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1.
Gynecol Oncol ; 188: 60-70, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38936282

RESUMO

OBJECTIVE: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer. METHODS: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed. RESULTS: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating ß-3 tubulin expression to suppress microtubule dynamics. CONCLUSION: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.

2.
Diabetes Obes Metab ; 22(8): 1302-1315, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32173999

RESUMO

AIM: Insulin resistance is a metabolic state where insulin sensitivity is lower than normal condition and strongly related to type 2 diabetes. However, an in vitro model mimicking insulin resistance is rare and thus screening drugs for insulin resistance severely depends on an in vivo model. Here, to increase anti-diabetic drug selectivity for humans, 3D ADMSCs and macrophages were co-cultured with in-house fabricated co-culture plates. MATERIAL AND METHODS: 3D co-culture plates were designed to load ADMSCs and RAW264.7 cells containing hydrogels in separate wells while allowing cell-cell interaction with co-culturing media. Hydrogels were constructed using a 3D cell-printing system containing 20 mg/ml alginate, 0.5 mg/ml gelatin and 0.5 mg/ml type I collagen. Cells containing hydrogels in 3D co-culture plates were incubated for 10 min to allow stabilization before the experiment. 3D co-culture plates were incubated with the CaCl2 solution for 5 min to complete the cross linking of alginate hydrogel. Cells in 3D co-culture plates were cultured for up to 12 days depending on the experiment and wells containing adipocytes and macrophages were separated and used for assays. RESULTS: KR-1, KR-2 and KR-3 compounds were applied during differentiation (12 days) in 3D co-cultured mouse 3T3-L1 adipocytes and 3D co-cultured human ADMSCs. Glucose uptake assay using 2-DG6P and 2-NBDG and western blot analysis were performed to investigate changes of insulin resistance in the 3D co-cultured model for interspecies selectivity of drug screening. KR-1 (mouse potent enantiomer) and KR-3 (racemic mixture) showed improvement of 2-DG and 2-NBDG uptake compared with KR-2 (human potent enantiomer) in 3D co-cultured 3T3-L1 adipocytes. In connection with insulin resistance in a 3D 3T3-L1 co-cultured model, KR-1 and KR-3 showed improvement of insulin sensitivity compared to KR-2 by markedly increasing GLUT4 expression. In contrast to the result of 3D co-cultured 3T3-L1 adipocytes, KR-1 failed to significantly improve 2-DG and 2-NBDG uptake in 3D co-cultured ADMSC adipocytes. Results of 2-NBDG accumulation and western blot analysis also showed that KR-2 and KR-3 improved insulin sensitivity relatively better than KR-1. CONCLUSIONS: Our 3D co-culture model with/without 3D co-culture plates can successfully mimic insulin resistance while allowing investigation of the effects of anti-obesity or anti-diabetic drugs on human or mouse co-culturing cell type. This 3D co-culture system may accelerate screening of drugs for insulin resistance depending on species.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Preparações Farmacêuticas , Células 3T3-L1 , Adipócitos , Animais , Técnicas de Cocultura , Glucose , Humanos , Insulina , Camundongos
3.
Bioorg Med Chem Lett ; 30(1): 126756, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31784318

RESUMO

SHP2, a non-receptor protein tyrosine phosphatase encoded by PTPN11 gene, plays an important role in the cell growth and proliferation. Activating mutations of SHP2 have been reported as a cause of various human diseases such as solid tumors, leukemia, and Noonan syndrome. The discovery of SHP2 inhibitor can be a potent candidate for the treatment of cancers and SHP2 related human diseases. Several reports on a small molecule targeting SHP2 have published, however, there are limitations on the discovery of SHP2 phosphatase inhibitors due to the polar catalytic site environment. Allosteric inhibitor can be an alternative to catalytic site inhibitors. 3,4,6-Trihydroxy-5-oxo-5H-benzo[7]annulene 1 was obtained as an initial hit with a 0.097 µM of IC50 from high-throughput screening (HTS) study. After the structure-activity relationship (SAR) study, compound 1 still showed the most potent activity against SHP2. Moreover, compound 1 exerted good potency against SHP2 expressing 2D and 3D MDA-MB-468.


