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1.
Int J Cancer ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32406930

RESUMO

EGFR is an oncogene with a high frequency of activating mutations in non-small cell lung cancer (NSCLC). EGFR inhibitors have been FDA-approved for NSCLC and have shown efficacy in patients with certain EGFR mutations. However, only 9-26% of these patients achieve objective responses. In this study, we developed an EGFR gene signature based on The Cancer Genome Atlas (TCGA) RNA-seq data of lung adenocarcinoma (LUAD) to direct the preselection of patients for more effective EGFR-targeted therapy. This signature infers baseline EGFR signaling pathway activity (denoted as EGFR score) in tumor samples, which is associated with tumor sensitivity to EGFR inhibitors and other tyrosine kinase inhibitors (TKIs). EGFR score predicted sensitivity of lung cancer cell lines to Erlotinib, Gefitinib and Sorafenib. Importantly, EGFR score calculated from pretreated samples was associated with patient response to Gefitinib and Sorafenib in lung cancer. Additionally, integration of the EGFR signature with TCGA LUAD data showed that it accurately predicted functional effects of different somatic EGFR mutations, and identified other mutations affecting EGFR pathway activity. Finally, using cancer cell line and clinical trial data, the EGFR score was associated with patient response to TKIs in liver cancer and other cancer types. The EGFR signature provides a useful biomarker that can expand the application of EGFR inhibitors or other TKIs and improve their treatment efficacy through patient stratification. This article is protected by copyright. All rights reserved.

2.
iScience ; 23(5): 101089, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32387961

RESUMO

Although Li-metal anodes are extremely attractive owing to the ultrahigh theoretical specific capacity, the low Coulombic efficiency and severe safety hazards resulting from uncontrollable Li dendrites growth hinder their widespread implementation. Herein, we propose a novel design of Ni macropore arrays for the functional Li deposition host. Benefiting from the regulated electric field distribution, Li nucleation and growth can be well confined within conductive Ni macropores. Consequently, the Ni macropore array electrode exhibits stable Li deposition behavior, i.e., high Coulombic efficiency of above 97% over 400 cycles for 1.0 mAh cm-2. Most importantly, the LiFePO4 || Li-Ni macropore arrays full cell also shows greatly enhanced cycling stability (90.3 mAh g-1 at 1 C after 700 cycles), holding great promise for high-performance rechargeable Li metal batteries.

3.
Medicine (Baltimore) ; 99(18): e19738, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358347

RESUMO

RATIONALE: Scrotal swelling is a rare complication of acute pancreatitis. It had been explained by fluid accumulation in scrotum originated from abdomen. Here we demonstrated a case of recurrent pancreatitis with hydrocele caused by impaired testicular venous drainage. PATIENT CONCERNS: A 53-year-old man presented with sudden onset epigastric pain after an alcohol binge. Recurrent acute pancreatitis was confirmed by medical history, physical examination, elevated lipase level and abdominal computed tomography (CT) scan. Right scrotal swelling was noticed on the next day. DIAGNOSIS: The scrotal ultrasonography demonstrated fluid accumulation around the testis and varicocele consistent with scrotal hydrocele. CT scans of the abdomen and pelvis showed encasement of the right testicular vein by pancreatic phlegmon. INTERVENTIONS: The patient was subject to Nulla per os, hydration, and opioid analgesics for pancreatitis. No intervention was performed for scrotal swelling. OUTCOMES: Hydrocele gradually resolved along with acute pancreatitis. LESSONS: Pancreatic phlegmon compromised testicular venous return which led to scrotal hydrocele and posed a threat to fertility. The study has provided a novel pathologic linkage. This complication should be taken into account.


Assuntos
Pancreatite/etiologia , Hidrocele Testicular/etiologia , Testículo/irrigação sanguínea , Doenças Vasculares/complicações , Doença Aguda , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
4.
Artigo em Inglês | MEDLINE | ID: mdl-32361787

