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1.
Pak J Med Sci ; 40(4): 617-622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545000

RESUMO

Objective: To explore relevant influencing factors of the prognosis of patients with winter sports-induced traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema after emergency surgical treatment. Methods: A retrospective analysis was performed on 73 cases of traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema in The First Hospital Affiliated to Hebei North University from January 2020 to October 2022. The enrolled patients were divided into the good prognosis (n=17) group and poor prognosis (n=56) group according to the recovery of neurological function after six months of follow-up. The risk factors affecting the prognosis of patients with traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema after emergency surgery were analyzed by binary Logistic regression. Results: Among the enrolled 73 patients with traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema, 56 cases showed significant improvement in ASIA Grade-6 months after operation, with an improvement rate of 76.71%. Further Logistic regression analysis revealed that concomitant diabetes, preoperative MSCC>40.83% and recovery rate of AMS <40.13% 3d after operation were independent risk factors affecting the poor prognosis of patients with traumatic cervical spinal cord injury complicated with intramedullary hemorrhage and edema. Conclusions: Emergency surgery can improve the neurological function of patients with cervical spinal cord injury complicated with intramedullary hemorrhage and edema caused by winter sports. Concomitant diabetes, preoperative MSCC and recovery rate of AMS 3d after operation are the main factors affecting the prognosis of patients with emergency surgery.

2.
Open Life Sci ; 18(1): 20220690, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671100

RESUMO

Alzheimer's disease (AD) is a relatively common senile neurodegenerative disease and the main manifestation of senile dementia. In the pathological changes of AD, the asymmetry of the brain also changes. Therefore, finding an early diagnosis method of AD based on asymmetry is the key to the treatment of Alzheimer's. Magnetic resonance (MR) imaging can quantitatively reflect the structural and functional changes of various tissues in the brain. It has the advantages of non-invasive, high spatial resolution, and non-radiation, and has been widely used in the early diagnosis of AD. In this work, asymmetric images were extracted from multiple brain MR images, and different morphological and texture features were extracted. By establishing a feature selection classification integration model, image features in the image were deeply fused to obtain higher and more stable recognition results than before. By filtering image samples, the corresponding sample feature matrix was obtained. Support vector machine was used for classification, and its classification accuracy had improved significantly compared with that before selection. In the experimental data of normal control group and AD group, the accuracy, sensitivity, and specificity of the feature selection algorithm were 93.34, 90.69, and 95.87%, respectively. In the normal control group and the mild cognitive impairment group, the accuracy, sensitivity, and specificity of the feature selection algorithm in this work were 85.31, 79.68, and 88.54%, respectively. On the whole, the classification accuracy of the feature selection algorithm in this work was much higher than that of other items. In addition, from the classification ability and distribution of asymmetric features, it can be seen that this asymmetric feature had a more significant consistent diagnostic role in clinical practice.

3.
Brief Bioinform ; 24(2)2023 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-36880207

RESUMO

Protein-protein interactions (PPIs) carry out the cellular processes of all living organisms. Experimental methods for PPI detection suffer from high cost and false-positive rate, hence efficient computational methods are highly desirable for facilitating PPI detection. In recent years, benefiting from the enormous amount of protein data produced by advanced high-throughput technologies, machine learning models have been well developed in the field of PPI prediction. In this paper, we present a comprehensive survey of the recently proposed machine learning-based prediction methods. The machine learning models applied in these methods and details of protein data representation are also outlined. To understand the potential improvements in PPI prediction, we discuss the trend in the development of machine learning-based methods. Finally, we highlight potential directions in PPI prediction, such as the use of computationally predicted protein structures to extend the data source for machine learning models. This review is supposed to serve as a companion for further improvements in this field.


Assuntos
Aprendizado de Máquina , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Proteínas/metabolismo , Biologia Computacional/métodos
4.
J Ultrasound Med ; 42(2): 363-371, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35841273

RESUMO

OBJECTIVES: Our study aimed to develop and validate an efficient ultrasound image-based radiomic model for determining the Achilles tendinopathy in skiers. METHODS: A total of 88 feet of skiers clinically diagnosed with unilateral chronic Achilles tendinopathy and 51 healthy feet were included in our study. According to the time order of enrollment, the data were divided into a training set (n = 89) and a test set (n = 50). The regions of interest (ROIs) were segmented manually, and 833 radiomic features were extracted from red, green, blue color channels and grayscale of ROIs using Pyradiomics, respectively. Three feature selection and three machine learning modeling algorithms were implemented respectively, for determining the optimal radiomics pipeline. Finally, the area under the receiver operating characteristic curve (AUC), consistency analysis, and decision analysis were used to evaluate the diagnostic performance. RESULTS: By comparing nine radiomics analysis strategies of three color channels and grayscale, the radiomic model under the green channel obtained the best diagnostic performance, using the Random Forest selection and Support Vector Machine modeling, which was selected as the final machine learning model. All the selected radiomic features were significantly associated with the Achilles tendinopathy (P < .05). The radiomic model had a training AUC of 0.98, a test AUC of 0.99, a sensitivity of 0.90, and a specificity of 1, which could bring sufficient clinical net benefits. CONCLUSIONS: Ultrasound image-based radiomics achieved high diagnostic performance, which could be used as an intelligent auxiliary tool for the diagnosis of Achilles tendinopathy.


