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1.
Anal Chem ; 96(26): 10714-10723, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38913030

RESUMO

Excessive intake of estrogen poses significant health risks to the human body; hence, there is a necessity to develop rapid detection methods to monitor its levels of addition. Gold nanoparticles (AuNPs), commonly utilized as colorimetric signal labels, find extensive application in lateral flow immunoassay (LFIA). However, the detection sensitivity of traditional AuNPs-LFIA is typically constrained by low molar extinction coefficients and reliance on a single signal. Herein, in this work, unique spark-type AuCuPt nanoflowers modified with tannic acid (AuCuPt@TA) were precisely designed by reasonable layer-by-layer element composition and green modification. The obtained AuCuPt displays robust broadband absorption spanning the visible to near-infrared spectrum, showcasing a notable molar extinction coefficient of 2.38 × 1012 M-1 cm-1 and a photothermal conversion efficiency of 48.5%. Based on this, selecting estriol (E3) as a model analyte, colorimetric/photothermal dual-signal LFIA (CLFIA and PLFIA) was developed. Limits of detection (LOD) of the CLFIA and PLFIA were achieved at 0.033 ng mL-1 and 0.021 ng mL-1, respectively, which represent a 9.3- and 14.6-fold improvement compared to the visual LOD of AuNPs-LFIA. Moreover, the application feasibility of the immunoassay was further evaluated in the milk and pork with satisfactory recoveries ranging from 86.21% to 117.91%. Thus, this work has enhanced the performance of LFIA for E3 detection and exhibited enormous potential for other sensing platform construction.


Assuntos
Ligas , Estriol , Ouro , Nanopartículas Metálicas , Imunoensaio/métodos , Nanopartículas Metálicas/química , Ouro/química , Estriol/análise , Ligas/química , Animais , Colorimetria , Limite de Detecção , Taninos/química , Taninos/análise
2.
Acta Pharmacol Sin ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871923

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1) is a DNA-binding protein that is involved in various biological functions, including DNA damage repair and transcription regulation. It plays a crucial role in cisplatin resistance. Nevertheless, the exact regulatory pathways governing PARP1 have not yet been fully elucidated. In this study, we present evidence suggesting that the hepatitis B X-interacting protein (HBXIP) may exert regulatory control over PARP1. HBXIP functions as a transcriptional coactivator and is positively associated with PARP1 expression in tissues obtained from hepatoma patients in clinical settings, and its high expression promotes cisplatin resistance in hepatoma. We discovered that the oncogene HBXIP increases the level of PARP1 m6A modification by upregulating the RNA methyltransferase WTAP, leading to the accumulation of the PARP1 protein. In this process, on the one hand, HBXIP jointly activates the transcription factor ETV5, promoting the activation of the WTAP promoter and further facilitating the promotion of the m6A modification of PARP1 by WTAP methyltransferase, enhancing the RNA stability of PARP1. On the other hand, HBXIP can also jointly activate the transcription factor CEBPA, enhance the activity of the PARP1 promoter, and promote the upregulation of PARP1 expression, ultimately leading to enhanced DNA damage repair capability and promoting cisplatin resistance in hepatoma. Notably, aspirin inhibits HBXIP, thereby reducing the expression of PARP1. Overall, our research revealed a novel mechanism for increasing PARP1 abundance, and aspirin therapy could overcome cisplatin resistance in hepatoma.

