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1.
Eur J Pharmacol ; 983: 176991, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39265883

RESUMO

BACKGROUND: Laryngocarcinoma is a common malignancy in the upper respiratory tract. Enabled homolog (ENAH) is an actin-binding protein that is associated with the development of various cancers. However, its role and mechanism in laryngocarcinoma remain unknown. METHODS: The ENAH level in laryngocarcinoma was examined in silico, in vitro and in vivo. The prognostic analysis of the ENAH level was assessed on laryngocarcinoma patients. Gain- and loss-of-function assays were conducted in AMC-HN-8 and TU686 cells. Sh-ENAH-containing AMC-HN-8 cells were implanted into naked mice. The role and mechanism of ENAH in laryngocarcinoma were investigated by CCK-8, transwell, immunofluorescence, dual luciferase, RT-qPCR, immunohistochemistry, and western blotting experiments. RESULTS: The ENAH level was upregulated in laryngocarcinoma, which predicted a poor prognosis in laryngocarcinoma patients. Gain- and loss-of-function results showed that ENAH promoted proliferation, invasion and EMT of laryngocarcinoma cells. Moreover, ENAH was transcriptionally activated by YY1, and YY1/ENAH axis enhanced these malignant progresses of laryngocarcinoma cells. Besides, ENAH activated the PI3K/AKT pathway, and 740Y-P abolished the accelerative role of ENAH in proliferation, invasion and EMT of laryngocarcinoma cells. Furthermore, knockdown of ENAH reduced tumor size and weight, and the expression level of vimentin and PI3K/AKT pathway in tumor-bearing mice. CONCLUSION: ENAH transcriptionally activated by YY1 promotes cell growth, invasion and EMT of laryngocarcinoma through the activation of PI3K/AKT signaling.


Assuntos
Proliferação de Células , Neoplasias Laríngeas , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Fator de Transcrição YY1 , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Fator de Transcrição YY1/metabolismo , Fator de Transcrição YY1/genética , Proliferação de Células/genética , Fosfatidilinositol 3-Quinases/metabolismo , Linhagem Celular Tumoral , Animais , Camundongos , Regulação Neoplásica da Expressão Gênica , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Masculino , Transição Epitelial-Mesenquimal/genética , Ativação Transcricional , Feminino , Camundongos Nus , Movimento Celular/genética
2.
BMC Public Health ; 24(1): 2670, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350112

RESUMO

OBJECTIVE: The relationship between vitamin D3 and asthma remains controversial. However, previous studies have largely overlooked the impact of epi-25-(OH)-vitamin D3. This study aims to investigate the effects of different forms of vitamin D3 on asthma attack in adults. METHODS: In this cross-sectional study, a total of 3,873 eligible adult participants were extracted from the national health and nutrition examination survey (NHANES) database from 2007 to 2018. Based on quartiles method, different levels of vitamin D were divided into four groups (Quartile 1-4). Bivariate correlation analysis was performed for vitamin D and covariates to avoid multicollinearity. Multivariate logistic regression was used to investigate the association between serum levels of vitamin D3 (epi-25-(OH)-vitamin D3 and 25-(OH)-vitamin D3) and asthma attack, adjusting for covariates including age, gender, race, length of time in the U.S., house poverty income ratio (PIR), education level, smoking history, hypertension history, and diabetes history. The ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 was used for secondary analysis of its association with asthma attack. The outcomes were assessed by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among the 3,873 eligible adults American with asthma, 1,508 (38.94%) had experienced at least one acute asthma attack in the past year. There was no significant correlation between vitamin D and covariates. After adjusting for covariates including age, gender, race, length of time in the U.S., house poverty income ratio (PIR), education level, smoking history, hypertension history and diabetes history, we found a positive correlation between the ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 and asthma attack. Additionally, a high ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 was more common among elder, male, of normal weight, non-Hispanic American, have a long time stay in the U.S., a high house PIR, and a history of hypertension individuals. CONCLUSION: Our findings suggest that attention should be given to asthma attack associated with a high ratio of epi-25-(OH)-vitamin D3 to 25-(OH)-vitamin D3 in American adults who are elderly, male, of normal weight, non-Hispanic Americans, have long-term residence in the U.S., a high house PIR, and a history of hypertension.


