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1.
Eur J Pharmacol ; 919: 174797, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35122867

RESUMO

Photodynamic therapy (PDT) is noninvasive, low toxicity, and photo-selective, but may be resisted by malignant cells. A previous study found chlorin e6 (Ce6) mediated PDT showed drug resistance in lung cancer cells (LLC), which may be associated with PDT-induced DNA damage response (DDR). DDR may up-regulate glutathione peroxidase 4 (GPX4), which in turn degrade ROS induced by PDT. However, dihydroartemisinin (DHA) was found to down-regulate GPX4. Accordingly, the DHA was hypothesized to improve the resistance to PDT. The present work explores the mechanism of Ce6 mediated drug resistance and reveals whether DHA can enhance the efficacy of PDT by suppressing GPX4. The in vitro experiments found Ce6 treatment did not inhibit the viability of LLC within 6 h without inducing significant apoptosis, suggesting LLC were resistant to PDT. Further investigation demonstrated PDT could damage DNA and up-regulate GPX4, thus degrading the generated ROS. DHA effectively inhibited the viability of LLC and induced apoptosis. Importantly, DHA displayed a prominent inhibitory effect on the GPX4 expression and thereby triggered ferroptosis. Combining DHA with Ce6 for treatment of LLC resulted in the suppressed GPX4 and elevated ROS. Finally, the findings showed DHA combined with Ce6 exhibited superb anti-lung cancer efficacy. In summary, Ce6 PDT damages DNA, up-regulates GPX4 to degrade ROS, thereby inducing drug resistance. Down-regulation of GPX4 by DHA-triggered ferroptosis significantly enhances the efficacy of PDT. This study provides an outstanding theoretical basis for the regulation of the intratumoral redox system and improving PDT efficacy against lung cancer by herbal monomer DHA.


Assuntos
Artemisininas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Apoptose/efeitos dos fármacos , Artemisininas/uso terapêutico , Linhagem Celular Tumoral/efeitos dos fármacos , Clorofilídeos/metabolismo , Ferroptose/efeitos dos fármacos , Humanos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
2.
J Cancer Res Clin Oncol ; 148(4): 867-879, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997349

RESUMO

BACKGROUND: Non-small-cell lung cancer (NSCLC) is the most common malignant lung tumor and is difficult to be eradicated due to its immunosuppressive microenvironment. Chlorin e6 (Ce6)-mediated photodynamic therapy (PDT) could improve immunogenicity while destroying malignant tumor cells. However, the clinic application of Ce6-mediated PDT is limited by Ce6's poor water solubility and insufficient accumulation in lung cancer. To address this issue, Ce6 was loaded onto functionalized iron oxide nanoparticles linked with glucose to improve the distribution of Ce6 in lung cancer. MATERIALS AND RESULTS: The results of transmission electron microscopy (TEM), UV-Vis spectrophotometry, dynamic light scattering and near-infrared (NIR) spectroscopy confirmed the successful preparation of the composites. Confocal and flow cytometry showed IO-PG-GLU-Ce6 significantly enhanced the uptake of Ce6 by lung cancer cells and produced more reactive oxygen species (ROS) under NIR light irradiation. In addition, the detection of cell viability, proliferation and apoptosis indicated IO-PG-GLU-Ce6 achieved stronger photo-toxicity to lung cancer cells. Moreover, IO-PG-GLU-Ce6 treatment effectively damaged the DNA of lung cancer cells and thereby activated STING, up-regulated the expression of IFN-ß, HMGB1 and HSP90, indicating augmented immunogenicity of lung cancer cells. Further results of in vivo, organ imaging and tissue fluorescence sections demonstrated IO-PG-GLU-Ce6 significantly improved the distribution of Ce6 in tumor tissues of lung cancer-bearing mice as well. Finally, the findings of in vivo study and immunohistochemistry confirmed the better efficacy of IO-PG-GLU-Ce6. HE staining results of vital organs suggested that the composites were less toxic. CONCLUSION: In conclusion, Ce6 loaded by functionalized iron oxide nanoparticles linked with glucose exhibited both target photodynamic efficacy and the ability to enhance its immunogenicity in lung cancer. This study provides a promising strategy for augment of the targeting delivery of Ce6 and its mediated photodynamic and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Clorofilídeos , Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Porfirinas , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Clorofilídeos/uso terapêutico , Glucose , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Magnéticas de Óxido de Ferro , Camundongos , Nanopartículas/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Microambiente Tumoral
3.
Eur J Orthop Surg Traumatol ; 32(8): 1459-1468, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34605989

