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Pholiota adiposa is an edible chestnut mushroom with many health benefits, such as antioxidant and anticancer activity. In this paper, polysaccharides were extracted from Pholidota adiposa using an acid extraction process. The crude polysaccharide was purified using DEAE-cellulose chromatography, and two polysaccharide fractions of SPAP2-1 and SPAP2-2 were obtained. The structure was characterized using UV, GPC, GC, FT-IR, methylation, and NMR analysis. Monosaccharide component analysis indicated that SPAP2-1 (19 kDa) and SPAP2-2 (20 kDa) contained mannose, glucose, and galactose with different molecular ratios. Their antitumor effects were investigated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium (MTT) assay, Annexin V-fluorescein isothiocyanate (FITC), propidium iodide (PI) staining, and flow cytometry. By analyzing the changes in the cells, SPAP2-1 caused damage and changed the proliferation rate of HeLa cells. SPAP2-1 showed strong interference to the cell cycle of HeLa cells and induced cell apoptosis. Overall, these results suggested that polysaccharides from Pholiota adiposa, especially SPAP2-1, may have the potential to be used as a tumor cell inhibitor, which needs further study.
Assuntos
Pholiota , Células HeLa , Humanos , Polissacarídeos/química , Polissacarídeos/farmacologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
Inonotus hispidus is a traditional medicinal that grows in Northeast China and produces various economically important compounds, including polysaccharide compounds and terpenoids; triterpenoid saponins is the main bioactive component. Our research group has found that the accumulation of triterpenoid was affected by exogenous inducers. Experimental results showed that treatment with methyl jasmonate (MeJA) and oleic acid significantly increased the triterpenoid content of I. hispidus. However, how exogenous inducers enhance production of secondary metabolites in I. hispidus is not well understood. In this study, metabolite changes were further investigated with UPLC-TOF/MS following exogenous inducer treatment. As a result, a total of eight types of triterpenoids in I. hispidus were identified. The RNA-seq analysis was used to evaluate the effects of exogenous inducers on the expression of triterpenoid-synthesis-related genes in I. hispidus in liquid fermentation. This study is the first exploration to profile the transcriptome of I. hispidus after adding exogenous inducers; the generated data and gene will facilitate further molecular studies on the physiology and metabolism in this fungi. By comparative transcriptomic analysis, a series of candidate genes involved in the biosynthetic pathway of triterpenoids are identified, providing new insights into their biosynthesis at the transcriptome level.
Assuntos
Triterpenos , RNA-Seq , Triterpenos/farmacologia , Transcriptoma , Perfilação da Expressão Gênica , Vias Biossintéticas/genéticaRESUMO
BACKGROUND: Atherosclerosis progression is modulated by interactions with the adaptive immune system. Humoral immunity can help protect against atherosclerosis formation; however, the existence, origin, and function of putative atherogenic antibodies are controversial. How such atherosclerosis-promoting antibodies could affect the specific composition and stability of plaques, as well as the vasculature generally, remains unknown. METHODS: We addressed the overall contribution of antibodies to atherosclerosis plaque formation, composition, and stability in vivo (1) with mice that displayed a general loss of antibodies, (2) with mice that had selectively ablated germinal center-derived IgG production, or (3) through interruption of T-B-cell interactions and further studied the effects of antibody deficiency on the aorta by transcriptomics. RESULTS: Here, we demonstrate that atherosclerosis-prone mice with attenuated plasma cell function manifest reduced plaque burden, indicating that antibodies promote atherosclerotic lesion size. However, the composition of the plaque was altered in antibody-deficient mice, with an increase in lipid content and decreases in smooth muscle cells and macrophages, resulting in an experimentally validated vulnerable plaque phenotype. Furthermore, IgG antibodies enhanced smooth muscle cell proliferation in vitro in an Fc receptor-dependent manner, and antibody-deficient mice had decreased neointimal hyperplasia formation in vivo. These IgG antibodies were shown to be derived from germinal centers, and mice genetically deficient for germinal center formation had strongly reduced atherosclerosis plaque formation. mRNA sequencing of aortas revealed that antibodies are required for the sufficient expression of multiple signal-induced and growth-promoting transcription factors and that aortas undergo large-scale metabolic reprograming in their absence. Using an elastase model, we demonstrated that absence of IgG results in an increased severity of aneurysm formation. CONCLUSIONS: We propose that germinal center-derived IgG antibodies promote the size and stability of atherosclerosis plaques, through promoting arterial smooth muscle cell proliferation and maintaining the molecular identity of the aorta. These results could have implications for therapies that target B cells or B-T-cell interactions because the loss of humoral immunity leads to a smaller but less stable plaque phenotype.