RESUMO

INTRODUCTION: EGFR mutations occur most frequently in patients with lung adenocarcinoma in East Asia. However, the prognostic and therapeutic impact of co-mutational status of EGFR and tumor suppressor genes is not fully understood. This study aims to provide a deeper understanding of lung adenocarcinoma patients with co-mutation of EGFR and tumor suppressor genes. METHODS: From November 2009 to May 2016, 675 patients with lung adenocarcinoma who underwent complete surgery were included in this study. Samples were collected and pathologically examined. Whole-exome sequencing was performed on 197 samples, while direct sequencing of major driver genes, including EGFR, KRAS, ERBB2 and BRAF and Ion-torrent targeted sequencing of tumor suppressor genes, including TP53, KEAP1, MGA, NF1, RB1, SMARCA4 and STK11, were performed on 478 samples. Tumor mutational burden was calculated and survival analyses were performed. RESULTS: The frequency of EGFR and TP53 mutation was 409 (60.6%) and 215 (31.9%), respectively. Co-mutation of EGFR and TP53 occured in 151 patients (22.4%), while co-mutation of EGFR and at least one tumor suppressor gene occured in 184 patients (27.3%). Compared with patients with only EGFR mutations, patients with co-mutations of EGFR and TP53 had a higher tumor mutational burden (p = 0.007) and worse recurrence-free survival (p = 0.010), while patients with co-mutations of EGFR and at least one tumor suppressor gene had a higher tumor mutational burden (p = 0.007), worse recurrence-free survival (p = 0.016) and worse overall survival (p = 0.018). CONCLUSIONS: Lung adenocarcinoma patients harboring EGFR and co-mutational tumor suppressor genes should be regarded as a unique subgroup.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32372138

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) has become the most frequent histologic type of lung cancer in the past several decades. Recent successes with immune checkpoint blockade therapy have demonstrated that the manipulation of the immune system is a very potent treatment for LUAD. This study aims to explore the role of immune-related genes in the development of LUAD and establish a signature that can predict overall survival for LUAD patients. METHODS: To identify the differential expression genes (DEGs) between normal and tumor tissues, we developed an analysis strategy to combine an independent-sample design and a paired-sample design using RNA-seq transcriptomic profiling data of The Cancer Genome Atlas LUAD samples. Further, we selected prognostic markers from DEGs and evaluated their prognostic value in a prediction model. RESULTS: We identified and validated PD1, PDL1 and CTLA4 genes as prognostic markers, which are well-known immune checkpoints, and revealed two new potential prognostic immune checkpoints for LUAD, HHLA2 (logFC = 2.55, FDR = 1.89 × 10-6) and VTCN1 (logFC = -2.86, FDR = 1.72 × 10-11). Furthermore, we identified an 18-gene LUAD prognostic biomarker panel and observed that the classified high-risk group presented a significantly shorter overall survival time (HR = 3.57, p value = 4.07 × 10-10). The prediction model was validated in five independent high-throughput gene expression datasets. CONCLUSIONS: The identified DEG features may serve as potential biomarkers for prognosis prediction of LUAD patients and immunotherapy. Based on that assumption, we identified a gene expression-based immune signature for lung adenocarcinoma prognosis.

6.
Pain Pract ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372561

RESUMO

OBJECTIVES: The ophthalmic branch of the trigeminal nerve is one of the most frequently involved sites of postherpetic neuralgia (PHN). A single-center randomized controlled study was conducted to evaluate the efficacy of local methylcobalamin injection for subacute ophthalmic herpetic neuralgia (SOHN). METHODS: One hundred and five patients with a pain score of 4 or greater were randomized to receive a combination of methylcobalamin and lidocaine via local injection (LM, N=35), intramuscular methylcobalamin and local lidocaine injection (IM, N=35), and oral methylcobalamin tablet and lidocaine local injection (OM, N=35) for four weeks. Multilevel mixed modeling was employed to examine treatment responses. RESULTS: Pain scores were reduced in all groups but this reduction was significantly greater in patients who received local methylcobalamin (6.7 at baseline vs 2.8 at endpoint) when compared with systemic administration (intramuscular 6.8 vs 4.9, oral 6.7 vs 5.1). Clinically relevant reduction of pain (>30%) was seen in 91% of patients in the local methylcobalamin group, a significantly greater proportion than in the systemic groups (66% intramuscular, 57% oral). Analgesic use reduced significantly in the local group (94% at baseline vs 6% at endpoint) but not in systemic groups (intramuscular 97% vs 86%, oral 94% vs 80%). Health-related Quality of Life was higher in the local group than in the systemic groups. In mixed modelling, increased age was associated with a lower response to methylcobalamin. CONCLUSIONS: This study indicates that the local injection of methylcobalamin produces significant pain relief from SOHN and is superior to the systemic administration.

