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1.
Appl Math Lett ; 125: 107783, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34776608

RESUMO

The 2019 novel coronavirus (COVID-19) emerged at the end of 2019 has a great influence on the health and lives of people all over the world. The spread principle is still unclear. This paper considers a novel evolution model of COVID-19 in terms of an integral-differential equation, involving vaccination effect and the incubation of COVID-19. The proposed mathematical model is rigorously analyzed on its asymptotic behavior with new probability functions, showing the final spread tendency. Moreover, our model is also verified numerically by the practical epidemic data of COVID-19 in Yangzhou from July to August 2021.

2.
J Cell Mol Med ; 25(1): 244-258, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33219747

RESUMO

miRNA-mediated pyroptosis play crucial effects in the development of myocardial ischaemia/reperfusion (I/R) injury (MIRI). Piperine (PIP) possesses multiple pharmacological effects especially in I/R condition. This study focuses on whether PIP protects MIRI from pyroptosis via miR-383-dependent pathway. Rat MIRI model was established by 30 minutes of LAD ligation and 4 hours of reperfusion. Myocardial enzymes, histomorphology, structure and function were detected to evaluate MIRI. Recombinant adenoviral vectors for miR-383 overexpression or miR-383 silencing or RP105 knockdown were constructed, respectively. Luciferase reporter analysis was used to confirm RP105 as a target of miR-383. Pyroptosis-related markers were measured by Western blotting assay. The results showed that I/R provoked myocardial injury, as shown by the increases of LDH/CK releases, infarcted areas and apoptosis as well as worsened function and structure. Pyroptosis-related mediators including NLRP3, cleaved caspase-1, cleaved IL-1ß and IL-18 were also reinforced after MIRI. However, PIP treatment greatly ameliorated MIRI in parallel with pyroptotic repression. In mechanistic studies, MIRI-caused elevation of miR-383 and decrease of RP105/PI3K/AKT pathway were reverted by PIP treatment. Luciferase reporter assay confirmed RP105 as a miR-383 target. miR-383 knockdown ameliorated but miR-383 overexpression facilitated pyroptosis and MIRI. Moreover, the anti-pyroptotic effect from miR-383 silencing was verified to be relied on the RP105/PI3K/AKT signalling pathway. Additionally, our present study further indicated the miR-383/RP105/AKT-dependent approach resulting from PIP administration against pyroptosis in MIRI. Therefore, PIP treatment attenuates MIRI and pyroptosis by regulating miR-383/RP105/AKT pathway, and it may provide a therapeutic manner for the treatment of MIRI.


Assuntos
Alcaloides/farmacologia , Antígenos CD/metabolismo , Benzodioxóis/farmacologia , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piroptose , Animais , Cardiotônicos/farmacologia , Masculino , MicroRNAs/genética , Piroptose/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
3.
BMC Cancer ; 21(1): 108, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530966

RESUMO

BACKGROUND: Currently, the choice of treatment for individuals with metastatic soft tissue sarcomas (MSTS) presents a significant challenge to clinicians. The aim of this retrospective study was to assess the efficacy and safety of nivolumab plus ipilimumab (NPI) versus nivolumab alone (NIV) in individuals with treatment-naive programmed death-ligand 1 (PD-L1) positive MSTS. METHODS: Prospectively maintained databases were reviewed from 2013 to 2018 to assess individuals with treatment-naive PD-L1 MSTS who received NPI (nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks) or NIV (3 mg/kg every 2 weeks) until disease progression, withdrawal, unendurable [AEs], or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: The median follow-up was 16.0 months (IQR 14.4-18.5) after targeted intervention. The median OS was 12.2 months (95% confidence interval [CI], 6.1-13.7) and 9.2 months (95% CI, 4.2-11.5) for the NPI and NIV groups, respectively (hazard ratio [HR] 0.49, 95% CI, 0.33-0.73; p=0.0002); the median PFS was 4.1 months (95% CI, 3.2-4.5) and 2.2 months (95% CI, 1.1-3.4) for the NPI and NIV groups, respectively (HR 0.51, 95% CI, 0.36-0.71; p< 0.0001). Key grade 3-5 AEs occurred more frequently in the NPI group than in the NIV group (94 [72.9%] for NPI vs. 35 [27.1%], p< 0.001). CONCLUSIONS: For treatment-naive PD-L1 positive MSTS, NPI seems to be less tolerated but has a greater survival advantage than NIV as the primary therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Sarcoma/tratamento farmacológico , Adulto , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Feminino , Seguimentos , Humanos , Ipilimumab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/administração & dosagem , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sarcoma/imunologia , Sarcoma/patologia , Taxa de Sobrevida
4.
J Cardiovasc Pharmacol ; 78(4): 622-629, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34282068

