most common renal complication of diabetes mellitus and a leading cause of end-stage renal disease. The renin-angiotensin system (RAS) is a major mediator of progressive renal injury in DN, and RAS inhibitors have been used as the mainstay treatment for DN. One major problem limiting the efficacy of the RAS inhibitors is the compensatory renin increase caused by disruption of renin feedback inhibition. Vitamin D negatively regulates the RAS by suppressing renin expression and thus plays a renoprotective role in DN. Diabetic vitamin D receptor-null mutant mice develop more severe renal injuries because of more robust RAS activation. Combination therapy with an RAS inhibitor and a vitamin D analogue markedly ameliorates renal injuries due to blockade of the compensatory renin increase by the analogue. These most recent data demonstrate that vitamin D and its analogues have renoprotective and therapeutic potentials in DN through targeting the RAS.
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- 2008
224. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier
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Yan Chun Li, Gang Ning, Marc Bissonnette, Zhongyi Zhang, John Hart, Mark W. Musch, Juan Kong, and Jun Sun
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Time Factors ,Colon ,Physiology ,Biology ,Severity of Illness Index ,Inflammatory bowel disease ,Calcitriol receptor ,Permeability ,vitamin D deficiency ,Tight Junctions ,Mice ,chemistry.chemical_compound ,Calcitriol ,Cell Movement ,Physiology (medical) ,Electric Impedance ,medicine ,Vitamin D and neurology ,Animals ,Humans ,Intestinal Mucosa ,RNA, Small Interfering ,Vitamin D ,Receptor ,Ulcer ,Mice, Knockout ,Wound Healing ,Hepatology ,Tight junction ,Dextran Sulfate ,Gastroenterology ,Membrane Proteins ,Epithelial Cells ,Colitis ,medicine.disease ,Ulcerative colitis ,Mice, Inbred C57BL ,Disease Models, Animal ,Dextran ,chemistry ,Immunology ,Receptors, Calcitriol ,RNA Interference ,Caco-2 Cells - Abstract
Emerging evidence supports a pathological link between vitamin D deficiency and the risk of inflammatory bowel disease (IBD). To explore the mechanism we used the dextran sulfate sodium (DSS)-induced colitis model to investigate the role of the vitamin D receptor (VDR) in mucosal barrier homeostasis. While VDR+/+ mice were mostly resistant to 2.5% DSS, VDR−/− mice developed severe diarrhea, rectal bleeding, and marked body weight loss, leading to death in 2 wk. Histological examination revealed extensive ulceration and impaired wound healing in the colonic epithelium of DSS-treated VDR−/− mice. Severe ulceration in VDR−/− mice was preceded by a greater loss of intestinal transepithelial electric resistance (TER) compared with VDR+/+ mice. Confocal and electron microscopy (EM) revealed severe disruption in epithelial junctions in VDR−/− mice after 3-day DSS treatment. Therefore, VDR−/− mice were much more susceptible to DSS-induced mucosal injury than VDR+/+ mice. In cell cultures, 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] markedly enhanced tight junctions formed by Caco-2 monolayers by increasing junction protein expression and TER and preserved the structural integrity of tight junctions in the presence of DSS. VDR knockdown with small interfering (si)RNA reduced the junction proteins and TER in Caco-2 monolayers. 1,25(OH)2D3 can also stimulate epithelial cell migration in vitro. These observations suggest that VDR plays a critical role in mucosal barrier homeostasis by preserving the integrity of junction complexes and the healing capacity of the colonic epithelium. Therefore, vitamin D deficiency may compromise the mucosal barrier, leading to increased susceptibility to mucosal damage and increased risk of IBD.
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- 2008
225. MicroRNA-192-5p Promote the Proliferation and Metastasis of Hepatocellular Carcinoma Cell by Targeting SEMA3A
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Yan-Chun, Li, primary, Hong-Mei, Yi, additional, Zhi-Hong, Chen, additional, Qing, Hu, additional, Yan-Hong, Zhou, additional, and Ji-Fang, Wen, additional
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- 2017
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226. Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer
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Yan Chun Li, George P. Studzinski, Surojit Sarkar, Vandana Kalia, and Martin Hewison
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0301 basic medicine ,Clinical Biochemistry ,chemical and pharmacologic phenomena ,Biology ,Calcitriol receptor ,Communicable Diseases ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,Neoplasms ,Vitamin D and neurology ,Cytotoxic T cell ,Animals ,Humans ,Vitamin D ,Innate immune system ,Biochemistry (medical) ,Acquired immune system ,CTL ,030104 developmental biology ,Immunology ,Dietary Supplements ,030215 immunology ,T-Lymphocytes, Cytotoxic - Abstract
The discovery of vitamin D receptor (VDR) expression in immune cells has opened up a new area of research into immunoregulation by vitamin D, a niche that is distinct from its classical role in skeletal health. Today, about three decades since this discovery, numerous cellular and molecular targets of vitamin D in the immune system have been delineated. Moreover, strong clinical associations between vitamin D status and the incidence/severity of many immune-regulated disorders (e.g. infectious diseases, cancers and autoimmunity) have prompted the idea of using vitamin D supplementation to manipulate disease outcome. While much is known about the effects of vitamin D on innate immune responses and helper T (T(H)) cell immunity, there has been relatively limited progress on the frontier of cytotoxic T lymphocyte (CTL) immunity--an arm of host cellular adaptive immunity that is crucial for the control of such intracellular pathogens as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and hepatitis C virus (HCV). In this review, we discuss the strong historical and clinical link between vitamin D and infectious diseases that involves cytotoxic T lymphocyte (CTL) immunity, present our current understanding as well as critical knowledge gaps in the realm of vitamin D regulation of host CTL responses, and highlight potential regulatory connections between vitamin D and effector and memory CD8 T cell differentiation events during infections.
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- 2015
227. Monolayer Ti₂CO₂: A Promising Candidate for NH₃ Sensor or Capturer with High Sensitivity and Selectivity
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Xue-fang, Yu, Yan-chun, Li, Jian-bo, Cheng, Zhen-bo, Liu, Qing-zhong, Li, Wen-zuo, Li, Xin, Yang, and Bo, Xiao
- Abstract
Ti2C is one of the thinnest layers in MXene family with high potential for applications. In the present study, the adsorption of NH3, H2, CH4, CO, CO2, N2, NO2, and O2 on monolayer Ti2CO2 was investigated by using first-principles simulations to exploit its potential applications as gas sensor or capturer. Among all the gas molecules, only NH3 could be chemisorbed on Ti2CO2 with apparent charge transfer of 0.174 e. We further calculated the current-voltage (I-V) relation using the nonequilibrium Green's function (NEGF) method. The transport feature exhibits distinct responses with a dramatic change of I-V relation before and after NH3 adsorption on Ti2CO2. Thus, we predict that Ti2CO2 could be a promising candidate for the NH3 sensor with high selectivity and sensitivity. On the other hand, the adsorption of NH3 on Ti2CO2 could be further strengthened with the increase of applied strain on Ti2CO2, while the adsorption of other gases on Ti2CO2 is still weak under the same strain, indicating that the capture of NH3 on Ti2CO2 under the strain is highly preferred over other gas molecules. Moreover, the adsorbed NH3 on Ti2CO2 could be escapable by releasing the applied strain, which indicates the capture process is reversible. Our study widens the application of monolayer Ti2CO2 not only as the battery material, but also as the potential gas sensor or capturer of NH3 with high sensitivity and selectivity.
