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1.
JCI Insight ; 6(3)2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33400692

RESUMO

2'3'-cGAMP is known as a nonclassical second messenger and small immune modulator that possesses potent antitumor and antiviral activities via inducing the stimulator of IFN genes-mediated (STING-mediated) signaling pathway. However, its function in regulating type 2 immune responses remains unknown. Therefore, we sought to determine a role of STING activation by 2'3'-cGAMP in type 2 inflammatory reactions in multiple mouse models of eosinophilic asthma. We discovered that 2'3'-cGAMP administration strongly attenuated type 2 lung immunopathology and airway hyperreactivity induced by IL-33 and a fungal allergen, Aspergillus flavus. Mechanistically, upon the respiratory delivery, 2'3'-cGAMP was mainly internalized by alveolar macrophages, in which it activated the STING/IFN regulatory factor 3/type I IFN signaling axis to induce the production of inhibitory factors containing IFN-α, which blocked the IL-33-mediated activation of group 2 innate lymphoid (ILC2) cells in vivo. We further demonstrated that 2'3'-cGAMP directly suppressed the proliferation and function of both human and mouse ILC2 cells in vitro. Taken together, our findings suggest that STING activation by 2'3'-cGAMP in alveolar macrophages and ILC2 cells can negatively regulate type 2 immune responses, implying that the respiratory delivery of 2'3'-cGAMP might be further developed as an alternative strategy for treating type 2 immunopathologic diseases such as eosinophilic asthma.

2.
Front Pharmacol ; 11: 1029, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848724

RESUMO

Objective: Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related death in the world. Platinum-based chemotherapy plays an important role in lung cancer treatment, but the therapeutic effect varies from person to person. Heat shock proteins (HSPs) have been reported to be associated with the survival time of lung cancer patients, which may be a potential biomarker in lung cancer treatment. The aim of this study was to investigate the association between genetic polymorphisms and the prognosis in lung cancer patients treated with platinum-based chemotherapy. Methods: We performed genotyping in 19 single nucleotide polymorphisms (SNPs) of HSP genes and Rho family genes of 346 lung cancer patients by SequenomMassARRAY. We used Cox proportional hazard models, state and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. Results: We found that the polymorphisms of HSPB1 rs2070804 and HSPA4 rs3088225 were significantly associated with lung cancer survival (p=0.015, p=0.049*, respectively). We also discovered the statistically significant differences between rs2070804 with age, gender, histology and stage, rs3088225 with gender and stage, which can affect lung cancer prognosis. Conclusion: The results of our study suggest that HSPB1 rs2070804 (G>T) and HSPA4 rs3088225 (A>G) may be useful biomarkers for predicting the prognosis of lung cancer patients treated with platinum-based chemotherapy.

3.
PLoS One ; 15(7): e0236744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730309

RESUMO

Repeated exposures to environmental allergens in susceptible individuals drive the development of type 2 inflammatory conditions such as asthma, which have been traditionally considered to be mainly mediated by Th2 cells. However, emerging evidence suggest that a new innate cell type, group 2 innate lymphoid cells (ILC2), plays a central role in initiating and amplifying a type 2 response, even in the absence of adaptive immunity. At present, the regulatory mechanisms for controlling ILC2 activation remain poorly understood. Here we report that respiratory delivery of immunogenic extracellular RNA (exRNAs) derived from RNA- and DNA-virus infected cells, was able to activate a protective response against acute type 2 lung immunopathology and airway hyperresponsiveness (AHR) induced by IL-33 and a fungal allergen, A. flavus, in mice. Mechanistically, we found that the innate immune responses triggered by exRNAs had a potent suppressive effect in vivo on the proliferation and function of ILC2 without the involvement of adaptive immunity. We further provided the loss-of-function genetic evidence that the TLR3- and MAVS-mediated signaling axis is essential for the inhibitory effects of exRNAs in mouse lungs. Thus, our results indicate that the host detection of extracellular immunostimulatory RNAs generated during respiratory viral infections have an important function in the regulation of ILC2-driven acute lung inflammation.


