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1.
Materials (Basel) ; 17(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38541512

RESUMO

Coke plays a key role as the skeleton of the charge column in BF. The gas path formed by the coke layer in the BF has a decisive influence on gas permeability. At high temperatures, the interface between coke and ore undergoes a melting reaction of coke and a reduction reaction of ore. The better the reducibility of the ore, the more conducive it is to the coupling reaction of ore and coke. The melting loss reaction of coke becomes more intense, and the corresponding strength of coke will decrease, which will affect the permeability of the blast furnace and is not conducive to the smooth operation of the blast furnace. Especially with a deterioration in iron ore quality, BF operation faces severe challenges, which makes it necessary to find an effective way to strengthen BF operation. In this study, a melting-dropping furnace was used to develop and clarify the high-temperature interaction between coke and iron ores with different layer thicknesses. The influencing factors were studied by establishing a gas permeability mathematical model and observing the metallographic microscope images of samples after the coke solution loss reaction. The relationships between coke layer thickness, distribution of gas flow, and pressure drop were obtained. The results showed that, under certain conditions, the gas permeability property of a furnace burden has been improved after the coke layer thickness increased. Upon observing the size of coke particles at the interface reaction site, the degree of melting loss reaction can be determined. A smaller particle size indicates more melting loss reaction. A dripping eigenvalue for molten metal was introduced to evaluate the dynamic changes in the comprehensive dripping properties of molten metal of furnace burden, which showed that the dripping eigenvalue for the molten metal could deteriorate because of the unruly thickness and the coke layer thickness should be limited through considering the operational indicators of the blast furnace.

2.
BMC Microbiol ; 23(1): 237, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37641037

RESUMO

BACKGROUND: Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. METHODS: Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. RESULTS: Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer. CONCLUSIONS: Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets.


Assuntos
Neoplasias Pulmonares , Microbiota , Humanos , Saliva , População do Leste Asiático , Estudos Retrospectivos , Microbiota/genética , Microambiente Tumoral
3.
J Hazard Mater ; 422: 126848, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34403943

RESUMO

Face masks are necessary for fighting against the coronavirus disease 2019 around the world. As the face mask is usually made from polymers and phthalates are widely-used additives into the polymers, the face mask could be a potential source of phthalate exposure to humans. However, limited knowledge is available on the occurrence and risks of the phthalates from the face mask. In this study, twelve phthalates were determined in 56 mask samples collected from different countries. The phthalates were detected in all the samples with total levels ranging from 115 ng/g to 37,700 ng/g. Estimated daily intakes (EDIs) of the phthalates from the masks ranged from 3.71 to 639 ng/kg-bw/day, and the EDIs of the phthalates from masks for toddlers were approximately 4-5 times higher than those for adults. Non-carcinogenic risks in relation to the phthalates in masks were found to be within safe levels, yet 89.3% of the mask samples exhibited potential carcinogenic effects to humans. The extent of the risks for wearing masks located at a moderate level comparing with other skin-contacted products. This study unveiled a potential source of phthalate exposure to human, and indicated necessity of managing types and levels of additives in the face masks.


Assuntos
COVID-19 , Ácidos Ftálicos , Adulto , Humanos , Máscaras , Ácidos Ftálicos/toxicidade , SARS-CoV-2
4.
J Recept Signal Transduct Res ; 42(1): 23-33, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33243063

