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1.
BMC Dev Biol ; 20(1): 22, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33203369

RESUMO

BACKGROUND: Tissue regeneration mediated by mesenchymal stem cells (MSCs) is deemed a desirable way to repair teeth and craniomaxillofacial tissue defects. Nevertheless, the molecular mechanisms about cell proliferation and committed differentiation of MSCs remain obscure. Previous researches have proved that lysine demethylase 2A (KDM2A) performed significant function in the regulation of MSC proliferation and differentiation. SNRNP200, as a co-binding factor of KDM2A, its potential effect in regulating MSCs' function is still unclear. Therefore, stem cells from the apical papilla (SCAPs) were used to investigate the function of SNRNP200 in this research. METHODS: The alkaline phosphatase (ALP) activity assay, Alizarin Red staining, and osteogenesis-related gene expressions were used to examine osteo-/dentinogenic differentiation potential. Carboxyfluorescein diacetate, succinimidyl ester (CFSE) and cell cycle analysis were applied to detect the cell proliferation. Western blot analysis was used to evaluate the expressions of cell cycle-related proteins. RESULTS: Depletion of SNRNP200 caused an obvious decrease of ALP activity, mineralization formation and the expressions of osteo-/dentinogenic genes including RUNX2, DSPP, DMP1 and BSP. Meanwhile, CFSE and cell cycle assays revealed that knock-down of SNRNP200 inhibited the cell proliferation and blocked cell cycle at the G2/M and S phase in SCAPs. In addition, it was found that depletion of SNRNP200 up-regulated p21 and p53, and down-regulated the CDK1, CyclinB, CyclinE and CDK2. CONCLUSIONS: Depletion of SNRNP200 repressed osteo-/dentinogenic differentiation potentials and restrained cell proliferation through blocking cell cycle progression at the G2/M and S phase, further revealing that SNRNP200 has crucial effects on preserving the proliferation and differentiation potentials of dental tissue-derived MSCs.

2.
IEEE Trans Med Imaging ; PP2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33245693

RESUMO

Clusters of viral pneumonia occurrences over a short period may be a harbinger of an outbreak or pandemic. Rapid and accurate detection of viral pneumonia using chest X-rays can be of significant value for large-scale screening and epidemic prevention, particularly when other more sophisticated imaging modalities are not readily accessible. However, the emergence of novel mutated viruses causes a substantial dataset shift, which can greatly limit the performance of classification-based approaches. In this paper, we formulate the task of differentiating viral pneumonia from non-viral pneumonia and healthy controls into a one-class classification-based anomaly detection problem. We therefore propose the confidence-aware anomaly detection (CAAD) model, which consists of a shared feature extractor, an anomaly detection module, and a confidence prediction module. If the anomaly score produced by the anomaly detection module is large enough, or the confidence score estimated by the confidence prediction module is small enough, the input will be accepted as an anomaly case (i.e., viral pneumonia). The major advantage of our approach over binary classification is that we avoid modeling individual viral pneumonia classes explicitly and treat all known viral pneumonia cases as anomalies to improve the one-class model. The proposed model outperforms binary classification models on the clinical X-VIRAL dataset that contains 5,977 viral pneumonia (no COVID-19) cases, 37,393 non-viral pneumonia or healthy cases. Moreover, when directly testing on the X-COVID dataset that contains 106 COVID-19 cases and 107 normal controls without any fine-tuning, our model achieves an AUC of 83.61% and sensitivity of 71.70%, which is comparable to the performance of radiologists reported in the literature.

3.
IEEE Trans Med Imaging ; PP2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33125324

RESUMO

Automated and accurate 3D medical image segmentation plays an essential role in assisting medical professionals to evaluate disease progresses and make fast therapeutic schedules. Although deep convolutional neural networks (DCNNs) have widely applied to this task, the accuracy of these models still need to be further improved mainly due to their limited ability to 3D context perception. In this paper, we propose the 3D context residual network (ConResNet) for the accurate segmentation of 3D medical images. This model consists of an encoder, a segmentation decoder, and a context residual decoder. We design the context residual module and use it to bridge both decoders at each scale. Each context residual module contains both context residual mapping and context attention mapping, the formal aims to explicitly learn the inter-slice context information and the latter uses such context as a kind of attention to boost the segmentation accuracy. We evaluated this model on the MICCAI 2018 Brain Tumor Segmentation (BraTS) dataset and NIH Pancreas Segmentation (Pancreas-CT) dataset. Our results not only demonstrate the effectiveness of the proposed 3D context residual learning scheme but also indicate that the proposed ConResNet is more accurate than six top-ranking methods in brain tumor segmentation and seven top-ranking methods in pancreas segmentation.

