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1.
Int J Clin Pharm ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861047

RESUMO

BACKGROUND: Vancomycin trough concentration is closely associated with clinical efficacy and toxicity. Predicting vancomycin trough concentrations in pediatric patients is challenging due to significant inter-individual variability and rapid physiological changes during maturation. AIM: This study aimed to develop a machine learning model to predict vancomycin trough concentrations and determine optimal dosing regimens for pediatric patients < 4 years of age using ML algorithms. METHOD: A single-center retrospective observational study was conducted from January 2017 to March 2020. Pediatric patients who received intravenous vancomycin and underwent therapeutic drug monitoring were enrolled. Seven ML models [linear regression, gradient boosted decision trees, support vector machine, decision tree, random forest, Bagging, and extreme gradient boosting (XGBoost)] were developed using 31 variables. Performance metrics including R-squared (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) were compared, and important features were ranked. RESULTS: The study included 120 eligible trough concentration measurements from 112 patients. Of these, 84 measurements were used for training and 36 for testing. Among the seven algorithms tested, XGBoost showed the best performance, with a low prediction error and high goodness of fit (MAE = 2.55, RMSE = 4.13, MSE = 17.12, and R2 = 0.59). Blood urea nitrogen, serum creatinine, and creatinine clearance rate were identified as the most important predictors of vancomycin trough concentration. CONCLUSION: An XGBoost ML model was developed to predict vancomycin trough concentrations and aid in drug treatment predictions as a decision-support technology.

2.
Photochem Photobiol Sci ; 23(6): 1051-1065, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38684635

RESUMO

As a member of the SMAD family, SMAD4 plays a crucial role in several cellular biological processes. However, its function in UVB radiation-induced keratinocyte damage is not yet clarified. Our study aims to provide mechanistic insight for the development of future UVB protective therapies and therapeutics involving SMAD4. HaCaT cells were treated with UVB, and the dose dependence and time dependence of UVB were measured. The cell function of UVB-treated HaCaT cells and the activity of epithelial-mesenchymal transition (EMT) after overexpression or silencing of SMAD4 was observed by flow cytometry, quantitative reverse transcription PCR (qRT-PCR) and Western Blots (WB). We found that a significant decrease in SMAD4 was observed in HaCaT cells induced by UVB. Our data confirm SMAD4 as a direct downstream target of miR-664. The down-regulation of SMAD4 preserved the viability of the UVB-treated HaCaT cells by inhibiting autophagy or apoptosis. Furthermore, the silencing of SMAD4 activated the EMT process in UVB-treated HaCaT cells. Down-regulation of SMAD4 plays a protective role in UVB-treated HaCaT cells via the activation of EMT.


Assuntos
Regulação para Baixo , Transição Epitelial-Mesenquimal , Células HaCaT , Estresse Oxidativo , Proteína Smad4 , Raios Ultravioleta , Proteína Smad4/metabolismo , Humanos , Transição Epitelial-Mesenquimal/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Queratinócitos/citologia , Sobrevivência Celular/efeitos da radiação , Apoptose/efeitos da radiação
3.
Pediatr Res ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431666

RESUMO

BACKGROUND: Precocious puberty is an endocrine disease that is diagnosed by sex, age, and Tanner stage of puberty. This study aimed to investigate the association between various dietary patterns and early or precocious puberty, especially Traditional dietary patterns, which have been rarely investigated. METHODS: A total of 4085 primary school students in grades 1-3 (6-9 years) completed individual characteristic surveys, health examinations, and food frequency questionnaires (FFQs). Physical examinations were also conducted to assess obesity and pubertal onset. Traditional, Westernized, and Protein dietary patterns were determined by factor analysis, and their associations with pubertal onset were analyzed by multiple logistic regression analysis. RESULTS: Compared to the other two patterns, children who predominant the Traditional dietary pattern were protectively associated with precocious puberty (OR = 0.72, 95% CI = 0.55, 0.94), even after adjusting the confounders (OR = 0.66, 95% CI = 0.48, 0.89). Neither the Westernized nor Protein dietary pattern demonstrated an association with pubertal onset. The Traditional dietary pattern was negatively associated with children's weight status, classified by body mass index (BMI), and was positively associated with parental education. The maternal education and the Protein dietary pattern were negatively related. CONCLUSIONS: Traditional dietary patterns were protective associated with early and precocious puberty among Chinese children. IMPACT: The Traditional dietary pattern was protective associated with early puberty or precocious puberty in children, as found in large-scale population-based public health research. Current research primarily focuses on Westernized dietary patterns, and we studied Traditional dietary patterns to further explore the influence of food on children's puberty development. We discovered that children's preference for Traditional dietary patterns is protective of pubertal development, which implies that society and parents can benefit from diet guidance to protect children's natural development during adolescence.