Assuntos
Aorta/imunologia , Doenças da Aorta/imunologia , Aterosclerose/imunologia , Centro Germinativo/imunologia , Imunoglobulina G/imunologia , Placa Aterosclerótica , Animais , Antígenos CD19/genética , Antígenos CD19/metabolismo , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Centro Germinativo/metabolismo , Imunoglobulina G/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Fator 1 de Ligação ao Domínio I Regulador Positivo/deficiência , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Ruptura Espontânea , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
RATIONALE: In the search for markers and modulators of vascular disease, microRNAs (miRNAs) have emerged as potent therapeutic targets. OBJECTIVE: To investigate miRNAs of clinical interest in patients with unstable carotid stenosis at risk of stroke. METHODS AND RESULTS: Using patient material from the BiKE (Biobank of Karolinska Endarterectomies), we profiled miRNA expression in patients with stable versus unstable carotid plaque. A polymerase chain reaction-based miRNA array of plasma, sampled at the carotid lesion site, identified 8 deregulated miRNAs (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210, and miR-500). miR-210 was the most significantly downregulated miRNA in local plasma material. Laser capture microdissection and in situ hybridization revealed a distinct localization of miR-210 in fibrous caps. We confirmed that miR-210 directly targets the tumor suppressor gene APC (adenomatous polyposis coli), thereby affecting Wnt (Wingless-related integration site) signaling and regulating smooth muscle cell survival, as well as differentiation in advanced atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable in 2 rodent models of vascular remodeling and plaque rupture. Modulating miR-210 in vitro and in vivo improved fibrous cap stability with implications for vascular disease. CONCLUSIONS: An unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic vascular events.
Assuntos
MicroRNAs/administração & dosagem , MicroRNAs/biossíntese , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/terapia , Animais , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/terapia , Estenose das Carótidas/metabolismo , Estenose das Carótidas/patologia , Estenose das Carótidas/terapia , Células Cultivadas , Estudos de Coortes , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Microdissecção e Captura a Laser/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/análise , Placa Aterosclerótica/patologia , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
Activation of both adenosine A2A and A2B receptors (A2BR) contributes to coronary vasodilation. We previously demonstrated that uridine adenosine tetraphosphate (Up4A) is a novel vasodilator in the porcine coronary microcirculation, acting mainly on A2AR in smooth muscle cells (SMC). We further investigated whether activation of A2BR is involved in Up4A-mediated coronary SMC relaxation. Both A2AR and A2BR may stimulate H2O2 production leading to activation of KATP channels in SMCs, we also studied the involvement of H2O2 and KATP channels in Up4A-mediated effect. Coronary small arteries dissected from the apex of porcine hearts were mounted on wire myograph for Up4A concentration responses. Up4A-induced coronary SMC relaxation was attenuated by A2AR but not A2BR antagonism or non-selective P2R antagonism, despite greater endogenous A2BR expression vs. A2AR in both coronary small arteries and primary cultured coronary SMCs. Moreover, Up4A-induced coronary SMC relaxation was blunted by H2O2 catabolism. This effect was not altered by KATP channel blockade. Combination of H2O2 catabolism and A2AR antagonism attenuated Up4A-induced coronary SMC relaxation to the similar extent as A2AR antagonism alone. Collectively, Up4A-induced porcine coronary SMC relaxation is mediated by activation of A2AR-H2O2 pathway. This process does not involve A2BR, P2R or KATP channels.
