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A new dicyanoisophorone-based ratiometric fluorescent probe NOSA was synthesized and characterized. It showed a fast fluorescence response to HClO with the emission color change from dark green to bright red. NMR, IR, and HRMS suggested that the detection of NOSA to HClO may originate from the hydroxyl deprotection reaction by HClO on the molecule NOSA, which caused a red-shift of fluorescence. The probe NOSA displayed high selectivity and excellent anti-interference performance with a limit of detection at 3.835 × 10-7 M. The convenient paper test strips were successfully obtained and applied to the detection of HClO based on fluorescence color change with the varied NaClO concentration. Moreover, spiked recovery experiments in real water samples indicated that the probe NSOA could quantitatively detect HClO, and the fluorescence bio-imagings in vivo were carried out, and HClO detection in biosystems using NOSA was realized.
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Exposure of biological systems to acute or chronic insults triggers a host of molecular and physiological responses to either tolerate, adapt, or fully restore homeostasis; these responses constitute the hallmarks of resilience. Given the many facets, dimensions, and discipline-specific focus, gaining a shared understanding of "resilience" has been identified as a priority for supporting advances in cardiovascular health. This report is based on the working definition: "Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges," developed after considering many factors contributing to cardiovascular resilience through deliberations of multidisciplinary experts convened by the National Heart, Lung, and Blood Institute during a workshop entitled: "Enhancing Resilience for Cardiovascular Health and Wellness." Some of the main emerging themes that support the possibility of enhancing resilience for cardiovascular health include optimal energy management and substrate diversity, a robust immune system that safeguards tissue homeostasis, and social and community support. The report also highlights existing research challenges, along with immediate and long-term opportunities for resilience research. Certain immediate opportunities identified are based on leveraging existing high-dimensional data from longitudinal clinical studies to identify vascular resilience measures, create a 'resilience index,' and adopt a life-course approach. Long-term opportunities include developing quantitative cell/organ/system/community models to identify resilience factors and mechanisms at these various levels, designing experimental and clinical interventions that specifically assess resilience, adopting global sharing of resilience-related data, and cross-domain training of next-generation researchers in this field.
Assuntos
National Heart, Lung, and Blood Institute (U.S.) , Pesquisadores , Estados Unidos , HumanosRESUMO
A new phenanthroimidazole-based fluorescence probe for selective detection of HClO was synthesized and characterized using 1HNMR, 13CNMR, IR, and HRMS. With benzenesulfonohydrazide as the identification group, the probe demonstrated a fast fluorescence response from yellow-green to blue when the HC = N double bond was oxidized and broken into an aldehyde group by HClO. The probe showed high selectivity and sensitivity towards HClO with approximately 4.5-fold fluorescence enhancement and has been successfully applied in the molecular logic gate, determination of HClO in environmental water samples, and portable HClO detection.
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Traditionally, much research effort has been invested into focusing on disease, understanding pathogenic mechanisms, identifying risk factors, and developing effective treatments. A few recent studies unraveling the basis for absence of disease, including cardiovascular disease, despite existing risk factors, a phenomenon commonly known as resilience, are adding new knowledge and suggesting novel therapeutic approaches. Given the central role of endothelial function in cardiovascular health, we herein provide a number of considerations that warrant future research and considering a paradigm shift toward identifying the molecular underpinnings of endothelial resilience.
Assuntos
Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/fisiopatologia , Vasodilatação/fisiologia , Animais , Humanos , Fatores de RiscoRESUMO
Claudin-4 (CLDN4), a crucial member of tight junction proteins, is aberrantly expressed in breast cancer cells and contributes to cell migration and invasion. However, the mechanisms controlling CLDN4 expression in breast cancer are poorly understood. Here, we reported that CLDN4 expression correlated positively with p21-activated kinase 4 (PAK4) expression in human breast cancer tissues. Knockdown of PAK4 in MDA-MB-231 and ZR-75-30â¯cells suppressed CLDN4 expression and significantly inhibited cell migration and invasion. Conversely, restoration of CLDN4 expression in PAK4-knockdown cells reversed the inhibition of migration and invasion. We identified CCAAT/enhancer-binding protein ß (CEBPB) as a novel transcriptional regulator of CLDN4 and confirmed that CEBPB bound to the -1093 to -991 bp region of the CLDN4 promoter. Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr-235. In summary, we showed that PAK4-mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion. Our results might contribute to understanding the mechanisms of CLDN4 regulation and suggest PAK4-CEBPB-CLDN4 axis as a potential therapeutic target for breast cancer.
