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1.
Opt Express ; 28(1): 369-378, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32118965

RESUMO

High-fidelity transmission of polarization encoded qubits plays a key role in long distance quantum communication. By establishing the channel between ground and satellite, the communication distance can even exceed thousands of kilometers. Aimed to achieve the efficient uplink quantum communication, here we describe a high-fidelity polarization design of a transmitting antenna with an average polarization extinction ratio of 887:1 by a local test. We also implement a feasible polarization-compensation scheme for satellite motions with a fidelity exceeding 0.995 ± 0.001. Based on these works, we demonstrate the ground-to-satellite entanglment distribution with a violation of Bell inequality by 2.312±0.096, which is well above the classic limit 2.

2.
J Environ Manage ; 261: 109665, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32148247

RESUMO

Biotechnology has proven effective in removing a wide variety of VOCs. In this study, the effects of pH (from 3 to 7), operating temperature (20-30 °C), empty bed residence time (EBRT, 10-40 s) and transient inlet concentration (400-4000 mg m-3) on the removal performance of an airlift packing bioreactor (ALPR) was investigated. The removal efficiency (RE) and stability of the ALPR was evaluated and compared with the conventional airlift bioreactor (ALR). The results showed that under the influence of single factor variation, the ALPR showed significant higher RE and better stability than the ALR in removing dichloromethane (DCM) and toluene. Besides, a factorial design was used to analyses the interaction of multiple factors and their influence on the removal of DCM and toluene in the ALPR and ALR. It shows that pH value has the most significant influence, and plays a crucial role in maintaining high RE of DCM and toluene in both of the ALPR and ALR. Temperature has a great effect on the removal of toluene. EBRT has certain effect on the removal of DCM in the ALPR. The transient concentration of a single substrate has a significant negative effect on the RE of this substrate, while it does not significantly affect the removal of another substrate in the ALPR. However, the steep increase of DCM concentration has an adverse effect on the RE of high concentration toluene in the ALR. The overall RE and degradation capacity of both toluene and DCM by the ALPR are much higher than that of the conventional ALR.


Assuntos
Cloreto de Metileno , Tolueno , Biodegradação Ambiental , Reatores Biológicos
4.
Chemosphere ; 251: 126368, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32171941

RESUMO

Mangrove sediments act as an important natural sink and a secondary source for trace metals. The main objective of this study was to investigate metal contamination and its relationship to mangrove-derived carbohydrates in mangrove sediments. Sixteen metals (Be, V, Cr, Co, Ni, Cu, Zn, Ga, As, Sr, Cd, Sn, Sb, Ba, Tl, and Pb)were analyzed in the surface sediments from four sites at different latitudes on the southeast coastline of China. The sedimentary organic matter was characterized by Rock-Eval pyrolysis, and the neutral sugars were examined by gas chromatograph mass spectrometry. Our results from the enrichment factors indicated that the mangrove sediments were no enriched by Ga, Sr, and Ba, minor enriched by Be, V, Cr, Co, Ni, Cu, Zn, As, Sn, Sb, Tl, and Pb, and moderate enriched by Cd. Litterfall was a major source of organic matter in the mangrove sediments, and the neutral sugars were mainly derived from this litterfall. Significant correlations were detected between the total organic carbon, pyrolytic parameters, neutral sugars, and enrichment factors of V, Cr, Co, Ni, Zn, and Cd, suggesting the input of neutral carbohydrates played an important role in enhancing the metal accumulation in the mangrove sediments. The mangrove litterfall itself was a major source of metals for the sediments, and the mangrove-derived organic matter enhanced the sediment's metal accumulation.

