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1.
Telemed J E Health ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674890

RESUMO

Background: User-generated content shared in the online health communities (OHCs) is becoming a valuable resource for researchers to understand patients' decision-making behaviors in the management of their health. Many studies have focused on how to obtain useful information from online reviews in OHCs. Introduction: This study focuses on a telemedicine service called Online Private Doctor (OPD), which is offered by a leading Chinese physician review website (PRW). OPD reviews have not received much attention. By data mining the reviews, our goal is to determine what patients are talking about when they use the OPD service and whether they are satisfied with the service or not. Materials and Methods: We used a Python web crawler to collect 41,029 reviews and 84,510 short reviews (labels) of all 5,645 physicians who offered the OPD service on a PRW (haodf.com) in China. Mixed methods (i.e., a literature review, topic discovery, annotation, and a sentiment analysis) were used to determine the information that the OPD reviews are meant to express. Results: We discovered that the OPD reviews can be categorized into four subjects: competence (35.1%), communication (29.4%), treatment (26.0%), and convenience (9.5%). In terms of previously discovered topics, we found that competence, communication, and treatment have been discussed before, but convenience is an emerging subject. The sentiment analysis indicated that 93.67% of the reviews indicated positive emotions, and the area under the receiver operating characteristic (ROC) curve is 0.64. Furthermore, the labels indicated that only 0.72% (603/84,570) of reviews were negative toward the OPD service. The subjects of the labels were distributed according to competence (34.7%), communication (23.8%), treatment (33.5%), and convenience (8.0%). Discussion: The findings of our study suggest that patients who ever used OPD have been quite satisfied with the service. From their reviews, we discovered that OPD has its special characteristics and is convenient. However, it still has some shortcomings, for example, the quality of the phone connection. In terms of both the platform and the doctors, more efforts should be made to make the OPD better and more regulated. Conclusion: OPD is an emerging telemedicine service that still needs more time and space to evolve. For patients, it helps reduce problems such as scheduling and queuing. Therefore, it brings more convenience to people's daily lives. In the future, more attention should be paid to this service, as it is helpful in reducing the uneven distribution of medical resources.

2.
J Biomed Mater Res A ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714657

RESUMO

Synthetic siRNA technology has emerged as a promising approach for molecular therapy of cancer but, despite its potential for post-transcriptional gene silencing, there is an urgent need to develop efficient delivery systems particularly for difficult-to-transfect, anchorage-independent cells. In this study, we designed highly hydrophobic cationic lipopolymers by grafting cholesterol (Chol) onto low molecular weight (0.6, 1.2 and 2.0 kDa) polyethylenimines (PEIs) to enable specific siRNA therapy to chronic myeloid leukemia (CML) cells. The siRNA binding by PEI-Chol led to nano-sized (100 to 200 nm diameter) polyplexes with enhanced ζ-potential (+20 to +35 mV) and ability to protect the loaded siRNA completely in fresh serum. The siRNA delivery to CML (K562) cells was proportional to degree of substitution and, unexpectedly, inversely proportional to molecular size of the polymeric backbone. Chol grafting with as little as ~1.0 Chol/PEI on 0.6 and 1.2 kDa PEIs enabled silencing of the reporter Green Fluorescent Protein (GFP) gene as well as the endogenous BCR-Abl oncogene in K562 cells. The PEI-Chol mediated delivery of siRNAs specific for BCR-Abl and KSP genes significantly arrested the growth the cells which was significantly reflected in colony formation potency of K562 cells. BCR-Able siRNA mediated therapeutic efficacy was also observed in significantly increased caspase activity and apoptosis of K562 cells. Thus, Chol-grafted low molecular weight PEIs appear to be unique siRNA carriers to realize the molecular therapy in CML cells. This article is protected by copyright. All rights reserved.