RESUMO

PURPOSE: Although various papers have reported on the clinical performance of cup retention with cementation of a new liner and bone grafting in the management of well-fixed cups with polyethylene wear and periacetabular osteolysis after total hip arthroplasty (THA), no systematic review of this topic has been published to date. METHODS: Medline, EMBASE and Cochrane Library were searched for articles published from January 1999 to January 2019 using "osteolysis" AND "well-fixed", "osteolysis" AND "retro-acetabular", "bone graft" AND ("retention" OR "retained" OR "stable") AND "cup", and "cemented liner" AND "well-fixed". RESULTS: Nine articles were selected for review (186 cases, 76.1 months mean follow-up). The overall revision rate was 11.3% (21 hips) most commonly due to aseptic loosening (9/186 hips), dislocation (8/186 hips), and liner wear progression (2/186 cases). The reported square size of osteolytic lesions ranged from a mean of 465.84 mm2 to a max of 4,770 mm2. Almost all reported lesions treated with bone grafts resolved or did not progress 97% (72/74). All studies indicated improved pain and functional scores at follow-up. CONCLUSION: Cementation of a new liner with periacetabular bone grafting provides an alternative option to isolated liner exchange and cup revision for the management of periacetabular osteolysis in well-fixed cups with a disrupted locking mechanism or unavailable exchange liner. Further higher quality studies are required in order to examine if the use of highly cross-linked polyethylene, highly porous-coated cups, hydroxyapatite-coated cups, and small-diameter cups influence the clinical outcome of liner cementation in well-fixed cups with periacetabular osteolysis.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Osteólise , Humanos , Polietileno/uso terapêutico , Cimentação , Falha de Prótese , Desenho de Prótese , Reoperação , Osteólise/etiologia , Osteólise/cirurgia , Artroplastia de Quadril/efeitos adversos , Acetábulo/cirurgia , Metais , Hidroxiapatitas , Seguimentos
4.
Photodiagnosis Photodyn Ther ; 37: 102645, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34823034

RESUMO

OBJECTIVE: Photodynamic therapy (PDT) is a promising strategy for the treatment of malignant tumors due to its high selectivity, limited-toxicity, and non-invasiveness. However, PDT can also induce DNA damage and subsequent repair response, which may reduce the efficacy of PDT. In the present study, we sought to explore the effect of chlorin e6 (Ce6)-mediated PDT on DNA damage and DNA damage response (DDR) in lung cancer cells. In addition, the effect of PDT combined with ATM inhibitor on molecules of DDR and the possibility of improving the efficacy of PDT were further investigated. MATERIALS AND METHODS: In the in vitro study, lewis cells were submitted to Ce6 treatment (2, 4, 8, 16, 32 µg/mL). To determine the concentration of Ce6, uptake and toxicity of Ce6 mediated PDT were detected using flow cytometry (FACS), Confocal microscopy, and CCK-8. In the subsequent research, 8 µg/mL of Ce6 was the treatment condition for inducing PDT. The different post-irradiation placement times were further grouped under this condition (2, 4, 6, 12 h). Cellular reactive oxygen species (ROS), damage of DNA were measured by DCFH-DA probe, comet assay respectively. Then the expression of p-ATM, p53, and γ-H2A.X proteins related to DNA damage response, was detected by WB. The efficacy of Ce6 induced PDT was also demonstrated by Annexin-V/PI staining as well as the expression of PCNA, cleaved-caspase-3. On this basis, ATM inhibitor was applied to treat lewis cells combined with Ce6 (2, 4 h) to investigate whether the efficacy of PDT induced by Ce6 can be improved after the ATM-related DDR was blocked. The cell viability, apoptosis, and expression of associated proteins were assayed. RESULTS: At 2-4 h after PDT treatment, ROS was dramatically elevated in lewis cells, DNA double-strand breaks (DDSB) occurred, as well as up-regulation of DDR proteins γ-H2A.X, p-ATM, and p53. At the same time, lewis cells did not undergo significant apoptosis. After ATM inhibition, the DDR was significantly blocked within 2-4 h after Ce6 induced PDT, along with a pronounced decrease in cell viability followed by a prominent increase of apoptosis. CONCLUSION: Ce6-mediated PDT generates ROS in a short period time, thus inducing DNA damage, ATM-related DDR as well as promoting resistance of lung cancer cells to PDT. Combining ATM inhibitor with PDT could effectively inhibit the DDR induced by PDT, thereby enhancing the efficacy. This study reveals a new resistance mechanism of PDT and proposes an intervention strategy.