5.
Int Immunopharmacol ; 82: 106346, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32120344

RESUMO

Increasing evidence suggests that infection promotes the initiation and progression of prostate cancer. This study investigated the effects of lipopolysaccharide (LPS), a major component of Gram-negative bacilli, on proliferation, migration and invasion of prostate cancer cells and the protective effects of 1α,25(OH)2D3 (calcitriol). PC-3 and DU145 cells were stimulated with LPS (2.0 µg/mL) in the presence or absence of 1α,25(OH)2D3 (100 nM). Our results shown that 1α,25(OH)2D3 reduced the proportion of S phase cells in LPS-stimulated PC-3 and DU145 cells, and down-regulated the nuclear protein levels of Cyclin D1 and PCNA in LPS-stimulated PC-3 cells. In addition, 1α,25(OH)2D3 inhibited migration and invasion, as determined by wound healing and transwell assay, in LPS-stimulated PC-3 and DU145 cells. Of interest, we observed that 1α,25(OH)2D3 inhibits NF-κB activation and subsequent synthesis and secretion of IL-6 and IL-8 by promoting VDR and NF-κB p65 interaction. Surprisingly, 1α,25(OH)2D3 blocks nuclear translocation of pSTAT3 by promoting physical interaction between VDR and pSTAT3 (Tyr705) in LPS-stimulated PC-3 and DU145 cells. These results suggest that 1α,25(OH)2D3 inhibits LPS-induced proliferation, migration and invasion in prostate cancer cells by directly and indirectly blocking STAT3 signal transduction.

6.
PLoS Negl Trop Dis ; 14(3): e0007675, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32119672

RESUMO

Orientia tsutsugamushi infection can cause acute lung injury and high mortality in humans; however, the underlying mechanisms are unclear. Here, we tested a hypothesis that dysregulated pulmonary inflammation and Tie2-mediated endothelial malfunction contribute to lung damage. Using a murine model of lethal O. tsutsugamushi infection, we demonstrated pathological characteristics of vascular activation and tissue damage: 1) a significant increase of ICAM-1 and angiopoietin-2 (Ang2) proteins in inflamed tissues and lung-derived endothelial cells (EC), 2) a progressive loss of endothelial quiescent and junction proteins (Ang1, VE-cadherin/CD144, occuludin), and 3) a profound impairment of Tie2 receptor at the transcriptional and functional levels. In vitro infection of primary human EC cultures and serum Ang2 proteins in scrub typhus patients support our animal studies, implying endothelial dysfunction in severe scrub typhus. Flow cytometric analyses of lung-recovered cells further revealed that pulmonary macrophages (MΦ) were polarized toward an M1-like phenotype (CD80+CD64+CD11b+Ly6G-) during the onset of disease and prior to host death, which correlated with the significant loss of CD31+CD45- ECs and M2-like (CD206+CD64+CD11b+Ly6G-) cells. In vitro studies indicated extensive bacterial replication in M2-type, but not M1-type, MΦs, implying the protective and pathogenic roles of M1-skewed responses. This is the first detailed investigation of lung cellular immune responses during acute O. tsutsugamushi infection. It uncovers specific biomarkers for vascular dysfunction and M1-skewed inflammatory responses, highlighting future therapeutic research for the control of this neglected tropical disease.

7.
PLoS One ; 15(3): e0227784, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160196

RESUMO

Pleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity.

8.
Colloids Surf B Biointerfaces ; 190: 110951, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32172167

RESUMO

Human hair is a readily available source for hair protein-based biomaterial and is increasingly explored as an alternative to existing hemostatic materials. The hair protein is a complex mixture of multiple proteins, which are preferably extracted at relatively high temperatures (50-90 °C) for increasing protein yields. However, the effect of processing temperature on the hemostatic property of the hair derived proteins are not yet well-understood. The objective of the current study was to characterize the influence of thermal treatments (37 °C, 50 °C, 75 °C, 80 °C, and 90 °C) on the (i) secondary structure of different fractions of hair proteins including keratin (40-65 kDa) and keratin-associated proteins (KAPs, 6-30 kDa), and (ii) their capability to precipitate the soluble fibrinogen in an in vitro fibrin clotting assay. Our results indicated that the thermal treatments induced changes to the helical contents of hair-derived protein extracts and also increased the precipitation amount and rate of soluble fibrinogen. While further studies are required to better understand the exact role of hair protein fractions on the coagulation process, the current research suggests that the hair proteins extracted under relatively high temperatures is a prerequisite approach for improving the hemostatic property of human hair-derived proteins.