Assuntos
Tendão do Calcâneo , Tendinopatia , Humanos , Tendão do Calcâneo/diagnóstico por imagem , Tendinopatia/diagnóstico por imagem , Algoritmos , , Algoritmo Florestas Aleatórias , Estudos Retrospectivos
5.
J Back Musculoskelet Rehabil ; 36(1): 71-77, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35988214

RESUMO

BACKGROUND: Acute central cord syndrome (ACCS) without fractures or dislocations is the most common form of incomplete spinal cord injury. OBJECTIVE: To evaluate the effectiveness of different surgical methods in the treatment of acute central cord syndrome without fractures or dislocations of the cervical spine. METHODS: A total of 164 patients with ACCS without fracture or dislocation of the cervical spine treated in our hospital from May 2012 to October 2019 were recruited and assigned to study group A and study group B according to different treatment modalities, with 82 cases in each group. Study group A underwent anterior cervical discectomy and fusion, and study group B was treated with posterior cervical laminectomy. The American Spinal Injury Association (ASIA) classification and motor scores of all cases at admission and at discharge were recorded, and the treatment outcomes of the two groups were compared. RESULTS: No significant differences were found in the ASIA classification and ASIA motor scores between the two groups at admission (P> 0.05). One year after surgery, the ASIA motor scores and sensory scores were not statistically significant between the two groups (P> 0.05) but showed significant improvement compared to the preoperative scores (P< 0.05). CONCLUSION: Both anterior cervical discectomy and fusion and posterior cervical laminectomy can improve the ASIA classification, ASIA motor scores, and sensory scores of ACCS patients without fractures or dislocations of the cervical spine. Therefore, surgical methods should be adopted based on the patients' conditions.


Assuntos
Síndrome Medular Central , Fraturas Ósseas , Luxações Articulares , Fraturas da Coluna Vertebral , Humanos , Síndrome Medular Central/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Luxações Articulares/cirurgia , Resultado do Tratamento , Vértebras Cervicais/cirurgia , Estudos Retrospectivos
6.
Comput Math Methods Med ; 2022: 8216339, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213573

RESUMO

This study is aimed at investigating the efficacy of anterior cervical corpectomy and fusion and posterior total laminectomy in the treatment of cervical spinal cord injury and assessing the impact of the two approaches on cervical spine function and patient quality of life. Retrospectively analyze the clinical data from 180 patients with cervical spinal cord injury who were admitted to the First Affiliated Hospital of Hebei North University from June 2019 to June 2021. The patients were divided into an anterior approach group (n = 89, treated with anterior cervical corpectomy and fusion) and a posterior approach group (n = 91, treated with posterior total laminectomy). The amount of blood loss in the posterior approach group was larger compared to the anterior approach group. Patients in the posterior approach group had higher wound diameters and operation times compared to the anterior approach group, as well as the operation cost. The visual analogue scale (VAS) scores of patients in the posterior approach group were significantly higher than in the anterior approach group one month after operation. The Japanese Orthopaedic Association (JOA), neck disability index (NDI), and American Spinal Injury Association (ASIA) scores of patients in both groups at 1, 6, and 9 months after surgery were higher compared to those before surgery, yet no significant differences were observed between the two groups. Also, no significant difference was observed in the incidence of complication and the quality of life between the two groups before and after treatment. Anterior cervical corpectomy and fusion and posterior total laminectomy can effectively restore the cervical nerve function in the treatment of cervical spinal cord injury. However, anterior subtotal vertebral resection is associated with improved perioperative indicators compared to posterior total laminectomy. Clinically, surgical methods can be selected according to imaging findings, the general condition of patients, and individual economic status.


