Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
1.
J Int Med Res ; 52(5): 3000605241255507, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38749907

RESUMO

Traumatic splenic rupture is rare in pregnant women; and multiple venous thromboses of the portal vein system, inferior vena cava and ovarian vein after caesarean section and splenectomy for splenic rupture has not been previously reported. This case report describes a case of multiple venous thromboses after caesarean section and splenectomy for traumatic splenic rupture in late pregnancy. A 34-year-old G3P1 female presented with abdominal trauma at 33+1 weeks of gestation. After diagnosis of splenic rupture, she underwent an emergency caesarean section and splenectomy. Multiple venous thromboses developed during the recovery period. The patient eventually recovered after anticoagulation therapy with low-molecular-weight heparin and warfarin. These findings suggest that in patients that have had a caesarean section and a splenectomy, which together might further increase the risk of venous thrombosis, any abdominal pain should be thoroughly investigated and thrombosis should be ruled out, including the possibility of multiple venous thromboses. Anticoagulant therapy could be extended after the surgery.


Assuntos
Cesárea , Esplenectomia , Ruptura Esplênica , Trombose Venosa , Humanos , Feminino , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Trombose Venosa/tratamento farmacológico , Adulto , Ruptura Esplênica/etiologia , Ruptura Esplênica/cirurgia , Ruptura Esplênica/diagnóstico , Gravidez , Cesárea/efeitos adversos , Período Pós-Parto , Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Varfarina/uso terapêutico
2.
Huan Jing Ke Xue ; 45(3): 1684-1691, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471880

RESUMO

The large input of mulch film and organic fertilizer have led to increasingly serious microplastic pollution in farmland soil of China. In this study, the microplastic pollution of peanut farmland in Dezhou City, Shandong Province was investigated. The effects of different mulching years (0, 3, 5, and 8 years) and organic fertilizer application on the abundance, particle size, color, and shape of microplastics in farmland soil were analyzed. The results showed that the average abundances of microplastics in peanut soil were 65.33, 316.00, 1 098.67, and 1 346.34 n·kg-1, respectively, after 0, 3, 5, and 8 years of film mulching. The abundance of microplastics decreased with the increase in soil depth. The abundance of microplastics in 0-10, 10-20, and 20-30 cm topsoil was 1 076.00, 603.5, and 440.25 n·kg-1, respectively, and the abundance of microplastics increased significantly with increasing years of film mulching and organic fertilizer application (P<0.05). The particle size of microplastics in the sample plot <1 mm accounted for 77.30% of the total content, and with the increase in film mulching age, the proportion of microplastics with small particle size (<1 mm) increased significantly (P < 0.05). With the increase in soil depth, the proportion of microplastics with small particle size also gradually increased, whereas the application of organic fertilizer had no significant effect on the particle size of microplastics. The color of microplastics in the plot was mainly transparent (49.77%), followed by black (16.35%) and white (16.27%). The planting age and organic fertilizer application had no significant effect on the color of microplastics in the soil (P > 0.05), but the mulching age significantly increased the proportion of transparent microplastics. The abundance proportion of the five types of microplastics were 49.77%, 25.41%, 19.15%, 3.26%, and 2.41%, respectively. These field soil microplastics were mainly composed of polyethylene (PE), polypropylene (PP), and polystyrene (PS) polymers, accounting for 21.37%, 18.57%, and 19.77% of the total, respectively. Therefore, microplastics were widely present in the soil of the peanut field cultivated layer in Dezhou, Shandong, and the applications of mulch film and organic fertilizer were the main source. This study provides an important basis for the prevention and control of soil microplastic pollution in peanut fields.

