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1.
Diagn Cytopathol ; 49(9): 1052-1055, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291890

RESUMO

OBJECTIVE: The parasite Trichomonas vaginalis (T. vaginalis) causes one of the most common non-viral sexually transmitted infections in humans. T. vaginalis is notorious for its inconspicuous appearance in vaginal smears. It can be missed under the microscope. METHOD: In the present study, we investigate the immunoreactivity of T. vaginalis to smooth muscle actin (SMA) in the vaginal smear. RESULT: T. vaginalis trophozoite and pseduocyst are immunoreactive for SMA in all of the study group cases (n = 21) and in none of the control group cases (n = 21). Thus, SMA immunostain is a sensitive method for the demonstration of T. vaginalis. Moreover, the protozoan attains a conspicuous and unique appearance. By SMA immunohistochemical stain, the apperance of T. vaginalis floated freely or located in the cytoplasm of the epithelial cells is easily identified. CONCLUSION: We recommend performing SMA immunostain in every vaginal smear with clinical or pathologic suspicion of trichomoniasis.

2.
World J Surg Oncol ; 18(1): 240, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891152

RESUMO

BACKGROUND: Thyroid cancer (TC) is the most common endocrine malignancy; basigin (also known as BSG) plays a crucial role in tumor cell invasion, metastasis, and angiogenesis. This study was designed to identify the change of BSG expression in TC and its possible potential mechanism. METHODS: The BSG expression levels in TC were demonstrated using data collected from in-house immunohistochemical (IHC), RNA-sequencing (RNA-seq), microarrays, and literatures. Integrated analysis was performed to determined BSG expression levels in TC comprehensively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed with the integration of BSG co-expressed genes and differentially expressed genes (DEGs) in TC tissues to explore the potential mechanisms of BSG in TC. RESULTS: The protein expression level of BSG was significantly higher in TC cases based on the IHC experiments. In addition, the combined SMD for BSG expression was 0.39 (p < 0.0001), the diagnostic odds ratio was 3.69, and the AUC of the sROC curve was 0.6986 using 1182 TC cases and 437 non-cancerous cases from 17 independent datasets. Furthermore, BSG co-expressed genes tended to be enriched in gene terms of the extracellular matrix (ECM), cell adhesion, and cell-cell interactions. The expression levels of nine hub BSG co-expressed genes were markedly upregulated in TC cases. CONCLUSION: BSG expression levels were closely correlated with the progression of TC and may affect the signals of the ECM, cell adhesion, and cell-cell interactions.


Assuntos
Basigina , Neoplasias da Glândula Tireoide , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Prognóstico , Neoplasias da Glândula Tireoide/genética
3.
Cancer Med ; 9(21): 8004-8019, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32931665

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role of MAOA in HCC has not been intensively investigated. METHODS: In-house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value of MAOA in HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes of MAOA related co-expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) on MAOA in HCC. RESULTS: MAOA was downregulated and possessed an excellent discriminatory capability in HCC patients. Decreased MAOA correlated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co-expressed genes that positively related to MAOA were clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulated MAOA in a nude mouse HCC model. CONCLUSIONS: A decreased MAOA level is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover, MAOA may play a role in AFB1 toxic transformation through its synergistic action with co-expressed genes, especially CYP3A4. MAOA also serves as a potential therapy target of NC in HCC patients.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/enzimologia , Neoplasias Hepáticas/enzimologia , Monoaminoxidase/análise , Animais , Antineoplásicos Fitogênicos/farmacologia , Benzofenantridinas/farmacologia , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Citocromo P-450 CYP2E1/genética , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Bases de Dados Genéticas , Regulação para Baixo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Camundongos Nus , Monoaminoxidase/genética , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Mapas de Interação de Proteínas , RNA-Seq , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Cancer Cell Int ; 20: 392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32818022

RESUMO

Background: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown. Methods: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer. Results: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways. Conclusions: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer.