Assuntos
Medula Cervical , Traumatismos da Medula Espinal , Fusão Vertebral , Medula Cervical/cirurgia , Vértebras Cervicais/cirurgia , Humanos , Laminectomia/métodos , Qualidade de Vida , Estudos Retrospectivos , Traumatismos da Medula Espinal/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Resultado do Tratamento
7.
Comput Math Methods Med ; 2022: 6088398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35132331

RESUMO

BACKGROUND: Short-track speed skating (STSS) is an extreme sport in pursuit of extreme speed and explosive force. In such a sport, once athletes fall down, they are susceptible to serious cervical spine injury (CSI) under the inertia of high-velocity movement. Nanohydroxyapatite/polyamide 66 (NHP66) bioactive cage is a high-tech product of nanotechnology in the medical field in recent years. With a structure similar to that of human cortical bone, NHP66 bioactive cage has extremely high toughness and strength, which tailors to the needs of STSS. OBJECTIVE: This study mainly analyzed the therapeutic effect of NHP66 on patients with CSI in STSS, aiming to provide new opportunities for the treatment of this patient population. METHODS: A total of 51 patients with CSI treated in our hospital were enrolled, including 19 cases of short-track speed skaters (observation group) and 32 cases of car accidents, falls from heights, or collision injuries (control group). The relevant surgical indicators (operation time, intraoperative blood loss, etc.), the incidence of adverse reactions, the Cobb angle of cervical lordosis before and after surgery, and the fusion segment height of the cage were observed and compared between the two groups. Postoperative pain was evaluated by the visual analog scale (VAS), improvement of spinal cord injury was assessed by the American Spinal Cord Injury Association (ASIA) Impairment Scale, and bone fusion, bone subsidence, and other motor functions were assessed by the Japanese Orthopaedic Association (JOA) score rating system. RESULTS: The operation time, intraoperative blood loss, and incidence of adverse reactions in the observation group were significantly lower than those in the control group. The Cobb angle of cervical lordosis and the fusion segment height of cage increased significantly higher in both groups after surgery. In addition, the VAS scores of the observation group 2 h and 3 d after operation were significantly lower than those of the control group. In terms of improvement of spinal cord injury, ASIA and JOA scores in the observation group were significantly higher than those before treatment and in the control group. There was no significant difference in bone fusion activity between the two groups. CONCLUSIONS: In this study, it is found through experiments that NHP66 has higher safety and application value than autogenous iliac bone, confirming that NHP66 can achieve significant results as a cage for anterior cervical decompression and iliac bone graft fusion and internal fixation in short-track speed skaters after CSI.


Assuntos
Traumatismos em Atletas/cirurgia , Substitutos Ósseos , Vértebras Cervicais/lesões , Vértebras Cervicais/cirurgia , Patinação , Fraturas da Coluna Vertebral/cirurgia , Adulto , Substitutos Ósseos/administração & dosagem , Substitutos Ósseos/química , Biologia Computacional , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Durapatita/administração & dosagem , Durapatita/química , Feminino , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia , Nylons/química , Adulto Jovem
8.
Drug Des Devel Ther ; 15: 4733-4740, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34848945

RESUMO

OBJECTIVE: The purpose of this study was to determine the clinical value of triple antibiotic therapy consisting of doxycycline, compound sulfamethoxazole and rifampicin in the treatment of brucellosis spondylitis. METHODS: A retrospective analysis was performed on 100 patients with brucellosis spondylitis admitted to the First Affiliated Hospital of Hebei North University from March 2016 to June 2019. Patients were divided into the following two groups: the control group (n = 50) treated with dual antibiotic therapy (rifampicin + compound sulfamethoxazole), and the observation group (n = 50) treated with triple antibiotic therapy (rifampicin + doxycycline + compound sulfamethoxazole). The treatment effect, low back pain relief, levels of erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and C-reactive protein (CRP), as well as the adverse reactions were compared between the two groups. RESULTS: The response rate of the observation group was significantly higher than that of the control group (P < 0.05). Before treatment, there was no significant difference in the low back pain assessed by the visual analogue scale (VAS), or levels of ESR, PCT and CRP between the two groups (P > 0.05). But after treatment, the VAS score and the levels of ESR, PCT and CRP in observation group were lower than those in the control group (P < 0.05). No significant difference was found in the incidence of adverse reactions (P > 0.05). CONCLUSION: The triple antibiotic therapy of doxycycline, compound sulfamethoxazole and rifampicin is effective in the treatment of brucellosis spondylitis. It can significantly alleviate patients' back pain and inflammation with a high safety profile, which is worthy of clinical application.


