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1.
J Hazard Mater ; 382: 121018, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31446354

RESUMO

The broad spectrum detection of veterinary drugs is very important for rapid and large-scale safe screen of animal-derived foods. Metal-organic frameworks (MOFs), as a kind of emerged functional porous materials are quite promising in the chemical sensing and molecular detection. In this work, we report the high-performance broad spectrum detection of 15 commonly-used veterinary drugs through the fluorescence quenching in a newly-designed chemically stable Al-based MOF, Al3(µ3-O)(OH)(H2O)2(PPTTA)3/2 (BUT-22). To the best of our knowledge, this is the first systematic investigation for the application of MOFs in the detection/sensing of veterinary drugs through fluorescence quenching method. The quenching efficiencies of the tested veterinary drugs on BUT-22 are all beyond 82%, and the limits of detection (LOD) are low at parts per billion (ppb) levels. Interestingly, BUT-22 also enables the selective detection of nicarbazin (NIC) through the clearly-observed red shift of its maximum fluorescence emission wavelength. Moreover, the fluorescence quenching mechanism was explored with the help of theoretical calculations. Our work indicates that MOFs are favorable materials for the detection of veterinary drugs, being potentially useful in monitoring drug residues of animal-derived foods.

2.
Fitoterapia ; 139: 104372, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669720

RESUMO

Four new sesquiterpene lactones, named artemargyinolides A-D (1-4), and seven known sesquiterpenoids (5-11) were isolated from Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. The absolute configuration of 1 was assigned by X-ray crystallographic analysis. Compound 1 is an unprecedented sesquiterpene dimer-monoterpene lactone. The cyclooxygenases (COX-1 and COX-2) inhibitory activities of all isolated compounds were evaluated. Compounds 1, 2, 4, and 6-11 showed inhibitory activity against COX-2 with IC50 values ranging from 35.78 ±â€¯0.39 to 256.07 ±â€¯0.38 µM. However, compounds 7, 9, and 10 exhibited weak inhibitory activity against COX-1 with IC50 values of 465.70 ±â€¯1.53, 281.43 ±â€¯3.56, and 490.45 ±â€¯6.07 µM, respectively. Other compounds are inactive against COX-1. Therefore, compounds 1, 2, 4, 6, 8, and 11 displayed selective COX-2 inhibitory activity.

3.
Acta Pharmacol Sin ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685977

RESUMO

At present, few available drugs can be used to either improve pathological features or prevent the progression of Alzheimer's disease (AD). DL0410 ((1,1'-([1,1'-biphenyl]-4,4'-diyl) bis (3-(piperidin-1-yl) propan-1-one) dihydrochloride) is a multiple-target small molecule that has been found to reverse cognitive impairment in different animal models of AD. In this study we evaluated the cognition-improving effects of DL0410 in APP/PS1 transgenic mice and explored the underlying mechanisms. APP/PS1 transgenic mice were administered DL0410 (3, 10, 30 mg· kg-1· d-1, ig) for 2 months. We found that DL0410 administration significantly ameliorated cognitive deficits in both the nest-building and Morris water maze tests. In electrophysiological analysis of hippocampal slices, we showed that DL0410 administration significantly enhanced the field EPSP slope and HFS-induced LTP in CA1 area. Furthermore, we revealed that DL0410 administration significantly increased the phosphorylation of AKT and the activity of GSK-3ß in the hippocampus and cortex. Moreover, DL0410 administration dose-dependently increased the expression level of phosphorylated ERK1/2 in the hippocampus and cortex. In addition, DL0410 dose-dependently decreased the neuronal loss by decreasing the production of Aß deposition, inhibited glial overactivation, and the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6. We conclude that DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission via activating the AKT/GSK-3ß and MAPK/ERK signaling pathway and reducing neuronal loss. DL0410 may be an effective agent for AD treatment in the future.