Assuntos
Neoplasias da Mama/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Claudina-4/metabolismo , Transdução de Sinais , Quinases Ativadas por p21/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Movimento Celular , Claudina-4/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Fosforilação , Quinases Ativadas por p21/genéticaRESUMO
Lamiophlomis rotata (L. rotata), is known as "Daba" in the Tibetan region, Ajuga ovalifolia and Oreosolen wartii have also been utilized as substitutes for "Daba", however, only L. rotata has been officially listed in the Chinese Pharmacopoeia for hemostasis preparations. To safely apply the traditional uses of the herb, internal transcribed spacer 2 (ITS2) DNA barcodes were employed to discriminate L. rotata from its adulterants. For further evaluation of the quality of different originating habitats, the chemical profiles of 25 samples were determined by ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with multivariate analyses. ITS2 DNA barcodes differentiated L. rotata from O. wartii and A. ovalifolia accurately. A neighbor-joining (NJ) tree showed that three origins clustered into three clades. Forty-nine compounds were identified in the total ion current (TIC) profile of L. rotata. Additionally, two pairs of isomers were identified for the first time by using mass spectrometry fragmentation. The differences between the variable habitats were determined by multivariate statistical analysis of the UPLC-QTOF-MS data from 25 specimens. Ten compounds were identified as the characteristic markers distinguishing the sample from four geographical origins. The results also suggest that samples from Qinghai and Sichuan province would be the most suitable choice for traditional prescriptions and preparations.
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Código de Barras de DNA Taxonômico/métodos , Lamiaceae/química , Lamiaceae/genética , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão/métodos , DNA Espaçador Ribossômico , Análise dos Mínimos Quadrados , Espectrometria de Massas/estatística & dados numéricos , Análise MultivariadaAssuntos
Pesquisa Biomédica/economia , Doenças Cardiovasculares/economia , National Heart, Lung, and Blood Institute (U.S.)/economia , Neovascularização Patológica/economia , Neovascularização Fisiológica/fisiologia , Apoio à Pesquisa como Assunto/economia , Pesquisa Biomédica/tendências , Doenças Cardiovasculares/terapia , Humanos , National Heart, Lung, and Blood Institute (U.S.)/tendências , National Institutes of Health (U.S.)/economia , National Institutes of Health (U.S.)/tendências , Neovascularização Patológica/terapia , Apoio à Pesquisa como Assunto/tendências , Estados Unidos/epidemiologiaRESUMO
Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer.
Assuntos
Processamento Alternativo , Neoplasias do Colo , Transição Epitelial-Mesenquimal , Metástase Neoplásica , Proteínas de Ligação a RNA , Humanos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Processamento Alternativo/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Animais , Camundongos , Camundongos Nus , Linhagem Celular Tumoral , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Camundongos Endogâmicos BALB C , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Células HCT116 , MasculinoRESUMO
AIMS: P21-activated kinase 4 (PAK4) belongs to the wider family of Serine/Threonine p21-activated kinases (PAKs) and functions as a hub for signaling pathways in cancer progression. Numerous studies have indicated the significance of PAK4 for tumorigenesis, but no systematic pan-cancer analysis has been performed. MAIN METHODS: The current study aimed to investigate the prognostic and immunological functions of PAK4 through bioinformatic analysis of datasets from The Cancer Genome Atlas, UALCAN, GEPIA2, cBioPortal, TIMER2, and Human Protein Atlas. PAK4 expression was correlated with prognosis, DNA methylation, tumor mutational burden, microsatellite instability, and immune cell infiltration. KEY FINDINGS: PAK4 was highly expressed in various cancers but showed decreased expression in colon adenocarcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, and thyroid carcinoma. PAK4 was found to have a positive or negative correlation with prognosis of different cancers. PAK4 expression was related to tumor mutational burden in 11 tumor types, and associated with microsatellite instability in 10 tumor types and was correlated with immune infiltration and immune checkpoint genes. SIGNIFICANCE: PAK4 could be considered as a prognostic and immunotherapeutic marker for some types of malignant tumor.
