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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang zhihui huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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Microglia Interact with Neurons by Forming Somatic Junctions

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Neuroscience Bulletin 2020年第9期36卷 1085-1088页

作者： Yongjie Wang zhihui huang Key Laboratory of Elemene Anti-Cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes Hangzhou Normal UniversityHangzhou 311121China Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province and Holistic Integrative Pharmacy Institutes Hangzhou Normal UniversityHangzhou 311121China Department of Neurosurgery The Affiliated Hospital of Hangzhou Normal UniversityHangzhou 310015China

Microglia are the main immune cells of the central nervous system that maintain normal neuronal *** cells are also linked with major diseases in humans including neurodegenerative disorders such as Alzheimer’ s disease,stroke,epilepsy,and psychiatric diseases such as schizophrenia [1].Microglia perform surveillance of the brain microenvironment through their motile processes.

关键词： epilepsy diseases functions.

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A Specific Peptide Vaccine Against IDH1(R132H) Glioma

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Neuroscience Bulletin 2022年第2期38卷 223-225页

作者： Yuqian huang Yongjie Wang zhihui huang College of Pharmacy Department of NeurosurgeryThe Affiliated HospitalHangzhou Normal UniversityHangzhou 311121ZhejiangChina Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou 311121ZhejiangChina

Malignant tumors of the central nervous system(CNS)have the poorest prognosis among the *** are the most commonly occurring tumors of the CNS[1],accounting for almost 30%of all primary brain tumors and 80%of all malignant brain tumors[2].In 2016,the World Health Organization(WHO)assigned gliomas into four grades(I-IV)based on molecular parameters and light microscopic features[3];WHO grade I is the least malignant while grade IV is the *** cells are believed to be derived from neuroglial stem or progenitor cells,and are characterized by active growth,strong invasion and rapid *** on morphological similarities to the neuroglial cell types found in the normal brain,gliomas are histologically classified into astrocytomas,oligodendrogliomas,mixed oligoastrocytic gliomas,and ependymomas.

关键词： IDH1 invasion Glioma

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Reversion of Injured Adult Neurons to an Embryonic State by Grafts of Neural Progenitor Cells After Spinal Cord Injury

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Neuroscience Bulletin 2021年第2期37卷 271-274页

作者： Liying Cao Yongjie Wang zhihui huang Laboratory of Aging and Cancer Biology of Zhejiang Province School of MedicineHangzhou Normal UniversityHangzhou 311121China Department of Neurosurgery of Affiliated Hospital and Holistic Integrative Pharmacy InstitutesHangzhou Normal UniversityHangzhou 311121China

Spinal cord injury(SCI)is a severe condition characterized by neurological dysfunction,dependence,respiratory failure,psychological morbidities,and an increased mortality rate[1].Globally,its incidence ranges from 250... 详细信息

关键词： Spinal mortality respiratory

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Targeting PTB as a One-Step Procedure for In Situ Astrocyte-to-Dopamine Neuron Reprogramming in Parkinson's Disease

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Neuroscience Bulletin 2021年第3期37卷 430-432页

作者： Yuanyuan Jiang Yongjie Wang zhihui huang Department of Neurosurgery of The Affiliated Hospital Holistic Integrative Pharmacy InstitutesHangzhou Normal UniversityHangzhou 311121China Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province Hangzhou Normal UniversityHangzhou 311121China

Parkinson disease(PD)is a progressive neurodegenerative disease characterized by the loss of dopamine neurons in the substantia nigra,resulting in striatal dopamine deficiency,hence eventually severe disability[1].Research carried out across the>200-year history of PD has led to important discoveries[2].Among them,efforts have been made to repair or promote regeneration using drugs,neurotrophic factors,cell-based disease modification。

关键词： dopamine drugs Neuron

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Loss of C9orf72 in Microglia Drives Neuronal Injury by Enhancing Synaptic Pruning in Aged and Alzheimer’s Disease Mice

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Neuroscience Bulletin 2022年第3期38卷 327-330页

作者： Mengmeng Wang Yuanyuan Jiang zhihui huang School of Pharmacy Hangzhou Normal UniversityHangzhou311121China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou311121China

Many diseases are caused by the expansion of simple sequence repeats scattered throughout the human genome;they are defined as repeat expansion *** size of the repeat unit ranges from trinucleotides(the vast majority)to tetranucleotides,pentanucleotides,hexan cleotides,and even dodecanucleotides[1].Expansions of the hexanucleotide GGGGCC in the C9orf72 gene are the most frequent genetic cause of amyotrophic lateral sclero・sis(ALS)and frontotemporal dementia(FTD)[2].In addition to ALS and FTD,C9orf72 repeat expansions may also be associated with Alzheimer's disease(AD),since the rate of such expansions in AD cases(0.57%)is higher than normal(0.11%)[3].However,the exact role of C9orf72 in AD is still unclear.

