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1.
JCI Insight ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34582376

RESUMO

mascRNA is a highly conserved tRNA-like noncoding RNA whose function remains largely unknown. We show here that this small RNA molecule played a role in the stringent control of Toll-like receptor (TLR)-mediated innate immune responses. mascRNA inhibited activation of NF-κB and mitogen-activated protein kinase (MAPK) signaling and the production of inflammatory cytokines in macrophages stimulated with lipopolysaccharide (LPS), a TLR4 ligand. Furthermore, exogenous mascRNA alleviated LPS-induced lung inflammation. On the contrary, mascRNA potentiated the phosphorylation of IRF3 and STAT1 and the transcription of interferon-related genes in response to the TLR3 ligand poly(I:C) both in vitro and in vivo. Mechanistically, mascRNA was found to enhance K48-linked ubiquitination and proteasomal degradation of TRAF6, thereby negatively regulating TLR-mediated MyD88-dependent proinflammatory signaling while positively regulating TRIF-dependent interferon signaling. Additionally, hnRNP H and hnRNP F were found to interact with mascRNA, promote its degradation, and contribute to the fine-tuning of TLR-triggered immune responses. Taken together, our data identify a dual role of mascRNA in both negative and positive regulation of innate immune responses.

2.
J Am Heart Assoc ; 10(16): e020854, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34387124

RESUMO

Background Current right ventricular (RV) volume overload (VO) is established in adult mice. There are no neonatal mouse VO models and how VO affects postnatal RV development is largely unknown. Methods and Results Neonatal VO was induced by the fistula between abdominal aorta and inferior vena cava on postnatal day 7 and confirmed by abdominal ultrasound, echocardiography, and hematoxylin and eosin staining. The RNA-sequencing results showed that the top 5 most enriched gene ontology terms in normal RV development were energy derivation by oxidation of organic compounds, generation of precursor metabolites and energy, cellular respiration, striated muscle tissue development, and muscle organ development. Under the influence of VO, the top 5 most enriched gene ontology terms were angiogenesis, regulation of cytoskeleton organization, regulation of vasculature development, regulation of mitotic cell cycle, and regulation of the actin filament-based process. The top 3 enriched signaling pathways for the normal RV development were PPAR signaling pathway, citrate cycle (Tricarboxylic acid cycle), and fatty acid degradation. VO changed the signaling pathways to focal adhesion, the PI3K-Akt signaling pathway, and pathways in cancer. The RNA sequencing results were confirmed by the examination of the markers of metabolic and cardiac muscle maturation and the markers of cell cycle and angiogenesis. Conclusions A neonatal mouse VO model was successfully established, and the main processes of postnatal RV development were metabolic and cardiac muscle maturation, and VO changed that to angiogenesis and cell cycle regulation.

3.
ACS Appl Mater Interfaces ; 13(33): 38979-38989, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433249

RESUMO

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.


Assuntos
Antibacterianos/química , Verde de Indocianina/química , Nanocápsulas/química , Fármacos Fotossensibilizantes/química , Polímeros/química , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/radioterapia , Células A549 , Animais , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Composição de Medicamentos , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Humanos , Verde de Indocianina/farmacologia , Raios Infravermelhos , Masculino , Metacrilatos/química , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Pseudomonas aeruginosa/efeitos dos fármacos
4.
Adv Sci (Weinh) ; : e2100351, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34453784

RESUMO

Engineered cartilage derived from mesenchymal stromal cells (MSCs) always fails to maintain the cartilaginous phenotype in the subcutaneous environment due to the ossification tendency. Vascular invasion is a prerequisite for endochondral ossification during the development of long bone. As an oral antitumor medicine, Inlyta (axitinib) possesses pronounced antiangiogenic activity, owing to the inactivation of the vascular endothelial growth factor (VEGF) signaling pathway. In this study, axitinib-loaded poly(ε-caprolactone) (PCL)/collagen nanofibrous membranes are fabricated by electrospinning for the first time. Rabbit-derived MSCs-engineered cartilage is encapsulated in the axitinib-loaded nanofibrous membrane and subcutaneously implanted into nude mice. The sustained and localized release of axitinib successfully inhibits vascular invasion, stabilizes cartilaginous phenotype, and helps cartilage maturation. RNA sequence further reveals that axitinib creates an avascular, hypoxic, and low immune response niche. Timp1 is remarkably upregulated in this niche, which probably plays a functional role in inhibiting the activity of matrix metalloproteinases and stabilizing the engineered cartilage. This study provides a novel strategy for stable subcutaneous chondrogenesis of mesenchymal stromal cells, which is also suitable for other medical applications, such as arthritis treatment, local treatment of tumors, and regeneration of other avascular tissues (cornea and tendon).