Assuntos
Proteína Tirosina Fosfatase não Receptora Tipo 11/antagonistas & inibidores , Linhagem Celular Tumoral , Humanos , Relação Estrutura-Atividade
4.
Int J Mol Sci ; 21(4)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102322

RESUMO

Commercially available boron nitride nanotubes (BNNTs) and their purified form (pBNNTs) were dispersed in aqueous solutions with various dispersants, and their cytotoxicity and drug encapsulation capacity were monitored. Our data suggest that pBNNTs showed an average increase in dispersibility of 37.3% in aqueous solution in the presence of 10 different dispersants. In addition, 100 µg of pBNNTs induced an average decrease in cytotoxicity of 27.4% compared to same amount of BNNTs in normal cell lines. The same amount of pBNNTs can encapsulate 10.4-fold more drug (camptothecin) compared to BNNTs. These data suggest that the purification of BNNTs improves several of their properties, which can be applied to biological experiments and are thus essential in the biological application of BNNTs.


Assuntos
Compostos de Boro/química , Nanotecnologia/métodos , Nanotubos/química , Água/química , Células 3T3-L1 , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Compostos de Boro/isolamento & purificação , Compostos de Boro/farmacologia , Células CHO , Células CACO-2 , Camptotecina/química , Camptotecina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Cricetulus , Composição de Medicamentos/métodos , Humanos , Camundongos
5.
Molecules ; 25(16)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784677

RESUMO

We conducted systemic assessments on the toxicity of silicon dioxide (SiO2) and titanium dioxide (TiO2) nanoparticles using different forms of normal colon cells (CCD-18Co), in vivo and in human colon organoids. The in vivo acute oral toxicity data showed that the LD50 values are greater than 2000 mg/kg for both the SiO2 and TiO2 nanoparticles; however, the SiO2 and TiO2 nanoparticles induced cytotoxicity in two-dimensional CCD-18Co cells and three-dimensional CCD-18Co spheroids and human colon organoids, with IC50 values of 0.6, 0.8 and 0.3 mM for SiO2 and 2.5, 1.1 and 12.5 mM for TiO2 nanoparticles, respectively. The data suggest that, when SiO2 and TiO2 are in nanoparticle form, cytotoxicity is induced; thus, care should be taken with these materials.


Assuntos
Colo/efeitos dos fármacos , Organoides/efeitos dos fármacos , Dióxido de Silício/toxicidade , Titânio/toxicidade , Animais , Linhagem Celular , Humanos , Camundongos , Camundongos Endogâmicos ICR , Nanopartículas/toxicidade , Dióxido de Silício/química , Titânio/química , Testes de Toxicidade
6.
Anal Chem ; 91(24): 15769-15776, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31663332

RESUMO

We developed Pyr1-infliximab: a two-photon probe for TNF-α. Pyr1-infliximab showed absorption maxima at 280 and 438 nm and an emission maximum at 610 nm in an aqueous buffer and effective two-photon action cross-section values of (520-2830) × 10-50 cm4s/photon in RAW 264.7 cells. After this probe was labeled, it was possible to detect Pyr1-infliximab-transmembrane TNF-α complexes in a live cell and to determine the relative proportion of these complexes in human colon tissues. This proportion among healthy, possibly inflamed, and inflamed tissues of patients with ulcerative colitis was found to be 1.0/4.5/10. This probe may find useful applications for selective detection of transmembrane TNF-α in a live cell or tissue, for quantification of inflammation in human colon tissue or of antidrug antibodies in patients who stop responding to anti-TNF therapy, and for monitoring of the response to this therapy.


Assuntos
Colo/metabolismo , Corantes Fluorescentes/química , Microscopia de Fluorescência por Excitação Multifotônica/métodos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Carbazóis/química , Sobrevivência Celular/efeitos dos fármacos , Colo/patologia , Corantes Fluorescentes/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Infliximab/química , Infliximab/imunologia , Camundongos , Fotólise , Células RAW 264.7 , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologia
7.
Small ; 12(4): 457-65, 2016 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-26663862

RESUMO

Rapid and sensitive detections of a variety of surface and intracellular proteins, nucleic acids, and other cellular biomarkers are important to elucidating biological signaling pathways and to devising disease diagnostics and therapeutics. Here, sensitive imaging and detection of cellular proteins on fluorescence-enhancing, nanostructured plasmonic gold (pGold) chips is presented. Imaging of fluorescently labeled cellular biomarkers on pGold is enhanced by 2-30-fold in the visible to near infrared (NIR) range of ≈500-900 nm. The high fluorescence enhancement of >700 nm significantly improves the dynamic range and signal/background ratios of NIR imaging, allowing high-performance multicolor imaging in the visible-NIR range using high quantum yield (QY) visible dyes and lower QY NIR fluorophores. Further, multiple cellular proteins of single cells of various cell types can be detected through microarraying of cells, useful for potentially hundreds and thousands different types of cells assayed on a single chip down to small cell numbers. This work suggests a simple, high throughput, high sensitivity, and multiplexed single-cell analysis method on fluorescence enhancing plasmonic substrates in the entire visible to NIR window.