关键词： C9orf72 Alzheimer diseases

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Neuronal Mechanisms Govern Glioblastoma Cell Invasion

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Neuroscience Bulletin 2023年第6期39卷 1027-1030页

作者： Xiaowu Lin zhihui huang Yongjie Wang School of Pharmacy Hangzhou Normal UniversityHangzhou311121China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Hangzhou Normal UniversityHangzhou311121China Engineering Laboratory of Development and Application of Traditional Chinese Medicines Hangzhou Normal UniversityHangzhou311121China Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province Hangzhou Normal UniversityHangzhou311121China

Glioblastoma(GBM)remains one of the most aggressive malignancies;it is characterized by genetic heterogeneity and resistance to *** main reason is that GBM cells(GBCs)communicate with other cells in the brain environm... 详细信息

关键词： Glioblastoma treatment. communicate

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An attention-based deep learning model for citywide traffic flow forecasting

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International Journal of Digital Earth 2022年第1期15卷 323-344页

作者： Tao Zhou Bo huang Rongrong Li Xiaoqian Liu zhihui huang Department of Surveying and Geoinformatics Faculty of Geosciences and Environmental EngineeringSouthwest Jiaotong University (SWJTU)ChengduPeople’s Republic of China Department of Geography and Resource Management The Chinese University of Hong KongHong KongPeople’s Republic of China Institute of Space and Earth Information Science The Chinese University of Hong KongHong KongPeople’s Republic of China

Prompt and accurate traffic flow forecasting is a key foundation of urban traffic ***,the flows in different areas and feature channels(inflow/outflow)may correspond to different degrees of importance in forecasting *** forecasting models inadequately consider this heterogeneity,resulting in decreased predictive *** overcome this problem,an attention-based hybrid spatiotemporal residual model assisted by spatial and channel information is proposed in this *** assigning different weights(attention levels)to different regions,the spatial attention module selects relatively important locations from all inputs in the modeling ***,the channel attention module selects relatively important channels from the multichannel feature map in the modeling process by assigning different *** proposed model provides effective selection and attention results for key areas and channels,respectively,during the forecasting process,thereby decreasing the computational overhead and increasing the *** the case involving Beijing,the proposed model exhibits a 3.7%lower prediction error,and its runtime is 60.9%less the model without attention,indicating that the spatial and channel attention modules are instrumental in increasing the forecasting ***,in the case involving Shanghai,the proposed model outperforms other models in terms of generalizability and practicality.

关键词： Attention mechanism long short-term memory model residual network spatiotemporal forecasting traffic flow

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An Empathic Pain-Regulated Neural Circuit

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Neuroscience Bulletin 2022年第12期38卷 1613-1616页

作者： Xiumin Xue Qian Wang zhihui huang Yongjie Wang School of Pharmacy Hangzhou Normal UniversityHangzhou 311121China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou 311121China

Empathy is a general term in psychology that refers to the correct understanding of the feelings and emotions of others,so as to achieve mutual understanding,care,and *** behavior is common in rodents[1],and various e... 详细信息

关键词： mutual harmony happiness

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Reprogramming Restores Vision in Mice by Changing DNA Methylation

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Neuroscience Bulletin 2021年第10期37卷 1526-1528页

作者： Jiali Shi Shanshan Sun Yongjie Wang zhihui huang College of Pharmacy School of Medicineand Department of NeurosurgeryThe Affiliated HospitalHangzhou Normal UniversityHangzhou 311121China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou 311121China

Cell reprogramming is the process of reverting mature,specialized cells into induced pluripotent stem *** also refers to the erasure and re-establishment of epigenetic markers during the development of mammalian germ cells,such as DNA methylation[1].At present,reprogramming mainly refers to two processes:the process of reverting differentiated cells to a pluripotent state,and the process of transforming one type of differentiated cell into another[2].Reprogramming mainly includes induced pluripotent stem(iPS)cells,direct transdifferentiation,and indirect lineage conversion.

关键词： programming differentiated specialized

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