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Purpose: The patterns and risk factors of postsurgical recurrence of patient with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) are not clarified. This study aimed to decipher and compare the postoperative recurrent patterns and the risk factors contributing to recurrence between MVI positive (MVI(+)) and MVI negative (MVI(-)) HCC after hepatectomy. Patients and methods: Patients with HCC who underwent hepatectomy in three Chinese academic hospitals between January 1, 2009, and December 31, 2018, were enrolled. Recurrent patterns included early (≤2 years) or late (>2 years) recurrence, recurrent sites and number, and risk factors of recurrence were compared between the MVI(+)and MVI(-) groups by propensity score-matching (PSM). Results: Of 1756 patients included, 581 (33.1%) were MVI(+), and 875 (49.8%) patients developed early recurrence. Compared with the MVI(-) group, the MVI(+) group had a higher 2-year recurrence rate in the PSM cohort (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.59-2.10; P < 0.001), and more patients with multiple tumor recurrence. Patients with early recurrence in the MVI(+) group had a worse overall survival (OS) than those in the MVI(-) group (HR, 1.24; 95% CI, 1.02-1.50; P = 0.034). Resection margin (RM) ≤1.0 cm is a surgical predictor of early recurrence for the MVI(+) group (HR, 0.68; 95% CI, 0.54-0.87; P = 0.002), but not for the MVI(-) group. Conclusion: Compared to MVI(-) HCC, MVI(+) HCC tends to be early, multiple recurrence and lung and lymph node metastasis after resection. RM ≤1.0 cm is a surgical risk factor of early recurrence for patient with MVI.
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Type 17 helper T cells (Th17)-dominant neutrophilic airway inflammation is critical in the pathogenesis of steroid-resistant airway inflammation such as severe asthma. Small extracellular vesicles (sEV) derived from human mesenchymal stem cells (MSCs) display extensive therapeutic effects and advantages in many diseases. However, the role of MSC-sEV in Th17-dominant neutrophilic airway inflammation and the related mechanisms are still poorly studied. Here we found that MSC-sEV significantly alleviated the infiltration of inflammatory cells in peribronchial interstitial tissues and reduced levels of inflammatory cells, especially neutrophils, in bronchoalveolar lavage fluids (BALF) of mice with neutrophilic airway inflammation. Consistently, MSC-sEV significantly decreased levels of IL-17A in BALF and Th17 in lung tissues. Furthermore, we found that labelled MSC-sEV were taken up by human CD4+ T cells most obviously at 12 h after incubation, and distributed mostly in mouse lungs. More importantly, potential signaling pathways involved in the MSC-sEV mediated inhibition of Th17 polarization were found using RNA sequencing. Using Western blot, JAK2-STAT3 pathway was identified as an important role in the inhibition of Th17 polarization by MSC-sEV. We found that proteins in MSC-sEV were mostly involved in the therapeutic effects of MSC-sEV. In total, our study suggested that MSC-sEV could be a potential therapeutic strategy for the treatment of neutrophilic airway inflammation.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Neutrófilos , Factor de Transcripción STAT3 , Células Th17 , Células Th17/inmunología , Humanos , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/inmunología , Células Madre Mesenquimatosas/inmunología , Células Madre Mesenquimatosas/metabolismo , Ratones , Neutrófilos/inmunología , Factor de Transcripción STAT3/metabolismo , Janus Quinasa 2/metabolismo , Interleucina-17/metabolismo , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos C57BL , Células Cultivadas , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/citología , Asma/inmunología , Asma/terapia , Masculino , Transducción de Señal , Femenino , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Mesenchymal stromal cells-derived small extracellular vesicles (MSC-sEVs) have recently attracted considerable attention because of their therapeutic potential in various immune diseases. We previously reported that MSC-sEVs could exert immunomodulatory roles in allergic airway inflammation by regulating group 2 innate lymphoid cell (ILC2) and dendritic cell (DC) functions. Therefore, this study aimed to investigate the indirect effects of MSC-sEVs on ILC2s from patients with allergic rhinitis (AR) via DCs. METHODS: Here, we isolated sEVs from induced pluripotent stem cells-MSCs using anion-exchange chromatography and mature DCs (mDCs) were treated with MSC-sEVs. sEV-mDCs were co-cultured with peripheral blood mononuclear cells from patients with AR or purified ILC2s. The levels of IL-13 and GATA3 in ILC2s were examined by flow cytometry. Bulk RNA sequence for mDCs and sEV-mDCs was employed to further probe the potential mechanisms, which were then validated in the co-culture systems. RESULTS: sEV-mDCs showed impaired capacity in priming the levels of IL-13 and GATA3 in ILC2s when compared with mDCs. Furthermore, there was higher PGE2 and IL-10 production from sEV-mDCs, and the blockade of them especially the former one reversed the inhibitory effects of sEV-mDCs. CONCLUSIONS: We demonstrated that MSC-sEVs were able to dampen the activating effects of mDCs on ILC2s in patients with AR. Mechanismly, the PGE2-EP2/4 axis played an essential role in the immunomodulatory effects of sEV-mDCs on ILC2s. Herein, we provided new insights into the mechanism underlying the therapeutic effects of MSC-sEVs in allergic airway inflammation.
