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Now showing items 17 - 28 of 28

  • Non-motor Symptoms in Parkinson's Disease Patients with Parkin Mutations:More Depression and Less Executive Dysfunction

    Song, Jie   Shen, Bo   Yang, Yu-Jie   Liu, Feng-tao   Zhao, Jue   Tang, Yi-Lin   Chen, Chen   Ding, Zheng-Tong   An, Yu   Wu, Jian-Jun   Sun, Yi-Min   Wang, Jian  

    The purpose of this study was to identify differences between genetically undefined (GU) early-onset Parkinson's disease (EOPD) patients and carriers of Parkin mutations on non-motor symptoms (NMSs). EOPD patients (N =3D 261) underwent targeted sequencing of Parkinson's disease (PD) related genes. Among them, 53 cases carried homozygous or compound heterozygous Parkin mutations (Parkin group) while 208 did not carry known causative PD mutations or risk factors of GBA or Parkin heterozygous mutations (GU group). NMSs were evaluated by face-to-face interviews, self-completed questionnaires and results on a neuropsychological battery. Linear regression and logistic regression models were applied to assess the predictors of NMSs. Parkin patients had younger ages of onset (AOO) (p < 0.001), longer disease durations (p < 0.001) and lower grades of Hoehn and Yarh (H&Y) (p =3D 0.007). Results on the neuropsychological battery showed a shorter time in Trail Making Test (TMT) (part B) in Parkin patients (p =3D 0.034) compared to GU patients. After adjusting for AOO, disease duration, H&Y, and levodopa equivalent daily dose (LEDD), there was a higher depression index on the Beck Depression Inventory (BDI) (p =3D 0.013) and better performance (p =3D 0.038) on executive function in the Parkin group compared to the GU group. No significant differences were found for autonomic functions, sleep-wake problems or other domains of cognitive function. Our study showed that the Parkin mutation status might be a good predictor of symptoms of depression without an impact on executive function. While these findings need to be confirmed in larger cohorts, they identify a need to screen for depression. Flow chart of genetic tests
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  • Sp5l is a mediator of fgf signals in anteroposterior patterning of the neuroectoderm in zebrafish embryo

    Sun, Zhihui   Zhao, Jue   Zhang, Yu   Meng, Anming  

    The neuroectoderm is patterned along the anterior-posterior axis in vertebrate embryos. Fgf signals are required to induce the posterior neuroectodermal fates, but they repress the anterior fate. Sp51/Spr2, an Sp1-like transcription factor family member, has been shown to be required for development of mesoderm and posterior neuroectoderm. We demonstrate here that repression of the anterior neuroectodermal markers fez and otx1 by fgf17b or fgf3 coincides with induction of sp5l in the anterior neuroectoderm, and that this repression is efficiently rescued by simultaneous sp5l knockdown. On the other hand, sp5l knockdown is able to inhibit inductive activity of ectopic Fgf signals on the expression of the posterior neuroectodermal markers gbx2, hoxb1b, and krox20. Furthermore, effect of overexpression of a dominant negative Fgf receptor on anteroposterior patterning of the neuroectoderm is rescued by sp5l overexpression. Taken together, these data suggest that sp5l mediates the functions of Fgf signals in anteroposterior patterning of the neuroectoderm during zebrafish embryogenesis.
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  • The transcription factor Vox represses endoderm development by interacting with Casanova and Pou2

    Zhao, Jue   Lambert, Guillaume   Meijer, Annemarie H.   Rosa, Frederic M.  

    Endoderm and mesoderm are both formed upon activation of Nodal signaling but how endoderm differentiates from mesoderm is still poorly explored. The sox-related gene casanova (sox32) acts downstream of the Nodal signal, is essential for endoderm development and requires the co-factor Pou2 (Pou5f1, Oct3, Oct4) in this process. Conversely, BMP signals have been shown to inhibit endoderm development by an as yet unexplained mechanism. In a search for Casanova regulators in zebrafish, we identified two of its binding partners as the transcription factors Pou2 and Vox, a member of the Vent group of proteins also involved in the patterning of the gastrula. In overexpression studies we show that vox and/or Vent group genes inhibit the capacity of Casanova to induce endoderm, even in the presence of its co-factor Pou2, and that Vox acts as a repressor in this process. We further show that vox, but not other members of the Vent group, is essential for defining the proper endodermal domain size at gastrulation. In this process, vox acts downstream of BMPs. Cell fate analysis further shows that Vox plays a key role downstream of BMP signals in regulating the capacity of Nodal to induce endoderm versus mesoderm by modulating the activity of the Casanova/Pou2 regulatory system.
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  • Evidence of Repurposing Drugs and Identifying Contraindications from Real World Study in Parkinson's Disease