7.
EMBO J ; : e103181, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32368828

RESUMO

N6-methyladenosine (m6 A) is an abundant nucleotide modification in mRNA, known to regulate mRNA stability, splicing, and translation, but it is unclear whether it is also has a physiological role in the intratumoral microenvironment and cancer drug resistance. Here, we find that METTL3, a primary m6 A methyltransferase, is significantly down-regulated in human sorafenib-resistant hepatocellular carcinoma (HCC). Depletion of METTL3 under hypoxia promotes sorafenib resistance and expression of angiogenesis genes in cultured HCC cells and activates autophagy-associated pathways. Mechanistically, we have identified FOXO3 as a key downstream target of METTL3, with m6 A modification of the FOXO3 mRNA 3'-untranslated region increasing its stability through a YTHDF1-dependent mechanism. Analysis of clinical samples furthermore showed that METTL3 and FOXO3 levels are tightly correlated in HCC patients. In mouse xenograft models, METTL3 depletion significantly enhances sorafenib resistance of HCC by abolishing the identified METTL3-mediated FOXO3 mRNA stabilization, and overexpression of FOXO3 restores m6 A-dependent sorafenib sensitivity. Collectively, our work reveals a critical function for METTL3-mediated m6 A modification in the hypoxic tumor microenvironment and identifies FOXO3 as an important target of m6 A modification in the resistance of HCC to sorafenib therapy.

8.
Cancer Commun (Lond) ; 40(2-3): 105-118, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32237073

RESUMO

BACKGROUND: Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between the genetic aberrations and clinical features, it remains one of the major challenges to predict prognosis and stratify patients for determining personalized therapy in this disease. The aim of this study was to develop an effective prognosis prediction model for NB patients. METHODS: We integrated diverse computational analyses to define gene signatures that reflect MYCN activity and chromosomal aberrations including deletion of chromosome 1p (Chr1p_del) and chromosome 11q (Chr11q_del) as well as chromosome 11q whole loss (Chr11q_wls). We evaluated the prognostic and predictive values of these signatures in seven NB gene expression datasets (the number of samples ranges from 94 to 498, with a total of 2120) generated from both RNA sequencing and microarray platforms. RESULTS: MYCN signature was a more effective prognostic marker than MYCN amplification status and MYCN expression. Similarly, the Chr1p_del score was more prognostic than Chr1p status. The activity scores of MYCN, Chr1p_del and Chr11q_del were associated with poor prognosis, while the Chr11q_wls score was linked to good outcome. We integrated the activity scores of MYCN, Chr1p_del, Chr11q_del, and Chr11q_wls and clinical variables into an integrative prognostic model, which displayed significant performance over the clinical variables or each genomic aberration alone. CONCLUSIONS: Our integrative gene signature model shows a significantly improved forecast performance with prognostic and predictive information, and thereby can be served as a biomarker to stratify NB patients for prognosis evaluation and surveillance programs.

9.
ACS Sens ; 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32268729

RESUMO

Nanomaterials of TiO2, (K0.5Na0.5)NbO3, and the TiO2/(K0.5Na0.5)NbO3 nanocomposite were successfully synthesized by a hydrothermal method. Impedance-type humidity sensors were fabricated based on these materials. Our results reveal that the impedance of the TiO2/(K0.5Na0.5)NbO3 sensor changes by 5 orders of magnitude with an ultrahigh sensing response of Sf = 166 470 recorded at 100 Hz in the tested relative humidity (RH) range of 12-94%. This value is almost 2 and 4 orders of magnitude larger than that of the (K0.5Na0.5)NbO3 and TiO2 sensors, respectively. Interestingly, satisfactory response/recovery time (25/38 s, within 5 min), very small hysteresis (<5%), excellent stability, and good repeatability were also achieved in the TiO2/(K0.5Na0.5)NbO3 sensor. The improved sensing properties are ascribed to the synergistic effect of TiO2/(K0.5Na0.5)NbO3 heterojunction, which contributes the impedance that is susceptible to environmental humidity. This work underscores that it is a facile way to boost humidity-sensing performance by constructing proper nanocomposites.