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Vesículas Extracelulares , Rinitis Alérgica , Humanos , Inmunidad Innata , Dinoprostona , Interleucina-13 , Leucocitos Mononucleares , Linfocitos , Inflamación , Células DendríticasRESUMEN
Mesenchymal stromal cells (MSCs) are well known for their immunoregulatory roles on allergic inflammation particularly by acting on T cells, B cells, and dendritic cells (DCs). MSC-derived small extracellular vesicles (MSC-sEV) are increasingly considered as one of the main factors for the effects of MSCs on immune responses. However, the effects of MSC-sEV on DCs in allergic diseases remain unclear. MSC-sEV were prepared from the induced pluripotent stem cells (iPSC)-MSCs by anion-exchange chromatography, and were characterized with the size, morphology, and specific markers. Human monocyte-derived DCs were generated and cultured in the presence of MSC-sEV to differentiate the so-called sEV-immature DCs (sEV-iDCs) and sEV-mature DCs (sEV-mDCs), respectively. The phenotypes and the phagocytic ability of sEV-iDCs were analyzed by flow cytometry. sEV-mDCs were co-cultured with isolated CD4+ T cells or peripheral blood mononuclear cells (PBMCs) from patients with allergic rhinitis. The levels of Th1 and Th2 cytokines produced by T cells were examined by ELISA and intracellular flow staining. And the following mechanisms were further investigated. We demonstrated that MSC-sEV inhibited the differentiation of human monocytes to iDCs with downregulation of the expression of CD40, CD80, CD86, and HLA-DR, but had no effects on mDCs with these markers. However, MSC-sEV treatment enhanced the phagocytic ability of mDCs. More importantly, using anti-IL-10 monoclonal antibody or IL-10Rα blocking antibody, we identified that sEV-mDCs suppressed the Th2 immune response by reducing the production of IL-4, IL-9, and IL-13 via IL-10. Furthermore, sEV-mDCs increased the level of Treg cells. Our study identified that mDCs treated with MSC-sEV inhibited the Th2 responses, providing novel evidence of the potential cell-free therapy acting on DCs in allergic airway diseases.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Rinitis Alérgica , Diferenciación Celular , Células Cultivadas , Células Dendríticas , Humanos , Leucocitos Mononucleares , Células Madre Mesenquimatosas/metabolismo , Rinitis Alérgica/metabolismo , Rinitis Alérgica/terapiaRESUMEN
Background: Allergic rhinitis (AR) is characterized by IgE-mediated mucosa response after exposure to allergens. Extracellular vesicles (EVs) are nano-size vesicles containing biological cargos for intercellular communications. However, the role of plasma EVs in pathogenesis of AR remains largely unknown. Methods: Plasma EVs from patients with AR were isolated, quantified, and characterized. The expression of Der p 1 and antigen-presenting molecules on EVs was determined by Western blot, flow cytometry, or ELISA. PKH26- and CFSE (carboxyfluorescein succinimidyl ester)-stained AR-EVs were used to determine the uptake of EVs by CD4+T cells and their effects on CD4+T cell proliferation, respectively. Results: Plasma EVs in healthy control (HC) and AR patients were similar in the concentration of particles, expression for specific EV markers, and both had structural lipid bilayer. However, the levels of Der p 1 on plasma EVs from both mild and moderate-severe AR patients were significantly higher than that on HC. The levels of antigen-presenting molecules on plasma EVs were similar from three subjects. Moreover, levels of Der p 1 on EVs in plasma, but not nasal secretion, were significantly associated with the symptom score of AR patients and level of plasma IL-13. Additionally, plasma EVs from patients with AR promoted the development of Th2 cells, while no effect was found on CD4+ T-cell proliferation. Conclusions: Plasma EVs derived from patients with AR exhibited antigen-presenting characteristics and promoted differentiation of Th2 cells, thus providing novel understanding of the pathogenesis of AR.