4.
Inorg Chem ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31725278

RESUMO

In recent years, more and more research on metal-organic frameworks (MOFs) has focused on exploring their practical applications, where the stability is crucial. Besides the metal-ligand coordination bond, the configuration of the ligand also plays an important role in determining the stability of resulting MOFs. In this work, we demonstrate that fixing flexible arms of core-shared ligands can enhance the stability of their Zr(IV)-MOFs. Two groups, four core-shared tetracarboxylate ligands, 3,3',3″,3‴-(pyrene-1,3,6,8-tetrayltetrakis(benzene-4,1-diyl))tetraacrylate (PTSA4-) and 6,6',6″,6‴-(pyrene-1,3,6,8-tetrayl)tetrakis(2-naphthoate) (PTNA4-) with the pyrene core and 3,3',3″,3‴-((9H-carbazole-1,3,6,8-tetrayl)tetrakis(benzene-4,1-diyl))-tetraacrylate (CTSA4-) and 6,6',6″,6‴-(9H-carbazole-1,3,6,8-tetrayl)tetrakis-(2-naphthoate) (CTNA4-) with the carbazole core are rationally designed. Two ligands in each group have different flexibilities due to the distinct side arms: the styrene arm is flexible, whereas the naphthalene is rigid. Constructed with Zr6 clusters, four 4,8-connected Zr(IV)-MOFs, Zr6O4(OH)8(H2O)4(PTSA)2 (BUT-72) and Zr6O4(OH)8(H2O)4(PTNA)2 (BUT-73) with a sqc-a topologic framework structure and Zr6O4(OH)8(H2O)4(CTSA)2 (BUT-74) and Zr6O4(OH)8(H2O)4(CTNA)2 (BUT-63) with a scu-a structure are obtained, respectively. It is found that the stability of BUT-73 and -63 with the rigid naphthoate-based ligands is significantly enhanced compared with that of BUT-72 and -74 with the flexible phenyl acrylate-based ones. Moreover, stable BUT-63 represents outstanding performance in the molecular recognition of most solvents commonly used in organic synthesis and industrial manufacture.

5.
J Cell Physiol ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710102

RESUMO

Hyperglycemia-induced cardiac fibrosis is a prominent characteristic of diabetic cardiomyopathy. Changes in proinflammatory cytokines have been shown to lead to cardiac fibrosis in patients with diabetes mellitus. This study aimed to investigate the role of miR-150-5p in mediating cardiac inflammation and fibrosis in cardiac fibroblasts (CFs). Herein, we found that high-glucose (HG) treatment significantly induced cardiac inflammation, as manifested by increased proinflammatory cytokine production (IL-1ß) and NF-κB activity in CFs. Moreover, HG markedly aggravated cardiac fibrosis and increased levels of fibrotic markers (CTGF, FN, α-SMA) and extracellular matrix proteins (Col-I, Col-III) in CFs. At the same time, HG disturbed the TGF-ß1/Smad signaling pathway, as evidenced by increases in TGF-ß1 and p-Smad2/3 levels and decreases in Smad7 levels in CFs. Furthermore, we found that miR-150-5p was upregulated by HG, which negatively regulated Smad7 expression at the posttranscription level. Further study demonstrated that cardiac inflammation and fibrosis in CFs were corrected following miR-150-5p knockdown, but exacerbated by miR-150-5p overexpression. These data indicated that miR-150-5p inhibition could ameliorate NF-κB-related inflammation and TGF-ß1/Smad-induced cardiac fibrosis through targeting Smad7. Thus, miR-150-5p may be a novel promising target for treating diabetic cardiomyopathy.

6.
Arch Pharm (Weinheim) ; : e1900174, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31657061

RESUMO

Four series of ferulic acid derivatives were designed, synthesized, and evaluated for their neuraminidase (NA) inhibitory activities against influenza virus H1N1 in vitro. The pharmacological results showed that the majority of the target compounds exhibited moderate influenza NA inhibitory activity, which was also better than that of ferulic acid. The two most potent compounds were 1m and 4a with IC50 values of 12.77 ± 0.47 and 12.96 ± 1.34 µg/ml, respectively. On the basis of the biological results, a preliminary structure-activity relationship (SAR) was derived and discussed. Besides, molecular docking was performed to study the possible interactions of compounds 1p, 2d, 3b, and 4a with the active site of NA. It was found that the 4-OH-3-OMe group and the amide group (CON) of ferulic acid amide derivatives were two key pharmacophores for NA inhibitory activity. It is meaningful to further modify the natural product ferulic acid to improve its influenza NA inhibitory activity.

