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1.
Oncogene ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435022

RESUMO

RASSF1A encodes a tumor suppressor that inhibits the RAS→RAF→MEK→ERK pathway and is one of the most frequently inactivated genes in human cancers. MUC1-C is an oncogenic effector of the cancer cell epigenome that is overexpressed in diverse carcinomas. We show here that MUC1-C represses RASSF1A expression in KRAS wild-type and mutant cancer cells. Mechanistically, MUC1-C occupies the RASSF1A promoter in a complex with the ZEB1 transcriptional repressor. In turn, MUC1-C/ZEB1 complexes recruit DNA methyltransferase 3b (DNMT3b) to the CpG island in the RASSF1A promoter. Targeting MUC1-C, ZEB1, and DNMT3b thereby decreases methylation of the CpG island and derepresses RASSF1A transcription. We also show that targeting MUC1-C regulates KRAS signaling, as evidenced by RNA-seq analysis, and decreases MEK/ERK activation, which is of importance for RAS-mediated tumorigenicity. These findings define a previously unrecognized role for MUC1-C in suppression of RASSF1A and support targeting MUC1-C as an approach for inhibiting MEK→ERK signaling.

2.
Int J Cancer ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31265121

RESUMO

Despite the identification of several ovarian cancer (OC) predisposition genes, a large proportion of familial OC risk remains unexplained. We adopted a two-stage design to identify new OC predisposition genes. We first carried out a large germline whole-exome sequencing study on 158 patients from 140 families with significant OC history, but without evidence of genetic predisposition due to BRCA1/2. We then evaluated the potential candidate genes in a large case-control association study involving 381 OC cases in the Cancer Genome Atlas project and 27,173 population controls from the Exome Aggregation Consortium. Two new putative OC risk genes were identified, namely, ANKRD11, a putative tumor suppressor, and POLE, an enzyme involved in DNA repair and replication. These two genes likely confer moderate OC risk. We performed in vitro experiments and showed an ANKRD11 mutation identified in our patients markedly lowered the protein expression by compromising protein stability. Upon future validation and functional characterization, these genes may shed light on cancer etiology along with improving ascertainment power and preventive care of individuals at high risk of OC.

3.
Int J Biol Sci ; 15(6): 1161-1176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223277

RESUMO

We previously found that hypoxia induced renal tubular epithelial cells (RTECs) release functional extracellular vesicles (EVs), which mediate the protection of remote ischaemic preconditioning (RIPC) for kidney ischaemia-reperfusion (I/R) injury. We intend to investigate whether the EVs were regulated by hypoxia-inducible factor 1α (HIF-1α) and Rab22 during RIPC. We also attempted to determine the potentially protective cargo of the EVs and reveal their underlying mechanism. Hypoxia preconditioning (HPC) of human kidney 2 (HK2) cells was conducted at 1% oxygen (O2) for different amounts of time to simulate IPC in vitro. EVs were isolated and then quantified. HIF-1α- and Rab22-inhibited HK2 cells were used to investigate the role of the HIF-1α/Rab22 pathway in HPC-induced EV production. Both normoxic and HPC EVs were treated in vivo to assess the protective effect of I/R injury. Moreover, microRNA (miRNA) sequencing analysis and bioinformatics analysis was performed. We revealed that the optimal conditions for simulating IPC in vitro was no more than 12 h under the 1% O2 culture circumstance. HPC enhanced the production of EVs, and the production of EVs was regulated by the HIF-1α/Rab22 pathway during HPC. Moreover, HPC EVs were found to be more effective at attenuating mice renal I/R injury. Furthermore, 16 miRNAs were upregulated in HPC EVs. Functional and pathway analysis indicated that the miRNAs may participate in multiple processes and pathways by binding their targets to influence the biochemical results during RIPC. We demonstrated that HIF-1α/Rab22 pathway mediated RTEC-derived EVs during RIPC. The HPC EVs protected renal I/R injury potentially through differentially expressed miRNAs. Further study is needed to verify the effective EV-miRNAs and their underlying mechanism.

