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BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve the in vitro biological activities of BMSCs inhibited by high-dose glucocorticoid in vitro. METHODS: In this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins. RESULTS: We observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic ability in vitro. CONCLUSION: Our vitro study showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.
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Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Animais , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Glucocorticoides/toxicidade , Osteogênese , RatosRESUMO
OBJECTIVES: Trigeminal nerve stimulation (TNS) is a promising strategy in treating diseases of the nervous system. In this study, the effects of TNS on traumatic brain injury (TBI) were investigated in a mouse model. MATERIALS AND METHODS: TBI was induced using a weight-drop device, and TNS treatment was delivered in the first hour after the TBI. Twenty-four hours later, the mice's behavior, brain edema, and expression of inflammatory factors were tested. Functional magnetic resonance imaging also was used to explore the possible effects of TNS on brain activity. RESULTS: TNS alleviates TBI-induced neurological dysfunction in animal behavior tests, besides protecting the blood-brain barrier and reducing the level of brain edema. TNS also effectively reduces the level of tumor necrosis factor-α and interleukin 6 and downregulates the cleaved caspase-3 signaling pathway. A series of brain areas was found to be possibly regulated by TNS, thus affecting the neural functions of animals. CONCLUSION: This study elucidates the role of TNS as an effective treatment for TBI by inhibiting the occurrence of a secondary brain injury.
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Edema Encefálico , Lesões Encefálicas Traumáticas , Lesões Encefálicas , Animais , Camundongos , Lesões Encefálicas Traumáticas/terapia , Nervo Trigêmeo/fisiologiaRESUMO
Transforaminal steroid injection is extensively used as a treatment in cases of herniated disc, but it is associated with complications. In comparison, platelet-rich plasma (PRP) injection has been used in musculoskeletal disorders and could be another option. This study is aimed at comparing the efficacy and safety aspects between ultrasound-guided transforaminal injections of PRP and steroid in patients who suffer from radicular pain due to lumbar disc herniation. In a randomized controlled trial, ultrasound-guided transforaminal injections of either PRP (n = 61) or steroid (n = 63) were administered to a total of 124 patients who suffer from radicular pain due to lumbar disc herniation. Patients were assessed by the visual analogue scale (VAS), pressure pain thresholds (PPTs), Oswestry disability index (ODI), and the physical function (PF) and bodily pain (BP) domains of the 36-item short form health survey (SF-36) before operation and 1 week, 1 month, 3 months, 6 months, and 12 months after operation. The rate and latency of F-wave were obtained before operation and 12 months postoperation. There was no statistical difference in terms of age and sex between both groups. Statistically significant improvements from the patients' data before operation to data obtained 1-month postoperation were observed in VAS, PPTs, ODI, and PF and BP of SF-36 in both groups and kept for 1 year. F-wave rate and latency were improved significantly at 1-year postoperation in both groups. Intergroup differences during follow-ups over a period of 1 year were not found to be significant in all the above assessment between the PRP and steroid groups. No complications were reported. The results showed similar outcome for both transforaminal injections using PRP and steroid in the treatment of lumbar disc herniation, suggesting the possible application of PRP injection as a safer alternative. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-17011825).
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Betametasona/uso terapêutico , Deslocamento do Disco Intervertebral/terapia , Vértebras Lombares , Plasma Rico em Plaquetas , Ultrassonografia de Intervenção/métodos , Adulto , Betametasona/administração & dosagem , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ciática/etiologia , Ciática/terapia , Resultado do Tratamento , Escala Visual AnalógicaRESUMO
Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the activation of NF-κB signaling by decreasing the translocation of NF-κB p65 to the nucleus and suppressed the MAPKs signaling pathway via inhibition of the phosphorylation of p38, ERK and JNK. Taken together, these findings suggest that neurotropin exerts anti-inflammatory effects by suppressing the production of pro-inflammatory mediators via inhibition of NF-κB and MAPKs signaling pathways in LPS-stimulated BV-2 cells.
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Lipopolissacarídeos/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/patologia , NF-kappa B/metabolismo , Inflamação Neurogênica/induzido quimicamente , Inflamação Neurogênica/prevenção & controle , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Animais , Anti-Inflamatórios , Células Cultivadas , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Camundongos , Inflamação Neurogênica/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.