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- 2015
228. The genus Retiboletus in China
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Nian-Kai Zeng, Zhi-Qun Liang, Gang Wu, Yan-Chun Li, and Zhu L. Yang
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0301 basic medicine ,Bolete ,Systematics ,China ,Physiology ,03 medical and health sciences ,Species Specificity ,Boletaceae ,Genetics ,Fruiting Bodies, Fungal ,Internal transcribed spacer ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Phylogeny ,Phylogenetic tree ,biology ,Boletales ,Basidiomycota ,Cell Biology ,General Medicine ,030108 mycology & parasitology ,biology.organism_classification ,030104 developmental biology ,Taxon ,Evolutionary biology ,Taxonomy (biology) - Abstract
Species of the genus Retiboletus (Boletaceae, Boletales) in China are investigated based on morphology and phylogenetic analyses of DNA sequences from nuc rDNA internal transcribed spacer (ITS) and partial 28S regions and sequences from the translation elongation factor 1-a gene (tef1a). Six lineages are recovered among the collections studied. Five of these are documented and presented in the present paper, including three new species and two new combinations. The remaining species is not described due to the paucity of material. The specimens from China identified as "R. ornatipes" or "R. retipes" are in fact R. sinensis or R. kauffmanii, those labeled "R. griseus" are either R. fuscus or R. pseudogriseus A key to all known taxa of the genus is provided. Phylogenetic relationships of taxa within Retiboletus are partially resolved. A preliminary biogeographical analysis shows that allied species of Retiboletus between eastern Asia and North/Central America are common but there are no Retiboletus species common to both continents. Species of Retiboletus in Japan and southern China are conspecific or closely related.
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- 2015
229. The Epidemiology and Geographic Distribution of Nontuberculous Mycobacteria Clinical Isolates from Sputum Samples in the Eastern Region of China
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Yan Shao, Leonardo Martinez, Qiao Liu, Limei Zhu, Yan Chun Li, Guoli Li, Cheng Ann Chen, Honghuan Song, and Wei bo Lu
- Subjects
medicine.medical_specialty ,China ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Mycobacterium Infections, Nontuberculous ,Disease ,Microbiology ,Mycobacterium tuberculosis ,Epidemiology ,medicine ,Humans ,biology ,lcsh:Public aspects of medicine ,Public Health, Environmental and Occupational Health ,Sputum ,lcsh:RA1-1270 ,Nontuberculous Mycobacteria ,biology.organism_classification ,bacterial infections and mycoses ,Nontuberculous mycobacterium ,Geographic distribution ,Infectious Diseases ,Nontuberculous mycobacteria ,medicine.symptom ,Mycobacterium ,Research Article - Abstract
Background Nontuberculous mycobacteria (NTM) have been reported to be increasing worldwide and its geographic distribution differs by region. The aim of this study was to describe the epidemiology and distribution of NTM in the eastern part of China. Methods Sputum samples were collected from 30 surveillance sites for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008. Identification was performed using a biochemical test, multiplex PCR and GenoType Mycobacterium CM/AS assay. Results A total of 1779 smear positive clinical isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM were identified; M. intracellulare was the predominated species (68.33%), followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%), M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%). Conclusion M. intracellulare was the main species of NTM in the eastern part of China and clinical physicians should pay more attention to NTM induced pulmonary disease., Author Summary Nontuberculous mycobacteria (NTM) exist ubiquitously in the environment and cause many kinds of diseases including pulmonary infection. Despite this, NTM does not match compulsory report policy in many countries, such as China. Thus, the epidemiology of NTM is generally unknown. Furthermore, misdiagnosis of nontuberculous mycobacterium disease as multi-drug resistant tuberculosis (MDR-TB) frequently occurs in clinical settings because of similar clinical manifestations. Therefore, elucidating the epidemiology and distribution of NTM species is important and may have a profound and lasting impact on the prevalence of pulmonary NTM disease. In our study, we enrolled smear-positive sputum samples during 2008 from Jiangsu province in the eastern region of China. Traditional biochemical tests and molecular biological methods were performed to distinguish NTM isolates to species/complex level. For the first time, we provide a snapshot of the epidemiology and geographic distribution of NTM in Jiangsu province. The proportion of NTM was 3.37% of all the Mycobacterium isolates and the species of NTM differed by area.
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- 2015
230. Impact of LPL gene rs283 polymorphism on exercise-induced changes in metabolism of obese adolescents and the regulatory mechanisms behind it
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Rui-Rui, Gao, Min, Wang, Yang, Hu, Chun-Yan, Xu, Yan-Chun, Li, Ze-Ya, Zhang, Si-Yun, Chen, and Xiao-Yun, Mao
- Subjects
Blood Glucose ,Male ,China ,Pediatric Obesity ,Time Factors ,Adolescent ,Genotype ,Transfection ,Sex Factors ,Asian People ,Gene Frequency ,Weight Loss ,Humans ,Adiposity ,Caloric Restriction ,Polymorphism, Genetic ,Age Factors ,Lipids ,Exercise Therapy ,Lipoprotein Lipase ,HEK293 Cells ,Phenotype ,Treatment Outcome ,Female ,Energy Metabolism ,Biomarkers - Abstract
What is the central question of this study? We investigated whether the LPL gene rs283 polymorphism affects exercise-induced changes in body composition and lipid and glucose metabolism in obese adolescents and whether it is functional. What is the main finding and its importance? Chinese obese adolescents of Han nationality with the GG genotype of the rs283 polymorphism were more sensitive to exercise-induced reduction of the body fat percentage, insulin resistance and plasma triglyceride levels. The G allele can significantly increase reporter gene expression level, which may be the molecular reason for the difference in exercise-induced parameter changes among obese adolescents. The aim of this investigation was to explore the association between the rs283 polymorphism located in the lipoprotein lipase (LPL) gene and exercise-induced changes in body composition and lipid and glucose metabolism in obese adolescents and to probe into the molecular regulatory mechanisms. Fifty-five obese adolescents of Han nationality underwent aerobic training for 4 weeks. Body composition and lipid and glucose metabolic parameters were tested before and after the training. The rs283 polymorphism was genotyped by PCR-restriction fragment length polymorphism, and association analysis with the weight-reducing effect was performed. The regulatory mechanisms of the rs283 polymorphism were explored through the dual-luciferase reporter assay. Exercise-induced change rates were as follows: the change in body fat percentage of GG genotype groups was 3.37 ± 1.60, significantly higher than that of GA genotype groups (2.09 ± 1.53, P 0.01); the change in the homeostasis model assessment of insulin resistance was 0.52 ± 0.13, obviously higher than that of GA genotype groups (0.44 ± 0.10, P 0.05); and the change in triglyceride was 51.91 ± 6.56, much higher than that of GA genotype groups (47.06 ± 5.36, P 0.01). The relative luciferase activity of the reporter gene in recombinant vector carrying the G allele was 2.67 ± 0.22, markedly higher than that in recombinant vector carrying the A allele (1.63 ± 0.03, P 0.01). Chinese obese adolescents of Han nationality with GG genotype of the rs283 polymorphism were more sensitive to exercise-induced parameter changes. The G allele can improve reporter gene expression level, indicating the effects of rs283 on gene expression.