3.
J Ethnopharmacol ; 325: 117641, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38151179

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Abelmoschus manihot (L.) Medik. Seeds (AMS, སོ་མ་ར་ཛ།), a Tibetan classical herbal in China, are rich in flavonoids and phenolic glycosides compounds, such as quercetin and its derivatives. Moreover, it has been found to possess anti-rheumatoid arthritis (RA) effects. Nonetheless, its anti-RA mechanism is yet unknown. AIM OF THE STUDY: This research aimed to examine the active ingredients of AMS as well as potential pharmacological mechanisms in AMS on RA. MATERIALS AND METHODS: The ultra-performance liquid chromatography-electrospray ionization-tandem multistage mass spectrometry (UPLC-ESI-IT-MSn) technique was used to determine the primary chemical components of AMS that were responsible for the therapeutic effects on RA. In addition, 36 male Wistar rats weighing between 200 and 220 g were classified at random into six groups [normal control group, collagen-induced arthritis (CIA) group, methotrexate group (positive control, 1.05 mg/kg), AMS group (157.5 mg/kg, 315 mg/kg, 630 mg/kg)]. CIA rats were given AMS extract by intragastric administration for 28 days, and their ankles were photographed to observe the degree of swelling. Further, the arthritis score, paws swelling, and body weight changes of CIA rats were determined to observe whether AMS has any effect on RA, and synovial and cartilage tissue injuries were identified by histopathology. Besides, the levels of IL-10, TNF-α, IL-1ß, INF-γ, etc. in serum were estimated by ELISA. Western blot experiments were implemented to identify the expression levels of protein involved in the JAK2/STAT3 signaling pathway in the CIA rats' synovial tissues. Moreover, the mechanisms and targets of active ingredient therapy of AMS for RA were predicted using network pharmacology and then verified using molecular docking. RESULT: In the present study, 12 compounds were detected by UPLC-ESI-IT-MSn, such as quercetin and its derivative which could be potential active ingredients that contribute to the anti-RA properties of AMS. Our in vivo studies on CIA rats revealed that an AMS-H dose of 630 mg/kg significantly improved joint damage while decreasing the arthritic index and paw swelling. Furthermore, AMS inhibited the INF-γ, IL-6, IL-17, IL-1ß, and TNF-α, levels while upregulating the expression of anti-inflammatory cytokines IL-10 and IL-4 in serum. Besides, AMS inhibited the protein Bcl-2/Bax, STAT3, and JAK2 levels, and promoted the expression of Caspase3, SOCS1, and SOCS3 in the JAK2/STAT3 pathway. Additionally, the JAK/STAT signaling pathway was found to perform a remarkable function in the AMS therapy of RA as evidenced by enrichment in GO terms and KEGG pathways. Meanwhile, data from molecular docking experiments indicated that the core targets of PIK3CA, JAK2, and SRC bound stably to the active ingredients of mimuone, 4'-methoxy-bavachromanol, and quercetin. CONCLUSION: According to these findings, the AMS could improve joint inflammation in CIA rats, and its underlying mechanism could be linked to the regulation of the JAK2/STAT3 pathway. Therefore, AMS might become a promising agent for alleviating inflammation in RA patients.


Assuntos
Abelmoschus , Artrite Experimental , Artrite Reumatoide , Humanos , Ratos , Masculino , Animais , Interleucina-10/metabolismo , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Simulação de Acoplamento Molecular , Quercetina/farmacologia , Artrite Reumatoide/tratamento farmacológico , Transdução de Sinais , Inflamação/tratamento farmacológico , Artrite Experimental/patologia , Sementes/metabolismo , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo
4.
Haematologica ; 108(9): 2487-2502, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37021526

