11 results on '"Nan-Nan, Li"'
Search Results
2. 1-Indanone retards cyst development in ADPKD mouse model by stabilizing tubulin and down-regulating anterograde transport of cilia
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Xiao-Wei, Li, Jian-Hua, Ran, Hong, Zhou, Jin-Zhao, He, Zhi-Wei, Qiu, Shu-Yuan, Wang, Meng-Na, Wu, Shuai, Zhu, Yong-Pan, An, Ang, Ma, Min, Li, Ya-Zhu, Quan, Nan-Nan, Li, Chao-Qun, Ren, and Bao-Xue, Yang more...
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Pharmacology ,Pharmacology (medical) ,General Medicine - Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease. Cyst development in ADPKD involves abnormal epithelial cell proliferation, which is affected by the primary cilia-mediated signal transduction in the epithelial cells. Thus, primary cilium has been considered as a therapeutic target for ADPKD. Since ADPKD exhibits many pathological features similar to solid tumors, we investigated whether targeting primary cilia using anti-tumor agents could alleviate the development of ADPKD. Twenty-four natural compounds with anti-tumor activity were screened in MDCK cyst model, and 1-Indanone displayed notable inhibition on renal cyst growth without cytotoxicity. This compound also inhibited cyst development in embryonic kidney cyst model. In neonatal kidney-specific Pkd1 knockout mice, 1-Indanone remarkably slowed down kidney enlargement and cyst expansion. Furthermore, we demonstrated that 1-Indanone inhibited the abnormal elongation of cystic epithelial cilia by promoting tubulin polymerization and significantly down-regulating expression of anterograde transport motor protein KIF3A and IFT88. Moreover, we found that 1-Indanone significantly down-regulated ciliary coordinated Wnt/β-catenin, Hedgehog signaling pathways. These results demonstrate that 1-Indanone inhibits cystic cell proliferation by reducing abnormally prolonged cilia length in cystic epithelial cells, suggesting that 1-Indanone may hold therapeutic potential to retard cyst development in ADPKD. more...
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- 2022
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3. Brain network topology and future development of freezing of gait in Parkinson’s disease: a longitudinal study
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Jun-Ying Li, Jiaxin Peng, Chao-Lan Chen, Li-Ren Duan, Qiyong Gong, Xueling Suo, Du Lei, Rong Peng, and Nan-Nan Li
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Cerebellum ,medicine.medical_specialty ,Longitudinal study ,Neurology ,Parkinson's disease ,genetic structures ,Gait Disturbance ,business.industry ,medicine.disease ,Topology ,Gait ,Visual cortex ,medicine.anatomical_structure ,medicine ,Neurology (clinical) ,business ,Centrality - Abstract
Freezing of gait (FOG) is a common disabling gait disturbance in Parkinson’s disease (PD). The objectives of this study were to explore alterations in the topological organization of whole-brain functional networks in patients with PD who will develop FOG. We recruited 20 patients with PD who developed FOG (PD-FOGt) during a 5-year follow-up period, 20 patients with PD who did not developed FOG (PD-FOGn) within the follow-up period, and 20 healthy control subjects. Using graph theory approaches, we performed a comparative analysis of the topological organization of whole-brain functional networks among the groups, and further explored their potential relationships with latency to develop FOG. At baseline, the global topological properties of functional brain networks in PD-FOGt and PD-FOGn showed no abnormalities. Additionally, regarding regional topological properties, compared with PD-FOGn patients, PD-FOGt patients exhibited decreased nodal centrality in the left middle frontal gyrus (MFG). Although there were no significant differences compared with PD-FOGn patients, the PD-FOGt group exhibited the lowest nodal centrality values in the frontal cortex (left gyrus rectus), and visual cortex (bilateral inferior occipital gyrus and left fusiform gyrus), and the highest nodal centrality values in the cerebellum (vermis_6) among the three groups. However, no relationship was found between the nodal centrality in above brain regions and latency to develop FOG. This study demonstrates the disrupted regional topological organization might contribute to the future development of FOG in PD patients, especially associated with damage to the left MFG. more...
