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Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao Hui Yang Ying Mao Department of neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer therapy.This pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal cells.Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical studies.However,to date,the clinical success of drugs targeting the innate immune pathway remains limited.Interestingly,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression.The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation.In this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell types.We propose that within the TME,the innate immune pathway exhibits multidimensional diversity.This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks.The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways.Refining our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

Metabolic regulation of innate immunity in cancer immunotherapy

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Cancer Biology & Medicine 2023年第12期20卷 898-902页

作者： Yuheng Liao Hui Yang Department of neurosurgery Huashan HospitalShanghai Key Laboratory of Medical EpigeneticsInternational Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesInstitute for Translational Brain ResearchShanghai Medical College of Fudan UniversityShanghai 200032China Shanghai Key laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200032China State Key laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghai 200032China

Innate immunity,originally recognized as the primary defense mechanism against pathogenic infections,has also been shown to have an important role in anti-tumor immunity.Host cells recognize cytosolic DNA and RNA,which triggers a cascade of signaling events via nucleic-acid sensing receptors,including endosomal Toll-like receptors(TLRs),cytoplasmic cyclic GMP-AMP synthase(cGAS)for double-stranded DNA sensing,and cytoplasmic retinoic acid-inducible gene I(RIG-I)for double-stranded RNA detection.

关键词： immunity immunotherapy Metabolic

SARS-CoV-2 infection and the antiviral innate immune response

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Journal of molecular Cell Biology 2020年第12期12卷 963-967页

作者： Hui Yang Yingying Lyu Fajian Hou Department of neurosurgery Huashan HospitalInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceShanghai Medical CollegeFudan UniversityShanghai 200032China State Key laboratory of molecular Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Shanghai Key laboratory of Brain Function Restoration and Neural Regeneration Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200032China

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)outbreak be-gan in December 2019,causing the illness known as the novel coronavirus disease 2019(COVID-19).The virus spread rapidly worldwide to become a global public health emergency.As of November 15,2020,more than 53 million confirmed cases and over 1 million deaths worldwide have been reported(World Health Organization,2020).

关键词： acute respiratory infection

Omics-based integrated analysis identified ATRX as a biomarker associated with glioma diagnosis and prognosis

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Cancer Biology & Medicine 2019年第4期16卷 784-796页

作者： Yingbin Xie Yanli Tan Chao Yang Xuehao Zhang Can Xu Xiaoxia Qiao Jianglong Xu Shaohui Tian Chuan Fang Chunsheng Kang Department of neurosurgery Affiliated Hospital of Hebei UniversityBaoding 071000China Department of neurosurgery Hebei University Medical CollegeBaoding 071000China Department of Pathology Hebei University Medical CollegeBaoding 071000China Department of Pathology Affiliated Hospital of Hebei UniversityBaoding 071000China lab of Neuro-oncology Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemTianjin Medical University General HospitalTianji n 300052China Department of Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou 510095China

Objective:ATRX is a multifunctional protein that is tightly regulated by and implicated in transcriptional regulation and chromatin remodeling.Numerous studies have shown that genetic alterations in ATRX play a significant role in gliomas.This study aims to further determine the relationship between ATRX and glioma prognosis and identify possible mechanisms for exploring the biological significance of ATRX using large data sets.Methods:We used The Cancer Genome Atlas(TCGA)database and 130 immunohistochemical results to confirm the difference in ATRX mutations in high-and low-grade gliomas.An online analysis of the TCGA glioma datasets using the cBioPortal platform was performed to study the relationship between ATRX mutations and IDH1,TP53,CDKN2 A and CDKN2 B mutations in the corresponding TCGA glioma dataset.In combination with clinical pathology data,the biological significance of the relationships were analyzed.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses and annotations of all adjacent genes in the network were performedin the Database for Annotation,Visualization and Integrated Discovery(DAVID)and R language.A protein-protein interaction(PPI)network was constructed,and the interactions of all adjacent nodes were analyzed by the String database and using Cytoscape software.Results:In the selected TCGA glioma datasets,a total of 2,228 patients were queried,21%of whom had ATRX alterations,which co-occurred frequently with TP53 and IDH1 mutations.ATRX alterations are associated with multiple critical molecular events,which results in a significantly improved overall survival(OS)rate.In low-grade gliomas,ATRX mutations are significantly associated with multiple important molecular events,such as ZNF274 and FDXR at mRNA and protein levels.A functional cluster analysis revealed that these genes played a role in chromatin binding and P53,and a link was observed between ATRX and IDH1 and TP53 in the interaction network.ATRX and TP53 are important nodes in the network and have pot