RESUMO

Enhancer of zeste homolog 2 (EZH2) is the lysine methyltransferase of polycomb repressive complex 2 (PRC2) that catalyzes H3K27 tri-methylation. Aberrant expression and loss-of-function mutations of EZH2 have been demonstrated to be tightly associated with the pathogenesis of various myeloid malignancies characterized by ineffective erythropoiesis, such as myelodysplastic syndrome (MDS). However, the function and mechanism of EZH2 in human erythropoiesis still remains largely unknown. Here, we demonstrated that EZH2 regulates human erythropoiesis in a stage-specific, dual-function manner by catalyzing histone and non-histone methylation. During the early erythropoiesis, EZH2 deficiency caused cell cycle arrest in the G1 phase, which impaired cell growth and differentiation. Chromatin immunoprecipitation sequencing and RNA sequencing discovered that EZH2 knockdown caused a reduction of H3K27me3 and upregulation of cell cycle proteindependent kinase inhibitors. In contrast, EZH2 deficiency led to the generation of abnormal nuclear cells and impaired enucleation during the terminal erythropoiesis. Interestingly, EZH2 deficiency downregulated the methylation of HSP70 by directly interacting with HSP70. RNA-sequencing analysis revealed that the expression of AURKB was significantly downregulated in response to EZH2 deficiency. Furthermore, treatment with an AURKB inhibitor and small hairpin RNAmediated AURKB knockdown also led to nuclear malformation and decreased enucleation efficiency. These findings strongly suggest that EZH2 regulates terminal erythropoiesis through a HSP70 methylation-AURKB axis. Our findings have implications for improved understanding of ineffective erythropoiesis with EZH2 dysfunction.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Eritropoese , Histonas , Humanos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Eritropoese/genética , Histonas/metabolismo , Metilação , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo
5.
J Enzyme Inhib Med Chem ; 38(1): 2205605, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37106478

RESUMO

EGFR mutations have been identified in 20,000 reported NSCLC (non-small cell lung cancer) samples, and exon 19 deletions and L858R mutations at position 21, known as "classical" mutations, account for 85-90% of the total EGFR (epidermal growth factor receptor) mutations. In this paper, two series of EGFR kinase inhibitors were designed and synthesised. Among them, compound B1 showed an IC50 value of 13 nM for kinase inhibitory activity against EGFRL858R/T790M and more than 76-fold selectivity for EGFRWT. Furthermore, in an in vitro anti-tumour activity test, compound B1 showed an effective anti-proliferation activity against H1975 cells with an IC50 value of 0.087 µΜ. We also verified the mechanism of action of compound B1 as a selective inhibitor of EGFRL858R/T790M by cell migration assay and apoptosis assay.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Receptores ErbB/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases , Pirimidinas/farmacologia
6.
Int J Cardiol ; 374: 108-114, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36496037

RESUMO

BACKGROUND: The antiphospholipid antibody (aPL)-positivity was suggested as a nontraditional risk of coronary artery disease (CAD) and it was associated with cigarette smoking. The co-occurrence of them was usually reported in individuals with cardiovascular diseases. This study was to demonstrate their interaction on the increasing risk of cardiovascular events. METHODS AND RESULTS: A total of 826 consecutive male individuals who underwent coronary angiography (CAG) /percutaneous coronary intervention (PCI) were prospectively followed and classified into three groups based on different smoking statuses. The current smoking subjects had the highest occurrence of aPL-positivity, including aCL IgM (20.1%) and aß2GP1 IgM (15.5%). IgM isotype positivity was an independent risk factor of CAD in the multivariate model, OR: 2.70 (1.52-4.80) for aCL IgM and OR:2.50 (1.35-4.63) for aß2GP1 IgM.The interaction of current smoking and IgM isotype positivity was significantly associated with increased risk of CAD, OR: 8.75(4.59-16.66) for aCL IgM and OR: 8.78(4.28-17.98) for aß2GP1 IgM. During about 3 years of follow-up, the smoking patients carrying persistent aPL positivity had the highest cumulative incidence of recurrent myocardial infarction and in-stent restenosis after CAD. CONCLUSION: The interaction of current smoking and IgM isotype positivity was significantly associated with the increased risk of CAD, including positive aCL IgM and aß2GP1 IgM. Cigarette smoking elevated the risk of subsequent cardiovascular events in the presence of IgM isotype positivity, including recurrent myocardial infarction and in-stent restenosis.


