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*** phenotype of a Slc4a11 knockout murine model for congenital hereditary endothelial dystrophy

Annals of Eye Science 2018年第1期 493-493页

作者： Sergiu Vlad Antoine Sylvestre-Bouchard Hasitha Alwis Weerasekera Rami Darwich marilyse piché Khampoun Sayasith Joseph Casey Isabelle Brunette Maisonneuve-Rosemont Hospital Research Center and Department of Ophthalmology University of MontrealQCCanada Faculty of Medicine and Health Sciences University of SherbrookeSherbrookeQCCanada Faculty of Medicine Universitéde MontréalMontrealQCCanada Faculty of Medicine McGill UniversityMontrealQCCanada Faculty of Medicine and Dentistry University of AlbertaEdmontonABCanada

Background:Congenital hereditary endothelial dystrophy(CHED)is characterized by blindness at birth or in early infancy resulting from bilateral corneal opacification,and is linked to mutation in the Slc4a11 gene.A Slc4a11 knockout(KO)mouse,generated by gene deletion(Vithana et *** Genet 2006),was acquired in order to study this *** confirm the phenotype of this Slc4a11 KO mouse model as a function of age,using the wild type(WT)mouse as a ***:Genotyping was performed by PCR(REDExtract-N-AmpTM Tissue PCR Kit,Sigma-Aldrich,Oakville,ON).Slc4a11 WT and KO mice populations aged from 5 to 50 weeks were studied(n=5 animals per age group;5-year age intervals).Slit lamp examination,anterior segment-ocular coherence tomography(OCT930SR;Thorlabs,Inc.,Newton,NJ),corneal endothelial cell staining,and scanning(SEM)and transmission(TEM)electron microscopy were used to assess the morphological and cellular differences between the two *** expression of basolateral membrane transporter NaBC1 within the corneal endothelium was also assessed using ***:Diffuse and progressive corneal opacification was observed at the slit lamp in the Slc4a11 KO mice,starting at 10 *** central corneal thickness(CCT)also increased progressively as a function of *** comparison,Slc4a11 WT corneas remained clear over the entire study *** TEM results showed vacuole degeneration of the corneal endothelium in the 15-week KO mouse,which was not seen in the same age WT ***:The corneal phenotype of this Slc4a11 KO mouse is representative of the clinical manifestations of CHED in human subjects,confirming the usefulness of this model for studying pathophysiology and therapeutic alternatives for Slc4a11-associated corneal dystrophies.

关键词： Slc4a11 mouse congenital hereditary endothelial dystrophy(CHED)

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A human translational model based on neuroplasticity for pharmacological agents potentially effective in Treatment-Resistant Depression: focus on dopaminergic system

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Neural Regeneration Research 2020年第6期15卷 1027-1029页

作者： Ginetta Collo Emilio Merlo pich Department of Molecular and Translational Medicine Section of PharmacologyUniversity of BresciaBresciaItaly Department of Biomedicine University of BaselBaselSwitzerland(Collo G)Neuroscience Therapeutic Area UnitTakeda Pharmaceuticals InternationalZurichSwitzerland Division of Brain Science Imperial CollegeLondonUK(Merlo Pich E

Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and *** 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently *** attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal *** breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this *** rationale is briefly described here.

关键词： breakthrough plasticity translational

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Ketamine enhances structural plasticity in human dopaminergic neurons:possible relevance for treatment-resistant depression

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Neural Regeneration Research 2018年第4期13卷 645-646页

作者： Ginetta Collo Emilio Merlo pich Department of Molecular and Translational Medicine Section of PharmacologyUniversity of Brescia Department of Biomedicine University of Basel Neuroscience Therapeutic Area Unit Takeda Pharmaceuticals International Division of Brain Science Imperial College

Depression refers to a series of mental health issues characterized by loss of interest and enjoyment in everyday life,low mood and selected emotional,cognitive,physical and behavioral *** is a common disorder,affecting 5–15%of the general *** diagnosed as major depressive disorder（MDD）,patients are currentlytreated with pharmacological agents such as serotonin or noradren- aline uptake inhibitors （SSRI or SNRI） or tricyclics.