7.
Cancer Lett ; 469: 22-34, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31634528

RESUMO

Hepatocellular carcinoma (HCC) has emerged as one of the most common malignancies worldwide. It is associated with a high mortality rate, as evident from its increasing incidence and extremely poor prognosis. The deubiquitinating enzyme 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) has been reported to act as an oncogene in several human cancers. The present study aimed to reveal the functional significance of PSMD14 in HCC progression and the underlying mechanisms. We found that PSMD14 was significantly upregulated in HCC tissues. Overexpression of PSMD14 correlated with vascular invasion, tumor number, tumor recurrence, and poor tumor-free and overall survival of patients with HCC. Knockdown and overexpression experiments demonstrated that PSMD14 promoted proliferation, migration, and invasion in HCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Mechanistically, we identified PSMD14 as a novel post-translational regulator of GRB2. PSMD14 inhibits degradation of GRB2 via deubiquitinating this oncoprotein in HCC cells. Furthermore, pharmacological inhibition of PSMD14 with O-phenanthroline (OPA) suppressed the malignant behavior of HCC cells in vitro and in vivo. In conclusion, our findings suggest that PSMD14 could serve as a novel promising therapeutic candidate for HCC.

8.
J Neuroimmunol ; 337: 577076, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31655425

RESUMO

To improve the clinical diagnosis of neural autoimmune diseases, we developed an in-house muscle-specific kinase (MuSK) antibody cell-based assay (CBA) and compared its performance with RIA, ELISA, and other CBAs. Sera from patients with myasthenia gravis (MG) and other autoimmune diseases were analyzed. We found 46 (18.3%) MuSK-CBA Ab positive cases among 251 AChR-Ab negative cases [patients] and 4 (0.6%) MuSK-CBA Ab positive cases [among] the 624 AChR-Ab positive samples. Comparing these with available clinic assays, our highly specific CBA method is more sensitive than commercial ELISA and IFA(indirect immunofluorescence assay).

9.
Artigo em Inglês | MEDLINE | ID: mdl-31498061

RESUMO

A Gram-reaction-negative, peach-brown-pigmented, slightly curved-rod-shaped, aerobic, non-motile bacterium, designated GSA243-2T, was isolated from fresh water samples collected from the Chishui River flowing through Maotai, Guizhou, south-west PR China. Phenotypic, chemotaxonomic and genomic traits were investigated. Results of phylogenetic analysis based on 16S rRNA gene sequences showed that the isolate belonged to the genus Rhodoferax. The closest phylogenetic relative was Rhodoferax saidenbachensis ATCC BAA-1852T (98.35 %). The major fatty acids were C16: 0 and C16 : 1ω6c and/or C16 : 1ω7c. The major respiratory quinone was ubiquinone Q-8 and the major polar lipid was phosphatidylethanolamine. Genome sequencing revealed a genome size of 3.67 Mbp and a G+C content of 61.17 mol%. Pairwise-determined whole genome average nucleotide identity values and digital DNA-DNA hybridization values suggested that strain GSA243-2T represents a new species, for which we propose the name Rhodoferaxbucti sp. nov. with the type strain GSA243-2T (=CGMCC 1.16288T=KCTC 62564T).