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Presentación de Antígeno/inmunología , Vesículas Extracelulares/inmunología , Rinitis Alérgica/inmunología , Células Th2/citología , Adulto , Antígenos Dermatofagoides/sangre , Proteínas de Artrópodos/sangre , Linfocitos T CD4-Positivos/inmunología , Diferenciación Celular , Cisteína Endopeptidasas/sangre , Femenino , Humanos , Masculino , Índice de Severidad de la EnfermedadRESUMEN
The diversity of immune responses in allergic diseases is critically mediated by dendritic cells (DCs), including myeloid and plasmacytoid DCs. Allergen inhalation increased the release of IL-33 from patients with allergic rhinitis (AR), which affecting the downstream cells by binding to its receptor (ST2). However, the effects of inhaled allergens on the expression of ST2 by DCs and IL-33 on the function of mDCs are unknown. The levels of ST2+mDCs and ST2+pDCs in the blood from patients with AR and healthy subjects were examined using flow cytometry. Moreover, the patients were challenged using the allergens and the levels of ST2+mDCs and ST2+pDCs were investigated at different time points. We found that there were higher levels of ST2+ mDCs and ST2+ pDCs in patients with AR, and these levels were further increased 0.5 h after allergen inhalation. Additionally, the type 2 immune response was upregulated after challenge. IL-33 treatment increased the expression of ST2 on mDCs. Our study demonstrated that ST2 was upregulated on DCs after allergen inhalation and that mDCs responded directly to IL-33 through ST2, suggesting that the IL-33/ST2 axis might play an important role in the pathogenesis of allergic rhinitis by DCs.
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Alérgenos/toxicidad , Células Dendríticas/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Células Mieloides/efectos de los fármacos , Rinitis Alérgica/metabolismo , Administración por Inhalación , Adulto , Células Dendríticas/metabolismo , Femenino , Humanos , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-33 , Masculino , Células Mieloides/metabolismoRESUMEN
Group 2 innate lymphoid cells (ILC2s) are recognized as key controllers and effectors of type 2 inflammation. Mesenchymal stem cells (MSCs) have been shown to alleviate type 2 inflammation by modulating T lymphocyte subsets and decreasing TH 2 cytokine levels. However, the effects of MSCs on ILC2s have not been investigated. In this study, we investigated the potential immunomodulatory effects of MSCs on ILC2s in peripheral blood mononuclear cells (PBMCs) from allergic rhinitis patients and healthy subjects. We further investigated the mechanisms involved in the MSC modulation using isolated lineage negative (Lin- ) cells. PBMCs and Lin- cells were cocultured with induced pluripotent stem cell-derived MSCs (iPSC-MSCs) under the stimulation of epithelial cytokines IL-25 and IL-33. And the ILC2 levels and functions were examined and the possible mechanisms were investigated based on regulatory T (Treg) cells and ICOS-ICOSL pathway. iPSC-MSCs successfully decreased the high levels of IL-13, IL-9, and IL-5 in PBMCs in response to IL-25, IL-33, and the high percentages of IL-13+ ILC2s and IL-9+ ILC2s in response to epithelial cytokines were significantly reversed after the treatment of iPSC-MSCs. However, iPSC-MSCs were found directly to enhance ILC2 levels and functions via ICOS-ICOSL interaction in Lin- cells and pure ILC2s. iPSC-MSCs exerted their inhibitory effects on ILC2s via activating Treg cells through ICOS-ICOSL interaction. The MSC-induced Treg cells then suppressed ILC2s by secreting IL-10 in the coculture system. This study revealed that human MSCs suppressed ILC2s via Treg cells through ICOS-ICOSL interaction, which provides further insight to regulate ILC2s in inflammatory disorders.