RESUMO

ABSTRACT: Doxorubicin (DOX) is a chemotherapeutic drug for treating various cancers. However, the DOX-induced cardiotoxicity greatly limits its clinical application. MicroRNAs are emerged as critical mediators of cardiomyocyte injury. This work explored the function of miR-215-5p in the regulation of DOX-induced mouse HL-1 cardiomyocyte injury. An in vitro model of DOX-treated cardiotoxicity was established in cardiac mouse cell line HL-1. Gene expression was measured by reverse transcription quantitative polymerase chain reaction. Cell viability was detected using CCK-8. Cell death and apoptosis were tested using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), flow cytometry, and caspase-3/7 activity assays. Luciferase reporter assay was used to examine the target of miR-215-5p. We found that DOX induced cardiomyocyte injury and upregulated miR-215-5p in HL-1 cells. Inhibition of miR-215-5p attenuated DOX-induced cardiomyocyte death and apoptosis in vitro. Mechanistical experiments indicated that zinc finger E-box-binding homeobox (ZEB2) was targeted by miR-215-5p. In addition, ZEB2 expression was reduced in DOX-treated HL-1 cells. Rescue assays indicated that ZEB2 knockdown reversed the effects of miR-215-5p inhibition. In conclusion, miR-215-5p inhibition protects HL-1 cells against DOX-induced injury by upregulating ZEB2 expression.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Doxorrubicina/toxicidade , MicroRNAs/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Cardiotoxicidade , Linhagem Celular , Regulação da Expressão Gênica , Camundongos , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
5.
Environ Toxicol ; 36(11): 2256-2265, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34355838

RESUMO

Acute myocardial infarction (AMI) is one of the most common and serious cardiovascular diseases. With high morbidity and mortality, AMI has attracted the most attention. Emerging studies indicated that long noncoding RNAs (lncRNAs) play an important role in the progression of AMI. However, the role of NORAD in AMI remained unclear. The current study aimed to investigate the function and mechanism of NORAD in AMI. Bioinformatics tools and a wide range of assays including RT-qPCR, flow cytometry, TTC staining, western blot, luciferase reporter and caspase-3 activity assays were conducted to investigate the function and mechanism of NORAD in AMI. We found out that NORAD was significantly upregulated in AMI rats. Knockdown of NORAD alleviated H9c2 cell injury by reducing apoptosis and decreasing expression levels of fibrogenic factors. In addition, NORAD inhibition ameliorated AMI in a rat model by decreasing infarct size and fibrosis. We confirmed that NORAD bound to miR-577, which was downregulated in ischemia-reperfusion (I/R) rats and hypoxia-exposed H9c2 cells. Additionally, miR-577 combined with the 3'UTR of COBLL1, which was upregulated in I/R rats and hypoxia-exposed H9c2 cells. At last, rescue assay validated that the suppressive effects of NORAD knockdown on apoptosis and expression levels of fibrogenic factors were counteracted by COBLL1 overexpression. Overall, NORAD aggravates acute myocardial infarction by promoting fibrosis and apoptosis via the miR-577/COBLL1 axis. This novel discovery suggested that NORAD may serve as a potential therapeutic target for AMI patients.