10.
Mol Ther Nucleic Acids ; 17: 636-643, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31400606

RESUMO

Diabetic cardiomyopathy (DCM) is a vital cause of fatalities in diabetic patients. The programmed death of cardiomyocytes and inflammation critically contribute to cardiac hypertrophy and fibrosis in DCM. Furthermore, circular RNA (circRNA) is a key regulator of various diseases. However, the role of circRNAs in DCM remains to be elucidated. Our previous study found that pyroptosis was markedly activated in the cardiomyocytes subjected to high-glucose conditions, and miR-214-3p regulated the expression of caspase-1. The aim of this study was to elucidate whether circRNA is involved in DCM pyroptosis via the miR-214-3p/caspase-1 pathway. Herein, we identified that hsa_circ_0076631, named caspase-1-associated circRNA (CACR), was increased both in high-glucose-treated cardiomyocytes and in the serum of diabetic patients. CACR also sponged an endogenous miR-214-3p to sequester and inhibit its expression. CACR knockdown in cardiomyocytes counteracted high-glucose-induced caspase-1 activation. Conversely, miR-214-3p knockdown partially abolished the beneficial effects of CACR silencing on pyroptosis in cardiomyocytes. Therefore, this study elucidated that CACR might be a novel therapeutic target via the CACR/miR-214-3p/caspase-1 pathway in DCM.

11.
Int J Nanomedicine ; 14: 5817-5829, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440049

RESUMO

Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.


Assuntos
Acetilcolinesterase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inibidores da Colinesterase/farmacologia , Portadores de Fármacos/química , Fígado/patologia , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Calixarenos/química , Sobrevivência Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Liberação Controlada de Fármacos , Fluoresceína/química , Hemólise , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Fenóis/química , Porosidade , Ratos , Dióxido de Silício/química , Temperatura Ambiente , Fatores de Tempo
12.
Nat Commun ; 10(1): 3861, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455843

RESUMO

Polychlorinated dibenzo-p-dioxins (PCDDs), as a class of persistent and highly toxic organic pollutants, have been posing a great threat to human health and the environment. The sensing of these compounds is important but challenging. Here, we report a highly stable zirconium-based metal-organic framework (MOF), Zr6O4(OH)8(HCOO)2(CPTTA)2 (BUT-17) with one-dimensional hexagonal channels and phenyl-rich pore surfaces for the recognition and sensing of two representative PCDDs, 2,3-dichlorodibenzo-p-dioxin (BCDD) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), based on the fluorescence quenching. BUT-17 exhibits high sensing ability with the detection limits as low as 27 and 57 part per billion toward BCDD and TCDD, respectively, and is very selective as well without the interference of similar compounds. The recognition of BUT-17 toward BCDD is demonstrated by single-crystal structure of its guest-loaded phase, in which the fluorescence-quenched complexes form between the adsorbed BCDD molecules and the MOF host through π-π stacking and hydrogen bonding interactions.

13.
Int J Biol Sci ; 15(5): 1010-1019, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182921

RESUMO

Metformin is a widely used antidiabetic drug for type 2 diabetes that can play a cardioprotective role through multiple pathways. It is a recognized agonist of AMP-activated protein kinase (AMPK) that blocks mitochondrial complex I. The NLRP3 inflammasome has been demonstrated to be activated in diabetic cardiomyopathy (DCM). However, the role of metformin in regulating the NLRP3 signaling pathway in DCM remains unclear. It has been reported that AMPK can inhibit NLRP3 by activating autophagy. The aim of this study was to investigate whether metformin can inhibit the NLRP3 inflammasome by activating the AMPK/mTOR pathway in DCM. In this study, streptozotocin-induced C57BL/6 mice and high glucose-treated primary cardiomyocytes from neonatal mice were treated with metformin or an AMPK inhibitor compound C. Echocardiography, hematoxylin-eosin and Masson staining showed that the function and morphology of the diabetic hearts were improved after metformin treatment, whereas these parameters deteriorated after intervention with an AMPK inhibitor. Immunohistochemical staining, immunofluorescence staining and western blot assays indicated that the expression levels of mTOR, NLRP3, caspase-1, IL-1ß and GSDMD-N were decreased in the diabetic model treated with metformin and were reversed after the administration of an AMPK inhibitor in vivo and in vitro. Mechanistically, our results demonstrated that metformin can activate AMPK, thus improving autophagy via inhibiting the mTOR pathway and alleviating pyroptosis in DCM. Thus, we provide novel information for the treatment of DCM.