Assuntos
Vasos Coronários/efeitos dos fármacos , Fosfatos de Dinucleosídeos/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Receptor A2A de Adenosina/metabolismo , Receptor A2A de Adenosina/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Células Cultivadas , Circulação Coronária/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Microcirculação/efeitos dos fármacos , Receptor A2B de Adenosina , SuínosRESUMO
miRNAs are potential regulators of carotid artery stenosis and concordant vulnerable atherosclerotic plaques. Hence, we analyzed miRNA expression in laser captured micro-dissected fibrous caps of either ruptured or stable plaques (n = 10 each), discovering that miR-21 was significantly downregulated in unstable lesions. To functionally evaluate miR-21 in plaque vulnerability, miR-21 and miR-21/apolipoprotein-E double-deficient mice (Apoe-/-miR-21-/-) were assessed. miR-21-/- mice lacked sufficient smooth muscle cell proliferation in response to carotid ligation injury. When exposing Apoe-/-miR-21-/- mice to an inducible plaque rupture model, they presented with more atherothrombotic events (93%) compared with miR-21+/+Apoe-/- mice (57%). We discovered that smooth muscle cell fate in experimentally induced advanced lesions is steered via a REST-miR-21-REST feedback signaling pathway. Furthermore, Apoe-/-miR-21-/- mice presented with more pronounced atherosclerotic lesions, greater foam cell formation, and substantially higher levels of arterial macrophage infiltration. Local delivery of a miR-21 mimic using ultrasound-targeted microbubbles into carotid plaques rescued the vulnerable plaque rupture phenotype. In the present study, we identify miR-21 as a key modulator of pathologic processes in advanced atherosclerosis. Targeted, lesion site-specific overexpression of miR-21 can stabilize vulnerable plaques.
Assuntos
Aterosclerose/genética , Aterosclerose/patologia , MicroRNAs/genética , Animais , Apoptose/genética , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/patologia , Modelos Animais de Doenças , Fibrose , Perfilação da Expressão Gênica , Técnicas de Transferência de Genes , Genótipo , Humanos , Imuno-Histoquímica , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/administração & dosagem , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologiaRESUMO
Aircraft service process is in a state of the composite load of pressure and temperature for a long period of time, which inevitably affects the inherent characteristics of some components in aircraft accordingly. The flow field of aircraft wing materials under different Mach numbers is simulated by Fluent in order to extract pressure and temperature on the wing in this paper. To determine the effect of coupling stress on the wing’s material and structural properties, the fluid-structure interaction (FSI) method is used in ANSYS-Workbench to calculate the stress that is caused by pressure and temperature. Simulation analysis results show that with the increase of Mach number, the pressure and temperature on the wing’s surface both increase exponentially and thermal stress that is caused by temperature will be the main factor in the coupled stress. When compared with three kinds of materials, titanium alloy, aluminum alloy, and Haynes alloy, carbon fiber composite material has better performance in service at high speed, and natural frequency under coupling pre-stressing will get smaller.
RESUMO
Uridine adenosine tetraphosphate (Up4A) exerts potent relaxation in porcine coronary arteries that is reduced following myocardial infarction, suggesting a crucial role for Up4A in the regulation of coronary flow (CF) in cardiovascular disorders. We evaluated the vasoactive effects of Up4A on CF in atherosclerosis using ApoE knockout (KO) mice ex vivo and in vivo. Functional studies were conducted in isolated mouse hearts using the Langendorff technique. Immunofluorescence was performed to assess purinergic P2X1 receptor (P2X1R) expression in isolated mouse coronary arteries. In vivo effects of Up4A on coronary blood flow (CBF) were assessed using ultrasound. Infusion of Up4A (10-9-10-5 M) into isolated mouse hearts resulted in a concentration-dependent reduction in CF in WT and ApoE KO mice to a similar extent; this effect was exacerbated in ApoE KO mice fed a high-fat diet (HFD). The P2X1R antagonist MRS2159 restored Up4A-mediated decreases in CF more so in ApoE KO + HFD than ApoE KO mice. The smooth muscle to endothelial cell ratio of coronary P2X1R expression was greater in ApoE KO + HFD than ApoE KO or WT mice, suggesting a net vasoconstrictor potential of P2X1R in ApoE KO + HFD mice. In contrast, Up4A (1.6 mg/kg) increased CBF to a similar extent among the three groups. In conclusion, Up4A decreases CF more in ApoE KO + HFD mice, likely through a net upregulation of vasoconstrictor P2X1R. In contrast, Up4A increases CBF in vivo regardless of the atherosclerotic model.
Assuntos
Aterosclerose/metabolismo , Circulação Coronária/efeitos dos fármacos , Fosfatos de Dinucleosídeos/farmacologia , Receptores Purinérgicos P2X1/metabolismo , Animais , Preparação de Coração Isolado , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Antagonistas do Receptor Purinérgico P2X/farmacologiaRESUMO
IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A-transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A-transgenic mice were treated with plasmid coding human IL-37 sequence-formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.
