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1.
AAPS PharmSciTech ; 21(2): 42, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897882

RESUMO

Mesoporous carriers have been widely used to deliver anticancer drugs due to their unique characteristics. In this work, mesoporous silica nanoparticles (MSN) and mesoporous carbon nanoparticles (MCN) with substantially similar and uniform particle size, specific surface area, and pore size were prepared to compare the photothermal effect, drug loading efficiencies (LE), and drug release properties. In order to improve the dispersion stability and biocompatibility of the carriers, MSN and MCN were grafted with PEG, respectively. The NIR-induced photothermal effect results indicated that MCN had a brilliant photothermal conversion efficiency due to its strong near-infrared absorption capacity, while MSN had no photothermal conversion capability. Moreover, LE of DOX in DOX/MCN-PEG reached 36.58%, higher than that in DOX/MSN-PEG, which was ascribed to non-covalent interaction of π-π stacking and electrostatic attraction. In addition, compared to DOX/MSN-PEG, DOX/MCN-PEG had a significantly increased release rate under NIR laser irradiation due to excellent photothermal conversion capability of MCN-PEG. Furthermore, cell viability assay and cellular uptake experiment results demonstrated that DOX/MCN-PEG showed a synergistic therapeutic effect in the combination of chemotherapy and phototherapy, with a combination index (CI) of 0.238.

2.
J Cell Mol Med ; 24(2): 1189-1199, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758636

RESUMO

Myeloid-derived growth factor (MYDGF) is a novel protein secreted by bone marrow cells that features important physiological functions. In recent years, MYDGF has gained considerable interest due to their extensive beneficial effect on cardiac repair and protects cardiomyocytes from cell death. However, its precise molecular mechanisms have not been well elucidated. The purpose of this study was to produce sufficient amount of biologically active recombinant human (rh) MYDGF more economically and effectively by using in vitro molecular cloning techniques to study its clinical application. The prokaryotic expression system of Escherichia coli was established for the preparation of rhMYDGF. Finally, a large amount of high biologically active and purified form of recombinant protein was obtained. Moreover, we investigated the potential mechanism of rhMYDGF-mediated proliferation and survival in human coronary artery endothelial cells (HCAECs). Mechanistically, the results suggested that MAPK/STAT3 and the cyclin D1 signalling pathways are indispensable for rhMYDGF-mediated HCAEC proliferation and survival. Therefore, this study successfully established a preparation protocol for biologically active rhMYDGF and it may be a most economical way to produce high-quality active rhMYDGF for future clinical application.

3.
ACS Appl Mater Interfaces ; 12(1): 904-913, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31797663

RESUMO

Enhancement of integrity and stability of crystal lattice are highly challenging for polycrystalline perovskite films. In this work, a strategy of incorporation of nickel (Ni) ions is presented to modulate the crystal structure of the CH3NH3PbI3 perovskite film. A broad range of experimental characterizations reveal that the incorporation of Ni ions can substantially eliminate the intrinsic halide vacancy defects, since Ni ions have a strong preference for octahedral coordination with halide ions, resulting in significantly improved integrity and short-range order of crystal lattice. Moreover, it is also demonstrated that the stronger chemical bonding interaction between Ni ions and halide ions as well as organic group can improve the stability of the perovskite material. Simultaneously, the surface morphology of the perovskite thin film is also improved by the incorporation of nickel ions. As a result, a planar heterojunction perovskite solar cell incorporated with 1.5% Ni exhibits a power conversion efficiency of 18.82%, which is improved by 25% compared with 14.92% for the pristine device. Simultaneously, the device formed incorpration of 1.5% Ni shows remarkable stability with 90% of the initial efficiency after storage in an air environment for 800 h. The studies provide a new insight into metal-incorporated perovskite materials for various optoelectronic applications.