4.
Langmuir ; 40(5): 2698-2707, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38268181

RESUMO

The effect of the water-soluble polymer (partially hydrolyzed polyacrylamide, HPAM) in produced water on the demulsification process of the electric field was studied by molecular dynamics simulations. By comparing the coalescence process of oil droplets in the electric field environment with or without HPAM, we find that HPAM in the water phase can promote the coalescence of nearly oil droplets but hinder the deformation and migration of oil droplets. By analyzing the radial distribution function and interaction energy between molecules, we conclude that the existence of HPAM molecules can reduce the hydrophilicity of other molecules through their strong interaction with water, and sodium ions (Na+) have strong interaction with bound water in the process of breaking away from HPAM, thus leading the movement of water molecules. At the same time, the influence of HPAM molecules located between the two oil droplets on the demulsification process was also studied. The HPAM molecules and sodium ions located between the two oil droplets also affected the coalescence process of oil droplets under an electric field by interacting with water.

5.
BMC Genomics ; 24(1): 678, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37950200

RESUMO

BACKGROUND: High oncogene expression in cancer cells is a major cause of rapid tumor progression and drug resistance. Recent cancer genome research has shown that oncogenes as well as regulatory elements can be amplified in the form of extrachromosomal DNA (ecDNA) or subsequently integrated into chromosomes as homogeneously staining regions (HSRs). These genome-level variants lead to the overexpression of the corresponding oncogenes, resulting in poor prognosis. Most existing detection methods identify ecDNA using whole genome sequencing (WGS) data. However, these techniques usually detect many false positive regions owing to chromosomal DNA interference. RESULTS: In the present study, an algorithm called "ATACAmp" that can identify ecDNA/HSRs in tumor genomes using ATAC-seq data has been described. High chromatin accessibility, one of the characteristics of ecDNA, makes ATAC-seq naturally enriched in ecDNA and reduces chromosomal DNA interference. The algorithm was validated using ATAC-seq data from cell lines that have been experimentally determined to contain ecDNA regions. ATACAmp accurately identified the majority of validated ecDNA regions. AmpliconArchitect, the widely used ecDNA detecting tool, was used to detect ecDNA regions based on the WGS data of the same cell lines. Additionally, the Circle-finder software, another tool that utilizes ATAC-seq data, was assessed. The results showed that ATACAmp exhibited higher accuracy than AmpliconArchitect and Circle-finder. Moreover, ATACAmp supported the analysis of single-cell ATAC-seq data, which linked ecDNA to specific cells. CONCLUSIONS: ATACAmp, written in Python, is freely available on GitHub under the MIT license: https://github.com/chsmiss/ATAC-amp . Using ATAC-seq data, ATACAmp offers a novel analytical approach that is distinct from the conventional use of WGS data. Thus, this method has the potential to reduce the cost and technical complexity associated ecDNA analysis.