关键词： MEK ERK Ketamine enhances structural plasticity in human dopaminergic neurons:possible relevance for treatment-resistant depression TRD MDD

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Malignant peritoneal effusion acting as a tumor environment in ovarian cancer progression: Impact and significance

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World Journal of Clinical Oncology 2018年第8期9卷 167-171页

作者： Alain piché Département de Microbiologie et Infectiologie Faculté de Médecine Université de Sherbrooke

Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal *** peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.

关键词： Ovarian cancer Tumor environment Peritoneal effusions Ascites Dissemination Multicellular spheroids

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The Impact of Macroeconomic Factors on Stock Market Index in Cambodia

The Impact of Macroeconomic Factors on Stock Market Index in...

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作者： Sreyly pich 上海交通大学

学位级别：硕士

This research investigates the effect of macroeconomic variables on the Cambodia stock exchange index（CSX）using monthly data over period April 2012 to April *** variables utilized in this study are Inflation Rate,Exchange Rate,Interest Rate and Money *** fundamental purpose of this present research is to explore the impact of those keys macroeconomic variables on Cambodia stock exchange index by applying ordinary least square（OLS）*** CSX index data has been collected from Cambodia Security Exchange official *** secondary data for macroeconomic variables is obtained from various sources mainly from National Bank of Cambodia,and IMF *** statistics are performed on the temporal properties of data and Augmented DickeyFuller（ADF）is used to check the stationary of *** has been examined among independent variables through a correlation *** Least Square has been employed to analyze the impact of each macroeconomic variable on the returns and combination of the four macroeconomic variables on the CSX index from lag one month to lag three month *** findings showed that interest rate and exchange rate have an inverse relationship with the performance of CSX all share index while inflation rate has a positive effect on the stock market index,excepted money supply that is found to have no significant effect on the stock exchange index.

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Intelligent nanogels with self-adaptive responsiveness for improved tumor drug delivery and augmented chemotherapy

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Bioactive Materials 2021年第10期6卷 3473-3484页

作者： Xin Li Helin Li Changchang Zhang Andrij pich Lingxi Xing Xiangyang Shi Department of Gynecology and Obstetrics XinHua Hospital Affiliated to Shanghai JiaoTong University School of MedicineShanghai200092China DWI-Leibniz-Institute for Interactive Materials e.V. 52056AachenGermany College of Chemistry Chemical Engineering and BiotechnologyDonghua UniversityShanghai201620China Institute for Technical and Macromolecular Chemistry RWTH Aachen University52074AachenGermany CQM-Centro de Química da Madeira Universidade da MadeiraCampus da Penteada9000-390FunchalPortugal Aachen Maastricht Institute for Biobased Materials Maastricht University6167RD GeleenNetherlands

For cancer nanomedicine,the main goal is to deliver therapeutic agents effectively to solid ***,we report the unique design of self-adaptive ultrafast charge-reversible chitosan-polypyrrole nanogels(CH-PPy NGs)for enhanced tumor delivery and augmented *** was first grafted with PPy to form CH-PPy polymers that were used to form CH-PPy NGs through glutaraldehyde cross-linking via a miniemulsion *** CH-PPy NGs could be finely treated with an alkaline solution to generate ultrafast charge-reversible CH-PPy-OH-4 NGs(R-NGs)with a negative charge at a physiological pH and a positive charge at a slightly acidic *** R-NGs display good cytocompatibility,excellent protein resistance,and high doxorubicin(DOX)loading ***,the prepared R-NGs/DOX have prolonged blood circulation time,enhanced tumor accumulation,penetration and tumor cell uptake due to their self-adaptive charge switching to be positively charged,and responsive drug delivery for augmented chemotherapy of ovarian carcinoma in ***,the tumor accumulation of R-NGs/DOX(around 4.7%)is much higher than the average tumor accumulation of other nanocarriers(less than 1%)reported *** developed self-adaptive PPy-grafted CH NGs represent one of the advanced designs of nanomedicine that could be used for augmented antitumor therapy with low side effects.

