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1.
Molecules ; 29(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39275071

RESUMO

Oligonucleotide drugs are shining in clinical therapeutics, but efficient and safe delivery systems severely limit their widespread use. A disulfide unit technology platform based on dynamic thiol exchange chemistry at the cell membrane has the potential for drug delivery. However, the alteration of the disulfide unit CSSC dihedral angle induced by different substituents directly affects the effectiveness of this technology and its stability. Previously, we constructed a trivalent low dihedral angle disulfide unit that can effectively promote the cellular uptake of small molecules. Here, we constructed a novel disulfide unit-masked oligonucleotide hybrid based on a low dihedral angle disulfide unit, motivated by prodrug design. Cellular imaging results showed that such a system exhibited superior cellular delivery efficiency than the commercial Lipo2000 without cytotoxicity. The thiol reagents significantly reduced its cellular uptake (57-74%), which proved to be endocytosis-independent. In addition, in vivo distribution experiments in mice showed that such systems can be rapidly distributed in liver tissues with a duration of action of more than 24 h, representing a potential means of silencing genes involved in the pathogenesis of liver-like diseases. In conclusion, this trivalent disulfide unit-masked system we constructed can effectively deliver large oligonucleotide drugs.


Assuntos
Dissulfetos , Oligonucleotídeos , Dissulfetos/química , Animais , Oligonucleotídeos/química , Camundongos , Humanos , Sistemas de Liberação de Medicamentos , Fígado/metabolismo , Fígado/efeitos dos fármacos
2.
Nat Commun ; 15(1): 7024, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39147746

RESUMO

To achieve high power conversion efficiency in perovskite/silicon tandem solar cells, it is necessary to develop a promising wide-bandgap perovskite absorber and processing techniques in relevance. To date, the performance of devices based on wide-bandgap perovskite is still limited mainly by carrier recombination at their electron extraction interface. Here, we demonstrate assembling a binary two-dimensional perovskite by both alternating-cation-interlayer phase and Ruddlesden-Popper phase to passivate perovskite/C60 interface. The binary two-dimensional strategy takes effects not only at the interface but also in the bulk, which enables efficient charge transport in a wide-bandgap perovskite solar cell with a stabilized efficiency of 20.79% (1 cm2). Based on this absorber, a monolithic perovskite/silicon tandem solar cell is fabricated with a steady-state efficiency of 30.65% assessed by a third party. Moreover, the tandem devices retain 96% of their initial efficiency after 527 h of operation under full spectral continuous illumination, and 98% after 1000 h of damp-heat testing (85 °C with 85% relative humidity).

3.
Science ; 385(6708): 554-560, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39088618

RESUMO

Wide-bandgap (WBG) absorbers in tandem configurations suffer from poor crystallinity and weak texture, which leads to severe mixed halide-cation ion migration and phase segregation during practical operation. We control WBG film growth insensitive to compositions by nucleating the 3C phase before any formation of bromine-rich aggregates and 2H phases. The resultant WBG absorbers show improved crystallinity and strong texture with suppressed nonradiative recombination and enhanced resistance to various aging stresses. Perovskite/silicon tandem solar cells achieve power conversion efficiencies of 29.4% (28.8% assessed by a third party) in a 25-square centimeter active area and 32.5% in a 1-square centimeter active area. These solar cells retained 98.3 and 90% of the original efficiency after 1301 and 800 hours of operation at 25° and 50°C, respectively, at the maximum power point (AM 1.5G illumination, full spectrum, 1-sun) when encapsulated.

