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Front Oncol ; 11: 751903, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868956


Here, we investigated the clinicopathological and prognostic potential of the long noncoding RNA Colon Cancer-Associated Transcript 2 (CCAT2) in human colorectal cancer (CRC). We used qPCR to quantify CCAT2 levels in 44 pairs of CRC tissues and adjacent nontumor and healthy colon mucosa tissues, and in several CRC cell lines (SW620, SW480, HT-29, LOVO, HCT116 and DLD-1) and normal human colorectal epithelial cells (HFC). We assessed the effects of CCAT2 overexpression or knockdown on the proliferation, migration and invasion by SW620 and LOVO cells using CCK-8, transwell, and wound-healing assays, respectively. We also investigated the potential interaction between CCAT2 and TAF15 through RNA pull down and rescue experiments. Lastly, we evaluated the expression of the cell cycle progression markers and GSK3ß signaling pathway proteins using Western blotting. Our results showed that CCAT2 was upregulated in CRC tissues and cell lines as com-pared to controls. Ectopic expression of CCAT2 promoted CRC cell proliferation, migration and invasion, likely through direct interaction with TAF15, transcriptional activation of RAB14, and activation of the AKT/GSK3ß signaling pathway. In vivo, CCAT2 promoted CRC cell growth and metastasis in nude mice. Taken together, these results highlight the actions of CCAT2 as a CRC oncogene.

Virulence ; 12(1): 2133-2148, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34384038


Changes in the intestinal microbiota indirectly impact the health of mucosa distal to the intestine, particularly the respiratory tract. However, the effects of intestinal microbiota dysbiosis on the regulation of respiratory syncytial virus (RSV) infection are not clear. In this study, we examined the effects of altering the intestinal microbiota on the pulmonary immune response against RSV infection. BALB/c mice were treated with streptomycin before infection with RSV to study the altered immune response. The ingestion of streptomycin led to a marked alteration in the intestinal microbiota with a reduced abundance of Lactobacillus and Clostridium genera, followed by greatly aggravated pulmonary inflammation in response to RSV infection. This aggravated inflammation was associated with a dysregulated immune response against RSV infection, characterized by the increased expression of IFN-γ and IL-17 and increased pulmonary M1-like macrophage polarization, and decreased expression of IL-5. Supplementation of Clostridium butyricum (CB) prevented aggravated inflammation and the dysregulated immune response characterized by greater M2 polarization of pulmonary macrophages and decreased release of IFN-γ and IL-17 as well as increased IL-5 levels. Furthermore, in vitro and in vivo experiments identified that butyrate, the main metabolite produced by CB, promoted M2 polarization of macrophages in RSV-infected mice exposed to streptomycin. Together, these results demonstrate the mechanism by which intestinal microbiota modulate the pulmonary immune response to RSV infection.

Clostridium butyricum , Microbioma Gastrointestinal , Pneumonia Viral , Infecções por Vírus Respiratório Sincicial , Administração Oral , Animais , Disbiose , Inflamação , Interferon gama/imunologia , Interleucina-17/imunologia , Interleucina-5/imunologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia Viral/terapia , Infecções por Vírus Respiratório Sincicial/terapia , Vírus Sincicial Respiratório Humano , Estreptomicina
Am J Transl Res ; 12(11): 7060-7078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33312351


This study aimed to explore immune-related lncRNAs for predicting the overall survival of patients with colon adenocarcinoma. RNA-sequencing data were downloaded from the TCGA data portal. The immune-related lncRNAs with differential expression were identified with Cox and LASSO regression analysis. With the stepwise regression analysis, a seven lncRNA signature was established for calculating the Risk Score with following formula: Risk Score = [Expression level of AC027307.2 * (0.156)] + [Expression level of AC074117.1 * (0.294)] + [Expression level of AC103702.2 * (-0.025)] + [Expression level of CYTOR * (0.205)] + [Expression level of LINC02381 * (0.251)] + [Expression level of MIR200CHG * (0.052)] + [Expression level of SNHG16 * (-0.101)]. The Risk Score was validated with survival analysis, achieving moderate area under the curve (AUC) of receiver operating characteristic (ROC) curve over 0.7. GSEA and immune-cell abundance analysis further supported the involved lncRNAs were immune-relevant. Finally, the prognosis prediction efficacy was verified with clinical samples with an AUC of 0.674 in ROC curve. Both the Risk Score and involved immune-related lncRNAs presented promising clinical significance.

