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1.
Insects ; 12(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34821821

RESUMO

The longan lanternfly, Pyrops candelaria (L.), has been invading mainland Taiwan since 2018, but the distribution of the species has been confined to northern Taiwan until now. The manual removal of the adult insects from the longan is still the main control strategy because of the uncertainty around other key host plants, especially for eggs and nymphs. In this study, large numbers of eggs and nymphs were found on Triadica sebifera (L.) Small and Acacia confusa Merr. The occurrence of immature individuals on Triadica sebifera increased with developmental stage from eggs to the last instar from May to July 2021. On 30 April, the first egg mass was recorded. More egg masses were recorded in May, and some could be found in July. In May, only two younger instars were detected. Third and fourth instars began to appear from June, while the fifth instar was mainly recorded from July onwards. The results of this study provide great strategic value for decision-makers to allow for effective control of the target tree species. For now, we proved that longan and pomelo trees, preferred by adults, are not the key hosts for the immature stages of this insect, because few immature individuals were found on them. Therefore, we suggest that the existence of Triadica sebifera should be considered when analyzing possible spreading areas of this invasive lanternfly in Taiwan.

2.
Chem Biol Drug Des ; 98(5): 835-849, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34416096

RESUMO

As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.

3.
Chemistry ; 27(38): 9814-9819, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-33834537

RESUMO

Based on the DFT-level-calculated molecular volume (Vmol ) of pyrrole and its liquid density, pyrrole manifests the highest liquid density coefficient LDc (defined as [Vmol ×density ×0.6023]/FW) value of 0.7. Normal liquids have LDc <0.63. This very high LDc is due to the strong N-H⋅⋅⋅π interactions in solution, and hence pyrrole can be considered to be a pseudo-crystalline liquid. When trapped inside the confined space of a crystalline sponge, a reorientation of the N-H⋅⋅⋅π interaction is observed leading to specific cyclic N-H⋅⋅⋅π tetramers and N-H⋅⋅⋅π dimers, as verified by single-crystal X-ray crystallographic and computational methods. These tetramers are of the same size as four pyrrole molecules in the solid-state of pyrrole, yet the cyclic N-H⋅⋅⋅π intermolecular interactions are circularly oriented instead of being in the linear zigzag structure found in the X-ray structure of a solid pyrrole. The confinement thus acts as an external driving force for tetramer formation.


Assuntos
Pirróis , Cristalografia por Raios X , Modelos Moleculares
4.
Int J Mol Sci ; 21(10)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32414036

RESUMO

Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with ß-catenin, leading to reduced and diffused staining of VE-cadherin and ß-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts.


Assuntos
Claudina-5/genética , Endotélio/efeitos dos fármacos , Pneumonia/genética , Óxido de Zinco/efeitos adversos , Proteína da Zônula de Oclusão-1/genética , Junções Aderentes/efeitos dos fármacos , Junções Aderentes/genética , Animais , Vasos Sanguíneos/efeitos dos fármacos , Humanos , Leucócitos/efeitos dos fármacos , Camundongos , Nanopartículas/efeitos adversos , Orofaringe/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/patologia
5.
Biomed Pharmacother ; 107: 1074-1081, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30257319

RESUMO

Cycloastragenol, a naturally occurring compound in Astragali Radix, has been demonstrated to possess various pharmacological actions including anti-aging, anti-inflammation, anti-fibrosis, antibacterial, liver and endothelium protection. However, whether cycloastragenol ameliorates heart failure remains unclear. Isoproterenol administration to rats triggered classic cardiac damage, as demonstrated by objective parameters of cardiac dysfunction. The treatment of cycloastragenol improved deranged cardiac parameters in the isoproterenol-induced heart damage model in a dose-dependent manner. At the same time, cycloastragenol markedly ameliorated cardiac histological changes and down-regulated serum levels of various neuroendocrine factors including norepinephrine, aldosterone, brain natriuretic peptide, endothelin 1, angiotensin II and so on. Moreover, the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in rat heart were also inhibited by cycloastragenol. Mechanistically, augmenting autophagy of myocardial cells via the inhibition of AKT1-RPS6KB1 signaling contributed to the improvement of isoproterenol-induced rat heart failure by cycloastragenol. These results suggest that cycloastragenol ameliorates cardiac dysfunction and remodeling through promoting autophagy in myocardial cells and suppressing MMP-2 and MMP-9 expressions, indicating that it could be a drug candidate for patients with congestive heart failure.


