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1.
Signal Transduct Target Ther ; 6(1): 405, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795208

RESUMO

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.


Assuntos
Transfusão de Eritrócitos , Talidomida/administração & dosagem , Talassemia beta/terapia , Adolescente , Adulto , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Talidomida/efeitos adversos
2.
Cartilage ; 13(2_suppl): 796S-807S, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34493119

RESUMO

OBJECTIVE: The goal of the present study was to observe the effect of autophagy in tibial plateau chondrocytes on apoptosis in spontaneous knee osteoarthritis (OA) in guinea pigs. DESIGN: Fifty 2-month-old female Hartley guinea pigs were divided into a normal group (10 animals, all euthanized after 7 months) and an OA group (40 animals, 10 of which were euthanized after 10 months). Immunohistochemistry, RT-qPCR and Western blotting were used to evaluate autophagy levels, intracellular glycogen accumulation and apoptosis in tibial plateau chondrocytes in vivo and in vitro. The remaining 30 guinea pigs in the OA group were divided into 3 groups: a rapamycin group, a normal saline group, and a 3-methyladenine (3-MA) group. Intracellular glycogen accumulation and chondrocyte apoptosis were assessed by altering the level of autophagy in chondrocytes in vivo. RESULTS: When spontaneous OA occurred in guinea pigs, autophagy levels in tibial plateau chondrocytes decreased, while intracellular glycogen accumulation and the rate of chondrocyte apoptosis increased. After enhancing the level of autophagy in tibial plateau chondrocytes in guinea pigs with OA, intracellular glycogen accumulation and the rate of chondrocyte apoptosis decreased, while inhibiting autophagy had the opposite effects. CONCLUSION: The results indicate that the function of autophagy in chondrocytes may at least partly involve the catabolism of glycogen. In guinea pigs with OA, the level of autophagy in tibial plateau chondrocytes decreased, and chondrocytes were unable to degrade intracellular glycogen into glucose, leading to less energy for chondrocytes and increased apoptosis.


Assuntos
Cartilagem Articular , Osteoartrite do Joelho , Animais , Apoptose , Autofagia , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Feminino , Cobaias , Osteoartrite do Joelho/metabolismo
3.
Nat Commun ; 12(1): 3070, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34031420

RESUMO

The construction of 7-membered ring via direct C7-H cyclization of benzoimidazoles with alkenes would provide a more atom- and step-economical route to tricyclic imidazoles and derivatives that widely exist in a broad range of bioactive molecules. However, transition metal-catalyzed C-H cyclization for medium-ring synthesis has been limited to reactive C-H bonds, instead, the activation of unreactive C-H bonds towards medium synthesis still remains an elusive challenge. Herein, we report a direct construction of 7-membered rings via Ni-Al co-catalyzed unreactive C7-H cyclization of benzoimidazoles with alkenes, providing a series of tricyclic imidazoles in 40-98% yield and with up to 95:5 er.

4.
Huan Jing Ke Xue ; 42(2): 699-711, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742864

RESUMO

We investigated the spatial distribution and storage of nitrogen and phosphorus in Lake Chaohu sediments and evaluated the sediment nitrogen and phosphorus pollution index. Results show that the average total nitrogen (TN) and total phosphorus (TP) content in the surface-layer sediments of Lake Chaohu were 1088 mg·kg-1 and 585 mg·kg-1, respectively, and 666 mg·kg-1 and 509 mg·kg-1 in the bottom-layer sediments, respectively. TN content in the surface layer was significantly higher than in the bottom layer (P<0.01). Spatially, TN, TP, and sediment thickness were ranked in the order western lake area > eastern lake area > middle lake area, and the TN and TP contents were significantly different in the surface sediments from the middle and eastern areas of the lake (P<0.05, P<0.01). TN and TP storage in the lake sediments was 1.58×105 t and 0.98×105 t, respectively. TN and TP were significantly correlated in both the western and middle parts of the lake (P<0.01). In addition, TN was significantly correlated with sediment thickness in middle area of the lake, which indicated that TN may have the same pollution sources as TP and both were affected by sediment thickness. TN pollution index (STN), TP pollution index (STP), and comprehensive pollution index (FF) values were 1.09, 1.39, and 1.32, respectively, indicating light-to-moderate levels of pollution. Specifically, the western lake surface sediments were heavily polluted with respect to TP, the eastern lake surface sediments were moderately polluted, and the middle lake surface sediments were slightly polluted. Nutrient pollution varied widely between different areas of the lake, with sediments in the western part of the lake presenting a higher safety risk. Overall, these observations indicate that Lake Chaohu is threatened by internal nutrient loading.