Assuntos
Inflamação/imunologia , Interleucina-1/metabolismo , Psoríase/imunologia , Animais , Linhagem Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Memória Imunológica/imunologia , Terapia de Imunossupressão , Interferon gama/genética , Interleucina-1/genética , Interleucina-10/metabolismo , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Queratina-14/genética , Queratinócitos/imunologia , Queratinócitos/metabolismo , Macrófagos/imunologia , Mastócitos/imunologia , Camundongos , Camundongos Transgênicos , Psoríase/metabolismo , Psoríase/patologia , Proteína A7 Ligante de Cálcio S100 , Proteínas S100/biossíntese , Pele/imunologia , Pele/patologia , Linfócitos T/imunologia , Transfecção , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Zn(1-x)Co(x)O (x = 0-0.07) single-crystalline nanorods were prepared by a modified microemulsion route. The crystalline structure, morphology, optical, and hysteresis loop at low and room temperature of as-prepared materials were characterized by XRD, TEM, PL spectra, and magnetic measurement respectively. The nanorods are 80-250 nm in diameter and about 3 µm in length. X-ray diffraction data, TEM images confirm that the materials synthesized in optimal conditions are ZnO:Co single crystalline solid solution without any impurities related to Co. The PL spectra show that the ferromagnetic samples exhibit strong Zn interstitials and oxygen vacancy emission indicating defects may stabilize ferromagnetic order in the obtained diluted magnetic semiconductors. Magnetic measurements show that the Zn(1-x)Co(x)O nanorods exist obvious ferromagnetic characteristics with T(c) above 300 K. M(s) and coercivities first increase and then decrease with dopant concentration increasing, reaching the highest for 3% doping level. The structural and magnetic properties of these samples support the hypothesis that the FM of DMS nanorods is due to a defect mediated mechanism instead of cobalt nanoclusters and carrier mediated.
Assuntos
Cobalto/química , Magnetismo , Nanotubos , Oxigênio/química , Óxido de Zinco/química , Microscopia Eletrônica de Transmissão , Difração de Raios XRESUMO
Vanillin is a commonly used synthetic flavoring agent in daily life. However, excessive intake of vanillin may pose risks to human health. Therefore, there is an urgent need for rapid and sensitive detection methods for vanillin. In this study, we developed a fluorescent sensor based on Cd-MOF for the sensitive and selective recognition of vanillin. The presence of vanillin leads to significant fluorescence quenching of Cd-MOF due to competitive absorption and photoinduced electron transfer (PET). The limit of detection was determined to be 39.6 nM, which is the lowest-among the reported fluorescent probes. The sensor was successfully applied for the detection of vanillin in real samples such as powdered milk and milk, with a recovery rate ranging from 96.88 % to 104.83 %. Furthermore, by immobilizing the Cd-MOF probe into a polyvinyl alcohol (PVA) film, we achieved a portable and visual detection composite materials for vanillin.
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Aniline is an organic pollutant with carcinogenicity and teratogenicity, while F- and Hg2+ are toxic ions that are easily soluble in water. When they are released to the environment, they will pose a threat to human health. Designing a material that can simultaneously detect three types of pollutants is of great significance. In this paper, a novel rare earth metal organic framework material (Eu-MOF) with three-dimensional structure based on 1-methylimidazole-4,5-dicarboxylic acid was synthesized for the first time through solvent thermal method. It has excellent luminescent performance and can be used as a multifunctional fluorescent probe to detect aniline, F-, and Hg2+ based on photoinduced electron transfer, energy competitive absorption, and ion exchange mechanisms, with detection limits of 1.79 × 10-8, 8.13 × 10-8, and 8.83 × 10-7 M, respectively. It is worth noting that Eu-MOF can detect F- and Hg2+ in real water samples, such as lake water and green tea water, with favorable recovery rates.
RESUMO
A novel class of acetylhydrazone derivatives (5a-x) containing 2-(phenylthiomethyl)-1H-benzo-[d]-imidazole moieties are synthesizer, and their antitumor activities against A549, HCT116, HepG2, PC-9, and A375 were determined by the MTT assay. Among them are N-(2,4-dihydroxybenzylidene)-2-(2-(phenylthiomethyl)-1H-benzo[d]-imidazol-1-yl)acetohydrazide (5a) and N-(5-bromo-2-hydroxy-benzylidene)-2-(2-(phenylthiomethyl)-1H-benzo[d]-imidazol-1-yl)acetohydrazide (5d) which displayed excellent cancer inhibitory activity against the tested cancer cells (IC(50) 4-17 µM), compared with 5-FU and SU11248. The others have moderate to weak inhibitory activity against the tested cancer cell lines.
