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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

Neural Regeneration research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner Department of Molecular Biosciences University of Texas at AustinAustinTXUSA Department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China national Clinical research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering research Center of Stem Cells Translational Medicine ShanghaiChina national Center for healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research Center of Digital healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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The role of nuclear receptors in regulation of Th 17/Treg biology and its implications for diseases

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Cellular & Molecular Immunology 2015年第5期12卷 533-542页

作者： Benjamin V. Park Fan Pan Immunology and Hematopoiesis Division Department of Oncology Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School ofMedicine Baltimore MD 21287 USA

Nuclear receptors in the cell play essential roles in environmental sensing, differentiation, development, homeostasis, and metabolism and are thus highly conserved across multiple species. The anti-inflammatory role of nuclear receptors in immune cells has recently gained recognition. Nuclear receptors play critical roles in both myeloid and lymphoid cells, particularly in helper CD4＋ T-cell type 17 （Th17） and regulatory T cells （Treg）. Th17 and Treg are closely related cell fates that are determined by orchestrated cytokine signaling. Recent studies have emphasized the interactions between nuclear receptors and the known cytokine signals and how such interaction affects Th 17/Treg development and function. This review will focus on the most recent discoveries concerning the roles of nuclear receptors in the context of therapeutic applications in autoimmune diseases.

关键词： nuclear receptors regulation

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ZBTB7A governs estrogen receptor alpha expression in breast cancer

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Journal of Molecular Cell Biology 2018年第4期10卷 273-284页

作者： Mary Ellen Molloy Monika Lewinska Amanda K. Williamson Thanh Thao Nguyen Gamze Kuser-Abali Lu Gong Jiawei Yan John B. Little Pier Paolo Pandolfi Zhi-Min Yuan Department of Environmental health John B. Little Center for Radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02215 USA Biotech research and Innovation Centre Department of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Cancer Genetics Program Beth Israel Deaconess Cancer Center Departments of Medicine and Pathology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 USA

ZBTB7A, a member of the POZ/BTB and Krüppel （POK） family of transcription factors, has been shown to have a context-dependent role in cancer development and progression. The role of ZBTB7A in estrogen receptor alpha （ERα）-positive breast cancer is largely unknown. Approximately 70% of breast cancers are classified as ERα-positive. ERα carries out the biological effects of estrogen and its expression level dictates response to endocrine therapies and prognosis for breast cancer patients. In this study, we find that ZBTB7A transcriptionally regulates ERα expression in ERα-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ERα. Inhibition of ZBTB7A in ERα-positive cells results in decreased estrogen responsiveness as demonstrated by diminished estrogen-response element-driven luciferase reporter activity, induction of estrogen target genes, and estrogen-stimulated growth. We also report that ERα potentiates ZBTB7A expression via a post-translational mechanism, suggesting the presence of a positive feedback loop between ZBTB7A and ERα, conferring sensitivity to estrogen in breast cancer. Clinically, we find that ZBTB7A and ERα are often co-expressed in breast cancers and that high ZBTB7A expression correlates with improved overall and relapse-free survival for breast cancer patients. Importantly, high ZBTB7A expression predicts a more favorable outcome for patients treated with endocrine therapies. Together, these findings demonstrate that ZBTB7A contributes to the transcriptional program maintaining ERα expression and potentially an endocrine therapy-responsive phenotype in breast cancer.

关键词： ZBTB7A ERα breast cancer endocrine therapies

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Insights into CYP2B6-mediated drug–drug interactions

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Acta Pharmaceutica Sinica B 2016年第5期6卷 413-425页

作者： William D.Hedrich Hazem E.Hassan Hongbing Wang Department of Pharmaceutical Sciences University of Maryland School of Pharmacy