5.
Opt Express ; 28(20): 30015-30034, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33114888

RESUMO

As the reference radiometric calibration standard of sensors on the Haiyang-1C (HY-1C) satellite platform, the satellite calibration spectrometer (SCS) is equipped with an onboard calibration system composed of double solar diffusers and an erbium-doped diffuser to monitor the postlaunch radiometric response change. Herein, through onboard calibration data analysis, the calibration diffuser performance remains stable without degradation, and the Moderate Resolution Imaging Spectroradiometer (MODIS) on Terra is adopted as a reference to repeatedly verify onboard radiometric calibration results by selecting different dates and reflectance scenes. The SCS equivalent reflectance is obtained by combining the mean digital number (DN) of the SCS crossing area image with the radiometric calibration coefficient. The spectral reflectance is obtained via interpolation and iteration, which is adopted as the actual MODIS incident pupil spectral reflectance because the small imaging time interval can be ignored and almost vertically observed, and it is convoluted with the MODIS spectral response function to obtain the predicted equivalent reflectance. Validation is completed by comparing the predicted MODIS equivalent reflectance to the measured value based on the onboard calibration coefficient. The results show that (1) the difference between the measured and predicted MODIS band equivalent reflectance is between -0.00466 and 0.0039, and (2) the percentage difference between the measured and predicted MODIS band equivalent reflectance ranges from 4.17% and 1.24%, indicating that the calibration system carried on HY-1C can perform high-precision SCS radiometric calibration, meeting the cross-calibration accuracy requirements of other loads on the same platform.

6.
J Diabetes Res ; 2020: 7574245, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32851097

RESUMO

The proliferation of vascular smooth muscle cells (VSMCs) induced by oxidative injury is one of the main features in diabetes-accelerated atherosclerosis. Geranylgeranyl transferase-I (GGTase-I) is an essential enzyme mediating posttranslational modification, especially the geranylgeranylation of small GTPase, Rac1. Our previous studies found that GGTase-I played an important role in diabetes-accelerated atherosclerosis. However, its exact role is largely unclear. In this study, mouse conditional knockout of VSMC GGTase-I (Pggt1b Δ/Δ mice) was generated using the CRISPR/Cas9 system. The mouse model of diabetes-accelerated atherosclerosis was induced by streptozotocin injections and an atherogenic diet. We found that GGTase-I knockout attenuated diabetes-accelerated atherosclerosis in vivo and suppressed high-glucose-induced VSMC proliferation in vitro. Moreover, after a 16-week duration of diabetes, Pggt1b Δ/Δ mice exhibited lower α-smooth muscle actin (α-SMA) and nitrotyrosine level, Rac1 activity, p47phox and NOXO1 expression, and phospho-ERK1/2 and phosphor-JNK content than wild-type mice. Meanwhile, the same changes were found in Pggt1b Δ/Δ VSMCs cultured with high glucose (22.2 mM) in vitro. In conclusion, GGTase-I knockout efficiently blocked diabetes-accelerated atherosclerosis, and this protective effect must be related to the inhibition of VSMC proliferation. The potential mechanisms probably involved interfering Rac1 geranylgeranylation, inhibiting the assembly of NADPH oxidase cytosolic regulatory subunits, reducing oxidative injury, and decreasing ERK1/2 and JNK phosphorylation.


