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Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3891-3904页

作者： Ping Bai Prasenjit Mondal Frederick A.Bagdasarian nisha Rani Yan Liu Ashley Gomm Darcy R.Tocci Se Hoon Choi Hsiao-Ying Wey Rudolph E.Tanzi Can Zhang Changning Wang Athinoula A.Martinos Center for Biomedical Imaging Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA Genetics and Aging Research Unit McCance Center for Brain HealthMassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA

Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for ***,we performed positron emission tomography(PET)imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in *** first developed[^(18)F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to *** studies of[^(18)F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals,with more pronounced changes identified in the cortex and *** translatability of this radiotracer for AD in a potential human use was supported by additional studies,including similar uptake profiles in non-human primates,an increase of HDAC6 in ADrelated human postmortem hippocampal tissues by Western blotting protein analysis,and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our ***,our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.

关键词： HDAC6 Alzheimer’s disease Radiotracer PET imaging Epigenetic

Retinoblastoma and treatment: A current evaluation of advanced therapy

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World Journal of Pharmacology 2013年第3期2卷 65-72页

作者： nisha V Shah Samuel K Houston Timothy G Murray Department of Ophthalmology Bascom Palmer Eye Institute University of Miami Miller School of Medicine

Retinoblastoma is the most common primary childhood ocular tumor, affecting nearly 3.5 per million children worldwide. A mutation in the RB1 gene, which presents as either germline or sporadic, along with additional mutational events, promote neoplastic growth in the retina. Fortunately, current treatment protocols result in success rates approaching 99% at specialized centers, with many children maintaining useful vision. Overall, treatment is guided by aggressiveness and size, and is classified by systems such as the ReeseEllsworth System and the International Classification of Retinoblastoma. Due to advances in chemotherapy protocols combined with use of focal laser consolidation, treatment paradigms have shifted from enucleation to external beam radiation therapy to chemotherapy as globe-salvaging therapies. Smaller, less complex tumors may be controlled by plaque radiotherapy or focal laser ablative therapy. However, larger and more complex tumors, such as those that have vitreous or subretinal seeding, require methods of chemoreduction combined with focal consolidation to yield better outcomes. Standard chemotherapy protocols utilize vincristine, etoposide, and carboplatin with or withoutcyclophosphamide. Finally, there has been a recent push in local treatments for retinoblastoma to minimize systemic toxicities. These modalities include intravitreal or subconjunctival injections and more recently, direct chemotherapy administration into the ophthalmic artery. As a result, enucleation is used less often, but remains an important treatment for the most aggressive, refractory cases. The advancement of retinoblastoma treatment looks promising; however, worldwide access to these treatments and the lack of long-term followup of new local treatment modalities constitute current and future challenges.

关键词： Retinoblastoma Treatment

Performance,litter quality and gaseous odour emissions of broilers fed phytase supplemented diets

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Animal Nutrition 2016年第4期2卷 288-295页

作者： Nishchal K.Sharma Mingan Choct Shu-Biao Wu Robert Smillie Natalie Morgan Amal S.Omar nisha Sharma Robert A.Swick School of Environmental and Rural Science University of New England Poultry Cooperative Research Centre University of New England Animal Production Research Institute Agricultural Research Centre

The effect of graded levels of phytase on performance, bone characteristics, excreta/litter quality and odorant emissions was examined using 720 Ross 308 male d-old broilers. A 2 x 4 factorial arrangement of treatments was employed with 6 replicates of 15 birds per pen. Factors were: diets-positive and negative control(PC, NC); phytase-0, 500,1,000.1,500 FTU/kg. The PC was formulated to meet the 2014 Ross 308 nutrient specifications, whereas the NC was formulated with lower Ca(-1.4 g/kg), available P(-1.5 g/kg), Na(-0.3 g/kg), dLys(-0.2 g/kg) and MEn(-0.28 MJ/kg) equivalent to nutrient matrix values for 500 FTU/kg phytase in the starter,grower and finisher periods(i.e.,downspec diet). On d 24, phytase decreased FCR by 1.6, 4.3 and 4.6 points at inclusion levels of 500.1,000 and 1,500 FTU/kg, respectively(P 0.05). Solid phase microextraction gas chromatography-mass spectrometry(SPME-GC-MS) analysis of gaseous emissions on d 39 indicated no difference in the emission of alcohols, aldehydes, ketones, volatile fatty acids and phenols between treatments(P> 0.05). The results indicate that phytase has greater benefits when formulated using nutrient matrix values as compared with adding it over the top in an already nutrient sufficient diet. The later method would be expected to increase feed costs without concomitant performance benefits.