Assuntos
Síndrome Antifosfolipídica , Fumar Cigarros , Doença da Artéria Coronariana , Reestenose Coronária , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Masculino , Estudos Transversais , Anticorpos Antifosfolipídeos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Imunoglobulina M
7.
Polymers (Basel) ; 14(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36365617

RESUMO

High-performance polyether-ether-ketone (PEEK) is highly desirable for a plethora of engineering applications. The incorporation of conductive carbon nanotubes (CNTs) into PEEK can impart electrical conductivity to the otherwise non-conductive matrix, which can further expand the application realm for PEEK composites. However, a number of physical properties, which are central to the functionalities of the composite, are affected by the complex interplay of the crystallinity and presence of the nanofillers, such as CNTs. It is therefore of paramount importance to conduct an in-depth investigation to identify the process that optimizes the mechanical and electrical performance. In this work, PEEK/CNTs composites with different carbon nanotubes (CNTs) content ranging from 0.5 to 10.0 wt% are prepared by a parallel twin-screw extruder. The effects of CNTs content and annealing treatment on the crystallization behavior, mechanical properties and electrical conductivity of the PEEK/CNTs composites are investigated in detail. A non-isothermal crystallization kinetics test reveals a substantial loss in the composites' crystallinity with the increased CNTs content. On the other hand, mechanical tests show that with 5.0 wt% CNTs content, the tensile strength reaches a maximum at 118.2 MPa, which amounts to a rise of 30.3% compared with the neat PEEK sample after annealing treatment. However, additional annealing treatment decreases the electrical conductivity as well as EMI shielding performance. Such a decrease is mainly attributed to the relatively small crystal size of PEEK, which excludes the conductive fillers to the boundaries and disrupts the otherwise conductive networks.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36065261

RESUMO

Glioma is an aggressive tumor, currently there is no satisfactory management available. Psoralen, as a natural product, has been found to have an effect of treating cancer in recent years, but its effect on glioma has not been explored. In this study, we investigated the in vitro inhibition effect and potential targets of psoralen on glioma through network pharmacology and in vitro glioma treatment experiments. First, we used network pharmacology to preliminarily predict the 21 core genes of psoralen in the treatment of glioma, including PIK3CA, PIK3CB, PIK3CG, and JAK2. The CCK-8 method was used to detect the effect of psoralen on the proliferation of glioma U87 and U251 cells, and the results showed that psoralen could significantly inhibit the proliferation of U87 and U251 cells. The flow cytometry was used to detect the apoptosis and cell cycle changes, and it was found that psoralen could significantly promote the early apoptosis of U87 and U251 cells and had a significant cycle arrest effect on the two cells. The cell scratch test showed that psoralen could significantly inhibit the migration of U87 and U251 cells. The relative expression levels of PIK3CA, PIK3CB, PIK3CG, and JAK2 were analyzed by Real-time Quantitative polymerase chain reaction (QT-PCR), and the results showed that psoralen could inhibit the gene expression of PIK3CA, PIK3CB, PIK3CG, and JAK2. Later, Western blotting (WB) experiments showed that psoralen could inhibit the protein expressions of PI3K and JAK2. This study has preliminarily explored and verified the antiglioma effect of psoralen in the form of inhibiting cell proliferation and migration, promoting cell apoptosis and organizing cell cycle in vitro. And may play a role by inhibiting the expression of PIK3CA, PIK3CB, PIK3CG, JAK2 gene and PI3K, JAK2 protein, psoralen has become a potential antiglioma drug.

9.
Int J Biol Macromol ; 193(Pt B): 1059-1067, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34798185

RESUMO

Environmentally friendly and non-toxic polylactic acid (PLA) foam has shown great application prospects in heat preservation, adsorption and other fields. However, it is still challenging to prepare high-expansion PLA foam. Herein, a cooling batch foaming process under supercritical CO2 (sc-CO2), based on pre-melted non-crystalline state, was proposed to prepare PLA foams with high expansion ratio. The CO2 dissolved in the polymer melt will lower the crystallization temperature of PLA. Due to the lack of crystallization, the foaming temperature of PLA can be reduced, which increases the CO2 saturation and helps foam. When foaming is triggered before crystallization, ultrahigh expansion foam can be produced. Based on pre-melting treatment, the maximum expansion ratio of PLA has reached 59.7-fold. At the same time, an open-pore structure is produced by this method, which can selectively absorb oil from water. In addition, the adsorption capacity of CCl4 reaches 15 g/g, and there is no significant attenuation in 20 adsorption-desorption cycles. This work provides a green, solvent-free method to prepare biodegradable oil-adsorbing foam.