Assuntos
Brucelose/tratamento farmacológico , Doxiciclina/uso terapêutico , Rifampina/uso terapêutico , Espondilite/tratamento farmacológico , Sulfametoxazol/uso terapêutico , Adulto , Brucelose/metabolismo , Doxiciclina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Dor Lombar/tratamento farmacológico , Dor Lombar/metabolismo , Masculino , Estudos Retrospectivos , Rifampina/administração & dosagem , Espondilite/metabolismo , Sulfametoxazol/administração & dosagem
9.
Am J Transl Res ; 13(9): 10341-10347, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650701

RESUMO

OBJECTIVE: To investigate the changes in the heart rates and the clinical effectiveness of aminophylline injections in acute cervical spinal cord injury (ACSCI) patients with bradycardia. METHODS: This retrospective study was conducted by studying the clinical data of 100 ACSCI patients also suffering from bradycardia admitted to our hospital from June 2019 to June 2020. The patients were randomly placed into a control group (n=50) that was administered atropine therapy and a test group (n=50) that was administered aminophylline injections. The changes in the patients' heart rates and the clinical effectiveness were analyzed. RESULTS: After the treatment, the test group had a significantly higher average heart rate, shorter heart rate recovery times, and a lower bradycardia recurrence rate than the control group (all P<0.05). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in the test group were significantly higher than they were in the control group (all P<0.05). Remarkably higher clinical effectiveness and satisfaction rates and a significantly lower incidence of adverse reactions were observed in the test group compared to the control group (all P<0.05). In addition, the Japanese Orthopaedic Association (JOA) cervical spine scores were similar in the two groups (P>0.05). CONCLUSION: For ACSCI patients also suffering from bradycardia, aminophylline injections ameliorate the clinical heart rate and have a good clinical effectiveness with few adverse reactions, so the treatment merits clinical promotion and application.

10.
Am J Transl Res ; 13(6): 7008-7014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306456

RESUMO

OBJECTIVE: To explore the effect of synchronized and integrated prehospital treatment strategies for on-site first aid, rescue transport and prehospital first aid in patients with acute cervical spinal cord injury. METHODS: A prospective non-randomized controlled study was designed to include patients with acute cervical spinal cord injury. A total of 50 patients were included in a Control group (before the implementation of synchronized and integrated prehospital treatment), and 50 patients were included in an Observation Group (after the implementation of synchronized and integrated prehospital treatment). We compared the timeliness of prehospital treatment, the proportion of patients received methylprednisolone treatment within 3 h after injury, the changes in Japanese Orthopaedic Association (JOA) score during transport, the incidence of adverse events, the clinical outcomes, the number of prehospital deaths, the case number of paralysis and the recovery of postoperative neural function between the two groups. RESULTS: Compared with the Control group, the Observation group showed significantly shorter time from injury to admission, from injury to receiving methylprednisolone pulse therapy, as well as from injury to receiving dehydrating agents and diuretics (all P<0.001). The proportion of patients received methylprednisolone treatment within 3 h after injury was significantly higher in the Observation group than that in the Control group (P<0.05). There was no significant change in the JOA score in the Observation group before and after the transport, while the score was significantly lower in the Control group after the transport (P<0.001). The JOA score was higher in the Observation group than that in the Control group at admission (P<0.001). The Observation group also showed decreased incidences of adverse events, mortality, and paralysis rate (all P<0.05) as well as better recovery of postoperative neural function (P<0.001) when compared with the Control group. CONCLUSION: Synchronized and integrated prehospital treatment has a significant effect in patients with acute cervical spinal cord injury through shortening the admission time, reducing the risk of adverse events, and improving the rescue effect and the prognosis of neural function.

11.
Am J Transl Res ; 13(5): 5051-5058, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150091

RESUMO

PURPOSE: To investigate the feasibility of multidisciplinary model of damage control (MMDC) in patients with acute cervical spinal cord injury (ACSCI) in winter Olympic sports. METHODS: A total of 110 patients with ACSCI who participated in winter Olympic sports were selected as the study subjects, and were divided into the study group (SG, n=60, MMDC) and the control group (CG, n=50, conventional intervention) according to the intervention mode. The clinical effects of intervention, changes in neurological function and muscle tone before and after intervention, the changes in motor function and activity of daily living during intervention, and patient satisfaction towards intervention were compared between the two groups. RESULTS: The effective rate of intervention in the SG was 98.33%, higher than 88.00% in the CG (P < 0.05), and the percentage of patients with Grade E injuries in the SG after intervention was 30.00%, significantly higher than 12.00% in the CG (P < 0.05). The scores of all dimensions of Ashworth scale in the SG were lower than those in the CG (P < 0.05). The patients in the SG exhibited higher FMA scale and modified Barthel index (MBI) scores than the CG from 1 to 6 months of intervention (P < 0.05). CONCLUSION: MMDC showed better efficacy, the patients' neurological function, muscle tone and motor function could be better restored, and patients' abilities of daily activities were improved after intervention.

