RESUMO
Using a nationwide survey of primary grocery shoppers conducted in August 2020, we examine household food spending when the economy had partially reopened and consumers had different spending opportunities in comparison to when the Covid-19 lockdown began. We estimate the impact of Covid-19 on household spending using interval and Order Probit regressions. Income levels, age, access to grocery stores and farmers markets, household demographic information, along with other independent variables are controlled in the model. Findings show that middle-class households (with income below $50,000, or with income between $50,000 and $99,999) are less likely to increase their grocery expenditures during the pandemic. Households with children or elderlies that usually require higher food quality and nutrition intakes had a higher probability of increasing their spending during Covid-19 than before. Furthermore, consumers' spending behaviors were also significantly affected by their safe handing levels and the Covid-19 severity and food accessibility in their residences.
Assuntos
COVID-19/prevenção & controle , Controle de Doenças Transmissíveis/economia , Características da Família , Alimentos/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Idoso , COVID-19/epidemiologia , COVID-19/virologia , Criança , Comportamento do Consumidor/estatística & dados numéricos , Custos e Análise de Custo , Epidemias/prevenção & controle , Habitação/normas , Habitação/estatística & dados numéricos , Humanos , Renda/estatística & dados numéricos , SARS-CoV-2/fisiologia , Fatores de Tempo , Estados UnidosRESUMO
Ten-eleven translocation 1 catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which plays an important role in epigenetics and is related to the malignant biological behavior of tumors. However, its regulatory role in glioma remains unclear. In this study, the levels of 5mC and 5hmC were detected using immunohistochemistry, dot-blot, hMeDIP-chip, and western blot in glioma tissues and normal brain tissues, whereas 5hmC differentially enriched genes were determined and further validated. The level of 5hmC in gliomas was decreased, whereas 5mC was increased. 5hmC highly enriched 10 functional protein-coding genes and 10 signaling pathways were identified using hMeGIP-chip in glioma tissues. Two autophagy-related genes, ATG13 and DNA damage-regulated autophagy modulator protein 1, with low enrichment of 5hmC in glioma tissues were verified in the promoter region, and hMeGIP-PCR further confirmed this result in U251 cells. Immunohistochemistry further confirmed that autophagy level in glioma tissues was lower than that of normal controls, and negatively correlated with WHO grade. This study indicates that ten-eleven translocation 1 may be involved in the development and progression of glioma through demethylation regulating a variety of cellular functions and signaling pathways, and autophagy is one of the regulatory mechanisms.
Assuntos
Autofagia/genética , Neoplasias Encefálicas/metabolismo , Metilação de DNA/fisiologia , Glioma/metabolismo , Oxigenases de Função Mista/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioma/genética , Glioma/patologia , Humanos , Gradação de TumoresRESUMO
In this study, a theoretical model was developed to analyze the stability of liquid elbow patterns and validated by experiments. An exemplar system of ethylene glycol continuously deposited on polyethylene terephthalate (PET) was used to study the effects of printing parameters on bulge formation near the elbow corners. In the elbow region, because of the capillary pressure differences, liquids flowed into the concave elbow corner and formed bulges easily after being printed. However, the bulge formation disappeared when the elbow angle is >90°. A simple model based on surface energy analysis was proposed to explain the bulging phenomenon and can successfully predict bulge sizes at steady state. A stability diagram was also calculated to map out the stable regimes. With the guidance of the stability diagram, stable elbow lines without any bulges can be printed with various angles by controlling the thickness of liquids. In summary, this stabilization strategy in this study is effective to maintain the fidelity of printed liquid patterns and provides useful guidelines for printed electronic applications.