5.
ACS Appl Mater Interfaces ; 13(29): 33790-33801, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34254513

RESUMO

Hypoxia, a common characteristic of bacterial infections, is known to be closely associated with the emergence of multidrug-resistant bacteria, which hastens the need to develop advanced microbicides and antibacterial techniques. Photodynamic therapy is a promising strategy to reduce bacterial antibiotic resistance and employs photosensitizers, excitation light sources, and sufficient oxygen to generate toxic reactive oxygen species (ROS). The inherent limitation of PDT is that the generation of ROS is restricted by the hypoxic microenvironment in infection sites. Here, an oxygen self-supplying nanotherapeutic is developed to enhance antibacterial activity against multidrug-resistant bacteria on the basis of fluorinated boron dipyrromethene (BODIPY)-based glycomimetics. The nanotherapeutic not only could capture the bacteria efficiently but also was able to act as an oxygen carrier to relieve the hypoxic microenvironment of bacterial infections, thus achieving enhanced PDT efficacy. In a Pseudomonas aeruginosa infection of a rat cornea, typical administration of the nanotherapeutic decreased the infiltrate and showed a faster healing capacity in comparison with BODIPY-based glycomimetics. Self-supplying oxygen nanotherapeutics that relieve the hypoxic microenvironment and interfere with bacterial colonization have been shown to be a promising candidate for the management of drug-resistant microbial keratitis.

6.
J Orthop Surg Res ; 16(1): 462, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281573

RESUMO

PURPOSE: This study aimed to investigate the outcomes of a mini-transverse incision with a bush-hook versus a conventional open incision for carpal tunnel release (CTR). METHODS: This was a prospective study. The decision to receive either technique (mini-transverse incision with a bush-hook or conventional open incision) was primarily based on patients' choice. Patients' symptom severity, functional status, and symptomatic pain were measured at pre-operation, 1 month, and 3 and 6 months postoperatively, and any relevant complications were recorded. Kelly's scale was used to evaluate the overall clinical efficacy. RESULTS: Eighty-nine patients were included in the open CTR group and 85 patients in the mini-transverse incision group. The mini-transverse incision group had a significantly smaller incision (4.4±0.6 vs 44.8±3.7 mm), shorter surgical time (7.8±1.9 vs 21.2±3.4 min), and shorter hospital stay (3.7±1.6 vs 5.9±2.0 days) than did the open CTR group. Both groups showed significant improvements from baseline levels (all P<0.001). At postoperative 1 month and 3 months, the transverse incision group showed a significantly better VAS, SSS, and FSS (all P<0.05), but the difference was non-significant at 6 months except for FSS (P=0.022). Also, mini-transverse incision showed a significantly reduced time to return to work and activities, trend to a higher rate of excellence, and good and fewer complications than did the open CTR. CONCLUSIONS: The mini-transverse incision exhibited better performance in surgery-related measures, symptomatic remission, functional recovery, and postoperative morbidity, thus could be considered a promising technique alternative.

7.
World J Surg Oncol ; 19(1): 163, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090483

RESUMO

BACKGROUND: The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. METHODS: The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. RESULTS: Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. CONCLUSION: LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1.


Assuntos
Neoplasias da Vesícula Biliar , MicroRNAs , RNA Longo não Codificante , Carcinógenos , Linhagem Celular Tumoral , China , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética
8.
J Mater Chem B ; 9(17): 3689-3695, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33861292

RESUMO

Exogenous reactive oxygen species (ROS) generation is a promising antibacterial strategy. The short diffusion distance coupled with the transient existence of ROS restrict their precise release at inflammation sites, so it is imperative to regulate the reactive sites of ROS donors. In this work, we developed a glycomimetic-decorated fluorescent nanobiocide to mediate the release of ROS generated from CuInS/ZnS quantum dots. The introduction of glycomimetics innovatively improved the biocompatibility of the hydrophobic quantum dots, allowing pathogenic bacteria to be targeted. The functionalized CuInS/ZnS quantum dots allowed simultaneous fluorescent reporting and sterilization under 660 nm illumination. Moreover, the nanobiocide can serve as a cell-binding glue causing bacterial aggregation, disrupting bacterial adhesion to host cells and inhibiting biofilm formation. Collectively, this work indicated the far-reaching future of ROS-generating biomimetic design for multifunctional nanobiocides to combat bacterial infections.


