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1.
Cell Signal ; : 109553, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32018056

RESUMEN

Macrophage polarization is the driving force of various inflammatory diseases, especially those involved in M1/M2 imbalance. N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in eukaryotes that affects multiple biological processes, including those involved developmental arrest and immune response. However, the role of m6A in macrophage polarization remains unclear. This study found that FTO silencing significantly suppressed both M1 and M2 polarization. FTO depletion decreased the phosphorylation levels of IKKα/ß, IκBα and p65 in the NF-κB signaling pathway. The expression of STAT1 was downregulated in M1-polarized macrophages while the expression of STAT6 and PPAR-γ decreased in M2 polarization after FTO knockdown. The actinomycin D experiments showed that FTO knockdown accelerated mRNA decay of STAT1 and PPAR-γ. Furthermore, the stability and expression of STAT1 and PPAR-γ mRNAs increased when the m6A reader YTHDF2 was silenced. In conclusion, our results suggest that FTO knockdown inhibits the NF-κB signaling pathway and reduces the mRNA stability of STAT1 and PPAR-γ via YTHDF2 involvement, thereby impeding macrophage activation. These findings indicated a previously unrecognized link between FTO and macrophage polarization and might open new avenues for research into the molecular mechanisms of macrophage polarization-related diseases.

2.
J Cell Mol Med ; 2020 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-31970862

RESUMEN

Atherosclerosis is regarded as a chronic progressive inflammatory disease and is a basic pathophysiological process in coronary artery disease which is life threatening in clinic. The formation of foam cell plays a key role in the pathogenesis of atherosclerosis. OxLDL is a significant factor in progression of coronary artery disease. Our studies have demonstrated that USP14 promotes cancer development and mediates progression of cardiac hypertrophy and LPS-induced inflammation. However, the underlying mechanism of USP14 is unknown. In this study, we found that the inhibition of USP14 significantly suppressed the oxLDL uptake, subsequently decreased the foam cell formation. Surprisingly, USP14 has an effect on the expression of CD36 but not SR-A, ABCA1, Lox-1, ABCG1 and SR-Bl. Furthermore, USP14 stabilizes CD36 protein via cleaving the ubiquitin chain on CD36. Blocking CD36 activation using antibody-dependent blocking assay remarkably attenuated the function of USP14 on the formation of foam cell. In summary, our results suggested that the inhibition of USP14 decreases foam cell formation by down-regulating CD36-mediated lipid uptake and provides a potential therapeutic target for atherosclerosis.

3.
Mol Med Rep ; 21(2): 959-968, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31974603

RESUMEN

Dental pulp inflammation is a pathological process characterized by local lesions in dental pulp and the accumulation of inflammatory mediators. DNA methylation of cytosine residues is a key epigenetic modification that is essential for gene transcription, and plays pivotal roles in inflammatory reactions and immune responses. However, the function of cytosine DNA methylation in the innate immune defense against the inflammation of dental pulp is poorly understood. To investigate the effect of DNA methylation in inflamed dental pulp upon innate immune responses, expression levels of the DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) in human dental pulp cells (hDPCs) after lipopolysaccharide (LPS) stimulation were evaluated by western blotting and reverse transcription­quantitative (RT­q) PCR. Only DNMT1 expression was decreased, while the transcription of inflammatory cytokines was increased. In the immune responses of LPS­induced hDPCs, the results of RT­qPCR and ELISA showed that DNMT1 knockdown promoted the production of the pro­inflammatory cytokines, interleukin (IL)­6 and IL­8. Western blotting demonstrated that DNMT1 knockdown increased the phosphorylation levels of IKKα/ß and p38 in the NF­κB and MAPK signaling pathways, respectively. Furthermore, MeDIP and RT­qPCR analysis demonstrated that the 5­methylcytosine levels of the IL­6 and TNF receptor­associated factor 6 (TRAF6) promoters were significantly decreased in DNMT1­deficient hDPCs. Taken together, these results indicated that the expression of DNMT1 was decreased after LPS stimulation in hDPCs. DNMT1 depletion increased LPS­induced cytokine secretion, and activated NF­κB and MAPK signaling; these mechanisms may involve the decreased methylation levels of the IL­6 and TRAF6 gene promoters. This study emphasized the role of DNMT1­dependent DNA methylation on the inflammation of LPS­infected dental pulp and provides a new rationale for the investigation of the molecular mechanisms of inflamed dental pulps.