4.
J Colloid Interface Sci ; 559: 51-64, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610305

RESUMO

Aiming at the inefficiency and toxicity in traditional antitumor therapy, a novel multifunctional nanoplatform was constructed based on hollow mesoporous carbon (HMC) to achieve triple stimuli response and dual model antitumor therapy via chemo-photothermal synergistic effect. HMC was used as an ideal nanovehicle with a high drug loading efficiency as well as a near-infrared (NIR) photothermal conversion agent for photothermal therapy. Acid-dissoluble, luminescent ZnO quantum dots (QDs) were used as the proper sealing agents for the mesopores of HMC, conjugated to HMC via disulfide linkage to prevent drug (doxorubicin, abbreviated as Dox) premature release from Dox/HMC-SS-ZnO. After cellular endocytosis, the Dox was released in a pH, GSH and NIR laser triple stimuli-responsive manner to realize accurate drug delivery. Moreover, the local hyperthermia effect induced by NIR irradiation could promote the drug release, enhance cell sensitivity to chemotherapeutic agents, and also directly kill cancer cells. As expected, Dox/HMC-SS-ZnO exhibited a high drug loading capacity of 43%, well response to triple stimuli and excellent photothermal conversion efficiency η of 29.7%. The therapeutic efficacy in 4T1 cells and multicellular tumor spheroids (MCTSs) demonstrated that Dox/HMC-SS-ZnO + NIR had satisfactory chemo-photothermal synergistic effect with a combination index (CI) of 0.532. The cell apoptosis rate of the combined treatment group was more than 95%. The biodistribution and pharmacodynamics studies showed its biosecurity to normal tissues and synergistic inhibition effect to tumor cells. These distinguished results indicated that the Dox/HMC-SS-ZnO nanoplatform is potential to realize efficient triple stimuli-responsive drug delivery and dual model chemo-photothermal synergistic antitumor therapy.


Assuntos
Antineoplásicos/química , Carbono/química , Terapia Combinada/métodos , Portadores de Fármacos/química , Nanopartículas/química , Pontos Quânticos/química , Óxido de Zinco/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Liberação Controlada de Fármacos , Corantes Fluorescentes/química , Humanos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Fototerapia/métodos , Porosidade , Propriedades de Superfície , Distribuição Tecidual , Óxido de Zinco/farmacocinética
5.
Thorac Cancer ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31837116

RESUMO

BACKGROUND: The objective of our study was to analyze the prognostic value of the combination of serum ALP and pleural effusion LDH (AL score) for malignant pleural effusion (MPE) patients. METHODS: This study includes retrospective, descriptive and observational research from 1 June 2006 to 1 December 2017, which aimed to identify prognostic factors related to MPE patients. We analyzed the association of various clinical features, routinely tested markers from peripheral blood and MPE at diagnosis and overall survival (OS). All MPE patients were assigned to three groups according to their AL score. The impact of the AL score and other prognostic factors were evaluated with multivariable regression. RESULTS: According to their AL score, 193 patients were assigned to three groups with 25 in group 0 (sALP < 65 U/L and pLDH < 155 U/L), 121 in group 1 (sALP > 65 U/L or pLDH > 155 U/L) and 47 (sALP > 65 U/L and pLDH > 155 U/L) in group 2. For groups 0, 1 and 2, median survival times (MST) were 23, 15 and 7 months, respectively. Among the three groups, MST, serum albumin level, C reactive protein, erythrocyte sedimentation rate, the ratios of platelet-to-lymphocyte, neutrophil-to-lymphocyte showed significant differences. The counts of neutrophils, monocytes, platelets and AL score (0 vs. 1, P = 0.038, hazard ratio [HR]: 1.858, 95% confidence interval [CI]: [1.034, 3.339]; 0 vs. 2, P = 0.001, HR: 2.993, 95% CI: [1.556, 5.531]) were independent prognostic indicators for OS of MPE patients. CONCLUSION: AL score is a promising indicator which can be used to predict the prognosis of MPE patients. It can assist physicians in the selection of patients for appropriate palliative treatment. KEY POINTS: To our knowledge, this paper is the first study that combined two enzymes (sALP and pLDH) from serum and pleural effusion and studied the prognostic value for MPE patients. It has been proved to be a promising indicator to assist physicians select patients for appropriate palliative treatment.

