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Lead halide perovskites are promising semiconductors for light-emitting applications because they exhibit bright, bandgap-tunable luminescence with high colour purity1,2. Photoluminescence quantum yields close to unity have been achieved for perovskite nanocrystals across a broad range of emission colours, and light-emitting diodes with external quantum efficiencies exceeding 20 per cent-approaching those of commercial organic light-emitting diodes-have been demonstrated in both the infrared and the green emission channels1,3,4. However, owing to the formation of lower-bandgap iodide-rich domains, efficient and colour-stable red electroluminescence from mixed-halide perovskites has not yet been realized5,6. Here we report the treatment of mixed-halide perovskite nanocrystals with multidentate ligands to suppress halide segregation under electroluminescent operation. We demonstrate colour-stable, red emission centred at 620 nanometres, with an electroluminescence external quantum efficiency of 20.3 per cent. We show that a key function of the ligand treatment is to 'clean' the nanocrystal surface through the removal of lead atoms. Density functional theory calculations reveal that the binding between the ligands and the nanocrystal surface suppresses the formation of iodine Frenkel defects, which in turn inhibits halide segregation. Our work exemplifies how the functionality of metal halide perovskites is extremely sensitive to the nature of the (nano)crystalline surface and presents a route through which to control the formation and migration of surface defects. This is critical to achieve bandgap stability for light emission and could also have a broader impact on other optoelectronic applications-such as photovoltaics-for which bandgap stability is required.
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The use of a small organic molecular passivator is proven to be a successful strategy for producing higher-performing quasi-2D perovskite light-emitting diodes (PeLEDs). The small organic molecule can passivate defects on the grain surround and surface of perovskite crystal structures, preventing nonradiative recombination and charge trapping. In this study, a new small organic additive called 2, 8-dibromodibenzofuran (diBDF) is reported and examines its effectiveness as a passivating agent in high-performance green quasi-2D PeLEDs. The oxygen atom in diBDF, acting as a Lewis base, forms coordination bonds with uncoordinated Pb2+, so enhancing the performance of the device. In addition, the inclusion of diBDF in the quasi-2D perovskite results in a decrease in the abundance of low-n phases, hence facilitating efficient carrier mobility. Consequently, PeLED devices with high efficiency are successfully produced, exhibiting an external quantum efficiency of 19.9% at the emission wavelength of 517 nm and a peak current efficiency of 65.0 cd A-1.
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Cesium lead halide perovskite nanocrystals (PNCs) exhibit promising prospects for application in optoelectronic devices. However, electroactivated near-infrared (NIR) PNC light-emitting diodes (LEDs) with emission peaks over 800 nm have not been achieved. Herein, we demonstrate the electroactivated NIR PNC LEDs based on Yb3+-doped CsPb(Cl1-xBrx)3 PNCs with extraordinary high NIR photoluminescence quantum yields over 170%. The fabricated NIR LEDs possess an irradiance of 584.7 µW cm-2, an EQE of 1.2%, and a turn-on voltage of 3.1 V. The ultrafast quantum cutting process from the PNC host to Yb3+ has been revealed as the main mechanism of electroluminescence (EL)-activated Yb3+ for the first time via exploring how the trend between the EL intensity of PNC and Yb3+ varies with different voltages along with the tendency of temperature- and doping-concentration-dependent PL and EL spectra. This work will extend the application of PNCs to optical communication, night-vision devices, and biomedical imaging.
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Although the efficiency of cloning remains very low, this technique has become the most reliable way to produce transgenic pigs. However, the high rate of abnormal offspring such as an enlarged tongue lowers the cloning efficiency by reducing the early survivability of piglets. Thus, the present study was conducted to identify the characteristics of the enlarged tongue from cloned piglets by histologic and transcriptomic analysis. As a result, it was observed that the tissues from enlarged tongues (n = 3) showed isolated and broken muscle bundles with wide spaces while the tissues from normal tongues (n = 3) showed the tight connection of muscle bundles without space by histological analysis. Additionally, transmission electron microscopy results also showed the formation of isolated and broken muscle bundles in enlarged tongues. The transcriptome analysis showed a total of 197 upregulated and 139 downregulated genes with more than 2-fold changes in enlarged tongues. Moreover, there was clear evidence for the difference between groups in the muscle system process with high relation in the biological process by gene ontology analysis. The analysis of the Kyoto Encyclopedia of Gene and Genomes pathway of differentially expressed genes indicated that the pentose phosphate pathway, glycolysis/gluconeogenesis, and glucagon signaling pathway were also involved. Conclusively, our results could suggest that the abnormal glycolytic regulation may result in the formation of an enlarged tongue. These findings might have the potential to understand the underlying mechanisms, abnormal development, and disease diagnosis in cloned pigs.