Assuntos
Armadilhas Extracelulares/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Pneumonia/imunologia , RNA/imunologia , Hipersensibilidade Respiratória/imunologia , Imunidade Adaptativa , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Alérgenos/imunologia , Alérgenos/metabolismo , Animais , Citocinas/metabolismo , Armadilhas Extracelulares/metabolismo , Interleucina-33/imunologia , Interleucina-33/metabolismo , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/metabolismo , Pneumonia/patologia , RNA/metabolismo , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Transdução de Sinais , Células Th2/imunologia , Células Th2/metabolismo , Receptor 3 Toll-Like/fisiologia
4.
J Vis Exp ; (159)2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32538919

RESUMO

Environmental allergens such as house dust mites (HDM) are often in complex forms containing both allergic proteins that drive aberrant type 2 responses and microbial substances that induce innate immune responses. These allergen-associated microbial components play an important role in regulating the development of type 2 inflammatory conditions such as allergic asthma. However, the underlying mechanisms remain largely undefined. The protocol presented here determines the structural characteristics and in vivo activity of allergen-associated immunostimulatory RNA. Specifically, common allergens are examined for the presence of double-stranded RNA (dsRNA) species that can stimulate IFN responses in lungs and restrain the development of severe lung eosinophilia in a mouse model of HDM-induced allergic asthma. Here, we have included the following three assays: Dot blot to show the dsRNA structures in total RNA isolated from allergens including HDM species, RT-qPCR to measure the activities of HDM RNA in interferon stimulating genes (ISGs) expression in mouse lungs and FACS analysis to determine the effects of HDM RNA on the number of eosinophils in BAL and lung, respectively.


Assuntos
Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Eosinofilia Pulmonar/imunologia , RNA de Cadeia Dupla/imunologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos C57BL , Pyroglyphidae/imunologia
5.
J Insect Sci ; 20(3)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32484869

RESUMO

Fall armyworm, Spodoptera frugiperda (Smith), has caused significant losses for crop production in China. The fall armyworm is mainly controlled by the chemical insecticides, whereas the frequent application of insecticides would result in the resistance development. Insect cytochrome P450 monooxygenases play an essential part in the detoxification of insecticides. In this study, five P450 genes were selected to determine the role in response to insecticides by RNA interference (RNAi). Developmental expression pattern analysis revealed that S. frugiperda CYP321A8, CYP321A9, and CYP321B1 were highest in second-instar larvae among developmental stages, with 2.04-, 3.39-, and 8.58-fold compared with eggs, whereas CYP337B5 and CYP6AE44 were highest in adult stage, with 16.3- and 10.6-fold in comparison of eggs, respectively. Tissue-specific expression pattern analysis exhibited that CYP321A8, CYP321B1, and CYP6AE44 were highest in the midguts, with 3.56-, 3.33-, and 3.04-fold compared with heads, whereas CYP321A9 and CYP337B5 were highest in wings, with 3.07- and 3.36-fold compared with heads, respectively. RNAi was also conducted to explore detoxification effects of the five P450 genes on chlorantraniliprole. The second-instar larvae became more sensitive to chlorantraniliprole with a higher mortality rate than the control, after silencing CYP321A8, CYP321A9, and CYP321B1, respectively. These findings strongly supported our viewpoint that CYP321A8, CYP321A9, and CYP321B1 may play a critical role in insecticide detoxification. It will provide a basis for further study on regulation of P450 genes and the management of S. frugiperda.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Inativação Gênica , Proteínas de Insetos/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Spodoptera/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Genes de Insetos , Inativação Metabólica , Proteínas de Insetos/metabolismo , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento , Interferência de RNA , Spodoptera/genética , Spodoptera/crescimento & desenvolvimento
6.
J Cancer ; 10(27): 6848-6857, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839819