关键词： ATRX mutation copy number variation glioma biomarkers

Local hypothermia and optimal temperature for stroke therapy in rats

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Chinese Medical Journal 2009年第13期122卷 1558-1563页

作者： WU Hao JIANG Li-dan Karsten H. Wrede JI Xun-ming ZHAO Xi-qing TIAN Xin GAO Yu-fei LING Feng Department of neurosurgery Xuan Wu Hospital Capital Medical University Beijing 100053 China Departement of neurosurgery International Neuroscience Institute Rudolf Pichlmayr Str. 4 30625 Hannover Germany Department of neurosurgery the People Hospital of Tangshan Tangshan Hebei 063000 China Central lab Xuan Wu Hospital Capital Medical University Beijing 100053 China Department of neurosurgery China-Japan Union Hospital Ji Lin University Changchun Jilin 130033 China

Background Local hypothermia induced by intravascular infusion of cold saline solution effectively reduces brain damage in stroke. We further determined the optimal temperature of local hypothermia in our study. Methods Seventy-eight adult male Sprague Dawley rats （260-300 g） were randomly divided into 3 groups： group A, ischemia/reperfusion without cold saline infusion （n=26）（control group）; group B, infusion with 20℃ saline before reperfusion （n=26）; group C： infusion with 10℃ saline before reperfusion （n=26）. In each group, we chose 15 rats for monitoring physical indexes and the temperature of the brain （cortex and striatum） and body （anus）, measurement of brain infarction volume, assessment of neurological deficits and the survival rate of reperfusion at 48 hours. Another 8 rats from each group was chosen for examining brain edema, another 3 from each group for histological observation by electron microscopy （EM） and light microscopy （LM） at 48 hours after reperfusion. Results There was no significant difference among the 3 groups for physical indexes during the examination （F（2. 45）= 0.577, P=0.568; F（2.45）= 0.42, P=0.78 for blood pressure and blood gas analysis, respectively）. The brain temperature was significantly reduced in the group C compared to the other groups （F（2.45）=37.074, P=0.000; F（2.45）=32.983, P=0.000, for cortex and striatum temperature respectively）, while the difference in rectal temperature between group A and B or C after reperfusion was not significant （F（2.45）= 0.17115,P=0.637）. And the brain infarct volume was significantly reduced in group C （from 40%±10% in group A, 26%±8% in group B, to 12%±6% in group C, F（2.45）=43.465, P=0.000） with the neurological deficits improving in group C （Х^2=27.626, P=0.000）. The survival rate at 48 hours after 10℃ and 20℃ saline reperfusion was increased by 132.5% and 150%, respectively, as compared to the control group （Х^2=10.489, P=0.005）. The extent of the brain edema showed no significant difference （F（2.21）=0.547, P=0.587） after cold saline infu

关键词： rat middle cerebral artery occlusion intra-arterial hyperthermia ischemia/reperfusion injury

Multiple olfactory pathways contribute to the lure process of Caenorhabditis elegans by pathogenic bacteria

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Science China(Life Sciences) 2021年第8期64卷 1346-1354页

作者： Man Zhu Yao Chen Ninghui Zhao Hua Bai Keqin Zhang Xiaowei Huang State Key lab for Conservation and Utilization of Bio-Resources and College of Life ScienceYunnan UniversityKunming 650091China neurosurgery of the Second Hospital Affiliated with Kunming Medical University Kunming 650101China College of Public Health Kunming Medical UniversityKunming 650500China