关键词： Ultrafast charge conversion Nanogels Active transportation Deep tumor penetration Enhanced antitumor activity

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Pathobiological role of MUC16 mucin(CA125) in ovarian cancer: Much more than a tumor biomarker

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World Journal of Obstetrics and Gynecology 2016年第1期5卷 39-49页

作者： Alain piché Département de Microbiologie et Infectiologie Faculté de Médecine Université de Sherbrooke

MUC16 （CA125） has remained the mainstay for ovarian cancer assessment and management since the early 1980’s. With the exception of HE4, it is the only reliable serum biomarker for ovarian cancer. MUC16 belongs to a family of high-molecular weight glycoproteins known as mucins. The mucin family is comprised of large secreted transmembrane proteins that includes MUC1, MUC4 and MUC16. These mucins are often overexpressed in a variety of malignancies. MUC1 and MUC4 have been shown to contribute to breast and pancreatic tumorigenesis. Recent studies have uncovered unique biological functions for MUC16 that go beyond its role as a biomarker for ovarian cancer. Here, we provide an overview of the literature to highlight the importance of MUC16 in ovarian cancer tumorigenesis. We focus on the growing literature describing the role of MUC16 in proliferation, migration, metastasis, tumorigenesis and drug resistance. Accumulating experimental evidence suggest that the C-terminal domain of MUC16 is critical to mediate theses effects. The importance of MUC16 in the pathogenesis of ovarian cancer emphasizes the need to fully understand the signaling capabilities of MUC16 C-terminal domain to develop more effcient strategies for the successful treatment of ovarian cancer.

关键词： MUC16 CA125 Mucin Ovarian cancer Tumorigenesis Biomarker

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Dendrimer-decorated nanogels:Efficient nanocarriers for biodistribution in vivo and chemotherapy of ovarian carcinoma

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Bioactive Materials 2021年第10期6卷 3244-3253页

作者： Xin Li Zhijun Ouyang Helin Li Chaolei Hu Pabitra Saha Lingxi Xing Xiangyang Shi Andrij pich DWI-Leibniz-Institute for Interactive Materials e.V 52056AachenGermany Institute for Technical and Macromolecular Chemistry RWTH Aachen University52074AachenGermany College of Chemistry Chemical Engineering and BiotechnologyDonghua UniversityShanghai201620China CQM-Centro de Química da Madeira Universidade da MadeiraCampus da Penteada9000-390FunchalPortugal Department of Gynecology and Obstetrics XinHua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200092China Aachen Maastricht Institute for Biobased Materials Maastricht UniversityNL-6167 RDGeleenthe Netherlands

Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient ***,the PAMAM dendrimer decorated PVCL-GMA nanogels(NGs)were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian *** an ingenious design,the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation *** G2 dendrimer decoration,the overall charge is changed from neutral to positive,and the NGs-G2 display the whole charge nature of positively charged corona and neutral ***,the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in *** a consequence of this alteration,the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation,enhanced tumor uptake,and promoted drug release,resulting in the significantly augmented antitumor efficacy with low side ***,this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver ***,the NGs-G2 also displayed thermal/pH dual-responsive behaviors,excellent biocompatibility,improved cellular uptake,and stimuli-responsive drug ***,this work demonstrates a novel insight into the strategy for optimizing design,improving biodistribution and enhancing theranostic efficacy of nanocarriers.