RESUMO

Adenylate cyclase 1 (ADCY1 or AC1) is a member of ADCY superfamily and was primarily found to be expressed in the brain. ADCY1 is responsible for catalyzing ATP to cyclic AMP (cAMP). As a secondary messenger, cAMP can regulate plenty of cellular activities. cAMP can perform its regulation in cellular transport through the binding to cAMP dependent protein kinases (PKAs), cAMP-activated guanine exchange factors (EPACs) and cyclic nucleotide-gated channels functioning in transduction of sensory signals (CNGs). Lung cancer is one of the leading factors of cancer-related death worldwide. Platinum-based chemotherapy is the first-line treatment for advanced lung cancer patients. In addition, surgical treatment, radiation treatment, and molecular targeted therapy are also therapeutic options for lung cancer patients in clinical settings. However, drug resistance and toxicity are the major obstacles that affect chemotherapy outcome and prognosis of lung cancer patients. And the therapeutic efficiency and adverse effects are varying with each individual. In recent years, investigations based on genetic sequencing have revealed the emerging role of ADCY1 mutations in affecting drug efficiency in various cancers such as lung cancer, esophageal cancer and colorectal cancer. The potential function of ADCY1 in chemotherapy resistance is of great importance to be noticed and investigated.

7.
J Cancer ; 10(27): 6910-6914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839826

RESUMO

CCL18 is a cytokine secreted by M2 type tumor associated macrophages, which frequently over-expressed in diverse human cancers. However, the clinical significance of serum CCL18 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, serum CCL18 was initially quantified by enzyme-linked immunosorbent assay (ELISA) in 146 patients with LSCC, 25 patients with precancerous lesions and 72 healthy volunteers. In addition, the correlations between serum CCL18 and clinicopathological parameters were analyzed. Our data revealed that serum CCL18 was obviously increased in patients with LSCC. Moreover, serum CCL18 level was significantly associated with primary tumor site (Glottic vs Others), T classification (T1+T2 vs T3+T4), clinical stage (I+II vs III+IV) and lymph node metastasis (N0 vs N+). Survival analysis demonstrated that patients with high serum CCL18 displayed a shorter survival time than those in patients with low serum CCL18. Importantly, serum CCL18 level and clinical stage were independent prognostic factors in patients with LSCC. Taken together, serum CCL18 could be used as a promising biomarker in patients with LSCC.

8.
J Immunol ; 203(9): 2520-2531, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31562213

RESUMO

The innate immune sensing of allergens or allergen-associated components regulate the development of type 2 inflammatory responses. However, the underlying molecular basis by which allergens or allergen-associated components are detected by innate immune receptors remains elusive. In this study, we report that the most common aeroallergen, house dust mite (HDM), harbors a dsRNA species (HDM-dsRNA) that can activate TLR3-mediated IFN responses and counteract the development of an uncontrolled type 2 immune response. We demonstrate that the mouse strains defective in the dsRNA-sensing pathways show aggravated type 2 inflammation defined by severe eosinophilia, elevated level of type 2 cytokines, and mucus overproduction in a model of allergic lung inflammation. The inability to sense HDM-dsRNA resulted in significant increases in airway hyperreactivity. We further show that the administration of the purified HDM-dsRNA at a low dose is sufficient to induce an immune response to prevent the onset of a severe type 2 lung inflammation. Collectively, these results unveil a new role for the HDM-dsRNA/TLR3-signaling axis in the modulation of a type 2 lung inflammation in mice.


Assuntos
Alérgenos/imunologia , Interferons/biossíntese , Pneumonia/etiologia , Pyroglyphidae/imunologia , RNA de Cadeia Dupla/imunologia , Animais , Humanos , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Hipersensibilidade Respiratória/etiologia , Transdução de Sinais/fisiologia , Receptor 3 Toll-Like/fisiologia
9.
J Cell Mol Med ; 23(4): 2689-2701, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30768878

RESUMO

Metastasis is one of the primary causes for high mortality in patients with squamous cell carcinoma of the head and neck (SCCHN). Our previous study showed that chemokine (C-C motif) ligand 18 (CCL18), derived from tumour-associated macrophages (TAMs), regulates SCCHN metastasis by promoting epithelial-mesenchymal transition (EMT) and preserving stemness. However, the underlying mechanism needs to be further investigation. Interestingly, metadherin (MTDH) expression was induced when SCCHN cells were stimulated with recombinant CCL18 protein in this study. Suppressing MTDH expression reversed CCL18-induced migration, invasion and EMT in SCCHN cells. Furthermore, the NF-κB signalling pathway was involved in the MTDH knock-down cells with CCL18 stimulation. We performed ELISA to evaluate the CCL18 levels in the serums of 132 treatment-naive SCCHN patients, 25 patients with precancerous lesion and 32 healthy donors. Our results demonstrated that serum CCL18 levels were significantly higher in SCCHN patients than patients with precancerous lesion and healthy individuals. CCL18 levels were found to be significantly correlated with tumour classification, clinical stage, lymph node metastasis and histological grade in SCCHN patients. Thus, our findings suggest that CCL18 may serve as a potential biomarker for diagnosis of SCCHN and promote SCCHN invasion, migration and EMT by MTDH-NF-κB signalling pathway.


