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Non-small-cell lung cancer (NSCLC), a common malignant tumor, requires deeper pathogenesis investigation. Autophagy is an evolutionarily conserved lysosomal degradation process that is frequently blocked during cancer progression. It is an urgent need to determine the novel autophagy-associated regulators in NSCLC. Here, we found that pirin was upregulated in NSCLC, and its expression was positively correlated with poor prognosis. Overexpression of pirin inhibited autophagy and promoted NSCLC proliferation. We then performed data-independent acquisition-based quantitative proteomics to identify the differentially expressed proteins (DEPs) in pirin-overexpression (OE) or pirin-knockdown (KD) cells. Among the pirin-regulated DEPs, ornithine decarboxylase 1 (ODC1) was downregulated in pirin-KD cells while upregulated along with pirin overexpression. ODC1 depletion reversed the pirin-induced autophagy inhibition and pro-proliferation effect in A549 and H460 cells. Immunohistochemistry showed that ODC1 was highly expressed in NSCLC cancer tissues and positively related with pirin. Notably, NSCLC patients with pirinhigh/ODC1high had a higher risk in terms of overall survival. In summary, we identified pirin and ODC1 as a novel cluster of prognostic biomarkers for NSCLC and highlighted the potential oncogenic role of the pirin/ODC1/autophagy axis in this cancer type. Targeting this pathway represents a possible therapeutic approach to treat NSCLC.
Assuntos
Autofagia , Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Ornitina Descarboxilase , Feminino , Humanos , Masculino , Células A549 , Autofagia/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Ornitina Descarboxilase/metabolismo , Ornitina Descarboxilase/genética , Prognóstico , Regulação para CimaRESUMO
Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell-specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell-derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX)-induced bone loss and age-related osteoporosis; (iii) MYDGF inhibited osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro; and (iv) PKCß-NF-κB and MAPK1/3-STAT3 pathways were involved in the regulation of MYDGF on bone metabolism. Thus, we concluded that myeloid cell-derived MYDGF is a positive regulator of bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF may become a potential novel therapeutic drug for osteoporosis, and bone marrow may become a potential therapeutic target for bone metabolic disorders.
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Reabsorção Óssea , Interleucinas , Osteogênese , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/prevenção & controle , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Interleucinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteogênese/genéticaRESUMO
BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high-throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low-, medium- and high-concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low-, medium- and high-concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different-concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid-ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti-ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry.
Assuntos
Antiulcerosos , Úlcera Gástrica , Camundongos , Animais , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Antioxidantes/metabolismo , Ácido Clorídrico , Úlcera/tratamento farmacológico , Úlcera/metabolismo , Antiulcerosos/metabolismo , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Etanol/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Extratos Vegetais/metabolismo , Aminoácidos/metabolismo , Mucosa Gástrica/metabolismoRESUMO
Six new ursane-type triterpenes with a phenylpropanoid unit and five known oleanane-type triterpenes were isolated from the leaves of Camellia ptilosperma. The undescribed compounds were identified by analysis of 1D and 2D NMR and HRESIMS spectroscopic data as ptilospermanols A-F. The cytotoxicity of new compounds against six human cancer cell lines and three mouse tumor cell lines was evaluated by MTT assay.
Assuntos
Antineoplásicos Fitogênicos , Antineoplásicos , Camellia , Triterpenos , Humanos , Animais , Camundongos , Triterpenos/farmacologia , Triterpenos/química , Camellia/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Estrutura Molecular , Linhagem Celular TumoralRESUMO
A novel short-chain alcohol dehydrogenase from Tarenaya hassleriana labeled as putative tropinone reductase was heterologously expressed in Escherichia coli. Purified recombinant protein had molecular weight of approximately 30 kDa on 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. T. hassleriana tropinone reductase-like enzyme (ThTRL) had not detected oxidative activity. The optimum pH for enzyme activity of ThTRL was weakly acidic (pH 5.0). 50°C was the optimum temperature for ThTRL. The highest catalytic efficiency and substrate affinity for recombinant ThTRL were observed with (+)-camphorquinone (kcat /Km = 814.3 s-1 mM-1 , Km = 44.25 µM). ThTRL exhibited a broad substrate specificity and reduced various carbonyl compounds, including small lipophilic aldehydes and ketones, terpene ketones, and their structural analogs.
