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Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 agonists as potential neuroprotective agents

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Neural Regeneration Research 2019年第5期14卷 745-748页

作者： shaker A.mousa Bassam M.Ayoub Pharmaceutical Research Institute Albany College of Pharmacy and Health Sciences The Center for Drug Research and Development (CDRD) Pharmaceutical Chemistry Department Faculty of Pharmacy The British University in Egypt

Repositioning of dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists is a breakthrough in the field of neural regeneration research increasing glucagon like peptide-1 bioavailability, hence its neuroprotective activities. In this article, the authors suggest not only crossing blood-brain barrier and neurodegenerative disease as off target for dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists, but also for ophthalmic preparations for diabetic retinopathy, which may be the latest breakthrough in the field if prepared and used in an appropriate nano-formulation to target the retinal nerves. The relation of neurodegenerative diseases' different mechanisms to the dipeptidyl peptidase-4 inhibitors and glucagon like peptide-1 receptor agonists should be further examined in preclinical and clinical settings. The repositioning of already marketed antidiabetic drugs for neurodegenerative diseases should save the high cost of the time-consuming normal drug development process. Drug repositioning is a hot topic as an alternative to molecular target based drug discovery or therapeutic switching. It is a relatively inexpensive pathway due to availability of previous pharmacological and safety data. The glucagon like peptide-1 produced in brain has been linked to enhanced learning and memory functions as a physiologic regulator in central nervous system by restoring insulin signaling. Intranasal administration of all marketed gliptins(or glucagon like peptide-1 receptor agonists) may show enhanced blood-brain barrier crossing and increased glucagon like peptide-1 levels in the brain after direct crossing of the drug for the olfactory region, targeting the cerebrospinal fluid. Further blood-brain barrier crossing tests may extend dipeptidyl peptidase-4 inhibitors' effects beyond the anti-hyperglycemic control to intranasal spray, intranasal powder, or drops targeting the blood-brain barrier and neurodegenerative diseases wit

关键词： repositioning DPP-4 inhibitors GLP-1RA neural regeneration blood-brain barrier Parkinson’s disease Alzheimer’s disease diabetic retinopathy

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Ameliorative effects of melatonin and zinc oxide nanoparticles treatment against adverse effects of busulfan induced infertility in male albino mice

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BIOCELL 2022年第2期46卷 535-545页

作者： AMOURA M.ABOU-EL-NAGA shaker A.mousa FAYEZ ALTHOBAITI EMAN FAYAD ENGY S.FAHIM Department of Zoology Faculty of ScienceMansoura UniversityMansouraEgypt The Pharmaceutical Research Institute Albany College of Pharmacy and Health SciencesRensselaerUSA Department of Biotechnology Faculty of SciencesTaif UniversityTaifSaudi Arabia

Testicular damage is one of the most hazardous effects as it’s associated with ***(Bu)is a highly toxic chemotherapeutic drug that affects *** male Swiss albino mice divided into six groups of 5 animals ***(oral 0.9%saline daily for 75 days);Mel(20 mg/kg/day orally for 30 days);ZnO NPs(5 mg/kg/day *** 30 days);BU(single *** of 40 mg/kg and then left for 45 days);BU+Mel(single 40 mg/kg dose of BU and left for 45 days followed by 20 mg/kg/day Mel for 30 days);BU+ZnO NPs(single dose of 40 mg/kg of BU and left for 45 days,then 5 mg/kg/day ZnO NPs for 30 days).Preparation and Characterization of ZnO *** from testis prepared for ultrastructural investigations using TEM after Masson’s trichrome and toluidine blue *** induced histological and ultrastructural damage of the ***,the present results could be concluded that Mel or ZnO NPs can protect the testicular tissue against ultrastructural alterations induced by BU by its antioxidant and anti-apoptotic effects.

关键词： Busulfan Melatonin Zinc oxide nanoparticles Ultrastructure Testis Mice

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Pomegranate peel extract lessens histopathologic changes and restores antioxidant homeostasis in the hippocampus of rats with aluminium chloride-induced Alzheimer’s disease

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Asian Pacific Journal of Tropical Medicine 2020年第10期13卷 456-463页

