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TRIP13:A promising cancer immunotherapy target

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Cancer Innovation 2024年第6期3卷 1-10页

作者： Shengnan jing Liya Zhao Liwen Zhao yong‐jing gao Tianzhen He Institute of Pain Medicine and Special Environmental Medicine Co‐innovation Center of NeuroregenerationNantong UniversityNantongJiangsuChina

The tumor microenvironment(TME)facilitates tumor development through intricate intercellular signaling,thereby supporting tumor growth and suppressing the immune *** hormone receptor interactor 13(TRIP13),an AAA+ATPase,modulates the conformation of client macromolecules,consequently influencing cellular signaling ***13 has been implicated in processes such as proliferation,invasion,migration,and metastasis during tumor *** studies have revealed that TRIP13 also plays a role in immune response suppression within the ***,inhibiting these functions of TRIP13 could potentially enhance immune responses and improve the efficacy of immune checkpoint *** review summarizes the recent research progress of TRIP13 and discusses the potential of targeting TRIP13 to improve immune‐based therapies for patients with cancer.

关键词： immune responses immune‐based therapies thyroid hormone receptor interactor 13 tumor microenvironment

Astrocytes in Chronic Pain:Cellular and Molecular Mechanisms

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Neuroscience Bulletin 2023年第3期39卷 425-439页

作者： Huan-Jun Lu yong-jing gao Institute of Pain Medicine and Special Environmental Medicine Co-innovation Center of NeuroregenerationNantong UniversityNantong 226019China

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of *** are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions,including chronic *** regulate nociceptive synaptic transmission and network function via neuron–glia and glia–glia interactions to exaggerate pain signals under chronic pain *** is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic ***,this review presents our current understanding of the roles of astrocytes in chronic pain,how they regulate nociceptive responses,and their cellular and molecular mechanisms of action.

关键词： Astrocyte Microglia Neuron-glia interaction Spinal cord Chronic pain

CCL2/CCR2 Contributes to the Altered Excitatory-inhibitory Synaptic Balance in the Nucleus Accumbens Shell Following Peripheral Nerve Injury-induced Neuropathic Pain

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Neuroscience Bulletin 2021年第7期37卷 921-933页

作者： Xiao-Bo Wu Qian Zhu yong-jing gao Institute of Pain Medicine and Special Environmental Medicine Nantong UniversityNantong 226019China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226001China

The medium spiny neurons(MSNs)in the nucleus accumbens(NAc)integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior *** we report that the relative intensity of excitatory and inhibitory synaptic inputs to MSNs of the NAc shell was decreased in mice with neuropathic pain induced by spinal nerve ligation(SNL).SNL increased the frequency,but not the amplitude of spontaneous inhibitory postsynaptic currents(sIPSCs),and decreased both the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs)in the *** also decreased the paired-pulse ratio(PPR)of evoked IPSCs but increased the PPR of evoked ***,acute bath application of C–C motif chemokine ligand 2(CCL2)increased the frequency and amplitude of sIPSCs and sEPSCs in the MSNs,and especially strengthened the amplitude of N-methyl-D-aspartate receptor(NMDAR)-mediated miniature *** Ccl2 overexpression in the NAc in vivo decreased the peak amplitude of the sEPSC/sIPSC ***,Ccr2 knock-down improved the impaired induction of NMDAR-dependent long-term depression(LTD)in the NAc after *** results suggest that CCL2/CCR2 signaling plays a role in the integration of excitatory/inhibitory synaptic transmission and leads to an increase of the LTD induction threshold at the synapses of MSNs during neuropathic pain.

关键词： E/I balance Synaptic transmission LTD CCL2 CCR2 Nucleus accumbens Neuropathic pain

Emerging role of Toll-like receptors in the control of pain and itch

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Neuroscience Bulletin 2012年第2期28卷 131-144页

作者： Tong Liu yong-jing gao Ru-Rong Ji Sensory Plasticity Laboratory Pain Research CenterDepartment of AnesthesiologyPerioperative and Pain MedicineBrigham and Women's Hospital and Harvard Medical SchoolBostonMassachusetts 02115USA Institute of Nautical Medicine Nantong UniversityNantong 226001China

Toll-like receptors （TLRs） are germline-encoded pattern-recognition receptors that initiate innate immune re- sponses by recognizing molecular structures shared by a wide range of pathogens, known as pathogen-associated molecular patterns （PAMPs）. After tissue injury or cellular stress, TLRs also detect endogenous ligands known as danger-associated molecular patterns （DAMPs）. TLRs are expressed in both non-neuronal and neuronal cell types in the central nervous system （CNS） and contribute to both infectious and non-infectious disorders in the CNS. Following tissue insult and nerve injury, TLRs （such as TLR2, TLR3, and TLR4） induce the activation of microglia and astrocytes and the production of the proinflammatory cytokines in the spinal cord, leading to the development and maintenance of inflammatory pain and neu- ropathic pain. In particular, primary sensory neurons, such as nociceptors, express TLRs （e.g., TLR4 and TLR7） to sense exogenous PAMPs and endogenous DAMPs released after tissue injury and cellular stress. These neuronal TLRs are new players in the processing of pain and itch by increasing the excitability of primary sensory neurons. Given the prevalence of chronic pain and itch and the suffering of affected people, insights into TLR signaling in the nervous system will open a new avenue for the management of clinical pain and itch.

