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Mild closed head traumatic brain injury-induced changes in monoamine neurotransmitters in the trigeminal subnuclei of a rat model:mechanisms underlying orofacial allodynias and headache

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Neural Regeneration Research 2017年第6期12卷 981-986页

作者： Golam Mustafa Jiamei Hou Rachel Nelson Shigeharu Tsuda Mansura Jahan Naweed S.Mohammad Joseph V.Watts Floyd J.Thompson Prodip Bose brain Rehabilitation Research Center of Excellence Malcom Randall VA Medical Center North Florida/South Georgia Veterans Health System Department of Physiological Sciences College of Veterinary Medicine University of Florida Department of Neuroscience McKnight Brain Institute College of Medicine University of Florida Department of Neurology McKnight Brain Institute College of Medicine University of Florida

Our recent findings have demonstrated that rodent models of closed head traumatic brain injury exhibit comprehensive evidence of progressive and enduring orofacial allodynias, a hypersensitive pain response induced by non-painful stimulation. These allodynias, tested using thermal hyperalgesia, correlated with changes in several known pain signaling receptors and molecules along the trigeminal pain pathway, especially in the trigeminal nucleus caudalis. This study focused to extend our previous work to investigate the changes in monoamine neurotransmitter immunoreactivity changes in spinal trigeminal nucleus oralis, pars interpolaris and nucleus tractus solitaries following mild to moderate closed head traumatic brain injury, which are related to tactile allodynia, touch-pressure sensitivity, and visceral pain. Our results exhibited significant alterations in the excitatory monoamine, serotonin, in spinal trigeminal nucleus oralis and pars interpolaris which usually modulate tactile and mechanical sensitivity in addition to the thermal sensitivity. Moreover, we also detected a robust alteration in the expression of serotonin, and inhibitory molecule norepinephrine in the nucleus tractus solitaries, which might indicate the possibility of an alteration in visceral pain, and existence of other morbidities related to solitary nucleus dysfunction in this rodent model of mild to moderate closed head traumatic brain injury. Collectively, widespread changes in monoamine neurotransmitter may be related to orofacial allodynhias and headache after traumatic brain injury.

关键词： traumatic trigeminal headache alteration visceral nucleus underlying moderate stimulation possibility

Development of glutamatergic innervation during maturation of adult-born neurons

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Frontiers in Biology 2015年第4期10卷 310-320页

作者： Cristina V. Dieni Adam J. Wieckert Linda Overstreet-Wadiche Department of Neurobiology and Evelyn mcknight brain institute University of Alabama at BirminghamBirmingham AL 35294 USA

The dentate gyrus is the entrance of the hippocampal formation and a primary target of excitatory afferents from the entorhinal cortex that carry spatial and sensory information. Mounting evidence suggests that continual adult neurogenesis contributes to appropriate processing of cortical information. The ongoing integration of adult born neurons dynamically modulates connectivity of the network, potentially contributing to dentate cognitive function. Here we review the current understanding of how glutamatergie innervation develops during the progression of adult-born neuron maturation. Summarizing the developmental stages of dentate neurogenesis, we also demonstrate that new neurons at an immature stage of maturation begin to process afferent activity from both medial and lateral entorhinal cortices.

关键词： dentate gyms adult neurogenesis glutamatergic innervation granule cell neuroprogenitor

TDP-35,a truncated fragment of TDP-43,induces dose-dependent toxicity and apoptosis in flies

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Neural Regeneration Research 2022年第11期17卷 2441-2442页

作者： Deepak Chhangani Diego E.Rincon-Limas Department of Neurology McKnight Brain Instituteand Norman Fixel Institute for Neurological DiseasesUniversity of Florida Department of Neuroscience Center for Translational Research in Neurodegenerative DiseaseGenetics InstituteUniversity of Florida

TAR DNA-binding protein 43(TDP-43)is an essential 414 amino acid protein that regulates multiple aspects of RNA biogenesis,processing,and *** localizes primarily in the nucleus,but abnormal translocation and accumulation in the cytosol occur under pathological conditions(Tziortzouda et al.,2021).TDP-43 abnormalities are typical pathological hallmarks of amyotrophic lateral sclerosis(ALS)and frontotemporal lobar *** in the TDP-43-encoding gene TARDBP cause familial ALS。

关键词： degeneration TDP

Highly Fluorescent Dye-Doped Silica Nanoparticles Increase Flow Cytometry Sensitivity for Cancer Cell Monitoring