- Published
- 2015
231. Trans-system mechanisms against ischemic myocardial injury
- Author
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Shu Q. Liu, Xin Liang Ma, Gangjian Qin, Yan Chun Li, Yu H. Wu, and Qingping Liu
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Tumor Necrosis Factor-alpha ,Regeneration (biology) ,Myocardial Infarction ,Adipose tissue ,Inflammation ,Endocrine System ,Biology ,medicine.disease ,Cell biology ,Paracrine signalling ,Downregulation and upregulation ,Fibrosis ,Cytoprotection ,Immunology ,medicine ,Animals ,Cytokines ,Humans ,medicine.symptom ,Signal transduction ,Stem cell ,Signal Transduction - Abstract
A mammalian organism possesses a hierarchy of naturally evolved protective mechanisms against ischemic myocardial injury at the molecular, cellular, and organ levels. These mechanisms comprise regional protective processes, including upregulation and secretion of paracrine cell-survival factors, inflammation, angiogenesis, fibrosis, and resident stem cell-based cardiomyocyte regeneration. There are also interactive protective processes between the injured heart, circulation, and selected remote organs, defined as trans-system protective mechanisms, including upregulation and secretion of endocrine cell-survival factors from the liver and adipose tissue as well as mobilization of bone marrow, splenic, and hepatic cells to the injury site to mediate myocardial protection and repair. The injured heart and activated remote organs exploit molecular and cellular processes, including signal transduction, gene expression, cell proliferation, differentiation, migration, mobilization, and/or extracellular matrix production, to establish protective mechanisms. Both regional and trans-system cardioprotective mechanisms are mediated by paracrine and endocrine messengers and act in coordination and synergy to maximize the protective effect, minimize myocardial infarction, and improve myocardial function, ensuring the survival and timely repair of the injured heart. The concept of the trans-system protective mechanisms may be generalized to other organ systems-injury in one organ may initiate regional as well as trans-system protective responses, thereby minimizing injury and ensuring the survival of the entire organism. Selected trans-system processes may serve as core protective mechanisms that can be exploited by selected organs in injury. These naturally evolved protective mechanisms are the foundation for developing protective strategies for myocardial infarction and injury-induced disorders in other organ systems.
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- 2015
232. Chronic Activation of the Renin-Angiotensin System Induces Lung Fibrosis
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Li Chen, Jiaolong Wang, Dilip K. Deb, Julian Solway, Shu Q. Liu, Tianjing Liu, Yan Chun Li, Bohao Chen, Angelo Y. Meliton, and Yongyan Shi
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medicine.medical_specialty ,Pathology ,Pulmonary Fibrosis ,Mice, Transgenic ,Pulmonary compliance ,Biology ,Lung injury ,Receptor, Angiotensin, Type 2 ,Article ,Pulmonary function testing ,Renin-Angiotensin System ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Internal medicine ,Pulmonary fibrosis ,medicine ,Animals ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Lung ,Angiotensin II ,Hydralazine ,medicine.disease ,3. Good health ,Losartan ,Endocrinology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hypertension ,Disease Progression ,medicine.drug - Abstract
Pulmonary fibrosis is a serious lung disorder that can lead to respiratory failure. Here we show that transgenic mice expressing active renin from the liver (RenTgMK) developed progressive pulmonary fibrosis leading to impaired pulmonary function. Histological analyses revealed a marked increase in extracellular matrix (ECM) deposition and decrease in alveolar size in the lungs of RenTgMK mice compared to wild-type (WT) littermates, accompanied with increased expression of ECM proteins and fibrogenic factors. The increase in lung fibrosis led to a substantial decrease in respiratory system compliance. Two-week treatment with aliskiren (renin inhibitor) or losartan (AT1 antagonist) ameliorated pulmonary ECM deposition, blocked the induction of ECM proteins and fibrogenic factors and improved respiratory compliance in RenTgMK mice, confirming a critical role of the renin-Ang II-AT1 cascade in promoting pulmonary fibrogenesis. However, when RenTgMK mice were treated with hydralazine (a smooth muscle relaxant), the blood pressure was normalized but the lung fibrotic abnormalities, fibrogenic gene induction and pulmonary elasticity were not corrected. Moreover, intratracheal instillation of lipopolysaccharide induced more severe lung injury in RenTgMK mice compared to WT littermates. These observations demonstrate that the renin-angiotensin system is a key mediator of lung fibrosis and its pro-fibrotic effect is independent of blood pressure.
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- 2015
233. Expression of vitamin D3 receptor in kidney tumors
- Author
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Muge Turkyilmaz, Maria Tretiakova, Juan Kong, Yan Chun Li, Wenhua Liu, and Thomas Krausz
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Male ,Pathology ,medicine.medical_specialty ,Gene Expression ,Chromophobe cell ,Biology ,urologic and male genital diseases ,Calcitriol receptor ,Pathology and Forensic Medicine ,Diagnosis, Differential ,Immunoenzyme Techniques ,Biomarkers, Tumor ,medicine ,Adenoma, Oxyphilic ,Humans ,Oncocytoma ,RNA, Messenger ,Carcinoma, Renal Cell ,Aged ,Aged, 80 and over ,Kidney ,Tissue microarray ,Reverse Transcriptase Polymerase Chain Reaction ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,female genital diseases and pregnancy complications ,medicine.anatomical_structure ,Vitamin D3 Receptor ,Tissue Array Analysis ,Receptors, Calcitriol ,Immunohistochemistry ,Female ,Clear cell - Abstract
The kidney is not only a primary vitamin D target organ but also is a key site of vitamin D metabolism. Recent studies have shown that vitamin D has important physiologic effects on proliferation and differentiation in a variety of benign and malignant cells. Our preliminary immunohistochemical study showed that vitamin D receptor (VDR) was highly expressed in renal distal tubules and collecting ducts, whereas the renal proximal tubules and glomeruli did not express VDR. These observations led us to study the expression of VDR in various kidney tumors to determine the possible diagnostic utility of VDR. Paraffin tissue microarray (TMA) blocks were constructed containing core cylinders from clear cell (52), papillary (35), chromophobe (20), sarcomatoid (20), and metastatic (59) renal cell carcinomas (RCCs). Oncocytomas (20), normal adult kidneys (12), and normal adult adrenals (6) were also included. In addition, 30 clear cell RCCs and 3 collecting duct carcinomas were also studied using conventional sections. Furthermore, VDR messenger RNA and protein expression was also quantified using real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. Vitamin D receptor was strongly positive in collecting duct carcinomas (100% [3/3], cytoplasmic), papillary RCCs (94% [33/35], cytoplasmic), chromophobe RCCs (85% [17/20], membranous), and oncocytomas (90% [18/20], cytoplasmic with perinuclear accentuation). In contrast, VDR expression was focal/weak and present only in the peripheral regions of clear cell RCCs. Vitamin D receptor was weakly positive in sarcomatoid variant RCCs (88% [14/16]) regardless of the type of associated original RCC. Overall, VDR is a discriminative marker for renal cell tumors. The preferential expression of VDR in chromophobe RCCs, oncocytomas, and collecting duct carcinomas is in agreement with the concept that these tumors differentiate toward epithelium lining the distal convoluted tubules and collecting ducts. Considering the different VDR expression patterns, VDR is a useful ancillary tool in distinguishing chromophobe RCCs from oncocytomas. In addition, the focal and much weaker VDR expression in clear cell RCCs makes VDR valuable in distinguishing clear cell RCC from other types of RCCs.
