1.Regulatory mechanisms of the corticospinal tract after spinal cord injury:combined therapeutic strategies targeting transcription factors and signaling pathways
Zhenjie GUAN ; Wenyuan LI ; Rui GENG ; Ying WANG
Chinese Journal of Tissue Engineering Research 2025;29(24):5158-5170
BACKGROUND:Current strategies for the treatment of the corticospinal tract after spinal cord injury mainly focus on exercise rehabilitation,drug therapy,transcranial magnetoelectric stimulation,endogenous regulation such as transcription factors and specific signaling pathways.Among them,transcription factors and their specific signaling pathways are the key factors regulating the axonal regeneration of corticospinal tract after spinal cord injury.A large number of preclinical studies have confirmed that the synergy between transcription factors and their signaling pathways has a significant regulatory effect on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.Therefore,it has broad application prospects to explore new combination therapy strategies targeting transcription factors and specific signaling pathways for spinal cord injury.OBJECTIVE:To systematically summarize the regulatory effects of transcription factors and their signaling pathways on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury and the underlying molecular mechanisms,and explore the application of combined therapy strategies targeting transcription factors and signaling pathways in the neuroplasticity of the corticospinal tract after spinal cord injury,in order to provide a new combination strategy for the treatment of spinal cord injury.METHODS:The search terms included"spinal cord injury,axon regeneration,transcription factors,signaling pathway,corticospinal tract,central nervous system,synergistic system,neuroprotective system"in Chinese and English.A literature retrieval was conducted in WanFang,Web of Science,and PubMed for relevant literature published from database inception to September 2024.Finally,101 articles were included for analysis and summary.RESULTS AND CONCLUSION:(1)The article outlines the biological properties and intervention strategies for axonal regeneration of the corticospinal tract after spinal cord injury,analyses the reasons for focusing on the corticospinal tract after spinal cord injury,and elucidates the response and possibility of regeneration of the corticospinal tract after spinal cord injury.(2)In this study,the combined regulatory strategy of transcription factors centered on Krüppel-like factor 6,Krüppel-like factor 7,and neuronal restriction silencing factor can significantly promote the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.(3)The phosphatidylinositol 3-kinase-protein kinase B-rapamycin target protein signaling pathway and Wnt5a pathway are the classical signaling pathways fortranscription factors to regulate the axonal regeneration of corticospinal tract neurons,and the combined treatment strategy can effectively promote the axonal regeneration and functional reconstruction of corticospinal tract neurons after spinal cord injury.(4)This article discusses the combined treatment strategies of transcription factors and specific signaling pathways in a comprehensive and detailed manner,such as Krüppel-like factor 6 combined with signal transducer and activator of transcription 3,Krüppel-like factor 7 combined with SOX11 transcription factor,combined inhibition of phosphatase and tensin homologs and neuronal restriction silencing factor,etc.,to exert a synergistic effect and promote the axonal regeneration of corticospinal tract neurons after spinal cord injury,which are significantly better than those of single treatment.It can effectively improve functional recovery and provide a reference scheme for the future treatment of axonal regeneration of corticospinal tract neurons after spinal cord injury.However,the specific mechanism of the combination therapy still needs to be further studied,and the current combination strategy is only widely used in animal models but not in clinical practice.(5)The combined therapy strategy based on transcription factors and specific signaling pathways has a significant therapeutic effect on the axonal regeneration of corticospinal tract neurons after spinal cord injury,and it is necessary to further explore the molecular mechanism of joint regulation in the future,in order to provide an effective combined therapy strategy for the rehabilitation and functional reconstruction of spinal cord injury.