RESUMO
As one of the natural herbal flavonoids, myricetin has attracted much research interest, mainly owing to its remarkable anticancer properties and negligible side effects. It holds great potential to be developed as an ideal anticancer drug through improving its bioavailability. This study was performed to investigate the effects of Pluronic-based micelle encapsulation on myricetin-induced cytotoxicity and the mechanisms underlying its anticancer properties in human glioblastoma cells. Cell viability was assessed using a methylthiazol tetrazolium assay and a real-time cell analyzer. Immunoblotting and quantitative reverse transcriptase polymerase chain reaction techniques were used for determining the expression levels of related molecules in protein and mRNA. The results indicated that myricetin-induced cytotoxicity was highly potentiated by the encapsulation of myricetin. Mitochondrial apoptotic pathway was demonstrated to be involved in myricetin-induced glioblastoma cell death. The epidermal growth factor receptor (EGFR)/PI3K/Akt pathway located in the plasma membrane and cytosol and the RAS-ERK pathway located in mitochondria served as upstream and downstream targets, respectively, in myricetin-induced apoptosis. MiR-21 inhibitors interrupted the expression of EGFR, p-Akt, and K-Ras in the same fashion as myricetin-loaded mixed micelles (MYR-MCs) and miR-21 expression were dose-dependently inhibited by MYR-MCs, indicating the interaction of miR-21 with MYR-MCs. This study provided evidence supportive of further development of MYR-MC formulation for preferentially targeting mitochondria of glioblastoma cells.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Flavonoides/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Micelas , Poloxâmero/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/enzimologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/metabolismo , Flavonoides/farmacologia , Glioblastoma/enzimologia , Humanos , MicroRNAs/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
MicroRNAs (miRs) serve a regulatory function in oxidative radical-mediated inflammation and apoptosis during ischemia/reperfusion (IR) injury. Lipocalin 2 (Lcn-2), a target protein of miR-138, is widely involved in the systemic response to IR injury. The aim of the present study was to investigate the association between miR-138 and Lcn-2 in a rat model of cerebral ischemia/reperfusion (CIR) injury and to verify the interaction between miR-138 and Lcn-2 in a PC12 cell model of hypoxia/reoxygenation injury. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the mRNA and protein expression levels of miR-138 and Lcn-2. Cell proliferation was determined by MTT assay. The results suggested that the expression of miR-138 was inversely correlated with the expression of Lcn-2 in the CIR rat model and the PC12 cells subjected to hypoxia and reoxygenation. The expression of Lcn-2 was inhibited by miR-138 mimics and enhanced by miR-138 inhibitors, thereby indicating that miR-138 functions as a negative regulator for Lcn-2 expression. This study provides an experimental basis for the further study of miR-138-based therapy for CIR injury.
RESUMO
Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.
Assuntos
Exossomos/transplante , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/transplante , Animais , Sistema Livre de Células , Citocinas/imunologia , Citocinas/metabolismo , Exossomos/genética , Exossomos/imunologia , Exossomos/metabolismo , Engenharia Genética , Humanos , Ativação Linfocitária , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Receptores de Antígenos de Linfócitos T/biossíntese , Receptores de Antígenos de Linfócitos T/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
MutS homolog 6 (MSH6) of the MSH2-MSH6 complex binds simple mispairs and small insertion-deletion loops (IDL) then initiates DNA mismatch repair in eukaryotes. We have shown the ability of Cd(2+) to downregulate msh2/msh6 expression in zebrafish embryos via oxidative stress. This study explored the effects of Cd(2+) and Hg(2+) on MSH6-mediated mismatch binding activities. MSH6-mediated G-T and IDL-specific binding activities were significantly inhibited at similar levels after exposing zebrafish embryos at 1 h postfertilization) to HgCl2 or CdCl2 at 1.0 to 2.5 µM for 9 h, but MSH6 synthesis was found to be less sensitive to Hg(2+) than to Cd(2+) . Real-time RT-PCR and in situ hybridization also detected a weaker susceptibility of MSH gene transcription to Hg(2+) . The weaker response of MSH gene activities to Hg(2+) correlated with the lower oxidative stress-inducing potential of Hg(2+) . Hence, Hg(2+) targets mismatch sensing capacity at protein function rather than at transcription level.
