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1.
Biochim Biophys Acta Mol Cell Res ; 1867(5): 118676, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32044386

RESUMO

In egress routes of malignancy, cancer cells are constantly subjected to shear stress imposed by blood/lymph flow. Increasing evidence points toward the regulatory roles of shear stress in tumor cell adhesion and motility. Although it is known that integrin endocytic trafficking governs focal adhesion (FA) turnover and cell migration, the effect and biological consequences of low shear stress (LSS) on integrin trafficking remain unclear. Here, we identified the critical role of integrin ß1 trafficking and caveolin-1 (Cav-1) mediated endocytosis in LSS-induced cell directional migration. LSS altered the distribution of integrin ß1 in MDA-MB-231 cells and significantly promoted its internalization and recycling, which in turn facilitated FA turnover and directional cell migration. Furthermore, LSS induced cytoskeleton remodeling, which was required for internalization of integrin ß1. LSS down-regulated the acetylation level of microtubules (MTs) via activating ROCK/HDAC6 pathway, resulting in elevation of MTs dynamics, Cav-1 motility, and Cav-1-dependent integrin ß1 recycling. We also showed that high HDAC6 expression was a ROCK-dependent prognostic factor, which was correlated with poor outcomes in breast cancer patients. Taken together, these results defined a novel mechanism by which LSS enhanced integrin ß1 trafficking via actin cytoskeleton remodeling and ROCK/HDAC6 mediated deacetylation of MTs, thereby promoting FAs turnover and directional cell migration.

2.
Biochim Biophys Acta Mol Basis Dis ; 1866(3): 165625, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31785406

RESUMO

One of the hallmarks of cancer progression is strong drug resistance during clinical treatments. The tumor microenvironment is closely associated with multidrug resistance, the optimization of tumor microenvironments may have a strong therapeutic effect. In this study, we configured polyacrylamide hydrogels of varying stiffness [low (10 kPa), intermediate (38 kPa) and high (57 kPa)] to simulate tissue physical matrix stiffness across different stages of breast cancer. After treatment with doxorubicin, cell survival rates on intermediate stiffness substrate are significantly higher. We find that high expression of ILK and YAP reduces the survival rates of breast cancer patients. Drug resistance is closely associated with the inactivation of the hippo pathway protein Merlin/MST/LATS and the activation of YAP. These results not only highlight the understanding of drug resistance mechanisms but also serve as a new basis for developing breast cancer treatment delivery systems.

3.
World J Clin Cases ; 7(16): 2189-2203, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31531314

RESUMO

BACKGROUND: Food antigens have been shown to participate in the etiopathogenesis of inflammatory bowel disease (IBD), but their clinical value in IBD is still unclear. AIM: To analyze the levels of specific immunoglobulin G (IgG) and E (IgE) antibodies against food antigens in IBD patients and to determine their clinical value in the pathogenesis of IBD. METHODS: We performed a retrospective study based on patients who visited the First Affiliated Hospital of Nanjing Medical University between August 2016 and January 2018. A total of 137 IBD patients, including 40 patients with ulcerative colitis (UC) and 97 patients with Crohn's disease (CD), and 50 healthy controls (HCs), were recruited. Serum food-specific IgG antibodies were detected by semi-quantitative enzyme-linked immunosorbent assay, and serum food-specific IgE antibodies were measured by Western blot. The value of food-specific IgG antibodies was compared among different groups, and potent factors related to these antibodies were explored by binary logistic regression. RESULTS: Food-specific IgG antibodies were detected in 57.5% of UC patients, in 90.72% of CD patients and in 42% of HCs. A significantly high prevalence and titer of food-specific IgG antibodies were observed in CD patients compared to UC patients and HCs. The number of IgG-positive foods was greater in CD and UC patients than in HCs (CD vs HCs, P = 0.000; UC vs HCs, P = 0.029). The top five food antigens that caused positive specific IgG antibodies in CD patients were tomato (80.68%), corn (69.32%), egg (63.64%), rice (61.36%), and soybean (46.59%). The foods that caused positive specific IgG antibodies in UC patients were egg (60.87%), corn (47.83%), tomato (47.83%), rice (26.09%), and soybean (21.74%). Significantly higher levels of total food-specific IgG were detected in IBD patients treated with anti-TNFα therapy compared to patients receiving steroids and immunosuppressants (anti-TNFα vs steroids, P = 0.000; anti-TNFα vs immunosuppressants, P = 0.000; anti-TNFα vs steroids + immunosuppressants, P = 0.003). A decrease in food-specific IgG levels was detected in IBD patients after receiving anti-TNFα therapy (P = 0.007). Patients who smoked and CD patients were prone to developing serum food-specific IgG antibodies [Smoke: OR (95%CI): 17.6 (1.91-162.26), P = 0.011; CD patients: OR (95%CI): 12.48 (3.45-45.09), P = 0.000]. There was no difference in the prevalence of food-specific IgE antibodies among CD patients (57.1%), UC patients (65.2%) and HCs (60%) (P = 0.831). CONCLUSION: CD patients have a higher prevalence of food-specific IgG antibodies than UC patients and HCs. IBD patients are prone to rice, corn, tomato and soybean intolerance. Smoking may be a risk factor in the occurrence of food-specific IgG antibodies. Food-specific IgG antibodies may be a potential method in the diagnosis and management of food intolerance in IBD.