RESUMO

PURPOSE: Pulsatilla saponins from pulsatilla chinensis (Bunge) Regel have potential anti-tumor activities to certain human cancers. However, the roles of pulsatilla saponin E separated from pulsatilla saponins in non-small cell lung cancer (NSCLC) have not been reported. MATERIALS AND METHODS: After treating NSCLC cells by pulsatilla saponin E at different concentrations, cell viability was measured by MTT and CCK-8 assays, and cell migration, invasion and apoptosis were detected by scratch wound-healing, transwell and flow cytometry assays. The contents of free cholesterol (FC) and total cholesterol (TC) were measured by high performance liquid chromatography (HPLC). The expression levels of flotillin-1, flotillin-2, Akt, fatty acid synthase (FASN) were detected by qRT-PCR and Western blot assays. RESULTS: Pulsatilla saponin E suppressed viability, migration, invasion and promoted apoptosis of NSCLC cells followed by regulation of apoptosis-related proteins, reduced contents of FC and TC, and the expression levels of flotillin-1, flotillin-2, Akt, and FASN in a concentration-dependent manner. However, the inhibitory effects of pulsatilla saponin E on viability, migration, invasion of A549 cells and the expression levels of flotillin-1, flotillin-2, Akt, and FASN were reversed by flotillin-2 overexpression. CONCLUSIONS: Our study revealed that pulsatilla saponin E suppressed migration, invasion and promoted apoptosis of NSCLC cells through negatively regulating Akt/FASN signaling pathway via the inhibition of flotillin-2 in lipid raft (LR). The current findings could be explored for developing a novel therapeutic drug for NSCLC treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pulsatilla , Saponinas , Apoptose , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ácido Graxo Sintase Tipo I , Ácido Graxo Sintases , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Microdomínios da Membrana/metabolismo , Proteínas de Membrana , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pulsatilla/metabolismo , Saponinas/farmacologia
6.
Heart Surg Forum ; 23(6): E725-E730, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33234221

RESUMO

BACKGROUND: To verify the validity and feasibility of using a mechanical compression method to locate the atrioventricular node in open-heart surgery. METHODS: Ten healthy miniature pigs were used to establish an animal model of the beating heart under cardiopulmonary bypass. During the operation, the atrioventricular node and its surrounding areas were stimulated by mechanical compression (mechanical compression method), and the occurrence of complete atrioventricular block was judged by real-time electrocardiograph monitoring and direct observation of the heart rhythm to identify the position of the atrioventricular node. The final localization of the atrioventricular node was determined using the iodine staining method, and the results were used as the "gold standard" to test the effectiveness and feasibility of the mechanical compression method for locating the atrioventricular node. RESULTS: With the beating heart model, complete atrioventricular block occurred after mechanical compression of the "atrioventricular node" area in 10 pigs. Nine pigs regained normal conduction immediately after the compression was released, and one pig failed to recover. No atrioventricular block or other arrhythmias occurred after mechanical compression of the "non-atrioventricular node" area. The sensitivity of the method was 86.6%, specificity was 100.0%, misdiagnosis rate was 0.0%, missed diagnosis rate was 13.4%, positive predictive value was 100.0%, negative predictive value was 97.9%, positive likelihood ratios were +∞, negative likelihood ratios were 13.4%, accuracy was 98.1%, and diagnostic odds ratio was +∞. CONCLUSION: This study innovatively proposes the application of the mechanical compression method to locate the atrioventricular node during operation and preliminarily proves that this method is effective and feasible through animal experiments.


Assuntos
Bloqueio Atrioventricular/diagnóstico , Nó Atrioventricular/fisiopatologia , Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias , Animais , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/fisiopatologia , Modelos Animais de Doenças , Eletrocardiografia/métodos , Suínos , Porco Miniatura
7.
Nature ; 578(7796): 577-581, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32076270

RESUMO

Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and cellular processes. However, whether sensors for H2O2 also exist on the cell surface remains unknown. In plant cells, H2O2 triggers an influx of Ca2+ ions, which is thought to be involved in H2O2 sensing and signalling. Here, by using forward genetic screens based on Ca2+ imaging, we isolated hydrogen-peroxide-induced Ca2+ increases (hpca) mutants in Arabidopsis, and identified HPCA1 as a leucine-rich-repeat receptor kinase belonging to a previously uncharacterized subfamily that features two extra pairs of cysteine residues in the extracellular domain. HPCA1 is localized to the plasma membrane and is activated by H2O2 via covalent modification of extracellular cysteine residues, which leads to autophosphorylation of HPCA1. HPCA1 mediates H2O2-induced activation of Ca2+ channels in guard cells and is required for stomatal closure. Our findings help to identify how the perception of extracellular H2O2 is integrated with responses to various external stresses and internal cues in plants, and have implications for the design of crops with enhanced fitness.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Peróxido de Hidrogênio/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Sinalização do Cálcio , Cisteína/química , Cisteína/metabolismo , Ativação Enzimática , Proteínas de Membrana/química , Proteínas de Membrana/genética , Mutação , Oxirredução , Células Vegetais/metabolismo , Domínios Proteicos , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética
8.
J Surg Res ; 249: 50-57, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31918330