Assuntos
Asma , Inquéritos Nutricionais , Humanos , Asma/epidemiologia , Asma/sangue , Masculino , Feminino , Estados Unidos/epidemiologia , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Calcifediol/sangue , Fatores de Risco , Idoso , Adulto Jovem
3.
Int J Biol Macromol ; 279(Pt 3): 135389, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39245121

RESUMO

Anthocyanins (ATH), which are plant pigments with potential health benefits, possess antioxidant and natural indicator properties. However, their inherent instability poses a hurdle for practical applications in the food industry. In the present study, we addressed this challenge by encapsulating ATHs in nisin/gelatin (GA)/pullulan (PUL) bioaerogels through freeze-drying. The results showed that the ATH + nisin@GA/PUL bioaerogels exhibited antibacterial activity against S. aureus and E. coli, and pH-responsiveness to the increase in biogenic amines during the spoilage of shrimp, indicating their potential as a freshness indicator. The bioaerogels also displayed sustained antioxidant effects after two months of storage at room temperature. In summary, the ATH + nisin@GA/PUL bioaerogel serves as a stable matrix for preserving the antioxidant activity of ATHs, and facilitates the indication of freshness in perishable foods. This innovative encapsulation technique represents an advancement in the utilization of ATHs in food packaging.


Assuntos
Antocianinas , Antibacterianos , Antioxidantes , Embalagem de Alimentos , Antioxidantes/farmacologia , Antioxidantes/química , Concentração de Íons de Hidrogênio , Antibacterianos/farmacologia , Antibacterianos/química , Embalagem de Alimentos/métodos , Antocianinas/química , Antocianinas/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Gelatina/química , Géis/química , Nisina/química , Nisina/farmacologia
4.
J Adv Res ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39236975

RESUMO

INTRODUCTION: Mechanical stresses incurred during post-harvest fruit storage and transportation profoundly impact decay and losses. Currently, the monitoring of mechanical forces is primarily focused on vibrational forces experienced by containers and vehicles and impact forces affecting containers. However, the detection of compressive forces both among interior fruit and between fruit and packaging surfaces remains deficient. Hence, conformable materials capable of sensing compressive stresses are necessary. OBJECTIVES: In the present study, a triple-network-reinforced PSA/LiCl/CCN@AgNP conductive hydrogel was synthesized for compression force detection on fruit surfaces based on changes in intrinsic impedance under mechanical loading. METHODS: The conductive hydrogel was characterized in terms of its adhesion, mechanics, frost resistance, water retention, conductivity, mechanical force-sensing properties, and feasibility for monitoring mechanical forces. Then, a portable complex impedance recorder was developed to interface with the conductive hydrogel and its mechanical force sensing ability was evaluated. RESULTS: Beyond its inherent conductivity, the hydrogel exhibited notable pressure sensitivity within the strain range of 1 % to 80 %. The conductive hydrogel also demonstrated a commendable adhesion property, favorable tensile property (580 % elongation at break), substantial compressive strength and durability, and a long-term water retention capability. After exposure to -20 °C for 96 h, the hydrogel maintained its mechanical strength, affirming its anti-freezing property. In addition, a portable complex impedance recorder with sustained signal measurement stability was developed to quantitatively acquire the hydrogel resistance changes in response to compression forces. Finally, the effectiveness of the conductive hydrogel for sensing compression force on the surface of apple fruits was validated. CONCLUSION: The conductive hydrogel holds promise for applications in smart packaging, wherein it can detect crucial mechanical stress on fruit, convert it into electrical signals, and further transmit these signals to the cloud, thereby enabling the real-time sensing of mechanical forces experienced by fruits and enhancing post-harvest fruit loss management.