作者： Steve Harakeh Wafaa S.Ramadan Mohammed S.Al Muhayawi Soad Al Jaouni shaker mousa Khalid Rehman Hakeem Special Infectious Agent Unit King Fahd Medical Research CenterKing Abdulaziz UniversityKingdom of Saudi Arabia Department of Anatomy Faculty of MedicineKing Abdulaziz UniversityKingdom of Saudi Arabia Department of Anatomy Faculty of MedicineAin Shams UniversityCairoEgypt Department of Medical Microbiology/Parasitology and Molecular Microbiology Laboratory KAUHKing Abdulaziz UniversityKingdom of Saudi Arabia Department of Hematology/Pediatric Oncology King Abdulaziz University Hospital(KAUH)Faculty of MedicineKing Abdulaziz UniversityKingdom of Saudi Arabia Yousef Abdul Latif Jameel Scientific Chair of Prophetic Medicine Application Faculty of MedicineKing Abdulaziz UniversityKingdom of Saudi Arabia Pharmaceutical Research Institute Albany College of Pharmacy and Health SciencesRensselaerNYUSA Department of Biological Sciences Faculty of SciencesKing Abdulaziz UniversityJeddahSaudi Arabia

Objective:To investigate the neuroprotective efficacy of pomegranate and ellagic acid on the histopathological changes in the hippocampus of an aluminium chloride(AlCl3)induced rat model of Alzheimer’s ***:Sprague Dawley rats were divided into 4 groups(n=10each):GroupⅠ:serving as negative control;GroupⅡ,Alzheimer model,induced by administration of 17 mg/kg bw AlCl3;GroupⅢ,administered the same dose of AlCl3 with 50 mg/kg of pomegranate peel extract and GroupⅣ:administered ellagic acid(50 mg/kg)in addition to the same dose of *** medication given to all groups continued for 28 *** were given the compounds by gastric *** arm maze test,hippocampus antioxidant markers,histopathology of the dentate gyrus,and CA3 of the hippocampus were ***:Rats treated with pomegranate peel extract exposed to radial arm maze test showed less number of errors and reduced time needed to reach the *** was an increase in the levels of glutathione,catalase,and total antioxidant capacity and decreased lipid peroxidation *** features in dentate gyrus and CA3 as apoptosis and chromatolysis of pyramidal cells and granular layer,respectively,were *** characteristic neurofibrillary tangles and senile plaques were *** with ellagic acid ameliorated the pathological results but to a statistically lower ***:Pomegranate peel extract alleviates memory deficit and restores antioxidant homeostasis following degenerative changes in the hippocampus induced by aluminium chloride in rats.

关键词： Pomegranate Peel extract Ellagic acid Antioxidants Hippocampus Behavioural test

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Aspirin resistance in young men with Type 2 diabetes

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Journal of Diabetes Mellitus 2014年第1期4卷 72-76页

作者： Subhashini Yaturu Emmy Dier Huadong Cui shaker mousa Endocrinology and Metabolism Stratton VA Medical Center Albany USA The Pharmaceutical Research Institute Albany College of Pharmacy and Health Sciences Rensselaer NY USA

Objective: Aspirin resistance (AR) or poor response to aspirin is said to be high among subjects with diabetes and more so in patients with poor glycemic control. The aim of our study was to evaluate the prevalence of AR among subjects with diabetes with moderate glycemic control and its association with inflammatory markers and cytokines. Design: This is a single-center open-label prospective clinical study. Methods: The study included 142 young male veterans (mean age of 49years) with Type 2 diabetes, with HbA1C of 7.7 ± 1.1. Urinary 11-dehydro-thromboxane beta-2 (11DhTx2) concentrations measured by immunoassay are the primary outcome measures. Results: Urinary 11DhTxB2 levels ≥ 1500 pg/mg of creatinine is considered as AR. Approximately 53% of subjects had AR. There are no significant differences in the clinical parameters, such as age, history of hypertension or BMI, waist to hip ratio;as well as biochemical parameters, such as HbA1C, lipid parameters or serum creatinine, between subjects with or without AR. Levels of 11DhTxB2 /cre correlated with history of CAD, abdominal fat content and IL-6 levels (p < 0.01) as well as abdominal fat content and IL-6 levels;duration of diabetes and history of CAD. Conclusions: Aspirin resistance is common in subjects with diabetes even with moderate control. Additional measures to improve aspirin response should be considered. Further studies with larger groups are needed to clarify the AR with various associated risk factors.

关键词： Aspirin Aspirin Resistance Type 2 Diabetes Men CRP IL-6 Adiponectin Body Composition Abdominal Fat

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The effects of EPA + DHA and aspirin on inflammatory cytokines and angiogenesis factors

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World Journal of Cardiovascular Diseases 2012年第1期2卷 14-19页

作者： Robert C. Block Usawadee Dier Pedro Calderon Artero Gregory C. Shearer Lisa Kakinami Mark K. Larson William S. Harris Steve Georas shaker A. mousa Department of Community and Preventive Medicine the University of Rochester School of Medicine and Dentistry Rochester New York.