3.
J Ovarian Res ; 12(1): 99, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639019

RESUMO

Ovarian cancer is the most common gynecological malignancy that causes cancer-related deaths in women today; this being the case, developing an understanding of ovarian cancer has become one of the major driving forces behind cancer research overall. Moreover, such research over the last 20 years has shown that the Jun N-terminal kinase (JNK) signaling pathway plays an important role in regulating cell death, survival, growth and proliferation in the mitogen-activated protein kinases (MAPK) signaling pathway, an important pathway in the formation of cancer. Furthermore, the JNK signaling pathway is often regulated by an abnormal activation in human tumors and is frequently reported in the literature for its effect on the progression of ovarian cancer. Although the FDA has approved some JNK inhibitors for melanoma, the agency has not approved JNK inhibitors for ovarian cancer. However, there are some experimental data on inhibitors and activators of the JNK signaling pathway in ovarian cancer, but related clinical trials need to be further improved. Although the Jun N-terminal kinase (JNK) signaling pathway is implicated in the formation of cancer in general, research has also indicated that it has a role in suppressing cancer as well. Here, we summarize this seemingly contradictory role of the JNK signaling pathway in ovarian cancer, that 'seesaws' between promoting and suppressing cancer, as well as summarizing the application of several JNK pathway inhibitors in cancer in general, and ovarian cancer in particular.

4.
Mol Biol Rep ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612408

RESUMO

AP-1 is a dimeric complex that is composed of JUN, FOS, ATF and MAF protein families. FOS-related antigen 1 (FRA1) which encoded by FOSL1 gene, belongs to the FOS protein family, and mainly forms an AP-1 complex with the protein of the JUN family to exert an effect. Regulation of FRA1 occurs at levels of transcription and post-translational modification, and phosphorylation is the major post-translational modification. FRA1 is mainly regulated by the mitogen-activated protein kinases signaling pathway and is degraded by ubiquitin-independent proteasomes. FRA1 can affect biological functions, such as tumor proliferation, differentiation, invasion and apoptosis. Studies have demonstrated that FRA1 is abnormally expressed in many tumors and plays a relevant role, but the specific condition varies from the target organs. FRA1 is overexpressed in breast cancer, lung cancer, colorectal cancer, prostate cancer, nasopharyngeal cancer, thyroid cancer and other tumors. However, the expression of FRA1 is decreased in cervical cancer, and the expression of FRA1 in ovarian cancer and oral squamous cell carcinoma is still controversial. In this review, we present a detailed description of the regulatory factors and functions of FRA1, also, the expression of FRA1 in various tumors and its function in relative tumor.

5.
Cancer Med ; 8(16): 7074-7085, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31568657

RESUMO

OBJECTIVE: Epithelial ovarian cancer (EOC) is a common gynecologic malignancy characterized by extensive peritoneal metastasis and high mortality rate. ABHD11 Antisense RNA1 (ABHD11-AS1) has recently been identified as a regulator of growth and metastasis in multiple tumors, including EOC. However, the biological function and potential mechanism of ABHD11-AS1 in EOC remains poorly understood. METHODS: Immunohistochemistry, western blot, and qRT-PCR analysis were used to determine the expression pattern of ABHD11-AS1 and epidermal growth factor receptor (EGFR) in both EOC tissues and cell lines, respectively. Colony formation, transwell and wound healing assays were performed to evaluate the roles of EGFR and ABHD11-AS1 on the capacity of cell proliferation, migration, and invasion. Western blot analysis was performed to measure the regulation of EGFR pathway on STAT3. Moreover, chromatin immunoprecipitation was employed to demonstrate the interaction between ABHD11-AS1 and STAT3. RNA immunoprecipitation was subjected to prove the direct binding between ABHD11-AS1 and EZH2. Immunofluorescence staining was performed to measure the expression and localization of TIMP2. EOC mouse model was conducted for validating the role of ABHD11-AS1 in vivo. RESULTS: EGFR and ABHD11-AS1 were highly expressed in EOC tissues and cell lines. Knockdown of EGFR or ABHD11-AS1 inhibited cell growth, migration, and invasion of EOC cells. Expression of ABHD11-AS1 was regulated by the activation of EGFR signaling pathway, mediated by STAT3. Besides, ABHD11-AS1 was shown to silence TIMP2 by binding to chromatin-modifying enzyme EZH2. Furthermore, inhibition of EGFR pathway or ABHD11-AS1 repressed the tumor growth of EOC. CONCLUSION: We defined the regulatory relationship between the EGFR signaling pathway, ABHD11-AS1, EZH2, and TIMP2 suggesting that ABHD11-AS1 may act as an oncogene and a potential target for antitumor therapies in ovarian cancer.

