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MicroRNAs as potential biomarkers in temporal lobe epilepsy and mesial temporal lobe epilepsy

Neural Regeneration Research 2023年第4期18卷 716-726页

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

Temporal lobe epilepsy is the most common form of focal epilepsy in adults,accounting for one third of all diagnosed epileptic patients,with seizures originating from or involving mesial temporal structures such as the hippocampus,and many of these patients being refractory to treatment with anti-epileptic *** lobe epilepsy is the most common childhood neurological disorder and,compared with adults,the symptoms are greatly affected by age and brain *** of temporal lobe epilepsy relies on clinical examination,patient history,electroencephalographic recordings,and brain *** or delay in diagnosis is common.A molecular biomarker that could distinguish epilepsy from healthy subjects and other neurological conditions would allow for an earlier and more accurate diagnosis and appropriate treatment to be *** possible biomarkers of pathological changes as well as potential therapeutic targets in the epileptic brain are micro *** of the recent studies had performed micro RNA profiling in body fluids such as blood plasma and blood serum and brain tissues such as temporal cortex tissue and hippocampal tissue.A large number of micro RNAs were dysregulated when compared to healthy controls and with some overlap between individual studies that could serve as potential *** example,in adults with temporal lobe epilepsy,possible biomarkers are miR-199a-3p in blood plasma and miR-142-5p in blood plasma and blood *** adults with mesial temporal lobe epilepsy,possible biomarkers are miR-153 in blood plasma and miR-145-3p in blood ***,in many of the studies involving patients who receive one or several anti-epileptic drugs,the influence of these on micro RNA expression in body fluids and brain tissues is largely *** studies are warranted with children with temporal lobe epilepsy and consideration should be given to utilizing mouse or rat and non-human primate models of temporal lobe epil

关键词： adults biomarkers blood plasma blood serum children hippocampal tissue mesial temporal lobe epilepsy microRNA temporal cortical tissue temporal lobe epilepsy

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MicroRNAs as biomarkers in glaucoma and potential therapeutic targets

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Neural Regeneration Research 2022年第11期17卷 2368-2375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

Glaucoma is a neurodegenerative disease in which optic nerve damage and visual field defects *** is a leading cause of irreversible *** pathogenesis is largely unknown although several risk factors have been identified,with an increase in intraocular pressure being the main *** of intraocular pressure is the only treatment ***-angle glaucoma is the most common form of the condition,accounting for~90%of all cases of glaucoma,with primary open-angle glaucoma and exfoliation glaucoma being the most frequent *** are strong indications that microRNAs play important roles in the pathogenesis of primary open-angle *** of the recent studies reviewed had performed microRNA profiling in aqueous humor from glaucoma patients compared to controls who were chiefly cataract patients.A very large number of microRNAs were dysregulated but with limited overlap between individual *** in aqueous humor that could be possible targets for therapeutic intervention are miR-143-3p,miR-125b-5p,and *** ove rlap of findings occurred within the dysregulated miRNAs for blood plasma,blood serum,peripheral blood mononuclear cells,and tears of primary open-angle glaucoma *** ral impo rtant limitations were identified in these *** studies are warranted of mic roRNA expression in aqueous humor and blood samples of primary open-angle glaucoma patients in the early stages of the disease so that validated biomarkers can be identified and treatment *** addition,whether modifying the levels of specific microRNAs in aqueous humor or tears has a beneficial effect on intraocular pressure and ophthalmic examination of the eyes should be investigated using suitable animal models of glaucoma.

关键词： aqueous humor biomarkers blood plasma blood serum glaucoma intraocular pressure microRNA peripheral blood mononuclear cells tears therapeutic targets

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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

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

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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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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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Rangeland hillslope lengths:A case study at the Walnut Gulch Experimental Watershed,southeastern Arizona

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International Soil and Water conservation Research 2022年第4期10卷 597-609页

作者： Li Li Mark A.Nearing philip Heilman Mary H.Nichols D.P.Guertin c.J.Williams School of Natural Resources and the Environment University of ArizonaTucsonAZ85705USA USDA-Agricultural Research Service Southwest Watershed Research CenterTucsonAZ85719USA