Assuntos
Cardiotônicos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Sapogeninas/farmacologia , Animais , Autofagia/efeitos dos fármacos , Cardiotônicos/administração & dosagem , Cardiotônicos/isolamento & purificação , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Insuficiência Cardíaca/fisiopatologia , Isoproterenol/toxicidade , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sapogeninas/administração & dosagem , Sapogeninas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos
6.
Cancer Res Treat ; 50(3): 894-907, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28934847

RESUMO

Purpose: Cancer-associated fibroblasts (CAFs) activated by cancer cells has a central role in development and malignant biological behavior in colorectal cancer (CRC). Adult fibroblasts do not express Snail, but Snail-positive fibroblasts are discovered in the stroma of malignant CRC and reported to be the key role to chemoresistance. However, the reciprocal effect of CAFs expressed Snail to chemoresistance on CRC cells and the underlying molecular mechanisms are not fully characterized. Materials and Methods: Snail-overexpressed 3T3 stable cell lines were generated by lipidosome and CT26 mixed with 3T3-Snail subcutaneous transplanted CRC models were established by subcutaneous injection. Cell Counting Kit-8, flow cytometry and western blotting assays were performed, and immunohistochemistry staining was studied. The cytokines participated in chemoresistance was validated with reverse transcriptase-polymerase chain reaction and heatmap. Results: Snail-expression fibroblasts are discovered in human and mouse spontaneous CRCs. Overexpression of Snail induces 3T3 fibroblasts transdifferentiation to CAFs. CT26 co-cultured with 3T3-Snail resisted the impairment from 5-fluorouracil and paclitaxel in vitro. The subcutaneous transplanted tumor models included 3T3-Snail cells develop without restrictions even after treating with 5-fluorouracil or paclitaxel. Moreover, these chemoresistant processes may be mediated by CCL1 secreted by Snail-expression fibroblasts via transforming growth factor ß/nuclear factor-κB signaling pathways. Conclusion: Taken together, Snail-expressing 3T3 fibroblasts display CAFs properties that support 5-fluorouracil and paclitaxel chemoresistance in CRC via participation of CCL1 and suggest that inhibition of the Snail-expression fibroblasts in tumor may be a useful strategy to limit chemoresistance.


Assuntos
Fibroblastos Associados a Câncer/citologia , Quimiocina CCL1/metabolismo , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fatores de Transcrição da Família Snail/metabolismo , Células 3T3 , Animais , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Quimiocina CCL1/genética , Técnicas de Cocultura , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/farmacologia , Humanos , Camundongos , NF-kappa B/metabolismo , Transplante de Neoplasias , Paclitaxel/farmacologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
7.
Acta paul. enferm ; 29(5): 506-517, set.-out. 2016. tab
Artigo em Inglês | LILACS-Express | LILACS, BDENF - Enfermagem | ID: biblio-837798

RESUMO

Abstract Objective: To investigate how the internal marketing perception of nurses could have a significant positive moderating effect on the relationship between service-oriented encounter and patient satisfaction in nursing negligence. Methods: The subjects were nurses in the surgery units of hospitals at the regional level or higher in Taiwan. A total of 669 questionnaires were distributed and 609 questionnaires were recovered between December 2014 and January 2015, the number of valid questionnaires was 534 for a valid questionnaire recovery rate of 79.8%. Finally, we adopted the SPSS 18.0 analysis software for analysis and processing. Results: Results indicate that service-oriented encounter has a significant positive influence on patient satisfaction and internal marketing perception among nurses has a significant positive moderating effect on the relationship between service-oriented encounter and patient satisfaction. Conclusions: This study suggests that hospital managers need to recognize the importance of internal marketing for the more expressions toward service-oriented encounter, and further improve patient satisfaction. This kind of relationship is rarely discussed in the research literature, and it can be applied for human resources management of nursing staff. Hospitals must integrate the goal of patients first into the individual performance evaluation of nursing personnel by providing nursing personnel with information related to the evaluation standards of the organizations to help them understand and determine the job performance or service-oriented behavior expected by the organizations while acknowledging the objectivity and fairness of the performance evaluation system.