5.
Oncol Rep ; 42(1): 151-175, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059074

RESUMO

Breast cancer (BC) has a complex etiology and pathogenesis, and is the most common malignant tumor type in females, in USA in 2018, yet its relevant molecular mechanisms remain largely unknown. The collagen type V α­1 chain (COL5A1) gene is differentially expressed in renal and ovarian cancer. Using bioinformatics methods, COL5A1 was determined to also be a significant gene in BC, but its association with BC has not been sufficiently reported. COL5A1 microarray and relevant clinical data were collected from the Gene Expression Omnibus, The Cancer Genome Atlas and other databases to summarize COL5A1 expression in BC and its subtypes at the mRNA and protein levels. All associated information was comprehensively analyzed by various software. The clinical significance of the mutation was obtained via the cBioPortal. Furthermore, Gene Ontology functional annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were also performed to investigate the mechanism of COL5A1 in BC. Immunohistochemistry was also conducted to detect and confirm COL5A1 expression. It was determined that COL5A1 was highly expressed in BC tissues, compared with normal tissues at the mRNA level [standard mean difference, 0.84; 95% confidence interval (CI), 0.60­1.07; P=0.108]. The area under the summary receiver operator characteristic curve for COL5A1 was 0.87 (95% CI, 0.84­0.90). COL5A1 expression was altered in 32/817 (4%) sequenced samples. KEGG analysis confirmed the most notable pathways, including focal adhesion, extracellular matrix­receptor interaction and regulation of the actin cytoskeleton. Immunohistochemical detection was used to verify the expression of COL5A1 in 136 selected cases of invasive BC tissues and 55 cases of adjacent normal tissues, while the rate of high expression of COL5A1 in BC was up to 90.4%. These results indicated that COL5A1 is highly expressed at the mRNA and protein levels in BC, and the prognosis of patients with BC with high COL5A1 expression may be reduced; therefore, COL5A1 may be used independently or combined with other detection factors in BC diagnosis.


Assuntos
Neoplasias da Mama/metabolismo , Colágeno Tipo V/genética , Colágeno Tipo V/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Análise de Sequência de RNA/métodos , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Mapas de Interação de Proteínas , Curva ROC , Análise de Sobrevida , Regulação para Cima
6.
Int J Mol Med ; 44(1): 67-78, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31115486

RESUMO

Lysophosphatidic acid (LPA), a simple water­soluble glycerophospholipid with growth factor­like activity, regulates certain behaviors of multiple cancer types by binding to its receptor, LPA receptor 2 (LPA2). Notch1 is a key mediator in multiple human cancer cell types. The association between LPA2 and Notch1 in gastric cancer cells is not well known. The present study aimed to investigate the function of LPA2 and Notch1 in controlling the migration and invasion activities of SGC­7901 gastric cancer cells following stimulation with LPA. It was revealed that LPA may stimulate the expression of Notch1 and Hes family bHLH transcription factor 1, and the phosphorylation of protein kinase B which belongs to the Notch pathway. Furthermore, by performing transwell migration and invasion assays, immunofluorescent staining, analyzing the expression of markers for the epithelial­mesenchymal transition (EMT) and downregulating LPA2 and Notch1 expression, it was verified that LPA2 and Notch1 mediated the metastasis, invasion, EMT and rebuilding of the cytoskeleton of SGC­7901 cells upon LPA treatment. An immunoprecipitation assay revealed that LPA2 interacted with Notch1 in SGC­7901 cells. The present study may provide novel ideas and an experimental basis for identifying the factors that affect the functions of SGC­7901 cells.


Assuntos
Movimento Celular/efeitos dos fármacos , Lisofosfolipídeos/farmacologia , Proteínas de Neoplasias/metabolismo , Receptor Notch1/metabolismo , Receptores de Ácidos Lisofosfatídicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/patologia
7.
BMC Pulm Med ; 19(1): 35, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744607

RESUMO

BACKGROUND: Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis. METHODS: We explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-ß1 (TGF-ß1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, α-smooth muscle actin (α-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, α-SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry. RESULTS: Long-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-ß1, CTGF, and Collagen I and III expression. CONCLUSIONS: Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.