Assuntos
Clorofilídeos , Neoplasias Pulmonares , Fotoquimioterapia , Porfirinas , Proteínas Mutadas de Ataxia Telangiectasia , Linhagem Celular Tumoral , Dano ao DNA , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia
5.
Ann Palliat Med ; 10(1): 597-605, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545788

RESUMO

BACKGROUND: Coronary heart disease (CHD) is a common clinical cardiovascular disease. This study aimed to analyze the effects of off-pump coronary artery bypass graft on the clinical efficacy, surgical indicators, and cardiac function of patients with CHD. METHODS: We retrospectively analyzed the clinical data of 120 patients with CHD who were treated in our hospital from May 2017 to May 2020. And they were divided into the control group (extracorporeal coronary artery bypass graft) and the observation group (off-pump coronary artery bypass graft). The clinical efficacy, surgical indicators, cardiac function, myocardial injury, the degree of cardiac autonomic nerve imbalance, incidence of complications and quality of life one year after the operation in the 2 groups were compared. RESULTS: The total effective rate of the observation group was significantly higher than that of the control group. Intraoperative blood loss, operation time, intraoperative blood transfusion, and hospital stay in the observation group were significantly better than those in the control group. After treatment, the levels of cardiac index (CI), ejection fraction (EF), stroke volume (SV), and cardiac output (CO) in the observation group and the control group were higher than those before treatment, especially in the observation group. Compared with those before operation, CK-MB and cTnI of the two groups significantly increased at all time points after surgery. After treatment, SDNN, LF, HF, and TP of patients in the two groups increased, which was significant in the observation group. The incidence of complications such as myocardial infarction, ischemic changes, respiratory insufficiency, and intraoperative ventricular fibrillation in the observation group was significantly lower than that in the control group. The score of quality of life in the observation group was significantly higher than the control group. CONCLUSIONS: In the treatment of patients with CHD, off-pump coronary artery bypass graft has good clinical effects, which can significantly improve the heart function, and cardiac autonomic nerve imbalance of patients, reduce myocardial damage, decrease the incidence of complications, and improve the quality of life. Therefore, off-pump coronary artery bypass graft is worthy of clinical application.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Doença das Coronárias , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença das Coronárias/cirurgia , Humanos , Complicações Pós-Operatórias , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
6.
J Arthroplasty ; 35(4): 1145-1153.e2, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31784362