3.
Acta Pharmacol Sin ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942954

RESUMO

C/EBP homologous protein (CHOP) triggers the death of multiple cancers via endoplasmic reticulum (ER) stress. However, the function and regulatory mechanism of CHOP in liver cancer remain elusive. We have reported that late endosomal/lysosomal adapter, mitogen-activated protein kinase and mTOR activator 5 (LAMTOR5) suppresses apoptosis in various cancers. Here, we show that the transcriptional and posttranscriptional inactivation of CHOP mediated by LAMTOR5 accelerates liver cancer growth. Clinical bioinformatic analysis revealed that the expression of CHOP was low in liver cancer tissues and that its increased expression predicted a good prognosis. Elevated CHOP contributed to destruction of LAMTOR5-induced apoptotic suppression and proliferation. Mechanistically, LAMTOR5-recruited DNA methyltransferase 1 (DNMT1) to the CpG3 region (-559/-429) of the CHOP promoter and potentiated its hypermethylation to block its interaction with general transcription factor IIi (TFII-I), resulting in its inactivation. Moreover, LAMTOR5-enhanced miR-182/miR-769 reduced CHOP expression by targeting its 3'UTR. Notably, lenvatinib, a first-line targeted therapy for liver cancer, could target the LAMTOR5/CHOP axis to prevent liver cancer progression. Accordingly, LAMTOR5-mediated silencing of CHOP via the regulation of ER stress-related apoptosis promotes liver cancer growth, providing a theoretical basis for the use of lenvatinib for the treatment of liver cancer.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38907838

RESUMO

Antibiotics are widely used as fungicides because of their antibacterial and bactericidal effects. However, it is necessary to control their dosage. If the amount of antbiotics is too much, it cannot be completely metabolized and absorbed, will pollute the environment, and have a great impact on human health. Many antibiotics usually left in factory or aquaculture wastewater pollute the environment, so it is vital to detect the content of antibiotics in wastewater. This article summarizes several common methods of antibiotic detection and pretreatment steps. The detection methods of antibiotics in wastewater mainly include immunoassay, instrumental analysis method, and sensor. Studies have shown that immunoassay can detect deficient concentrations of antibiotics, but it is affected by external factors leading to errors. The detection speed of the instrumental analysis method is fast, but the repeatability is poor, the price is high, and the operation is complicated. The sensor is a method that is currently increasingly studied, including electrochemical sensors, optical sensors, biosensors, photoelectrochemical sensors, and surface plasmon resonance sensors. It has the advantages of fast detection speed, high accuracy, and strong sensitivity. However, the reproducibility and stability of the sensor are poor. At present, there is no method that can comprehensively integrate the advantages. This paper aims to review the enrichment and detection methods of antibiotics in wastewater from 2020 to the present. It also aims to provide some ideas for future research directions in this field.

5.
J Stroke Cerebrovasc Dis ; 33(3): 107563, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38215554

RESUMO

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are effective interventions for treating extracranial carotid artery stenosis (ECAS), but long-term prognosis is limited by postoperative restenosis. Carotid restenosis is defined as carotid stenosis >50% by various examination methods in patients after carotid revascularization. This retrospective cohort study examined the value of the triglyceride-glucose (TyG) index for predicting vascular restenosis after carotid revascularization. METHODS: A total of 830 patients receiving CEA (408 cases, 49.2%) or CAS (422 cases, 50.8%) were included in this study. Patients were stratified into three subgroups according to TyG index tertile (high, intermediate, and low), and predictive value for restenosis was evaluated by constructing multivariate Cox proportional hazard regression models. RESULTS: Incidence of postoperative restenosis was significantly greater among patients with a high TyG index according to univariate analysis. Kaplan-Meier survival curve analysis revealed a progressive increase in restenosis prevalence with rising TyG index. Multivariate Cox regression models also identified TyG index as an independent predictor of restenosis, while receiver operating characteristic (ROC) curve analysis showed that TyG index predicted restenosis with moderate sensitivity (57.24%) and specificity (67.99%) (AUC: 0.619, 95% CI 0.585-0.652, z-statistic=4.745, p<0.001). Addition of the TyG index to an established risk factor model incrementally improved restenosis prediction (AUC: 0.684 (0.651-0.715) vs 0.661 (0.628-0.694), z-statistic =2.027, p = 0.043) with statistical differences. CONCLUSION: The TyG index is positively correlated with vascular restenosis risk after revascularization, which can be used for incremental prediction and has certain predictive value.