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Demência/etiologia , Perda de Dente/psicologia , Adulto , Idoso , Demência/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Razão de Chances , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND: Cystic brain radionecrosis (CBRN) is a late-onset devastating complication after radiotherapy for head and neck neoplasms, especially for nasopharyngeal carcinoma (NPC). To our knowledge, it has scarcely been reported. METHODS: We retrospectively reviewed all available medical records of NPC patients with CBRN who were treated with surgical intervention. RESULTS: Sixteen patients were identified in this study and the mean latency of CBRN was 9.2 ± 0.9 years. The total irradiation dose of the nasopharynx ranged from 60 to 78 Gy. Cyst-like lesions were observed and there were slightly enhancements on the cyst wall in five patients on patients' brain MRI. All the included patients underwent surgical resection of the cystic necrotic lesion thought temporal approach. Specimens from surgery revealed reactive gliosis and immunopositive cytokines including TNF-α, IL-6 and HIF-2α. Only one patient experienced recurrence and received reoperation after surgery. All the other patients made a good recovery and no operation-related mortality was observed. CONCLUSIONS: CBRN is a delayed but irreversible neurological sequel in irradiated NPC patients. Post-radiotherapy follow-up is quite necessary for those with high risk of CBRN. Proper treatment is needed for early CBRN patients to suppress inflammation in the brain. Timely neurosurgery may benefit patients with late-stage CBRN by alleviating increased intracranial pressure and inflammatory responses.
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Encéfalo/patologia , Carcinoma/radioterapia , Cistos/patologia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/etiologia , Adulto , Idoso , Carcinoma/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Necrose , Recidiva Local de Neoplasia/patologia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Observational studies suggested an association between hearing impairment and cognitive disorders. However, whether hearing impairment is an independent risk factor or a harbinger of Alzheimer's disease remains controversial. Our goal was to assess the association between hearing impairment (HI) and the risk of Alzheimer's disease (AD) by conducting a meta-analysis of prospective cohort studies. We comprehensively searched the PubMed, Embase, Web of Science and Cochrane Library databases on January 19, 2016 to incorporate all the prospective cohort studies meeting the inclusion criteria to perform a systematic review and meta-analysis. Four prospective cohort studies with comparison between hearing impairment and normal hearing were incorporated, with 7461 participants. The outcomes of three studies were the incidence of Alzheimer's disease and the outcome of the fourth study was the incidence of mild cognitive impairment. The overall combined relative risk of people with hearing impairment to develop Alzheimer's disease was 4.87 (95% CI 0.90-26.35; p = 0.066), compared with the control group. Since both Alzheimer's disease and mild cognitive impairment are cognitive disorders, we incorporated all the four studies and the overall combined relative risk was 2.82 (95% CI 1.47-5.42; p = 0.002), indicating that the difference was significant. This meta-analysis suggests that hearing impairment significantly increases the risk of cognitive disorders and future well-designed prospective cohort studies are awaited to confirm the association between hearing impairment and risk of Alzheimer's disease.
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Doença de Alzheimer/epidemiologia , Transtornos Cognitivos/epidemiologia , Perda Auditiva/epidemiologia , Doença de Alzheimer/etiologia , Transtornos Cognitivos/etiologia , Perda Auditiva/complicações , HumanosRESUMO
BACKGROUND: Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis that may progress to panniculitis-like T-cell lymphoma. We report a case of CHP that first manifested as bilateral ptosis, which is the first reported case of this presentation. CASE PRESENTATION: A 25-year-old woman without medical history was referred to the neurology department of our hospital for evaluation of bilateral ptosis. Three months previously, she suddenly complained of bilateral ptosis without apparent cause. Simultaneously, non-painful tender subcutaneous nodules and eschar-like skin lesions were observed on her extremities and trunk. A diagnosis of CHP was made based on skin biopsy from the left thigh showing lobular panniculitis, vasculitis, and adiponecrosis, with infiltration of inflammatory cells, including lymphocytes, histiocytes, and phagocytic histiocytes. Her condition continued to worsen with corticosteroid and immunosuppressive agent (thalidomide) treatment. Significant improvement was noticed after three cycles of chemotherapy of THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone). CONCLUSIONS: CHP is a rare condition whose clinical presentation may include bilateral ptosis and biopsy is required for diagnosis of CHP.