Assuntos
Ouro/química , Raios Infravermelhos , Imagem Molecular/métodos , Linhagem Celular Tumoral , Humanos , Indóis , Proteínas de Membrana/metabolismo , Análise em Microsséries , Microscopia de Fluorescência
8.
J Clin Microbiol ; 54(7): 1726-1733, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27008879

RESUMO

Toxoplasmosis is an infection caused by the protozoan parasite Toxoplasma gondii that can lead to severe sequelae in the fetus during pregnancy. Definitive serologic diagnosis of the infection during gestation is made mostly by detecting T. gondii-specific antibodies, including IgG and IgM, individually in a single serum sample by using commercially available kits. The IgA test is used by some laboratories as an additional marker of acute infection. Most of the commercial tests have failed to reach 100% correlation with the reference method, the Sabin-Feldman dye test for the detection of Toxoplasma IgG antibodies. For Toxoplasma IgM and IgA antibodies, there is no reference method and their evaluation is done by comparing the results of one assay to those of another. There is a need for multiplexed assay platforms, as the serological diagnosis of T. gondii infection does not rely on the detection of a single Ig subtype. Here we describe the development of a plasmonic gold chip with vast fluorescence enhancement in the near-infrared region for simultaneous detection of IgG, IgM, and IgA antibodies against T. gondii in an ∼1-µl serum or whole-blood sample. When 168 samples were tested on this platform, IgG antibody detection sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were all 100%. IgM antibody detection achieved 97.6% sensitivity and 96.9% specificity with a 90.9% PPV and a 99.2% NPV. Thus, the nanoscience-based plasmonic gold platform enables a high-performance, low-cost, multiplexed assay requiring ultrasmall blood volumes, paving the way for the implementation of universal screening for toxoplasmosis infection during gestation.


Assuntos
Anticorpos Antiprotozoários/sangue , Imunoensaio/métodos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Programas de Rastreamento/métodos , Toxoplasmose/diagnóstico , Humanos , Sensibilidade e Especificidade , Toxoplasma/imunologia
9.
Langmuir ; 30(36): 10899-909, 2014 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-25144606

RESUMO

Single-walled carbon nanotubes (SWCNTs) dispersed in aqueous medium have many potential applications in chemistry, biology, and medicine. Reversible aggregation of SWCNTs dispersed in water has been frequently reported, but the mechanisms behind are not well understood. Here we show that SWCNTs dispersed into aqueous medium assisted by various charged molecules can be reversibly aggregated by a variety of electrolytes with two distinct mechanisms. Direct binding of counterions to SWCNTs leads to aggregation when the surface charge is neutralized from 74 to 86%. This aggregation is driven by electrostatic instead of van der Waals interactions, thus showing similarity to that of DNA condensation induced by multivalent cations. Sequestration of counterions by chelating reagents leads to the redispersion of SWCNT aggregates. In contrast to various metal ions, polyelectrolytes have the unique ability to induce SWCNT aggregation by bridging between individual SWCNTs. Aggregation through the latter mechanism can be engineered to be reversible by exploiting various mechanisms of chain breaking, including reduction of disulfide bond in the polymer chain, and the cleavage action of proteolytic enzymes. These findings clarify the mechanisms of SWCNT aggregation, and have broad implications in various applications of SWCNTs in water.


Assuntos
Nanotubos de Carbono/química , Meios de Cultura/química , Eletrólitos/química , Peptídeo Hidrolases/química , Peptídeo Hidrolases/metabolismo , Eletricidade Estática , Água/química , Água/metabolismo
10.
Tissue Eng Regen Med ; 21(1): 159-169, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153672

RESUMO

BACKGROUND: The mammalian target of rapamycin (mTOR) signaling is critical for the maintenance and differentiation of neurogenesis, and conceivably for many other brain developmental processes. However, in vivo studies of mTOR functions in the brain are often hampered due to the essential role of the associated signaling in brain development. METHODS: We monitored the long- and short-term effects of mTOR signaling regulation on cerebral organoids growth, differentiation and function using an mTOR inhibitor (everolimus) and an mTOR activator (MHY1485). RESULTS: Short-term treatment with MHY1485 induced faster organoid growth and differentiation, while long-term treatment induced the maturation of cerebral organoids. CONCLUSION: These data suggest that the optimal activity of mTOR is crucial in maintaining normal brain development, and its role is not confined to the early neurogenic phase of brain development.