9.
ACS Nano ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32083843

RESUMO

Mixed-dimensional van der Waals (vdW) heterostructures composed of one-dimensional (1D) and two-dimensional (2D) materials have exhibited great potential in nanoelectronics and nano-optoelectronics. In this study, we present a vertical point p-n junction (VPpnJ), in which a vertical stacked molybdenum disulfide/tungsten diselenide p-n junction is sandwiched between two cross-stacked metallic carbon nanotubes (CNTs). The device can be transformed from p-n junction to n-n junction via gate modulation. As a photodetector, the VPpnJ device can work in three different modes by setting the appropriate gating voltages. The photosensitive areas are localized around the top CNT, bottom CNT, and the cross point at VG = -10 V, 10 V, and ∼0 V, respectively. In the p-n regime at the negative gate voltage, the VPpnJ device showed an obvious photovoltaic effect. The external quantum efficiency of the VPpnJ can reach 42.7%. The electrical control of the electronic and optoelectronic characteristics can be mainly attributed to the gate-tunable interfacial built-in electric fields in the heterostructures. The progress also reveals the functional diversity of such 1D/2D mixed-dimensional heterostructures, which will be prospects for future nanoelectronics and nano-optoelectronics.

10.
BMC Complement Med Ther ; 20(1): 13, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32020862

RESUMO

BACKGROUND: Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease. Buyang Huanwu Tang (BYHWT), a classical traditional Chinese medicine formula, has been widely utilized for the treatment of PF in China. This present study aimed to explore the mechanism of BYHWT in the treatment of PF in vitro. METHODS: TGF-ß1 stimulated human alveolar epithelial A549 cells were used as in vitro model for PF. Post the treatment of BYHWT, cell viability was measured by MTT assay, and cell morphology was observed under microscope. The epithelial-to-mesenchymal transition (EMT) markers (E-cadherin, Vimentin) and collagen I (Col I) were detected by western blot, immunofluorescence staining and real-time quantitative polymerase chain reaction. With the co-administration of activators (IGF-1, SC79) and inhibitors (LY294002, MK2206), the effect of BYHWT on PI3K/Akt pathway was analyzed by western blot. RESULTS: BYHWT inhibited cell growth, and prevented cell morphology changed from epithelial to fibroblasts in TGF-ß1 induced A549 cells. BYHWT decreased Vimentin and Col I, while increased E-cadherin at both protein and mRNA levels. Moreover, phosphorylation of PI3K (p-PI3K) and phosphorylation of Akt (p-Akt) were significantly down-regulated by BYHWT in TGF-ß1 stimulated A549 cells. CONCLUSION: These results indicate that BYHWT suppressed TGF-ß1-induced collagen accumulation and EMT of A549 cells by inhibiting the PI3K/Akt signaling pathway. These findings suggest that BYHWT may have potential for the treatment of PF.