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The severely insufficient operational lifetime of perovskite light-emitting diodes (LEDs) is incompatible with the rapidly increasing external quantum efficiency, even as it approaches the theoretical limit, thereby significantly impeding the commercialization of perovskite LEDs. In addition, Joule heating induces ion migration and surface defects, degrades the photoluminescence quantum yield and other optoelectronic properties of perovskite films, and induces the crystallization of charge transport layers with low glass transition temperatures, resulting in LED degradation under continuous operation. Here, a novel thermally crosslinked hole transport material, poly(FCA60 -co-BFCA20 -co-VFCA20 ) (poly-FBV), with temperature-dependent hole mobility is designed, which is advantageous for balancing the charge injection of the LEDs and limiting the generation of Joule heating. The optimised CsPbI3 perovskite nanocrystal LEDs with poly-FBV realise approximately a 2-fold external quantum efficiency increase over the LED with commercial hole transport layer poly(4-butyl-phenyl-diphenyl-amine) (poly-TPD), owing to the balanced carrier injection and suppressed exciton quenching. Moreover, because of the Joule heating control provided by the novel crosslinked hole transport material, the LED utilising crosslinked poly-FBV has a 150-fold longer operating lifetime (490 min) than that utilizing poly-TPD (3.3 min). The study opens a new avenue for the use of PNC LEDs in commercial semiconductor optoelectronic devices.
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Compounds with ordered and interconnected channels have versatile multifunctional applications in technological fields. In this work, we report the intrinsic- and Eu3+-activated luminescence in NbAlO4 with a wide channel structure. NbAlO4 is an n-type semiconductor with an indirect allowed transition and a band-gap energy of 3.26 eV. The conduction band and valence band are composed of Nb 3d and O 2p states, respectively. Unlike the common niobate oxide Nb2O5, NbAlO4 exhibits efficient self-activated luminescence with good thermal stability even at room temperature. The AlO4 tetrahedron effectively blocks the transfer/dispersion of excitation energy between NbO6 chains in NbAlO4, allowing for effective self-activated luminescence from NbO6 activation centers. Moreover, Eu3+-doped NbAlO4 displayed a bright red luminescence of 5D0 â 7F2 transition at 610 nm. The site-selective excitation and luminescence of Eu3+ ions in a spectroscopic probe were utilized to investigate the doping mechanism. It is evidenced that Eu3+ is doped in the structure channel in NbAlO4 lattices, not in the normal cation sites of Nb5+ or Al3+. The experimental findings are valuable in developing new luminescent materials and improving the understanding of the material's channel structure.
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Mepirapim is a novel synthetic cannabinoid that first appeared on the illicit drug market in 2013. In recent years, recreational abuse of Mepirapim has caused serious emergencies, posing a threat to public health. However, there are no legal regulations to prohibit the use of Mepirapim, as there is no scientific evidence for the dangerous pharmacological effects of the drug. In the present study, we investigated the dangerous neurotoxic effects of Mepirapim through behavioral and molecular experiments in mice (ICR/CD1, male, 25-30 g). In particular, based on a previous study that Mepirapim activates the dopamine system, we evaluated whether high-dose Mepirapim [single (15, 30, or 60 mg·kg-1, i.p.) or multiple (8, 15, or 30 mg·kg-1, i.p. × 4 at 2 h intervals)] treatment causes Parkinson's disease-related symptoms through damage to the dopamine system. In the result, we found that Mepirapim treatment caused comprehensive Parkinson's disease-related symptoms, including motor impairment, cognitive deficits and mood disorders. Furthermore, we confirmed the maladaptation in dopamine-related neurochemicals, including decreased dopamine levels, decreased tyrosine hydroxylase expression, and increased α-synuclein expression, in the brains of mice treated with Mepirapim. Taken together, these results indicate that Mepirapim has dangerous neurotoxic effects that induces Parkinson's disease-related behaviors by causing maladaptation of the dopamine system in the brain. Based on these findings, we propose the strict regulation of recreational abuse and therapeutic misuse of Mepirapim.