    Tang, Yilin   Yang, Ke   Zhao, Jue   Liang, Xiaoniu   Wang, Jian  

    There is great unmet need in discovering novel treatment for Parkinson's disease (PD) and identifying the new agents potentially causing drug-induced parkinsonism. New indications and contraindications of drugs are typically approved following rigorous randomized controlled trial (RCT) evaluation. However, RCTs have their inherent limitations, since they are usually conducted in ideal conditions, with high cost and limited follow-up periods. In the past decade, large cohort studies with long follow-up outcome data was derived from a PD database in a real-world setting. Studies based on real world data (RWD) can help to augment and extrapolate data obtained in,RCTs and provide information about the safety and effectiveness of a medication in heterogeneous, large populations. In the present review, we focus on the published real world studies designed to develop new treatment strategies for repurposing drugs and identifying contraindications for PD. We also outline the challenges and limitations in these studies. Subsequently we introduce PaWei app platform, which hopefully can facilitate PD management and address real-world problems associated with PD. Better understanding of RWD collection and analysis is needed if RWD is to achieve its full potential.
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  • Cognitive characteristics in Chinese non-demented PD patients based on gender difference

    Yang, Ke   Shen, Bo   Li, Da-ke   Wang, Ying   Zhao, Jue   Zhao, Jian   Yu, Wen-Bo   Liu, Zhen-yang   Tang, Yi-lin   Liu, Feng-tao   Yu, Huan   Wang, Jian   Guo, Qi-hao   Wu, Jian-jun  

    Background: Cognitive impairment is one of the non-motor symptoms in Parkinson's disease (PD). In the present study, we aim to examine the cognitive function of non-demented Parkinson's disease patients and compare the results between male and female patients as well as control groups in search of any gender effect. Methods: Sixty PD Patients (30 males and 30 females) from the Movement Disorders Clinic at Huashan Hospital Affiliated to Fudan University were recruited to participate in the study. One hundred age and gender matched control subjects without neurological or psychiatric disorders were voluntarily recruited. The participants were administered measures of cognition in five domains including memory, language, spatial processing abilities, attention and executive function. Results: PD patients attained significantly lower scores in the visual spatial function, language and attention/executive function compared with the control group. Anti-parkinsonian treated patients performed worse in Rey-copy score, Clock Drawing Test (CDT) and Verbal Fluency-City than untreated ones. In regard to gender differences, though no general cognitive differences were found in Mini-mental State Examination (MMSE), men surpassed women on Boston naming test (BNT) while women were superior on Auditory Verbal Learning Test-long (AVLT) delayed cued recall test. Conclusions: Cognitive impairments were common in PD patients even in the absence of dementia. PD patients with anti-parkinsonian medication had worse cognitive impairment than untreated patients. Genders may have different manifestations of cognitive impairment in PD patients.
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  • Purification procedure sensitizes Bacillus endospores to free radicals from UVA radiation and photocatalysis

    Krishna, Vijay   Zhao, Jue   Koopman, Ben   Moudgil, Brij  

    Many researchers are investigating the extreme resilience of bacterial endospores against chemical and physical inactivating agents. The presence of vegetative cells in spore suspensions can result in overly optimistic assessment of inactivating agents; therefore, various spore purification methods have been applied to separate spores from vegetative cells prior to testing. The present study was undertaken to evaluate the effect of two widely used spore purification methodologies on spore integrity and susceptibility to ultraviolet-A (UVA) radiation and free radicals generated from photocatalysts. Bacillus subtilis and Bacillus cereus spores were purified by procedures that involved heat shock alone or chemical washes, lysozyme treatment and heat shock (CLH). The purified spores were exposed to UVA radiation or free radicals generated by photocatalyst and susceptibility were evaluated in terms of survival ratio. The effect of purification procedure on the spore morphology was investigated with electron microscopy. The CLH purification process significantly damages spore coats and increases the susceptibility of Bacillus spores to UVA radiation and photocatalytic inactivation. It is therefore likely that the survival of CLH treated spores in extra-terrestrial environments would be less than that of the same spores purified by a less aggressive procedure.
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  • Predictors to quality of life improvements after subthalamic stimulation in Parkinson's disease