4.
Int J Biol Macromol ; 268(Pt 2): 131721, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649079

RESUMO

Interferon (IFN) alpha/beta receptor 1 (IFNAR1) is indispensable for antiviral responses and the immune regulation. Dysregulation of the IFNAR1-mediaetd signaling pathways leads to deleterious autoimmune diseases such as systemic lupus erythematosus (SLE). QX006N, a humanized therapeutic monoclonal antibody, specifically targets human IFNAR1 and is in the clinical trial phase for treating SLE, but the molecular mechanism underlying the QX006N-mediated recognition of IFNAR1 remains unclear. Here, we report the high neutralization activities of QX006N against IFNAR1-mediated signal transduction. Meanwhile, we determine the structures of the fragment antigen-binding domain (Fab) of QX006N (QX006N-Fab) and QX006N-Fab in complex with the subdomains 1-3 of IFNAR1 (IFNAR1-SD123) at 2.87 Å and 2.68 Å resolutions, respectively. In the structure of the QX006N-Fab/IFNAR1-SD123 complex, QX006N-Fab only recognizes the SD3 subdomain of IFNAR1 by the hydrophobic, hydrogen-bonding and electrostatic interactions. Compared with the structure of the IFN/IFNAR1/IFNAR2 complex, the binding of QX006N-Fab to IFNAR1-SD3 blocks its association with IFN due to steric hindrance, which inhibits the IFN/IFNAR1/IFNAR2 complex formation for signal transduction. The results of this study provide the structural evidence for the specific targeting of IFNAR1 by the therapeutic antibody QX006N and pave the way for the rational design of antibody drugs to combat IFNAR1-related autoimmune diseases.


Assuntos
Anticorpos Monoclonais Humanizados , Lúpus Eritematoso Sistêmico , Receptor de Interferon alfa e beta , Receptor de Interferon alfa e beta/metabolismo , Receptor de Interferon alfa e beta/química , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Humanos , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Ligação Proteica , Modelos Moleculares , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/imunologia , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade
5.
Environ Toxicol ; 39(4): 2077-2085, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38100242

RESUMO

Colorectal cancer (CRC) exhibits highly metastatic potential even in the early stages of tumor progression. Gallic acid (GA), a common phenolic compound in plants, is known to possess potent antioxidant and anticancer activities, thereby inducing cell death or cell cycle arrest. However, whether GA reduces the invasiveness of CRC cells without inducing cell death remains unclear. Herein, we aimed to investigate the antimetastatic activity of low-dose GA on CRC cells and determine its underlying mechanism. Cell viability and tumorigenicity were analyzed by MTS, cell adhesion, and colony formation assay. Invasiveness was demonstrated using migration and invasion assays. Changes in protein phosphorylation and expression were assessed by Western blot. The involvement of microRNAs was validated by microarray analysis and anti-miR antagonist. Our findings showed that lower dose of GA (≤100 µM) did not affect cell viability but reduced the capabilities of colony formation, cell adhesion, and invasiveness in CRC cells. Cellularly, GA downregulated the cellular level of integrin αV/ß3, talin-1, and tensin and diminished the phosphorylated FAK, paxillin, Src, and AKT in DLD-1 cells. Microarray results revealed that GA increased miR-1247-3p expression, and pretreatment of anti-miR antagonist against miR-1247-3p restored the GA-reduced integrin αV/ß3 and the GA-inhibited paxillin activation in DLD-1 cells. Consistently, the in vivo xenograft model showed that GA administration inhibited tumor growth and liver metastasis derived from DLD-1 cells. Collectively, our findings indicated that GA inhibited the metastatic capabilities of CRC cells, which may result from the suppression of integrin/FAK axis mediated by miR1247-3p.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Paxilina/genética , Paxilina/metabolismo , Integrinas/genética , Integrinas/metabolismo , Ácido Gálico/farmacologia , Antagomirs , Integrina alfaV/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/metabolismo , Movimento Celular , Regulação Neoplásica da Expressão Gênica
6.
Adv Mater ; 35(17): e2211257, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36753745

RESUMO

Metal halide perovskites are promising as next-generation photovoltaic materials, but stability issues are still a huge obstacle to their commercialization. Here, the formation and evolution of cracks in perovskite films during thermal cycling, which affect their mechanical stability, are investigated. Compressive strain is employed to suppress cracks and delamination by in situ formed polymers with low elastic modulus during crystal growth. The resultant devices pass the thermal-cycling qualification (IEC61215:2016), retaining 95% of the initial power conversion efficiency (PCE) and compressive strain after 230 cycles. Meanwhile, the p-i-n devices deliver PCEs of 23.91% (0.0805 cm2 ) and 23.27% (1 cm2 ). The findings shed light on strain engineering with respect to their evolution, which enables mechanically stable perovskite solar cells.