12.
Spine J ; 18(12): 2323-2332, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30121323

RESUMO

BACKGROUND CONTEXT: Spondylitis is a rare infection in bone requiring multiple diagnostic strategies for verification. PURPOSE: This study aimed to compare the diagnostic values of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) in detecting spondylitis. METHODS: Online PubMed, Embase, and Cochrane Library databases were systematically searched through September 2017 for studies comparing the diagnostic values of 18F-FDG-PET and MRI. The summary sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve were calculated using Stata software. The ratio of these indexes between 18F-FDG-PET and MRI was also determined. RESULTS: The summary results for 18F-FDG-PET were as follows: sensitivity=0.96 [95% confidence intervals (CI), 0.84-0.99]; specificity=0.90 (95% CI, 0.79-0.96); PLR=9.83 (95% CI, 4.39-22.03); NLR=0.05 (95% CI, 0.01-0.19); DOR=124.08 (95% CI, 39.04-394.34); and area under the SROC=0.97 (95% CI, 0.95-0.98). The summary sensitivity, specificity, PLR, NLR, DOR, and area under the SROC for MRI were 0.76 (95% CI, 0.65-0.84), 0.62 (95% CI, 0.45-0.77), 2.01 (95% CI, 1.36-2.98), 0.39 (95% CI, 0.27-0.56), 5.08 (95% CI, 2.66-9.69), and 0.77 (95% CI, 0.73-0.80), respectively. The summary results of sensitivity (p=.034), specificity (p=.006), PLR (p<.001), DOR (p<.001), and area under the SROC (p<.001) were higher in 18F-FDG-PET than in MRI. However, NLR (p=.003) was lower in 18F-FDG-PET than in MRI. CONCLUSIONS: 18F-FDG-PET had a higher diagnostic value compared with MRI in detecting spondylitis.


Assuntos
Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Espondilite/diagnóstico por imagem , Feminino , Humanos , Razão de Chances , Curva ROC , Sensibilidade e Especificidade
13.
Int J Biochem Cell Biol ; 84: 22-34, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28064010

RESUMO

Endothelial dysfunction caused by endothelial cells senescence and chronic inflammation is tightly linked to the development of cardiovascular diseases. NLRP3 (NOD-like receptor family pyrin domain-containing3) inflammasome plays a central role in inflammatory response that is associated with diverse inflammatory diseases. This study explores the effects and possible mechanisms of NLRP3 inflammasome in endothelial cells senescence. Results show an increment of pro-inflammatory cytokine interleukin (IL) -1ß secretion and caspase-1 activation during the senescence of endothelial cells induced by bleomycin. Moreover, secreted IL-1ß promoted endothelial cells senescence through up-regulation of p53/p21 protein expression. NLRP3 inflammasome was found to mediate IL-1ß secretion through the production of ROS (reactive oxygen species) during the senescence of endothelial cells. Furthermore, the association of TXNIP (thioredoxin-interacting protein) with NLRP3 induced by ROS promoted NLRP3 inflammasome activation in senescent endothelial cells. In addition, the expressions of NLRP3 inflammasome related genes, ASC (apoptosis associated speck-like protein containing a CARD), TXNIP, cleaved caspase-1 and IL-1ß, were also increased in vitro and in vivo studies. These findings indicate that endothelial senescence could be mediated through ROS and NLRP3 inflammasome signaling pathways, suggesting a potential target for the prevention of endothelial senescence-related cardiovascular diseases.


Assuntos
Proteínas de Transporte/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Aorta/metabolismo , Aorta/patologia , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Bleomicina/toxicidade , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Cardiovasculares , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Tiorredoxinas/metabolismo
14.
Cell Prolif ; 50(2)2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27878894