    Liu, Feng-Tao   Lang, Li-Qin   Yang, Yu-Jie   Zhao, Jue   Feng, Rui   Hu, Jie   Wang, Jian   Wu, Jian-Jun  

    Introduction Subthalamic deep brain stimulation (STN DBS) has been reported to improve the quality of life (QoL) related to Parkinson's disease (PD). However, not all subjects are satisfied with the postsurgical QoL outcome. We aimed to detect the related factors and possible predictors to QoL improvement for those PD patients one year after STN DBS. Materials and Methods A total of 45 PD patients with bilateral STN DBS surgery were included and followed up for 1 year. The Reliable Change Index (RCI) was adapted to determine the individual postsurgical QoL outcome. The changes of QoL were correlated with baseline parameters and the changes of progression parameters using Pearson's correlation. The exploratory stepwise regressions were adopted to detect the extents of baseline variables and progression parameters. The predictors to QoL outcome were detected using the logistic regression analysis. Results A total of 51.1% of the patients reported a better QoL, 40.0% of patients reported an unchanged QoL, while 8.9% of patients reported a worsening of QoL. The subdomains of mobility, activity of daily living, cognition, and bodily discomfort improved significantly after the surgery. The presurgical factors including QoL, dopaminergic medication burden, disease stages, depression scores, and postsurgical reductions in depression and nonmotor scores were found to correlate with QoL changes. Furthermore, the greater presurgical QoL burden, lesser dopaminergic medication exposure, and earlier disease stages were predictors to QoL improvements. Conclusion The clinicians should carefully evaluate the nonmotor symptoms and life quality in those patients at relatively earlier stages and with lower medicine dosage to get more successful DBS outcomes.
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  • Zwitterionic stealth peptide-protected gold nanoparticles enable long circulation without the accelerated blood clearance phenomenon.

    Zhao, Jue   Qin, Zhihui   Wu, Jina   Li, Lijie   Jin, Qiao   Ji, Jian  

    Poly(ethylene glycol) (PEG), which is considered as a gold standard for surface modification of nanoparticles in biomedical applications, has been reported to encounter the accelerated blood clearance (ABC) phenomenon after repeated administration. Herein, as an ideal substitute for PEG, a zwitterionic peptide sequence of alternating negatively charged glutamic acid (E) and positively charged lysine (K) was designed as a good candidate for surface modification of nanoparticles without the ABC phenomenon in vivo. PEG-protected gold nanoparticles (AuNP-PEG) suffered from a serious ABC phenomenon with very fast blood clearance after repeated injection. Meanwhile, the plasma IgM and IgG levels were significantly increased after the repeated injection of AuNP-PEG. However, zwitterionic stealth peptide-protected gold nanoparticles (AuNP-EK10) could avoid the activation of the ABC phenomenon. The increase of IgM and IgG levels was not observed after the repeated injection of AuNP-EK10. More interestingly, compared to AuNP-PEG, more AuNP-EK10 could be accumulated in tumor tissues after repeated injection of the nanoparticles to tumor-bearing nude mice, which might be especially important for the design of drug nanocarriers in cancer therapy.=20
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  • Fgf-signaling-dependent Sox9a and Atoh1a regulate otic neural development in zebrafish.

    Wang, Jialiang   Wu, Ying   Zhao, Feng   Wu, Yuting   Dong, Wei   Zhao, Jue   Zhu, Zuoyan   Liu, Dong  

    Fibroblast growth factors (Fgfs) play important roles in developmental processes of the inner ear, including the ontogeny of the statoacoustic ganglia (SAG) and hair cells. However, the detailed genetic mechanism(s) underlying Fgf/Fgfr-dependent otic neural development remains elusive. Using conditional genetic approaches and inhibitory small molecules, we have revealed that Fgfr-PI3K/Akt signaling is mainly responsible for zebrafish SAG development and have determined that Sox9a and Atoh1a act downstream of Fgfr-Akt signaling to specify and/or maintain the otic neuron fate during the early segmentation stage. Sox9a and Atoh1a coregulate numerous downstream factors identified through our ChIP-seq analyses, including Tlx2 and Eya2. Fgfr-Erk1/2 signaling contributes to ultricular hair cell development during a critical period between 9 and 15 hours postfertilization. Our work reveals that a genetic network of the previously known sensory determinant Atoh1 and the neural crest determinant Sox9 plays critical roles in SAG development. These newly uncovered roles for Atoh1and Sox9 in zebrafish otic development may be relevant to study in other species. Copyright =C2=A9 2015 the authors 0270-6474/15/350234-11$15.00/0.
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  • A cascade enzymatic reaction activatable gemcitabine prodrug with an AIE-based intracellular light-up apoptotic probe for in situ self-therapeutic monitoring