4.
J Immunother Cancer ; 7(1): 156, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221207

RESUMO

BACKGROUND: Efficient identification of neoantigen-specific T-cell responses in epithelial ovarian cancer (EOC) remains a challenge. Existing investigations of spontaneous T-cell response to tumor neoepitope in EOC have taken the approach of comprehensive screening all neoantigen candidates, with a validation rate of 0.5-2%. METHODS: Whole-exome and transcriptome sequencing analysis of treatment-naive EOC patients were performed to identify neoantigen candidates, and the immunogenicity of prioritized neoantigens was evaluated by analyzing spontaneous neoantigen-specfic CD4+ and CD8+ T-cell responses in the tumor and/or peripheral blood. The biological relevance of neoantigen-specific T-cell lines and clones were analyzed by evaluating the capacity of autologous ovarian tumor recognition. Genetic transfer of T-cell receptor (TCR) from these neoantigen-specific T-cell clones into peripheral blood T-cells was conducted to generate neoepitope-specific T-cells. The molecular signature associated with positive neoantigen T-cell responses was investigated, and the impacts of expression level and lymphocyte source on neoantigen identification were explored. RESULTS: Using a small subset of prioritized neoantigen candidates, we were able to detect spontaneous CD4+ and/or CD8+ T-cell responses against neoepitopes from autologous lymphocytes in half of treatment-naïve EOC patients, with a significantly improved validation rate of 19%. Tumors from patients exhibiting neoantigen-specific T-cell responses exhibited a signature of upregulated antigen processing and presentation machinery, which was also associated with favorable patient survival in the TCGA ovarian cohort. T-cells specific against two mutated cancer-associated genes, NUP214 and JAK1, recognized autologous tumors. Gene-engineering with TCR from these neoantigen-specific T-cell clones conferred neoantigen-reactivity to peripheral T-cells. CONCLUSIONS: Our study demonstrated the feasibility of efficiently identifying both CD4+ and CD8+ neoantigen-specific T-cells in EOC. Autologous lymphocytes genetically engineered with tumor antigen-specific TCR can be used to generate cells for use in the personalized adoptive T-cell transfer immunotherapy.

5.
Appl Opt ; 58(16): 4277-4282, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251230

RESUMO

In this work, the four optimum azimuthal angles are determined for a full-Stokes scanning polarimeter comprising a rectangular prism, quarter-wave plate, and four linear polarizers. The determinant and condition numbers of the measurement matrix are used as objective functions in an optimization procedure. Illustrative examples with optimum angles and commonly used angles of linear polarizers are presented to evaluate the sensitivity of the polarimeter in estimating the incident Stokes vector, in error cases involving fluctuations in the detected flux and/or errors in the azimuthal angles of the linear polarizers. Our results show that optimum angles produce smaller errors than commonly used angles, when deriving the incident Stokes vectors.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31114974

RESUMO

A novel Gram-stain negative, aerobic, rod-shaped, asporogenous, propanil-degrading bacterial strain, TY50T, was isolated from a herbicide-contaminated soil in Nanjing, China. Strain TY50T was found to grow optimally at pH 9.0, 30 °C and in the absence of NaCl. The G + C content of the total DNA was determined to be 55.5 mol%. The 16S rRNA gene sequence of strain TY50T shows high identity to that of Spirosoma lacussanchae CPCC 100624T (99.3%), Spirosoma metallicum PR1014kT (94.8%) and Spirosoma soli MIMBbqt12T (94.6%). DNA-DNA hybridization indicated that the isolate had relatively low levels of DNA-DNA relatedness with S. lacussanchae CPCC 100624T (48.3%). Average nucleotide identity and the digital DNA-DNA hybridizations for draft genomes between strain TY50T and S. lacussanchae CPCC 100624T were 93.2% and 51.0%, respectively. The major cellular fatty acids of strain TY50T were identified as C16:1ω5c (24.5%) and summed feature 3 (C16:1ω6c/C16:1ω7c, 40.7%). MK-7 was found to be the predominant respiratory quinone. The major polar lipid profile includes phosphatidylethanolamine, an unidentified lipid and an unidentified aminolipid. These chemotaxonomic data support the affiliation of strain TY50T with the members of the genus Spirosoma. Strain TY50T can be distinguished from its close phylogenetic neighbours based on its phenotypic, genotypic, and chemotaxonomic features. Therefore, strain TY50T represents a novel member of the genus Spirosoma, for which the name Spirosoma sordidisoli sp. nov. is proposed. The type strain is TY50T (= KCTC 62494T = CCTCC AB 2018041T).

