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Role of the metabolism of branched-chain amino acids in the development of Alzheimer’s disease and other metabolic disorders

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Neural Regeneration Research 2020年第8期15卷 1460-1470页

作者： Baruh Polis abraham o.samson Drug Discovery Laboratory The Azrieli Faculty of Medicine Bar-Ilan University

Alzheimer’s disease is an incurable chronic neurodegenerative disorder and the leading cause of dementia,imposing a growing economic burden upon *** disease progression is associated with gradual deposition of amyloid plaques and the formation of neurofibrillary tangles within the brain parenchyma,yet severe dementia is the culminating phase of the enduring *** evidence suggests that Alzheimer’s disease-related cognitive decline is the outcome of an extremely complex and persistent pathophysiological *** disease is characterized by distinctive abnormalities apparent at systemic,histological,macromolecular,and biochemical ***,besides the well-defined and self-evident characteristic profuse neurofibrillary tangles,dystrophic neurites,and amyloid-beta deposits,the Alzheimer’s disease-associated pathology includes neuroinflammation,substantial neuronal loss,apoptosis,extensive DNA damage,considerable mitochondrial malfunction,compromised energy metabolism,and chronic oxidative ***,distinctive metabolic dysfunction has been named a leading cause and a hallmark of Alzheimer’s disease that is apparent decades prior to disease ***-of-theart metabolomics studies demonstrate that altered branched-chain amino acids(BCAAs)metabolism accompanies Alzheimer’s disease *** plasma valine levels are correlated with accelerated cognitive decline,and,conversely,an increase in valine concentration is associated with reduced risk of Alzheimer’s ***,a clear BCAAs-related metabolic signature has been identified in subjects with obesity,diabetes,and ***,arginine metabolism is dramatically altered in Alzheimer’s disease human brains and animal ***,a potential role of the urea cycle in the Alzheimer’s disease development has been hypothesized,and preclinical studies utilizing intervention in the urea cycle and/or BCAAs metabolism have demonstrated clinical pot

关键词： arginase arginine branched-chain aminotransferase BCAAs dementia mToR norvaline urea cycle valine

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Neurogenesis versus neurodegeneration:the broken balance in Alzheimer's disease

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Neural Regeneration Research 2021年第3期16卷 496-497页

作者： Baruh Polis abraham o.samson Drug Discovery Laboratory The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael

Alzheimer's disease(AD)is a progressive neurodegenerative disorder,eventually manifesting in severe cognitive *** the recent proliferation of encouraging preclinical studies and clinical trials,scientific society is still far from a complete consensus regarding the AD etiology and ***,no approved AD-modifying therapies are currently ***,novel concepts predicated upon the latest discoveries and comprehension of the disease as a multifactorial disorder are paving the road to the successful AD treatment.

关键词： Alzheimer clinical eventually

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L-Norvaline, a new therapeutic agent against Alzheimer’s disease

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Neural Regeneration Research 2019年第9期14卷 1562-1572页

作者： Baruh Polis Kolluru D.Srikanth Vyacheslav Gurevich Hava Gil-Henn abraham o.samson Drug Discovery Laboratory The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael Laboratory of Cell Migration and Invasion The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael Laboratory of Cancer Personalized Medicine and Diagnostic Genomics The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael

Growing evidence highlights the role of arginase activity in the manifestation of Alzheimer’s disease(AD).Upregulation of arginase was shown to contribute to *** of arginase activity appears to be a promising approach for interfering with the pathogenesis of ***,the enzyme represents a novel therapeutic *** this study,we administered an arginase inhibitor,L-norvaline(250 mg/L),for 2.5 months to a triple-transgenic model(3×Tg-AD)harboring PS1M146V,APPSwe,and tauP301L ***,the neuroprotective effects of L-norvaline were evaluated using immunohistochemistry,proteomics,and quantitative polymerase chain reaction ***,we identified the biological pathways activated by the ***,L-norvaline treatment reverses the cognitive decline in AD *** treatment is neuroprotective as indicated by reduced beta-amyloidosis,alleviated microgliosis,and reduced tumor necrosis factor transcription ***,elevated levels of neuroplasticity related postsynaptic density protein 95 were detected in the hippocampi of mice treated with ***,we disclosed several biological pathways,which were involved in cell survival and neuroplasticity and were activated by the *** these modes of action,L-norvaline has the potential to improve the symptoms of AD and even interferes with its *** such,L-norvaline is a promising neuroprotective molecule that might be tailored for the treatment of a range of neurodegenerative *** study was approved by the Bar-Ilan University Animal Care and Use Committee(approval No.82-10-2017)on october 1,2017.