关键词： astrocytes microglia Toll-like receptor pain itch danger-associated molecular patterns pathogen-associatedmolecular patterns

Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice

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Neuroscience Bulletin 2018年第1期34卷 54-63页

作者： Peng-Bo jing De-Li Cao Si-Si Li Meixuan Zhu Xue-Qiang Bai Xiao-Bo Wu yong-jing gao Pain Research Laboratory Institute of Nautical MedicineJiangsu Key Laboratory of Neuroregeneration Nantong University Co-innovation Center of Neuroregeneration Nantong University

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund＇s adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water （AEW）. Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch （alloknesis） after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

关键词： Chronic itch Alloknesis Dry skin CXCR3 CXCL10 - Spinal cord

Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion

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Neuroscience Bulletin 2019年第4期35卷 613-623页

作者： Xiao-Bo Wu Li-Na He Bao-Chun Jiang Xue Wang Ying Lu yong-jing gao Institute of Pain Medicine Institute of Special Environmental Medicine Nantong University Nantong 226019 China Department of Nutrition and Food Hygiene School of Public Health Nantong University Nantong 226019 China Co-innovation Center of Neuroregeneration Nantong University Nantong 226001 China

Pain consists of sensory-discriminative and emotional-affective *** anterior cingulate cortex(ACC)is a critical brain area in mediating the affective ***,the molecular mechanisms involved remain largely *** recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains ***,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after *** of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance ***,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic ***,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous ***-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by ***,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.

关键词： CXCL13 CXCR5 Anterior cingulate cortex Neuropathic pain Conditioned place aversion Synaptic transmission

CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice

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Neuroscience Bulletin 2021年第3期37卷 339-352页

作者： Yan-Fang Kong Wei-Lin Sha Xiao-Bo Wu Lin-Xia Zhao Ling-Jie Ma yong-jing gao Institute of Pain Medicine Institute of Nautical MedicineNantong UniversityNantong 226019China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China

Chemokines and receptors have been implicated in the pathogenesis of chronic ***,we report that spinal nerve ligation(SNL)increased CXCR3 expression in dorsal root ganglion(DRG)neurons,and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat *** also increased the m RNA levels of CXCL9,CXCL10,and CXCL11,whereas only CXCL10 increased the number of action potentials(APs)in DRG ***,in Cxcr3^(-/-)mice,CXCL10 did not increase the number of APs,and the SNL-induced increase of the numbers of APs in DRG neurons was ***,CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG *** of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by *** data indicate that CXCR3,activated by CXCL10,mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability,which contributes to the maintenance of neuropathic pain.

关键词： CXCR3 CXCL10 DRG Neuropathic pain Mice

A Cauchy integral formula for(p,q)-monogenic functions withα-weight

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Applied Mathematics(A Journal of Chinese Universities) 2024年第3期39卷 545-553页

作者： gao Long DU Xiao-jing LIU Yue XIE yong-hong School of Mathematical Sciences Hebei Normal UniversityShijiazhuang 050024China

Firstly,some properties for(p,q)-monogenic functions withα-weight in Clifford analysis are ***,the Cauchy-Pompeiu formula is ***,the Cauchy integral formula and the Cauchy integral theorem for(p,q)-monogenic function... 详细信息

关键词： (p q)-monogenic functions with-weight Cauchy-Pompeiu formula Cauchy integral formula Cauchy integral theorem

Auxin-brassinosteroid crosstalk:Regulating rice plant architecture and grain shape

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The Crop Journal 2024年第4期12卷 953-963页

作者： Meidi Wu jing Zhou Qian Li Dunfan Quan Qingwen Wang yong gao Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genetics and Physiology Yangzhou UniversityYangzhou 225009JiangsuChina Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of EducationYangzhou UniversityYangzhou 225009JiangsuChina

Rice(Oryza sativa)plant architecture and grain shape,which determine grain quality and yield,are modulatedby auxin and brassinosteroid via regulation of cell elongation and *** review the signaltransduction of these h... 详细信息

关键词： Auxin Brassinosteroid Auxin-brassinosteroid crosstalk Plant architecture Grain shape