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RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39℃

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Neural Regeneration Research 2020年第5期15卷 865-874页

作者： Li-Min Guo Zhen Wang Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong department of Neurobiology and Human Anatomy School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina department of Basic Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu ProvinceChina department of neurology People’s Hospital of LianhuaPingxiangJiangxi ProvinceChina department of Human Anatomy School of Basic Medical ScienceXinjiang Medical UniversityUrumqiXinjiang Uygur Autonomous RegionChina department of Forensic Science School of Basic Medical ScienceCentral South UniversityChangshaHunan ProvinceChina Narcotics Division Municipal Security BureauChangshaHunan ProvinceChina

Methamphetamine is one of the most prevalent drugs abused in the *** abusers usually present with hyperpyrexia (39℃),hallucination and other psychiatric ***,the detailed mechanism underlying its neurotoxic action remains *** study investigated the effects of methamphetamine + 39℃ on primary cortical neurons from the cortex of embryonic Sprague-Dawley *** cortex neurons were exposed to 1 mM methamphetamine + 39℃.Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39℃ triggered obvious necrosis-like death in cultured primary cortical neurons,which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 *** blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39℃ for 3 *** pre-treatment with RIP3 inhibitor GSK’872,propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased;RIP3 and MLKL protein expression significantly *** staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine *** together,the above results suggest that methamphetamine + 39℃ can induce RIP3/MLKL regulated necroptosis,thereby resulting in *** study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University,China (approval numbers: 2017-S026 and 2017-S033) on March 7,2017.

关键词： GSK'872 human brain tissue hyperpyrexia methamphetamine mixed lineage kinase domain-like protein necrostatin-1 necroptosis nerve regeneration neural regeneration rat cortical neurons receptor-interacting protein-3 synergistic effect

Beauty of the beast: anticholinergic tropane alkaloids in therapeutics

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Natural Products and Bioprospecting 2022年第1期12卷 515-529页

作者： Kyu Hwan Shim Min Ju Kang Niti Sharma Seong Soo A.An Bionano Research Institute Gachon University1342 Seongnam-daeroSujeong-GuSeongnam 461-701South Korea department of neurology Veterans Health Service Medical CenterVeterans Medical Research InstituteSeoulSouth Korea

Tropane alkaloids(TAs)are among the most valued chemical compounds known since pre-historic *** plants from Solanaceae family(Hyoscyamus niger,Datura,Atropa belladonna,Scopolia lurida,Mandragora officinarum,Duboisia)and Erythroxylaceae(Erythroxylum coca)are rich sources of tropane *** compounds possess the anticholinergic properties as they could block the neurotransmitter acetylcholine action in the central and peripheral nervous system by binding at either muscarinic and/or nicotinic ***,they are of great clinical impor-tance and are used as antiemetics,anesthetics,antispasmodics,bronchodilator and *** also serve as the lead compounds to generate more effective *** to the important pharmacological action they are listed in the WHO list of essential medicines and are available in market with FDA ***,being anticholinergic in action,TA medication are under the suspicion of causing dementia and cognitive decline like other medications with anticholinergic action,interestingly which is *** are published reviews on chemistry,biosynthesis,phar-macology,safety concerns,biotechnological aspects of TAs but the detailed information on anticholinergic mecha-nism of action,clinical pharmacology,FDA approval and anticholinergic burden is *** the present review tries to fill this lacuna by critically summarizing and discussing the above mentioned aspects.

关键词： Tropane alkaloids Poisonous plants Anticholinergic action Muscarinic and nicotinic receptors Therapeutics Anticholinergic burden

Celeboxib-mediated neuroprotection in focal cerebral ischemia: an interplay between unfolded protein response and inflammation

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Neural Regeneration Research 2022年第2期17卷 302-303页

作者： Maria Santos-Galdiano Diego Perez-Rodriguez Arsenio Fernandez-Lopez Area de Biologia Celular Instituto de BiomedicinaCampus de Vegazana s/nUniversidad de LeonLeonSpain Neural Therapies SL Campus de Vegazana s/nLeónSpain department of Clinical and Movement Neurosciences UCL Queen Square Institute of NeurologyLondonUK

Ischemic stroke results from the temporary or permanent lack of blood supply in the brain due to the occlusion of a brain blood vessel. Around 85% of patients with cerebrovascular accidents suffer from ischemic strokes.