5.
Food Chem ; 463(Pt 2): 141308, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39298854

RESUMO

Using 2,3-diaminopyridine and citric acid as precursors, blue fluorescent nitrogen-doped carbon quantum dots (NCQDs) with a narrow size distribution (∼7.2 nm) were prepared and applied in the following assay for mercury ion detection at a weight ratio of 2,3-diaminopyridine:citric acid = 1:1 (0.2 g: 0.2 g, 20 mL for H2O), 220 °C, and 10 h. NCQDs was characterized by TEM, FT-IR, XPS, UV-Vis and EDS, and the prepared NCQDs display excitation-independent behavior due to less surface defects and uniform size. The optimal excitation and emission wavelengths of the NCQDs were 380 nm and 430 nm, respectively. Interestingly, the fluorescence of the NCQDs could be rapidly and selectively quenched by Hg2+ within 9 min at room temperature without further modification. Under optimal conditions, the limit of detection (LOD) was measured to be at the nanomolar level (42.4 nmol/L) with a linear range of 0-5.0 µmol/L, and fluorescence analysis of NCQDs was successfully used for the qualitative and quantitative analysis of mercury ions in food samples. Furthermore, our results revealed that fluorescence quenching occurred under the common fluences of the inner filter effect, and the static quenching effect was authenticated in the process in which Hg2+ coordinates with the NCQDs to form nonfluorescent complexes.

6.
Fish Shellfish Immunol ; 153: 109842, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153580

RESUMO

Molting is a crucial biological process of crustaceans. Crustaceans go through three separate stages throughout their molting process, including pre-molt, post-molt and inter-molt. However, the exact mechanism of immunological modulation during molting remains unclear. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been extensively documented to participate in immune defense. In the present study, a TRAF6 gene with two TRAF-type zinc finger domains was identified from Eriocheir sinensis (designed as EsTRAF6), and its role in regulating immune response during molting process was explored. The mRNA expression level of EsTRAF6 at pre-molt stage was higher than that at post-molt stage and inter-molt stage. After Aeromonas hydrophila stimulation, the expression levels of EsTRAF6, EsRelish and anti-lipopolysaccharide factors (ALFs) genes exhibited a considerable increase at three molting stages. Subsequently, the expression patterns of EsTRAF6 and EsRelish in response to the treatment with 20-hydroxyecdysone (20E) were examined. The mRNA expression of EsTRAF6 and EsRelish were significantly increased at 12 h after 20E injection. Additionally, the protein expression level of TRAF6 was also up-regulated in 20E group compared to control group. Furthermore, the role of EsTRAF6 in regulating the anti- ALFs expression at pre-molt stage post A. hydrophila stimulation was investigated. Following the inhibition of the EsTRAF6 transcript using RNAi or the injection of inhibitor (TMBPS), there was a notable decrease of the EsALF1, EsALF2 and EsALF3 transcripts. Moreover, a significant reduction in the phosphorylation level of NF-κB at pre-molt stage was observed after A. hydrophila stimulation in TRAF6-inhibited crabs. Collectively, our results suggest that EsTRAF6 could be induced by 20E and promoted the EsALFs expression by activating NF-κB at pre-molt stage, which provides a novel insight into the research of immune regulatory mechanism during the process of molting of crustaceans.


Assuntos
Proteínas de Artrópodes , Decápodes , NF-kappa B , Fator 6 Associado a Receptor de TNF , Animais , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Proteínas de Artrópodes/química , Perfilação da Expressão Gênica/veterinária , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Muda/imunologia , Muda/genética , NF-kappa B/genética , NF-kappa B/metabolismo , NF-kappa B/imunologia , Filogenia , Alinhamento de Sequência/veterinária , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/imunologia
7.
Anal Chim Acta ; 1316: 342860, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38969429

RESUMO

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.


Assuntos
Biotina , Glutationa , Técnicas Fotoacústicas , Fotoquimioterapia , Glutationa/química , Glutationa/metabolismo , Animais , Humanos , Camundongos , Biotina/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Imagem Óptica , Feminino , Terapia Fototérmica , Camundongos Nus , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico
8.
Discov Oncol ; 15(1): 265, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967843

RESUMO

In this study, we investigated the role of the newly discovered lncRNA FLJ20021 in laryngeal cancer (LC) and its resistance to cisplatin treatment. We initially observed elevated lncRNA FLJ20021 levels in cisplatin-resistant LC cells (Hep-2/R). To explore its function, we transfected lncRNA FLJ20021 and cyclin-dependent kinase 1 (CDK1) into Hep-2/R cells, assessing their impact on cisplatin sensitivity and PANoptosis. Silencing lncRNA FLJ20021 effectively reduced cisplatin resistance and induced PANoptosis in Hep-2/R cells. Mechanistically, lncRNA FLJ20021 primarily localized in the nucleus and interacted with CDK1 mRNA, thereby enhancing its transcriptional stability. CDK1, in turn, promoted panapoptosis in a ZBP1-dependent manner, which helped overcome cisplatin resistance in Hep-2/R cells. This study suggests that targeting lncRNA FLJ20021 can be a promising approach to combat cisplatin resistance in laryngeal cancer by regulating CDK1 and promoting PANoptosis via the ZBP1 pathway. These findings open up possibilities for lncRNA-based therapies in the context of laryngeal cancer.