4.
Sci Rep ; 9(1): 4861, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890715

RESUMO

Temperature is the primary factor that affects seed dormancy and germination. However, the molecular mechanism that underlies its effect on dormancy alleviation remained largely unknown. In this study, we investigate hormone involvement in temperature induced germination as compared to that caused by after-ripening. Dormant (D) sunflower seeds cannot germinate at 10 °C but fully germinate at 20 °C. After-ripened seeds become non-dormant (ND), i.e. able to germinate at 10 °C. Pharmacological experiments showed the importance of abscisic acid (ABA), gibberellins (GAs) and ethylene in temperature- and after-ripening-induced germination of sunflower seeds. Hormone quantification showed that after-ripening is mediated by a decline in both ABA content and sensitivity while ABA content is increased in D seeds treated at 10 or 20 °C, suggesting that ABA decrease is not a prerequisite for temperature induced dormancy alleviation. GAs and ethylene contents were in accordance with germination potential of the three conditions (GA1 was higher in D 20 °C and ND 10 °C than in D 10 °C). Transcripts analysis showed that the major change concerns ABA and GAs metabolism genes, while ABA signalling gene expression was significantly unchanged. Moreover, another level of hormonal regulation at the subcellular localization has been revealed by immunocytolocalization study. Indeed, ABA, protein Abscisic acid-Insensitive 5 (ABI5), involved in ABA-regulated gene expression and DELLA protein RGL2, a repressor of the gibberellins signalling pathway, localized mainly in the nucleus in non-germinating seeds while they localized in the cytosol in germinating seeds. Furthermore, ACC-oxidase (ACO) protein, the key ethylene biosynthesis enzyme, was detected in the meristem only in germinating seeds. Our results reveal the importance of hormone actors trafficking in the cell and their regulation in specialized tissue such as the meristem in dormancy alleviation and germination.

5.
Plant Sci ; 280: 408-415, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30824019

RESUMO

Using various inhibitors and scavengers we took advantage of the size of sunflower (Helianthus annuus) seeds to investigate in vivo the effects of hormones, namely abscisic acid (ABA) and ethylene (ET), and reactive oxygen species (ROS) on the polarization of dormant (D) and non-dormant (ND) embryonic seed cells using microelectrodes. Our data show that D and ND seed cells present different polarization likely due to the regulation of plasma membrane (PM) H+-ATPase activity. The data obtained after addition of hormones or ROS scavengers further suggest that ABA dependent inhibition of PM H+-ATPases could participate in dormancy maintenance and that ET-and ROS-dependent PM H+-ATPase stimulation could participate in dormancy release in sunflower seeds.


