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1.
J Neurointerv Surg ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034104

RESUMO

BACKGROUND AND PURPOSE: In-stent restenosis (ISR) is one of the long-term adverse outcomes of endovascular angioplasty and stenting for symptomatic intracranial arterial stenosis. In this study, we try to evaluate the safety and efficacy of endovascular treatment for intracranial ISR. METHODS: We retrospectively collected patients with intracranial ISR who underwent endovascular treatment from June 2012 to August 2019 at a high-volume stroke center. Successful recanalization was defined as ≤30% residual stenosis. Stroke, myocardial infarction, and death after stenting within 30 days were used to evaluate periprocedural safety. Recurrent stroke in the territory of the culprit vessel and re-ISR in patients with clinical and vascular imaging follow-up data were used to evaluate the long-term outcome. RESULTS: 32 patients (59.6±7.2 years old) with ISR were recruited, including 22 patients (68.8%) treated with balloon dilatation, 8 patients (25%) with stenting, and 2 patients (6.3%) with failed procedures. Successful recanalization was achieved in 71.9% (23/32) of patients. There was no stroke, myocardial infarction or death within 30 days after the procedure. Recurrent stroke was found in 10.7% (3/28) of the patients, and re-ISR was found in 42.1% (8/19) of the patients. The re-ISR rate was lower in patients with stenting than in those with balloon dilatation (0% vs 57.1%, p=0.090), and in patients with successful recanalization than in those with unsuccessful recanalization (33.3% vs 75.0%, p=0.352), but with no statistically significant difference. CONCLUSIONS: The periprocedural safety of endovascular treatment for intracranial ISR may be acceptable, but the long-term rates of recurrent stroke and re-ISR remain at high levels.

2.
Medicine (Baltimore) ; 98(51): e18386, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861001

RESUMO

RATIONALE: Pulmonary embolisms (PEs) are caused by emboli, which mostly originate from deep venous thrombi that travel to and suddenly block the pulmonary arteries. The emboli are usually thrombi, and right atrial myxoma emboli are rare. PATIENT CONCERNS: A 55-year-old man presented with shortness of breath and syncope. We proceeded with computed tomography pulmonary angiography (CTPA) and transthoracic echocardiogram (TTE), the results of which suggested that the diagnosis was a right atrial mass. DIAGNOSIS: A definitive diagnosis compatible with a right atrial myxoma (RAM) with tumoral pulmonary emboli after surgical excision was made. INTERVENTION: Right atrial and pulmonary artery embolectomy. OUTCOMES: The patient followed an uneventful course during the 6 years of follow-up after surgery. According to a review of the literature, RAMs are often not diagnosed in a timely manner or even go completely undiagnosed. TTE, transesophageal echocardiography (TEE), CT, magnetic resonance imaging (MRI), and positron emission tomography/computed tomography may be helpful in the preoperative diagnosis. Surgical removal of the masses from the atrium and pulmonary arteries was relatively uneventful. LESSONS: RAMs should be considered unlikely reasons for fatal pulmonary embolisms.


Assuntos
Átrios do Coração/diagnóstico por imagem , Neoplasias Cardíacas/diagnóstico por imagem , Mixoma/diagnóstico por imagem , Embolia Pulmonar/etiologia , Angiografia por Tomografia Computadorizada , Ecocardiografia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/patologia , Mixoma/cirurgia , Embolia Pulmonar/cirurgia
3.
Mol Cancer Res ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672701

RESUMO

The programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) pathway plays a pivotal role in the immune escape of tumors. Many tumor cells show "glutamine dependence." However, the relationship between glutamine metabolism and PD-L1 expression has not been reported. In this study, changes in PD-L1 expression in renal carcinoma cells were evaluated during glutamine deprivation and recovery. Although PD-L1 expression differed in two renal cancer cell lines, both cell lines upregulated PD-L1 during glutamine deprivation, and the upregulated PD-L1 was restored to normal after glutamine recovery. Mechanistically, glutamine deprivation resulted in activation of EGFR signaling via ERKs 1 and 2 (ERK1/2) and c-Jun. In addition, treatment of renal cancer cells with EGF also induced PD-L1 expression and ERK1/2 phosphorylation. Finally, inhibitors of EGFR, ERK, and c-Jun all inhibited phosphorylation of c-Jun and downregulated PD-L1 expression induced by glutamine deprivation. Taken together, the data suggest that glutamine regulates the expression of PD-L1 through the EGFR/ERK/c-Jun pathway in renal cancer. IMPLICATIONS: This study reveals glutamine deprivation induces PD-L1 expression via activation of EGFR/ERK/c-Jun signaling in renal cancer and provides novel markers for the treatment of renal cancer.

