50 results on '"Qi Zhu"'
Search Results
2. Overexpression and Biological Function of Ubiquitin-Specific Protease 42 in Gastric Cancer.
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Kun Hou, Zhenya Zhu, Yong Wang, Chunhui Zhang, Shiyong Yu, Qi Zhu, and Bo Yan
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Medicine ,Science - Abstract
Ubiquitin-specific protease 42 (USP42) is a member of deubiquitinating enzymes (DUBs). The alterations of DUBs are implicated in the pathogenesis of a wide variety of tumors. However, there are few studies on the expression and biological function of USP42 in gastric cancer (GC). Here, the expression levels of USP42 were significantly higher in GC tissues than in non-tumorous tissues. USP42 expression was significantly correlated with tumor size, TNM stage, lymph node metastasis and overall survival of patients with GC. Moreover, USP42 silencing in two GC cell lines, AGS and MKN-45, notably inhibited cell proliferation, but stimulated G1 phase arrest. The proteins promoting cell cycle progression (Cyclin D1, Cyclin E1 and PCNA) were down-regulated in USP42-suppressed cells. Moreover, inhibition of USP42 in GC cells impaired cell invasion via affecting the expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) regulators. In conclusion, USP42 overexpression could be a potential prognostic marker for GC, regulate the survival and invasive properties of GC, and may represent a novel therapeutic molecular target for this tumor.
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- 2016
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3. Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.
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Baiwen Li, Xinjian Wan, Qi Zhu, Lei Li, Yue Zeng, Duanmin Hu, Yueqin Qian, Lungen Lu, Xingpeng Wang, and Xiangjun Meng
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Medicine ,Science - Abstract
Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.
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- 2013
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4. Motor training increases the stability of activation patterns in the primary motor cortex.
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Yi Huang, Zonglei Zhen, Yiying Song, Qi Zhu, Song Wang, and Jia Liu
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Medicine ,Science - Abstract
Learning to be skillful is an endowed talent of humans, but neural mechanisms underlying behavioral improvement remain largely unknown. Some studies have reported that the mean magnitude of neural activation is increased after learning, whereas others have instead shown decreased activation. In this study, we used functional magnetic resonance imaging (fMRI) to investigate learning-induced changes in the neural activation in the human brain with a classic motor training task. Specifically, instead of comparing the mean magnitudes of activation before and after training, we analyzed the learning-induced changes in multi-voxel spatial patterns of neural activation. We observed that the stability of the activation patterns, or the similarity of the activation patterns between the even and odd runs of the fMRI scans, was significantly increased in the primary motor cortex (M1) after training. By contrast, the mean magnitude of neural activation remained unchanged. Therefore, our study suggests that learning shapes the brain by increasing the stability of the activation patterns, therefore providing a new perspective in understanding the neural mechanisms underlying learning.
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- 2013
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5. Improved minimum squared error algorithm with applications to face recognition.
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Qi Zhu, Zhengming Li, Jinxing Liu, Zizhu Fan, Lei Yu, and Yan Chen
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Medicine ,Science - Abstract
Minimum squared error based classification (MSEC) method establishes a unique classification model for all the test samples. However, this classification model may be not optimal for each test sample. This paper proposes an improved MSEC (IMSEC) method, which is tailored for each test sample. The proposed method first roughly identifies the possible classes of the test sample, and then establishes a minimum squared error (MSE) model based on the training samples from these possible classes of the test sample. We apply our method to face recognition. The experimental results on several datasets show that IMSEC outperforms MSEC and the other state-of-the-art methods in terms of accuracy.
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- 2013
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6. MicroRNAome of porcine pre- and postnatal development.
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Mingzhou Li, Youlin Xia, Yiren Gu, Kai Zhang, Qiulei Lang, Lei Chen, Jiuqiang Guan, Zonggang Luo, Haosi Chen, Yang Li, Qinghai Li, Xiang Li, An-an Jiang, Surong Shuai, Jinyong Wang, Qi Zhu, Xiaochuan Zhou, Xiaolian Gao, and Xuewei Li
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Medicine ,Science - Abstract
The domestic pig is of enormous agricultural significance and valuable models for many human diseases. Information concerning the pig microRNAome (miRNAome) has been long overdue and elucidation of this information will permit an atlas of microRNA (miRNA) regulation functions and networks to be constructed. Here we performed a comprehensive search for porcine miRNAs on ten small RNA sequencing libraries prepared from a mixture of tissues obtained during the entire pig lifetime, from the fetal period through adulthood. The sequencing results were analyzed using mammalian miRNAs, the precursor hairpins (pre-miRNAs) and the first release of the high-coverage porcine genome assembly (Sscrofa9, April 2009) and the available expressed sequence tag (EST) sequences. Our results extend the repertoire of pig miRNAome to 867 pre-miRNAs (623 with genomic coordinates) encoding for 1,004 miRNAs, of which 777 are unique. We preformed real-time quantitative PCR (q-PCR) experiments for selected 30 miRNAs in 47 tissue-specific samples and found agreement between the sequencing and q-PCR data. This broad survey provides detailed information about multiple variants of mature sequences, precursors, chromosomal organization, development-specific expression, and conservation patterns. Our data mining produced a broad view of the pig miRNAome, consisting of miRNAs and isomiRs and a wealth of information of pig miRNA characteristics. These results are prelude to the advancement in pig biology as well the use of pigs as model organism for human biological and biomedical studies.
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- 2010
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7. Correction: A Comprehensive Sequence and Disease Correlation Analyses for the C-Terminal Region of CagA Protein of.
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Youlin Xia, Yoshio Yamaoka, Qi Zhu, Ivan Matha, and Xiaolian Gao
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Medicine ,Science - Published
- 2010
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8. A comprehensive sequence and disease correlation analyses for the C-terminal region of CagA protein of Helicobacter pylori.
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Youlin Xia, Yoshio Yamaoka, Qi Zhu, Ivan Matha, and Xiaolian Gao
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Medicine ,Science - Abstract
Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B', B'') and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease.
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- 2009
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9. The part task of the part-spacing paradigm is not a pure measurement of part-based information of faces.
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Qi Zhu, Xiaobai Li, Kari Chow, and Jia Liu
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Medicine ,Science - Abstract
BACKGROUND:Faces are arguably one of the most important object categories encountered by human observers, yet they present one of the most difficult challenges to both the human and artificial visual systems. A variety of experimental paradigms have been developed to study how faces are represented and recognized, among which is the part-spacing paradigm. This paradigm is presumed to characterize the processing of both the featural and configural information of faces, and it has become increasingly popular for testing hypotheses on face specificity and in the diagnosis of face perception in cognitive disorders. METHODOLOGY/PRINCIPAL FINDINGS:In two experiments we questioned the validity of the part task of this paradigm by showing that, in this task, measuring pure information about face parts is confounded by the effect of face configuration on the perception of those parts. First, we eliminated or reduced contributions from face configuration by either rearranging face parts into a non-face configuration or by removing the low spatial frequencies of face images. We found that face parts were no longer sensitive to inversion, suggesting that the previously reported inversion effect observed in the part task was due in fact to the presence of face configuration. Second, self-reported prosopagnosic patients who were selectively impaired in the holistic processing of faces failed to detect part changes when face configurations were presented. When face configurations were scrambled, however, their performance was as good as that of normal controls. CONCLUSIONS/SIGNIFICANCE:In sum, consistent evidence from testing both normal and prosopagnosic subjects suggests the part task of the part-spacing paradigm is not an appropriate task for either measuring how face parts alone are processed or for providing a valid contrast to the spacing task. Therefore, conclusions from previous studies using the part-spacing paradigm may need re-evaluation with proper paradigms.
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- 2009
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10. Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events
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Qi Zhu Wu, David R. Badcock, Gary F. Egan, Kabilan Pitchaimuthu, Allison M McKendrick, Olivia Carter, and Yu Man Chan
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Male ,Migraine without Aura ,Central Nervous System ,Visual perception ,Magnetic Resonance Spectroscopy ,genetic structures ,Vision ,Glutamine ,Migraine with Aura ,Social Sciences ,Pathology and Laboratory Medicine ,Biochemistry ,Nervous System ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Psychology ,gamma-Aminobutyric Acid ,Visual Cortex ,Cerebral Cortex ,0303 health sciences ,Neurotransmitter Agents ,Multidisciplinary ,Headaches ,Brain ,Neurochemistry ,Neurotransmitters ,Middle Aged ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Visual Perception ,GABAergic ,Female ,Sensory Perception ,Occipital Lobe ,medicine.symptom ,Anatomy ,Research Article ,Binocular rivalry ,Adult ,Science ,Migraine Disorders ,Glutamic Acid ,Context (language use) ,03 medical and health sciences ,Young Adult ,Neurochemical ,Signs and Symptoms ,Diagnostic Medicine ,Humans ,Migraine ,030304 developmental biology ,business.industry ,Cognitive Psychology ,Biology and Life Sciences ,Migraine with aura ,Visual cortex ,Case-Control Studies ,Cognitive Science ,Perception ,Percept ,business ,Occipital lobe ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.