7.
Rev Sci Instrum ; 90(3): 035113, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30927789

RESUMO

Light scattering is an important tool for gathering information about the structure and origin of atmospheric aerosols. We build a polarized scanning nephelometer to measure the properties of aerosol particles. However, the accuracy of the backward-scattered light measurements is limited by stray forward-scattered light reflected back into the collection optics. We briefly analyze this stray light. A new form of light trap with multiple hollow cones is introduced to suppress backward-scattered stray light. To evaluate the effect of the light trap on suppressing stray light for our nephelometer, a simulation model with and without the light trap was analyzed. Our results show that without the light trap, the percentage of backward-scattered stray light can be more than 50% for some kinds of particles. With the light trap with multiple hollow cones, the percentage of stray light with a backward-scattered angle can be less than 0.7%, which remains stable over different angles. Our results indicate that this structure could be particularly suitable for a light trap with a very large aperture but limited space.

8.
Genomics Proteomics Bioinformatics ; 17(2): 211-218, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30959223

RESUMO

As next-generation sequencing (NGS) technology has become widely used to identify genetic causal variants for various diseases and traits, a number of packages for checking NGS data quality have sprung up in public domains. In addition to the quality of sequencing data, sample quality issues, such as gender mismatch, abnormal inbreeding coefficient, cryptic relatedness, and population outliers, can also have fundamental impact on downstream analysis. However, there is a lack of tools specialized in identifying problematic samples from NGS data, often due to the limitation of sample size and variant counts. We developed SeqSQC, a Bioconductor package, to automate and accelerate sample cleaning in NGS data of any scale. SeqSQC is designed for efficient data storage and access, and equipped with interactive plots for intuitive data visualization to expedite the identification of problematic samples. SeqSQC is available at http://bioconductor.org/packages/SeqSQC.

9.
Mar Drugs ; 17(4)2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30935028

RESUMO

Marine cyanobacteria represent a large untapped source of functional glycolipids enriched with polyunsaturated fatty acids (PUFAs) for human health. However, advanced methods for scalable isolation of diverse species containing high-purity PUFA-rich glycolipids will have to be developed and their possible pharmaceutical and nutraceutical functions identified. This paper introduces a novel solid matrix-supported supercritical CO2 extraction method for scalable isolation of the PUFA γ-linolenic acid (GLA)-enriched glycolipids from the cyanobacterium Arthrospira (Spirulina) platensis, which has been the most widely used among microalgae in the nutraceutical and pharmaceutical industries. Of various porous materials studied, diatomite was the best to facilitate extraction of GLA-rich glycolipids, resulting in an extraction efficiency of 98%. Gamma-linolenic acid made up 35% of total fatty acids (TFAs) in the extracts, which was considerably greater than that obtained with ethanol (26%), Bligh and Dyer (24%), and in situ transesterification (24%) methods, respectively. Lipidomics analysis revealed that GLA was exclusively associated with galactolipids. Pharmaceutical functions of GLA-rich galactolipids were investigated on a zebrafish caudal fin regeneration model. The results suggested that GLA extracted from A. platensis possessed anti-oxidative, anti-inflammatory, and anti-allergic activities, which acted in a concerted manner to promote post-injury regeneration of zebrafish.


