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Does mesenchymal stem cell’s secretome affect spinal sensory circuits?Implication for pain therapies

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Neural Regeneration Research 2025年第1期20卷 181-183页

作者： Francesco Ferrini Esri h.Juárez Adalberto Merighi department of Veterinary Sciences University of TurinGrugliascoTOItaly department of Psychiatry and neuroscience UniversitéLavalQuébec CityQCCanada

Mesenchymal stem cells(MSCs)are multipotent adult stem cells of mesodermal origin that can be isolated from various tissues,including bone marrow,tooth pulp,adipose tissue,and umbilical *** have gained significant attention in regenerative medicine due to their ability to modulate the immune system and favor tissue *** enrich the medium in which they are cultivated with a broad range of bioactive molecules,including growth factors,cytokines,chemokines,enzymes,nucleic acids,and extracellular vesicles that collectively compose the MSC *** increasing number of pre-clinical studies suggest that delivering in vivo an MSC-conditioned medium(i.e.,the medium collected from MSC cultures after at least 3 days of exposure)exerts neuroprotective and anti-inflammatory effects in a variety of neurological conditions.

关键词： protective clinical collective

Locus coeruleus-norepinephrine: basic functions and insights into Parkinson’s disease

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Neural Regeneration Research 2020年第6期15卷 1006-1013页

作者： Bilal Abdul Bari Varun Chokshi Katharina Schmidt The solomon h.snyder department of neuroscience Brain Science InstituteKavli Neuroscience Discovery InstituteThe Johns Hopkins University School of MedicineBaltimoreMDUSA department of Physiology The Johns Hopkins University School of MedicineBaltimoreMDUSA

The locus coeruleus is a pontine nucleus that produces much of the brain's *** its small size,the locus coeruleus is critical for a myriad of functions and is involved in many neurodegenerative and neuropsychiatric *** this review,we discuss the physiology and anatomy of the locus coeruleus system and focus on norepinephrine's role in synaptic *** highlight Parkinson's disease as a disorder with motor and neuropsychiatric symptoms that may be understood as aberrations in the normal functions of locus coeruleus.

关键词： catecholamines copper neurodegenerative diseases neuromodulation neuronal circuits neuropsychiatric symptoms noradrenaline synaptic plasticity

Signaling pathways that regulate axon regeneration

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neuroscience Bulletin 2013年第4期29卷 411-420页

作者： Saijilafu Bo-Yin Zhang Feng-Quan Zhou department of Orthopaedic Surgery The Johns Hopkins University department of The solomon h. snyder department of neuroscience The Johns Hopkins University

Neurons in the mammalian central nervous system （CNS） cannot regenerate axons after injury. In contrast, neurons in the mammalian peripheral nervous system and in some non-mammalian models, such as C. elegans and Drosophila, are able to regrow axons. Understanding the molecular mechanisms by which these neurons support axon regeneration will help us find ways to enhance mammalian CNS axon regeneration. here, recent studies in which signaling pathways regulating naturally-occurring axon regeneration that have been identified are reviewed, focusing on how these pathways control gene expression and growth-cone function during axon regeneration.

关键词： axon regeneration axonal growth signal transduction

Sialylation of TLR2 initiates osteoclast fusion

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Bone Research 2022年第2期10卷 286-296页

作者： Ce Dou Gehua Zhen Yang Dan Mei Wan Nathachit Limjunyawong Xu Cao department of Orthopedic Surgery Institute of Cell Engineering and Department of Biomedical EngineeringJohns Hopkins University School of MedicineBaltimoreMDUSA The solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMDUSA

The molecular control of osteoclast formation is still not clearly elucidated. here, we show that a process of cell recognition mediated by Siglec15-TLR2 binding is indispensable and occurs prior to cell fusion in RANKL-mediated osteoclastogenesis. Siglec15 has been shown to regulate osteoclastic bone resorption. however, the receptor for Siglec15 has not been identified, and the signaling mechanism involving Siglec15 in osteoclast function remains unclear. We found that Siglec15 bound sialylated TLR2 as its receptor and that the binding of sialylated TLR2 to Siglec15 in macrophages committed to the osteoclast-lineage initiated cell fusion for osteoclast formation, in which sialic acid was transferred by the sialyltransferase ST3 Gal1. Interestingly, the expression of Siglec15 in macrophages was activated by M-CSF, whereas ST3 Gal1 expression was induced by RANKL. Both Siglec15-specific deletion in macrophages and intrafemoral injection of sialidase abrogated cell recognition and reduced subsequent cell fusion for the formation of osteoclasts, resulting in increased bone formation in mice. Thus, our results reveal that cell recognition mediated by the binding of sialylated TLR2 to Siglec15 initiates cell fusion for osteoclast formation.

