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1.
Allergol Immunopathol (Madr) ; 52(3): 1-7, 2024.
Article in English | MEDLINE | ID: mdl-38721949

ABSTRACT

INTRODUCTION: Many chronic spontaneous urticaria (CSU) patients have highly stressful life events and exhibit psychiatric comorbidities. Emotional stress can cause or exacerbate urticaria symptoms by causing mast cell degranulation via neuromediators. OBJECTIVES: To investigate the frequency of stressful life events and compare psychiatric comorbidities and serum neuromediator levels in patients with CSU who responded to omalizumab with healthy controls. METHODS: In this cross-sectional study, we included 42 patients with CSU who received at least 6 months of omalizumab treatment and a control group of 42 healthy controls. Stressful life events were evaluated with the Life Events Checklist for DSM-5 (LEC-5). The Depression Anxiety Stress Scale-42 (DASS-42) was used to evaluate depression, anxiety and stress levels. Serum nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and substance P (SP) levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Twenty-six (62%) patients reported at least one stressful life event a median of 3.5 months before the onset of CSU. There were no significant differences in all three variables in the DASS subscales between the patient and control groups. Serum NGF levels were found to be significantly lower in patients with CSU (p <0.001), whereas CGRP levels were found to be significantly higher (p <0.001). There was no significant difference for SP. CONCLUSIONS: The psychological status of patients with CSU who benefited from omalizumab was similar to that of healthy controls. Omalizumab may affect stress-related neuromediator levels.


Subject(s)
Anti-Allergic Agents , Chronic Urticaria , Nerve Growth Factor , Omalizumab , Stress, Psychological , Humans , Omalizumab/therapeutic use , Female , Male , Adult , Chronic Urticaria/drug therapy , Chronic Urticaria/blood , Cross-Sectional Studies , Middle Aged , Stress, Psychological/drug therapy , Stress, Psychological/blood , Nerve Growth Factor/blood , Anti-Allergic Agents/therapeutic use , Substance P/blood , Calcitonin Gene-Related Peptide , Comorbidity , Depression/drug therapy , Depression/blood , Depression/epidemiology , Mental Disorders/drug therapy , Mental Disorders/blood , Mental Disorders/epidemiology
2.
Biotechnol J ; 19(5): e2300734, 2024 May.
Article in English | MEDLINE | ID: mdl-38719571

ABSTRACT

Self-assembly of biological elements into biomimetic cargo carriers for targeting and delivery is a promising approach. However, it still holds practical challenges. We developed a functionalization approach of DNA origami (DO) nanostructures with neuronal growth factor (NGF) for manipulating neuronal systems. NGF bioactivity and its interactions with the neuronal system were demonstrated in vitro and in vivo models. The DO elements fabricated by molecular self-assembly have manipulated the surrounding environment through static spatially and temporally controlled presentation of ligands to the cell surface receptors. Our data showed effective bioactivity in differentiating PC12 cells in vitro. Furthermore, the DNA origami NGF (DON) affected the growth directionality and spatial capabilities of dorsal root ganglion neurons in culture by introducing a chemotaxis effect along a gradient of functionalized DO structures. Finally, we showed that these elements provide enhanced axonal regeneration in a rat sciatic nerve injury model in vivo. This study is a proof of principle for the functionality of DO in neuronal manipulation and regeneration. The approach proposed here, of an engineered platform formed out of programmable nanoscale elements constructed of DO, could be extended beyond the nervous system and revolutionize the fields of regenerative medicine, tissue engineering, and cell biology.


Subject(s)
DNA , Ganglia, Spinal , Nerve Growth Factor , Nerve Regeneration , Animals , Rats , PC12 Cells , DNA/chemistry , Ganglia, Spinal/cytology , Nerve Growth Factor/chemistry , Nerve Growth Factor/pharmacology , Nanostructures/chemistry , Neurons , Sciatic Nerve , Tissue Scaffolds/chemistry , Rats, Sprague-Dawley
3.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 220-225, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38814212