4.
Stem Cells Int ; 2020: 8881021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082788

RESUMO

Understanding the regulation mechanisms of mesenchymal stem cells (MSCs) can assist in tissue regeneration. The histone demethylase (KDM) family has a crucial role in differentiation and cell proliferation of MSCs, while the function of KDM3B in MSCs is not well understood. In this study, we used the stem cells from the apical papilla (SCAPs) to test whether KDM3B could regulate the function of MSCs. By an alkaline phosphatase (ALP) activity assay, Alizarin red staining, real-time RT-PCR, and western blot analysis, we found that KDM3B enhanced the ALP activity and mineralization of SCAPs and promoted the expression of runt-related transcription factor 2 (RUNX2), osterix (OSX), dentin sialophosphoprotein (DSPP), and osteocalcin (OCN). Additionally, the CFSE, CCK-8, and flow cytometry assays revealed that KDM3B improved cell proliferation by accelerating cell cycle transition from the G1 to S phase. Scratch and transwell migration assays displayed that KDM3B promoted the migration potential of SCAPs. Mechanically, microarray results displayed that 98 genes were upregulated, including STAT1, CCND1, and FGF5, and 48 genes were downregulated after KDM3B overexpression. Besides, we found that the Toll-like receptor and JAK-STAT signaling pathway may be involved in the regulating function of KDM3B in SCAPs. In brief, we discovered that KDM3B promoted the osteo-/odontogenic differentiation, cell proliferation, and migration potential of SCAPs and provided a novel target and theoretical basis for regenerative medicine.

5.
Dose Response ; 18(3): 1559325820950061, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973416

RESUMO

Increasing evidence shows that eukaryotic initiation factor subunit (EIF3C) plays a crucial role in development of tumors. However, the underlying roles of EIF3Cin the development of pancreatic cancer (PC) remain unknown. In this study, we examined the expression of EIF3C in PC tissues, their adjacent normal tissues and 3 cell lines (SW1990, PANC-1 and AsPC-1). Moreover, the EIF3C-shRNA lentivirus was constructed to suppress EIF3C expression. Following this, the cell colony formation assay was employed to evaluate proliferation ability of PC cells. Meanwhile, the cell cycle and apoptotic assays were also performed by flow cytometry. We found that level of EIF3C in PC tissues was significantly increased compared with that in adjacent normal tissues. Furthermore, the knockdown of EIF3C can significantly reduce cell proliferation, block cell cycle in G2/M and induce apoptosis in both SW1990 and PANC-1 cells. Our findings suggest that EIF3C plays a crucial role in the progression of PC and may be a potential target in the treatment of PC.

6.
IEEE Trans Med Imaging ; PP2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32956049

RESUMO

Medical image segmentation is an essential task in computer-aided diagnosis. Despite their prevalence and success, deep convolutional neural networks (DCNNs) still need to be improved to produce accurate and robust enough segmentation results for clinical use. In this paper, we propose a novel and generic framework called Segmentation-Emendation-reSegmentation-Verification (SESV) to improve the accuracy of existing DCNNs in medical image segmentation, instead of designing a more accurate segmentation model. Our idea is to predict the segmentation errors produced by an existing model and then correct them. Since predicting segmentation errors is challenging, we design two ways to tolerate the mistakes in the error prediction. First, rather than using a predicted segmentation error map to correct the segmentation mask directly, we only treat the error map as the prior that indicates the locations where segmentation errors are prone to occur, and then concatenate the error map with the image and segmentation mask as the input of a re-segmentation network. Second, we introduce a verification network to determine whether to accept or reject the refined mask produced by the re-segmentation network on a region-by-region basis. The experimental results on the CRAG, ISIC, and IDRiD datasets suggest that using our SESV framework can improve the accuracy of DeepLabv3+ substantially and achieve advanced performance in the segmentation of gland cells, skin lesions, and retinal microaneurysms. Consistent conclusions can also be drawn when using PSPNet, U-Net, and FPN as the segmentation network, respectively. Therefore, our SESV framework is capable of improving the accuracy of different DCNNs on different medical image segmentation tasks.

