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Biomaterial and tissue-engineering strategies for the treatment of brain neurodegeneration

Neural Regeneration Research 2022年第10期17卷 2108-2116页

作者： Bridget Martinez philip V.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

The incidence of neurodegenerative diseases is increasing due to changing age demographics and the incidence of sports-related traumatic brain injury is tending to increase over *** approved medicines for neurodegenerative diseases only temporarily reduce the symptoms but cannot cure or delay disease *** transplantation strategies offer an alternative approach to facilitating central nervous system repair,but efficacy is limited by low in vivo survival rates of cells that are injected in *** cells that are attached to or encapsulated within a suitable biomaterial construct has the advantage of enhancing cell survival in vivo.A variety of biomaterials have been used to make constructs in different types that included nanoparticles,nanotubes,microspheres,microscale fibrous scaffolds,as well as scaffolds made of gels and in the form of *** these,Tween 80-methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid)nanoparticles loaded with rhynchophylline had higher transport across a blood-brain barrier model and decreased cell death in an in vitro model of Alzheimer’s disease than rhynchophylline or untreated nanoparticles with *** an in vitro model of Parkinson’s disease,trans-activating transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin had a similar protective ability as free non-Fe hemin.A positive effect on neuron survival in several in vivo models of Parkinson’s disease was associated with the use of biomaterial constructs such as trans-activating transcriptor bioconjugated with zwitterionic polymer poly(2-methacryoyloxyethyl phosphorylcholine)and protein-based nanoparticles loaded with non-Fe hemin,carbon nanotubes with olfactory bulb stem cells,poly(lactic-co-glycolic acid)microspheres with attached DI-MIAMI cells,ventral midbrain neurons mixed with short fibers of poly-(L-lactic acid

关键词： Alzheimer’s disease biomaterial cell transplantation neurodegeneration neurodegenerative disease Parkinson’s disease tissue-engineering traumatic brain injury

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MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

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Neural Regeneration Research 2022年第4期17卷 728-740页

作者： Bridget Martinez philip V.Peplow Physical Chemistry and Applied Spectroscopy Chemistry DivisionLos Alamos National LaboratoryLos AlamosNMUSA Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of mi RNAs had altered levels of expression in the brain and spinal cord,motor neurons of spinal cord and brainstem,and hypoglossal,facial,and red motor nuclei and were mostly *** the mi RNAs found to be upregulated in two of the studies were mi R-21,mi R-155,mi R-125 b,mi R-146 a,mi R-124,mi R-9,and mi R-19 b,while those downregulated in two of the studies included mi R-146 a,mi R-29,mi R-9,and mi R-125 b.A change of direction in mi RNA expression occurred in some tissues when compared(e.g.,mi R-29 b-3 p in cerebellum and spinal cord of wobbler mice at 40 days),or at different disease stages(e.g.,mi R-200 a in spinal cord of SOD1(G93 A)mice at 95 days vs.108 and 112 days).In the animal models,suppression of mi R-129-5 p resulted in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and tended to improve motor neuron survival in the SOD1(G93 A)mouse *** of mi R-155 was also associated with increased lifespan,while lowering of mi R-29 a tended to improve lifespan in males and increase muscle strength in SOD1(G93 A)*** of members of mi R-17~92 cluster improved motor neuron survival in SOD1(G93 A)*** with an artificial mi RNA designed to target h SOD1 increased lifespan and improved muscle strength in SOD1(G93 A)*** studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific mi RNAs whose suppression or directed against h SOD1 results in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and improved motor neuron survival in SOD1(G93 A)animals.

关键词： amyotrophic lateral sclerosis animal model brain brainstem microRNA motor neuron degeneration spinal cord therapeutic approaches

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MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

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Neural Regeneration Research 2023年第10期18卷 2108-2118页

作者： Bridget Martinez philip V.Peplow Department of Pharmacology University of Nevada-RenoRenoNVUSA Department of Medicine University of Nevada-RenoRenoNVUSA Department of Anatomy University of OtagoDunedinNew Zealand

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

关键词： epilepsy experimental models microRNA mouse rat seizures therapeutic targets

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Altered microRNA expression in animal models of Huntington’s disease and potential therapeutic strategies

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Neural Regeneration Research 2021年第11期16卷 2159-2169页

A review of recent animal models of Huntington’s disease showed many microRNAs had altered expression levels in the striatum and cerebral cortex,and which were mostly *** the altered microRNAs were miR-9/9*,miR-29b,miR-124a,miR-132,miR-128,miR-139,miR-122,miR-138,miR-23b,miR-135b,miR-181(all downregulated)and miR-448(upregulated),and similar changes had been previously found in Huntington’s disease *** the animal cell studies,the altered microRNAs included miR-9,miR-9*,miR-135b,miR-222(all downregulated)and miR-214(upregulated).In the animal models,overexpression of miR-155 and miR-196a caused a decrease in mutant huntingtin mRNA and protein level,lowered the mutant huntingtin aggregates in striatum and cortex,and improved performance in behavioral *** performance in behavioral tests also occurred with overexpression of miR-132 and *** the animal cell models,overexpression of miR-22 increased the viability of rat primary cortical and striatal neurons infected with mutant huntingtin and decreased huntingtin-enriched foci of≥2μ***,overexpression of miR-22 enhanced the survival of rat primary striatal neurons treated with 3-nitropropionic *** expression of miR-214,miR-146a,miR-150,and miR-125b decreased endogenous expression of huntingtin mRNA and protein in HdhQ111/HdhQ111 *** studies with animal models of Huntington’s disease are warranted to validate these findings and identify specific microRNAs whose overexpression inhibits the production of mutant huntingtin protein and other harmful processes and may provide a more effective means of treating Huntington’s disease in patients and slowing its progression.

