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

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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Analytical estimation of ATF beam halo distribution

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Chinese Physics C 2014年第12期38卷 64-69页

作者：王逗 philip Bambade Kaoru Yokoya 高杰 Institute of High Energy Physics Chinese Academy of Sciences LAL Univ Paris-Sud CNRS/IN2P3 Orsay France KEK Tsukuba Ibaraki Japan

In order to study the backgrounds in the ATF2 beam line and the interaction point（IP）, this paper has developed an analytical method to give an estimation of the ATF beam halo distribution based on K. Hirata and K. Yokoya＇s theory. The equilibrium particle distribution of the beam tail in the ATF damping ring is presented,with each electron affected by several stochastic processes such as beam-gas scattering, beam-gas bremsstrahlung and intra-beam scattering, in addition to the synchrotron radiation damping effects. This is a general method which can also be applied to other electron rings.

关键词： ATF halo distribution beam-gas scattering beam-gas bremsstrahlung intra-beam scattering

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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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New serological biomarkers of inflammatory bowel disease

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World Journal of Gastroenterology 2008年第33期14卷 5115-5124页

作者： Xuhang Li Laurie Conklin philip Alex Division of Gastro- enterology Department of Medicine Johns Hopkins University School of Medicine Baltimore MD 21205 United States Division of Gastroenterology and Nutrition Department of Pediatrics Johns Hopkins University School of Medicine Baltimore MD 21205 United States

Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and character-ization of new serological biomarkers (identifi ed since 2007). These include fi ve new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibod-ies against chemically synthesized (∑) two major oligomannose epitopes, Man α-1,3 Man α-1,2 Man (∑Man3) and Man α-1,3 Man α-1,2 Man α-1,2 Man (∑Man4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-likereceptors (TLR) 2 and 4, and β-defensin-1. Further-more, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/ plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and mul-tiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically use-ful novel diag

关键词： Serological biomarkers Inflammatory bowel disease Ulcerative colitis Crohn's disease Anti-chitobioside IgA Anti-laminaribioside IgG Anti-manobioside IgG Anti-synthetic mannoside antibodies Multiplex enzyme-linked immunosorbent assay Proteomics

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Blood microRNAs as potential diagnostic markers for hemorrhagic stroke

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Neural Regeneration Research 2017年第1期12卷 13-18页

作者： Bridget Martinez philip V.Peplow Department of Molecular and Cellular Biology University of California Department of Anatomy University of Otago

Proper medical treatment of a stroke victim relies on accurate and rapid differentiation between ischemic and hemorrhagic stroke,which in current practice is performed by computerized tomography（CT） or magnetic resonance imaging（MRI） scans.A panel of micro RNAs could be an extremely useful clinical tool for distinguishing between hemorrhagic and ischemic *** review has shown that blood miRNA profile can distinguish hemorrhagic from ischemic stroke in patients and in experimental animal *** also seems likely they can differentiate between intracerebral and subarachnoid hemorrhage *** miRNA profile in cerebrospinal fluid could be a useful diagnostic tool for subarachnoid hemorrhagic *** or increased miRNA levels may be needed either as prevention or treatment of *** in vivo of miR-130 a inhibitor or miRNA mimic（miR-367,miR-223） in an intracerebral hemorrhage animal model improved neurological outcomes.

关键词： blood microRNAs diagnostic biomarkers hemorrhagic stroke human patients rat and mouse models

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Paclitaxel-associated reticulate hyperpigmentation:Report and review of chemotherapy-induced reticulate hyperpigmentation

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World Journal of Clinical Cases 2016年第12期4卷 390-400页

