Wincon TheraCells Biotechnologies Co.

Nanning, China

Wincon TheraCells Biotechnologies Co.

Nanning, China
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Ren G.,Capital Medical University | Ren G.,Beijing Institute for Brain Disorders | Yan J.,North China University of Technology | Tao G.,Wincon TheraCells Biotechnologies Co. | And 12 more authors.
Experimental Neurology | Year: 2017

Rapid focal cooling is an attractive nondestructive strategy to control and possibly prevent focal seizures. However, the temperature threshold necessary to abort seizures in primates is still unknown. Here, we explored this issue in a primate epilepsy model and observed the effect of rapid cooling on different electroencephalogram frequency bands, aiming at providing necessary experimental data for future clinical translational studies and exploring the mechanism of focal cooling in terminating seizures. We induced focal neocortical seizures using microinjection of 4-aminopyridine into premotor cortex in five anesthetized cynomolgus monkeys. The rapid focal cooling was implemented by using a thermoelectric (Peltier) device. As a result, the average durations of seizures and interictal intervals before cooling were 94.3 ± 4.0 s and 62.3 ± 6.9 s, respectively. When the cortex was cooled to 20 °C or 18 °C, there was no effect on seizure duration (109.4 ± 30.0 s, 91.3 ± 19.3 s) or interictal duration (99.4 ± 26.8 s, 83.2 ± 11.5 s, P > 0.05). But when the cortex was cooled to 16 °C, the seizure duration was reduced to 54.1 ± 4.9 s and the interictal duration was extended to 175.0 ± 16.7 s (P < 0.05). Electroencephalogram spectral analysis showed that the power of delta, alpha, beta, gamma and ripples bands in seizures were significantly reduced at 20 °C and 18 °C. At 16 °C, the power of theta band in seizures was also significantly reduced along with the other bands. Our data reveal that the temperature threshold in rapid focal cooling required to significantly shorten neocortical seizures in nonhuman primates is 16 °C, and inhibition of electroencephalogram broadband spectrum power, especially power of theta band, may be the underlying mechanism to control seizures. © 2017


Yue F.,Capital Medical University | Zhang G.,Wincon TheraCells Biotechnologies Co. | Zhang G.,Guangxi Medical University | Quintero J.E.,University of Kentucky | And 2 more authors.
Experimental Gerontology | Year: 2017

Type 2 diabetes mellitus is the most common form of diabetes that occurs in both human and nonhuman primates. Although spontaneously diabetic nonhuman primates are used extensively in diabetic related research and are a proven valuable tool for the study of the natural history of diabetes, little is known about the key factors that can cause this metabolic disorder and the preventative measures that could be employed to minimize the consequences of diabetes. Using a model of developing and untreated diabetes, this study describes the effects of housing arrangement (socially group- versus individually single-housed), exercise, diet, age, and sex on fasting plasma glucose, key lipids associated with diabetes, and bodyweight in two large cohorts of nonhuman primates. Key findings include exercise/housing arrangement's contribution to significant differences in bodyweight, levels of fasting plasma glucose, total cholesterol, and high- and low-density lipoproteins. Age also had profound effects on glucose, triglyceride and high-density lipoproteins, particularly in single-caged animals. Moreover, females had higher fasting glucose, total cholesterol and triglyceride levels than male counterparts within the same housing situations. These factors may be critical to identifying preventive measures that could eventually be used to minimize obesity and diabetes in humans. © 2017 Elsevier Inc.


Wu D.,Capital Medical University | Jiang W.Y.,Peoples Hospital of Sichuan Province | Yang F.,Peoples Hospital of Sichuan Province | Wei S.Y.,Wincon TheraCells Biotechnologies Co. | And 5 more authors.
Journal of Medical Primatology | Year: 2013

Background: Limited physiological data for Tibetan macaques are available at present. This study will provide more rationale for evaluating this species. Methods: Thirty-seven Tibetan macaques (15 males and 22 females) were used in this study. Somatometric measurements, clinical chemistry and hematology parameters, insulin, and C-peptide were analyzed. Results: Females had higher values of waist and waist hip ratio (WHR) than males in somatometric measurements. There were no significant differences between the two genders in hematology. Significant differences between males and females were only found for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in biochemistry testing. In addition, females had higher fasting insulin and C-peptide than males. There was a strongly positive correlation between age and some somatometric parameters. Conclusions: These physiological data will provide veterinarians and researchers with baseline values to evaluate experimental results using Tibetan macaques. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Zhu L.,Beijing Normal University | Zhu L.,University of Pennsylvania | Qiao H.,Beijing Normal University | Qiao H.,University of Pennsylvania | And 13 more authors.
Nuclear Medicine and Biology | Year: 2012

Objectives: Recently, 9-[18F]fluoropropyl-(+)-dihydrotetrabenazine (18F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of 18F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). Methods: To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using 18F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative 18F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding. Results: The radiochemical purity of the 18F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of 18F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction). Conclusions: The pseudo-carrier, AV-149, did not affect the 18F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable 18F-AV-133 to be widely available for routine clinical application in determining changes in monoamine neurons for patient with movement disorders or other psychiatric illnesses. © 2012 Elsevier Inc.