7.
Nutrients ; 14(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36432495

RESUMO

Mulberry leaf (Morus alba L.) is used as a traditional medicine and potential health food to treat various metabolic diseases, such as hypertension, diabetes, and hyperlipidemia. However, we sought the mechanisms by which functional components of mulberry leaves mediate diabetic steatohepatitis. We applied an in vitro model of HepG2 cells induced by glucolipotoxicity and evaluated the effects of MLE and its major components nCGA, Crp, and CGA. The results showed that MLE and nCGA reduced liver fat accumulation by inhibiting SREBP-1/FASN, SREBP-2/HMG-CoAR, and activating PPARα/CPT-1. Additionally, MLE and nCGA decreased inflammatory responses associated with NF-κB, TNF-α, and IL-6 to alleviate steatohepatitis. Furthermore, we showed that MLE and nCGA exerted anti-glucolipotoxicity effects by downregulating miR-34a, thus activating SIRT1/AMPK signaling, and subsequently suppressing hepatic lipid accumulation.


Assuntos
Fígado Gorduroso , MicroRNAs , Morus , Ácido Clorogênico/farmacologia , Ácido Clorogênico/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Folhas de Planta/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fígado Gorduroso/metabolismo , Lipídeos
8.
Int J Med Sci ; 19(10): 1557-1566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185329

RESUMO

Extra-proliferation and increased migration of vascular smooth cells con-tribute to the formation of atherosclerosis. Ras small G proteins play a critical role in the prolif-eration and migration of a wide range of cells. Mulberry, an economic fruit in Asia, exhibits anti-inflammation, anti-migration, and anti-oxidant properties. The mechanisms of action of mulberry extracts on K-Ras small G protein-induced proliferation and migration of vascular smooth muscle cell have not been extensively investigated. In this study, we explored the effects of mulberry polyphenol extracts (MPE) on the proliferation and migration of K-Ras-overexpressing A7r5 smooth muscle cells. The overexpression of K-Ras enhanced the ex-pression and activity of matrix metalloproteinase (MMP)-2, promoted vascular endothelial growth factor (VEGF) production, and eventually triggered the migration of A7r5 cells. Treatment with MPE attenuated K-Ras-induced phenomenon. In addition, MPE blocked K-Ras-induced actin fibril stress. MPE dose-dependently diminished K-Ras-induced Rho A, Rac1, CDC42, and phosphorylated focal adhesion kinase (FAK) expression. MPE elevated Rho B ex-pression. Phosphorylated AKT and glycogen synthase kinase (GSK) induced by K-Ras were also repressed by MPE treatment. MPE enhanced the interaction of IκB with NFκB. MPE restored the G0/G1 population and p21 and p27 expressions, which were repressed by K-Ras. Finally, MPE triggered the degradation of K-Ras by ubiquitination. MPE inhibited the migration and proliferation of vascular smooth cell through K-Ras-induced pathways and eventually pre-vented atherosclerosis.


Assuntos
Aterosclerose , Proteínas Monoméricas de Ligação ao GTP , Morus , Actinas/metabolismo , Antioxidantes/farmacologia , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/metabolismo , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Frutas/metabolismo , Quinases da Glicogênio Sintase/metabolismo , Humanos , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Monoméricas de Ligação ao GTP/farmacologia , Músculo Liso Vascular , Miócitos de Músculo Liso , Polifenóis/metabolismo , Polifenóis/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-36011604