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- 2018
11. Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events
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Chan, Yu Man, primary, Pitchaimuthu, Kabilan, additional, Wu, Qi-Zhu, additional, Carter, Olivia L., additional, Egan, Gary F., additional, Badcock, David R., additional, and McKendrick, Allison M., additional
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- 2019
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12. Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients
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Gui-Qi Zhu, Ming-Hua Zheng, Wen-Yue Liu, Shi-Gang Lin, Martin Braddock, Sven Van Poucke, Zhongheng Zhang, Fei-Xia Shen, and Zhi Mao
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Blood Glucose ,Male ,Physiology ,Organ Dysfunction Scores ,lcsh:Medicine ,Severity of Illness Index ,Endocrinology ,0302 clinical medicine ,Medicine and Health Sciences ,030212 general & internal medicine ,Simplified Acute Physiology Score ,lcsh:Science ,Multidisciplinary ,Organic Compounds ,Monosaccharides ,Area under the curve ,Hematology ,Middle Aged ,Prognosis ,Hospitals ,Blood Sugar ,Body Fluids ,Chemistry ,Intensive Care Units ,Blood ,SAPS II ,Physical Sciences ,Female ,Anatomy ,Research Article ,medicine.medical_specialty ,Death Rates ,Endocrine Disorders ,Critical Illness ,Carbohydrates ,03 medical and health sciences ,Population Metrics ,Intensive care ,Internal medicine ,Severity of illness ,Diabetes Mellitus ,medicine ,Humans ,Risk factor ,Intensive care medicine ,Demography ,Proportional Hazards Models ,Population Biology ,Receiver operating characteristic ,Proportional hazards model ,business.industry ,Organic Chemistry ,lcsh:R ,Chemical Compounds ,Biology and Life Sciences ,Reproducibility of Results ,030208 emergency & critical care medicine ,Hypoglycemia ,Health Care ,Glucose ,Health Care Facilities ,Metabolic Disorders ,Hyperglycemia ,People and Places ,lcsh:Q ,business - Abstract
Background and Aims Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality. Methods Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve. Results 4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813–0.834, P< 0.001) and 0.738 (95% CI: 0.725–0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001). Conclusions We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group.
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- 2016
13. Percutaneous Aspiration Thrombectomy for Arterial Thromboembolism during Infrainguinal Endovascular Recanalization
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Pei-Lei Zhang, Yue-Qi Zhu, Li-Ming Wei, Xiaocong Li, Jun-Gong Zhao, Fang Liu, and Hai-Tao Lu
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medicine.medical_specialty ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,lcsh:R ,lcsh:Medicine ,Retrospective cohort study ,medicine.disease ,Surgery ,body regions ,Stenosis ,Intraluminal angioplasty ,Restenosis ,Internal medicine ,Angioplasty ,Occlusion ,Arterial Occlusive Diseases ,Angiography ,Cardiology ,Medicine ,lcsh:Q ,business ,lcsh:Science - Abstract
Objectives To evaluate the efficacy of percutaneous aspiration thrombectomy (PAT) for infrainguinal arterial thromboembolism in patients undergoing endovascular recanalization (EVR) and to investigate the predictors for thromboembolic complications. Materials and Methods In total, 23 patients (23 limbs) who underwent PAT for thromboembolism (PAT group, PG) during EVR and 237 patients (302 limbs) who underwent successful EVR without thromboembolic complications (control group, CG) were enrolled. Immediate post-operation and follow-up outcomes were compared between the two groups. Multivariate analysis was performed to identify the predictors of thromboembolic complications. Technical success of PAT was defined as achievement of
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- 2015
14. Establishment and Validation of SSCLIP Scoring System to Estimate Survival in Hepatocellular Carcinoma Patients Who Received Curative Liver Resection
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Ke-Qing Shi, Ming-Hua Zheng, Xiao Bo Wang, Gui-Qi Zhu, Gui-Qian Huang, Yong-Ping Chen, Guo-Liang Chen, Wen-Yue Liu, Mengtao Zhou, Jie You, Jian-Feng Fang, Martin Braddock, Sha Huang, Han-Yang Che, and Yi Zhou
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Scoring system ,Carcinoma, Hepatocellular ,lcsh:Medicine ,Gastroenterology ,Resection ,Liver disease ,Internal medicine ,Cox proportional hazards regression ,medicine ,Biomarkers, Tumor ,Humans ,lcsh:Science ,Survival analysis ,Aged ,Prothrombin time ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,lcsh:R ,Liver Neoplasms ,Cancer ,Middle Aged ,medicine.disease ,Prognosis ,Survival Analysis ,Hepatocellular carcinoma ,lcsh:Q ,Female ,Neoplasm Grading ,business ,Algorithms ,Research Article - Abstract
BACKGROUND AND AIMS There is no prognostic model that is reliable and practical for patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). This study aimed to establish and validate a Surgery-Specific Cancer of the Liver Italian Program (SSCLIP) scoring system for those patients. METHODS 668 eligible patients who underwent CLR for HCC from five separate tertiary hospitals were selected. The SSCLIP was constructed from a training cohort by adding independent predictors that were identified by Cox proportional hazards regression analyses to the original Cancer of the Liver Italian Program (CLIP). The prognostic performance of the SSCLIP at 12 and 36-months was compared with data from existing models. The patient survival distributions at different risk levels of the SSCLIP were also assessed. RESULTS Four independent predictors were added to construct the SSCLIP, including age (HR = 1.075, 95%CI: 1.019-1.135, P = 0.009), albumin (HR = 0.804, 95%CI: 0.681-0.950, P = 0.011), prothrombin time activity (HR = 0.856, 95%CI: 0.751-0.975, P = 0.020) and microvascular invasion (HR = 19.852, 95%CI: 2.203-178.917, P = 0.008). In both training and validation cohorts, 12-month and 36-month prognostic performance of the SSCLIP were significantly better than those of the original CLIP, model of end-stage liver disease-based CLIP, Okuda and Child-Turcotte-Pugh score (all P < 0.05). The stratification of risk levels of the SSCLIP showed an enhanced ability to differentiate patients with different outcomes. CONCLUSIONS A novel SSCLIP to predict survival of HCC patients who received CLR based on objective parameters may provide a refined, useful prognosis algorithm.
- Published
- 2014
15. Early detection of ventilation-induced brain injury using magnetic resonance spectroscopy and diffusion tensor imaging: an in vivo study in preterm lambs
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Samantha K. Barton, Jeanie Ling Yoong Cheong, Graeme R. Polglase, Peter G Davis, Mary Tolcos, Richard McIntyre, Stuart B. Hooper, James T. Pearson, Beatrice Skiold, Ruth Vreys, Qi-Zhu Wu, and Gary F. Egan
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Pathology ,medicine.medical_specialty ,lcsh:Medicine ,Brain damage ,Pediatrics ,Diagnostic Radiology ,White matter ,Diagnostic Medicine ,Fractional anisotropy ,Medicine and Health Sciences ,medicine ,Animals ,lcsh:Science ,Sheep, Domestic ,Tidal volume ,Positive end-expiratory pressure ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Radiology and Imaging ,lcsh:R ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,Respiration, Artificial ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Animals, Newborn ,Brain Injuries ,Breathing ,lcsh:Q ,Neonatology ,medicine.symptom ,Nuclear medicine ,business ,Research Article ,Diffusion MRI - Abstract
BACKGROUND AND AIM: High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. METHODS: Newborn lambs (0.85 gestation) were stabilized with a "protective ventilation" strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of "injurious ventilation" (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. RESULTS: No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. CONCLUSION: Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury.
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- 2014
16. Classification of cirrhotic patients with or without minimal hepatic encephalopathy and healthy subjects using resting-state attention-related network analysis
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Pei-Cheng Li, Xi-Qi Zhu, Hua-Jun Chen, Gao-Jun Teng, and Yu Wang
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Liver Cirrhosis ,Male ,Pathology ,Epidemiology ,Precuneus ,lcsh:Medicine ,Brain mapping ,Diagnostic Radiology ,Functional Magnetic Resonance Imaging ,Medicine and Health Sciences ,Attention ,Clinical Epidemiology ,lcsh:Science ,Hepatic encephalopathy ,Default mode network ,Brain Mapping ,Multidisciplinary ,Cognitive Neurology ,Liver Diseases ,Radiology and Imaging ,Brain ,Discriminant Analysis ,Middle Aged ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Cirrhosis ,Neurology ,Cardiology ,Female ,Research Article ,Adult ,medicine.medical_specialty ,Rest ,Cognitive Neuroscience ,Neuroimaging ,Gastroenterology and Hepatology ,Sensitivity and Specificity ,Text mining ,Diagnostic Medicine ,Internal medicine ,Task-positive network ,medicine ,Humans ,Resting state fMRI ,business.industry ,lcsh:R ,Biology and Life Sciences ,Inferior parietal lobule ,medicine.disease ,Case-Control Studies ,Hepatic Encephalopathy ,lcsh:Q ,Nerve Net ,business ,human activities ,Neuroscience - Abstract
BACKGROUND: Attention deficit is an early and key characteristic of minimal hepatic encephalopathy (MHE) and has been used as indicator for MHE detection. The aim of this study is to classify the cirrhotic patients with or without MHE (NMHE) and healthy controls (HC) using the resting-state attention-related brain network analysis. METHODS AND FINDINGS: Resting-state fMRI was administrated to 20 MHE patients, 21 NMHE patients, and 17 HCs. Three attention-related networks, including dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN), were obtained by independent component analysis. One-way analysis of covariance was performed to determine the regions of interest (ROIs) showing significant functional connectivity (FC) change. With FC strength of ROIs as indicators, Linear Discriminant Analysis (LDA) was conducted to differentiate MHE from HC or NMHE. Across three groups, significant FC differences were found within DAN (left superior/inferior parietal lobule and right inferior parietal lobule), VAN (right superior parietal lobule), and DMN (bilateral posterior cingulate gyrus and precuneus, and left inferior parietal lobule). With FC strength of ROIs from three networks as indicators, LDA yielded 94.6% classification accuracy between MHE and HC (100% sensitivity and 88.2% specificity) and 85.4% classification accuracy between MHE and NMHE (90.0% sensitivity and 81.0% specificity). CONCLUSIONS: Our results suggest that the resting-state attention-related brain network analysis can be useful in classification of subjects with MHE, NMHE, and HC and may provide a new insight into MHE detection.