Assuntos
MicroRNAs , Infarto do Miocárdio , RNA Longo não Codificante , Animais , Apoptose , Linhagem Celular , Fibrose , MicroRNAs/genética , Infarto do Miocárdio/genética , RNA Longo não Codificante/genética , Ratos , Fatores de Transcrição
6.
Molecules ; 26(22)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34834131

RESUMO

A novel soluble copolymer poly(S-MVT) was synthesized using a relatively quick one-pot solvent-free method, inverse vulcanization. Both of the two raw materials are sustainable, i.e., elemental sulfur is a by-product of the petroleum industry and 4-Methyl-5-vinylthiazole (MVT) is a natural monoene compound. The microstructure of poly(S-MVT) was characterized by FT-IR, 1H NMR, XPS spectroscopy, XRD, DSC SEM, and TEM. Test results indicated that the copolymers possess protonated thiazole nitrogen atoms, meso/macroporous structure, and solubility in tetrahydrofuran and chloroform. Moreover, the improved electronic properties of poly(S-MVT) relative to elemental sulfur have also been investigated by density functional theory (DFT) calculations. The copolymers are utilized successfully as the cathode active material in Li-S batteries. Upon employment, the copolymer with 15% MVT content provided good cycling stability at a capacity of ∼514 mA h g-1 (based on the mass of copolymer) and high Coulombic efficiencies (∼100%) over 100 cycles, as well as great rate performance.

7.
Appl Math Model ; 89: 1965-1982, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32836696

RESUMO

The 2019 novel coronavirus (COVID-19) emerged at the end of 2019 has a great impact on China and all over the world. The transmission mechanism of COVID-19 is still unclear. Except for the initial status and the imported cases, the isolation measures and the medical treatments of the infected patients have essential influences on the spread of COVID-19. In this paper, we establish a mathematical model for COVID-19 transmission involving the interactive effect of various factors for the infected people, including imported cases, isolating rate, diagnostic rate, recovery rate and also the mortality rate. Under the assumption that the random incubation period, the cure period and the diagnosis period are subject to the Weibull distribution, the quantity of daily existing infected people is finally governed by a linear integral-differential equation with convolution kernel. Based on the asymptotic behavior and the quantitative analysis on the model, we rigorously prove that, for limited external input patients, both the quantity of infected patients and its variation ratio will finally tend to zero, if the infected patients are sufficiently isolated or the infection rate is small enough. Finally, numerical performances for the proposed model as well as the comparisons between our simulations and the clinical data of the city Wuhan and Italy are demonstrated, showing the validity of our model with suitably specified model parameters.

8.
Hepatology ; 69(1): 76-93, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30063256

RESUMO

Nonalcoholic fatty liver disease (NAFLD), ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), is the leading cause of chronic liver diseases. Until now, no medications for NAFLD have been approved by relevant governmental agencies. Dual-specificity phosphatase 9 (Dusp9) is a member of the DUSP protein family. Dusp9 is expressed in insulin-sensitive tissues, and its expression may be modified with the development of insulin resistance (IR). However, the molecular targets and mechanisms of Dusp9 action on NAFLD and NASH remain poorly understood. In this study, using conditional liver-specific Dusp9-knockout (Dusp9-CKO) mice and Dusp9-transgenic mice, we showed that Dusp9 was a key suppressor of high-fat diet-induced hepatic steatosis and inflammatory responses and that Dusp9 deficiency aggravated high-fat high-cholesterol diet-induced liver fibrosis. Dusp9 was shown to exert its effects by blocking apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and the subsequent activation of p38 and c-Jun NH2-terminal kinase signaling. Conclusion: Hepatocyte Dusp9 prevents NAFLD and NASH progression in mice, including lipid accumulation, glucose metabolism disorders, and enhanced inflammation and liver fibrosis, in an ASK1-dependent manner; these findings suggest that Dusp9 may be a promising therapeutic target for the treatment of NAFLD and NASH.