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Nano Research 2009年第6期2卷 448-461页

作者： M.-Carmen Estévez Meghan B.OʼDonoghue Xiaolan Chen Weihong Tan Center for Research at the Bio/Nano Interface Departments of Chemistry and Department of Physiology and Functional GenomicsShands Cancer Center and UF Genetics InstituteMcKnight Brain InstituteUniversity of FloridaGainesvilleFlorida 32611-7200USA

Early and accurate diagnosis and treatment of cancer depend on rapid,sensitive,and selective detection of tumor *** diagnosis of cancers,especially leukemia,relies on histology and fl ow cytometry using single dye-labeled ***,this combination may not lead to high signal output,which can hinder detection,especially when the probes have relatively weak affi nities or when the receptor is expressed in a low concentration on the target cell *** solve these problems,we have developed a novel method for sensitive and rapid detection of cancer cells using dye-doped silica nanoparticles(NPs)which increases detection sensitivity in fl ow cytometry analyses between 10-and 100-fold compared to standard *** NPs are~60 nm in size and can encapsulate thousands of individual dye molecules within their *** have extensively investigated surface modifi cation strategies in order to make the NPs suitable for selective detection of cancer cells using fl ow *** NPs are functionalized with polyethylene glycol(PEG)to prevent nonspecifi c interactions and with neutravidin to allow universal binding with biotinylated *** virtue of their reliable and selective detection of target cancer cells,these NPs have demonstrated their promising usefulness in conventional fl ow ***,they have shown low background signal,high signal enhancement,and effi cient functionalization,either with antibody-or aptamer-targeting moieties.

关键词： Silica nanoparticle flow cytometry aptamer cell detection polyethylene glycol fl uorophore

Addiction Research Update 2009

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Addiction Research Update 2009

Total tumor RNA pulsed dendritic cells plus adoptive transfer of ex-vivo enriched autologous T-lymphocytes in the treatment of children with primary brain tumors

自主创新与持续增长第十一届中国科协年会

作者： Mark S.GOLD Lisa J.MERLO Department of psychiatry McKnight Brain Institute University of Florida

Dr. Gold has worked in this field since the early 1970s. Since that time, the United States’ leading causes of death are still related to alcohol and drug use, tobacco smoke exposure, and behavioral addictions. Each year, more than 400,000 Americans die as a result of smoking, overeating, substance use, and related accidents and suicide. There are notable advances in the treatment of addiction disorders. Animal models have improved and research is currently ongoing with addicted rats. In addition, advances in neurobiology and imaging, proteomics, nanotechnology, pharmacology, and behavioral research have impacted the addiction field. Several components of the neurological reward system (eg, the nucleus accumbens, the ventral tegmental area, and the neurotransmitters (particularly dopamine)) have been implicated in addiction. Similarly, morphine, cannabis, nicotine, and ethanol administration result in increased dopamine release in the nucleus accumbens. In addition, the brain’s endogenous opioid and cannabinoid systems, within the pathway connecting the ventral tegmental area and the nucleus accumbens, are activated by several drugs of abuse. Increased glutamate release in the pathway connecting the prelimbic cortex to the accumbens is associated with drug- seeking behavior. Research findings indicate that individual differences in sensitivity to substances of abuse may be affected by developmental factors such as when the person begins using drugs and dosage. Developmental neurobiology, genetic factors and early environmental factors, all appear critical. Several pharmacological interventions for the treatment of addiction and the prevention of relapse target these systems and their receptors. Findings from recent studies indicate that drug effects are long-lasting and recovery is slow and difficult. Drug dependence appears to be related to changes and dysregulation of the reward system and stress system. Many persons with substance abuse actually choose to change

关键词： dopamine stress behavioral addictions drug addiction neurobiology proteomics genomics

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Neuroimmunology and Neuroinflammation 2018年第10期5卷 28-42页

作者： Sridharan Gururangan Elias Sayour Duane A. Mitchell Department of Neurosurgery Preston A. Wells Center for Brain Tumor Therapy McKnight Brain Institute Gainesville FL 32608 USA

The therapeutic approach of adoptive lymphocyte transfer (ALT) using lymphocytes primed and expanded ex-vivo by exposure to total tumor RNA (ttRNA) containing dendritic cells (DCs) and administered after lymphodepletive host conditioning in patients with refractory melanoma with brain metastases has shown excellent objective responses indicating that the central nervous system (CNS) is not an immune privileged site and further paved the way for utilization of a similar approach in other cancers. We have shown that the use of ALT + ttRNA DCs following either myeloablative or non-myeloablative host conditioning is feasible and safe and appears to prolong survival in a proportion of children with recurrent medulloblastoma who had failed standard cytotoxic therapy. Further refinements in this promising approach are needed to improve outcomes and extend this treatment to a broad range of CNS malignancies.