关键词： inflammation cerebral ischemia

Volumetric Assessment of Corticospinal Tract Infiltration by Astrocytoma Using Diffusion Tensor Tractography

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Open Journal of Medical Imaging 2014年第2期4卷 65-71页

作者： Marwa Adel Shaaban Taha Kamel Alloush Mohamed Hamdy Ibrahim Ahmed Abd el bar Sherif Hashim Morad department of neurology Ain Shams University Cairo Egypt department of Neurosurgery Ain Shams University Cairo Egypt department of Radiology Misr University for Science and Technology Cairo Egypt

Objectives: The aim of the study is to assess volumetric Corticospinal Tract infiltration by Astro-cytoma using Diffusion Tensor Tractography. Material and Methods: Preoperative, anatomic (T1- and T2-weighted) and diffusion tensor MRI were performed in 9 patients with supratentorial gliomas (WHO grade II and III). The tumors were manually segmented from the T1- and T2-weighted MRI, and their volume calculated. A three-dimensional tractography was performed in each case. A second segmentation and volume measurement was performed on the tumor regions intersecting adjacent white matter fiber tracts. Results: We identified that white matter tracts were infiltrated by 6 Astrocytoma tumors. The median tumor volume (±standard deviation) in our patient population was 33 ± 26.82 ml. The median tumor volume (±standard deviation) infiltrating white matter fiber tracts was 4.15 ± 9.23 ml. The median fraction of tumor volume infiltrating white matter fiber tracts was 26.3% ± 10.1%. Conclusions: Diffusion tensor MR Tractography is a reliable preoperative assessment tool since it detects extensive white matter infiltration by Astrocytoma irrespective of brain tumors volume. Recommendations: Prospective large population studies are required to clarify how infiltration relates to tumor location.

关键词： Tractography Astrocytoma Brain Tumor Corticospinal Tract Infiltration

Malignant peripheral nerve sheath tumor with hemophilic syndrome and bone marrow fibrosis:A rare case report

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World Journal of Clinical Cases 2023年第31期11卷 7673-7679页

作者： Hui Li Li Wang Ying-Hong Wu Gang Chen Hong-Xia Li Li-Fen Fan Min Gu Cai-Hong Jiang department of Medical Oncology Ordos Central HospitalOrdos 017000Inner Mongolia Autonomous RegionChina department of Pathology Ordos Central HospitalOrdos 017000Inner Mongolia Autonomous RegionChina department of neurology Baogang HospitalBaotou 014010Inner Mongolia Autonomous Region 014010China department of Pharmacy Ordos Central HospitalOrdos 017000Inner Mongolia Autonomous RegionChina department of Orthopedics Ordos Central HospitalOrdos 017000Inner Mongolia Autonomous RegionChina

BACKGROUND Malignant schwannoma is a rare tumor in the peripheral nervous system,accounting for approximately 5%to 10%of systemic soft tissue ***,malignant schwannoma occurring in the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis is extremely rare in clinical ***,we report the first case of an patient diagnosed with malignant peripheral nerve sheath tumor(MPNST)of the broad ligament of the uterus with hemophilic syndrome and bone marrow fibrosis,and share our reference clinical diagnosis and treatment *** SUMMARY A patient was diagnosed with MPNST of the uterus harboring hemophilic syndrome and bone marrow *** received combination,and repeated imaging revealed further encountered rare complications(hemophilia syndrome and bone marrow fibrosis)after two cycles of ***,combined treatment with pazopanib,gemcitabine,and dacarbazine was ***,the patient succumbed to death at hospital after two *** This report firstly provided reference clinical practice for a patient with MPNST of the uterus harboring hemophilic syndrome and bone marrow *** case raises a reminder about the tolerance and safety of combination therapy,especially in young women.

关键词： Malignant peripheral nerve sheath tumor Hemophilic syndrome Bone marrow fibrosis Case report

Regulation of Myelination in the Central Nervous System by Nuclear Lamin B1 and Non-coding RNAs

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Translational Neurodegeneration 2014年第1期3卷 13-20页

作者： Shu-Ting Lin Mary Y Heng Louis J Ptáček Ying-Hui Fu department of neurology University of California1550 Fourth streetUCSF-Mission BayRock Hall 548San FranciscoCA 94158USA Howard Hughes Medical Institute University of CaliforniaSan FranciscoCA 94158USA

Adult-onset autosomal dominant leukodystrophy(ADLD)is a progressive and fatal hereditary demyelination disorder characterized initially by autonomic dysfunction and loss of myelin in the central nervous system(CNS).Majority of ADLD is caused by a genomic duplication of the nuclear lamin B1 gene(LMNB1)encoding lamin B1 protein,resulting in increased gene dosage in brain *** vitro,excessive lamin B1 at the cellular level reduces transcription of myelin genes,leading to premature arrest of oligodendrocyte *** models of ADLD overexpressing LMNB1 exhibited age-dependent motor deficits and myelin defects,which are associated with reduced occupancy of the Yin Yang 1 transcription factor at the promoter region of the proteolipid protein *** B1 overexpression mediates oligodendrocyte cell-autonomous neuropathology in ADLD and suggests lamin B1 as an important regulator of myelin formation and maintenance during *** of microRNA-23(miR-23)as a negative regulator of lamin B1 can ameliorate the consequences of excessive lamin B1 at the cellular ***-23a-overexpressing mice display enhanced oligodendrocyte differentiation and myelin ***-23a targets include a protein coding transcript PTEN(phosphatase and tensin homolog on chromosome 10),and a long noncoding RNA(2700046G09Rik),indicating a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy ***,we provide a concise review of the current literature on clinical presentations of ADLD and how lamin B1 affects myelination and other developmental ***,we address the emerging role of non-coding RNAs(ncRNAs)in modulating gene networks,specifically investigating miR-23 as a potential target for the treatment of ADLD and other demyelinating disorders.