Assuntos
DNA de Forma B , Neoplasias , Humanos , Sequenciamento de Cromatina por Imunoprecipitação , Cromatina , DNA/genética , Oncogenes , Neoplasias/genética
6.
J Pharm Biomed Anal ; 234: 115578, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37459833

RESUMO

Vincristine (VCR) is a vital component in numerous treatment regimens for pediatric blood cancer. VCR-induced peripheral neuropathy (VIPN) represents a type of VCR toxicity influenced by multiple factors, including age, race, genetic traits, dosage, interactions, and administration regimen. However, the dose-response relationship of VIPN remains elusive. VCR is primarily metabolized by cytochrome P450 (CYP) 3 A to generate the major metabolite M1. To date, there is a lack of literature documenting the pharmacokinetics (PK) characteristics of VCR and M1 in Chinese children within a 96 h timeframe. To address the gap, a developed LC-MS/MS method was successfully employed in the PK study of VCR and M1 in Chinese pediatric acute lymphoblastic leukemia (ALL) patients. M1 was obtained through in vitro metabolism experiments, and mixed plasma samples of M1 and VCR were prepared. Plasma samples were pre-processed using the solid-phase extraction (SPE) technique. Samples were loaded into ProElut C18 Cartridges, washed with 5% methanol aqueous solution, and eluted with methanol. The eluent was concentrated and reconstituted for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The standard calibration curves for VCR and M1 were 0.1-50 ng/mL and 0.05-5 ng/mL, respectively, with linear coefficients exceeding 0.99. Accuracy and precision of quality control (QC) samples fell within 115%. The analytical approach satisfied the quantitative demands for VCR and M1 in plasma samples within 96 h. VCR was metabolized to M1 at a relatively constant proportion (5.37%-18.06%) of VCR in vivo. No significant differences were observed in PK parameters of VCR in Chinese children compared to other countries and races. Further investigation is required to identify the key factors influencing VIPN in Chinese children.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Espectrometria de Massas em Tandem , Vincristina , Criança , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , População do Leste Asiático , Metanol , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Espectrometria de Massas em Tandem/métodos , Vincristina/metabolismo , Vincristina/farmacocinética , Vincristina/uso terapêutico , China
7.
Ultrason Sonochem ; 95: 106401, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37060713

RESUMO

Dicaffeoylquinic acids (diCQAs) are found in a variety of edible and medicinal plants with various biological activities. An important issue is the low stability of diCQAs during extraction and food processing, resulting in the degradation and transformation. This work used 3,5-diCQA as a representative to study the influence of different parameters in ultrasonic treatment on the stability of diCQAs, including solvent, temperature, treatment time, ultrasonic power, duty cycle, and probe immersion depth. The generation of free radicals and its influence were investigated during the treatment. The stability of three diCQAs (3,5-diCQA, 4,5-diCQA and 3,4-diCQA) under the certain ultrasonic condition at different pH conditions was evaluated and found to decrease with the increase of pH, further weakened by ultrasonic treatment. Ultrasound was found to accelerate the degradation and isomerization of diCQAs. Different diCQAs showed different pattern of degradation and isomerization. The stability of diCQAs could be improved by adding epigallocatechin gallate and vitamin C.

8.
Environ Res ; 224: 115447, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36758919

RESUMO

A green, high-efficiency, and wide pH tolerance water remediation process has been urgently acquired for the increasingly exacerbating contaminated water. In this study, a Fe3+/persulfate (Fe3+/PS) system was employed and enhanced with a green natural ligand cysteine (Cys) for the degradation of quinclorac (QNC). The introduction of Cys into the Fe3+/PS system widened the effective pH range to 9 with a superior removal rate for QNC. The mechanism revealed that the Fe3+/Cys/PS system can enhance the ability of degrading QNC by accelerating the Fe3+/Fe2+ redox cycle, maintaining Fe2+ concentration and thereby generating more HO• and SO4•-. The impact factors (i.e., pH, concentrations of PS, Fe3+ and Cys) were optimized as well. This work provides a promising strategy with high catalytic activity and wide pH tolerance for organic contaminated water remediation.