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- 2021
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4. A compound heterozygous PINK1-associated juvenile Parkinson’s disease with pregnancy in Chinese
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Chao-Lan Chen, Jiaxin Peng, Rong Peng, Jun-Ying Li, Nan-Nan Li, Ling Wang, and Li-Ren Duan
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Levodopa ,Pregnancy ,Pediatrics ,medicine.medical_specialty ,Benserazide ,Parkinson's disease ,business.industry ,Nonsense mutation ,Compound heterozygosity ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Neurology ,medicine ,030212 general & internal medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Postpartum period ,Exome sequencing ,medicine.drug - Abstract
PINK1 mutations are the second most common cause of recessive, early-onset Parkinson’s disease (EOPD), of which 15% are cases of juvenile PD. PD is a progressive neurological disease that primarily affects middle-aged and older people. Thus PD patients experiencing pregnancy is uncommon, especially in patients with juvenile PD caused by PINK1 mutations. We are first to report a woman from a Chinese family diagnosed with sporadic juvenile PD and treated with levodopa/benserazide throughout pregnancy. Whole exome sequencing was performed on this patient, and pedigree verification was performed on her parents. This patient received levodopa/benserazide treatment with regular outpatient follow-up exams. Whole exome sequencing and Sanger sequencing identified a heterozygous nonsense mutation (c.1474C > T, p.R492X) and a splicing mutation (c.1488 + 1G > A) that were in exon 7 of the PINK1 gene, co-segregating with the PD phenotype and exhibiting an autosomal recessive pattern. With regular outpatient follow-up exams, this patient delivered a healthy boy without complications. Her PD symptoms were stable with the levodopa/benserazide treatment throughout her pregnancy except in the postpartum period. Our findings further demonstrated the safety of levodopa with dopa-decarboxylase treatment in PINK1-associated juvenile PD during pregnancy. more...
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- 2021
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5. Altered spontaneous brain activity in essential tremor with and without resting tremor: a resting-state fMRI study
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Du Lei, Rong Peng, Ling Wang, Xueling Suo, Qiyong Gong, Jing-Xi, Jun-Ying Li, Li-Ren Duan, Nan-Nan Li, Jiaxin Peng, Zhong-Jiao Lu, and Yi-Jiang
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endocrine system diseases ,Brain activity and meditation ,Essential Tremor ,Biophysics ,Hippocampus ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Limbic system ,Tremor ,Basal ganglia ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Resting tremor ,Brain Mapping ,Radiological and Ultrasound Technology ,Resting state fMRI ,medicine.diagnostic_test ,Essential tremor ,business.industry ,Brain ,medicine.disease ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Functional magnetic resonance imaging ,business ,Neuroscience - Abstract
Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naive patients of rET and ETwr. We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed. Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum. Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease. more...
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- 2020
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6. Patterns of intrinsic brain activity in essential tremor with resting tremor and tremor-dominant Parkinson’s disease
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Jing Xi, Ling Wang, Xueling Suo, Li-Ren Duan, Yi Jiang, Nan-Nan Li, Rong Peng, Jiaxin Peng, Qiyong Gong, Zhong-Jiao Lu, Jun-Ying Li, and Du Lei
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medicine.medical_specialty ,Parkinson's disease ,Essential Tremor ,Cognitive Neuroscience ,050105 experimental psychology ,03 medical and health sciences ,Behavioral Neuroscience ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,Tremor ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,Resting tremor ,Default mode network ,Supplementary motor area ,Essential tremor ,business.industry ,Putamen ,05 social sciences ,Brain ,Precentral gyrus ,Parkinson Disease ,medicine.disease ,SMA ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,medicine.anatomical_structure ,Neurology ,Cardiology ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson’s disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, and the correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p more...