- Published
- 2014
17. p120RasGAP is a mediator of rho pathway activation and tumorigenicity in the DLD1 colorectal cancer cell line
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Josephine Hai, Lisa Leung, Shawna Organ, Mitsuhiko Ikura, Nikolina Radulovich, Senji Shirasawa, Chang-Qi Zhu, Takehiko Sasazuki, Ming-Sound Tsao, Roya Navab, and Christopher B. Marshall
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endocrine system diseases ,Carcinogenesis ,Mutant ,lcsh:Medicine ,Signal transduction ,medicine.disease_cause ,0302 clinical medicine ,Molecular cell biology ,Cell Movement ,Stress Fibers ,Tyrosine Kinase Signaling Cascade ,Gastrointestinal Cancers ,Basic Cancer Research ,Guanine Nucleotide Exchange Factors ,Phosphorylation ,Somatic recombination ,lcsh:Science ,0303 health sciences ,Mutation ,Multidisciplinary ,p120 GTPase Activating Protein ,Signaling in Selected Disciplines ,Signaling Cascades ,Gene Expression Regulation, Neoplastic ,Phenotype ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,KRAS ,Guanine nucleotide exchange factor ,Colorectal Neoplasms ,Research Article ,Molecular Sequence Data ,Signaling in cellular processes ,P120 GTPase Activating Protein ,Gastroenterology and Hepatology ,Biology ,Models, Biological ,Signaling Pathways ,Proto-Oncogene Proteins p21(ras) ,Rectal Cancer ,03 medical and health sciences ,Cell Line, Tumor ,Proto-Oncogene Proteins ,Gastrointestinal Tumors ,medicine ,Cell Adhesion ,Humans ,RNA, Messenger ,neoplasms ,GTPase signaling ,030304 developmental biology ,Ras signaling ,Oncogenic Signaling ,Base Sequence ,lcsh:R ,Cancers and Neoplasms ,Molecular biology ,digestive system diseases ,respiratory tract diseases ,Repressor Proteins ,Cell movement signaling ,Cancer research ,ras Proteins ,lcsh:Q ,Mutant Proteins - Abstract
KRAS is mutated in ∼40% of colorectal cancer (CRC), and there are limited effective treatments for advanced KRAS mutant CRC. Therefore, it is crucial that downstream mediators of oncogenic KRAS continue to be studied. We identified p190RhoGAP as being phosphorylated in the DLD1 CRC cell line, which expresses a heterozygous KRAS G13D allele, and not in DKO4 in which the mutant allele has been deleted by somatic recombination. We found that a ubiquitous binding partner of p190RhoGAP, p120RasGAP (RasGAP), is expressed in much lower levels in DKO4 cells compared to DLD1, and this expression is regulated by KRAS. Rescue of RasGAP expression in DKO4 rescued Rho pathway activation and partially rescued tumorigenicity in DKO4 cells, indicating that the combination of mutant KRAS and RasGAP expression is crucial to these phenotypes. We conclude that RasGAP is an important effector of mutant KRAS in CRC.
- Published
- 2013
18. Loss of canonical Smad4 signaling promotes KRAS driven malignant transformation of human pancreatic duct epithelial cells and metastasis
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Christine To, Nikolina Radulovich, Dennis Wang, Ming-Sound Tsao, Lisa Leung, Chang-Qi Zhu, and Emin Ibrahimov
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lcsh:Medicine ,medicine.disease_cause ,Malignant transformation ,Metastasis ,Mice ,0302 clinical medicine ,Transforming Growth Factor beta ,Neoplasm Metastasis ,RNA, Small Interfering ,lcsh:Science ,Smad4 Protein ,0303 health sciences ,Multidisciplinary ,biology ,3. Good health ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,KRAS ,Carcinoma, Pancreatic Ductal ,Signal Transduction ,Research Article ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Cell Line, Tumor ,Proto-Oncogene Proteins ,medicine ,Animals ,Humans ,Neoplastic transformation ,Neoplasm Invasiveness ,Gene Silencing ,neoplasms ,030304 developmental biology ,Pancreatic duct ,Oncogene ,lcsh:R ,Pancreatic Ducts ,Epithelial Cells ,Transforming growth factor beta ,medicine.disease ,Survival Analysis ,digestive system diseases ,Cancer research ,biology.protein ,ras Proteins ,lcsh:Q ,Carcinogenesis - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in North America. Activating KRAS mutations and Smad4 loss occur in approximately 90% and 55% of PDAC, respectively. While their roles in the early stages of PDAC development have been confirmed in genetically modified mouse models, their roles in the multistep malignant transformation of human pancreatic duct cells have not been directly demonstrated. Here, we report that Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE) cell line model. Marked Smad4 downregulation by shRNA in KRAS (G12V) expressing HPDE cells failed to cause tumorigenic transformation. However, KRAS-mediated malignant transformation occurred in a new HPDE-TGF-β resistant (TβR) cell line that completely lacks Smad4 protein expression and is resistant to the mito-inhibitory activity of TGF-β. This transformation resulted in tumor formation and development of metastatic phenotype when the cells were implanted orthotopically into the mouse pancreas. Smad4 restoration re-established TGF-β sensitivity, markedly increased tumor latency by promoting apoptosis, and decreased metastatic potential. These results directly establish the critical combination of the KRAS oncogene and complete Smad4 inactivation in the multi-stage malignant transformation and metastatic progression of normal human HPDE cells.
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- 2013
19. Net Expression Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Cell PL45 In Vitro and In Vivo
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Lungen Lu, Qi Zhu, Yue Zeng, Baiwen Li, Xiangjun Meng, Lei Li, Xingpeng Wang, Xinjian Wan, Yueqin Qian, and Duanmin Hu
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Male ,Cell ,lcsh:Medicine ,Apoptosis ,Proto-Oncogene Mas ,Mice ,Molecular Cell Biology ,Basic Cancer Research ,Cyclin D1 ,lcsh:Science ,Multidisciplinary ,Cell Death ,Cell Cycle ,Cell cycle ,Middle Aged ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Oncology ,Medicine ,Female ,Signal transduction ,Research Article ,Carcinoma, Pancreatic Ductal ,Signal Transduction ,Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,medicine.medical_specialty ,Tumor suppressor gene ,Gastroenterology and Hepatology ,Biology ,Cell Growth ,Pancreatic Cancer ,Internal medicine ,Pancreatic cancer ,Cell Line, Tumor ,Gastrointestinal Tumors ,medicine ,Genetics ,Cancer Genetics ,Animals ,Humans ,Transcription factor ,Pancreas ,Aged ,Cell Proliferation ,Norepinephrine Plasma Membrane Transport Proteins ,Cell growth ,lcsh:R ,Cancers and Neoplasms ,Cyclin-Dependent Kinase 4 ,medicine.disease ,Pancreatic Neoplasms ,Endocrinology ,Cancer research ,lcsh:Q - Abstract
Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.
- Published
- 2013
20. Improved minimum squared error algorithm with applications to face recognition
- Author
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Zhengming Li, Yan Chen, Qi Zhu, Jin-Xing Liu, Zizhu Fan, and Lei Yu
- Subjects
Databases, Factual ,Biometrics ,Mean squared error ,Image Processing ,Statistics as Topic ,lcsh:Medicine ,Facial recognition system ,Computer Applications ,Engineering ,Linear regression ,Data Mining ,Statistical Signal Processing ,Humans ,Statistical Methods ,lcsh:Science ,Test sample ,Physics ,Multidisciplinary ,Applied Mathematics ,Statistics ,lcsh:R ,Control Engineering ,Linear discriminant analysis ,Test (assessment) ,Statistical Theories ,Biometric Identification ,Face (geometry) ,Computer Science ,Signal Processing ,lcsh:Q ,Information Technology ,Algorithm ,Algorithms ,Mathematics ,Research Article ,Computer Modeling - Abstract
Minimum squared error based classification (MSEC) method establishes a unique classification model for all the test samples. However, this classification model may be not optimal for each test sample. This paper proposes an improved MSEC (IMSEC) method, which is tailored for each test sample. The proposed method first roughly identifies the possible classes of the test sample, and then establishes a minimum squared error (MSE) model based on the training samples from these possible classes of the test sample. We apply our method to face recognition. The experimental results on several datasets show that IMSEC outperforms MSEC and the other state-of-the-art methods in terms of accuracy.