RESUMO

OBJECTIVES: To reveal whether B-myb is involved in preventing senescence of vascular endothelial cells, and if so, to identify possible mechanisms for it. MATERIALS AND METHODS: C57/BL6 male mice and primary human aortic endothelial cells (HAECs) were used. Bleomycin was applied to induce stress-related premature senescence. B-myb knockdown was achieved using an siRNA technique and cell senescence was assessed using the senescence-associated ß-galactosidase (SA-ß-gal) assay. Intracellular reactive oxygen species (ROS) production was analysed using an ROS assay kit and cell proliferation was evaluated using KFluor488 EdU kit. Capillary tube network formation was determined by Matrigel assay. Expressions of mRNA and protein levels were detected by real-time PCR and western blotting. RESULTS: B-myb expression significantly decreased, while p53 and p21 expressions increased in the aortas of aged mice. This expression pattern was also found in replicative senescent HAECs and senescent HAECs induced by bleomycin. B-myb knockdown resulted in upregulation of p22phox , ROS accumulation and cell senescence of HAECs. Downregulation of B-myb significantly inhibited cell proliferation and capillary tube network formation and activated the p53/p21 signalling pathway. Blocking ROS production or inhibiting p53 activation remarkably attenuated SA-ß-gal activity and delayed cell senescence induced by B-myb-silencing. CONCLUSION: Downregulation of B-myb induced senescence by upregulation of p22phox and activation of the ROS/p53/p21 pathway, in our vascular endothelial cells, suggesting that B-myb may be a novel candidate for regulating cell senescence to protect against endothelial senescence-related cardiovascular diseases.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/fisiologia , Células Endoteliais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Transativadores/metabolismo , Animais , Senescência Celular/fisiologia , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/fisiologia , Proteína Supressora de Tumor p53/metabolismo
15.
Hum Immunol ; 76(10): 775-80, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26429311

RESUMO

Cell-cell communication depends on cytokine and growth factor network. Bound to their receptors on the surface of target cell, these glycoproteins initiate a range of intracellular events. Subsequent dissipation of receptor signaling is essential to ensure the response of the cell does not become pathogenic. The Suppressors of cytokine signaling (SOCS) proteins are a family of proteins induced to attenuate cytokine signal transduction in response to signals from a diverse range of cytokines and growth factors. Current evidence indicates that intracellular JAK-STAT (Janus kinase-signal transducer and activator of transcription) signaling not only governs cytokine-induced immunological responses but also rapidly initiates SOCS expression and its biological functions. This review focuses on current understanding of SOCS3, a member of SOCS family. SOCS3 binds to JAK, certain cytokine receptors in intracellular domain, and some signaling molecules, which results in suppressing further signaling events in the cell. Studies using conditional knockout mice have shown that SOCS3 protein is the key physiological regulator and plays an important pathological role in immune homeostasis. Dysregulation of SOCS3 functions can cause a variety of diseases, including allergy, autoimmune diseases, inflammation and cancer.


Assuntos
Artrite Reumatoide/genética , Asma/genética , Doenças Inflamatórias Intestinais/genética , Esclerose Múltipla/genética , Neoplasias/genética , Proteínas Supressoras da Sinalização de Citocina/genética , Animais , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Asma/imunologia , Asma/patologia , Comunicação Celular/imunologia , Regulação da Expressão Gênica , Humanos , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Janus Quinases/genética , Janus Quinases/imunologia , Camundongos , Camundongos Knockout , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Neoplasias/imunologia , Neoplasias/patologia , Ligação Proteica , Receptores de Citocinas , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/imunologia , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/imunologia
16.
Inflammation ; 37(3): 880-92, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24408010

RESUMO

The 6-kDa early secretory antigenic target (ESAT-6) of Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. To understand the role of ESAT-6 in macrophage response against M. tuberculosis, the effects of ESAT-6 on macrophage generation of reactive oxygen species (ROS) and production of cytokines were studied. ESAT-6-induced macrophage secretion of monocyte chemoattractant protein-1 and TNF-α was found in a time- and dose-dependent manner. Signaling inhibition experiments indicate that NF-κB activation mediated by p38/JNK mitogen-activated protein kinase (MAPK) was involved in ESAT-6-triggered cytokine production. Moreover, TLR2 was engaged in ESAT-6-stimulated macrophage activation via rapidly induced ROS production and regulated activation of JNK/p38 MAPKs and NF-κB. More importantly, NADPH oxidase-mediated ROS generation is required during this process. Our study has identified a novel signal transduction pathway involving NADPH-ROS-JNK/p38-NF-κB in ESAT-6-induced cytokine production from macrophages. These findings provide an important evidence to understand the pathogenesis of M. tuberculosis infection in the modulation of the immune response.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Macrófagos/imunologia , Mycobacterium tuberculosis/imunologia , NADPH Oxidases/genética , Espécies Reativas de Oxigênio/imunologia , Animais , Linhagem Celular , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Quinase I-kappa B/imunologia , Proteínas Quinases JNK Ativadas por Mitógeno/imunologia , Sistema de Sinalização das MAP Quinases , Ativação de Macrófagos/imunologia , Camundongos , Interferência de RNA , RNA Interferente Pequeno , Receptor 2 Toll-Like/imunologia , Fator de Transcrição RelA/antagonistas & inibidores , Fator de Transcrição RelA/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
17.
Inflamm Res ; 63(1): 33-43, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24121974