Assuntos
Quimiocinas CC/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Membrana/genética , NF-kappa B/genética , Proteínas de Ligação a RNA/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocinas CC/sangue , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , NF-kappa B/sangue , Estadiamento de Neoplasias , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/sangue , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
J Cancer ; 9(19): 3593-3602, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310517

RESUMO

Long non-coding RNAs (lncRNAs) are potentially critical regulators of cancer malignant behaviours. Aberrant expression and dysfunction of lncRNA PVT1 have been reported in multiple human cancers. However, its role in squamous cell carcinoma of the head and neck (SCCHN) remains largely unknown. Our current study demonstrated that PVT1 expression was increased in SCCHN. High PVT1 expression was positively correlated with SCCHN clinical parameters including T classification, clinical stages and cervical lymph node metastasis. More importantly, high PVT1 expression predicted a poor prognosis in SCCHN patients. Gain-of function and loss-of function studies further indicated that PVT1 promoted the proliferation and invasion of SCCHN both in vitro and in vivo, which was accompanied by epithelial-mesenchymal transition and enhanced cancer stem cell-like properties. Further mechanistic investigation revealed that PVT1 activated Wnt/ß-catenin signalling pathway, and inhibition of Wnt/ß-catenin signalling reversed the malignant progression caused by PVT1 overexpression. Together, our study reveals that PVT1 accelerates the malignant progression of SCCHN and represents a potential biomarker and therapeutic target in SCCHN.

11.
Zhen Ci Yan Jiu ; 43(8): 476-9, 2018 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-30232848

RESUMO

Since the invention of optogenetic technology, it has greatly promoted the development of neuroscience. Currently, optogenetic approaches have been mostly used to map neural circuits and new neuropharmacology but are rarely seen in the research field of acupuncture analgesia. The mechanism of neural circuits contributing to acupuncture analgesia, an important research hotspot in recent years, has not been fully determined. The optogenetic techniques can be used to modulate and control specific cells, provides highly precise spatial and temporal resolution, is repeatable, and may functionally dissect neuronal networks in vivo. The neuronal activities and their information transmission, processing and storage in intercluster neural networks in different brain regions, and the correlation between behavioral changes and electrical activities of neurons in vivo studies are mainly captured by the implanted microelectropode array, etc. If these two (or more) approaches are combined together, it is definitely and highly helpful to reveal the driving dynamics of neural circuits, plasticity and temporal-spatial activity mode of neurons, as well as behavioral reactions of animals with chronic pain during acupuncture analgesia and may open a new prospect for the application of acupuncture analgesia study.


Assuntos
Analgesia por Acupuntura , Optogenética , Animais , Encéfalo , Neurônios
12.
Cancer Cell Int ; 18: 120, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30181713

RESUMO

Background: Alternatively activated macrophages in tumor microenvironment is defined as M2 tumor-associated macrophages (M2 TAMs) that promote cancer progression. However, communicative mechanisms between M2 TAMs and cancer cells in squamous cell carcinoma of head and neck (SCCHN) remain largely unknown. Methods: Quantitative real-time PCR, western blotting, enzyme-linked immunosorbent assay and flow cytometry were applied to quantify mRNA and protein expression of genes related to M2 TAMs, epithelial-mesenchymal transition (EMT) and stemness. Wounding-healing and Transwell invasion assays were performed to detect the invasion and migration. Sphere formation assay was used to detect the stemness of SCCHN cells. RNA-sequencing and following bioinformatics analysis were used to determine the alterations of transcriptome. Results: THP-1 monocytes were successfully polarized into M2-like TAMs, which was manifested by increased mRNA and protein expression of CCL18, IL-10 and CD206. Conditioned medium from M2-like TAMs promoted the migration and invasion of SCCHN cells, which was accompanied by the occurrence of EMT and enhanced stemness. Importantly, CCL18 neutralizing antibody partially abrogated these effects that caused by conditional medium from M2-like TAMs. In addition, recombinant human CCL18 (rhCCL18) correspondingly promoted the malignant biological behaviors of SCCHN in vitro. Finally, RNA-sequencing analysis identified 331 up-regulated and 363 down-regulated genes stimulated by rhCCL18, which were statistically enriched in 10 cancer associated signaling pathways. Conclusion: These findings indicate that CCL18 derived from M2-like TAMs promotes metastasis via inducing EMT and cancer stemness in SCCHN in vitro.