Assuntos
Everolimo , Sirolimo , Organoides/metabolismo , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Encéfalo/crescimento & desenvolvimento
11.
RSC Adv ; 13(5): 2833-2840, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36756445

RESUMO

Environmental pollution, including the annual resurgence of particulate matter derived from road dust, is a serious issue worldwide. Typically, the size of road dust is less than 10 µm; thus, road dust can penetrate into human organs, including the brain, through inhalation and intake by mouth. Therefore, the toxicity of road dust has been intensively studied in vitro and in vivo. However, in vitro systems, including 2D cell cultures, cannot mimic complex human organs, and there are several discrepancies between in vivo and human systems. Here, we used human colon cells and organoids to evaluate the cytotoxicity of particulate matter derived from road dust. The toxicity of road dust collected in industrialized and high traffic areas and NIST urban particulate matter reference samples were evaluated in 2D and 3D human colon cells as well as colon organoids and their characteristics were carefully examined. Data suggest that the size and elemental compositions of road dust can correlate with colon organoid toxicity, and thus, a more careful assessment of the size and elemental compositions of road dust should be conducted to predict its effect on human health.

12.
Tissue Eng Regen Med ; 20(1): 49-58, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36374371

RESUMO

BACKGROUND: Microplastics (MPs) are small fragments from any type of plastic formed from various sources, including plastic waste and microfibers from clothing. MPs degrades slowly, resulting in a high probability of human inhalation, ingestion and accumulation in bodies and tissues. As its impact on humans is a prolonged event, the evaluation of its toxicity and influence on human health are critical. In particular, MPs can enter the human digestive system through food and beverage consumption, and its effect on the human colon needs to be carefully examined. METHODS: We monitored the influence of small MPs (50 and 100 nm) on human colon cells, human colon organoids and also examined their toxicity and changes in gene expression in vivo in a mouse model. RESULTS: The data suggested that 5 mg/mL concentrations of 50 and 100 nm MPs induced a > 20% decrease in colon organoid viability and an increase in the expression of inflammatory-, apoptosis- and immunity-related genes. In addition, in vivo data suggested that 50 nm MPs accumulate in various mouse organs, including the colon, liver, pancreas and testicles after 7 d of exposure. CONCLUSION: Taken together, our data suggest that smaller MPs can induce more toxic effects in the human colon and that human colon organoids have the potential to be used as a predictive tool for colon toxicity.


Assuntos
Microplásticos , Plásticos , Humanos , Camundongos , Animais , Microplásticos/toxicidade , Plásticos/toxicidade , Colo , Apoptose , Organoides
13.
RSC Adv ; 13(50): 35583-35591, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38077981

RESUMO

Tirbanibulin, an FDA-approved microtubule-targeting agent (MTA) introduced in 2020, represents a pioneering treatment for precancerous actinic keratosis. Despite its failure to gain approval as an anticancer agent due to insufficient efficacy, there remains potential value in extending its application into malignancy treatment through tirbanibulin-based derivatives. Tirbanibulin possesses a distinctive dual mechanism of action involving microtubule and Src inhibition, distinguishing it from other MTAs. In spite of its unique profile, exploration of tirbanibulin's structure-activity relationship (SAR) and the development of its derivatives are significantly limited in the current literature. This study addresses this gap by synthesizing various tirbanibulin derivatives and exploring their SAR through modifications in the core amide motif and the eastern benzylamine part. Our results underscore the critical role of the pyridinyl acetamide core structure for optimal cellular potency, with favorable tolerance observed for modifications at the para position of the benzylamine moiety. Particularly noteworthy is the analogue modified with p-fluorine benzylamine, which exhibited favorable in vivo PK profiles. These findings provide crucial insights into the potential advancement of tirbanibulin-based compounds as promising anticancer agents.