Assuntos
Autofagia/efeitos dos fármacos , MicroRNAs/metabolismo , Fibrose Pulmonar/metabolismo , Pirazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Animais , Colágeno Tipo I/metabolismo , Feminino , Humanos , Camundongos , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
8.
Opt Express ; 25(10): 11329-11339, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28788815

RESUMO

In this paper, a three-layered chiral metamaterial is proposed to achieve broad dual-band and high magnitude asymmetric transmission (AT) in near-infrared communication band for circularly polarized waves. The asymmetric parameter reaches to 0.9/0.86 at 174/235 THz, over 0.6 in broad dual bands from 160 to 183 THz and from 220 to 245 THz. Remarkably, the AT effect of circularly and linearly polarized waves can be modulated to appear or vanish with variants of the G shapes that has not been found in previous reports. The proposed structure shows great potential applications in high performance multi-band circular and linear polarizers.

9.
Asian Pac J Trop Med ; 9(7): 702-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27393102

RESUMO

OBJECTIVE: To discover the effect of partial splenic embolization on the immune function of cirrhotic patients with hypersplenism. METHODS: Patients involved in the study were enrolled and divided into three groups, including control group, experimental group, and complication group. Numbers of CD3(+), CD4(+) and CD8(+) T cells and CD4(+)CD25(+)CDl27(low/-) Treg cells in the peripheral blood of patients before surgery, 1 month, 6 months, 1 year, and 2 years after surgery were analyzed by fluorescence active cell sorting (FACS). Contents of immunoglobulins (IgA, IgG and IgM) were analyzed by auto immunoassay analyzer. RESULTS: In the peripheral blood of patients from experimental group, numbers of CD3(+), CD4(+) and CD8(+) T cells initially declined, but afterwards increased to normal level; in the peripheral blood of patients from complication group, CD3(+) and CD8(+) T cells showed the same trend, but the number of CD4(+) T cells was below normal level at all detection times. Furthermore, CD3(+), CD4(+) and CD8(+) T cells in the peripheral blood of patients from complication group were initially less than those in experimental group, and afterwards were comparable between two groups. In patients from both experimental group and complication group, the number of CD4(+) CD25(+) CDl27(low/-)Treg cells increased 1 month and 6 months after surgery, and gradually restored to normal level. CD4(+)CD25(+)CDl27(low/-) Treg cell counts in patients from complication group were initially more than those in patients from experimental group 1 month and 6 months after surgery, but then they were comparable. Furthermore, contents of immunoglobulins (IgA, IgG and IgM) were comparable in three groups at all detection times. CONCLUSION: Partial splenic embolization influenced the immune function of cirrhotic patients with hypersplenism in the short term but the immune function could afterwards gradually restore to normal. Our results implicated that measures that prevent infection and improve immune function were necessary in early stage after undergoing PSE in order to reduce complications.

10.
Huan Jing Ke Xue ; 37(6): 2195-2201, 2016 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964886

RESUMO

In order to remove low concentration of phosphorus in wastewater and realize resource utilization of reed, reed biochar(RB) was prepared using reed and then modified by ferric chloride, and the adsorption behavior of low concentration phosphorus was investigated. The results showed that the iron content of modified reed biochar(MRB) was 11.98 mg·g-1, which was 44.7 times that of RB; pHpzc of the MRB was 7.49, and the adsorption effect was the best when the solution pH was 7.0; at the initial concentration of 4.0 mg·L-1 and temperature of 298K, the adsorption capacity of MRB was 0.658 mg·g-1, which was 34.6 times that of RB. The adsorption isotherms at different temperatures were well fitted to Langmiur equation, which indicated the adsorption was monolayer adsorption, and increasing temperature was favorable for adsorption. ΔGθ<0, ΔHθ>0 and ΔSθ>0 indicated that the adsorption was a spontaneous, entropy increasing and endothermic process. The kinetic experimental data of the adsorption fitted well to the pseudo-second-order equation, the initial adsorption rate increased with the increasing initial concentration of solution, and the adsorption was mainly controlled by intraparticle diffusion. The research will provide basic data for application of MRB in deep removal of low concentration phosphorus from sewage treatment plant and water body.