Assuntos
Pareamento Incorreto de Bases , Cádmio/toxicidade , Proteínas de Ligação a DNA/metabolismo , Mercúrio/toxicidade , Peixe-Zebra/embriologia , Animais , Estresse Oxidativo , Ligação ProteicaRESUMO
BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is considered as a tumor cell-specific cytotoxic agent. Through the aid of mesenchymal stem cells (MSCs), TRAIL is capable of inducing apoptosis of tumor cells in tumor sites. The present study was performed to investigate the cytotoxic effects of TRAIL-engineered MSCs on glioblastoma cells (C6) in vitro. MATERIALS AND METHODS: An expression vector of secreting form of TRAIL was used to engineer MSCs. The cytotoxic effects of TRAIL-transfected MSCs on C6 cells were invstigated using the MTT method and Hochest33258 staining after co-culture of the two cell types. RESULTS: TRAIL and control plasmid transfection of MSCs showed no significant effect on MSC's viability (p>0.05). A significant inhibition of C6 cells was observed when they were co-cultured with TRAIL-engineered MSCs (63.7%±0.12, p<0.05). CONCLUSION: Mesenchymal stem cells were very well tolerant to the transfection of TRAIL-bearing vectors. The cytotoxic effects of TRAIL-engineered MSCs on C6 cells indicates the therapeutic potential of this strategy for treatment of glioblastoma patients.
Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Células-Tronco Mesenquimais/fisiologia , Ligante Indutor de Apoptose Relacionado a TNF/genética , Animais , Neoplasias Encefálicas/patologia , Técnicas de Cocultura , Engenharia Genética/métodos , Glioblastoma/patologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Transgênicos , Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , TransfecçãoRESUMO
DNA mismatch repair (MMR) of simple base mismatches and small insertion-deletion loops in eukaryotes is initiated by the binding of the MutS homolog 2 (MSH2)-MSH6 heterodimer to mismatched DNA. Cadmium (Cd) is a genotoxic heavy metal that has been recognized as a human carcinogen. Oxidant stress and inhibition of DNA repair have been proposed as major factors underlying Cd genotoxicity. Our previous studies indicated the ability of Cd to disturb the gene expression of MSH6 in zebrafish (Danio rerio) embryos. This study was undertaken to explore if Cd-induced oxidative stress down-regulated MSH gene activities. Following the exposure of zebrafish embryos at 1 h post fertilization (hpf) to sublethal concentrations of Cd at 3-5 µM for 4 or 9 h, a parallel down-regulation of MSH2, MSH6 and Cu/Zn superoxide dismutase (Cu/Zn-SOD) gene expression was detected by real-time RT-PCR and the expression levels were 40-50% of control after a 9-h exposure. Cd exposure also induced oxidative stress, yet no inhibition of catalase gene activity was observed. Whole mount in situ hybridization revealed a wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and pretreatment of embryos with antioxidants butylhydroxytoluene (BHT), d-mannitol or N-acetylcysteine (NAC) at 1-10 µM restored Cd-suppressed msh6 expression. QPCR confirmed the protective effects of antioxidants on Cd-suppressed msh2/msh6 mRNA production. Down-regulated MSH gene activities reaching about 50% of control were also induced in embryos exposed to paraquat, a reactive oxygen species (ROS)-generating herbicide, or hydrogen peroxide at 200 µM. Hence, Cd at sublethal levels down-regulates msh2/msh6 expression primarily via ROS as signaling molecules. The transcriptional activation of human msh6 is known to be fully dependent on the specificity factor 1 (Sp1). Cd failed to inhibit the DNA binding activity of zebrafish Sp1 unless at lethal concentrations based on band shift assay, therefore excluding the involvement of Sp1 inactivation in Cd-induced MSH gene inhibition in zebrafish embryos.
Assuntos
Cádmio/toxicidade , Proteínas de Ligação a DNA/genética , Regulação para Baixo/efeitos dos fármacos , Proteína 2 Homóloga a MutS/genética , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Antioxidantes/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Peixe-Zebra/embriologiaRESUMO
Glioma, a type of brain tumor originating from glioma cells, varies widely in aggressiveness and causes serious symptoms, but the treatments are limited. Studies have shown that cryosurgery has multiple effects on tumor treatments, and administration of human tumor necrosis factor-alpha (rhTNF-α) arguments the anti-tumor effect of cryotherapy in breast and prostate cancers. To test the hypothesis that cryosurgery and rhTNF-α play synergistic effects against brain tumors, we established a brain glioma model on rat cortex regions following different treatments: the G1 group was sham-operated; the G2 group was treated with cryosurgery; the G3 group was treated with rhTNF-α; and G4 group received combined treatment with cryosurgery and rhTNF-α. Tumor sizes were measured by magnetic resonance imaging; DNA fragmentation was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL assay); P21(WAF1/CIP1) and proliferating cell nuclear antigen (PCNA) expression levels were scored using immunohistochemical staining. G2 and G4 rats had significantly longer survival time than did G1 rats. Tumor sizes in each group were significantly decreased as compared with those in G1 rats. PCNA-positive cells were significantly decreased in G2, G3 and G4 rats as compared with G1 rats. In contrast, DNA fragmentation and P21(WAF1/CIP1)-positive cells were significantly increased in each treatment group. Importantly, a combined treatment enhanced the effects of cryosurgery. Combined treatment with cryosurgery and rhTNF-α may have a synergistic effect on glioma tumor therapy, enhancing the inhibition of proliferation and the induction of apoptosis.