RESUMO

BACKGROUND: A number of articles have been published reporting on the clinical outcomes of various acetabular reconstructions for the management of chronic pelvic discontinuity (PD). However, no systematic review of the literature has been published to date comparing the outcome and complications of different approaches to reconstruction. METHODS: The US National Library of Medicine (PubMed/MEDLINE) and EMBASE were queried for publications from January 1980 to January 2019 using keywords pertinent to total hip arthroplasty, PD, acetabular dissociation, clinical or functional outcomes, and revision total hip arthroplasty or postoperative complications. RESULTS: Overall, 18 articles were included in this analysis (569 cases with chronic PD). The overall survival rate of the acetabular components used for the treatment of chronic PD was 84.7% (482 of 569 cases) at mid-term follow-up, whereas the most common reasons for revision were aseptic loosening (54 of 569 hips; 9.5%), dislocations (45 of 569 hips; 7.9%), periprosthetic joint infection (30 of 569 hips; 5.3%), and periprosthetic fractures (11 of 569 hips; 1.9%). Both pelvic distraction technique (combined with highly porous shells) and custom triflanges resulted in less than 5% failure rates (96.2% and 95.8%, respectively) at final follow-up. Also, highly effective in the treatment of PD were cup-cages and highly porous shells with and/or without augments with 92% survivorship free of revision for aseptic loosening for both reconstruction methods. Inferior outcomes were reported for conventional cementless shells combined with acetabular plates (72.7%) as well as ilioischial cages and reconstruction rings (66.7% and 60.6% survivorship, respectively). CONCLUSION: The current literature contains moderate quality evidence in support of the use of custom triflange implants and pelvic distraction techniques for the treatment of chronic PD, with a less than 5% all-cause revision rate and low complication rates at mean mid-term follow-up. Cup-cages and highly porous shells with or without augments could also be considered for the treatment of PD because both resulted in greater than 90% survival rates. Finally, there is still no consensus regarding the impact of different types of acetabular reconstruction methods on optimizing the healing potential of PD, and further studies are required in this area to better understand the influence of PD healing on construct survivorship and functional outcomes with each reconstruction method.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Acetábulo/cirurgia , Artroplastia de Quadril/efeitos adversos , Seguimentos , Prótese de Quadril/efeitos adversos , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação , Estudos Retrospectivos
7.
Huan Jing Ke Xue ; 40(1): 488-495, 2019 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-30628309

RESUMO

Emergent cadmium pollution can cause water quality deterioration in rivers, which destroys the aquatic eco-environment and poses threats to human health. Fish species in these aquatic systems are prone to such pollution incidents and act as important indicators of the pollution level. Because cadmium enters the systematic circulation of fish and is non-biodegradable, the investigation of cadmium accumulation in fish bodies provides insights into the detrimental effects of cadmium pollution on the aquatic biological system. This research aims to validate the eco-environmental risks associated with emergent cadmium pollution incidents based on the investigation of the different tissues and organs of diverse fish species. The investigation was conducted six times along the Longjiang River using sampling methods during which all fish species were also classified and analyzed based on the water layer they reside in and their feeding habits. The results show that the cadmium concentration in the fish tissues is significantly higher in the former three investigations compared with that of the latter three analyses. For herbivorous, carnivorous, and omnivorous fish species, the cadmium concentration of their different tissues and organs follows the order:kidney > liver > gut > gill > egg > scale ≈ muscle. The cadmium concentration in the kidney is significantly higher (P<0.05) than that in any other organs of the fish species. This agrees with the fact that the kidney intensively metabolizes and accumulates heavy metals. The cadmium concentration in the same tissues or organs of the fish species living in different water layers follows the trend:demersal fish species > middle lower-layer species > middle upper-layer species. The sequence of the cadmium bioaccumulation factors in the muscles of different fish species is omnivore > carnivorous > herbivorous, that is, 8.32, 6.33, and 5.15, respectively, while the bioaccumulation factors in the muscles of the fish species in different water layers decrease in the following sequence:demersal fish species (8.18) > middle bottom-layer fish species (7.70) > middle upper-layer fish species (4.99). These experimental results indicate the biomagnification effects in heavy metal-polluted aquatic environments, where the bioaccumulation of heavy metals by fish is related to both the overall pollution level and local residential environment.