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Células Madre Mesenquimatosas , Linfocitos T Reguladores , Citocinas/metabolismo , Humanos , Inmunidad Innata , Ligando Coestimulador de Linfocitos T Inducibles/metabolismo , Proteína Coestimuladora de Linfocitos T Inducibles/metabolismo , Leucocitos Mononucleares , Linfocitos , Células Madre Mesenquimatosas/metabolismo , Linfocitos T Reguladores/metabolismoRESUMEN
To clarify the effects of soil salinity on the insect-resistance of flower buds in transgenic Bt cotton of Xinmian 33B (salt-sensitive) and Zhong 07 (salt-tolerant), five levels (0, 0.15%, 0.30%, 0.45% and 0.60%) of soil salinity were set to investigate the impacts of soil salinity on Bt protein content, relative expression of Bt gene, activities of nitrogen metabolism-related enzymes and substances in flower buds during flowering stage. The results showed that Bt protein contents of flower buds decreased with increasing soil salinity. The Bt protein contents of flower buds decreased significantly when the soil salinity level was above 0.30% in both cotton cutivars. Greater reduction of Bt protein content occurred under severe than moderate soil salinity stress. However, the relative expression of Cry1Ac gene increased in flower buds of both cultivars when the stress level increased. Greater decreases of Bt protein content of flower buds was observed in Xinmian 33B compared to Zhong 07 under the same salinity level. The cultivars with greater reduction in Bt protein contents of flower buds also had greater reduction in the soluble protein content, glutamate pyruvate transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities, and greater increments in free amino acid contents, protease activities and peptidase activities. Therefore, the decrease of Bt protein content was caused by decreased synthesis and increased decomposition of protein in flower buds of Bt cotton under soil salinity stress.
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Gossypium/genética , Plantas Modificadas Genéticamente , Salinidad , Suelo/química , Animales , Flores , InsecticidasRESUMEN
Insect-resistance of transgenic Bacillus thuringiensis (Bt) cotton varies among plants organs and with different environmental conditions. The objective of this study was to examine the influence of soil salinity on Bt protein concentration in cotton squares and to elucidate the potential mechanism of Bt efficacy reduction. Two cotton cultivars (NuCOTN 33B and CCRI 07, salt-sensitive and salt-tolerant) were subjected to salinity stress under four natural saline levels in field conditions in 2015 and 2016 and seven regimes of soil salinity ranged from 0.5 to 18.8 dS m-1 in greenhouse conditions in 2017. Results of field studies revealed that Bt protein content was not significantly changed at 7.13 dS m-1 salinity, but exhibited a significant drop at the 10.41 and 14.16 dS m-1 salinity. The greenhouse experiments further showed similar trends that significant declines of the insecticidal protein contents in squares were detected when soil salinity exceeded 9.1 dS m-1. Meanwhile, high salinity resulted in significant reduction in contents of soluble protein and total nitrogen, activities of nitrate reductase (NR), glutamine synthetase (GS) and glutamic-pyruvic transaminase (GPT), but increased amino acid content, activities of protease and peptidase in cotton squares. High salinity also decreased root vigor (RV), root total absorption area (RTA) and root active absorption area (RAA). The extent of decrease of Bt protein content was more pronounced in NuCOTN 33B than CCRI 07, and CCRI07 exhibited stronger enzymes activities involved in square protein synthesis and higher levels of RV, RTA and RAA. Therefore, the results of our present study indicated that insecticidal protein expression in cotton squares were significantly affected by higher salinity (equal to or higher than 9.1 dS m-1), reduced protein synthesis and increased protein degradation in squares and reduced metabolic activities in roots might lead to the decrease of Bt protein content in squares.