Biosci. j. (Online) ; 34(3): 778-789, mai/jun. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-967000


Usually, weak inorganic acids have been used to disperse collagen as green solvents for fabricating kinds of biomaterials all the time. However, it is an open question how much the dissolving process preserves or alters the native structure of collagen till now. Herein, we have examined the effect of three different solvents (HAc, HCl, H3PO4) on the secondary structures of collagen, based on circular dichroism (CD) spectra of collagen from 185 to 260 nm together with CDNN programs. We have found that collagen almost completely preserved its triple helical structure in the three inorganic acids at pH=3.0 or so, which demonstrated that it was the concentration of free H+ in the above three solutions whose pH was fixed at 3.0 that can maintain an proper amount of surface charge on the collagen colloidal particles and appropriately loose the three-helix structure, which can not only lead to a better dispersion behavior, but also maximize the preservation of the integrity of the collagen structure. Although the fractions of kinds of secondary structures in collagen were different from all the three solvents based on CDNN data, which gave very similar results for each other. These results was tested for the first time in this work to estimate the secondary structures for collagen in the different common inorganic acids, which provides a new avenue for green collagen solvents to prepare collagen-based composite with well triple-helical structure for tissue engineering.

Habitualmente, os ácidos inorgânicos fracos têm sido usados para dispersar colágeno como solventes verdes para fabricar tipos de biomateriais o tempo todo. No entanto, é uma questão aberta quanto o processo de dissolução preserva ou altera a estrutura nativa do colágeno até agora. Aqui, examinamos o efeito de três solventes diferentes (HAc, HCl, H3PO4) nas estruturas secundárias de colágeno, com base em espectros de dicroísmo circular (CD) de colágeno de 185 a 260 nm em conjunto com programas CDNN. Descobrimos que o colágeno preservou quase completamente sua estrutura helicoidal tripla nos três ácidos inorgânicos a pH = 3,0 ou mais, o que demonstrou que foi a concentração de H+ livre nas três soluções acima cujo pH foi fixado em 3,0 que pode manter uma boa quantidade de carga superficial sobre as partículas coloidais de colágeno e destrói adequadamente a estrutura de três hélices, o que não só pode levar a um melhor comportamento de dispersão, mas também maximizar a preservação da integridade da estrutura de colágeno. Embora as frações de tipos de estruturas secundárias em colágeno fossem diferentes de todos os três solventes com base em dados CDNN, que deram resultados muito semelhantes entre si. Estes resultados foram testados pela primeira vez neste trabalho para estimar as estruturas secundárias para o colágeno nos diferentes ácidos inorgânicos comuns, o que fornece uma nova alternativa para solventes de colágeno verdes para preparar compósitos à base de colágeno com a estrutura helicoidal tripla para engenharia de tecidos.

Dicroísmo Circular , Colágeno Tipo I , Ácidos Inorgânicos , Solventes , Materiais Biocompatíveis
J Cancer Res Clin Oncol ; 144(2): 295-308, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29270670


PURPOSE: B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore the effects and the role of a possible BTG3 molecular mechanism on aggressive colorectal cancer behavior. METHODS: BTG3 expression was assessed by immunohistochemistry (IHC) on specimens from 140 patients with CRC. The association of BTG3 expression with clinicopathological features was examined. To confirm the biological role of BTG3 in CRC, two CRC cell lines expressing BTG3 were used and BTG3 expression was knocked down by shRNA. CCK-8, cell cycle, apoptosis, migration, and invasion assays were performed. The influence of BTG3 knockdown was further investigated by genomic microarray to uncover the potential molecular mechanisms underlying BTG3-mediated CRC development and progression. RESULTS: BTG3 was downregulated in colorectal cancer tissues and positively correlated with pathological classification (p = 0.037), depth of invasion (p = 0.016), distant metastasis (p = 0.024), TNM stage (p = 0.007), and overall survival (OS) and disease-free survival (DFS). BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G2 arrest, and inhibited apoptosis in HCT116 and LoVo cells. A genomic microarray analysis showed that numerous tumor-associated signaling pathways and oncogenes were altered by BTG3 knockdown. At the mRNA level, nine genes referred to the extracellular-regulated kinase/mitogen-activated protein kinase pathway were differentially expressed. Western blotting revealed that BTG3 knockdown upregulated PAK2, RPS6KA5, YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data. CONCLUSIONS: BTG3 expression might contribute to CRC carcinogenesis. BTG3 knockdown might strengthen the aggressive colorectal cancer behavior.

