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1.
Cell Biochem Biophys ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39093515

RESUMO

Thyroid cancer, as one of the most common cancers in many countries, has attracted increasing attention, but its pathogenesis is still unclear. This research explored the effects of miR-144-3p and GABRB2 on thyroid cancer cells and the underlying mechanism. Gene expression data was obtained from the GEO database to analyze differential expression of mRNAs and miRNAs in patients with thyroid cancer. CCK-8, transwell, scratch, and flow cytometry assays were performed to detect cell proliferation, invasion, migration, and apoptosis, respectively. Dual-luciferase reporters were used to detect the binding of miR-144-3p to GABRB2. GABRB2 was highly expressed and miR-144-3p was underexpressed in thyroid cancer. In thyroid cancer cells, inhibiting GABRB2 or upregulating miR-144-3p reduced proliferation, invasion, and migration and increased apoptotic rates; GABRB2 overexpression or miR-144-3p inhibition brought about the opposite results. miR-144-3p targeted GABRB2 and negatively regulated its expression. PI3K/AKT activation was reduced in thyroid cancer cells overexpressing miR-144-3p. GABRB2 overexpression partially mitigated the tumor-suppressive effect of miR-144-3p overexpression. In conclusion, miR-144-3p targets GABRB2 to inhibit PI3K/AKT activation, thereby inhibiting the progression of thyroid cancer in vitro.

2.
J Anesth ; 36(2): 303-315, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34757497

RESUMO

Low tidal volume ventilation strategy may lead to atelectasis without proper positive end-expiratory pressure (PEEP) and recruitment maneuver (RM) settings. RM followed by individualized PEEP was a new method to optimize the intraoperative pulmonary function. We conducted a systematic review and network meta-analysis of randomized clinical trials to compare the effects of individualized PEEP + RM on intraoperative pulmonary function and hemodynamic with other PEEP and RM settings. The primary outcomes were intraoperative oxygenation index and dynamic compliance, while the secondary outcomes were intraoperative heart rate and mean arterial pressure. In total, we identified 15 clinical trials containing 36 randomized groups with 3634 participants. Ventilation strategies were divided into eight groups by four PEEP (L: low, M: moderate, H: high, and I: individualized) and two RM (yes or no) settings. The main results showed that IPEEP + RM group was superior to all other groups regarding to both oxygenation index and dynamic compliance. LPEEP group was inferior to LPEEP + RM, MPEEP, MPEEP + RM, and IPEEP + RM in terms of oxygenation index and LPEEP + RM, MPEEP, MPEEP + RM, HPEEP + RM, IPEEP, and IPEEP + RM in terms of dynamic compliance. All comparisons were similar for secondary outcomes. Our analysis suggested that individualized PEEP and RM may be the optimal low tidal volume ventilation strategy at present, while low PEEP without RM is not suggested.


Assuntos
Respiração com Pressão Positiva , Atelectasia Pulmonar , Humanos , Metanálise em Rede , Respiração com Pressão Positiva/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume de Ventilação Pulmonar/fisiologia
3.
Zhongguo Zhong Yao Za Zhi ; 46(23): 6216-6223, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951248

RESUMO

This study aims to explore the effect of extract of Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Chuanxiong Rhizoma(hereinafter referred to as GNS) on the SIRT1-autophagy pathway of endothelial cell senescence induced by hydrogen peroxide(H_2O_2). To be specific, vascular endothelial cells were classified into the blank control group(control), model group(model), model + DMSO group(DMSO), resveratrol group(RESV), and GNS low-dose(GNS-L), medium-dose(GNS-M), and high-dose(GNS-H) groups. They were treated with H_2O_2 for senescence induction except the control. After intervention of cells in each group with corresponding drugs for 24 h, cell growth status was observed under an inverted microscope, and the formation of autophagosome under the transmission electron microscope. In addition, the changes of microtubule-associated protein 1 light chain 3ß(LC3 B) were detected by immunofluorescence staining. The autophagy flux was tracked with the autophagy double-labeled adenovirus(mRFP-GFP-LC3) fusion protein. Dansylcadaverine(MDC) staining was employed to determine the autophagic vesicles, and Western blot the expression of sirtuin 1(SIRT1), ubiquitin-binding protein p62, and LC3Ⅱ. After H_2O_2 induction, cells demonstrated slow growth, decreased adhesion ability, raised number of SA-ß-gal-stained blue ones, a certain number of autophagosomes with bilayer membrane and secondary lysosomes in the cytoplasm, and slight rise of autophagy flux level. Compared with the model group, GNS groups showed improved morphology, moderate adhesion ability, complete and smooth membrane, decreased SA-ß-gal-stained blue cells, many autophagosomes, autophagic vesicles, and secondary lysosomes in the cytoplasm, increased autophagolysosomes, autophagy flux level, and fluorescence intensity of LC3 B and MDC, up-regulated expression of SIRT1 and LC3Ⅱ, and down-regulated expression of p62, suggesting the improvement of autophagy level. GNS can delay the senescence of vascular endothelial cells. After the intervention, the autophagy flux and related proteins SIRT1, LC3Ⅱand p62 changed significantly, and the autophagy level increased significantly. However, EX527 weakened the effect of Chinese medicine in delaying vascular senescence. GNS may delay the senescence of vascular endothelial cells through the SIRT1 autophagy pathway.


