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2.
Comput Med Imaging Graph ; 113: 102345, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38330636

RESUMO

Robust and interpretable image reconstruction is central to imageology applications in clinical practice. Prevalent deep networks, with strong learning ability to extract implicit information from data manifold, are still lack of prior knowledge introduced from mathematics or physics, leading to instability, poor structure interpretability and high computation cost. As to this issue, we propose two prior knowledge-driven networks to combine the good interpretability of mathematical methods and the powerful learnability of deep learning methods. Incorporating different kinds of prior knowledge, we propose subband-adaptive wavelet iterative shrinkage thresholding networks (SWISTA-Nets), where almost every network module is in one-to-one correspondence with each step involved in the iterative algorithm. By end-to-end training of proposed SWISTA-Nets, implicit information can be extracted from training data and guide the tuning process of key parameters that possess mathematical definition. The inverse problems associated with two medical imaging modalities, i.e., electromagnetic tomography and X-ray computational tomography are applied to validate the proposed networks. Both visual and quantitative results indicate that the SWISTA-Nets outperform mathematical methods and state-of-the-art prior knowledge-driven networks, especially with fewer training parameters, interpretable network structures and well robustness. We assume that our analysis will support further investigation of prior knowledge-driven networks in the field of ill-posed image reconstruction.


Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Aprendizagem
3.
Cureus ; 16(2): e53395, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38314382

RESUMO

BACKGROUND: Hydroxychloroquine (HCQ) influences both toll-like receptor (TLR) signaling and leukocyte activation, which are speculated to play a role in the pathogenesis of IgA nephropathy (IgAN). METHODS: This is a single-centered retrospective study involving 426 IgAN patients diagnosed from May 2016 to August 2020. All patients were matched according to a propensity score matching (PSM) to produce three groups: renin-angiotensin-aldosterone system inhibitors (RAASi) group (RAASi only), corticosteroids group (corticosteroids only or combined with RAASi), and HCQ group (HCQ only or combined with RAASi), consisting of 63 patients for each group. RESULTS: After PSM, the median urine protein/creatinine ratio (UPCR) of overall patients was 0.91 g/g, while their median serum creatinine was 87.00 µmol/L. After the median follow-up period of 11.03 months, the total remission rates of the RAASi group, corticosteroids group, and HCQ groups were 49.21% (n = 31), 74.60% (n = 47), and 52.38% (n = 33), respectively (p = 0.017). Thirteen (6.88%) patients experienced a decline in estimated glomerular filtration rate (eGFR) of more than 25% from baseline, including six (9.52%) patients in the RAASi group, three (4.76%) patients in the corticosteroids group, and four (6.35%) patients in HCQ group (p = 0.677). One (1.59%) patient in the HCQ group had blurred vision and continued to use HCQ after ruling out retinal lesions by ophthalmic examination. CONCLUSION: HCQ is effective in inducing remission and well-tolerated in IgAN patients with mild to moderate proteinuria.

4.
Sci Bull (Beijing) ; 68(22): 2779-2792, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-37863773

RESUMO

Immunotherapy has revolutionized cancer therapy, using chemical or biological agents to reinvigorate the immune system. However, most of these agents have poor tumor penetration and inevitable side effects that complicate therapeutic outcomes. Electrical stimulation (ES) is a promising alternative therapy against cancers that does not involve chemical or biological agents but is limited in the fabrication and operation of complex micrometer-scale ES devices. Here, we present an optically microprinted flexible interdigital electrode with a gold-plated polymer microneedle array to generate alternating electric fields for cancer treatment. A flexible microneedle-array-integrated interdigital electrode (FMIE) was fabricated by combining optical 3D microprinting and electroless plating processes. FMIE-mediated ES of cancer cells induced necrotic cell death through mitochondrial Ca2+ overload and increased intracellular reactive oxygen species (ROS) production. This led to the release of damage-associated molecular patterns that activated the immune response and potentiated immunogenic cell death (ICD). FMIE-based ES has an excellent safety profile and systemic anti-tumor effects, inhibiting the growth of primary and distant tumors as well as melanoma lung metastasis. FMIE-based ES-driven cancer immunomodulation provides a new pathway for drug-free cancer therapy.