Assuntos
Quinolinas , Poluentes Químicos da Água , Purificação da Água , Cisteína/química , Concentração de Íons de Hidrogênio , Oxirredução , Água , Poluentes Químicos da Água/análise , Química Verde
9.
Molecules ; 28(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36677893

RESUMO

Novel furoxan/coumarin hybrids were synthesized, and pharmacologic studies showed that the compounds displayed potent antiproliferation activities via downregulating both the phosphatidylinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway. To investigate the preclinical pharmacokinetic (PK) properties of three candidate compounds (CY-14S-4A83, CY-16S-4A43, and CY-16S-4A93), liquid chromatography, in tandem with the mass spectrometry LC-MS/MS method, was developed and validated for the simultaneous determination of these compounds. The absorption, distribution, metabolism, and excretion (ADME) properties were investigated in in vitro studies and in rats. Meanwhile, physiologically based pharmacokinetic (PBPK) models were constructed using only in vitro data to obtain detailed PK information. Good linearity was observed over the concentration range of 0.01−1.0 µg/mL. The free drug fraction (fu) values of the compounds were less than 3%, and the clearance (CL) values were 414.5 ± 145.7 mL/h/kg, 2624.6 ± 648.4 mL/h/kg, and 500.6 ± 195.2 mL/h/kg, respectively. The predicted peak plasma concentration (Cmax) and the area under the concentration-time curve (AUC) were overestimated for the CY-16S-4A43 PBPK model compared with the experimental ones (fold error > 2), suggesting that tissue accumulation and additional elimination pathways may exist. In conclusion, the LC-MS/MS method was successively applied in the preclinical PK studies, and the detailed information from PBPK modeling may improve decision-making in subsequent new drug development.


Assuntos
Oxidiazóis , Espectrometria de Massas em Tandem , Ratos , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Cumarínicos , Modelos Biológicos , Farmacocinética
10.
Environ Technol ; 44(16): 2451-2461, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35084294

RESUMO

The disadvantages of narrow working pH range (2.5-4.0), accumulation of iron sludge and incomplete degradation have hindered the practical application of the traditional homogeneous Fenton technique. In this research, Fe@FeS core-shell nanowires were synthesised and the innovative Fe@FeS/Fe2+/H2O2 system was adopted for norfloxacin (NOR) degradation at an initial circumneutral pH. More than 95% NOR has been removed in the Fe@FeS/Fe2+/H2O2 system within 30 min at pH 7. After investigating the concentration change of total iron, Fe2+ and H2O2 during the degradation process, NOR degradation in the Fe@FeS/Fe2+/H2O2 system might be attributed to the combined effect of homogeneous Fenton reaction and heterogeneous Fenton process. Besides that, the added Fe@FeS has accelerated Fe3+/Fe2+ redox cycle with extremely high degree. The generated reactive ●OH has been identified by electron paramagnetic resonance spectrometer results, possible degradation intermediates have also been proposed according to Gas chromatography-mass spectrometry analysis results. Moreover, Fe@FeS core-shell nanowires showed excellent reusability, it is a promising heterogeneous Fenton catalyst that is applicable for practical application.


Assuntos
Antibacterianos , Nanofios , Norfloxacino , Catálise , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Ferro/química , Nanofios/química , Oxirredução , Antibacterianos/química
11.
Ultrason Sonochem ; 92: 106240, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36470128

RESUMO

The ß-lactoglobulin-chlorogenic acid (LG-CA) conjugate was explored to be formed through ultrasonication, redox-pair method and their combination, the ultrasonication used a probe ultrasonic machine with a 6 mm probe at 270 W, and the frequency was 20-25 kHz. The formation of the conjugate was confirmed by SDS-PAGE with a larger molecular weight. Besides, Fourier infrared spectroscopy (FTIR) and Circular dichroism (CD) indicated changes in the secondary structure of the LG-CA conjugate. The α-helix and ß-sheet contents of LG decreased and the unordered content increased significantly after the formation of covalent complexes. In addition, both the ultrasonic treatment and its combination with redox-pair method could significantly improve the antioxidant properties of LG. The former increased to 23.16 µmol Trolox/g sample, the latter 82-106 µmol Trolox/g sample. Therefore, ultrasonication could be used both individually and in combination with the redox-pair method to produce LG-CA conjugates with stronger antioxidant activities.