Assuntos
Neoplasias Encefálicas/terapia , Criocirurgia , Glioma/terapia , Fator de Necrose Tumoral alfa/uso terapêutico , Animais , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Córtex Cerebral/patologia , Terapia Combinada , Fragmentação do DNA , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/cirurgia , Marcação In Situ das Extremidades Cortadas , Antígeno Nuclear de Célula em Proliferação/biossíntese , Ratos , Ratos Wistar , Proteínas Recombinantes/uso terapêuticoRESUMO
MutS homolog 6 (MSH6) is the major mismatch contacting component of the MSH2-MSH6 heterodimeric complex (MutSα) that mediates DNA mismatch repair (MMR) of simple mispairs and small insertion-deletion loops in eukaryotes. This study examined the potential of cadmium (Cd) to disturb the gene expression of MSH6 in vertebrates using zebrafish (Danio rerio) embryo as a model organism. Semiquantitative RT-PCR indicated that msh2 and msh6 expressions were suppressed in embryos at 1h post fertilization (hpf), then drastically up-regulated in 2 hpf embryos and actively expressed in 3-25 hpf embryos. In the presence of a constitutive ß-actin expression, exposure of 1 hpf embryos to sublethal concentrations of CdCl(2) at 0.5-3 µM for 4 or 9h caused a time and concentration-dependent down-regulation of msh6 transcription. Cd failed to inhibit msh2 transcription except at 3 µM, reflecting the higher sensitivity of msh6 than msh2 transcription to Cd. Whole mount in situ hybridization showed a wide distribution of msh6 transcripts in the front body portions of 10 hpf embryos and Cd-induced a general suppression of msh6 expression in zebrafish tissues. Cd-induced down-regulation of msh6 transcription paralleled with reduced levels of MSH6 protein synthesis and MSH6-mediated G-T mismatch binding activities identified by band shift assay using recombinant zebrafish MSH6 and an anti-human MSH6 antibody. Our results revealed the inhibition of Cd on MSH6 expression at both mRNA and protein levels and this mechanism may play a role in Cd genotoxicity.
Assuntos
Cádmio/toxicidade , Proteínas de Ligação a DNA/genética , Embrião não Mamífero/metabolismo , Expressão Gênica/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Proteínas de Ligação a DNA/metabolismo , RNA Mensageiro/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismoRESUMO
This paper describes how irradiation with light influences the preparation of Au-Ag-Hg trimetallic nanoparticles (NPs) from gold nanorods (AuNRs) in glycine solutions (pH 8.5-10.5). Silver, gold, and mercury ions were reduced by ascorbic acid and deposited on AuNRs to form Au-Ag-Hg trimetallic NPs of different sizes and shapes. In addition to the amounts of ascorbic acid, Au seeds, and glycine, others parameters such as pH, irradiation, and the concentrations of Ag, Au, and Hg ions are important for the preparation of these Au-Ag-Hg trimetallic NPs. Transmission electron and dark-field microscopy images indicated that irradiation with light induced the self-assembly of the thus-prepared Au-Ag-Hg trimetallic NPs, in addition to slightly affecting their shapes, but suggested no photoreduction effect during their formation. At pH 10.5, the Au-Ag-Hg trimetallic NPs possessed dumbbell- and millet-like shapes, having the sizes of 51 +/- 3 and 48 +/- 4 nm, respectively, when synthesized in the dark and under illumination, respectively. Time-evolution UV-Vis extinction spectroscopy and inductively coupled plasma mass spectrometry data obtained from solutions at various periods during the formation of the Au-Ag-Hg trimetallic NPs reveal that reduction of the Au and Ag ions occurred prior to reduction of the Hg ions. To the best of our knowledge, this study presents the first example of the light-induced self-assembly of Au-Ag-Hg trimetallic NPs in a liquid phase.