Assuntos
Fósforo/metabolismo , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Adsorção , Carvão Vegetal , Concentração de Íons de Hidrogênio , Cinética , Termodinâmica , Água
11.
Circ J ; 78(11): 2760-70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25262842

RESUMO

BACKGROUND: Both clinical data and basic science studies suggest that advanced oxidation protein products (AOPPs) may contribute to the progression of atherosclerosis. The aim of this study was to investigate the effects of AOPPs on ATP-binding cassette transporter (ABC) A1 and ABCG1 expression, lipid accumulation and atherosclerotic lesions in apolipoprotein E knockout (apoE-KO) mice. METHODS AND RESULTS: Male 8-week-old apoE-KO mice were fed a high-fat/high-cholesterol diet. Mice received intraperitoneal injections of AOPPs (5 mg/kg) and/or Janus Kinase (JAK) inhibitor AG-490 (5 mg/kg) once every other day for 8 weeks. As shown in our data, AOPPs increased lipid levels of plasma, and promoted advanced lesions in the aortic regions in apoE-KO mice. The ABCA1, ABCG1 and liver X receptor alpha (LXRα) expression were downregulated in apoE-KO mice treated with AOPPs, whereas the lesions in the aortas were decreased, and the ABCA1, ABCG1 and LXRα expression were upregulated in mice treated with AOPPs plus AG-490, compared to the mice treated with AOPPs only. The ABCA1 and LXRα expressions of aortas, liver and intestine were downregulated in the AOPPs group, while the expressions were upregulated in the AOPPs-plus-AG-490 group when compared to the AOPPs group. The same results can be also observed in peritoneal macrophages. CONCLUSIONS: AOPPs increase accumulation of lipids and exacerbate atherosclerosis through downregulation of ABCA1 and ABCG1 expression, and the JAK-LXRα signaling pathway in apoE-KO mice.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/biossíntese , Produtos da Oxidação Avançada de Proteínas/metabolismo , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Regulação para Baixo , Metabolismo dos Lipídeos , Lipoproteínas/biossíntese , Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Produtos da Oxidação Avançada de Proteínas/genética , Animais , Aterosclerose/genética , Lipoproteínas/genética , Masculino , Camundongos , Camundongos Knockout
12.
Atherosclerosis ; 236(1): 215-26, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25084135

RESUMO

RATIONALE: Macrophage accumulation of cholesterol leads to foam cell formation which is a major pathological event of atherosclerosis. Recent studies have shown that microRNA (miR)-19b might play an important role in cholesterol metabolism and atherosclerotic diseases. Here, we have identified miR-19b binding to the 3'UTR of ATP-binding cassette transporter A1 (ABCA1) transporters, and further determined the potential roles of this novel interaction in atherogenesis. OBJECTIVE: To investigate the molecular mechanisms involved in a miR-19b promotion of macrophage cholesterol accumulation and the development of aortic atherosclerosis. METHODS AND RESULTS: We performed bioinformatics analysis using online websites, and found that miR-19b was highly conserved during evolution and directly bound to ABCA1 mRNA with very low binding free energy. Luciferase reporter assay confirmed that miR-19b bound to 3110-3116 sites within ABCA1 3'UTR. MiR-19b directly regulated the expression levels of endogenous ABCA1 in foam cells derived from human THP-1 macrophages and mouse peritoneal macrophages (MPMs) as determined by qRT-PCR and western blot. Cholesterol transport assays revealed that miR-19b dramatically suppressed apolipoprotein AI-mediated ABCA1-dependent cholesterol efflux, resulting in the increased levels of total cholesterol (TC), free cholesterol (FC) and cholesterol ester (CE) as revealed by HPLC. The excretion of (3)H-cholesterol originating from cholesterol-laden MPMs into feces was decreased in mice overexpressing miR-19b. Finally, we evaluated the proatherosclerotic role of miR-19b in apolipoprotein E deficient (apoE(-/-)) mice. Treatment with miR-19b precursor reduced plasma high-density lipoprotein (HDL) levels, but increased plasma low-density lipoprotein (LDL) levels. Consistently, miR-19b precursor treatment increased aortic plaque size and lipid content, but reduced collagen content and ABCA1 expression. In contrast, treatment with the inhibitory miR-19b antisense oligonucleotides (ASO) prevented or reversed these effects. CONCLUSION: MiR-19b promotes macrophage cholesterol accumulation, foam cell formation and aortic atherosclerotic development by targeting ABCA1.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/antagonistas & inibidores , Doenças da Aorta/etiologia , Aterosclerose/etiologia , Colesterol/metabolismo , Macrófagos/metabolismo , MicroRNAs/fisiologia , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/fisiologia , Animais , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Apolipoproteína A-I/metabolismo , Apolipoproteínas E/deficiência , Aterosclerose/genética , Aterosclerose/metabolismo , Sequência de Bases , Linhagem Celular , Ésteres do Colesterol/metabolismo , Colágeno/análise , Células Espumosas/metabolismo , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Placa Aterosclerótica/metabolismo , RNA Mensageiro/metabolismo , Homologia de Sequência do Ácido Nucleico
13.
Atherosclerosis ; 235(2): 519-25, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24953492

