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1.
Cell Death Dis ; 12(5): 420, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33911067

RESUMO

Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a "miRNAs sponge" to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes ß-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan-Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-ß-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.

2.
Ann Thorac Surg ; 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-33823147

RESUMO

Peratrial balloon pulmonary valvotomy, an alternative technique for severe pulmonary valve stenosis (PVS) in infants, performed exclusively under transesophageal echocardiographic guidance is hereby described. The technique is performed using a hollow-probe via a right mini-thoracotomy in the fourth-intercostal space. The hollow- probe introduces a guidewire through PVS without touching the right ventricular wall, therefore, avoiding eliciting ventricular arrhythmias, spasm of right ventricular outflow tract, and subsequent hemodynamic instability. Unlike conventional approaches, peratrial technique permits quicker orientation, dilatation, and allows quick conversion to open-heart surgery when needed.

3.
J Virol ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762408

RESUMO

The latent reservoir of HIV-1 is a major barrier for viral eradication. Potent HIV-1 broadly neutralizing antibodies (bNabs) have been used to prevent and treat HIV-1 infections in animal models and clinical trials. Combination of bNabs and latency-reversing agents (LRAs) is considered a promising approach for HIV-1 eradication. PCR-based assays that can rapidly and specifically measure singly spliced HIV-1 vpu/env mRNA are needed to evaluate the induction of the viral envelope production at the transcription level and bNab-mediated reservoir clearance. Here we reported a PCR-based method to accurately quantify the production of intracellular HIV-1 vpu/env mRNA. With the vpu/env assay, we determined the LRA combinations that could effectively induce vpu/env mRNA production in CD4+ T cells from ART-treated individuals. None of the tested LRAs were effective alone. A comparison between the quantitative viral outgrowth assay (Q-VOA) and the vpu/env assay showed that vpu/env mRNA production was closely associated with the reactivation of replication-competent HIV-1, suggesting that vpu/env mRNA was mainly produced by intact viruses. Finally, antibody-mediated in vitro killing in HIV-1-infected humanized mice demonstrated that the vpu/env assay could be used to measure the reduction of infected cells in tissues and was more accurate than the commonly used gag-based PCR assay which measured unspliced viral genomic RNA. In conclusion, the vpu/env assay allows convenient and accurate assessment of HIV-1 latency reversal and bNab-mediated therapeutic strategies.ImportanceHIV-1 persists in individuals on antiretroviral therapy (ART) due to the long-lived cellular reservoirs that contain dormant viruses. Recent discoveries of HIV-1-specific broadly neutralizing antibodies (bNabs) targeting HIV-1 Env protein rekindled the interest in antibody-mediated elimination of latent HIV-1. Latency-reversing agents (LRAs) together with HIV-1 bNabs is a possible strategy to clear residual viral reservoirs, which makes the evaluation of HIV-1 Env expression upon LRA treatment critical. We developed a PCR-based assay to quantify the production of intracellular HIV-1 vpu/env mRNA. Using patient CD4+ T cells, we found that induction of HIV-1 vpu/env mRNA required a combination of different LRAs. Using in vitro, ex vivo and humanized mouse models, we showed that the vpu/env assay could be used to measure antibody efficacy in clearing HIV-1 infection. These results suggest that the vpu/env assay can accurately evaluate HIV-1 reactivation and bNab-based therapeutic interventions.

4.
Science ; 371(6533): 1019-1025, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674488

RESUMO

In vivo models that recapitulate human erythropoiesis with persistence of circulating red blood cells (RBCs) have remained elusive. We report an immunodeficient murine model in which combined human liver and cytokine humanization confer enhanced human erythropoiesis and RBC survival in the circulation. We deleted the fumarylacetoacetate hydrolase (Fah) gene in MISTRG mice expressing several human cytokines in place of their murine counterparts. Liver humanization by intrasplenic injection of human hepatocytes (huHep) eliminated murine complement C3 and reduced murine Kupffer cell density. Engraftment of human sickle cell disease (SCD)-derived hematopoietic stem cells in huHepMISTRGFah -/- mice resulted in vaso-occlusion that replicated acute SCD pathology. Combined liver-cytokine-humanized mice will facilitate the study of diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, and malaria, and also preclinical testing of therapies.