9.
Sleep Breath ; 28(5): 2165-2173, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39042240

RESUMO

OBJECTIVE: This study aimed to investigate the impact of surgical intervention on peripheral blood T lymphocyte subsets and natural killer (NK) cell activity in pediatric patients with obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 36 OSAHS children, 32 children with tonsillar hypertrophy, and 30 healthy children were enrolled. Clinical data and polysomnography (PSG) results were collected. Peripheral blood samples were analyzed for T lymphocyte subsets, NK cells, and cytokine levels including Th1 (IFN-γ, IL-2, TNF-α), Th2 (IL-4, IL-10), and Th17 (IL-17). RESULTS: At baseline, OSAHS children exhibited lower LSaO2 levels and higher AHI values compared to healthy children. They also showed decreased percentages of CD3 + T cells, CD4 + T cells, NK cells, and elevated CD8 + T cells and CD4+/CD8 + ratio. Levels of IFN-γ, IL-2, TNF-α, IL-4, and IL-17 were significantly lower in OSAHS children. Post-surgery improvements were observed in LSaO2, AHI, and immune markers at 3 months and 6 months. Pearson's correlation analysis revealed significant associations between LSaO2, AHI, and peripheral blood immune parameters at baseline and 6 months post-surgery. CONCLUSION: Surgical intervention in pediatric OSAHS influences peripheral blood T lymphocyte subsets and NK cell activity. Early intervention and monitoring of immune function are crucial for the recovery and healthy development of affected children.


Assuntos
Células Matadoras Naturais , Apneia Obstrutiva do Sono , Subpopulações de Linfócitos T , Humanos , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/imunologia , Apneia Obstrutiva do Sono/sangue , Células Matadoras Naturais/imunologia , Masculino , Feminino , Criança , Subpopulações de Linfócitos T/imunologia , Pré-Escolar , Polissonografia , Citocinas/sangue , Tonsilectomia
10.
Bioorg Chem ; 149: 107531, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38850779

RESUMO

Nitroreductase (NTR) overexpression often occurs in tumors, highlighting the significance of effective NTR detection. Despite the utilization of various optical methods for this purpose, the absence of an efficient tumor-targeting optical probe for NTR detection remains a challenge. In this research, a novel tumor-targeting probe (Cy-Bio-NO2) is developed to perform dual-modal NTR detection using near-infrared fluorescence and photoacoustic techniques. This probe exhibits exceptional sensitivity and selectivity to NTR. Upon the reaction with NTR, Cy-Bio-NO2 demonstrates a distinct fluorescence "off-on" response at 800 nm, with an impressive detection limit of 12 ng/mL. Furthermore, the probe shows on-off photoacoustic signal with NTR. Cy-Bio-NO2 has been successfully employed for dual-modal NTR detection in living cells, specifically targeting biotin receptor-positive cancer cells for imaging purposes. Notably, this probe effectively detects tumor hypoxia through dual-modal imaging in tumor-bearing mice. The strategy of biotin incorporation markedly enhances the probe's tumor-targeting capability, facilitating its engagement in dual-modal imaging at tumor sites. This imaging capacity holds substantial promise as an accurate tool for cancer diagnosis.


Assuntos
Corantes Fluorescentes , Nitrorredutases , Imagem Óptica , Animais , Humanos , Camundongos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias/diagnóstico por imagem , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Nitrorredutases/metabolismo , Nitrorredutases/análise , Técnicas Fotoacústicas , Dióxido de Nitrogênio/síntese química , Dióxido de Nitrogênio/química
11.
Int J Immunopathol Pharmacol ; 38: 3946320241227320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38248871

