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Biomimetic chitosan scaffolds with long-term controlled release of nerve growth factor repairs 20-mm-long sciatic nerve defects in rats

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Neural Regeneration Research 2022年第5期17卷 1146-1155页

作者： Fa-Dong Liu Hong-Mei Duan Fei Hao Wen Zhao Yu-Dan Gao Peng Hao Zhao-Yang Yang Xiao-Guang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology Capital Medical UniversityBeijingChina Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration Beijing Advanced Innovation Center for Biomedical EngineeringBeihang UniversityBeijingChina

Although autogenous nerve transplantation is the gold standard for treating peripheral nerve defects of considerable length,it still has some shortcomings,such as insufficient donors and secondary *** chitosan scaffolds loaded with controlled release of nerve growth factor can promote neuronal survival and axonal regeneration after short-segment sciatic nerve ***,the effects on extended nerve defects remain poorly *** this study,we used chitosan scaffolds loaded with nerve growth factor for 8 weeks to repair long-segment(20 mm)sciatic nerve defects in adult *** results showed that treatment markedly promoted the recovery of motor and sensory *** regenerated sciatic nerve not only reconnected with neurons but neural circuits with the central nervous system were also *** addition,the regenerated sciatic nerve reconnected the motor endplate with the target ***,this novel biomimetic scaffold can promote the regeneration of extended sciatic nerve defects and reconstruct functional *** provides a promising method for the clinical treatment of extended peripheral nerve *** study was approved by the Animal Ethics Committee of Capital Medical University,China(approval ***-2017-033)on March 21,2017.

关键词： axon chitosan functional recovery myelin sheath nerve growth factor peripheral nerve injury pseudorabies virus regeneration scaffold sciatic nerve

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Effects of Qingre Huoxue Jiedu Formula on nerve growth factor-Induced Psoriasis

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Chinese Journal of Integrative Medicine 2022年第3期28卷 236-242页

作者： WANG Jun-hui JIANG Ying-juan LI Min WANG Ning CUI Bing-nan LIU Wa-li Dermatology Department Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijing(100053)China Dermatology Department Dongfang HospitalBeijing University of Chinese MedicineBeijing(100078)China Laboratory of Molecular Biology Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijing(100053)China

Objective:To elucidate the mechanisms of 4 effective components from a Chinese medicine formula,namely Qingre Huoxue Jiedu Formula(QHJ heat-and toxin-clearing and blood-activating formula),in the treatment of nerve growth factor(NGF)-induced ***:Keratinocyte proliferation and T cell proliferation models were developed using *** NGF solution(NGF+DMEM,100 ng/mL)was added to all induced groups and treated groups and were cultured for 24 h,while a solution with NTRK1 antagonist(K252 a+DEME,300 nmol/L)was added and cultured for 1 *** models were used to evaluate the effects of the treatment with each of the 4 components of QHJ,namely shikonin,paeonol,astilbin and ursolic *** apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay,*** mRNA expression levels of Bax,Bcl-xl,and NGF receptor(NGFR)were assessed by quantitative real-time PCR(qRT-PCR)and Western blot analysis,***:(1)All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups(P<0.05).In addition,treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only(P<0.05),particularly in cells treated with ursolic acid.(2)QHJ-treated groups showed higher protein expression levels of Bax,Bcl-xl compared with other groups(P<0.05).Additionally,treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax,Bcl-xl and NGFR compared with those treated with QHJ only(all P<0.05),especially in those treated with ***:The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation,and upregulating the expression level of Bax,Bcl-xl and NGFR.

关键词： psoriasis inflammatory dermatosis nerve growth factor keratinocyte Chinese medicine formula

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Intranasal nerve growth factor for prevention and recovery of the outcomes of traumatic brain injury

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Neural Regeneration Research 2023年第4期18卷 773-778页

作者： Luigi Manni Giorgio Conti Antonio Chiaretti Marzia Soligo Institute of Translational Pharmacology National Research Council of Italy(CNR)RomeItaly Intensive Pediatric Therapy and Pediatric Trauma Center Department of EmergencyAnesthesiological and Reanimation SciencesFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly Institute of Pediatrics Department of Woman and Child HealthFondazione Policlinico Universitario A.Gemelli IRCCSRomeItaly