Assuntos
Anemia Falciforme/sangue , Circulação Sanguínea , Modelos Animais de Doenças , Eritrócitos/citologia , Eritropoese/fisiologia , Camundongos , Animais , Citocinas/metabolismo , Eritropoese/genética , Feminino , Deleção de Genes , Células-Tronco Hematopoéticas/citologia , Humanos , Hidrolases/genética , Fígado/fisiologia , Camundongos Mutantes , Pessoa de Meia-Idade
5.
Science ; 371(6535)2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33542150

RESUMO

HIV-1 has high mutation rates and exists as mutant swarms within the host. Rapid evolution of HIV-1 allows the virus to outpace the host immune system, leading to viral persistence. Approaches to targeting immutable components are needed to clear HIV-1 infection. Here, we report that the caspase recruitment domain-containing protein 8 (CARD8) inflammasome senses HIV-1 protease activity. HIV-1 can evade CARD8 sensing because its protease remains inactive in infected cells before viral budding. Premature intracellular activation of the viral protease triggered CARD8 inflammasome-mediated pyroptosis of HIV-1-infected cells. This strategy led to the clearance of latent HIV-1 in patient CD4+ T cells after viral reactivation. Thus, our study identifies CARD8 as an inflammasome sensor of HIV-1, which holds promise as a strategy for the clearance of persistent HIV-1 infection.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Infecções por HIV/virologia , Protease de HIV/metabolismo , HIV-1/fisiologia , Inflamassomos/metabolismo , Proteínas de Neoplasias/metabolismo , Piroptose , Alquinos/farmacologia , Fármacos Anti-HIV/farmacologia , Benzoxazinas/farmacologia , Proteínas Adaptadoras de Sinalização CARD/química , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD4-Positivos/virologia , Caspase 1/metabolismo , Ciclopropanos/farmacologia , Ativação Enzimática , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Humanos , Macrófagos/fisiologia , Macrófagos/virologia , Proteínas de Neoplasias/química , Inibidores da Transcriptase Reversa/farmacologia , Rilpivirina/farmacologia , Células THP-1 , Latência Viral
6.
J Card Surg ; 36(3): 928-938, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33503678

RESUMO

BACKGROUND/AIM: Both open heart surgery and percutaneous approaches retain several limitations in closing large apical muscular ventricular septal defects (AmVSD) in infants. We present probe-assisted percardiac device closure (PDC), an exclusively transoesophageal-echocardiography guided technique, as an alternative with midterm results. METHODS: Thirty-six infants with large AmVSDs (single or multiple-holed) underwent PDC in our department. Mean AmVSD for single and multiple-holed measured 7.2 ± 2.4 mm and 6.3 ± 3.4 mm, respectively. Subjects presented with a spectrum of cardiopulmonary sequelae and growth retardation, either alone or combined. Some were ventilator dependent and re-do cases. In addition, AmVSDs were categorized: cylindrical, tunnel and cave-like shaped as per color Doppler interrogation. Pursuant to cardiac access and deployment technique, subjects were apportioned: group A; inferior median sternotomy (perventricular), B; right mini-thoracotomy (peratrial) and C; complete median sternotomy (perventricular). Under exclusive echocardiography, the Z- or J probe-assisted delivery system was utilized to access AmVSDs and implant device(s) via aforementioned techniques. RESULTS: Forty-two muscular ventricular septal devices (8.4 ± 2.6 mm) were implanted in 36 subjects uneventfully. Seventeen "complex," and 10 cylindrical or straight tunnel-shapedAmVSDs (including 2 re-do patients) suited perventricular and peratrial techniques respectively. Comparatively, group B exhibited shorter procedural indices than A (p < .01). Five of 15 multiple-holed AmVSDs (four Swiss cheese) required two or three devices for a satisfactory occlusion. Nevertheless, post occlusion insignificant residual shunts( ≤ 2 mm) seldom achieved spontaneous closure, and at 36-month follow-up complete closure was 67%. Residual shunt persisted amongst multiple-holed. All patients improved during follow up. CONCLUSION: PDC is feasible, safe and effective alternative technique for AmVSD in infants.