4.
Angew Chem Int Ed Engl ; 59(5): 1980-1984, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31749276

RESUMEN

A cyclic (R2 SnAu)3 anion (3- , R2 Sn=2,2,5,5-tetrakis(trimethylsilyl)-1-stannacyclopentane-1,1-diyl) has been synthesized as a stable blue salt with K+ (THF)6 through the reaction of stable dialkylstannylene 1 with R'3 PAuCl (R'=Et, Ph) followed by the reduction with KC8 . Crystallographic and NMR analysis shows that the six-membered (SnAu)3 ring of 3- is planar and highly symmetric with an equal distance of six Au-Sn bonds. A UV/Vis spectrum of 3- in hexane reveals an intense absorption maximum at 598 nm. While cyclic Au3 - with four valence electrons is known as unstable anti-aromatic anion, 3- with three divalent tin ligands is stable σ aromatic anion with an unprecedented Möbius orbital array as predicted by the perturbation MO and CCSD analysis of 3- .

5.
J Cell Physiol ; 235(4): 3823-3834, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31612488

RESUMEN

Neuroblastoma (NBL) is the most frequently encountered extracranial solid neoplasm and impacts significantly on the survival of patients, especially in cases of advanced tumor stage or relapse. A long noncoding RNA (lncRNA) signature to predict the survival of patients with NBL is proposed in this paper. Differentially expressed lncRNA (DElncRNA) was selected using the Limma plus Voom package in R based on the RNA-sequencing data downloaded from the Therapeutically Applicable Research To Generate Effective Treatments database and Genotype-Tissue Expression database. Univariate cox regression analysis, least absolute shrinkage and selection operator regression analysis, and multivariate cox regression analysis were conducted to identify candidate DElncRNAs for the risk signature. Consequently, 10 DElncRNAs were designated as candidate DElncRNAs for the risk signature. Time-dependent receiver operating characteristic curves and Kapan-Meier survival curves confirmed the efficacy of the risk signature in predicting the survival of patients with NBL (area under the curve = 0.941; p ≤ .001). One of the DElncRNA constituent subparts (LINC01010) was significantly associated with the survival outcome of patients with NBL in GSE62564 (p = .004). Thus, a risk signature comprising 10 DElncRNAs was identified as effective for individual risk stratification and the survival prediction outcomes of patients with NBL.

6.
Med Phys ; 47(1): 190-200, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31661161

RESUMEN

PURPOSE: While cone beam computed tomography (CBCT) is able to provide patient anatomical information, its image quality is severely degraded due to scatter contamination, which degrades the accuracy of CBCT-based dose distribution estimation in proton therapy. In this work, we combined two existing scatter kernel correction methods: the point-spread function (PSF)-based scatter kernel derivation method and the fast adaptive scatter kernel superposition (fASKS) model, and evaluated the impact of the modified fASKS (mfASKS) correction on the accuracy of proton dose distribution estimation. To evaluate feasibility of the mfASKS approach using accurate scatter distributions, both Monte Carlo simulations and experiments were performed for an on-board CBCT machine integrated with a proton therapy machine. METHODS: We developed a strategy to modify central intensity, constant intensity, and amplitude of the scatter kernels derived from PSFs for the fASKS model. A parameter required for the fASKS model was derived by optimizing uniformity in the mfASKS-corrected reconstructed images. Subsequently, the mfASKS model was used to remove scatter in CBCT imaging. We quantitatively compared the Hounsfield Unit (HU) and proton stopping power ratio (SPR) images for five different phantoms. To assess improvement of dose calculation accuracy, a series of proton treatment plans were produced using the CBCT images with and without the mfASKS correction. RESULTS: The accuracies of both HU and SPR intensity quantifications are improved as a result of the mfASKS correction. Mean absolute water-equivalent path length difference to the true value decreases from 10.3 to 0.934 mm for the Gammex phantom (simulation). At the same time, mfASKS is able to offer more accurate dose distributions, especially at the distal fall-off region where noticeable dose overestimation is observed in the uncorrected scenario. Mean absolute relative error of proton range in the pelvic phantom improves from 5.03% to 2.57% (experiment). CONCLUSIONS: mfASKS enables more accurate CBCT-based proton dose calculation. This technique has significant implications in image-guided radiotherapy and dose verifications in adaptive proton therapy.