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Transtornos Cognitivos , Síndromes Neurotóxicas , Doença de Parkinson , Masculino , Animais , Camundongos , Camundongos Endogâmicos ICR , Dopamina , EncéfaloRESUMO
We describe a measles outbreak among previously vaccinated healthcare workers (HCWs) and inpatients and the control measures implemented at a tertiary care hospital in 2019. Case-patients were laboratory-confirmed measles with throat swabs tested by quantitative polymerase chain reactions (PCR), during April-May 2019. Medical histories and documented immunization records were obtained. We compared attack rates (ARs) among HCWs by occupational subgroup and age and examined the outbreak-associated costs. The index case was not ascertained. Among 26 measles case-patients (22 HCWs, four inpatients) aged 18-28 years, 25 had previously received measles-mumps-rubella (MMR) vaccine (12/26, 46% (two doses); 13/26, 50% (one dose)), and 16 (62%) had positive results of measles IgG prior to measles diagnosis. ARs were higher among HCWs aged < 30 years (1.88%), especially in the subgroup under 25 years of age (2.22%). Control measures included work restrictions for seronegative HCWs (218/2320, 9.4%) in immunity verification, administration of the MMR vaccine (207 HCWs) or intravenous immunoglobulin (2 HCWs and 11 inpatients), enhanced health surveillance of HCWs, and mandatory assessment of patients with measles-like symptoms at the infectious diseases screening units. The hospital spent 90,417,132 Korean won (US $79,733) in response to the outbreak. Measles outbreaks can occur in healthcare settings despite high population immunity, highlighting the importance of stronger vaccination policies, particularly among young HCWs. Moreover, an effective outbreak response comprising immunization activities and enhanced surveillance of HCWs and patients to rapidly detect measles-like symptoms at a prodromal phase is essential to control nosocomial measles outbreaks.
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Infecção Hospitalar , Sarampo , Adolescente , Adulto , Anticorpos Antivirais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Surtos de Doenças , Hospitais , Humanos , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola , República da Coreia/epidemiologia , Vacinação , Adulto JovemRESUMO
The phylogenomics and comparative functional genomics of avian species were investigated in the Bird 10,000 Genomes (B10K) project because of the important evolutionary position of birds and their value as a research model. However, the systematic profiling of transcriptional changes prior to oviposition has not been investigated in avian species because of the practical difficulties in obtaining pre-oviposited eggs. In this study, a total of 137 pre-oviposited embryos were collected from hen ovaries and oviducts and subjected to RNA-sequencing analyses. Two waves of chicken zygotic genome activation (ZGA) were observed. Functionally distinct developmental programs involving Notch, MAPK, Wnt and TGFß signaling were separately detected during cleavage and area pellucida formation. Furthermore, the early stages of chicken development were compared with the human and mouse counterparts, highlighting chicken-specific signaling pathways and gradually analogous gene expression via ZGA. These findings provide a genome-wide understanding of avian embryogenesis and comparisons among amniotes.
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Galinhas/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Transcriptoma/genética , Animais , Separação Celular , Embrião de Galinha , Feminino , Perfilação da Expressão Gênica , Genoma , Humanos , Hibridização In Situ , Camundongos , Análise de Sequência de RNA , Transdução de Sinais , ZigotoRESUMO
The stability and survival of germ cells are controlled by the germline-specific genes, however, such genes are less known in the avian species. Using a microarray-based the National Center for Biotechnology Information Gene Expression Omnibus dataset, we found an unigene (Gga.9721) that upregulated in the chicken primordial germ cells (PGCs). The unigene showed 97% identities with an uncharacterized chicken cyclin F like gene. The predicted chicken cyclin F like gene was further characterized through expression and regulation in the chicken PGCs. The sequence analysis revealed that the gene shows identities with cyclin F gene and contains an F-box domain. The expression of chicken cyclin F like was detected specifically in the gonads, PGCs, and germline cells. The knockdown of cyclin F like gene resulted in DNA damage and apoptosis in the PGCs. The genes related to stemness and germness were downregulated, whereas, genes related to apoptosis and DNA damage response were increased in the PGCs after the knockdown of chicken cyclin F like. We further observed that the Nanog homeobox controlled the transcriptional activity of chicken cyclin F like gene in PGCs. Collectively, the chicken cyclin F like gene, which is not reported in any other species, is required for maintaining the genome stability of germ cells.