Chemosensation is indispensable for the survival of Caenorhabditis elegans to discriminate food and pathogenic bacteria in their living environment. Food-like odors emitted by the pathogen Bacillus nematocida B16 for trapping its hosts and an olfactory signaling pathway responsible to sense the attractant 2-heptanone were identified in our previous study. Here, we further explore how the worms recognize the attractive molecules indole and 2-ethyl hexanol, which have different chemical properties and modest nematode-luring ability. We show that the chemotaxis toward indole and 2-ethyl hexanol requires the G protein-coupled receptors encoded by str-193 on AWC and str-7 on AWA. In a further genetic screen for downstream effectors in olfactory signaling cascades, the Gα subunit GSA-1, guanylyl cyclase ODR-1 and DAF-11 and the c GMP-gated channel TAX-2/TAX-4 were found to be necessary for indole sensation, whereas the TRPV channels OSM-9/OCR-2 and the PLC pathway activated by GPA-6 are responsible for the detection of 2-ethyl hexanol. Altogether, our current work further clarifies the distinct olfactory signaling pathways through which C. elegans senses different chemicals and is lured by B. nematocida B16, improving our comprehensive understanding of the mechanisms by which bacterial pathogens effectively infect their hosts.

关键词： attractive trapping process

All optical artificial synapses based on long-afterglow material for optical neural network

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Nano Research 2023年第7期16卷 10004-10010页

作者： Wenjie Lu Qizhen Chen Huaan Zeng Hui Wang Lujian Liu Tailiang Guo Huipeng Chen Rui Wang Institute of Optoelectronic Display National&Local United Engineering Lab of Flat Panel Display TechnologyFuzhou UniversityFuzhou 350002China Department of neurosurgery Fujian Medical University Union HospitalFuzhou 350001China Fujian Science&Technology Innovation laboratory for Optoelectronic Information of China Fuzhou 350100China

Artificial neural network with broad application prospect has attracted particular attention due to the promise of solving the memory wall bottleneck.The neural devices that mix light and electricity provide more degrees of freedom for the design of artificial neural network,but they still do not get rid of the shackles that the response signal needs circuit to transmission.The exploration of all-optical neural devices(optical signal input and output)is expected to solve this problem.Here,an all-optical synaptic device simply based on a long-afterglow material is reported.The optical properties of the all-optical synaptic device are similar to the responses in biological synapses.Unique image displays and memory functions can be achieved by combining alloptical synaptic arrays with synaptic memory behavior.Furthermore,the optical summation of all-optical synaptic array pixels can be completed by combining the focusing characteristics of convex lens,which realizes the photon transmission after preprocessing multiple input signals.Particularly,the simple single-layer structure of all-optical synapses with polydimethylsiloxane(PDMS)as the carrier has high plasticity and is expected to achieve large-scale preparation.This work enriches the diversity of artificial synapses and shows the huge development potential of photoelectric artificial neural networks.

关键词： synaptic plasticity all optical optical computation optical neural network

SrTiO_(3)-CaCr_(0.5)Nb_(0.5)O_(3) solid solutions as p-type photocatalysts for Z-scheme water splitting under visible light illumination

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Journal of Materials Science & Technology 2021年第28期87卷 46-53页

作者： Zeming Gu Qi Wang Xiaoqin Sun Lingwei Lu Yuwei Zhang Ran Wang Shu Jin Yinlin Shao Jun Qian Xiaoxiang Xu Clinical and Central lab Putuo People’s HospitalDepartment of NeurosurgeryTongji HospitalTongji University School of MedicineShanghai Key Lab of Chemical Assessment and SustainabilitySchool of Chemical Science and EngineeringTongji UniversityShanghaiChina State Key laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou310027China

P-type semiconductivity has been observed in solid solution series(SrTiO_(3))_(1-x)(CaCr_(0.5)Nb_(0.5)O_(3))x(0.0≤x≤0.15),which all adopt cubic symmetry and own intense absorption in the visible light region.These solid solutions are superior H2 evolution photocatalysts under visible light illumination(λ≥400 nm).An AQE as high as 1.02%at 420±20 nm has been achieved at optimal composition(SrTiO_(3))_(0.85)(CaCr_(0.5)Nb_(0.5)O_(3))0.15 which significantly surpasses the parent compounds.Stoichiometric H_(2)/O_(2) production under visible light illumination has been successfully realized using Z-scheme system containing(SrTiO_(3))_(0.85)(CaCr_(0.5) Nb_(0.5) O_(3))_(0.15),WO_(3) and I^(-)/IO_(3)^(-)redox couple.

关键词： p-Type semiconductor Photocatalyst Z-scheme Water splitting Solid solution

Regenerative medicine focus on brain and nerve repair

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Regenerative medicine focus on brain and nerve repair