关键词： Broiler Litter quality Meat chickens Odour Performance Phytase

Enhanced osseointegration of drug eluting nanotubular dental implants: An in vitro and in vivo study

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Bioactive Materials 2023年第10期28卷 432-447页

作者： Pankaj Chauhan Alok Srivastava Pooja Bhati Manish Chaturvedi Vinay Patil Sriram Kunnoth nisha Kumari Vedpal Arya Madhur Pandya Mohit Agarwal Smiti Bhardwaj Farrukh Faraz Sanjay Chauhan Mahesh Verma Veena Koul Naresh Bhatnagar Homi Bhabha Cancer Hospital and Research Centre VizagAndhra PradeshIndia Centre for Biomedical Engineering Indian Institute of Technology DelhiIndia Department of Mechanical Engineering Indian Institute of Technology DelhiIndia Mechanical&Automation Engineering Indira Gandhi Delhi Technical University for WomenNew DelhiIndia Rajasthan Technical University Kota RajasthanIndia Applied Mechanics Indian Institute of Technology DelhiIndia National University of Singapore Singapore Department of Periodontics Maulana Azad Institute of Dental SciencesNew DelhiIndia Rajasthan Dental College and Hospital JaipurRajasthanIndia Department of Prosthodontics Maulana Azad Institute of Dental SciencesNew DelhiIndia

Faster and predictable osseointegration is crucial for the success of dental implants, especially in patients with compromised local or systemic conditions. Despite various surface modifications on the commercially available Titanium (Ti) dental implants, the bioactivity of Ti is still low. Thus, to achieve both biological and therapeutic activity on titanium surfaces, surface modification techniques such as titanium nanotubes have been studied as nanotube surfaces can hold therapeutic drugs and molecules. The main aim of the present research work is to study the early osseointegration around the novel Simvastatin drug eluting nanotubular dental implant. In the present research, the titanium nanotubes were fabricated on the screw-shaped dental implant surface and the Simvastatin drug was loaded into the nanotubes using the ultrasonication dip method. In vitro and In vivo studies were carried out on the modified dental implants. In vitro cell culture study reported enhanced osteogenic activity on the drug-loaded nanotube surface implants. The in vivo animal studies were evaluated by micro-CT, histopathology, and reverse torque removal analysis methods. The test results showed faster osseointegration with the strong interface on the Simvastatin drug-loaded implant surface at 4 weeks of healing as compared to the control implants.

关键词： Titanium Biocompatibility Simvastatin Nanotube Micro CT Histopathology Nanoscale

Prevalence and outcome of acute kidney injury,as defined by the new Kidney Disease Improving Global Outcomes guideline,in very low birth weight infants

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World Journal of Nephrology 2017年第5期6卷 229-235页

作者： Maisa Al Malla nisha Viji Varghese Mustafa AlAbdullatif Hassib Narchi Mohammad Khassawneh Department of Paediatrics Tawam HospitalP.O.Box 15258Al AinUnited Arab Emirates Department of Paediatrics United Arab Emirates UniversityP.O.Box 15551Al AinUnited Arab Emirates Department of paediatrics Jordan University of Science and TechnologyIrbid 22110Jordan

AIMTo evaluate the prevalence, risk factors and outcome of acute kidney injury （AKI） in very low birth weight （VLBW） infants. METHODSIn this retrospective study of VLBW infants, we analyzed the prevalence of AKI, as defined by changes in serum creatinine and urine output, associated risk factors and *** total of 293 VLBW infants （mean gestational age 28.7 wk） were included, of whom 109 weighed less than 1000 g at birth. The overall prevalence of AKI was 11.6% （22% in infants with a birth weight under 1000 g and 5.4% those heavier）. A total of 19 （55%） affected infants died, with a mortality rate of 58% in infant less than 1000 g and 50% in those heavier. After adjusting for confounding variables, only necrotizing enterocolitis （NEC） remained associated with AKI, with odds ratio of 4.9 （95%CI： 1.9-18.6）. Blood pressure and glomerular filtration rate （GFR） were not different between affected infants and the others upon discharge from hospital. A normal GFR was documented in all affected infants at one year of *** Using Kidney Disease Improving Global Outcomes defnition of AKI, it occurred in over 10% of VLBW infants, more commonly in infants with lower birth weight. NEC was an independent associated risk factor. Renal function, as defined by GFR, was normal in all surviving affected infants 10 to 12 mo later.