7.
Mol Ther Nucleic Acids ; 22: 1078-1091, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33294294

RESUMO

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have emerged as important mediators of intercellular communication in response to cartilage damage. In this study, we sought to characterize the inhibitory role of microRNA (miR)-31 encapsulated in synovial MSC (SMSC)-derived EVs in knee osteoarthritis (OA). The expression of miR-31, lysine demethylase 2A (KDM2A), E2F transcription factor 1 (E2F1), and pituitary tumor transforming gene 1 (PTTG1) was validated in cartilage tissues of knee OA patients. Following SMSC-EV extraction and identification, chondrocytes with the miR-31 inhibitor were added with SMSC-EVs, whereupon the effects of miR-31 on proliferation and migration of chondrocytes were assessed. The interaction among miR-31, KDM2A, E2F1, and PTTG1 in chondrocyte activities was probed in vitro, along with an in vivo mouse knee OA model. We identified downregulated miR-31, E2F1, and PTTG1 and upregulated KDM2A in cartilage tissues of knee OA patients. SMSC-EV-packaged miR-31 potentiated chondrocyte proliferation and migration as well as cartilage formation by targeting KDM2A. Mechanistically, KDM2A bound to the transcription factor E2F1 and inhibited its transcriptional activity. Enrichment of E2F1 in the PTTG1 promoter region activated PTTG1 transcription, accelerating chondrocyte proliferation and migration. SMSC-EVs and EVs from miR-31-overexpressed SMSCs alleviated cartilage damage and inflammation in knee joints in vivo. SMSC-EV-encapsulated miR-31 ameliorates knee OA via the KDM2A/E2F1/PTTG1 axis.

8.
Onco Targets Ther ; 13: 12015-12025, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33244243

RESUMO

Purpose: Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment. Our previous studies demonstrated that Huaier enhanced chemotherapy sensitivity and restrained HCC proliferation. This study aimed to identify differentially expressed proteins with Huaier treatment in HCC cells, providing molecular targets for future targeted therapy of HCC. Materials and Methods: The effects of Huaier on the cell cycle were determined by flow cytometry and Western blot (WB). Xenograft models were used to verify the effects of Huaier on tumor growth. Then, proteomics was performed to identify the potential proteins regulated by Huaier. The enrichment analysis of GO and KEGG was performed for the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were used to detect the levels of proteins after Huaier treatment. After that the correlation of differentially expressed proteins with pathological stages was analyzed via the GEPIA database. We also analyzed candidate expression after Huaier treatment in HCC cells by WB and qRT-PCR. Furthermore, siRNA was performed to verify the targeted regulation of Huaier on candidate proteins. Results: First, the proteomics data showed that a total of 160 proteins were identified as differentially expressed proteins, among which six minichromosome maintenance (MCM) family members were enriched in the tumor-associated pathways after Huaier treatment. Moreover, MCM proteins were highly expressed in HCC and closely correlated with the survival of HCC patients. Finally, we confirmed that MCM proteins were targets of Huaier treatment in HCC cells. Conclusion: Huaier treatment was closely associated with the activation and inhibition of cancer-related pathways, and the MCM family was identified as a potential target in the antitumor process of Huaier. This study is helpful in understanding the molecular alterations and clinical relevance of HCC after Huaier treatment, which is beneficial for finding new targets and designing effective chemotherapy regimens for the future treatment of HCC.