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- 2020
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7. Deformation Mechanism and Hot Workability of Extruded Magnesium Alloy AZ31
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Jian Wang, Jing Bai, Hongbiao Dong, Kai Yan, Zhaoyang Jin, and Nan-Nan Li
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010302 applied physics ,Materials science ,Metals and Alloys ,02 engineering and technology ,Plasticity ,Strain rate ,Flow stress ,021001 nanoscience & nanotechnology ,01 natural sciences ,Industrial and Manufacturing Engineering ,Stress (mechanics) ,Deformation mechanism ,0103 physical sciences ,Dynamic recrystallization ,Composite material ,Deformation (engineering) ,Magnesium alloy ,0210 nano-technology - Abstract
Using the flow stress curves obtained by Gleeble thermo-mechanical testing, the processing map of extruded magnesium alloy AZ31 was established to analyze the hot workability. Stress exponent and activation energy were calculated to characterize the deformation mechanism. Then, the effects of hot deformation parameters on deformation mechanism, microstructure evolution and hot workability of AZ31 alloy were discussed. With increasing deformation temperature, the operation of non-basal slip systems and full development of dynamic recrystallization (DRX) contribute to effective improvement in hot workability of AZ31 alloy. The influences of strain rate and strain are complex. When temperature exceeds 350 °C, the deformation mechanism is slightly dependent of the strain rate or strain. The dominant mechanism is dislocation cross-slip, which favors DRX nucleation and grain growth and thus leads to good plasticity. At low temperature (below 350 °C), the deformation mechanism is sensitive to strain and strain rate. Both the dominant deformation mechanism and inadequate development of DRX deteriorate the ductility of AZ31 alloy. The flow instability mainly occurs in the vicinity of 250 °C and 1 s−1. more...
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- 2017
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8. Controlling Flow Instability in Straight Spur Gear Forging Using Numerical Simulation and Response Surface Method
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Jing-Xin Chen, Nan-Nan Li, Kai Yan, Zhenshan Cui, Dong-lai Wei, and Zhaoyang Jin
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010302 applied physics ,Materials science ,Computer simulation ,business.industry ,Metals and Alloys ,02 engineering and technology ,Structural engineering ,Deformation (meteorology) ,Flow stress ,021001 nanoscience & nanotechnology ,01 natural sciences ,Industrial and Manufacturing Engineering ,Finite element method ,Forging ,Deformation mechanism ,0103 physical sciences ,Dynamic recrystallization ,0210 nano-technology ,Reduction (mathematics) ,business - Abstract
Workability domain without the onset of flow instability was developed by numerical simulation and response surface method (RSM) for complex-shaped straight spur gear forging. The processing map of AZ31B alloys was calculated from flow stress curves and then integrated with the finite element model to simulate the distribution of flow instability in the straight spur gear undergoing isothermal forging process. Occurrence of flow instability depends on forging temperature, punch velocity and billet reduction. Taking forging temperature and punch velocity as design variables, while billet reduction as response variable, RSM of workability domain was established. Analysis of variance indicates that forging temperature is the most significant factor determining the appearance of flow instability in the forged gear. Flow instability is easier to take place at lower temperatures of 250 and 300 °C in the early stage of forging but at higher temperatures of 350 and 400 °C in the later stage of forging, which is attributed to different deformation mechanisms and dynamic recrystallization behaviors at different temperatures or deformation levels. Meanwhile, increasing punch velocity further reduces the workability of the forged gear. Four different processing paths were chosen to carry out the gear forging trials. Visual observations and metallographic examinations demonstrate that the developed workability domain contributes to optimization of forging parameters. more...
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- 2017
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9. Isolation and characterization of regulators involved in PHOT1-mediated inhibition of hypocotyl phototropism in Arabidopsis
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Xiao Zhang, Nan-Nan Li, Zi-Yi Zhu, Qing-Ping Zhao, Guo Xining, and Xiang Zhao
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0106 biological sciences ,0301 basic medicine ,animal structures ,Mutant ,Mutagenesis (molecular biology technique) ,Plant Science ,01 natural sciences ,Biochemistry ,Hypocotyl ,03 medical and health sciences ,Arabidopsis ,Botany ,Genetics ,Molecular Biology ,Gene ,Ecology, Evolution, Behavior and Systematics ,Phototropism ,biology ,Cell Biology ,biology.organism_classification ,Phenotype ,Cell biology ,030104 developmental biology ,Animal Science and Zoology ,Function (biology) ,010606 plant biology & botany - Abstract
Blue light receptor phot1 and phot2 regulate hypocotyl phototropism induced by high intensity blue light (HBL) in functional redundancy. The phenotype of rpt2 single mutant is similar with double mutant phot1phot2 that lost phototropism, but rpt2phot1 double mutant shows normal phototropic response, which indicating that phot1 has dual opposite function with inducing and inhibiting hypocotyls phototropism. However, the mechanism of phot1-mediated inhibition remains to be elucidated. Here, we screened mutants with phototropism from EMS mutagenesis of rpt2 and cloned the gene P1SA1 (underlinePhototropinunderline1 underlineSignaling underlineAssociated underline1), which maybe locate downstream of phot1 and function in regulating phot1-mediated inhibitory response. The rpt2 p1sa1 mutant shows normal phototropism to unilateral HBL and overexpression of PHOT1 in rpt2 p1sa1 lost hypocotyl phototropism again, which indicated that P1SA1 may be the allelic of PHOT1. These results will open new perspectives about the screening and identification of genes involved in phot1-mediated inhibitory response, and provide theoretical basis for the self-regulation mechanism of plant to reduce high light damage. more...
