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1.
Adv Healthc Mater ; : e2400930, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847291

RESUMO

Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here we offer a comprehensive overview of EHD direct-writing, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed. This article is protected by copyright. All rights reserved.

2.
Exp Biol Med (Maywood) ; 248(23): 2393-2407, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38159074

RESUMO

Palmitoylation, which is mediated by protein acyltransferase (PAT) and performs important biological functions, is the only reversible lipid modification in organism. To study the effect of protein palmitoylation on hypopharyngeal squamous cell carcinoma (HPSCC), the expression levels of 23 PATs in tumor tissues of 8 HPSCC patients were determined, and high mRNA and protein levels of DHHC9 and DHHC15 were found. Subsequently, we investigated the effect of 2-bromopalmitate (2BP), a small-molecular inhibitor of protein palmitoylation, on the behavior of Fadu cells in vitro (50 µM) and in nude mouse xenograft models (50 µmol/kg), and found that 2BP suppressed the proliferation, invasion, and migration of Fadu cells without increasing cell apoptosis. Mechanistically, the effect of 2BP on the transduction of BMP, Wnt, Shh, and FGF signaling pathways was tested with qRT-PCR, and its drug target was explored with western blotting and acyl-biotinyl exchange assay. Our results showed that 2BP inhibited the transduction of the FGF/ERK signaling pathway. The palmitoylation level of Ras protein decreased after 2BP treatment, and its distribution in the cell membrane structure was reduced significantly. The findings of this work reveal that protein palmitoylation mediated by DHHC9 and DHHC15 may play important roles in the occurrence and development of HPSCC. 2BP is able to inhibit the malignant biological behaviors of HPSCC cells, possibly via hindering the palmitoylation and membrane location of Ras protein, which might, in turn, offer a low-toxicity anti-cancer drug for targeting the treatment of HPSCC.


Assuntos
Neoplasias de Cabeça e Pescoço , Proteínas ras , Camundongos , Animais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Palmitatos/farmacologia
3.
Mycopathologia ; 188(6): 995-1005, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37723360

RESUMO

The present study was designed to identify the microbial community as well as to analyze its diversity by means of metagenomic Next Generation Sequencing (mNGS) in 17 patients with otomycosis treated with terbinafine in the Department of Otolaryngology of Shandong Provincial Hospital from June 2021 to June 2022, so as to evaluate the relationship between microbial community and terbinafine resistance. Those 17 patients were divided into two groups, i.e., Terbinafine Effective Group (TEG, n = 14 cases) and Terbinafine Resistance Group (TRG, n = 3 cases) according to the therapy effect, whose microbial community of secretion of external auditory canal was identified using mNGS. We found that the sequence of bacteria was significantly more than that of fungi and, whereas, the difference between the two groups of bacteria was not significant. There were significant differences in fungal community between the two groups. Aspergillus was the main pathogenic fungus of TEG patients while Malassezia was a dominant fungus in TRG patients. In conclusion, the results from this work indicate that Aspergillus terreusis is the main pathogenic fungus in this cohort of otomycosis patients and MNGS sequencing can offer comprehensive information about the microbial community of otomycosis. The fungus community dominated by Malassezia is more likely to be resistant to terbinafine, which provides certain guidance for clinical treatment of otomycosis with terbinafine.


Assuntos
Microbiota , Otomicose , Humanos , Terbinafina/uso terapêutico , Otomicose/tratamento farmacológico , Otomicose/microbiologia , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Aspergillus/genética , Fungos/genética
4.
Funct Integr Genomics ; 23(3): 280, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612343

RESUMO

In this study, we aimed to explore the molecular role of Deltex E3 ubiquitin ligase 4 (DTX4) in thyroid cancer (TC) both in vitro and in vivo. The expression level of DTX4 in TC tissues was compared using The Cancer Genome Atlas (TCGA) database. We subsequently evaluated cell proliferation and migration in DTX4 knock down or DTX4 overexpression TC cell lines (TPC-1 and K1) by CCK-8, cell colony formation, and transwell assays. RNA sequencing and KEGG analysis were employed to identify potential genes that interact with DTX4. Our results showed that DTX4 was expressed at higher levels in both TC tissues and cells compared to normal controls. Knock down of DTX4 expression significantly inhibited TC cell progression in vitro. Furthermore, knockdown of endogenous DTX4 by shDTX4 markedly abrogated tumor growth, with significantly smaller tumor size and lower tumor weight in the shDTX4 group compared to the shCtrl group. Conversely, overexpression of DTX4 enhanced TC cell proliferation and migration. Through RNA sequencing, we identified 590 Differentially Expressed Genes (DEGs), with stearoyl-CoA desaturase 1 (SCD) ranking as the top gene. A positive correlation between DTX4 and SCD was observed in TC samples. Additionally, treatment with an SCD inhibitor, A939572, significantly rescued the enhanced growth effect induced by DTX4 overexpression. In conclusion, this study demonstrated that DTX4 promotes TC progression through SCD, indicating that the DTX4/SCD axis could be a promising target for TC therapy.