Yue F.,Capital Medical University | Yue F.,Key Laboratory On Parkinsons Disease | Zeng S.,Guilin Medical College | Tang R.,Wincon TheraCells Biotechnologies Co. | And 3 more authors.
Neuroscience Bulletin | Year: 2016

In this study, we developed a systemic PD model in middle-aged cynomolgus monkeys using individualized low-dose MPTP, to explore effective indicators for the early prediction of clinical outcomes. MPTP was not stopped until the animals showed typical PD motor symptoms on days 10 to 13 after MPTP administration when the Kurlan score reached 10; this abrogated the differences in individual susceptibility to MPTP. The clinical symptoms persisted, peaking on days 3 to 12 after MPTP withdrawal (rapid progress stage), and then the Kurlan score plateaued. A Kurlan score at the end of the rapid progress stage >15 reflected stable or slowly-progressive PD, while a score <15 indicated spontaneous recovery. The entire clinical evolution and outcome of the systemic PD model was characterized in this study, thus providing options for therapeutic and translational research. © 2016 Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore


Zou C.,Capital Medical University | Zou C.,Key Laboratory of Neurodegeneration | Zou C.,Guangxi Medical University | Wang S.,Capital Medical University | And 4 more authors.
Cornea | Year: 2012

Purpose: The purpose of this study was to investigate the ultrastructural corneal changes of chronic diabetic monkeys and explore the relationship between advanced glycation end products and ultrastructural changes in diabetic corneas. Methods: A total of 8 cynomolgus monkeys were used in this experiment. Four monkeys were induced into insulin-dependent diabetes mellitus for 4 years. Four age-matched healthy monkeys were used as the controls. Ultrathin sections obtained from the corneas were examined by transmission electron microscopy. Results: Advanced glycation end product immunoreactivity was observed in the epithelial cells, epithelial basement membrane, and stromal keratocytes of diabetic corneas, whereas advanced glycation end product immunoreactivity was not found in the corresponding area in normal corneas. Abnormal collagen fibril bundles of variable thickness were identified in corneal stroma in all diabetic monkeys. Epithelial and endothelial cell degeneration was also observed in 1 diabetic monkey. Conclusions: Abnormal aggregates of collagen fibrils in stromal matrix were common among long-term diabetic monkeys, and the formation of the abnormal collagen fibril aggregates might result from excessive nonenzymatic glycosylation. Copyright © 2012 by Lippincott Williams and Wilkins.


PubMed | University of Kentucky, WinconTheraCells Biotechnologies Co and Xuanwu Hospital of Capital Medical University
Type: Journal Article | Journal: Neurobiology of aging | Year: 2014

Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop -amyloid (A) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associated changes in A and tau protein in cerebrospinal fluid. The present study was an attempt to specifically address these issues. Cerebrospinal fluid levels of A and phosphorylated tau were measured in 37 and 22 cynomolgus monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from the present study revealed significant age-associated declines in A42 levels but not in A40 and phosphorylated tau levels. This finding appears to parallel changes seen with human aging, in which decreased levels of A42 can be seen in normal older adults, and supporting that cynomolgus monkeys would be a useful model for studying age-related neurologic disorders associated with Alzheimer-like cerebral proteopathy.


Yue F.,Capital Medical University | Yue F.,Xuanwu Hospital | Zeng S.,Guilin Medical College | Wu D.,Capital Medical University | And 5 more authors.
Journal of Neural Transmission | Year: 2012

Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by 99mTc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of 99mTc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys. © 2012 Springer-Verlag.


Yue F.,Capital Medical University | Yue F.,Key Laboratory on Neurodegenerative Disease of Ministry of Education | Lu C.,WinconTheraCells Biotechnologies Co LTD | Ai Y.,University of Kentucky | And 3 more authors.
Neurobiology of Aging | Year: 2014

Nonhuman primates (NHPs) are useful for the study of age-associated changes in the brain as a model that is biologically closely related to humans. For example, with age, all NHPs analyzed to date, develop β-amyloid (Aβ) plaques as seen in humans. Nevertheless, it is still unclear if NHPs have human-like age-associated changes in Aβ and tau protein in cerebrospinal fluid. The present study was an attempt to specifically address these issues. Cerebrospinal fluid levels of Aβ and phosphorylated tau were measured in 37 and 22 cynomolgus monkeys, respectively, with ages ranging from 4 to 22-year-old. The result from the present study revealed significant age-associated declines in Aβ42 levels but not in Aβ40 and phosphorylated tau levels. This finding appears to parallel changes seen with human aging, in which decreased levels of Aβ42 can be seen in normal older adults, and supporting that cynomolgus monkeys would be a useful model for studying age-related neurologic disorders associated with Alzheimer-like cerebral proteopathy. © 2014 Elsevier Inc.


Wu D.,Capital Medical University | Liu Q.,Wincon TheraCells Biotechnologies Co. | Liu Q.,Guangxi University | Wei S.,Wincon TheraCells Biotechnologies Co. | And 2 more authors.
Lipids in Health and Disease | Year: 2014

Background: Oral fat tolerance test (OFTT) has been widely used to assess the postprandial lipemia in human beings, but there is few studies concerning OFTT in nonhuman primates. This study is designed to explore the feasibility of OFTT in rhesus monkeys. Methods. In a cross-over study, a total of 8 adult female rhesus monkeys were fed with normal monkey diet (NND), high sugar high fat diet (HHD), and extremely high fat diet (EHD), respectively. Each monkey consumed NND, HHD and EHD respectively, each weighing 60 g. Serial blood samples were collected at 1, 2, 3, 4, 5, and 6 h after ingesting each kind of food. Triglyceride, cholesterol, glucose, and insulin at each time point were measured. The area under the curve of triglyceride (TG-AUC) and triglyceride peak response (TG-PR) were also calculated. Results: All monkeys ingested 3 kinds of foods within 15 minutes. TG-AUC and TG-PR of HHD group were higher than those of the other two groups. Postprandial triglyceride levels at 2, 3, 4, and 5 hours in HHD group during OFTT were also higher than those in NND and EHD group. Conclusions: HHD diet can be used in OFTT for nonhuman primates. © 2014 Wu et al.; licensee BioMed Central Ltd.

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