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Ciclinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Instabilidade Genômica , Células Germinativas/citologia , Animais , Apoptose , Proliferação de Células , Sobrevivência Celular , Galinhas , Dano ao DNA , Feminino , Masculino , Domínios Proteicos , RNA Interferente Pequeno/metabolismoRESUMO
2C (2C-x) is the general name for the family of phenethylamines containing two methoxy groups at the 2 and 5 positions of the benzene ring. The abuse of 2C family drugs has grown rapidly, although the abuse potential and neurotoxic properties of 2C drugs have not yet been fully investigated. In this study, we investigated the abuse potential and neurotoxicity of 4-chloro-2,5-dimethoxyphenethylamine (2C-C) and 2,5-dimethoxy-4-propylphenethylamine (2C-P). We found that 2C-C and 2C-P produced conditioned place preference in a dose-dependent manner in mice, and increased self-administration in rats, suggesting that 2C-C and 2C-P have abuse potential. To investigate the neurotoxicity of 2C-C and 2C-P, we examined motor performance and memory impairment after high doses of 2C-C and 2C-P. High doses of 2C-C and 2C-P decreased locomotor activity, rota-rod performance, and lower Y-maze test, novel objective recognition test, and passive avoidance test scores. We also observed that 2C-C and 2C-P affected expression levels of the D1 dopamine receptor, D2 dopamine receptor, dopamine transporter, and phospho-dopamine transporter in the nucleus accumbens and the medial prefrontal cortex, and increased c-Fos immuno-positive cells in the nucleus accumbens. Moreover, high doses of 2C-C and 2C-P induced microglial activation, which is involved in the inflammatory reaction in the striatum. These results suggest that 2C-C and 2C-P have abuse potential by affecting dopaminergic signaling and induce neurotoxicity via initiating neuroinflammation at high doses.
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Drogas Desenhadas/toxicidade , Síndromes Neurotóxicas/etiologia , Fenetilaminas/toxicidade , Animais , Drogas Desenhadas/administração & dosagem , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Inflamação/induzido quimicamente , Inflamação/patologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Síndromes Neurotóxicas/fisiopatologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Fenetilaminas/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Cancer targeting nanoparticles have been extensively studied, but stable and applicable agents have yet to be developed. Here, we report stable nanoparticles based on hepatitis B core antigen (HBcAg) for cancer therapy. HBcAg monomers assemble into spherical capsids of 180 or 240 subunits. HBcAg was engineered to present an affibody for binding to human epidermal growth factor receptor 1 (EGFR) and to present histidine and tyrosine tags for binding to gold ions. The HBcAg engineered to present affibody and tags (HAF) bound specifically to EGFR and exterminated the EGFR-overexpressing adenocarcinomas under alternating magnetic field (AMF) after binding with gold ions. Using cryogenic electron microscopy (cryo-EM), we obtained the molecular structures of recombinant HAF and found that the overall structure of HAF was the same as that of HBcAg, except with the affibody on the spike. Therefore, HAF is viable for cancer therapy with the advantage of maintaining a stable capsid form. If the affibody in HAF is replaced with a specific sequence to bind to another targetable disease protein, the nanoparticles can be used for drug development over a wide spectrum.
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Adenocarcinoma/metabolismo , Antígenos do Núcleo do Vírus da Hepatite B/química , Nanopartículas/química , Microscopia Crioeletrônica , Receptores ErbB/metabolismo , Ouro/química , Células HT29 , Humanos , Nanopartículas/ultraestrutura , Ligação Proteica , Proteínas Recombinantes/químicaRESUMO
The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects. Considering that NPSs have caused unexpected harmful effects leading to emergency and even death, scientific confirmation of the potential adverse effects of 25C-NBF is essential. In the present study, we investigated whether 25C-NBF has addictive and neurotoxic potential and causes neurochemical changes. In addictive potential assessments, high conditioned place preference (CPP) scores and stable self-administration (SA) were observed in the 25C-NBF groups (CPP [3 mg kg-1]; SA [0.01, 0.03, 0.1 mg kg-1]), suggesting the addictive liability of 25C-NBF. In neurotoxic potential assessments, 25C-NBF treatment (single super-high dose [1 × 15, 30, 40 mg kg-1]; repeated high dose [4 × 8, 15, 30 mg kg-1]) resulted in reduced motor activity (open field test), abnormal motor coordination (rota-rod test) and impaired recognition memory (novel object recognition test), suggesting that 25C-NBF is neurotoxic leading to motor impairment and memory deficits. Subsequently, immunohistochemistry showed that 25C-NBF treatment decreased tyrosine hydroxylase (TH) expression and increased ionized calcium-binding adapter molecule 1 (Iba-1) expression in the striatum. Taken together, our results clearly demonstrate the dangers of recreational use of 25C-NBF, and we suggest that people stop using 25C-NBF and other NPSs whose pharmacological effects are not precisely known.