Assuntos
Estearoil-CoA Dessaturase , Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular , Proliferação de Células , Estearoil-CoA Dessaturase/genética , Neoplasias da Glândula Tireoide/genética , Ubiquitina-Proteína Ligases/genética
5.
Adv Healthc Mater ; 12(29): e2301809, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37571957

RESUMO

3D printing has been widely applied for preparing artificial blood vessels, which will bring innovation to cardiovascular disorder intervention. However, the printing resolution and anti-infection properties of small-diameter vessels (Φ < 6 mm) have been challenging in 3D printing. The primary objective of this research is to design a novel coaxial 3D-printing postprocessing method for preparing small-size blood vessels with improved antibacterial and angiogenesis properties. The coaxial printing resolution can be more conveniently improved. Negatively charged polyvinyl alcohol (PVA) and alginate (Alg) interpenetrating networks artificial vessels are immersed in positively charged chitosan (CTS) solution. Rapid dimensional shrinkage takes place on its outer surface through electrostatic interactions. The maximum shrinkage size of wall thickness can reach 61.2%. The vessels demonstrate strong antibacterial properties against Escherichia coli (98.8 ± 0.5%) and Staphylococcus aureus (97.6 ± 1.4%). In rat dorsal skin grafting experiments, Cu2+ can promote angiogenesis by regulating hypoxia-inducible factor-1 pathway. No artificial blood vessel blockage occurs after 5 days of blood circulation in vitro.


Assuntos
Antibacterianos , Quitosana , Ratos , Animais , Antibacterianos/farmacologia , Quitosana/farmacologia , Pele , Escherichia coli , Staphylococcus aureus , Impressão Tridimensional
6.
Hortic Res ; 10(8): uhad136, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37564270

RESUMO

Ginkgo biloba is an economically valuable tree worldwide. The species has nearly become extinct during the Quaternary, which has likely resulted in reduction of its genetic variability. The genetic variability is now conserved in few natural populations in China and a number of cultivars that are, however, derived from a few ancient trees, helping the species survive in China through medieval times. Despite the recent interest in ginkgo, however, detailed knowledge of its genetic diversity, conserved in cultivated trees and cultivars, has remained poor. This limits efficient conservation of its diversity as well as efficient use of the existing germplasm resources. Here we performed genotyping-by-sequencing (GBS) on 102 cultivated germplasms of ginkgo collected to explore their genetic structure, kinship, and inbreeding prediction. For the first time in ginkgo, a genome-wide association analysis study (GWAS) was used to attempt gene mapping of seed traits. The results showed that most of the germplasms did not show any obvious genetic relationship. The size of the ginkgo germplasm population expanded significantly around 1500 years ago during the Sui and Tang dynasties. Classification of seed cultivars based on a phylogenetic perspective does not support the current classification criteria based on phenotype. Twenty-four candidate genes were localized after performing GWAS on the seed traits. Overall, this study reveals the genetic basis of ginkgo seed traits and provides insights into its cultivation history. These findings will facilitate the conservation and utilization of the domesticated germplasms of this living fossil plant.