关键词： dementia arginase inhibition arginine urea cycle microgliosis neuroinflammation cytokines tumor necrosis factor mToR neurodegeneration

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Arginase as a Potential Target in the Treatment of Alzheimer’s Disease

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Advances in Alzheimer's Disease 2018年第4期7卷 119-140页

作者： Baruh Polis abraham o. samson The Azrieli Faculty of Medicine Bar-Ilan University Safed Israel

Alzheimer’s disease (AD) is a slowly progressive, neurodegenerative disorder with an insidious onset that is characterized by severe decline in memory, thinking and reasoning skills. Advanced age is a prominent risk factor for AD and other metabolic diseases, such as type II diabetes and atherosclerosis. Their causal mechanisms are multifaceted and not fully understood. The precise pathophysiology of AD remains a mystery despite decades of intensive investigation. Thus far, there is no truly successful AD therapy. Arginase is the central enzyme of the urea cycle. Recent studies have identified arginase function in the brain and associated this enzyme with the development of neurodegenerative diseases. Upregulation of arginase has been shown to contribute to endothelial dysfunction, ischemia-reperfusion, atherosclerosis, diabetes, and neurodegeneration. other state-of-the-art discoveries of the precise molecular machinery of neurodegeneration have provided new directions for the rational development of innovative therapeutic strategies in the treatment of common neurodegenerative diseases. In this context, the regulation of arginase activity appears to be a universal approach in interfering with the pathogenesis of AD and providing relief for it and other metabolic disorders. Therefore, the enzyme represents a novel therapeutic target. Arginase inhibition has been shown to reverse amyloid-driven neuronal dysfunction and microgliosis and prevent the development of other AD symptoms in rodent models of AD. Consequently, the methodology represents a promising direction for clinical development.

关键词： Alzheimer’s Disease L-Norvaline L-Arginine Arginase

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Tuning of interactions between cathode and lithium polysulfide in Li-S battery by rational halogenation

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Journal of Energy Chemistry 2020年第10期29卷 147-152页

作者： samson o.olanrele Zan Lian Chaowei Si Shuo Chen Bo Li Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016LiaoningChina School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016LiaoningChina Key Laboratory of Functional Inorganic Material Chemistry(Ministry of Education of China) School of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080HeilongjiangChina Chemical Sciences Department Mountain Top UniversityOgun StateNigeria

Li-S batteries have aroused intense interests as one of the most promising high-energy-density storage ***,the complex undesired shuttle effect induced by dissolution and diffusion of lithium polysulfide intermediates remains the major setback of this *** modification of carbon cathode through heteroatom-doping is widely accepted as an effective method to inhibit the shuttle effect in Li-S battery ***,using first principle calculations,we systematically examined the interaction between halogenated graphene and lithium polysulfide *** is found that the halogen dopants(F,Cl,Br,I)significantly modify the local electronic structure of adsorption site and further induce a polarization to trap the ***,a concave curve is observed from F to I for lithium polysulfide adsorption rather than a linear *** exceptions demonstrated from iodine dopant is carefully analyzed and attributed to its unique charge ***,boron as second dopant further strengthens the interaction between halogenated graphene and polysulfide *** on halogenation strategy,lithium polysulfide/cathode interactions are tuned in a wide range,which can also be of great importance to accelerate redox reaction in Li-S ***,an effective method by halogenation is verified to regulate the adsorption of lithium polysulfide and also enhance the reaction kinetics of the Li-S battery system.

关键词： Li-S battery Halogenation Shuttle effect Co-doping

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Boosting electrocatalytic activity for Co_(2) reduction on nitrogen-doped carbon catalysts by co-doping with phosphorus

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Journal of Energy Chemistry 2021年第3期30卷 143-150页

作者： Shuo Chen Tianfu Liu samson o.olanrele Zan Lian Chaowei Si Zhimin Chen Bo Li Key Laboratory of Functional Inorganic Material Chemistry(Ministry of Education of China) School of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080HeilongjiangChina Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016LiaoningChina