RESUMO

The aim of the current study was to evaluate the combined effect of the single nucleotide polymorphism (SNP) in long non-coding RNA growth arrest-specific 5 (GAS5) and the phenotypes of epidermal growth factor receptor (EGFR) on the clinicopathological characteristics of lung adenocarcinoma. The present study examined the relationship between the GAS5 single-nucleotide polymorphisms (SNPs; rs145204276 Ins/Del, rs55829688 T/C) and the clinicopathological factors in 539 lung adenocarcinoma patients with or without EGFR mutations. We found that the genotype distributions of the two GAS5 SNPs between different EGFR genotypes were similar after adjusting for age, gender and smoking history. The GAS5 SNP rs145204276 Ins/Del + Del/Del illustrated a higher distribution with an advanced tumor stage (p = 0.030), larger tumor T status (p = 0.019), positive lymph node status (p = 0.014) and distal metastases (p = 0.011) in the EGFR wild type group. In the subgroup analysis of the EGFR wild type population, the presence of GAS5 SNP rs145204276 Ins/Del + Del/Del was correlated to an advanced tumor stage (p = 0.014) and distal metastases (p = 0.020) in non-smokers. In conclusion, these data indicate that the GAS5 SNP rs145204276 variant may help predict tumor stage, lymph node metastasis and distal metastases in patients with EGFR wild type lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , RNA Longo não Codificante , Adenocarcinoma de Pulmão/genética , Receptores ErbB/genética , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/genética , Mutação , Fenótipo , Polimorfismo Genético , RNA Longo não Codificante/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-36011700

RESUMO

Periodontitis (PD) is a common oral disease associated with various other diseases, particularly those affecting the cardiovascular system. This study explored whether peripheral artery occlusive disease (PAOD) is associated with PD and dental scaling. This study was a retrospective cohort study design from 2000 to 2018. The study population was newly diagnosed with periodontitis. The comparison group was defined as never diagnosed with periodontitis. The outcome variable was defined with the diagnosis of peripheral arterial occlusive disease (PAOD). The propensity score matching was performed by age, sex, comorbidities, and dental scaling between the two groups. Kaplan-Meier analysis was used to calculate the cumulative incidence of PAOD among the two groups. To perform the independent risk of the PAOD group, the multivariate Cox proportional hazard model was used to estimate the hazard ratios. First, 792,681 patients with PD and 458,521 patients with no history of PD were selected from Taiwan's Longitudinal Health Insurance Database, which comprises the data of two million beneficiaries. After propensity score matching between the PD and non-PD groups for age, sex, comorbidities, and dental scaling, 357,106 patients in each group were analyzed for PAOD risk. The incidence density, relative risk, and cumulative incidence of PAOD were higher in the PD group than in the non-PD group. After adjusting for all variables, the risk of PAOD for the PD group was greater than for the non-PD group (adjusted hazard ratio = 1.03; 95% CI, 1.01-1.06). Undergoing at least one dental scaling procedure reduced the risk of PAOD. Age over 65 years was also a risk factor. In conclusion, patients with PD have an increased risk of PAOD. In addition, our results can lead to increased attention to oral hygiene, as dental scaling has a trend towards a lower risk of PAOD.


Assuntos
Arteriopatias Oclusivas , Periodontite , Doença Arterial Periférica , Idoso , Arteriopatias Oclusivas/complicações , Estudos de Coortes , Raspagem Dentária , Humanos , Periodontite/complicações , Periodontite/epidemiologia , Doença Arterial Periférica/complicações , Doença Arterial Periférica/epidemiologia , Estudos Retrospectivos , Fatores de Risco
11.
Nutrients ; 14(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35893859

RESUMO

Mulberry leaf (Morus alba L.) has been used as a health food and in traditional medicine to treat several metabolic diseases, including diabetes, hypertension, and hyperlipidemia. However, the mechanism by which mulberry leaf and its functional components mediate atherosclerosis remains unclear. This study aimed to determine the effect of mulberry leaf extract (MLE) and its major component, neochlorogenic acid (nCGA), on the proliferation and migration of rat aortic vascular smooth muscle cells (VSMCs, A7r5 cell line) under diabetic cultured conditions (oleic acid and high glucose, OH). Our findings showed that MLE and nCGA significantly inhibited cell proliferation and migration in A7r5 cells as determined by a scratch wound assay and a Transwell assay. Furthermore, we observed MLE and nCGA inhibited cell proliferation and migration, such as reducing the phosphoinositide 3-kinases (PI3K)/protein kinase B (Akt), focal adhesion kinase (FAK), and small GTPase proteins using Western blot analysis. In conclusion, we confirmed the anti-atherosclerotic effects of MLE and nCGA in reducing vascular smooth muscle cell (VSMC) migration and proliferation under diabetic cultured conditions via inhibition of FAK/small GTPase proteins, PI3K/Akt, and Ras-related signaling.