Assuntos
Helianthus/enzimologia , Dormência de Plantas , Reguladores de Crescimento de Planta/metabolismo , ATPases Translocadoras de Prótons/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ácido Abscísico/metabolismo , Membrana Celular/enzimologia , Etilenos/metabolismo , Germinação , Helianthus/genética , Helianthus/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ATPases Translocadoras de Prótons/genética , Sementes/enzimologia , Sementes/genética , Sementes/fisiologia
7.
Int J Mol Sci ; 19(8)2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30127315

RESUMO

Dormancy is an adaptive trait that blocks seed germination until the environmental conditions become favorable for subsequent vegetative plant growth. Seed dormancy is defined as the inability to germinate in favorable conditions. Dormancy is alleviated during after-ripening, a dry storage period, during which dormant (D) seeds unable to germinate become non-dormant (ND), able to germinate in a wide range of environmental conditions. The treatment of dormant seeds with ethylene (D/ET) promotes seed germination, and abscisic acid (ABA) treatment reduces non-dormant (ND/ABA) seed germination in sunflowers (Helianthus annuus). Metabolomic and transcriptomic studies have been performed during imbibition to compare germinating seeds (ND and D/ET) and low-germinating seeds (D and ND/ABA). A PCA analysis of the metabolites content showed that imbibition did not trigger a significant change during the first hours (3 and 15 h). The metabolic changes associated with germination capacity occurred at 24 h and were related to hexoses, as their content was higher in ND and D/ET and was reduced by ABA treatment. At the transcriptional level, a large number of genes were altered oppositely in germinating, compared to the low-germinating seeds. The metabolomic and transcriptomic results were integrated in the interpretation of the processes involved in germination. Our results show that ethylene treatment triggers molecular changes comparable to that of after-ripening treatment, concerning sugar metabolism and ABA signaling inhibition.


Assuntos
Etilenos/metabolismo , Germinação , Helianthus/crescimento & desenvolvimento , Reguladores de Crescimento de Planta/metabolismo , Sementes/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Helianthus/genética , Helianthus/metabolismo , Metaboloma , Dormência de Plantas , Sementes/genética , Sementes/metabolismo , Transcriptoma
8.
Plant Sci ; 269: 118-125, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29606208

RESUMO

Temperature is an important environmental factor affecting seed dormancy and germination. The mechanism by which temperature induces germination in dormant seeds is however still unclear. Proteomic study has been performed in dormant sunflower seeds during imbibition at permissive and non-permissive temperatures for germination, 20 and 10 °C, respectively. Proteome analysis showed an increase of proteins belonging to metabolism and energy from the first hours of imbibition followed by a decrease of proteins involved in protein metabolism and seed storage in germinating compared to non-germinating seeds. Proteomic study was completed by polysome and proteasome activity assessment and enzymatic profiling on several altered proteins involved in metabolism and energy. Results showed that 20 °C treatment induced the activation of both protein synthesis and degradation processes, the latter being related to proteasome activity during the germination sensu stricto, and to other degradation processes such as proteases during the post-germination. Interestingly, enzymatic profiles showed that TCA cycle and glycolysis were more active in non-germinating seeds in the phase I of the germination sensu stricto. This result suggests the regulation of central metabolism activity in germinating seeds. The control of energy production during imbibition seems to be involved in molecular networks controlling seed dormancy and germination.


Assuntos
Germinação , Helianthus/crescimento & desenvolvimento , Helianthus/genética , Dormência de Plantas , Proteoma , Sementes/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica , Sementes/metabolismo , Temperatura Ambiente
9.
Medicine (Baltimore) ; 96(32): e7760, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28796070

RESUMO

Meckel diverticulum is the most prevalent congenital abnormality of the gastrointestinal tract in children. The aim of this study was to review and analyze clinical data on the diagnosis and management of Meckel diverticulum in pediatric patients. The records of 102 pediatric patients (<14 years old) who underwent surgery for Meckel diverticulum at our institute between 2001 and 2015 were reviewed. Clinical, imaging, laboratory, surgical, and pathological data were recorded. The series comprised 65 males and 37 females with a median age of 5.6 years. Lower gastrointestinal bleeding was the most frequently identified clinical manifestation of Meckel diverticulum, and this manifestation was observed in 41 patients. Intussusception secondary to Meckel diverticulum was identified in 32 patients. Twelve patients presented clinical features of peritonitis; of these patients, 8 had perforated Meckel diverticulum and 4 had Meckel diverticulitis. In 10 patients, Meckel diverticulum was incidentally diagnosed during other surgeries, including appendectomy and neonatal enterostomy. Seven patients were diagnosed with intestinal obstruction. Technetium-99m pertechnetate imaging offered high diagnostic yield. Open surgery was performed on 59 patients, while a laparoscopic approach was employed in 35 patients. The remaining 8 patients did not undergo resection of the Meckel diverticulum. Histology revealed ectopic gastric mucosa in 42 patients (44.7%), ectopic pancreatic tissue in 35 patients (37.2%), mucosa of the small intestine in 15 patients (16.0%), and both gastric and pancreatic ectopic tissue in 2 patients (2.1%). All patients recovered uneventfully except 2 patients in whom an intestinal adhesion obstruction was identified after discharge. Meckel diverticulum had various clinical manifestations in children. Technetium-99m pertechnetate imaging may be useful for diagnosing Meckel diverticulum. Surgical excision of the Meckel diverticulum may be safe and effective in symptomatic patients, and relatively better outcomes can be achieved using this approach.