Assuntos
Ácido Clorogênico , Lactoglobulinas , Lactoglobulinas/química , Antioxidantes/farmacologia , Estrutura Secundária de Proteína , Conformação Proteica em alfa-Hélice , Dicroísmo Circular
12.
Front Pharmacol ; 13: 895556, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35645843

RESUMO

Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive, and time-consuming procedures, pharmacokinetic profiling is still irreplaceable in preclinical studies. With physiologically based pharmacokinetic (PBPK) modeling, the in vivo profiles of drug absorption, distribution, metabolism, and excretion can be predicted. To evaluate the application of such an approach in preclinical investigations, the plasma pharmacokinetic profiles of seven commonly used probe substrates of microsomal enzymes, including phenacetin, tolbutamide, omeprazole, metoprolol, chlorzoxazone, nifedipine, and baicalein, were predicted in rats using bottom-up PBPK models built with in vitro data alone. The prediction's reliability was assessed by comparison with in vivo pharmacokinetic data reported in the literature. The overall predicted accuracy of PBPK models was good with most fold errors within 2, and the coefficient of determination (R2) between the predicted concentration data and the observed ones was more than 0.8. Moreover, most of the observation dots were within the prediction span of the sensitivity analysis. We conclude that PBPK modeling with acceptable accuracy may be incorporated into preclinical studies to refine in vivo investigations, and PBPK modeling is a feasible strategy to practice the principles of 3Rs.

13.
Ultrason Sonochem ; 86: 106025, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35533432

RESUMO

It is essential to understand the ultrasound-induced changes in assembly of proteins and polyphenols into non covalent nanocomplex. ß-Lactoglobulin (LG) and chlorogenic acid (CA) with various biological activities can be combined to form food-grade nanocomplexes. This study systematically explored the role of high-intensity ultrasound pretreatment on the binding mechanisms of LG and CA, and the potential biological function for embedding curcumin (Cur). The scanning electron microscopy (SEM) revealed that ultrasound treatment could destroy the structure of LG, and the particle size of the protein was reduced to<50 nm. The change in secondary structure of the protein by ultrasound treatment could be revealed by the fourier transform infrared (FTIR) and fluorescence spectra. Besides, it was found that LG and CA were combined to form a complex under the hydrophobic interaction, and CA was bound in the internal cavity of LG with a relatively extended conformation. The result demonstrated that the ratio of Cur embedded in the ultrasonic sample could be effectively increased by 7% - 10%, the particle size in the emulsion was smaller, and the dispersion was more stable. This work contributes to the development of protein-polyphenol functional emulsion systems with the ability to deliver Cur.


Assuntos
Curcumina , Lactoglobulinas , Ácido Clorogênico , Curcumina/química , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Lactoglobulinas/química , Polifenóis
14.
J Dermatol Sci ; 105(1): 18-26, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34930675

RESUMO

BACKGROUND: Dysregulation of miR-486-3p was related to the growth and development of a variety of cancers, but the specific function of miR-486-3p in cutaneous squamous cell carcinoma (cSCC) is not to be confirmed yet. OBJECTIVE: Our present study aimed to validate the potential molecular mechanisms of miR-486-3p in cSCC and the potential of miR-486-3p as a novel target for future treatment. METHODS: Human cSCC samples and normal skin tissues were applied to determine the expression level of miR-486-3p and FLOT2 by fluorescence in situ hybridization (FISH) and quantitative reverse transcription PCR (qRT-PCR), respectively. As well as BALB/C nude mouse tumor model, three cSCC cells lines including HSC-1, HSC-5 and A431 were utilized to demonstrate the potential function of miR-486-3p and FLOT2 in tumorigenesis. RESULTS: Our experimental results showed that miR-486-3p was highly expressed both in tumor samples and cell lines of cSCC. Upregulation of miR-486-3p enhanced the proliferation and migration ability of cSCC cell lines and promoted tumorigenicity in vivo. Furthermore, we confirmed that FLOT2 was a direct targeted gene of miR-486-3p. In contrary to the expression level of miR-486-3p, FLOT2 was low expressed in cSCC patient specimens and cell lines. Knockdown of FLOT2 promoted tumorigenesis of cSCC; whereas FLOT2 reversed the tumor-promoting effect of miR-486-3p. CONCLUSION: Our data exhibited that miR-486-3p exerted its effects on carcinogenesis as an oncogene in cSCC via suppression of FLOT2. This discovery will develop new therapeutic targets of cSCC.