Assuntos
Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , Panax , Células Cultivadas , Senescência Celular , Peróxido de Hidrogênio , Panax/química , Sirtuína 1/genética
4.
Pathol Oncol Res ; 27: 584466, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257531

RESUMO

Objective: Laryngeal squamous cell carcinoma (LSCC) belongs to head and neck squamous cell carcinoma (HNSCC), with dismal prognosis. Here, this study aims to disclose the role of LINC-PINT in cancer development, which may contribute to improving the clinical outcomes of LSCC treatment. Methods: LINC-PINT expression in LSCC tissues and in TU-177 and Hep-2 cells was quantified, and subsequently, the association between LINC-PINT and LSCC malignancies was analyzed. pcDNA3.1-LINC-PINT or pcDNA3.1-EZH2 was introduced into Hep-2 and TU-177 cells. qRT-PCR and Western blot analyses examined the levels of proteins related to the AKT/mTOR pathway and their phosphorylated proteins in Hep-2 and TU-177 cells. The viability as well as migration and invasion abilities of Hep-2 and TU-177 cells were determined. Also, the distribution of LINC-PINT in Hep-2 cells was investigated as well as the interplay between LINC-PINT and EZH2. The downstream genes that might interact with EZH2 were screened. Results: LINC-PINT expression was inhibited in LSCC tissues and in Hep-2 and TU-177 cells, whose downregulation was associated with unsatisfactory prognosis. LINC-PINT overexpression suppressed the proliferative, migratory and invasive capacities of Hep-2 and TU-177 cells. LINC-PINT, mainly expressing in nuclei, could enrich EZH2 to silence ZEB1. In Hep-2 and TU-177 cells, the inhibition of LINC-PINT or overexpression of ZEB1 could enhance cell proliferation, migration and invasion. The phosphorylated levels of proteins related to the AKT/mTOR pathway were declined in cells with LINC-PINT overexpression, and the levels of these phosphorylated proteins were increased in cells with LINC-PINT inhibition. Conclusion: LINC-PINT enriches EZH2 to silence ZEB1 and thus inhibits the proliferative, migratory, and invasive capacities of Hep-2 and TU-177 cells. In addition, LINC-PINT might exert its biological function through the AKT/mTOR pathway.


Assuntos
Neoplasias Laríngeas/genética , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Serina-Treonina Quinases TOR , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo
5.
Ann Nutr Metab ; 77(2): 90-99, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34289482

RESUMO

PURPOSE: The aim of this study was to retrospectively identify the effect of iodine on the papillary thyroid cancer (PTC) process and investigate the risk clinicopathologic characteristics of cervical lymph node metastasis (CLNM) for achieving a better preventive strategy of PTC. METHODS: Totally 187 patients with CLNM and 279 without CLNM (NCLNM) were enrolled, and their urinary iodine concentration (UIC) and serum iodine concentration (SIC) were measured. Logistic regressions were used to reveal the effects of iodine nutrition on the CLNM status of PTC. RESULTS: The levels of thyroid-stimulating hormone (TSH) and thyroglobulin (TG) were higher in the CLNM group than in the NCLNM group. UIC and SIC were positively correlated, and both of them were correlated with TSH, free thyroxine, and TG. The proportions of UIC >300 µg/L and of SIC >90 µg/L were higher in the CLNM than in the NCLNM. Logistic analysis showed that SIC >90 µg/L was an independent predictor for CLNM in PTC. Additionally, age ≥45, female, TG, multifocality, and diameter of cancer invasion >1 cm also affected CLNM status in PTC, and their logistic regression model showed a certain diagnostic accuracy (area under the receiver-operating characteristic curve = 0.72). CONCLUSIONS: Relatively high iodine nutrition seemed to be a significant risk factor for the occurrence of CLNM in PTC and may promote lymphatic metastasis in PTC.