13.
J Cancer ; 9(1): 198-204, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29290786

RESUMO

Purpose: Lysine demethylase (KDM) 5B, as a member of the histone lysine demethylase family, is overexpressed and functions abnormally in various human cancers. However, its expression in the squamous cell carcinoma of the head and neck (SCCHN) remains unclear. Methods: KDM5B expression was analyzed by immunohistochemistry and correlated with clinicopathological parameters in 103 archival SCCHN tissue samples and 24 adjacent noncancerous epithelial tissues. Results: We found that KDM5B expression was higher in SCCHN than that in adjacent noncancerous tissues. This was closely associated with lymph node metastasis and tumor recurrence. In addition, Kaplan-Meier analysis revealed that patients with high KDM5B expression had shorter disease-free and overall survival times than those with low KDM5B expression. Importantly, both univariate and multivariate analysis demonstrated that KDM5B level was an independent prognostic factor in SCCHN patients. Conclusions: These results indicate that KDM5B is a valuable biomarker that can be used to predict SCCHN patient outcome.

14.
Oncol Rep ; 38(5): 2893-2900, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901527

RESUMO

Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions. Furthermore, the study indicated that there is a positive feedback loop between HIF-1α and MTDH in HNSCC cells, and that hypoxia promotes HNSCC cell metastasis and epithelial-mesenchymal transition by mediating the HIF-1α-MTDH loop. These findings implicate HIF-1α-MTDH as a promising target for anticancer drugs in solid tumors, and help to explain the pro-tumorigenic and unfavorable effect of MTDH on HNSCC observed in our previous studies.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Moléculas de Adesão Celular/metabolismo , Glicólise , Neoplasias de Cabeça e Pescoço/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana , Invasividade Neoplásica , Proteínas de Ligação a RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço
15.
J Cancer ; 8(12): 2336-2345, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28819438

RESUMO

Derlin-1 is over-expressed to function as an oncoprotein in breast, lung and colon cancers. However, the implications of Derlin-1 involved in squamous cell carcinoma of the head and neck (SCCHN) remain unknown. This study aims to investigate the effects of Derlin-1 expression on SCCHN tissues and cells. The potential mechanism of Derlin-1 regulating SCCHN cell proliferation, apoptosis and metastasis was also indicated in this work. Western blot and immunohistochemistry (IHC) assays showed that Derlin-1 was over-expressed in 114 SCCHN samples and five SCCHN cell lines. We found that the expression of Derlin-1 was positively associated with lymph node metastasis, clinical stage and recurrence in our SCCHN patients' samples. Survival analysis indicated that high expression of Derlin-1 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). Knock down expression of Derlin-1 in SCCHN cell lines was found to inhibit cell proliferation, metastasis and promote cell apoptosis. Further experiments showed that signals of PI3K/Akt, p53 and Smad2/3 may involve in these processes. In all, Derlin-1 might be a novel prognostic marker of SCCHN patients and plays an oncogenic role in SCCHN cell progression.