Assuntos
Cromatografia com Fluido Supercrítico/métodos , Spirulina/química , Ácido gama-Linolênico/isolamento & purificação , Ácido gama-Linolênico/farmacologia , Nadadeiras de Animais/efeitos dos fármacos , Nadadeiras de Animais/fisiologia , Animais , Cianobactérias/química , Modelos Animais , Regeneração/efeitos dos fármacos , Peixe-Zebra
10.
Cancer Med ; 8(4): 1845-1853, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30864286

RESUMO

Young black women are at higher risk of triple-negative breast cancer (TNBC); however, a majority of the genetic studies on cancer predisposition were carried out in White populations. The underrepresentation of minority racial/ethnic populations in cancer genetic studies may have led to disproportionate gaps in our knowledge of cancer predisposition genes in these populations. We surveyed the protein-truncating mutations at the exome-wide scale and in known breast cancer predisposition genes among 170 patients of multiple racial/ethnic groups with early-onset (≤age 50) TNBC from two independent cohorts. Black patients, on average, had a higher number of truncating mutations than Whites at the exome-wide level, but fewer truncating mutations in the panel of known breast cancer genes. White TNBC patients showed a strong enrichment of truncating variants in known breast cancer genes, whereas no such enrichment was found among Black patients. Our findings indicate likely more breast cancer disposition genes yet to be discovered in minority racial/ethnic groups, and the current multigene panels may result in unequal benefits from cancer genetic testing.

11.
Metab Eng ; 54: 96-108, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30904735

RESUMO

Improving acid tolerance is pivotal to the development of microalgal feedstock for converting flue gas to biomass or oils. In the industrial oleaginous microalga Nannochloropsis oceanica, transcript knockdown of a cytosolic carbonic anhydrase (CA2), which is a key Carbon Concentrating Mechanism (CCM) component induced under 100 ppm CO2 (very low carbon, or VLC), results in ∼45%, ∼30% and ∼40% elevation of photosynthetic oxygen evolution rate, growth rate and biomass accumulation rate respectively under 5% CO2 (high carbon, or HC), as compared to the wild type. Such high-CO2-level activated biomass over-production is reproducible across photobioreactor types and cultivation scales. Transcriptomic, proteomic and physiological changes of the mutant under high CO2 (HC; 5% CO2) suggest a mechanism where the higher pH tolerance is coupled to reduced biophysical CCM, sustained pH hemostasis, stimulated energy intake and enhanced photosynthesis. Thus "inactivation of CCM" can generate hyper-CO2-assimilating and autonomously containable industrial microalgae for flue gas-based oil production.

12.
Clin Epigenetics ; 11(1): 45, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30867049

RESUMO

BACKGROUND: Little is known about the effects of chemotherapeutic drugs on DNA methylation status of leukocytes, which may be predictive of treatment benefits and toxicities. Based on a prospective national study, we characterize the changes in leukocyte DNA methylome from pre- to post-chemotherapy (approximately 4 months apart) in 93 patients treated for early stage breast cancer and 48 matched non-cancer controls. We further examined significant methylation changes with perceived cognitive impairment, a clinically significant problem related to cancer and chemotherapy. RESULTS: Approximately 4.2% of the CpG sites measured using the Illumina 450K methylation array underwent significant changes after chemotherapy (p < 1e-7), in comparison to a stable DNA methylome in controls. Post-chemotherapy, the estimated relative proportions of B cells and CD4+ T cells were decreased by a median of 100% and 39%, respectively, whereas the proportion of monocytes was increased by a median of 91%. After controlling for leukocyte composition, 568 CpGs from 460 genes were still significantly altered following chemotherapy. With additional adjustment for chemotherapy regimen, cumulative infusions, growth factors, and steroids, changes in four CpGs remained significant, including cg16936953 in VMP1/MIR21, cg01252023 in CORO1B, cg11859398 in SDK1, and cg19956914 in SUMF2. The most significant CpG, cg16936953, was also associated with cognitive decline in breast cancer patients. CONCLUSIONS: Chemotherapy profoundly alters the composition and DNA methylation landscape of leukocytes in breast cancer patients. Our results shed light on the epigenetic response of circulating immune cell populations to cytotoxic chemotherapeutic drugs and provide possible epigenetic links to the degeneration of cognitive function associated with chemotherapy.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cognição/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Leucócitos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ilhas de CpG/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Feminino , Humanos , Leucócitos/efeitos dos fármacos , Estadiamento de Neoplasias , Estudos Prospectivos , Resultado do Tratamento
13.
J Biosci Bioeng ; 128(1): 103-109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30792124