关键词： osteoclast TLR2 injection

heterologous expression of bovine lactoferrin C‑lobe in Bacillus subtilis and comparison of its antibacterial activity with N‑lobe

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Systems Microbiology and Biomanufacturing 2022年第2期2卷 345-354页

作者： Liang Jin Lihong Li Wenchi Zhang Rongzhen Zhang Yan Xu The Key Laboratory of Industrial Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMD 21205USA

The natural concentration of bovine lactoferrin C-lobe is low and its separation by proteolytic enzyme digestion is ***,we expressed the codon-optimized fragment of C-lobe on plasmid pMA0911 with the P_(veg) promoter in Bacillus subtilis 168 at 20℃.The yield was 7.5 mg/L,and 90.6%purity was achieved using ammonium sulfate precipitation,Ni–NTA and molecular *** C-lobe at 10 mg/mL completely inhibited cell growth of Escherichia coli JM109(DE3)and Pseudomonas aeruginosa CGMCC 1.6740,and 48.4%of growth of Staphylococcus aureus CGMCC 1.282,the result is similar to that of 200 ng/mL *** minimum inhibitory concentrations of C-lobe were 4,8 and 16 mg/mL,while those of N-lobe were 128,256 and 512μg/mL for ***,*** and ***,*** is the frst report on bovine lactoferrin C-lobe expression and the comparative resistance of the recombinant N-and C-lobes in a food-safe strain of *** fndings ofer the potential to study the structure–function relationship of the N-and C-lobes recombinantly produced in the same host.

关键词： Bovine lactoferrin C-lobe Bacillus subtilis Expression and purifcation Codon optimization Antibacterial activity Comparative resistance

Transcription Factor MAFA Regulates Mechanical Sensation by Modulating Piezo2 Expression

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neuroscience Bulletin 2022年第8期38卷 933-937页

作者： Chang-ming Wang Dustin P.Green Xinzhong Dong The solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMD21205USA department of neuroscience Cell Biologyand AnatomyUniversity of Texas Medical BranchGalvestonTXUSA solomon h.snyder department of neuroscience Johns Hopkins University School of MedicineBaltimoreMD21205USA department of Dermatology Johns Hopkins University School of MedicineBaltimoreMD21205USA department of Neurosurgery Johns Hopkins University School of MedicineBaltimoreMD21205USA howard hughes Medical Institute Chevy ChaseMDUSA

Dear Editor,Essential for survival,mechanical sensation is detected and transmited to the spinal cord by primary sensory afferents and their cell bodies located in the dorsal root ganglia(DRG).Multiple types of mechanically sensitive DRG neurons have been identified that mediate various mechanosensation modalities(***-painful versus painful).

关键词： sensation modalities Essential

Local manipulation of the growth cone cytoskeleton:new strategies to promote axon regeneration

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Neural Regeneration Research 2015年第12期10卷 1959-1960页

作者： Zi-wei huang Feng-quan Zhou Saijilafu department of Orthopedics the First Affiliated HospitalOrthopedic InstituteSoochow University department of Orthopedic Surgery and the solomon h.snyder department of neuroscience the Johns Hopkins University School of Medicine

Thousands of spinal cord injuries occur worldwide as a result of traumatic or non-traumatic *** cord injury usually results in axonal damage,leading to permanent functional deficits and ***,axonal regeneration is the ... 详细信息

关键词： CSPG OMgp CNS

Peripheral mechanisms of itch

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neuroscience Bulletin 2012年第2期28卷 100-110页

作者： Benjamin McNeil Xinzhong Dong The solomon h. snyder department of neuroscience Center for Sensory Biology howard hughes Medical Institute Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA

Detection of environmental stimuli that provoke an aversive response has been shown to involve many receptors in the periphery. Probably the least-studied of these stimuli are those that induce the perception of itch （pruritus）, an often-experienced unpleasant stimulus. This review covers the ligands and their receptors which are known to cause primary sensory neuron activation and initiate itch sensation. Also covered are several itch-inducing substances which may act indirectly by activating other cell types in the periphery which then signal to primary neurons. Finally, progress in identifying candidate neurotransmitters that sensory neurons use to propagate the itch signal is discussed.

关键词： itch primary sensory neurons receptors

Closed-loop control of epileptiform activities in a neural population model using a proportional-derivative controller

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Chinese Physics B 2015年第3期24卷 434-441页

作者：王俊松王美丽李小俚 Ernst Niebur School of Biomedical Engineering Tianjin Medical University Zanvyl Krieger Mind/Brain Institute and solomon snyder department of neuroscience Johns Hopkins University National Key Laboratory of Cognitive neuroscience and Learning Beijing Normal University

Epilepsy is believed to be caused by a lack of balance between excitation and inhibitation in the brain. A promising strategy for the control of the disease is closed-loop brain stimulation. how to determine the stimulation control parameters for effective and safe treatment protocols remains, however, an unsolved question. To constrain the complex dynamics of the biological brain, we use a neural population model（NPM）. We propose that a proportional-derivative（PD） type closed-loop control can successfully suppress epileptiform activities. First, we determine the stability of root loci, which reveals that the dynamical mechanism underlying epilepsy in the NPM is the loss of homeostatic control caused by the lack of balance between excitation and inhibition. Then, we design a PD type closed-loop controller to stabilize the unstable NPM such that the homeostatic equilibriums are maintained; we show that epileptiform activities are successfully suppressed. A graphical approach is employed to determine the stabilizing region of the PD controller in the parameter space, providing a theoretical guideline for the selection of the PD control parameters. Furthermore, we establish the relationship between the control parameters and the model parameters in the form of stabilizing regions to help understand the mechanism of suppressing epileptiform activities in the NPM. Simulations show that the PD-type closed-loop control strategy can effectively suppress epileptiform activities in the NPM.

关键词： neural population model epileptiform activities proportional-derivative controller stabilizing region