关键词： animal model cerebral cortex huntingtin Huntington’s disease microRNA neurodegeneration striatum therapeutic strategies

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MicroRNA biomarkers in frontotemporal dementia and to distinguish from Alzheimer's disease and amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第7期17卷 1412-1422页

作者： Bridget Martinez philip V.Peplow Department of Medicine St.Georges University School of MedicineGrenada Department of Anatomy University of OtagoDunedinNew Zealand

Frontotemporal lobar degeneration describes a group of progressive brain disorders that primarily are associated with atrophy of the prefrontal and anterior temporal *** lobar degeneration is considered to be equivalent to frontotemporal *** dementia is characterized by progressive impairments in behavior,executive function,and *** are two main clinical subtypes:behavioral-variant frontotemporal dementia and primary progressive *** early diagnosis of frontotemporal dementia is critical for developing management strategies and interventions for these *** validated biomarkers,the clinical diagnosis depends on recognizing all the core or necessary neuropsychiatric features,but misdiagnosis often occurs due to overlap with a range of neurologic and psychiatric *** the studies reviewed a very large number of microRNAs were found to be dysregulated but with limited overlap between individual *** of specific miRNAs singly or in combination,or as miRNA pairs(as a ratio)in blood plasma,serum,or cerebrospinal fluid enabled frontotemporal dementia to be discriminated from healthy controls,Alzheimer’s disease,and amyotrophic lateral ***,upregulation of miR-223-3p and downregulation of miR-15a-5p,which occurred both in blood serum and cerebrospinal fluid,distinguished behavioral-variant frontotemporal dementia from healthy *** of miR-132-3p in frontal and temporal cortical tissue distinguished frontotemporal lobar degeneration and frontotemporal dementia,respectively,from healthy *** strong miRNA biofluid biomarker contenders for behavioral-variant frontotemporal dementia are miR-223-3p,miR-15a-5p,miR-22-3p in blood serum and cerebrospinal fluid,and miR-124 in cerebrospinal *** miRNAs were identified able to distinguish between behavioral-variant frontotemporal dementia and primary progressive aphasia *** studies are

关键词： Alzheimer’s disease amyotrophic lateral sclerosis behavioral variant biomarker blood plasma blood serum brain cerebrospinal fluid cortical tissue frontotemporal dementia frontotemporal lobar degeneration microRNA primary progressive aphasia

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MicroRNAs in laser-induced choroidal neovascularization in mice and rats:their expression and potential therapeutic targets

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Neural Regeneration Research 2021年第4期16卷 621-627页

Choroidal neovascularization characterizes wet age-related macular *** neovascularization formation involves a primarily angiogenic process that is combined with both inflammation and proteolysis.A primary cause of choroidal neovascularization pathogenesis is alterations in pro-and anti-angiogenic factors derived from the retinal pigment epithelium,with vascular endothelium growth factor being mainly responsible for both clinical and experimental choroidal ***(miRNAs)which are short,non-coding,endogenous RNA molecules have a major role in regulating various pathological processes,including inflammation and angiogenesis.A review of recent studies with the mouse laser-induced choroidal neovascularization model has shown alterations in miRNA expression in choroidal neovascularization tissues and could be potential therapeutic targets for wet age-related macular *** of miR-505(days 1 and 3 post-laser),miR-155(day 14)occurred in retina;miR-342-5p(days 3 and 7),miR-126-3p(day 14)in choroid;miR-23a,miR-24,miR-27a(day 7)in retina/choroid;miR-505(days 1 and 3)in retinal pigment epithelium/choroid;downregulation of miR-155(days 1 and 3),miR-29a,miR-29b,miR-29c(day 5),miR-93(day 14),miR-126(day 14)occurred in retinal pigment epithelium/*** using miRNA mimics or inhibitors were found to decrease choroidal neovascularization *** neovascularization development was reduced by overexpression of miR-155,miR-188-5p,miR-(5,B,7),miR-126-3p,miR-342-5p,miR-93,miR-126,miR-195a-3p,miR-24,miR-21,miR-31,miR-150,and miR-184,or suppression of miR-505,miR-126-3p,miR-155,and miR-23/*** studies are warranted to determine miRNA expression in mouse laser-induced choroidal neovascularization models in order to validate and extend the reported *** experimental variables need to be standardized;these include the strain and age of animals,gender,number and position of laser burns to the e