Assuntos
Imunoterapia , Neoplasias Pulmonares , Humanos , Eletrodos , Estimulação Elétrica , Fatores Biológicos
5.
Nano Lett ; 23(19): 9133-9142, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37767907

RESUMO

Immunotherapy has emerged as a triumph in the treatment of malignant cancers. Nevertheless, current immunotherapeutics are insufficient in addressing tumors characterized by tumor cells' inadequate antigenicity and the tumor microenvironment's low immunogenicity (TME). Herein, we developed a novel multifunctional nanoassembly termed FMMC through the self-assembly of indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor 1-methyl-tryptophan prodrug (FM), Ce6, and ionic manganese (Mn2+) via noncovalent interactions. The laser-ignited FMMC treatment could induce effective immunogenic cell death and activate the STING/MHC-I signaling pathway, thus deeply sculpting the tumor-intrinsic antigenicity to achieve dendritic cell (DC)-dependent and -independent T cell responses against tumors. Meanwhile, by inhibiting IDO-1, FMMC could lead to immunosuppressive TME reversion to an immunoactivated one. FMMC-based phototherapy led to the up-regulation of programmed death-ligand 1 (PD-L1), enhancing the sensitivity of tumors to anti-PD-1 therapy. Furthermore, the incorporation of Mn2+ into FMMC resulted in an augmented longitudinal relaxivity and enhanced the MRI for monitoring the growth of primary tumors and lung metastases. Collectively, the superior reprogramming performance of immunosuppressive tumor cells and TME, combined with excellent anticancer efficacy and MRI capability, made FMMC a promising immune nanosculptor for cancer theranostics.


Assuntos
Imunoterapia , Fototerapia , Linfócitos T , Transdução de Sinais , Células Dendríticas , Microambiente Tumoral , Linhagem Celular Tumoral
6.
J Periodontol ; 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37531239

RESUMO

BACKGROUND: Alveolar mucosa could be a promising source of mesenchymal stem cells (MSCs) for regeneration therapeutics because it exhibits faster healing potential and can be easily collected with minimal periodontal disturbance. This study aimed to evaluate the potential of alveolar mucosal cell (AMC) spheroids for promoting extraction socket healing and calvarial osseous defect regeneration. METHODS: AMCs were isolated from Sprague-Dawley rats. Antigenic and MSC surface marker expressions and trilineage differentiation capability were assessed. AMCs were then osteogenically stimulated (OAs) or unstimulated (UAs), self-aggregated to form spheroids, and encapsulated in gelatin hydrogel to fill rat extraction sockets or combined with freeze-dried bone graft (FDBG) to fill rat calvarial osseous defects. The outcome was assessed by gross observation, micro-CT imaging, and immunohistochemistry. RESULTS: AMCs highly expressed MSC surface markers, showed weak antigenicity, and were capable of trilineage differentiation at Passage 3. In the extraction sockets, wound closure, socket fill, keratinization, and proliferative activities were accelerated in those with AMC spheroids treatment. Socket fill and maturation were further promoted by OA spheroids. In the calvarial osseous defects, the mineralized tissue ratio was promoted with AMC spheroids/FDBG treatment, and bone sialoprotein expression and cell proliferation were more evident with OA spheroids/FDBG treatment. CONCLUSION: AMCs exhibited MSC properties with weak antigenicity. AMC spheroids promoted extraction socket healing, AMC spheroids/FDBG promoted calvarial osseous defect regeneration, and the outcomes were further enhanced by osteogenically stimulation of AMCs.