作者： philip R Cohen Department of Dermatology University of California San Diego

Drug-induced reticulate hyperpigmentation is uncommon. Including the patient described in this report, chemotherapy-associated reticulate hyperpigmentation has only been described in ten individuals. This paper describes the features of a woman with recurrent and metastatic breast cancer who developed paclitaxelinduced reticulate hyperpigmentation and reviews the characteristics of other oncology patients who developed reticulate hyperpigmentation from their antineoplastic treatment. A 55-year-old Taiwan Residents woman who developed reticulate hyperpigmentation on her abdomen, back and extremities after receiving her initial treatment for metastatic breast cancer with paclitaxel is described. The hyperpigmentation became darker with each subsequent administration of paclitaxel. The drug was discontinued after five courses and the pigment faded within two months. Pub Med was searched with the key words: Breast, cancer, chemotherapy, hyperpigmentation, neoplasm, reticulate, tumor, paclitaxel, taxol. The papers generated by the search, and their references, were reviewed. Chemotherapy-induced reticulate hyperpigmentation has been described in four men and six women. Bleomycin, cytoxan, 5-fluorouracil, idarubacin, and paclitaxel caused the hyperpigmentation. The hyperpigmentation faded in 83% of the patients between two to six months after the associated antineoplastic agent was discontinued. In conclusion, chemotherapy-induced reticulate hyperpigmentation is a rare reaction that may occur during treatment with various antineoplastic agents. The hyperpigmentation fades in most individuals once thetreatment is discontinued. Therefore, cancer treatment with the associated drug can be continued in patients who experience this cutaneous adverse event.

关键词： Breast Cancer Chemotherapy Hyperpigmentation Neoplasm Reticulate Tumor Paclitaxel Taxol

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Neuroprotection by immunomodulatory agents in animal models of Parkinson's disease

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Neural Regeneration Research 2018年第9期13卷 1493-1506页

作者： Bridget Martinez philip V.Peplow Department of Molecular & Cellular Biology University of CaliforniaMercedCAUSA Department of Medicine St.Georges University School of Medicine Department of Physics and Engineering Los Alamos National Laboratory Department of Anatomy University of Otago

Parkinson’s disease（PD） is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing *** cell bodies of these neurons are present in the substantia nigra,with the nerve terminals being in the *** innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to *** in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic *** of neuroinflammation is the activation of brain glial cells,principally microglia and astrocytes that release various soluble *** of these factors are proinflammatory and neurotoxic and harmful to nigral dopaminergic *** studies have identified several different agents with immunomodulatory properties that protected dopaminergic neurons from degeneration and death in animal models of *** of the agents were effective in reducing the motor deficit and alleviating dopaminergic neurotoxicity and,when measured,preventing the decrease of dopamine upon being administered therapeutically after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,6-hydroxydopamine,rotenone-lesioning or delivery of adeno-associated virus-α-synuclein to the ventral midbrain of *** of these agents were shown to exert an anti-inflammatory action,decrease oxidative stress,and reduce lipid peroxidation *** of microglia and astrocytes was also decreased,as well as infiltration of T cells into the substantia *** with fingolimod,tanshinoine I,dimethyl fumarate,thalidomide,or cocaine-and amphetamine-regulated transcript peptide as a preventive strategy ameliorated motor deficits and nigral dopaminergic neurotoxicity in brain-lesioned *** agents could be used to treat patients with early clinical signs of the disease or potentially

关键词： Parkinson's disease immunomodulatory agents neuroprotection inflammation oxidative stress animal models microgliosis astrogliosis

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Follicular contact dermatitis revisited: A review emphasizing neomycin-associated follicular contact dermatitis

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World Journal of Clinical Cases 2014年第12期2卷 815-821页

作者： philip R Cohen Division of Dermatology University of California San Diego San Diego CA 92131-3643 United States