14.
ACS Chem Neurosci ; 14(20): 3761-3771, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37796021

RESUMO

In the human brain, neurophysiological activity is modulated by the movement of neurotransmitters and neurosteroids. To date, the similarity between cerebral organoids and actual human brains has been evaluated using comprehensive multiomics approaches. However, a systematic analysis of both neurotransmitters and neurosteroids from cerebral organoids has not yet been reported. Here, we performed quantitative and qualitative assessments of neurotransmitters and neurosteroids over the course of cerebral organoid differentiation. Our multiomics approaches revealed that the expression levels of neurotransmitter-related proteins and RNA, including neurosteroids, increase as cerebral organoids mature. We also found that the electrophysiological activity of human cerebral organoids increases in tandem with the expression levels of both neurotransmitters and neurosteroids. Our study demonstrates that the expression levels of neurotransmitters and neurosteroids can serve as key factors in evaluating the maturity and functionality of human cerebral organoids.


Assuntos
Neuroesteroides , Humanos , Neuroesteroides/metabolismo , Neurotransmissores/farmacologia , Neurotransmissores/metabolismo , Encéfalo/metabolismo , Organoides , Diferenciação Celular
15.
Langmuir ; 28(32): 11676-86, 2012 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-22812904

RESUMO

DNA short oligo, surfactant, peptides, and polymer-assisted dispersion of single-walled carbon nanotube (SWCNTs) in aqueous solution have been intensively studied. It has been suggested that van der Waals interaction, π-π stacking, and hydrophobic interaction are major factors that account for the SWCNTs dispersion. Fluorophore and dye molecules such as Rhodamine B and fluorescein have both hydrophilic and hydrophobic moieties. These molecules also contain π-conjugated systems that can potentially interact with SWCNTs to induce its dispersion. Through a systematic study, here we show that SWCNTs can be dispersed in aqueous solution in the presence of various fluorophore or dye molecules. However, the ability of a fluorophore or dye molecule to disperse SWCNTs is not correlated with the stability of the fluorophore/dye-SWCNT complex, suggesting that the on-rate of fluorophore/dye binding to SWCNTs may dominate the efficiency of this process. We also examined the uptake of fluorophore molecules by mammalian cells when these molecules formed complexes with SWCNTs. The results can have potential applications in the delivery of poor cell-penetrating fluorophore molecules.


Assuntos
Corantes Fluorescentes/metabolismo , Nanotubos de Carbono/química , Água/química , Transporte Biológico , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Humanos , Soluções
16.
Bioelectrochemistry ; 137: 107670, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32971483

RESUMO

The recent extensive spread of Zika virus has led to increased interest in the development of early diagnostic tests. To the best of our knowledge, this is the first study to demonstrate the successful use of phage display to identify affinity peptides for quantitative analysis of AXL, a tyrosine kinase receptor involved in Zika virus entry. Biopanning of M13 phage library successfully identified a high affinity peptide, with the sequence AHNHTPIKQKYL. To study the feasibility of using free peptides for molecular recognition, we synthesized a series of amino acid-substituted peptides and examined their binding affinity for AXL using electrochemical impedance spectroscopy and square wave voltammetry. Most synthetic peptides had non-identical random coil structures based on circular dichroism spectroscopy. Of the peptides tested, AXL BP1 exhibited nanomolar binding affinity for AXL. To verify whether AXL BP1 could be used as a peptide inhibitor at the cellular level, two functional tests were carried out: a WST assay for cell viability and qRT-PCR for quantification of RNA levels in Zika virus-infected Huh7 cells. The results showed that AXL BP1 had low cytotoxicity and could block Zika virus entry. These results indicate that newly identified affinity peptides could potentially be used for the development of Zika virus entry inhibitors.


Assuntos
Peptídeos/farmacologia , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos , Zika virus/fisiologia , Sequência de Aminoácidos , Linhagem Celular , Dicroísmo Circular , Espectroscopia Dielétrica , Ensaio de Imunoadsorção Enzimática , Humanos , Peptídeos/química , Peptídeos/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/fisiologia , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/fisiologia , Receptor Tirosina Quinase Axl
17.
Sci Rep ; 10(1): 14259, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868817

RESUMO

This study investigated the chemical profiles of fine urban road dust as a set of indicators for major air pollutants at sampling sites or as proxies for potential human health impacts. We examined the chemical compositions of fine particles (< 100 µm) or re-suspended ultrafine particles (< 2.5 µm) in the urban road dust collected from the cities with major emission sources of CO, NH3, NOx, PM2.5, SOx, and volatile organic compounds. The elemental compositions, including metal contents and volatile or semi-volatile organic compound species were determined to constitute comprehensive chemical profiles of the solid road dust samples. The water-extractable organic compounds and fluorescent species of the size-fractionated re-suspended fine particulate matter (RPM) were also incorporated in the chemical profiles. The metal content and aliphatic hydrocarbons could partly distinguish emission sources, and clearer distinctions were achieved with the inclusion of fluorescence excitation-emission matrix (EEM) results. The dose-response test results showed positive correlations between cytotoxicity and relative abundance of hydrocarbons or metal contents of urban road dust. The set of chemical profiles suggested in this study could be further utilized for site identification or human health impact assessment using urban road dust.


