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BACKGROUND: Allergic rhinitis (AR) is regarded as one of the most common allergic disease of nasal mucosa affecting many people worldwide. Long noncoding RNAs are critical modulators affecting AR progression, whereas the pathogenesis of Linc00632 in the development of AR remains unclear. METHODS: T helper cell 2 (Th2) differentiation of CD4+ T cells was measured by flow cytometry. Real-time quantitative PCR assay and Western blot were applied to determine the levels of RNA and proteins, respectively. The interleukin (IL)-4 and IL-13 levels were quantitatively assessed through ELISA. Subcellular fractionation was conducted to detect the cellular localization of Linc00632. RNA immunoprecipitation experiment was employed to validate the interaction relationship between Linc00632 and enhancer of zeste homolog 2 (EZH2). Chromatin immunoprecipitation assay was used for determination of protein-DNA interactions. RESULTS: The expression of Linc00632 was significantly decreased by 4 times in nasal mucosa of AR patients. Human umbilical cord mesenchymal stem cell-derived exosome dramatically inhibited Th2 differentiation, decreased GATA binding protein-3 (GATA-3) protein expressions and IL-4 levels by about 2 times in CD4+ T cells. Knockdown Linc00632 partially reversed the effects of exosomes on Th2 differentiation, IL-4 and IL-13 levels, and GATA-3 expression. Linc00632 overexpression could suppress Th2 differentiation of CD4+ T cells, reduced IL-4 and IL-13 levels, and GATA-3 expressions roughly 2 times. Linc00632 repressed the expression of GATA-3 by interacting with EZH2. GATA-3 overexpression partially reversed the effect of Linc00632 on Th2 differentiation of CD4+ T cells. CONCLUSION: Linc00632 acted as a suppression factor in Th2 differentiation by inhibiting the expression of GATA-3 via interacting with EZH2, which might provide a new insight for understanding the action mechanism of Linc00632 in AR.
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Proteína Potenciadora do Homólogo 2 de Zeste/genética , Exossomos/metabolismo , Fator de Transcrição GATA3/genética , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/metabolismo , RNA Longo não Codificante/genética , Células Th2/metabolismo , Biomarcadores , Diferenciação Celular/genética , Citocinas/metabolismo , Suscetibilidade a Doenças , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Fator de Transcrição GATA3/metabolismo , Humanos , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Ligação Proteica , Interferência de RNA , RNA Longo não Codificante/metabolismo , Rinite Alérgica/diagnóstico , Rinite Alérgica/etiologia , Rinite Alérgica/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Células Th2/imunologiaRESUMO
Strengthening existing reinforced concrete (RC) columns using a partial wrapping strengthening technique (PWST) by fiber-reinforced polymer (FRP) strips has been widely implemented. However, compared with the confinement mechanism of confined concrete in columns strengthened with the FRP full wrapping strengthening technique (FWST), the confinement mechanism of confined concrete in FRP partially wrapped columns is less understood. This paper presents the results of an experimental investigation into the behavior of confined concrete in FRP partially wrapped square columns under axial compression. The effects of FRP strip width and thickness on stressâ»strain behavior were thoroughly investigated. The novel particle image velocimetry (PIV) non-contact strain sensing technique was adopted to measure the strain in the specimens. Results show that the axial strains as well as the hoop strains are generally larger at the mid-plane of adjacent FRP strips than those at the mid-plane of each FRP strip, and considerable variation in hoop strains along the height of the specimens was observed. Comparisons between the experimental results and predictions by existing design-oriented stressâ»strain models were carried out to examine the accuracy of the models. A new design-oriented stressâ»strain model is proposed for confined concrete in FRP partially wrapped square columns and the comparisons between laboratory results and predictions from the proposed model show that the proposed model is superior to the existing models.
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Oxidation of low density lipoprotein (LDL) has been considered as the critical factor which led to atherosclerosis (AS). Lipid and protein in LDL were oxidized to cause change of spectra during oxidation. Clove has been demonstrated to possess the strongest antioxidant capacity among 87 both medical and edible plants proclaimed by China. However, whether LDL oxidation is inhibited by clove? If so, whether it inhibits the oxidation of lipid and protein in LDL, and how does spectral characteristic of LDL change during oxidation when clove was added into LDL. Currently, these questions are still unclear. Therefore, the inhibition efficiency of the effective fraction from clove (EFC) on oxidation of LDL was studied by UV-Visible spectra and fluorescence spectra. The results indicated that EFC might effectively delay propagation of conjugated diene (CD) during LDL oxidation and postpone reaching maximum of its content. Likewise, it might inhibit cholesterol degradation, tryptophan (Trp) fluorescence quenching, lysine (Lys) residues from being modified, and lipofuscins from being generated in peroxidatic reaction among lipid and protein. Besides, EFC also might affect variation of UV-Visible spectra of LDL during oxidation. This study provides reference for future research and development of clove functional food inhibiting AS.