7.
Stem Cell Res Ther ; 11(1): 271, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631410

RESUMO

BACKGROUND: Mesenchymal stem cell (MSC)-based cartilage tissue regeneration is a treatment with great potential. How to enhance the MSC chondrogenic differentiation is a key issue involved in cartilage formation. In the present study, we seek to expound the phenotypes and mechanisms of DLX5 in chondrogenic differentiation function in MSCs. METHODS: Stem cells from apical papilla (SCAPs) were used. The Alcian Blue staining, pellet culture system, and cell transplantation in rabbit knee cartilage defect were used to evaluate the chondrogenic differentiation function of MSCs. Western blot, real-time RT-PCR, and ChIP assays were used to evaluate the molecular mechanisms. RESULTS: DLX5 and HOXC8 expressions were upregulated during chondrogenic differentiation. In vitro results showed that DLX5 and HOXC8 enhanced the expression of chondrogenic markers including collagen II (COL2), collagen V (COL5), and sex-determining region Y box protein 9 (SOX9) and promoted the chondrogenic differentiation and the formation of cartilage clumps in the pellet culture system. Mechanically, DLX5 and HOXC8 formed protein complexes and negatively regulated the LncRNA, LINC01013, via directly binding its promoter. In vivo transplantation experiment showed that DLX5 and HOXC8 could restore the cartilage defect in the rabbit knee model. In addition, knock-down of LINC01013 enhanced the chondrogenic differentiation of SCAPs. CONCLUSIONS: In conclusion, DLX5 and HOXC8 enhance the chondrogenic differentiation abilities of SCAPs by negatively regulating LINC01013 in SCAPs, and provided the potential target for promoting cartilage tissue regeneration.

8.
Insect Sci ; 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32558234

RESUMO

The fall armyworm (FAW), Spodoptera frugiperda, is a major pest native to the Americas that has recently invaded the Old World. Point mutations in the target-site proteins acetylcholinesterase-1 (ace-1), voltage-gated sodium channel (VGSC) and ryanodine receptor (RyR) have been identified in S. frugiperda as major resistance mechanisms to organophosphate, pyrethroid and diamide insecticides respectively. Mutations in the adenosine triphosphate-binding cassette transporter C2 gene (ABCC2) have also been identified to confer resistance to Cry1F protein. In this study, we applied a whole-genome sequencing (WGS) approach to identify point mutations in the target-site genes in 150 FAW individuals collected from China, Malawi, Uganda and Brazil. This approach revealed three amino acid substitutions (A201S, G227A and F290V) of S. frugiperda ace-1, which are known to be associated with organophosphate resistance. The Brazilian population had all three ace-1 point mutations and the 227A allele (mean frequency = 0.54) was the most common. Populations from China, Malawi and Uganda harbored two of the three ace-1 point mutations (A201S and F290V) with the 290V allele (0.47-0.58) as the dominant allele. Point mutations in VGSC (T929I, L932F and L1014F) and RyR (I4790M and G4946E) were not detected in any of the 150 individuals. A novel 12-bp insertion mutation in exon 15 of the ABCC2 gene was identified in some of the Brazilian individuals but absent in the invasive populations. Our results not only demonstrate robustness of the WGS-based genomic approach for detection of resistance mutations, but also provide insights for improvement of resistance management tactics in S. frugiperda.

9.
Oncol Lett ; 19(3): 1683-1692, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32194660

RESUMO

The underlying molecular mechanisms of pancreatic neuroendocrine tumor (pNET) development have not yet been clearly identified. The present study revealed that thrombospondin 2 (THBS2) was downregulated in pNET tissues and cells. Forced expression of THBS2 inhibited the proliferation and migration of pNET cells in vitro. MicroRNA(miR)-744-5p was indicated to be a direct regulator of THBS2. Upregulation of miR-744-5p potentially caused THBS2 repression. Furthermore, THBS2 inhibited the production of matrix metalloproteinase (MMP) MMP9 through suppressing the transcriptional activity of CUT-like homeobox 1 (CUX1). CUX1 and MMP9 mediated the effect of THBS2 on pNET proliferation and migration, respectively. The results of the present study revealed a mechanistic role for THBS2 in pNET proliferation and migration, indicating that THBS2 was downregulated by miR-744-5p and further affected the CUX1/MMP9 cascade, which promoted the development of pNET.