关键词： Newborn Case-control Risk factors Acute renal failure Mortality Kidney Disease Improving Global Outcomes

Efficacy of Hypertonic Saline and Normal Saline in the Treatment of Chronic Sinusitis

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International Journal of Otolaryngology and Head & Neck Surgery 2013年第3期2卷 90-96页

作者： Ramabhadraiah Anil Kumar Borlingegowda Viswanatha nisha Krishnamurthy Niveditha Jayanna Disha Ramesh Shetty Department of ENT Bangalore Medical College & Research Institute Bangalore India

Introduction: Chronic sinusitis affects all age groups and is a cause for significant morbidity. Recent realization that noninfectious inflammatory causes can predispose to infectious sinusitis has evoked renewed interest in developing and documenting efficacious ancillary therapies that could supplement antibiotic use. Hypertonic saline solution has been shown to increase mucociliary clearance and ciliary beat frequency. Objectives: A double blinded randomized comparative study was undertaken to evaluate the effect of hypertonic saline (3.5%) nasal drops and normal saline (0.9%) nasal drops, to assess the tolerance of hypertonic saline nasal drops and to know if hypertonic nasal drops improve the “quality of life” in patients with chronic sinusitis. Methods: Fifty patients diagnosed as chronic sinusitis in the age group of 18-45 years were randomized into two groups;Group A was treated with normal saline and Group B with 3.5% hypertonic saline for a period of 4 weeks. Pre and Post treatment x-rays of the paranasal sinuses (Water’s view) were graded and radiological scores were given accordingly. The symptoms were evaluated before and after treatment using visual analogue score. Patients were queried about tolerance to the nasal solution and scores were given. Conclusion: Hypertonic saline nasal solution is more efficacious than normal saline solution in the treatment of patients with chronic sinusitis. Hypertonic saline nasal solution was well tolerated and it improved quality of life in these patients.

关键词： Chronic Sinusitis Hypertonic Saline Normal Saline

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萨满文化与蒙古族民间手工艺

南京艺术学院学报（美术与设计） 2009年第4期 141-145页

作者：达妮莎大连理工大学建筑艺术学院辽宁大连116024

本文通过对蒙古萨满教的观念分析,揭示在蒙古人的精神世界里始终存在萨满信仰。作为与蒙古人生产生活、知识体系相关的民间信仰以或直接或间接的方式渗透到民间手工艺品中,影响其门类、造型、纹样、色彩等。同时,多样的存在形式也沉淀... 详细信息

本文通过对蒙古萨满教的观念分析,揭示在蒙古人的精神世界里始终存在萨满信仰。作为与蒙古人生产生活、知识体系相关的民间信仰以或直接或间接的方式渗透到民间手工艺品中,影响其门类、造型、纹样、色彩等。同时,多样的存在形式也沉淀了蒙古族民间信仰的历史发展变化。

关键词：蒙古萨满教民间手工艺

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蒙古族婚俗中的民间手工艺

装饰 2009年第8期 110-111页

作者：达妮莎大连理工大学建筑艺术学院

作为蒙古族风俗中一项重要内容的蒙古族婚俗,孕育着丰富灿烂的蒙古族民间手工艺,本文即试图展现它们以何种方式影响着蒙古人的生产生活、精神世界,以及在历史洪流中的传承、变异和凸现出的蒙古民族特征。

关键词：蒙古族婚俗民间手工艺

Micro-CT重建时分析区域变化对颅顶骨骨量参数的影响

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重庆医科大学学报 2017年第9期42卷 1077-1081页

作者：郑仁建张一弓邵华英 nisha-Mahato 吴小红重庆医科大学附属口腔医院修复科重庆401147

目的:在分析区域包含整个颅顶骨的前提下,改变颅顶骨显微CT(micro-computed tomography,Micro-CT)扫描后二维图像的重建层数或者位置,比较进行重建后的骨量参数(骨表面积、骨体积)是否出现改变。方法:4日龄小鼠颅顶骨培养后置于含培养液... 详细信息

目的:在分析区域包含整个颅顶骨的前提下,改变颅顶骨显微CT(micro-computed tomography,Micro-CT)扫描后二维图像的重建层数或者位置,比较进行重建后的骨量参数(骨表面积、骨体积)是否出现改变。方法:4日龄小鼠颅顶骨培养后置于含培养液的EP管中,进行连续Micro-CT扫描。根据重建时改变层数或位置来分别分析:(1)996~22层组与800~50层组,分析层数不同(n=3);(2)996~22层组与随机选择层组,分析层数不同(n=3);(3)近边界上缘组与近边界下缘组,分析层数相同(n=3)的骨量参数变化。结果:在分析区域包含整个颅顶骨的前提下:(1)增加或者减少层数导致骨表面积变化(F=47.798,P=0.002),而骨体积无变化(F=7.083,P=0.056)。(2)随机选择层数组与996~22层数组分析比较时骨表面积(F=359.392,P=0.000)、骨体积(F=51.844,P=0.002)均有变化。(3)重建层数相同的前提下,改变分析区域位置时骨表面积(F=0.000,P=0.991)、骨体积(F=0.000,P=0.995)无变化。结论:(1)Micro-CT三维重建时,改变重建层数可影响骨量参数。(2)Micro-CT三维重建时,随机选择重建层数可影响骨量参数。(3)Micro-CT三维重建时,保证分析层数相同而改变空白分析区域的位置不会影响骨量参数。

关键词：显微CT 分析区域三维重建器官培养