- Published
- 2006
234. Molecular mechanism of 1,25-dihydroxyvitamin D3inhibition of adipogenesis in 3T3-L1 cells
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Yan Chun Li and Juan Kong
- Subjects
medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,Cellular differentiation ,Gene Expression ,Antineoplastic Agents ,Tretinoin ,Biology ,Transfection ,Calcitriol receptor ,Mice ,Troglitazone ,Calcitriol ,3T3-L1 Cells ,Physiology (medical) ,Internal medicine ,CCAAT-Enhancer-Binding Protein-alpha ,medicine ,Animals ,Chromans ,Receptor ,Adipogenesis ,CCAAT-Enhancer-Binding Protein-beta ,Cell Differentiation ,Vitamins ,Fibroblasts ,In vitro ,PPAR gamma ,Lipoprotein Lipase ,Retinoid X Receptors ,Endocrinology ,Adipose Tissue ,Transcription Factor AP-2 ,Receptors, Calcitriol ,Thiazolidinediones ,Signal Transduction ,medicine.drug - Abstract
We have investigated the molecular mechanism whereby 1,25-dihydroxyvitamin D3[1,25(OH)2D3] inhibits adipogenesis in vitro. 1,25(OH)2D3blocks 3T3-L1 cell differentiation into adipocytes in a dose-dependent manner; however, the inhibition is ineffective 24–48 h after the differentiation is initiated, suggesting that 1,25(OH)2D3inhibits only the early events of the adipogenic program. Treatment of 3T3-L1 cells with 1,25(OH)2D3does not block the mitotic clonal expansion or C/EBPβ induction; rather, 1,25(OH)2D3blocks the expression of C/EBPα, peroxisome proliferator-activated receptor-γ (PPARγ), sterol regulatory element-binding protein-1, and other downstream adipocyte markers. The inhibition by 1,25(OH)2D3is reversible, since removal of 1,25(OH)2D3from the medium restores the adipogenic process with only a temporal delay. Interestingly, although the vitamin D receptor (VDR) protein is barely detectable in 3T3-L1 preadipocytes, its levels are dramatically increased during the early phase of adipogenesis, peaking at 4–8 h and subsiding afterward throughout the rest of the differentiation program; 1,25(OH)2D3treatment appears to stabilize the VDR protein levels. Consistently, adenovirus-mediated overexpression of human (h) VDR in 3T3-L1 cells completely blocks the adipogenic program, confirming that VDR is inhibitory. Inhibition of adipocyte differentiation by 1,25(OH)2D3is ameliorated by troglitazone, a specific PPARγ antagonist; conversely, hVDR partially suppresses the transacting activity of PPARγ but not of C/EBPβ or C/EBPα. Moreover, 1,25(OH)2D3markedly suppresses C/EBPα and PPARγ mRNA levels in mouse epididymal fat tissue culture. Taken together, these data indicate that the blockade of 3T3-L1 cell differentiation by 1,25(OH)2D3occurs at the postclonal expansion stages and involves direct suppression of C/EBPα and PPARγ upregulation, antagonization of PPARγ activity, and stabilization of the inhibitory VDR protein.
- Published
- 2006
235. Regulation of IL-1 Family Cytokines IL-1α, IL-1 Receptor Antagonist, and IL-18 by 1,25-Dihydroxyvitamin D3 in Primary Keratinocytes
- Author
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Yan Chun Li, Sergei A. Grando, and Juan Kong
- Subjects
Keratinocytes ,medicine.medical_specialty ,medicine.drug_class ,RNA Stability ,Sialoglycoproteins ,Immunology ,Biology ,Calcitriol receptor ,Mice ,Interleukin 20 ,Calcitriol ,Psoriasis ,Internal medicine ,Phorbol Esters ,medicine ,Vitamin D and neurology ,Animals ,Humans ,Immunology and Allergy ,RNA, Messenger ,Receptor ,Cells, Cultured ,Mice, Knockout ,Messenger RNA ,Interleukin-18 ,medicine.disease ,Receptor antagonist ,Interleukin 1 Receptor Antagonist Protein ,Endocrinology ,Gene Expression Regulation ,Receptors, Calcitriol ,Calcium ,Interleukin 18 ,Interleukin-1 - Abstract
IL-1 family cytokines are key mediators of inflammatory response. Excessive production of these cytokines by keratinocytes has been implicated in inflammatory and hyperproliferative skin diseases. Given the immunosuppressive role of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its clinical application in treatment of psoriasis, we investigated the effect of 1,25(OH)2D3 on the expression of IL-1α, intracellular IL-1 receptor antagonist (icIL-1Ra), and IL-18 in mouse primary keratinocytes. Treatment of keratinocytes with 1,25(OH)2D3 increased the expression of IL-1α and icIL-1Ra and decreased the expression of IL-18 in dose- and time-dependent manners. The magnitude of icIL-1Ra induction was much greater than that of IL-1α so that the ratio of icIL-1Ra to IL-1α was markedly increased, leading to repression of IL-1 activity. The regulation of these three cytokines by 1,25(OH)2D3 was mediated by vitamin D receptor (VDR), as 1,25(OH)2D3 had no effect in VDR−/− keratinocytes, whereas the effect was restored in cells derived from VDR−/− mice expressing human VDR. 1,25(OH)2D3 appeared to use different mechanisms to regulate the biosynthesis of IL-1α and icIL-1Ra: it increased IL-1α mRNA stability whereas it enhanced icIL-1Ra gene transcription. The basal IL-18 expression and activity were much higher in VDR−/− keratinocytes and skin, underscoring the importance of the repressive role of vitamin D in IL-18 production. Similar regulation of these cytokines was also seen in primary human keratinocytes. Collectively, these results suggest that vitamin D modulates cutaneous inflammatory reactions, at least in part, by increasing the IL-1Ra to IL-1α ratio and suppressing IL-18 synthesis in keratinocytes.