6.
Biosci Rep ; 39(10)2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31652453

RESUMO

Many clinical studies have been conducted on ketamine-associated cystitis. However, the underlying mechanisms of ketamine-associated cystitis still remain unclear. Bladder tissues of rats were stained by Hematoxylin and Eosin (HE). The viability of human uroepithelial cells (SV-HUC-1 cells) was determined by cell counting kit-8 (CCK-8). Apoptosis and reactive oxygen species (ROS) were examined by flow cytometry. Additionally, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß and IL-18 were respectively determined by reverse transcription quantitative (RTq)-PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA and protein levels of B-cell lymphoma/leukemia-2 (Bcl2), Bcl-2-associated X protein (Bax), cleaved caspase 3, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), NOD-like receptor 3 (NLRP3), thioredoxin-interacting protein (TXNIP), Catalase and MnSOD were examined by RT-qPCR and Western blot. Small interfering RNA target TXNIP transfection was performed using Lipofectamine™ 2000. We found that ketamine effectively damaged bladder tissues of rats and promoted apoptosis through regulating the expression levels of GRP78, CHOP, Bcl-2, Bax and cleaved Caspase-3 proteins in vivo and in vitro. NLRP3 inflammatory body and TXNIP were activated by ketamine, which was supported by the changes in TNF-α, IL-6, IL-1 and IL-18 in vivo and in vitro. Furthermore, knocking down TXNIP reversed the effects of ketamine on apoptosis and NLRP3 inflammatory body in SV-HUC-1 cells. Meanwhile, the changes of Catalase and MnSOD showed that ROS was enhanced by ketamine, however, such an effect was ameliorated by down-regulation of TXNIP in SV-HUC-1 cells. Ketamine promoted cell apoptosis and induced inflammation in vivo and in vitro by regulating NLRP3/TXNIP aix.

7.
J Control Release ; 310: 141-154, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31430499

RESUMO

Despite development of effective tyrosine kinase inhibitors for treatment of chronic myeloid leukemia (CML), some patients do not effectively respond to the therapy and can display resistance in response to the drug therapy. To develop an alternative approach to CML therapy, we are exploring siRNA mediated silencing of the primary CML oncogene, BCR-ABL, by using non-viral (polymeric) delivery systems. In this study, a group of lipopolymers derived from low molecular PEIs substituted with linoleic acid (LA), α-linolenic acid (αLA) and cholesterol (Chol) was investigated for the first time for siRNA delivery to CML primary samples. The delivery efficiency in primary cells was equivalent to CML K562 cell line, and the lipopolymers gave effective internalization of siRNA depending on the nature of lipid substituent. The PEI-αLA (2.5 αLA/PEI), PEI-Chol (2.2 Chol/PEI), and PEI-LA (2.6 LA/PEI) lipopolymers used as BCR-ABL siRNA carriers (at 60 nM siRNA) reduced the BCR-ABL mRNA expression by 17% to 45%, and inhibited the formation of colonies by 24% to 41% in comparison with control siRNA in mononuclear cells. BCR-ABL siRNA treatment reduced the BCR-ABL mRNA expression by 50% in one of two CD34+ samples tested, and combination of BCR-ABL siRNA with imatinib (IM) treatment decreased the colony formation by 65% in one of two samples evaluated. The fact that no single polymer was universally effective in all patient samples may suggest patient-to-patient variability in terms of therapeutic responses to siRNA therapy. These results showed that a low dose of BCR-ABL siRNA could be used with lipopolymers to reduce BCR-ABL mRNA expression, CML cell survival and colony formation. This proof of principle study in CML primary cells can be applied to silencing of other therapeutic targets besides BCR-ABL and a study with larger patient samples is warranted for better identification of effective siRNA carriers.