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is the most invasive type of cancer, with a high risk of metastasis and recurrence. Therefore, there is an urgent need to identify novel prognostic predictors and therapeutic targets of ccRCC. Activating transcription factor 3 (ATF3), a tumor oncogene or repressor, has rarely been examined in ccRCC. In the present study, we comprehensively elucidate the prognostic value and potential functions of ATF3 in ccRCC.Methods: Several TCGA-based online databases were used to analyze ATF3 expression in ccRCC and determine ccRCC prognosis. The upstream-binding micro (mi) RNAs of ATF3 and long non-coding (lnc)RNAs were predicted using the StarBase database.Results: Analysis of several TCGA-based online databases showed that ATF3 expression is decreased in ccRCC, suggesting a significant association with the prognosis of patients with ccRCC. Furthermore, we found hsa-miR-221-3p to be potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of the upstream lncRNAs indicated that PAXIP1-AS2 and OIP5-AS1 were the most potent upstream lncRNAs of the hsa-miR-221-3p/ATF3 axis in ccRCC. The results of the GO and KEGG analyses implied that ATF3 is likely involved in the regulation of apoptotic signaling in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis revealed a positive relationship between ATF3 expression and ER stress.Conclusions: Our in silico findings highlighted that ATF3 expression was low in ccRCC and negatively correlated with poor prognosis. Furthermore, PAXIP1-AS2 and the OIP5-AS1/hsa-miR-221-3p/ATF3 axis were identified as significant potential regulators of ER stress-mediated apoptosis in ccRCC.


Assuntos
Fator 3 Ativador da Transcrição , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Fator 3 Ativador da Transcrição/genética , Biomarcadores , Carcinoma , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/genética , RNA Longo não Codificante/genética
12.
Front Microbiol ; 14: 1228700, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965545

RESUMO

Increasing evidence suggests that the pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to the gut microbiota. Polyphenols have been shown to alleviate T2DM, but the effects of L. caerulea L. polyphenols (LPs) on the gut microbiota and metabolites remain elusive. In this study, the inhibitory effects of fermented L. caerulea L. polyphenols (FLPs) and unfermented L. caerulea L. polyphenols (ULPs) on α-amylase and α-glucosidase and the impact of LP on the gut microbiota and metabolites were investigated. Furthermore, the relationship between the two was revealed through correlation analysis. The results showed that ULP and FLP had the highest inhibitory rates against α-amylase and α-glucosidase at 4 mg ml-1, indicating a strong inhibitory ability. In addition, LP plays a regulatory role in the concentration of short-chain fatty acids (SCFAs) and tends to restore them to their normal levels. LP reversed the dysbiosis of the gut microbiota caused by T2DM, as evidenced by an increase in the abundance of bacterial genera such as Lactobacillus, Blautia, and Bacteroides and a decrease in the abundance of bacterial genera such as Escherichia-Shigella and Streptococcus. Similarly, after LP intervention, the relationships among microbial species became more complex and interconnected. In addition, the correlation between the gut microbiota and metabolites was established through correlation analysis. These further findings clarify the mechanism of action of LP against T2DM and provide a new target for T2DM interventions.

13.
Nat Commun ; 14(1): 7857, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030638

RESUMO

Deep learning transformer-based models using longitudinal electronic health records (EHRs) have shown a great success in prediction of clinical diseases or outcomes. Pretraining on a large dataset can help such models map the input space better and boost their performance on relevant tasks through finetuning with limited data. In this study, we present TransformEHR, a generative encoder-decoder model with transformer that is pretrained using a new pretraining objective-predicting all diseases and outcomes of a patient at a future visit from previous visits. TransformEHR's encoder-decoder framework, paired with the novel pretraining objective, helps it achieve the new state-of-the-art performance on multiple clinical prediction tasks. Comparing with the previous model, TransformEHR improves area under the precision-recall curve by 2% (p < 0.001) for pancreatic cancer onset and by 24% (p = 0.007) for intentional self-harm in patients with post-traumatic stress disorder. The high performance in predicting intentional self-harm shows the potential of TransformEHR in building effective clinical intervention systems. TransformEHR is also generalizable and can be easily finetuned for clinical prediction tasks with limited data.