9.
Ann Allergy Asthma Immunol ; 125(6): 652-657.e3, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32931909

RESUMO

BACKGROUND: Sex differences exist in asthma susceptibility and severity. Accumulating evidence has linked airway microbiome dysbiosis to asthma, and airway microbial communities have been found to differ by sex. However, whether sex modifies the link between airway microbiome and asthma has not been investigated. OBJECTIVE: To evaluate sex effects in the association between airway microbiome and asthma. METHODS: We analyzed induced sputum samples from 47 subjects (n = 23 patients with asthma and n = 24 normal controls) using 16S ribosomal RNA gene sequencing methods. The bacterial composition was analyzed for sex differences. Bacterial associations with asthma were assessed for each sex at the core taxa and genus levels. RESULTS: The microbiome in induced sputum differed in women vs men at the community level. A total of 5 core bacterial taxa were found in all samples. No sex-specific core taxa were detected. The most abundant core taxon, Streptococcus salivarius, was significantly enriched in women than in men (P = .02). Within each sex, individuals with relatively lower abundance of S salivarius were more likely to have asthma (P = .006). For both sexes, increased Lactobacillus species were found in sputum samples of patients with patients compared with normal controls (adjusted P = .01). Haemophilus species were associated with asthma in men and not in women. CONCLUSION: The airway microbiome differed by sex, and sex effects exist in the association of airway microbial markers and asthma. Future airway microbiome studies may yield better resolution if the context of specific sex is considered. The airway microbiome is a potential mechanism driving sex differences in asthma.

10.
J Med Chem ; 63(21): 12403-12428, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-32659083

RESUMO

Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interest of pharmaceutical chemists and is expected to bring new hope for AML therapy. In this review, we specifically highlighted FLT3 mediated JAK/STAT, RAS/MAPK, and PI3K/AKT/mTOR signaling. The structural properties and biological activities of representative FLT3 inhibitors reported from 2014 to the present were also summarized. In addition, the major challenges in the current advance of novel FLT3 inhibitors were further analyzed, with the aim to guide future drug discovery.

11.
Clin Genet ; 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32583420

RESUMO

Long non-coding RNAs (lncRNAs), a class of long RNAs, are longer than 200 nucleotides in length but lack protein-coding capacity. LncRNAs, as critical genomic regulators, are involved in genomic imprinting regulation, histone modification and gene expression regulation as well as tumor initiation and progression. However, it is also found that lncRNAs are associated with drug resistance in several types of cancer. Drug resistance is an important reason for clinical chemotherapy failure, and the molecular mechanism of tumor resistance is complex, which is a process of multi-cause, multi-gene and multi-signal transduction pathway interaction. Then comprehending the mechanisms of chemoresistance will help find ways to control the tumor progression effectively. Therefore, in this review, we will construct lncRNAs /drug resistance interaction network and shed light on the role of lncRNAs in drug resistance.

12.
Pediatr Res ; 88(6): 917-924, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32172280

RESUMO

BACKGROUND: Hurricane Maria struck Puerto Rico on 20 September 2017 causing catastrophic devastation. Prolonged shortage of food had been a substantial challenge to the residents after Maria. Experiencing food insecurity in utero has been associated with negative health outcomes later in life. We aim to examine whether there is any alteration in the infant gut microbiome that is associated with prenatal food insecurity. METHODS: We established a cohort of infants aged 2-6 months who were exposed in utero to Hurricane Maria near San Juan, Puerto Rico and examined the gut microbiota (n = 29) using 16S ribosomal RNA gene sequencing. RESULTS: Among the enrolled infants, 30% of their mothers experienced "post-Maria poor access to food" for at least 1 month during pregnancy. The relative abundance of gut Veillonella spp. is significantly decreased among infants who experienced prenatal food insecurity, compared to those who did not (adjusted p = 0.025). There is no significant difference observed by prenatal food insecurity at the microbial community level in this cohort. CONCLUSIONS: Our finding indicated that infants who experienced prenatal food insecurity post hurricane harbor microbial alternations of specific bacterial taxa, which may further influence the microbial maturation and place the individual at a high-risk health trajectory. IMPACT: We identified that in utero exposure to food insecurity post Hurricane Maria is associated with decreased abundance of Veillonella in the infant gut. Our findings indicated that infants who experienced prenatal food insecurity post hurricane may harbor alterations of specific bacterial taxa in their gut microbiota. This study showed the association between prenatal adverse exposure and alterations of gut microbiome early in life in the context of an extreme event. This study provided insights into the mechanisms underlying prenatal adverse exposure and increased disease risks later in life. Our findings will potentially raise awareness of the negative impact of extreme climate events on the unborn.