Assuntos
Fosfatases de Especificidade Dupla/fisiologia , MAP Quinase Quinase Quinase 5/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/enzimologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
9.
Hepatology ; 69(5): 1946-1964, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30582764

RESUMO

Nonalcoholic fatty liver disease (NAFLD), which has a wide global distribution, includes different stages ranging from simple steatosis to nonalcoholic steatohepatitis, advanced fibrosis, and liver cirrhosis according to the degree of severity. Chronic low-grade inflammation, insulin resistance, and lipid accumulation are the leading causes of NAFLD. To date, no effective medicine for NAFLD has been approved by governmental agencies. Our study demonstrated that the expression of dual-specificity phosphatase 26 (Dusp26), a member of the Dusp protein family, was decreased in the liver tissue of mice with hepatic steatosis and genetically obese (ob/ob) mice. In our study, hepatic steatosis, inflammatory responses, and insulin resistance were exacerbated in liver-specific Dusp26-knockout (KO) mice but ameliorated in liver-specific Dusp26-transgenic mice induced by a high-fat diet. In addition, the degree of liver fibrosis was aggravated in high-fat high-cholesterol diet-induced Dusp26-KO mice. We further found that the binding of Dusp26 to transforming growth factor beta-activated kinase 1 (TAK1) to block the phosphorylation of TAK1 regulated the TAK1-p38/c-Jun NH2-terminal kinase signaling axis to alleviate hepatic steatosis and metabolic disturbance. Conclusion: These findings suggest that Dusp26 is a good TAK1-dependent therapeutic target for NAFLD.


Assuntos
Fosfatases de Especificidade Dupla/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Hepatopatia Gordurosa não Alcoólica/enzimologia , Obesidade/enzimologia , Animais , Linhagem Celular , Dieta Hiperlipídica/efeitos adversos , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos , Cirrose Hepática/etiologia , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações
10.
J Opt Soc Am A Opt Image Sci Vis ; 37(2): 231-239, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32118903

RESUMO

A fast algorithm for fluorescence diffuse optical tomography is proposed. The algorithm is robust against the choice of initial guesses. We estimate the position of a fluorescent target by assuming a cuboid (rectangular parallelepiped) for the fluorophore target. The proposed numerical algorithm is verified by a numerical experiment and an experiment with a meat phantom. The target position is reconstructed with a cuboid from measurements in the time domain. Moreover, the long-time behavior of the emission light is investigated making use of the analytical solution to the diffusion equation.

11.
Aging Clin Exp Res ; 32(1): 21-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30863943

RESUMO

BACKGROUND: Whether vitamin D receptor (VDR) genetic variants influence individual susceptibility to neurodegenerative disorders remains controversial. AIMS: This meta-analysis was conducted to analyze correlations of VDR genetic variants with two types of most common neurodegenerative disorders, Parkinson's disease (PD) and Alzheimer's disease (AD). METHODS: Systematic literature research of PubMed and Embase was performed to identify eligible articles. Q test and I2 statistic were employed to decide whether pooled analyses would be performed with random-effect models (REMs) or fixed-effect models (FEMs). All statistical analyses were conducted with Review Manager. RESULTS: Totally sixteen studies were enrolled for analyses. Among these eligible studies, ten studies were about PD (2356 cases and 2815 controls) and six studies were about AD (1256 cases and 1205 controls). Pooled overall analyses suggested that VDR rs7975232 (additive model: p = 0.03, OR = 1.19, 95% CI 1.01-1.39) and rs2228570 (recessive model: p < 0.008, OR = 1.26, 95% CI 1.06-1.50; allele model: p < 0.001, OR = 0.80, 95% CI 0.71-0.91) variants were significantly correlated with PD, and VDR rs731236 (dominant model: p = 0.003, OR = 0.70, 95% CI 0.56-0.89; additive model: p = 0.02, OR = 1.32, 95% CI 1.06-1.66; allele model: p = 0.02, OR = 0.82, 95% CI 0.69-0.96) variant was significantly correlated with AD. Further subgroup analyses by ethnicity revealed that the positive results were mainly driven by the Asians, whereas no significant associations were observed in Caucasians. CONCLUSION: Our meta-analysis suggested that VDR rs7975232 and rs2228570 variants might serve as genetic biomarkers of PD, whereas VDR rs731236 variant might serve as a genetic biomarker of AD.