Assuntos
Estenose das Carótidas , Endarterectomia das Carótidas , Humanos , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Stents , Endarterectomia das Carótidas/efeitos adversos , Constrição Patológica
6.
Compr Rev Food Sci Food Saf ; 23(4): e13407, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39030802

RESUMO

This research presents a comprehensive review of Salmonella presence in retail fresh fruits and vegetables from 2010 to 2023, utilizing data from recognized sources such as PubMed, Scopus, and Web of Science. The study incorporates a meta-analysis of prevalence, serovar distribution, antimicrobial susceptibility, and antimicrobial resistance genes (ARGs). Additionally, it scrutinizes the heterogeneous sources across various food categories and geographical regions The findings show a pooled prevalence of 2.90% (95% CI: 0.0180-0.0430), with an increase from 4.63% in 2010 to 5.32% in 2022. Dominant serovars include S. Typhimurium (29.14%, 95% CI: 0.0202-0.6571) and S. Enteritidis (21.06%, 95% CI: 0.0181-0.4872). High resistance rates were noted for antimicrobials like erythromycin (60.70%, 95% CI: 0.0000-1.0000) and amoxicillin (39.92%, 95% CI: 0.0589-0.8020). The most prevalent ARGs were blaTEM (80.23%, 95% CI: 0.5736-0.9692) and parC mutation (66.67%, 95% CI: 0.3213-0.9429). Factors such as pH, water activity, and nutrient content, along with external factors like the quality of irrigation water and prevailing climatic conditions, have significant implications on Salmonella contamination. Nonthermal sterilization technologies, encompassing chlorine dioxide, ozone, and ultraviolet light, are emphasized as efficacious measures to control Salmonella. This review stresses the imperative need to bolster prevention strategies and control measures against Salmonella in retail fresh fruits and vegetables to alleviate related food safety risks.


Assuntos
Frutas , Salmonella , Sorogrupo , Verduras , Verduras/microbiologia , Frutas/microbiologia , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Salmonella/genética , Prevalência , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Contaminação de Alimentos/análise , Microbiologia de Alimentos
7.
Acta Pharmacol Sin ; 44(3): 622-634, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36109580

RESUMO

Sorafenib, which inhibits multiple kinases, is an effective frontline therapy for hepatocellular carcinoma (HCC). Ferroptosis is a form of iron-dependent programmed cell death regulated by lipid peroxidation, which can be induced by sorafenib treatment. Oncoprotein hepatitis B X-interacting protein (HBXIP) participates in multiple biological pro-tumor processes, including growth, metastasis, drug resistance, and metabolic reprogramming. However, the role of HBXIP in sorafenib-induced ferroptotic cell death remains unclear. In this study, we demonstrated that HBXIP prevents sorafenib-induced ferroptosis in HCC cells. Sorafenib decreased HBXIP expression, and overexpression of HBXIP blocked sorafenib-induced HCC cell death. Interestingly, suppression of HBXIP increased malondialdehyde (MDA) production and glutathione (GSH) depletion to promote sorafenib-mediated ferroptosis and cell death. Ferrostatin-1, a ferroptosis inhibitor, reversed the enhanced anticancer effect of sorafenib caused by HBXIP silencing in HCC cells. Regarding the molecular mechanism, HBXIP transcriptionally induced the expression of stearoyl-CoA desaturase (SCD) via coactivating the transcriptional factor ZNF263, resulting in the accumulation of free fatty acids and suppression of ferroptosis. Functionally, activation of the HBXIP/SCD axis reduced the anticancer activity of sorafenib and suppressed ferroptotic cell death in vivo and in vitro. HBXIP/SCD axis-mediated ferroptosis can serve as a novel downstream effector of sorafenib. Our results provide new evidence for clinical decisions in HCC therapy.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Ferroptose/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Estearoil-CoA Dessaturase/efeitos dos fármacos , Estearoil-CoA Dessaturase/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
8.
J Integr Plant Biol ; 65(1): 82-99, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36114789