关键词： Children brain tumors immunotherapy adoptive lymphocyte transfer dendritic cell vaccine lymphodepletion total tumor RNA

New record of the feather star Palaeocomatella hiwia(Echinodermata:Crinoidea:Comatulida)from Zhenbei Seamount in South China Sea:new insights into the taxonomic position of Palaeocomatella

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Journal of Oceanology and Limnology 2024年第1期42卷 244-251页

作者： Shao’e SUN Zijie MEI Zhongli SHA Jing WANG Nansheng CHEN Department of Marine Organism Taxonomy and Phylogeny Institute of OceanologyChinese Academy of SciencesQingdao 266071China CAS Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdao 266071China Laoshan Laboratory Qingdao 266237China Shandong Province Key Laboratory of Experimental Marine Biology Institute of OceanologyChinese Academy of SciencesQingdao 266071China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China University of Chinese Academy of Sciences Beijing 100049China

One specimen belonging to the family Comatellinae was collected from the Zhenbei Seamount(332.5–478.2 m)in the South China Sea in July *** on the morphological characters,the specimen was identified as Palaeocomatella hiwia mcknight,*** is first recorded from China Sea and redescribed in *** specimen differs from the original description from New Zealand for never showing syzygy at br4+5 or br5+6 on interior and br1+2 on exterior ***,it is much conform to the redescription to specimens from Indonesia,with only differences in position of the second syzygy and distalmost pinnule *** is deposited in the institute of Oceanology,Chinese Academy of *** analyses based on the mitochondrial c oxidase subunit I(COI)and 16S rRNA genes indicated that *** was nested within the tribe Phanogeniini and clustered with Aphanocomaster ***,*** showed same morphological features in terms of mouth placement,comb location,and number of comb teeth rows as other genera of ***,we suggest that the genus Palaeocomatella should be put in the tribe Phanogeniini.

关键词： new record Palaeocomatella hiwia mcknight 1977 South China Sea phylogenetic relationship taxonomy

Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy

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Science China Chemistry 2018年第4期61卷 497-504页

作者： Jin Li Liping Qiu Sitao Xie Jing Zhang Liqin Zhang Honglin Liu Juan Li Xiaobing Zhang Weihong Tan Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of Life SciencesAptamer Engineering Center of Hunan ProvinceHunan University Center for Research at Bio/Nano Interface Department of Chemistry and Department of Physiology and Functional GenomicsHealth Cancer CenterUF Genetics Institute and McKnight Brain InstituteUniversity of Florida key Laboratory for Analytical Science of Food Safety and Biology (Ministry of Education) College of ChemistryFuzhou University

Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411,and a replaceable anti-biomarker probe(ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS 1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.

关键词： aptamer drug delivery personalized medicine antisense oligonucleotides

Nature can still be the strongest help against aging and neurodegeneration:the sirtuins way

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Neural Regeneration Research 2023年第6期18卷 1271-1272页

作者： David Della-Morte Francesca Pacifici Department of Systems Medicine University of Rome“Tor Vergata”RomeItaly Department of Human Sciences and Quality of Life Promotion San Raffaele Roma Open UniversityIRCCS San Raffaele RomaRomeItaly Department of Neurology and Evelyn F.mcknight brain institute Miller School of MedicineUniversity of MiamiMiamiFLUSA

Unfortunately,ag ing is not a reversible phenomenon and the processes of senescence are ***,the biological effects of aging may be turned back,and with those,it can be reduced risk of all age-related illnesses,such as cardiovascular diseases,cancer,diabetes,and neurodegenerative diseases,including Alzheimer’s disease(AD),and Parkinson’s diseases(PD).In the latest decades,scientists worldwide therefore have developed several strategies,either natural or pharmacological,to counteract aging phenomena,with the final goal to improve human life *** main scientific rationale beyond these strategies focuses on the opportunity to reduce chronic low-grade inflammation(inflammaging),the increase in oxidative stress damage,and the impairment in the immune system,all typical mechanisms of senescence(Verdaguer et al.,2012).

关键词： diseases aging inflammation