Objective: In a recent study, we showed that the combination of aspirin plus the ω3 fatty acids eicosapen-taenoic acid (EPA) and docosahexaenoic acid (DHA) synergistically inhibited platelet function. As aspirin, EPA, and DHA have demonstrated anti-inflammatory properties, we hypothesized that the ingestion of EPA and DHA, with and without aspirin, would reduce plasma levels of inflammatory cytokines and angiogenesis factors more than aspirin alone and before aspirin was ingested. Methods: Using multiplex technology, we investigated the effects of aspirin (single-dose 650 mg on day 1), EPA + DHA (3.4 g/d for days 2 - 29), and aspirin with EPA + DHA (day 30) on plasma levels of inflammatory cytokines and angiogenesis factors in healthy adults. Results: Aspirin alone had no effect on any factor versus baseline, but EPA + DHA, with and without aspirin, significantly reduced concentrations of 8 of 9 factors. Although EPA + DHA plus aspirin reduced concentrations of a subset of the factors compared to baseline, neither aspirin alone nor the combination significantly reduced the level of any analyte more robustly than EPA + DHA alone. Conclusions: These data suggest that EPA + DHA has more pronounced down-regulatory effects on inflammation and angiogenesis than aspirin. The implications of these findings for the use of combined therapy for cardiovascular disease remain to be clarified.

关键词： Eicosapentaenoic Acid Docosahexaenoic Acid Lipid Mediators Fatty Acids Angiogenesis Hemostasis Platelet Function Cytokines Aspirin

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Radiometric normalization of overlapping LiDAR intensity data for reduction of striping noise

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International Journal of Digital Earth 2016年第7期9卷 649-661页

作者： Wai Yeung Ahmed shaker Department of Civil Engineering Ryerson UniversityTorontoOntarioCanada

Airborne LiDAR data are usually collected with partially overlapping strips in order to serve a seamless and fine resolution mapping *** of the factors limiting the use of intensity data is the presence of striping noise found in the overlapping *** recent researches have proposed physical and empirical approaches for intensity data correction,the effect of striping noise has not yet been *** paper presents a radiometric normalization technique to normalize the intensity data from one data strip to another one with partial *** normalization technique is built based on a second-order polynomial function fitted on the joint histogram plot,which is generated with a set of pairwise closest data points identified within the overlapping *** proposed method was tested with two individual LiDAR datasets collected by Teledyne Optech’s Gemini(1064 nm)and Orion(1550 nm)*** experimental results showed that radiometric correction and normalization can significantly reduce the striping noise found in the overlapping LiDAR intensity data and improve its capability in land cover *** coefficient of variation of five selected land cover features was reduced by 19–65%,where a 9–18%accuracy improvement was achieved in different classification *** the proven capability of the proposed method,both radiometric correction and normalization should be applied as a pre-processing step before performing any surface classification and object recognition.

关键词： LiDAR intensity striping noise radiometric correction radiometric normalization joint histogram land cover classification

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Frequency-domain generelaized singular peruturbation method for relative error model order reduction

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控制理论与应用（英文版） 2009年第1期7卷 57-62页

作者： Hamid Reza shaker Section for Automation and Control Institute for Electronic SystemsAalborg University

A new mixed method for relative error model order reduction is proposed. In the proposed method the frequency domain balanced stochastic truncation method is improved by applying the generalized singular perturbation method to the frequency domain balanced system in the reduction procedure. The frequency domain balanced stochastic truncation method, which was proposed in [15] and [17] by the author, is based on two recently developed methods, namely frequency domain balanced truncation within a desired frequency bound and inner-outer factorization techniques. The proposed method in ttiis paper is a carry over of the frequency-domain balanced stochastic truncation and is of interest for practical model order reduction because in this context it shows to keep the accuracy of the approximation as high as possible without sacrificing the computational efficiency and important system properties. It is shown that some important properties of the frequency domain stochastic balanced reduction technique are extended to the proposed reduction method by using the concept and properties of the reciprocal systems. Numerical results show the accuracy, simplicity and flexibility enhancement of the method.