Assuntos
Aterosclerose , Proteínas Monoméricas de Ligação ao GTP , Morus , Animais , Aterosclerose/metabolismo , Movimento Celular , Proliferação de Células , Células Cultivadas , Ácido Clorogênico/análogos & derivados , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Músculo Liso Vascular , Miócitos de Músculo Liso , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ácido Quínico/análogos & derivados , Ratos , Transdução de Sinais
12.
Nature ; 601(7894): 573-578, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35082415

RESUMO

Owing to rapid development in their efficiency1 and stability2, perovskite solar cells are at the forefront of emerging photovoltaic technologies. State-of-the-art cells exhibit voltage losses3-8 approaching the theoretical minimum and near-unity internal quantum efficiency9-13, but conversion efficiencies are limited by the fill factor (<83%, below the Shockley-Queisser limit of approximately 90%). This limitation results from non-ideal charge transport between the perovskite absorber and the cell's electrodes5,8,13-16. Reducing the electrical series resistance of charge transport layers is therefore crucial for improving efficiency. Here we introduce a reverse-doping process to fabricate nitrogen-doped titanium oxide electron transport layers with outstanding charge transport performance. By incorporating this charge transport material into perovskite solar cells, we demonstrate 1-cm2 cells with fill factors of >86%, and an average fill factor of 85.3%. We also report a certified steady-state efficiency of 22.6% for a 1-cm2 cell (23.33% ± 0.58% from a reverse current-voltage scan).

13.
Protein Expr Purif ; 187: 105950, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34363980

RESUMO

Interleukin-17A (IL-17A) produced by Th17 cells, contributes to the pathogenesis of various autoimmune diseases by stimulating the release of cytokines and chemokines and its regulation. Anti-IL-17A antibody which blocks the function of IL-17A has been proved to be an effective treatment of autoimmune disease. The aim of our study was to generate a potential humanized anti-IL-17A therapeutic monoclonal antibody (mAb) through a comprehensive panel of in vitro and in vivo biological activity studies, as well as physicochemical characterization. HZD37-5, a humanized monoclonal antibody specifically recognizing N78 loci of IL-17A, binds to human and rhesus monkeys, blocks IL-17 induced signal transduction and the release of IL-6, IL-8, CXCL-1 and G-GSF. In an in vivo efficacy mouse model, HZD37-5 significantly inhibited human IL-17A induced-keratinocyte chemoattractant (KC) secretion in a dose-dependent manner. The pharmacokinetics (PK) study result of HZD37-5 in rhesus monkeys indicated that HZD37-5 had favorable PK characteristics with limited distribution (78.0-78.8 ml/kg), slow elimination (5.00-6.45 ml/day/kg), long half-life (9.1-10.7 days) and high bioavailability (103%) following a single IV or SC dose at 1.5 mg/kg. These findings provided a comprehensive preclinical characterization of HZD37-5 and supported that it may be developed as a potential therapeutic for the treatment of autoimmune diseases, including psoriasis, psoriatic arthritis, axial spondyloarthritis, etc.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Doenças Autoimunes/tratamento farmacológico , Interleucina-17/imunologia , Animais , Anticorpos Monoclonais Humanizados/imunologia , Quimiocina CXCL1/imunologia , Fatores Quimiotáticos/imunologia , Relação Dose-Resposta a Droga , Humanos , Interleucina-6/imunologia , Interleucina-8/imunologia , Queratinócitos/imunologia , Macaca mulatta , Camundongos , Coelhos , Transdução de Sinais
15.
Science ; 371(6527): 390-395, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33479151

RESUMO

Polymer passivation layers can improve the open-circuit voltage of perovskite solar cells when inserted at the perovskite-charge transport layer interfaces. Unfortunately, many such layers are poor conductors, leading to a trade-off between passivation quality (voltage) and series resistance (fill factor, FF). Here, we introduce a nanopatterned electron transport layer that overcomes this trade-off by modifying the spatial distribution of the passivation layer to form nanoscale localized charge transport pathways through an otherwise passivated interface, thereby providing both effective passivation and excellent charge extraction. By combining the nanopatterned electron transport layer with a dopant-free hole transport layer, we achieved a certified power conversion efficiency of 21.6% for a 1-square-centimeter cell with FF of 0.839, and demonstrate an encapsulated cell that retains ~91.7% of its initial efficiency after 1000 hours of damp heat exposure.