ABSTRACT

This study explored the impact of penehyclidine hydrochloride on cognitive function in rats with brain injury. Sprague-Dawley rats (n=36) were randomly assigned to sham-operation, model, and penehyclidine hydrochloride groups. Rats in the sham-operation group underwent craniotomy, while the model and penehyclidine hydrochloride groups received brain injury models and interventions with normal saline and penehyclidine hydrochloride, respectively. Specimens were obtained two weeks post-intervention. Neurological deficits were evaluated using Zea-Longa scores, and memory was assessed with the Morris water maze test. ELISA determined brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) content. mRNA expressions of BDNF and NGF were assessed via qPCR, and phosphorylated CREB (p-CREB) protein expression was measured by Western blotting. Compared to the sham-operation group, both model and penehyclidine hydrochloride groups showed increased Zea-Longa scores. Escape latencies were longer and platform crossings were fewer in model and penehyclidine hydrochloride groups compared to the sham-operation group, but penehyclidine hydrochloride demonstrated a shorter latency and more platform crossings than the model group. BDNF and NGF content decreased in model and penehyclidine hydrochloride groups compared to the sham-operation group, with an increase in the penehyclidine hydrochloride group compared to the model group. mRNA expression levels declined in model and penehyclidine hydrochloride groups but were higher in the latter. p-CREB protein expression was lower in model and penehyclidine hydrochloride groups compared to the sham-operation group but higher in the penehyclidine hydrochloride group than the model group. Penehyclidine hydrochloride exhibited neuroprotective effects by upregulating the cAMP/CREB signaling pathway, improving cognitive function in rats with brain injury.


Subject(s)
Brain Injuries , Brain-Derived Neurotrophic Factor , Cognition , Cyclic AMP Response Element-Binding Protein , Cyclic AMP , Quinuclidines , Rats, Sprague-Dawley , Signal Transduction , Animals , Signal Transduction/drug effects , Cyclic AMP Response Element-Binding Protein/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Quinuclidines/pharmacology , Quinuclidines/therapeutic use , Cognition/drug effects , Male , Brain Injuries/drug therapy , Brain Injuries/metabolism , Cyclic AMP/metabolism , Rats , Nerve Growth Factor/metabolism , Nerve Growth Factor/genetics , Phosphorylation/drug effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Disease Models, Animal
4.
Biomolecules ; 14(5)2024 May 15.
Article in English | MEDLINE | ID: mdl-38785989

ABSTRACT

Endometriosis is a gynecological disorder associated with local inflammation and neuroproliferation. Increased nerve bundle density has been attributed to increased expression of nerve growth factor (NGF) and interleukin-1ß (IL-1ß). Immunohistochemical analysis was carried out on 12 patients presenting with all three anatomic subtypes of endometriosis (deep, superficial peritoneal, endometrioma) at surgery, with at least two surgically excised subtypes available for analysis. Immunolocalization for nerve bundle density around endometriosis using protein gene product 9.5 (PGP9.5), as well as NGF and IL-1ß histoscores in endometriosis epithelium/stroma, was performed to evaluate differences in scores between lesions and anatomic subtypes per patient. Intra-individual heterogeneity in scores across lesions was assessed using the coefficient of variation (CV). The degree of score variability between subtypes was evaluated using the percentage difference between mean scores from one subtype to another subtype for each marker. PGP9.5 nerve bundle density was heterogenous across multiple subtypes of endometriosis, ranging from 50.0% to 173.2%, where most patients (8/12) showed CV ≥ 100%. The percentage difference in scores showed that PGP9.5 nerve bundle density and NGF and IL-1ß expression were heterogenous between anatomic subtypes within the same patient. Based on these observations of intra-individual heterogeneity, we conclude that markers of neuroproliferation in endometriosis should be stratified by anatomic subtype in future studies of clinical correlation.


Subject(s)
Endometriosis , Interleukin-1beta , Nerve Growth Factor , Humans , Female , Endometriosis/metabolism , Endometriosis/pathology , Interleukin-1beta/metabolism , Nerve Growth Factor/metabolism , Adult , Ubiquitin Thiolesterase/metabolism , Middle Aged
5.
CNS Neurosci Ther ; 30(5): e14743, 2024 May.
Article in English | MEDLINE | ID: mdl-38780008