7.
Eur Arch Otorhinolaryngol ; 280(12): 5565-5574, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37540271

RESUMO

BACKGROUND: The prevalence of cervical central lymph-node metastasis (CLNM) is high in patients with papillary thyroid carcinoma (PTC). There is considerable controversy surrounding the benefits of prophylactic central lymph-node dissection (pCLND) in patients with clinically negative central compartment lymph nodes (cN0). Therefore, it is crucial to accurately predict the likelihood of cervical CLNM before surgery to make informed surgical decisions. METHODS: Date from 214 PTC patients (cN0) who underwent partial or total thyroidectomy and pCLND at the Guizhou Provincial People's Hospital were collected and retrospectively analyzed. They were divided into two groups in accordance with cervical CLNM or not. Their information, including clinical characteristics, ultrasound (US) features, pathological results of fine-needle aspirations biopsy (FNAB), and other characteristics of the groups, was analyzed and compared using univariate and multivariate logistic regression analyses. RESULTS: A total of 214 patients were eligible in this study. Among them, 43.5% (93/214) of PTC patients had cervical CLNM, and 56.5% (121/214) did not. The two groups were compared using a univariate analyses, and there were no significant differences between the two groups in aspect ratio, boundary, morphology, component, and BRAFV600E (P > 0.05), and there were significant differences between gender, age, maximum tumor size, tumor location, capsule contact, microcalcifications, color Doppler flow imaging (CDFI), and Hashimoto's thyroiditis (HT) (P < 0.05). A multivariate logistic regression analysis was performed to further clarify the correlation of these indices. However, only age (OR = 2.455, P = 0.009), maximum tumor size (OR = 2.586, P = 0.010), capsule contact (OR = 3.208, P = 0.001), and CDFI (OR = 2.225, P = 0.022) were independent predictors of cervical CLNM. Combining these four factors, the area under the receiver-operating characteristic (ROC) curve for the joint diagnosis is 0.8160 (95% 0.7596-0.8725). Univariate analysis indicated that capsule contact (P = 0.001) was a possible predictive factor of BRAFV600E mutation. CONCLUSIONS: In conclusion, four independent predictors of cervical CLNM, including age < 45 years, tumor size > 1.0 cm, capsule contact, and rich blood flow, were screened out. Therefore, a comprehensive assessment of these risk factors should be conducted when designing individualized treatment regimens for PTC patients.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Biópsia por Agulha Fina , Estudos Retrospectivos , Carcinoma Papilar/patologia , Linfonodos/patologia , Fatores de Risco , Mutação
8.
Genes (Basel) ; 14(2)2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36833387

RESUMO

The camellia flower is a famous woody plant with a long-cultivated history and high ornamental value. It is extensively planted and utilized around the world and owns a massive germplasm resource. Camellia 'Xiari Qixin' belongs to one of the typical cultivars in the four seasons camellia hybrids series. Due to its long flowering period, this kind of cultivar is identified as a precious resource of camellia flowers. In this study, the complete chloroplast genome sequence of C. 'Xiari Qixin' was first reported. Its whole chloroplast genome is 157,039 bp in length with an overall GC content of 37.30%, composed of a large single copy region (LSC, 86,674 bp), a small single copy region (SSC, 18,281 bp), and a pair of inverted repeat regions (IRs, 26,042 bp each). A total of 134 genes were predicted in this genome, including 8 ribosomal RNA genes, 37 transfer RNA genes, and 89 protein-coding genes. In addition, 50 simple sequence repeats (SSRs) and 36 long repeat sequences were detected. By comparing C. 'Xiari Qixin' and seven Camellia species on the chloroplast genome, seven mutation hotspot regions were identified, including psbK, trnS (GCU)-trnG(GCC), trnG(GCC), petN-psbM, trnF(GAA)-ndhJ, trnP(UGG)-psaJ, and ycf1. Phylogenetic analysis of 30 chloroplast genomes showed that the genetic relationship between C. 'Xiari Qixin' and Camellia azalea is quite close in evolution. These results could not only provide a valuable database for determining the maternal origin of Camellia cultivars, but also contribute to the exploration of the phylogenetic relationship and utilization of germplasm resources for Camellia.


Assuntos
Genoma de Cloroplastos , Filogenia , Sequências Repetitivas de Ácido Nucleico
9.
J Oncol ; 2022: 2151396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35957802

RESUMO

Background: Lung adenocarcinoma (LUAD) is the commonest of the subtypes of lung cancer histologically. For this study, we intended to analyze the expression profiling of the immune-related genes (IRGs) from an independently available public database and developed a potent signature predictive of patients' prognosis. Methods: Gene expression profiles and the clinical data of lung adenocarcinoma were gathered from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), and the obtained data were split into a training set (n = 226), test set (n = 83), and validation set (n = 400). IRGs were then gathered from the ImmPort database. A prognostic model was constructed by analyzing the training set. Then the GO and KEGG analysis was performed, and a gene correlation prognostic nomogram was constructed. Finally, external validation, such as immune infiltration and immunohistochemistry, was performed. Results: The 110 genes were significant by univariate Cox regression analysis and randomized survival forest algorithm for the training set and showed a good distinction between the low-risk-score and high-risk-score groups in the training set (P < 0.0001) by screening for four prognosis-related genes (HMOX1, ARRB1, ADM, PDIA3) and validated by the test set GSE30219 (P=0.0025) and TCGA dataset (P=0.00059). Multivariate Cox showed that the four gene signatures were an individual risk factor for LUAD. In addition, the genes in the signatures were externally verified using an online database. In particular, PDIA3 and HMOX1 are essential genes in the prognostic nomogram and play an important role in the model of immune-related genes. Conclusion: Four immune-related genetic signatures are reliable prognostic indicators for patients with LUAD, providing a relevant theoretical basis and therapeutic rationale for immunotherapy.