Assuntos
Divertículo Ileal/fisiopatologia , Divertículo Ileal/cirurgia , Adolescente , Criança , Pré-Escolar , Diverticulite/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Lactente , Obstrução Intestinal/etiologia , Masculino , Divertículo Ileal/complicações , Divertículo Ileal/patologia , Estudos Retrospectivos
10.
Pediatr Surg Int ; 33(7): 793-797, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28584905

RESUMO

OBJECTIVE: Intussusception secondary to pathologic lead points (PLPs) is a challenging condition for pediatric surgeons, and few studies have been published on this subject. The aim of this study was to review and analyze clinical data on the diagnosis and management of intussusception secondary to PLPs in children. METHODS: Between 2002 and 2016, a total of 65 pediatric patients with a diagnosis of intussusception secondary to PLPs were retrospectively reviewed. RESULTS: The series comprised 47 males and 18 females. The average age of the patients was 4.9 years old. All patients had typical clinical manifestations, and intussusception was proven by ultrasound. Fifty-one patients had recurrent intussusception, of whom 21 had one, 14 had two, 10 had three, and 6 had more than three. There were 20 episodes of recurrence within 24 h (39.2%), 15 episodes were found between 24 and 72 h (29.4%), and the remaining 31.4% (16/51) of recurrences occurred after 72 h. All patients received surgical intussusception reduction. Meanwhile, enterectomy was the procedure of choice in 55 patients, polypectomy in 5 patients, and cystectomy in 3 patients. The types of intussusception secondary to PLPs included small intestinal (n = 25), ileocolic (n = 19), ileocecal (n = 11), ileo-ileocolic (n = 9) and cecalcolic (n = 1). The types of PLPs included Meckel diverticulum (n = 32), intestinal duplication (n = 14), benign polyps (n = 5), malignant lymphoma (n = 4), Peutz-Jeghers syndrome (n = 3), mesenteric cyst (n = 3), intestinal wall hematoma of hemophilia (n = 2), allergic purpura (n = 1), and hamartoma (n = 1). All patients recovered well with no relapse during follow-up, except for one patient who had an intestinal obstruction from adhesions that occurred approximately 3 months after discharge and who was curable after conservative treatment. CONCLUSIONS: Intussusception secondary to PLPs tends to exhibit recurrence. There are various types of intussusception secondary to PLPs. It is necessary to improve auxiliary examinations to identify the etiology and avoid intraoperative omission. Surgical reduction of intussusception secondary to PLPs is the preferred clinical management.


Assuntos
Intussuscepção/etiologia , Intussuscepção/cirurgia , Criança , Pré-Escolar , Doenças do Sistema Digestório/complicações , Feminino , Humanos , Lactente , Pólipos Intestinais/complicações , Intussuscepção/diagnóstico , Masculino , Púrpura de Schoenlein-Henoch/complicações , Recidiva , Estudos Retrospectivos , Ultrassonografia
11.
Front Plant Sci ; 8: 363, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28377781