7.
Adv Healthc Mater ; 12(18): e2202977, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36878223

RESUMO

Peptide-based immune checkpoint inhibitors exhibit remarkable therapeutic benefits although their application is hindered by quick blood clearance and low affinity with receptors. The modification of the peptides into artificial antibodies is an ideal platform to solve these problems, and one of the optional pathways is the conjugation of peptides with a polymer. More importantly, the bridging effect, mediated by bispecific artificial antibodies, could promote the interaction of cancer cells and T cells, which will benefit cancer immunotherapy. Herein, a bispecific peptide-polymer conjugate (octa PEG-PD1-PDL1) is prepared by simultaneously conjugating PD1-binding and PDL1-binding peptides onto 8-arm-PEG. octa PEG-PD1-PDL1 bridges T cells and cancer cells and thus enhances T cell-mediated cytotoxicity against cancer cells. Meanwhile, the tumor-targeting octa PEG-PD1-PDL1 increases the infiltration of cytotoxic T lymphocytes in tumors and reduces their exhaustion. It effectively activates the tumor immune microenvironment and exerts a potent antitumor effect against CT26 tumor models with a tumor inhibition rate of 88.9%. This work provides a novel strategy to enhance tumor immunotherapy through conjugating bispecific peptides onto a hyperbranched polymer to effectively engage target-effector cells.


Assuntos
Anticorpos Biespecíficos , Neoplasias , Humanos , Imunoterapia , Linfócitos T Citotóxicos , Anticorpos Biespecíficos/farmacologia , Peptídeos , Microambiente Tumoral
8.
Stem Cell Res Ther ; 14(1): 20, 2023 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-36737813

RESUMO

BACKGROUND: Diabetes mellitus deteriorates the destruction and impairs the healing of periodontal wounds and craniofacial defects. This study is to evaluate the potential of self-assembled adipose-derived stem cell spheroids (ADsp) in microbial transglutaminase cross-linked gelatin hydrogel (mTG) for treating diabetic periodontal wounds and craniofacial defects. METHODS: Human adipose-derived stem cells (ADSCs) were isolated by lipoaspiration, pluripotent genes and trilineage differentiation were examined, and the maintenance of ADsp properties in mTG was verified. Oral mucosal wounds and calvarial osseous defects were created in diabetic rats. Gross observation, histologic evaluation, and immunohistochemistry for proliferating cells and keratinization were conducted in the mucosal wounds within 4-28 days. Micro-CT imaging, histologic evaluation, and immunohistochemistry for proliferating cells and osteogenic differentiation were conducted in the osseous defects at 7 and 28 days. RESULTS: ADSCs expressed pluripotent genes and were capable of trilineage differentiation. ADsp retained morphology and stemness in mTG. In diabetic mucosal wounds, wound closure, epithelization, and keratinization were accelerated in those with ADsp and ADsp-mTG. In diabetic osseous defects, osteogenic differentiation markers were evidently expressed, cell proliferation was promoted from day 7, and bone formation was significantly promoted at day 28 in those with osteogenically pretreated ADsp-mTG. CONCLUSIONS: ADsp-mTG accelerated diabetic oral mucosal wound healing, and osteogenically pretreated ADsp-mTG promoted diabetic osseous defect regeneration, proving that ADsp-mTG facilitated diabetic periodontal wound healing and craniofacial osseous defect regeneration.


Assuntos
Diabetes Mellitus Experimental , Hidrogéis , Ratos , Humanos , Animais , Hidrogéis/química , Gelatina , Transglutaminases/genética , Osteogênese , Tecido Adiposo , Células-Tronco
9.
Ther Apher Dial ; 27(1): 83-90, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35670149