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Neoplasias , Humanos , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Instabilidade de Microssatélites , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/imunologia , Prognóstico , Neoplasias/genética , Neoplasias/imunologiaRESUMO
A novel preparation scheme of thioglycerol-modified silica through thiol-epoxy click reaction was proposed aiming at introducing additional quantities of hydroxyl groups into the structure. When applied as the stationary phase of hydrophilic interaction liquid chromatography (HILIC) for separation of oligosaccharide compounds, the material revealed higher polar separation capability than which synthesized through traditional thiol-ene click reaction. Hydrogen-bond interactions were speculated to be the predominant retention mechanism, while partitioning also participated in the retention of disaccharides and trisaccharides. The column also showed good stability and inter-batch reproducibility. Finally, the column was employed for determination of oligosaccharide compounds in commercial beverages, and good linearities, high accuracy, favorable precision, satisfactory reproducibility and resistance to matrix interference were achieved. In the detection of real samples, the determined content was consistent with the labeled content. This work provided an efficient and practicable method for quantity monitoring of commercial diet drinks in routine laboratory.
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Dióxido de Silício , Compostos de Sulfidrila , Dióxido de Silício/química , Reprodutibilidade dos Testes , Química Click , Interações Hidrofóbicas e Hidrofílicas , Cromatografia Líquida/métodos , Oligossacarídeos , BebidasRESUMO
Neuropathic pain (NP) is associated with sleep disturbances, which may substantially influence the quality of life. Clinical and animal studies demonstrated that neurotransmitter is one of the main contributors to cause sleep disturbances induced by NP. Recently, it was reported that P2X7 receptors (P2X7R) are widely expressed in microglia, which serves crucial role in neuronal activity in the pain and sleep-awake cycle. In this study, we adopted the chronic constriction injury (CCI) model to establish the progress of chronic pain and investigated whether P2X7R of microglia in cortex played a critical role in sleep disturbance induced by NP. At electroencephalogram (EEG) level, sleep disturbance was observed in mice treated with CCI as they exhibited mechanical and thermal hypersensitivity, and inhibition of P2X7R ameliorated these changes. We showed a dramatic high level of P2X7R and Iba-1 co-expression in the cortical region, and the inhibition of P2X7R also adversely affected it. Furthermore, the power of LFPs in ventral posterior nucleus (VP) and primary somatosensory cortex (S1) which changed in the CCI group was adverse after the inhibition of P2X7R. Furthermore, inhibition of P2X7R also decreased the VP-S1 coherence which increased in CCI group. Nuclear magnetic resonance demonstrated inhibition of P2X7R decreased glutamate (Glu) levels in thalamic and cortical regions which were significantly increased in the CCI mice. Our findings provide evidence that NP has a critical effect on neuronal activity linked to sleep and may built up a new target for the development of sleep disturbances under chronic pain conditions.
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A spectroscopic probe CMBT was synthesized and characterized. CMBT showed the specific recognition for HClO based on the turn-on blue fluorescence and naked-eye change from pink to colorless. NMR, IR, HRMS-ESI, and spectral analysis suggested that colorimetric and fluorescent change of CMBT to HClO originated from the conversion of CMBT to starting material coumarin-aldehyde 1 caused by the oxidization of HClO, which was responsible for the fluorescence recovery. The detection limit was calculated to be 1.61 µM and 6.58 µM for fluorescence and UV-vis analysis with a range up to 1 mM. HClO's fluorescence detection was successfully achieved in tap and river water samples. The prepared convenient paper test strips showed a distinct color change in varying concentrations of HClO. A multi-input molecular logic circuit was constructed.
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Corantes Fluorescentes , Ácido Hipocloroso , Colorimetria , Microscopia de Fluorescência , Espectrometria de FluorescênciaRESUMO
L-glutamate (L-Glu) has gained much attention owing to its contribution to the umami taste and it plays important roles in the central nervous system. Herein, an enzyme-free amperometric biosensor based on a peptide possessing an electroactive ferrocene linker as ferrocene-Gly-Gly-Gly-Gly-Ile- Pro-Val-Tyr-Cys-Gly-Leu-Ile-Gly-Gly-Gly-Gly-Lys-(CH2)4- thioctic acid self- assembled on gold electrode was designed and fabricated for specific determination of L-Glu. The biosensor was characterised via cyclic voltammetry, electrochemical impedance spectroscopy, atomic force microscopy and scanning electron microscopy. The biosensor showed optimum response within 200 s at 0.10 V in phosphate-buffered saline. Moreover, the biosensor exhibited excellent sensitivity and a low detection limit of 1.00 × 10-10 M. The sensitivity at an L-Glu concentration of 1.00 × 10-7 M - 1.00 × 10-3 M was 0.1572 µA/M, and that at an L-Glu concentration of 1.00 × 10-10 M - 1.00 × 10-7 M was 0.0293 µA/M. The peptide-based biosensor had excellent specificity and a wider linear range. The relative standard deviation of the L-Glu concentrations measured by the biosensor in a hundred-fold dilution of mouse serum samples was less than 5.00% compared with the high-performance liquid chromatography results, and the recovery rate of L-Glu was from 93.32% to 105.15%.