10.
BMJ Open ; 12(6): e058852, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732392

RESUMO

OBJECTIVES: This study aimed to investigate the status of the current knowledge about laryngopharyngeal reflux disease (LPRD) among Chinese otolaryngologists. DESIGN: Multi-centre cross-sectional survey. SETTING: 220 medical centres in different regions of China. PARTICIPANTS: A total of 2254 otolaryngologists from 220 medical centres in China who were successfully on-site surveyed between November 2019 and December 2020. MAIN OUTCOME MEASURES: Awareness about LPRD included knowledge about risk factors, symptoms, laryngoscope signs, related diseases, current diagnostic methods and treatments. RESULTS: The percentage of participants who had heard of LPRD was 96.4%, with academic conferences as the most common source of information (73.3%). The most commonly known risk factor, symptom, laryngoscope sign, related disease, diagnostic method and treatment were alcohol consumption (44.0%), pharyngeal foreign body sensation (66.9%), hyperaemia (52.4%), pharyngolaryngitis (54.8%), pH monitoring (47.6%) and medication (82.1%), respectively. Only 28.3% of all participants knew that 24 h pH or multichannel intraluminal impedance pH monitoring was the most accurate diagnostic test. As many as 73.1% of all participants knew that proton pump inhibitors were the first-line treatment drugs. An analysis of the overall status of awareness using a scoring system suggested that otolaryngologists were better aware owing to more access, working at 3A hospitals, and postgraduate or above educational background (all p<0.05). CONCLUSION: Although the majority of Chinese otolaryngologists had heard of LPRD, their overall awareness about the disease was not encouraging. More efforts are needed to increase the knowledge about LPRD among this group of physicians. TRIAL REGISTRATION NUMBER: ChiCTR1900025581.


Assuntos
Refluxo Laringofaríngeo , Estudos Transversais , Humanos , Refluxo Laringofaríngeo/diagnóstico , Otorrinolaringologistas , Inibidores da Bomba de Prótons/uso terapêutico , Inquéritos e Questionários
11.
Front Genet ; 12: 710113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34917124

RESUMO

The U-box gene encodes a ubiquitin ligase that contains a U-box domain. The plant U-box (PUB) protein plays an important role in the plant stress response; however, very few studies have investigated the role of these proteins in Moso bamboo (Phyllostachys edulis). Thus, more research on PUB proteins is necessary to understand the mechanisms of stress tolerance in P. edulis. In this study, we identified 121 members of the PUB family in P. edulis (PePUB), using bioinformatics based on the P. edulis V2 genome build. The U-box genes of P. edulis showed an uneven distribution among the chromosomes. Phylogenetic analysis of the U-box genes between P. edulis and Arabidopsis thaliana suggested that these genes can be classified into eight subgroups (Groups I-VIII) based on their structural and phylogenetic features. All U-box genes and the structure of their encoded proteins were identified in P. edulis. We further investigated the expression pattern of PePUB genes in different tissues, including the leaves, panicles, rhizomes, roots, and shoots. The qRT-PCR results showed that expression of three genes, PePUB15, PePUB92, and PePUB120, was upregulated at low temperatures compared to that at 25°C. The expression levels of two PePUBs, PePUB60 and PePUB120, were upregulated under drought stress. These results suggest that the PePUB genes play an important role in resistance to low temperatures and drought in P. edulis. This research provides new insight into the function, diversity, and characterization of PUB genes in P. edulis and provides a basis for understanding their biological roles and molecular mechanisms.