RESUMO

BACKGROUND: Immunosuppressive medications are widely used for the prevention of allograft rejection in transplantation and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Despite their clinical utility, these medications are accompanied by multiple off-target effects, some of which may be mediated by their effects on mitochondria. METHODS: We examined the effect of commonly used immunosuppressive reagents, mycophenolate mofetil (MMF), cyclosporine A (CsA), rapamycin, and tacrolimus on mitochondrial function in human T-cells. T-cells were cultured in the presence of immunosuppressive medications in a range of therapeutic doses. After incubation, mitochondrial membrane potential, reactive oxygen species (ROS) production, and apoptotic cell death were measured by flow cytometry after staining with DiOC6, MitoSOX Red, and Annexin V and 7-AAD, respectively. Increases in cytosolic cytochrome c were demonstrated by Western blot. T-cell basal oxygen consumption rates were measured using a Seahorse bioanalyzer. RESULTS: T-cells demonstrated significant levels of mitochondrial depolarization after treatment with therapeutic levels of MMF but not after treatment with CsA, tacrolimus, or rapamycin. Only MMF induced T-cell ROS production and induced significant levels of apoptotic cell death that were associated with increased levels of cytosolic cytochrome c. MMF decreased T-cell basal oxygen consumption within its therapeutic range, and CsA demonstrated a trend toward this result. CONCLUSIONS: The impairment of mitochondrial function by commonly used immunosuppressive reagents may impair T-cell differentiation and function by decreasing energy production, producing toxic ROS, and inducing apoptotic cell death.


Assuntos
Imunossupressores/efeitos adversos , Mitocôndrias/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ciclosporina/efeitos adversos , Metabolismo Energético/efeitos dos fármacos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Células Jurkat , Potencial da Membrana Mitocondrial , Mitocôndrias/patologia , Ácido Micofenólico/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Sirolimo/efeitos adversos , Linfócitos T/citologia , Linfócitos T/patologia , Tacrolimo/efeitos adversos
9.
Int J Biol Markers ; 35(1): 26-32, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31841062

RESUMO

BACKGROUND AND AIM: Our aim was to compare the prognostic value of the American Joint Committee on Cancer (AJCC) 7th and 8th editions staging systems for patients with gastric cancer in China. METHODS: A total of 1326 gastric cancer patients diagnosed between 2008 and 2012 were included. The discriminative ability of the AJCC 8th and 7th editions was compared using the Harrell's concordance index (C-index). RESULTS: There are two main modifications in the 8th edition. (i) pN3 staging was divided into pN3a and pN3b. The gastric cancer patients with pN3a experienced significantly better overall survival compared with those with pN3b (5-year overall survival: 34.5% vs. 15.6%, P < 0.001) (stratified by pT: pT3: 5-year overall survival: 33.9% vs. 13.2%, P < 0.001; pT4a: 32.8% vs. 16.9%, P = 0.056; pT4b: 17.0% vs. 11.1%, P = 0.048). (ii) Subgroup staging adjustments. The subgroup staging adjustments (T3N3bM0 (IIIB→IIIC), T4aN3aM0 (IIIC→IIIB), T4bN0M0 (IIIB→IIIA), and T4bN2M0 (IIIC→IIIB)) resulted in more gastric cancer patients being accurately staged. Furthermore, the C-index value of the 8th edition tumor node metastasis (TNM) staging system was significantly higher than that of the AJCC 7th TNM staging system to predict the survival of gastric cancer patients (0.701 vs. 0.685, P < 0.001). CONCLUSIONS: The 8th edition of the TNM staging system is superior to the 7th edition staging system for prediction of survival of gastric cancer patients in China.