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Proteínas Bacterianas/metabolismo , Endotoxinas/metabolismo , Gossypium/metabolismo , Proteínas Hemolisinas/metabolismo , Suelo/química , Alanina Transaminasa/metabolismo , Aminoácidos/metabolismo , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Endotoxinas/análisis , Endotoxinas/genética , Ensayo de Inmunoadsorción Enzimática , Gossypium/crecimiento & desarrollo , Proteínas Hemolisinas/análisis , Proteínas Hemolisinas/genética , Nitrato-Reductasa/metabolismo , Nitrógeno/análisis , Péptido Hidrolasas/metabolismo , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/metabolismo , Salinidad , Tolerancia a la SalRESUMEN
In order to clarify the effects of soil salinity on the insect-resistance of boll in transgenic Bt cotton, potted plants of two Bt cotton cultivars Xinmian 33B (salt-sensitive) and Zhong 07 (salt-tolerant) were exposed to five levels of soil salinity (0, 0.15%, 0.30%, 0.45% and 0.60%). The results showed that Bt protein content of boll shell decreased with increasing soil salinity. Compared with the control (0% soil salinity level), the Bt protein content of boll shell decreased significantly when the soil salinity level was above 0.15% for Xinmian 33B and above 0.30% for Zhong 07. The reduction extent of Bt protein content of boll shell at 30 days post anthesis (DPA) was greater than that at 10 DPA under the same soil salinity level. Significant reductions of soluble protein contents, nitrate reductase (NR), and glutamate pyruvate transaminase (GPT) activities were observed when the boll shell Bt protein content was significantly reduced. The content of free amino acid, protease, and peptidase activity of boll shell significantly increased when the soil salinity level was above 0.30%. In conclusion, soil salinity affected boll shell nitrogen metabolism and reduced Bt protein synthesis. Middle and high soil salinity levels could enhance decomposition of Bt protein, which further decreases the expression level of insecticidal protein.
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Proteínas Bacterianas/metabolismo , Salinidad , Suelo/química , Animales , Bacillus thuringiensis , Gossypium , Proteínas Hemolisinas , Insectos , Insecticidas , Nitrógeno , Plantas Modificadas GenéticamenteRESUMEN
To provide theoretical basis for the safety of insecticidal efficiency in Bt cotton, the effects of high temperature and drought stress on insecticidal protein expression and protein diffe-rently expression profile was studied. In this study, the Bt cotton cultivar Sikang 3 was used as expe-rimental material, with two treatments (40% field capacity and 38 â, HD, and 60% field capacity and 32 â, CK). Differences in proteomics of Bt cotton between HD and CK were compared using label-free quantitative proteomics technology. The results showed that high temperature and drought caused a significant reduction of insecticidal protein content in bolls, with a decrease of 38.2 ng·g-1 FM. The analysis of differential protein expression by label-free quantitative proteomic approach showed that 83 proteins were significantly up-regulated, but 104 proteins were significantly down-regulated in HD stressed cotton plants compared with CK. 122 new proteins were detected and 167 proteins expression was not observed under stressed conditions. Results from the enrichment analysis of differently expressed protein between two treatments showed that 14 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were affected under stress. Three KEGG pathways were related to the Bt protein synthesis and degradation: carbohydrate digestion and absorption pathway, protein export pathway, and protein processing in endoplasmic reticulum pathway. In the carbohydrate digestion and absorption pathway, the starch hydrolysis ability of HD treated cotton plants increased, while the ability to phosphorylate the hexoses, fructose and glucose decreased. In protein export pathway, the peptide synthesis in HD treatment was not significantly affected, while the process of transferring peptides into the endoplasmic reticulum was prohibited. In the protein processing in endoplasmic reticulum pathway, the ability of ubiquitin mediated proteolysis was increased in HD treatment.