12.
Front Oncol ; 11: 771749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760708

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal cancers in the world. The 5-year survival rate of ESCC is <30%. However, few biomarkers can accurately predict the prognosis of patients with ESCC. We aimed to identify potential survival-associated biomarkers for ESCC to improve its poor prognosis. METHODS: ImmuneAI analysis was first used to access the immune cell abundance of ESCC. Then, ESTIMATE analysis was performed to explore the tumor microenvironment (TME), and differential analysis was used for the selection of immune-related differentially expressed genes (DEGs). Weighted gene coexpression network analysis (WGCNA) was used for selecting the candidate DEGs. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to build the immune-cell-associated prognostic model (ICPM). Kaplan-Meier curve of survival analysis was performed to evaluate the efficacy of the ICPM. RESULTS: Based on the ESTIMATE and ImmuneAI analysis, we obtained 24 immune cells' abundance. Next, we identified six coexpression module that was associated with the abundance. Then, LASSO regression models were constructed by selecting the genes in the module that is most relevant to immune cells. Two test dataset was used to testify the model, and we finally, obtained a seven-genes survival model that performed an excellent prognostic efficacy. CONCLUSION: In the current study, we filtered seven key genes that may be potential prognostic biomarkers of ESCC, and they may be used as new factors to improve the prognosis of cancer.

13.
Front Genet ; 12: 664393, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149805

RESUMO

Breast cancer (BRCA) is the second leading cause of cancer-related mortality in women worldwide. However, the molecular mechanism involved in the development of BRCA is not fully understood. In this study, based on the miRNA-mediated long non-coding RNA (lncRNA)-protein coding gene (PCG) relationship and lncRNA-PCG co-expression information, we constructed and analyzed a specific dysregulated lncRNA-PCG co-expression network in BRCA. Then, we performed the random walk with restart (RWR) method to prioritize BRCA-related lncRNAs through comparing their RWR score and significance. As a result, we identified 30 risk lncRNAs for BRCA, which can distinguish normal and tumor samples. Moreover, through gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that these risk lncRNAs mainly synergistically exerted functions related to cell cycle and DNA separation and replication. At last, we developed a four-lncRNA prognostic signature (including AP000851.1, LINC01977, MAFG-DT, SIAH2-AS1) and assessed the survival accuracy of the signature by performing time-dependent receiver operating characteristic (ROC) analysis. The areas under the ROC curve for 1, 3, 5, and 10 years of survival prediction were 0.68, 0.61, 0.62, and 0.63, respectively. The multivariable Cox regression results verified that the four-lncRNA signature could be used as an independent prognostic biomarker in BRCA. In summary, these results have important reference value for the study of diagnosis, treatment, and prognosis evaluation of BRCA.

14.
Biomed Tech (Berl) ; 66(4): 335-343, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-33544475

RESUMO

Sleep staging is an important basis for diagnosing sleep-related problems. In this paper, an attention based convolutional network for automatic sleep staging is proposed. The network takes time-frequency image as input and predict sleep stage for each 30-s epoch as output. For each CNN feature maps, our model generate attention maps along two separate dimensions, time and filter, and then multiplied to form the final attention map. Residual-like fusion structure is used to append the attention map to the input feature map for adaptive feature refinement. In addition, to get the global feature representation with less information loss, the generalized mean pooling is introduced. To prove the efficacy of the proposed method, we have compared with two baseline method on sleep-EDF data set with different setting of the framework and input channel type, the experimental results show that the paper model has achieved significant improvements in terms of overall accuracy, Cohen's kappa, MF1, sensitivity and specificity. The performance of the proposed network is compared with that of the state-of-the-art algorithms with an overall accuracy of 83.4%, a macro F1-score of 77.3%, κ = 0.77, sensitivity = 77.1% and specificity = 95.4%, respectively. The experimental results demonstrate the superiority of the proposed network.


Assuntos
Fases do Sono , Algoritmos , Eletroencefalografia , Humanos , Projetos de Pesquisa , Sensibilidade e Especificidade
15.
EBioMedicine ; 50: 135-143, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31780396