Assuntos
Publicações Periódicas como Assunto , Neoplasias Gástricas/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Taxa de Sobrevida , Estados Unidos
10.
Invest New Drugs ; 38(2): 350-359, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31124054

RESUMO

Intrinsic chemoresistance is the main reason for the failure of human pancreatic ductal adenocarcinoma (PDAC) therapy. To identify the candidate protein, we compared the protein expression profiling of PDAC cells and its distinct surviving cells following primary treatment with gemcitabine (GEM) and 5-fluorouracil (5-FU) by two-dimensional electrophoresis combined with liquid chromatography-mass spectrometry or mass spectrometry. A total of 20 differentially expressed proteins were identified, and annexin A1 (ANXA1) was analyzed for further validation. The functional validation showed that the downregulation of ANXA1 contributes to GEM and 5-FU resistance in PDAC cells through protein kinase C/c-Jun N-terminal kinase/P-glycoprotein signaling pathway. Our findings provide a platform for the further elucidation of the underlying mechanisms of PDAC intrinsic chemoresistance and demonstrated that ANXA1 may be a valid marker for anticancer drug development.


Assuntos
Anexina A1 , Biomarcadores Tumorais , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Neoplasias Pancreáticas , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Anexina A1/genética , Anexina A1/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Regulação para Baixo , Feminino , Fluoruracila/farmacologia , Humanos , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais , Gencitabina
11.
J Am Soc Cytopathol ; 8(5): 250-257, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543224

RESUMO

INTRODUCTION: Cervical cancer rates in China remain high, with only limited opportunistic screening in urban centers and large mostly unscreened rural areas. Cervical cytology practices in China have been changing over the last decade with introduction of The Bethesda System reporting terminology, liquid-based cytology (LBC), and programs for cervical cytology screening of underserved rural populations. An effort was undertaken for the first time to collect nationwide data on cervical cytology laboratory practices in China, a possible first step toward increased standardization and potential development of nationwide cytology quality benchmarks. MATERIALS AND METHODS: Data on cervical cytology practices from 1572 laboratories operating in 26 nationwide Provisional Level Administrative Divisions was collected in an online survey approved through the Obstetrics and Gynecology Hospital of Fudan University in Shanghai. RESULTS: Over 90% of cervical cytology laboratories in China now solely use Bethesda System reporting terminology. LBC is now the most commonly utilized form of cervical cytology, with lower-cost Chinese-manufactured LBC formulations used in almost 70% of laboratories. Nationwide, significantly higher abnormal cytology rates were reported with LBC than with the conventional Papanicolaou smear (CPS); however, the CPS remains a useful low-cost alternative as China strives to extend cervical screening to large underserved rural areas. CONCLUSIONS: Abnormal cytology rates were not significantly different when different levels of hospitals were compared. The survey identified nationwide opportunities for cytology quality improvement, including low rates of reporting of unsatisfactory cases and low rates for atypical glandular cells.


Assuntos
Citodiagnóstico , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , China , Feminino , Geografia , Humanos , Teste de Papanicolaou
12.
Front Oncol ; 9: 329, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131256

RESUMO

Background and Objectives: Our aim was to investigate whether the modified American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system based on the node ratio can further improve the capacity of prognosis assessment for gastric cancer (GC) patients regardless of the number of lymph nodes examined (eLNs). Methods: A total of 17,187 GC patients in the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a training set of 7,660 GC patients, we built the tumor-node ratio-metastasis (TNrM) staging system, which was then externally validated with a validation set of 9,527 GC patients. Results: For the training set, the C-index value of the TNrM staging system was significantly higher than that of the AJCC 8th TNM staging system to predict survival for GC patients (C-index: 0.688 vs. 0.671, P < 0.001). Moreover, the C-index value of the TNrM staging system was significantly higher than that of the 8th TNM staging system to predict survival for GC patients with ≤15 eLNs (C-index: 0.682 vs. 0.673, P < 0.001), as well as for GC patients with >15 eLNs (C-index: 0.700 vs. 0.694, P < 0.001). Similar results were found in the validation set. Conclusions: The TNrM staging system predicted survival more accurately and discriminatively than the AJCC 8th TNM staging system for GC patients regardless of the number of eLNs.