Assuntos
Doença de Alzheimer/genética , Doença de Parkinson/genética , Receptores de Calcitriol/genética , Alelos , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos
12.
Xenobiotica ; 49(2): 211-215, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29412757

RESUMO

Triptolide and fenofibrate are often used together for the treatment of nephrotic syndrome in Chinese clinics. This study investigates the effects of triptolide on the pharmacokinetics of fenofibrate in rats and it potential mechanism. The pharmacokinetics of fenofibrate (20 mg/kg) with or without triptolide pretreatment (2 mg/kg/day for seven days) were investigated. Additionally, the inhibitory effects of triptolide on the metabolic stability of fenofibrate were investigated using rat liver microsome incubation systems. The results indicated that the Cmax (35.34 ± 7.52 vs. 30.43 ± 6.45 µg/mL), t1/2 (6.17 ± 1.15 vs. 4.90 ± 0.82 h) and AUC(0-t) (468.12 ± 35.84 vs. 416.35 ± 32.68 mg h L-1) of fenofibric acid decreased significantly (p < .05). The Tmax of fenofibric acid increased significantly (p < .05) from 5.12 ± 0.36 to 6.07 ± 0.68 h. Additionally, the metabolic stability of fenofibrate was prolonged from 35.8 ± 6.2 to 48.6 ± 7.5 min (p < .05) with the pretreatment of triptolide. In conclusion, these results indicated that triptolide could affect the pharmacokinetics of fenofibric acid, possibly by inhibiting the metabolism of fenofibrate in rat liver when they were co-administered.


Assuntos
Diterpenos/farmacocinética , Fenofibrato/farmacocinética , Fenantrenos/farmacocinética , Animais , Diterpenos/farmacologia , Interações Medicamentosas , Compostos de Epóxi/farmacocinética , Compostos de Epóxi/farmacologia , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Fenantrenos/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Eur Spine J ; 28(8): 1855-1863, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30903293

RESUMO

PURPOSE: Application of AOSpine subaxial cervical spine injury classification system to explore the optimal surgical decompression timing for different types of traumatic cervical spinal cord injury (CSCI). METHODS: A single-center prospective cohort study was conducted that included patients with traumatic CSCIs (C3-C7) between February 2015 and October 2016. After enrollment, patients underwent either early (< 72 h after injury) or late (≥ 72 h after injury) decompressive surgery of the cervical spinal cord. Each group was divided into A0, A1-4, B, C/F4 and F1-3 subgroups. The primary outcomes were ordinal changes in the ASIA Impairment Scale (AIS) and the Spinal Cord Independence Measure III (SCIM version 3) at a 12-month follow-up. The secondary outcomes included length of hospital stay, postoperative neurological deterioration, other complications and mortality. RESULTS: A total of 402 patients were included. Of these, 187 patients underwent early decompression surgery, and 215 patients underwent delayed decompression surgery. Statistical results included the following comparisons of the early vs late groups: AIS improvement ≥ 1 grade (combined groups: P < 0.0001; A0: P = 0.554; A1-4: P = 0.084; B: P = 0.013; C/F4: P = 0.040; F1-3: P = 0.742); AIS improvement ≥ 2 grades, P = 0.003 for all groups; SCIM version 3 (combined groups: P < 0.0001; A0: P = 0.126; A1-4: P = 0.912; B: P = 0.006; C/F4: P = 0.111; F1-3: P = 0.875). CONCLUSION: Type A and F1-3 fractures are not required to undergo aggressive early decompression. Type B and type C/F4 fractures should receive early surgical treatment for better clinical outcomes. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Medula Cervical , Descompressão Cirúrgica/estatística & dados numéricos , Traumatismos da Medula Espinal , Tempo para o Tratamento , Medula Cervical/lesões , Medula Cervical/cirurgia , Vértebras Cervicais/cirurgia , Humanos , Tempo de Internação/estatística & dados numéricos , Estudos Prospectivos , Traumatismos da Medula Espinal/classificação , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/cirurgia , Resultado do Tratamento
15.
Cell Physiol Biochem ; 43(4): 1425-1435, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29017159