16.
Small ; 16(49): e2005022, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33201580

RESUMO

Dimensional engineering of perovskite solar cells has attracted significant research attention recently because of the potential to improve both device performance and stability. Here, a novel 2D passivation scheme for 3D perovskite solar cells is demonstrated using a mixed cation composition of 2D perovskite based on two different isomers of butylammonium iodide. The dual-cation 2D perovskite outperforms its single cation 2D counterparts in surface passivation quality, resulting in devices with an impressive open-circuit voltage of 1.21 V for a perovskite composition with an optical bandgap of ≈1.6 eV, and a champion efficiency of 23.27%. Using a combination of surface elemental analysis and valence electron spectra decomposition, it is shown that an in situ interaction between the 2D perovskite precursor and the 3D active layer results in surface intermixing of 3D and 2D perovskite phases, providing an effective combination of defect passivation and enhanced charge transfer, despite the semi-insulating nature of the 2D perovskite phase. The demonstration of the synergistic interaction of multiple organic spacer cations in a 2D passivation layer offers new opportunities for further enhancement of device performance with mixed dimensional perovskite solar cells.

17.
Food Funct ; 11(10): 8602-8611, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084700

RESUMO

Nelumbo nucifera leaf water extract (NLE) attenuates high-fat diet (HFD)-induced rabbit atherosclerosis, but its mechanism of action and the relevant compounds remain unclear. Modulating the proliferation and migration of vascular smooth muscle cells (VSMCs) may be an enforceable strategy for atherosclerosis prevention. Therefore, we investigated the potential mechanisms of N. nucifera leaf polyphenol extract (NLPE) and its active ingredient gallic acid (GA) in VSMC proliferation and migration. A7r5 rat aortic VSMCs were provoked using 50 ng mL-1 tumor necrosis factor (TNF)-α; the NLPE or GA reduced the TNF-α-induced migration by inhibiting the transforming protein RhoA/cell division cycle protein 42 pathway. The NLPE or GA suppressed the TNF-α-induced VSMC proliferation by inhibiting the Ras pathway and increasing the expression of phosphatase and tensin homolog (PTEN), kinase suppressor of Ras 2, and inducible nitric oxide synthase. The NLPE or GA increased PTEN expression by downregulating microRNA (miR)-21 expression and reduced Ras and RhoA expression by upregulating miR-143 and miR-145 expression. The NLPE and GA use potentially prevents atherosclerosis by inhibiting the VSMC migration and proliferation. The mechanisms involve the regulation of the miRNA in PTEN, the Ras/extracellular-signal-regulated kinase pathway, and Rho family proteins.


Assuntos
Ácido Gálico/farmacologia , MicroRNAs/genética , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Nelumbo/química , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Folhas de Planta , Polifenóis , Ratos , Transdução de Sinais , Proteínas ras/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
18.
J Cancer ; 10(13): 2907-2914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281467