Mounting evidence demonstrates that CYP2B6 plays a much larger role in human drug metabolism than was previously *** discovery of multiple important substrates of CYP2B6 as well as polymorphic differences has sparked increasing interest in the genetic and xenobiotic factors contributing to the expression and function of the *** expression of CYP2B6 is regulated primarily by the xenobiotic receptors constitutive androstane receptor(CAR) and pregnane X receptor(PXR) in the *** addition to CYP2B6,these receptors also mediate the inductive expression of CYP3A4,and a number of important phase II enzymes and drug ***2B6 has been demonstrated to play a role in the metabolism of 2%–10% of clinically used drugs including widely used antineoplastic agents cyclophosphamide and ifosfamide,anesthetics propofol and ketamine,synthetic opioids pethidine and methadone,and the antiretrovirals nevirapine and efavirenz,among *** inter-individual variability in the expression and function of the human CYP2B6 gene exists and can result in altered clinical outcomes in patients receiving treatment with CYP2B6-substrate *** variances arise from a number of sources including genetic polymorphism,and xenobiotic *** this review,we will provide an overview of the key players in CYP2B6 expression and function and highlight recent advances made in assessing clinical ramifications of important CYP2B6-mediated drug–drug interactions.

关键词： CYP2B6 CAR PXR Polymorphism Drug–drug interaction Cyclophosphamide Efavirenz

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Vitamin D,calcium homeostasis and aging

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Bone research 2016年第3期4卷 133-139页

作者： Vaishali Veldurthy Ran Wei Leyla Oz Puneet Dhawan Yong Heui Jeon Sylvia Christakos Department of Microbiology Biochemistry and Molecular GeneticsRutgersThe State University of New JerseyNew Jersey Medical School

Osteoporosis is characterized by low bone mass and microarchitecture deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Evidence is accumulating for an important role of calcium deficiency as the process of aging is associated with disturbed calcium balance. Vitamin D is the principal factor that maintains calcium homeostasis. Increasing evidence indicates that the reason for disturbed calcium balance with age is inadequate vitamin D levels in the elderly. In this article, an overview of our current understanding of vitamin D, its metabolism, and mechanisms involved in vitamin D-mediated maintenance of calcium homeostasis is presented. In addition, mechanisms involved in age-related dysregulation of 1,25（OH）2D3 action, recommended daily doses of vitamin D and calcium, and the use of vitamin D analogs for the treatment of osteoporosis （which remains controversial） are reviewed. Elucidation of the molecular pathways of vitamin D action and modifications that occur with aging will be an active area of future research that has the potential to reveal new therapeutic strategies to maintain calcium balance.

关键词： BMD VDR Vitamin D,calcium homeostasis and aging

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A silent two-photon imaging system for studying in vivo auditory neuronal functions

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Light(Science & Applications) 2022年第5期11卷 888-900页

作者： Xindong Song Yueqi Guo Chenggang Chen Xiaoqin Wang Laboratory of Auditory Neurophysiology Department of Biomedical EngineeringJohns Hopkins University School of MedicineBaltimoreMD 21205USA

Two-photon laser-scanning microscopy has become an essential tool for imaging neuronal functions in vivo and has been applied to different parts of the neural system,including the auditory ***,many components of a two-photon microscope,such as galvanometer-based laser scanners,generate mechanical vibrations and thus acoustic artifacts,making it difficult to interpret auditory responses from recorded ***,we report the development of a silent two-photon imaging system and its applications in the common marmoset(Callithrix Jacchus),a non-human primate species sharing a similar hearing range with *** utilizing an orthogonal pair of acoustooptical deflectors(AODs),full-frame raster scanning at video rate was achieved without introducing mechanical *** depth can be optically controlled by adjusting the chirping speed on the AODs without any mechanical motion along the ***,all other sound-generating components of the system were acoustically isolated,leaving the noise floor of the working system below the marmoset’s hearing *** with the system in awake marmosets revealed many auditory cortex neurons that exhibited maximal responses at low sound levels,which were not possible to study using traditional two-photon imaging *** is the first demonstration of a silent two-photon imaging system that is capable of imaging auditory neuronal functions in vivo without acoustic *** capacity opens new opportunities for a better understanding of auditory functions in the brain and helps isolate animal behavior from microscope-generated acoustic interference.