RESUMO

BACKGROUND: This study aimed to analyze the change of serum uric acid (SUA) level post peritoneal dialysis (PD), and the correlation between follow-up SUA and prognosis in patients with PD. METHODS: A total of 1402 patients with PD were evaluated. We graded SUA levels into four grades at baseline, 6 months, 12 months, 18 months, and 24 months post PD, and then compared all-cause mortality and cardiovascular mortality among patients with different SUA grades at each time point. Kaplan-Meier and Cox proportional-hazards regression models were used in the analysis. RESULTS: The SUA levels were 7.97 ± 1.79, 7.12 ± 1.48, 7.05 ± 1.33, 7.01 ± 1.30, and 6.93 ± 1.26 mg/dl at baseline, 6, 12, 18, and 24 months, respectively. There was significant difference on all-cause mortality among patients with PD with different graded SUA levels at 6 months post PD (p = 0.010), and the all-cause mortality was lowest in patients with the grade of 5.65 mg/dl ≤ SUA <7.13 mg/dl. CONCLUSION: SUA level decreased after PD during follow-up. At 6 months post PD, the grade of 5.65 mg/dl ≤ SUA <7.13 mg/dl was appropriate for better patients' survival.


Assuntos
Doenças Cardiovasculares , Diálise Peritoneal , Humanos , Ácido Úrico , Seguimentos , Prognóstico , Diálise Peritoneal/efeitos adversos , Fatores de Risco
10.
Hum Gene Ther ; 34(1-2): 42-55, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36373826

RESUMO

Histone H3 is a nucleosome scaffold protein that is involved in a variety of intracellular processes. Aberrant modification of H3 is important in carcinogenesis. In contrast, free histones in cells can act as stimuli to trigger cellular immune responses and cell death. In this study, we linked cell-penetrating peptide HIV Tat to a histone H3 fragment to achieve intracellular delivery in tumor cells. We found that Tat-conjugated histone polypeptides localized to nuclei of lung and breast cancer cells and caused cell death. A trans-configured Tat sequence displayed dramatically improved peptide half-life and cytotoxicity. Mechanistic studies demonstrated that treatment with the peptides significantly elevated mitogen-activated protein kinase (MAPK) signaling, reactive oxygen species (ROS) production, as well as levels of stress-inducible transcription factor ATF3 (activating transcription factor 3) and AP-1 (activating protein-1). Cytotoxicity of the peptide was significantly reduced by inhibition of AP-1 activity and ROS production. These results suggest the potential of Tat-conjugated H3 peptides as antitumor agents to induce cell death via increased cellular stress response by activating p38-MAPK signaling and intracellular ROS production.


Assuntos
Infecções por HIV , Histonas , Humanos , Histonas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição AP-1/metabolismo , Morte Celular , Peptídeos/farmacologia
11.
Commun Biol ; 5(1): 300, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365735

RESUMO

TOX4 is one of the regulatory factors of PP1 phosphatases with poorly understood functions. Here we show that chromatin occupancy pattern of TOX4 resembles that of RNA polymerase II (Pol II), and its loss increases cellular level of C-terminal domain (CTD) phosphorylated Pol II but mainly decreases Pol II occupancy on promoters. In addition, elongation rate analyses by 4sUDRB-seq suggest that TOX4 restricts pause release and early elongation but promotes late elongation. Moreover, TT-seq analyses indicate that TOX4 loss mainly decreases transcriptional output. Mechanistically, TOX4 may restrict pause release through facilitating CTD serine 2 and DSIF dephosphorylation, and promote Pol II recycling and reinitiation through facilitating CTD serines 2 and 5 dephosphorylation. Furthermore, among the PP1 phosphatases, TOX4 preferentially binds PP1α and is capable of facilitating Pol II CTD dephosphorylation in vitro. These results lay the foundation for a better understanding of the role of TOX4 in transcriptional regulation.


Assuntos
Regulação da Expressão Gênica , Proteínas de Neoplasias/metabolismo , RNA Polimerase II , Cromatina/genética , Humanos , Regiões Promotoras Genéticas , RNA Polimerase II/genética , RNA Polimerase II/metabolismo
12.
Transportation (Amst) ; 49(5): 1339-1383, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34400848

