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Curcumin inhibits endoplasmic reticulum stress induced by cerebral ischemia-reperfusion injury in rats
Zhu, HY;Fan, YX;Sun, HY;Chen, LY;Man, X
EXPERIMENTAL AND THERAPEUTIC MEDICINE 2017年 14卷5期 页码:4047-4052
UNFOLDED PROTEIN RESPONSE; NF-KAPPA-B; ER STRESS; CELL-DEATH; ALZHEIMERS-DISEASE; ARTERY OCCLUSION; DOWN-REGULATION; BRAIN ISCHEMIA; AGGREGATION; ACTIVATION
The aim of the present study was to observe the dynamic changes of the growth arrest and DNA damage-inducible 153 (GADD153) gene and caspase-12 in the brain tissue of rats with cerebral ischemia-reperfusion injury (CIRI) and the impact of curcumin pretreatment. A total of 60 rats were randomly divided into the normal group (N), the sham operation group (S), the dimethyl sulfoxide control group (D) and the curcumin treatment group (C). For group D and C, 12 (T1), 24 (T2) and 72 h (T3) of reperfusion were performed after 2 h ischemia. The expression levels of GADD153 and caspase-12 in the brain tissue were detected and compared among the groups by immunohistochemistry, immunofluorescence double staining and western blotting. The expression levels of GADD153 and caspase-12 were increased at T1compared with groups N and S, and the expression of caspase-12 peaked at T2 in group D, while GADD153 was increased until T3 in group D. Compared with group D, the expression levels of GADD153 and caspase-12 in group C at T2 and T3 were significantly decreased (P<0.05). Endoplasmic reticulum stress is involved in the pathological process of CIRI. Curcumin may decrease the expression levels of the above two factors, thus exhibiting protective effects against CIRI in rats.
Spectrum construction of differentially expressed circular RNAs in patients with leukoaraiosis and function analysis of differentially expressed genes
Mi, T;Luo, CJ;Hu, YW;Qu, CQ;Wang, X;Guo, SG;Du, YF
MOLECULAR MEDICINE REPORTS 2017年 16卷3期 页码:2563-2569
PRESSURE
Circular RNAs (circRNAs) are class of endogenous RNAs that have a role in the regulation of gene expression. The present study aimed to investigate the diagnostic value and role of circRNA in the pathogenesis of leukoaraiosis (LA). The present study performed Arraystar Human circRNA Array analysis of 6 samples from LA cases and 6 samples from control cases. Differentially expressed (DE) circRNAs between two samples were identified through fold-change (>1.5-fold) screening. Afterwards, based on DE circRNAs, the gene ontology (GO) analysis of upregulated DE genes identified from DE circRNAs demonstrated that DE genes were primarily associated with cellular metabolic processes, membrane-bound organelles and binding. However, none were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Downregulated DE genes were enriched in cellular localization, cytoplasm and kinase binding. For the KEGG pathways, the downregulated DE genes were primarily associated with the insulin signaling pathway. The results of the present study indicated that the DE genes from differently expressed circRNAs may have an important role in the pathogenesis of LA and may be a novel targfet for further research.
Loss of succinyl-CoA synthase ADP-forming beta subunit disrupts mtDNA stability and mitochondrial dynamics in neurons
Zhao, YJ;Tian, J;Sui, SM;Yuan, XD;Chen, H;Qu, CQ;Du, YF;Guo, L;Du, H
SCIENTIFIC REPORTS 2017年 7卷
ALZHEIMERS-DISEASE; LIGASE DEFICIENCY; MAMMALIAN-CELLS; PROTEIN DLP1; SYNTHETASES; EXPRESSION; MUTATIONS; DEPLETION; FISSION; FUSION
Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS ADP-forming beta subunit (SCS A-beta) is linked to lethal infantile Leigh or leigh-like syndrome. However, the impacts of SCS A-beta deficiency on mitochondria specifically in neurons have not yet been comprehensively investigated. Here, by down-regulating the expression levels of SCS A-beta in cultured mouse neurons, we have found that SCS A-beta deficiency induces severe mitochondrial dysfunction including lowered oxidative phosphorylation (OXPHOS) efficiency, increased mitochondrial superoxide production, and mtDNA depletion as well as aberrations of mitochondrial fusion and fission proteins, which eventually leads to neuronal stress. Our data also suggest that the deregulation of mitochondrial nucleoside diphosphate kinase (NDPK) together with defects in mitochondrial transcription factors including mitochondrial DNA pol gamma and Twinkle contribute to SCS A-beta deficiency-mediated mtDNA instability. Furthermore, we have found that SCS A-beta deficiency has detrimental influence on neuronal mitochondrial dynamics. Put together, the results have furnished our knowledge on the pathogenesis of SCS A-beta deficiency-related mitochondrial diseases and revealed the vital role of SCS A-beta in maintaining neuronal mitochondrial quality control and neuronal physiology.