16.
Am J Cancer Res ; 7(12): 2554-2565, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29312808

RESUMO

PURPOSE: MicroRNAs function through regulating specific target mRNA expression and then participate in the development and progression of diverse human cancers. MiR-98 shows aberrant expression and dysfunction in tumors. However, its clinical significance and exact role in squamous cell carcinoma of the head and neck (SCCHN) remain elusive. METHODS: MiR-98 expression was examined by qRT-PCR and correlated with clinicopathological variables and prognosis in SCCHN patients. Effects of miR-98 on epithelial-mesenchymal transition (EMT) and the malignant phenotypes of SCCHN were studied. Finally, the role of target gene metadherin (MTDH) in miR-98 mediated effects were assayed. RESULTS: Our results demonstrated that miR-98, as an endogenous inhibitor of MTDH via directly binding to its 3'-untranslated region (UTR) region, decreased significantly in SCCHN tissues. Decreased miR-98 expression was negatively correlated with T classification, clinical stage, lymph node metastasis and a shorter survival status in SCCHN patients. Loss-of-function and gain-of-function analyses confirmed that miR-98 inhibited cell proliferation, migration and invasion of SCCHN cells in vitro. Moreover, miR-98 repression led to increased MTDH expression and induced EMT alteration. Importantly, ectopic expression of MTDH partially reversed the effects caused by miR-98 overexpression. CONCLUSIONS: Our study identifies that miR-98 serves as a suppressor in SCCHN progression via targeting oncogene MTDH.

17.
Jundishapur J Microbiol ; 9(10): e37897, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27942365

RESUMO

BACKGROUND: Due to the overuse of antibiotics in livestock as a growth-promoting agent, the emergence of multi-antibiotic resistant bacteria is becoming a concern. OBJECTIVES: In this study, we aimed to detect the presence and discover the molecular determinants of foodborne bacteria in retail sausages resistant towards the antibacterial agent amoxicillin-clavulanate. METHODS: Two grams of sausages were chopped into small pieces and transferred into sterile Luria-Bertani (LB) enrichment broths overnight before they were plated on MacConkey agar petri dishes. The bacteria isolated were then screened for amoxicillin-clavulanate resistance, and an antimicrobial susceptibility test of each isolate was performed by using the disc diffusion method. Double synergy and phenotypic tests were carried out to detect the presence of extended spectrum ß-lactamase (ESBL). API 20E kit was used to identify the Enterobacteriaceae. All isolates were further examined by polymerase chain reaction (PCR) for resistant genes blaOXA-1, blaOXA-10, plasmid-mediated AmpC (blaCMY and blaDHA), and the chromosome-mediated AmpC, Sul1, blaTEM, and blaSHV genes. RESULTS: A total of 18 amoxicillin-clavulanate resistant isolates were obtained from seven different types of retail sausages. Only half of them were identified as Enterobacteriaceae, but none were ESBL-producers. All the 18 isolated strains demonstrated resistance towards amoxicillin-clavulanate, penicillin and oxacillin (100%), cefotaxime (71.4%), cefpodoxime (66.7%), and ampicillin (83.3%). blaTEM was the most frequently detected ß-lactamase gene. Both plasmid- and chromosomal-bound blaTEM genes were detected in all of the isolated Enterobacteriaceae. blaSHV and Sul1 accounted for 22.2% and 11.1% of the amoxicillin-clavulanate resistant isolates, respectively, whereas blaAMPC, blaCMY, blaDHA, blaOXA-1, and blaOXA-10 were not found in any of the isolates. The only one ESBL-producing bacteria detected in this study was Chryseobacterium meningosepticum, which harbored the blaTEM gene. CONCLUSIONS: The multidrug resistant bacteria that carry antibiotic resistant genes from retail sausages may increase the risk of transmission to humans via the consumption of contaminated sausages. Stricter measures must be taken to address the use of antibiotics in animal agriculture and to consider their potential impact on human health.

18.
Oncol Rep ; 36(4): 1861-7, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27498905

RESUMO

Paclitaxel chemoresistance restricts the therapeutic efficacy and prognosis of patients with nasopharyngeal carcinoma (NPC). Accumulating evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) contributes to cancer progression. Therefore, we aimed to identify lncRNAs associated with paclitaxel resistance in NPC. First, paclitaxel-resistant CNE-2 cells (CNE-2-Pr) were successfully established and confirmed to be 33.26±8.70 times more resistant than parental CNE-2 cells. Then, differential expression profile of lncRNAs associated with NPC paclitaxel resistance, which contained a total of 2,670 known lncRNAs and 4,820 novel lncRNAs, was constructed via next generation sequencing technology. Our qRT-PCR confirmed that 7 of the top 8 lncRNAs were expressed with the same trend as the prediction, including 4 known lncRNAs (n375709, n377806, n369241 and n335785) and 3 novel lncRNAs (Unigene6646, Unigene6644 and Unigene1654). Our group initially focused on lncRNA n375709, which was the most significantly overexpressed lncRNA of the known lncRNAs. CCK-8 assays demonstrated that further inhibition of lncRNA n375709 increased the paclitaxel sensitivity in NPC 5-8F and 6-10B cells. In conclusion, the present study provided an overview of the expression profiles of lncRNAs correlated with paclitaxel resistance. lncRNA n375709 was identified to be involved in the regulation of NPC paclitaxel resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Nasofaríngeas/genética , RNA Longo não Codificante/genética , Antineoplásicos Fitogênicos/farmacologia , Carcinoma , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo , Paclitaxel/farmacologia , Reação em Cadeia da Polimerase , Transfecção
19.
Biomed Res Int ; 2015: 137024, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26636095