6.
Medicine (Baltimore) ; 98(52): e18465, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876730

RESUMO

This study aimed to investigate the correlation of long noncoding RNA zinc finger antisense 1 (lncRNA ZFAS1) expression with disease risk, disease severity and inflammatory cytokines levels in lumbar disc degeneration (LDD) patients.83 LDD patients underwent surgery and 28 traumatized, non-LDD patients underwent lumbar disc surgery (controls) were consecutively enrolled in this case-control study. Lumbar disc tissue was obtained during surgery and herniated nucleus pulposus (HNP) was isolated to detect lncRNA ZFAS1 expression and inflammatory cytokines mRNA levels by RT-qPCR, and determine protein levels of inflammatory cytokines by western blot.HNP lncRNA ZFAS1 expression in LDD patients was up-regulated compared with controls (P < .001), and receiver operating characteristic (ROC) curve showed lncRNA ZFAS1 expression disclosed a good predictive value for LDD risk with area under curve (AUC) 0.753 (95% CI 0.646-0.859). And after adjustment by age, gender and body mass index (BMI), lncRNA ZFAS1 (P = .017) remained to be an independent predictive factor for higher LDD risk. In addition, lncRNA ZFAS1 expression was positively associated with Modified Pfirrmann Grade (P = .015). As to inflammatory cytokines, lncRNA ZFAS1 expression was observed to be positively correlated with TNF-α (P = .002), IL-1ß (P = .007) and IL-6 (P = .015) mRNAs expressions while reversely associated with IL-10 mRNA level (P = .014); and lncRNA ZFAS1 expression was also positively correlated with protein levels of TNF-α (P = .038) and IL-6 (P = .027) while reversely associated with IL-10 protein expression (P = .039).lncRNA ZFAS1 expression associates with increased risk, elevated disease severity and higher inflammatory cytokines levels in LDD patients.


Assuntos
Citocinas/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Deslocamento do Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Vértebras Lombares , RNA Antissenso/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Biomarcadores/análise , Western Blotting , Estudos de Casos e Controles , Citocinas/análise , Feminino , Humanos , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-1beta/análise , Interleucina-1beta/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Disco Intervertebral/química , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
7.
Cancer Cell Int ; 19: 265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632199

RESUMO

Background: Tumor-infiltrating immune cells (TIICs) are highly relevant to clinical outcome of glioma. However, previous studies cannot account for the diverse functions that make up the immune response in malignant transformation (MT) from low-grade glioma (LGG) to high-grade glioma (HGG). Methods: Transcriptome level, genomic profiles and its relationship with clinical practice were obtained from TCGA and CGGA database. The "Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)" algorithm was used to estimate the fraction of 22 immune cell types. We divided the TCGA and CGGA set into an experiment set (n = 174) and a validation set (n = 74) by random number table method. Univariate and multivariate analyses were performed to evaluate the 22 TIICs' value for MT in LGG. ROC curve was plotted to calculate area under curve (AUC) and cut-off value. Results: Heterogeneity between TIICs exists in both intra- and inter-groups. Several TIICs are notably associated with tumor grade, molecular subtypes and survival. T follicular helper (TFH) cells, activated NK Cells and M0 macrophages were screened out to be independent predictors for MT in LGG and formed an immune risk score (IRS) (AUC = 0.732, p < 0.001, 95% CI 0.657-0.808 cut-off value = 0.191). In addition, the IRS model was validated by validation group, Immunohistochemistry (IHC) and functional enrichment analyses. Conclusions: The proposed IRS model provides promising novel signatures for predicting MT from LGG to HGG and may bring a better design of glioma immunotherapy studies in years to come.

8.
J Phys Chem A ; 123(39): 8365-8369, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31525035

RESUMO

Benzene cation is a prototypical complex system that exhibits ultrafast conical intersections of different electronic states located close to the Franck-Condon region, yet little information is available about the dynamics of the cationic excited states. Here we utilize femtosecond time-resolved strong field ionization-photo fragmentation (SFI-PF) method to prepare and probe the electronic states of benzene cations. The transient of both the parent ion and the daughter ions are obtained, which present distinct behaviors at different pulse energies of the SFI laser. The results provide the first experimental evidence of B2E2g-X2E1g ultrafast relaxation of benzene cation, which occurs in about 250-270 fs. Our study should pave the way to revealing the ultrafast photochemistry of complex molecular cations.