ABSTRACT

AIMS: Nerve growth factor (NGF) loss is a potential factor for the degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD), and Rab5a is a key regulatory molecule of NGF signaling transduction. Here, we investigated the changes of Rab5a in 5 × FAD mice and further explored the mechanism of Electroacupuncture (EA) treatment in improving cognition in the early stage of AD. METHODS: The total Rab5a and Rab5a-GTP in 5-month-old 5 × FAD mice and wild-type mice were detected using WB and IP technologies. 5 × FAD mice were treated with EA at the Bai hui (DU20) and Shen ting (DU24) acupoints for 4 weeks and CRE/LOXP technology was used to confirm the role of Rab5a in AD mediated by EA stimulation. The Novel Object Recognition and Morris water maze tests were used to evaluate the cognitive function of 5 × FAD mice. The Nissl, immunohistochemistry, and Thioflavin S staining were used to observe pathological morphological changes in the basal forebrain circuit. The Golgi staining was used to investigate the synaptic plasticity of the basal forebrain circuit and WB technology was used to detect the expression levels of cholinergic-related and NGF signal-related proteins. RESULTS: The total Rab5a was unaltered, but Rab5a-GTP increased and the rab5a-positive early endosomes appeared enlarged in the hippocampus of 5 × FAD mice. Notably, EA reduced Rab5a-GTP in the hippocampus in the early stage of 5 × FAD mice. EA could improve object recognition memory and spatial learning memory by reducing Rab5a activity in the early stage of 5 × FAD mice. Moreover, EA could reduce Rab5a activity to increase NGF transduction and increase the levels of phosphorylated TrkA, AKT, and ERK in the basal forebrain and hippocampus, and increase the expression of cholinergic-related proteins, such as ChAT, vAchT, ChT1, m1AchR, and m2AchR in the basal forebrain and ChAT, m1AchR, and m2AchR in the hippocampus, improving synaptic plasticity in the basal forebrain hippocampal circuit in the early stage of 5 × FAD mice. CONCLUSIONS: Rab5a hyperactivation is an early pathological manifestation of 5 × FAD mice. EA could suppress Rab5a-GTP to promote the transduction of NGF signaling, and enhance the synaptic plasticity of the basal forebrain hippocampal circuit improving cognitive impairment in the early stage of 5 × FAD mice.


Subject(s)
Alzheimer Disease , Electroacupuncture , Mice, Transgenic , Nerve Growth Factor , rab5 GTP-Binding Proteins , Animals , rab5 GTP-Binding Proteins/metabolism , Nerve Growth Factor/metabolism , Mice , Electroacupuncture/methods , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Signal Transduction/physiology , Male , Memory/physiology , Learning/physiology , Maze Learning/physiology , Mice, Inbred C57BL , Neuronal Plasticity/physiology
6.
Cell Death Dis ; 15(5): 381, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816365

ABSTRACT

Osteosarcoma (OS) therapy presents numerous challenges, due largely to a low survival rate following metastasis onset. Nerve growth factor (NGF) has been implicated in the metastasis and progression of various cancers; however, the mechanism by which NGF promotes metastasis in osteosarcoma has yet to be elucidated. This study investigated the influence of NGF on the migration and metastasis of osteosarcoma patients (88 cases) as well as the underlying molecular mechanisms, based on RNA-sequencing and gene expression data from a public database (TARGET-OS). In osteosarcoma patients, the expression of NGF was significantly higher than that of other growth factors. This observation was confirmed in bone tissue arrays from 91 osteosarcoma patients, in which the expression levels of NGF and matrix metallopeptidase-2 (MMP-2) protein were significantly higher than in normal bone, and strongly correlated with tumor stage. In summary, NGF is positively correlated with MMP-2 in human osteosarcoma tissue and NGF promotes osteosarcoma cell metastasis by upregulating MMP-2 expression. In cellular experiments using human osteosarcoma cells (143B and MG63), NGF upregulated MMP-2 expression and promoted wound healing, cell migration, and cell invasion. Pre-treatment with MEK and ERK inhibitors or siRNA attenuated the effects of NGF on cell migration and invasion. Stimulation with NGF was shown to promote phosphorylation along the MEK/ERK signaling pathway and decrease the expression of microRNA-92a-1-5p (miR-92a-1-5p). In in vivo experiments involving an orthotopic mouse model, the overexpression of NGF enhanced the effects of NGF on lung metastasis. Note that larotrectinib (a tropomyosin kinase receptor) strongly inhibited the effect of NGF on lung metastasis. In conclusion, it appears that NGF promotes MMP-2-dependent cell migration by inhibiting the effects of miR-92a-1-5p via the MEK/ERK signaling cascade. Larotrectinib emerged as a potential drug for the treatment of NGF-mediated metastasis in osteosarcoma.