RESUMO

Mobile device location data (MDLD) contains abundant travel behavior information to support travel demand analysis. Compared to traditional travel surveys, MDLD has larger spatiotemporal coverage of the population and its mobility. However, ground truth information such as trip origins and destinations, travel modes, and trip purposes are not included by default. Such important attributes must be imputed to maximize the usefulness of the data. This paper targets at studying the capability of MDLD on estimating travel mode share at aggregated levels. A data-driven framework is proposed to extract travel behavior information from MDLD. The proposed framework first identifies trip ends with a modified Spatiotemporal Density-based Spatial Clustering of Applications with Noise algorithm. Then three types of features are extracted for each trip to impute travel modes using machine learning models. A labeled MDLD dataset with ground truth information is used to train the proposed models, resulting in a 95% recall rate in identifying trip ends and over 93% tenfold cross-validation accuracy in imputing the five travel modes (drive, rail, bus, bike and walk) with a random forest (RF) classifier. The proposed framework is then applied to two large-scale MDLD datasets, covering the Baltimore-Washington metropolitan area and the United States, respectively. The estimated trip distance, trip time, trip rate distribution, and travel mode share are compared against travel surveys at different geographies. The results suggest that the proposed framework can be readily applied in different states and metropolitan regions with low cost in order to study multimodal travel demand, understand mobility trends, and support decision making.

13.
Nat Chem Biol ; 18(1): 70-80, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34916619

RESUMO

An RNA-involved phase-separation model has been proposed for transcription control. However, the molecular links that connect RNA to the transcription machinery remain missing. Here we find that RNA-binding proteins (RBPs) constitute half of the chromatin proteome in embryonic stem cells (ESCs), some being colocalized with RNA polymerase (Pol) II at promoters and enhancers. Biochemical analyses of representative RBPs show that the paraspeckle protein PSPC1 inhibits the RNA-induced premature release of Pol II, and makes use of RNA as multivalent molecules to enhance the formation of transcription condensates and subsequent phosphorylation and release of Pol II. This synergistic interplay enhances polymerase engagement and activity via the RNA-binding and phase-separation activities of PSPC1. In ESCs, auxin-induced acute degradation of PSPC1 leads to genome-wide defects in Pol II binding and nascent transcription. We propose that promoter-associated RNAs and their binding proteins synergize the phase separation of polymerase condensates to promote active transcription.


Assuntos
RNA Polimerase II/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transcrição Gênica , Regulação da Expressão Gênica , Fosforilação , Regiões Promotoras Genéticas , Ligação Proteica
14.
PLoS One ; 16(11): e0259803, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34762685

RESUMO

Racial/ethnic disparities are among the top-selective underlying determinants associated with the disproportional impact of the COVID-19 pandemic on human mobility and health outcomes. This study jointly examined county-level racial/ethnic differences in compliance with stay-at-home orders and COVID-19 health outcomes during 2020, leveraging two-year geo-tracking data of mobile devices across ~4.4 million point-of-interests (POIs) in the contiguous United States. Through a set of structural equation modeling, this study quantified how racial/ethnic differences in following stay-at-home orders could mediate COVID-19 health outcomes, controlling for state effects, socioeconomics, demographics, occupation, and partisanship. Results showed that counties with higher Asian populations decreased most in their travel, both in terms of reducing their overall POIs' visiting and increasing their staying home percentage. Moreover, counties with higher White populations experienced the lowest infection rate, while counties with higher African American populations presented the highest case-fatality ratio. Additionally, control variables, particularly partisanship, median household income, percentage of elders, and urbanization, significantly accounted for the county differences in human mobility and COVID-19 health outcomes. Mediation analyses further revealed that human mobility only statistically influenced infection rate but not case-fatality ratio, and such mediation effects varied substantially among racial/ethnic compositions. Last, robustness check of racial gradient at census block group level documented consistent associations but greater magnitude. Taken together, these findings suggest that US residents' responses to COVID-19 are subject to an entrenched and consequential racial/ethnic divide.