Cerebral gray matter volume reduction in subcortical vascular mild cognitive impairment patients and subcortical vascular dementia patients, and its relation with cognitive deficits
Li, MY;Meng, Y;Wang, MZ;Yang, S;Wu, H;Zhao, B;Wang, GB
BRAIN AND BEHAVIOR 2017年 7卷8期
BRAIN; DISEASE; LEUKOARAIOSIS; ISCHEMIA; CRITERIA; DECLINE; STROKE
Introduction: Subcortical vascular mild cognitive impairment (svMCI) is the predementia stage of subcortical vascular dementia (SVaD). The aim of this research is to explore and compare cerebral gray matter (GM) volume reduction in svMCI patients and SVaD patients, and to investigate the relationship between cerebral GM volume reduction and cognitive deficits.;-;Methods: Thirty one svMCI patients, 29 SVaD patients, and 31 healthy controls were recruited in our research. They conducted neuropsychological tests and brain structural magnetic resonance imaging (MRI) examination. To detect cerebral GM volume reduction in svMCI patients and SVaD patients, we used statistical parametric mapping 8-voxel-based morphometry 8 (SPM8-VBM8) method to analyze MRI data. To detect the relationship between cerebral GM volume reduction and cognitive deficits, multiple linear regression analysis was used.;-;Results: Compared with healthy controls, svMCI patients showed cerebral GM volume reduction in hippocampus and parahippocampal gyrus, insula and superior temporal gyrus. Compared with healthy controls, SVaD patients exhibited more atrophy which encompasses all of these areas plus anterior and middle cingulate, inferior temporal gyrus, orbitofrontal cortex, and superior frontal gyrus. In svMCI patients, cerebral GM volume reduction correlated with memory loss, attention dysfunction, and language dysfunction; in SVaD patients, besides those cognitive deficits, cerebral GM volume reduction correlated with more cognitive impairments, including executive dysfunction, neuropsychiatric symptom, and depression.;-;Conclusions: Our findings prove that both svMCI patients and SVaD patients exhibit cerebral GM volume reduction and there may exist a hierarchy between svMCI and SVaD, and cerebral GM volume reduction in both svMCI patients and SVaD patients correlates with cognitive deficits, which can help us understand the mechanism of cognitive impairments in svMCI patients and SVaD patients, and diagnose SVaD at its early stage.
Subtypes evaluation of motor dysfunction in Parkinson's disease using neuromelanin-sensitive magnetic resonance imaging
Xiang, YY;Gong, T;Wu, JW;Li, JF;Chen, Y;Wang, YX;Li, S;Cong, L;Lin, YT;Han, YX;Yin, L;Wang, GB;Du, YF
NEUROSCIENCE LETTERS 2017年 638卷 页码:145-150
SUBSTANTIA-NIGRA; PROGRESSION; ASYMMETRY; NEURONS; IRON; MRI
Parkinson's disease (PD) is characterized by the loss of neuromelanin (NM)-containing neurons in the substantia nigra pars compacta (SNc), and it is divided into two motor subtypes: the postural instability gait difficulty (PIGD) and the tremor dominant (TD) subtypes. With NM-sensitive Magnetic Resonance Imaging (NM-MRI), investigators have been able to accurately detect signal attenuation in SNc of PD; however, the difference of NM loss between PIGD and TD subtypes is still unclear. Thus, the aim of this study was to evaluate the differences in NM-MRI between PD motor subtypes. PD patients were classified into PIGD (n= 14) and TD groups (n= 9); 20 age and sex matched controls were recruited. We compared the signal intensity contrast ratios in medial and lateral regions of the SNc using NM-MRI in PIGD, TD, and controls, respectively. Remarkable signal attenuation was observed in the lateral part of SNc in PD when compared with the controls, and we were able to detect more severe signal attenuation in the medial part of SNc in PIGD patients in comparison with that in the TD group. Also, the medial part of SNc, ipsilateral to the most clinically affected side, showed the highest power to discriminate the PD motor subtypes (AUC, 81%; sensitivity, 71.4%; specificity, 77.8%). Our results indicated a potential diagnostic value of NM-MRI to discriminate the PD motor subtypes, providing new evidence for the neuropathology-based differences between the two subtypes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Brainstem injury associated with supratentorial lesions is revealed by electronystagmography of the cold caloric reflex test
Fu, QZ;Qi, ZG;Yang, RR;Cheng, K;Yang, YT;Xie, P
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH 2017年 9卷5期 页码:2119-+
DEATH; HERNIATION; MOVEMENTS; NYSTAGMUS; DIAGNOSIS; ISCHEMIA