13.
Med Sci Monit ; 25: 3983-3988, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31138775

RESUMO

BACKGROUND Gambogic acid (AG) is believed to be a potent anti-cancer agent. ER (endoplasmic reticulum) stress-induced cell apoptosis was identified as one of the anti-proliferative mechanisms of several anti-cancer agents. In this study, we investigated the involvement of ER stress-induced apoptosis in the anti-proliferative effect of GA on NSCLC (non-small cell lung cancer) cells. MATERIAL AND METHODS GA at 0, 0.5, and 1.0 µmol/l was used to treat A549 cells. We also used the ER stress-specific inhibitor 4-PBA (4-phenylbutyric acid) (1 µmol/l) to co-treat the cells incubated with GA. Cell viability was assessed by MTT (methyl thiazolyl tetrazolium) assay. Cell apoptosis was evaluated by MTT (methyl thiazolyl tetrazolium) assay. Intracellular ROS (reactive oxygen species) production was detected by DCFH-DA (2,7- dichloro-dihydrofluorescein diacetate) florescent staining. Western blotting was used to assess the expression and phosphorylation levels of protein. RESULTS GA treatment significantly reduced cell viabilities of NSCLC cells in a concentration-dependent manner. GA treatment increased intracellular ROS level, expression levels of GRP (glucose-regulated protein) 78, CHOP (C/EBP-homologous protein), ATF (activating transcription factor) 6 and caspase 12, as well as the phosphorylation levels of PERK (protein kinase R-like ER kinase) and IRE (inositol-requiring enzyme) 1alpha. Co-treatment of 4-PBA dramatically impaired the inhibitory effect of GA on cell viability. 4PBA co-treatment also decreased expression levels of GRP78, CHOP, ATF6, and caspase12, as well as the phosphorylation levels of PERK and IRE1alpha, in GA-treated NSCLC cells, without affecting ROS levels. CONCLUSIONS GA inhibited NSCLC cell proliferation by inducing ROS-induced ER stress-medicated apoptosis of NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Xantonas/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , China , Chaperona BiP do Retículo Endoplasmático , Endorribonucleases , Proteínas de Choque Térmico/análise , Humanos , Neoplasias Pulmonares/metabolismo , Fenilbutiratos/farmacologia , Proteínas Serina-Treonina Quinases , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição CHOP/análise , Xantonas/metabolismo
14.
Int J Biol Macromol ; 132: 213-221, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30926500

RESUMO

As iron supplement, the antioxidant activities of APS-iron (III) complex were comprehensively evaluated by 5-axe cobweb charts, which indicated the APS-iron (III) complex had a certain antioxidant activity and been weaker than that of APS. The results of immunological activity experiments indicated the stimulation index increased with APS-iron (III) complex concentration increase. When the concentration of the APS-iron (III) complex was 50 µg/mL, the lymphocytes proliferation increased by 35.7% compared with APS. APS-iron (III) complex also had better complement fixing activity than APS, 0.589 mg/mL of which achieved 50% complement fixing activities. Through the iron supplement experiments on iron-deficiency anemia mouse model, we found the APS-iron (III) complex faster increased hemoglobin concentration, SOD, CAT and faster decreased MDA to the normal level than Niferex and ferrous sulfate. Histological results revealed that the tissue sections were clear without obvious pathological changes and bone marrow had most hematopoietic cells from APS-iron (III) complex rat group, which also proved the APS-iron (III) complex had no significant side effects. Therefore, APS-iron (III) complex may be developed as a multifunctional iron supplement for clinical application.