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- 2006
236. Differential effects of Vitamin D analogs on bone formation and resorption
- Author
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Thomas A. Fey, Junli Ma, Michael E. Brune, Masaki Nakane, Yan Chun Li, Doug Dixon, and J. Ruth Wu-Wong
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Metabolite ,Osteocalcin ,Clinical Biochemistry ,chemistry.chemical_element ,Calcium ,Biochemistry ,Calcitriol receptor ,Bone resorption ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,Organ Culture Techniques ,Endocrinology ,Calcitriol ,Osteogenesis ,Internal medicine ,polycyclic compounds ,medicine ,Vitamin D and neurology ,Animals ,RNA, Messenger ,Bone Resorption ,Vitamin D ,Molecular Biology ,Calcium metabolism ,Mice, Inbred ICR ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Skull ,Cell Biology ,Rats ,Resorption ,Calcium Channel Agonists ,chemistry ,Ergocalciferols ,biology.protein ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) - Abstract
Deficiency in Vitamin D and its metabolites leads to a failure in bone formation primarily caused by dysfunctional mineralization, suggesting that Vitamin D analogs might stimulate osteoblastic bone formation and mineralization. In this study, we compare the effect of selected Vitamin D analogs and active metabolite, 1alpha,25-dihydroxyvitamin D(3), 19-nor-1alpha, 25-dihydroxyvitamin D(2), and 1alpha-hydroxyvitamin D(2) or 1alpha,25-dihydroxyvitamin D(2) on bone formation and resorption. In a mouse calvariae bone primary organ culture system, all Vitamin D analogs and metabolite tested-stimulated collagen synthesis in a dose-dependent manner and 19-nor-1alpha, 25-dihydroxyvitamin D(2) was the most efficacious among three. 19-nor-1alpha, 25-dihydroxyvitamin D(2) and 1alpha,25-dihydroxyvitamin D(2) showed similar potencies and 1alpha,25-dihydroxyvitamin D(3) was less potent than others. Osteocalcin was also up-regulated in a dose-dependent manner, suggesting that the three Vitamin D analogs have the equal potencies on bone formation. 25-Hydroxyvitamin D-24-hydroxylase expression was induced in a dose-dependent manner and 19-nor-1alpha, 25-dihydroxyvitamin D(2) was less potent than other two compounds. In a mouse calvariae organ culture, all induced a net calcium release from calvariae in a dose-dependent manner, but the potency is in the order of 1alpha,25-dihydroxyvitamin D(2) congruent with1alpha,25-dihydroxyvitamin D(3)>19-nor-1alpha, 25-dihydroxyvitamin D(2). In a Vitamin D/calcium-restricted rat model, all caused an elevation in serum calcium in a dose-dependent manner. There is no significant difference between 1alpha,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(2) in potencies, but 19-nor-1alpha, 25-dihydroxyvitamin D(2) is at least 10-fold less potent than the other two compounds. Our results suggest that Vitamin D analogs have direct effects on bone resorption and formation, and 19-nor-1alpha, 25-dihydroxyvitamin D(2) may be more effective than 1alpha,25-dihydroxyvitamin D(3) and 1alpha-hydroxyvitamin D(2) on stimulating anabolic bone formation.
- Published
- 2006
237. Osteoporosis biomarkers act as predictors for diagnosis of chronic renal insufficiency in elder patients
- Author
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Zhong-Xin, Li, Chen, Xu, Yan-Chun, Li, and Qian-Mei, Sun
- Subjects
Original Article - Abstract
Chronic renal insufficiency and osteoporosis have become very common among old people in China. Hyperparathyroidism caused by renal insufficiency would result in turbulence of bone metabolism and unbalance between serum calcium and phosphorus. The aim of this study is to investigate the BMD, PTH, CT and 25(OH)-Vit’s significance for screening and diagnosing chronic renal insufficiency. In this study, seventy cases with chronic renal insufficiency from Jun. 2010 to Oct. 2013 were selected as the observation group. Meanwhile, another 70 volunteers with normal renal functions were set as the control group. The level of BMD, PTH, CT and 25(OH)-Vit were detected by using ELISA assay. DPX bone density meters (UNIGAMMA X-RAY PLUS) were used for the detection of BMD. The results indicated that BMD levels of the proximal femur (include Troch, Shaft, Total, Neck, Ward) and lumbar vertebra in the observation group were significantly lower while the PTH and CT were significantly higher compared with the control group (P
- Published
- 2014
238. Transgenic Expression of Vitamin D Receptor in Gut Epithelial Cells Ameliorates Spontaneous Colitis Caused by Interleukin-10 Deficiency
- Author
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Weicheng Liu, Tianjing Liu, Li Chen, Jiaolong Wang, Yan Chun Li, Yongyan Shi, and Maya Aharoni Golan
- Subjects
medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Inflammation ,Mice, Transgenic ,Calcitriol receptor ,Mice ,Immune system ,Intestinal mucosa ,Internal medicine ,medicine ,Animals ,Colitis ,Intestinal Mucosa ,Mice, Knockout ,Chemistry ,Gastroenterology ,Interleukin ,Epithelial Cells ,medicine.disease ,Interleukin-10 ,Interleukin 10 ,Cytokine ,Endocrinology ,Gene Expression Regulation ,Receptors, Calcitriol ,medicine.symptom - Abstract
Vitamin D deficiency is common in patients with inflammatory bowel diseases. The vitamin D receptor (VDR) is a nuclear hormone receptor mediating the activity of vitamin D hormone. Our previous studies showed that intestinal epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this activity is independent of non-epithelial immune VDR actions. Interleukin (IL)-10-deficient mouse is a chronic colitis model that develops colitis due to aberrant immune responses. Here we used IL-10 null (IL-10KO) model to assess the anti-colitic activity of epithelial VDR in the setting of an aberrant immune system. We crossed IL-10KO mice with villin promoter-driven human (h) VDR transgenic (Tg) mice to generate IL-10KO mice that carry the hVDR transgene in intestinal epithelial cells (IL-10KO/Tg). IL-10KO and IL-10KO/Tg littermates were studied in parallel and followed for up to 25 weeks. By 25 weeks of age, accumulatively 79 % IL-10KO mice developed prolapse, whereas only 40 % IL-10KO/Tg mice did so (P