RESUMO

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a disastrous disease with substantial morbidity and mortality. This study aims to explore the effective diagnostic and prognostic biomarkers for HNSCC. METHODS: MiRNA expression data and corresponding clinical information of HNSCC from The Cancer Genome Atlas (TCGA) database were analyzed comprehensively to identify the miRNAs with diagnostic and prognostic power. The predictive ability of different classifications was analyzed for the three-miRNA combinations. Diagnostic and prognostic value were then evaluated and verified in clinical patients. FINDINGS: 128 differentially expressed miRNAs in HNSCC tissues were identified in the TCGA dataset, and 10 miRNAs were finally selected for further study. Classification analysis developed a three-miRNA signature of hsa-mir-383, hsa-mir-615, and hsa-mir-877 with the best diagnosis power, which was verified in validation patients. Survival analysis indicated that different expression levels of hsa-mir-383, rather than that of hsa-mir-615 or hsa-mir-877 led to significantly different survival rates in both cohorts. Furthermore, the multivariate Cox hazards analysis suggested that the microRNA signature yielded statistical significance to predict clinical outcome independently from other clinical variables in validation patients. INTERPRETATION: A three-miRNA signature of hsa-mir-383, hsa-mir-615, and hsa-mir-877 may serve as an excellent diagnostic biomarker for HNSCC, and potential prognostic significance for HNSCC patients. FUNDING: This work was supported by the grants of the National Natural Science Foundation of China (81901021), Key Research and Development Program of Shandong (2019GSF108277), China postdoctoral Scinence Foundation Grant (2019M652380), Fundamental Research Funds of Shandong University (2018CJ047).


Assuntos
Biomarcadores Tumorais , MicroRNAs/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Área Sob a Curva , Biologia Computacional/métodos , Bases de Dados de Ácidos Nucleicos , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Máquina de Vetores de Suporte
16.
Cancer Cell Int ; 19: 289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749661

RESUMO

BACKGROUND: SNAI2, a member of the snail zinc finger protein family, plays an important role in the metastasis of several types of carcinoma. OBJECTIVE: This study aims to investigate the upstream miRNAs of SNAI2 and their influence on the metastasis of gastrointestinal stromal tumors (GISTs). METHODS: The expression levels of SNAI2, CDH1, and CDH2 in GISTs were determined by immunohistochemistry, and the correlations with their clinicopathologic characteristics were analyzed. Subsequently, the miRNAs involved in regulating SNAI2 expression were predicted by bioinformatics technique, screened by miRNA microarray tests, and verified by real-time PCR, dual luciferase reporter assay, and invasion assay. The influence of SNAI2 and miRNAs on the invasive ability of the GIST cells and the related mechanism were detected. OUTCOMES: SNAI2 expression significantly increased and CDH1 expression markedly decreased in the cases of GISTs with distant metastasis. Silencing of the SNAI2 gene impaired the invasiveness of GIST cells in vitro. MiR-200b-3p, miR-30c-1-3P, and miR-363-3P were verified as the upstream metastasis-associated miRNAs of SNAI2 in GISTs by miRNA microarray, real-time PCR, dual luciferase reporter assay, and invasion assay. They bound to the 3'-UTR of SNAI2, downregulated SNAI2 expression, and inhibited the invasiveness of GIST cells. SNAI2 targetedly bound to the promoter of the CDH1 gene, downregulated the expression of CDH1, and contributed to the metastasis of GISTs. CONCLUSION: SNAI2 and CDH1 correlated with the metastasis of GISTs, and silencing of the SNAI2 gene impaired the invasiveness of GIST cells. MiR-200b-3p, miR-30c-1-3P, and miR-363-3P contribute to the metastasis of GISTs in vitro by mediating the SNAI2/CDH1 axis. SNAI2 may be a potential target for the treatment of GISTs in the future.

17.
Acta Otolaryngol ; 139(10): 895-901, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373241

RESUMO

Background: Obstructive sleep apnea syndrome (OSAS) is a public health problem that affects a large amount of people. Surgery sometimes is considered a better treatment modality that does not require the use of a device such as CPAP. Objectives: To explore the value of anesthetic-induced sleep computed tomography (DI-SCT) in the diagnosis of OSAS. Materials and methods: A total of 124 patients with OSAS aged between 18 and 65 years old were enrolled in this study. The upper airway was scanned by computed tomography (CT) while they were wake and went sleep. Sleep was induced by dexmedetomidine under electrocardiograph and oxyhemoglobin saturation monitoring. Parameters relevant to OSAS were then collected and counted. Results: CT scanning revealed that 119 occurred stenosis in oropharynx, in which 5 cases were accompanied with stenosis or occlusion at retroglossal area. About 38 (30.67%) cases existed deviation of nasal septum with retropalatal problems. About 61.33% of patients had multi-level obstructions and the most common obstructive site was oropharynx (90.67%). Conclusions and significance: DI-SCT is a safe and non-invasive modality for diagnosing the obstructive sites in OSAS patients.