9.
J Thorac Dis ; 11(7): 2730-2736, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31463100

RESUMO

Background: Pleural effusions are common complications of various diseases. Patients with malignant pleural effusion (MPE) usually face poor prognosis and short life expectancy. Discriminating between MPE and benign pleural effusion remains to be difficult. The aim of our current study was to evaluate whether CD206+CD14+ macrophages could be a diagnostic biomarker for MPE. Methods: The percentages of CD14+, CD86+CD14+ and CD206+CD14+ macrophages in pleural effusions were determined by flow cytometry in 34 patients with MPE and 26 with benign pleural effusion, and their diagnostic performances were evaluated by receiver operating characteristic (ROC) curves. Results: The percentages of CD14+, CD86+CD14+ and CD206+CD14+ macrophages were remarkably higher in MPE than in benign pleural effusion (all P<0.05). With a cutoff value of 39.8%, a high sensitivity of 88.2% and high specificity of 100.0% were found in CD206+CD14+ macrophages to diagnose MPE. The area under the curve, positive predictive value and negative predictive value of CD206+CD14+ macrophages were 0.980 (95% CI, 0.905 to 0.999), 100.0 (88.4 to 100.0) and 86.7 (69.3 to 96.2), respectively. The diagnostic performance of CD206+CD14+ macrophages was more accurate than those of CD14+ and CD86+CD14+ macrophages. Conclusions: CD206+CD14+ macrophages could be used to discriminate MPE from benign pleural effusion.

10.
Cancer Med ; 8(12): 5735-5749, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31392826

RESUMO

Liver cancer is the most common cancer and is the epitome of a recalcitrant cancer. Increasing evidence shown that long noncoding RNAs (lncRNA) were associated with cancer-related death and could function as a competing endogenous RNA (ceRNA). To explore regulatory roles and potential prognostic biomarkers of lncRNA for liver cancer, RNA-sequencing expression data were downloaded from the TCGA database and GEO database. A total of 357 patients were randomly divided into a discovery group and a validation group, of which 313 patients can obtain clinical data. In discovery phrase, 58 lncRNAs, 16 miRNAs, and 34 mRNAs were screened to construct the ceRNA network based on 252 patients employed from discovery group. Univariate and multivariate Cox hazard regression analysis model revealed that five lncRNAs (AATK-AS1, C10orf91, LINC00162, LINC00200, and LINC00501) from 58 lncRNAs were formulated to predict the overall survival (OS). We used the value of gene expression and regression coefficients to construct a risk score based on the five lncRNAs. Next, we validated our model in the GSE116174 dataset (n = 64) and the validation group (n = 94) from TCGA database. Subgroup analysis suggest that the five lncRNAs played critical parts in early stage in cancer from both discovery and validation groups. The five lncRNAs were also found to be associated with immune cells infiltration including CD4+ memory activated, NK cells activated and mast cells activated, then the results were also validated according to the validation group. Furthermore, KEGG pathway enrichment analysis showed that these nine coexpressed modules using the method of WGCNA, and many of these pathways are associated with the development and progression of disease. At last, the transcription factor binding sites (TFBS) of the five lncRNAs were predicted, which help us to understand the potential mechanism that the TFBS adjusted the ceRNA network. In summary, the ceRNA regulatory network may contribute to a better understanding of liver cancer mechanism and provide potential prognostic biomarkers and therapeutic targets.

11.
Mol Cancer Res ; 17(10): 1975-1984, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31266817

RESUMO

Epithelial-mesenchymal transition (EMT) represents one of the most important events in the invasion of glioblastomas (GBM); therefore, better understanding of mechanisms that govern EMT is crucial for the treatment of GBMs. In this study, we report that the deubiquitinase ubiquitin-specific protease 3 (USP3) is significantly upregulated in GBMs and correlates with a shorter median overall and relapse-free survival. Silencing of USP3 attenuates the migration and invasion abilities of GBM cells in vitro and tumor growth in an orthotopic xenograft mouse model. Mechanistically, we identify USP3 as a bona fide deubiquitinase for Snail, a master transcription factor that promotes EMT, in GBM cells. USP3 interacts directly with Snail and stabilizes Snail via deubiquitination. Ectopic expression of Snail could largely rescue the inhibitory effects of USP3 depletion on migration, invasion, and tumor growth of GBM cells. In addition, we found that USP3 strongly correlates with Snail expression in primary human GBM samples. Overall, our findings reveal a critical USP3-Snail signaling axis in EMT and invasion, and provide an effective therapeutic approach against GBM. IMPLICATIONS: Our study establishes USP3-mediated Snail stabilization as an important mechanism underlying GBM invasion and progression, and provides a rationale for potential therapeutic interventions in the treatment of GBM.