8.
Oncotarget ; 7(42): 67760-67776, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27626316

RESUMO

Abdominal aortic aneurysm (AAA) is a chronic but often fatal disease in elderly population. Heme oxygenase-1 (HO-1) is a stress response protein with antioxidative and anti-inflammatory properties. HO-1 has been shown to protect against atherogenesis and arterial intimal thickening. Emerging evidences suggest that AAA and arterial occlusive disease have distinct pathogenic mechanisms. Thus, in this study we investigated the role of HO-1 in angiotensin II-induced AAA formation in HO-1+/+apoE-/- and HO-1-/-apoE-/- mice. We found that complete loss of HO-1 increased AAA incidence and rupture rate, and drastically increased aneurysmal area and severity, accompanied with severe elastin degradation and medial degeneration. Interestingly, we often observed not only AAA but also thoracic aortic aneurysm in HO-1-/-apoE-/- mice. Furthermore, reactive oxygen species levels, vascular smooth muscle cell (VSMC) loss, macrophage infiltration, matrix metalloproteinase (MMP) activity were markedly enhanced in the aneurysmal aortic wall in HO-1-/-apoE-/- mice. In addition, HO-1-/-apoE-/- VSMCs were more susceptible to oxidant-induced cell death and macrophages from HO-1-/-apoE-/- mice had aggravated responses to angiotensin II with substantial increases in inflammatory cytokine productions and MMP9 activity. Taken together, our results demonstrate the essential roles of HO-1 in suppressing the pathogenesis of AAA. Targeting HO-1 might be a promising therapeutic strategy for AAA.


Assuntos
Anemia Hemolítica/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Transtornos do Crescimento/metabolismo , Heme Oxigenase-1/deficiência , Distúrbios do Metabolismo do Ferro/metabolismo , Anemia Hemolítica/genética , Angiotensina II , Animais , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Citocinas/metabolismo , Transtornos do Crescimento/genética , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Distúrbios do Metabolismo do Ferro/genética , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo
9.
Arch Biochem Biophys ; 608: 34-41, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27592306

RESUMO

Nodal is a member of transforming growth factor beta (TGF-ß) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the ß-catenin nuclear translocation. This increase was attributed to GSK-3ß dephosphorylating, and activin receptor-like kinase 4/7 (ALK4/7) played a major role in human cancer cells. Our study provides a positive understanding of Nodal function in cancer cells and suggests a potential novel target for clinical therapeutic research.


Assuntos
Transporte Ativo do Núcleo Celular , Regulação Neoplásica da Expressão Gênica , Proteína Nodal/metabolismo , Fator 3 de Transcrição de Octâmero/metabolismo , Neoplasias da Próstata/metabolismo , beta Catenina/metabolismo , Células A549 , Receptores de Ativinas Tipo I/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Proliferação de Células , Citoplasma/metabolismo , Humanos , Masculino , Transdução de Sinais , Transfecção
10.
Biomed Pharmacother ; 83: 1089-1094, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27551754

RESUMO

Our previous study showed that Icariin (ICA) has anti-cardiac hypertrophy effect in rats with an unknown mechanism. In the present study, we aimed to clarify the cardiac protective effect and mechanism of ICA in vitro. H9C2 cardiac myocytes were incubated with H2O2 to build up the oxidative stress injury model. The results showed that pre-treatment of ICA protected cells against the toxicity induced by H2O2. H2O2 treatment significantly reduced H2O2-induced apoptosis, evidenced by lower Annexin V/PI stained cells and less PARP and caspase-3/9 activation. Mitochondria membrane potential (MMP) dissipation occurred following the exposure of H2O2, which could be prevented by ICA treatment. Moreover, Ca2+ homeostasis was preserved by ICA and ROS generation was significantly suppressed by ICA incubation. Interestingly, ICA treatment increased the phosphorylation of upstream ERK mitogen-activated protein kinase (MAPK) while ERK inhibitor U1026 could reverse the protective effect of ICA. Overall, ICA seems to protect the cardiac cells from oxidative stress injury through ROS scavenge and stimulation of ERK pathway which may explain its effects in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Flavonoides/farmacologia , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Cálcio/metabolismo , Cardiotônicos/farmacologia , Linhagem Celular , Citocromos c/metabolismo , Ativação Enzimática/efeitos dos fármacos , Flavonoides/química , Homeostase/efeitos dos fármacos , Peróxido de Hidrogênio/toxicidade , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
11.
Sci Rep ; 6: 25374, 2016 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-27146795