Assuntos
Neoplasias Pancreáticas , Transtornos de Estresse Pós-Traumáticos , Humanos , Registros Eletrônicos de Saúde , Fontes de Energia Elétrica , Rememoração Mental
14.
Soft Matter ; 19(42): 8164-8171, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850350

RESUMO

Functionalized metal-organic frameworks (MOFs) that integrate targeted tumor imaging and drug delivery are expected to significantly enhance the therapeutic efficacy of cancer. However, the complicated synthesis process has greatly limited their utilization in clinical application. Herein, a one-step simple method was used to construct novel multifunctional MOFs by co-loading doxorubicin (DOX) and Fe3O4 into the ZIF-8 with sodalite topology. DOX serves as a fluorescence imaging reagent and an anticancer drug and Fe3O4 is used as a magnetic resonance imaging and magnetic targeting anticancer reagent. The fabricated DOX/Fe3O4@ZIF-8 nanocomposite showed excellent fluorescence and magnetic resonance imaging performances in tumors. Moreover, DOX/Fe3O4@ZIF-8 can be accumulated in tumors via a magnetic targeting effect and tumor growth could be inhibited in vivo due to the release of DOX. Additionally, the apoptosis process of DOX/Fe3O4@ZIF-8 on HepG2 cells is well investigated. Overall, DOX/Fe3O4@ZIF-8 synthesized in simple one step can be used for simultaneous targeted bioimaging and cancer therapy.


Assuntos
Antineoplásicos , Estruturas Metalorgânicas , Sistemas de Liberação de Medicamentos , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Apoptose , Liberação Controlada de Fármacos
15.
Anal Chem ; 95(33): 12478-12486, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37555783

RESUMO

Cysteine (Cys) is a crucial biological thiol that has a vital function in preserving redox homeostasis in organisms. Studies have shown that Cys is closely related to the development of cancer. Thus, it is necessary to design an efficient method to detect Cys for an effective cancer diagnosis. In this work, a novel tumor-targeting probe (Bio-Cy-S) for dual-modal (NIR fluorescence and photoacoustic) Cys detection is designed. The probe exhibits high selectivity and sensitivity toward Cys. After reaction with Cys, both NIR fluorescence and photoacoustic signals are activated. Bio-Cy-S has been applied for the dual-modal detection of Cys levels in living cells, and it can be used to distinguish normal cells from cancer cells by different Cys levels. In addition, the probe is capable of facilitating dual-modal imaging for monitoring changes in Cys levels in tumor-bearing mice. More importantly, the excellent tumor-targeting ability of the probe greatly improves the signal-to-noise ratio of imaging. To the best of our knowledge, this is the first Cys probe to combine targeting and dual-modal imaging performance for cancer diagnosis.


Assuntos
Cisteína , Corantes Fluorescentes , Humanos , Camundongos , Animais , Linhagem Celular Tumoral , Células HeLa , Imagem Óptica/métodos
16.
Environ Sci Technol ; 57(26): 9874-9883, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37335829

RESUMO

Advanced techniques for nickel (Ni(II)) removal from polluted waters have long been desired but challenged by the diversity of Ni(II) species (most in the form of complexes) which could not be readily discriminated by the traditional analytical protocols. Herein, a colorimetric sensor array is developed to address the above issue based on the shift of the UV-vis spectra of gold nanoparticles (Au NPs) after interaction with Ni(II) species. The sensor array is composed of three Au NP receptors modified by N-acetyl-l-cysteine (NAC), tributylhexadecylphosphonium bromide (THPB), and the mixture of 3-mercapto-1-propanesulfonic acid and adenosine monophosphate (MPS/AMP), to exhibit possible coordination, electrostatic attraction, and hydrophobic interaction toward different Ni(II) species. Twelve classical Ni(II) species were selected as targets to systematically demonstrate the applicability of the sensor array under various conditions. Multiple interactions with Ni(II) species were evidenced to trigger the diverse Au NP aggregation behaviors and subsequently produce a distinct colorimetric response toward each Ni(II) species. With the assistance of multivariate analysis, the Ni(II) species, either as the sole compound or as mixtures, can be unambiguously discriminated with high selectivity in simulated and real water samples. Moreover, the sensor array is very sensitive with the detection limit in the range of 4.2 to 10.5 µM for the target Ni(II) species. Principal component analysis signifies that coordination dominates the response of the sensor array toward different Ni(II) species. The accurate Ni(II) speciation provided by the sensor array is believed to assist the rational design of specific protocols for water decontamination and to shed new light on the development of convenient discrimination methods for other toxic metals of concern.