11.
Hepatology ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32086945

RESUMO

Alcohol-associated liver disease (ALD) is a common chronic liver disease worldwide with high morbidity and mortality, and no FDA-approved therapies. Fructose (dietary or endogenous), its metabolite uric acid, and aldose reductase (AR, the only endogenous enzyme that produces fructose) are strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). However, the role of AR or its metabolites in ALD remains understudied and was examined using human specimens, cultured cells and mouse model systems. We demonstrated for the first time in liver specimens from alcoholic hepatitis (AH) patients, AR upregulation and elevated AR metabolites (sorbitol, fructose, and uric acid) which correlated significantly with (i) increased lipid peroxidation byproducts and ER stress, (ii) decreased protective ER chaperones, and (iii) greater cell death and liver injury. Further, we established a causal role for AR in ALD by showing that the genetic deficiency of AR (knockout mice) prevented alcohol-induced increase in harmful AR metabolites, toxic aldehydes, steatosis, ER stress, apoptosis and liver injury. Lastly, we demonstrated the therapeutic potential of pharmacological AR inhibition against alcohol-induced hepatic injury in experimental ALD CONCLUSIONS: Our data demonstrate that hepatic AR upregulation, and consequent elevation in fructose, sorbitol and/or uric acid, are important factors contributing to alcohol-induced steatosis, ER stress, apoptosis and liver injury in both experimental and human ALD. Our study provides a strong rationale to evaluate AR as a potential therapeutic target and to test AR inhibitors to ameliorate alcohol-induced liver injury.

12.
Semin Cell Dev Biol ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32033828

RESUMO

Helicobacter pylori colonizes human stomach mucosa and its infection causes gastrointestinal diseases with variable severity. Bacterial infection stimulates autophagy, which is a part of innate immunity used to eliminate intracellular pathogens. Several intracellular bacteria have evolved multipronged strategies to circumvent this conserved system and thereby enhance their chance of intracellular survival. Nonetheless, studies on H. pylori have produced inconsistent results, showing either elevated or reduced clearance efficiency of intracellular bacteria through autophagy. In this review, we summarize recent studies on the mechanisms involved in autophagy induced by H. pylori and the fate of intracellular bacteria.

13.
Chemosphere ; 249: 126093, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32045754

RESUMO

In order to harness the full capability of ultraviolet and visible light in the dielectric barrier discharge induced non-thermal plasma (DBD-NTP) process, g-C3N4/TiO2 catalysts were prepared and utilized in this process. Synergistic degradation of acid orange 7 (AO7) dye by DBD-NTP and g-C3N4/TiO2 was conducted, and the performance, degradation pathways and synergistic catalytic mechanism were investigated. The results showed that the degradation rate of AO7 in the DBD-NTP and g-C3N4-15/TiO2 process increased by 39.1% compared with that in the single DBD-NTP process at 12 min discharge time. At 20 W input power, initial concentration of AO7 was 5 mg/L, catalytic dosage was 0.5 g/L, initial pH value was 10.0 and air flow rate was 52 L/h, the degradation rate of AO7 reached 100.0% after 12 min discharge time. Higher discharge power and initial concentration of AO7 inhibited AO7 degradation, whereas increasing the air flow rate and initial pH value of the solution promoted AO7 degradation. The degradation pathways of AO7 consisted of azo structure destruction, ring opening reaction, hydroxylation, carboxylation and mineralization reaction. The results of radical trapping experiment showed that O2-, h+, OH, O3 and H2O2 were the main reactive species for AO7 degradation in the DBD-NTP and g-C3N4-15/TiO2 process. The Z-scheme photocatalytic mechanism for the g-C3N4/TiO2 catalyst was proposed.

14.
Food Funct ; 11(3): 2126-2136, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32073014

RESUMO

Osteoarthritis (OA) is a serious and frequently occurring disease in the elderly, characterized by cartilage degeneration and proliferation of bone structure. Glycyrrhizin, a compound extracted from licorice, has been reported to have various important biological activities, such as antioxidant properties and anti-inflammatory action. However, it has not been reported whether glycyrrhizin has a positive effect on OA development. Our study aimed to evaluate the effects of glycyrrhizin on human OA chondrocytes. In the present study, we discovered that glycyrrhizin remarkably suppressed the interleukin (IL)-1ß-induced level of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) and the production of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOs), metalloproteinase3 (MMP3), metalloproteinase13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs5 (ADAMTS5). In addition, glycyrrhizin inverted the degradation of aggrecan and collagen II. Moreover, it significantly inhibited IL-1ß-stimulated PI3K/AKT phosphorylation and NF-κB mobilization in human OA chondrocytes. In vivo, glycyrrhizin treatment prevented the destruction of cartilage in mice OA models. In summary, all the results demonstrate that glycyrrhizin may be a potential therapeutic approach for OA.