Assuntos
Anemia Ferropriva/imunologia , Anemia Ferropriva/metabolismo , Astragalus propinquus/química , Complexos de Coordenação/farmacologia , Ferro/química , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Ratos , Ratos Wistar
15.
Liver Transpl ; 25(4): 610-626, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30734488

RESUMO

Machine preservation (MP) has emerged as a promising technology in liver transplantation, but the cellular processes occurring during MP have not been characterized. Recent studies have noted the presence of inflammatory molecules generated during MP. We hypothesized that there is a metabolism-dependent accumulation of damage-associated molecular patterns (DAMPs) and inflammatory cytokines during MP and that these molecules provoke inflammation in the graft. To stratify groups by metabolic rate, MP was performed on rat livers from standard donors at 3 different temperatures: room temperature (RT), subnormothermic (30°C), and normothermic (37°C). Static cold storage at 4°C was included as a reference group. Following a 4-hour preservation period, graft reperfusion was performed ex vivo at 37°C (n = 6 for all groups). Levels of DAMPs and inflammatory cytokines were measured, and their biological activity was assessed by determining toll-like receptor (TLR) stimulation, inflammatory gene expression, and activation of cell death pathways. There was a time-dependent increase in levels of DAMPs during MP with high-mobility group box 1 and extracellular DNA levels increasing for all groups (P < 0.05, 30 versus 240 minutes). Tumor necrosis factor α levels in the perfusate also increased during MP for all groups (P < 0.05, 30 minutes versus 240 minutes). Levels of inflammatory molecules correlated with increased activation of TLRs (TLR3, P = 0.02, normothermic machine preservation [MP37] versus machine preservation at room temperature [MPRT]; TLR9, P = 0.02, MP37 versus MPRT). Priming of the NLRP3 inflammasome and activation of cell death pathways were reduced in grafts preserved by MP at room temperature. In conclusion, inflammatory molecules produced during MP have a biological impact on the graft. Therapies to attenuate DAMP-mediated inflammation during MP may further enhance this promising technology.


Assuntos
Alarminas/metabolismo , Transplante de Fígado , Preservação de Órgãos/efeitos adversos , Perfusão/efeitos adversos , Traumatismo por Reperfusão/imunologia , Alarminas/imunologia , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Fígado/irrigação sanguínea , Fígado/imunologia , Fígado/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Preservação de Órgãos/instrumentação , Preservação de Órgãos/métodos , Perfusão/instrumentação , Perfusão/métodos , Ratos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais/imunologia , Temperatura , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
16.
Phytomedicine ; 57: 18-29, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30668319

RESUMO

BACKGROUND: Luteolin (3,4,5,7-tetrahydroxy flavone) is a natural flavonoid abundant in fruits and vegetables. Although luteolin has shown pro-apoptotic activity in hepatocellular carcinoma (HCC) cells, the underlying molecular mechanism has not yet been clarified. PURPOSE: The aim of this study is to identify novel miRNAs involved in the action of luteolin in HCC cells and to explore the biological roles of these miRNAs. METHODS: The effect of luteolin on HCC cell growth was assessed using CCK-8 colony formation assay, flow cytometric analysis in vitro, and a xenograft model in vivo. miRNA expression profiles were assessed using next-generation sequencing. Differentially expressed miRNAs were validated by quantitative PCR. Bioinformatics analysis and luciferase reporter assay were utilized to confirm the binding of miR-6809-5p to the 3'-untranslated region (3'-UTR) of flotillin 1 (FLOT1). Furthermore, the effects of ectopic FLOT1 and miR-6809-5 expression on cell proliferation, colony formation, and cell apoptosis were also assessed. Western blotting analysis was used to detect activation of multiple signaling molecules including Erk1/2, p38, JNK, and NF-κB/p65 in the MAPK pathway. RESULTS: It was found that luteolin significantly inhibited HCC growth and caused apoptosis and cell cycle arrest at the G0/G1 phase in Huh7 cells, at the G2/M phase in HepG2 cells in vitro. Tumorigenic studies revealed that luteolin treatment significantly suppressed HCC growth in vivo. miR-6809-5p was upregulated by luteolin. Overexpression of miR-6809-5p suppressed HCC cell growth, while knockdown of miR-6809-5p reversed the anticancer effect of luteolin. With regards to its signaling mechanism, miR-6809-5p directly targets FLOT1in HCC cells. Enforced expression of FLOT1 prevented miR-6809-5p-mediated growth suppression. Downregulation of FLOT1 exerted growth-suppressive effects on HCC cells. Multiple signaling pathways including Erk1/2, p38, JNK, and NF-κB/p65 were inactivated by miR-6809-5p overexpression or FLOT1 downregulation. CONCLUSION: These findings indicated that miR-6809-5p mediates the growth-suppressive activity of luteolin in HCC, which is causally linked to FLOT1 downregulation. Induction of miR-6809-5p may provide therapeutic benefits in the treatment of HCC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Luteolina/farmacologia , MicroRNAs/genética , Animais , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Proteínas de Membrana/genética , Camundongos Nus , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
17.
World Neurosurg ; 121: e15-e21, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30189308