- Published
- 2013
21. Lipocalin2 Promotes Invasion, Tumorigenicity and Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma
- Author
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Chang-Qi Zhu, Ming-Sound Tsao, Devang Panchal, Nikolina Radulovich, Bizhan Bandarchi, Melania Pintilie, Shawna Organ, Christine To, and Lisa Leung
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Pathology ,lcsh:Medicine ,Deoxycytidine ,Basement Membrane ,Mice ,0302 clinical medicine ,Molecular Cell Biology ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Cell Death ,Immunohistochemistry ,Lipocalins ,3. Good health ,Extracellular Matrix ,Oncology ,030220 oncology & carcinogenesis ,Medicine ,medicine.drug ,Research Article ,Carcinoma, Pancreatic Ductal ,medicine.medical_specialty ,Histology ,Motility ,Biology ,In Vitro Techniques ,03 medical and health sciences ,Pancreatic Cancer ,Downregulation and upregulation ,In vivo ,Diagnostic Medicine ,Cell Line, Tumor ,Gastrointestinal Tumors ,Carcinoma ,medicine ,Cell Adhesion ,Animals ,Humans ,Extracellular Matrix Adhesions ,030304 developmental biology ,lcsh:R ,Cancer ,Cancers and Neoplasms ,medicine.disease ,Gemcitabine ,Pancreatic Neoplasms ,HIF1A ,Drug Resistance, Neoplasm ,Cancer research ,lcsh:Q ,General Pathology - Abstract
Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.
- Published
- 2012
22. Overexpression and Biological Function of Ubiquitin-Specific Protease 42 in Gastric Cancer
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Qi Zhu, Zhenya Zhu, Chunhui Zhang, Bo Yan, Kun Hou, Yong Wang, and Shiyong Yu
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Male ,0301 basic medicine ,lcsh:Medicine ,Biochemistry ,Metastasis ,Deubiquitinating enzyme ,0302 clinical medicine ,Basic Cancer Research ,Medicine and Health Sciences ,Small interfering RNAs ,Cell Cycle and Cell Division ,lcsh:Science ,Cyclin ,Multidisciplinary ,biology ,Animal Models ,Middle Aged ,Neoplasm Proteins ,Nucleic acids ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Oncology ,Cell Processes ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Female ,Research Article ,Adult ,Epithelial-Mesenchymal Transition ,Mouse Models ,Research and Analysis Methods ,Disease-Free Survival ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,Model Organisms ,Cyclin D1 ,Stomach Neoplasms ,Cyclins ,Cell Line, Tumor ,Gastrointestinal Tumors ,Genetics ,Biomarkers, Tumor ,medicine ,Humans ,Gene silencing ,Epithelial–mesenchymal transition ,Non-coding RNA ,Cell Proliferation ,Aged ,Biology and life sciences ,Cell growth ,lcsh:R ,Cancers and Neoplasms ,Cell Biology ,medicine.disease ,Gene regulation ,Gastric Cancer ,Cyclin E1 ,030104 developmental biology ,Immunology ,Cancer research ,biology.protein ,RNA ,lcsh:Q ,Gene expression ,Thiolester Hydrolases - Abstract
Ubiquitin-specific protease 42 (USP42) is a member of deubiquitinating enzymes (DUBs). The alterations of DUBs are implicated in the pathogenesis of a wide variety of tumors. However, there are few studies on the expression and biological function of USP42 in gastric cancer (GC). Here, the expression levels of USP42 were significantly higher in GC tissues than in non-tumorous tissues. USP42 expression was significantly correlated with tumor size, TNM stage, lymph node metastasis and overall survival of patients with GC. Moreover, USP42 silencing in two GC cell lines, AGS and MKN-45, notably inhibited cell proliferation, but stimulated G1 phase arrest. The proteins promoting cell cycle progression (Cyclin D1, Cyclin E1 and PCNA) were down-regulated in USP42-suppressed cells. Moreover, inhibition of USP42 in GC cells impaired cell invasion via affecting the expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) regulators. In conclusion, USP42 overexpression could be a potential prognostic marker for GC, regulate the survival and invasive properties of GC, and may represent a novel therapeutic molecular target for this tumor.
- Published
- 2016
23. IL-33 attenuates anoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibition of PKCβ/JNK pathway
- Author
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Qi-Zhu Tang and Tao Rui
- Subjects
Anatomy and Physiology ,medicine.medical_treatment ,lcsh:Medicine ,Apoptosis ,medicine.disease_cause ,Cardiovascular ,Mice ,Immune Physiology ,Molecular Cell Biology ,Myocyte ,Signaling in Cellular Processes ,Myocytes, Cardiac ,Phosphorylation ,RNA, Small Interfering ,lcsh:Science ,Hypoxia ,Cells, Cultured ,Protein Kinase C ,Apoptotic Signaling Cascade ,Apoptotic Signaling ,Multidisciplinary ,TUNEL assay ,medicine.diagnostic_test ,Protein Kinase Signaling Cascade ,Mechanisms of Signal Transduction ,Antiapoptotic Signaling ,Signaling Cascades ,Cell biology ,Cytokine ,Cytokines ,Medicine ,RNA Interference ,Cardiomyopathies ,Research Article ,Signal Transduction ,MAP Kinase Signaling System ,Myocardial Reperfusion Injury ,Biology ,Western blot ,Protein Kinase C beta ,medicine ,Animals ,Mitogen-Activated Protein Kinase 8 ,Protein kinase C ,Interleukins ,lcsh:R ,Interleukin-33 ,Mice, Inbred C57BL ,Oxidative Stress ,lcsh:Q ,Oxidative stress ,Gene Deletion - Abstract
Background Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family. The objectives of present study are to assess whether IL-33 can protect cardiomyocytes from anoxia/reoxygenation (A/R)-induced injury and the mechanism involved in the protection. Methods Cardiomyocytes derived from either wild type or JNK1−/− mice were challenged with an A/R with or without IL-33. Myocyte apoptosis was assessed by measuring caspase 3 activity, fragmented DNA and TUNEL staining. In addition, cardiomyocyte oxidative stress was assessed by measuring DHR123 oxidation; PKCβII and JNK phosphorylation were assessed with Western blot. Results Challenge of cardiomyocytes with an A/R resulted in cardiomyocyte oxidative stress, PKCβII and JNK phosphorylation, and myocyte apoptosis. Treatment of the cardiomyocytes with IL-33 attenuated the A/R-induced myocyte oxidative stress, prevented PKCβII and JNK phosphorylation and attenuated the A/R-induced myocyte apoptosis. The protective effect of the IL-33 did not show in cardiac myocytes with siRNA specific to PKCβII or myocytes deficient in JNK1. Inhibition of PKCβII prevented the A/R-induced JNK phosphorylation, but inhibition of JNK1 showed no effect on A/R-induced PKCβII phosphorylation. Conclusions Our results indicate that IL-33 prevents the A/R-induced myocyte apoptosis through inhibition of PKCβ/JNK pathway.
- Published
- 2012
24. IKKi deficiency promotes pressure overload-induced cardiac hypertrophy and fibrosis
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Heng Zhou, Rui Zhang, Qi-Zhu Tang, Lu Gao, Hongliang Li, Difei Shen, Hua-Wen Gan, Wei Deng, Jing Zong, Zhen-Guo Ma, Zhou-Yan Bian, Yuan Yuan, Jia Dai, Fangfang Li, and Qing-Qing Wu
- Subjects
Male ,Mouse ,Myocardial Infarction ,lcsh:Medicine ,Apoptosis ,IκB kinase ,Coronary Artery Disease ,Cardiovascular ,Gene Knockout Techniques ,Glycogen Synthase Kinase 3 ,Mice ,GSK-3 ,Fibrosis ,Molecular Cell Biology ,Myocyte ,Myocytes, Cardiac ,lcsh:Science ,Multidisciplinary ,Forkhead Box Protein O1 ,TOR Serine-Threonine Kinases ,Forkhead Transcription Factors ,Heart ,Animal Models ,Angina ,Signaling Cascades ,I-kappa B Kinase ,Hypertension ,Medicine ,Signal transduction ,Signal Transduction ,Research Article ,Cardiac function curve ,medicine.medical_specialty ,Cardiomegaly ,Biology ,Gene Expression Regulation, Enzymologic ,Model Organisms ,Internal medicine ,medicine ,Akt Signaling Cascade ,Animals ,Protein kinase B ,Pressure overload ,Heart Failure ,Glycogen Synthase Kinase 3 beta ,lcsh:R ,Hemodynamics ,Immunity ,medicine.disease ,Atherosclerosis ,Mice, Inbred C57BL ,Endocrinology ,lcsh:Q ,Clinical Immunology ,Proto-Oncogene Proteins c-akt - Abstract
The inducible IκB kinase (IKKi/IKKε) is a recently described serine-threonine IKK-related kinase. Previous studies have reported the role of IKKi in infectious diseases and cancer. However, its role in the cardiac response to pressure overload remains elusive. In this study, we investigated the effects of IKKi deficiency on the development of pathological cardiac hypertrophy using in vitro and in vivo models. First, we developed mouse models of pressure overload cardiac hypertrophy induced by pressure overload using aortic banding (AB). Four weeks after AB, cardiac function was then assessed through echocardiographic and hemodynamic measurements. Western blotting, real-time PCR and histological analyses were used to assess the pathological and molecular mechanisms. We observed that IKKi-deficient mice showed significantly enhanced cardiac hypertrophy, cardiac dysfunction, apoptosis and fibrosis compared with WT mice. Furthermore, we recently revealed that the IKKi-deficient mice spontaneously develop cardiac hypertrophy. Moreover, in vivo experiments showed that IKKi deficiency-induced cardiac hypertrophy was associated with the activation of the AKT and NF-κB signaling pathway in response to AB. In cultured cells, IKKi overexpression suppressed the activation of this pathway. In conclusion, we demonstrate that IKKi deficiency exacerbates cardiac hypertrophy by regulating the AKT and NF-κB signaling pathway.