8.
JAMA Ophthalmol ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415060

RESUMO

Importance: Given the estimates of increasing prevalence of myopia, especially in Asia, it is important to determine the current prevalence of myopia among populations of schoolchildren in Japan. Objective: To investigate the current prevalence rate of myopia and the association between environmental factors and myopia in Japanese schoolchildren. Design, Setting, and Participants: This cross-sectional study assessed 1478 participants, including 726 elementary school students and 752 junior high school students, at 2 schools in Tokyo, Japan, who underwent eye examinations from April 1 to May 31, 2017, that included measurement of the refractive errors by autorefractometry with noncycloplegic refraction and ocular biometric factors. After excluding those who had been treated with atropine or orthokeratology (n = 11), had a history of eye disease (n = 2), had no parental consent (n = 41), and were absent (n = 8), 1416 schoolchildren were analyzed. Main Outcomes and Measures: The primary outcome was the prevalence of myopia and high myopia. Secondary outcomes were environmental factors that were associated with myopia. Results: A total of 1416 schoolchildren (mean [SD] age, 10.8 [2.7] years; 792 [55.9%] male) were studied. The prevalence rates of myopia (spherical equivalent ≤-0.5 diopters [D]) were 76.5% (95% CI, 73.4%-79.7%) among the elementary school students and 94.9% (95% CI, 93.3%-96.5%) among the junior high school students. The prevalence rates of high myopia (spherical equivalent ≤-6.0 D) were 4.0% (95% CI, 2.5%-5.4%) among the elementary school students and 11.3% (95% CI, 8.8%-13.7%) among the junior high school students. The prevalence rates of high myopia classified based on axial length of 26.0 mm or longer were 1.2% (95% CI, 0.4%-2.0%) among elementary school students and 15.2% (95% CI, 12.5%-17.8%) among junior high school students. Multiple regression analysis showed that higher-order aberrations and dry eye disease were associated with refractive error in elementary school students (spherical aberration: ß = 6.152; 95% CI, 3.161-9.143; P < .001; dry eye disease: ß = -0.626; 95% CI, -1.189 to -0.063; P = .03) and with axial length in junior high school students (spherical-like aberration: ß = 26.546; 95% CI, 18.708-34.385; P < .001; dry eye disease: ß = 0.354; 95% CI, 0.131-0.578; P < .002). Conclusions and Relevance: Although the use of noncycloplegic autorefraction with a cutoff of -0.50 D could lead to overestimation of results, these findings suggest that the current prevalence rates of myopia among elementary and junior high school students in Asia are high, especially if the results from these 2 schools are generalizable to all schoolchildren in Japan and Asia.

9.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1126-1127: 121734, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31401450

RESUMO

Non-small cell lung cancer (NSCLC), as the most common histological type of lung cancer with high mortality rates, has been widely treated by Compound Kushen Injection (CKI) in China. Among various active components with many pharmacologic properties, matrine, oxymatrine, sophoridine, oxysophocarpine and N-methylcytisine, are the main bioactive alkaloids of CKI. Therefore, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to simultaneously quantify the five alkaloids in nude rat plasma in this study. With aminopyrine as internal standard (IS), plasma samples were extracted by alkalified chloroform and then separated on an Agela Venusil MP C18 column (2.1 mm × 100 mm, 3 µm) using gradient elution. Water containing 10 mmol/L ammonium acetate (adjusted to pH 8.0 with ammonia water, A) and methanol (B) constituted the mobile phase system. Notably, the analysis was rapid and accurate due to a short running time of 6 min and a stereoisomer separation between matrine and sophoridine. Detection was implemented in MRM mode with an electrospray positive ionization source. Validation parameters were all in accordance with current criterion. The established method has been effectively employed to compare the pharmacokinetic behaviors of five alkaloids between normal and NSCLC nude rats. Results indicated that the pharmacokinetic behaviors of oxymatrine, sophoridine and N-methylcytisine from CKI could be changed when it was intravenously administrated to the NSCLC model rats, and possible reasons have been proposed. This study could provide meaningful reference for further clinical medication of CKI when combined with time-effect curve and clinical symptoms.

10.
Virol J ; 16(1): 88, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31272463

RESUMO

BACKGROUND: Currently, there is no consensus on the effects and safety of lamivudine therapy for chronic hepatitis B (CHB) in children. METHOD: Both English and Chinese databases were searched comprehensively. An odds ratio (OR) and a standard mean difference (SMD) were used to assess the effects and safety of lamivudine therapy for CHB in children. RESULTS: Thirteen eligible studies were included in our analysis. The rates of Hepatitis B virus (HBV) response, biochemical response, hepatitis B e antigen (HBeAg) loss, HBeAg seroconversion, and hepatitis B surface antigen (HBsAg) loss were significantly higher in the lamivudine (LAM) therapy group than in the control group. The changes in children's weight and height were similar between the two groups. CONCLUSIONS: LAM therapy was efficacious for CHB in children. Additionally, it had no side effect on children's height and weight.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Criança , Farmacorresistência Viral , Humanos , Lamivudina/administração & dosagem , Razão de Chances
11.
Int J Mol Sci ; 20(15)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344984

RESUMO

To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation.

