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Nogo receptor expression in microglia/macrophages during experimental autoimmune encephalomyelitis progression

Neural Regeneration Research 2018年第5期13卷 896-907页

作者： Amani A.Alrehaili Jae Young Lee Maha M.Bakhuraysah Min Joung Kim pei-mun aui Kylie A.Magee Steven Petratos Department of Neuroscience Central Clinical School Monash University Department of Clinical Laboratories College of Applied Medical Sciences Taif University Toolgen Inc. Gasan Digital-Ro

Myelin-associated inhibitory factors within the central nervous system（CNS） are considered to be one of the main obstacles for axonal regeneration following disease or injury. The nogo receptor 1（NgR1） has been well documented to play a key role in limiting axonal regrowth in the injured and diseased mammalian CNS. However, the role of nogo receptor in immune cell activation during CNS inflammation is yet to be mechanistically elucidated. Microglia/macrophages are immune cells that are regarded as pathogenic contributors to inflammatory demyelinating lesions in multiple sclerosis（MS）. In this study, the animal model of MS, experimental autoimmune encephalomyelitis（EAE） was induced in ngr1^＋/＋ and ngr1^–/– female mice following injection with the myelin oligodendrocyte glycoprotein（MOG_（35–55）） peptide. A fatemap analysis of microglia/macrophages was performed throughout spinal cord sections of EAE-induced mice at clinical scores of 0, 1, 2 and 3, respectively（increasing locomotor disability） from both genotypes, using the CD11 b and Iba1 cell markers. Western immunoblotting using lysates from isolated spinal cord microglia/macrophages, along with immunohistochemistry and flow cytometric analysis, was performed to demonstrate the expression of nogo receptor and its two homologs during EAE progression. Myelin protein engulfment during EAE progression in ngr1^＋/＋ and ngr1^–/– mice was demonstrated by western immunblotting of lysates from isolated spinal cord microglia/macrophages, detecting levels of Nogo-A and MOG. The numbers of M1 and M2 microglia/macrophage phenotypes present in the spinal cords of EAE-induced ngr1^＋/＋ and ngr1^–/– mice, were assessed by flow cytometric analysis using CD38 and Erg-2 markers. A significant difference in microglia/macrophage numbers between ngr1^＋/＋ and ngr1^–/– mice was identified during the progression of the clinical symptoms of EAE, in the white versus gray matter regions of the spinal cord. This difference was unrelated to the e

关键词： microglia experimental autoimmune encephalomyelitis nogo receptor myelin-associated inhibitory factors (MAIFs) Nogo A neural regeneration

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Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer＇s disease

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Neural Regeneration Research 2018年第6期13卷 1066-1080页

作者： Sara H.Mokhtar Min Joung Kim Kylie A.Magee pei mun aui Speros Thomas Maha M.Bakhuraysah Amani A.Alrehaili Jae Young Lee David L.Steer Rachel Kenny Catriona Mc Lean Michael F.Azari Antonis Birpanagos Ewlina Lipiec Philip Heraud Bayden Wood Steven Petratos Department of Neuroscience Central Clinical School Monash University Prahran Victoria Australia Department of Biochemistry and Molecular Biology Monash Universityl Clayton Victoria Australia Department of Anatomy & Developmental Biology Monash University Clayton Victoria Australia Department of Anatomical Pathology Alfred Hospital Prahran Victoria Australia School of Health and Biomedical Sciences RMIT University Bundoora Victoria Australia Division of Animal and Human Physiology Department of Biology National and Kapodistrian University of Athens Ilisia Athens Greece The Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences Department of Applied Spectroscopy RadzikowskiegoKrakow Poland Centre for Biospectroscopy and Department of Microbiology Monash University Clayton Victoria Australia

Alzheimer’s disease（AD）is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary *** to the development of these characteristic pathological hallmarks of AD,anterograde axonal transport is ***,the key proteins that initiate these intracellular impairments remain *** collapsin response mediator protein-2（CRMP-2）plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2releases ***,we tested the hypothesis that amyloid-beta（Aβ）-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1（an anterograde axonal motor transport protein）in *** found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 ***,in the transgenic Tg2576 mouse model of familial AD（FAD）that exhibits Aβaccumulation in the brain with age,we found substantial co-localization of p T555CRMP-2and dystrophic *** SH-SY5Y differentiated neuronal cultures,Aβ-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with *** overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon *** data suggest that Aβ-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function,leading to neuronal defects.

关键词： amyloid-beta protein kinases collapsin response mediator protein microtubules kinesin tubulin

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Effects of palbociclib on oral squamous cell carcinoma and the role of PIK3CA in conferring resistance

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Cancer Biology & Medicine 2019年第2期16卷 264-275页

作者： Nur Syafinaz Zainal Bernard Kok Bang Lee Zheng Wei Wong Iuan Sheau Chin pei San Yee Chai Phei Gan Kein Seong mun Zainal Ariff Abdul Rahman J. Silvio Gutkind Vyomesh Patel Sok Ching Cheong Head and Neck Team Cancer Research Malaysia Selangor 47500 Malaysia Department of Oral & Maxillofacial Clinical Sciences Faculty of Dentistry University of Malaya Kuala Lumpur 50603 Malaysia Department of Pathology Faculty of Medicine University of Malaya Kuala Lumpur 50603 Malaysia Oral Cancer Research and Co-ordinating Centre (OCRCC) Faculty of Dentistry University of Malaya Kuala Lumpur 50603 Malaysia Department of Pharmacology University of California San Diego 92093-5004 CA USA

Objective: Lack of effective therapies remains a problem in the treatment of oral squamous cell carcinoma(OSCC), especially in patients with advanced tumors. OSCC development is driven by multiple aberrancies within the cell cycle pathway, including amplification of cyclin D1 and loss of p16. Hence, cell cycle inhibitors of the CDK4/6-cyclin D axis are appealing targets for OSCC treatment. Here, we determined the potency of palbociclib and identified genetic features that are associated with the response of palbociclib in ***: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib ***: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar ***, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin E1 protein levels. We further demonstrated that the combination of a PI3 K/mTOR inhibitor(PF-04691502) and palbociclib completely controlled tumor growth in ***: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies.