Subject(s)
Bone Neoplasms , Cell Movement , Matrix Metalloproteinase 2 , Nerve Growth Factor , Osteosarcoma , Pyrazoles , Pyrimidines , Humans , Osteosarcoma/drug therapy , Osteosarcoma/pathology , Osteosarcoma/metabolism , Osteosarcoma/genetics , Nerve Growth Factor/metabolism , Animals , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Cell Line, Tumor , Cell Movement/drug effects , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Mice , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/drug therapy , Bone Neoplasms/pathology , Bone Neoplasms/genetics , Mice, Nude , Male , Neoplasm Metastasis , Female , Gene Expression Regulation, Neoplastic/drug effects , Mice, Inbred BALB C
7.
Biomaterials ; 309: 122603, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38713972

ABSTRACT

Sympathetic nerves play a pivotal role in promoting tumor growth through crosstalk with tumor and stromal cells. Chemotherapy exacerbates the infiltration of sympathetic nerves into tumors, thereby providing a rationale for inhibiting sympathetic innervation to enhance chemotherapy. Here, we discovered that doxorubicin increases the density and activity of sympathetic nerves in breast cancer mainly by upregulating the expression of nerve growth factors (NGFs) in cancer cells. To address this, we developed a combination therapy by co-encapsulating small interfering RNA (siRNA) and doxorubicin within breast cancer-targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles, aiming to suppress NGF expression post-chemotherapy. Incorporating NGF blockade into the nanoplatform for chemotherapy effectively mitigated the chemotherapy-induced proliferation of sympathetic nerves. This not only bolstered the tumoricidal activity of chemotherapy, but also amplified its stimulatory impact on the antitumor immune response by increasing the infiltration of immunostimulatory cells into tumors while concurrently reducing the frequency of immunosuppressive cells. Consequently, the combined nanodrug approach, when coupled with anti-PD-L1 treatment, exhibited a remarkable suppression of primary and deeply metastatic tumors with minimal systematic toxicity. Importantly, the nanoplatform relieved chemotherapy-induced peripheral neuropathic pain (CIPNP) by diminishing the expression of pain mediator NGFs. In summary, this research underscores the significant potential of NGF knockdown in enhancing immunochemotherapy outcomes and presents a nanoplatform for the highly efficient and low-toxicity treatment of breast cancer.


Subject(s)
Doxorubicin , Immunotherapy , Nanoparticles , Neuralgia , Neuralgia/chemically induced , Animals , Doxorubicin/pharmacology , Female , Nanoparticles/chemistry , Cell Line, Tumor , Humans , Immunotherapy/methods , Mice , RNA, Small Interfering , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Nerve Growth Factor/metabolism , Mice, Inbred BALB C , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Antineoplastic Agents/pharmacology
8.
Traffic ; 25(5): e12936, 2024 May.
Article in English | MEDLINE | ID: mdl-38725127

ABSTRACT

Endosomal trafficking of TrkA is a critical process for nerve growth factor (NGF)-dependent neuronal cell survival and differentiation. The small GTPase ADP-ribosylation factor 6 (Arf6) is implicated in NGF-dependent processes in PC12 cells through endosomal trafficking and actin cytoskeleton reorganization. However, the regulatory mechanism for Arf6 in NGF signaling is largely unknown. In this study, we demonstrated that EFA6A, an Arf6-specific guanine nucleotide exchange factor, was abundantly expressed in PC12 cells and that knockdown of EFA6A significantly inhibited NGF-dependent Arf6 activation, TrkA recycling from early endosomes to the cell surface, prolonged ERK1/2 phosphorylation, and neurite outgrowth. We also demonstrated that EFA6A forms a protein complex with TrkA through its N-terminal region, thereby enhancing its catalytic activity for Arf6. Similarly, we demonstrated that EFA6A forms a protein complex with TrkA in cultured dorsal root ganglion (DRG) neurons. Furthermore, cultured DRG neurons from EFA6A knockout mice exhibited disturbed NGF-dependent TrkA trafficking compared with wild-type neurons. These findings provide the first evidence for EFA6A as a key regulator of NGF-dependent TrkA trafficking and signaling.