关键词： Lamin Long non-coding RNA MicroRNA Myelin

Single-versus multi-fraction radiation treatment for metastatic spinal cord compression:functional outcome study

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The Chinese-German Journal of Clinical Oncology 2011年第9期10卷 535-540页

作者： Mohammad Abu-Hegazy Hanan A.Wahba department of neurology Faculty of MedicineMansoura UniversityMansouraEgypt department of Clinical Oncology and Nuclear Medicine Faculty of MedicineMansoura UniversityMansouraEgypt

Objective:The optimal treatment of patients with metastatic spinal cord compression(MSCC) is still being *** randomized trial was planned to compare the functional outcome and its related prognostic factors,toxicity and in-field recurrence of the three schedules of ***:Two hundred and eighty five patients enrolled in the study of which 95 received 1 × 8 Gy,100 received 10 x 3 Gy and 90 received the radiation treatment of 20 × 2 *** was performed with 6-10 Mv linear accelerators or cobalt-60 units by single posterior field or parallel opposed fields according to depth of irradiation *** with dexamethasone was started from the first day of clinico-radiologic diagnosis till 4-5 days after the end of radiotherapy(RT) then tapered off during 10 *** prognostic factors were evaluated with respect to functional ***:All groups were balanced for patient's characteristics and potential prognostic *** statistically significant difference was observed between the 3 groups as regard functional outcome and toxicity while single fraction was associated with higher in-field recurrences(22.8%) with statistically significant difference between the 3 groups(P = 0.01).Functional outcome was significantly better with younger age(≤ 60 y),Eastern Cooperative Oncology Group performance status(ECOG-PS) of 1-2,involved vertebra of 1-2,favorable tumor type,absence of visceral or other bone metastasis,decreased time of developing motor deficit before radiotherapy,long interval between cancer diagnosis to metastatic spinal cord compression,and normal ambulatory ***:The three schedules provided similar functional ***-radiation dose was associated with higher in-field *** minimize treatment time and costs,the dose of 1 × 8 Gy is recommended for patients with poor predicated survival and 10 × 3 Gy for other patients.

关键词： metastatic spinal cord compression(MSCC) outcome irradiation prognostic factor

Ophthalmic manifestations of Cryptococcus gattii species complex:a case series and review of the literature

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International Journal of Ophthalmology(English edition) 2022年第1期15卷 119-127页

作者： Grace A.McCabe Jack W.McHugh Todd Goodwin Douglas F.Johnson Anthony Fok Thomas G.Campbell department of Ophthalmology the Royal Melbourne HospitalMelbourneVictoria 3050Australia department of Internal Medicine Mayo ClinicRochesterMinnesota 55902USA James Cook University TownsvilleQueensland 4811Australia NQ Eye Foundation TownsvilleQueensland 4811Australia department of Infectious Disease the Royal Melbourne HospitalMelbourneVictoria 3050Australia department of neurology the Royal Melbourne HospitalMelbourneVictoria 3050Australia Centre for Eye Research Australia East MelbourneVictoria 3002Australia Ophthalmology Department of Surgerythe University of MelbourneMelbourneVictoria 3010Australia

AIM:To report 4 cases of Cryptococcus gattii(***)species complex infection with diverse ophthalmic manifestations,and to review the literature to examine pathobiology of disease,classical ophthalmic presentations and outcomes,and treatment modalities for this emerging ***:Cases of *** meningoencephalitis with ophthalmic manifestations were identified via chart review at two institutions in Australia and one institution in the mid-west region of the United States and are reported as a case ***,a MEDLINE literature review was conducted to identify all reported cases of *** with ophthalmic manifestations from *** were reviewed and tabulated,together with our series of patients,in this ***:Four cases of *** with ophthalmic manifestations are presented;three from Australia and one from the USA.A literature review identified a total of 331 cases of *** with visual *** majority of cases occurred in immunocompetent *** vision and diplopia were the most common presenting symptoms,with papilloedema the most common sign,reported in 10%-50%of *** loss was reported in 10%-53%of cases,as compared to rates of visual loss of 1%-9%in *** *** intracranial pressure,cerebrospinal fluid(CSF)fungal burden,and abnormal neurological exam at presentation correlated with poor visual *** mainstays of treatment are anti-fungal agents and aggressive management of intracranial hypertension with serial lumbar *** diversion procedures should be considered for refractory *** and mannitol are associated with high complication rates,and adjuvant corticosteroids have demonstrated higher mortality rates;these treatments should be ***:Permanent visual loss represents a devastating yet potentially preventable sequelae of *** *** hypertension needs to be recognised early and aggressively ***

关键词： Cryptococcus Cryptococcus gattii cryptococcosis ophthalmic manifestation

Hydrogen Sulfide Enhances Hippocampal Autophagic Flux to Inhibit Cognitive Impairment in Streptozotocin-induced Diabetic Rats by Up-regulation of Ornithine Decarboxylase/Spermidine Pathway

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Hydrogen Sulfide Enhances Hippocampal Autophagic Flux to Inh...