Assuntos
Alquil e Aril Transferases/genética , Aterosclerose/genética , Diabetes Mellitus Experimental/genética , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/genética , Alquil e Aril Transferases/metabolismo , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Camundongos , Camundongos Knockout , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Fosforilação , Transdução de Sinais/genética
7.
Mol Med Rep ; 22(1): 165-174, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32319638

RESUMO

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)­induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription­quantitative PCR results indicated that inhibition of miR­125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR­125a abrogated this effect. Furthermore, dual­luciferase reporter assay results identified that 3­hydroxy­3-methyglutaryl­coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR­125a. Moreover, HMGCR knockdown, similarly to miR­125a overexpression, suppressed HG­induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin­induced diabetes mellitus, it was demonstrated that miR­125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG­induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR­125a mimic. Therefore, the present results suggest that decreased miR­125a expression contributed to HG­induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR­125a­mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.


Assuntos
Hiperglicemia/genética , Ácido Mevalônico/metabolismo , MicroRNAs/genética , Músculo Liso Vascular/citologia , Transdução de Sinais , Animais , Proliferação de Células , Células Cultivadas , Regulação para Baixo , Glucose/metabolismo , Hiperglicemia/metabolismo , Masculino , Músculo Liso Vascular/metabolismo , Ratos Sprague-Dawley
9.
Acta Otolaryngol ; 140(5): 418-421, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32068453

RESUMO

Background: It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors.Objective: The purpose of this research was to determine the serum miR-632 levels in patients with laryngeal squamous cell carcinoma (LSCC) and to investigate its diagnostic and prognostic value.Materials and methods: We detected serum miR-632 levels in 162 LSCC patients and 42 healthy volunteers. The ROC curve was carried out to determine diagnostic accuracy.Results: We observed that serum miR-632 levels were upregulated in LSCC patients compared with healthy volunteers (p < .01). Subsequent results from ROC indicated that high sensitivity and specificity of serum miR-632 for diagnosing LSCC (area under the curve 0.8828). In addition, it was found that high expressions of serum miR-632 were significantly associated with advanced N stage (p = .020), histological grade (p = .001), and TNM stage (p = .014). Furthermore, patients with higher serum miR-632 expression had a shorter OS and DFS time than those with lower serum miR-632 levels.Conclusion: Our data revealed that serum miR-632 may be a potential noninvasive biomarker which may become a potential diagnostic and prognostic biomarker for LSCC patients.


Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Laríngeas/sangue , MicroRNAs/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade
10.
Sci Prog ; 103(1): 36850419891046, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31791191

RESUMO

Breast cancer, as one of the most malignant tumors, poses a serious threat to the lives of females. Nucleotide exchange factor SIL1 is an important regulator of endoplasmic reticulum function that might have a specific role in tumor progression. In this study, we aimed to investigate the effect of SIL1 on the proliferation, apoptosis, and metastasis of human breast cancer. SIL1-specific small interfering RNA was transfected into two breast cancer cell lines, MCF7 and MDA-MB-231, to generate SIL1 knockdown cells. Clone formation and Cell Counting Kit-8 assays were performed to determine cell proliferation. Wound healing and transwell assays were used to detect the cell migration and invasion, respectively. Cell cycle and apoptosis were determined by flow cytometry. The messenger RNA and protein levels of target genes were analyzed using quantitative real-time PCR and western blot. According to the results of TCGA and GTEx database analysis, we determined that SIL1 was overexpressed in 1085 breast cancer samples compared with 291 normal samples. Knockdown of SIL1 inhibited the proliferation, migration, and invasion of MCF7 and MDA-MB-231 cells, accordingly. The cell cycle was blocked at the G1 phase following transfection of SIL1-specific small interfering RNA through the inhibition of Cyclin D1, CDK4, and CDK6. SIL1 knockdown induced apoptosis and also promoted the activity of Caspase9 and Bax. Furthermore, SIL1 was able to promote phosphorylation of ERK1/2. Based on these results, SIL1 might act as an oncogene and accelerate the progression of human breast cancer.