Assuntos
COVID-19/epidemiologia , Disparidades nos Níveis de Saúde , Pandemias , Racismo/psicologia , Negro ou Afro-Americano/psicologia , Idoso , COVID-19/psicologia , COVID-19/virologia , Etnicidade/psicologia , Humanos , Renda , Análise de Mediação , Pessoa de Meia-Idade , Grupos Minoritários/psicologia , Avaliação de Resultados em Cuidados de Saúde/normas , Grupos Raciais/psicologia , SARS-CoV-2/patogenicidade
15.
Food Chem ; 335: 127566, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32745839

RESUMO

In this work, we developed an optical colorimetric sensor array for the discrimination of Chinese teas. The sensor array was carefully designed based on tea polyphenol induced indicators displacement assay (IDA), using phenylboronic acids with different substituents as the receptors to polyphenols. The accurate identification for polyphenols with different species or concentrations proved the potential of the sensor array. The sensor array successfully distinguished tea samples within different categories, grades and origins, coupling with PLS-DA. This work offered an efficient and rapid method to distinguish teas and tea-related products. Besides, the assay is supposed to be suitable for the identification of other polyphenol-related natural products.


Assuntos
Camellia sinensis/química , Colorimetria/instrumentação , Polifenóis/análise , Qualidade dos Alimentos , Limite de Detecção
16.
Sci Rep ; 10(1): 20742, 2020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33244071

RESUMO

Since the first case of the novel coronavirus disease (COVID-19) was confirmed in Wuhan, China, social distancing has been promoted worldwide, including in the United States, as a major community mitigation strategy. However, our understanding remains limited in how people would react to such control measures, as well as how people would resume their normal behaviours when those orders were relaxed. We utilize an integrated dataset of real-time mobile device location data involving 100 million devices in the contiguous United States (plus Alaska and Hawaii) from February 2, 2020 to May 30, 2020. Built upon the common human mobility metrics, we construct a Social Distancing Index (SDI) to evaluate people's mobility pattern changes along with the spread of COVID-19 at different geographic levels. We find that both government orders and local outbreak severity significantly contribute to the strength of social distancing. As people tend to practice less social distancing immediately after they observe a sign of local mitigation, we identify several states and counties with higher risks of continuous community transmission and a second outbreak. Our proposed index could help policymakers and researchers monitor people's real-time mobility behaviours, understand the influence of government orders, and evaluate the risk of local outbreaks.


Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Distanciamento Físico , Quarentena/métodos , SARS-CoV-2 , Viagem , COVID-19/transmissão , COVID-19/virologia , Comportamento Cooperativo , Monitoramento Epidemiológico , Regulamentação Governamental , Humanos , Modelos Estatísticos , Quarentena/legislação & jurisprudência , Estados Unidos/epidemiologia
17.
PLoS One ; 15(11): e0241468, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33166301

RESUMO

In March of this year, COVID-19 was declared a pandemic, and it continues to threaten public health. This global health crisis imposes limitations on daily movements, which have deteriorated every sector in our society. Understanding public reactions to the virus and the non-pharmaceutical interventions should be of great help to fight COVID-19 in a strategic way. We aim to provide tangible evidence of the human mobility trends by comparing the day-by-day variations across the U.S. from January 2020 to early April 2020. Large-scale public mobility at an aggregated level is observed by leveraging mobile device location data and the measures related to social distancing. Our study captures spatial and temporal heterogeneity as well as the sociodemographic variations and teleworking trends regarding the pandemic propagation and the non-pharmaceutical mobility interventions. All metrics adapted capture decreased public movements after the national emergency declaration. The population staying home has increased in all states before the stay-at-home mandates implemented and becomes more stable after the order with a smaller range of fluctuation. The public had been taking active responses, voluntarily staying home more, to the in-state confirmed cases while the stay-at-home orders stabilize the variations. As the estimated teleworking rates also continue to incline throughout the study period, the teleworking trend can be another driving factor for the growing stay-at-home population. We confirm that there exists overall mobility heterogeneity between the income or population density groups. The study suggests that public mobility trends are in line with the government message urging to stay home. We anticipate our data-driven analysis offers integrated perspectives and serves as evidence to raise public awareness and, consequently, reinforce the importance of social distancing while assisting policymakers.