RESUMO

5-Methoxytryptophan (5-MTP), a 5-methoxyindole metabolite of tryptophan metabolism, was recently shown to suppress inflammatory mediator-induced cancer cell proliferation and migration. However, the role of 5-MTP in vascular disease is unknown. In this study, we investigated whether 5-MTP protects against vascular remodeling following arterial injury. Measurements of serum 5-MTP levels in healthy subjects and patients with coronary artery disease (CAD) showed that serum 5-MTP concentrations were inversely correlated with CAD. To test the role of 5-MTP in occlusive vascular disease, we subjected mice to a carotid artery ligation model of neointima formation and treated mice with vehicle or 5-MTP. Compared with vehicle-treated mice, 5-MTP significantly reduced intimal thickening by 40% 4 weeks after ligation. BrdU incorporation assays revealed that 5-MTP significantly reduced VSMC proliferation both in vivo and in vitro. Furthermore, 5-MTP reduced endothelial loss and detachment, ICAM-1 and VCAM-1 expressions, and inflammatory cell infiltration in the ligated arterial wall, suggesting attenuation of endothelial dysfunction. Signaling pathway analysis indicated that 5-MTP mediated its effects predominantly via suppressing p38 MAPK signaling in endothelial and VSMCs. Our data demonstrate a novel vascular protective function of 5-MTP against arterial injury-induced intimal hyperplasia. 5-MTP might be a therapeutic target for preventing and/or treating vascular remodeling.


Assuntos
Artérias/lesões , Doença da Artéria Coronariana/sangue , Músculo Liso Vascular/efeitos dos fármacos , Neointima/tratamento farmacológico , Triptofano/análogos & derivados , Lesões do Sistema Vascular/tratamento farmacológico , Idoso , Animais , Células Cultivadas , Doença da Artéria Coronariana/metabolismo , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Triptofano/administração & dosagem , Triptofano/sangue , Triptofano/farmacologia , Lesões do Sistema Vascular/metabolismo
12.
Virol J ; 12: 142, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26377407

RESUMO

BACKGROUND: Citrus exocortis viroid (CEVd) and Hop stunt viroid (HSVd) are commonly found simultaneously infecting different citrus cultivars in Taiwan. A crucial question to be addressed is how accumulations of these two viroids affect each other in an infected plant. In this study, we investigated the relationship between the two viroids at macroscopic and microscopic levels. METHODS: CEVd and HSVd titers were examined by real-time RT-PCR in 17 plants of two citrus cultivars (blood orange and Murcott mandarin) every 3 months (spring, summer, fall and winter) from 2011 to 2013. Three nonparametric tests (Spearman's rank correlation coefficient, Kendall's tau rank correlation coefficient and Hoeffding's inequality) were performed to test the correlation between CEVd and HSVd. Cellular and subcellular localizations of the two viroids were detected by digoxigenin- and colloidal gold-labeled in situ hybridization using light and transmission electron microscopy. RESULTS: The two viroids were unevenly distributed in four different types of citrus tissues (rootstock bark, roots, twig bark and leaves). Compared with blood orange, Murcott mandarin was generally more susceptible to CEVd and HSVd infection. Both viroids replicated and preferentially accumulated in the underground tissues of the two citrus cultivars. Except for blood orange at high temperatures, significant positive correlations were observed between the two viroids in specific tissues of both cultivars. Relative to concentrations under single-infection conditions, the CEVd population significantly increased under double infection during half of the 12 monitored seasons; in contrast, the population of HSVd significantly increased under double infection during only one season. At cellular/subcellular levels, the two viroids showed similar localization patterns in four tissues and the cells of these tissues in the two citrus cultivars. CONCLUSIONS: Our findings of titer enhancement, localization similarity, and lack of symptom aggravation under CEVd and HSVd double infection suggest that the two viroids have a positive relationship in citrus. The combination of molecular and cellular techniques used in this study provided evidence of titer correlation and localization of co-infecting viroids in the host. These methods may thus be useful tools for exploring viroid-viroid and viroid-host interactions.