Traumatic brain injury is one of the main causes of mortality and disability *** brain injury is characterized by a primary injury directly induced by the impact,which progresses into a secondary injury that leads to cellular and metabolic damages,starting in the first few hours and days after primary mechanical *** date,traumatic brain injury is not targetable by therapies aimed at preventing and/or limiting the outcomes of secondary damage but only by palliative *** growth factor is a neurotrophin targeting neuronal and non-neuronal cells,potentially useful in preventing/limiting the outcomes of secondary damage in traumatic brain *** potential has further increased in the last two decades since the possibility of reaching neurotrophin targets in the brain through its intranasal delivery has been ***,molecules intranasally delivered to the brain parenchyma may easily bypass the blood-brain barrier and reach their therapeutic targets in the brain,with favorable kinetics,dynamics,and safety *** the first part of this review,we aimed to report the traumatic brain injury-induced dysfunctional mechanisms that may benefit from nerve growth factor *** the second part,we then exposed the experimental evidence relating to the action of nerve growth factor(both in vitro and in vivo,after administration routes other than intranasal)on some of these *** the last part of the work,we,therefore,discussed the few manuscripts that analyze the effects of treatment with nerve growth factor,intranasally delivered to the brain parenchyma,on the outcomes of traumatic brain injury.

关键词： intranasal delivery nerve growth factor pharmacology traumatic brain injury

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nerve growth factor in muscle afferent neurons of peripheral artery disease and autonomic function

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Neural Regeneration Research 2021年第4期16卷 694-699页

作者： Lu Qin Jianhua Li Heart&Vascular Institute Penn State University College of MedicineHersheyPAUSA

In peripheral artery disease patients,the blood supply directed to the lower limbs is *** results in severe limb ischemia and thereby enhances pain sensitivity in lower *** painful perception is induced and exaggerate during walking,and is relieved by *** symptom is termed by intermittent *** limb ischemia also amplifies autonomic responses during *** the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic *** review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active *** the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.

关键词： acid sensing ion channel subtype 3 exercise pressor reflex muscle afferents nerve growth factor P2X purinoceptor 3 peripheral artery disease transient receptor potential vanilloid type 1

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nerve growth factor and Vascular Endothelial growth factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

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International Journal of Oral Science 2010年第1期2卷 35-44页

作者： Hao Li Xiao-lin Nong Qi Chen Yi-ping Yang Jia-quan Li Yan-ning Li Department of Oral and Maxillofacial Surgery College of Stomatology Guangxi Medical University Nanning China Department of Pathology Stomatological Hospital Affiliated to Guangxi Medical University Nanning China Laboratory Center Guangxi Medical University Nanning China Department of Epidemiology and Health Statistics College of Public Health Guangxi Medical University Nanning China

Aim To detect the expression of nerve growth factor （NGF） and vascular endothelial growth factor （VEGF） in salivary adenoid cystic carcinoma （SACC） tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Methodology Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox＇s proportional hazard regression model were applied to assess predictors of survival. Results NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues （P〈0.05）, and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high- expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates （P〈0.05）. Conclusion NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent prognosis factors for survival.

关键词： nerve growth factor vascular endothelial growth factor salivary adenoid cystic carcinoma prognosis

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nerve growth factor expression in astrocytoma and cerebrospinal fluid： a new biomarker for prognosis of astrocytoma

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Chinese Medical Journal 2011年第14期124卷 2222-2227页

作者： LI Qiao-yu YANG Yong ZHANG Yan ZHANG Zhi-jian GONG Ai-hua YUAN Zhi-cheng LU Pei-son ZHAN Li-ping WANG Peng FENG Yun XU Wen-lin .Department of Neurosurgery the Affiliated People's Hospital of Jiangsu University ZhenjiangJiangsu 212002 China Institute of Clinical Laboratory Medicine Jiangsu UniversityZhenjiang Jiangsu 212013 China Central Laboratory the Affiliated People's Hospital of Jiangsu University ZhenjiangJiangsu 212002 China