- Published
- 2012
25. Aberrant resting-state corticostriatal functional connectivity in cirrhotic patients with hyperintense globus pallidus on T1-weighted MR imaging
- Author
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Ying Cui, Hua-Jun Chen, Gao-Jun Teng, Yu Wang, and Xi-Qi Zhu
- Subjects
Adult ,Liver Cirrhosis ,Male ,Pathology ,medicine.medical_specialty ,Inferior frontal gyrus ,lcsh:Medicine ,Neuroimaging ,Gastroenterology and Hepatology ,Striatum ,Neuropsychological Tests ,Biology ,Globus Pallidus ,Brain mapping ,Diagnostic Radiology ,medicine ,Humans ,lcsh:Science ,Cerebral Cortex ,Brain Mapping ,Manganese ,Multidisciplinary ,medicine.diagnostic_test ,Resting state fMRI ,Cognitive Neurology ,Liver Diseases ,Putamen ,fMRI ,lcsh:R ,Middle Aged ,Magnetic Resonance Imaging ,Globus pallidus ,medicine.anatomical_structure ,Cirrhosis ,Neurology ,nervous system ,Cerebral cortex ,Medicine ,Female ,lcsh:Q ,Cognition Disorders ,Radiology ,Functional magnetic resonance imaging ,Research Article ,Neuroscience - Abstract
Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting-state brain dysfunction in real time.
- Published
- 2012
26. MicroRNAome of porcine pre- and postnatal development
- Author
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Xiaochuan Zhou, Qiulei Lang, Yiren Gu, Jinyong Wang, Xiang Li, Qi Zhu, Xuewei Li, Xiaolian Gao, Kai Zhang, Qinghai Li, Youlin Xia, An an Jiang, Yang Li, Lei Chen, Surong Shuai, Jiuqiang Guan, Zonggang Luo, Haosi Chen, and Mingzhou Li
- Subjects
Small RNA ,Genetics and Genomics/Animal Genetics ,Swine ,ved/biology.organism_classification_rank.species ,Sequence assembly ,lcsh:Medicine ,Genomics ,Sequence alignment ,Computational Biology/Comparative Sequence Analysis ,Biology ,Polymerase Chain Reaction ,Chromosomes ,Genetics and Genomics/Epigenetics ,Animals ,Genomic library ,Model organism ,lcsh:Science ,Expressed Sequence Tags ,Genetics ,Expressed sequence tag ,Multidisciplinary ,ved/biology ,lcsh:R ,Gene Expression Regulation, Developmental ,Genetics and Genomics/Gene Expression ,MicroRNAs ,Domestic pig ,Genetics and Genomics/Gene Discovery ,lcsh:Q ,Genetics and Genomics/Comparative Genomics ,Research Article - Abstract
The domestic pig is of enormous agricultural significance and valuable models for many human diseases. Information concerning the pig microRNAome (miRNAome) has been long overdue and elucidation of this information will permit an atlas of microRNA (miRNA) regulation functions and networks to be constructed. Here we performed a comprehensive search for porcine miRNAs on ten small RNA sequencing libraries prepared from a mixture of tissues obtained during the entire pig lifetime, from the fetal period through adulthood. The sequencing results were analyzed using mammalian miRNAs, the precursor hairpins (pre-miRNAs) and the first release of the high-coverage porcine genome assembly (Sscrofa9, April 2009) and the available expressed sequence tag (EST) sequences. Our results extend the repertoire of pig miRNAome to 867 pre-miRNAs (623 with genomic coordinates) encoding for 1,004 miRNAs, of which 777 are unique. We preformed real-time quantitative PCR (q-PCR) experiments for selected 30 miRNAs in 47 tissue-specific samples and found agreement between the sequencing and q-PCR data. This broad survey provides detailed information about multiple variants of mature sequences, precursors, chromosomal organization, development-specific expression, and conservation patterns. Our data mining produced a broad view of the pig miRNAome, consisting of miRNAs and isomiRs and a wealth of information of pig miRNA characteristics. These results are prelude to the advancement in pig biology as well the use of pigs as model organism for human biological and biomedical studies.
- Published
- 2010
27. A Comprehensive Sequence and Disease Correlation Analyses for the C-Terminal Region of CagA Protein of Helicobacter pylori
- Author
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Qi Zhu, Xiaolian Gao, Yoshio Yamaoka, Youlin Xia, and Ivan Matha
- Subjects
Gastroenterology and Hepatology/Gastrointestinal Cancers ,Sequence analysis ,Amino Acid Motifs ,Molecular Sequence Data ,Stomach Diseases ,lcsh:Medicine ,Virulence ,Sequence alignment ,Biology ,Bioinformatics ,Helicobacter Infections ,03 medical and health sciences ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Bacterial Proteins ,Sequence Analysis, Protein ,Stomach Neoplasms ,medicine ,CagA ,Humans ,Amino Acid Sequence ,lcsh:Science ,Databases, Protein ,Peptide sequence ,Phylogeny ,030304 developmental biology ,Genetics ,0303 health sciences ,Antigens, Bacterial ,Multidisciplinary ,Sequence Homology, Amino Acid ,Gastric lymphoma ,lcsh:R ,Computational Biology ,Helicobacter pylori ,biology.organism_classification ,medicine.disease ,digestive system diseases ,3. Good health ,Protein Structure, Tertiary ,Gastroenterology and Hepatology/Gastrointestinal Infections ,030220 oncology & carcinogenesis ,lcsh:Q ,Bacterial antigen ,Microbiology/Cellular Microbiology and Pathogenesis ,Research Article - Abstract
Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B', B'') and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease.
- Published
- 2009
28. Clinical Significance of Tumor Necrosis Factor-α Inhibitors in the Treatment of Sciatica: A Systematic Review and Meta-Analysis
- Author
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Fi Qi Zhu, Yun Fu Wang, Ping You Chen, Guang Jian Liu, Jie Luo, Li Ying Chang, Li Li Xu, Wei Chang, and Song Lin Wang
- Subjects
medicine.medical_specialty ,Spinal stenosis ,medicine.medical_treatment ,lcsh:Medicine ,Surgical and Invasive Medical Procedures ,law.invention ,Disability Evaluation ,Sciatica ,Randomized controlled trial ,law ,Internal medicine ,Discectomy ,Medicine and Health Sciences ,medicine ,Humans ,Pain Management ,Clinical significance ,lcsh:Science ,Pharmacology ,Multidisciplinary ,Tumor Necrosis Factor-alpha ,Pharmaceutics ,business.industry ,lcsh:R ,medicine.disease ,Surgery ,Clinical trial ,Meta-analysis ,Relative risk ,lcsh:Q ,Female ,Clinical Medicine ,medicine.symptom ,business ,Follow-Up Studies ,Research Article - Abstract
Background and objective Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. Methods Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. Results Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). Conclusion The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.
- Published
- 2014
29. Never in Mitosis Gene A Related Kinase-6 Attenuates Pressure Overload-Induced Activation of the Protein Kinase B Pathway and Cardiac Hypertrophy
- Author
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Heng Zhou, Qi-Zhu Tang, Yan Zhang, Hai-Han Liao, Difei Shen, Zheng Yang, Teng Wang, Jinrong Fu, Hongliang Li, Ling Yan, Zhou-Yan Bian, and Qing-Qing Wu
- Subjects
Male ,Gene Expression ,lcsh:Medicine ,Blood Pressure ,Vascular Medicine ,Muscle hypertrophy ,Mice ,Cell Signaling ,Molecular Cell Biology ,Medicine and Health Sciences ,NIMA-Related Kinases ,lcsh:Science ,Cells, Cultured ,Mice, Knockout ,Multidisciplinary ,Cell cycle ,Extracellular Matrix ,Cell biology ,Cell Processes ,Cardiovascular Diseases ,Hypertension ,cardiovascular system ,Cellular Structures and Organelles ,Signal transduction ,Cardiomyopathies ,Research Article ,Signal Transduction ,Cardiology ,Aortic Diseases ,Mitosis ,Cardiomegaly ,Phosphoinositide Signal Transduction ,Protein Serine-Threonine Kinases ,Biology ,Cell Growth ,Genetics ,Animals ,Humans ,Protein kinase B ,Heart Failure ,Pressure overload ,Muscle Cells ,Akt/PKB signaling pathway ,Cell growth ,lcsh:R ,Biology and Life Sciences ,Cell Biology ,Extracellular Matrix Composition ,Cancer research ,lcsh:Q ,Proto-Oncogene Proteins c-akt - Abstract
Cardiac hypertrophy appears to be a specialized form of cellular growth that involves the proliferation control and cell cycle regulation. NIMA (never in mitosis, gene A)-related kinase-6 (Nek6) is a cell cycle regulatory gene that could induce centriole duplication, and control cell proliferation and survival. However, the exact effect of Nek6 on cardiac hypertrophy has not yet been reported. In the present study, the loss- and gain-of-function experiments were performed in Nek6 gene-deficient (Nek6-/-) mice and Nek6 overexpressing H9c2 cells to clarify whether Nek6 which promotes the cell cycle also mediates cardiac hypertrophy. Cardiac hypertrophy was induced by transthoracic aorta constriction (TAC) and then evaluated by echocardiography, pathological and molecular analyses in vivo. We got novel findings that the absence of Nek6 promoted cardiac hypertrophy, fibrosis and cardiac dysfunction, which were accompanied by a significant activation of the protein kinase B (Akt) signaling in an experimental model of TAC. Consistent with this, the overexpression of Nek6 prevented hypertrophy in H9c2 cells induced by angiotonin II and inhibited Akt signaling in vitro. In conclusion, our results demonstrate that the cell cycle regulatory gene Nek6 is also a critical signaling molecule that helps prevent cardiac hypertrophy and inhibits the Akt signaling pathway.