Assuntos
Cádmio/análise , Peixes , Rios , Poluentes Químicos da Água/análise , Animais , China , Monitoramento Ambiental , Metais Pesados
8.
Chemosphere ; 194: 107-116, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29197813

RESUMO

In early January 2012, the Longjiang River was subjected to a serious cadmium (Cd) pollution accident, which led to negatively environmental and social impacts. A series of measures of emergency treatment were subsequently taken to reduce water Cd level. However, little information was available about the change of Cd level in environmental matrices and long-term effect of this pollution accident to aquatic ecosystem. Thus, this study investigated the distribution of Cd in water and sediment of this river for two years since pollution accident, as well as assessed its ecological risk to aquatic ecosystem of Longjiang River. The results showed that it was efficient for taking emergency treatment measures to decrease water Cd concentration to below the threshold value of national drinking water quality standard of China. There was high risk (HQ > 1) to aquatic ecosystem in some of reaches between February and July 2012, but low or no risk (HQ < 1) between December 2012 to December 2013. Cd concentration in sediment in polluted reaches increased after pollution accident and emergency treatments in 2012, but decreased in 2013. During flood period, the sediment containing high concentration of Cd in Longjiang River was migrated to downstream Liujiang River. Cd content in sediment was reduced to background level after two years of the pollution accident occurrence. The study provides basic information about Cd levels in different media after pollution accident, which is helpful in evaluating the effectiveness of emergency treatments and the variation of ecological risk, as well as in conducting water management and conservation.


Assuntos
Cádmio/análise , Sedimentos Geológicos/química , Rios/química , Poluentes Químicos da Água/análise , Qualidade da Água , Acidentes , China , Ecossistema , Monitoramento Ambiental , Metais Pesados/análise , Medição de Risco
9.
Biomaterials ; 154: 234-247, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29144982

RESUMO

Although it has been well established that osteogenic differentiation of bone mesenchymal stem cells (bMSCs) as well as osteoclastic differentiation of macrophages can be manipulated by the nanostructure of biomaterial surfaces, the interactions among the effects of the surface on immune cells and bMSCs remained unknown. Therefore, in this study, the osteogenic behaviors and secretion of osteoclastogenesis-related cytokines of human bMSCs on TiO2 nanotubular (NT) surfaces in conditioned medium (CM) generated by macrophages cultured on the respective NT surfaces (NT-CM) were analyzed. Although bMSCs showed consistent osteogenic behaviors on the NT5 and NT20 surfaces in both standard culture medium and both types of NT-CM, collagen synthesis and extracellular matrix mineralization were partially impeded on the NT20 surface in NT20-CM and bMSC cytokine secretions on the NT20 surface in NT20-CM elicited remarkable multinuclear giant cell and osteoclast formation compared with that observed on the NT5 surface in NT5-CM. After implantation in vivo, mineralized bone formation was significantly delayed around the NT20 implant compared with the NT5 implant, but both surfaces contributed to good bone formation after 12 weeks. The results obtained in this study advance our understanding of the confounding influence of the implant surface nanostructure, macrophage inflammatory response, and osteogenic differentiation of bMSCs as well as the retro-regulative effects of bMSCs on the osteoclastic differentiation of macrophages, and the culture system based on different NT surfaces and CM generated on the respective surfaces may provide a systematic research model for evaluating the performance of endosseous implants as well as a prospective approach for improving implant osseointegration via immune-regulation.


Assuntos
Osso e Ossos/citologia , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/metabolismo , Células-Tronco Mesenquimais/citologia , Osteogênese , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Titânio/farmacologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Implantes Experimentais , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Monócitos/citologia , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Osseointegração/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Solubilidade , Propriedades de Superfície
10.
Oncotarget ; 8(17): 29318-29327, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28404977