    Han, Haijie   Teng, Wenzhuo   Chen, Tingting   Zhao, Jue   Jin, Qiao   Qin, Zhihui   Ji, Jian  

    A targeted cathepsin B-activatable gemcitabine prodrug with caspase-3 specific light-up tetraphenylene (TPE) as an apoptotic probe based on aggregation-induced emission (AIE) properties was designed for in situ self-therapeutic monitoring of pancreatic cancer cells.
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  • Depressive Symptoms Are Associated With Color Vision but not Olfactory Function in Patients With Parkinson's Disease

    Li, Da-Ke   Liu, Feng-Tao   Chen, Kui   Bu, Lu-Lu   Yang, Ke   Chen, Chen   Liu, Zhen-Yang   Tang, Yi-Lin   Zhao, Jue   Sun, Yi-Min   Wang, Jian   Wu, Jian-Jun  

    Depressive symptoms and sensory dysfunction, such as reduction in visual and olfactory function, are common in Parkinson's disease (PD). Previous studies have suggested that depressive symptoms are associated with visual impairments and potentially with hyposmia in several types of mood disorders. However, the relationship between depressive symptoms and sensory dysfunction remains unclear in PD. To examine the association of depressive symptoms with color vision and olfactory function in PD, the authors conducted a cross-sectional study in 159 patients with PD. Depressive symptoms were measured with the Beck Depression Inventory-II (BDI-II) and the 30-item Geriatric Depression Scale (GDS-30); color vision was tested with the Farnsworth-Munsell 100 Hue Test (FMT); and olfactory function was tested with the Sniffin' Sticks Screening 12 Test. Results showed that the total error score (TES) for the FMT was significantly and independently correlated with scores on both the BDI-II and GDS-30 in a positive manner, suggesting that more severe depressive symptoms are associated with poorer color vision in PD. In addition, both somatic and effective subscores for the BDI-II were correlated with the TES on the FMT, while no significant correlation was observed between total scores on the Sniffin' Sticks Screening 12 Test and BDI-II or GDS-30. The decrease in color vision but not olfactory function was found to be associated with the severity of depressive symptoms in PD patients, supporting the idea that the occurrence of depressive symptoms in PD is linked with disruption of the visual system.
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  • Fasudil,a Rho kinase inhibitor,promotes the autophagic degradation of A53T alpha-synuclein by activating the JNK 1/Bcl-2/beclin 1 pathway

    Liu, Feng-Tao   Yang, Yu-Jie   Wu, Jian-Jun   Li, Shan   Tang, Yi-Lin   Zhao, Jue   Liu, Zhen-Yang   Xiao, Bao-Guo   Zuo, Ji   Liu, Wen   Wang, Jian  

    Accumulation of alpha-synuclein (alpha-syn) is pivotally implicated in the pathogenesis of Parkinson's disease (PD), and enhancing its clearance might be a promising strategy in PD treatment. It has recently been shown that Rho kinase (ROCK) activation is involved in many neurodegenerative diseases, and some ROCK inhibitors might promote the degradation of abnormal protein aggregates. However, it is not known if fasudil, the only ROCK inhibitor available in clinical setting, could promote the degradation of alpha-syn, and ameliorate the alpha-syn induced neurotoxicity. In this regard, we investigated the effect of fasudil on neurite injury caused by A53T alpha-syn overexpression and the implicated pathway it might mediate. In the current study, we found that under the condition of A53T alpha-syn overexpression, the neurite outgrowth decreased significantly with the increasing expression of ROCK2. Fasudil, the ROCK inhibitor, ameliorated such neurotoxicity and promoted the clearance of A53T alpha-syn. Its underlying mechanism was supported by that fasudil could increase the macroautophagy activation via JNK 1 and Bcl-2 phosphorylation and beclin 1/Vps34 complex formation. Taken together, fasudil might be able to provide a novel and promising strategy for PD treatment by enhancing alpha-syn clearance and activating the JNK 1/Bcl-2/beclin 1 pathway. (C) 2015 Elsevier B.V. All rights reserved.
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