15.
Science ; 363(6431): 1085-1088, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30705153

RESUMO

Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.


Assuntos
Colesterol/biossíntese , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Hipercolesterolemia/metabolismo , Animais , Anticolesterolemiantes/farmacologia , Atorvastatina/farmacologia , Sequência de Bases , Imunoprecipitação da Cromatina , Doença da Artéria Coronariana/metabolismo , Regulação da Expressão Gênica , Hematopoese/genética , Receptores Notch/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Peixe-Zebra
16.
Gynecol Endocrinol ; 35(5): 385-389, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30614301

RESUMO

17α-Hydroxylase/17,20-lyase deficiency (17-OHD) is a rare disease caused by mutations of the CYP17A1 gene. Slipped capital femoral epiphysis (SCFE) rarely occurs in adults. There are occasional reports of adrenal myelolipoma (AML) in 17-OHD. A 27-year-old Chinese female (46, XX) visited the hospital for SCFE and presented with continuous hypokalemia, absent spontaneous puberty, and hypertension. Hypergonadotropic hypogonadism was detected. The laboratory tests were consistent with 17-OHD. AML was considered based on the imaging examinations. A mutation analysis of the CYP17A1 gene identified the following compound heterozygous mutation: a frame-shift mutation, i.e. c.985_987delTACinsAA (p.Tyr329fs), that had been reported to be a common mutation in the Chinese population was found in exon 6. Another new nonsense mutation, i.e. c.1270C > T (p.Gln424*), that causes a premature termination codon was found in exon 8. Treatment with prednisone had poor efficacy. The administration of 0.75 mg dexamethasone and estradiol/dydrogesterone cyclic treatment significantly improved the patient's symptoms. For the first time, we report a 17-OHD case accompanied by SCFE, AML, and a novel mutation site in the CYP17A1 gene. We provide insight into the clinical manifestations, genetic analysis, and treatment options of 17-OHD.

17.
ACS Appl Mater Interfaces ; 11(7): 6717-6723, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30633491

RESUMO

Nonfullerene acceptors (NFAs) based on calamitic-shaped small molecules are being developed rapidly to improve the photoelectron conversion efficiencies (PCEs) of organic solar cells. NFAs with light absorption extended to the near-infrared (NIR) region are of interest because they play a pivotal role in both organic tandem cells and semitransparent devices. In this work, two simple acceptor-donor-acceptor-structured NFAs (CPDT-4Cl and CPDT-4F) have been designed and synthesized. Featured with dimerized 4H-cyclopenta[1,2-b:5,4-b']dithiophene (CPDT) as the electron-donating core and Cl- or F-substituted 2-(3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile as the electron-accepting unit, the absorption spectra of two NFAs are extended to the NIR region with an absorption edge at approximately 910 nm. In conjunction with the polymer donor material PBDB-T, a PCE of 9.47% was achieved by using a CPDT-4F-based device with a short-circuit current density of up to 20.1 mA/cm2, which slightly outperforms its counterpart CPDT-4Cl (PCE = 9.28%) under the same condition. This work broadens the scope of developing new NIR NFAs with both high efficiency and easy accessibility.


Assuntos
Fontes de Energia Elétrica , Fulerenos , Energia Solar
18.
Int J Mol Med ; 43(3): 1193-1202, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30592266