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Comportamento Aditivo/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Fenetilaminas/toxicidade , Psicotrópicos/toxicidade , Transtornos Relacionados ao Uso de Substâncias/etiologia , Animais , Comportamento Aditivo/metabolismo , Comportamento Aditivo/psicologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Proteínas de Ligação ao Cálcio/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Proteínas dos Microfilamentos/metabolismo , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Teste de Campo Aberto/efeitos dos fármacos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/psicologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Metal halide perovskites are promising candidates for use in light emitting diodes (LEDs), due to their potential for color tunable and high luminescence efficiency. While recent advances in perovskite-based light emitting diodes have resulted in external quantum efficiencies exceeding 12.4% for the green emitters, and infrared emitters based on 3 D/2D mixed dimensional perovskites have exceeded 20%, the external quantum efficiencies of the red and blue emitters still lag behind. A critical issue to date is creating highly emissive and stable perovskite emitters with the desirable emission band gap to achieve full-color displays and white LEDs. Herein, we report the preparation and characterization of a highly luminescent and stable suspension of cubic-shaped methylammonium lead triiodide (CH3NH3PbI3) perovskite nanocrystals, where we synthesize the nanocrystals via a ligand-assisted reprecipitation technique, using an acetonitrile/methylamine compound solvent system to solvate the ions and toluene as the antisolvent to induce crystallization. Through tuning the ratio of the ligands, the ligand to toluene ratio, and the temperature of the toluene, we obtain a solution of CH3NH3PbI3 nanocrystals with a photoluminescence quantum yield exceeding 93% and tunable emission between 660 and 705 nm. We also achieved red emission at 635 nm by blending the nanocrystals with bromide salt and obtained perovskite-based light emitting diodes with maximum electroluminescent external quantum efficiency of 2.75%.
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Here, a simplified synthesis of graphitic carbon nitride quantum dots (g-C3 N4 -QDs) with improved solution and electroluminescent properties using a one-pot methylamine intercalation-stripping method (OMIM) to hydrothermally exfoliate QDs from bulk graphitic carbon nitride (g-C3 N4 ) is presented. The quantum dots synthesized by this method retain the blue photoluminescence with extremely high fluorescent quantum yield (47.0%). As compared to previously reported quantum dots, the g-C3 N4 -QDs synthesized herein have lower polydispersity and improved solution stability due to high absolute zeta-potential (-41.23 mV), which combine to create a much more tractable material for solution processed thin film fabrication. Spin coating of these QDs yields uniform films with full coverage and low surface roughness ideal for quantum dot light-emitting diode (QLED) fabrication. When incorporated into a functional QLED with OMIM g-C3 N4 -QDs as the emitting layer, the LED demonstrates ≈60× higher luminance (605 vs 11 Cd m-2 ) at lower operating voltage (9 vs 21 V), as compared to the previously reported first generation g-C3 N4 QLEDs, though further work is needed to improve device stability.
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As a potential treatment of type 2 diabetes, a novel PPARγ non-TZD full agonist, compound 18 (BR102375) was identified from the original lead BR101549 by the SAR efforts of the labile metabolite control through bioisosteres approach. In vitro assessments of BR102375 demonstrated its activating potential of PPARγ comparable to Pioglitazone as well as the induction of related gene expressions. Further in vivo evaluation of BR102375 in diabetic rodent models successfully proved its glucose lowering effect as a potential antidiabetic agent, but the anticipated suppression of weight gain was not evident. The X-ray co-crystal analysis of BR102375-PPARγ LBD unexpectedly revealed binding modes totally different from those of BR101549, which was found, instead, closely resembled to those of TZD full agonists.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Hipoglicemiantes/farmacologia , Oxidiazóis/farmacologia , PPAR gama/agonistas , Cristalografia por Raios X , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Modelos Moleculares , Estrutura Molecular , Oxidiazóis/química , PPAR gama/metabolismo , Relação Estrutura-AtividadeRESUMO