关键词： system utilizing generating

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AXL receptor signalling suppresses p53 in melanoma through stabilization of the MDMX-MDM2 complex

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Journal of Molecular Cell Biology 2017年第2期9卷 154-165页

作者： Anna de Polo Zhongling Luot Casimiro Gerarduzzi Xiang Chen John B. Little Zhi-Min Yuan John B. Little Center for Radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02115 USA Department of Dermatology Xiangya Hospital Central South University Changsha 410008 China

Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the sta- biUty of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpres- sion or activation through growth arrest-specific 6 （Gas6） Ugand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity. Upon activation, AXL stabilizes MDMX through a post-translational modification that involves phosphoryl- ation of MDMX on the phosphosite Ser314, leading to increased affinity between MDMX and MDM2 and favouring MDMX nuclear translocation. Ser314 phosphorylation can also protect MDMX from MDM2-mediated degradation, leading to stabilization of the MDMX-MDM2 complex. We identified CDK4/6 and p38 MAPK as the two kinases mediating AXL-induced modulation of the MDMX-MDM2 complex, and demonstrated that suppression of AXL, either through siRNA silencing or pharmacological inhibition, increases expression levels of p53 target genes P21, MDM2, and PUMA, improves p53 pathway response to chemotherapy, and sensitizes cells to both Cisplatin and Vemurafenib. Our findings offer an insight into a novel signalling axis linking AXL to p53 and provide a potentially druggable pathway to restore p53 function in melanoma.

关键词： MDMX MDM2 AXL CDK4/6 p53 melanoma

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Can soil microbial diversity influence plant metabolites and life history traits of a rhizophagous insect？ A demonstration in oilseed rape

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Insect Science 2017年第6期24卷 1045-1056页

作者： Tom Lachaise Morgane Ourry Lionel Lebreton Anne-Yvonne Guillerm-Erckelboudt Juliette Linglin Chrystelle Paty Valerie Chaminade Nathalie Marnet Julie Aubert Denis Poinsot Anne-Marie Cortesero Christophe Mougel IGEPP Agrocampus Ouest INRA Universite de Rennes 1 Le Rheu France IGEPP Agrocampus Ouest INRA Universite de Rennes 1 Universite Bretagne-Loire Rennes France INRA UR1268 BIA-Le Rheu France INRA-AgroParisTech UMR 518 Applied Mathematics and Computer Sciences-Paris France

Interactions between plants and phytophagous insects play an important part in shaping the biochemical composition of plants. Reciprocally plant metabolites can influ- ence major life history traits in these insects and largely contribute to their fitness. Plant rhizospheric microorganisms are an important biotic factor modulating plant metabolites and adaptation to stress. While plant-insects or plant-microorganisms interactions and their consequences on the plant metabolite signature are well-documented, the impact of soil microbial communities on plant defenses against phytophagous insects remains poorly known. In this study, we used oilseed rape （Brassica napus） and the cabbage root fly （Delia radicum） as biological models to tackle this question. Even though D. radicum is a belowground herbivore as a larva, its adult life history traits depend on aboveground signals. We therefore tested whether soil microbial diversity influenced emergence rate and fitness but also fly oviposition behavior, and tried to link possible effects to modifications in leaf and root metabolites. Through a removal-recolonization experiment, 3 soil microbial modalities （＂high,＂＂medium,＂＂low＂） were established and assessed through amplicon sequencing of 16S and 18S ribosomal RNA genes. The ＂medium＂ modality in the rhizosphere significantly improved insect development traits. Plant-microorganism interactions were marginally associated to modulations of root metabolites profiles, which could partly explain these results. We highlighted the potential role of plant-microbial interaction in plant defenses against Delia radicum. Rhizospheric microbial communities must be taken into account when analyzing plant defenses against herbivores, being either below or aboveground.

关键词： Brassica napus Delia radicum life history traits plant primary and secondary metabolites rhizophagous pest soil microbial diversity

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