RESUMO

The aim of the present study was to determine the effect of 60% normobaric oxygen (NBO) on neurological function, brain edema and the expression of hypoxia­inducible factor­1α (HIF­1α), aquaporin 4 (AQP4) and Na+/H+ exchanger 1 (NHE1) in a rat model of cerebral ischemia­reperfusion injury. Male Sprague­Dawley rats underwent transient focal cerebral ischemia via right middle cerebral artery occlusion (MCAO) for 120 min followed by 48 h of reperfusion. The rats were exposed to NBO at 60 and 100% or no treatment during reperfusion for 48 h. Neurological impairment score (NIS) was evaluated prior to the sacrifice of all rats. Hematoxylin­eosin staining was performed after 48 h of reperfusion with NBO treatment. The infarct volume and brain water content (BWC) were determined to assess brain ischemic injury at 24 and 48 h. The levels of HIF­1α, AQP4 and NHE1 expression in brain tissue samples were determined by western blotting and reverse transcription­quantitative polymerase chain reaction analysis. During reperfusion, the protein and mRNA expression of HIF­1α, AQP4 and NHE1 increased over time (up to 48 h). Exposure to 60 and 100% NBO during reperfusion following MCAO improved NIS, and alleviated BWC and infarct volume after 24 and 48 h, with further improvements in the 100% NBO group, compared with 60%. Additionally, the molecular mechanisms involved in the effects of NBO may be associated with reduced AQP4 and NHE1 expression and increased HIF­1α expression. However, 60% NBO therapy during reperfusion following an acute ischemic stroke did not achieve the same effects as 100% NBO. Further experimental studies should be performed to elucidate the mechanism and beneficial effects of 60% NBO, as it is more cost­effective to use, compared with 100% NBO.


Assuntos
Aquaporina 4/genética , Regulação da Expressão Gênica , Oxigênio/metabolismo , Trocador 1 de Sódio-Hidrogênio/genética , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismo , Animais , Biomarcadores , Infarto Encefálico/metabolismo , Infarto Encefálico/patologia , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imuno-Histoquímica , Masculino , Ratos , Acidente Vascular Cerebral/patologia
19.
BioDrugs ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30511316

RESUMO

OBJECTIVE: The objective of this study was to compare the pharmacokinetics (PKs), safety, and immunogenicity of GB242 as a potential biosimilar infliximab with those of reference infliximab in healthy Chinese subjects. METHODS: We conducted a randomized, single-center, double-blind, parallel-controlled phase I study in which 48 healthy subjects were divided equally into a GB242 group and reference infliximab group. Both the test and reference drug were administered as a single intravenous dose of 3 mg/kg. Blood samples were collected as per a designated schedule to evaluate PKs and immunogenicity. Safety was assessed throughout the study. PK similarity was concluded if the 90% confidence intervals (CIs) for the geometric mean ratios of the GB242 to reference infliximab for maximum concentration (Cmax), area under the concentration-time curve (AUC) from time zero to the last quantifiable concentration (AUCt), and AUC from time zero to infinity (AUC∞) were within the predefined bioequivalence range of 80-125%. RESULTS: The mean serum concentration-time curves were similar between GB242 and reference infliximab. The 90% CIs for the geometric mean ratios of the GB242 to reference infliximab for Cmax, AUCt, and AUC∞ were completely within 80-125% for the PK similarity comparison. The proportion of subjects with treatment-emergent adverse events was similar between the GB242 group and the reference infliximab group. Antidrug antibody profiles were comparable between the two treatments groups. CONCLUSIONS: This study demonstrated high PK similarity between GB242 and its marketed reference infliximab in healthy subjects. Both treatments showed comparable safety and immunogenicity. REGISTRATION NUMBER: ChiCTR-IPR-15007098.

20.
J Asian Nat Prod Res ; : 1-8, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30585504

RESUMO

Two new nordammarane-type triterpenoids, 3ß-acetoxy-20-oxo-21-nordammaran-23-carboxylic acid methyl ester (1) and 3ß-acetoxy-17ß-dammaranic acid (2), along with two known cycloartane-type triterpenoids (3-4), were isolated from the petroleum ether-soluble extract of Artemisia argyi. Their structures were elucidated based on 1D and 2D NMR spectroscopic data analysis. All compounds were evaluated for their α-glucosidase inhibitory activity in vitro. Compounds 1-4 exhibited significant inhibitory effects on α-glucosidase with IC50 values ranging from 38.34 ± 0.23 to 105.54 ± 0.33 µM.

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