关键词： Nanogels Dendrimer Surface charge Thermal/pH dual-responsiveness Drug delivery

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Complex regional pain syndrome: From diagnosis to rehabilitation

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World Journal of Anesthesiology 2014年第1期3卷 46-60页

作者： Alexandra Lecours Mathieu piché Department of Chiropractic Université du Québec à Trois-Rivières Trois-Rivières G9A 5H7 Québec Canada Department of Occupational Therapy Université du Québec à Trois-Rivières Trois-Rivières G9A 5H7Québec Canada Groupe de Recherche sur les Affections Neuro-musculo-squelettiques Université du Québec à Trois-Rivières Trois-Rivières G9A 5H7 Québec Canada Groupe de Recherche en Neuroscience Université du Québec à Trois-Rivières Trois-Rivières G9A 5H7 Québec Canada Centre de Recherche en Neuropsychologie et Cognition Université de Montréal Montréal H3C 3J7 Québec Canada Centre de recherche de l’Institut universitaire de gériatrie de Montréal Université de Montréal Montréal H3C 3J7 QuébecCanada

Complex regional pain syndrome(CRPS) is a debilitating pathology characterised by intense chronic pain associated with vasomotor, sensory and motor dysfunction of the affected limb. Although the pathophysiology of CRPS is not fully understood, it is recognised that inflammatory processes and autonomic dysfunction are involved. These processes are associated with peripheral and central sensitisation as well as changes in brain structure and function, and are reflected in the clinical presentation of CRPS. CRPS management requires an interdisciplinary team and requires the therapeutic approach to be individualised. With regard to pharmacological treatment, bisphosphonates, corticosteroids, ketamine and anticonvulsants have been demonstrated to be effective for CRPS management. Psychotherapy, including cognitive-behavioural therapy, has produced promising results but more studies are needed to confirm its efficacy. Among rehabilitation interventions, there is evidence of the efficacy of physiotherapy and occupational therapy in diminishing CRPS symptoms and achieving a higher level of functioning. In this regard, the rehabilitation modality that seems the most promising according to the actual literature is graded motor imagery, which can help to reverse the maladaptive neuroplasticity occurring in CRPS.

关键词： Complex regional pain syndrome Autonomic Inflammation Plasticity Rehabilitation

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基于标准化降水蒸散指数的甘肃省干旱时空特征分析

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干旱地区农业研究 2019年第3期37卷 256-266页

作者：李亮 pich Linvolak 蔡焕杰西北农林科技大学旱区农业水土工程教育部重点实验室陕西杨凌712100 西北农林科技大学中国旱区节水农业研究院陕西杨凌712100 西北农林科技大学水利与建筑工程学院陕西杨凌712100

为明确气候变化条件下甘肃省不同时间尺度的干旱特征,选用1951-2015年甘肃省33个气象站点逐日气象数据,计算了不同时间尺度的标准化降水蒸散指数SPEI,同时结合Mann-Kendall突变检验、复小波分析、经验正交函数分解、旋转经验正交函数分... 详细信息

为明确气候变化条件下甘肃省不同时间尺度的干旱特征,选用1951-2015年甘肃省33个气象站点逐日气象数据,计算了不同时间尺度的标准化降水蒸散指数SPEI,同时结合Mann-Kendall突变检验、复小波分析、经验正交函数分解、旋转经验正交函数分解等方法,对甘肃省65 a来干旱时空格局特征进行了分析。结果表明:在年际变化趋势方面,甘肃省干旱情势为由干变湿再变干,近年干旱趋势逐渐加重;四季均呈现由干变湿然后变干的趋势,近年春季变干趋势显著;干旱强度在全省范围内主要为轻旱和中旱等级,并表现为局域性轻旱和全域性中旱。在周期性变化方面,甘肃省的干旱时间周期性强弱依次为39、13、7、22 a尺度,但不同时间尺度表现出了不同的干湿震荡规律。在空间格局方面,甘肃省整体上呈西北部干旱缓解、东南部干旱加剧的趋势;春季干旱加剧最明显,冬季次之,夏季和秋季干湿状况基本相似。按照干旱区域敏感性强弱可将甘肃省分为东南地区东部(Ⅰ区)、西北地区(Ⅱ区)、中部地区(Ⅲ区)和东南地区西部(Ⅳ区),其中Ⅲ区呈干旱缓解趋势,其他地区基本呈干旱加剧的趋势。

关键词：干旱标准化降水蒸散指数(SPEI) 时空特性经验正交函数旋转经验正交函数甘肃省

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