Assuntos
Oxirredutases do Álcool , Escherichia coli , Especificidade por Substrato , Oxirredutases do Álcool/química , Proteínas Recombinantes/química , Escherichia coli/genética , Escherichia coli/metabolismo , Cetonas/metabolismo , Cinética , Peso MolecularRESUMO
BACKGROUND: Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive. RESULTS: In this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug-drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy. CONCLUSION: A novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system.
Assuntos
Camptotecina/administração & dosagem , Camptotecina/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Terapia Fototérmica/métodos , Pró-Fármacos/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Feminino , Humanos , Verde de Indocianina , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fototerapia , SolubilidadeRESUMO
AIMS/HYPOTHESIS: Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney disease (DKD). Here, we investigated whether MYDGF can prevent the progression of DKD. METHODS: In vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of MYDGF on albuminuria and pathological glomerular lesions. We used streptozotocin-treated Mydgf knockout and wild-type mice on high fat diets to induce a model of DKD. Then, albuminuria, glomerular lesions and podocyte injury were evaluated in Mydgf knockout and wild-type DKD mice treated with adeno-associated virus-mediated Mydgf gene transfer. In vitro and ex vivo experiments, the expression of slit diaphragm protein nephrin and podocyte apoptosis were evaluated in conditionally immortalised mouse podocytes and isolated glomeruli from non-diabetic wild-type mice treated with recombinant MYDGF. RESULTS: MYDGF deficiency caused more severe podocyte injury in DKD mice, including the disruption of slit diaphragm proteins (nephrin and podocin) and an increase in desmin expression and podocyte apoptosis, and subsequently caused more severe glomerular injury and increased albuminuria by 39.6% compared with those of wild-type DKD mice (p < 0.01). Inversely, MYDGF replenishment attenuated podocyte and glomerular injury in both wild-type and Mydgf knockout DKD mice and then decreased albuminuria by 36.7% in wild-type DKD mice (p < 0.01) and 34.9% in Mydgf knockout DKD mice (p < 0.01). Moreover, recombinant MYDGF preserved nephrin expression and inhibited podocyte apoptosis in vitro and ex vivo. Mechanistically, the renoprotection of MYDGF was attributed to the activation of the Akt/Bcl-2-associated death promoter (BAD) pathway. CONCLUSIONS/INTERPRETATION: The study demonstrates that MYDGF protects podocytes from injury and prevents the progression of DKD, providing a novel strategy for the treatment of DKD. Graphical abstract.
Assuntos
Albuminúria/genética , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/genética , Interleucinas/genética , Podócitos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Albuminúria/metabolismo , Animais , Apoptose/genética , Desmina/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Dieta Hiperlipídica , Técnicas de Transferência de Genes , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Podócitos/patologia , Transdução de SinaisRESUMO
Achieving highly sensitive and selective detection of trace-level As(III) and clarifying the underlying mechanism is still a intractable problem. The electroanalysis of As(III) relies on the electrocatalytic ability of the sensing interface. Herein, we first adopt single-atom catalysts as the electrocatalyst in As(III) detection. Cobalt single-atoms anchored on nitrogen-doped carbon material (Co SAC) were found to have an extraordinary sensitivity of 11.44 µA ppb-1 with excellent stability and repeatability, which so far is the highest among non-noble metal nanomaterials. Co SAC also exhibited a superior selectivity toward As(III) compared with some bivalent heavy metal ions (HMIs). Combining X-ray absorption spectroscopy (XAFS), density functional theory (DFT) calculation, and reaction kinetics simulation, we demonstrated that Co single atoms stabilized in N2C2 support serve as active sites to catalyze H3AsO3 reduction via the formation of Co-O hybridization bond, leading to a lower energy barrier, promoting the breakage of As-O bonds. Importantly, the first electron transfer is the rate-limiting step of arsenic reduction and is found to be more favorable on Co-SAC both thermodynamically and kinetically. This work not only expands the potential applicaiton of single-atom catalysts in the detection and treatment of As(III), but also provides atomic-level catalytic insights into HMIs sensing interfaces.