RESUMO

There are no large samples or exact prediction models for assessing the cancer risk factors of solitary pulmonary nodules (SPNs) in the Chinese population. We retrospectively analyzed the clinical and imaging data of patients with SPNs who underwent computer tomography guided needle biopsy in our hospital from Jan 1st of 2011 to March 30th of 2016. These patients were divided into a development data set and a validation data set. These groups included 1078 and 344 patients, respectively. A prediction model was developed from the development data set and was validated with the validation data set using logistic regression. The predictors of cancer in our model included female gender, age, pack-years of smoking, a previous history of malignancy, nodule size, lobulated and spiculated edges, lobulation alone and spiculation alone. The Area Under the Curves, sensitivity and specificity of our model in the development and validation data sets were significantly higher than those of the Mayo model and VA model (p < 0.001). We established the largest sampling risk prediction model of SPNs in a Chinese cohort. This model is particularly applicable to SPNs > 8 mm in size. SPNs in female patients, as well as SPNs featuring a combination of lobulated and spiculated edges or lobulated edges alone, should be evaluated carefully due to the probability that they are malignant.


Assuntos
Nódulo Pulmonar Solitário/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Nódulo Pulmonar Solitário/patologia , Adulto Jovem
11.
J Thorac Dis ; 8(6): 1227-33, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27293841

RESUMO

BACKGROUND: Pneumonectomy (PN) has traditionally been the treatment of choice for central lung tumors for which the alternative is sleeve lobectomy (SL). The aim of this study was to compare early and long-term results after SL and PN in focusing on T3 central non-small cell lung cancer (NSCLC). METHODS: Patients who underwent SL (n=58) or PN (n=42) were retrospectively analyzed. For bias reduction, these 100 patients had been selected according to the following criteria: (I) tumor located in the main bronchus less than 2 cm distal to the carina; (II) there were no N2 disease; (III) no induction therapy was applied; (IV) complete resection (R0) was achieved. RESULTS: SL and PN patients had comparable mean ages, gender distribution, mean forced expiratory volume in 1 second (FEV1), stage and tumor grade. Postoperative mortality (3.4% vs. 4.8%, P=1.0) and morbidity (41% vs. 38%, P=0.74) were similar between the two groups. Recurrences occurred in 48% of patients after SL and in 31% of those after PN (P=0.08). The 5-year survival after SL (64.8%) and PN (61.4%) was not significantly different (P=0.20). Multivariable survival analysis showed that there were no independent prognostic factors. CONCLUSIONS: SL does not compromise survival for NSCLC with T3 central disease compared with PN. It is an adequate oncologic resection and should be treated as the first line intervention whenever complete resection can be achieved.

12.
Am J Physiol Heart Circ Physiol ; 309(8): H1303-13, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26371161

RESUMO

A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b(+) cells and F4/80(+) macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.


Assuntos
Células Endoteliais/metabolismo , Terapia Genética/métodos , Molécula 1 de Adesão Intercelular/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/metabolismo , Regiões 3' não Traduzidas , Animais , Adesão Celular , Técnicas de Cocultura , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Feminino , Regulação da Expressão Gênica , Células HL-60 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/genética , Leucócitos/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , RNA Mensageiro/metabolismo , Fatores de Tempo , Transfecção , Fator de Necrose Tumoral alfa/farmacologia
13.
Biomaterials ; 35(37): 9853-9867, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25201737

RESUMO

The use of endosseous implanted materials is often limited by undesirable effects that may be due to macrophage-related inflammation. The purpose of this study was to fabricate a nanostructured surface on a titanium implant to regulate the macrophage inflammatory response and improve the performance of the implant. Anodization at 5 and 20 V as well as UV irradiation were used to generate hydrophilic, nanostructured TiO2 surfaces (denoted as NT5 and NT20, respectively). Their surface characteristics and in vivo osseointegration as well as the inflammatory response they elicit were analyzed. In addition, the behavior of macrophages in vitro was evaluated. Although the in vitro osteogenic activity on the two surfaces was similar, the NT5 surface was associated with more bone formation, less inflammation, and a reduced CD68(+) macrophage distribution in vivo compared to the NT20 and polished Ti surfaces. Consistently, further experiments revealed that the NT5 surface induced healing-associated M2 polarization in vitro and in vivo. By contrast, the NT20 surface promoted the pro-inflammatory M1 polarization, which could further impair bone regeneration. The results demonstrate the dominant role of macrophage-related inflammation in bone healing around implants and that surface nanotopography can be designed to have an immune-regulating effect in support of the success of implants.