Assuntos
Neoplasias da Mama , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Fatores de Troca do Nucleotídeo Guanina/farmacologia , Humanos , Nucleotídeos/farmacologia
11.
Chin Med J (Engl) ; 132(24): 2920-2926, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31833906

RESUMO

BACKGROUND: Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas. The p.R132H mutation of IDH1 is the most frequently observed IDH mutation, while IDH2 mutations were relatively rarely studied. The aim of the study was to determine the pathological and genetic characteristics of lower-grade gliomas that carry IDH2 mutations. METHODS: Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed. The status of IDH1/2 gene mutations, telomerase reverse transcriptase (TERT) promoter mutations, O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, 1p/19q co-deletion and the expressions of IDH1 R132H, alpha-thalassemia X-linked mental retardation, and p53 were evaluated. Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test. RESULTS: Totally, 71% (169/238) of patients were positive for IDH mutations, including 12 patients harboring mutations in IDH2. Among the 12 patients with IDH2 mutations, ten patients harbored the R172K mutation, one patient harbored the R172S mutation and one harbored the R172W mutation. Of these, 11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma. The proportion of grade II tumors was higher than that of grade III tumors in IDH2 mutant-gliomas. IDH2 mutations were frequently associated with TERT promoter mutations, 1p/19q co-deletion and MGMT promoter methylation. IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P < 0.05). However, the PFS and OS did not differ from that of IDH1 mutant patients (P = 0.95 and P = 0.60, respectively). CONCLUSIONS: IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis. IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas, and therefore may merit routine investigation.


Assuntos
Neoplasias Encefálicas/genética , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Glioma/mortalidade , Glioma/patologia , Humanos , Estudos Retrospectivos
12.
Opt Lett ; 44(21): 5354-5357, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675006

RESUMO

Flower-like silver vanadium oxide (SVO) micropatterns were realized by femtosecond laser in situ writing from its precursor. Self-assembled petals irradiated by a femtosecond laser were observed standing on the substrate along the scanned routine assisted by the formation of silver seeds and plasmonic-mediated effects. By controlling the concentration of ammonium monovanadate and the laser exposure time, a different thickness of petals was manipulated from ∼100 nm to micrometers. The SVO products were confirmed Ag4V2O7, AgVO3, and part of Ag3VO4 by x-ray diffraction (XRD) measurement. Photon-driven self-assembly for in situ fabrication of microstructures looks to be an effective and facile technique for SVO and other functional compounds.

15.
ACS Nano ; 13(9): 10359-10365, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31480845

RESUMO

The actual light absorption photovoltaic responses realized in three-dimensional (3D) radial junction (RJ) units can be rather different from their planar counterparts and remain largely unexplored. We here adopt a laser excitation photoelectric microscope (LEPM) technology to probe the local light harvesting and photoelectric signals of 3D hydrogenated amorphous silicon (a-Si:H) RJ thin film solar cells constructed over a Si nanowire (SiNW) matrix, with a high spatial resolution of 600 nm thanks to the use of a high numerical aperture objective. The LEPM scan can help to resolve clearly the impacts of local structural damages, which are invisible to optical and SEM observations. More importantly, the high-resolution photoelectric mapping establishes a straightforward link between the local 3D geometry of RJ units and their light conversion performance. Surprisingly, it is found that the maximal photoelectric signals are usually recorded in the void locations among the standing SiNW RJs, instead of the overhead positions above the RJs. This phenomenon can be well explained and reproduced by finite element simulation analysis, which highlights unambiguously the dominant contribution of inter-RJ-unit scattering against direct mode incoupling in the 3D solar cell architecture. This LEPM mapping technology and the results help to achieve a straightforward and high-resolution evaluation of the local photovoltaic responses among the 3D RJ units, providing a solid basis for further structural optimization and performance improvement.