RESUMO

OBJECTIVES: ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol from macrophages and plays a protective role in the development of atherosclerosis. This study was to determine the effects and potential mechanisms of Chlamydia pneumoniae (C. pneumoniae) on ABCA1 expression and cellular cholesterol efflux in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: C. pneumoniae significantly decreased the expression of ABCA1 and reduced cholesterol efflux. Furthermore, we found that C. pneumoniae suppressed ABCA1 expression via up-regulation of miR-33s. The inhibition of C. pneumoniae-induced NF-κB activation decreased miR-33s expression and enhanced ABCA1 expression. In addition, C. pneumoniae increased Toll-like receptor 2 (TLR2) expressions, inhibition of which by siRNA could also block NF-κB activation and miR-33s expression, and promot the expression of ABCA1. CONCLUSION: Taken together, these results reveal that C. pneumoniae may negatively regulate ABCA1 expression via TLR2-NF-κB and miR-33 pathways in THP-1 macrophage-derived foam cells, which may provide new insights for understanding the effects of C. pneumoniae on the pathogenesis of atherosclerosis.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/biossíntese , Chlamydophila pneumoniae/fisiologia , Células Espumosas/metabolismo , MicroRNAs/fisiologia , NF-kappa B/fisiologia , Receptor 2 Toll-Like/fisiologia , Colesterol/metabolismo , Células Espumosas/microbiologia , Humanos , Macrófagos/metabolismo
14.
Atherosclerosis ; 234(1): 54-64, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24608080

RESUMO

RATIONALE: Macrophage cholesterol homeostasis maintenance is the result of a balance between influx, endogenous synthesis, esterification/hydrolysis and efflux. Excessive accumulation of cholesterol leads to foam cell formation, which is the major pathology of atherosclerosis. Previous studies have shown that miR-27 (miR-27a and miR-27b) may play a key role in the progression of atherosclerosis. OBJECTIVE: We set out to investigate the molecular mechanisms of miR-27a/b in intracellular cholesterol homeostasis. METHODS AND RESULTS: In the present study, our results have shown that the miR-27 family is highly conserved during evolution, present in mammals and directly targets the 3' UTR of ABCA1, LPL, and ACAT1. apoA1, ABCG1 and SR-B1 lacking miR-27 bind sites should not be influenced by miR-27 directly. miR-27a and miR-27b directly regulated the expression of endogenous ABCA1 in different cells. Treatment with miR-27a and miR-27b mimics reduced apoA1-mediated cholesterol efflux by 33.08% and 44.61% in THP-1 cells, respectively. miR-27a/b also regulated HDL-mediated cholesterol efflux in THP-1 macrophages and affected the expression of apoA1 in HepG2 cells. However, miR-27a/b had no effect on total cellular cholesterol accumulation, but regulated the levels of cellular free cholesterol and cholesterol ester. We further found that miR-27a/b regulated the expression of LPL and CD36, and then affected the ability of THP-1 macrophages to uptake Dil-oxLDL. Finally, we identified that miR-27a/b regulated cholesterol ester formation by targeting ACAT1 in THP-1 macrophages. CONCLUSION: These findings indicate that miR-27a/b affects the efflux, influx, esterification and hydrolysis of cellular cholesterol by regulating the expression of ABCA1, apoA1, LPL, CD36 and ACAT1.