4.
Mar Pollut Bull ; 146: 466-475, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31426182

RESUMO

Ecological risk assessment of metals (As, Cd, Cr, Cu, Hg, Ni, Pb and Zn) in surface sediments from 31 small craft harbours (SCHs) in Nova Scotia, Canada was conducted using multiple risk assessment approaches. Approaches used were contamination factor, pollution load index, geoaccumulation index, potential ecological risk factor for individual metals, comprehensive potential ecological risk index, mean probable effect level quotient and mean effects range median quotient. Results indicated most SCHs exhibited low ecological risk from sediment metal concentrations, except for two harbours. Metal contamination was highest in Canso Harbour, followed by Clarks Harbour. SCH sediments were only slightly contaminated with low probability of pollution according to mean probable effect level and mean effects range median quotients. However, pollution load and geoaccumulation indexes indicated Cd and Hg had the highest metal contamination across SCH sediments. Cadmium and Hg had the highest potential ecological risk, respectively compared to other metals.


Assuntos
Monitoramento Ambiental , Sedimentos Geológicos , Metais/análise , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Animais , China , Monitoramento Ambiental/métodos , Mercúrio/análise , Metais/toxicidade , Nova Escócia , Medição de Risco , Poluentes do Solo/toxicidade , Poluentes Químicos da Água/toxicidade
5.
Artigo em Inglês | MEDLINE | ID: mdl-31163571

RESUMO

The construction of smart cities is a theme of urban development, and building fires greatly threaten public safety and urban environmental governance, in which fire emergency management is one of the key factors. However, most studies on the evaluation of emergency response capacity ignore the process of improvement, as well as the intelligence and practicality of the results. The evaluation system of building fire emergency response capability maturity (FE-CMM) was innovatively proposed based on the capability maturity model (CMM), including the evaluation index, evaluation grade, evaluation method, and evaluation process. At the same time, a plug-in for evaluating fire emergency response capability was developed based on the building information modeling (BIM) platform. Finally, an empirical study was carried out in combination with the case of a district fire center. The research demonstrates that the evaluation system can effectively judge the maturity of fire emergency response capability, and the established plug-in can preliminarily realize the intelligent evaluation of building fire emergency response capability, which improves the practice and intelligence of the fire emergency response capability evaluation system when fully considering the process of improvement. It has guiding significance for ex ante control and refined management of building fires, thus providing support for urban public safety and environmental governance.


Assuntos
Emergências , Socorristas/estatística & dados numéricos , Fogo/estatística & dados numéricos , China , Humanos
6.
Mar Pollut Bull ; 140: 493-502, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30803670

RESUMO

Spatiotemporal (2001-2017) characterization of sediment metal concentrations were assessed in 31 small craft harbours (SCHs) in Nova Scotia, Canada by analyzing secondary data from government sediment assessment reports. Surficial sediment samples (n = 576) were collected prior to routine maintenance or constriction dredging activities. Sediment metal concentration ranges were 0.5-62 (As), 0.05-3.8 (Cd), 1-305 (Cr), 0.5-220 (Cu), 0.003-1.85 (Hg), 0.73-583 (Pb) and 5-2300 (Zn) mg/kg (dw), respectively. Most sediment metal concentrations (>56% of samples) were below low effect level and >96% were below high effect level sediment quality guidelines, suggesting limited ecological impairment to marine biota. Despite wide temporal coverage (16 years), large variation in sediment concentrations across SCHs were likely due to regular dredging activities preventing long-term accumulation of contaminants. Spatial distribution and enrichment factor results revealed that Canso was most impacted by metals, followed by Clarks Harbour.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/química , Metais Pesados/análise , Navios , Poluentes Químicos da Água/análise , Nova Escócia , Análise Espaço-Temporal
7.
Thromb Res ; 176: 85-94, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30784777