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Blefaroptose/etiologia , Histiócitos/fisiologia , Paniculite/complicações , Adulto , Biópsia , Blefaroptose/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Paniculite/diagnóstico , Pele/patologia , Tomografia Computadorizada por Raios X , Acuidade VisualRESUMO
BACKGROUND: Trigeminal nerve stimulation (TNS) has been proposed as a promising intervention for coma awakening. However, the effect of TNS on patients with prolonged disorders of consciousness (pDoC) is still unclear. OBJECTIVE: This study aimed to investigate the therapeutic effects of TNS in pDoC caused by stroke, trauma, and anoxia. METHODS: A total of 60 patients (male =25, female =35) aged over 18 who were in a vegetative state or minimally conscious state were randomly assigned to the TNS (N = 30) or sham TNS (N = 30) groups. 4 weeks of intervention and a followed up for 8 weeks were performed. The Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) scores as primary outcomes were assessed at baseline and at 2, 4, 8, and 12 weeks. RESULTS: The score changes in the TNS group over time for CRS-R (2-week: mean difference = 0.9, 95% CI = [0.3, 1.5], P = 0.006; 4-week: 1.6, 95% CI = [0.8, 2.5], P < 0.001; 8-week: mean difference = 2.4, 95% CI = [1.3, 3.5], P < 0.001; 12-week: mean difference = 2.3, 95% CI = [1.1, 3.4], P < 0.001) and GCS (4-week: mean difference = 0.7, 95% CI = [0.3, 1.2], P = 0.002; 8-week: mean difference = 1.1, 95% CI = [0.6, 1.7], P < 0.001; 12-week: 1.1, 95% CI = [0.5, 1.7], P = 0.003) were higher than those in the sham group. 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) revealed that the metabolism of the right parahippocampal cortex, right precuneus, and bilateral middle cingulate cortex was significantly increased in TNS group. CONCLUSION: The results of this study indicate that TNS could increase local brain metabolism and may promote functional recovery in patients with prolonged disorders of consciousness. REGISTRATION INFORMATION: Name of the registry: Chinese Clinical Trial Registry. REGISTRATION NUMBER: ChiCTR1900025573. The date that the study was submitted to a registry: 2019-09-01. The date when the first patient was enrolled was 2021-01-20.
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Coma , Transtornos da Consciência , Humanos , Masculino , Feminino , Adolescente , Adulto , Resultado do Tratamento , Transtornos da Consciência/terapia , Estado de Consciência/fisiologia , Estado Vegetativo Persistente/terapia , Nervo TrigêmeoRESUMO
Background: Electrical stimulation of the cerebellar fastigial nucleus (FNS) has been shown to protect animals against cerebral ischemic injury. However, the changes in cortical activation as a response to FNS have not been illustrated in humans. Objective: This study aims to detect functional connectivity changes in the brain of stroke patients, and investigate the cortical activation caused by FNS through measuring the oxygenated hemoglobin concentration (HBO) in the cerebral cortex of stroke patients and healthy controls (HCs). Methods: This study recruited 20 patients with stroke and 20 HCs with all the following factors matched: age, gender and BMI. The experiment session was made up of the pre-task baseline, FNS task period, and post-task baseline. FNS task period contains 5 blocks, each block encompassing the resting state (30 s) and the FNS state (30 s). HBO signals were acquired by functional near-infrared spectroscopy (fNIRS) from the Prefrontal Cortex (PFC), the Motor Cortex (MC) and the Occipital Cortex (OC) throughout the experiment. The Pearson correlation coefficient was used to calculate the resting-state functional connectivity strength between the two groups, and the general linear model (GLM) was used to calculate the activation of 39 fNIRS channels during FNS in stroke patients and HCs, respectively. Results: The coupling strength of stroke patients were significantly decreased in the following regions: right MC and left MC (t = 4.65, p = 0.0007), right MC and left OC (t = 2.93, p = 0.04), left MC and left OC (t = 2.81, p = 0.04). In stroke patients, the changes in cerebral oxygenated hemoglobin (ΔHBO) among 12 channels (CH) in the bilateral PFC and bilateral MC regions were significantly increased during the FNS state (FDR corrected p < 0.05) compared with the resting state. In HCs, only 1 channel was increased (FDR corrected p < 0.05) in the left PFC during FNS. Conclusion: By using the FNS and fNIRS techniques, the characteristics of functional connectivity were found to decrease in stroke patients. It was also noticed that FNS activates the PFC and MC regions. These findings may help to guide functional rehabilitation in stroke patients.
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BACKGROUND AND OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients. METHODS: A total of 60 patients aged 40-79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the "group by time" interaction effects. RESULTS: There were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P<0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = -0.82, 95% CI [-1.39, -0.25], P=0.005), WOMAC (mean difference = -4.19, 95% CI [-7.00, -1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported. CONCLUSION: This study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.