Subject(s)
ADP-Ribosylation Factor 6 , ADP-Ribosylation Factors , Endosomes , Guanine Nucleotide Exchange Factors , Nerve Growth Factor , Neuronal Outgrowth , Receptor, trkA , Animals , Mice , Rats , ADP-Ribosylation Factors/metabolism , ADP-Ribosylation Factors/genetics , Endosomes/metabolism , Ganglia, Spinal/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Guanine Nucleotide Exchange Factors/genetics , Mice, Knockout , Nerve Growth Factor/metabolism , PC12 Cells , Protein Transport , Receptor, trkA/metabolism
9.
Colloids Surf B Biointerfaces ; 239: 113967, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761494

ABSTRACT

The re-bridging of the deficient nerve is the main problem to be solved after the functional impairment of the peripheral nerve. In this study, a directionally aligned polycaprolactone/triiron tetraoxide (PCL/Fe3O4) fiber scaffolds were firstly prepared by electrospinning technique, and further then grafted with IKVAV peptide for regulating DRG growth and axon extension in peripheral nerve regeneration. The results showed that oriented aligned magnetic PCL/Fe3O4 composite scaffolds were successfully prepared by electrospinning technique and possessed good mechanical properties and magnetic responsiveness. The PCL/Fe3O4 scaffolds containing different Fe3O4 concentrations were free of cytotoxicity, indicating the good biocompatibility and low cytotoxicity of the scaffolds. The IKVAV-functionalized PCL/Fe3O4 scaffolds were able to guide and promote the directional extension of axons, the application of external magnetic field and the grafting of IKVAV peptides significantly further promoted the growth of DRGs and axons. The ELISA test results showed that the AP-10 F group scaffolds promoted the secretion of nerve growth factor (NGF) from DRG under a static magnetic field (SMF), thus promoting the growth and extension of axons. Importantly, the IKVAV-functionalized PCL/Fe3O4 scaffolds could significantly up-regulate the expression of Cntn2, PCNA, Sox10 and Isca1 genes related to adhesion, proliferation and magnetic receptor function under the stimulation of SMF. Therefore, IKVAV-functionalized PCL/Fe3O4 composite oriented scaffolds have potential applications in neural tissue engineering.


Subject(s)
Polyesters , Tissue Scaffolds , Animals , Polyesters/chemistry , Rats , Tissue Scaffolds/chemistry , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Ganglia, Spinal/drug effects , Nerve Growth Factor/pharmacology , Nerve Growth Factor/chemistry , Nerve Regeneration/drug effects , Magnetic Fields , Ferric Compounds/chemistry , Ferric Compounds/pharmacology , Rats, Sprague-Dawley , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , PC12 Cells
10.
Transl Psychiatry ; 14(1): 193, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38632257

ABSTRACT

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Mice , Animals , Humans , Autistic Disorder/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Acetylcholine , Dopamine , Nerve Growth Factor/metabolism , Mice, Inbred C57BL , Mice, Inbred Strains , Synaptic Transmission/physiology , Autism Spectrum Disorder/metabolism , Amygdala/metabolism , gamma-Aminobutyric Acid , Disease Models, Animal
11.
Amino Acids ; 56(1): 32, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637413

ABSTRACT

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.


Subject(s)
Diabetes Mellitus, Experimental , Proto-Oncogene Proteins c-akt , Animals , Rats , Axons/metabolism , Axons/pathology , Diabetes Mellitus, Experimental/metabolism , Nerve Growth Factor/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Taurine/pharmacology , Taurine/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism
12.
Sci Rep ; 14(1): 8943, 2024 04 18.
Article in English | MEDLINE | ID: mdl-38637604

ABSTRACT

Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.


Subject(s)
Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Humans , Arthroplasty, Replacement, Knee/adverse effects , Synovial Fluid/metabolism , Nerve Growth Factor/metabolism , Osteoarthritis, Knee/surgery , Osteoarthritis, Knee/metabolism , Pain, Postoperative/metabolism , Cytokines/metabolism , Lipids
13.
Eur Rev Med Pharmacol Sci ; 28(7): 2654-2661, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38639504