关键词： OSCC palbociclib CDK4/6 inhibitors PIK3CA

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Fluorescent nanoswitch for monitoring specific pluripotency-related microRNAs of induced pluripotent stem cells： Development of polyethyleneimine- oligonucleotide hybridization probes

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Nano Research 2017年第8期10卷 2545-2559页

作者： Seungmin Han Hye Young Son Byunghoon Kang Eunji Jang Jisun Ki Na Geum Lee Jongjin Park Moo-Kwang Shin Byeonggeol mun Jeong-Ki Min Seungjoo Haam Department of Chemical and Biomolecular Engineering College of Engineering Yonsei University Seou1120-749 Republic of Korea Department of Radiology College of Medicine Yonsei University Seou1120-752 Republic of Korea Severance Biomedical Science Institute College of Medicine Yonsei University Seou1120-752 Republic of Korea Biotherapeutics Translational Research Center Korea Research Institute of Bioscience and Biotechnology Daejeon 34141 Republic of Korea Department of Biomolecular Science University of Science & Technology Daejeon 34113 Republic of Korea

The isolation of high-grade （i.e. high-pluripotency） human induced pluripotent stem cells （hiPSCs） is a decisive factor for enhancing the purity of hiPSC populations or differentiation efficiency. A non-invasive imaging system that can monitor microRNA （miRNA） expression provides a useful tool to identify and analyze specific cell populations. However, previous studies on the monitoring/isolation of hiPSCs by miRNA expression have limited hiPSCs＇ differentiation system owing to long-term incubation with miRNA imaging probe-nanocarriers. Therefore, we focused on monitoring high-grade hiPSCs without influencing the pluripotency of hiPSCs. We reduced nanoparticle transfection time, because hiPSCs are prone to spontaneous differentiation under external factors during incubation. The fluorescent nanoswitch （＂ON＂ with target miRNA）, which can be applied for either imaging or sorting specific cells by fluorescence signals, contains an miRNA imaging probe （miP） and a pei-PEG nanoparticle （miP-P）. Consequently, this nanoswitch can sense various endogenous target miRNAs within 30 min in vitro, and demonstrates strong potential for not only imaging but also sorting pluripotent hiPSCs without affecting pluripotency. Moreover, miP-P-treated hiPSCs differentiate well into endothelial cells, indicating that miP-P does not alter the pluripotency of hiPSCs. We envisage that this miRNA imaging system could be valuable for identifying and sorting high-grade hiPSCs for improved practical applications.

关键词： induced pluripotent stem cells (iPSCs) pluripotency microRNA (miRNA) fluorescence imaging nanoparticle

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蛋氨酸羟基类似物异丙酯(HMBi)对奶牛产奶性能、繁殖性能及血清生化指标的影响

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中国兽医学报 2023年第2期43卷 396-404页

作者：裴明财曾涵芳林红朱靖韩兆玉南京农业大学动物科技学院/乳牛科学研究所江苏南京210095

旨在研究在日粮中添加蛋氨酸羟基类似物异丙酯(HMBi)对奶牛产奶性能、繁殖性能及血清生化指标的影响,为HMBi在奶牛生产中的应用提供理论依据。选取40头健康的中国荷斯坦奶牛,随机分为对照组和试验组,每组20头。从围产期开始,对照组饲喂... 详细信息

旨在研究在日粮中添加蛋氨酸羟基类似物异丙酯(HMBi)对奶牛产奶性能、繁殖性能及血清生化指标的影响,为HMBi在奶牛生产中的应用提供理论依据。选取40头健康的中国荷斯坦奶牛,随机分为对照组和试验组,每组20头。从围产期开始,对照组饲喂基础日粮,试验组在对照组的基础上,每头奶牛添加25 g/d的HMBi,试验期从产前21 d至产后80 d。结果显示,日粮添加25 g/d HMBi可以显著提高奶牛产奶量、乳尿素氮(mun)、乳糖率(P0.05)。日粮添加25 g/d HMBi可以显著提高奶牛血清中白蛋白(ALB)、球蛋白(GLB)、总蛋白(TP)、血清BUN含量(P0.05)。日粮添加25 g/d HMBi可以显著提高奶牛血清中谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、总抗氧化能力(T-AOC)(P<0.05),显著降低丙二醛(MDA)、乳酸脱氢酶(LDH)含量(P<0.05)。日粮添加25 g/d HMBi可以显著提高奶牛血清中促卵泡素(FSH)含量(P<0.05),对雌二醇(E2)无显著影响(P<0.05);极显著提高后代公犊初生体质量(P<0.01);产后奶牛总受胎率、第一情期受胎率、情期受胎率有提高的趋势,配种指数有降低的趋势,胎衣不下、子宫炎、妊娠毒血症等产后疾病发生率有降低的趋势。结果表明,在奶牛日粮中添加25 g/d的HMBi可以提高产奶性能、繁殖性能和抗氧化能力,降低产后疾病发生率。

关键词：蛋氨酸羟基类似物异丙酯奶牛产奶性能繁殖性能血清生化指标

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