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Proteínas Bacterianas/metabolismo , Sequías , Plantas Modificadas Genéticamente , Proteómica , Animales , Bacillus thuringiensis , Endotoxinas , Gossypium , Proteínas Hemolisinas , Calor , Insecticidas , TemperaturaRESUMEN
OBJECTIVE: To explore the core mechanism of long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) in the regulation of multidrug resistance of pancreatic cancer cells. METHODS: mRNA levels of GAS5, miR-181c-5p and Hippo pathway related genes were detected by quantitative real-time PCR (qRT-PCR). Protein levels of MDR-1, MST1, YAP and TAZ were measured by western blot. Cell viability was detected by MTT assay. The combination between GAS5 and miR-181c-5p was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assay. We also established pancreatic cancer-bearing mice model and analyzed tumor volumes. RESULTS: Our data showed GAS5 expression was significantly down-regulated, miR-181c-5p expression was significantly up-regulated in pancreatic cancer cells. Besides, Overexpresson of GAS5 obviously inhibited cell viability, while GAS5 knockdown showed the opposite outcome. Additionally, we also found that GAS5 negatively regulated miR-181c-5p, and miR-181c-5p dramatically promoted pancreatic cancer cell chemoresistance through inactivating the Hippo signaling. GAS5 regulated chemoresistance and Hippo pathway of pancreatic cancer cells via miR-181c-5p/Hippo. Finally, we confirmed that overexpression of GAS5 inhibited tumor growth in pancreatic cancer-bearing mice model. CONCLUSION: GAS5 regualtes Hippo signaling pathway via miR-181c-5p to antagonize the development of multidrug resistance in pancreatic cancer cells.
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Resistencia a Antineoplásicos/genética , MicroARNs/genética , Neoplasias Pancreáticas/genética , ARN Largo no Codificante/genética , Animales , Western Blotting , Línea Celular Tumoral , Supervivencia Celular , Regulación hacia Abajo , Resistencia a Múltiples Medicamentos , Femenino , Regulación Neoplásica de la Expresión Génica , Vía de Señalización Hippo , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/patología , Proteínas Serina-Treonina Quinasas/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. The precise role of GAS5 in pancreatic cancer (PC) progression is currently unknown, so the aim of this study was to explore the functional participation of GAS5 in PC metastasis. METHODS: The expression changes of GAS5, miR-32-5p and PTEN in human PC specimens and cell lines were compared by means of molecular biology methods. Transfection of the recombinant plasmid was applied to modulate the expression levels of the target genes. RIP and RNA pull-down assays were designed to investigate the interaction between GAS5 and miR-32-5p. The effect of GAS5 and miR-32-5p on PC progression was assessed with cell proliferation, migration, invasion and apoptosis in vitro. RESULTS: GAS5 and PTEN protein were decreased in human PC tissues and cells, but miR-32-5p was increased. GAS5 induction greatly inhibited the proliferation, migration and invasion of PC cells PANC-1 and BxPC-3 in vitro and simultaneously induced cell apoptosis. Moreover, GAS5 positively regulated the expression of PTEN through miR-32-5p. Furthermore, GAS5 suppressed the proliferation, migration and invasion of PC cells through regulating miR-32-5p/PTEN axis. Additionally, this finding was further supported by the results of in vivo experiments. CONCLUSION: GAS5 could positively regulate PTEN-induced tumor-suppressor pathway via miR-32-5p, thereby suppressing PC metastasis.
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Group 2 innate lymphoid cells (ILC2s) are essential in initiating and driving allergic immune responses. However, there were inconsistent findings of the ILC2 levels in allergic rhinitis (AR) patients. This study investigated the ILC2 levels in the peripheral blood of house dust mite (HDM)-sensitized AR patients and their ability to secrete type 2 cytokines. The levels of ILC2s with phenotypic ILC2 characteristics were increased in the HDM-AR patients. The AR patients' symptom score and IL-13 levels were positively associated with the ILC2s in HDM-AR patients. The epithelial cytokine stimulation induced dramatic production of IL-5 and IL-13 in PBMCs of AR patients. We successfully sorted ILC2s from AR patients and identified their ability of type 2 cytokines production. The number of ILC2s increased in the HDM-AR patients and ILC2s produced the amount of TH2 cytokines in the presence of epithelial cytokines, which suggested the important role of ILC2 in AR patients.