7.
Cancer Chemother Pharmacol ; 85(1): 95-103, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31676986

RESUMEN

PURPOSE: The present study was aimed at assessing the value of serum NGAL in identifying early acute kidney injury induced by HDMTX. METHODS: Children aged 1-14 years with newly diagnosed ALL receiving MTX over 3 g/m2 were enrolled. Serum NGAL concentrations, serum creatinine (Scr) and MTX concentrations were measured. The area under the receiver-operating characteristic curve (ROC) was used for evaluating variables' ability of early diagnosis of AKI. RESULTS: A total of 196 courses of 62 patients were assessed, and 22 courses (11.2%) developed AKI. Twenty-four hours serum NGAL concentrations, 24 h Scr ratio, 48 h Scr ratio, CMTX24 h, CMTX48 h, CMTX72 h were significantly higher in patients with AKI. The combination of 24 h Scr ratio and 24 h serum NGAL had higher value for detecting HDMTX induced AKI compared with the 24 h Scr ratio. And the combination had similar value for detecting HDMTX induced AKI compared with the 48 h Scr ratio. After 48 h, CMTX48 h had a satisfying accuracy in predicting AKI. The proportion of post-HDMTX sepsis in patients with AKI was significantly higher than that in patients without AKI. CONCLUSIONS: Serum NGAL levels could be used as a marker in identifying the direct kidney tubular damage induced by HDMTX. The combination of 24 h Scr ratio and 24 h serum NGAL had higher value for early diagnosis of HDMTX associated AKI compared with the 24 h Scr ratio.

8.
Arch Oral Biol ; 111: 104637, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31884335

RESUMEN

OBJECTIVE: The aim of this study was to evaluate whether individual genetic factors involved in amelogenesis, the immune response and water channel proteins may increase the susceptibility to Molar-Incisor Hypomineralization (MIH) in Chinese children. DESIGN: DNA samples were collected from 86 cases with MIH cases and 344 controls. Sixteen single-nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was performed to assess association between SNPs and the risk of MIH. RESULTS: Our results showed that the risk of MIH in the rs13115627-AA genotype carriers and the rs1784418-TT genotype carriers were significantly higher than that among those with the rs13115627-GG genotype (OR (95 % CI)) = 4.942 (0.658-37.131) and the rs1784418-CT genotype (OR (95 % CI)) = 2.023 (1.63-3.521). The population with the rs1800972-CC genotype and the rs1800972-C allele had a higher risk to develop MIH, OR (95 % CI) = 2.284 (1.267-4.115), OR (95 % CI) = 2.427 (1.493-3.953) respectively. In the Aquaporin 5(AQP5) gene, we individually analyzed two SNPs, rs1996315 and rs923911. We found no significant associations between them and MIH. However, in the analysis of the gene-gene interactions, we discovered a significant two-locus model (P = 0.023) involving rs1996315 and rs923911. Participants with the rs1996315-AG and rs923911-AC genotypes had the highest MIH risk, compared to participants with the rs1996315-GG and rs923911-CC genotypes, OR (95 % CI) = 3.603 (1.147-11.318). CONCLUSION: This study showed that genetic variants in the AMBN, MMP20 and DEFB1 genes may contribute to MIH in the permanent dentition of children. Moreover, interactions among AQP5 gene may also increase the MIH susceptibility.