RESUMO
Metal hydroxide nanomaterials are widely applied in the energy and environment fields. The electrochemical performance of such materials is strongly dependent on their crystal phases. However, as there are always multiple factors relating to the phase-dependent electrochemistry, it is still difficult to identify the determining one. The well-defined crystal phases of α- and ß-FeOOH nanorods are characterized through the transmission electron microscopy by a series of rotation toward one rod, where the cross-section shape and the growth direction along the [001] crystalline are first verified for 1D FeOOH nanostructures. The electrosensitivity of the two materials toward Pb(II) is tested, where α-FeOOH performs an outstanding sensitivity whilst it is only modest for ß-FeOOH. Experiments via Fourier transform infrared spectroscopy, X-ray absorption fine structure (XAFS), etc., show that α-FeOOH presents a larger Pb(II) adsorption capacity due to more surficial hydroxyl groups and weaker PbO bond strength. The reaction kinetics are simulated and the adsorption capacity is found to be the determining factor for the distinct Pb(II) sensitivities. Combining experiment with simulation, this work reveals the physical insights of the phase-dependent electrochemistry for FeOOH and provides guidelines for the functional application of metal hydroxide nanomaterials.
RESUMO
The rising demand for helium resources makes the effective separation of helium from natural gas increasingly important in the cryogenics industry and welding technology. However, most commonly used membranes cannot efficiently separate helium from the small molecules in natural gas. In this work, using first-principles calculations, combined with molecular dynamics simulations, we showed that efficient separation of helium from natural gas molecules (H2O, CO2, CO, CH4, and N2) as well as noble gas molecules (Ne and Ar) can be achieved in an inorganic graphenylene (IGP) membrane with high selectivities. In particular, molecular dynamics simulations demonstrated that high helium permeance (approximately 10-4 mol m-2 s-1 Pa-1) can be achieved over a wide range of temperatures (100 to 500 K) with high selectivity over other gas molecules. The high permeance and selectivity of the IGP monolayer membrane to helium are quite promising for industrial applications.
RESUMO
Krüppel-like factor 5 (KLF5) both suppresses and promotes tumor growth depending on cellular context. The mechanisms underlying tumor promotion could be targetable for therapy. Although a number of transcriptional targets of KLF5 have been identified and implicated in KLF5-mediated tumor growth, how KLF5 regulates these genes remains to be addressed. Here we performed coimmunoprecipitation (co-IP) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the TSU-Pr1 bladder cancer cell line, in which KLF5 is shown to promote tumor growth, to identify KLF5-interacting nuclear proteins that are necessary for KLF5's tumor promoting function. LC-MS/MS revealed 122 potential KLF5 binding proteins in the nuclear proteins precipitated by the KLF5 antibody, and the top nine candidates included AHNAK, TFAM, HSDL2, HNRNPC, CINP, IST1, FBL, PABPC1 and SNRNP40. SRB assays of these nine proteins indicated that silencing CINP had the most potent inhibitory effect on cell growth in KLF5-expressing cells but did not affect parental TSU-Pr1 cells. Further analyses not only confirmed the physical interaction between KLF5 and CINP, also demonstrated that knockdown of CINP attenuated the effects of KLF5 on cell cycle progression, apoptosis and tumorigenesis. Silencing CINP also attenuated the effect of KLF5 on the expression of a number of genes and signaling pathways, including cell cycle regulator Cyclin D1 and apoptosis-related Caspase 7. These results suggest that CINP is a cofactor of KLF5 that is crucial for the promotion of tumor growth, and that the KLF5-CINP interaction could be a novel therapeutic target for inhibiting KLF5-promoted tumor growth.