RESUMO

INTRODUCTION: Acute pulmonary embolism (APE) is a cardiovascular disease with high morbidity and mortality. Although the anatomical obstruction of the pulmonary vascular bed initiates APE, recent studies have suggested that vasoconstrictors in the renin-angiotensin system (RAS) play a role in the severity of APE. MATERIALS AND METHODS: We performed a 5-year retrospective clinical study to analyze the key RAS components in APE patients, including angiotensin converting enzyme (ACE), ACE2, angiotensin II (Ang II) and angiotensin 1-7(Ang(1-7)). The role of RhoA-Rho associated kinase (ROCK) signaling in regulating RAS vasoconstrictors was detected in rat pulmonary artery endothelial cells and in an APE rat model. RESULTS: In clinical study, we found that the levels of RAS vasoconstrictors were correlated with the clinical classification of APE patients, ACE and Ang II were unregulated, whereas ACE2 and Ang(1-7) were downregulated in the high-risk group compared to the healthy volunteers. In animal study, we found that activated RhoA-ROCK signaling was responsible for the imbalance in RAS vasoconstrictors both in vitro and in vivo, and further evidence indicated that ROCK inhibitors (Y27632 or HA1077) and an ACE2 activator (Resorcinol naphthalein) restored the dysregulated RAS vasoconstrictors significantly and had a protective role in an APE rat model. CONCLUSIONS: Our study revealed that RhoA-ROCK signaling leads to RAS imbalance in APE patients, and ACE2 activation might be a novel therapeutic target in APE treatment.


Assuntos
Peptidil Dipeptidase A/metabolismo , Embolia Pulmonar/metabolismo , Transdução de Sinais , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , Doença Aguda , Animais , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Sistema Renina-Angiotensina
8.
Am J Physiol Lung Cell Mol Physiol ; 316(3): L547-L557, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30628484

RESUMO

Angiotensin-converting enzyme 2 (ACE2) protects against hypoxic pulmonary hypertension (HPH) by inhibiting the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Under hypoxia, the hypoxia-inducible factor 1α (HIF-1α) inhibits ACE2 indirectly; however, the underlying mechanism is unclear. In the present study, we found that exposure to chronic hypoxia stimulated microRNA (miRNA) let-7b expression in rat lung via a HIF-1α-dependent pathway. Let-7b downregulated ACE2 expression by directly targeting the coding sequence of ACE2. Our in vitro and in vivo results revealed that let-7b contributed to the pathogenesis of HPH by inducing PASMCs proliferation and migration. Let-7b knockout mitigated right ventricle hypertrophy and pulmonary vessel remodeling in HPH by restoring ACE2 expression. Overall, we demonstrated that HIF-1α inhibited ACE2 expression via the HIF-1α-let-7b-ACE2 axis, which contributed to the pathogenesis of HPH by stimulating PASMCs proliferation and migration. Since let-7b knockout alleviated the development of HPH, let-7b may serve as a potential clinical target for the treatment of HPH.


Assuntos
Hipertensão Pulmonar/genética , MicroRNAs/genética , Peptidil Dipeptidase A/genética , Remodelação Vascular/genética , Animais , Proliferação de Células/fisiologia , Técnicas de Inativação de Genes , Hipertensão Pulmonar/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Pulmão/metabolismo , Masculino , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/patologia , Ratos Sprague-Dawley , Remodelação Vascular/fisiologia
9.
Cell Cycle ; 18(1): 34-45, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30563407