Asunto(s)
Acuaporina 5/genética , Hipoplasia del Esmalte Dental/genética , Incisivo , Diente Molar , Amelogénesis , Estudios de Casos y Controles , Niño , Proteínas del Esmalte Dental , Humanos , Polimorfismo de Nucleótido Simple , Prevalencia , beta-Defensinas
9.
Yi Chuan ; 41(12): 1099-1109, 2019 Dec 20.
Artículo en Chino | MEDLINE | ID: mdl-31857281

RESUMEN

Somatic cell nuclear transfer (SCNT) is the only reproductive engineering technique that can confer genomic totipotency on somatic cell. SCNT is of great significance for animal germplasm conservation, animal husbandry development, and biomedical research. Although many research advances have been made in this technology, the developmental rate of SCNT mammalian embryos is very low, which seriously limits the application of SCNT in animal husbandry and biomedicine. The primary reason for the low efficiency of cloned embryos is somatic cell reprogramming errors or incomplete reprogramming. These errors or incompleteness present as the abnormal expression of imprinted gene Xist, abnormal DNA methylation, and abnormal histone modification. In this review, we summarize the main factors that influence the low development efficiency of mammalian cloned embryos to provide theoretical reference for the research and practice of improving somatic cell cloning efficiency.


Asunto(s)
Reprogramación Celular , Epigénesis Genética , Técnicas de Transferencia Nuclear , Animales , Clonación de Organismos , Metilación de ADN , Embrión de Mamíferos , Desarrollo Embrionario , Mamíferos
10.
J Exp Clin Cancer Res ; 38(1): 476, 2019 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-31775892

RESUMEN

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. The dismal outcome of ICC patients is due to lack of early diagnosis, the aggressive biological behavior of ICC and the lack of effective therapeutic options. Early diagnosis and prognosis of ICC by non-invasive methods would be helpful in providing valuable information and developing effective treatment strategies. METHODS: Expression of microfibrillar-associated protein 5 (MFAP5) in the serum of ICC patients was detected by ELISA. Human ICC specimens were immunostained by MFAP5 antibodies. The growth rate of human ICC cell lines treated with MFAP5 or MFAP5 shRNAs was examined by CCK8 and colony formation assays. Cell cycle analysis was performed with PI staining. The effect of MFAP5 inhibition was assessed by xenograft models in nude mice. RNA-seq and ATAC-seq analyses were used to dissect the molecular mechanism by which MFAP5 promoted ICC aggressiveness. RESULTS: We identified MFAP5 as a biomarker for the diagnosis and prognosis of ICC. Upregulated MFAP5 is a common feature in aggressive ICC patients' tissues. Importantly, MFAP5 level in the serum of ICC patients and healthy individuals showed significant differential expression profiles. Furthermore, we showed that MFAP5 promoted ICC cell growth and G1 to S-phase transition. Using RNA-seq expression and ATAC-seq chromatin accessibility profiling of ICC cells with suppressed MFAP5 secretion, we showed that MFAP5 regulated the expression of genes involved in the Notch1 signaling pathway. Furthermore, FLI-06, a Notch signaling inhibitor, completely abolished the MFAP5-dependent transcriptional programs. CONCLUSIONS: Raised MFAP5 serum level is useful for differentiating ICC patients from healthy individuals, and could be helpful in ICC diagnosis, prognosis and therapies.

11.
World J Clin Cases ; 7(21): 3671-3682, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31750352

RESUMEN

BACKGROUND: Primitive neuroectodermal tumors are rare, highly malignant small round cell tumors belonging to the Ewing sarcoma family. The purpose of this article is to present clinical manifestation, histology, treatment, and prognosis of two primitive neuroectodermal tumors (PNETs) in extremely rare anatomic locations, the abdominal wall and vulva. CASE SUMMARY: Case 1 was a 66-month-old girl with lesions on the abdominal wall; tumor size was about 3.4 cm × 6.1 cm × 2 cm. The patient underwent radical resection of the tumor. After the operation, an alternating vincristine, doxorubicin, and cyclophosphamide/ifosfamide and etoposide (IE) regimen was given for eight cycles, and the patient survived for 66 mo without progression. Case 2 was a 40-month-old girl, with a vulvar lesion; tumor size was about 3.3 cm × 5 cm × 2.5 cm. The tumor was partially resected by surgery. The family left treatment after two cycles of vincristine, pirarubicin, and cyclophosphamide/IE chemotherapy, and the patient died at home six months after surgery. CONCLUSION: PNET is a rare, fast-growing, highly malignant tumor that requires histologic and molecular analyses for exact diagnosis, and multimodal treatment is required to achieve a good prognosis.