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Aptâmeros de Peptídeos , Ácido Glutâmico , Sequência de Aminoácidos , Animais , Metalocenos , Camundongos , Fragmentos de Peptídeos , Peptídeos , TripsinaRESUMO
The health benefits of exercise are well-recognized and are observed across multiple organ systems. These beneficial effects enhance overall resilience, healthspan and longevity. The molecular mechanisms that underlie the beneficial effects of exercise, however, remain poorly understood. Since the discovery in 2000 that muscle contraction releases IL-6, the number of exercise-associated signalling molecules that have been identified has multiplied. Exerkines are defined as signalling moieties released in response to acute and/or chronic exercise, which exert their effects through endocrine, paracrine and/or autocrine pathways. A multitude of organs, cells and tissues release these factors, including skeletal muscle (myokines), the heart (cardiokines), liver (hepatokines), white adipose tissue (adipokines), brown adipose tissue (baptokines) and neurons (neurokines). Exerkines have potential roles in improving cardiovascular, metabolic, immune and neurological health. As such, exerkines have potential for the treatment of cardiovascular disease, type 2 diabetes mellitus and obesity, and possibly in the facilitation of healthy ageing. This Review summarizes the importance and current state of exerkine research, prevailing challenges and future directions.
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Diabetes Mellitus Tipo 2 , Adipocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Exercício Físico/fisiologia , Humanos , Músculo Esquelético/metabolismo , Obesidade/metabolismoRESUMO
The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.
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Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Memória Imunológica , Modelos Imunológicos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , COVID-19/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
This study determined effects of dietary supplementation with L-arginine (Arg) or N-carbamylglutamate (NCG) on intestinal health and growth in early-weaned pigs. Eighty-four Landrace x Yorkshire pigs (average body weight of 5.56+/-0.07 kg; weaned at 21 days of age) were fed for 7 days one of the three isonitrogenous diets: (1) a corn- and soybean meal-based diet (CSM), (2) CSM+0.08% NCG (0.08%), and (3) CSM+0.6% Arg. There were four pens of pigs per diet (7 pigs/pen). At the end of a 7-day feeding period, six piglets were randomly selected from each treatment for tissue collections. Compared with the control group, Arg or NCG supplementation increased (P<0.05): (1) Arg concentrations in plasma, (2) small-intestinal growth, (3) villus height in duodenum, jejunum and ileum, (4) crypt depth in jejunum and ileum, (5) goblet cell counts in intestinal mucosae, and (6) whole-body weight gain in pigs. Real-time polymerase chain reaction and western blotting analyses revealed that both mRNA and protein levels for heat shock protein-70 (HSP70) were higher (P<0.05) in the intestinal mucosae of Arg- or NCG-supplemented pigs than in the control group. Furthermore, the incidence of diarrhea in the NCG group was 18% lower (P<0.01) than that in the control group. Collectively, these results indicate that dietary supplementation with 0.6% Arg or 0.08% NCG enhances intestinal HSP70 gene expression, intestinal growth and integrity, and the availability of dietary nutrients for whole-body weight gain in postweaning pigs fed a CSM-based diet. Thus, Arg or NCG is a functional ingredient in the weaning diet to improve nutrition, health, and growth performance of these neonates.
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Ração Animal/análise , Arginina/metabolismo , Suplementos Nutricionais/análise , Expressão Gênica , Glutamatos/metabolismo , Proteínas de Choque Térmico HSP70/genética , Intestino Delgado/crescimento & desenvolvimento , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/fisiologia , Animais , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Intestino Delgado/metabolismo , Masculino , Glycine max/química , Sus scrofa/genética , Desmame , Zea mays/químicaRESUMO
To identify genes involved in pigment gland morphogenesis in cotton, gene expression was profiled using genechip (Affymetrix) during pigment gland morphogenesis in cotton variety Xiangmian-18, which has glandless seeds but glanded plants, and a glandless line, N5. The results showed that 303 genes were differentially expressed by a factor greater than two during gland morphogenesis; 59% (180) of these genes shared similarity with known genes in GenBank. These genes play roles in defense response, response to oxidative stress, peroxidase activity, and other metabolic pathways. KOBAS (KEGG Orthology-Based Annotation System) indicate that these genes are involved in 68 biochemical pathways. These findings suggest that the related defense response, gossypol biosynthesis pathway and other complex regulation may be associated with pigment gland morphogenesis in cotton. The results may provide a basis for further study and serve as a guide for related research.