Assuntos
Iodo/sangue , Iodo/urina , Linfonodos/patologia , Metástase Linfática/patologia , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tireoglobulina/sangue , Tireotropina/sangue
6.
Endocrine ; 74(3): 582-591, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34075541

RESUMO

PURPOSE: To investigate the applicability of metabolomics to select thyroid cancer-associated biomarkers and discover the effects of iodine on metabolic changes in thyroid cancer. METHODS: In this study, a total of 33 papillary thyroid cancer (PTC) patients from areas with iodine excess and 32 PTC patients from areas with adequate iodine were recruited, and their cancerous tissue and paracancerous tissue were collected. These specimens were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/QTOF/MS) in conjunction with multivariate statistical analysis. RESULTS: Good separations were obtained for PTC tissue vs. paracancerous tissue, and 15 metabolites, including L-octanoylcarnitine, N-arachidonoylglycine, and others were found to be disturbed in PTC tissue. Moreover, the metabolic profile presented considerable separation between PTC tissue from different iodine areas, and 15 metabolomic biomarkers were found to be differentially expressed. Among them, 10 metabolites, including arachidonoylcarnitine and LysoPCs, were related to thyroid cancer and excess iodine. These biomarkers play a role in arachidonic acid metabolism pathways and others. In addition, biomarkers such as 3,5-tetradecadiencarnitine and oxidized glutathione were significantly correlated with thyroid function, and biomarkers such as L-octanoylcarnitine and arachidonic acid were significantly correlated with the clinical characteristics of PTC. CONCLUSIONS: Distinct differences in metabolic profiles were found to exist between PTCs from areas with different levels of iodine nutrition. The identified biomarkers have significant potential for diagnosing PTC and investigating its underlying mechanisms.


Assuntos
Carcinoma Papilar , Iodo , Neoplasias da Glândula Tireoide , Biomarcadores Tumorais , Humanos , Nutrientes , Câncer Papilífero da Tireoide
7.
Future Oncol ; 17(9): 1025-1037, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33543648

RESUMO

Aims: To investigate the prognostic relevance of platelet volume indices for survival in laryngeal cancer. Patients & methods: The study included 640 patients with laryngeal cancer. We analyzed the optimal cutoff values through receiver operating characteristic analysis, then analyzed the univariate factor and multivariate variables. Kaplan-Meier curves and log-rank tests were conducted to compare the overall survival (OS) and recurrence-free survival rates between the groups. Results: In multivariate analysis, elevated platelet distribution width (PDW) and PDW/platelet count ratio were significantly correlated with poor prognosis for OS; however, elevated mean platelet volume (MPV) and MPV/platelet count ratio suggested a notable correlation with favorable prognosis for OS. Meanwhile, elevated PDW and decreased MPV were significantly correlated with poor prognosis for recurrence-free survival. Conclusions: Our findings indicate that elevated PDW and decreased MPV could serve as independent biomarkers for worse survival in laryngeal cancer.


Assuntos
Plaquetas/patologia , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/mortalidade , Idoso , Biomarcadores/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Curva ROC , Taxa de Sobrevida
8.
Cancer Control ; 27(1): 1073274820978795, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33297727

RESUMO

The aim is to estimate the prognostic value of lactate dehydrogenase (LDH) in patients undergoing surgical resection for laryngeal squamous cell carcinoma (LSCC). A total of 640 resected LSCC patients were included. Preoperative lactate dehydrogenase (LDH) was assessed. Kaplan-Meier survival analysis and Cox regression analysis were conducted for overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier analysis, univariate analysis and multivariate analysis demonstrated significant prognostic value for preoperative LDH. Although LDH was predictor of OS, it failed to be a predictor of RFS. The univariate HR and 95% CI of LDH were 0.484 and 0.357-0.658 (P < 0.0001). The multivariate analysis showed that LDH (HR = 0.518, 95% CI: 0.380-0.705, p < 0.0001) was related to OS. Elevated preoperative LDH >132 IU/L was significantly associated with better survival. Preoperative LDH might be an independent prognostic marker of OS in LSCC patients undergoing surgical resection.