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Antígenos Dermatofagoides/inmunología , Inmunidad Innata/fisiología , Pyroglyphidae/inmunología , Rinitis Alérgica/inmunología , Adulto , Animales , Femenino , Regulación de la Expresión Génica/inmunología , Humanos , Interleucinas/genética , Interleucinas/metabolismo , Linfocitos/fisiología , Masculino , Adulto JovenRESUMEN
Primary non-neoplastic polyps originating from the nasopharynx have not been reported in the English language literature. We present the clinical and histopathological features of three primary nasopharyngeal polyps. Clinical data of three patients with primary nasopharyngeal polyps treated at the Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-sen University between 2005 and 2015 were analyzed and presented. Three male patients from 45 to 63 years presented with nasopharyngeal masses. CT or MRI examination showed nasopharyngeal space-occupying lesions. Two patients were initially diagnosed with nasopharyngeal angiofibroma and one patient with nasopharyngeal carcinoma. After surgical excision, based on the histological examination, the tissue masses were all diagnosed as inflammatory polyps. Histologically, the polyps demonstrated significant oedema, collagen deposition, leukocytic infiltration, and epithelial remodelling. Primary nasopharyngeal polyps represent a distinct clinical entity and should be considered in the differential diagnosis of nasopharyngeal masses.
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Angiofibroma/diagnóstico , Carcinoma/diagnóstico , Procedimientos Quírurgicos Nasales/métodos , Enfermedades Nasofaríngeas , Neoplasias Nasofaríngeas/diagnóstico , Nasofaringe , Pólipos , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Enfermedades Nasofaríngeas/diagnóstico , Enfermedades Nasofaríngeas/patología , Enfermedades Nasofaríngeas/cirugía , Nasofaringe/diagnóstico por imagen , Nasofaringe/patología , Pólipos/diagnóstico , Pólipos/patología , Pólipos/cirugía , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
Field experiments were conducted in 2014 and 2015 at the "Inner Mongolia cotton comprehensive test station" (39°27' N, 105°39' E) in Alxa Left Banner of Alxa League in Inner Mongolia. By using cotton cultivar CCRI-50 as material and the "6 cotton rows with 3 dripping pipes under a plastic film mulching" plantation pattern, different sowing dates (20-Apr, 30-Apr and 10-May) were set to study the effect of sowing dates on cotton yield, fiber quality and nutrient uptake and utilization. The results showed that as the sowing date delayed, the development of cotton plant was delayed, the yield forming stage shortened, and the mean daily temperature of boll deve-lopment reduced, but the harvesting density increased. Sowing date influenced the biomass accumulation, fiber yield and fiber quality, it also influenced the absorption and distribution of N, P and K. Among the three sowing dates, the biomass distribution proportion to reproductive organ, nutrition (N, P and K) accumulation, lint production efficiency of nutrient and yield were higher in the cotton plant that was sowing at 30-Apr, the seed cotton and lint yield were the highest which could reach up to 6505.9 kg·hm-2 and 2660.9 kg·hm-2, respectively, and the fiber quality was better than that of 10-Mar. For the plant which was sowed at 20-Apr, harvesting density, biomass and nutrient accumulation were the lowest, although economic coefficients of biomass and nutrient were the highest, and the seed cotton and lint yield were respectively 10.9%-14.0% and 11.1%-14.2% lower than that of 30-Apr. When sowing at 10-May, cotton could avoid the low temperature during seed germination, but mean daily temperature during boll development were the lowest, although biomass and nutrient accumulation were the highest. The economic index, lint production efficiency of nutrient were the lowest, which leading to the poorest fiber quality, lowest seed cotton and lowest lint yield which were respectively 32.5%-34.7% and 35.9%-36.2% lower than that of 30-Apr. These results suggested that the optimum sowing date for cotton planting was about 30-Apr in Inner Mongolia west desert area.