RESUMO

CYP27A1, an enzyme involved in regulating cellular cholesterol homeostasis, converts cholesterol into 27-hydroxycholesterol (27-HC). The relationship between CYP27A1 and cell proliferation was studied to determine the role of CYP27A1 in bladder cancer. The expression of CYP27A1 in three bladder cancer cell lines (T24, UM-UC-3 and 5637) were assessed by qRT-PCR and Western blotting, and cells with stable CYP27A1 expression were generated by lentiviral infection. Cell proliferation was detected by MTT assays, colony formation assays and a tumor xenograft model in vitro and in vivo, and the intracellular 27-HC and cholesterol secretion levels were detected by enzyme-linked immunosorbent assays (ELISA). The results revealed that CYP27A1 expression was downregulated in androgen receptor (AR)-positive T24/UM-UC-3 cells compared with AR-negative 5637 cell. After CYP27A1 expression was restored, cell proliferation was inhibited in vitro and in vivo because much more intracellular 27-HC was produced in the CYP27A1-overexpressing cells than in the control cells. Both T24 and UM-UC-3 cells treated with 27-HC showed similar results. In addition, CYP27A1/27HC could reduce the cellular cholesterol level in both T24 and UM-UC-3 cells by upregulating ATP-binding cassette transporters G1 and A1 (ABCG1 and ABCA1) through Liver X receptors (LXRs) pathway and downregulating low-density lipoprotein receptor (LDLR) expression. These findings all suggest that CYP27A1 is a critical cholesterol sensor in bladder cancer cells that may contribute significantly to bladder cancer proliferation.

10.
Onco Targets Ther ; 11: 7229-7243, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425515

RESUMO

Background: Metabolic reprogramming occurs in the tumor microenvironment and influences the survival and function of tumor and immune cells. Interferon-γ (IFN-γ) produced by T cells up-regulates PD-L1 expression in tumors. However, reports regarding the relationship between nutrient metabolism and the up-regulation of PD-L1 expression are lacking. Materials and methods: In this paper, we analyzed the metabolic changes in T cells and bladder cancer cells in a simulated tumor microenvironment to provide evidence regarding their relevance to PD-L1 up-regulation. Results: The glutaminolysis was increased in both activated T cells and glucose-deprived T cells. IFN-γ production by T cells was decreased in a glucose-free medium and severely decreased when cells were simultaneously deprived of glutamine. Furthermore, the glutaminolysis of the bladder cancer cells under glucose deprivation exhibited a compensatory elevation. The glucose concentration of T cells co-cultured with bladder cancer cells was decreased and T cell proliferation was reduced, but IFN-γ production and glutaminolysis were increased. However, in bladder cancer cells, the elevation in glutaminolysis under co-culture conditions did not compensate for glucose deprivation because the glucose concentration in the culture medium did not significantly differ between the cultures with and without T cells. Our data also show that inhibiting glutamine metabolism in bladder cancer cells could reduce the elevation in PD-L1 expression induced by IFN-γ. Conclusion: In a simulated tumor microenvironment, elevated glutaminolysis may play an essential role in IFN-γ production by T cells, ultimately improving the high PD-L1 expression, and also directly contributing to producing more PD-L1 in bladder cancer cells.

11.
Bull Cancer ; 105(10): 925-931, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30243478

RESUMO

Bladder cancer is a widespread and highly heterogeneous malignancy. Moreover, bladder cancer recurrence and treatment failure are common, making this disease a challenge for genito-urinary surgeons. Precision medicine represents a new medical concept and model. It is based on personalized medicine, and employs genomics, proteomics, and other omics and cutting-edge medical technologies to classify disease at the molecular level, enabling accurate identification of its cause and therapeutic targets, ultimately offering precise, personalized medicine. The existence of heterogeneity in bladder cancer, resulting in different molecular phenotypes, constitutes a huge challenge for precision medicine. Studying phenotypic differences will be of substantial clinical significance and far-reaching research value with respect to the natural history of tumor development, reduction of drug resistance, the early diagnosis and prognosis of patients with bladder cancer, and the realization of fully developed precision medicine. This paper reviews the possible mechanisms underlying tumor heterogeneity and their impact on precision medicine. The manner in which precision medicine may be performed in the presence of bladder cancer heterogeneity and the prospects of this discipline are also discussed.


Assuntos
Medicina de Precisão/métodos , Neoplasias da Bexiga Urinária/terapia , Evolução Clonal , Resistencia a Medicamentos Antineoplásicos , Genômica , Genótipo , Humanos , Imunidade Celular , Mutação , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas , Fenótipo , Proteômica , Microambiente Tumoral , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
12.
J Colloid Interface Sci ; 528: 271-280, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-29859452

RESUMO

Platinum (Pt) free micro/nanomotors (MNMs) using a low content of fuels are highly desired for many applications. Herein, we demonstrate that cathodic electrofabrication can produce modified MnO2 based microtubes and microrods as highly efficient MNMs in hydrogen peroxide (H2O2) as low as 0.2%. The speed of graphene/Ag-MnO2 micromotors could be smartly regulated using a surfactant and the maximum speed of an individual micromotor exceeds 1.3 mm s-1 in 0.5% H2O2. The propelling force and output power of the micromotors are 3.4 and 10 times as high as those of the best Pt-based micromotors reported. These Ag-MnO2 based micromotors are envisioned to be a great promise for practical applications from biomedical delivery to environmental decontamination.