10.
Cells ; 9(4)2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32290365

RESUMO

Compromised pumping function of the corneal endothelium, due to loss of endothelial cells, results in corneal edema and subsequent visual problems. Clinically and experimentally, oxidative stress may cause corneal endothelial decompensation after phacoemulsification. Additionally, in vitro and animal studies have demonstrated the protective effects of intraoperative infusion of ascorbic acid (AA). Here, we established a paraquat-induced cell damage model, in which paraquat induced reactive oxygen species (ROS) production and apoptosis in the B4G12 and ARPE-19 cell lines. We demonstrate that oxidative stress triggered autophagic flux blockage in corneal endothelial cells and that addition of AA ameliorated such oxidative damage. We also demonstrate the downregulation of Akt phosphorylation in response to oxidative stress. Pretreatment with ascorbic acid reduced the downregulation of Akt phosphorylation, while inhibition of the PI3K/Akt pathway attenuated the protective effects of AA. Further, we establish an in vivo rabbit model of corneal endothelial damage, in which an intracameral infusion of paraquat caused corneal opacity. Administration of AA via topical application increased its concentration in the corneal stroma and reduced oxidative stress in the corneal endothelium, thereby promoting corneal clarity. Our findings indicate a perioperative strategy of topical AA administration to prevent oxidative stress-induced damage, particularly for those with vulnerable corneal endothelia.

11.
Perfusion ; : 267659120915140, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32308124

RESUMO

BACKGROUND: Rho-associated protein kinase (ROCK) plays a vital role in the pathogenesis of many cardiovascular diseases. Previous studies have demonstrated that ROCK is overactivated and involved in myocardial ischemia/reperfusion in vivo. But the role of ROCK in circulating leukocytes during myocardial ischemia/reperfusion is not well studied. MATERIAL AND METHODS: This study was performed to evaluate ROCK activity in circulating leukocytes in rats with myocardial ischemia/reperfusion injury. Myocardial ischemia/reperfusion Wistar rats were subjected to 30-min ischemia followed by 180-min reperfusion. ROCK activity in circulating leukocytes was examined by the phosphorylation state of myosin phosphatase targeting subunit 1, a substrate of ROCK. RESULTS: ROCK activity significantly increased in leukocytes in rat ischemia/reperfusion models compared to the sham group. ROCK1 not ROCK2 level in circulating leukocytes was significantly elevated in ischemia/reperfusion. Administration of the selective inhibitor of ROCK, fasudil, significantly reduced myocardial infarct size, myocyte apoptosis, and inflammatory cytokine, including interleukin 6 and tumor necrosis factor α. Furthermore, fasudil upregulated ischemia/reperfusion-induced reduction of nitric oxide production. CONCLUSION: Increased ROCK1 not ROCK2 in circulating leukocytes plays a role in the pathogenesis of myocardial ischemia/reperfusion injury. Inhibition of ROCK1 in circulating leukocytes has an important role in fasudil-induced cardioprotective effects. ROCK1 in circulating leukocytes might be a new biomarker in myocardial ischemia/reperfusion injury.

12.
Autoimmunity ; : 1-9, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32338082

RESUMO

Cytokines and growth factors participate in immune responses, and the pathogenesis of autoimmune diseases. Herein, we simultaneously examined differential levels of 29 circulating factors to determine their associations in female patients with overt autoimmune thyroid disease (AITD). We enrolled 40 patients with Graves' disease (GD), 20 patients with Hashimoto's thyroiditis (HT), and 14 healthy controls. Twenty-nine circulating factors were simultaneously measured. GD patients with low thyroid-stimulating hormone at the time of sample collection were defined as having active GD. B-cell activating factor (BAFF) levels were associated with GD and HT (p = .001 and .001, respectively) and interferon (IFN)-α levels were higher in the HT group than in the control group (p = .021). Significant associations of serum BAFF and tumour necrosis factor (TNF)-α levels with free thyroxin (FT4) were present in HT (r = -0.498, p = .026, and r = 0.544, p = .013, respectively). Meanwhile, there were significant associations of FT4 with interleukin (IL)-4 and eotaxin levels in GD (r = 0.354, p = .025 and r = 0.384, p = .014, respectively). In active GD, serum BAFF and eotaxin level were correlated with FT4 levels (r = 0.465, p = .034, and r = 0.463, p = .035, respectively). In conclusion, BAFF is the best circulating indicator to identify GD and HT among all chosen 29 biomarkers, and it could be used to predict the disease severity in HT and active GD. Meanwhile, IFN-α could be another reliable parameter for recognising HT.