关键词： age-related macular degeneration angiogenesis animal model blood plasma choroid laser microRNAs neovascularization retina retinal pigment epithelium therapeutic targets vascular endothelial growth factor

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MicroRNAs as potential biomarkers for diagnosis of schizophrenia and influence of antipsychotic treatment

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Neural Regeneration Research 2024年第7期19卷 1523-1531页

Chara cterized by positive symptoms(such as changes in behavior or thoughts,including delusions and hallu cinations),negative symptoms(such as apathy,anhedonia,and social withdrawal),and cognitive impairments,schizophrenia is a chro nic,severe,and disabling mental disorder with late adolescence or early adulthood onset,Antipsychotics are the most commonly used drugs to treat schizophrenia,but those currently in use do not fully reverse all three types of symptoms characte rizing this *** is frequently misdiagnosed,resulting in a delay of or inappropriate *** expression of microRNAs is connected to brain development and disease and could provide novel biomarkers for the diagnosis and prognosis of *** recent studies reviewed included microRNA profiling in blood-and urine-based materials and nervous tissue mate *** the studies that had validated the preliminary findings,potential candidate biomarkers for schizophrenia in adults could be miR-22-3p,-30e-5p,-92a-3p,-148b-5p,-181a-3p,-181a-5p,-181b-5p,-199 b-5p,-137 in whole blood,and miR-130b,-193a-3p in blood *** treatment of schizophrenia patients was found to modulate the expression of certain microRNAs including miR-130b,-193a-3p,-132,-195,-30e,-432 in blood *** studies are warranted with adolescents and young adults having schizophrenia and consideration should be given to using animal models of the disorder to investigate the effect of suppressing or overexpressing specific microRNAs.

关键词： antipsychotics biomarkers blood exosomes blood plasma brain tissue exosomes brain tissues leukocytes microRNAs neural stem cells olfactory neuroepithelium schizophrenia whole blood

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Tribology of Ti6Al4V: A review

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Friction 2019年第6期7卷 497-536页

作者： Jibin T philip Jose MATHEW Basil KURIACHEN Department of Mechanical Engineering National Institute of Technology MizoramAizawl 796012India Department of Mechanical Engineering National Institute of Technology CalicutCalicut 673601India

The deleterious innate attribute of Ti6 Al4 V, the workhorse material among the alloy series of titanium is its incompetent tribo-behavior. Infinite surface modification techniques, viz., the accretion of adherent appendage layers, diffusion hardening, infusion of residual stresses, microstructural evolution, and phase transformations were attempted to enhance the wear resistance of the alloy. The need lies to establish a bridge between the indigenous material properties and the tribo-characteristics of Ti6 Al4 V so that the enforced improvement techniques can raise the barriers of its applicability. A critical review of the microstructural transitions, mechanisms governing tribo-behavior and the parametric conditions leading to material removal at dry sliding conditions of Ti6 Al4 V, falls under the scope of this manuscript. Hence, the prime focus of the approach is to impart a clear-cut perception of the minute variations in mechanical, metallurgical, and tribological characteristics of the alloy at interactive instances with distinct counter-body surfaces.

关键词： Ti6Al4V tribology sliding behavior microstructure

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PREPARATION OF ASYMMETRIC POLYETHERKETONE FLAT AND HOLLOW FIBER MEMBRANES FOR GAS SEPARATION USING ACETIC ACID BASED COAGULANTS

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Chinese Journal of Polymer Science 2008年第3期26卷 263-273页

作者：杨继萍 philip J.Brown School of Material Science and Engineering Beihang UniversityBeijing 100083China School of Materials Science and Engineering Clemson UniversitySC29634USA

Membranes for gas separation have developed significantly in the last twenty years,however,there is still a need for high temperature and chemically resistant membranes that exhibit good selectivity and gas *** study examines the fundamental properties of polyetherketone (PEK,a thermally stable and chemically resistant polymer) membranes prepared using concentrated sulphuric acid (98% H_2SO_4) as the ***-solvents used in the work included acetic acid,ethanol,methanol,glycerol,and water....

关键词： Polyetherketones Membranes Gas permeation Internal coagulant effect Morphology

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Extent and chronology of Quaternary glaciation

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Episodes 2008年第2期31卷 211-218页

作者： Jurgen Ehlers philip Gibbard Geologisches Landesamt Billstrasse 84. D-20539 Hamburg Germany Cambndge Quaternary Department Of Geography University of cambridge Downing Street Cambridge CB2 3EN England.

In a recent INQUA project the extent of Pleistocene glaciations has been digitally mapped and the chronology of events reviewed. The onset of the present Ice Age in both hemispheres dates back to the Palaeogene. In Greenland, Iceland, North America and southernmost South America sizeable ice sheets formed well before 2.6 ka BP. In Alaska and on Tierra del Fuego the ice advanced further than in any later glaciations. Evidence for Early Pleistocene glaciation （2.6-0. 78 Ma） has been reported from many parts of the world, but in most cases dating remains problematic, and the size of the glaciers and ice sheets is unknown.

关键词：第四纪地质时代冰川范围年代

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