RESUMO

OBJECTIVE: To analyze treatment of microvascular decompression using the retrosigmoid approach (RA) in primary trigeminal neuralgia and hemifacial spasm using preoperative images combined with intraoperative microscopic navigation to avoid unnecessarily opening the mastoid air cells (MACs). METHODS: Ten patients with primary trigeminal neuralgia and 20 patients with hemifacial spasm (test group) were treated using RA for microvascular decompression. Preoperative head magnetic resonance angiography and temporal bone computed tomography were performed and the images registered using SPM12 and fused with MRIcron to determine the relationship between MACs and sigmoid sinuses. An O-arm was used for navigation, and the transverse sigmoid sinus was projected under a microscope to guide RA. A control group comprised 139 patients who had the same surgical procedure as the test group but without image processing or intraoperative navigation. RESULTS: The relationship between MACs and the ipsilateral sigmoid sinus was classified as follows: I, MACs did not exceed the lateral edge of the ipsilateral sigmoid sinus (10/60); II, MACs exceeded the ipsilateral lateral edge of the sigmoid sinus but did not exceed the medial edge (42/60); and III, MACs exceeded the medial edge of the ipsilateral sigmoid sinus (8/60). Test and control groups showed significant differences in the incidences of opening MACs (P = 0.003). There was no cerebrospinal fluid leakage or scalp and intracranial infection at follow-up. CONCLUSIONS: Image processing and intraoperative microscopic navigation can avoid unnecessarily opening MACs and might reduce postoperative cerebrospinal leakage and scalp infection after RA craniotomy.


Assuntos
Craniotomia/métodos , Espasmo Hemifacial/cirurgia , Processo Mastoide/cirurgia , Neuralgia do Trigêmeo/cirurgia , Adulto , Cavidades Cranianas/cirurgia , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Cirurgia de Descompressão Microvascular/métodos , Pessoa de Meia-Idade , Imagem Multimodal , Cuidados Pré-Operatórios/métodos , Osso Temporal , Tomografia Computadorizada por Raios X
18.
J Gastrointest Surg ; 23(3): 460-467, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225793