Assuntos
Poeira/análise , Material Particulado/análise , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Avaliação do Impacto na Saúde , Humanos , Hidrocarbonetos/efeitos adversos , Hidrocarbonetos/análise , Pulmão/citologia , Pulmão/efeitos dos fármacos , Metais/efeitos adversos , Metais/análise , Tamanho da Partícula , Material Particulado/efeitos adversos , Pele/citologia , Pele/efeitos dos fármacos
18.
RSC Adv ; 10(33): 19382-19389, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35515479

RESUMO

Neural cell differentiation has been extensively studied in two-dimensional (2D) cell culture plates. However, the cellular microenvironment and extracellular matrix (ECM) are much more complex and flat 2D surfaces are hard to mimic in ECM. Carbon nanotubes (CNTs) and graphenes are multidimensional carbon-based nanomaterials and may be able to provide extra dimensions on cell growth and differentiation. To determine the effect of CNTs and graphene surfaces on the growth, gene expression, differentiation and functionality of neuroblastoma to a neural cell, SH-SY5Y cells were grown on a 2D (control) surface, a CNT network and a graphene film. The data suggest that SH-SY5Y cells grown on CNT surfaces show an average 20.2% increase in cell viability; 5.7% decrease in the ratio of cells undergoing apoptosis; 78.3, 43.4 and 38.1% increases in SOX2, GFAP and NeuN expression, respectively; and a 29.7% increase in mean firing rate on a multi-electrode array. SH-SY5Y cells grown on graphene film show little or no changes in cell properties compared to cells grown in 2D. The data indicate that the three-dimensional (3D) surface of CNTs provides a favorable environment for SH-SY5Y cells to proliferate and differentiate to neurons.

19.
ACS Omega ; 4(12): 15134-15138, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31552358

RESUMO

Monitoring of long-term stability of proteins on paper-based membranes is important as it is directly related to paper-based sensor fabrication. By using a simple piezo printhead inkjet printer, recombinant proteins and antibodies were printed on paper-based membranes to test their stability and sensitivity under varying lengths of storage and temperature conditions. Our data show that a printed IgG-HRP antibody on simple printing paper maintains >50% functionality up to ∼2 months under 4 and -20 °C storage. Antibodies printed on polyvinylidene difluoride (PVDF) and nitrocellulose showed 5.3 and 9.7% decreases, respectively, in initial signal intensities compared to printing paper. Prostate-specific membrane antigen and tumor necrosis factor alpha recombinant proteins printed on paper-based membranes can be detected by antibodies, and antibody signal intensities can be detected up to 28 days after storage at 4 and -20 °C when printed on PVDF membrane or printing paper. These data suggest that printed proteins on simple printing paper and PVDF membrane can maintain their functionality up to few months when stored at 4 °C or lower and can be potentially applied in paper-based sensor development.

20.
Environ Pollut ; 255(Pt 2): 113156, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31563770

RESUMO

This study investigated the chemical components of fine urban road dust from seven sampling sites, based on which we could predict potential human health effects. The elemental compositions, including the contents of metals and volatile or semivolatile organic compounds, were determined to establish comprehensive chemical profiles of solid road dust. The chemical profiles, consisting of C: H ratio, metal contents, and relative abundances of organic compounds, provided a chemical signature for road dust. To overall cytotoxicity values ranging between 7 and 58%, water extracts contributed less than 15%, and cell death mainly occurred via direct contact with solid-phase components, which possibly indicates that the selected chemical profile of solid-phase road dust components could serve as a strong predictor for BJ and WI-38 cytotoxicity. Pure metal oxides (Cr2O3, CuO, Fe2O3, MnO2, NiO, or ZnO) exhibited a positive dose-response, and the corresponding metal contents in solid road dust were well correlated with cell viability. The principal component analysis (PCA) results suggested that the metal contents were stronger predictors of cytotoxicity than the benzene derivative or hydrocarbon contents. The chemical profiles established in this study could be further utilized to identify candidate health hazard factors in road dust.


Assuntos
Poeira/análise , Monitoramento Ambiental , Poluentes Ambientais/análise , Humanos , Compostos de Manganês/análise , Metais/análise , Óxidos/análise
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