The new class of PPARgamma non-TZD agonist originally derived from the backbone of anti-hypertensive Fimasartan, BR101549, was identified as a potential lead for anti-diabetic drug development. The X-ray crystallography of BR101549 with PPARgamma ligand binding domain (LBD) revealed unique binding characteristics versus traditional TZD full agonists. The lead candidate, BR101549, has been found activating PPARgamma to the level of Pioglitazone in vitro and indeed has demonstrated its effects on blood glucose control in mouse proof-of-concept evaluation. The attempts to improve its metabolic stability profile through follow-up SAR including deuterium incorporation have been also described.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Oxidiazóis/uso terapêutico , PPAR gama/agonistas , Pirimidinas/uso terapêutico , Pirimidinonas/uso terapêutico , Células 3T3-L1 , Animais , Humanos , Camundongos , Estudo de Prova de Conceito , Pirimidinonas/farmacologia , Relação Estrutura-AtividadeRESUMO
Lespedeza bicolor, a traditional herbal medicine widely used in Australia, North America, and Eastern Asia, has various therapeutic effects on inflammation, nephritis, hyperpigmentation, and diuresis. In this study, to evaluate the effects of L. bicolor on cognitive function, we examined whether L. bicolor improved amyloid beta-induced memory impairment and assessed the possible mechanisms in mice. Catechin, rutin, daidzein, luteolin, naringenin, and genistein were identified in the powdered extract of L. bicolor by HPCL-DAD analyses. In behavioral experiments, L. bicolor (25 and 50 mg/kg, p.âo.) significantly improved amyloid beta25â-â35 (6 nmol, intracerebroventricular)-induced cognitive dysfunction in the Y-maze, novel recognition, and passive avoidance tests. Our molecular studies showed L. bicolor (25 and 50 mg/kg, p.âo.) significantly recovered the reduced glutathione content as well as increased thiobarbituric acid reactive substance and acetylcholinesterase activities in the hippocampus. Furthermore, we found that L. bicolor significantly increased the expression of brain-derived neurotrophic factor, and phospho-Akt, extracellular signal-regulated kinase, and cAMP response element binding caused by amyloid beta25â-â35 in the hippocampus. In conclusion, L. bicolor exerts a potent memory-enhancing effect on cognitive dysfunction induced by amyloid beta25â-â35 in mice.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Lespedeza/química , Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Peptídeos beta-Amiloides , Animais , Cognição/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Fragmentos de Peptídeos , Transdução de Sinais/efeitos dos fármacos , Regulação para CimaRESUMO
Chronic neuroinflammation is a common feature of the aged brain, and its association with the major neurodegenerative changes involved in cognitive impairment and motor dysfunction is well established. One of the most potent antiaging interventions tested so far is dietary restriction (DR), which extends the lifespan in various organisms. Microglia and astrocytes are two major types of glial cells involved in the regulation of neuroinflammation. Accumulating evidence suggests that the age-related proinflammatory activation of astrocytes and microglia is attenuated under DR. However, the molecular mechanisms underlying DR-mediated regulation of neuroinflammation are not well understood. Here, we review the current understanding of the effects of DR on neuroinflammation and suggest an underlying mechanistic link between DR and neuroinflammation that may provide novel insights into the role of DR in aging and age-associated brain disorders.
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Astrócitos/metabolismo , Inflamação/metabolismo , Microglia/metabolismo , Animais , Astrócitos/imunologia , Encefalopatias/imunologia , Encefalopatias/metabolismo , Restrição Calórica , Humanos , Inflamação/imunologia , Microglia/imunologiaRESUMO
The endocytosis-mediating performances of two types of peptide ligands, cell receptor binding peptide (CRBP) and cell membrane penetrating peptide (CMPP), were analyzed and compared using a common carrier of peptide ligands-human ferritin heavy chain (hFTH) nanoparticle. Twenty-four copies of a CMPP(human immunodeficiency virus-derived TAT peptide) and/or a CRBP (peptide ligand with strong and specific affinity for either human integrin(αv ß3 ) or epidermal growth factor receptor I (EGFR) that is overexpressed on various cancer cells) were genetically presented on the surface of each hFTH nanopariticle. The quantitative level of endocytosis and intracellular localization of fluorescence dye-labeled CRBP- and CMPP-presenting nanoparticles were estimated in the in vitro cultures of integrin- and EGFR-overexpressing cancer and human dermal fibroblast cells(control). From the cancer cell cultures treated with the CMPP- and CRBP-presenting nanoparticles, it was notable that CRBPs resulted in quantitatively higher level of endocytosis than CMPP (TAT) and successfully transported the nanoparticles to the cytosol of cancer cells depending on concentration and treatment period of time, whereas TAT-mediated endocytosis localized most of the nanoparticles within endosomal vesicles under the same conditions. These novel findings provide highly useful informations to many researchers both in academia and in industry who are interested in developing anticancer drug delivery systems/carriers.