12.
J Clin Oncol ; 37(24): 2141-2151, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31283409

RESUMO

PURPOSE: To compare the survival outcomes of neoadjuvant three-dimensional conformal radiotherapy (RT) followed by hepatectomy with hepatectomy alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). PATIENTS AND METHODS: A randomized, multicenter controlled study was conducted from January 2016 to December 2017 in patients with resectable HCC and PVTT. Patients were randomly assigned to receive neoadjuvant RT followed by hepatectomy (n = 82) or hepatectomy alone (n = 82). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines were used to evaluate the therapeutic effects of RT. The primary end point was overall survival. The expression of interleukin-6 (IL-6) in patients' serum before RT and in surgical specimens was correlated with response to RT. RESULTS: In the neoadjuvant RT group, 17 patients (20.7%) had partial remission. The overall survival rates for the neoadjuvant RT group at 6, 12, 18, and 24 months were 89.0%, 75.2%, 43.9%, and 27.4%, respectively, compared with 81.7%, 43.1%, 16.7%, and 9.4% in the surgery-alone group (P < .001). The corresponding disease-free survival rates were 56.9%, 33.0%, 20.3%, and 13.3% versus 42.1%, 14.9%, 5.0%, and 3.3% (P < .001). On multivariable Cox regression analyses, neoadjuvant RT significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone (hazard ratios, 0.35 [95% CI, 0.23 to 0.54; P < .001] and 0.45 [95% CI, 0.31 to 0.64; P < .001]). Increased expressions of IL-6 in pre-RT serum and tumor tissues were significantly associated with resistance to RT. CONCLUSION: For patients with resectable HCC and PVTT, neoadjuvant RT provided significantly better postoperative survival outcomes than surgery alone. IL-6 may predict response to RT in these patients.

13.
Neuroimage ; 199: 273-280, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158482

RESUMO

People are exposed to various magnetic fields, including the high static/steady magnetic field (SMF) of MRI, which has been increased to 9.4 T in preclinical investigations. However, relevant safety studies about high SMF are deficient. Here we examined whether 3.5-23.0 T SMF exposure for 2 h has severe long-term effects on mice using 112 C57BL/6J mice. The food/water consumption, blood glucose levels, blood routine, blood biochemistry, as well as organ weight and HE stains were all examined. The food consumption and body weight were slightly decreased for 23.0 T-exposed mice (14.6%, P < 0.01, and 1.75-5.57%, P < 0.05, respectively), but not the other groups. While total bilirubin (TBIL), white blood cells, platelet and lymphocyte numbers were affected by some magnetic conditions, most of them were still within normal reference range. Although 13.5 T magnetic fields with the highest gradient (117.2 T/m) caused spleen weight increase, the blood count and biochemistry results were still within the control reference range. Moreover, the highest field 23.0 T with no gradient did not cause organ weight or blood biochemistry abnormality, which indicates that field gradient is a key parameter. Collectively, these data suggest 3.5-23.0 T static magnetic field exposure for 2 h do not have severe long-term effects on mice.

14.
J Innate Immun ; : 1-16, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31141808

RESUMO

Prostaglandin E2 (PGE2), an essential endogenous lipid mediator for normal physiological functions, can also act as an inflammatory mediator in pathological conditions. We determined whether Staphylococcus aureus lipoproteins are essential for inducing PGE2 secretion by immune cells and whether pattern recognition receptors mediate this process. PGE2 levels secreted by mouse peritoneal macrophages infected with the S. aureus isogenic mutant, lgt::ermB (Δlgt; deficient in lipoprotein maturation), decreased compared with those from macrophages infected with wild-type (WT) S. aureus. Experiments using toll-like receptors 2 (TLR2)-deficient, TLR4-deficient, and NLRP3-deficient mice indicated that these 3 proteins are involved in macrophage PGE2 secretion in response to S. aureus, and lipoproteins were essential for S. aureus invasion and survival within macrophages. Inhibition of endogenous PGE2 synthesis had no effect on bacterial invasion. Exogenous PGE2 inhibited phagocytosis in the WT S. aureus and its isogenic mutant but increased intracellular killing accompanied by enhanced IL-1ß secretion. Our data demonstrate that S. aureus can induce macrophage TLR/mitogen-activated protein kinase/NF-κB signaling and that PGE2 treatment upregulates NLRP3/caspase-1 signaling activation. Thus, macrophage PGE2 secretion after S. aureus infection depends on bacterial lipoprotein maturation and macrophage receptors TLR2, TLR4, and NLRP3. Moreover, exogenous PGE2 regulates S. aureus-induced macrophage activation through TLRs and NLRP3 inflammasome signaling.