Rangeland hillslopes provide much of the sediment supplied to channel systems and their lengths exert a fundamental constraint on hillslope diffusive ***,information regarding lengths of rangeland hillslopes,and how best to estimate them,is *** this study,three groups of watersheds(10 in total)were selected from the Walnut Gulch Experimental Watershed according to their geology,soil and vegetation *** 1 watersheds were at lower elevations dominated by shrubs,Group 3 were at high elevations dominated by grass,and Group 2 were mixed shrub and *** hillslope lengths were calculated from 1 m-resolution DEMs using three methods:a flow routing algorithm,slope-area relationships,and inverted relationship with drainage *** that characterize the current watersheds,including Hack's exponent and coefficient,watershed shape coefficient,channel concavity and steepness,and surface roughness,were quantified and related to hillslope *** shows:(1)estimated hillslope lengths were different for the three methods and between the three groups of watersheds;(2)hillslope lengths that measured from the flow routing algorithm for the ten selected watersheds primarily ranged from 30 to 100 m,with a median value of 63.0 m,which was 20%e50%greater than those derived from slope-area plots or drainage densities;(3)hillslope lengths estimated from the flow routing method were greater in Group 3 watersheds than in Group 2 and then in Group 1 *** attributed these differences in hillslope lengths to the historic epeirogenic pulses,watershed and drainage network morphology,and differences in vegetation characteristics;(4)measured hillslope lengths from the flow routing algorithm were best correlated with hillslope relief,then surface roughness,channel steepness and *** results would benefit the applications of hydrological and erosion models in rangelands.

关键词： Rangeland hillslope Slope length Drainage density Slope-area relationship Hillslope hydrology

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Denitrification and the challenge of scaling microsite knowledge to the globe

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mLife 2023年第3期2卷 229-238页

作者： G.philip Robertson W.K.Kellogg Biological Station Michigan State UniversityHickory CornersMichiganUSA Department of Plant Soiland Microbial SciencesMichigan State UniversityEast LansingMichiganUSA Great Lakes Bioenergy Research center Michigan State UniversityEast LansingMichiganUSA

Our knowledge of microbial processes—who is responsible for what,the rates at which they occur,and the substrates consumed and products produced—is imperfect for many if not most taxa,but even less is known about how microsite processes scale to the ecosystem and thence the *** both natural and managed environments,scaling links fundamental knowledge to application and also allows for global assessments of the importance of microbial *** rarely is scaling straightforward:More often than not,process rates in situ are distributed in a highly skewed fashion,under the influence of multiple interacting controls,and thus often difficult to sample,quantify,and *** date,quantitative models of many important processes fail to capture daily,seasonal,and annual fluxes with the precision needed to effect meaningful management *** cycle processes are a case in point,and denitrification is a prime *** models based on machine learning can improve predictability and identify the best environmental predictors but are—by themselves—insufficient for revealing process-level knowledge gaps or predicting outcomes under novel environmental *** models that incorporate well-calibrated process models as predictors for machine learning algorithms can provide both improved understanding and more reliable forecasts under environmental conditions not yet *** trait-based models into such efforts promises to improve predictions and understanding still further,but much more development is needed.

关键词： ecosystems microsites N_(2) N_(2)O modeling

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The Infinity Tree: Representing Infinities of Real Numbers with countably Infinite Tree Structures

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Advances in Pure Mathematics 2023年第4期13卷 198-205页

作者： philip c. Jackson TalaMind LLc Troy MI USA

This paper discusses how the infinite set of real numbers between 0 and 1 could be represented by a countably infinite tree structure which would avoid cantor’s diagonalization argument that the set of real numbers is not countably infinite. Likewise, countably infinite tree structures could represent all real numbers, and all points in any number of dimensions in multi-dimensional spaces. The objective of this paper is not to overturn previous research based on cantor’s argument, but to suggest that this situation may be treated as a definitional or axiomatic choice. This paper proposes a “non-cantorian” branch of cardinality theory, representing all these infinities with countably infinite tree structures. This approach would be consistent with the continuum Hypothesis.

关键词： Infinity countable Diagonalization Real Numbers Tree Structure Infinity Tree continuum Hypothesis

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Organoids as a model to study the human endometrium

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Reproductive and Developmental Medicine 2022年第4期6卷 215-224页

作者： Jianlin Li Leqian Lin Jiangming Zhong Xintong Li cheuklun Lee philip c.N.chiu Department of Obstetrics and Gynaecology LKS Faculty of MedicineThe University of Hong Kong21 Sassoon RoadPokfulamHong KongChina

The endometrium is composed of glandular and luminal epithelia supported by stromal connective tissue and multiple other cell *** is a dynamic organ that undergoes physiological and functional alteration during the menstrual *** resemble the primary tissue of origin to recapitulate their corresponding biological and pathological *** are known for their ability to undergo extensive expansion while maintaining their genomic stability,facilitating their long-term storage and high-throughput *** development of the three-dimensional endometrial organoid system,which recapitulates the structural and functional characteristics of the endometrial glands,provides a powerful tool to study the normal endometrium and its related *** Web of Science was searched for relevant literature using the keywords"endometrium","endometrial gland","organoid",and"culture model";a total of 134 articles were *** this review,the characteristics,applications,and limitations of endometrial epithelial organoids are discussed.

关键词： Endometrial gland Endometrium Epithelial cell Estrous cycle Organoid Three-dimensional culture model

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