RESUMO

Ultrafiltration membrane harvesting of Scenedesmus acuminatus was tested using alternative feed (AF) directions, i.e., bottom feed-top feed cycle and traditional bottom feed (BF). Both operations were investigated to compare the membrane performance and membrane fouling in microalgal harvesting process by scanning electron microscope (SEM), confocal laser scanning microscopy (CLSM) and Fourier transform infrared (FTIR). The results showed that when the AF was used with and without backwashing, average flux increased by 27.9% and 17.9%, respectively, comparing with BF (68 L m-2 h-1) and the final dry weight reached 197 g L-1 and 175.8 g L-1, respectively. Microalgal cell deposition on AF membrane was reduced from 1.44 × 105 cell cm-2 on BF membrane to 7.12 × 104 cell cm-2 on AF membrane, according to SEM observation. The protein and polysaccharides on the AF membrane surface were also reduced according to CLSM and FTIR analysis. Fouling analysis along the fiber length revealed that fouling was most severe at the top section for BF as a result of a lower shear rate at the outlet. AF operation generated dynamic filtration by frequently switching flow directions, increasing the shear rate at both the top and bottom of the fibers, and therefore filtration and clean process simultaneously provided good performance.


Assuntos
Separação Celular , Filtração , Membranas Artificiais , Scenedesmus/isolamento & purificação , Purificação da Água , Reatores Biológicos/microbiologia , Separação Celular/instrumentação , Separação Celular/métodos , Filtração/instrumentação , Filtração/métodos , Hidrodinâmica , Microalgas , Ultrafiltração/instrumentação , Ultrafiltração/métodos , Purificação da Água/instrumentação , Purificação da Água/métodos
14.
Oncogene ; 38(23): 4496-4511, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30742064

RESUMO

Sustained reliance on androgen receptor (AR) after failure of AR-targeting androgen deprivation therapy (ADT) prevents effective treatment of castration-recurrent (CR) prostate cancer (CaP). Interfering with the molecular machinery by which AR drives CaP progression may be an alternative therapeutic strategy but its feasibility remains to be tested. Here, we explore targeting the mechanism by which AR, via RhoA, conveys androgen-responsiveness to serum response factor (SRF), which controls aggressive CaP behavior and is maintained in CR-CaP. Following a siRNA screen and candidate gene approach, RNA-Seq studies confirmed that the RhoA effector Protein Kinase N1 (PKN1) transduces androgen-responsiveness to SRF. Androgen treatment induced SRF-PKN1 interaction, and PKN1 knockdown or overexpression severely impaired or stimulated, respectively, androgen regulation of SRF target genes. PKN1 overexpression occurred during clinical CR-CaP progression, and hastened CaP growth and shortened CR-CaP survival in orthotopic CaP xenografts. PKN1's effects on SRF relied on its kinase domain. The multikinase inhibitor lestaurtinib inhibited PKN1 action and preferentially affected androgen regulation of SRF over direct AR target genes. In a CR-CaP patient-derived xenograft, expression of SRF target genes was maintained while AR target gene expression declined and proliferative gene expression increased. PKN1 inhibition decreased viability of CaP cells before and after ADT. In patient-derived CaP explants, lestaurtinib increased AR target gene expression but did not significantly alter SRF target gene or proliferative gene expression. These results provide proof-of-principle for selective forms of ADT that preferentially target different fractions of AR's transcriptional output to inhibit CaP growth.