关键词： Large-scale systems Model reduction Balanced realization Frequency-domain Grammian

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Extending the Lifetime of Copper-beryllium Alloys as Plastic Injection High-end Needle Valve Mold Nozzle Tips Through a Heat-treatment-based Microstructure Optimization Approach

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Journal of Wuhan University of Technology(Materials Science) 2023年第3期38卷 665-668页

作者：孟晓敏 ZHAO Dong MAJID shaker Chongqing 2D Materials Institute Chongqing 400701China Chengdu Lianyu Precision Machinery Co. Ltd.Chengdu 611730China Lehrstuhl Für Physikalische Chemie II Universitat Erlangen-NürnbergEgerlandstraBe 391058ErlangenGermany

The relationship between the microstructure and the practical performance of two different copper-beryllium alloys including their lifetime has been ***,two valves made of two different alloys with very similar compositions and the same heat treatment methods were investigated by various standard techniques including metallography,X-ray diffraction,chemical composition,microhardness,and thermal conductivity *** both alloys experienced the same heat-treatment processes,they revealed different thermal and mechanical properties due to the minor difference in their chemical *** alloy providing a longer lifetime (40%more) as the tip had a higher thermal conductivity of 280.3 W(m·K)^(-1) (about two times that of the other alloy).Regarding the metallography images and the measured thermal conductivity values of the alloys,the extended lifetime of the nozzle with the optimum performance is ascribed to its biphasic microstructure and the minor grain boundaries and interfacial thermal *** important difference in the chemical composition was investigated in this study.

关键词： crystal structure grain boundaries metals and alloys thermal properties needle valve

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μPMU-based smart adaptive protection scheme for microgrids

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Journal of Modern Power Systems and Clean Energy 2019年第4期7卷 887-898页

作者： Mohamed Salah ELBANA Nabil ABBASY Ashraf MEGHED Nahil shaker Electrical Engineering Department Faculty of EngineeringAlexandria UniversityLotfy El-Sied St.P.O.ElhadaraAlexandria 21544Egypt

The concepts of microgrids(MGs)and smart grid represent the recent targeted revolution towards fully smart electrical network integrated with high penetration of renewable energy sources(RESs).The protection system of MGs becomes a challenge due to variable characteristics of its currents,bidirectional power flow and output power fluctuations of RES,causing selectivity and sensitivity issues for conventional protective devices(PDs)with fixed *** this paper,a smart protection scheme(SPS)is proposed using micro-phasor measurement units(μPMUs)to obtain the continuous rapid synchronized phasor measurement *** it is communicated with a microgrid central controller(MGCC)through highly reliable communication architecture to carry out online smart adaptive protection *** index coefficients and abnormality coefficients are calculated for each feeder to detect the fault location and the abnormality *** modeling of an MG including 10-bus connected distribution system with integrated distributed generation(DG)is simulated using ETAP *** proposed protection algorithm is modeled and evaluated using MATLAB *** proposed fault detector and abnormality detector can enable quick and accurate fault identification and isolation.

关键词： Fault index coefficients Microgrid(MG) Micro-phasor measurement unit(μPMU) Renewable energy source(RES) Smart protection scheme(SPS)

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Monitoring and evaluation of building ventilation system fans operation using performance curves

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Energy and Built Environment 2020年第3期1卷 307-318页

作者： Mahendra Singh Muhyiddine Jradi Hamid Reza shaker Center for Energy Informatics University of Southern DenmarkCampusvej 555230Denmark

Ventilation fans are an important component of any mechanically ventilated *** fan performance could significantly affect the whole building performance *** are several issues such as dirty blades,mechanical wear,aging of fans could impact the fan’s *** present work,a novel,indirect and data-driven methodology is introduced to monitor the ventilation fan unit *** proposed method is able to perform continuous monitoring of ventilation fan unit in *** real-time performance of 3 Air handling unit(AHU)fans is examined in an academic *** fan performance is modeled with the help of manufacturer data and compared against the real-time *** data-driven models are developed and *** first model is used to compute expected total fan pressure at a given airflow rate while second is a Support Vector Regression(SVR)model,to predict the fan *** performance monitoring of the ventilation fan unit is determined in terms of expected and actual fan energy *** indicated a significant performance gap in three ventilation fan unit in a case building known as OU44,located in city Odense,*** advantage of this method comprises simplicity,no direct human intervention and scalability to the series of ventilation units.

关键词： Buildings Ventilation system Fan unit Performance curve Modeling Fan efficiency Energy consumption HVAC Performance testing Support vector regression(SVR) Polynomial regression

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