Assuntos
Carcinoma de Células Escamosas/etiologia , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Neoplasias Cutâneas/etiologia , Adulto , Idoso , Animais , Carcinogênese , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Pharmaceutics ; 13(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34684027

RESUMO

In order to improve the benefit-risk ratio of pharmacokinetic (PK) research in the early development of new drugs, in silico and in vitro methods were constructed and improved. Models of intrinsic clearance rate (CLint) were constructed based on the quantitative structure-activity relationship (QSAR) of 7882 collected compounds. Moreover, a novel in vitro metabolic method, the Bio-PK dynamic metabolic system, was constructed and combined with a physiology-based pharmacokinetic model (PBPK) model to predict the metabolism and the drug-drug interaction (DDI) of azidothymidine (AZT) and fluconazole (FCZ) mediated by the phase II metabolic enzyme UDP-glycosyltransferase (UGT) in humans. Compared with the QSAR models reported previously, the goodness of fit of our CLint model was slightly improved (determination coefficient (R2) = 0.58 vs. 0.25-0.45). Meanwhile, compared with the predicted clearance of 61.96 L/h (fold error: 2.95-3.13) using CLint (8 µL/min/mg) from traditional microsomal experiment, the predicted clearance using CLint (25 µL/min/mg) from Bio-PK system was increased to 143.26 L/h (fold error: 1.27-1.36). The predicted Cmax and AUC (the area under the concentration-time curve) ratio were 1.32 and 1.84 (fold error: 1.36 and 1.05) in a DDI study with an inhibition coefficient (Ki) of 13.97 µM from the Bio-PK system. The results indicate that the Bio-PK system more truly reflects the dynamic metabolism and DDI of AZT and FCZ in the body. In summary, the novel in silico and in vitro method may provide new ideas for the optimization of drug metabolism and DDI research methods in early drug development.

16.
J Dermatol Sci ; 102(3): 184-192, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34016486

RESUMO

BACKGROUND: Aberrant expression of Armadillo repeat containing 8 (ARMC8) plays crucial roles in tumor growth and metastasis of various cancers. The specific role of ARMC8 in cutaneous squamous cell carcinoma (cSCC) is yet to be elucidated. OBJECTIVE: The present study aimed to investigate the molecular mechanisms of ARMC8 and epithelial-mesenchymal transition (EMT) in cSCC development and provide translational insights for future therapeutics. METHODS: cSCC tumor specimens were used to determine the ARMC8 by immunohistochemistry. Three cSCC cell lines including HSC-1, HSC-5 and A431 as well as BALB/C mouse tumor model was utilized to study the potential mechanisms in tumorigenesis. RESULTS: Our data identified ARMC8 as a direct downstream target of miR-664. We found that ARMC8 was remarkably low expression in cSCC patient specimens and cSCC cell lines. Knockdown of ARMC8 promotes tumorigenic behaviors such as increased cell proliferation, migration and invasion capacities in vitro and enhanced tumorigenicity in xenograft mouse model. Whereas ARMC8 over-expression inhibits tumorigenesis in cSCC. Together, it revealed ARMC8 functions as a tumor suppressor via restraining Wnt/ß-catenin pathway and epithelial-mesenchymal transition in cSCC. CONCLUSION: Our data verifies that aberrant expression of ARMC8 plays a vital role in carcinogenesis of cSCC. And overexpression of ARMC8 will facilitate future development of cSCC therapeutic interventions.


Assuntos
Proteínas do Domínio Armadillo/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/genética , MicroRNAs/metabolismo , Neoplasias Cutâneas/genética , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Regulação para Baixo , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Cutâneas/patologia , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
17.
Dose Response ; 18(2): 1559325820929234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547335