Assuntos
Antibacterianos/química , Corantes Fluorescentes/química , Infecções/tratamento farmacológico , Pontos Quânticos/química , Células 3T3 , Adesivos/química , Animais , Antibacterianos/farmacologia , Biofilmes , Cobre/química , Eritrócitos , Humanos , Índio/química , Camundongos , Imagem Óptica , Pseudomonas aeruginosa/efeitos dos fármacos , Esterilização , Sulfetos/química , Propriedades de Superfície , Compostos de Zinco/química
9.
J Mater Chem B ; 9(5): 1364-1369, 2021 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-33458729

RESUMO

Obstinate infections caused by drug-resistant bacteria severely threaten human health. And the emergence of multidrug-resistant bacteria increases the morbidity and mortality of patients, thus necessitating the development of innovative or alternative therapeutics. Here, a light-activated nanotherapeutic with broad-spectrum bacterial recognition is established as an antibiotic-free therapeutic agent against pathogens. The nanotherapeutic with external phenylboronic acid-based glycopolymers increases the stability and biocompatibility and shows the ability of bacterial recognition. Once irradiated with near-infrared light, this nanotherapeutic with high photothermal conversion efficiency disrupts the cytoplasmic membrane, thus killing bacterial cells. Importantly, it also eliminates the biofilms formed by both drug-resistant Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus) effectively. Thus, this antibiotic-free nanotherapeutic with hypotoxicity offers a promising approach to fight increasingly serious antimicrobial resistance.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Bactérias Gram-Positivas/patogenicidade , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Nanotecnologia/métodos , Antibacterianos/farmacologia , Humanos
10.
Cell Stress Chaperones ; 26(1): 115-127, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32880058

RESUMO

Heat shock protein 60 (HSP60) is a well-recognized multifunctional protein, playing a substantial role in protecting organisms from environmental stress. The domestic pigeon (Columba livia) is a promising model organism, with important economic and ecological value, and its health is susceptible to temperature stress. To explore the molecular characteristics, tissue expression profile, and response to temperature stress for HSP60 of Columba livia (ClHSP60), we firstly cloned and characterized the complete cDNA sequence and investigated its expression profile under optimal conditions and acute temperature stress. The cDNA of ClHSP60 contained 2257 nucleotides, consisting of 12 exons with length ranging from 65 to 590 bp. The open reading frame (ORF) encoded 573 amino acids with calculated molecular weight of 60.97 kDa that contained a number of structurally prominent domains or motifs. Under optimal temperature conditions, levels of ClHSP60 expression differed between all the tested tissues (the highest was noted in liver and the lowest in pectoralis major muscle). Under acute temperature stress, five patterns of change were detected in the tested tissues, suggesting that different tissues in domestic pigeons differentially responded to various temperature stress conditions. Upregulation of ClHSP60 expression was highest in the lung and pectoralis major muscle, reflecting the crucial role of these two tissues in temperature regulation. However, the crop, cerebrum, and heart showed little change or decreased ClHSP60 expression. The results indicate that ClHSP60 may be sensitive to and play pivotal roles in responding to acute temperature stress.

11.
Cutis ; 106(1): E9-E11, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32915944
13.
Analyst ; 145(10): 3697-3704, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32297602