RESUMO

BACKGROUND/AIMS: Osteoporosis is a metabolic bone disorder that tortures about millions of people worldwide. Recent study demonstrated agents derived from picrasma quassioides is a promising drug for targets multiple signaling pathways. However its potential in treatment of bone loss has not been fully understood. METHODS: The bone marrow macrophages (BMMs) were cultured and induced with M-CSF and RANKL followed by picrasidine I (PI) treatment. Then the effects of PI on osteoclast formation were evaluated by counting tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Moreover, effects of PI on bone resorption activity of mature osteoclast were studied through bone resorption pit counting and actin ring structure analysis. Further, the involved potential signaling pathways cross-talking were investigated by performed Western blotting and quantitative real-time PCR examination. RESULTS: Results demonstrated PI strongly inhibited RANKL induced osteoclast formation from its precursors. Mechanistically, the inhibitory effect of PI on osteoclast differentiation was due to the suppression of osteoclastogenic transcription factors, c-Fos and NFATc1. Moreover, PI markedly blocked the RANKL-induced osteoclastogenesis by attenuating MAPKs and NF-κB signaling pathways. In addition, PI decreased the ROS generation in osteoclast and osteoblast. CONCLUSION: Taken together our data demonstrate that PI has antiosteoclastogenic effect by inhibiting inflammation induced activation of MAPKs, NF-κB and ROS generation followed by suppressing the gene expression of c-Fos and NFATc1 in osteoclast precursors.


Assuntos
Carbolinas/farmacologia , Osteoclastos/efeitos dos fármacos , Ligante RANK/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Carbolinas/química , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Fatores de Transcrição NFATC/genética , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Picrasma/química , Proteínas Proto-Oncogênicas c-fos/genética
16.
BMC Musculoskelet Disord ; 18(1): 81, 2017 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-28196468

RESUMO

BACKGROUND: The most common site of fractures in patients with ankylosing spondylitis (AS) is the cervical spine, especially the lower cervical spine and cervicothoracic junction. The optimal treatment for cervical spine fractures secondary to AS is controversial. This study aimed to explore the effects of posterior pedicle screw fixation alone on fractures of the lower cervical spine in patients with AS. METHODS: From January 2006 to January 2013, a total of 35 patients with AS and a lower cervical spine fracture were treated using only posterior cervical/thoracic pedicle screw fixation. In this retrospective study, we reviewed the patients' charts to assess their case histories, operations, neurological outcomes, and complications. We also evaluated their postoperative radiographs to determine the time of bone fusion. RESULTS: Altogether, 32 (91.4%) of the 35 fractures resulted from an acute injury and 3 (8.6%) from a chronic injury. In 25 cases, the fracture resulted from a low-energy spinal injury and in 8 cases from a high-energy injury. Posterior pedicle screw fixation was successful in all patients, with radiographic fusion confirmed by computed tomography. The average time of bone fusion was 3.6 months (range 3 - 6 months). The surgery improved the American Spinal Injury Association grade in 15 (42.9%) patients. No intraoperative complications occurred. None of the corrections resulted in neurological decompensation. The average postoperative correction was 18°. CONCLUSIONS: Pedicle screw fixation and autologous bone grafting through a single posterior approach to lower cervical spine fractures in AS patients could stabilize the spine, correct kyphosis, and relieve pressure. It is thus reasonable to recommend this surgical strategy for AS-associated fractures of the lower cervical spine. TRIAL REGISTRATION: Not applicable.