13.
J Mater Chem B ; 8(5): 878-894, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31956883

RESUMO

Continuous blood purification technology such as hemodiafiltration has been used worldwide for saving patients suffering from severe diseases or organ function failure, especially in the intensive care unit and emergency setting. The filters as core devices are commonly made of polymer materials as hollow fiber membranes. However, the membrane is often inductively blocked by blood clot formation due to its interactions with blood components. Heparin is the anticoagulant often used in clinical practice for anti-coagulation. Recently, heparin is also employed to modify the hollow fiber membranes either chemically or physically to improve the filtration performance. This review summarizes recent advances in methodology for surface heparinization of such hollow fiber membranes, and their filtration performance improvement. The review also provides expert opinions for further research in this rapidly expanding field.

14.
Ying Yong Sheng Tai Xue Bao ; 31(1): 309-318, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957409

RESUMO

Procambarus clarkii was introduced into China as an important aquatic product in early 20th century. It has characteristics of high fertility, rapid growth, adaptability and digging burrows, which could cause damage of crops, cropland and facilities, decrease local biodiversity and thus threaten local ecosystem. Thus, predicting the potential distribution of P. clarkii in response to climate change was essential for preventing and monitoring this species. Based on the distribution of P. clarkii, the maximum entropy (MaxEnt) and genetic algorithm for rule-set production (GARP) models were used to predict its distribution in China under current climate and four climate scenarios (RCP 2.6, RCP 4.5, RCP 6.0, RCP 8.5) in two periods, 2041-2060 and 2061-2080. Then, the modeling results were tested by ROC curves. The results showed that under current climate, the highly suitable region for distribution predicted by the MaxEnt and GARP models were Shanghai, Jiangsu, Zhejiang and Anhui along the Yangtze River. The main environmental variables affecting its distribution were mean temperature of the coldest quarter, minimum temperature of the warmest month, and temperature seasonality, maximum temperature of the warmest month, precipitation of the driest month. Under the future climate scenarios, the suitable area of P. clarkii distribution varied in 2061-2080. The total suitable area of P. clarkii would increase under RCP2.6 and RCP 4.5, whereas under RCP 8.5 the suitable area of P. clarkii would increase, and then decrease. In RCP 6.0, there was no change. The suitable areas of P. clarkii would disperse to different latitude areas and migrate toward high altitude.


Assuntos
Ecossistema , Espécies Introduzidas , Animais , Astacoidea , China , Mudança Climática
15.
Mol Cell Biochem ; 466(1-2): 91-102, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989367

RESUMO

Purine signaling pathway plays an important role in inflammation and tissue damage. To investigate the role of purine signaling pathway in acute alcoholic liver injury and chronic alcoholic liver fibrosis, we replicated two animal models and two cellular models. We found that body weights, liver indexes, serum biochemical parameters, serum fibrosis indexes, and pathological and immunohistochemical results had significant changes in two treatment groups compared with two control groups. In addition, gene expressions of purine receptors, inflammatory cytokines, fibrogenic cytokines, and inflammasomes increased obviously in two animal models and two cellular models. Furthermore, purine receptor inhibitors could significantly inhibit protein expressions of purine receptors and reduce protein expressions of inflammatory cytokines, fibrogenic cytokines, and inflammasomes. Besides, P2X7R small interfering ribonucleic acid (siRNA) had the same effects. Meanwhile, we detected protein expressions of inflammatory cytokines secreted by inflammasomes, and we found that purine receptor-mediated inflammasomes activation was a key event in the process of chronic alcoholic liver fibrosis. In summary, this study shows that inhibition of purine receptors can alleviate acute alcoholic liver injury and chronic alcoholic liver fibrosis in mice. Therefore, purine receptor is a potential new target for the treatment of acute alcoholic liver injury and chronic alcoholic fibrosis.