Neoplasias Colorretais/metabolismo , Proteínas/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Células HCT116 , Células HT29 , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Inclusão em Parafina , Proteínas/genética , Transdução de Sinais , Células Tumorais Cultivadas
Int J Mol Med ; 41(2): 649-658, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207043


Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.

Aquaporina 3/genética , Constipação Intestinal/tratamento farmacológico , Flavanonas/administração & dosagem , Proteínas Proto-Oncogênicas c-kit/genética , Fator de Células-Tronco/genética , Animais , Constipação Intestinal/sangue , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/genética , Endotelinas/sangue , Gastrinas/sangue , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células Intersticiais de Cajal/efeitos dos fármacos , Laxantes/administração & dosagem , Loperamida/toxicidade , Camundongos , Motilina/sangue
Onco Targets Ther ; 9: 1011-21, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27013894


Livin is a novel member of the inhibitors of apoptosis protein family and has been implicated in the development and progression of colorectal cancer (CRC). However, the underlying mechanisms of Livin in CRC remain not fully understood. In this study, we investigated the effects of Livin expression on the proliferation and metastasis of CRC cells and also addressed its related molecular mechanism to metastasis. The expression of Livin in CRC cells (HCT116, SW480, and HT-29 cell lines) was determined by Western blot analysis. Our results show that the overexpression of Livin significantly promotes the proliferation, migration, and invasion of SW480 cells. Concurrently, the inhibition of Livin reduces the proliferation, migration, and invasion of HCT116 cells. In addition, Livin overexpression promotes the epithelial-mesenchymal transition, as evidenced by a decrease in epithelial E-cadherin expression and an increase in mesenchymal markers, including vimentin, Slug, and Snail. Furthermore, adding the NF-κB inhibitor, BAY 11-7028, or transfecting with small interfering RNA against p65 notably restores the expression level of E-cadherin and attenuates the invasive ability of Livin-overexpressing cells. Taken together, these results indicate that Livin potentiates migration and invasion of CRC cells partially through the induction of epithelial-mesenchymal transition via NF-κB activation. Livin may be a potential therapeutic target for CRC.

Int J Nanomedicine ; 10: 3203-15, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25995630


In bone tissue engineering, collagen/hydroxyapatite (HAP) fibrous composite obtained via electrospinning method has been demonstrated to support the cells' adhesion and bone regeneration. However, electrospinning of natural collagen often requires the use of cytotoxic organic solvents, and the HAP crystals were usually aggregated and randomly distributed within a fibrous matrix of collagen, limiting their clinical potential. Here, an effective and greener method for the preparation of collagen/HAP composite fibers was developed for the first time, and this green product not only had 40 times higher mechanical properties than that previously reported, but also had an excellent microstructure similar to that of natural bone. By dissolving type I collagen in environmentally friendly phosphate buffered saline/ethanol solution instead of the frequently-used cytotoxic organic solvents, followed with the key step of desalination, co-electrospinning the collagen solution with the HAP sol, generates a collagen/HAP composite with a uniform and continuous fibrous morphology. Interestingly, the nano-HAP needles were found to preferentially orient along the longitudinal direction of the collagen fibers, which mimicked the nanostructure of natural bones. Based on the characterization of the related products, the formation mechanism for this novel phenomenon was proposed. After cross-linking with 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride/N-hydroxysuccinimide, the obtained composite exhibited a significant enhancement in mechanical properties. In addition, the biocompatibility of the obtained composite fibers was evaluated by in vitro culture of the human myeloma cells (U2-OS). Taken together, the process outlined herein provides an effective, non-toxic approach for the fabrication of collagen/HAP composite nanofibers that could be good candidates for bone tissue engineering.

Osso e Ossos/citologia , Colágeno , Durapatita , Nanofibras , Engenharia Tecidual , Linhagem Celular Tumoral , Colágeno/química , Colágeno/toxicidade , Durapatita/química , Durapatita/toxicidade , Química Verde , Humanos , Nanofibras/química , Nanofibras/toxicidade