ABSTRACT

OBJECTIVE: This study aimed to explore the effect of flipped venous catheters combined with spinal cord electrical stimulation on functional recovery in patients with sciatic nerve injury. PATIENTS AND METHODS: 160 patients with hip dislocation and sciatic nerve injury were divided into conventional release and flipped catheter + electrical stimulation groups according to the treatment methods (n=80). Motor nerve conduction velocity (MCV) and lower limb motor function were compared. Serum neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were compared. The frequency of complications and quality of life were also compared. RESULTS: The MCV levels of the common peroneal nerve and tibial nerve in the flipped catheter + electrical stimulation group were greater than the conventional lysis group (p<0.05). After treatment, the lower extremity motor score (LMEs) in the flipped catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). The serum levels of BDNF and NGF in the flip catheter + electrical stimulation group were higher than the conventional lysis group (p<0.05). The complication rate in the flipped catheter + electrical stimulation group was lower than in the conventional release group (6.25% vs. 16.25%, p<0.05). The quality-of-life score in the flip catheter + electrical stimulation group was greater than the conventional lysis group (p<0.05). CONCLUSIONS: The flipped venous catheter combined with spinal cord electrical stimulation can improve nerve conduction velocity, lower limb motor function, serum BDNF and NGF levels, reduce complications, and help improve the quality of life of sufferers with sciatic nerve injury. Chictr.org.cn ID: ChiCTR2400080984.


Subject(s)
Brain-Derived Neurotrophic Factor , Sciatic Neuropathy , Rats , Animals , Humans , Brain-Derived Neurotrophic Factor/metabolism , Rats, Sprague-Dawley , Nerve Growth Factor/metabolism , Quality of Life , Sciatic Neuropathy/metabolism , Sciatic Neuropathy/therapy , Spinal Cord/metabolism , Sciatic Nerve , Catheters , Electric Stimulation/methods
14.
Nat Commun ; 15(1): 3225, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622181

ABSTRACT

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. Recent clinical trials of the nerve growth factor (NGF) inhibitors in OA patients have suggested adverse effects of NGF inhibition on joint structure. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNFα to attenuate NF-κB activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression in mice. NGFR deficiency hyper-activates NF-κB in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-κB activation. Together, this study suggests a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.


Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Mice , Animals , Receptor, Nerve Growth Factor , NF-kappa B , Nerve Growth Factor/metabolism , Receptors, Nerve Growth Factor , Inflammation , Cartilage, Articular/metabolism , Joints/metabolism
15.
J Control Release ; 369: 591-603, 2024 May.
Article in English | MEDLINE | ID: mdl-38582336

ABSTRACT

Ischemia stroke is one of the leading causes of death and disability worldwide. Owing to the limited delivery efficiency to the brain caused by the blood-brain barrier (BBB) and off-target effects of systemic treatment, it is crucial to develop an in situ drug delivery system to improve the therapeutic effect in ischemic stroke. Briefly, we report a multifunctional in situ hydrogel delivery system for the co-delivery of reactive oxygen species (ROS)-responsive nanoparticles loaded with atorvastatin calcium (DSPE-se-se-PEG@AC NPs) and ß-nerve growth factor (NGF), which is expected to remodel pathological microenvironment for improving cerebral ischemia injury. The in vitro results exhibited the multifunctional hydrogel scavenged oxygen-glucose deprivation (OGD)-induced free radical, rescued the mitochondrial function, and maintained the survival and function of neurons, hence reducing neuronal apoptosis and neuroinflammation, consequently relieving ischemia injury in hippocampal neurons cell line (HT22). In the rat ischemia stroke model, the hydrogel significantly minified cerebral infarction by regulating inflammatory response, saving apoptotic neurons, and promoting angiogenesis and neurogenesis. Besides, the hydrogel distinctly improved the rats' neurological deficits after cerebral ischemia injury over the long-term observation. In conclusion, the in-situ hydrogel platform has demonstrated promising therapeutic effects in both in vitro and in vivo studies, indicating its potential as a new and effective therapy.


Subject(s)
Atorvastatin , Brain Ischemia , Hydrogels , Rats, Sprague-Dawley , Animals , Hydrogels/administration & dosage , Brain Ischemia/drug therapy , Male , Atorvastatin/administration & dosage , Atorvastatin/therapeutic use , Atorvastatin/pharmacology , Cell Line , Reactive Oxygen Species/metabolism , Nanoparticles/administration & dosage , Brain/drug effects , Brain/pathology , Brain/metabolism , Nerve Growth Factor/administration & dosage , Mice , Neurons/drug effects , Neurons/pathology , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/pharmacology , Rats , Apoptosis/drug effects , Polyethylene Glycols/chemistry , Polyethylene Glycols/administration & dosage , Drug Delivery Systems , Ischemic Stroke/drug therapy , Ischemic Stroke/pathology
16.
Int J Mol Sci ; 25(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38612839

ABSTRACT

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression patterns of NGF in rat skin (epidermis) during adjuvant-induced arthritis (AIA). Sprague Dawley rats were randomly divided into control and complete Freund's adjuvant (CFA)-treated groups. Levels of NGF were evaluated following unilateral AIA at different time points, and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.