- Published
- 2014
30. IKKi Deficiency Promotes Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis
- Author
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Dai, Jia, primary, Shen, Di-Fei, additional, Bian, Zhou-Yan, additional, Zhou, Heng, additional, Gan, Hua-Wen, additional, Zong, Jing, additional, Deng, Wei, additional, Yuan, Yuan, additional, Li, FangFang, additional, Wu, Qing-Qing, additional, Gao, Lu, additional, Zhang, Rui, additional, Ma, Zhen-Guo, additional, Li, Hong-Liang, additional, and Tang, Qi-Zhu, additional
- Published
- 2013
- Full Text
- View/download PDF
31. 3,3′-Diindolylmethane Protects against Cardiac Hypertrophy via 5′-Adenosine Monophosphate-Activated Protein Kinase-α2
- Author
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Zong, Jing, primary, Deng, Wei, additional, Zhou, Heng, additional, Bian, Zhou-yan, additional, Dai, Jia, additional, Yuan, Yuan, additional, Zhang, Jie-yu, additional, Zhang, Rui, additional, Zhang, Yan, additional, Wu, Qing-qing, additional, Guo, Hai-peng, additional, Li, Hong-liang, additional, and Tang, Qi-zhu, additional
- Published
- 2013
- Full Text
- View/download PDF
32. Motor Training Increases the Stability of Activation Patterns in the Primary Motor Cortex
- Author
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Qi Zhu, Zonglei Zhen, Yiying Song, Yi Huang, Song Wang, and Jia Liu
- Subjects
Adult ,Male ,Anatomy and Physiology ,Time Factors ,Cognitive Neuroscience ,education ,Stability (learning theory) ,lcsh:Medicine ,Neuroimaging ,Biology ,Brain mapping ,Neurological System ,Motor Reactions ,Behavioral Neuroscience ,Learning and Memory ,medicine ,Humans ,Learning ,lcsh:Science ,Motor Systems ,Brain Mapping ,Multidisciplinary ,medicine.diagnostic_test ,fMRI ,lcsh:R ,Perspective (graphical) ,Motor Cortex ,Magnetic resonance imaging ,Human brain ,Magnetic Resonance Imaging ,medicine.anatomical_structure ,Neurology ,Medicine ,Female ,lcsh:Q ,Primary motor cortex ,Functional magnetic resonance imaging ,Neuroscience ,Psychomotor Performance ,Research Article ,Motor cortex - Abstract
Learning to be skillful is an endowed talent of humans, but neural mechanisms underlying behavioral improvement remain largely unknown. Some studies have reported that the mean magnitude of neural activation is increased after learning, whereas others have instead shown decreased activation. In this study, we used functional magnetic resonance imaging (fMRI) to investigate learning-induced changes in the neural activation in the human brain with a classic motor training task. Specifically, instead of comparing the mean magnitudes of activation before and after training, we analyzed the learning-induced changes in multi-voxel spatial patterns of neural activation. We observed that the stability of the activation patterns, or the similarity of the activation patterns between the even and odd runs of the fMRI scans, was significantly increased in the primary motor cortex (M1) after training. By contrast, the mean magnitude of neural activation remained unchanged. Therefore, our study suggests that learning shapes the brain by increasing the stability of the activation patterns, therefore providing a new perspective in understanding the neural mechanisms underlying learning.
- Published
- 2013
33. Activating Transcription Factor 3 Deficiency Promotes Cardiac Hypertrophy, Dysfunction, and Fibrosis Induced by Pressure Overload
- Author
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Zhou, Heng, primary, Shen, Di-Fei, additional, Bian, Zhou-Yan, additional, Zong, Jing, additional, Deng, Wei, additional, Zhang, Yan, additional, Guo, Yuan-Yuan, additional, Li, Hongliang, additional, and Tang, Qi-Zhu, additional
- Published
- 2011
- Full Text
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34. Improvement of Pest Resistance in Transgenic Tobacco Plants Expressing dsRNA of an Insect-Associated Gene EcR
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Wenqing Zhang, Zhao-Jun Wei, Yao Ma, Jin-Qi Zhu, Jia-Qi Zhang, Qiong Yao, Shumin Liu, Hai-Sheng Qi, and Sheng Li
- Subjects
Receptors, Steroid ,Transgene ,lcsh:Medicine ,Plant Science ,Genetically modified crops ,Molting ,Moths ,Helicoverpa armigera ,Plant disease resistance ,Spodoptera ,Host-Parasite Interactions ,Microbiology ,Integrated Control ,Beet armyworm ,Tobacco ,Molecular Cell Biology ,Animals ,Membrane Receptor Signaling ,lcsh:Science ,Biology ,Disease Resistance ,Plant Diseases ,RNA, Double-Stranded ,Nicotiana ,Plant Pests ,Multidisciplinary ,biology ,business.industry ,lcsh:R ,fungi ,food and beverages ,Agriculture ,Plant Pathology ,Plants, Genetically Modified ,Hormone Receptor Signaling ,biology.organism_classification ,Biotechnology ,Larva ,Insect Proteins ,lcsh:Q ,Pest Control ,PEST analysis ,Nuclear Receptor Signaling ,business ,Zoology ,Entomology ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Signal Transduction - Abstract
The adoption of pest-resistant transgenic plants to reduce yield loss and pesticide utilization has been successful in the past three decades. Recently, transgenic plant expressing double-stranded RNA (dsRNA) targeting pest genes emerges as a promising strategy for improving pest resistance in crops. The steroid hormone, 20-hydroxyecdysone (20E), predominately controls insect molting via its nuclear receptor complex, EcR-USP. Here we report that pest resistance is improved in transgenic tobacco plants expressing dsRNA of EcR from the cotton bollworm, Helicoverpa armigera, a serious lepidopteran pest for a variety of crops. When H. armigera larvae were fed with the whole transgenic tobacco plants expressing EcR dsRNA, resistance to H. armigera was significantly improved in transgenic plants. Meanwhile, when H. armigera larvae were fed with leaves of transgenic tobacco plants expressing EcR dsRNA, its EcR mRNA level was dramatically decreased causing molting defects and larval lethality. In addition, the transgenic tobacco plants expressing H. armigera EcR dsRNA were also resistant to another lepidopteran pest, the beet armyworm, Spodoptera exigua, due to the high similarity in the nucleotide sequences of their EcR genes. This study provides additional evidence that transgenic plant expressing dsRNA targeting insect-associated genes is able to improve pest resistance.
- Published
- 2012
35. Activating Transcription Factor 3 Deficiency Promotes Cardiac Hypertrophy, Dysfunction, and Fibrosis Induced by Pressure Overload
- Author
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Wei Deng, Qi-Zhu Tang, Jing Zong, Difei Shen, Zhou-Yan Bian, Heng Zhou, Hongliang Li, Yan Zhang, and Yuanyuan Guo
- Subjects
Male ,Mouse ,Activating transcription factor ,lcsh:Medicine ,Signal transduction ,ERK signaling cascade ,Cardiovascular ,Diagnostic Radiology ,Mice ,Molecular cell biology ,Fibrosis ,Myocyte ,Myocytes, Cardiac ,lcsh:Science ,Extracellular Signal-Regulated MAP Kinases ,Multidisciplinary ,Signaling cascades ,Animal Models ,Echocardiography ,Hypertension ,Ventricular pressure ,Medicine ,Cardiomyopathies ,Radiology ,Research Article ,Cardiomyopathy, Dilated ,medicine.medical_specialty ,Cell signaling ,MAP Kinase Signaling System ,Cardiomegaly ,Biology ,Model Organisms ,Internal medicine ,Ventricular Pressure ,medicine ,Animals ,Humans ,Mitogen-Activated Protein Kinase Kinases ,Heart Failure ,Pressure overload ,ATF3 ,Activating Transcription Factor 3 ,Myocardium ,lcsh:R ,Hemodynamics ,JNK Mitogen-Activated Protein Kinases ,medicine.disease ,Angiotensin II ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,lcsh:Q - Abstract
Activating transcription factor 3 (ATF3), which is encoded by an adaptive-response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways.
- Published
- 2011
36. 3,3'-Diindolylmethane Protects against Cardiac Hypertrophy via 5'-Adenosine Monophosphate- Activated Protein Kinase-α2.