10.
IEEE Trans Med Imaging ; 39(7): 2482-2493, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32070946

RESUMO

Automated skin lesion segmentation and classification are two most essential and related tasks in the computer-aided diagnosis of skin cancer. Despite their prevalence, deep learning models are usually designed for only one task, ignoring the potential benefits in jointly performing both tasks. In this paper, we propose the mutual bootstrapping deep convolutional neural networks (MB-DCNN) model for simultaneous skin lesion segmentation and classification. This model consists of a coarse segmentation network (coarse-SN), a mask-guided classification network (mask-CN), and an enhanced segmentation network (enhanced-SN). On one hand, the coarse-SN generates coarse lesion masks that provide a prior bootstrapping for mask-CN to help it locate and classify skin lesions accurately. On the other hand, the lesion localization maps produced by mask-CN are then fed into enhanced-SN, aiming to transfer the localization information learned by mask-CN to enhanced-SN for accurate lesion segmentation. In this way, both segmentation and classification networks mutually transfer knowledge between each other and facilitate each other in a bootstrapping way. Meanwhile, we also design a novel rank loss and jointly use it with the Dice loss in segmentation networks to address the issues caused by class imbalance and hard-easy pixel imbalance. We evaluate the proposed MB-DCNN model on the ISIC-2017 and PH2 datasets, and achieve a Jaccard index of 80.4% and 89.4% in skin lesion segmentation and an average AUC of 93.8% and 97.7% in skin lesion classification, which are superior to the performance of representative state-of-the-art skin lesion segmentation and classification methods. Our results suggest that it is possible to boost the performance of skin lesion segmentation and classification simultaneously via training a unified model to perform both tasks in a mutual bootstrapping way.

11.
Cell Biol Int ; 44(4): 1046-1058, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31930610

RESUMO

Mesenchymal stem cells (MSCs) exists low efficiency to trans-differentiate into other germinal layer cell types. One key issue is to discover the effect of important factor on MSCs differentiation abiltiy. In this study, we investigated the role and mechanism of epiregulin (EREG) on the osteogenic differentiation and neurogenic trans-differentiation in adipose-derived stem cells (ADSCs). We discovered that the depletion of EREG inhibited the osteogenic differentiation in vitro. And 25 ng/mL recombinant human epiregulin protein (rhEREG) effectively improved the osteogenic differentiation of EREG-depleted-ADSCs. Depletion of EREG promoted the formation of neural spheres, and increased the expressions of nestin, ßIII-tubulin, NeuroD, NCAM, TH, and NEF in ADSCs. Then, 25 ng/mL rhEREG significantly inhibited these neurogenic differentiation indicators. Inhibition of p38 MAPK, JNK, or Erk1/2 signaling pathway separately, blocked the rhEREG-enhanced osteogenic differentiation ability and the rhEREG-inhibited neurogenic trans-differentiation ability of ADSCs. In conclusions, EREG promoted the osteogenic differentiation and inhibited the neurogenic trans-differentiation potentials of ADSCs via MAPK signaling pathways.


Assuntos
Transdiferenciação Celular , Epirregulina/metabolismo , Neurogênese , Osteogênese , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
12.
Connect Tissue Res ; 61(5): 498-508, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31096797