Assuntos
Biomarcadores Tumorais/sangue , L-Lactato Desidrogenase/sangue , Neoplasias Laríngeas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Idoso , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/sangue , Neoplasias Laríngeas/cirurgia , Laringectomia/estatística & dados numéricos , Laringe/patologia , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia
9.
Medicine (Baltimore) ; 99(38): e21973, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957316

RESUMO

OBJECTIVE: The goal of this study was to review relevant studies in order to determine the efficacy of decompression with fusion versus decompression in the treatment of lumbar spinal stenosis. METHODS: Using appropriate keywords, we identified relevant studies using PubMed, the Cochrane library, and Embase. Key pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we used odds ratios, mean difference (MD), and 95% confidence interval (95% CI) to assess and synthesize outcomes. RESULTS: We found 13 studies that were consistent with this meta-analysis with a total of 29066 patients. Compared with decompression, decompression with fusion significantly increased the incidence of complications (RR: 1.41, 95%CI: 1.26-1.57), the length of hospital stay (WMD: 1.868, 95%CI: 1.394-2.343), operative time (WMD: 80.399, 95%CI: 44.397-116.401), estimated blood loss (WMD: 309.356, 95%CI: 98.008-520.704) and Zurich claudication questionnaire in symptom severity (WMD: 0.200, 95%CI: 0.006-0.394). The reoperation rate was lower in the decompression with fusion group than the decompression group but without significant difference (RR: 0.91, 95%CI: 0.82-1.00). There was no significant difference between 2 groups in visual analog scale (leg pain and back pain), ODI, Short Form 36 Health Survey physical component summary, Short Form 36 Health Survey mental component summary, and Zurich claudication questionnaire physical function. CONCLUSION: Decompression with fusion has no significant clinical advantages in treatment of lumbar spinal stenosis when compared with decompression.


Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Perda Sanguínea Cirúrgica , Avaliação da Deficiência , Humanos , Tempo de Internação , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Reoperação
10.
J Surg Res ; 253: 69-78, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32335393

RESUMO

BACKGROUND: This study aimed to explore the new factors that can predict central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) independently from ultrasound characteristics, elastic parameters, and endocrine indicators. METHODS: A total of 391 patients with PTC undergoing thyroidectomy and prophylactic central lymph node dissection from January 2017 to June 2019 were collected to determine the independent predictors of CLNM by single-factor and multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed 9 independent predictors of CLNM, age, male, tumors in the middle or lower poles (without tumors in the isthmus), tumors in the isthmus, multiple tumors, and maximum tumor diameter measured by ultrasound, microcalcification, visible surrounding blood flow signal, and the maximum value of elastic modulus (Emax).We used the aforementioned factors to establish a scoring prediction model: predictive score Y(P) = 1/[1 + exp (1.444 + 0.084 ∗ age - 0.834 ∗ men - 0.73 ∗ multifocality - 2.718 ∗ tumors in the isthmus - 0.954 ∗ tumors in the middle or lower poles - 0.086 ∗ tumor maximum diameter - 1.070 ∗ microcalcification - 0.892 ∗ visible surrounding blood flow signal - 0.021 ∗ Emax)]. The area under the curve of the receiver operating characteristic was 0.827. It was found that 0.524 was the highest index of Youden, and the best cutoff value for predicting CLNM. When Y(P)≥0.524, the risk of CLNM in patients with PTC is predicted to be high. Predictive accuracy was 78.5% and 72.4% in the internal validation group and 78.6% in the external validation group. CONCLUSIONS: These data indicate that the scoring prediction model could provide a scientific and quantitative way to predict CLNM in patients with PTC.


Assuntos
Metástase Linfática/diagnóstico , Câncer Papilífero da Tireoide/secundário , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia Doppler em Cores/estatística & dados numéricos , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina , Elasticidade , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/estatística & dados numéricos , Adulto Jovem
12.
Int J Ophthalmol ; 12(12): 1839-1847, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850165