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Ecossistema , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Gossypium/anatomia & histologia , Gossypium/genética , Morfogênese/genética , Mutação/genética , Regulação para Baixo/genética , Genes de Plantas/genética , Gossypium/crescimento & desenvolvimento , Redes e Vias Metabólicas/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Plantas/genética , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/genéticaRESUMO
The biological function of nuclear PAK4 in ERα-positive breast cancer osteolytic bone destruction remains unclear. Here, we find that the nuclear PAK4 promotes osteoclastogenesis and tumor-induced osteolysis via phosphorylating RUNX1. We show that nuclear PAK4 interacts with and phosphorylates RUNX1 at Thr-207, which induces its localization from the nucleus to the cytoplasm and influences direct interaction with SIN3A/HDAC1 and PRMT1. Furthermore, we reveal that RUNX1 phosphorylation by PAK4 at Thr-207 promotes osteolytic bone destruction via targeting downstream genes related to osteoclast differentiation and maturation. Importantly, we verify changes in RUNX1 subcellular localization when nuclear PAK4 is positive in breast cancer bone metastasis tissues. Functionally, we demonstrate that RUNX1 phosphorylation promotes osteolytic bone maturation and ERα-positive breast cancer-induced osteolytic bone damage in the mouse model of orthotopic breast cancer bone metastasis. Our results suggest PAK4 can be a therapeutic target for ERα-positive breast cancer osteolytic bone destruction.
Assuntos
Neoplasias da Mama/complicações , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Receptor alfa de Estrogênio/metabolismo , Osteólise/etiologia , Quinases Ativadas por p21/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Diferenciação Celular , Linhagem Celular Tumoral , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Receptor alfa de Estrogênio/genética , Feminino , Histona Desacetilase 1/genética , Histona Desacetilase 1/metabolismo , Humanos , Camundongos , Camundongos Nus , Neoplasias Experimentais , Osteoclastos/fisiologia , Osteogênese/fisiologia , Osteólise/metabolismo , Fosforilação , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , Células RAW 264.7 , Distribuição Aleatória , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Complexo Correpressor Histona Desacetilase e Sin3/genética , Complexo Correpressor Histona Desacetilase e Sin3/metabolismo , Quinases Ativadas por p21/genéticaRESUMO
The ground state and lowest triplet-state structures of [Re(4,4'-(COOEt)(2)-2,2'-bpy)(CO)(3)py]PF(6) photosensitizer (bpy=bipyridine, py=pyridine) have been studied with density functional theory (DFT). Time-dependent density functional theory (TD-DFT) was carried out to predict the photophysical properties of the photosensitizer. The effects of the solvents were evaluated using the conductor-like polarizable continuum (CPCM) method in dichloromethane, chloroform, acetonitrile, acetone, ethanol and dimethylsulfoxide. The electronic transition energies computed with BLYP, MPWPW91, B3LYP and MPW1PW91 functionals are compared with the experimental spectra. Based on the calculated excited energies, the experimental absorption maximum is assigned as metal-to-ligand charge transfer (MLCT) and ligand-to-ligand charge transfer (LLCT) mixed transition, and the luminescence originates from the lowest triplet state that is ascribed as the mixed transition of MLCT/LLCT.
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Elétrons , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Piridinas/química , Rênio/química , Absorção , Simulação por Computador , Substâncias Macromoleculares/química , Modelos Biológicos , Modelos Moleculares , Conformação Molecular , Espectrofotometria AtômicaRESUMO
An aza-BODIPY-CNOH probe attached aldoxime group demonstrated the specific detection for hypochlorous acid by the turn-on red emission signal. NMR and HRMS experiments confirmed that the fluorescence originated from the oxidation degradation of the non-fluorescence, aldoxime-based aza-BODIPY-CNOH probe into the red-fluorescence, nitrile oxide-based aza-BODIPY compound aza-BODIPY-CNO. The aza-BODIPY-CNOH probe showed good biocompatibility and was low toxic to living cells as shown from MTT experiments. Living RAW264.7 cells imaging indicated the aza-BODIPY-CNOH probe had good permeability and either exogenous or endogenous HClO caused the intracellular bright-red fluorescence, showing its potential hypochlorous acid-specific sensing ability in biological systems.