To explore the brainstem injury associated with supratentorial lesions, we conducted analysis of ICP levels and detected ENG parameters by using the cold caloric reflex test and histopathological examinations of the brainstem. Rat model of intracerebral hemorrhage was well-established in the study of supratentorial lesions of varying severities (n=210). Intracerebral pressure monitoring and electronystagmography of the cold caloric reflex test were simultaneously performed in animals. Apoptotic, immunohistochemical, and histopathological changes in different segments of the brainstem were investigated at various time intervals. Electronystagmography parameters were analyzed by cold caloric reflex test. The result showed that the increase of intracerebral pressure was correlated with lesion severity including elevating levels and rostral-caudal progression of neuronal apoptosis, demyelination, N-methyl-D-aspartate cell receptor down-regulation (r=0.815), and histopathological changes. Mutiple discrimination analysis of electronystagmography parameters presented a diagnostic accuracy rate of 79.5% in localizing brainstem injury. In conclusion, our data demonstrated that electronystagmography monitoring along with the cold caloric reflex test performed a favorable effect on the estimation of brainstem injury in ICH rat model, which provided a potential bedside diagnostic tool to assess and predict the progress of supratentorial lesion patient in future.
Physcion 8-O-beta-glucopyranoside suppresses the metastasis of breast cancer in vitro and in vivo by modulating DNMT1
Chen, X;Guo, H;Li, FX;Fan, D
PHARMACOLOGICAL REPORTS 2017年 69卷1期 页码:36-44
DNA METHYLTRANSFERASE 1; ACTIVATED PROTEIN-KINASE; CELL-CYCLE ARREST; EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTION FACTOR SOX2; LUNG-CANCER; COLORECTAL-CANCER; RUMEX-JAPONICUS; INHIBITION; EXPRESSION
Background: The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-beta-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis.;-;Methods: Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of beta-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR.;-;Results: The present study showed that PG suppressed the migration, invasion, and EMT of breast cancer cells MDA-MB-231 in a dose-dependent manner. The results also revealed that impairment of the metastatic potential caused by PG was associated with the activation of AMPK and downregulation of both DNMT1 and Sp1. Moreover, the data from the in vivo model also supported the in vitro findings, which showed that inhibition of metastasis by PG was associated with the downregulation of DNMT1 and Spl as well as increased level of phosphorylated AMPK.;-;Conclusion: The present study showed that PG could suppress the metastasis of breast cancer, which highlighted a novel pharmacological application of this compound. Given the aggressive properties of breast cancer, the current study suggests that PG can serve as a safe therapeutic agent for suppressing breast cancer metastasis, although additional data is necessitated. (C) 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.
Relationship between dyslipidemia and carotid plaques in ahigh-stroke-risk population in Shandong Province, China
Mi, T;Sun, SW;Zhang, GQ;Carora, Y;Du, YF;Guo, SG;Cao, MF;Zhu, Q;Wang, YX;Sun, QJ;Wang, X;Qu, CQ
BRAIN AND BEHAVIOR 2016年 6卷6期
INTIMA-MEDIA THICKNESS; CARDIOVASCULAR-DISEASE; CHOLESTEROL; WOMEN; ATHEROSCLEROSIS; PREDICTION; AGE
IntroductionThe precise associations between stroke and carotid plaques and dyslipidemia are unclear. This population-based study aimed to examine the relationship between carotid plaques and dyslipidemia in a high-stroke-risk population.;-;MethodsUltrasonography of left and right carotid arteries was conducted in 22,222 participants in a second screening survey of individuals with high stroke risk. Subjects were divided into two groups according to the presence or absence of carotid plaques. Blood TC (total cholesterol), TG (total triglycerides), and LDL-C (low-density lipoprotein cholesterol) levels were recorded.;-;ResultsMultivariate logistic regression analysis, controlled for gender, age, education, geographic region, smoking, exercise, and overweight (Model 2), identified TG as a predictor of carotid-plaque risk (odds ratio [OR]=1.109, 95% confidence interval [CI]: 1.038-1.185, P=0.002), and the association between carotid plaques and LDL-C (OR=0.967, 95%CI: 0.949-0.994, P=0.019) was less significant, whereas there was no association between carotid plaques and TC (OR=1.002, 95%CI: 0.932-1.007, P=0.958). After additional adjustment for hypertension, diabetes, and atrial fibrillation (Model 3), TG remained a risk factor for carotid plaques (OR=1.086, 95%CI: 1.016-1.161, P=0.015), but no associations were observed between carotid plaques and LDL-C (OR=0.972, 95%CI: 0.910-1.038, P=0.394) or TC (OR=1.003, 95%CI: 0.933-1.079, P=0.928). Only the association between TG and carotid plaques (OR=1.084, 95%CI: 1.014-1.159, P=0.017) was independent of all covariates (covariates in Model 3 plus history of stroke or transient ischemic attack, and stroke family history) in Model 4.;-;ConclusionThese findings indicate that TG was an independent risk factor for carotid plaques in high-risk population for stroke, whereas LDL-C and TC were not associated with the appearance of carotid plaques independently.