RESUMO

Clathrin-mediated endocytosis (CME) is the major endocytic pathway in eukaryotic cells that directly regulates abundance of plasma membrane proteins. Clathrin triskelia are composed of clathrin heavy chains (CHCs) and light chains (CLCs), and the phytohormone auxin differentially regulates membrane-associated CLCs and CHCs, modulating the endocytosis and therefore the distribution of auxin efflux transporter PIN-FORMED2 (PIN2). However, the molecular mechanisms by which auxin regulates clathrin are still poorly understood. Transmembrane kinase (TMKs) family proteins are considered to contribute to auxin signaling and plant development; it remains unclear whether they are involved in PIN transport by CME. We assessed TMKs involvement in the regulation of clathrin by auxin, using genetic, pharmacological, and cytological approaches including live-cell imaging and immunofluorescence. In tmk1 mutant seedlings, auxin failed to rapidly regulate abundance of both CHC and CLC and to inhibit PIN2 endocytosis, leading to an impaired asymmetric distribution of PIN2 and therefore auxin. Furthermore, TMK3 and TMK4 were shown not to be involved in regulation of clathrin by auxin. In summary, TMK1 is essential for auxin-regulated clathrin recruitment and CME. TMK1 therefore plays a critical role in the establishment of an asymmetric distribution of PIN2 and an auxin gradient during root gravitropism.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Arabidopsis/metabolismo , Clatrina/metabolismo , Membrana Celular/metabolismo , Raízes de Plantas/metabolismo
9.
J Biol Chem ; 296: 100686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33891944

RESUMO

Using a variety of activating and inhibitory receptors, natural killer (NK) cells protect against disease by eliminating cells that have downregulated class I major histocompatibility complex (MHC) proteins, such as in response to cell transformation or viral infection. The inhibitory murine NK receptor Ly49C specifically recognizes the class I MHC protein H-2Kb. Unusual among NK receptors, Ly49C exhibits a peptide-dependent sensitivity to H-2Kb recognition, which has not been explained despite detailed structural studies. To gain further insight into Ly49C peptide sensitivity, we examined Ly49C recognition biochemically and through the lens of dynamic allostery. We found that the peptide sensitivity of Ly49C arises through small differences in H-2Kb-binding affinity. Although molecular dynamics simulations supported a role for peptide-dependent protein dynamics in producing these differences in binding affinity, calorimetric measurements indicated an enthalpically as opposed to entropically driven process. A quantitative linkage analysis showed that this emerges from peptide-dependent dynamic tuning of electrostatic interactions across the Ly49C-H-2Kb interface. We propose a model whereby different peptides alter the flexibility of H-2Kb, which in turn changes the strength of electrostatic interactions across the protein-protein interface. Our results provide a quantitative assessment of how peptides alter Ly49C-binding affinity, suggest the underlying mechanism, and demonstrate peptide-driven allostery at work in class I MHC proteins. Lastly, our model provides a solution for how dynamic allostery could impact binding of some, but not all, class I MHC partners depending on the structural and chemical composition of the interfaces.


Assuntos
Células Matadoras Naturais/metabolismo , Subfamília A de Receptores Semelhantes a Lectina de Células NK/metabolismo , Regulação Alostérica , Animais , Cinética , Camundongos , Modelos Moleculares , Simulação de Dinâmica Molecular , Subfamília A de Receptores Semelhantes a Lectina de Células NK/química , Ligação Proteica , Domínios Proteicos , Especificidade por Substrato
10.
Nano Lett ; 21(11): 4584-4591, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34037402

RESUMO

Recently, a two-dimensional Dion-Jacobson (DJ) perovskite (AMP)PbI4 (AMP = 4-(aminomethyl)piperidinium) is emerging with remarkable Rashba effect and ferroelectricity. However, the origin of the giant Rashba splitting remains elusive and the current synthetic strategy via slow cooling is time- and power-consuming, hindering its future applications. Here, we report on an economical aqueous method to obtain (AMP)PbI4 crystals and clarify the origin of the giant Rashba effect by temperature- and polarization-dependent photoluminescence (PL) spectroscopy. The strong temperature-dependent PL helicity indicates the thermally assisted structural distortion as the main origin of the Rashba effect, suggesting that valley polarization still preserves at high temperatures. The Rashba effect was further confirmed by the circular photogalvanic effect near the indirect bandgap. Our study not only optimizes the synthetic strategies of this DJ perovskite but also sheds light on its potential applications in room/high-temperature spintronics and valleytronics.