13.
Chem Commun (Camb) ; 54(37): 4653-4656, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29623976

RESUMO

Herein, we demonstrate that iron oxide modified MnO2 (FeOx-MnO2) catalyzed micromotors can be fabricated via electrochemical co-reduction and exhibit exceptional high performance at an extremely low hydrogen peroxide (H2O2) fuel concentration. We observed that graphene/FeOx-MnO2 microtubes could show motion behaviors at fuel concentration as low as 0.03% H2O2, which is nearly one order of magnitude lower than Pt-based micromotors (normally at above 0.2% H2O2). Moreover, the micromotors exhibit higher speeds than any other reported catalytic micro/nanomotors (MNMs) at low peroxide levels. The FeOx-MnO2 systems are better catalytic MNMs, due to their excellent catalytic activity, easy fabrication, robust structure and movement, as well as low-cost, biocompatible and abundance nature, showing great potential for future applications.

14.
Medicine (Baltimore) ; 97(2): e9469, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29480834

RESUMO

BACKGROUND: Exposure to crystalline silica results in silicosis with initiation and progression of pulmonary fibrosis. The impaired lung parenchyma leads to pulmonary arterial hypertension and increased pressure in the right ventricle of the heart. Usually, the silicosis may be followed by enlargement of hilar lymphnodes, but silicosis-induced pulmonary artery stenosis with severe pulmonary hypertension is rare. Percutaneous pulmonary artery stenting and balloon angioplasty were performed to relieve stenosis and pulmonary hypertension. METHODS: We report the case of a 52-year-old man who was admitted for persistent dyspnea for 2 years and progressive dyspnea for half a month. He had been a stonemason for 20 years. The computer tomography pulmonary angiography scan images showed partially fibrotic lungs with a disseminated nodular pattern and enlarged bilateral hilar and mediastinal lymphnodes. The echocardiogram and right heart catheterization confirmed the diagnosis of severe pulmonary arterial hypertension. RESULTS: Pulmonary angiograms showed severe stenosis of the proximal upper right and lower left pulmonary artery. Moderate stenosis occured in a branch of the lower right pulmonary artery and a branch of the upper left pulmonary artery. A total of 2 stents and 4 balloons were used to relieve lesions. The final angiograms showed a significantly increased pulmonary artery caliber. The clinical symptom and 6-minute walk distance of the patient were much improved. CONCLUSION: To our knowledge, this is the first reported case of percutaneous treatment for silicosis-induced pulmonary artery stenosis and pulmonary hypertension. The clinical symptom, 6-minute walking test, and vessel caliber at areas of stenosis improved significantly following stent implantation and balloon dilatation. However, the patient was followed up for a short period and long-term outcomes have not yet been sufficiently evaluated.


Assuntos
Silicose/complicações , Estenose de Artéria Pulmonar/etiologia , Estenose de Artéria Pulmonar/terapia , Angioplastia com Balão , Humanos , Masculino , Pessoa de Meia-Idade , Silicose/diagnóstico por imagem , Estenose de Artéria Pulmonar/diagnóstico por imagem , Stents
15.
Environ Technol ; 39(17): 2168-2177, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28678616

RESUMO

The availability and phytotoxicity of heavy metals in sewage sludge is the key restrictive factor that limits sludge application. In this study, municipal sewage sludge was stabilized by alkaline slag or coal fly ash, then the leaching characteristic and fraction distributions of Cu, Cd, Pb and Zn were studied, and their effects on seed germination, root length, and plant accumulating were compared. The results showed that mixed sewage sludge with alkaline slag and coal fly ash decreased the percentage of available heavy metals in sewage sludge. The percentage of exchangeable Cu, Pb, Zn and Cd in stabilized sewage sludge (S1-S4) was 1.50-8.67 times lower than that in SS-only treatment. Leachate Cd, Cu, Pb and Zn from stabilized SS was much lower than the limit threshold. The addition of alkaline materials to SS reduced the inhibitory effect on seed germination and root growth. Pearson's correlation analysis indicated that there was a significant negative correlation between pH and available heavy metals, while a significant positive correlation between the percentage of exchangeable fraction of heavy metals, the leaching potential, tissue concentration and accumulation of heavy metal and toxicity for seed germination was observed.