Assuntos
Glicina/química , Ouro/química , Mercúrio/química , Nanopartículas Metálicas/química , Nanotecnologia/métodos , Prata/química , Ácido Ascórbico/química , Concentração de Íons de Hidrogênio , Luz , Espectrometria de Massas/métodos , Microscopia Eletrônica de Transmissão , Nanopartículas/química , Nanoestruturas/química , Tamanho da Partícula , Soluções , Espectrofotometria UltravioletaRESUMO
This paper describes the preparation of Au core-Au-Ag shell nanoparticles (NPs) in different morphologies by controlling both the pH and the glycine concentration. Using a seed-growth method, we prepared high-quality Au core-Au-Ag shell NPs from a glycine solution under alkaline conditions (pH>8.5). By controlling both the pH and the glycine concentration, we prepared dumbbell-shaped and peanut-shaped Au core-Au-Ag shell NPs readily by depositing gold and silver, reduced by ascorbate, onto the gold nanorods. We have found that the glycine concentration that is optimal for preparing high-quality Au core-Au-Ag shell NPs differs at the various values of pH. At pH<8.5, the glycine concentration is not important, but, when preparing dumbbell- and peanut-shaped Au core-Au-Ag shell NPs, it should be greater than 50 mM and greater than 20 mM at pH 9.5 and 10.5, respectively. Glycine plays a number of roles during the synthesis of the Au core-Au-Ag shell NPs by controlling the solution pH, altering the reduction potentials of gold and silver ions through forming complexes with metal ions (Au(+) and Ag(+)), minimizing the formation of Ag(2)O, AgCl, and AgBr precipitates, and stabilizing the thus-prepared NPs. At pH 9.7, we observed the changes in the morphologies of the Au core-Au-Ag shell NPs-from regular (rectangular) to peanut- and dumbbell-shaped, and finally to jewel-, diamond-, and/or sphere-shaped-that occurred during the course of a 60-min reaction. In addition, we were able to affect the shapes and sizes of the Au core-Au-Ag shell NPs by controlling the reaction time.
RESUMO
BACKGROUND & OBJECTIVE: It was unknown whether the combination of cryotherapy and 5-fluorouracil (5-FU) could produce a synergistic effect, though both of them could induce apoptosis of glioma cells. The aim of this study was to observe the effect of cryotherapy and 5-fluorouracil on apoptosis of G422 glioma cells and to investigate the potential mechanism. METHODS: (1)Experimental mice models with G422 glioma were established. Cryotherapy (-180 degrees C,90s),chemotherapy (5-FU, 18 mg/kg), and cryochemotherapy were performed on them,respectively.(2)TUNEL was used to determine the apoptosis of glioma cells in each group at different time points.(3)The expression of the p53 and the HSP90alpha gene of the frozen glioma were analyzed by immunohistochemical staining. RESULTS: Cryotherapy or 5-FU induced apoptosis of G422 glioma cells, while the combination of cryotherapy and 5-FU remarkably increased the apoptosis rate. The numbers of apoptotic cells of combination group were 30.6+/-11.7, 86.4+/-21.5, 128.1+/-4.1, 237.0+/-30.1, 72.8+/-23.0 at 6h, 12h, 24h, 48h, 72h after cryochemotherapy, respectively, which were significantly higher than those of other groups. There was no expression of HSP90alpha and p53 in the center of freezing area. The p53 and the HSP90alpha proteins increased obviously in the periphery area especially at 48h after freezing compared with control group [(73.1+/-9.3)% vs (60.6+/-9.9)%, (35.6+/-6.6)% vs (13.7+/-6.5)%](P< 0.01). The expression of p53 was positively correlated with expression of HSP90alpha in frozen glioma (r=0.3610, P< 0.01). CONCLUSION: Combination of cryotherapy with 5-FU could enhance the apoptosis of G422 glioma cells presumably through modulating the HSP90alpha and p53 expression pattern. Cryochemotherapy showed better effect than that of cryotherapy or chemotherapy alone.