RESUMO

The cyclin-dependent kinase inhibitor p21 protein is a critical regulator that mediates various biological activities, such as cell cycle progression, apoptosis, and cellular senescence. As a DNA damage-inducing agent, doxorubicin could reactivate the transcriptional activity of p53 and modulate the p21 protein level. In this work, sensitive and selective monitoring of the intracellular p21 protein in doxorubicin-treated breast cancer cells was conducted using surface plasmon resonance (SPR). The fluidic channels were pre-immobilized with double stranded (ds) DNA/proliferating cell nuclear antigen (PCNA) for the capture of the p21 protein. The incorporation of the anti-p21 antibody-streptavidin conjugate pre-formed between streptavidin and biotinylated anti-p21 antibody that specifically recognizes the p21 protein leads to signal amplification. The detection limit of 0.85 pM for the p21 protein was lower than that using the commercial enzyme-linked immunosorbent assay (ELISA) kit. The treatment of MCF-7 breast cancer cells with wild-type p53 by various doses of doxorubicin leads to differences in the extent of DNA damage. Low-level DNA damage by low-dose doxorubicin up-regulates the p21 level, and p21 exerts its anti-apoptotic function, causing p53-dependent cell cycle arrest and DNA repair. However, massive DNA damage by high-dose doxorubicin represses the expression of the p21 protein through increased proteasome activity, leading to cell apoptosis. The proposed method is sensitive, selective and label-free, holding great promise for the assay of the DNA damage-induced intracellular p21 protein and understanding of p21 protein-mediated cell cycle arrest, DNA repair, and cell apoptosis.


Assuntos
Apoptose , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Dano ao DNA , Reparo do DNA , Espaço Intracelular/metabolismo , Ressonância de Plasmônio de Superfície , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Humanos , Espaço Intracelular/efeitos dos fármacos , Células MCF-7
14.
J Clin Lab Anal ; 34(6): e23214, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32068307

RESUMO

BACKGROUND: Atopic dermatitis (AD) is an inflammatory disease with diverse clinical features. Although AD is diagnosed mainly by clinical features, the laboratory abnormalities can be found in most patients and may be of diagnostic value. However, few studies have been performed on the clinical significance of laboratory abnormalities in adult and adolescent AD. METHODS: Adult and adolescent patients with AD were included in this study. The questionnaire and dermatological examination were completed by investigators. Laboratory tests included complete blood count, serum total IgE, and allergen-specific IgE. RESULTS: A total of 473 patients were recruited and 396 of them were diagnosed as AD. Increased serum total IgE level, peripheral eosinophils, and basophils were seen more frequently in AD patients than in non-AD patients (P < .05). Positive aeroallergens were seen more in AD patients than in non-AD patients (P < .05). Both total serum IgE level (R = .286, P < .001) and peripheral eosinophils (R = .444, P < .001) significantly correlated with EASI score. Serum total IgE level and extrinsic type AD decreased with age. Patients with elevated serum total IgE are more likely to have a personal history of atopic diseases (P = .014). AD-associated symptoms (such as flexural dermatitis, white dermographism, and anterior neck folds) are more frequently observed in AD patients with high serum IgE or eosinophilia (P < .05). CONCLUSION: The serum total IgE level, allergen-specific IgE, peripheral eosinophils, and basophils are important for the diagnosis of AD. And they are associated with the severity, age groups, and clinical manifestations.


Assuntos
Alérgenos/imunologia , Basófilos , Dermatite Atópica/etiologia , Eosinófilos , Imunoglobulina E/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Dermatite Atópica/sangue , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Eosinofilia/etiologia , Feminino , Humanos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Chin Med J (Engl) ; 133(2): 148-153, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31868801

RESUMO

BACKGROUND: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is critically involved in the pathogenesis of a variety of skin diseases. The aim of this study was to detect AhR and its downstream regulators including cytochrome P450 (CYP1A1), AhR nuclear translocation (ARNT), and aryl hydrocarbon receptor repressor (AhRR) in serum, peripheral blood mononuclear cells (PBMCs), and skin lesions in patients with atopic dermatitis (AD). METHODS: Twenty-nine AD patients defined according to the criteria of Hanifin and Rajka and Chinese criteria of AD were included. Subjects without allergic and chronic diseases were recruited as controls. Patients and controls were selected from the dermatology outpatient clinic of Peking University People's Hospital from August 1 to December 31 in 2018. Enzyme-linked immunosorbent assay was performed to detect serum AhR level. The mRNA of AhR, AhRR, ARNT, and CYP1A1 in PBMCs were measured by real-time quantitative polymerase chain reaction. AhR expression in skin lesions was measured by immunohistochemistry. RESULTS: AhR was significantly higher expressed in serum (41.26 ±â€Š4.52 vs. 33.73 ±â€Š2.49 pmol/L, t = 6.507, P < 0.001) and skin lesions (0.191 ±â€Š0.041 vs. 0.087 ±â€Š0.017, t = 10.036, P < 0.001) of AD patients compared with those of controls. The mRNA levels of AhR (1.572 ±â€Š0.392 vs. 1.000 ±â€Š0.173, t = 6.819, P < 0.001), AhRR (2.402 ±â€Š1.716 vs. 1.000 ±â€Š0.788, t = 3.722, P < 0.001), CYP1A1 (2.258 ±â€Š1.598 vs. 1.000 ±â€Š0.796, t = 3.400, P = 0.002) in PBMCs of AD patients were higher compared with those of controls. The difference in mRNA levels of ARNT was not statistically significant between the patients and controls (1.383 ±â€Š0.842 vs. 1.000 ±â€Š0.586, t = 1.653, P = 0.105). AhR mRNA levels in PBMCs positively correlated with eczema area and severity index score and serum interleukin-6 levels. CONCLUSION: AhR and its downstream regulators were highly expressed in serum, PBMCs, and skin of AD patients, which might contribute to the pathogenesis of AD.