13.
Biomacromolecules ; 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32315168

RESUMO

A hydrolysis-resistant polymer bearing new quasi-choline phosphate (quasi-CP) structures as side groups, poly(2-methacryloyloxyethyl choline methylphosphonate) (PMCPm), was designed and synthesized. Radical polymerization and sub-surface-initiated radical polymerization were used to prepare homopolymer and polymer brush on polymer substrates. Hydrolytic stability and hydrophilicity of the polymer were confirmed by nuclear magnetic resonance and contact angle measurements. Furthermore, the hydration states were investigated using Fourier-transform infrared spectroscopy and differential scanning calorimetry. The similar hydration behavior of PMCPm to poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) sheds light on understanding the interfacial functions of quasi-CP-bearing zwitterionic biomaterials.

14.
Curr Med Sci ; 40(2): 320-326, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337692

RESUMO

Vascular remodeling is an adaptive response to various stimuli, including mechanical forces, inflammatory cytokines and hormones. In the present study, we investigated the role of angiotensin II type 1 receptor (AT1R) and calcium channel in carotid artery remodeling in response to increased biomechanical forces by using the transverse aortic constriction (TAC) rat model. TAC was induced on ten-week-old male Sprague-Dawley rats and these models were treated with AT1R blocker olmesartan (1 mg/kg/day) or/and calcium channel blocker (CCB) amlodipine (0.5 mg/kg/day) for 14 days. After the treatment, the right common carotid artery proximal to the band (RCCA-B) was collected for further assay. Results showed that olmesartan, but not amlodipine, significantly prevented TAC-induced adventitial hyperplasia. Similarly, olmesartan, but not amlodipine, signifcantly prevented vascular infammation, as indicated by increased tumor necrosis factor α (TNF-α) and increased p65 phosphorylation, an indicator of nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) activation in RCCA-B. In contrast, both olmesartan and amlodipine reversed the decreased expression of endothelial nitric oxidase synthase (eNOS) and improved endothelium-dependent vasodilation, whereas combination of olmesartan and amlodipine showed no further synergistic protective effects. These results suggest that AT1R was involved in vascular remodeling and inflammation in response to pressure overload, whereas AT1R and subsequent calcium channel were involved in endothelial dysfunction.

15.
Int J Mol Sci ; 21(7)2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32260319

RESUMO

Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (w/w/w) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that Cmax/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.

16.
Oncol Rep ; 43(5): 1536-1546, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323860

RESUMO

Post­transcriptional mechanisms are an important approach in the treatment of cancer, and may also be hijacked by tumor cells to help adapt to the local microenvironment. Filamin B (FLNB), an actin­binding protein that provides crucial scaffolds for cell motility and signaling, has also been identified as an RNA­binding protein. Recent studies demonstrated that FLNB might play an important role, not only in skeletal development, but also in regulating tumorigenesis; however, the effects of dysregulated expression of FLNB at the molecular level are not clear. In the present study, RNA­sequencing was performed to analyze changes in overall transcriptional and alternative splicing between the knocked­down FLNB and the control in HeLa cells. Decreased FLNB levels resulted in significantly lower apoptosis compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport and cartilage development. Moreover, FLNB regulated alternative splicing of a large number of genes involved in 'cell death' and the 'apoptotic process'. Some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Reverse transcription­quantitative­PCR identified FLNB­regulated transcription and alternative splicing of genes, such as NLR family apoptosis inhibitory protein, interleukin 23 subunit α, metastasis associated lung adenocarcinoma transcript 1, phosphofurin acidic cluster sorting protein 2, bone morphogenetic protein 7, matrix metallopeptidase 13, collagen type II α 1 chain, fibroblast growth factor receptor 2 and vitamin D receptor. The present study is the first study, to the best of the authors' knowledge, to provide transcriptome­wide analysis of differential gene expression and alternative splicing upon FLNB silencing. The present results suggested that FLNB may play an important regulatory role in cervical cancer cell apoptosis via regulation of transcription and alternative splicing, which provide insight for the current understanding of the mechanisms of FLNB­mediated gene regulation.