Assuntos
Citrus/virologia , Viroides/genética , Replicação Viral , Coinfecção/virologia , Doenças das Plantas/virologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taiwan , Carga Viral
13.
Virol J ; 12: 11, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25645458

RESUMO

BACKGROUND: Two citrus viroids, Citrus exocortis viroid (CEVd) and Hop stunt viroid (HSVd), have been reported and become potential threats to the citrus industry in Taiwan. The distributions and infection rates of two viroids have not been investigated since the two diseases were presented decades ago. The genetic diversities and evolutionary relationships of two viroids also remain unclear in the mix citrus planted region. METHODS: Multiplex RT-PCR was used to detect the two viroids for the first time in seven main cultivars of citrus. Multiplex real-time RT-PCR quantified the distributions of two viroids in four citrus tissues. Sequence alignment and phylogenetic analysis were performed using the ClustalW and MEGA6 (neighbor-joining with p-distance model), respectively. RESULTS: HSVd was found more prevalent than CEVd (32.2% vs. 30.4%). Both CEVd and HSVd were commonly found simultaneously in the different citrus cultivars (up to 55%). Results of the multiplex quantitative analysis suggested that uneven distributions of both viroids with twig bark as the most appropriate material for studies involving viroid sampling such as quarantine inspection. Sequence alignment against Taiwanese isolates, along with analysis of secondary structure, revealed the existence of 10 and 5 major mutation sites in CEVd and HSVd, respectively. The mutation sites in CEVd were located at both ends of terminal and variability domains, whereas those in HSVd were situated in left terminal and pathogenicity domains. A phylogenetic analysis incorporating worldwide viroid isolates indicated three and two clusters for the Taiwanese isolates of CEVd and HSVd, respectively. CONCLUSIONS: Moderately high infection and co-infection rates of two viroids in certain citrus cultivars suggest that different citrus cultivars may play important roles in viroid infection and evolution. These data also demonstrate that two multiplex molecular detection methods developed in the present study provide powerful tools to understand the genetic diversities among viroid isolates and quantify viroids in citrus host. Our field survey can help clarify citrus-viroid relationships as well as develop proper prevention strategies.


Assuntos
Citrus/virologia , Variação Genética , Doenças das Plantas/virologia , Viroides/classificação , Viroides/isolamento & purificação , Genótipo , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Multiplex , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência , Taiwan , Viroides/genética
14.
Mol Biol Rep ; 41(11): 7033-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25034893

RESUMO

Vascular smooth muscle cells (VSMCs) of the arterial wall normally display a differentiated and contractile phenotype. In response to arterial injury, VSMCs switch to a synthetic phenotype, contributing to vascular remodeling. Cysteine-rich protein 2 (CRP2) is a cytoskeletal protein expressed in VSMCs and blunts VSMC migration in part by sequestering the scaffolding protein p130Cas at focal adhesions. CRP2 deficiency in mice increases neointima formation following arterial injury. The goal of this study was to use Csrp2 promoter-lacZ transgenic mice to analyze CRP2 expression during VSMC phenotypic modulation. In a neointima formation model after carotid artery cessation of blood flow, lacZ reporter activity and smooth muscle (SM) α-actin expression in the media were rapidly downregulated 4 days after carotid ligation. Fourteen days after ligation, there was a high level expression of both Csrp2 promoter activity and SM α-actin protein expression in neointimal cells. In atherosclerosis prone mice fed an atherogenic diet, Csrp2 promoter activity was detected within complex atherosclerotic lesions. Interestingly, Csrp2 promoter activity was also present in the fibrous caps of complicated atherosclerotic lesions, indicating that CRP2 might contribute to plaque stability. These findings support the concept that CRP2 contributes to the phenotypic modulation of VSMCs during vascular disease. Modulating transcription to increase CRP2 expression during vascular injury might attenuate vascular remodeling. In addition, increased CRP2 expression at the fibrous caps of advanced lesions might also serve to protect atherosclerotic plaques from rupture.