Assuntos
Petróleo , Poliésteres/química , Água/química
10.
Cell Death Dis ; 12(2): 223, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637692

RESUMO

MYB plays vital roles in regulating proliferation and differentiation of hematopoietic progenitor cells, dysregulation of MYB has been implicated in the pathogenesis of leukemia. Although the transcription of MYB has been well studied, its detailed underlying regulatory mechanisms still remain elusive. Here, we detected the long-range interaction between the upstream regions, -34k and -88k, and the MYB promoter in K562, U937, and HL-60 cells using circularized chromosome conformation capture (4C) assay, which declined when MYB was downregulated during chemical-induced differentiation. The enrichment of enhancer markers, H3K4me1 and H3K27ac, and enhancer activity at the -34k and -88k regions were confirmed by ChIP-qPCR and luciferase assay respectively. ChIP-qPCR showed the dynamic binding of GATA1, TAL1, and CCAAT/enhancer-binding protein (C/EBPß) at -34k and -88k during differentiation of K562 cells. Epigenome editing by a CRISPR-Cas9-based method showed that H3K27ac at -34k enhanced TF binding and MYB expression, while DNA methylation inhibited MYB expression. Taken together, our data revealed that enhancer elements at -34k are required for MYB expression, TF binding, and epigenetic modification are closely involved in this process in human myeloid leukemia cells.


Assuntos
Elementos Facilitadores Genéticos , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide/genética , Proteínas Proto-Oncogênicas c-myb/genética , Sítios de Ligação , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular , Metilação de DNA , Epigênese Genética , Fator de Transcrição GATA1/metabolismo , Células HL-60 , Humanos , Células K562 , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo , Células U937
11.
Hematol Oncol ; 39(2): 162-169, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32869900

RESUMO

Mesenchymal stem cells (MSCs) are a subset of multifunctional stem cells with self-renewal and multidirectional differentiation properties that play a pivotal role in tumor progression. MSCs are reported to exert biological functions by secreting specialized vesicles, known as exosomes, with tumor cells. Exosomes participate in material and information exchange between cells and are crucial in multiple physiological and pathological processes. This study provides a comprehensive overview of the roles, mechanisms of action and sources of MSC exosomes in hematological malignancies, and different tumor types.


Assuntos
Exossomos/metabolismo , Neoplasias Hematológicas/genética , Células-Tronco Mesenquimais/metabolismo , Neoplasias Hematológicas/patologia , Humanos
12.
Biomed Pharmacother ; 120: 109529, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606620

RESUMO

The enhancement of the anticancer activity by disulfiram (DSF) chelated with copper (DSF/Cu2+) has been investigated recently, while the underlying molecular mechanisms still need to be fully elucidated. Chloride channel-3 (ClC-3) is over-expressed in a variety of cancers and involves multiple tumor biological events. However, whether the over-expression of ClC-3 in tumor cells affects the sensitivity of anti-tumor drugs remains unclear. Here, we showed that the involvement of ClC-3 chloride channel in the selective cytotoxicity of DSF/Cu2+ in the poorly-differentiated nasopharyngeal carcinoma. The EC50 of DSF alone and DSF/Cu2+ in activating the Cl- channel were 95.36 µM and 0.31 µM in the CNE-2Z cells, respectively. DSF/Cu2+ exhibited a positive correlation between the induction of the Cl- currents and the inhibition of cell proliferation. DSF/Cu2+ increased the ClC-3 protein expression and induced the cell apoptosis. Cl- channel blockers, NPPB and DIDS, and ClC-3 siRNA partially inhibited the cell apoptosis, and depleted the Cl- currents induced by DSF/Cu2+ in CNE-2Z cells. However, these effects could not be observed in the normal nasopharyngeal epithelium NP69-SV40 T cells. In vivo, the transplanted human nasopharyngeal carcinoma tumors size in the DSF/Cu2+ group decreased about 73.2% of those in the solvent control group. The chloride blockers partially inhibited the antitumor action of DSF/Cu2+. These data demonstrated that the selective cytotoxicity of DSF/Cu2+ may relate to its selective activation of ClC-3 Cl- channel pathways in CNE-2Z cells. ClC-3 Cl- channel can be viewed as a new and promising target for the treatment of nasopharyngeal carcinoma.