Assuntos
Infecções por Coronavirus/patologia , Movimento , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , COVID-19 , Uso do Telefone Celular/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Processamento Eletrônico de Dados , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , SARS-CoV-2 , Análise Espaço-Temporal , Estados Unidos/epidemiologia
18.
Anal Bioanal Chem ; 410(12): 2921-2935, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29532194

RESUMO

Herein, a novel magnetic effervescence tablet-assisted microextraction coupled to in situ metathesis reaction of ionic liquid (IS-META-ILDM) is presented for the determination of four endogenous steroids in human urine, pregnant women's blood, and fetal umbilical cord blood. The magnetic effervescent tablets, which were composed of Fe3O4 nanoparticles, sodium carbonate (alkaline source), and tartaric acid (acidic source), were used to disperse the extractant and for convenient magnetic separation. After the effervescent reaction, in situ reaction between NH4PF6 and [C6MIM]BF4 was adopted to change hydrophilic ionic liquid to hydrophobic liquid, which could be separated from the aqueous phase. The newly developed method has three obvious advantages: (1) combination of effervescent dispersion and magnetic nanoparticles' retrieval is cost-effective and the dispersion and collection of the extractant can be completed almost simultaneously; (2) as compared to temperature-controlled ionic liquid dispersive microextraction and cold-induced solidified microextraction, this method avoids a heating and cooling process which significantly reduces the extraction time and energy cost; and (3) the combination of adsorption by magnetic nanoparticles with extraction by in situ metathesis reaction easily produces high recoveries for target analytes. The optimized composition of effervescent tablet and experimental parameters are as follows: 0.64 g mixture of sodium carbonate and tartaric acid, 7 mg of Fe3O4 (20 nm) as magnetic sorbents, 40 µL of [C6MIM]BF4 as the extraction solvent, 0.15 g NH4PF6, and 300 µL of elution solvent. Under the optimized conditions, the newly developed method provided high extraction recoveries (90.0-118.5%) and low LODs (0.14-0.17 µg L-1) in urine and blood samples. In total, this IS-META-ILDM method provided high extraction efficiency, fast and convenient separation, and underutilization of any organic solvent, and thus it has great potential for the determination of trace endogenous steroids in complex human fluids. Graphical abstract The newly developed method has three obvious advantages: combination of effervescent dispersion and magnetic nanoparticles' retrieval is cost-effective and the dispersion and collection of the extractant can be completed almost simultaneously. It avoids a heating and cooling process which significantly reduces the extraction time and energy cost and easily produces high recoveries for target analytes.


Assuntos
Líquidos Iônicos/química , Microextração em Fase Líquida/instrumentação , Nanopartículas de Magnetita/química , Esteroides/sangue , Esteroides/urina , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia Líquida de Alta Pressão/métodos , Desenho de Equipamento , Feminino , Hormônios/sangue , Hormônios/isolamento & purificação , Hormônios/urina , Humanos , Limite de Detecção , Microextração em Fase Líquida/métodos , Magnetismo/instrumentação , Magnetismo/métodos , Masculino , Gravidez , Esteroides/isolamento & purificação
19.
Braz J Med Biol Res ; 51(4): e6891, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29513793

RESUMO

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Camellia sinensis/química , Neoplasias da Vesícula Biliar/patologia , Polifenóis/farmacologia , Fase S/efeitos dos fármacos , Chá/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Xenoenxertos , Humanos , Polifenóis/isolamento & purificação
20.
Braz. j. med. biol. res ; 51(4): e6891, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-889070

RESUMO

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.


Assuntos
Humanos , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Camellia sinensis/química , Neoplasias da Vesícula Biliar/patologia , Polifenóis/farmacologia , Fase S/efeitos dos fármacos , Chá/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias da Vesícula Biliar/tratamento farmacológico , Xenoenxertos , Polifenóis/isolamento & purificação
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