2.Regulatory mechanisms of the corticospinal tract after spinal cord injury:combined therapeutic strategies targeting transcription factors and signaling pathways
Zhenjie GUAN ; Wenyuan LI ; Rui GENG ; Ying WANG
Chinese Journal of Tissue Engineering Research 2025;29(24):5158-5170
BACKGROUND:Current strategies for the treatment of the corticospinal tract after spinal cord injury mainly focus on exercise rehabilitation,drug therapy,transcranial magnetoelectric stimulation,endogenous regulation such as transcription factors and specific signaling pathways.Among them,transcription factors and their specific signaling pathways are the key factors regulating the axonal regeneration of corticospinal tract after spinal cord injury.A large number of preclinical studies have confirmed that the synergy between transcription factors and their signaling pathways has a significant regulatory effect on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.Therefore,it has broad application prospects to explore new combination therapy strategies targeting transcription factors and specific signaling pathways for spinal cord injury.OBJECTIVE:To systematically summarize the regulatory effects of transcription factors and their signaling pathways on the axonal regeneration of neurons in the corticospinal tract after spinal cord injury and the underlying molecular mechanisms,and explore the application of combined therapy strategies targeting transcription factors and signaling pathways in the neuroplasticity of the corticospinal tract after spinal cord injury,in order to provide a new combination strategy for the treatment of spinal cord injury.METHODS:The search terms included"spinal cord injury,axon regeneration,transcription factors,signaling pathway,corticospinal tract,central nervous system,synergistic system,neuroprotective system"in Chinese and English.A literature retrieval was conducted in WanFang,Web of Science,and PubMed for relevant literature published from database inception to September 2024.Finally,101 articles were included for analysis and summary.RESULTS AND CONCLUSION:(1)The article outlines the biological properties and intervention strategies for axonal regeneration of the corticospinal tract after spinal cord injury,analyses the reasons for focusing on the corticospinal tract after spinal cord injury,and elucidates the response and possibility of regeneration of the corticospinal tract after spinal cord injury.(2)In this study,the combined regulatory strategy of transcription factors centered on Krüppel-like factor 6,Krüppel-like factor 7,and neuronal restriction silencing factor can significantly promote the axonal regeneration of neurons in the corticospinal tract after spinal cord injury.(3)The phosphatidylinositol 3-kinase-protein kinase B-rapamycin target protein signaling pathway and Wnt5a pathway are the classical signaling pathways fortranscription factors to regulate the axonal regeneration of corticospinal tract neurons,and the combined treatment strategy can effectively promote the axonal regeneration and functional reconstruction of corticospinal tract neurons after spinal cord injury.(4)This article discusses the combined treatment strategies of transcription factors and specific signaling pathways in a comprehensive and detailed manner,such as Krüppel-like factor 6 combined with signal transducer and activator of transcription 3,Krüppel-like factor 7 combined with SOX11 transcription factor,combined inhibition of phosphatase and tensin homologs and neuronal restriction silencing factor,etc.,to exert a synergistic effect and promote the axonal regeneration of corticospinal tract neurons after spinal cord injury,which are significantly better than those of single treatment.It can effectively improve functional recovery and provide a reference scheme for the future treatment of axonal regeneration of corticospinal tract neurons after spinal cord injury.However,the specific mechanism of the combination therapy still needs to be further studied,and the current combination strategy is only widely used in animal models but not in clinical practice.(5)The combined therapy strategy based on transcription factors and specific signaling pathways has a significant therapeutic effect on the axonal regeneration of corticospinal tract neurons after spinal cord injury,and it is necessary to further explore the molecular mechanism of joint regulation in the future,in order to provide an effective combined therapy strategy for the rehabilitation and functional reconstruction of spinal cord injury.
3.Mechanism of the immediate analgesic effect of the"three methods and three points"tuina technique based on the IL-17F/IL-17RC signaling pathway and M1 microglia
Jinping CHEN ; Zhifeng LIU ; Tianyuan YU ; Hourong WANG ; Yingqi ZHANG ; Qian GUAN ; Yajing XU ; Zhenjie YANG ; Chula SA ; Runlong ZHANG ; Hanyu ZHANG ; Jiayue LIU ; Jiawei SUN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(1):116-123