Assuntos
Dermatite Atópica/sangue , Dermatite Atópica/metabolismo , Leucócitos Mononucleares/metabolismo , Receptores de Hidrocarboneto Arílico/sangue , Receptores de Hidrocarboneto Arílico/metabolismo , Dermatopatias/sangue , Dermatopatias/metabolismo , Adulto , Idoso , Translocador Nuclear Receptor Aril Hidrocarboneto/sangue , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sistema Enzimático do Citocromo P-450/sangue , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Proteínas Repressoras/sangue , Proteínas Repressoras/metabolismo
17.
Analyst ; 144(20): 6033-6040, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31502598

RESUMO

Phosphorylation serves as an important post-translational modification implicated in cellular signaling and regulation. In this work, real-time monitoring of site-specific phosphorylation of p53 protein by several protein kinases, followed by its interaction with MDM2 protein was conducted using surface plasmon resonance (SPR). The binding of phosphorylated p53 to MDM2 yields a smaller SPR signal in comparison with that in the case of unphosphorylated p53 protein. Three specific protein kinases were involved in the in situ phosphorylation of the surface-confined p53 protein, and the binding kinetics between the phosphorylated p53 and MDM2 protein was monitored. The results indicate that phosphorylation of Ser15 and Ser37 at the p53 transactivation domain 1 (TAD1) by DNA-dependent protein kinase (DNA-PK) is critical for inhibiting the p53-MDM2 interaction, and the weaker binding affinity is most likely caused by the hydrophobicity change in the vicinity of the MDM2-binding motif or phosphorylation-induced p53 conformational change. In contrast, phosphorylation of Ser46 at the p53 TAD2 domain by c-Jun NH2-terminal kinase 2α2 (JNK2α2) exerts a weaker influence on the binding affinity, whereas phosphorylation of Ser376 and Ser378 at the C-terminus of p53 by protein kinase C (PKC) appears to have little effect. The feasibility of the method for the screening of the DNA-PK inhibitor and the inhibitor of p53-MDM2 interaction has been demonstrated and the half-maximal inhibitory concentration (IC50) values of wortmannin and Nutlin-3 (21 nM and 83 nM, respectively) were highly comparable with those obtained by other methods. The proposed method holds great promise for monitoring protein phosphorylation and unraveling the post-translational modification mechanism.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2/química , Ressonância de Plasmônio de Superfície , Proteína Supressora de Tumor p53/química , Sítios de Ligação , Ligação Competitiva , Cinética , Fosforilação , Ligação Proteica , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Ressonância de Plasmônio de Superfície/métodos , Proteína Supressora de Tumor p53/metabolismo
18.
Nanoscale ; 11(36): 16928-16934, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31490526