12.
BMJ Open ; 9(10): e028464, 2019 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-31672709

RESUMEN

INTRODUCTION: Postoperative pulmonary complications (PPCs), strongly associated with higher mortality risk, can develop in up to 58% of patients undergoing abdominal surgery. More and more evidence shows that the use of a lung-protective ventilation strategy has a lung protection effect in patients undergoing abdominal surgery, however, the role of positive end-expiratory pressure (PEEP) during the intraoperative period in preventing PPCs for laparoscopic surgery is not clearly defined. METHODS AND ANALYSIS: A total of 208 patients with a high risk of PPC, undergoing laparoscopic abdominal surgery, will be enrolled and randomised into a standard PEEP (6-8 cm H2O) group and a low PEEP (≤2 cm H2O) group. Both groups will receive a fraction of inspired oxygen of 0.50 and a tidal volume of 8 mL/kg ideal body weight (IBW). Standard perioperative fluid management and analgesic treatments are applied in both groups. The primary end point is PPC within 7 days after surgery. Secondary end points are the modified Clinical Pulmonary Infection Score, postoperative extrapulmonary complications, postoperative surgical complications, intensive care unit length of stay, hospital length of stay, 30-day mortality. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medicine College) (registration number KY2018026) on 22 October 2018. The first participant was recruited on 15 April 2019 and the estimated completion date of the study is October 2021. The results of this trial will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: http://www.chictr.org.cn, ID: ChiCTR1800019865. Registered on 2 December 2018; preresults.

13.
Materials (Basel) ; 12(21)2019 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-31731493

RESUMEN

In this study, the influence of rotary-die equal channel angular pressing (RD-ECAP) processing on the mechanical properties and rolling formability of AZ91 alloys was investigated. The as-cast and pre-homogenized AZ91 alloys were pre-processed by RD-ECAP for 16 passes at 573 K and subjected to post-ECAP rolling at 573 K with a rolling speed of 10 m/min. The microstructure and deformation characteristics of the AZ91 alloys were characterized. Results demonstrated that fine-grained AZ91 alloys with improved strength and ductility were obtained via the high-pass RD-ECAP processing, indicating a good plastic formability. The ECAP-ed alloys were easily rolled at 573 K from 4.5 mm to 1.1 mm in thickness without edge cracking. After rolling, heterogeneous grain structures were observed with large numbers of twins and shear bands that created strong basal textures. The rolled AZ91 alloys exhibited higher tensile strength and appropriate elongation. The post-ECAP rolling was successfully used in the high productivity of AZ91 rolled plates with good mechanical properties.

14.
J Cell Mol Med ; 23(11): 7617-7631, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31557396

RESUMEN

Exosomes are served as substitutes for stem cell therapy, playing important roles in mediating heart repair during myocardial infarction injury. Evidence have indicated that lipopolysaccharide (LPS) pre-conditioning bone marrow-derived mesenchymal stem cells (BMSCs) and their secreted exosomes promote macrophage polarization and tissue repair in several inflammation diseases; however, it has not been fully elucidated in myocardial infarction (MI). This study aimed to investigate whether LPS-primed BMSC-derived exosomes could mediate inflammation and myocardial injury via macrophage polarization after MI. Here, we found that exosomes derived from BMSCs, in both Exo and L-Exo groups, increased M2 macrophage polarization and decreased M1 macrophage polarization under LPS stimulation, which strongly depressed LPS-dependent NF-κB signalling pathway and partly activated the AKT1/AKT2 signalling pathway. Compared with Exo, L-Exo had superior therapeutic effects on polarizing M2 macrophage in vitro and attenuated the post-infarction inflammation and cardiomyocyte apoptosis by mediating macrophage polarization in mice MI model. Consequently, we have confidence in the perspective that low concentration of LPS pre-conditioning BMSC-derived exosomes may develop into a promising cell-free treatment strategy for clinical treatment of MI.