RESUMO

PURPOSE: Periodontal ligament mesenchymal stem cells (PDLSCs) are important for periodontal tissue regeneration, but how these cells are regulated remains unclear. PRDM (PRDI-BF1 and RIZ homology domain containing) genes play key roles in cell proliferation and differentiation. The present study aimed to investigate the role of one PRDM gene, PRDM9, in the proliferation, migration and chemotaxis potential of PDLSCs. MATERIALS AND METHODS: Cell proliferation was examined on the basis of the cell doubling time, cell counting kit-8 (CCK8) assays, and flow cytometry analysis of the cell cycle. Gene expression was detected by Western blotting and real-time RT-PCR. Scratch migration and Transwell chemotaxis assays were used to analyse cell migration and chemotaxis abilities. Microarray analysis and ChIP assays were used to examine the downstream genes of PRDM9 and the corresponding mechanism. RESULTS: The results showed that knock-down of PRDM9 enhanced cell proliferation by promoting cell cycle progression and rapid transition from the G1 to S phase via downregulation of p21 and p27 and upregulation of cyclin E. Additionally, depletion of PRDM9 increased the migration and chemotaxis potential of PDLSCs. Microarray results showed that 13 genes, including IGFBP5, IFI44L, and POSTN, were upregulated and 34 genes, including PIP, were downregulated after the depletion of PRDM9. Furthermore, we observed that the depletion of PRDM9 promoted the transcription of IGFBP5 by increasing H3K4me3 methylation in the IGFBP5 promoter. CONCLUSION: These discoveries indicated that depletion of PRDM9 increased the cell proliferation, migration and chemotaxis potential of PDLSCs and revealed important downstream genes.

13.
World J Clin Cases ; 7(22): 3718-3727, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31799296

RESUMO

BACKGROUND: Many patients have inadequate long-term analgesia, respiratory distress, and hypoxemia due to a long-standing substantial smoking history or the presence of primary pulmonary diseases; analgesic treatment is not valid in these patients. Even if the imaging findings of rib fractures are relatively mild, rib fractures may cause severe position limitation, respiratory distress, and hypoxemia. AIM: To investigate the curative effect of surgical treatment for patients with severe non-flail chest rib fractures. METHODS: A total of 78 patients from our hospital with severe noncontinuous thoracic rib fractures from September 2016 to September 2018 were enrolled in our study. Thirty-nine patients underwent surgical treatment, and 39 underwent conservative treatment. The surgical treatment group received surgery performed with titanium plates, and the screws were inserted with open reduction and internal fixation. The conservative treatment group received analgesia and symptomatic treatment. The pain scores at 72 h, 1 wk, 2 wk, 4 wk, 6 wk, 3 mo, and 6 mo were compared, and the SF-36 quality of life scores were compared atthe 3rd and 6th months. RESULTS: Pain relief in the surgical group was significantly better than that in the conservative group at each time point (72 h, 1 wk, 2 wk, 4 wk, 6 wk, 3 mo, and 6 mo after surgery, P < 0.001). ( The SF-36 scores were significantly higher in the surgical group than in the conservative group at 1 mo and 6 mo (P < 0.05). CONCLUSION: Patients with severe non-flail chest rib fractures have a better quality of life following surgical treatment than following conservative treatment, and surgical treatment is also useful for relieving pain. We should pay more attention to the physiological functions and clinical manifestations of patients with severe rib fractures. In patients with non-flail chest rib fractures, surgical treatment is feasible and effective.

14.
J Nat Prod ; 82(11): 3089-3095, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31702148

RESUMO

The Arctic fungus Eutypella sp. D-1, previously found to produce a variety of cytotoxic cyclopropyl-fused and cyclobutyl-fused pimarane diterpenoids when grown in the defined medium, was induced to produce unusual metabolites by growing on solid rice medium. A chemical investigation on the rice medium extract led to the isolation of four new meroterpenoids, eutypellacytosporins A-D (1-4), along with the known biogenetically related compound cytosporin D (5). The structures of the new compounds were elucidated by their detailed spectroscopic analysis and modified Mosher's method. Compounds 1-4 may be formed by the 12,32-ester linkage of two moieties, cytosporin D (5) and decipienolide A or B. All isolated compounds, except 5, showed weak cytotoxicity against DU145, SW1990, Huh7, and PANC-1 cell lines with IC50 values ranging from 4.9 to 17.1 µM.