Assuntos
Antineoplásicos/síntese química , Hidrazonas/síntese química , Imidazóis/síntese química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrazonas/farmacologia , Imidazóis/farmacologia , Concentração Inibidora 50 , Relação Estrutura-AtividadeRESUMO
In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, 1a and 1b, were found. However, the poor solubility of 1a and 1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through introducing N-methyl-piperazine groups at the 2-position and 6-position. To our delight, the optimized analogue 1d showed comparable antiproliferative activity in vitro with better solubility, compared with 1a. Based on this result, the replacement of the benzothiazole scaffold with benzimidazole and benzoxazole moieties afforded 1f and 1g, whose activities were fundamentally retained. In the preliminary in vitro biological evaluation, the immunofluorescence staining of HCT116 cells indicated that 1d, 1f and 1g led to cytosolic vacuolization which was not induced by 1a at low micromolecular concentrations. These results suggest that these optimized compounds might potentially constitute a novel class of anticancer agents, which merit further studies.
Assuntos
Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Benzotiazóis/farmacologia , Benzoxazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Benzimidazóis/síntese química , Benzimidazóis/química , Benzotiazóis/síntese química , Benzotiazóis/química , Benzoxazóis/síntese química , Benzoxazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Solubilidade , Relação Estrutura-AtividadeRESUMO
In the title complex, [Co(C(10)H(7)O(4))(2)(C(12)H(12)N(2))(H(2)O)(2)](n), the Co(II) ion is located on a crystallographic centre of symmetry and is six-coordinated by two N atoms from two 1,2-bis-(4-pyrid-yl)ethane ligands, two carboxylate O atoms from two 1,3-dihydro-3-oxo-1-isobenzofuran-acetate ligands and two terminal water ligands. The 1,2-bis(4-pyrid-yl)ethane ligands act as bidentate ligands, and bridge the Co(II) ions into infinite chains extending parallel to [010]. In these chains, there are intra-mol-ecular O-Hâ¯O hydrogen bonding between the coordination water mol-ecules and carboxyl-ate groups. Inter-mol-ecular O-Hâ¯O hydrogen bonding between the adjacent chains and πâ¯π stacking inter-actions result in the formation of a three-dimensional supra-molecular network.
RESUMO
In the title mol-ecule, C(28)H(18)O(10), the two central benzene rings form a dihedral angle of 31.0â (1)°. In the phthalic acid fragments, the carb-oxy groups in the meta positions are approximately coplanar with the attached benzene rings, being inclined to their planes at 2.7â (1) and 10.3â (1)°, while the carb-oxy groups in the ortho positions are twisted from the benzene ring planes by 83.5â (1) and 75.4â (1)°. In the crystal, O-Hâ¯O hydrogen bonds link the mol-ecules into layers parallel to the bc plane. Weak C-Hâ¯O hydrogen bonds and π-π inter-actions between the aromatic rings [centroid-centroid distance = 3.7674â (3)â Å] further consolidate the crystal packing.
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Red blood cells (RBC) act as mediators of vascular injury in type 2 diabetes mellitus (T2DM). miR-210 plays a protective role in cardiovascular homeostasis and is decreased in whole blood of T2DM mice. We hypothesized that downregulation of RBC miR-210 induces endothelial dysfunction in T2DM. RBC were coincubated with arteries and endothelial cells ex vivo and transfused in vivo to identify the role of miR-210 and its target protein tyrosine phosphatase 1B (PTP1B) in endothelial dysfunction. RBC from patients with T2DM and diabetic rodents induced endothelial dysfunction ex vivo and in vivo. miR-210 levels were lower in human RBC from patients with T2DM (T2DM RBC) than in RBC from healthy subjects. Transfection of miR-210 in human T2DM RBC rescued endothelial function, whereas miR-210 inhibition in healthy subjects RBC or RBC from miR-210 knockout mice impaired endothelial function. Human T2DM RBC decreased miR-210 expression in endothelial cells. miR-210 expression in carotid artery plaques was lower in T2DM patients than in patients without diabetes. Endothelial dysfunction induced by downregulated RBC miR-210 involved PTP1B and reactive oxygen species. miR-210 mimic attenuated endothelial dysfunction induced by RBC via downregulating vascular PTP1B and oxidative stress in diabetic mice in vivo. These data reveal that the downregulation of RBC miR-210 is a novel mechanism driving the development of endothelial dysfunction in T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Endotélio Vascular/fisiopatologia , Eritrócitos/metabolismo , MicroRNAs/genética , Animais , Estudos de Casos e Controles , Células Cultivadas , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/genética , Angiopatias Diabéticas/metabolismo , Angiopatias Diabéticas/fisiopatologia , Endotélio Vascular/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 1/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Currently, designing novel noble-metal-free photocatalysts with efficient carriers migration and catalytically active sites have been a researching hotspot in photocatalytic hydrogen evolution. In this paper, a novel noble-metal-free Mo2C-In2S3 heterojunction was synthesized by a simple hydrothermal method. Morphology characterization revealed In2S3 was attached to Mo2C. Electrochemical results showed Mo2C improved the interface conductivity, and promoted the transportation of photogenerated carriers. Under visible light, the optimal Mo2C-In2S3 composite achieved a H2 generation rate of 535.58 µmol h-1 g-1, which was 175.6 and 25.8 times higher than pristine In2S3 (3.05 µmol h-1 g-1) and In2S3-1% Pt (20.73 µmol h-1 g-1). In addition, a reasonable mechanism of the elevated photocatalytic activity was also discussed. This study demonstrates commercial Mo2C has an important effect of separating carriers and replacing Pt as co-catalyst in heterojunctions. This research also provides a method to design and synthesize new noble-metal-free photocatalysts for excellent hydrogen production activity.