12.
Sci Transl Med ; 11(501)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31316004

RESUMO

LB100 sensitizes resistant chronic phase CML stem and progenitor cells to TKIs and spares healthy bone marrow cells.

13.
J Biol Chem ; 294(32): 12167-12179, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235520

RESUMO

Chronic myeloid leukemia (CML) is caused by the fusion of the BCR activator of RhoGEF and GTPase activating protein (BCR) and ABL proto-oncogene, the nonreceptor tyrosine kinase (ABL) genes. Although the tyrosine kinase inhibitors (TKIs) imatinib (IM) and nilotinib (NI) have remarkable efficacy in managing CML, the malignancies in some patients become TKI-resistant. Here, we isolated bone marrow (BM)-derived mesenchymal stem cells (MSCs) from several CML patients by Ficoll-Hypaque density-gradient centrifugation for coculture with K562 and BV173 cells with or without TKIs. We used real-time quantitative PCR to assess the level of interleukin 7 (IL-7) expression in the MSCs and employed immunoblotting to monitor protein expression in the BCR/ABL, phosphatidylinositol 3-kinase (PI3K)/AKT, and JAK/STAT signaling pathways. We also used a xenograft tumor model to examine the in vivo effect of different MSCs on CML cells. MSCs from patients with IM-resistant CML protected K562 and BV173 cells against IM- or NI-induced cell death, and this protection was due to increased IL-7 secretion from the MSCs. Moreover, IL-7 levels in the BM of patients with IM-resistant CML were significantly higher than in healthy donors or IM-sensitive CML patients. IL-7 elicited IM and NI resistance via BCR/ABL-independent activation of JAK1/STAT5 signaling, but not of JAK3/STAT5 or PI3K/AKT signaling. IL-7 or JAK1 gene knockdown abrogated IL-7-mediated STAT5 phosphorylation and IM resistance in vitro and in vivo Because high IL-7 levels in the BM mediate TKI resistance via BCR/ABL-independent activation of JAK1/STAT5 signaling, combining TKIs with IL-7/JAK1/STAT5 inhibition may have significant utility for managing CML.

14.
Nat Commun ; 10(1): 2745, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227705

RESUMO

Small molecule probes are indispensable tools to explore diverse cellular events. However, finding a specific probe of a target remains a high challenge. Here we report the discovery of Fast-TRFS, a specific and superfast fluorogenic probe of mammalian thioredoxin reductase, a ubiquitous enzyme involved in regulation of diverse cellular redox signaling pathways. By systematically examining the processes of fluorophore release and reduction of cyclic disulfides/diselenides by the enzyme, structural factors that determine the response rate and specificity of the probe are disclosed. Mechanistic studies reveal that the fluorescence signal is switched on by a simple reduction of the disulfide bond within the probe, which is in stark contrast to the sensing mechanism of published probes. The favorable properties of Fast-TRFS enable development of a high-throughput screening assay to discover inhibitors of thioredoxin reductase by using crude tissue extracts as a source of the enzyme.


Assuntos
Descoberta de Drogas/métodos , Corantes Fluorescentes/química , Imagem Molecular/métodos , Sondas Moleculares/química , Tiorredoxina Redutase 1/metabolismo , Animais , Produtos Biológicos/farmacologia , Misturas Complexas , Dissulfetos/química , Corantes Fluorescentes/metabolismo , Células HeLa , Ensaios de Triagem em Larga Escala/métodos , Humanos , Microscopia Intravital/métodos , Microscopia de Fluorescência/métodos , Sondas Moleculares/metabolismo , Oxirredução , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Tiorredoxina Redutase 1/antagonistas & inibidores , Tiorredoxina Redutase 1/genética
15.
Parasit Vectors ; 12(1): 319, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31238963

RESUMO

BACKGROUND: Bacillus thuringiensis israelensis (Bti) is a widely used mosquitocidal microbial pesticide due to its high toxicity. ATP-binding proteins (ABP) are prevalently detected in insects and are related to reaction against Bti toxins. However, the function of ABP in mosquito biocontrol is little known, especially in Aedes aegypti. Therefore, this study aimed to clarify the function of ABP in Ae. aegypti against Bti toxin. RESULTS: Aedes aegypti ABP (GenBank: XM_001661856.2) was cloned, expressed and purified in this study. Far-western blotting and ELISA were also carried out to confirm the interaction between ABP and Cry11Aa. A bioassay of Cry11Aa was performed both in the presence and absence of ABP, which showed that the mortality of Ae. aegypti is increased with an increase in ABP. CONCLUSIONS: Our results suggest that ABP in Ae. aegypti can modulate the toxicity of Cry11Aa toxin to mosquitoes by binding to Bti toxin. This could not only enrich the mechanism of Bt toxin, but also provide more data for the biocontrol of this transmission vector.