Assuntos
Ouro , Nanopartículas Metálicas , Ouro/química , Nanopartículas Metálicas/química , Níquel/química , Colorimetria , Água
17.
Polymers (Basel) ; 15(3)2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36771797

RESUMO

This paper presents an empirical torsional spring model for the inclined crack on a 3D-printed ABS cantilever beam. The work outlined deals mainly with our previous research about an improved torsional spring model (Khan-He model), which can represent the deep vertical (90°) crack in the structure. This study used an experimental approach to investigate the relationships between the crack angle and torsional spring stiffness. ABS cantilever beams with different crack depths (1, 1.3 and 1.6 mm) and angles (30, 45, 60, 75 and 90°) were manufactured by fused deposition modelling (FDM). The impact tests were performed to obtain the dynamic response of cracked beams. The equivalent spring stiffness was calculated based on the specimen's fundamental frequency. The results suggested that an increased crack incline angle yielded higher fundamental frequency and vibration amplitude, representing higher spring stiffness. The authors then developed an empirical spring stiffness model for inclined cracks based on the test data. These results extended the Khan-He model's application from vertical to inclined crack prediction in FDM ABS structures.

18.
Chin J Integr Med ; 29(5): 394-404, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36607588

RESUMO

OBJECTIVE: To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action. METHODS: This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 ß (IL-1 ß), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively. RESULTS: GSE reduced the secretion of TNF-α, IL-1 ß and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 ß, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05). CONCLUSION: GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.


Assuntos
Encefalomielite Autoimune Experimental , Extrato de Sementes de Uva , Camundongos , Animais , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Extrato de Sementes de Uva/farmacologia , Extrato de Sementes de Uva/uso terapêutico , Interleucina-17 , Interleucina-1beta , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Células Th1 , Camundongos Endogâmicos C57BL , Interferon gama/metabolismo , Interferon gama/farmacologia , Interferon gama/uso terapêutico , Células Th17/metabolismo , Interleucina-12/farmacologia , Interleucina-12/uso terapêutico , Citocinas/metabolismo
19.
Environ Sci Technol ; 56(19): 14059-14068, 2022 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-36129786

RESUMO

In the past decades, extensive efforts have been devoted to the mechanistic understanding of various heterogeneous Fenton reactions. Nevertheless, controversy still remains on the oxidation mechanism/pathway toward different organic compounds in the classical iron oxide-based Fenton reaction, largely because the role of the interaction between the organic compounds and the catalyst has been scarcely considered. Here, we revisited the classic heterogeneous ferrihydrite (Fhy)/H2O2 system toward different organic compounds on the basis of a series of degradation experiments, alcohol quenching experiments, theoretical modeling, and intermediate analysis. The Fhy/H2O2 system exhibited highly selective oxidation toward the group of compounds that bear carboxyl groups, which tend to complex with the surface ≡Fe(III) sites of the Fhy catalyst. Such interaction results in a nonradical inner sphere electron transfer process, which seizes one electron from the target compound and features negligible inhibition by the radical quencher. In contrast, for the oxidation of organic compounds that could not complex with the catalyst, the traditional HO· process makes the main contribution, which proceeds via hydroxyl addition reaction and could be readily suppressed by the radical quencher. This study implies that the interaction between the organic compounds and the catalyst plays a decisive role in the oxidation pathway and mechanism of the target compounds and provides a holistic understanding on the iron oxide-based heterogeneous Fenton system.


Assuntos
Compostos Férricos , Peróxido de Hidrogênio , Catálise , Ferro , Compostos Orgânicos , Oxirredução
20.
Carbohydr Polym ; 292: 119702, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35725186

RESUMO

Much attention and endeavor have been paid to developing biocompatible food packaging films. Here, ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) were fabricated into films through a facile method, microfluidic spinning. Morphology observations showed that the fibers were neatly arranged with an average diameter of 1-4 µm. FTIR and X-ray diffraction analysis suggested the existence of good compatibility and interaction between EC and PVP. Thermogravimetric analysis demonstrated that PVP ameliorates the thermal properties; moreover, the tensile properties were improved, with tensile strength (TS) and Young's modulus up to 11.10 ± 1.04 MPa and 350.16 ± 45.46 MPa, respectively. The optimal formula was EC/PVP (2:3), of which the film displayed an enhanced TS of 4.61 ± 1.15 MPa and a modified water contact angle of 61.8 ± 4.4°, showing fine tensile and hydrophilic performance. This study provides a facile and green film fabrication method promising to be used for food wrapping.


Assuntos
Microfluídica , Povidona , Celulose/análogos & derivados , Resistência à Tração
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