17.
J Cell Mol Med ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32333497

RESUMO

The short supply of donor corneas is exacerbated by the unsuitability of donors with insufficient endothelial cell density. Few studies have investigated promoting corneal endothelial cell proliferation to increase the endothelial cell density. We hypothesize that pre-transplantation treatment of proliferative tissue-cultivated corneas may increase corneal endothelial cell density. We observed that the airlift cultures were superior to immersion cultures with respect to both transparency and thickness. In this tissue culture system, we observed that lysophosphatidic acid increased the rabbit corneal endothelial cell density, number of BrdU-positive cells and improve wound healing. We also observed an indirect effect of lysophosphatidic acid on corneal endothelial cell proliferation mediated by the stimulation of interleukin-1ß secretion from stromal cells. Human corneal tissues treated with lysophosphatidic acid or interleukin-1ß contained significantly more Ki-67-positive cells than untreated group. The lysophosphatidic acid- or interleukin-1ß-treated cultured tissue remained hexagon-shaped, with ZO-1 expression and no evidence of the endothelial-mesenchymal transition. Our novel protocol of tissue culture may be applicable for eye banks to optimize corneal grafting.

18.
Diagnostics (Basel) ; 10(3)2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197339

RESUMO

At the end of 2019, the novel coronavirus disease (COVID-19), a fast-spreading respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China and has now affected over 123 countries globally [...].

19.
Medicine (Baltimore) ; 99(10): e19465, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150104

RESUMO

The aim of this study was to elucidate the molecular mechanisms and to identify the differential expression of circular RNAs (circRNAs) for steroid-associated osteonecrosis of the femoral head (SONFH) using bioinformatics analysis.circRNA microarray was performed with 3 SONFH tissues and the adjacent normal tissues, and differentially expressed circRNA were identified by limma package in R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery database. In addition, a differentially expressed genes (DEG)-associated circRNA/microRNA (miRNA) interaction was predicted by combination of TargetScan and miRanda, and the circRNA/miRNA interaction network generated by the cytoscape software.A total of 647 differentially expressed circRNAs, including 433 upregulated and 214 downregulated circRNA were identified. The most enriched GO terms for upregulated and downregulated circRNA were extracellular matrix organization and leukocyte activation in biological process; extracellular matrix and spindle pole in cellular component; integrin binding and ATP binding in molecular function, and KEGG pathway enrichment analyses showed that the upregulated and downregulated circRNA were strongly associated with Protein digestion and absorption and Cell cycle. Moreover, a total of 212 differentially expressed messenger RNAs (mRNAs), including 113 upregulated and 99 downregulated genes were identified. In addition, from the analysis of miRNA, long noncoding RNAs, mRNA, and circRNA networks, we found that hsa_circ_0008136 and hsa_circ_0074758 were respectively the upregulated and downregulated circRNA with highest degrees.The identified circRNA and mRNA could be implicated in the progression of human SONFH. The findings could lead to a better understanding of SONFH pathogenesis.


Assuntos
Necrose da Cabeça do Fêmur/genética , RNA Circular/genética , Biologia Computacional , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Regulação para Cima
20.
Pathol Res Pract ; 216(4): 152868, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32111444

RESUMO

BACKGROUND: miR-129-5p has been reported to be abnormally expressed and plays an important role in the progression of various malignancies. However, its role in gliomas and its exact molecular mechanism need further research. METHODS AND MATERIALS: RT-qPCR was performed to evaluate miR-129-5p and HOXC10 mRNA expression levels in tissues and cell lines. Cell proliferation was detected via Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and clone formation assays. Luciferase assays were used to validate the binding of seeds between miR-129-5p and HOXC10. A tumor xenograft model was developed to study the effect of miR-129-5p on glioma growth in vivo. RESULTS: miR-129-5p was expressed at low levels in glioma tissues and cell lines. miR-129-5p overexpression inhibited glioma proliferation, migration and invasion. miR-129-5p negatively and directly targeted HOXC10. At the same time, HOXC10 was upregulated in glioma cancer, and HOXC10 knockdown inhibited cell proliferation, migration and invasion. CONCLUSION: miR-129-5p inhibits glioma development by altering HOXC10 expression and may therefore serve as a new diagnostic marker and therapeutic target for glioma in the future.

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