Assuntos
Aedes/genética , Bacillus thuringiensis/patogenicidade , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Aedes/microbiologia , Animais , Proteínas de Bactérias/metabolismo , Bioensaio , Clonagem Molecular , Endotoxinas/metabolismo , Proteínas Hemolisinas/metabolismo , Mosquitos Vetores/microbiologia , Controle Biológico de Vetores , Ligação Proteica
16.
Bull Environ Contam Toxicol ; 103(3): 453-460, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31183504

RESUMO

The accumulation of strontium (Sr) in lettuce and radish under 0 (control), 0.5, 1, 2.5, 5, and 10 mM Sr treatments in hydroponic solution at 16, 23 and 30 days and the effects of Sr stress on six nutrient elements in plants were investigated. The results showed that Sr concentrations in plant aerial and underground parts increased in low-Sr treatments (0.5, 1 and 2.5 mM) and fluctuated in high-Sr treatments (5 and 10 mM) throughout the three sampling periods. Sr concentrations were higher in roots than in leaves, reaching 108.8 ± 14.7 and 134.1 ± 1.2 mg/g in lettuce and radish roots, respectively, after 10 mM Sr treatment. Translocation factor (TF) values (ratio of the Sr concentrations in aerial parts to that in roots) were inversely related to the Sr content in the hydroponic solution, and reached 1.45 ± 0.17 to 0.15 ± 0.03 and 1.06 ± 0.20 to 0.12 ± 0.004 for lettuce and radish. The variation in chlorophyll content was consistent with that in plant biomass.


Assuntos
Hidroponia , Alface/metabolismo , Raphanus/metabolismo , Estrôncio/metabolismo , Poluentes Químicos da Água/metabolismo , Transporte Biológico/efeitos dos fármacos , Biomassa , Clorofila/metabolismo , Alface/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raphanus/efeitos dos fármacos , Estrôncio/toxicidade , Poluentes Químicos da Água/toxicidade
17.
Mol Med Rep ; 19(6): 4631-4636, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059029

RESUMO

Immediate­early response gene 5 (IER5) is a gene involved in the regulation of the cell cycle, and its structure and function have been investigated by bioinformatics analyses. The present study determined the sites of promoter methylation and gene ontology (GO) annotations associated with IER5. In addition, we conducted a prediction analysis to determine the physical and chemical properties, hydrophobicity/hydrophilicity, posttranslational modification, subcellular localization, transmembrane structure, signal peptide and secondary and tertiary structures of IER5. One CpG island and several methylated sites were identified close to the promoter of IER5. The GO analysis suggested that IER5 could bind ions and proteins that were mainly associated with metabolic processes. IER5 comprised 327 amino acids and was reported to be an unstable hydrophilic protein with an isoelectric point of 4.91. A total of 18 O­glycosylation sites and 22 phosphorylation sites were identified within this protein. The subcellular localization of IER5 was mainly in the nucleus, and its main secondary structural element was the α­helix. Bioinformatic analyses of the features of IER5 may improve understanding of its structure and function; however, experimental verification is required.


Assuntos
Biologia Computacional , Proteínas Imediatamente Precoces/genética , Proteínas Nucleares/genética , Sequência de Aminoácidos , Ciclo Celular/genética , Ilhas de CpG , Proteínas de Ligação a DNA , Ontologia Genética , Humanos , Interações Hidrofóbicas e Hidrofílicas , Regiões Promotoras Genéticas , Conformação Proteica , Processamento de Proteína Pós-Traducional , Fatores de Transcrição , Transcrição Genética
18.
Drug Discov Today ; 24(7): 1355-1369, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102734

RESUMO

Chronic myeloid leukemia cells are armed with several resistance mechanisms that can make current drugs ineffective. A better understanding of resistance mechanisms is yielding new approaches to management of the disease. Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm the hallmark of which, the breakpoint cluster region-Abelson (BCR-ABL) oncogene, has been the target of tyrosine kinase inhibitors (TKIs), which have significantly improved the survival of patients with CML. However, because of an increase in TKI resistance, it is becoming imperative to identify resistance mechanisms so that drug therapies can be better prescribed and new agents developed. In this review, we discuss the various BCR-ABL-dependent and -independent mechanisms of resistance observed in CML, and the range of therapeutic solutions available to overcome such resistance and to ultimately improve the survival of patients with CML.