Assuntos
Terpenos/química , Terpenos/farmacologia , Xylariales/química , Antibacterianos , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Regiões Árticas , Linhagem Celular Tumoral , Meios de Cultura , Ensaios de Seleção de Medicamentos Antitumorais , Fermentação , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular
15.
Braz J Med Biol Res ; 52(11): e8549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31664304

RESUMO

The published data on the association between MCP-1 -2518A>G polymorphism and asthma susceptibility are inconclusive. Therefore, we performed a meta-analysis to estimate the impact of MCP-1 -2518A>G polymorphism on asthma susceptibility. PubMed, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases were used to identify eligible studies. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to calculate the strength of association. Sensitivity analysis was performed to evaluate the influence of individual studies on the estimates of overall effect, and funnel plots and Egger's test were used to assess publication bias. Eight publications with 1562 asthma patients and 1574 controls were finally identified. Overall, we found no significant association between MCP-1 -2518A>G polymorphism and asthma susceptibility in any of the genetic model comparisons. After stratified analysis by ethnicity, the results showed that a significant association with asthma risk was found in Caucasians in all the genetic models. However, a protective association was found in Africans under the dominant model. The present meta-analysis suggested that the MCP-1 -2518 A>G polymorphism is a risk factor for asthma in the Caucasian population, nevertheless it has a protective effect in the African population.


Assuntos
Asma/genética , Quimiocina CCL2/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Frequência do Gene/genética , Humanos , Fatores de Proteção , Fatores de Risco
16.
Med Image Anal ; 57: 237-248, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31352126

RESUMO

Classification of benign-malignant lung nodules on chest CT is the most critical step in the early detection of lung cancer and prolongation of patient survival. Despite their success in image classification, deep convolutional neural networks (DCNNs) always require a large number of labeled training data, which are not available for most medical image analysis applications due to the work required in image acquisition and particularly image annotation. In this paper, we propose a semi-supervised adversarial classification (SSAC) model that can be trained by using both labeled and unlabeled data for benign-malignant lung nodule classification. This model consists of an adversarial autoencoder-based unsupervised reconstruction network R, a supervised classification network C, and learnable transition layers that enable the adaption of the image representation ability learned by R to C. The SSAC model has been extended to the multi-view knowledge-based collaborative learning, aiming to employ three SSACs to characterize each nodule's overall appearance, heterogeneity in shape and texture, respectively, and to perform such characterization on nine planar views. The MK-SSAC model has been evaluated on the benchmark LIDC-IDRI dataset and achieves an accuracy of 92.53% and an AUC of 95.81%, which are superior to the performance of other lung nodule classification and semi-supervised learning approaches.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Aprendizado de Máquina Supervisionado , Tomografia Computadorizada por Raios X/métodos , Algoritmos , Conjuntos de Dados como Assunto , Humanos , Neoplasias Pulmonares/patologia , Lesões Pré-Cancerosas/diagnóstico por imagem , Radiografia Torácica , Nódulo Pulmonar Solitário/patologia
17.
Nat Prod Res ; : 1-7, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31232106

RESUMO

Three new sesquiterpene quinones/hydroquinones, 20-demethoxy-20-isopentylaminodactyloquinone D (1), 20-demethoxy-20-isobutylaminodactyloquinone D (2), and 19-methoxy-dictyoceratin-A (3), and five known related compounds (4-8) were isolated from the marine sponge Dactylospongia elegans. Their structures were elucidated by spectroscopic analysis, ECD calculation, single-crystal X-ray diffraction, and comparison with the literature. Compounds 3 and 5-8 exhibited activities against the human cancer cell lines DU145, SW1990, Huh7, and PANC-1 with IC50 values ranging from 2.33 to 37.85 µM.