Differences in the distribution of risk factors for stroke among the high-risk population in urban and rural areas of Eastern China
Mi, T;Sun, SW;Du, YF;Guo, SG;Cong, L;Cao, MF;Sun, QJ;Sun, Y;Qu, CQ
BRAIN AND BEHAVIOR 2016年 6卷5期
CORONARY-HEART-DISEASE; ATRIAL-FIBRILLATION; CARDIOVASCULAR-DISEASES; ISCHEMIC-STROKE; MORTALITY; ADULTS; PREVALENCE; DYSLIPIDEMIA; HYPERTENSION; METAANALYSIS
Introduction: Considering the program of screening for risk factors of stroke in Eastern China, the aim of this study was to compare the distribution differences in risk factors for stroke among the high-risk population living in urban and rural areas. Methods: A total of 231,289 residents were screened and basic information collected. Risk factors for stroke among the high-risk population were compared between the urban and rural groups. Results: A total of 117,776 high-risk residents from urban areas and 113,513 from rural areas were included in the analysis. The prevalence of hypertension was much higher in rural areas (73.3%) than that in urban areas (64.1%). Dyslipidemia (48.9% vs. 26.9%), sport lack (46.6% vs. 31.6%), diabetes mellitus (21.3% vs. 16.5%), and atrial fibrillation (18.7% vs. 9.8%) were more prevalent in the urban group, while smoking (26.5% vs. 28.8%), previous stroke (10.1% vs. 16.9%), and transient ischemic attack (20.9% vs. 24.6%) were less prevalent. Conclusion: Among the population at high risk of stroke, there were significant differences in the distribution of the following risk factors between the urban and rural groups: hypertension, atrial fibrillation, dyslipidemia, lack of physical exercise, and a previous stroke.
Deregulation of mitochondrial F1FO-ATP synthase via OSCP in Alzheimer's disease
Beck, SJ;Guo, L;Phensy, A;Tian, J;Wang, L;Tandon, N;Gauba, E;Lu, L;Pascual, JM;Kroener, S;Du, H
NATURE COMMUNICATIONS 2016年 7卷
CYTOCHROME-C-OXIDASE; PERMEABILITY TRANSITION PORE; SENSITIVITY CONFERRING PROTEIN; F1F0 ATP SYNTHASE; AMYLOID-BETA; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; MOUSE MODEL; A-BETA; ENTORHINAL CORTEX
F1FO-ATP synthase is critical for mitochondrial functions. The deregulation of this enzyme results in dampened mitochondrial oxidative phosphorylation (OXPHOS) and activated mitochondrial permeability transition (mPT), defects which accompany Alzheimer's disease (AD). However, the molecular mechanisms that connect F1FO-ATP synthase dysfunction and AD remain unclear. Here, we observe selective loss of the oligomycin sensitivity conferring protein (OSCP) subunit of the F1FO-ATP synthase and the physical interaction of OSCP with amyloid beta (A beta) in the brains of AD individuals and in an AD mouse model. Changes in OSCP levels are more pronounced in neuronal mitochondria. OSCP loss and its interplay with A beta disrupt F1FO-ATP synthase, leading to reduced ATP production, elevated oxidative stress and activated mPT. The restoration of OSCP ameliorates A beta-mediated mouse and human neuronal mitochondrial impairments and the resultant synaptic injury. Therefore, mitochondrial F1FO-ATP synthase dysfunction associated with AD progression could potentially be prevented by OSCP stabilization.
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