19.
Medicine (Baltimore) ; 98(20): e15626, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096473

RESUMO

BACKGROUND: Because of the heterogeneity of hepatitis C virus (HCV) distribution of different genotypes, large-scale clinical trials on direct-acting antiviral (DAA) mainly included patients with genotype 1 and genotype 3 infection. Data on the efficacy of direct-acting antiviral agents in patients with chronic genotype 6 HCV infection are limited. METHODS: The PubMed, Embase, and the Cochrane Libraries were searched comprehensively. All published clinical trials assessing the efficacy of DAA therapy for patients with chronic genotype 6 HCV infection were included. Sustained virological response (SVR) and rapid virological response (RVR) were pooled. Additional meta-analyses were also performed to compare the efficacy of DAA therapy in HCV-6 versus HCV-1 or HCV-3 patients. RESULTS: Seventeen studies met the inclusion criteria and were included in our meta-analysis. The pooled SVR of all single arms was 95% [95% confidence interval (CI): 0.90-0.97]. The pooled RVR of all single arms was 97% (95% CI: 0.95-0.99). The SVR and RVR were both similar between HCV-6 and HCV-1 or HCV-3. Adverse events were common but rarely caused treatment interruption. CONCLUSION: Based on the available data, our results indicate that DAA treatment is effective and safe for patients with genotype 6 HCV infection, and the efficacy was similar compared to patients with genotype 1 HCV or genotype 3 HCV infection.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Quimioterapia Combinada , Genótipo , Humanos , Resposta Viral Sustentada
20.
Cancer Biol Ther ; 20(7): 956-966, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31062668

RESUMO

Background: Ovarian cancer (OC) is the gynecologic malignant tumor with high mortality. Accumulating evidence indicates that M2-like tumor-associated macrophages (TAMs) can secret EGF to participate in ovarian cancer growth, migration, and metastasis. An EGF-downregulated lncRNA, LIMT (lncRNA inhibiting metastasis), was identified as a critical regulator of mammary cell migration and invasion. Nevertheless, whether EGF secreted from M2-like TAMs regulates LIMT expression in ovarian cancer progression remains largely unknown. Methods: The human OC cell lines OV90 and OVCA429 were recruited in this study. The differentiation of the human monocyte cell line THP-1 into M2-like TAMs was confirmed using flow cytometry within the application of phorbol 12-myristate 13-acetate (PMA). ELISA was performed to detect EGF concentration in co-culture system of M2-like TAMs and OC cell lines. Moreover, CCK-8, flow cytometry and immunofluorescence staining of Ki67 were performed to assess the capacity of cell proliferation. Besides, cell migration and invasion were determined by wound healing and transwell assays. Furthermore, the expression levels of epithelial-mesenchymal transition (EMT) markers and EGFR/ERK signals were analyzed by qRT-PCR and western blot. Female athymic nude mice (8-12 weeks of age; n = 8 for each group) were recruited for in vivo study. Results: In the present study, THP-1 cells exhibited the phenotype markers of M2-like TAMs with low proportion of CD14+ marker and high proportion of CD68+, CD204+, CD206+ markers within the application of PMA. After co-culturing with M2-like TAMs, EGF concentration in the supernatants was significantly increased in a time-dependent manner. Besides, OC cells presented better cell viability, higher cell proliferation, and stronger migration and invasion. The expression of EMT-related markers N-cadherin, Vimentin and EGFR/ERK signals were markedly up-regulated, while E-cadherin was significantly decreased. However, these effects induced by co-culture system were reversed by the application of AG1478 (an EGFR inhibitor) or LIMT overexpression. Furthermore, the endogenous expression of LIMT was decreased in OC cell lines compared with the control group. Also, the in vivo experiments verified that the inhibition of EGFR signaling by AG1478 or overexpression of LIMT effectively repressed the tumor growth. Conclusion: Taken together, we demonstrated that EGF secreted by M2-like TAMs might suppress LIMT expression via activating EGFR-ERK signaling pathway to promote the progression of OC.

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