RESUMO

AIM: To study the change in ocular refraction in patients with pediatric cataracts (PCs) after lens extraction. METHODS: A total of 1258 patients who were undergoing cataract extraction with/without intraocular lens (IOL) implantation were recruited during preoperative examinations between Jan 2010 and Oct 2013. Patient ages ranged from 1.5mo to 14y. Follow-ups were conducted at 1wk, 1, and 3mo postoperatively and every 3mo in the first year, then 6mo thereafter. Ocular refraction [evaluated as spherical equivalent (SE)] and yearly myopic shift (YMS) were recorded and statistically analyzed among patients with age at surgery, baseline ocular refraction, gender, postoperative time and laterality (bilateral vs unilateral). RESULTS: By Dec 31st 2015, 1172 participants had been followed for more than 2y. The median follow-up period was 3y. The critical factors affecting the ocular refraction of PC patients were baseline ocular refraction, postoperative time for both aphakic and pseudophakic eyes. YMS grew most rapidly in young childhood and early adolescence. CONCLUSION: After lens surgeries, ocular refraction in PC patients shows an individual difference of change. Further concerns should be raising to monitor the rapid myopic shift at early adolescence of these patients.

13.
Math Biosci Eng ; 16(6): 7494-7509, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-31698625

RESUMO

The present paper investigated the relationship between low temperature impact toughness and microstructure of bainite in coarse-grained heat affected zone (CGHAZ) and intercritically rehazed CGHAZ (ICCGHAZ) of an offshore engineering steel from both the microstructure morphological and crystallographic aspects. In this work, six groups of samples simulated CGHAZ and ICCGHAZ were designated at three different cooling rates. The Charpy test results showed that the toughness in CGHAZ decreases dramatically with decrease of cooling rate, which was attributed to the microstructural evolution from lath bainite to granular bainite, accompanying with the size increase of Bain zone and the change of M/A morphology from film to block. The increase in hardenability by cooling rate promotes more crystallographic variants from different Bain groups. Meanwhile, the combination with controlled inter-spacing of block boundaries by self-accommodation below the critical Griffith crack length, micro-crack can be arrested by these high angle grain boundaries thereby suppressed brittle fracture initiation and increased fracture properties. However, the variation in toughness of ICCGHAZ is not a concern, since obtaining excellent toughness is scarcely accessible even if the matrix microstructure is analogous to CGHAZ. It was due to the formation of coarse M/A constituents (~2 µm) necklacing at the prior austenite grain boundary. The visualized crystallography suggested that the impact toughness was partially correlated to the configuration manner and the size of Bain zones as well via promoting highly misoriented angle (>45°) boundaries, which in turn effectively deflected or arrested the brittle crack propagation.

14.
J Cell Physiol ; 234(12): 23111-23122, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31131448

RESUMO

Functional, noncoding RNA of about 200 nucleotides in length are known as long noncoding RNA (lncRNA). Advances in -omics have revolutionized the information with respect to the coding and noncoding regions of the genome. Several studies have illustrated the role of lncRNA in cell growth and cancer. Profiling and bioinformatic studies of laryngeal cancer has identified LINC-PINT as one of the lncRNA. However, the functional aspects of the deregulation have not been studied in laryngeal tumors. In this study, LINC-PINT expression in normal and tumor tissues were studied. Using a bioinformatic approach, microRNA (miRNA) targets of LINC-PINT and gene targets of the miRNA were determined. The impact of LINC-PINT on cell proliferation and chemoresistance was determined. Further through a set of silencing and re-expression studies phenotype rescue was studied. LINC-PINT expression was downregulated in laryngeal tumors. LINC-PINT targeted miR-425-5p by three sites. miR-425-5p also targeted PTCH1 a protein of the Hedgehog pathway. Downregulation of LINC-PINT was associated with increased cancer stemness and chemoresistance to cisplatin. Our results indicate a probable role of LINC-PINT in the pathology of laryngeal tumors. LINC-PINT re-expression in laryngeal tumors may be explored for reversion of cancer cell stemness and also for rescue of drug resistance phenotype.


Assuntos
Carcinoma/tratamento farmacológico , Neoplasias Laríngeas/tratamento farmacológico , MicroRNAs/genética , Receptor Patched-1/genética , RNA Longo não Codificante/genética , Carcinoma/genética , Carcinoma/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Hedgehog/genética , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/efeitos dos fármacos
15.
J Cell Biochem ; 119(11): 8897-8908, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30105826