16.
Medicine (Baltimore) ; 97(47): e13205, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30461621

RESUMO

We investigated the effects of tonsillectomy by low-temperature plasma on the growth development and psychological behavior in children with obstructive sleep apnea hypopnea syndrome (OSAHS).This study included 72 moderate and severe OSAHS children with tonsils or adenoids hypertrophy, which were randomly assigned into either the study group (n = 36) or the control group (n = 36). Patients in study group underwent tonsillectomy by low-temperature plasma, while in the control group underwent tonsil-pecking, then the efficacy were compared.The time of surgery, VAS scores on postoperative day 1, 3, and 7 were significantly lower in the study group than in the control group, and the efficiency was significantly higher in the study group than the control group (P = .018). In the study group, the BMI was lower, the score of C-WISC (VIQ, PIQ, and FIQ) was higher, the score of CBCL social competence was higher and the score of behavioral questions was lower than that in the control group; differences were statistically significant (P = .022). The serum levels of IgA, IgG, and IgM, as well as the percentage of T lymphocytes, between the study group and the control group were not significantly different (P = .132).Tonsillectomy by low-temperature plasma was effective on the treatment of children with severe OSAHS, and could improve growth development and psychological behavior.


Assuntos
Coagulação com Plasma de Argônio/métodos , Comportamento Infantil/fisiologia , Desenvolvimento Infantil , Apneia Obstrutiva do Sono , Tonsilectomia/métodos , Tonsila Faríngea/patologia , Tonsila Faríngea/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Tonsila Palatina/patologia , Tonsila Palatina/cirurgia , Polissonografia/métodos , Período Pós-Operatório , República da Coreia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/psicologia , Resultado do Tratamento
17.
Int J Nanomedicine ; 12: 6461-6470, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28919747

RESUMO

In this study, dual therapeutic-loaded GE11 peptide-conjugated liposomes were developed and applied to enhance therapeutic efficacies of standard-of-care regimens for the treatment of laryngeal cancer. The therapeutic strategy used here was a combination treatment with the chemotherapeutic docetaxel (DTX) and siRNA against the ABCG2 gene that regulates multidrug resistance in many tumor types. Liposome-encapsulated DTX/ABCG2-siRNA molecules were targeted to recognize tumor cells of squamous morphology by conjugation to the EGFR-targeting ligand, GE11. Targeted, drug-infused liposomes were nanosized and exhibited controlled release of DTX. Presence of GE11 peptides on liposomal surfaces enhanced the quantities of liposomal constructs taken up by Hep-2 laryngeal cancer cells. GE11 peptide-conjugated liposomes also enhanced cytotoxic effects against Hep-2 laryngeal cancer cells when compared to treatment with free DTX, thereby reducing IC50 values. Additionally, GE11 peptide-conjugated liposomes had significantly increased anti-tumor and apoptotic effects. Treatments with the GDSL nanoparticle formulation inhibited tumor growth in Hep-2 xenograft-bearing nude mouse models when compared to treatments with non-targeted NP constructs. Treatment of the mouse models with GE11 peptide-conjugated liposomes mitigated toxicities observed after treatment with free DTX. Taken together, liposomal encapsulation of DTX and ABCG2-siRNA improved the anti-tumor effects of treatment with free DTX in Hep-2 cell lines, and conjugation of GE11 peptides to liposomal constructs enhanced anti-tumor efficacies and specificities in laryngeal cancer cells.


Assuntos
Neoplasias Laríngeas/tratamento farmacológico , Nanopartículas/química , Peptídeos/química , RNA Interferente Pequeno/administração & dosagem , Taxoides/administração & dosagem , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Docetaxel , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Bicamadas Lipídicas/química , Lipossomos/administração & dosagem , Lipossomos/química , Camundongos Nus , Nanopartículas/administração & dosagem , Proteínas de Neoplasias/genética , Eletricidade Estática , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
18.
J Zhejiang Univ Sci B ; 18(7): 567-576, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28681581