Electrochemical reduction of Co_(2)(CERR)to value-added chemicals is an attractive strategy for greenhouse gas mitigation,and carbon recycles *** metal catalysts suffered from low durability and sluggish kinetics impede the practical *** the other hand,doped carbon materials recently demonstrate superior catalytic performance in CERR,which shows the potential to diminish the problems of metal catalysts to some ***,we present the design and fabrication of nitrogen(N),phosphorus(P)co-doped metal-free carbon materials as an efficient and stable electrocatalyst for reduction of Co_(2) to Co,which exhibits an excellent performance with a high faradaic efficiency of 92%(-0.55 V ***)and up to 24 h stability.A series of characterizations including TEM and XPS verified that nitrogen and phosphorous are successfully incorporated into the carbon ***,the comparisons between co-doping and single doping catalysts reveal that co-doping can significantly increase CERR *** improved catalytic activity is attributed to the synergetic effects between nitrogen and phosphorous dopants,which effectively modulate properties of the active *** density functional theory(DFT)calculations were also performed to understand the synergy effects of *** is revealed that the phosphorous doping can significantly lower the Gibbs free energy of CooH^(*)***,the introduction of the second dopants phosphorous can reduce the reaction barrier along the reaction path and cause polarization of density of states at the Fermi *** changes can greatly enhance the activity of the *** a combined experimental and computational exploration,current work provides valuable insights into the reaction mechanism of CERR on N,P co-doped carbon catalysts,and the influence from synergy effects between dopants,which paves the way for the rational design of novel metal-free catalysts for Co2 electro-reduction.

关键词： Metal-free catalyst Co_(2)reduction Co-doping,DFT

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Spontaneous combustion liability between coal seams: A thermogravimetric study

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International Journal of Mining Science and Technology 2020年第5期30卷 691-698页

作者： Moshood onifade Bekir Genc samson Bada Department for Management of Science and Technology Development Ton Duc Thang UniversityHo Chi Minh City 700000Viet Nam Faculty of Applied Sciences Ton Duc Thang UniversityHo Chi Minh City 700000Viet Nam School of Mining Engineering University of the WitwatersrandJohannesburg 2050South Africa Clean Coal and Sustainable Energy Research Group Faculty of Engineering and the Built EnvironmentUniversity of the WitwatersrandJohannesburg 2050South Africa

The spontaneous combustion liability of coal can be determined by using different experimental *** techniques are well-known in their application,but no certain test method has become a standard to prove the reliability of all of them.A general characterisation which included proximate and ultimate analyses,petrographic properties and spontaneous combustion tests(thermogravimetric analysis(TGA)and the Wits-Ehac tests)were conducted on fourteen coal and four coal-shale *** spontaneous combustion liability of these samples collected between coal seams(above and below)were predicted using the TGA and the Wits-Ehac *** different heating rates(3,6,9,15,20 and 25C/min)were selected based on the deviation coefficient to obtain different derivative slopes and a liability index termed the TGspc *** study found that coal and coal-shale undergo spontaneous combustion between coal seams when exposed to oxygen in the *** intrinsic properties and proneness towards spontaneous combustion differ considerably from one seam to the *** Wits-Ehac test results agreed with the TGspc results to a certain extent and revealed the incidents of spontaneous combustion in the coal mines.

关键词： Crossing-point temperature Thermogravimetric analysis Wits-Ehac index TGspc index

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Subcutaneous Sustained-Release of Poly-Arginine Ameliorates Cognitive Impairment in a Transgenic Mouse Model of Alzheimer’s Disease

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Advances in Alzheimer's Disease 2018年第4期7卷 153-182页

作者： Gennadiy Fonar Baruh Polis Tomer Meirson Alexander Maltsev abraham o. samson Faculty of Medicine in the Galilee Bar Ilan University Safed Israel Institute of Higher Nervous Activity and Neurophysiology Russian Academy of Sciences Moscow Russia

Poly-arginine peptides are a promising class of bioactive compounds that are capable of crossing the blood-brain barrier (BBB) and present neuroprotective properties. In this study, we test the activity of poly-arginine peptides in a triple-transgenic mouse model of Alzheimer’s disease. To identify the best candidate, we examined the relative neuroprotective efficacy of the compounds with various lengths (R7, R9, and R11) via assessment of memory acquisition, long-term hippocampal potentiation (LTP), and cytotoxicity. Also, we explored the expression profiles of hundreds of key cell signaling proteins, and perform a high content antibody microarray comparative analysis of brain samples. The chronically treated animals with poly-arginine R9 show significantly improved acquisition of memory. This compound rescues hippocampal LTP deteriorated by Aβ at a better rate than other agents tested in this study and induces cellular pathways involved in neuroprotection and neuroplasticity. The treatment escalates the expression levels of Synapsin Ia in the mice hippocampi;however, it has no significant effect upon the rate of beta-amyloidosis. Poly-arginine R9 peptide is a well-tolerated compound that crosses the BBB and presents unique neuroprotective qualities. The substance halters the development of AD symptoms in a murine model and can be recommended for clinical investigation.