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- 2017
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10. Genetic analysis of FGF20 in Chinese patients with Parkinson’s disease
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Zhong-Jiao Lu, Lan Cheng, Nan-Nan Li, Xiao-Yi Sun, Rong Peng, Jun-Ying Li, and Ling Wang
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Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Parkinson's disease ,Genotype ,Dermatology ,Disease ,Lower risk ,Polymorphism, Single Nucleotide ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Gene Frequency ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Young adult ,Allele ,Allele frequency ,Aged ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Parkinson Disease ,General Medicine ,Middle Aged ,medicine.disease ,Fibroblast Growth Factors ,Psychiatry and Mental health ,030104 developmental biology ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Sequence variants in fibroblast growth factor 20 (FGF20) have been reported to be associated with Parkinson's disease (PD). We genotyped the rs591323 variant in a total of 2220 Han Chinese subjects, including 1051 patients with sporadic PD and 1169 controls, to investigate the association between rs591323 and the risk of PD. In addition, we also conducted a stratified analysis according to age at onset of PD and compared the clinical characteristics of AA + AG subjects with GG subjects. In this study, we confirmed that the A allele of rs591323 in FGF20 reduces the risk of developing sporadic PD (P = 0.013). Additionally, subjects with the AA + AG genotype have a reduced risk compared to individuals with the GG genotype (P = 0.024). This association was significant among females (P = 0.036), but was not significant among males (P = 0.266). Furthermore, no significant association was observed among either the early-onset PD group (P = 0.051) or the late-onset PD group (P = 0.187). Moreover, we demonstrated that the AA + AG subjects could not be distinguished from the GG subjects based on their clinical features. Our study is the first to demonstrate that FGF20 (rs591323) is associated with a lower risk of PD in a Southern Han Chinese population from mainland China. more...
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- 2017
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11. GWAS-linked GAK locus in Parkinson’s disease in Han Chinese and meta-analysis
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Jin-Hong Zhang, Nan-Nan Li, Rong Peng, Dong-Mei Zhao, Xue-Ye Mao, Eng-King Tan, and Xue-Li Chang
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Adult ,Male ,Oncology ,China ,medicine.medical_specialty ,Adolescent ,Genotype ,Population ,Locus (genetics) ,Genome-wide association study ,Protein Serine-Threonine Kinases ,Biology ,Polymorphism, Single Nucleotide ,Young Adult ,Asian People ,Gene Frequency ,Internal medicine ,Genetics ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Age of Onset ,education ,Genetics (clinical) ,Aged ,Genetic association ,Aged, 80 and over ,education.field_of_study ,Intracellular Signaling Peptides and Proteins ,Parkinson Disease ,Middle Aged ,Minor allele frequency ,Case-Control Studies ,Female ,Age of onset ,Genome-Wide Association Study - Abstract
Genome-wide association studies of Parkinson’s disease (PD) have recently identified a new susceptibility locus GAK (PARK17) (rs1564282 variant) in subjects of European ancestry. Its role in other races is still unclear. The potential differences of the clinical characteristics between carriers and non-carriers have not been examined in detail. Using a case–control methodology, we analyzed the GAK rs1564282 variant in an ethnic Han Chinese population and conducted a meta-analysis combining our result and available published data. A total of 1,574 ethnic Han Chinese study subjects comprising 812 sporadic PD patients and 762 control individuals were included. The minor allele frequency was significantly different at SNP rs1564282 between the cases and the controls (OR = 1.59, 95% CI = 1.09, 1.69, P = 0.007) in the overall PD population. Subjects with CT + TT genotypes have an increased risk (OR = 1.34, 95% CI = 1.05, 1.72, P = 0.017) compared to those with CC genotype. A meta-analysis revealed that the frequency of carrier's genotypes was significantly higher in PD than in control subjects (OR = 1.31, 95% CI = 1.19, 1.44, P more...
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- 2011
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