RESUMO

Segmentation of retinal blood vessels is significant to diagnosis and evaluation of ocular diseases like glaucoma and systemic diseases such as diabetes and hypertension. The retinal blood vessel segmentation for small and low contrast vessels is still a challenging problem. To solve this problem, a new method based on cake filter is proposed. Firstly, a quadrature filter band called cake filter band is made up in Fourier field. Then the real component fusion is used to separate the blood vessel from the background. Finally, the blood vessel network is got by a self-adaption threshold. The experiments implemented on the STARE database indicate that the new method has a better performance than the traditional ones on the small vessels extraction, average accuracy rate, and true and false positive rate.


Assuntos
Algoritmos , Técnicas de Diagnóstico Oftalmológico , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Reconhecimento Automatizado de Padrão/métodos , Vasos Retinianos/anatomia & histologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
20.
Medicine (Baltimore) ; 94(6): e502, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25674742

RESUMO

Our previous study indicated overexpression of metadherin (MTDH) is an adverse prognostic factor in squamous cell carcinoma of the head and neck (SCCHN) and promotes SCCHN cell proliferation and invasion. However, its mechanism remains unclear. Recent studies have indicated that MTDH is a cancer-metastasis-associated molecule that participates in the process of angiogenesis. Therefore, the study is aimed to investigate that whether vascular endothelial growth factor (VEGF), as one of the most potent proangiogenic cytokines, is regulated by MTDH and the role of the phosphatidylinositide 3-kinases/Protein Kinase B (PI3K/Akt) pathway in this process of regulation and the clinical significance of both MTDH and VEGF in SCCHN.Immunohistochemistry was used to assay the expression of MTDH and VEGF in a cohort of 189 SCCHN patients with intact follow-up information. The expression of MTDH was then upregulated or inhibited by lentivirus-mediated MTDH Complementary deoxyribonucleic acid or MTDH short hairpin ribonucleic acid (shRNA) to observe the resulting alterations in VEGF expression and the PI3K/Akt signaling pathway in SCCHN cell lines. In addition, the PI3K/Akt pathway was modulated to observe the resulting changes in the MTDH-mediated expression of VEGF.The immunohistochemistry data showed that MTDH expression is positively correlated with VEGF expression in SCCHN tissues. Moreover, the overexpression of MTDH in SCCHN Tu686 and 5-8F cells led to increases in the expression of VEGF, and this effect was accompanied by activation of the PI3K/Akt pathway. Conversely, shRNA-mediated knockdown of MTDH led to decreased VEGF expression. In addition, inhibition of the Akt signaling pathway reversed the upregulation of VEGF resulting from MTDH overexpression. Moreover, the survival analysis revealed that VEGF is an independent prognostic factor, and a combined survival analysis based on both MTDH and VEGF showed synergistic effects in the prognosis evaluation of SCCHN patients.The findings of the present study demonstrate that MTDH regulates the expression of VEGF via the PI3K/Akt signaling pathway, indicating the potential role of the MTDH-mediated activation of VEGF signaling pathway in SCCHN angiogenesis and metastasis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Moléculas de Adesão Celular/fisiologia , Neoplasias de Cabeça e Pescoço/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Proteínas de Membrana , Prognóstico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , RNA Interferente Pequeno/fisiologia , Proteínas de Ligação a RNA , Transdução de Sinais/fisiologia , Transfecção , Regulação para Cima
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