Subject(s)
Nerve Growth Factor , Neurogenic Inflammation , Animals , Rats , Rats, Sprague-Dawley , Nerve Growth Factor/genetics , Adjuvants, Immunologic , Adjuvants, Pharmaceutic , Inflammation
17.
Lasers Med Sci ; 39(1): 119, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38679671

ABSTRACT

Orofacial nerve injuries may result in temporary or long-term loss of sensory function and decreased quality of life in patients. B vitamins are required for DNA synthesis and the repair and maintenance of phospholipids. In particular, vitamins B1, B6, and B12 are essential for neuronal function. Deficiency in vitamin B complex (VBC) has been linked to increased oxidative stress, inflammation and demyelination. Photobiomodulation (PBM) has antioxidant activity and is neuroprotective. In addition, a growing literature attests to the positive effects of PBM on nerve repair. To assess the effect of PBM and VBC on regenerative process we evaluated the expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), myelin basic protein (MBP), laminin and neurofilaments (NFs) using Western blotting to identify regenerative pattern after chronic constriction injury of the infraorbital nerve (CCI IoN) treated by PBM, VBC or its combination. After CCI IoN, the rats were divided into six groups naive, sham, injured (CCI IoN), treated with photobiomodulation (904 nm, 6.23 J/cm2, CCI IoN + PBM), treated with VBC (containing B1, B6 and B12) 5 times, CCI IoN + VBC) and treated with PBM and VBC (CCI IoN + VBC + PBM). The treatments could revert low expression of BDNF, MBP and laminin. Also reverted the higher expression of neurofilaments and enhanced expression of NGF. PBM and VBC could accelerate injured infraorbital nerve repair in rats through reducing the expression of neurofilaments, increasing the expression of BDNF, laminin and MBP and overexpressing NGF. These data support the notion that the use of PBM and VBC may help in the treatment of nerve injuries. This finding has potential clinical applications.


Subject(s)
Brain-Derived Neurotrophic Factor , Disease Models, Animal , Low-Level Light Therapy , Nerve Growth Factor , Nerve Regeneration , Vitamin B Complex , Animals , Rats , Nerve Regeneration/radiation effects , Low-Level Light Therapy/methods , Brain-Derived Neurotrophic Factor/metabolism , Nerve Growth Factor/metabolism , Male , Laminin/metabolism , Facial Nerve Injuries/radiotherapy , Facial Nerve Injuries/therapy , Rats, Wistar , Myelin Basic Protein/metabolism
18.
Biomed Mater ; 19(3)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38626779

ABSTRACT

It is well-established that multi-scale porous scaffolds can guide axonal growth and facilitate functional restoration after spinal cord injury (SCI). In this study, we developed a novel mussel shell-inspired conductive scaffold for SCI repair with ease of production, multi-scale porous structure, high flexibility, and excellent biocompatibility. By utilizing the reducing properties of polydopamine, non-conductive graphene oxide (GO) was converted into conductive reduced graphene oxide (rGO) and crosslinkedin situwithin the mussel shells.In vitroexperiments confirmed that this multi-scale porous Shell@PDA-GO could serve as structural cues for enhancing cell adhesion, differentiation, and maturation, as well as promoting the electrophysiological development of hippocampal neurons. After transplantation at the injury sites, the Shell@PDA-GO provided a pro-regenerative microenvironment, promoting endogenous neurogenesis, triggering neovascularization, and relieving glial fibrosis formation. Interestingly, the Shell@PDA-GO could induce the release of endogenous growth factors (NGF and NT-3), resulting in the complete regeneration of nerve fibers at 12 weeks. This work provides a feasible strategy for the exploration of conductive multi-scale patterned scaffold to repair SCI.