RESUMO

DNA methylation is an integral component of the epigenetic code in most higher eukaryotes. Exploring the extent to which DNA methylation can be altered under a specific condition and its heritability is important for elucidating the biological functions of this epigenetic modification. Here, we conducted MSAP analysis of rice plants with altered phenotypes subsequent to a low-dose Nd3+YAG laser irradiation. We found that all four methylation patterns at the 5'-CCGG sites that are analyzable by MSAP showed substantial changes in the immediately treated M0 plants. Interestingly, the frequencies of hypo- and hypermethylation were of similar extents, which largely offset each other and render the total methylation levels unchanged. Further analysis revealed that the altered methylation patterns were meiotically heritable to at least the M2 generation but accompanied with further changes in each generation. The methylation changes and their heritability of the metastable epigenetic state were verified by bisulfite sequencing of portion of the retrotranspon, Tos17, an established locus for assessing DNA methylation liability in rice. Real-time PCR assay indicated that the expression of various methylation-related chromatin genes was perturbed, and a Pearson correlation analysis showed that many of these genes, especially two AGOs (AGO4-1 and AGO4-2), were significantly correlated with the methylation pattern alterations. In addition, excisions of a MITE transposon, mPing, occurred rampantly in the laser irradiated plants and their progenies. Together, our results indicate that heritable DNA methylation changes can be readily induced by low-dose laser irradiation, and which can be accompanied by transpostional activation of transposable elements.

12.
Sci Rep ; 6: 38504, 2016 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-27917953

RESUMO

ATP-dependent chromatin remodeling complexes play essential roles in the regulation of diverse biological processes by formulating a DNA template that is accessible to the general transcription apparatus. Although the function of chromatin remodelers in plant development has been studied in A. thaliana, how it affects growth and development of major crops (e.g., maize) remains uninvestigated. Combining genetic, genomic and bioinformatic analyses, we show here that the maize core subunit of chromatin remodeling complex, ZmCHB101, plays essential roles in growth and development of maize at both vegetative and reproductive stages. Independent ZmCHB101 RNA interference plant lines displayed abaxially curling leaf phenotype due to increase of bulliform cell numbers, and showed impaired development of tassel and cob. RNA-seq-based transcriptome profiling revealed that ZmCHB101 dictated transcriptional reprogramming of a significant set of genes involved in plant development, photosynthesis, metabolic regulation, stress response and gene expressional regulation. Intriguingly, we found that ZmCHB101 was required for maintaining normal nucleosome density and 45 S rDNA compaction. Our findings suggest that the SWI3 protein, ZmCHB101, plays pivotal roles in maize normal growth and development via regulation of chromatin structure.


Assuntos
Montagem e Desmontagem da Cromatina , Desenvolvimento Vegetal , Proteínas de Plantas/metabolismo , Subunidades Proteicas/metabolismo , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Genes de Plantas , Nucleossomos/metabolismo , Proteínas de Plantas/genética , Raízes de Plantas/genética , Brotos de Planta/genética , Plantas Geneticamente Modificadas , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Transcrição Genética , Zea mays/genética
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(8): 1110-6, 2016 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-27578582

RESUMO

OBJECTIVE: To detect the expression of miR-124 in colorectal carcinoma (CRC) cells and tissue specimens and analyze its association with the radiosensitivity of the cells. METHODS: The expression of miR-124 in CRC cell lines and tissues were detected using qRT-PCR. The effect of miR-124 in modulating cell radiosensitivity was assessed in CRC cells with miRNA-124 overexpression and miRNA-124 knockdown, and bioinformatics prediction and dual luciferase reporter system were employed to identify the direct target of miR-124. RESULTS: s miR-124 expression was down-regulated in CRC cell lines and tissues. CRC cells over-expressing miR-124 showed an obviously enhanced radiosensitivity, whereas miR-124 knockdown resulted in a reduced radiosensitivity of the cells. Bioinformatics prediction and dual luciferase reporter system verified PRRX1 as a direct target of miR-124, which regulated the radiosensitivity of CRC cells by directly inhibiting PRRX1. CONCLUSION: miR-124 can enhance the radiosensitivity of CRC cells by directly targeting PRRX1, which provides a target for improving the therapeutic effect of radiotherapy of CRC.