Background Recent studies have discovered that nuclear translocation of nerve growth factor （NGF） and its receptor fragments function differently from the traditional model. This study aimed to uncover the nuclear expression of NGF in astrocytoma and its biological *** Ninety-four paraffin-embedded astrocytoma specimens were subjected to immunohistochemical （IHC） and hemotoxylin ＆ eosin （HE） staining. Preoperative cerebrospinal fluid （CSF） specimens and intraoperative snap-frozen astrocytoma tissues were assayed for NGF expression by ELISA and Western blotting. The outcome of patients who contributed samples was tracked. Each ten tissue samples from patients with traumatic brain injury who had received decompression surgery and CSF samples from patients undergoing spinal anesthesia but with no history of nervous system disease were taken as *** NGF-positive immunoreactive products were distributed in both the cytoplasm and nucleus of astrocytoma, but were only located in the cytoplasm of traumatic brain injury （TBI） tissue. NGF nuclear-positive rate （NPR） of grades Ⅲ-Ⅳ astrocytomas （70.0%） was higher than that of grades Ⅰ-Ⅱ astrocytoma （28.6%, P＜0.05）. NGF-NP expression positively correlated with the NGF concentration in cerebrospinal fluid （CSF）（r=0.755, P＜0.01）. Kaplan-Meier survival analysis indicated that the median survival time was 25 months for NGF-NP astrocytoma grade Ⅰ-Ⅱ patients and 42 months in NGF nuclear negative （NGF-NN） astrocytoma grade Ⅰ-Ⅱ patients （P＜0.05）. In astrocytoma Ⅲ-Ⅳ patients, the median survival was 7 months for NGF-NP patients and 24 months for NGF-NN patients （P＜0.01）. Two types of NGF with molecular weights of 13 and 36 kDa were present in astrocytoma, but only the 36 kDa NGF was found in the CSF. NGF expression elevated as the malignancy *** NGF-NP expression and NGF level in CSF were significant prognostic factors in astrocytoma *** of the easy access of CSF, it may be deve

关键词： nerve growth factor astrocytoma cell nucleus prognosis

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nerve growth factor Promotes Angiogenesis and Skeletal Muscle Fiber Remodeling in a Murine Model of Hindlimb Ischemia

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Chinese Medical Journal 2016年第3期129卷 313-319页

作者： Yong-Peng Diao Feng-Kui Cui Sheng Yan Zuo-Guan Chen Li-Shan Lian Li-Long Guo Yong-Jun Li Department of Vascular Surgery Beijing Shijitan Hospital Capital Medical University Beijing 100038 China Department of Vascular Surgery Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Science Beijing 100730 China Department of Vascular Surgery Daqing Oilfield General Hospital Heilongjiang 163001 China

Background： Therapeutic angiogenesis has been shown to promote blood vessel growth and improve tissue *** growth factor （NGF） has been reported to play an important role in both physiological and pathological *** study aimed to investigate the effects of NGF on angiogenesis and skeletal muscle fiber remodeling in a murine model of hindlimb ischemia and study the relationship between NGF and vascular endothelial growth factor （VEGF） in ***： Twenty-four mice were randomly allocated to normal control group （n =6）, blank control group （n =6）, VEGF gene transfection group （n =6）, and NGF gene transfection group （n =6）.The model of left hindlimb ischemia model was established by ligating the femoral ***165 plasmid （125 μg） and NGF plasmid （125 μg） was injected into the ischemic gastrocnemius of mice from VEGF group and NGF group, *** hindlimb function and ischemic damage were assessed with terminal points at 21th day postischemia *** gastrocnemius of four groups was tested by hematoxylin-eosin staining, proliferating cell nuclear antigen and CD34 immunohistochemistry staining, and myosin ATPase *** and VEGF protein expression was detected by enzyme-linked immunosorbent ***： On the 21th day after surgery, the functional assessment score and skeletal muscle atrophy degree of VEGF group and NGF group were significantly lower than those of normal control group and blank control *** endothelial cell proliferation index and the capillary density of VEGF group and NGF group were significantly increased compared with normal control group and blank control group （P 〈 0.05）.The NGF and VEGF protein expression of NGF group showed a significant rise when compared with blank control group （P 〈 0.05）.Similarly, the VEGF protein expression of VEGF group was significantly higher than that of blank control group （P 〈 0.05）, but there was no significant difference of the NGF protein expressi

关键词： Angiogenesis Limb lschemia Muscle Fiber Type nerve growth factor Vascular Endothelial growth factor

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nerve growth factor pretreatment against glutamate-induced hippocampal neuronal injury Action mechanism of phosphatase and tensin homologue deleted on chromosome 10

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Neural Regeneration Research 2010年第1期5卷 5-9页

作者： Yae Hu Jiahui Mao Yan Zhu Ailing Zhou Department of Pathophysiology Medical School of Nantong University Nantong 226001 Jiangsu Province China