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CD38 is a multifunctional enzyme that has both ADP-ribosyl cyclase and cADPR hydrolase activities, being capable of cleaving NAD(+) to cyclic ADP ribose (cADPR) and hydrolyzing cADPR to ADPR. It has been reported that there is markedly a reduction of cADPR and elevation of NAD in many tissues from CD38 knockout (CD38(-/-)) mice. Cyclic ADPR is a potent second messenger for intracellular Ca(2+) mobilization, and NAD is a key cellular metabolite for cellular energetic and a crucial regulator for multiple signaling pathways in cells. We hypothesize that CD38 knockout may have a protective effect in oxidative stresses through elevating NAD and decreasing cADPR. In the present study, we observed that the mouse embryonic fibroblasts (MEFs) from CD38(-/-) mice were significantly resistant to oxidative stress such as H(2)O(2) injury and hypoxia/reoxygenation compared with wild type MEFs (WT MEFs). We further found that production of reactive oxygen species (ROS) and concentrations of intracellular Ca(2+) ([Ca(2+)](i)) in CD38(-/-) MEFs were markedly reduced compared with WT MEFs during hypoxia/reoxygenation. Coincidence with these results, a remarkably lower mRNA level of Nox1, one of the enzymes responsible for ROS generation, was observed in CD38(-/-) MEFs. Furthermore, we found that transcription of Nox1 mRNA in WT MEFs could be elevated by calcium ionophore ionomycin in a dose-dependent manner, indicating that the expression of Nox1 mRNA can be regulated by elevation of intracellular [Ca(2+)]. Therefore we concluded that CD38(-/-) MEFs are resistant to oxidative stresses through inhibiting intracellular Ca(2+) overload and ROS production which may be regulated by Ca(2+)-mediated inhibition of Nox1 expression. Our data should provide an insight for elucidating the roles of CD38 in oxidative stresses and a novel perspective of dealing with the ischemia/reperfusion-related diseases.
Assuntos
ADP-Ribosil Ciclase 1/genética , Cálcio/metabolismo , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Animais , Embrião de Mamíferos/citologia , Fibroblastos/enzimologia , Camundongos , Camundongos Knockout , NADH NADPH Oxirredutases/biossíntese , NADPH Oxidase 1RESUMO
A new Schiff base derivative fluorescence-colorimetric chemosensor 2-hydroxy-5-[(2-hydroxy-1-naphthyl)methylideneamino]benzoic acid (H3L), has been designed and synthesized. H3L displayed high selectivity and sensitivity for detecting Cr3+, Cu2+, Fe3+ and Al3+ ions in DMF/H2O (v/vâ¯=â¯1/1) solution. When Cr3+, Cu2+ or Fe3+ ions were added, the solution of H3L in DMF/H2O exhibited different color changes. While with the addition of Fe3+ or Al3+ ions, the solution of H3L in DMF/H2O displayed different fluorescence responses. The bonding modes and bonding ratios of H3L and metal ions were explored by the Job's plot, 1H NMR titration, and electrospray ionization mass spectrometry (ESI-MS). The detection limits of H3L with Cr3+, Cu2+, Fe3+and Al3+ ions were 3.37â¯×â¯10-7â¯M, 4.65â¯×â¯10-7â¯M, 3.58â¯×â¯10-7â¯M and 4.89â¯×â¯10-7â¯M, respectively.