15.
J Liposome Res ; : 1-8, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30741056

RESUMO

The aim of this study was to evaluate whether lycopene-loaded liposomes (L-LYC) could interfere with the antitumor efficacy and cardiotoxicity of doxorubicin (DOX). L-LYC were prepared by a thin-film hydration method to overcome the instability, insolubility, and low bioavailability of lycopene. The mean diameter and morphology of the liposomes were determined by dynamic light scattering and transmission electron microscopy, respectively, and then, in vitro cytotoxicity and in vivo antitumor activity were determined to evaluate the effects of L-LYC and their combination with DOX. Finally, we evaluated whether L-LYC could decrease the DOX-induced cardiotoxicity in vivo. The results showed that the particle size of L-LYC appeared uniform, and the average diameter was approximately 160.4 nm. Compared with DOX treatment alone, the combination of L-LYC and DOX showed significantly increased cytotoxicity in vitro and decreased the tumor size in B16 melanoma-bearing mice in vivo. Furthermore, the DOX-induced cardiotoxicity was clearly relieved in combination with L-LYC. The overall findings indicated that L-LYC have a great potential for improving the therapeutic efficacy and attenuating the cardiotoxicity of the chemotherapy drug DOX.

16.
J Urol ; 201(6): 1105-1114, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30730413

RESUMO

PURPOSE: Bladder cancer recurrence following cystectomy remains a significant cause of bladder cancer specific mortality. Residual cancer cells contribute to cancer recurrence due to tumor spillage or undetectable preexisting micrometastatic tumor clones. We detected and quantified residual cancer cells in pelvic washing using ultradeep targeted sequencing. We compared the levels of residual cancer cells with clinical variables and cancer recurrence. MATERIALS AND METHODS: The primary tumor specimen was available in 17 patients who underwent robot-assisted radical cystectomy. All tumors had negative surgical margins. Pelvic washes and blood were collected intraoperatively before and after robot-assisted radical cystectomy, after pelvic lymph node dissection and in the suction fluid collected during the procedure. Two-step sequencing, including whole exome sequencing followed by ultradeep targeted sequencing (× greater than 50,000), was done to quantify residual cancer cells in each sample. Eight patients were excluded from study due to sample quality issues. The final analysis cohort comprised 9 patients. The residual cancer cell level was quantified for each sample as the relative cancer cell fraction and compared between time points. The peak relative cancer cell fraction of each patient was correlated with clinical and pathological variables. RESULTS: Residual cancer cells were detected in approximately half of the pelvic washing specimens during or after but not before robot-assisted radical cystectomy. Higher residual cancer cell levels were associated with aggressive variant histology and cancer recurrence. Verifying the feasibility of using residual cancer cells as a novel biomarker for recurrence requires larger cohorts. CONCLUSIONS: Detection of residual cancer cells in intraoperative peritoneal washes of patients with bladder cancer who undergo radical cystectomy may represent a robust biomarker of tumor aggressiveness and metastatic potential.


Assuntos
Cistectomia/métodos , Recidiva Local de Neoplasia/patologia , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Contagem de Células , Humanos , Neoplasia Residual , Pelve , Reprodutibilidade dos Testes , Irrigação Terapêutica
17.
Cell Death Differ ; 26(10): 2100-2114, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30692641

RESUMO

Lysine-specific demethylase 6A (KDM6A) and members of the Switch/Sucrose Non-Fermentable (SWI/SNF) family are known to counteract the activity of Enhancer of Zeste Homolog 2 (EZH2), which is often overexpressed and is associated with poor prognosis in muscle-invasive bladder cancer. Here we provide evidence that alterations in chromatin modifying enzymes, including KDM6A and members of the SWI/SNF complex, are frequent in muscle-invasive bladder cancer. We exploit the loss of function mutations in KDM6A and SWI/SNF complex to make bladder cancer cells susceptible to EZH2-based epigenetic therapy that activates an immune response to drive tumor cell differentiation and death. We reveal a novel mechanism of action of EZH2 inhibition, alone and in combination with cisplatin, which induces immune signaling with the largest changes observed in interferon gamma (IFN-γ). This upregulation is a result of activated natural killer (NK) signaling as demonstrated by the increase in NK cell-associated genes MIP-1α, ICAM1, ICAM2, and CD86 in xenografts treated with EZH2 inhibitors. Conversely, EZH2 inhibition results in decreased expression of pluripotency markers, ALDH2 and CK5, and increased cell death. Our results reveal a novel sensitivity of muscle-invasive bladder cancer cells with KMD6A and SWI/SNF mutations to EZH2 inhibition alone and in combination with cisplatin. This sensitivity is mediated through increased NK cell-related signaling resulting in tumor cell differentiation and cell death.