Assuntos
Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , MicroRNAs/metabolismo , Tolerância a Radiação , Linhagem Celular Tumoral , Neoplasias Colorretais/radioterapia , Regulação para Baixo , Proteínas de Homeodomínio/genética , Humanos , Luciferases , MicroRNAs/genética
14.
Methods Mol Biol ; 1450: 205-12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27424756

RESUMO

Reactive oxygen species (ROS) have been shown to be toxic but also function as signaling molecules in a process called redox signaling. In seeds, ROS are produced at different developmental stages including dormancy release and germination. Main targets of oxidation events by ROS in cell are lipids, nucleic acids, and proteins. Protein oxidation has various effects on their function, stability, location, and degradation. Carbonylation represents an irreversible and unrepairable modification that can lead to protein degradation through the action of the 20S proteasome. Here, we present techniques which allow the quantification of protein carbonyls in complex protein samples after derivatization by 2,4-dinitrophenylhydrazine (DNPH) and the determination proteasome activity by an activity-based protein profiling (ABPP) using the probe MV151. These techniques, routinely easy to handle, allow the rapid assessment of protein carbonyls and proteasome activity in seeds in various physiological conditions where ROS may act as signaling or toxic elements.


Assuntos
Biologia Molecular/métodos , Complexos Multiproteicos/isolamento & purificação , Complexo de Endopeptidases do Proteassoma/isolamento & purificação , Carbonilação Proteica/genética , Estresse Oxidativo/genética , Plantas/química , Plantas/genética , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/genética , Espécies Reativas de Oxigênio/química , Sementes/química , Transdução de Sinais
15.
BMC Cancer ; 16: 238, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26993269

RESUMO

BACKGROUND: In previous investigation, we reported that stably knocking down cyclin-dependent kinase 4(CDK4) induced expression of let-7c, which further suppressed cell cycle transition and cell growth by modulating cell cycle signaling in nasopharyngeal carcinoma (NPC). In this study, we further explored the molecular function and mechanism of CDK4 modulating miRNAs to stimulate cell cycle transition, cell growth, and Cisplatin (DDP) -resistance on in NPC. METHODS: We identified changes in miRNAs by miRNA array and real-time PCR and the effect on DDP after knocking down CDK4 in NPC cells. Further, we investigated the molecular mechanisms by which CDK4 modulated miR-15a in NPC. Moreover, we also explored the role of miR-15a and the effect on DDP in NPC. Finally, we analyzed the correlation of miR-15a and CDK4 expression in NPC tissues. RESULTS: In addition to let-7 family members, we observed that upregulated expression of miR-15a was significantly induced in CDK4-suppressed NPC cells. Further, we found that knocking down CDK4 suppressed c-Myc expression, and the latter directly suppressed the expression of miR-15a in NPC. Furthermore, miR-15a as a tumor suppressor antagonized CDK4 repressing cell cycle progression and cell growth in vitro and in vivo and induced the sensitivity of cells to DDP by regulating the c-Myc/CCND1/CDK4/E2F1 pathway in NPC. Finally, miR-15a was negatively weak correlated with the expression of CDK4 in NPC. CONCLUSIONS: Our studies demonstrate that CDK4 and miR-15a comprise an abnormal automodulatory feedback loop stimulating the pathogenesis and inducing chemotherapy resistance in NPC.


Assuntos
Quinase 4 Dependente de Ciclina/genética , MicroRNAs/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/genética , Carcinoma , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Quinase 4 Dependente de Ciclina/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , MicroRNAs/genética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Transdução de Sinais/efeitos dos fármacos
16.
Virology ; 492: 32-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26896933

RESUMO

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. Infection of ISKNV is characterized by a unique pathological phenomenon in that the infected cells are attached by lymphatic endothelial cells (LECs). ISKNV mediates the formation of a virus-mock basement membrane (VMBM) structure on the surface of infected cells to provide attaching sites for LECs. The viral protein VP08R is an important component of VMBM. In this study, a novel ISKNV-encoded microRNA, temporarily named ISKNV-miR-1, was identified. ISKNV-miR-1 is complementary to the VP08R-coding sequence and can modulate VP08R expression through reducing its mRNA level. This suggests that formation of VMBM may be under fine regulation by ISKNV.