关键词： L-Arginine Memory LTP Amyloid Beta Cytotoxicity Apoptosis

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Synthesis of zinc-carboxylate metal-organic frameworks for the removal of emerging drug contaminant(amodiaquine)from aqueous solution

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Journal of Environmental Sciences 2018年第2期30卷 264-275页

作者： Adedibu C.Tella samson o.owalude Sunday J.olatunji Vincent o.Adimula Sunday E.Elaigwu Lukman o.Alimi Peter A.Ajibade oluwatobi S.oluwafemi Department of Chemistry University of Ilorin Department of Chemistry and Polymer Science Stellenbosch University School of Chemistry and Physics University of Kwa Zulu-Natal Department of Applied Chemistry University of Johannesburg Doornfontein Campus Centre for Nanomaterials Science Research University of Johannesburg

We herein report the removal of amodiaquine, an emerging drug contaminant from aqueous solution using [Zn2（fum）2（bpy）] and [Zn4 o（bdc）3]（fum = fumaric acid; bpy =4,4-bipyridine; bdc = benzene-1,4-dicarboxylate） metal–organic frameworks（MoFs） as adsorbents. The adsorbents were characterized by elemental analysis, Fourier transform infrared（FT-IR） spectroscopy, and powder X-ray diffraction（PXRD）. Adsorption process for both adsorbents were found to follow the pseudo-first-order kinetics, and the adsorption equilibrium data fitted best into the Freundlich isotherm with the R2 values of 0.973 and0.993 obtained for [Zn2（fum）2（bpy）] and [Zn4 o（bdc）3] respectively. The maximum adsorption capacities foramodiaquine in this study were found to be 0.478 and 47.62 mg/g on the[Zn2（fum）2（bpy）] and [Zn4 o（bdc）3] MoFs respectively, and were obtained at p H of 4.3 for both adsorbents. FT-IR spectroscopy analysis of the MoFs after the adsorption process showed the presence of the drug. The results of the study showed that the prepared MoFs could be used for the removal of amodiaquine from wastewater.

关键词： Adsorption Metal–organic frameworks Amodiaquine Wastewater

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Systematic physicochemical characterization,carbon balance and cost of production analyses of activated carbons derived from(Co)-HTC of coal discards and sewage sludge for hydrogen storage applications

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Waste Disposal and Sustainable Energy 2023年第2期5卷 125-149页

作者： Gentil Mwengula Kahilu samson Bada Jean Mulopo DSI-NRF SARChI Clean Coal Technology Research Group School of Chemical and Metallurgical EngineeringFaculty of Engineering and the Built EnvironmentUniversity of the WitwatersrandJohannesburgWits 2050South Africa Sustainable Energy and Environment Research Group School of Chemical EngineeringUniversity of WitwatersrandPO Box 3JohannesburgWits 2050South Africa

Hydrothermal carbonization(HTC)technologies for producing value-added carbonaceous material(hydrochar)from coal waste and sewage sludge(SS)waste might be a long-term recycling strategy for hydrogen storage applications,cutting disposal costs and solving waste disposal *** this study,hydrochars(HC)with high carbon content were produced using a combination of optimal HTC(HTC and Co-HTC)and chemical activation of coal tailings(CT),coal slurry(CS),and a mixture of coal discard and sewage sludge(CB).At 850℃and 800℃,respectively,with a KoH/HC ratio of 4:1 and a residence time of 135 min,activated carbons(ACs)with the highest Brunauer–Emmett–Teller specific surface(S_(BET))of 2299.25 m^(2)g^(−1)and 2243.57 m^(2)g^(−1)were *** hydrogen adsorption capability of the produced ACs was further studied using gas adsorption isotherms at 77 *** 35 bars,the values of hydrogen adsorbed onto AC-HCT(AC obtained from HTC of CT),AC-HCS(AC obtained from HTC of CS),and AC-HCB(AC obtained from HTC of the blending of coal discard(CD)and SS)were approximately 6.12%,6.8%,and 6.57%in weight,***,the cost of producing synthetic ACs for hydrogen storage is equivalent to the cost of commercial ***,the high proportion of carbon retained(>70%)in ACs synthesized by HTC from CD and SS precursors should restrict their potential carbon emissions.

关键词： Hydrothermal carbonization Coal slurry Coal tailing Sewage sludge Hydrogen storage Activated carbons Carbon emissions Production cost

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