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Agricultura , Fibra de Algodón , Gossypium , Biomasa , China , TemperaturaRESUMEN
Allergic rhinitis (AR) has been a significant healthcare burden on individuals and society. However, the detailed effect of different patterns of allergen exposure on the development of AR remains controversial. A mouse model of AR was established to address the complex relationships between allergen exposure and the development of AR. Allergic symptom, OVA-specific IgE in serum and nasal lavage fluid, allergic inflammation in nasal tissues were evaluated after intranasal sensitization and challenge of ovalbumin (OVA) in mice treated with two different doses of allergen for different sensitized durations. Exposure to different doses and sensitized durations of OVA were capable of inducing allergic nasal response. Repetitive OVA exposure in the sensitization phase induced the recruitment of eosinophils and goblet cell hyperplasia. The level of OVA-specific IgE in serum depended on OVA exposure and was mediated in a duration-related manner. In addition, mice treated with low-dose OVA for prolonged duration manifested the major features of human local allergic rhinitis. There were dose- and duration-related effects of allergen exposure on the development of AR. LAR was associated with repetitive exposure to low-dose allergen. Thus, allergen avoidance should be an important aim of AR management.
Asunto(s)
Alérgenos/inmunología , Exposición a Riesgos Ambientales/efectos adversos , Inmunoglobulina E/metabolismo , Ovalbúmina/inmunología , Rinitis Alérgica/inmunología , Administración Intranasal , Alérgenos/efectos adversos , Animales , Biomarcadores/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Mucosa Nasal/inmunología , Ovalbúmina/efectos adversos , Distribución Aleatoria , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/metabolismoRESUMEN
Epidermal growth factor receptors play an important role in airway epithelial cell growth and differentiation. The current study investigates the expression profiles of EGF, EGFR and ERBB4 in patients with nasal polyps (NP), and their response to glucocorticosteroid (GC) treatment. Fifty patients with NP (40 without GC treatment and 10 with oral GC) and 20 control subjects with septal deviation were recruited into the study. Protein levels of EGF, EGFR, and ERBB4 were evaluated by immune-staining. In healthy nasal epithelium, EGF and EGFR localized within p63+ basal cells, while ERBB4 localized within ciliated cells. GC-naïve NP epithelium showed weak expression of EGF in 90% of samples versus 5% of controls. EGFR was significantly increased in the epithelium with basal cell hyperplasia from GC-naïve NPs (78%, 31/40) compared to controls (23%, 4/17). EGFR was also found in some degranulating goblet cells. ERBB4 expression was significantly higher in hyperplastic epithelium from GC-naïve NPs (65%, 26/40) than in controls (6%, 1/17). GC treatment restored the EGF expression and normalized the EGFR and ERBB4 expression in NPs. Differential expression patterns of EGF, EGFR, and ERBB4 are essential in epithelial restitution and remodeling in nasal epithelium.
Asunto(s)
Factor de Crecimiento Epidérmico/genética , Receptores ErbB/genética , Pólipos Nasales/genética , Receptor ErbB-4/genética , Adulto , Estudios de Casos y Controles , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Mucosa Nasal/fisiología , Pólipos Nasales/metabolismo , Pólipos Nasales/patología , Receptor ErbB-4/metabolismo , Regeneración , Adulto JovenRESUMEN
Bt cotton cultivar Sikang 1 (a conventional cultivar) and Sikang 3 (a hybrid cultivar) from China, and 99B (a conventional cultivar) and Daiza 1 (a hybrid cultivar) from USA were selected as experimental materials, the ball wall Bt protein content and nitrogen metabolic physiology were investigated under different high temperature levels at peak boll stage. The results showed that the Bt protein content of boll wall decreased with the increasing temperature. Compared with the control (32 °C, the boll wall Bt protein content decreased significantly when the temperature was above 38 °C for the conventional cultivars and above 40 °C for the hybrid cultivars. The Bt protein contents of cultivar Sikang 1 and 99B decreased by 53.0% and 69.5% respectively with the temperature at 38 °C, and that of cultivar Sikang 3 and Daiza 1 decreased by 64.8% and 54.1% respectively with the temperature at 40 °C. Greater reductions in the boll wall soluble protein contents and GPT activities, larger increments for the boll wall free amino acid contents and proteinsase activities were also observed when the boll wall Bt protein content was significantly reduced. Therefore, high temperature resulted in the reduction of Bt protein synthesis and increase of the insecticidal protein degradation in the boll wall significantly, which caused the reductions in boll wall Bt protein content and insect resistance.