RESUMO

As a common cause of shoulder pain and disability, rotator cuff injury (RCI) represents a debilitating condition affecting an individual's quality of life. Although surgical repair has been shown to be somewhat effective, many patients may still suffer from reduced shoulder function. The aim of the current study was to identify a more effective mode of RCI treatment by investigating the effect of platelet-derived growth factor subunit B (PDGF-B) on tendon-bone healing after RCI repair by modifying bone marrow-derived mesenchymal stem cells (BMSCs). Surface markers of BMSCs were initially detected by means of flow cytometry, followed by establishment of the rat models and construction of the lentiviral vector. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay, alizarin red staining, and oil red O staining were used to provide verification that PDGF-B was indeed capable of promoting BMSC viability, osteogenic and adipogenic differentiation capability. Furthermore, biomechanical assessment results indicated that PDGF-B could increase the ultimate load and stiffness of the tendon tissue. Real-time reverse-transcription quantitative polymerase chain reaction and Western blot analysis methods provided evidence suggesting that PDGF-B facilitated the expression of tendon-bone healing-related genes and proteins, while contrasting results were obtained after PDGF-B silencing. Taken together, the key findings of the current study provided evidence suggesting that overexpressed PDGF-B could act to enhance tendon-bone healing after RCI repair, thus highlighting the potential of the functional promotion of PDGF-B as a future RCI therapeutic approach.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/fisiologia , Lesões do Manguito Rotador/reabilitação , Tendões/fisiologia , Cicatrização/fisiologia , Adipogenia/fisiologia , Análise de Variância , Animais , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Expressão Ectópica do Gene/genética , Regulação da Expressão Gênica , Vetores Genéticos , Lentivirus/genética , Masculino , Osteogênese/fisiologia , Ratos , Ratos Sprague-Dawley , Transfecção
16.
J Cell Mol Med ; 22(9): 4253-4262, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29971915

RESUMO

AFAP1-AS1 is a long non-coding RNA that is associated with tumorigenesis and poor prognosis in a variety of cancers. We have been suggested that AFAP1-AS1 increases tumorigenesis in laryngeal carcinoma specifically by enhancing stemness and chemoresistance. We assessed AFAP1-AS1 expression in human laryngeal specimens, paired adjacent normal tissues and human HEp-2 cells. Indeed, we found not only that AFAP1-AS1 was up-regulated in laryngeal carcinoma specimens and cells, but also that stemness-associated genes were overexpressed. Silencing of AFAP1-AS1 promoted HEp-2 cell chemoresistance under cisplatin treatment. Expression of AFAP1-AS1 was increased in drug-resistant Hep-2 cells. We then probed the mechanism of AFAP1-AS1 activity and determined that miR-320a was a potential molecular target of AFAP1-AS1. Luciferase reporter and qRT-PCR assays of AFAP1-AS1 and miR-320a levels in human specimens and cell cultures indicated that AFAP1-AS1 negatively regulates miR-320a. To discover the molecular mechanism of miR-320a, we again used the DIANA Tools algorithm to predict its genetic target, RBPJ. After cloning the 3'-untranslated regions (3'-UTR) of RBPJ into a luciferase reporter, we determined that miR-320a did in fact reduce RBPJ mRNA and protein levels. Ultimately, we determined that AFAP1-AS1 increases RBPJ expression by negatively regulating miR-320a and RBPJ overexpression rescues stemness and chemoresistance inhibited by AFAP1-AS1 silencing. Taken together, these results suggest that AFAP1-AS1 can serve as a prognostic biomarker in laryngeal carcinoma and that miR-320a has the potential to improve standard therapeutic approaches to the disease, especially for cases in which cancer cell stemness and drug resistance present significant barriers to effective treatment.


Assuntos
Carcinoma/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Neoplasias Laríngeas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Antígeno AC133/genética , Antígeno AC133/metabolismo , Antineoplásicos/farmacologia , Sequência de Bases , Sítios de Ligação , Carcinoma/metabolismo , Carcinoma/patologia , Carcinoma/cirurgia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , MicroRNAs/metabolismo , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais
17.
Zhongguo Zhong Yao Za Zhi ; 43(3): 577-584, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29600625