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Antioxidantes/farmacologia , Lipoproteínas LDL/metabolismo , Syzygium/química , Lipídeos , OxirreduçãoRESUMO
The implementation of shape modification (SM) to reinforced concrete (RC) columns has been demonstrated to be effective when enhancing the effectiveness of the fiber-reinforced polymer (FRP) confinement of the columns, particularly for non-circular columns. The SM approach generally includes modifying a square section into a circular one, modifying a rectangular section into an elliptical/oval one and modifying a square/rectangular section into a curvilinearized square/rectangular section. In this paper, a state-of-the-art review of studies on FRP-confined non-circular columns with SM is conducted. The effects of key parameters on the effectiveness of FRP confinement are discussed, and different methods for the implementation of SM in real applications are briefly introduced. The findings of the review further confirm the effectiveness of the SM approach, and the test results demonstrate the effectiveness and advantages of section curvilinearization with a limited increase in cross-sectional area. Additionally, existing theoretical models for FRP-confined concrete in columns with SM are summarized. Further research opportunities associated with FRP-confined non-circular columns with SM are identified.
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Fiber-reinforced polymer (FRP) composites have been widely used for strengthening or constructing structures due to their excellent corrosion resistance and high tensile strength. An emerging hybrid structural member form with FRP composites-which consist of a steel section as internal reinforcement, an external FRP wrap/tube, and concrete filled between them (referred to as FRP-confined steel-reinforced concrete (FCSRC) systems)-has attracted increasing research interest. To date, the concept has been adopted to strengthen/repair steel structures or used as new hybrid structural members (e.g., hybrid columns or beams, including buckling restrained braces (BRBs)). The FRP confinement and composite action between the three components in FCSRCs result in the excellent performance of the hybrid member. This paper presents a state-of-the-art review of FCSRCs for structural applications. The gaps in knowledge and future research opportunities on FCSRC structural members are also identified.
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AIM: To investigate the regulatory effect of microRNA-221 (miR-221) on CDKN1C/p57 expression in colorectal carcinoma (CRC). METHODS: Thirty four CRC and adjacent non-tumorous tissue samples were collected individually. Total RNA and protein were isolatedand from these samples and four human CRC-derived cell lines (including HT-29, Lovo, SW-480 and Caco2). MiR-221 expression was examined using real-time RT-PCR. CRC cells were treated with or without anti-p57-siRNA prior to the addition of pre-miR-221 or anti-miR-221. The mRNA and protein levels of CDKN1C/p57 were examined using semi-quantitative RT-PCR and Western blot, respectively. CRC cell proliferation and apoptosis were assessed using MTT assay and flow cytometry, respectively. The CDKN1C/p57 3'-UTR fragment was amplified using PCR from the genomic DNA of human colon cells and inserted into a luciferase reporter construct. The reporter construct was then transfected into CRC cells together with pre-miR-221 or anti-miR-221, and the luciferase activity in the transfected cells was examined. RESULTS: MiR-221 expression was significantly up-regulated in 90% of CRC samples compared to that in the adjacent non-tumorous tissue, and the expression level was positively correlated to an advanced TNM stage and local invasion. There was no significant difference in CDKN1C/p57 mRNA expression between CRC and corresponding non-tumorous tissues, whereas CDKN1C/p57 protein expression was markedly decreased in the CRC samples. A significant inverse correlation between miR-221 and CDKN1C/p57 expression was found in CRC cells. Moreover, a miR-221-specific inhibitor significantly increased CDKN1C/p57 protein expression in CRC cells. Anti-miR-221 markedly inhibited CRC cell proliferation and induced apoptosis. This inhibitory effect was abolished by pretreatment with anti-p57-siRNA, suggesting that the inhibition was mediated by CDKN1C/p57. A significant increase of the luciferase activity was observed in CRC cells co-transfected with the luciferase reporter construct and anti-miR-221. CONCLUSION: MiR-221 binds to the target site in the 3'-UTR of the CDKN1C/p57 mRNA to inhibit CDKN1C/p57 expression by post-transcriptional gene silencing to promote CRC occurrence and progress, therefore serving as a potential therapeutic target for the prevention and treatment of CRC.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p57/genética , MicroRNAs/genética , Interferência de RNA , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Inibidor de Quinase Dependente de Ciclina p57/biossíntese , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Genes cdc , Humanos , MicroRNAs/metabolismo , Regulação para CimaRESUMO
The diagnostic efficiency of radiation encephalopathy (RE) remains heterogeneous, and prediction of RE is difficult at the pre-symptomatic stage. We aimed to analyze the whole-brain resting-state functional connectivity density (FCD) of individuals with pre-symptomatic RE using multivariate pattern analysis (MVPA) and explore its prediction efficiency. Resting data from NPC patients with nasopharyngeal carcinoma (NPC; consisting of 20 pre-symptomatic RE subjects and 26 non-RE controls) were collected in this study. We used MVPA to classify pre-symptomatic RE subjects from non-RE controls based on FCD maps. Classifier performances were evaluated by accuracy, sensitivity, specificity, and area under the characteristic operator curve. Permutation tests and leave-one-out cross-validation were applied for assessing classifier performance. MVPA was able to differentiate pre-symptomatic RE subjects from non-RE controls using global FCD as a feature, with a total accuracy of 89.13%. The temporal lobe as well as regions involved in the visual processing system, the somatosensory system, and the default mode network (DMN) revealed robust discrimination during classification. Our findings suggest a good classification efficiency of global FCD for the individual prediction of RE at a pre-symptomatic stage. Moreover, the discriminating regions may contribute to the underlying mechanisms of sensory and cognitive disturbances in RE.