- Published
- 2014
239. ATP-citrate lyase is an epigenetic regulator to promote obesity-related kidney injury.
- Author
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Yinyin Chen, Deb, Dilip K., Xiao Fu, Bin Yi, Yumei Liang, Jie Du, Lei He, and Yan Chun Li
- Published
- 2019
- Full Text
- View/download PDF
240. Glial S100A6 Degrades β-amyloid Aggregation through Targeting Competition with Zinc Ions.
- Author
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Zhi-Ying Tian, Chun-Yan Wang, Tao Wang, Yan-Chun Li, and Zhan-You Wang
- Subjects
ALZHEIMER'S disease ,CHRONIC diseases - Abstract
Evidence has been accumulating that zinc ions can trigger β-amyloid (Aβ) deposition and senile plaque formation in the brain, a pathological hallmark of Alzheimer's disease (AD). Chelating zinc inhibits Aβ aggregation and may hold promise as a therapeutic strategy for AD. S100A6 is an acidic Ca
2+ /Zn2+ -binding protein found only in a small number of astrocytes in the normal brain. However, in the AD brain, S100A6 is highly expressed in astrocytes around Aβ plaques. The role of the astrocytic S100A6 upregulation in AD is unknown. In the present study, we examined the effects of S100A6 on Aβ plaques and intracellular zinc levels in a mouse model of AD. Chronic exposure to zinc increased Aβ deposition and S100A6 expression, both reversible by the zinc chelator clioquinol, in the brains of amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice. To examine whether exogenous S100A6 could induce Aβ plaque disaggregation through competition for zinc in vitro, we incubated APP/PS1 mouse brain sections with recombinant human S100A6 protein or co-incubated them with human S100A6-expressing cells. Both treatments efficiently reduced the Aβ plaque burden in situ. In addition, treatment with exogenous S100A6 protected cultured COS-7 cells against zinc toxicity. Our results show for the first time that increased S100A6 levels correlate with both Aβ disaggregation and decrease of Aβ plaque-associated zinc contents in brain sections with AD-like pathology. Astrocytic S100A6 in AD may protect from Aβ deposition through zinc sequestration. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
241. Renin-angiotensin system promotes colonic inflammation by inducing TH17 activation via JAK2/STAT pathway.
- Author
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Lei He, Jie Du, Yinyin Chen, Chunyan Liu, Min Zhou, Adhikari, Sarbani, Rubin, David T., Pekow, Joel, and Yan Chun Li
- Abstract
Previous studies suggest that the renin-angiotensin system (RAS) is a pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (ANG II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn's disease, and colonic renin and ANG II levels were markedly increased in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis. Renin transgenic (RenTg) mice exhibited increased phosphorylation in Janus kinase-2 (JAK2) and signal transducer and activator of transcription1/3 (STAT1/3) within colonic mucosa at baseline and following TNBS induction, suggesting that ANG II promotes colonic inflammation via the JAK2/STAT1/3 pathway. Treatment with pan-JAK inhibitor tofacitinib blocked JAK2 and STAT1/3 phosphorylation, attenuated T helper (T
H )1 and TH 17 responses, alleviated colitis, and prevented death of RenTg mice in TNBS model. ANG II stimulated JAK2/STAT1/3 phosphorylation in both Jurkat T lymphocytes and HCT116 epithelial cells. In vitro polarization assays demonstrated that ANG II directly promoted TH 17 polarization, but not TH 1 polarization, via JAK2/STAT1/3. ANG II stimulation of transforming growth factor-β1 (TGFβ1), IL-6, myosin light chain kinase, and p53 upregulated modulator of apoptosis in HCT116 cells was also mediated by JAK2/STAT1/3. These observations suggest that ANG II promotes TH 17 polarization directly as well as indirectly by inducing production of TH 17-polarizing cytokines (e.g., TGFβ1 and IL-6) from colonic epithelial cells, both via the JAK2/STAT pathway. Therefore, colonic RAS promotes colonic inflammation, at least in part, by stimulating TH 17 activation. NEW & NOTEWORTHY This study demonstrates that the local renin-angiotensin system in the colon is activated in colitis development, which promotes mucosal T helper cell activation through the JAK2/STAT pathway. These observations provide molecular evidence that the renin-angiotensin system is a pathogenic factor for the development of inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
242. Vitamin D receptor activation protects against lipopolysaccharide-induced acute kidney injury through suppression of tubular cell apoptosis.
- Author
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Jie Du, Siqing Jiang, Zhaoxin Hu, Shiqi Tang, Yue Sun, Jinrong He, Zhi Li, Bin Yi, Jianwen Wang, Hao Zhang, and Yan Chun Li
- Abstract
Acute kidney injury (AKI) is a common complication of sepsis characterized by a rapid degradation of renal function. The effect of vitamin D on AKI remains poorly understood. Here, we showed that vitamin D receptor (VDR) activation protects against lipopolysaccharide (LPS)-induced AKI by blocking renal tubular epithelial cell apoptosis. Mice lacking VDR developed more severe AKI than wild-type (WT) control mice after LPS treatment, which was manifested by marked increases in body weight loss and accumulation of serum blood urea nitrogen and creatinine as well as the magnitude of apoptosis of tubular epithelial cells. In the renal cortex, LPS treatment led to more dramatic downregulation of Bcl-2, more robust induction of p53-upregulated modulator of apoptosis (PUMA) and miR-155, and more severe caspase-3 activation in VDR knockout mice compared with WT control mice. Conversely, paricalcitol pretreatment markedly prevented LPS-induced AKI. Paricalcitol ameliorated body weight loss, attenuated serum blood urea nitrogen and creatinine accumulation, blocked tubular cell apoptosis, prevented the suppression of Bcl-2, and reversed PUMA and miR-155 induction and caspase-3 activation in LPS-treated WT mice. In HK2 cells, LPS induced PUMA and miR-155 by activating NF-κB, whereas 1,25(OH)2D3 blocked PUMA and miR-155 induction by repressing NF-κB activation. Both PUMA and miR-155 target Bcl-2 to promote apoptosis; namely, PUMA inhibits Bcl-2 activity, whereas miR-155 promotes Bcl-2 mRNA degradation and inhibits Bcl-2 protein translation. Collectively, these data provide strong evidence that LPS induces tubular cell apoptosis via upregulating PUMA and miR-155, whereas vitamin D/VDR signaling protects against AKI by blocking NF-κB-mediated PUMA and miR-155 upregulation. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
243. Vitamin D/VDR signaling suppresses microRNA-802-induced apoptosis of keratinocytes in oral lichen planus.
- Author
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Bin Zhao, Na Xu, Ran Li, Feiyan Yu, Fang Zhang, Fang Yang, Xuejun Ge, Yan Chun Li, and Jie Du