Assuntos
Germinação/efeitos dos fármacos , Metais Pesados/toxicidade , Esgotos/química , Disponibilidade Biológica , Chumbo , Metais Pesados/química , Plantas , Sementes , Zinco
16.
Medicine (Baltimore) ; 95(39): e5030, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27684876

RESUMO

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of pulmonary arterial hypertension with a non-specific clinical presentation and a relatively specific presentation in high-resolution thoracic CT scan images. Definitive diagnosis is made by histological examination in previous. According to the 2015 ESC/ERS Guidelines, detection of a mutation in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) without histological confirmation is recommended to validate the diagnosis of PVOD. METHODS: We report the case of a 27-year-old man who was admitted for persistent cough and dyspnea that had lasted for 5 months and had developed and experienced progressive dyspnea for the last 2 months. The echocardiogram and right heart catheterization without vasodilator challenge confirmed the diagnosis of pulmonary arterial hypertension. Other tests, such as high-resolution thoracic CT scan, V/Q scan, pulmonary function test with diffusion capacity, and blood tests, excluded other associated diseases which could have caused pulmonary hypertension. RESULTS: The initial diagnosis at admission was idiopathic pulmonary arterial hypertension and an oral vasodilator (sildenafil) was given. However, the dyspnea subsequently worsened, and the patient was transferred to a regional lung transplant center, where he died of heart failure 1 week later. Using exome sequencing, we found an EIF2AK4 mutation, which was sufficient to confirm the diagnosis of PVOD. CONCLUSION: This is the first reported case of EIF2AK4 mutation in PVOD in a Chinese patient population. We found the frameshift EIF2AK4 mutation c.1392delT (p.Arg465fs) in this case. Up to now, there has been a paucity of data on this rare disease, and the exact role of EIF2AK4 loss-of-function mutations in the pathogenesis of PVOD is still unknown. More investigations should be conducted in the future.


Assuntos
DNA/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Pneumopatia Veno-Oclusiva/genética , Adulto , Análise Mutacional de DNA , Humanos , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Pneumopatia Veno-Oclusiva/diagnóstico , Pneumopatia Veno-Oclusiva/metabolismo , Tomografia Computadorizada por Raios X
17.
Thromb Res ; 135(5): 816-22, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25728496

RESUMO

OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and safety of direct factor Xa inhibitors (rivaroxaban and apixaban) with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee replacement. METHODS: A systematic literature search in Medline, EMBASE, EBSCO, Springer, Ovid and Cochrane library databases was performed to identify RCTs comparing rivaroxaban/apixaban with enoxaparin for the prevention of VTE after total knee replacement. The outcomes including deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding were pooled using risk ratios (RRs) with their 95% confidence intervals (95% CIs) as statistic. RESULTS: A total of 6 RCTs with 13,790 patients were included in this meta-analysis. Overall, the incidence of DVT was significantly decreased with the use of direct Xa inhibitors (both twice daily [b.i.d] and once daily [q.d.] regimes) comparing with the enoxaparin treatment (P<0.01); however, there was no significant influencing difference between direct Xa inhibitors (b.i.d. regime) and enoxaparin on the incidence of PE (P=0.06), while significantly lower rate was found for q.d. regime of direct Xa inhibitors (P=0.02). With respect to major bleeding, the pooled analysis did not demonstrate a significant difference between direct Xa inhibitors (b.i.d. and q.d. regimes) and enoxaparin (30mg and 40mg b.i.d.). CONCLUSION: In conclusion, our results confirmed that direct Xa inhibitors (rivaroxaban and apixaban) were more effective for prevention of VTE after total knee replacement as compared with enoxaparin, without increasing major bleeding risk.