Assuntos
Proteínas de Transporte/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Animais , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Células HEK293 , Células HeLa , Xenoenxertos , Humanos , Imuno-Histoquímica , Imunoprecipitação , Fatores de Transcrição Kruppel-Like/genética , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologiaRESUMO
The measurement of ultralow concentrations of heavy metal ions (HMIs) in blood is challenging. A new strategy for the determination of mercury ions (Hg2+ ) based on an oriented ZnO nanobelt (ZnO-NB) film solution-gated field-effect transistor (FET) chip is adopted. The FET chips are fabricated with ZnO-NB film channels with different orientations utilizing the Langmuir-Blodgett (L-B) assembly technique. The combined simulation and I-V behavior results show that the nanodevice with ZnO-NBs parallel to the channel has exceptional performance. The sensing capability of the oriented ZnO-NB film FET chips corresponds to an ultralow minimum detectable level (MDL) of 100 × 10-12 m in deionized water due to the change in the electrical double layer (EDL) arising from the synergism of the field-induced effect and the specific binding of Hg2+ to the thiol groups (-SH) on the film surface. Moreover, the prepared FET chips present excellent selectivity toward Hg2+ , excellent repeatability, and a rapid response time (less than 1 s) for various Hg2+ concentrations. The sensing performance corresponds to a low MDL of 10 × 10-9 m in real samples of a drop of blood.
Assuntos
Dispositivos Lab-On-A-Chip , Mercúrio/sangue , Nanoestruturas , Óxido de Zinco/química , Humanos , Limite de DetecçãoRESUMO
Nanocrystals generally suffer from agglomeration because of the spontaneous reduction of the system surface energy, resulting in blocking the active sites from reacting with target ions, and then severely reducing the electrochemical sensitivity. In this article, a highly ordered self-assembled monolayer array is successfully constructed using â¼14 nm Co0.6Fe2.4O4 nanocubes uniformly and controllably distributed on the surface of a working electrode (glass carbon plate). The large area and high exposure of the surface defects on Co0.6Fe2.4O4 nanocubes are clearly characterized by high-resolution transmission electron microscopy (HRTEM) and atomic-resolution high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM). Expectedly, a considerable sensitivity of 2.12 µA ppb-1 and a low limit of detection of 0.093 ppb are achieved for As(III) detection on this highly homogeneous sensing interface; this excellent electroanalysis performance is even better than that of noble metals electrodes. Most importantly, this approach of uniformly distributing the small-sized defective nanoparticles on the electrode surface provides a new opportunity for modifying the electrodes, as well as the realization of their applications in the field of environmental electroanalysis for heavy metal ions.
RESUMO
Krüppel-like factor 5 (KLF5) is a basic transcription factor that regulates diverse cellular processes during tumor development. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. In this study, we examined the regulation of KLF5 by histone deacetylases in the prostate cancer cell line DU 145. While confirming the functions of HDAC1/2 in KLF5 deacetylation and the promotion of cell proliferation, we found that the knockdown of HDAC1/2 upregulated KLF5 protein but not KLF5 mRNA, and the increase in KLF5 protein level by silencing HDAC1/2 was at least in part due to decreased proteasomal degradation. Deacetylase activity was required for HDAC1/2-mediated KLF5 degradation, and mutation of KLF5 to an acetylation-mimicking form prevented its degradation, even though the mutation did not affect the binding of KLF5 with HDAC1/2. Mutation of K369 to arginine, which prevents acetylation, did not affect the binding of KLF5 to HDAC1 or the response of KLF5 to HDAC1/2-promoted degradation. These findings provide a novel mechanistic association between the acetylation status of KLF5 and its protein stability. They also suggest that maintaining KLF5 in a deacetylated form may be an important mechanism by which KLF5 and HDACs promote cell proliferation and tumor growth.