- Published
- 2019
- Full Text
- View/download PDF
244. Vitamin D and its analogues: Do they protect against cardiovascular disease in patients with kidney disease?
- Author
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Yan Chun Li and Adeera Levin
- Subjects
medicine.medical_specialty ,Population ,030232 urology & nephrology ,Parathyroid hormone ,renin-angiotensin system ,Disease ,030204 cardiovascular system & hematology ,Bioinformatics ,vitamin D deficiency ,03 medical and health sciences ,0302 clinical medicine ,Cardiovascular calcification ,vitamin D analogues ,cardiovascular disease ,Internal medicine ,Vitamin D and neurology ,medicine ,Humans ,Risk factor ,Vitamin D ,education ,education.field_of_study ,mechanisms ,business.industry ,cardiac hypertrophy ,medicine.disease ,3. Good health ,Endocrinology ,inflammation ,Cardiovascular Diseases ,Nephrology ,dialysis ,Kidney Diseases ,business ,chronic kidney disease ,Kidney disease - Abstract
Vitamin D and its analogs: Do they protect against cardiovascular disease in patients with kidney disease ? Background Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, and despite recent advances in hypertension control, anemia management, and dialysis adequacy, mortality remains high. Improved understanding of nontraditional risk factors, including those present at early phases in CKD, may lead to novel therapeutic strategies. CKD has been demonstrated to be an independent risk factor for cardiovascular disease in the general population, but data are lacking as to the associated potential abnormalities that occur in association with reduced glomerular filtration rate (GFR), which may contribute to this increased risk. Data are accumulating regarding the role of abnormalities of calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) in cardiovascular disease. Vitamin D deficiency is present even in the early stages of CKD. Vitamin D plays a central role in calcium-phosphorus homeostasis, regulation of PTH, and formation and maintenance of bone. However, until recently, vitamin D has not been considered to have a biologic role in CKD beyond mineral regulation, or has been considered as a negative factor contributing to soft tissue and cardiovascular calcification. In light of recent observational studies showing an association of vitamin D therapy and survival benefit in hemodialysis patients, the effects of vitamin D on cardiovascular system have become a heavily debated issue. Methods A Medline search was performed to identify relevant literature describing the role of vitamin D in the pathogenesis of cardiovascular disease. Both the experimental and clinical literatures in English were reviewed. Results The accumulating published data demonstrate both associative relationships and mechanisms for biologic plausibility. The following three potential mechanisms may be important for the protective effects of vitamin D against cardiovascular disease mortality: vitamin D can inhibit various aspects of inflammation, which have been established as a key pathogenic mechanism in atherosclerosis; vitamin D exerts an antiproliferative effect on myocardial cell hypertrophy and proliferation, which underlies the pathogenesis of congestive heart failure; and vitamin D acts as a negative endocrine regulator for the renin-angiotensin system, which itself plays an important independent role in hypertension and cardiovascular health. Conclusion Vitamin D deficiency might be an underestimated nonclassical risk factor for cardiovascular disease in CKD. Based on a review of the evidence, from both basic science and clinical studies, this article supports the possible protective role of vitamin D beyond its effect on mineral metabolism, and suggests the need for ongoing evaluation of the role of vitamin D in cardiovascular health in the CKD population.
- Published
- 2005
- Full Text
- View/download PDF
245. Mechanisms of Disease: vitamin D and inflammatory bowel disease
- Author
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Wee Chian Lim, Stephen B. Hanauer, and Yan Chun Li
- Subjects
Vitamin ,T-Lymphocytes ,chemistry.chemical_element ,Inflammation ,Calcium ,Pharmacology ,Calcitriol receptor ,Inflammatory bowel disease ,Monocytes ,chemistry.chemical_compound ,Immune system ,Vitamin D and neurology ,Animals ,Humans ,Medicine ,Vitamin D ,Crohn's disease ,Hepatology ,business.industry ,Gastroenterology ,General Medicine ,Inflammatory Bowel Diseases ,Vitamin D Deficiency ,medicine.disease ,chemistry ,Models, Animal ,medicine.symptom ,business - Abstract
Until recently, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-the active form of vitamin D-was thought to function primarily as a regulator of calcium and phosphate metabolism. More diverse functionality was indicated by the discovery of the vitamin D receptor in tissues that are not involved in calcium and phosphate homeostasis. Detection of the vitamin D receptor in monocytes and activated T cells has sparked interest in the immunomodulatory properties of vitamin D. Here, we review the role of vitamin D in regulation of the immune system, and evidence for its involvement in the pathogenesis of inflammatory bowel disease.
- Published
- 2005
246. Analogs of 1α,25-dihydroxyvitamin D3 as novel inhibitors of renin biosynthesis
- Author
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Juan Kong, Yan Chun Li, Milan R. Uskokovic, and Guilin Qiao
- Subjects
medicine.medical_specialty ,Calcitriol ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Biology ,Biochemistry ,Renin inhibitor ,Cell Line ,Renin-Angiotensin System ,Mice ,Endocrinology ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Vitamin D and neurology ,Animals ,Humans ,Northern blot ,Enzyme Inhibitors ,Molecular Biology ,Cell Biology ,Juxtaglomerular apparatus ,Juxtaglomerular cell ,Juxtaglomerular Apparatus ,medicine.anatomical_structure ,Cell culture ,Molecular Medicine ,medicine.drug - Abstract
The renin-angiotensin system (RAS) plays a central role in the pathogenesis of hypertension. Recently, we discovered that 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] functions as a negative endocrine regulator of renin biosynthesis, which provides a molecular basis to explore the potential of Vitamin D analogs as renin inhibitors to control the RAS. To search for renin-inhibiting Vitamin D analogs, we screened 20 Vitamin D analog compounds using As4.1-hVDR cell (a juxtaglomerular cell line) culture by Northern blot and luciferase reporter assays. We found that the Gemini compounds, which have two side-chains at carbon-20 position, were particularly active in suppressing renin expression. Eight Gemini compounds were identified that were equally or 10- to 100-times more potent than 1,25(OH)(2)D(3) in renin inhibition. These Gemini compounds also potently stimulate 25-hydroxyvitamin D 24-hydroxylase expression in As4.1-hVDR cells. Administration of compound RO-27-5646 [1,25-dihydroxy-21-(3-methyl-3-hydroxy-butyl)-19-nor-cholecalciferol] in mice caused a marked reduction in renal renin mRNA expression without invoking severe hypercalcemia as seen in 1,25(OH)(2)D(3) treatment. These data establish in principle that Vitamin D analogs can indeed inhibit renin expression in vitro and in vivo, and support the notion that low calcemic Vitamin D analogs can potentially be used as therapeutic agents to control the RAS.