Subject(s)
Biocompatible Materials , Bivalvia , Graphite , Nerve Regeneration , Polymers , Spinal Cord Injuries , Tissue Scaffolds , Animals , Spinal Cord Injuries/therapy , Tissue Scaffolds/chemistry , Porosity , Graphite/chemistry , Polymers/chemistry , Biocompatible Materials/chemistry , Indoles/chemistry , Animal Shells/chemistry , Cell Differentiation , Electric Conductivity , Neurons , Rats , Rats, Sprague-Dawley , Cell Adhesion , Neurogenesis , Tissue Engineering/methods , Nerve Growth Factor/metabolism , Nerve Growth Factor/chemistry , Hippocampus
19.
Sheng Li Xue Bao ; 76(2): 301-308, 2024 Apr 25.
Article in Chinese | MEDLINE | ID: mdl-38658378

ABSTRACT

Delayed-onset muscle soreness (DOMS) is a common phenomenon that occurs following a sudden increase in exercise intensity or unfamiliar exercise, significantly affecting athletic performance and efficacy in athletes and fitness individuals. DOMS is characterized by allodynia and hyperalgesia, and their mechanisms remain unclear. Recent studies have reported that neurotrophic factors, such as nerve growth factor (NGF) and glial cell derived neurotrophic factor (GDNF), are involved in the development and maintenance of DOMS. This article provides a review of the research progress on the signaling pathways related to the involvement of NGF and GDNF in DOMS, hoping to provide novel insights into the mechanisms underlying allodynia and hyperalgesia in DOMS, as well as potential targeted treatment.


Subject(s)
Glial Cell Line-Derived Neurotrophic Factor , Myalgia , Nerve Growth Factor , Humans , Myalgia/physiopathology , Nerve Growth Factor/metabolism , Nerve Growth Factor/physiology , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Glial Cell Line-Derived Neurotrophic Factor/physiology , Signal Transduction , Animals , Hyperalgesia/physiopathology , Muscle, Skeletal/physiopathology , Muscle, Skeletal/physiology , Exercise/physiology
20.
Biomed Pharmacother ; 174: 116552, 2024 May.
Article in English | MEDLINE | ID: mdl-38599061

ABSTRACT

AIMS: Pulmonary hypertension (PH) is characterised by an increase in pulmonary arterial pressure, ultimately leading to right ventricular failure and death. We have previously shown that nerve growth factor (NGF) plays a critical role in PH. Our objectives here were to determine whether NGF controls Connexin-43 (Cx43) expression and function in the pulmonary arterial smooth muscle, and whether this mechanism contributes to NGF-induced pulmonary artery hyperreactivity. METHODS AND RESULTS: NGF activates its TrkA receptor to increase Cx43 expression, phosphorylation, and localization at the plasma membrane in human pulmonary arterial smooth muscle cells, thus leading to enhanced activity of Cx43-dependent GAP junctions as shown by Lucifer Yellow dye assay transfer and fluorescence recovery after photobleaching -FRAP- experiments. Using both in vitro pharmacological and in vivo SiRNA approaches, we demonstrate that NGF-dependent increase in Cx43 expression and activity in the rat pulmonary circulation causes pulmonary artery hyperreactivity. We also show that, in a rat model of PH induced by chronic hypoxia, in vivo blockade of NGF or of its TrkA receptor significantly reduces Cx43 increased pulmonary arterial expression induced by chronic hypoxia and displays preventive effects on pulmonary arterial pressure increase and right heart hypertrophy. CONCLUSIONS: Modulation of Cx43 by NGF in pulmonary arterial smooth muscle cells contributes to NGF-induced alterations of pulmonary artery reactivity. Since NGF and its TrkA receptor play a role in vivo in Cx43 increased expression in PH induced by chronic hypoxia, these NGF/Cx43-dependent mechanisms may therefore play a significant role in human PH pathophysiology.


Subject(s)
Connexin 43 , Myocytes, Smooth Muscle , Nerve Growth Factor , Pulmonary Artery , Animals , Humans , Male , Rats , Cells, Cultured , Connexin 43/metabolism , Gap Junctions/metabolism , Gap Junctions/drug effects , Hypertension, Pulmonary/metabolism , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Nerve Growth Factor/metabolism , Phosphorylation , Pulmonary Artery/drug effects , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Rats, Sprague-Dawley , Rats, Wistar , Receptor, trkA/metabolism
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