Assuntos
Histona Desacetilase 1/metabolismo , Histona Desacetilase 2/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Acetilação , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Inativação Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Lisina/metabolismo , Ligação Proteica , Estabilidade Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Porous single-crystalline nanostructures are of tremendous interest for their application in the catalytic, electronic and sensing fields due to their large active surfaces, favorable diffusion, and good electronic transport. Despite the recent advances of various other components, photoelectric chalcogenides remain almost undeveloped. The present study contributes a facile strategy to prepare porous single-crystalline CdSe nanobelts through a cation-exchange reaction, in which ZnSeâ 0.5 N2 H4 hybrid nanobelts are employed as precursors. The detailed characterizations indicate the preservation of the belt-like morphology of the precursors due to the spatial confinement effect, which arises from the coated surfactant layer during the cation-exchange process. Simultaneously, CdSe nanobelts with porous and single-crystalline structures are formed following a complete exchange between Zn2+ and Cd2+ , the release of N2 H4 , and the atomic arrangement. The native photoelectric properties of the as-prepared porous single-crystalline CdSe nanobelts are systematically addressed based on the nanodevices fabricated with a single nanobelt and assembled nanobelt array. The results indicate that they present a rapid, stable, and repeatable photoelectric response. Moreover, as-prepared nanobelts exhibit highly selective photoelectric sensing toward Cu2+ with a low detection limit down to 0.1â ppm. To illuminate this phenomenon, a possible sensing mechanism is also discussed.
RESUMO
Porous ZnO nanobelts sensitized with Ag nanoparticles have been prepared via a partial cation-exchange reaction assisted by a thermal oxidation treatment, employing ZnSe·0.5N2H4 nanobelts as precursors. After partially exchanged with Ag+ cations, the belt-like morphology of the precursors is still preserved. Continuously calcined in air, they are in situ transformed into Ag nanoparticles sensitized porous ZnO nanobelts. The size of the Ag nanoparticles can be tuned through manipulating the amount of exchanging Ag+ cations. Considering the porous and belt-like nanostructure, sensing characteristics of ZnO and the catalytic activity of Ag nanoparticles, the gas sensing performances of the as-prepared Ag nanoparticles sensitized porous ZnO nanobelts have been carefully investigated. The results indicate that Ag nanoparticles significantly enhance the sensing performances of porous ZnO nanobelts toward typical volatile organic compounds. Especially, a good selectivity has been demonstrated toward acetic acid gas with a low detection limit less than 1 ppm. Furthermore, they also display a good reproducibility with a short response/recovery time due to the thin, uniform and porous sensing film, which is fabricated with the assembled technique and in situ calcined approach. Finally, their sensing mechanism has been further discussed.
RESUMO
Growth differentiation factor 11 (GDF11) reduces cardiac hypertrophy, improves cerebral vasculature and enhances neurogenesis in ageing mice. Higher growth differentiation factor 11/8 (GDF11/8) is associated with lower risk of cardiovascular events in humans. Here, we showed that adeno-associated viruses-GDF11 and recombinant GDF11 protein improve endothelial dysfunction, decrease endothelial apoptosis, and reduce inflammation, consequently decrease atherosclerotic plaques area in apolipoprotein E-/- mice. Moreover, adeno-associated viruses-GDF11 and recombinant GDF11 stabilize atherosclerotic plaques by selectively decreasing in macrophages and T lymphocytes, while increasing in collagen and vascular smooth muscle cells within plaques. In addition, GDF11 inhibit palmitic acid-induced endothelial apoptosis and ameliorate palmitic acid-induced inflammatory response in RAW264.7 macrophages in vitro. Mechanistically, GDF11 activates the TGF-ß/Smad2/3, AMPK/endothelial nitricoxide synthase (eNOS) while suppresses JNK and NF-κB pathways. In humans, circulating GDF11/8 is positively associated with flow-mediated endothelium-dependent dilation in overweight subjects. We concluded that adeno-associated viruses-GDF11 and recombinant GDF11 protect against endothelial injury and reduce atherosclerosis in apolipoprotein E-/- mice, thus may be providing a novel approach to the treatment of atherosclerosis.