RESUMO

BACKGROUND: MiR-664 has been demonstrated to play an important role in dermal diseases. However, the functions of miR-664 in ultraviolet B (UVB) radiation-induced keratinocytes damage remain to be elucidated. OBJECTIVE: The present study aimed to investigate the molecular mechanisms under the UVB-induced keratinocytes damage and provide translational insights for future therapeutics and UVB protection. METHODS: HaCaT cells were transfected with miR-664, either alone or combined with UVB irradiation. Levels of messenger RNA and protein were tested by quantitative real-time polymerase chain reaction and Western blot analyses. Cell proliferation, percentage of apoptotic cells, and expression levels of apoptosis-related factors were measured by Cell Counting Kit-8 assay, flow cytometry assay, and Western blot analysis, respectively. RESULTS: We found that a significant increase in miR-664 was observed in UVB-induced HaCaT cells. Overexpressed miR-664 promoted cell vitalities and suppressed apoptosis of UVB-induced HaCaT cells. Additionally, the loss/gain of armadillo-repeat-containing protein 8 (ARMC8) rescued/blocked the effects of miR-664 on the proliferation of UVB-induced HaCaT cells. CONCLUSIONS: Our data demonstrate that miR-664 functions as a protective regulator in UVB-induced HaCaT cells via regulating ARMC8.

18.
RSC Adv ; 10(35): 20438-20444, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35517744

RESUMO

In this work, chemical vapor deposition (CVD) method-grown graphene on plasma-etched quartz glass supported platinum nanoparticles (PtNPs/eQG) was constructed as an independent transparent electrode for non-enzymatic hydrogen peroxide (H2O2) detection. Graphene grown on quartz glass by the CVD method can effectively reduce the wrinkles and pollution caused by traditional transfer methods. The addition of the CF4 plasma-etched process accelerates the growth rate of graphene on quartz glass. The platinum nanoparticles (PtNPs) prepared by in situ sputtering have favorable dispersibility and maximize exposed active catalytic sites on graphene, providing performance advantages in the application of H2O2 detection. The resulting sensor's detection limit (3.3 nM, S/N = 3), detection linear range (10 nM to 80 µM) and response time (less than 2 s) were significantly superior to other graphene supported PtNPs materials in sensing of H2O2. In addition, the material preparation method was related to the non-transfer CVD method and in situ sputtering technology, allowing for the creation of independent electrodes without additional electrode modification processes. This primitive material preparation and electrode assembly process were promoted for the application and development of practical H2O2 sensors.

19.
Rev Med Virol ; 29(1): e2021, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30548722

RESUMO

Owing to the large-scale epidemic of Zika virus disease and its association with microcephaly, properties that allow flaviviruses to cause nervous system diseases are an important area of investigation. At present, although potential pathogenic mechanisms of flaviviruses in the nervous system have been examined, they have not been completely elucidated. In this paper, we review the possible mechanisms of blood-brain barrier penetration, the pathological effects on neurons, and the association between virus mutations and neurotoxicity. A hypothesis on neurotoxicity caused by the Zika virus is presented. Clarifying the mechanisms of virulence of flaviviruses will be helpful in finding better antiviral drugs and optimizing the treatment of symptoms.


Assuntos
Pesquisa Biomédica/tendências , Infecções do Sistema Nervoso Central/patologia , Infecções do Sistema Nervoso Central/fisiopatologia , Infecções por Flavivirus/patologia , Infecções por Flavivirus/fisiopatologia , Flavivirus/patogenicidade , Humanos , Virulência
20.
Langmuir ; 28(17): 6726-30, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22506631

RESUMO

The freestanding Sb(2)S(3) films were easily synthesized at the interface of water and toluene at room temperature, where Na(2)S and (C(2)H(5)OCS(2))(3)Sb (xanthate, O-ethyldithiocarbonate) acted as sulfur and antimony source, respectively. After 3 h of aging, the Sb(2)S(3) films with a flat surface toward organic side and rough surface toward aqueous side were assembled by sheaflike Sb(2)S(3) nanowires. The Sb(2)S(3) nanorings formed by end-to-end connection of the bundled nanowires appeared in the water layer when the reaction time reached 24 h. The Sb(2)S(3) nanorings showed higher photocatalytic activity for methyl orange degradation under visible light than the Sb(2)S(3) films owing to broader spectrum response and better aqueous dispersion.


Assuntos
Antimônio/química , Nanoestruturas/química , Nanotecnologia/métodos , Temperatura , Sulfetos/química , Fatores de Tempo , Tolueno/química , Água/química
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