Assuntos
Aterosclerose/metabolismo , Proteínas de Transporte/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas com Domínio LIM/metabolismo , Músculo Liso Vascular/metabolismo , Lesões do Sistema Vascular/metabolismo , Actinas/metabolismo , Animais , Artérias Carótidas/cirurgia , Proteínas de Transporte/genética , Movimento Celular/fisiologia , Primers do DNA/genética , Galactosídeos , Regulação da Expressão Gênica/genética , Genótipo , Técnicas Histológicas , Imuno-Histoquímica , Indóis , Proteínas com Domínio LIM/genética , Ligadura , Masculino , Camundongos , Camundongos Transgênicos , Neointima/fisiopatologia , Reação em Cadeia da Polimerase
15.
Cell Commun Signal ; 12: 22, 2014 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-24674138

RESUMO

BACKGROUND: Vascular smooth muscle cells (VSMCs) of the arterial wall play a critical role in the development of occlusive vascular diseases. Cysteine-rich protein 2 (CRP2) is a VSMC-expressed LIM-only protein, which functionally limits VSMC migration and protects against pathological vascular remodeling. The multifunctional cytokine TGFß has been implicated to play a role in the pathogenesis of atherosclerosis through numerous downstream signaling pathways. We showed previously that TGFß upregulates CRP2 expression; however, the detailed signaling mechanisms remain unclear. RESULTS: TGFß treatment of VSMCs activated both Smad2/3 and ATF2 phosphorylation. Individually knocking down Smad2/3 or ATF2 pathways with siRNA impaired the TGFß induction of CRP2, indicating that both contribute to CRP2 expression. Inhibiting TßRI kinase activity by SB431542 or TßRI knockdown abolished Smad2/3 phosphorylation but did not alter ATF2 phosphorylation, indicating while Smad2/3 phosphorylation was TßRI-dependent ATF2 phosphorylation was independent of TßRI. Inhibiting Src kinase activity by SU6656 suppressed TGFß-induced RhoA and ATF2 activation but not Smad2 phosphorylation. Blocking ROCK activity, the major downstream target of RhoA, abolished ATF2 phosphorylation and CRP2 induction but not Smad2 phosphorylation. Furthermore, JNK inhibition with SP600125 reduced TGFß-induced ATF2 (but not Smad2) phosphorylation and CRP2 protein expression while ROCK inhibition blocked JNK activation. These results indicate that downstream of TßRII, Src family kinase-RhoA-ROCK-JNK signaling pathway mediates TßRI-independent ATF2 activation. Promoter analysis revealed that the TGFß induction of CRP2 was mediated through the CRE and SBE promoter elements that were located in close proximity. CONCLUSIONS: Our results demonstrate that two signaling pathways downstream of TGFß converge on the CRE and SBE sites of the Csrp2 promoter to cooperatively control CRP2 induction in VSMCs, which represents a previously unrecognized mechanism of VSMC gene induction by TGFß.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas com Domínio LIM/metabolismo , Músculo Liso Vascular/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Fator 2 Ativador da Transcrição/genética , Fator 2 Ativador da Transcrição/metabolismo , Animais , Proteínas de Transporte/genética , Células Cultivadas , Proteínas com Domínio LIM/genética , Camundongos , Músculo Liso Vascular/efeitos dos fármacos , Regiões Promotoras Genéticas , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
16.
Arterioscler Thromb Vasc Biol ; 32(11): 2751-60, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22995520

RESUMO

OBJECTIVE: Migration of vascular smooth muscle cells (VSMCs) from the media into intima contributes to the development of atherosclerosis. Gene deletion experiments implicate a role for toll-like receptor 2 (TLR2) in atherogenesis. However, the underlying mechanisms remain unclear. We postulate that TLR2 promotes VSMC migration by enhancing interleukin (IL)-6 production. METHODS AND RESULTS: Migration assays revealed that TLR2 agonists promoted VSMC migration but not cell proliferation or viability. TLR2 deficiency or inhibition of TLR2 signaling with anti-TLR2 antibody suppressed TLR2 agonist-induced VSMC migration and IL-6 production, which was mediated via p38 mitogen-associated protein kinase and extracellular signal-regulated kinase 1/2 signaling pathways. Neutralizing anti-IL-6 antibodies impaired TLR2-mediated VSMC migration and formation of filamentous actin fiber and lamellipodia. Blockade of p38 mitogen-associated protein kinase or extracellular signal-regulated kinase 1/2 activation inhibited TLR2 agonist pam3CSK4-induced phosphorylation of cAMP response element-binding protein, which regulates IL-6 promoter activity through the cAMP response element site. Moreover, cAMP response element-binding protein small interfering RNA inhibited pam3CSK4-induced IL-6 production and VSMC migration. Additionally, Rac1 small interfering RNA inhibited pam3CSK4-induced VSMC migration but not IL-6 production. CONCLUSIONS: Our results suggest that on ligand binding, TLR2 activates p38 mitogen-associated protein kinase and extracellular signal-regulated kinase 1/2 signaling in VSMCs. These signaling pathways act in concert to activate cAMP response element-binding protein and subsequent IL-6 production, which in turn promotes VSMC migration via Rac1-mediated actin cytoskeletal reorganization.