Assuntos
Vértebras Cervicais/lesões , Fixação Interna de Fraturas/instrumentação , Fraturas da Coluna Vertebral/cirurgia , Espondilite Anquilosante/complicações , Adulto , Idoso , Parafusos Ósseos , Vértebras Cervicais/cirurgia , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fraturas da Coluna Vertebral/etiologia
17.
BMC Musculoskelet Disord ; 18(1): 270, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28633648

RESUMO

BACKGROUND: To compare radiologic results of posterior release, internal distraction, and final pedicle subtraction osteotomy (PSO) and spinal fusionwith one-stage posterior vertebral column resection (PVCR) in treating multi-level severe congenital scoliosis. METHODS: Forty-onesevere congenital scoliosis patients were used in the study. Group A comprised 24 patients who underwent one-stage PVCR. Group B comprised 17 patients who underwent posterior release with internal distraction, followed by final posterior fusion and instrumentation. The average preoperative main curve was 110.4° (95-130°) in group A and 109.4° (range 90°-126°) in group B. Postoperative follow-up time was ≥2 years (2.0-4.5 years) to analyze the radiographic and clinical outcomes. RESULTS: A comparison of posterior release, internal distraction, and final spinal fusion with PVCR showed no significant differences in postoperative main curve and compensatory caudal curve correction, coronal and sagittal imbalance. However, significant differences were found between the 2 groups in compensatory cranial curve correction. CONCLUSIONS: Posterior release, internal distraction, and final spinal fusion produce better corrective results in compensatory cranial curve correction than PVCR in treating severe multi-level congenital scoliosis.


Assuntos
Osteotomia/métodos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Índice de Gravidade de Doença , Fusão Vertebral/métodos , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
BMC Musculoskelet Disord ; 17: 66, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26862044

RESUMO

BACKGROUND: The objective of this study was to compare the outcomes of one-stage posterior surgery involving debridement, bone grafting, and instrumentation with and without local continuous chemotherapy and postural drainage for the treatment of lumbar spinal tuberculosis. METHODS: From January 2009 to January 2013, 109 patients with lumbar spinal tuberculosis were treated in our center using a posterior surgical approach. Patients underwent one-stage posterior debridement, bone grafting, and instrumentation, without (group A) and with (group B) local continuous chemotherapy and postural drainage. Clinical and radiographic results for the two groups were analyzed and compared. Clinical efficacy was evaluated based on surgery duration and blood loss. The Frankel scale was used to evaluate neurological function. A visual analog scale was used to assess low back pain. Bone graft fusion and instrumentation failure were monitored by radiography, and tuberculosis activity was monitored by erythrocyte sedimentation rate (ESR) and C-reactive protein testing. RESULTS: Groups A and B contained 52 and 57 patients, respectively. Patients were followed for 18-36 (mean, 26.64 ± 4.2) months. All bone grafts ultimately fused, but the fusion rate was significantly more rapid in group B [6.4 ± 0.5 (range, 5-10) months] than in group A [8.9 ± 0.6 (range, 6-12) months; P < 0.05]. At 6 weeks postoperatively, ESR levels differed significantly between groups A and B (24.6 ± 1.5 vs. 16.3 ± 1.1 mm/h; P < 0.05). ESR levels normalized in both groups at 16 weeks. CONCLUSIONS: Local continuous chemotherapy and postural drainage effectively eliminated infection foci caused by abscess remnants and accelerated interbody bone fusion in patients with lumbar spinal tuberculosis undergoing one-stage posterior surgery involving debridement, bone grafting, and instrumentation.