15.
J Cell Sci ; 132(11)2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31076511

RESUMO

Endothelial cell (EC) sensing of fluid shear stress direction is a critical determinant of vascular health and disease. Unidirectional flow induces EC alignment and vascular homeostasis, whereas bidirectional flow has pathophysiological effects. ECs express several mechanoreceptors that respond to flow, but the mechanism for sensing shear stress direction is poorly understood. We determined, by using in vitro flow systems and magnetic tweezers, that ß1 integrin is a key sensor of force direction because it is activated by unidirectional, but not bidirectional, shearing forces. ß1 integrin activation by unidirectional force was amplified in ECs that were pre-sheared in the same direction, indicating that alignment and ß1 integrin activity has a feedforward interaction, which is a hallmark of system stability. En face staining and EC-specific genetic deletion studies in the murine aorta revealed that ß1 integrin is activated and is essential for EC alignment at sites of unidirectional flow but is not activated at sites of bidirectional flow. In summary, ß1 integrin sensing of unidirectional force is a key mechanism for decoding blood flow mechanics to promote vascular homeostasis.This article has an associated First Person interview with the first author of the paper.

16.
Minerva Med ; 110(6): 564-574, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30994320

RESUMO

INTRODUCTION: Endoscopic ultrasound-guided (EUS) biliary drainage was used as an alternative method for patients who failed endoscopic retrograde cholangiopancreatography (ERCP). In recent years, an increasing number of patients was treated with EUS-biliary drainage (BD), but lack of data was available to value the efficacy and safety between EUS and ERCP. Therefore, a review was needed to evaluate the similarities and differences between the two methods and explored whether EUS-guided biliary drainage could be considered as first-line treatment. EVIDENCE ACQUISITION: We searched the Pubmed/Medline, Embase, Web of science, Google scholar, the Cochrane Library and Clinical trials of electronic databases till October 2018 for all English language. Primary outcomes to comparison included technical success, clinical success and adverse events. Secondary outcomes consisted of stent dysfunction requiring reintervention and procedure duration, Data from selected studies were collected to calculate the odds ratios (OR) and standard mean difference (SMD). EVIDENCE SINTHESIS: We searched 469 studies and at last identified 4 eligible trials. These included a total of 428 patients, 215 in the EUS group and 213 in the ERCP group. There was no difference in technical success (OR, 0.95; 95% CI: 0.45-2.02; I2=0%), clinical success (OR, 0.87; 95% CI: 0.42-1.79; I2=0%) and adverse events between 2 procedures (OR, 0.76; 95% CI: 0.29-2.00; I2=55%) but EUS-BD consisted of lower rate of reintervention (OR, 0.30; 95% CI: 0.14-0.63; I2=0%),and fewer procedure-related adverse events in pancreatitis and cholangitis (OR, 0.14; 95% CI: 0.04-0.51; I2=0%).There was no difference in length of procedure duration, with a pooled standard mean difference of 0.26 (95% CI: -0.15 to 0.66). CONCLUSIONS: EUS-BD and ERCP-BD in terms of relief of malignant biliary obstruction presented the similarity rate of technical success, clinical success and there is no significant difference in adverse events of two procedures. EUS-BD could be used as a substitute for ERCP-BD, even considered as first-line treatment.