11.
Clin Infect Dis ; 72(2): 332-339, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33501949

RESUMO

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China's response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.


Assuntos
COVID-19 , China/epidemiologia , Humanos , Pandemias , Saúde Pública , SARS-CoV-2
12.
Small ; 17(47): e2103855, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34643061

RESUMO

Full-Stokes polarimeters, equipped with the capability of discriminating light polarization states, can find important applications in various optical and optoelectronic devices. Nevertheless, currently most full-Stokes polarimeters require complex and bulky optical elements or optical metasystems integrated with metasurfaces, which can increase the cost and cause energy loss. Here, the anisotropy of chiral 2D perovskite single crystals is explored and the full-Stokes polarimeter based on pure chiral 2D perovskite single crystals is reported. By using optical anisotropy and the ability to distinguish the helicity of the circularly polarized light, chiral 2D perovskite polarimeter integrates the polarizer, waveplate, and photodetector together and thus can be able to discriminate the polarization states of light. The as-fabricated device exhibits a photoresponsivity of 0.136 A W-1 and a detectivity of 1.2 × 1010 Jones. This study provides a paradigm to construct filterless on-chip Stokes polarimeter with great simplicity and low cost.

13.
J Nanobiotechnology ; 19(1): 188, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162396

RESUMO

BACKGROUND: The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (ß-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. RESULTS: The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. CONCLUSION: Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Diterpenos/química , Compostos de Epóxi/química , Receptores de Hialuronatos/química , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Fenantrenos/química , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Liberação Controlada de Fármacos , Feminino , Humanos , Ácido Hialurônico/farmacologia , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oxirredução , Cicatrização
14.
Nano Lett ; 20(4): 2339-2347, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32163293

RESUMO

Optical anisotropy plays an indispensable role in a variety of optical components. Organic halide perovskites often rely on artificially oriented nanostructures to enhance optical anisotropy due to their in-plane isotropic crystal structure, which results in unnecessary optical losses and fabrication difficulties. Here, we report the large optical anisotropy in two-dimensional perovskite [CH(NH2)2][C(NH2)3]PbI4 crystals. Without specially designing their morphology, we achieved a large photoresponse linear dichroic ratio of 2 and a photoluminescence linear dichroic ratio of 4.7. Furthermore, we identified that the polarization orientation is parallel to the corrugated inorganic layers on every crystal plane by density functional theory calculations. The anisotropy of the ab-plane and ac-plane changes in opposite trend with temperature, suggesting that the perovskite can selectively generate polarized light or unpolarized light from different crystal planes by tuning the temperature. Our studies provide a new platform toward two-dimensional perovskite-based optical polarization devices.

15.
J Integr Plant Biol ; 63(11): 1922-1936, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34478221

RESUMO

PIN-FORMED (PIN)-dependent directional auxin transport is crucial for plant development. Although the redistribution of auxin mediated by the polarization of PIN3 plays key roles in modulating hypocotyl cell expansion, how PIN3 becomes repolarized to the proper sites within hypocotyl cells is poorly understood. We previously generated the clathrin light chain clc2-1 clc3-1 double mutant in Arabidopsis thaliana and found that it has an elongated hypocotyl phenotype compared to the wild type. Here, we performed genetic, cell biology, and pharmacological analyses combined with live-cell imaging to elucidate the molecular mechanism underlying the role of clathrin light chains in hypocotyl elongation. Our analyses indicated that the defects of the double mutant enhanced auxin maxima in epidermal cells, thus, promoting hypocotyl elongation. PIN3 relocated to the lateral sides of hypocotyl endodermal cells in clc2-1 clc3-1 mutants to redirect auxin toward the epidermal cell layers. Moreover, the loss of function of PIN3 largely suppressed the long hypocotyl phenotype of the clc2-1 clc3-1 double mutant, as did treatment with auxin transport inhibitors. Based on these data, we propose that clathrin modulates PIN3 abundance and polarity to direct auxin flux and inhibit cell elongation in the hypocotyl, providing novel insights into the regulation of hypocotyl elongation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cadeias Leves de Clatrina/metabolismo , Hipocótilo/crescimento & desenvolvimento , Ácidos Indolacéticos/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Cadeias Leves de Clatrina/genética , Hipocótilo/metabolismo , Epiderme Vegetal/metabolismo
16.
Biochemistry ; 59(43): 4163-4175, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33074657