Objective By observing the effects of"three methods and three points"tuina technique on the expression of interleukin-17F(IL-17F),interleukin-17 receptor C(IL-17RC),activator 1 of nuclear transcription factor-κB(Act1),tumour necrosis factor receptor-associated factor 6(TRAF6)and M1 microglial cell expression in the spinal dorsal horn of rats with mild chronic compressive injury(minor CCI)model,we explored the immediate analgesic mechanism of tuina on peripheral neuropathic pain(pNP).Methods Thirty-six SD rats were divided into the sham group,the model group and the tuina group according to the random number method,twelve rats in each group,and the minor CCI model was replicated by ligating the right sciatic nerve.The rats in the tuina group were subjected to pointing,plucking and kneading at the BL37,BL57 and GB34 points on the affected side using a tuina simulator,while the sham group and the model group were only grasped and restrained,and were intervened for one time.The mechanical pain test and cold plate test were used to evaluate the response of rats to mechanical stimulation and cold stimulation after immediate intervention.The protein expression of IL-17F and TRAF6 in the spinal dorsal horn of rats in each group was detected by Western blotting.The mRNA expression of IL-17F,IL-17RC,Act1 and TRAF6 in the spinal dorsal horn of rats in each group was detected by real-time PCR.The average fluorescence intensity of M1 microglia in the spinal dorsal horn of rats in each group was detected by immunofluorescence.Results Behavioral results showed that before intervention,compared with the sham group,paw mechanical withdraw threshold(PMWT)decreased and cold sensitivity threshold(CST)increased in the model group and the tuina group;after tuina intervention,PMWT in the tuina group was increased,and CST was decreased compared with the model group;after intervention,PMWT in the tuina group was increased,while CST was decreased(P<0.05).RT-PCR results showed that compared with the sham group,mRNA expression levels of IL-17F,IL-17RC,TRAF6 and Act1 in the spinal dorsal horn of the model group were increased;compared with model group,the mRNA expression levels of above indexes in the tuina group were decreased(P<0.05).Western boltting results showed that compared with the sham group,the expression levels of IL-17F and TRAF6 protein in the spinal dorsal horn of the model group were increased;compared with the model group,the expression levels of IL-17F and TRAF6 protein in the tuina group decreased(P<O.05).Immunofluorescence results showed that the mean fluorescence intensity of CD40 in the spinal dorsal horn of model group was enhanced compared with the sham group;compared with the model group,the mean fluorescence intensity of CD40 in the tuina group was decreased(P<0.05).Conclusion The"three methods and three points"tuina technique can produce immediate analgesia by inhibiting the expression of IL-17F,IL-17RC,Act1,TRAF6 and the activation of M1 microglia in the dorsal horn of the spinal cord after one intervention.
4.Expression and significance of Bone Morphogenetic Protein 2 and phosphatase and tensin homolog deleted on chromosome ten in incipient, recurrent and malignant salivary gland pleomorphic adenoma
Guan′e LI ; Xinhao FAN ; Haiyang LI ; Zhenjie DAI ; Jinyuan LI
Clinical Medicine of China 2019;35(4):306-311
Objective To investigate the expression and significance of bone morphogenetic protein?2 (BMP?2) and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in incipient,recurrent and malignant salivary gland pleomorphic adenoma??Methods A total of 93 cases of salivary gland pleomorphic adenoma in Kailuan general hospital from 2008 to 2017 were collected,including 54 in incipient group (group A,47 cases in benign group A1,7 cases in malignant group A2),39 cases in recurrent group (group B,26 cases in benign group B1,13 cases in malignant group B2)??The expression of BMP?2 and PTEN were detected by immunohistochemical detection and western blot,the correlation of BMP?2 and PTEN was analyzed by Spearman analysis??Results The immunohistochemical and western blot analysis both showed expression of BMP?2 in recurrent group was significantly higher than that in incipient cases((129??03 ±15??52) vs??(87??88±18??11),t=-8??094,P=0??000),and it was lower in malignant cases than that in benign cases(( 100??24 ± 25??07) vs ( 116??66 ± 26??19), t=2??125, P=0??040)??There was no significant difference in PTEN expression between incipient and recurrent groups (( 89??15 ± 13??92 ) vs??( 96??19 ±28??02),t=1??055,P=0??279),but lower PTEN expression was found in malignant cases than benign cases ((76??06±11??16) vs??(109??28±17??05),t=7??543,P=0??000)??BMP?2 was positively correlated with PTEN expression (r=0??313,P<0??05)??Conclusion BMP?2 is associated with the recurrence of salivary gland pleomorphic adenoma, and both BMP?2 and PTEN are associated with malignant in the salivary gland pleomorphic adenoma??
5.Technical specification for clinical application of critical ultrasonography
Wanhong YIN ; Xiaoting WANG ; Dawei LIU ; Yangong CHAO ; Xiangdong GUAN ; Yan KANG ; Jing YAN ; Xiaochun MA ; Yaoqing TANG ; Zhenjie HU ; Kaijiang YU ; Dechang CHEN ; Yuhang AI ; Lina ZHANG ; Hongmin ZHANG ; Jun WU ; Lixia LIU ; Ran ZHU ; Wei HE ; Qing ZHANG ; Xin DING ; Li LI ; Yi LI ; Haitao LIU ; Qinbing ZENG ; Xiang SI ; Huan CHEN ; Junwei ZHANG ; Qianghong XU ; Wenjin CHEN ; Xiukai CHEN ; Daozheng HUANG ; Shuhan CAI ; Xiuling SHANG ; Jian GUAN ; Juan DU ; Li ZHAO ; Minjia WANG ; Song CUI ; Xiaomeng WANG ; Ran ZHOU ; Xueying ZENG ; Yiping WANG ; Liwen LYU ; Weihua ZHU ; Ying ZHU ; Jun DUAN ; Jing YANG ; Hao YANG ; Chinese Critical Ultrasound Study Group ; Gritical Hemodynamic Therapy Collabration Group
Chinese Journal of Internal Medicine 2018;57(6):397-417
Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.