BACKGROUND： nerve growth factor （NGF） attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 （PTEN） promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE： To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SE＇I＇rlNG： The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS： Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide （M-I-F）, and lactate dehydrogenase kit （Sigma, USA）, fluorescence microscope and inverted phase contrast microscope （Olympus, Japan） were used in this study. METHODS： Hippocampal neurons were obtained from newborn （〈 24 hours） Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate （0.2 mmol/L）, and NGF groups were treated with NGF （10, 50, 100, and 200 μg/L, respectively） prior to glutamate treatment. MAIN OUTCOME MEASURES： The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2- phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS： Glutamate （0.2 mmol/L） induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group （P 〈 0.01）. However, compared with the glutamate group, cell viability significantly increased and lac

关键词： nerve growth factor glutamate phosphatase and tensin homologue deleted on chromosome 10 hippocampus neurons nerve factor

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nerve growth factor affects focal cerebral cortical neuronal Bcl-2 and Bax expression in a mouse model of oxyhemoglobin-induced subarachnoid hemorrhage

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Neural Regeneration Research 2008年第8期3卷 813-816页

作者： Xianfeng Jiang Wei Shi Jin Liang Department of Neurosurgery Affiliated Hospital of Medical College of the Chinese People＇s Armed Police Force Tianjin 300162 China Department of Neurosurgery Second Hospital of Xi＇an Jiaotong University Xi＇an 710004 Shaanxi Province China

BACKGROUND： Studies have demonstrated that oxyhemoglobin （OxyHb） can induce brain cell apoptosis in ***： To observe the effects of exogenous nerve growth factor （NGF） on cerebral cortical neuronal Bcl-2 and Bax expression in mice with OxyHb-induced subarachnoid hemorrhage. DESIGN, TIME AND SETTING： A completely randomized grouping, controlled animal experiment was performed at the Experimental Center for Biomedicine, College of Medicine, Xi＇an Jiaotong University between February and April 2005. MATERIALS： Fifty-four healthy, male, adult, ICR mice were included in this study. Subarachnoid hemorrhage was induced by a subarachnoid injection of OxyHb in 48 mice. Mouse NGF was obtained from Xiamen Beidazhilu Bioengineering Co., Ltd., ***： All 54 mice were randomly divided into three groups： control （n = 6）, injury （n = 24）, and NGF （n = 24）. The NGF group received a subarachnoidal administration of OxyHb, immediately followed by a caudal vein injection of NGF （1 μg）. The injury group was injected with OxyHb, and subsequently with physiological saline. The control group only received intravenous physiological saline. MAIN OUTCOME MEASURES： At 1,6, 24, and 48 hours following subarachnoid hemorrhage induction, expression levels of Bcl-2 and Bax were detected by immunohistochemistry in the cerebral cortex 3 mm anterior and posterior to the injection site. RESULTS： At all time points following OxyHb injection, cerebral cortical Bax levels were significantly higher in the injured group than in the control and NGF groups （P 〈 0.01）. During the first 24 hours following OxyHb injection, cerebral cortical Bcl-2 levels were significantly lower in the injury group compared to the control group （P 〈 0.05 0.01）. Between 1 and 48 hours, Bcl-2 levels were significantly higher in the NGF group than in the injury group （P 〈 0.01 ）. CONCLUSION： Exogenous NGF can inhibit increased neuronal Bax expression and decreased Bcl-2 expression in the cerebral cortex of mice wit

关键词： apoptosis Bcl-2 Bax nerve growth factor oxyhemoglobin

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nerve growth factor protects against palmitic acid- induced injury in retinal ganglion cells

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Neural Regeneration Research 2016年第11期11卷 1851-1856页

作者： Pan-shi Yan Shu Tang Hai- feng Zhang Yuan-yuan Guo Zhi-wen Zeng Qiang Wen Department of Ophthalmology First Affiliated Hospital of Zhengzhou University Zhengzhou Henan Province China Department of Pharmacy First Affiliated Hospital of Zhengzhou University Zhengzhou Henan Province China Department of Biochemistry and Molecular Biology School of Basic Medicine Zhengzhou University Zhengzhou Henan Province China Shenzhen Mental Health Center and Shenzhen Key Lab for Psychological Healthcare Shenzhen Guangdong Province China Department of Clinical Pharmacology School of Basic Medicine Zhengzhou University Zhengzhou Henan Province China

Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.

关键词： nerve regeneration RGC-5 cells palmitic acid nerve growth factor apoptosis PI3K Akt FoxOl ERK1/2 neural regeneration

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