Assuntos
Artroplastia do Joelho/efeitos adversos , Enoxaparina/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/complicações , Tromboembolia Venosa/prevenção & controle , Anticoagulantes/uso terapêutico , Hemorragia/prevenção & controle , Humanos , Embolia Pulmonar/complicações , Embolia Pulmonar/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Trombose Venosa/complicações , Trombose Venosa/prevenção & controle
18.
Am J Physiol Lung Cell Mol Physiol ; 306(6): L574-83, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24464808

RESUMO

We previously observed that transgelin was preferentially expressed in human pulmonary arterial smooth muscle cells (PAMSCs) under hypoxia and that the upregulation of transgelin was independent of hypoxia-inducible factor 1α (HIF-1α). Reduced transgelin expression was accompanied by significantly impaired migration ability in vitro. However, the regulation mechanism of transgelin and its function in preventing hypoxic pulmonary hypertension (HPH) was unclear. In the present study, RNA interference with hypoxia-inducible factor 2α (HIF-2α) was employed in human PASMCs. Transgelin expression was diminished in HIF-2α-siRNA-treated cells at both the mRNA and protein levels under hypoxia. However, HIF-2α did not transactivate the transgelin promoter directly. TGF-ß1 concentration in human PASMCs culture medium was higher under hypoxia, and the accumulated TGF-ß1 under hypoxia was regulated by HIF-2α. Furthermore, luciferase and chromatin immunoprecipitation assays indicated that TGF-ß1/Smad3 could bind to the transgelin promoter, resulting in increased transgelin expression. In addition to nonintact cellular migration, inhibition of transgelin expression resulted in impaired proliferation in vitro under hypoxia. A lentiviral vector used to inhibit transgelin expression was constructed and intratracheally instilled in rats 3 wk prior to hypoxia treatment. Our final results indicated that inhibition of transgelin expression locally could attenuate increased right ventricular systolic pressure and its associated cardiac and pulmonary vessel remodeling under hypoxia. Our findings indicate that HIF-2α upregulates transgelin indirectly and that accumulated TGF-ß1 is a mediator in the upregulation of transgelin by HIF-2α under hypoxia. Inhibition of transgelin expression locally could prevent HPH and pulmonary vascular remodeling in vivo.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/prevenção & controle , Proteínas dos Microfilamentos/metabolismo , Proteínas Musculares/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Pressão Sanguínea/genética , Hipóxia Celular , Proliferação de Células , Células Cultivadas , Imunoprecipitação da Cromatina , Proteínas de Ligação a DNA/metabolismo , Humanos , Masculino , Proteínas dos Microfilamentos/biossíntese , Proteínas Musculares/biossíntese , Miócitos de Músculo Liso/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica , Artéria Pulmonar/metabolismo , Veias Pulmonares/metabolismo , Interferência de RNA , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Proteína Smad3/metabolismo
20.
J Biomed Mater Res A ; 92(2): 641-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19235220

RESUMO

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor with a very limited expression in healthy tissues. It was hypothesized that foreign body wear debris induces it to participate in handling of implant-derived particles in human synovial membrane-like tissue around aseptically loosening total hip replacement implants. A DNA microarray study showed that MARCO was upregulated in human monocytes by polymethyl methacrylate particles in cell culture. MARCO mRNA and protein were strongly expressed in numerous CD68 positive macrophages and foreign body giant cells in interface membrane lining and stroma around cemented implants, but was only present in a few cells in synovial membrane from osteoarthritis patients. A 65-kDa MARCO-reactive band was only found in interface tissue extracts. This is the first work to show upregulation of MARCO mRNA by foreign bodies in vitro. This is paralleled in vivo as MARCO mRNA and protein were over-expressed in chronic foreign body synovitis. As scavenger receptor MARCO apparently participates in handling of wear particles, which due to their nondegradable, irritating nature initiate/perpetuate foreign body inflammation, and peri-implant osteolysis.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Próteses e Implantes , Falha de Prótese , Receptores Imunológicos/biossíntese , Membrana Sinovial/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Western Blotting , Cimentos para Ossos , Cães , Feminino , Imunofluorescência , Humanos , Hibridização In Situ , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Polimetil Metacrilato , RNA Mensageiro/biossíntese , RNA Mensageiro/genética
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