15.
Bone ; 133: 115247, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31968281

RESUMO

Bone mineral density (BMD) is a key indicator for diagnosis and treatment for osteoporosis; the reduction of BMD could increase the risk of osteoporotic fracture. It was very recently found that Piezo1 mediated mechanically evoked responses in bone and further participated in bone formation in mice. Here, we performed cross phenotype meta-analysis for human BMD at lumbar spine (LS), femoral neck (FN), distal radius/forearm (FA) and heel and screened out 14 top SNPs for PIEZO1, these SNPs were overlapped with putative enhancers, DNase-I hypersensitive sites and active promoter flanking regions. We found that the signal of the best SNP rs62048221 was mainly from heel ultrasound estimated BMD (-0.02 SD per T allele, P = 8.50E-09), where calcaneus supported most of the mechanical force of body when standing, walking and doing physical exercises. Each copy of the effect allele T of SNP rs62048221 was associated with a decrease of 0.0035 g/cm2 BMD (P = 4.6E-27, SE = 0.0003) in UK Biobank data within 477,760 samples. SNP rs62048221 was located at the enhancer region (HEDD enhancer ID 2331049) of gene PIEZO1, site-directed ChIP assays in human mesenchymal stem cells (hMSCs) showed significant enrichment of H3K4me1 and H3K27ac in this region, luciferase assays showed that rs62048221 could significantly affect the activity of the enhancer where it resides. Our results first suggested that SNP rs62048221 might mediate the PIEZO1 expression level via modulating the activity of cis-regulatory elements and then further affect the BMD.

16.
Sci Rep ; 10(1): 1155, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980705

RESUMO

The preparation of chitosan-tripolyphosphate (chitosan-TPP) particles by the spray drying had been reported word widely for a sustained release of drugs to prevent rapid drug metabolism. Although the spray drying is a straightforward procedure turning a liquid feed into a well-defined dry powder, seldom research works were focusing on how the processing parameters and liquid feeding constitutions of spray drying system might affect the properties of spray-dried chitosan particles loaded with drugs, such as the particle size and morphologies, which would be very important to drug encapsulation and dissolution of the drug delivery design. This study thus prepared the chitosan particles with theophylline (TH) loaded as a model drug and TPP as cross-linker at various spray drying conditions. Our results indicate the diameter of the TH/chitosan-TPP particles made by customized spray drying apparatus spans from 424 to 497 nm with a geometric standard deviation of less than 2. The corresponding release of TH was tunable by the chitosan-TPP matrix density under the selected spray drying temperature and the carrying air flow rate. These results suggest an indeed need for optimized spray drying processing conditions to make the ideal spray-dried TH/chitosan-TPP particles for the desired drug delivery.

17.
J Agric Food Chem ; 68(5): 1405-1418, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31940190

RESUMO

The aim of this study was to develop a novel system for the co-delivery of resveratrol and coenzyme Q10 (CoQ10). It was achieved with a combination of resveratrol-loaded composite nanoparticles and CoQ10-loaded Pickering emulsions. Different levels of resveratrol (0.05-0.30%, w/v) were entrapped into composite nanoparticles by the method of emulsification-evaporation. The size of composite nanoparticles was around 300-600 nm, and the maximum loading capacity of resveratrol was up to 13.88% (w/w). Hydrogen bonds, hydrophobic effects, and electrostatic attraction participated in the self-assembly of composite nanoparticles. The stability of CoQ10 Pickering emulsions was monitored under simulated environmental stresses (pH, ionic strength, UV radiation, and heat) and accelerated storage conditions. The physical stability of Pickering emulsions was dependent on the particle compositions, and the CoQ10 entrapped was also protected by the resveratrol-loaded nanoparticles. The morphology of Pickering emulsions was observed with the aid of optical microscopy, confocal laser scanning microscopy, and cryo-scanning electronic microscopy. The nutraceutical Pickering emulsions were designed for the co-delivery of resveratrol and CoQ10, which has the potential to be a novel vehicle for bioactive ingredients.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Resveratrol/química , Ubiquinona/análogos & derivados , Estabilidade de Medicamentos , Emulsões/química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Concentração Osmolar , Tamanho da Partícula , Ubiquinona/química
18.
Mol Genet Genomics ; 295(1): 95-106, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31489484