RESUMO

BACKGROUND: Antithrombotic therapy using new oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) has been generally shown to have a favorable risk-benefit profile. Since there has been dispute about the risks of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH), we sought to conduct a systematic review and network meta-analysis using Bayesian inference to analyze the risks of GIB and ICH in AF patients taking NOACs. METHODS: We analyzed data from 20 randomized controlled trials of 91 671 AF patients receiving anticoagulants, antiplatelet drugs, or placebo. Bayesian network meta-analysis of two different evidence networks was performed using a binomial likelihood model, based on a network in which different agents (and doses) were treated as separate nodes. Odds ratios (ORs) and 95% confidence intervals (CIs) were modeled using Markov chain Monte Carlo methods. RESULTS: Indirect comparisons with the Bayesian model confirmed that aspirin+clopidogrel significantly increased the risk of GIB in AF patients compared to the placebo (OR 0.33, 95% CI 0.01-0.92). Warfarin was identified as greatly increasing the risk of ICH compared to edoxaban 30 mg (OR 3.42, 95% CI 1.22-7.24) and dabigatran 110 mg (OR 3.56, 95% CI 1.10-8.45). We further ranked the NOACs for the lowest risk of GIB (apixaban 5 mg) and ICH (apixaban 5 mg, dabigatran 110 mg, and edoxaban 30 mg). CONCLUSIONS: Bayesian network meta-analysis of treatment of non-valvular AF patients with anticoagulants suggested that NOACs do not increase risks of GIB and/or ICH, compared to each other.


Assuntos
Administração Oral , Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/prevenção & controle , Hemorragia/prevenção & controle , Hemorragias Intracranianas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Teorema de Bayes , Ensaios Clínicos como Assunto , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Metanálise em Rede , Razão de Chances , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Varfarina/administração & dosagem , Varfarina/efeitos adversos
19.
Sci Rep ; 7(1): 1161, 2017 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-28442768

RESUMO

The uptake of formaldehyde (HCHO) on mineral dust affects its budget as well as particle properties, yet the process has not yet been fully investigate. Here, TiO2 and nitrate-doped TiO2 aerosols were used as proxies for mineral dust, and the uptake of HCHO was explored in a chamber under both dark and illuminated conditions. The uptake loss of HCHO on UV-illuminated aerosols is 2-9 times faster than its gaseous photolysis in our experimental system. The uptake coefficient in the range of 0.43-1.68 × 10-7 is 1-2 orders of magnitude higher than previous reports on model mineral dust particles. The reaction rate exhibits a Langmuir-Hinshelwood-type dependence on nitrate content and relative humidity, suggesting the competitive role of nitrate salts, water vapor and HCHO on the TiO2 surface. The reaction produces carbon dioxide as the main product and gaseous formic acid as an important intermediate. The hydroxyl radical produced on illuminated TiO2 primarily drives the fast oxidation of HCHO. The nitrate radical arising from the TiO2-catalyzed photoreaction of nitrate synergistically promotes the oxidation process. This study suggests a novel oxidation route for HCHO in the atmosphere, taking into account high abundance of both mineral dust and anthropogenic TiO2 aerosols.

20.
Oncotarget ; 8(18): 30422-30437, 2017 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-28418930

RESUMO

H5N1 avian influenza viruses are a major pandemic concern. In contrast to the highly virulent phenotype of H5N1 in humans and many animal models, guinea pigs do not typically display signs of severe disease in response to H5N1 virus infection. Here, proteomic and transcriptional profiling were applied to identify host factors that account for the observed attenuation of A/Tiger/Harbin/01/2002 (H5N1) virulence in guinea pigs. RIG-I and numerous interferon stimulated genes were among host proteins with altered expression in guinea pig lungs during H5N1 infection. Overexpression of RIG-I or the RIG-I adaptor protein MAVS in guinea pig cell lines inhibited H5N1 replication. Endogenous GBP-1 expression was required for RIG-I mediated inhibition of viral replication upstream of the activity of MAVS. Furthermore, we show that guinea pig complement is involved in viral clearance, the regulation of inflammation, and cellular apoptosis during influenza virus infection of guinea pigs. This work uncovers features of the guinea pig innate immune response to influenza that may render guinea pigs resistant to highly pathogenic influenza viruses.


Assuntos
Imunidade Inata , Virus da Influenza A Subtipo H5N1/imunologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Animais , Biomarcadores , Linhagem Celular , Proteínas do Sistema Complemento/imunologia , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genômica/métodos , Cobaias , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Virus da Influenza A Subtipo H5N1/patogenicidade , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/metabolismo , Carga Viral , Replicação Viral
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