6.Effects of 3 desensitizers on bond strength of luting agents.
Lei CHEN ; Fei XU ; Zhenjie GUAN
Journal of Central South University(Medical Sciences) 2014;39(2):185-189
OBJECTIVE:
To explore the effect of Hybrid Coat, Prime & Bond NT, and anti-sensitivity toothpaste on the bond strength of glass ionomer cement (GIC), polycarboxylat cement (PCC), resin cement (RC), and to provide reference for clinical operations.
METHODS:
A total of 96 isolated human premolar samples, which were prepared to expose dentine, were randomly divided into a GIC group, a PCC group, and an RC group. Each group was divided into 4 subgroups according different desensitizers: a control subgroup, a Hybrid Coat subgroup, a Prime & Bond NT subgroup, and an anti-sensitivity toothpaste subgroup (n=8 in each subgroup). After using Hybrid Coat, Prime & Bond NT, and anti-sensitivity toothpaste in the corresponding groups, the castings of cobalt-chromium alloy were bonded to dentine surfaces by GIC, PCC, and RC. All the dentinesurfaces were treated with selected desensitizers. Specimens were tested by a universal testing machine to obtain the shear bond strength of each specimen, and the data of the shear bond strength was analyzed by one-way analysis of variance.
RESULTS:
The shear bond strength of GIC significantly was increased in the Hybrid Coat subgroups compared with that in the control subgroups, the Prime & Bond NT subgroups, and the antisensitivity toothpaste subgroups (P<0.05); the shear bond strength of PCC significantly reduced in the Prime & Bond NT subgroups compared with that in the control subgroups, and the antisensitivity toothpaste subgroups(P<0.05); the shear bond strength of RC was obviously enhanced in the anti-sensitivity toothpaste subgroups compared with that in a control subgroup, a Hybrid Coat subgroup, a Prime & Bond NT subgroup (P<0.05).
CONCLUSION
When GIC is adopted as adhesive agent, we shoud choose Hybrid Coat; if PCC is chosen, the Prime & Bond NT should be avoided; if RC is chosen to adhere crown, the antisensitivity toothpaste is applicable. Among the selected luting agents, GIC has the lowest shear bond strength while RC has the highest.
Bicuspid
;
Dental Bonding
;
Dental Cements
;
Dentin
;
Glass Ionomer Cements
;
Humans
;
Materials Testing
;
Polymethacrylic Acids
;
Resin Cements
;
Shear Strength
7.Comparison of the occlusion effect of three kinds of desensitizers on dentinal tubules.
Lei CHEN ; Fei XU ; Zhenjie GUAN ; Weidan ZHANG ; Xiaojuan WANG
Journal of Central South University(Medical Sciences) 2014;39(9):959-963
OBJECTIVE:
To explore the effects of three dentine desensitizers on the surface morphology of freshly exposed dentin and to evaluate their occlusion effects on dentinal tubules using scanning electron microscope (SEM).
METHODS:
A total of 16 isolated human premolar samples, which were prepared to expose dentine, were randomly divided into a control group (n=4), a Hybrid Coat group (n=4), a Prime & Bond NT group (n=4), and a anti-sensitivity toothpaste group (n=4). After treatment with dentine desensitizers, one half of the samples in each group were vertically cleaved. Finally, the surfaces and cross sections of the samples were observed by SEM.
RESULTS:
The exposed tubule was almost occluded in the Hybrid Coat group and the Prime & Bond NT group, while only the majority of tubules could be sealed in the anti-sensitivity toothpaste group. The cross-section images showed that sediments were visible in all groups except the control group.
CONCLUSION
Hybrid Coat and Prime & Bond NT are able to effectively seal tubules, while the effect of anti-sensitivity toothpaste is slightly poor.
Dentin
;
ultrastructure
;
Dentin Desensitizing Agents
;
pharmacology
;
Dentin Permeability
;
drug effects
;
Humans
;
Microscopy, Electron, Scanning
;
Polymethacrylic Acids
;
pharmacology
;
Toothpastes
;
pharmacology

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