RESUMO

OBJECTIVE: IL-1ß is a master switch of inflammation and plays an important role in the pathogenesis of vascular disease. During early atherosclerosis development, it is not clearly understood how oxidized low density lipoprotein (oxLDL)induced signaling pathways control NLRP3 inflammasome activation and produce IL-1ß and promote foam cells formation. METHODS: The study used THP-1 macrophage as cell model. Western blot quantified the oxLDL-induced NLRP3 inflammasome related proteins. The FACS detected the expression of SR-A and CD36 receptors on the cells, and caspase-1 activation in the cells. The DCFH-DA assayed the reactive oxygen species (ROS). Oil red O staining techniques examined the intracellular lipid droplet. RESULTS: The OxLDL remarkably increased not only IL-1ß mRNA transcription and pro-IL-1ß protein synthesis but also IL-1ß secretion in human macrophages. The activation of the NLRP3 inflammasome depended on oxLDL-induced generation of ROS, potassium efflux and cathepsin B activity. The OxLDL-induced ROS production that mediates IL-1ß maturation mainly depended on the scavenger receptor of CD36 but not SR-A. The secreted IL-1ß served as an autocrine function for promoting macrophage foam cells formation. CONCLUSIONS: These findings suggest that oxLDL-induced NLRP3 inflammasome activation mainly depends on CD36 involved in the progression of atherosclerosis by promoting oxLDL-mediated inflammation and foam cell formation.


Assuntos
Antígenos CD36/genética , Proteínas de Transporte/genética , Células Espumosas/citologia , Inflamassomos/genética , Lipoproteínas LDL/farmacologia , Caspase 1/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/citologia , Macrófagos/citologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Receptores Depuradores Classe A/genética
18.
Eur J Cell Biol ; 92(4-5): 150-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23498167

RESUMO

Interleukin-10 (IL-10) may have therapeutic potential in various inflammatory diseases, including atherosclerosis, as it can inhibit oxLDL-induced foam cell formation and apoptosis in macrophages. This study investigated the effect of IL-10 on mitogen-activated protein kinase (MAPK) activation, and apoptosis induced by oxidized low-density lipoprotein (oxLDL) in cultured human umbilical vein endothelial cells (HUVEC). The results demonstrated that IL-10 significantly blocked the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) and apoptosis induced by oxLDL. The inhibitory effect of IL-10 on oxLDL-induced apoptosis was partially dependent on reduced p38, but not JNK, phosphorylation. This study also discovered a linkage between IL-10 and p38 MAPK signaling in oxLDL-induced endothelial cell apoptosis. Interestingly, this study found that lectin-like oxidized LDL receptor-1 (LOX-1) was the only scavenger receptor, on the surface of HUVEC, that was upregulated by oxLDL and the increase in LOX-1 was not suppressed by IL-10. This study confirmed that IL-10 significantly upregulated the expression of suppressor of cytokine signaling-3 (SOCS3), whereas SOCS3 knockdown by siRNA effectively blocked the inhibitory effect of IL-10 on p38 MAPK-dependent apoptosis induced by oxLDL. These results showed for the first time, that IL-10 modulated oxLDL-induced apoptosis by upregulating SOCS3, which then interrupted p38 MAPK activation in endothelial cells. These findings support the essential role of p38 MAPK in the interplay of oxLDL and IL-10 in endothelial apoptosis.


Assuntos
Apoptose , Células Endoteliais da Veia Umbilical Humana/fisiologia , Interleucina-10/fisiologia , Lipoproteínas LDL/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia , Células Cultivadas , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosforilação , Processamento de Proteína Pós-Traducional , Receptores Depuradores Classe E/genética , Receptores Depuradores Classe E/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Regulação para Cima
19.
Artigo em Chinês | MEDLINE | ID: mdl-22506459