RESUMO

This study aimed to investigate the effect of notoginsenoside R1 in delaying H2O2-induced vascular endothelial cell senescence through microRNA-34a/SIRT1/p53 signal pathway. In this study, human umbilical vein endothelial cells(HUVECs) were selected as the study object; the aging model induced by hydrogen peroxide(H2O2) was established, with resveratrol as the positive drug. HUVECs were randomly divided into four groups, youth group, senescence model group, notoginsenoside R1 group and resveratrol group. Notoginsenoside R1 group and resveratrol group were modeled with 100 µmoL·L⁻¹ H2O2 for 4 h after 24 h treatment with notoginsenoside R1(30 µmoL·L⁻¹) and resveratrol(10 µmoL·L⁻¹) respectively. At the end, each group was cultured with complete medium for 24 h. The degree of cellular senescence was detected by senescence-associated ß-galactosidase(SA-ß-Gal) staining kit, the cell viability was detected by cell counting kit-8, the cell cycle distribution was analyzed by flow cytometry, and the cellular SOD activity was detected by WST-1 method in each group. The expressions of SIRT1, p53, p21 and p16 proteins in HUVECs were detected by Western blot. In addition, the mRNA expressions of miRNA-34a, SIRT1 and p53 in HUVECs were assayed by Real-time PCR. These results indicated that notoginsenoside R1 significantly reduced the positive staining rate of senescent cells, enhanced the cell proliferation capacity and intracellular SOD activity, decreased the proportion of cells in G0/G1 phase, and increased the percentage of cells in S phase simultaneously compared with the senescence model group. Moreover, notoginsenoside R1 decreased the mRNA expressions of miRNA-34a and p53 and the protein expression of p53, p21 and p16.At the same time, notoginsenoside R1 increased the protein and mRNA expressions of SIRT1. The differences in these results between the senescence model group and the notoginsenoside R1 group were statistically significant(P<0.05). However, there was not statistically significant difference in these results between the notoginsenoside R1 group and the resveratrol group. In conclusion, the senescence of endothelial cells induced by H2O2 can be used as a model for studying aging. Notoginsenoside R1 has an obvious anti-aging effect on vascular endothelial cells in this study. The possible mechanism is that notoginsenoside R1 can delay the senescence process of vascular endothelial cells induced by H2O2 by regulating microRNA-34a/SIRT1/p53 signal pathway.


Assuntos
Senescência Celular/efeitos dos fármacos , Ginsenosídeos/farmacologia , MicroRNAs/genética , Transdução de Sinais , Sirtuína 1/genética , Proteína Supressora de Tumor p53/genética , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio
18.
Oncotarget ; 8(37): 62143-62153, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977933

RESUMO

High incidences of laryngeal cancer have been reported recently. Increasing our understanding of the molecular mechanisms underlying this malignancy could reveal more effective approaches to treating laryngeal cancer patients and so improve their prognoses. In this study, we explored the biological effects of miR-217 on laryngeal cancer. miR-217 potently inhibited multiple metastatic traits, including cell migration, invasion, proliferation, apoptosis, and EMT, as well as angiogensis. These effects were achieved through downregulation of the miR-217 target gene, AEG-1 and PD-L1. Clinical expression and animal model studies further confirmed our results. These findings provide new insight into the physiological effects of miR-217 in laryngeal cancer and its potential therapeutic use.

19.
PeerJ ; 5: e3631, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28852586

RESUMO

Identification of appropriate reference genes (RGs) is critical to accurate data interpretation in quantitative real-time PCR (qPCR) experiments. In this study, we have utilised next generation RNA sequencing (RNA-seq) to analyse the transcriptome of a panel of non-melanoma skin cancer lesions, identifying genes that are consistently expressed across all samples. Genes encoding ribosomal proteins were amongst the most stable in this dataset. Validation of this RNA-seq data was examined using qPCR to confirm the suitability of a set of highly stable genes for use as qPCR RGs. These genes will provide a valuable resource for the normalisation of qPCR data for the analysis of non-melanoma skin cancer.

20.
Eur J Med Chem ; 138: 170-181, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-28667873

RESUMO

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of new phenyl-pyrazoline-coumarin derivatives (4a∼4m) were designed and synthesized. Compounds 4a and 4b were determined by X-ray crystallography. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 release. Among them, compound 4m showed the highest anti-inflammatory activity with inhibiting IL-6, TNF-α and nitric oxide (NO) production lipopolysaccharide (LPS)-stimulated. The further study showed that title compound 4m could significantly suppress expressions of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and the productions of IL-6, TNF-α, NO through NF-κB/MAPK signaling pathway. The anti-inflammatory activity of compound 4m was determined by carrageenan induced paw edema. Furthermore in vivo evaluation results indicated that compound 4m could inhibit AA-induced rat ankle joints.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cumarínicos/farmacologia , Interleucina-6/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Pirazóis/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Animais , Articulação do Tornozelo/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Carragenina , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cumarínicos/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Interleucina-6/biossíntese , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/biossíntese , Pirazóis/química , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/biossíntese
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