15.
Iran J Pharm Res ; 18(2): 995-1009, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31531080

RESUMEN

Today, an increase in vancomycin dose has been proposed to ensure efficacy. However, the risk of nephrotoxicity will increase with the dose. The aim of this study was to evaluate the dosage regimens of vancomycin in pediatric patients based on pharmacokinetics/pharmacodynamics (PK/PD) and to optimize dosage individualization. Population pharmacokinetics analysis was performed on 155 Chinese children (aged 1 month to 16 years), which were divided into various renal function subpopulations. Monte Carlo simulation was carried to evaluate the efficacy and safety of vancomycin dosage regimens on each subpopulation. Compared with children with normal renal function as glomerular filtration rate (GFR) ≥ 90 mL/min·1.73 m2, the clearance of vancomycin decreased by 39.4% and the half life increased 1.74 fold respectively in children with moderate renal inadequacy (30 ≤ GFR < 60 mL/min·1.73 m2). When vancomycin was administered as conventional dosage (40-60mg·kg-1·d-1) to against methicillin-resistant staphylococcus aureus (MRSA) with higher MICs of 1-2 mg·L-1 for children with normal renal function, the probability of efficacy target attainment ( PTA) at AUC0-24h/MIC ≥ 400 (where AUC is the area under curve and MIC is the minimum inhibitory concentration) achieved ≤ 63.64%. While vancomycin dosage exceeded 70mg·kg-1·d-1 for children with normal renal function, 50mg·kg-1·d-1 for mild renal inadequacy (60 ≤ GFR < 90 mL/min·1.73 m2), 30 mg·kg-1·d-1 for moderate renal inadequacy respectively, the PTA at trough concentration above 20 mg·L-1 achieved > 20%, that not to be suggested for high risk of nephrotoxicity. Considering both efficacy and safety, the conventional vancomycin dosage is not enough and adjustable interval is narrow for pediatric patients with MIC 1-2 mg·L-1 MRSA infection and normal renal function.

16.
Front Chem ; 7: 584, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31475141

RESUMEN

A new series of 3-substituted 4-methylene-quinazolinthiones and 4-methylene-quinazolinones were synthesized in moderate to excellent yield through a simple reaction of 2-aminoacetophenones with isocyanates or isothiocyanates. The reaction shows good tolerance of many important functional groups in the presence of air and water under metal-free conditions. Only water is produced as a coproduct, rendering this "green" methodology a highly versatile and eco-friendly alternative to the existing methods for the construction of the quinazolinone/quinazolinthione framework. We have interpreted the reaction mechanism by use of quantum chemical calculations on the basis of state-of-the-art computational methods SMD-B3LYP-D3(BJ)/BS1//B3LYP/BS1.

17.
J Infect Chemother ; 25(12): 1074-1077, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31401030

RESUMEN

Enterovirus 71 (EV71), a newly emerging life-threatening pathogen induces hand-foot-mouth disease (HFMD), no effective vaccines or specific anti-viral treatments are currently available. In this study, the activity of hederacolchiside C (HSC) against EV71 was investigated, and the antiviral mechanism was explored. HSC displayed apparent antiviral activity in EV71-infected cells probably through activating the host innate immunity. Comparing with EV71-infected group at 24 hpi, the group pretreated with HSC dramatically increased the expression of MAVS, p-IRF3, IRF3 and IFN-ß, the innate immune effectors related to innate immunity. In addition, HSC displayed stronger antiviral activity in EV71-infected suckling mice in comparison with Ribavirin, a broad-spectrum antiviral drug. The results suggest that HSC could have potential as a pharmaceutical drug for HFMD.