- Author
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Jing Zong, Wei Deng, Heng Zhou, Zhou-yan Bian, Jia Dai, Yuan Yuan, Jie-yu Zhang, Rui Zhang, Yan Zhang, Qing-qing Wu, Hai-peng Guo, Hong-liang Li, and Qi-zhu Tang
- Subjects
BRASSICACEAE ,ANTIOXIDANTS ,APOPTOSIS ,TUMORS ,CARDIAC hypertrophy ,HISTOPATHOLOGY - Abstract
Purpose: 3,3'-Diindolylmethane (DIM) is a natural component of cruciferous plants. It has strong antioxidant and anti- angiogenic effects and promotes the apoptosis of a variety of tumor cells. However, little is known about the critical role of DIM on cardiac hypertrophy. In the present study, we investigated the effects of DIM on cardiac hypertrophy. Methods: Multiple molecular techniques such as Western blot analysis, real-time PCR to determine RNA expression levels of hypertrophic, fibrotic and oxidative stress markers, and histological analysis including H&E for histopathology, PSR for collagen deposition, WGA for myocyte cross-sectional area, and immunohistochemical staining for protein expression were used. Results: In pre-treatment and reverse experiments, C57/BL6 mouse chow containing 0.05% DIM (dose 100 mg/kg/d DIM) was administered one week prior to surgery or one week after surgery, respectively, and continued for 8 weeks after surgery. In both experiments, DIM reduced to cardiac hypertrophy and fibrosis induced by aortic banding through the activation of 5'-adenosine monophosphate-activated protein kinase-α2 (AMPKα2) and inhibition of mammalian target of the rapamycin (mTOR) signaling pathway. Furthermore, DIM protected against cardiac oxidative stress by regulating expression of estrogen-related receptor-alpha (ERRα) and NRF2 etc. The cardioprotective effects of DIM were ablated in mice lacking functional AMPKα2. Conclusion: DIM significantly improves left ventricular function via the activation of AMPKα2 in a murine model of cardiac hypertrophy. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
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37. IKKi Deficiency Promotes Pressure Overload-Induced Cardiac Hypertrophy and Fibrosis.
- Author
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Jia Dai, Di-Fei Shen, Zhou-Yan Bian, Heng Zhou, Hua-Wen Gan, Jing Zong, Wei Deng, Yuan Yuan, FangFang Li, Qing-Qing Wu, Lu Gao, Rui Zhang, Zhen-Guo Ma, Hong-Liang Li, and Qi-Zhu Tang
- Subjects
KINASES ,CARDIAC hypertrophy ,APOPTOSIS ,HEART diseases ,CELL death ,HEART size - Abstract
The inducible IkB kinase (IKKi/IKKε) is a recently described serine-threonine IKK-related kinase. Previous studies have reported the role of IKKi in infectious diseases and cancer. However, its role in the cardiac response to pressure overload remains elusive. In this study, we investigated the effects of IKKi deficiency on the development of pathological cardiac hypertrophy using in vitro and in vivo models. First, we developed mouse models of pressure overload cardiac hypertrophy induced by pressure overload using aortic banding (AB). Four weeks after AB, cardiac function was then assessed through echocardiographic and hemodynamic measurements. Western blotting, real-time PCR and histological analyses were used to assess the pathological and molecular mechanisms. We observed that IKKi-deficient mice showed significantly enhanced cardiac hypertrophy, cardiac dysfunction, apoptosis and fibrosis compared with WT mice. Furthermore, we recently revealed that the IKKi-deficient mice spontaneously develop cardiac hypertrophy. Moreover, in vivo experiments showed that IKKi deficiency-induced cardiac hypertrophy was associated with the activation of the AKT and NF-κB signaling pathway in response to AB. In cultured cells, IKKi overexpression suppressed the activation of this pathway. In conclusion, we demonstrate that IKKi deficiency exacerbates cardiac hypertrophy by regulating the AKT and NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
38. Aberrant Resting-State Corticostriatal Functional Connectivity in Cirrhotic Patients with Hyperintense Globus Pallidus on T1-Weighted MR Imaging.
- Author
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Xi-Qi Zhu, Hua-Jun Chen, Yu Wang, Ying Cui, and Gao-Jun Teng
- Subjects
- *
GENETICS , *KIN recognition , *SOCIAL bonds , *BEHAVIOR , *DYADS , *PHILOPATRY - Abstract
Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The twosample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting-state brain dysfunction in real time. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
39. Lipocalin2 Promotes Invasion, Tumorigenicity and Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.
- Author
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Leung, Lisa, Radulovich, Nikolina, Chang-Qi Zhu, Organ, Shawna, Bandarchi, Bizhan, Pintilie, Melania, To, Christine, Panchal, Devang, and Ming Sound Tsao
- Subjects
LIPOCALIN-1 ,PROTEINS ,APOPTOSIS ,METALLOPROTEINASES ,TUMOR growth ,PANCREATIC cancer - Abstract
Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
40. Improvement of Pest Resistance in Transgenic Tobacco Plants Expressing dsRNA of an Insect-Associated Gene EcR.
- Author
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Jin-Qi Zhu, Shumin Liu, Yao Ma, Jia-Qi Zhang, Hai-Sheng Qi, Zhao-Jun Wei, Qiong Yao, Wen-Qing Zhang, and Sheng Li
- Subjects
- *
TRANSGENIC plants , *RNA , *DISEASE resistance of plants , *TOBACCO , *BEET armyworm - Abstract
The adoption of pest-resistant transgenic plants to reduce yield loss and pesticide utilization has been successful in the past three decades. Recently, transgenic plant expressing double-stranded RNA (dsRNA) targeting pest genes emerges as a promising strategy for improving pest resistance in crops. The steroid hormone, 20-hydroxyecdysone (20E), predominately controls insect molting via its nuclear receptor complex, EcR-USP. Here we report that pest resistance is improved in transgenic tobacco plants expressing dsRNA of EcR from the cotton bollworm, Helicoverpa armigera, a serious lepidopteran pest for a variety of crops. When H. armigera larvae were fed with the whole transgenic tobacco plants expressing EcR dsRNA, resistance to H. armigera was significantly improved in transgenic plants. Meanwhile, when H. armigera larvae were fed with leaves of transgenic tobacco plants expressing EcR dsRNA, its EcR mRNA level was dramatically decreased causing molting defects and larval lethality. In addition, the transgenic tobacco plants expressing H. armigera EcR dsRNA were also resistant to another lepidopteran pest, the beet armyworm, Spodoptera exigua, due to the high similarity in the nucleotide sequences of their EcR genes. This study provides additional evidence that transgenic plant expressing dsRNA targeting insect-associated genes is able to improve pest resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
41. Relating excitatory and inhibitory neurochemicals to visual perception: A magnetic resonance study of occipital cortex between migraine events.
- Author
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Yu Man Chan, Kabilan Pitchaimuthu, Qi-Zhu Wu, Olivia L Carter, Gary F Egan, David R Badcock, and Allison M McKendrick
- Subjects
Medicine ,Science - Abstract
Certain perceptual measures have been proposed as indirect assays of brain neurochemical status in people with migraine. One such measure is binocular rivalry, however, previous studies have not measured rivalry characteristics and brain neurochemistry together in people with migraine. This study compared spectroscopy-measured levels of GABA and Glx (glutamine and glutamate complex) in visual cortex between 16 people with migraine and 16 non-headache controls, and assessed whether the concentration of these neurochemicals explains, at least partially, inter-individual variability in binocular rivalry perceptual measures. Mean Glx level was significantly reduced in migraineurs relative to controls, whereas mean occipital GABA levels were similar between groups. Neither GABA levels, nor Glx levels correlated with rivalry percept duration. Our results thus suggest that the previously suggested relationship between rivalry percept duration and GABAergic inhibitory neurotransmitter concentration in visual cortex is not strong enough to enable rivalry percept duration to be reliably assumed to be a surrogate for GABA concentration, at least in the context of healthy individuals and those that experience migraine.
- Published
- 2019
- Full Text
- View/download PDF
42. Establishment and Validation of GV-SAPS II Scoring System for Non-Diabetic Critically Ill Patients.
- Author
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Wen-Yue Liu, Shi-Gang Lin, Gui-Qi Zhu, Sven Van Poucke, Martin Braddock, Zhongheng Zhang, Zhi Mao, Fei-Xia Shen, and Ming-Hua Zheng
- Subjects
Medicine ,Science - Abstract
Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiology Score II scoring system (SAPS II), integrated with GV parameters and named GV-SAPS II, specifically for non-diabetic critically ill patients to predict short-term and long-term mortality.Training and validation cohorts were exacted from the Multiparameter Intelligent Monitoring in Intensive Care database III version 1.3 (MIMIC-III v1.3). The GV-SAPS II score was constructed by Cox proportional hazard regression analysis and compared with the original SAPS II, Sepsis-related Organ Failure Assessment Score (SOFA) and Elixhauser scoring systems using area under the curve of the receiver operator characteristic (auROC) curve.4,895 and 5,048 eligible individuals were included in the training and validation cohorts, respectively. The GV-SAPS II score was established with four independent risk factors, including hyperglycemia, hypoglycemia, standard deviation of blood glucose levels (GluSD), and SAPS II score. In the validation cohort, the auROC values of the new scoring system were 0.824 (95% CI: 0.813-0.834, P< 0.001) and 0.738 (95% CI: 0.725-0.750, P< 0.001), respectively for 30 days and 9 months, which were significantly higher than other models used in our study (all P < 0.001). Moreover, Kaplan-Meier plots demonstrated significantly worse outcomes in higher GV-SAPS II score groups both for 30-day and 9-month mortality endpoints (all P< 0.001).We established and validated a modified prognostic scoring system that integrated glucose variability for non-diabetic critically ill patients, named GV-SAPS II. It demonstrated a superior prognostic capability and may be an optimal scoring system for prognostic evaluation in this patient group.