RESUMO

T cell receptors (TCRs) orchestrate cellular immunity by recognizing peptides presented by a range of major histocompatibility complex (MHC) proteins. Naturally occurring TCRs bind the composite peptide/MHC surface, recognizing peptides that are structurally and chemically compatible with the TCR binding site. Here we describe a molecularly evolved TCR variant that binds the human class I MHC protein HLA-A2 independent of the bound peptide, achieved by a drastic perturbation of the TCR binding geometry that places the molecule far from the peptide binding groove. This unique geometry is unsupportive of normal T cell signaling. A substantial divergence between affinity measurements in solution and in two dimensions between proximal cell membranes leads us to attribute the lack of signaling to steric hindrance that limits binding in the confines of a cell-cell interface. Our results provide an example of how receptor binding geometry can impact T cell function and provide further support for the view that germline-encoded residues in TCR binding loops evolved to drive productive TCR recognition and signaling.


Assuntos
Receptores de Antígenos de Linfócitos T/metabolismo , Sítios de Ligação , Antígenos HLA-A/metabolismo , Humanos , Complexo Principal de Histocompatibilidade/genética , Complexo Principal de Histocompatibilidade/fisiologia , Ligação Proteica , Conformação Proteica
17.
J Cell Mol Med ; 24(7): 4082-4091, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32073735

RESUMO

To investigate the prevention of cardiac remodelling and inflammatory immune response after myocardial infarction (MI) via ACEI regulating dendritic cells (DCs), we explored whether the protective effect of ACEI was repressed under hyperlipidemic environment. In vivo, the survival rate and left ventricular function of the mice were recorded on day 7 after MI. Tissue samples of the myocardium, spleen, bone marrow and peripheral blood were assessed for Ang II concentration, inflammatory cytokines and DCs expression. In vitro, DCs were treated with ox-LDL + Ang II, simulating the internal environment of MI in ApoE-/- mice to explore the mechanism involved in the DCs maturation and inflammation. Under hyperlipidemic circumstances, we found that the cardioprotective effect of ACEI was attenuated through regulating DCs maturation and inflammation after MI, affecting survival rate and left ventricular function. Effects of lisinopril on the release of spleen-derived DCs and myocardial infiltration were also reduced under hyperlipidemic conditions. In vitro, immune maturation and inflammation of DCs were further induced by ox-LDL on the basis of Ang II treatment, as indicated by the upregulation of CD83, CD86, and the expressions of cytokines and chemokines. Furthermore, ox-LDL could activate TLR4-MyD88 signalling pathway, promoting IRAK-4 and NF-κB. The present study demonstrated that ACEI reduced the recruitment of DCs to the infarct site, leading to a higher survival rate and improved function. However, this effect was inhibited under hyperlipidemic environment. TLR4-MyD88 signalling pathway may be responsible for the molecular mechanism involved in the immune maturation and inflammation of DCs induced by ox-LDL.


Assuntos
Apolipoproteínas E/genética , Lisinopril/farmacologia , Fator 88 de Diferenciação Mieloide/genética , Infarto do Miocárdio/tratamento farmacológico , Receptor 4 Toll-Like/genética , Angiotensina II/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Humanos , Hiperlipidemias/complicações , Hiperlipidemias/genética , Hiperlipidemias/imunologia , Hiperlipidemias/patologia , Lipoproteínas LDL/genética , Camundongos , Camundongos Knockout , Infarto do Miocárdio/complicações , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/genética
18.
J Cell Biochem ; 121(2): 1747-1758, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31633225