Assuntos
Antineoplásicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Canais de Cloreto/metabolismo , Cobre/farmacologia , Dissulfiram/farmacologia , Ativação do Canal Iônico/efeitos dos fármacos , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Masculino , Camundongos Nus , RNA Interferente Pequeno/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nano Lett ; 19(6): 3505-3518, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31034238

RESUMO

Despite recent advances in enhancing photodynamic therapy efficacy, high-efficiency reactive oxygen species (ROS)-based therapy approach, especially in malignancy tumor treatment, remains challenging. Relieving the hypoxia of tumor tissue has been considered to be an attractive strategy for enhancing ROS-based treatment effect. Nevertheless, it is frequently neglected that the hypoxic regions are usually located deep in the tumors and therefore are usually inaccessible. To address these limitations, herein we constructed a sequential intercellular delivery system (MFLs/LAOOH@DOX) that consists of a membrane fusion liposomes (MFLs) doped with linoleic acid hydroperoxide (LAOOH) in the lipid bilayer and antitumor doxorubicin (DOX) encapsulated inside. In this report, LAOOH, one of the primary products of lipid peroxidation in vivo, was selected as ROS-generated agent herein, which depends on Fe2+ rather than oxygen and other external stimuli to produce ROS. Upon the enhanced permeation and retention effect, MFLs/LAOOH@DOX first fused with tumor cell membranes in the perivascular region in synchrony with selective delivery of LAOOH into the plasma membrane and the on-demand intracellular release of DOX. By hitchhiking with extracellular vesicles, LAOOH, as a cell membrane natural ingredient, spread gradually to neighboring cells and throughout the entire tumor eventually. Combined with subsequent administration of nano Fe3O4, ROS was specifically generated on the tumor cell membrane by LAOOH throughout the tumor tissues. This study offers a new method to enhance ROS-based antitumor treatment efficiency.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Ácidos Linoleicos/administração & dosagem , Peróxidos Lipídicos/administração & dosagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Ácidos Linoleicos/uso terapêutico , Peróxidos Lipídicos/uso terapêutico , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Peixe-Zebra
14.
J Diabetes ; 10(9): 708-714, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29437292

RESUMO

BACKGROUND: Dyslipidemia predicts the development and progression of diabetes. A higher non-high-density lipoprotein cholesterol (HDL-C): HDL-C ratio is reportedly associated with metabolic syndrome and insulin resistance, but its relationship with glycemic levels and diabetes remains unclear. METHODS: In all, 4882 subjects aged ≥40 years without diabetes and not using lipid-lowering drugs were enrolled in the study. The non-HDL-C: HDL-C ratio was log10 transformed to achieve normal distribution. Multivariate logistic regression was used to investigate the association between the log10 -transformed non-HDL-C: HDL-C ratio and diabetes. Stratified analyses of the association by age, gender, and body mass index (BMI) were also performed. RESULTS: After 3 years of follow-up, 704 participants developed diabetes. After adjustment for age, gender, current smoking, current drinking, physical activity, BMI, systolic blood pressure, and family history of diabetes, each 1-SD increase in the log(non-HDL-C: HDL-C ratio) was associated with higher fasting blood glucose (FPG) levels (ß = 0.1; 95% confidence interval [CI] 0.1-0.1), 2-h postload plasma glucose levels (2-h glucose; ß = 0.2; 95% CI 0.1-0.2), and risk of diabetes (odds ratio [OR] 1.1; 95% CI 1.0-1.2). In a multivariate model, subjects in the top quartile of non-HDL-C: HDL-C ratio had higher FPG (ß = 0.2; 95% CI 0.2-0.3), 2-h glucose (ß = 0.5; 95% CI 0.3-0.7) and HbA1c (ß = 0.1; 95% CI 0.1-0.2) levels, and a 40% increased risk of diabetes (OR 1.4; 95% CI 1.1-1.8) than participants in the bottom quartile. CONCLUSIONS: The non-HDL-C: HDL-C ratio was found to be an independent risk factor for diabetes.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Diabetes Mellitus/sangue , Glicemia/análise , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco
15.
Int J Biochem Cell Biol ; 84: 96-108, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28111334