Follicular contact dermatitis clinically presents as individual papules that include a central hair follicle. Pathologic features involve the follicle and the surrounding dermis: spongiosis and vesicle formation of the follicular epithelium associated with perifollicular and perivascular lymphocytic inflammation. Using the Pub Med database, an extensive literature search was performed on follicular contact dermatitis and neomycin. Relevant papers were reviewed and the clinical and pathologic features, the associated chemicals(including a more detailed description of neomycin), the hypothesized pathogenesis, and the management of follicular contact dermatitis were described. Several agentseither as allergens or irritants-have been reported to elicit follicular contact dermatitis. Several hypotheses have been suggested for the selective involvement of the follicles in follicular contact dermatitis: patient allergenicity, characteristics of the agent, vehicle containing the agent, application of the agent, and external factors. The differential diagnosis of follicular contact dermatitis includes not only recurrent infundibulofolliculitis, but also drug eruption, mite infestation, viral infection, and dermatoses that affect hair follicles. The primary therapeutic intervention for follicular contact dermatitis is withdrawal of the causative agent; treatment with a topical corticosteroid preparation may also promote resolution of the dermatitis. In conclusion, follicular contact dermatitis may be secondary to allergens or irritants; topical antibiotics, including neomycin, may cause this condition. Several factors may account for the selective involvement of the hair follicle in this condition. Treatment of the dermatitis requires withdrawal of the associated topical agent; in addition, topical corticosteroids may be helpful to promote resolution of lesions.

关键词： Allergic Contact Dermatitis Follicular Irritant Neomycin Papular

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MicroRNAs as disease progression biomarkers and therapeutic targets in experimental autoimmune encephalomyelitis model of multiple sclerosis

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Neural Regeneration Research 2020年第10期15卷 1831-1837页

Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to *** demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal *** tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and ***(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord *** expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord *** using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis ***,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and *** studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease ***,studies should be performed with male mice of a similar age,and with aged male and female mice.

关键词： animal model blood plasma blood serum brain tissue disease biomarkers experimental autoimmune encephalomyelitis microRNAs multiple sclerosis spinal cord therapeutic targets urine exosomes

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Sediment generation and soil mound denudation in areas of high-density tree throw along a river valley in the Jura Mountains, Switzerland

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Journal of Mountain Science 2021年第2期18卷 377-391页

作者： philip GREENWOOD Jan BAUER Nikolaus J KUHN Physical Geography&Environmental Change Research Group Department of Environmental SciencesUniversity of BaselKlingelbergstrasse 27Basel-4056Switzerland

A preliminary field-based investigation was undertaken in a small(<10 km^(2))river valley located in the mountainous Jura region of northwest *** aims of the work were to assess sediment generation and annual sediment transport rates by tree throw on forested hillslopes,and to document surface hydrology characteristics on four fresh soil mounds associated with recent tree throws over a 24-day monitoring *** the soil mounds,average sediment recovery ranged from 7.7-28.2 g(dry weight),equivalent to a suspended sediment concentration of 145.2-327.8 g L^(-1),and runoff coefficients ranged from 1.0%-4.2%.Based on a soil bulk density value of 1,044 kg m^(-3),upslope runoff generation areas were denuded by an average 0.14 mm by the end of the 24-day monitoring period,representing an erosion rate equivalent to 2.1 mm yr^(-1).A ca.50 cm high soil mound could therefore feasibly persist for around 200-250 *** tree throw work,the dimensions of 215 individual tree throws were measured and their locations mapped in 12 separate locations along the river valley representing a cumulative area equivalent to 5.3 ha(***,43 per ha).Tree throws generated a total of 20.1 m^(3) of fine-sediment(<2 mm diameter),or the equivalent of 3.8×10^(-4) m^(3) m^(-2).The process of tree throw was originally attributed to two extreme weather events that occurred in west and central Europe in late December *** the 18-year period since both storms,this represents an annual sediment transport rate of 2.7×10^(-5) m^(3) m^(-1) yr^(-1).Exploring the relationship with wind on fall direction,65.5%of tree throws(143)generally fell in a downslope direction irrespective of hillslope aspect on which they were *** infers that individual storms may not have been responsible for the majority of tree throws,but instead,could be associated with root *** the high density of tree throws and their relative maturity(average age 41 years),we hypothesise that once tr

关键词： Tree throw Hillslope processes Sediment generation mechanism Sediment transport rate Soil mound Ibach river valley

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