RESUMO

OBJECTIVE: To discuss the surgical treatment method and effectiveness of brucellar spondylitis. METHODS: Between January 2002 and October 2010, 78 patients underwent one-stage radical debridement and posterior pedicle internal fixation, who were definitely diagnosed as having brucellar spondylitis of the thoracic and lumbar vertebrae. There were 42 males and 36 females, aged 24 to 65 years (mean, 45 years). The disease duration was 8-29 months (mean, 12 months). Two vertebrae were involved in 70 cases and three vertebrae were involved in 8 cases. All of the cases complicated by nerve function damage in different extent before operation. The patients were followed up regularly after operation. The pain score (visual analogue score, VAS), nerve function Frankel classification, effectiveness evaluation, and the blind test evaluation of X-ray and MRI were performed. RESULTS: All 78 cases were followed up 12 to 30 months (mean, 26 months). No sinus tract and recurrence occurred. The VAS scores were significantly improved at 1 month (2.4 +/- 0.3), 3 months (1.0 +/- 0.2), 6 months (0.5 +/- 0.4), and 12 months (0) when compared with preoperative score (9.2 +/- 0.6) (P < 0.05). The nerve function Frankel classification after operation was significantly improved when compared with preoperative one (P < 0.05); the patients in grade C and grade D had the most obvious improvement. The effectiveness evaluation indicated no aggravated cases. As time went on, the improved and unchanged patients were cured gradually and the improvement rate and the curative rate were 100% and 91.03%, respectively at 12 months after operation. The imaging scores were significantly improved at 1 month (4.11 +/- 0.09), 3 months (4.68 +/- 0.04), 6 months (4.92 +/- 0.08), and 12 months (5) when compared with the preoperative score (0.17 +/- 0.03) (P < 0.05). CONCLUSION: One-stage radical debridement combined with posterior pedicle internal fixation is an ideal therapeutic method for brucellar spondylitis of the thoracic and lumbar vertebrae, which has obvious superiority in pain relief, the spine stability, the nerve function recovery, and early rehabilitation.


Assuntos
Brucelose/cirurgia , Desbridamento , Fixação Interna de Fraturas , Espondilite/cirurgia , Adulto , Idoso , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Espondilite/microbiologia , Vértebras Torácicas , Resultado do Tratamento
20.
Artigo em Chinês | MEDLINE | ID: mdl-21735789

RESUMO

OBJECTIVE: To compare the effect between vascularization osteogenesis and membrane guided osteogenesis in the bone repair by the tissue engineered bone with pedicled fascial flap packing autologous red bone marrow (ARBM), so as to provide a reference for the bone defect repair in clinic. METHODS: The tissue engineered bone was constructed with ARBM and the osteoinductive absorbing recombinant human materials with recombinant human bone morphogenetic protein 2. Sixty New Zealand rabbits (aged 4-5 months, weighing 2.0-2.5 kg) were randomly divided into group A (n = 16), group B (n = 22), and group C (n = 22). The complete periosteum defect model of 1.5 cm in length was prepared in right ulnar bone, then the tissue engineered bone was implanted in the bone defect area in group A, the tissue engineered bone with free fascial flap in group B, and the tissue engineered bone with pedicled fascial flap in group C. At 4, 8, 12, and 16 weeks, the tissue of bone defect area was harvested from 4 rabbits of each group for the general, histological, and immunohistochemical staining observations; at 8, 12, and 16 weeks, 2 rabbits of groups B and C, respectively were selected to perform ink perfusion experiment by axillary artery. RESULTS: The general observation showed that the periosteum-like tissues formed in the fascial flap of groups B and C, chondroid tissues formed in group B, new bone formed in group C, and the fibrous and connective tissues in group A at 4 and 8 weeks; a few porosis was seen in group A, more new bone in group B, and bone stump formation in group C at 12 and 16 weeks. Histological observation showed that there were few new blood vessels and new bone trabeculae in groups A and B, while there were large amounts of new blood vessels and mature bone trabeculae in group C at 4 and 8 weeks. There were a few new blood vessels and new bone trabeculae in group A; more blood vessels, significantly increased mature trabeculae, and the medullary cavity formation in group B; and gradually decreased blood vessels, the mature bone structure formation, and the re-opened medullary cavity in group C at 12 and 16 weeks. The immunohistochemical staining observation showed that the levels of CD105, CD34, and factor VIII were higher in group C than in groups A and B at different time points. The bone morphometry analysis showed that the trabecular volume increased gradually with time in 3 groups after operation; the trabecular volume in group C was significantly more than those in groups A and B at different time points (P < 0.05); and there was significant difference between groups A and B (P < 0.05) except the volume at 4 weeks (P > 0.05). The vascular image analysis showed that the vascular regenerative area ratio in group C was significantly higher than those in groups A and B at different time points (P < 0.05). The ink perfusion experiment showed that the osteogenic zone had sparse ink area with no obvious change in group B, while the osteogenic zone had more intensive ink area and reached the peak at 8 weeks, then decreased in group C. CONCLUSION: The tissue engineered bone with pedicled fascial flap packing ARBM has the vascularization osteogenesis effect at early stage, but the effect disappears at late stage gradually when the membrane guided osteogenesis is main.


Assuntos
Transplante de Medula Óssea , Fáscia/transplante , Neovascularização Fisiológica , Osteogênese , Engenharia Tecidual/métodos , Animais , Medula Óssea , Regeneração Óssea , Substitutos Ósseos , Células Cultivadas , Feminino , Coelhos , Retalhos Cirúrgicos , Alicerces Teciduais , Transplante Autólogo
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