RESUMO

High-mobility group protein box 1 (HMGB1) is overexpressed and reported to be a prognostic factor in patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutants play an important role in NSCLC progression. The aim of this study was to explore potential associations between genetic polymorphisms of HMGB1 and EGFR mutations in a cohort that included 280 patients with NSCLC, some of whom were smokers and others who never smoked. Four tagged single-nucleotide polymorphisms (SNPs) of HMGB1 were detected by a TaqMan-based real-time polymerase chain reaction (PCR) in patients. We found that after adjusting for other covariates, NSCLC patients who smoked and who respectively had CG, CT, and TC heterozygotes of HMGB1 rs2249825, rs1045411, and rs1360485, were at lower risk of developing mutant EGFR, compared to those patients with wild-type homozygotes. Moreover, significant inverse associations between the CG and CG + GG genotypes of HMGB1 rs2249825 and the EGFR hotspot mutation, an exon 19 in-frame deletion, were also observed among NSCLC patients. Within patients harboring mutant EGFR, HMGB1 rs1360485 C (TC + CC) allele carriers were at higher risk of developing poorly differentiated cancer types (odds ratio=5.493, 95% confidence interval: 1.130~26.696, p=0.019), compared to patients with TT homozygotes. Furthermore, we found that HMGB1 rs1360485 polymorphisms seemed to be related to susceptibility to developing poorly differentiated cancer linked to tobacco consumption in EGFR mutant patients. In conclusion, our results suggested that HMGB1 variants are significantly inversely associated with EGFR mutations among NSCLC patients who smoked. HMGB1 variants and tobacco consumption might contribute to the pathological development of NSCLC.

19.
Carbohydr Polym ; 221: 10-20, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31227148

RESUMO

ß-carotene has been often used as a hydrophobic nutrient in many functional foods owning to its excellent antioxidant activity. However, the poor orally bioavailability of ß-carotene limits its utilization. To overcome such limitation, a delivery system was designed for the encapsulation of ß-carotene based on oil-in-water emulsion stabilized by oat protein isolate - Pleurotus ostreatus ß-glucan Maillard conjugate. The results showed that such conjugate protected emulsion against environmental stresses by increasing steric and electrostatic repulsion between droplets, mainly manifesting as their smaller particle size and higher surface charge. Additionally, conjugate promoted lipid digestion and formation of mixed micelles, leading to an improved gastrointestinal fate of encapsulated ß-carotene, especially for its in vitro bioavailability. Such effects could enhance the cellular antioxidant activity of encapsulated ß-carotene in Caco-2 cells. Our findings confirmed that Maillard conjugate can structure an emulsion-based delivery system for the encapsulation of hydrophobic ingredients to improve their utilization.


Assuntos
Antioxidantes/farmacologia , Emulsões/química , Trato Gastrointestinal/metabolismo , Glucanos/química , Proteínas de Plantas/química , beta Caroteno/farmacologia , Antioxidantes/química , Antioxidantes/metabolismo , Avena/química , Células CACO-2 , Óleo de Milho/química , Óleo de Milho/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Emulsões/metabolismo , Glucanos/metabolismo , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Reação de Maillard , Concentração Osmolar , Proteínas de Plantas/metabolismo , Pleurotus/química , beta Caroteno/química , beta Caroteno/metabolismo
20.
Nanoscale ; 11(15): 7497-7505, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30942202

RESUMO

Heterojunction solar cells with transition-metal-oxide-based carrier-selective contacts have been gaining considerable research interest owing to their amenability to low-cost fabrication methods and elimination of parasitic absorption and complex semiconductor doping process. In this work, we propose tantalum oxide (Ta2O5) as a novel electron-selective contact layer for photo-generated carrier separation in InP solar cells. We confirm the electron-selective properties of Ta2O5 by investigating band energetics at the InP-Ta2O5 interface using X-ray photoelectron spectroscopy. Time-resolved photoluminescence and power dependent photoluminescence reveal that the Ta2O5 inter-layer also mitigates parasitic recombination at the InP/transparent conducting oxide interface. With an 8 nm Ta2O5 layer deposited using an atomic layer deposition (ALD) system, we demonstrate a planar InP solar cell with an open circuit voltage, Voc, of 822 mV, a short circuit current density, Jsc, of 30.1 mA cm-2, and a fill factor of 0.77, resulting in an overall device efficiency of 19.1%. The Voc is the highest reported value to date for an InP heterojunction solar cells with carrier-selective contacts. The proposed Ta2O5 material may be of interest not only for other solar cell architectures including perovskite cells and organic solar cells, but also across a wide range of optoelectronics applications including solid state emitting devices, photonic crystals, planar light wave circuits etc.

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