Assuntos
Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Sono , Tomografia Computadorizada por Raios X , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Apneia Obstrutiva do Sono/etiologia
18.
Saudi J Biol Sci ; 25(7): 1468-1472, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30505196

RESUMO

The aim of the present study was to investigate the effect of resveratrol on acute pharyngitis in the mice models induced by xylene and carrageenan treatment. The mice treated with various doses of resveratrol (5, 10, 15, 20 and 30 mg/kg) showed inhibition of edema in a dose dependent manner. The edema formation was reduced by 67% in the mice treated with 20 mg/kg of resveratrol compared to those in the control group. A significant (P < 0.02) reduction of paw swelling was observed in the mice treated with 20 mg/kg dose of resveratrol compared to the control group. The inhibition of paw swelling in mice was also caused by votalin by the extent of reduction was significantly (P < 0.02) lower compared to the resveratrol treatment. In the mice model of paw swelling, treatment with 20 mg/kg doses of resveratrol significantly (P < 0.02) reduced the expression of PGE2 compared to the control group. On the other hand, resveratrol played a vital role in the inhibition of carrageenan induced increase in the expression of COX-2 in mice. The inhibition in the COX-2 expression by 20 mg/kg doses of resveratrol was significantly higher compared to the known drug, votalin. Thus the current study revealed that resveratrol treatment inhibits acute pharyngitis in the mice model through inhibition of PGE2/COX-2 expression. Thus resveratrol can be used for the treatment of acute pharyngitis.

19.
Oncol Lett ; 15(3): 3127-3132, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29435046

RESUMO

The role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of tumors has been receiving increasing attention. Colon cancer-associated transcript 2 (CCAT2), a type of oncogenic lncRNA, is regarded as a novel biomarker of poor prognosis and metastasis in various types of cancer. However, the molecular contributions of CCAT2 to gastric cancer (GC) progression remain largely unclear. The aim of the present study was to demonstrate the effect of silencing CCAT2 on the biological behavior of GC BGC-823 cells and illustrate the potential underlying molecular mechanisms. A short hairpin RNA interference plasmid pRNAT-U6.1-CCAT2 targeting CCAT2 was successfully constructed. At 48 h after transfection with the interference plasmid, the survival rate of BGC-823 cells was significantly decreased, as determined by the MTT assay. In addition, RT-qPCR results revealed that CCAT2 gene expression was effectively suppressed by the transfection, while POU domain class 5 transcription factor 1B (POU5F1B) gene expression was significantly decreased. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay further revealed that the apoptotic index was significantly higher in the interference group. Western blot analysis also demonstrated that the expression of beclin-1 protein was significantly increased, whereas the expression levels of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) proteins were downregulated in the interference group. In conclusion, CCAT2 was able to positively regulate the expression of POU5F1B gene. Furthermore, silencing of CCAT2 gene inhibited the proliferation of BGC-823 cells, as well as induced apoptosis and autophagy in BGC-823 cells, by suppression of the PI3K/mTOR signaling pathways.

20.
Toxicol Appl Pharmacol ; 343: 16-28, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29454061

RESUMO

To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member ×1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus. We found that NLRX1 expression was increased concurrent with the increase of autophagy activation in HEI-OC1 cells under the cisplatin insult. NLRX1 overexpression led to the amount of accumulation of autophagsomes in HEI-OC1 cells in normal condition and a higher activation of autophagy concurrent with cell injury in HEI-OC1 cells treated with cisplatin, whereas, NLRX1 silencing decreased the activation level of autophagy concurrent with increased cell viability in HEI-OC1 cells treated with cisplatin. Mechanistic studies showed that NLRX1 potentiated mitochondrial-derived ROS generation in response to cisplatin exposure. Inhibition of ROS generation significantly prevented autophagy activation and apoptosis both in HEI-OC1cells and cochlear explants treated with cisplatin. The findings from this work reveal that NLRX1 sensitizes auditory cells in vitro to cisplatin-induced ototoxity via autophagic cell death pathway, providing another strategy against cisplatin-induced ototoxity.


Assuntos
Antineoplásicos/toxicidade , Autofagia/fisiologia , Cisplatino/toxicidade , Células Ciliadas Auditivas/metabolismo , Proteínas Mitocondriais/metabolismo , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Órgão Espiral/efeitos dos fármacos , Órgão Espiral/metabolismo , Órgão Espiral/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo
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