RESUMO

Perovskite oxides with luminescent ions hold great promise in optoelectronic devices because of their outstanding thermal stabilities and electro-optic performance. As one typical perovskite upconversion (UC) host material, lead-free potassium sodium niobate ((K, Na)NbO3/(KxNa1-x)NbO3 or KNN) has attracted much attention in recent years. In the present work, a novel routine was developed to tune the upconversion photoluminescence (UC PL) performance by controlling the oxygen vacancy concentration in the KNN matrix, based on the 0.1% Er3+-doped KNN (Er-KNN) single crystals grown for the first time. UC PL properties, conductivity and defect chemistry of the single crystals were systematically investigated. The UC PL intensity of the as-grown Er-KNN material could be enhanced by 20 times after oxygen atmosphere annealing at 800 °C and fully quenched after vacuum annealing. What's more, by annealing under an oxygen atmosphere and vacuum, the conductivity of the Er-KNN sample was successfully tuned for more than 8 orders of magnitude. The super-wide range tunability of UC PL performance and conductivity could be explained by oxygen vacancies which gave rise to Nb5+-Nb4+ valence alternation. Because of the modulated photoluminescence properties and conductivity, our grown Er-KNN single crystals have great potential for use in multifunctional devices.

19.
Analyst ; 144(13): 3959-3966, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31134974

RESUMO

MDM2 can mediate the degradation of tumor suppressor p53 through an autoregulatory feedback loop, in which MDM2 abolishes wild-type p53 function and accelerates malignant transformation. However, the incorporation of MDM2 antagonist Nutlin-3 could reactivate the transcriptional activity of p53, up-regulate caspase-3, and induce apoptosis. In this work, the simultaneous and label-free monitoring of p53-MDM2 complex and caspase-3 levels in cancer cells before and after Nutlin-3 treatment was conducted using dual-channel surface plasmon resonance (SPR). The p53-MDM2 complex was captured in one fluidic channel covered with consensus double-stranded (ds)-DNA, while the other channel was pre-immobilized with caspase-3-specific biotinylated DEVD-containing peptides. To amplify the SPR signals, the attachment of streptavidin (SA)-conjugated anti-MDM2 antibody in both channels was achieved. The signal diversity before and after Nutlin-3 treatment is indicative of the difference in the levels of the intracellular p53-MDM2 complex and caspase-3. The limit of detection for p53-MDM2 and caspase-3 down to 4.54 pM and 0.03 ng mL-1, respectively, was attained. Upon treatment with Nutlin-3, MCF-7 cancer cells with wild-type p53 showed decreased expression of the p53-MDM2 complex and an increased caspase-3 level, while MDA-MB-231 cancer cells with mutant p53 exhibited an elevated caspase-3 level and unchanged p53-MDM2 complex expression. The apoptosis of MCF-7 and MDA-MB-231 cancer cells upon Nutlin-3 treatment follows a p53-dependent and a p53-independent pathway, respectively. The proposed method is sensitive, selective and label-free, holding great promise for assaying intracellular p53-MDM2 complex and caspase-3 levels and differentiating Nutlin-3-mediated p53-dependent or p53-independent apoptotic pathways.


Assuntos
Caspase 3/análise , Imidazóis/farmacologia , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-mdm2/análise , Ressonância de Plasmônio de Superfície/métodos , Proteína Supressora de Tumor p53/análise , Apoptose/efeitos dos fármacos , Biotina/química , Caspase 3/química , Caspase 3/metabolismo , Linhagem Celular Tumoral , DNA/química , Relação Dose-Resposta a Droga , Humanos , Limite de Detecção , Ligação Proteica , Proteínas Proto-Oncogênicas c-mdm2/química , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptavidina/química , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo
20.
Dermatol Ther ; 32(4): e12952, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31025475

RESUMO

Pyoderma gangrenosum (PG) is a rare ulcerating inflammatory neutrophilic dermatosis. Different clinical manifestations have been described, including ulcerative, pustular and bullous, and vegetative variants. Classic PG usually occurs on the lower extremities (~70% of cases) but can also involve the hands, head, neck, and scrotum. Genital involvement of PG has rarely been reported. Treatment of the genital PG is usually difficult and resistance to conventional therapeutic regimens was frequently observed. The present authors reported a 16-year-old male patient who presented with progressive genital ulceration for 3 weeks. He was treated successfully low dose thalidomide (50 mg/d) and minocycline.


Assuntos
Minociclina/administração & dosagem , Doenças do Pênis/tratamento farmacológico , Pioderma Gangrenoso/tratamento farmacológico , Talidomida/administração & dosagem , Adolescente , Antibacterianos/administração & dosagem , Quimioterapia Combinada , Humanos , Imunossupressores/administração & dosagem , Masculino , Doenças do Pênis/patologia , Pioderma Gangrenoso/patologia , Resultado do Tratamento
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