18.
Cancer Sci ; 110(10): 3110-3121, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31385398

RESUMEN

Hepatocellular carcinoma (HCC) is one of the most common malignancies and the fourth leading cause of cancer-related death worldwide. Our previous study showed that EYA4 functioned by suppressing growth of HCC tumor cells, but its molecular mechanism is still not elucidated. Based on the results of gene microassay, EYA4 was inversely correlated with MYCBP and was verified in human HCC tissues by immunohistochemistry and western blot. Overexpressed and KO EYA4 in human HCC cell lines confirmed the negative correlation between EYA4 and MYCBP by qRT-PCR and western blot. Transfected siRNA of MYCBP in EYA4 overexpressed cells and overexpressed MYCBP in EYA4 KO cells could efficiently rescue the proliferation and G2/M arrest effects of EYA4 on HCC cells. Mechanistically, armed with serine/threonine-specific protein phosphatase activity, EYA4 reduced nuclear translocation of ß-catenin by dephosphorylating ß-catenin at Ser552, thereby suppressing the transcription of MYCBP which was induced by ß-catenin/LEF1 binding to the promoter of MYCBP. Clinically, HCC patients with highly expressed EYA4 and poorly expressed MYCBP had significantly longer disease-free survival and overall survival than HCC patients with poorly expressed EYA4 and highly expressed MYCBP. In conclusion, EYA4 suppressed HCC tumor cell growth by repressing MYCBP by dephosphorylating ß-catenin S552. EYA4 combined with MYCBP could be potential prognostic biomarkers in HCC.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Proteínas de Unión al ADN/genética , Neoplasias Hepáticas/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Factores de Transcripción/genética , beta Catenina/metabolismo , Adulto , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular , Proteínas de Unión al ADN/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Fosforilación , Pronóstico , Serina/metabolismo , Análisis de Supervivencia , Factores de Transcripción/metabolismo , Transcripción Genética , beta Catenina/química
19.
Biosci Biotechnol Biochem ; 83(11): 2016-2026, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31272310

RESUMEN

Exposure of PC12 cells to 10 mM glutamate caused significant viability loss, cell apoptosis, decreased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as increased levels of malondialdehyde (MDA). In parallel, glutamate significantly increased the intracellular levels of ROS and intracellular calcium. However, pretreatment of the cells with acteoside and isoacteoside significantly suppressed glutamate-induced cellular events. Moreover, acteoside and isoacteoside reduced the glutamate-induced increase of caspase-3 activity and also ameliorated the glutamate-induced Bcl-2/Bax ratio reduction in PC12 cells. Furthermore, acteoside and isoacteoside significantly inhibited glutamate-induced DNA damage. In the mouse model, acteoside significantly attenuated cognitive deficits in the Y maze test and attenuated neuronal damage of the hippocampal CA1 regions induced by glutamate. These data indicated that acteoside and isoacteoside play neuroprotective effects through anti-oxidative stress, anti-apoptosis, and maintenance of steady intracellular calcium.


Asunto(s)
Antioxidantes/química , Antioxidantes/farmacología , Ácido Glutámico/toxicidad , Glicósidos/química , Glicósidos/farmacología , Neurotoxinas/toxicidad , Alcohol Feniletílico/química , Animales , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Supervivencia Celular/efectos de los fármacos , Hipocampo/citología , Hipocampo/efectos de los fármacos , Hipocampo/fisiología , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Malondialdehído/metabolismo , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo
20.
J Agric Food Chem ; 67(30): 8339-8347, 2019 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-31291543

RESUMEN

The dried seeds of Cuminum cyminum L. have been traditionally used as food and medicine. To explore its chemical composition and anti-inflammatory activity, four new compounds (1-4) along with five known compounds (5-9) were isolated from the seeds in the present study. The chemical structures of the new compounds were identified as follows: methyl 3-((7H-purin-2-yl) amino)-3-(4-isopropylphenyl) propanoate (1), 8-(amino(4-isopropylphenyl)methyl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4-oxo-4H-chromene-6-carboxylic acid (2), (3,4,5-trihydroxy-6-((4-isopropylbenzyl)oxy)tetrahydro-2H-pyran-2-yl)methyl (E)-3-(4-propoxyphenyl)acrylate (3), and (3,4,5-trihydroxy-6-((5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)tetrahydro-2H-pyran-2-yl)methyl 3-(4-isopropylphenyl)-2-methoxypropanoate (4). Compound 2, an atypical nitrogen-containing flavonoid, exhibited the most active inhibitory effect on nitride oxide, with IC50 of 5.25 µM in the lipopolysaccharide-stimulated RAW264.7 cell assay. Compound 2 was found to suppress the expression levels of inducible nitric oxide synthase and cyclooxygenase-2. Furthermore, it was revealed that both nuclear factor κB and mitogen-activated protein kinase were involved in the anti-inflammatory process of compound 2.


Asunto(s)
Antiinflamatorios/química , Antiinflamatorios/farmacología , Cuminum/química , Flavonoides/química , Flavonoides/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Frutas/química , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/inmunología , Estructura Molecular , FN-kappa B/genética , FN-kappa B/inmunología , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/inmunología , Células RAW 264.7 , Semillas/química
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