Assuntos
Apolipoproteínas E/genética , Aterosclerose/terapia , Proteínas Morfogenéticas Ósseas/genética , Células Endoteliais/efeitos dos fármacos , Terapia Genética/métodos , Fatores de Diferenciação de Crescimento/genética , Proteínas Recombinantes/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Aterosclerose/genética , Aterosclerose/metabolismo , Células Cultivadas , Dependovirus/genética , Modelos Animais de Doenças , Células Endoteliais/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/farmacologia , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Ácido Palmítico/efeitos adversos , Células RAW 264.7 , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
Ginsenoside Rb1 (GS-Rb1) is a well-known antioxidant derived from traditionally used herbal medicine ginseng. It has been suggested that reactive oxygen species (ROS) is involved in chronic kidney disease (CKD) in which GS-Rb1 may play a protective role. The aim of this study was to evaluate prospectively the effects of GS-Rb1 in patients with early chronic kidney disease. 197 patients who have been diagnosed with early CKD (stage 2 or 3) were recruited and randomly assigned to receive GS-Rb1 (500 mg daily oral administration, n = 103) or placebo (n = 94) for consecutive 6 months. Analytical procedures performed at baseline, the end of the treatments, and 6 months after the treatments included renal function evaluation (creatinine and urea clearance), oxidative stress measurement, inflammation assessment, and lipid profile. Of 177 patients completing the study, the GS-Rb1 group (n = 91) showed a positive response in significantly alleviating renal function impairments compared to the placebo group (n = 86). In addition, GS-Rb1 treatment was effective in reducing the extent of oxidative stress and inflammation in CKD patients, whereas continued deterioration was observed in the placebo group. Thus, extended treatment of patients using GS-Rb1 may present an antioxidant-based approach to slow the progression of CKD at the early stages.
Assuntos
Ginsenosídeos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Panax , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Esquema de Medicação , Diagnóstico Precoce , Feminino , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Estudos Prospectivos , Insuficiência Renal Crônica/diagnósticoRESUMO
Pyropolyporus fomentarius (L. ex Fr.) Teng is a unique woody mushroom due to its medicinal value with numerous pharmacological activities. This study presented the potential antitumor and immunomodulatory properties of ethanol extract of P. fomentarius. The results showed that P. fomentarius extract inhibited the viability of murine leukemia L1210 cells in a dose-dependent manner with IC50 value of 69.35 µg/ml. Flow cytometry analysis demonstrated that the extract induced apoptosis in L1210 cells. Additionally, the decline of mitochondrial membrane potential was observed as well as the changes of caspase-3, caspase-9, Bcl-2, and Bax, suggesting that proapoptosis effect of the extract involved mitochondria-related pathway. Simultaneously, the P. fomentarius extract significantly enhanced the proliferation and activation of splenic lymphocytes in a dose-dependent manner. This P. fomentarius extract has potential applications as a natural antitumor agent with immunomodulatory activity.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Linfócitos/efeitos dos fármacos , Polyporaceae/química , Animais , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Fatores Imunológicos/química , Leucemia L1210 , Linfócitos/imunologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Baço/citologiaRESUMO
Porous and single-crystalline ZnO nanobelts have been prepared through annealing precursors of ZnSe · 0.5N2H4 well-defined and smooth nanobelts, which have been synthesized via a simple hydrothermal method. The composition and morphology evolutions with the calcination temperatures have been investigated in detail for as-prepared precursor nanobelts, suggesting that they can be easily transformed into ZnO nanobelts by preserving their initial morphology via calcination in air. In contrast, the obtained ZnO nanobelts are densely porous, owing to the thermal decomposition and oxidization of the precursor nanobelts. More importantly, the achieved porous ZnO nanobelts are single-crystalline, different from previously reported ones. Motivated by the intrinsic properties of the porous structure and good electronic transporting ability of single crystals, their gas-sensing performance has been further explored. It is demonstrated that porous ZnO single-crystalline nanobelts exhibit high response and repeatability toward volatile organic compounds, such as ethanol and acetone, with a short response/recovery time. Furthermore, their optoelectronic behaviors indicate that they can be promisingly employed to fabricate photoelectrochemical sensors.