RESUMO

Regulatory factors function by modulating a variety of cascade mechanisms in cells. RBM4 is a multifunctional RNA-binding protein in post-transcriptional gene regulation. Cytoplasmic RBM4 interacts with Ago2 to regulate inflammatory responses by affecting mRNA decay and cap-dependent translation. However, it is unclear whether RBM4 functions in inflammation regulation by its splicing factor role. Here, the cell biology, gene expression profile and alternative splicing pattern of HeLa cells with RBM4 overexpression (RBM-OE) were compared with the control. The results showed that RBM4-OE inhibited proliferation. RBM4-OE extensively affects the transcriptional level of genes involved in cell surface receptor signalling pathway, inflammatory responses and the response to lipopolysaccharide. RBM4 broadly regulated the alternative splicing of hundreds of genes with functions of protein binding, helicase activity, DNA binding and transcription co-activator. RBM4-regulated splicing of these genes plays an important role in apoptotic process and gene transcription regulation. As an example, exon inclusion of TNIP1 mediated by RBM4 affects the expression of its targets in inflammatory pathways. These results indicated that RBM4 can mediate the inflammatory response via splicing regulation, which adds to the understanding of the critical role of RBM4 in cancer complicated by inflammation. In conclusion, this study indicated a mechanism in which the dysregulation of alternative splicing can influence cellular biology and lead to various immune-related diseases.


Assuntos
Processamento Alternativo/genética , Proliferação de Células/genética , Inflamação/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Apoptose/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Éxons/genética , Células HeLa , Humanos , Processamento de RNA/genética , RNA Mensageiro/genética , Transdução de Sinais/genética , Transcrição Genética/genética , Ativação Transcricional/genética , Transcriptoma/genética
19.
Int J Oncol ; 56(1): 151-164, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31814034

RESUMO

Tumour­associated macrophages (TAMs) compose a major component of the tumour microenvironment and form in this microenvironment prior to cancer metastasis. However, the detailed mechanisms of TAM remodelling in the context of bladder cancer have not been clearly defined. The present study collected exosomes from the conditioned medium of human bladder T24 cancer cells. The effects of macrophages treated with exosomes derived from T24 cells on bladder cancer cell migration and invasion were analysed by Transwell assays. The expression levels of endogenous and exosomal microRNA­21 (miR­21) were examined by reverse transcription­quantitative PCR, while the expression level of the target protein was analysed by western blot analysis. Luciferase reporter plasmids and mutants were used to confirm direct targeting. The effects of miR­21 on bladder cancer cell migration and invasion were analysed by Transwell and Matrigel assays following miR­21 transfection. It was identified that exosomes derived from bladder cancer cells polarized THP­1 cell­derived macrophages into the M2 phenotype, and TAM­mediated pro­migratory and pro­invasive activity was determined. Moreover, it was found that miR­21 was highly expressed in exosomes derived from bladder cancer cells as well as in macrophages treated with exosomes. In addition, macrophages transfected with miR­21 exhibited M2 polarization and promoted T24 cell migratory and invasive ability. Mechanistically, exosomal miR­21 derived from bladder cancer cells inhibited phosphatase and tensin homolog activation of the PI3K/AKT signalling pathway in macrophages and enhanced STAT3 expression to promote M2 phenotypic polarization. The present results suggest that exosomal miR­21 can promote cancer progression by polarizing TAMs.

20.
J Gynecol Oncol ; 31(1): e5, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31788995

RESUMO

OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

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