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Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a refractory disease. The treatment options for ONFH, especially nonsurgical ones, merit further investigation. To evaluate the combinatorial therapeutic effects of platelet-rich plasma clot releasate (PRCR) and umbilical cord mesenchymal stem cells (UC-MSCs) on glucocorticoid-induced ONFH, a dexamethasone (DEX)-treated cell model and a high-dose methylprednisolone (MPS)-treated rat model were established. Cell counting kit-8 (CCK-8) assay was performed in vitro to determine the optimum dosage of PRCR for UC-MSC viability. The effects of PRCR, UC-MSCs, and PRCR + UC-MSCs on cell viability, apoptosis, migration, and differentiation capacities of DEX-treated bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cell (HUVECs) were explored via Transwell assays. Western blotting was conducted to evaluate the expression levels of RUNX2, VEGF, caspase-3, and Bcl-2 in the coculture systems. Ultrasound-guided intra-articular PRCR, UC-MSCs, and PRCR + UC-MSC injections were performed on the ONFH model rats. Microcomputed tomography, histological and immunohistochemical analyses, tartrate-resistant acid phosphatase (TRAP) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to assess the therapeutic effects of PRCR and UC-MSCs on bone loss and necrosis induced by high-dose MPS. Results of this study revealed that the in vitro application of PRCR, UC-MSCs, and PRCR + UC-MSCs reversed the impaired proliferation and migration capacities and resisted apoptosis of BMSCs and HUVECs induced by DEX. Moreover, the PRCR and UC-MSC application significantly improved the alkaline phosphatase (ALP) and alizarin red (ALR) staining of BMSCs and tube formation capacity of HUVECs and promoted the protein expression of RUNX2 in BMSCs and VEGF in HUVECs. Similarly, in the ONFH rat model, the intra-articular injection of UC-MSCs and PRCR improved the subchondral bone mass parameters; promoted the expression of ALP, RUNX2, and VEGF; suppressed osteoclast overactivity; and resisted cell apoptosis. The combination of PRCR and UC-MSCs shows promising therapeutic effects in treating glucocorticoid-induced ONFH. The current study provides important information on intra-articular therapy, paving the way for the clinical management of ONFH in the future.
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BACKGROUND: Cricopharyngeal muscle dysfunction (CPD) management has been challenging in clinical practice. OBJECTIVE: To compare the efficacy and safety of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in treating CPD. METHODS: Forty patients with CPD were randomly divided into two groups, namely the botulinum toxin injection group (BTX group) and balloon dilatation group (BD group). Patients in the BTX group received a single ultrasound-guided injection of 50 units of botulinum toxin type A, while the BD group received dilatation therapy five times per week, consecutively for two weeks. Relative opening percentage of the upper esophageal sphincter (UES), the penetration-aspiration scale (PAS), and the Dysphagia Outcome Severity Scale (DOSS) were evaluated by a videofluoroscopic swallowing study (VFSS) at baseline, 1-month, and 3-months posttreatment. The Functional Oral Intake Scale (FOIS) and Standardized Swallowing Assessment (SSA) were also used to evaluate participants' swallowing function at baseline and the 1-week, 2-week, 1-month, and 3-month follow-ups. RESULTS: A generalized estimating equation (GEE) model revealed the significant main effect for time in UES, PAS, DOSS, FOIS, and SSA compared to baseline (P <0.05), while no group-by-time interactions (except for the PAS assessment) or main effect for treatment was detected among the above multiple variances. No systematic complications or severe adverse effects were noted. CONCLUSION: Both ultrasound-guided botulinum toxin type A injections and balloon dilatation therapy have been proven as safe and effective treatments for CPD patients. Future clinical trials with longer follow-up periods and more participants are warranted.
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Toxinas Botulínicas Tipo A , Transtornos de Deglutição , Toxinas Botulínicas Tipo A/uso terapêutico , Catéteres , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Dilatação , Esfíncter Esofágico Superior , Humanos , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness. METHODS: Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Microarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH). RESULTS: TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities. Then we proved that LH activation and upregulated neuropeptide hypocretin are beneficial for promotion of consciousness recovery. We then applied gene microarray experiment and found hypocretin might be mediated by a well-known transcription factor Early growth response gene 1 (EGR1), and the results were confirmed by ChIP and Dual-luciferase reporter experiment. CONCLUSION: This study illustrates that TNS is an effective arousal strategy Treatment for LOC state via the activation of Sp5 and LH neurons and upregulation of hypocretin expression.