Assuntos
Proliferação de Células , Citocinas/metabolismo , Células Estreladas do Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , Purinas/metabolismo , Transdução de Sinais , Animais , Células Estreladas do Fígado/patologia , Inflamação/metabolismo , Inflamação/patologia , Hepatopatias Alcoólicas/patologia , Camundongos , Receptores Purinérgicos P2X7/metabolismo
16.
Epigenomics ; 12(2): 101-125, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31920098

RESUMO

Aim: Circular RNAs (circRNAs) still have many potential functions in the process of tumor development that are not completely understood. The study aims to explore novel circRNAs and their mechanisms of action in breast cancer (BCa). Materials & methods: A combination strategy of RNA-sequencing (RNA-seq) technique, quantitative real-time PCR and bioinformatic analysis was employed to identify the potential mechanisms involving differentially expressed circRNAs in the serum exosomes and tissues of BCa patients. Results: The expression levels of hsa-circRNA-0005795 and hsa-circRNA-0088088 were significantly different both in serum exosomes and tissues and might function as competing endogenous RNAs and play vital roles in BCa development. Conclusion: We constructed two circRNA-miRNA networks and provided new insight into the prognosis and therapy of BCa using circRNAs from serum exosomes.

17.
Epigenomics ; 12(4): 303-317, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31920104

RESUMO

Aim: We aimed to explore the roles of circular RNA, circVAPA in regulating cell migration and invasion of breast cancer. Materials & methods: CircVAPA expression was detected in breast cancer tissues and cells. The role of circVAPA was evaluated by MTT assay, wound-healing and transwell assay. The relationship between circVAPA and miR-130a-5p and the location of circVAPA were explored. Results: We discovered that circVAPA was dysregulated in breast cancer tissues and cells. Ectopic circVAPA regulated breast cancer migration, invasion and proliferation. CircVAPA was mainly expressed in the cytoplasm and could act as a miRNA sponge for miR-130a-5p, but did not regulate its parental gene. Conclusion: CircVAPA may promote migration and invasion capacity of breast cancer via harboring miR-130a-5p.

19.
Alzheimers Dement ; 15(9): 1208-1217, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399333

RESUMO

INTRODUCTION: We aimed to estimate the frequency of each AT(N) (ß-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.


Assuntos
Doença de Alzheimer , Biomarcadores , Progressão da Doença , Sintomas Prodrômicos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Tomografia por Emissão de Pósitrons , Prognóstico , Proteínas tau/metabolismo
20.
Oncol Lett ; 18(3): 2923-2930, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452773

RESUMO

The regulatory roles of circular RNAs (circRNAs) in cancer are attracting increasing attention. The aim of the present study was to explore the roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) using microarray data. The circRNA and microRNA (miRNA) microarray data were downloaded from Gene Expression Omnibus. A total of 256 differentially expressed circRNAs were obtained by analyzing the circRNA microarray data from 26 pairs of PDAC and adjacent normal tissues. Differentially expressed miRNAs were analyzed using a dataset of 6 PDAC tissues and 5 non-neoplastic pancreas samples (GSE43796); 20 differentially expressed miRNAs were detected. circRNA/miRNA interactions were predicted between differentially expressed circRNAs and miRNAs using miRanda and RNAhybrid algorithms and 51 circRNA/miRNA interactions were obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using gene symbols of differentially expressed circRNAs demonstrated that 41 circRNAs were enriched in 17 pathways. Subnetworks that were associated with apoptosis or proliferation were extracted from the 17 pathways and a new network was constructed using Cytoscape software, which identified that mitogen-activated protein kinase, PI3K/AKT and WNT/ß-catenin signaling pathways may be associated with PDAC development. In conclusion, 256 differentially expressed circRNAs and 20 differentially expressed miRNAs were identified in PDAC tissues compared with normal tissues; the circRNA/miRNA interactions and the networks of KEGG pathways provided a global view of the function of these differentially expressed circRNAs and miRNAs.

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