RESUMO

BACKGROUND: Our aim was to evaluate the prognostic value of the number of lymph nodes examined (eLNs) in patients with node-negative gastric cancer (GC) and further to adjust the American Joint Committee on Cancer (AJCC) 8th staging system based on the number of eLNs. METHODS: Node-negative GC patients diagnosed during 1988-2015 from the Surveillance, Epidemiology, and End Results (SEER) database were included. On the basis of a primary cohort of 4159 node-negative GC patients, we built the adjusted AJCC 8th staging system, which was then internally validated by a bootstrap method, and externally validated with an independent cohort of 5565 node-negative GC patients. RESULTS: The median number of eLNs was 10. For the training set, the optimal eLNs thresholds were determined to be 9 for node-negative GC patients. The adjusted AJCC 8th staging system for node-negative GC patients based on the number of eLNs had a significantly higher Harrell's concordance index than the initial AJCC 8th staging system (C-index, 0.635 versus 0.616; P < 0.001). Thus, the adjusted AJCC 8th staging system had superior prognostic stratification. Similar results were found in the validation set. CONCLUSIONS: For node-negative GC patients in the United States, the adjusted AJCC 8th staging system based on the number of eLNs predicted survival more accurately and discriminatively.


Assuntos
Adenocarcinoma/patologia , Razão entre Linfonodos , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Gastrectomia , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Programa de SEER , Neoplasias Gástricas/cirurgia , Estados Unidos
19.
Med Sci Monit ; 24: 7146-7151, 2018 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-30293083

RESUMO

BACKGROUND Activation of Notch signaling was found to be associated with cancer. Gambogic acid (GA) was reported to be an anti-cancer agent. This study investigated the anti-cancer effect of GA on human non-small cell lung cancer (NSCLC) cells. Involvement of the Notch pathway was also studied. MATERIAL AND METHODS GA at 0, 0.5, 0.75, and 1.0 µmol/l was used to incubate A549 and SPC-A1 cells. MTT assay was used to determine the cell viability. TUNEL assay was used to detect the apoptosis. Western blotting was used to evaluate protein expression levels, protein phosphorylation levels, and nuclear translocation levels. RESULTS Notch signaling pathway was activated in NSCLC cells. GA treatment significantly inhibited NSCLC cell viability and increased cell apoptosis. GA treatment significantly decreased the expression levels of DLL1, DLL3, DLL4, Jagged1, Jagged2, Bcl2, and PK3K, inhibited NICD nuclear translocation and Akt phosphorylation, and increased expression level of active caspase3. CONCLUSIONS GA inhibited NSCLC cell viability by inducing apoptosis. Inhibition of the Notch signaling pathway was the mechanism involved in the anti-proliferation effect of GA on NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptores Notch/metabolismo , Xantonas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Int J Biol Macromol ; 118(Pt B): 1438-1448, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30170361

RESUMO

Selenium is an essential trace element in human body. Se-deficiency is common phenomenon in all over the world, which severely harms the health of organism and causes the etiology of many chronic, degenerative diseases, such as atherosclerosis, arthritis, cancers, hypoimmunity, hypothyroidism and viral diseases. So, the research on preparation of Se-supplementing with the effective, safe and high Se content was imperative. In this study, Se-enriched Astragalus polysaccharide nanoparticles (Se-APS) were prepared by the previous optimization experimental conditions, as follows: reaction temperature 80.5 °C, pH 7.8, ratio of catalyst to APS 0.57:1.0 g·g-1, and reaction time 62 min. The Se content of Se-APS was as high as 13.42 ±â€¯0.37%, characterized by energy spectrometer, thermogravimetry, X-ray diffraction, fourier transform infrared, particle size, zeta potential and atomic force. Se release of the Se-APS in vitro followed the Higuchi's kinetics model and exhibited the basically same release pattern in artificial gastric juice (pH 2.0), artificial intestinal juice (pH 8.0) and PBS (pH 7.4). The proliferation of T-lymphocytes with Se-APS incubation increased at an average of 13.87%, comparing with APS. It could not only enhance the proliferation of T-lymphocytes, but also effectively suppress malignant proliferation of HepG2 cells and reduce cell migration and invasion. We prepared a novel water-soluble Se-APS by using a chelating method, which was promising as a novel Se supplements with high Se content and good bioactivity.


Assuntos
Antineoplásicos/química , Antioxidantes/química , Astrágalo/química , Nanopartículas/química , Polissacarídeos/química , Selênio/química , Água/química , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Células Hep G2 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Tamanho da Partícula , Polissacarídeos/farmacologia , Solubilidade
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