Assuntos
Substitutos Ósseos/química , Inflamação/etiologia , Macrófagos/imunologia , Nanoestruturas/química , Osseointegração , Próteses e Implantes/efeitos adversos , Titânio/química , Animais , Substitutos Ósseos/metabolismo , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/metabolismo , Fêmur/lesões , Fêmur/fisiologia , Humanos , Inflamação/imunologia , Masculino , Ratos Sprague-Dawley , Propriedades de Superfície , Titânio/imunologia
14.
J Thorac Dis ; 5(6): 862-3, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24409367

RESUMO

An open radical surgery for lung cancer of the right upper lobe is performed under suitable conditions in this case. According to the actual conditions, the horizontal fissure is made a "tunnel" dissociation during the operation to fully expose hilar structures (artery, vein, and bronchus). Since intraoperative frozen section diagnosis shows malignant result, lymph nodes are dissected. Hemostasis, protection of the important peripheral organs and standard postoperative placement of drainage tube should be noted. The observability of this surgery is the clear exposure and brief operation.

15.
Zhonghua Wai Ke Za Zhi ; 47(14): 1058-60, 2009 Jul 15.
Artigo em Chinês | MEDLINE | ID: mdl-19781268

RESUMO

OBJECTIVE: To evaluate the surgical therapeutic strategy and prognostic factors for non-small cell lung cancer (NSCLC) with mediastinal lymph node metastasis (N2). METHODS: The survival rate of 117 patients with N2 NSCLC treated surgically from January 1999 to May 2003 were analyzed. There were 88 male cases and 29 female cases, aged from 29 to 79 years. The procedure of operation (lobectomy, pneumonectomy and palliative resection), histological classification (squamous cell carcinoma, adenocarcinoma, mixed carcinoma, and large cell carcinoma and others), T primary tumor status, and adjuvant therapy were analyzed to determine their impact on the 5-year survival rate. RESULTS: The median survival time was 22 months, and the over-all 3- and 5-year survival rate was 28.1% and 19.0%. Survival was higher in patients with lobectomy than with palliative resection, with T1 and T2 than with T4. The 5-year survival rate had no deference in age, sex and different histological classification. The 5-year survival rates of lobectomy and pneumonectomy (22.2% and 25.0% respectively) was higher than palliative resection (9.1%). CONCLUSIONS: Surgical procedures (especially lobectomy) is the best choice for N2 NSCLC patients with T1 or T2. But it can not prolong T4 patients' life significantly.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Masculino , Mediastino/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pneumonectomia/métodos , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
16.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(12): 3388-91, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20210176

RESUMO

A method for determining 33 elements in lung tissues of patients with lung cancer was developed by using vacuum freeze-drying microwave digestion-ICP-MS. The lung tissue samples were treated by vacuum freeze-drying equipment. After microwave digestion in HNO3-H2O2 solution system, the samples were diluted with the method of constant volume. Under the optimized conditions the samples were analyzed by ICP-MS. The double internal standard elements Rh and Re were used to compensate for matrix suppression effect and sensitivity drift. The analytical results showed that the detection limits of the 33 elements were 0.01-0.45 ng x mL(-1). The national standard reference material GBW(E)080193 bovine liver was analyzed by the described method and the measured element values accorded with the standard values or the reference values. The relative standard deviation (RSD) of the method was 2.1%-14.3%. The recovery rates of the studied elements were 90.1%-117.5%. The contents of 33 elements in lung cancer tissues, paracancerous lung tissues and benign lung tissues of 6 patients with lung cancer were determined by the method. It was indicated that the method is rapid, simple and accurate for determining multi-elements in human lung tissue and other biological samples.


Assuntos
Neoplasias Pulmonares/química , Espectrometria de Massas , Elementos Químicos , Humanos , Micro-Ondas
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