- Published
- 2016
- Full Text
- View/download PDF
43. Percutaneous Aspiration Thrombectomy for Arterial Thromboembolism during Infrainguinal Endovascular Recanalization.
- Author
-
Li-Ming Wei, Yue-Qi Zhu, Fang Liu, Pei-Lei Zhang, Xiao-Cong Li, Jun-Gong Zhao, and Hai-Tao Lu
- Subjects
Medicine ,Science - Abstract
To evaluate the efficacy of percutaneous aspiration thrombectomy (PAT) for infrainguinal arterial thromboembolism in patients undergoing endovascular recanalization (EVR) and to investigate the predictors for thromboembolic complications.In total, 23 patients (23 limbs) who underwent PAT for thromboembolism (PAT group, PG) during EVR and 237 patients (302 limbs) who underwent successful EVR without thromboembolic complications (control group, CG) were enrolled. Immediate post-operation and follow-up outcomes were compared between the two groups. Multivariate analysis was performed to identify the predictors of thromboembolic complications. Technical success of PAT was defined as achievement of
- Published
- 2015
- Full Text
- View/download PDF
44. Establishment and Validation of SSCLIP Scoring System to Estimate Survival in Hepatocellular Carcinoma Patients Who Received Curative Liver Resection.
- Author
-
Sha Huang, Gui-Qian Huang, Gui-Qi Zhu, Wen-Yue Liu, Jie You, Ke-Qing Shi, Xiao-Bo Wang, Han-Yang Che, Guo-Liang Chen, Jian-Feng Fang, Yi Zhou, Meng-Tao Zhou, Yong-Ping Chen, Martin Braddock, and Ming-Hua Zheng
- Subjects
Medicine ,Science - Abstract
There is no prognostic model that is reliable and practical for patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). This study aimed to establish and validate a Surgery-Specific Cancer of the Liver Italian Program (SSCLIP) scoring system for those patients.668 eligible patients who underwent CLR for HCC from five separate tertiary hospitals were selected. The SSCLIP was constructed from a training cohort by adding independent predictors that were identified by Cox proportional hazards regression analyses to the original Cancer of the Liver Italian Program (CLIP). The prognostic performance of the SSCLIP at 12 and 36-months was compared with data from existing models. The patient survival distributions at different risk levels of the SSCLIP were also assessed.Four independent predictors were added to construct the SSCLIP, including age (HR = 1.075, 95%CI: 1.019-1.135, P = 0.009), albumin (HR = 0.804, 95%CI: 0.681-0.950, P = 0.011), prothrombin time activity (HR = 0.856, 95%CI: 0.751-0.975, P = 0.020) and microvascular invasion (HR = 19.852, 95%CI: 2.203-178.917, P = 0.008). In both training and validation cohorts, 12-month and 36-month prognostic performance of the SSCLIP were significantly better than those of the original CLIP, model of end-stage liver disease-based CLIP, Okuda and Child-Turcotte-Pugh score (all P < 0.05). The stratification of risk levels of the SSCLIP showed an enhanced ability to differentiate patients with different outcomes.A novel SSCLIP to predict survival of HCC patients who received CLR based on objective parameters may provide a refined, useful prognosis algorithm.
- Published
- 2015
- Full Text
- View/download PDF
45. p120RasGAP is a mediator of rho pathway activation and tumorigenicity in the DLD1 colorectal cancer cell line.
- Author
-
Shawna L Organ, Josephine Hai, Nikolina Radulovich, Christopher B Marshall, Lisa Leung, Takehiko Sasazuki, Senji Shirasawa, Chang-Qi Zhu, Roya Navab, Mitsuhiko Ikura, and Ming-Sound Tsao
- Subjects
Medicine ,Science - Abstract
KRAS is mutated in ∼40% of colorectal cancer (CRC), and there are limited effective treatments for advanced KRAS mutant CRC. Therefore, it is crucial that downstream mediators of oncogenic KRAS continue to be studied. We identified p190RhoGAP as being phosphorylated in the DLD1 CRC cell line, which expresses a heterozygous KRAS G13D allele, and not in DKO4 in which the mutant allele has been deleted by somatic recombination. We found that a ubiquitous binding partner of p190RhoGAP, p120RasGAP (RasGAP), is expressed in much lower levels in DKO4 cells compared to DLD1, and this expression is regulated by KRAS. Rescue of RasGAP expression in DKO4 rescued Rho pathway activation and partially rescued tumorigenicity in DKO4 cells, indicating that the combination of mutant KRAS and RasGAP expression is crucial to these phenotypes. We conclude that RasGAP is an important effector of mutant KRAS in CRC.
- Published
- 2014
- Full Text
- View/download PDF
46. Classification of cirrhotic patients with or without minimal hepatic encephalopathy and healthy subjects using resting-state attention-related network analysis.
- Author
-
Hua-Jun Chen, Yu Wang, Xi-Qi Zhu, Pei-Cheng Li, and Gao-Jun Teng
- Subjects
Medicine ,Science - Abstract
BACKGROUND: Attention deficit is an early and key characteristic of minimal hepatic encephalopathy (MHE) and has been used as indicator for MHE detection. The aim of this study is to classify the cirrhotic patients with or without MHE (NMHE) and healthy controls (HC) using the resting-state attention-related brain network analysis. METHODS AND FINDINGS: Resting-state fMRI was administrated to 20 MHE patients, 21 NMHE patients, and 17 HCs. Three attention-related networks, including dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN), were obtained by independent component analysis. One-way analysis of covariance was performed to determine the regions of interest (ROIs) showing significant functional connectivity (FC) change. With FC strength of ROIs as indicators, Linear Discriminant Analysis (LDA) was conducted to differentiate MHE from HC or NMHE. Across three groups, significant FC differences were found within DAN (left superior/inferior parietal lobule and right inferior parietal lobule), VAN (right superior parietal lobule), and DMN (bilateral posterior cingulate gyrus and precuneus, and left inferior parietal lobule). With FC strength of ROIs from three networks as indicators, LDA yielded 94.6% classification accuracy between MHE and HC (100% sensitivity and 88.2% specificity) and 85.4% classification accuracy between MHE and NMHE (90.0% sensitivity and 81.0% specificity). CONCLUSIONS: Our results suggest that the resting-state attention-related brain network analysis can be useful in classification of subjects with MHE, NMHE, and HC and may provide a new insight into MHE detection.
- Published
- 2014
- Full Text
- View/download PDF
47. Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.
- Author
-
Yun Fu Wang, Ping You Chen, Wei Chang, Fi Qi Zhu, Li Li Xu, Song Lin Wang, Li Ying Chang, Jie Luo, and Guang Jian Liu
- Subjects
Medicine ,Science - Abstract
Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica.Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria.Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065).The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.
- Published
- 2014
- Full Text
- View/download PDF
48. Loss of canonical Smad4 signaling promotes KRAS driven malignant transformation of human pancreatic duct epithelial cells and metastasis.
- Author
-
Lisa Leung, Nikolina Radulovich, Chang-Qi Zhu, Dennis Wang, Christine To, Emin Ibrahimov, and Ming-Sound Tsao
- Subjects
Medicine ,Science - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer death in North America. Activating KRAS mutations and Smad4 loss occur in approximately 90% and 55% of PDAC, respectively. While their roles in the early stages of PDAC development have been confirmed in genetically modified mouse models, their roles in the multistep malignant transformation of human pancreatic duct cells have not been directly demonstrated. Here, we report that Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE) cell line model. Marked Smad4 downregulation by shRNA in KRAS (G12V) expressing HPDE cells failed to cause tumorigenic transformation. However, KRAS-mediated malignant transformation occurred in a new HPDE-TGF-β resistant (TβR) cell line that completely lacks Smad4 protein expression and is resistant to the mito-inhibitory activity of TGF-β. This transformation resulted in tumor formation and development of metastatic phenotype when the cells were implanted orthotopically into the mouse pancreas. Smad4 restoration re-established TGF-β sensitivity, markedly increased tumor latency by promoting apoptosis, and decreased metastatic potential. These results directly establish the critical combination of the KRAS oncogene and complete Smad4 inactivation in the multi-stage malignant transformation and metastatic progression of normal human HPDE cells.
- Published
- 2013
- Full Text
- View/download PDF
49. Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.
- Author
-
Lisa Leung, Nikolina Radulovich, Chang-Qi Zhu, Shawna Organ, Bizhan Bandarchi, Melania Pintilie, Christine To, Devang Panchal, and Ming Sound Tsao
- Subjects
Medicine ,Science - Abstract
Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.
- Published
- 2012
- Full Text
- View/download PDF
50. Activating transcription factor 3 deficiency promotes cardiac hypertrophy, dysfunction, and fibrosis induced by pressure overload.
- Author
-
Heng Zhou, Di-Fei Shen, Zhou-Yan Bian, Jing Zong, Wei Deng, Yan Zhang, Yuan-Yuan Guo, Hongliang Li, and Qi-Zhu Tang
- Subjects
Medicine ,Science - Abstract
Activating transcription factor 3 (ATF3), which is encoded by an adaptive-response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways.
- Published
- 2011
- Full Text
- View/download PDF
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