Assuntos
Aterosclerose/metabolismo , Quimiotaxia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Interleucina-6/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Receptor 2 Toll-Like/metabolismo , Animais , Anticorpos Neutralizantes/farmacologia , Aterosclerose/genética , Aterosclerose/imunologia , Aterosclerose/patologia , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Quimiotaxia/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Relação Dose-Resposta a Droga , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Ligantes , Lipopeptídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/imunologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/imunologia , Miócitos de Músculo Liso/patologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , Transdução de Sinais , Fibras de Estresse/metabolismo , Fatores de Tempo , Receptor 2 Toll-Like/agonistas , Receptor 2 Toll-Like/deficiência , Receptor 2 Toll-Like/genética , Transfecção , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas rac de Ligação ao GTP/genética , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP
17.
Toxicol Mech Methods ; 22(5): 323-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22394342

RESUMO

In the US, lung disease is the number three killer and accounts for one of every six deaths. Furthermore, more than 35 million US populations are now living with a chronic lung disease. Therefore, it is of urgent need to develop novel strategies that can protect against the development and progression of lung disease. Inhalation of air pollutants or environmental toxins induces inflammation and oxidative stress in the lung, resulting in tissue damage with subsequent decline in lung function. Heme oxygenase-1 (HO-1) is a stress response protein, which is highly inducible in response to pathological stimulation. Due to the cumulative effects of HO-1 on heme catabolism and the generation of biologically active downstream products, induction of HO-1 might serve as a protective mechanism against oxidative stress and inflammation-induced injury. Accumulating evidences have indicated a protective function of HO-1 against lung injury. This review highlights the roles of HO-1 in lung disease induced by environmental toxins such as cigarette smoke (CS), silica, and asbestos.


Assuntos
Poluentes Atmosféricos/toxicidade , Heme Oxigenase-1/biossíntese , Heme Oxigenase-1/fisiologia , Lesão Pulmonar , Animais , Indução Enzimática , Humanos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Fumar/efeitos adversos
18.
Stem Cells Dev ; 21(10): 1675-87, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22034921

RESUMO

Embryonic stem cells (ESCs) are promising donor sources in cell therapies for various diseases. Although low levels of reactive oxygen species (ROS) are necessary for the maintenance of stem cells, increased ROS levels initiate differentiation and cell damage. We and others have previously demonstrated that heme oxygenase (HO)-1, a stress response protein with antioxidative and anti-inflammatory properties, plays critical protective functions in cardiovascular and other diseases. However, the functions of HO-1 in ESCs remain to be elucidated. Our goal was to investigate the roles of HO-1 in ESC survival and differentiation. Due to the lack of HO-1-deficient ESCs, we used Oct3/4, Sox2, c-Myc, and Klf4 retroviruses to reprogram mouse embryonic fibroblasts into induced pluripotent stem (iPS) cells of different HO-1 genotypes. These iPS-HO-1 cells exhibited characteristics of mouse ESCs (mESCs) and formed teratomas that were composed of cell types of all 3 germ layers after injected into severe combined immunodeficiency mice. In response to oxidant stress, iPS-HO-1(-/-) cells accumulated higher levels of intracellular ROS compared with D3 mESCs or iPS-HO-1(+/+) cells and were more prone to oxidant-induced cell death. Spontaneous differentiation experiments revealed that Oct4 levels were significantly lower in iPS-HO-1(-/-) cells after leukemia inhibitory factor withdrawal and removal of feeders. Further, during the course of spontaneous differentiation, iPS-HO-1(-/-) cells had enhanced Erk1/2 phosphorylation, which has been linked to ESC differentiation. By the loss-of-function approach using iPS-HO-1(-/-) cells, our results demonstrate that a lack of HO-1 renders iPS cells more prone to oxidative stress-induced cell death and differentiation.