18.
Cell Cycle ; 18(15): 1727-1744, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31204561

RESUMO

MicroRNAs (miRNAs) have been demonstrated to participate in a variety of human cancers by functioning as post-transcriptional regulators of oncogenes or antioncogenes including non-small cell lung cancer (NSCLC). The aim of the current study was to identify the role of miR-422a in NSCLC via sulfatase 2 (SULF2) to further elucidate the mechanism of NSCLC. Initially, the expression of miR-422a and SULF2 was determined in NSCLC tissues and cells. The role of miR-422a in NSCLC was identified in relation with a miR-422a mimic or inhibitor, siRNA against SULF2 and TGF-ß1. The regulatory effects of miR-422a were examined following detection of the related epithelial mesenchymal transition (EMT)-related genes, and the apoptosis-related genes and evaluation of their cellular biological functions. The expression pattern of miR-422a, SULF2, and the TGF-ß/SMAD pathway-related genes was detected to elucidate the mechanism by which miR-422a influences the progression of NSCLC. Finally, xenograft tumors in nude mice were observed for tumorigenicity evaluation purposes. Our results showed that miR-422a was poorly expressed while SULF2 was highly expressed in NSCLC. Dual luciferase reporter gene assay further verified that miR-422a targeted SULF2. Altogether, this study demonstrated that miR-422a downregulated SULF2 to inhibit the TGF-ß/SMAD pathway. NSCLC cell proliferation, migration, invasion, colony formation, EMT and tumorigenesis were all inhibited while apoptosis was promoted upon restoration of miR-422a or silencing of SULF2. However, the activation of the TGF-ß/SMAD pathway was determined to reverse the tumor-suppressive effects of si-SULF2. miR-422a restoration, which ultimately inhibited the progression of NSCLC by suppressing the TGF-ß/SMAD pathway via SULF2.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Proteínas Smad/metabolismo , Sulfatases/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Biologia Computacional , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Inativação Gênica , Genes Supressores de Tumor , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Nus , MicroRNAs/genética , RNA Interferente Pequeno , Transdução de Sinais/genética , Proteínas Smad/genética , Sulfatases/genética , Fator de Crescimento Transformador beta1/farmacologia , Transplante Heterólogo
19.
Sensors (Basel) ; 19(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146328

RESUMO

Epidermal electronic sensors (EESs) possess great advantages in the real-time and enduring monitoring of human vital information compared to the traditional medical device for intimately making contact with human skin. Skin strain is a significant and effective routine to monitor motion, heart rate, wrist pulse, and skin growth in wound healing. In this paper, a novel skin sensor combined with a ternary conductive nanocomposite (Carbon black (CB)/Decamethylcyclopentasiloxane (D5)/Silbione) and a two-stage serpentine connector is designed and fabricated to monitor skin strain. The ultrasoft (~2 kPa) and adhesive properties of the ternary conductive nanocomposite ensure the capacity of the EES to intimately couple with human skin in order to improve accuracy with a relative error of 3.39% at strain 50% as well as a large strain range (0~50%) and gauge factor (GF ~2.5). The millimeter scale EES (~5 mm × 1 mm × 100 µm), based on the micro-nano fabrication technique, consisted of a two-stage serpentine connector and screen print of the ternary conductive nanocomposite. EESs with high comprehensive performance (electrical and mechanical properties) are fabricated to confirm the analytical results and monitor the motion of a human hand. The good agreement between experimental and analytical results paves the way for bettering monitoring of skin growth during wound healing in order to avoid necrosis and scarring. This EES in monitoring the motion of a human exhibit presents a promising application for assisting prosthetic movement.


Assuntos
Epiderme/patologia , Monitorização Fisiológica , Dispositivos Eletrônicos Vestíveis , Adesividade , Condutividade Elétrica , Mãos/fisiologia , Humanos , Movimento , Nanocompostos/química , Desenho de Prótese , Fuligem/análise , Viscosidade
20.
J Am Chem Soc ; 141(20): 8372-8380, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31060356

RESUMO

Structurally complex and bioactive ent-kaurane diterpenoids have well-characterized biological functions and have drawn widespread attention from chemists for many decades. However, construction of highly oxidized forms of such diterpenoids still presents considerable challenges to synthetic chemists. Herein, we report the first total syntheses of C19 oxygenated spiro-lactone ent-kauranoids, including longirabdiol, longirabdolactone, and effusin. A concise synthesis of the common intermediate used for all three syntheses was enabled via three free-radical-based reactions: (1) a newly devised tandem decarboxylative cyclization/alkenylation sequence that forges the cis-19, 6-lactone concomitantly with vicinal alkenylation, (2) a Ni-catalyzed decarboxylative Giese reaction that constructs C10 quaternary center stereoselectively, and (3) a vinyl radical cyclization that generates a rigid bicyclo[3.2.1]octane. A series of late-stage oxidations from the common intermediate then provided each of the natural products in turn. Further biological evaluation of these synthetic natural products reveals broad anticancer activities.


Assuntos
Dicetopiperazinas/síntese química , Diterpenos de Caurano/síntese química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ciclização , Descarboxilação , Dicetopiperazinas/farmacologia , Diterpenos de Caurano/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Esterificação , Humanos , Oxirredução , Estereoisomerismo
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