- Published
- 2005
247. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems
- Author
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Wenhua Liu, Xin-Min Li, Li Ping Cao, Juan Kong, Songcang Chen, Wei Zheng, Yan Chun Li, Guilin Qiao, David G. Gardner, and Wei Xiang
- Subjects
medicine.medical_specialty ,Captopril ,Physiology ,Endocrinology, Diabetes and Metabolism ,Cardiomegaly ,Biology ,medicine.disease_cause ,Calcitriol receptor ,Renin-Angiotensin System ,Mice ,Atrial natriuretic peptide ,Physiology (medical) ,Internal medicine ,Renin–angiotensin system ,medicine ,Vitamin D and neurology ,Animals ,Endocrine system ,Myocytes, Cardiac ,Antihypertensive Agents ,Mice, Knockout ,Mutation ,Endocrinology ,Circulatory system ,Knockout mouse ,cardiovascular system ,Receptors, Calcitriol ,Atrial Natriuretic Factor - Abstract
Our recent studies suggest that 1,25-dihydroxyvitamin D3functions as an endocrine suppressor of renin biosynthesis. Genetic disruption of the vitamin D receptor (VDR) results in overstimulation of the renin-angiotensin system (RAS), leading to high blood pressure and cardiac hypertrophy. Consistent with the higher heart-to-body weight ratio, the size of left ventricular cardiomyocytes in VDR knockout (KO) mice was markedly increased compared with wild-type (WT) mice. As expected, levels of atrial natriuretic peptide (ANP) mRNA and circulating ANP were also increased in VDRKO mice. Treatment of VDRKO mice with captopril reduced cardiac hypertrophy and normalized ANP expression. To investigate the role of the cardiac RAS in the development of cardiac hypertrophy, the expression of renin, angiotensinogen, and AT-1a receptor in the heart was examined by real-time RT-PCR and immunostaining. In VDRKO mice, the cardiac renin mRNA level was significantly increased, and this increase was further amplified by captopril treatment. Consistently, intense immunostaining was detected in the left ventricle of captopril-treated WT and VDRKO mice by use of an anti-renin antibody. Levels of cardiac angiotensinogen and AT-1a receptor mRNAs were unchanged in the mutant mice. These data suggest that the cardiac hypertrophy seen in VDRKO mice is a consequence of activation of both the systemic and cardiac RAS and support the notion that 1,25-dihydroxyvitamin D3regulates cardiac functions, at least in part, through the RAS.
- Published
- 2005
248. Vitamin D: a negative endocrine regulator of the renin–angiotensin system and blood pressure
- Author
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Guilin Qiao, Wei Zheng, Juan Kong, Milan R. Uskokovic, Wei Xiang, and Yan Chun Li
- Subjects
Vitamin ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Blood Pressure ,Biology ,Biochemistry ,Calcitriol receptor ,Renin-Angiotensin System ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Renin–angiotensin system ,medicine ,Vitamin D and neurology ,Humans ,Vitamin D ,Molecular Biology ,Calcium metabolism ,Angiotensin II receptor type 1 ,Cell Biology ,Vitamin D Deficiency ,chemistry ,Hypertension ,ACE inhibitor ,Molecular Medicine ,Homeostasis ,medicine.drug - Abstract
The renin-angiotensin system (RAS) plays a central role in the regulation of blood pressure, volume and electrolyte homeostasis. Inappropriate activation of the RAS may lead to hypertension. Clinical and epidemiological studies have suggested a correlation between Vitamin D-deficiency and high blood pressure. Our recent studies demonstrate that Vitamin D is a potent endocrine suppressor of renin biosynthesis to regulate the RAS. Mice lacking the Vitamin D receptor (VDR) have elevated production of renin and angiotensin (Ang) II, leading to hypertension, cardiac hypertrophy and increased water intake. These abnormalities can be prevented by treatment with an ACE inhibitor or AT(1) receptor antagonist. Vitamin D repression of renin expression is independent of calcium metabolism, the volume- and salt-sensing mechanisms and the Ang II feedback regulation. In normal mice, Vitamin D-deficiency stimulates renin expression, whereas injection of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] reduces renin synthesis. In cell cultures, 1,25(OH)(2)D(3) directly suppresses renin gene transcription by a VDR-dependent mechanism. Furthermore, we have found that Gemini compounds have more potent renin-suppressing activity than 1,25(OH)(2)D(3). Collectively, our studies reveal a critical role of the Vitamin D endocrine system in the regulation of blood pressure and volume homeostasis, and suggest that low calcemic Vitamin D analogs may potentially be developed into a new class of anti-hypertensive agents to control renin production and blood pressure.
- Published
- 2004
249. Su2055 Pharmacological Blockade or Epithelial Deletion of ADAM17 Suppresses Western Diet Promoted APC Min Mouse Tumorigenesis and Azoxymethane-Induced Colon Cancer
- Author
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Urszula Dougherty, Reba Mustafi, Marc Bissonnette, Sarbani Adhikari, Farhana Sadiq, Loren Joseph, Fatma Ayaloglu-Butun, John Hart, Alessandro Fichera, Michelle Fletcher, Haider Haider, Devkumar Mustafi, Abdurahman Khalil, Joel Pekow, Yan Chun Li, and Vani J. Konda
- Subjects
Hepatology ,Colorectal cancer ,Azoxymethane ,Gastroenterology ,Biology ,medicine.disease ,medicine.disease_cause ,Molecular biology ,Blockade ,chemistry.chemical_compound ,chemistry ,Western diet ,medicine ,Cancer research ,Carcinogenesis - Published
- 2016
250. Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice
- Author
-
Yan Chun Li and Juan Kong
- Subjects
Male ,medicine.medical_specialty ,Captopril ,Physiology ,Submandibular Gland ,Gene Expression ,Angiotensin-Converting Enzyme Inhibitors ,Kidney ,Calcitriol receptor ,Losartan ,Receptor, Angiotensin, Type 1 ,Angiotensin Receptor Antagonists ,Mice ,Physiology (medical) ,Internal medicine ,Renin ,Renin–angiotensin system ,medicine ,Animals ,Receptor ,Aldosterone ,Antihypertensive Agents ,biology ,Chemistry ,Water ,Water-Electrolyte Balance ,Angiotensin II ,Mice, Mutant Strains ,Endocrinology ,Enzyme inhibitor ,ACE inhibitor ,biology.protein ,Receptors, Calcitriol ,Female ,Salts ,medicine.drug - Abstract
We recently showed that vitamin D receptor (VDR) inactivation results in deregulated stimulation of the renin-angiotensin system (RAS). To address further the relation between RAS activation and the abnormalities in electrolyte and volume homeostasis, we studied the effect of the ANG II type I receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on VDR-null mice. Treatment with losartan or captopril normalized the water intake and urine excretion of VDR-null mice. However, the increase in salt excretion in VDR-null mice was not affected by either drug, suggesting that this abnormality is independent of the RAS. Northern blot and immunohistochemical analyses revealed that both drugs caused a drastic stimulation of renin expression in wild-type and VDR-null mice, but renin expression remained much higher in the treated VDR-null mice than in the treated wild-type mice, suggesting that the ANG II feedback mechanism remains intact in the mutant mice. These data firmly established a causative relation between RAS overstimulation and the abnormal volume homeostasis in VDR-null mice and demonstrated that vitamin D repression of renin expression is independent of the ANG II feedback regulation in vivo.
- Published
- 2003
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