Assuntos
Apoptose , Diferenciação Celular , Heme Oxigenase-1/deficiência , Células-Tronco Pluripotentes Induzidas/fisiologia , Estresse Oxidativo , Fosfatase Alcalina/metabolismo , Animais , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Técnicas de Cocultura , Células-Tronco Embrionárias/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Teste de Complementação Genética , Heme Oxigenase-1/genética , Células-Tronco Pluripotentes Induzidas/enzimologia , Células-Tronco Pluripotentes Induzidas/transplante , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Neoplasias Experimentais/enzimologia , Neoplasias Experimentais/patologia , Fator 3 de Transcrição de Octâmero/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Teratoma/enzimologia , Teratoma/patologia
19.
Antioxid Redox Signal ; 15(7): 1835-46, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21091076

RESUMO

The intrinsic defense mechanisms of the body are critical in protecting tissues from injury in response to pathological stress. Heme oxygenase-1 (HO-1), a stress response protein, is induced in response to various pathological stimuli to serve a cytoprotective function. By degrading the oxidant heme and generating the antioxidant bilirubin and anti-inflammatory molecule carbon monoxide, HO-1 may protect cell from injury due to oxidative and pathological stress. Oxidative stress in the heart caused by ischemia and reperfusion leads to cardiomyocyte death and subsequent myocardial infarction. Vascular diseases including atherosclerosis, graft failure, and restenosis are all associated with reactive oxygen species-induced injury and inflammation. Given that cardiovascular disease is the leading cause of death worldwide, there is considerable interest in developing new strategies for preventing and treating cardiovascular disease. Since HO-1 is induced in the heart and blood vessels in response to various stresses, a role of HO-1 has been implicated in cardiovascular homeostasis. Numerous studies using pharmacological method or genetic approach have since demonstrated the cardiovascular protective function of HO-1. Importantly, a number of studies have associated human HO-1 gene promoter polymorphisms with risk for vascular diseases. Taken together, HO-1 has a great therapeutic potential for cardiovascular disease.


Assuntos
Cardiopatias/enzimologia , Heme Oxigenase-1/metabolismo , Animais , Artérias/enzimologia , Artérias/lesões , Aterosclerose/enzimologia , Aterosclerose/patologia , Vasos Coronários/enzimologia , Vasos Coronários/patologia , Complicações do Diabetes , Terapia Genética , Oclusão de Enxerto Vascular/enzimologia , Oclusão de Enxerto Vascular/patologia , Rejeição de Enxerto/enzimologia , Rejeição de Enxerto/patologia , Cardiopatias/etiologia , Cardiopatias/patologia , Cardiopatias/terapia , Heme Oxigenase-1/genética , Humanos , Hipóxia , Repetições de Microssatélites , Miocárdio/enzimologia , Miocárdio/patologia , Neovascularização Patológica/enzimologia , Placa Aterosclerótica/enzimologia , Placa Aterosclerótica/patologia , Trombose/enzimologia , Trombose/patologia
20.
Am J Cardiovasc Dis ; 1(2): 150-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22254194

RESUMO

Cardiovascular disease accounts for 1 of every 2.9 deaths in the United States, thus the burden of the disease remains high. Given the high mortality and escalating healthcare cost for the disease, it is of urgent need to treat cardiovascular disease effectively. Heme oxygenase-1 (HO-1) catalyzes the oxidation of heme to generate carbon monoxide, biliverdin, and iron. These reaction products of HO-1 have potent anti-inflammatory and anti-oxidative functions. Although HO-1 is expressed at low levels in most tissues under normal basal conditions, it is highly inducible in response to various pathophysiological stresses. Numerous studies have indicated that HO-1 induction is an adaptive defense mechanism to protect cells and tissues against injury in many disease settings. This review highlights the role of HO-1 in inflammation and several cardiovascular diseases-atherosclerosis, myocardial infarction, graft survival after heart transplantation, and abdominal aortic aneurysm. Given that inflammation and oxidative stress are associated with development of cardiovascular disease and that HO-1 has anti-inflammatory and anti-oxidative properties, HO-1 is emerging as a great potential therapeutic target for treating cardiovascular disease.

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