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Terapia por Estimulação Elétrica/métodos , Neurônios/fisiologia , Nervo Trigêmeo/fisiopatologia , Inconsciência/terapia , Animais , Nível de Alerta/fisiologia , Comportamento Animal/fisiologia , Eletroencefalografia , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Inconsciência/fisiopatologiaRESUMO
Glioblastoma Multiforme (GBM) is the most frequent glioma with a poor prognosis. The mainstay treatment for GBM is chemotherapy, but the average survival of GBM remains unsatisfactory due to therapeutic resistance. Poor permeability restricted by the Blood Brain Barrier (BBB) and the presence of Glioblastoma Stem Cells (GSCs) remain as two problems for chemotherapy. Recently, nanocarriers have attracted much attention in the research of GBM, owing to their advantages in self-assembly, biosafety, release controllability, and BBB penetrability, making them promising candidates for GBM treatment. This article aims to review the biologic signatures of BBB and GSCs, as well as the new development of nano-drug delivery systems to facilitate our understanding of targeted treatment for GBM.
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Antineoplásicos/uso terapêutico , Glioblastoma/tratamento farmacológico , Nanopartículas/química , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismoRESUMO
Alzheimer's disease (AD) is a devastating neurodegenerative disease with limited treatments and no cure. Neurotropin (NTP) is an analgesic drug widely prescribed for neuropathic pain. Increasing evidence suggests that NTP may also protect against neurodegeneration, but NTP's treatment potential against memory impairments of AD remains to be explored. APP/PS1 mice, which model AD, were given NTP for three months then cognitively tested with the Morris water maze. Their Aß burden, microglial and astrocytic activation, and BDNF levels were compared to untreated controls using immunofluorescent staining. Expression of pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and NF-κB pathway related proteins (p65 and IκB-α) were examined by ELISA or Western blots in vivo and in vitro in the microglia cell line. Lastly, BV-2 cells were pre-treated with the selective BDNF inhibitor ANA-12 and with NTP to examine mechanistic pathways. Taken together, NTP treatment reduced cognitive impairment, Aß deposits, and glial activation in cortex and hippocampus APP/PS1 mice. IL-1ß, IL-6 and TNF-α also decreased after NTP treatment in vivo and in vitro, and BDNF levels rose. Also, NTP reduced p65 and IκB-α activation and the effect of NTP on pro-inflammatory cytokines and NF-κB pathway related proteins was abolished by BDNF inhibitor. Our results indicate that NTP reduces neuroinflammation and improves the cognitive deficits in APP/PS1 mice possibly via BDNF/NF-κB pathway. NTP may be a new promising drug candidate for patients with AD.
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Neuroinflammation is a complex pathological process usually results from abnormal microglial activation, thus, intervention in a microglial stimulation pathway could be a promising approach for the treatment of neurodegenerative diseases. Luteolin is an important bioflavonoid possesses anti-inflammatory properties, which is widely studied over these years. Light emitting diode (LED) therapy is reported to be a potential therapeutic strategy for many diseases including neurodegenerative diseases. However, little is known about the anti-inflammatory effect of LED therapy on activated microglial cells, even less is known whether there is a synergistic anti-inflammatory effect exist in LED and luteolin therapy. In this study, we aimed to confirm the anti-inflammatory effect of luteolin and LED combination therapy in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. We showed that luteolin inhibited LPS-induced cytotoxicity, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) production through modulation of p38 and extracellular signal-regulated kinase (ERK) signaling in BV2 cells. In addition, LED therapy enhanced the anti-inflammatory effect of luteolin. These results suggest that a synergistic effect between luteolin and LED could be a new effective therapy in relieving neuroinflammation.
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Radiotherapy (RT) serves as the most efficient treatment for nasopharyngeal carcinoma (NPC) and can cause carotid stenosis. This work compared the incidence of significant carotid stenosis between intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-RT) for NPC and explored the risk factors. We retrospectively reviewed 233 cases with NPC who underwent carotid ultrasound post IMRT or 2D-RT from 2006 to 2015. The incidence of significant stenosis after RT was 19.3%. Significant stenosis was identified in 20 (14.6%) of 137 patients treated with IMRT and 25 (26.0%) of 96 patients with 2D-RT, respectively (p = 0.035). Multivariate logistic analysis indicated age (odds ratio = 1.054, 95% CI = 1.011-1.099, p = 0.014), radiation technique (IMRT) (odds ratio = 0.471, 95%CI = 0.241-0.919, p = 0.027) and time interval (odds ratio = 1.068, 95%CI = 1.033-1.105, p = 0.001) as independent predictors for significant carotid stenosis. Our study suggests that IMRT was associated with decreased incidence of significant carotid stenosis versus 2D-RT for NPC. Prevention and carotid ultrasound should be considered for older NPC survivors with longer interval from RT, especially those treated with 2D-RT.
Assuntos
Estenose das Carótidas/etiologia , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Alzheimer's disease is a neurodegenerative disorder mainly characterized by ß-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer's disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal ß-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer's disease.