Assuntos
Infecções por Vírus de DNA/virologia , Doenças dos Peixes/virologia , Regulação Viral da Expressão Gênica , Iridoviridae/genética , MicroRNAs/genética , Proteínas Virais/genética , Animais , Sequência de Bases , Membrana Basal , Adesão Celular , Infecções por Vírus de DNA/patologia , Células Endoteliais/patologia , Células Endoteliais/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Doenças dos Peixes/patologia , Peixes , Interações Hospedeiro-Patógeno , Iridoviridae/patogenicidade , Rim/patologia , Rim/virologia , Linfa/citologia , Linfa/virologia , MicroRNAs/metabolismo , Mimetismo Molecular , Dados de Sequência Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Baço/patologia , Baço/virologia , Proteínas Virais/metabolismo
17.
J Am Heart Assoc ; 4(8): e002128, 2015 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-26304941

RESUMO

BACKGROUND: Interleukin (IL)-1ß, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1ß and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. METHODS AND RESULTS: Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1ß, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1ß, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1ß, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1ß, IL-18, and IL-6, respectively). CONCLUSIONS: ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Colchicina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Citocinas/sangue , Mediadores da Inflamação/sangue , Miocárdio/metabolismo , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/imunologia , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/imunologia , Seio Coronário , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-18/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Miocárdio/imunologia , New South Wales , Fatores de Tempo , Resultado do Tratamento
18.
Front Plant Sci ; 5: 539, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25346747

RESUMO

Ethylene is an important component of the gaseous environment, and regulates numerous plant developmental processes including seed germination and seedling establishment. Dormancy, the inability to germinate in apparently favorable conditions, has been demonstrated to be regulated by the hormonal balance between abscisic acid (ABA) and gibberellins (GAs). Ethylene plays a key role in dormancy release in numerous species, the effective concentrations allowing the germination of dormant seeds ranging between 0.1 and 200 µL L(-1). Studies using inhibitors of ethylene biosynthesis or of ethylene action and analysis of mutant lines altered in genes involved in the ethylene signaling pathway (etr1, ein2, ain1, etr1, and erf1) demonstrate the involvement of ethylene in the regulation of germination and dormancy. Ethylene counteracts ABA effects through a regulation of ABA metabolism and signaling pathways. Moreover, ethylene insensitive mutants in Arabidopsis are more sensitive to ABA and the seeds are more dormant. Numerous data also show an interaction between ABA, GAs and ethylene metabolism and signaling pathways. It has been increasingly demonstrated that reactive oxygen species (ROS) may play a significant role in the regulation of seed germination interacting with hormonal signaling pathways. In the present review the responsiveness of seeds to ethylene will be described, and the key role of ethylene in the regulation of seed dormancy via a crosstalk between hormones and other signals will be discussed.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 34(7): 1071-4, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-25057088

RESUMO

OBJECTIVE: To assess the effect of small interfering RNA (siRNA)-mediated suppression of CDK6 expression on the proliferation and cell cycles of nasopharyngeal carcinoma (NPC) cells in vitro. METHODS: QRT-PCR was used to examine the differential expression of CDK6 in 30 NPC tissues and 18 normal nasopharyngeal tissues. A siRNA targeting CDK6 was transfected in NPC CNE2 cells, and MTT assay and flow cytometry were used to analyze the changes in cell proliferation and cell cycle distribution. Western blotting was used to examine the expressions of the cell cycle-related factors. RESULTS: Compared with normal nasopharyngeal tissues, NPC tissues showed an increased expression of CDK6 mRNA. Knocking down CDK6 expression obviously inhibited tumor cell growth and cell cycle transition from G1 to S phase and caused reduced expressions of CDK4, CCND1, and E2F1 and enhanced expression of the tumor suppressor p21. CONCLUSION: NPC tissues overexpress CDK6. Knocking down CDK6 expression inhibits the growth and cell cycle transition of NPC cells in vitro by inhibiting the expressions of CDK4, CCND1, and E2F1 and upregulating tumor suppressor p21 expression.


Assuntos
Ciclo Celular , Quinase 6 Dependente de Ciclina/genética , Neoplasias Nasofaríngeas/patologia , RNA Interferente Pequeno , Carcinoma , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fator de Transcrição E2F1/metabolismo , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Carcinoma Nasofaríngeo , RNA Mensageiro , Transfecção , Regulação para Cima
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