18.
Sci Total Environ ; 660: 25-31, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30639715

RESUMO

Cellular characteristics and algogenic organic matter (AOM) properties change with culture time. This study aims to understand the changes throughout the growth phase, and their effect on Scenedesmus acuminatus harvesting using ultrafiltration. The variations in cellular particle size distribution, cellular EPS content, and the biochemical composition and molecular weight of AOM were analyzed, followed by the membrane harvesting of the original S. acuminatus suspension, AOM-free cells and cell-free AOM. The results showed that the average flux for the original suspension increased with growth phase and reached an increase of 36.3% in the declining phase. AOM played a greater role than S. acuminatus cells in flux decline for all growth phases. Exponential-phase AOM contained a greater high-MW fraction and more carbohydrates, and the exponential cells were smaller cells and had a higher EPS content; these characteristics resulted in a reduced average flux.


Assuntos
Scenedesmus/crescimento & desenvolvimento , Ultrafiltração/métodos , Aquicultura , Compostos Orgânicos/química
19.
Ecotoxicol Environ Saf ; 167: 122-129, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30317116

RESUMO

Propanil, one of the most extensively used post-emergent contact herbicides, has also been reported to have adverse effect on environmental safety. A bacterial strain of Ochrobactrum sp. PP-2, which was capable of transforming propanil, was isolated from a propanil-contaminated soil collected from a chemical factory. An arylamidase gene mah responsible for transforming propanil to 3,4-dichloroaniline (3,4-DCA) was cloned from strain PP-2 by shotgun method and subsequently confirmed by function expression. The arylamidase Mah shares low amino acid sequence identity (27-50%) with other biochemically characterized amidases and shows less than 30% identities to other reported propanil hydrolytic enzymes. Mah was most active at pH 8 and 35 °C. Mah had a remarkable activity toward propanil (Km = 6.3 ±â€¯1.2 µM), showing the highest affinity efficiency for propanil as compared with other reported propanil hydrolytic enzymes. Our study also provides a new arylamidase for the hydrolysis of propanil.


Assuntos
Amidoidrolases/metabolismo , Herbicidas/metabolismo , Ochrobactrum/enzimologia , Propanil/metabolismo , Amidoidrolases/química , Compostos de Anilina/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Propanil/química
20.
Bioresour Technol ; 275: 53-60, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30576914

RESUMO

In this study, biochar obtained from pyrolysis of woody shavings at 550 °C was reacted with iron ore in N2 to investigate its inert chemical looping conversion properties, including the gas products conversion kinetics and structural evolution process. Results found that both the release of CO and CO2 could be divided into rapid release stage and stable chemical looping reaction stage with activation energies of 17.69 and 45.65 kJ/mol, respectively. During the chemical looping process, the reaction reactivity of biochar reduced gradually with the amorphous char structure turning into fused ring structure and finally into graphite crystal structure. Simultaneously, Fe2O3 was reduced into Fe3O4, FeO and Fe. This work highlighted the chemical conversion of biochar using natural iron ore as oxygen carrier in inert N2 atmosphere from the common in-situ gasification chemical looping process using CO2/H2O as agent.


Assuntos
Carvão Vegetal/química , Ferro/química , Oxigênio/química , Dióxido de Carbono/química , Cinética
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