RESUMO

miR-19a has been shown to be involved in coronary microvascular obstruction injury; however, the underlying molecular mechanisms remain unknown. In our study, we tried to explore the role of miR-19a in cardiomyocyte apoptosis and calcium overload in vivo and in vitro induced by hypoxia. We established the acute myocardial infarction (AMI) rat model by ligating the left anterior descending artery. The expression of miR-19a in the infarct zone of AMI rats and myocardial tissue in the same position in sham rats was analyzed using RT-qPCR while Na(+) /H(+) exchanger 1 (NHE-1) was detected by Western blotting. We also observed the effects of overexpressing miR-19a or administering an NHE-1 inhibitor (cariporide) on hypoxia-induced (HI) calcium overload and apoptosis in primary cardiomyocytes. In addition, dual-luciferase reporter assays were conducted to investigate the potential target of miR-19a on NHE-1. Decreased miR-19a expression, as well as increased apoptosis and NHE-1 expression, were observed in the AMI model. Furthermore, after hypoxia stimulation, miR-19a was gradually reduced as time increased in primary cardiomyocytes. Overexpressing miR-19a using mimics ameliorated the increase in NHE-1 in hypoxic cardiomyocytes and thereby reduced the HI cell calcium overload and cell apoptosis rate from 12.32% to 9.5% (P < .01). In addition, the dual-luciferase reporter gene assay results verified that NHE-1 was the direct target of miR-19a. Our findings suggest that miR-19a activation can attenuate HI cardiomyocyte apoptosis by downregulating NHE-1 expression and decreasing calcium overload.


Assuntos
Apoptose , Cálcio/metabolismo , Hipóxia/fisiopatologia , MicroRNAs/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/patologia , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Animais , Proliferação de Células , Células Cultivadas , Masculino , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo
19.
Inorg Chem ; 58(11): 7426-7432, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31091094

RESUMO

Two perovskite-type compounds, (MA)2[B'Co(CN)6] (MA = methylammonium, B' = K(I) and Na(I)), have very similar structures, but exhibit marked differences in the phase and dielectric transitions. Solid state 2H NMR studies reveal the detailed dynamic changes of the caged methylammonium (MA) cations before and after the phase transitions, which are correlated with the different dielectric states of the compounds. Using solid state 59Co NMR, the dynamic changes of the host lattices before and after the transitions, which accompany the changes in the dynamics of the caged MA cations, are unveiled, demonstrating the intriguing interplay between the MA cations and the host lattices. On the basis of these observations, the molecular origins of the dielectric transitions are discussed in detail.

20.
Bioelectromagnetics ; 39(2): 98-107, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29251353

RESUMO

A new non-toxic ferromagnetic biological patch (MBP) was designed in this paper. The MBP consisted of two external layers that were made of transparent silicone, and an internal layer that was made of a mixture of pure iron powder and silicon rubber. Finite-element analysis showed that the local inhomogeneous magnetic field (MF) around the MBP was generated when MBP was placed in a uniform MF. The local MF near the MBP varied with the uniform MF and shape of the MBP. Therefore, not only could the accumulation of paramagnetic particles be adjusted by controlling the strength of the uniform MF, but also the distribution of the paramagnetic particles could be improved with the different shape of the MBP. The relationship of the accumulation of paramagnetic particles or cells, magnetic flux density, and fluid velocity were studied through in vitro experiments and theoretical considerations. The accumulation of paramagnetic particles first increased with increment in the magnetic flux density of the uniform MF. But when the magnetic flux density of the uniform MF exceeded a specific value, the magnetic flux density of the MBP reached saturation, causing the accumulation of paramagnetic particles to fall. In addition, the adsorption morphology of magnetic particles or cells could be improved and the uniform distribution of magnetic particles could be achieved by changing the shape of the MBP. Also, MBP may be used as a new implant to attract magnetic drug carrier particles in magnetic drug targeting. Bioelectromagnetics. 39:98-107, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Campos Magnéticos , Imãs , Adsorção , Animais , Imãs/química , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/química
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