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Radiation encephalopathy (RE) is an important potential complication in patients with nasopharyngeal carcinoma (NPC) who undergo radiotherapy (RT) that can affect the quality of life. However, a functional imaging biomarker of pre-symptomatic RE has not yet been established. This study aimed to assess radiation-induced gray matter functional alterations and explore fractional amplitude of low-frequency fluctuation (fALFF) as an imaging biomarker for predicting or diagnosing RE in patients with NPC. A total of 60 patients with NPC were examined, 21 in the pre-RT cohort and 39 in the post-RT cohort. Patients in the post-RT cohort were further divided into two subgroups according to the occurrence of RE in follow-up: post-RT non-RE (n = 21) and post-RT REproved infollow-up (n = 18). Surface-based and volume-based fALFF were used to detect radiation-induced functional alterations. Functional derived features were then adopted to construct a predictive model for the diagnosis of RE. We observed that surface-based fALFF could sensitively detect radiation-induced functional alterations in the intratemporal brain regions (such as the hippocampus and superior temporal gyrus), as well as the extratemporal regions (such as the insula and prefrontal lobe); however, no significant intergroup differences were observed using volume-based fALFF. No significant correlation between fALFF and radiation dose to the ipsilateral temporal lobe was observed. Support vector machine (SVM) analysis revealed that surface-based fALFF in the bilateral superior temporal gyri and left insula exhibited impressive performance (accuracy = 80.49%) in identifying patients likely to develop RE. We conclude that surface-based fALFF may serve as a sensitive imaging biomarker in the prediction of RE.
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OBJECTIVE: To investigate miRNA-221 expression in human colorectal carcinoma (CRC) cells and the effects of miR-221-specific inhibitor on the proliferation and apoptosis of CRC cells. METHODS: Four human CRC cell lines (HT-29, Lovo, SW-480, and CaCO2) were examined for miRNA-221 expression using real-time Q-PCR. The specific 2,-methoxy-modified RNA oligonucleotides of miR-221 (anti-miR-221) were synthesized and transfected into Caco2 cells via liposome, and the changes in the expression of miR-221 in the cells were detected by real-time Q-PCR. The proliferation and apoptosis of the transfected CRC cells were detected using MTT assay and flow cytometry. RESULTS: The 4 human CRC cells showed significantly upregulated expression of miR-221 compare with HUVECs (P<0.01). The miR-221-specific inhibitor, anti-miR-221, significantly inhibited the expression of miR-221 in Caco2 cells and suppressed the cell proliferation, causing also obvious cell apoptosis (P<0.01). CONCLUSION: The miR-221-specific inhibitor shows potent inhibitory effect on the growth of CRC cells, suggesting its value as a potential anti-tumor candidate for treatment of CRC.
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Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/patologia , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Linhagem Celular Tumoral , HumanosRESUMO
OBJECTIVE: To investigate the expression of microRNA-221 (miR-221) and CDKN1C/P57 in colorectal carcinoma (CRC) and adjacent non-cancerous tissues. The effect of miR-221-specific inhibitor on cell proliferation and apoptosis in CRC cells was also assessed. METHODS: The expression of miR-221 was detected by real-time RT-PCR. CDKN1C/P57 mRNA and corresponding protein expression pattern were detected by semi-quantitative RT-PCR and Western-blot. The specific 2'-methoxy-modified RNA oligonucleotide of miR-221(miRNA inhibitor,anti-miR-221) was designed, synthesized and transfected into Caco2 cell by liposome. Finally, the status of CRC cell proliferation and apoptosis were detected by MTT assay and flow cytometry. RESULTS: The expression of miR-221 was significantly up-regulated in CRC tissues as compared to the adjacent non-cancerous tissues(2.041±1.401 vs. 0.806±0.341, P<0.01). There was no significant difference in CDKN1C/P57 mRNA expression between CRC and non-cancerous tissues, whereas CDKN1C/P57 protein markedly decreased in CRC (3.019±1.708 vs. 0.972±0.316, P<0.01). miR-221-specific inhibitor significantly enhanced CDKN1C/P57 protein expression, inhibited proliferation of CRC cells and induced apoptosis of CRC cells(P<0.01). CONCLUSIONS: miR-221 inhibits CDKN1C/P57 expression by post-transcriptional gene silencing to promote CRC development and progression. miR-221-specific inhibitor potentially inhibits the growth of CRC cells. Therefore, it may be a new target for the biologic therapy for CRC.