Assuntos
Colesterol/metabolismo , Macrófagos/metabolismo , MicroRNAs/fisiologia , Células Cultivadas , Esterificação , Humanos , Hidrólise
15.
Biochem Biophys Res Commun ; 444(3): 325-31, 2014 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-24462860

RESUMO

OBJECTIVE: The aim of this study was to determine whether ATP-binding cassette transporter A1 (ABCA1) was up-regulated by growth differentiation factor-15 (GDF-15) via the phosphoinositide 3-kinase (PI3K)/protein kinase Cζ (PKCζ)/specificity protein 1 (SP1) pathway in THP-1 macrophages. METHODS AND RESULTS: We investigated the effects of different concentrations of GDF-15 on ABCA1 expression in THP-1 macrophages. The results showed that GDF-15 dramatically increased cholesterol efflux and decreased cellular cholesterol levels. In addition, GDF15 increased ABCA1 mRNA and protein levels. The effects of GDF-15 on ABCA1 protein expression and cellular cholesterol efflux were abolished by wither inhibition or depletion of PI3K, PKCζ and SP1, respectively, suggesting the potential roles of PI3K, PKCζ and SP1 in ABCA1 expression. Taken together, GDF-15 appears to activate PI3K, PKCζ and SP1 cascade, and then increase ABCA1 expression, thereby promoting cholesterol efflux and reducing foam cell formation. CONCLUSION: Our results suggest that GDF-15 has an overall protective effect on the progression of atherosclerosis, likely through inducing ABCA1 expression via the PI3K/PKCζ/SP1 signaling pathway and enhancing cholesterol efflux.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Fator 15 de Diferenciação de Crescimento/fisiologia , Macrófagos/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteína Quinase C/metabolismo , Fator de Transcrição Sp1/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transporte Biológico , Linhagem Celular , Colesterol/metabolismo , Humanos , Macrófagos/enzimologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real
17.
Huan Jing Ke Xue ; 28(3): 654-8, 2007 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-17633650

RESUMO

By the BCR extraction procedures and HG-ICP-AES technique, the chemical speciation and pollution characteristics of soil mercury in typical mercury deposit areas of Western Hunan-Eastern Guizhou province were studied. It was found that the concentrations of mercury in soils are dominated by residual form, followed by organic-sulfide form. Fe-Mn oxides and acid-exchangeable form are rather low. The percent of the four mercury species in soils are 85.77%, 12.44%, 0.93% and 0:86%, respectively. The total concentrations and each species of mercury in soils show positive relationship with the concentration of sands, and negative relationship with the concentration of clays in soils. They also increase with the soil pH value. Mercury concentration in soils has spatial changes. In general, the concentrations in the surface soil are higher than those of sub-surface soils. Furthermore, the concentrations rapidly decrease with the distance from the pollution source increased and vary among different soil samples from different location and land use type. The results indicated that exogenous mercury pollution caused by human activities provides significant influence on environmental toxicity and pollution characteristics of mercury in soils of mercury deposit area.


Assuntos
Mercúrio/análise , Mercúrio/química , Mineração , Poluentes do Solo/análise , China , Monitoramento Ambiental
18.
Appl Opt ; 44(20): 4205-10, 2005 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-16045206

RESUMO

A new technique for testing a ball grid array (BGA) package substrate that uses the electro-optic (EO) probing technique is investigated. This technique can detect open circuits in the BGA substrate with a high spatial resolution. An experimental setup that uses an EO probe tip made of LiNbO3 crystal is reported along with the measurement results from a real BGA substrate.

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