17.
J Clin Invest ; 129(5): 2043-2055, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30958800

RESUMO

The mesenchymal (MES) subtype of glioblastoma (GBM) stem cells (GSCs) represents a subpopulation of cancer cells that are notorious for their highly aggressive nature and resistance to conventional therapy. Aldehyde dehydrogenase 1A3 (ALDH1A3) has been recently suggested as a key determinant for the maintenance of MES features of GSCs. However, the mechanisms underpinning aberrant ALDH1A3 expression remain elusive. Here, we identified ubiquitin-specific protease 9X (USP9X) as a bona fide deubiquitinase of ALDH1A3 in MES GSCs. USP9X interacted with, depolyubiquitylated, and stabilized ALDH1A3. Moreover, we showed that FACS-sorted USP9Xhi cells were enriched for MES GSCs with high ALDH1A3 activity and potent tumorigenic capacity. Depletion of USP9X markedly downregulated ALDH1A3, resulting in a loss of self-renewal and tumorigenic capacity of MES GSCs, which could be largely rescued by ectopic expression of ALDH1A3. Furthermore, we demonstrated that the USP9X inhibitor WP1130 induced ALDH1A3 degradation and showed marked therapeutic efficacy in MES GSC-derived orthotopic xenograft models. Additionally, USP9X strongly correlated with ALDH1A3 expression in primary human GBM samples and had a prognostic value for patients with the MES subgroup. Collectively, our findings unveil USP9X as a key deubiquitinase for ALDH1A3 protein stabilization and a potential target for GSC-directed therapy.

18.
Genes (Basel) ; 10(4)2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-31003538

RESUMO

Temperature is one of the most important environmental factors affecting flowering in plants. Adonis amurensis, a perennial herbaceous flower that blooms in early spring in northeast China where the temperature can drop to -15 °C, is an ideal model for studying the molecular mechanisms of flowering at extremely low temperatures. This study first investigated global gene expression profiles at different developmental stages of flowering in A. amurensis by RNA-seq transcriptome and iTRAQ proteomics. Finally, 123 transcription factors (TFs) were detected in both the transcriptome and the proteome. Of these, 66 TFs belonging to 14 families may play a key role in multiple signaling pathways of flowering in A. amurensis. The TFs FAR1, PHD, and B3 may be involved in responses to light and temperature, while SCL, SWI/SNF, ARF, and ERF may be involved in the regulation of hormone balance. SPL may regulate the age pathway. Some members of the TCP, ZFP, MYB, WRKY, and bHLH families may be involved in the transcriptional regulation of flowering genes. The MADS-box TFs are the key regulators of flowering in A. amurensis. Our results provide a direction for understanding the molecular mechanisms of flowering in A. amurensis at low temperatures.


Assuntos
Adonis/fisiologia , Flores/crescimento & desenvolvimento , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Adonis/genética , Adonis/metabolismo , Cromatografia Líquida , Temperatura Baixa , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Família Multigênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica/métodos , Análise de Sequência de RNA/métodos , Espectrometria de Massas em Tandem
19.
J Phys Chem A ; 123(16): 3435-3440, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30951309

RESUMO

HS2 molecules play an important role in the photochemical processes in combustion, atmosphere, and interstellar medium, yet our knowledge about the electronic excited states in the UV region is limited. In this study, we perform high-level ab initio calculations on electronic states of HS2 using the internally contracted multireference configuration interaction method including the Davidson correction (icMRCI + Q) method. The vertical transition energies, oscillator strengths, electron configurations, and transitions of thirteen electronic states of HS2 with energy up to 8 eV are calculated at the icMRCI + Q/aug-cc-pv(5 + d)Z level. Based on the calculated potential energy curves, we investigate the interaction and photodissociation mechanism of the electronic states, which should shed some light on the decomposition processes of the gas-phase HS2 molecules in the ultraviolet region.

20.
Neurotherapeutics ; 16(2): 381-393, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30843154

RESUMO

Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelin-associated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes. Therefore, we hypothesized that the choice and modification of self-antigens, and co-regulating multiple targets, may be more effective in repairing the injured spinal cord and improving functional recovery. In this study, NgR and PirB were selected to construct a double-targeted granulocyte-macrophage colony stimulating factor-NgR-PirB (GMCSF-NgR-PirB) nucleic acid vaccine, and investigate the efficacy of this immunotherapy in a spinal cord injury model in rats. The results showed that this vaccination could stimulate the production of antibodies against NgR and PirB, block the inhibitory effects mediated by various MAIs, and promote nerve regeneration and functional recovery after spinal cord injury. These findings suggest that nucleic acid vaccination against NgR and PirB can be a promising therapeutic strategy for SCI and other central nervous system diseases and injuries.


Assuntos
Imunoterapia/métodos , Regeneração Nervosa/imunologia , Receptor Nogo 1/imunologia , Traumatismos da Medula Espinal/terapia , Vacinas de DNA/uso terapêutico , Animais , Feminino , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/imunologia , Traumatismos da Medula Espinal/imunologia , Vacinação
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