Assuntos
Antituberculosos/administração & dosagem , Drenagem/métodos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/cirurgia , Procedimentos Ortopédicos , Posicionamento do Paciente , Tuberculose da Coluna Vertebral/terapia , Adulto , Idoso , Antituberculosos/efeitos adversos , Perda Sanguínea Cirúrgica , Parafusos Ósseos , Transplante Ósseo , Terapia Combinada , Desbridamento , Drenagem/efeitos adversos , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/microbiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/instrumentação , Osseointegração , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Tuberculose da Coluna Vertebral/diagnóstico , Tuberculose da Coluna Vertebral/microbiologia , Adulto Jovem
19.
J Orthop Sci ; 20(4): 689-94, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25875232

RESUMO

BACKGROUND: Type C3 thoracic fracture is a severe spinal injury, but one that is clinically rare, and there are few reports pertaining to the treatment of this type of fracture. No consensus has been achieved on the proper timing of spine fracture fixation; therefore, we focused on evaluating the surgical effects using a posterior approach and determining the influence of surgical timing on surgical outcomes. METHODS: This was a retrospective cohort study of 36 cases of type C3 thoracic fracture in patients admitted to the hospital from April 2005 to October 2012, and who were divided into two groups according to the timing of surgery: early fixation (<72 h) and late fixation (>72 h). Surgical outcomes were analyzed based on surgery duration, intraoperative blood loss, intensive care unit and hospital stay, mortality rate, and complications. RESULTS: There were 13 patients in the early fixation group and 23 patients in the late fixation group. Patients were treated with posterior decompression, intervertebral titanium mesh support, pedicle screw fixation, and fusion. All fractures involved a single segment: T7/T8 (8 patients), T9/T10 (11 patients), and T11/T12 (17 patients). All injuries were classified as American Spinal Injury Association (ASIA) grade A. Patients underwent periodic follow-up over a period of 12-30 months (average, 22.5 months). One patient developed ascending myelitis and died of respiratory failure 1 month after early fixation, and two patients died of pulmonary infection after late fixation procedures. Other patients achieved bone fusion without improvement in ASIA grade. No statistically significant difference in parameters was observed between groups. CONCLUSIONS: Though type C3 thoracic fracture is one of the most severe spinal injuries, complete reduction and recovery of spinal stability can be achieved using a posterior approach. As clinical outcomes in this study were similar between early and late fixation procedures, early surgical intervention may not be helpful for improving neurologic recovery in type C3 thoracic fractures.


Assuntos
Fixação Interna de Fraturas/métodos , Fixação de Fratura/métodos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Adulto , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Parafusos Pediculares , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico , Vértebras Torácicas/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Índices de Gravidade do Trauma , Resultado do Tratamento , Adulto Jovem
20.
Pak J Pharm Sci ; 28(2 Suppl): 773-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25796153

RESUMO

Regarding the Artemisia annua extract derivatives called dihydroarteminin (DHA) as the object, we studied about its influence to the proliferation, apoptosis and metastasis of human osteosarcoma cells. First, we cultured in vitro the osteosarcoma cell strain and divided them into groups, then detected the cell proliferation, apoptosis and cell metastasis, etc by multiple measurement technique. Finally, we observed the influence of DHA to human osteosarcoma cells. Osteosarcoma cells were all sensitive to DHA, and the appropriate concentration range was 10~40µM. DHA could effectively restrain its protein expression, and there was a significant difference between experimental group and control group. These finding suggest that, the Artemisia annua extract derivatives (DHA) has a biological effect of observably restraining the proliferation and metastasis of human osteosarcoma cells and promoting the tumour cell apoptosis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Artemisia annua , Artemisininas/farmacologia , Neoplasias Ósseas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Osteossarcoma/secundário , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Artemisia annua/química , Artemisininas/isolamento & purificação , Neoplasias Ósseas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Relação Dose-Resposta a Droga , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , Osteossarcoma/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Fator A de Crescimento do Endotélio Vascular/metabolismo
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