RESUMO

Cancer initiation and progression follow complex changes of cellular architecture and biomechanical property. Cancer cells with more submissive (or "softer") than their healthy counterparts attributed to the reorganization of the complex cytoskeleton structure, may be considered as a potential anti-tumor therapeutic target. In this study, atomic force microscopy (AFM) was carried out to detect the topographical and biophysical changes of nasopharyngeal carcinoma CNE-2Z cells and normal nasopharyngeal epithelial cells NP69-SV40T by treating the Disulfiram chelated with Cu2+ (DSF-Cu). DSF-Cu induced the apoptotic population, ROS production and decreased the NF-κB-p65 expression of CNE-2Z cells, which was much higher than those of NP69-SV40T cells. DSF-Cu caused the obvious changes of cell morphology and membrane ultrastructure in CNE-2Z cells. The roughness decreased and stiffness increased significantly in CNE-2Z cells, which correlated with the rearrangement of intracellular F-actin, FLNa and α-tubulin structures in CNE-2Z cells. And the adhesion force of CNE-2Z cells was also increased accompanied with the increased E-cadherin expression. However, these results could not be observed in the NP69-SV40T cells even the concentration of DSF reached up to 400nM. Finally, the detection of cell wound scratch assay confirmed DSF-Cu could inhibit the migration of CNE-2Z cells, but no effect on NP69-SV40T cells. These findings demonstrated the selective cytotoxicity of DSF-Cu in CNE-2Z cells may attribute to the different mechanical properties and cytoskeleton rearrangement from the normal nasopharyngeal epithelial cells.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Dissulfiram/análogos & derivados , Neoplasias Nasofaríngeas/tratamento farmacológico , Actinas/metabolismo , Apoptose/efeitos dos fármacos , Fenômenos Biomecânicos , Carcinoma/patologia , Carcinoma/fisiopatologia , Adesão Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/patologia , Citoesqueleto/fisiologia , Dissulfiram/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/fisiologia , Filaminas/metabolismo , Humanos , Microscopia de Força Atômica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/fisiopatologia , Nasofaringe/citologia , Nasofaringe/efeitos dos fármacos , Nasofaringe/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição RelA/antagonistas & inibidores , Tubulina (Proteína)/metabolismo
16.
Scanning ; 38(6): 825-836, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27353661

RESUMO

Disulfiram (DSF) has been proved to have broad-spectrum anti-alcoholism effects, and it is also found to show stronger anti-tumor effects after chelating with Cu2+ to form DSF-Cu complex. In this work, we studied the anti-tumor activity of DSF-Cu in MCF-7 cells by flow cytometry, confocal laser scanning microscope, and atomic force microscopy to clarify the underlying anti-tumor mechanisms. MCF-7 cells were incubated with 50, 100, 150, 200, and 250 nM DSF chelated with 10 µM CuCl2 for 24 h. The results showed that DSF-Cu could induce the accumulation of MCF-7 cells in G2/M phase and apoptosis in a concentration-dependent manner. Additionally, atomic force microscope (AFM) analysis at nanoscale level showed that the morphology of cell was significantly shrunk with destroyed filopodia and ultrastructure presented many irregular protuberances on the cell membrane after DSF-Cu treatment, which was closely associated with the re-arrangement of cytoskeleton. DSF-Cu induced the production of reactive oxygen species (ROS), increased the concentration of intracellular Ca2+ and decreased the mitochondrial membrane potential (MMP) in MCF-7 cells resulting in a mitochondria-dependent apoptosis pathway. The results indicated that DSF-Cu has a potential anti-tumor activity in breast cancer by impairing the mitochondria functions. SCANNING 38:825-836, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Cobre/farmacologia , Dissulfiram/farmacologia , Mitocôndrias/efeitos dos fármacos , Neoplasias da Mama/patologia , Neoplasias da Mama/ultraestrutura , Cálcio/metabolismo , Citoesqueleto/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Microscopia de Força Atômica , Espécies Reativas de Oxigênio/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA