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1.
J Proteomics ; : 103691, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068187

RESUMO

Acute myocardial infarction (AMI) is an acute heart disease. Cycloastragenol, as a natural product, inhibits inflammation and protects cardiomyocytes. Cycloastragenol (Y006) modulates inflammation in AMI is not known. To explore the function of Cycloastragenol in AMI, this study investigated the effect of Y006 and its mechanisms both in vitro and in vivo. Y006 influences the concentration of 11 proteins, as shown by a proteomics analysis, immunohistochemistry and western blotting. Among these 11 proteins, Erk1/2, PLCG1, IKBKG, and ZEB1 are related to inflammatory regulation. BAX, COX2, and GSK3ß are involved in modulating cardiomyocyte apoptosis, and RhoA and DSC2 are directly associated with myocardial function. However, the functions of ARHGAP17 and Rit2 in heart are less well established. Additionally, Y006 suppressed TNF-α, IFN-γ and IL-17 production in PBMCs (peripheral blood monocytes) from patients with acute myocardial infarction and enhanced IL-10 and IL-4 expression. Similar results were obtained in a rat model of AMI by flow cytometry detection and ELISA. Our findings indicate that Y006 protects rats from AMI through direct or indirect inhibition of inflammation and cardiomyocyte apoptosis. However, the specific mechanism of Y006's protective function requires further study. Nonetheless, this research revealed a novel aspect for the treatment of myocardial infarction. SIGNIFICANCE: In the present study, we undertook the first proteomic evaluation of Cycloastragenol (Y006) function in acute myocardial infarction (AMI). Y006 significantly improved myocardial function in vivo by regulating multiple molecular expressions. Hypoxia is a direct reason for AMI. And our data support a role of Y006 in gene expression, cell apoptosis under hypoxia. The conclusions of this research assist to explain the potential molecular mechanism in Cycloastragenol treating AMI and supply a new method for ameliorating AMI.

2.
Dalton Trans ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32022052

RESUMO

We present the syntheses of trigonal planar coordinated Fe(ii) carbodiphosphorane (CDPR) complexes, starting from iron(ii)-bis(trimethylsilylamide) [Fe{N(SiMe3)2}2] and hexaphenyl-(CDPPh) and sym-dimethyltetraphenyl-carbodiphosphoranes (CDPMe), respectively. Both complexes [CDPPh-Fe{N(SiMe3)2}2] (1) and [CDPMe-Fe{N(SiMe3)2}2] (2) were examined in solution and in the solid state. 1 shows a dissociation equilibrium in solution which we monitored by variable temperature 1H-NMR spectroscopy. Magnetic measurements of 1 and 2 yielded a high spin configuration (S = 2) for both complexes. Quantum chemical calculations were performed to analyze the bonding situation in compound 1.

3.
J Clin Invest ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027624

RESUMO

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BAF chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to interferon (IFN) responsive genes, caused impaired IFN-gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies as well as in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN-responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.

4.
Ecotoxicol Environ Saf ; 192: 110308, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32058168

RESUMO

PM2.5 particles are regarded as prominent risk factors that contribute to the development of atherosclerosis. However, the composition of PM2.5 is rather complicated. This study aimed to provide a model particle that simulates the behavior of actual PM2.5, for subsequent use in exploring mechanisms and major complications arising from PM2.5. To establish model particles of PM2.5, a series of monodisperse SiO2 microspheres with different average grain diameters were mixed according to the size distribution of actual PM2.5. The organic carbon (OC) was removed from PM2.5 and coated onto the SiO2 model particle, to formulate simulant PM2.5. Results showed that the size distribution of the model particle was highly approximate to that of the PM2.5 core. The polycyclic aromatic hydrocarbon (PAHs) composition profile of the simulated PM2.5 were approximate to PM2.5, and loading efficiency was approximately 80%-120%. Furthermore, compared to the control, SiO2-only model particle had negligible cytotoxicity on cell viability and oxidative stress of HUVECs, and marginal effect on the lipid metabolism and atherosclerotic plaque formation in ApoE-/- mice. In contrast, simulated PM2.5 exhibited similar cytotoxic and detrimental effects on lipid metabolism and atherosclerotic plaque formation with actual PM2.5. Traffic-related PM2.5 had negative effects on endothelial function and led to the formation of atherosclerosis via oxidative stress. The simulated PM2.5 simulated the outcomes of actual PM2.5 exposure. Here, we show that SiO2 particle model cores coated with OC could significantly assist in the evaluation of the effects of specific organic compositions bound on PM2.5, specifically in the context of environmental health and safety.

5.
Neuro Oncol ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31950181

RESUMO

BACKGROUND: High grade gliomas are aggressive and immunosuppressive brain tumors. Molecular mechanisms that regulate the inhibitory immune tumor microenvironment (TME) and glioma progression remain poorly understood. FYN tyrosine kinase is a downstream target of the oncogenic receptor tyrosine kinases pathway and is overexpressed in human gliomas. FYN's role in vivo in glioma growth remains unknown. We investigated whether FYN regulates glioma initiation, growth and invasion. METHODS: We evaluated the role of FYN using genetically engineered mouse glioma models (GEMM). We also generated FYN knockdown stem cells to induce gliomas in immune-competent and immune-deficient mice (NSG, CD8-/-, CD4-/-). We analyzed molecular mechanism by RNA-Seq and bioinformatics analysis. Flow cytometry was used to characterize immune cellular infiltrates in the FYN knockdown glioma TME. RESULTS: We demonstrate that FYN knockdown in diverse immune-competent GEMMs of glioma reduced tumor progression and significantly increased survival. Gene ontologies (GOs) analysis of differentially expressed genes in wild type vs. FYN knockdown gliomas showed enrichment of GOs related to immune reactivity. However, in NSG, CD8-/- and CD4-/- immune-deficient mice, FYN knockdown gliomas failed to show differences in survival. These data suggest that the expression of FYN in glioma cells reduces anti-glioma immune activation. Examination of glioma immune infiltrates by flow-cytometry displayed reduction in the amount and activity of immune suppressive myeloid derived cells (MDSCs) in the FYN glioma TME. CONCLUSIONS: Gliomas employ FYN mediated mechanisms to enhance immune-suppression and promote tumor progression. We propose that FYN inhibition within glioma cells could improve the efficacy of anti-glioma immunotherapies.

6.
Chem Commun (Camb) ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990014

RESUMO

An efficient [3+3] benzannulation of Morita-Baylis-Hillman carbonates with 1-indanylidenemalononitrile was achieved under metal-free reaction conditions selectively delivering a wide range of functional multi-substituted fluorene or fluorenone compounds in high yields, respectively (up to 86% yield). Moreover, experiments and quantum chemical calculations were also performed to study the mechanism of the transformation.

7.
J Am Chem Soc ; 142(4): 2023-2030, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31910008

RESUMO

Upconversion nanoparticles (UCNPs), typically converting near-infrared (NIR) light into visible luminescence, are promising for bioimaging applications. However, optical multiplexed in vivo upconversion experiments have long been hampered by the exceptional rarity of available luminescence bands in UCNPs that can penetrate deep in tissues. Herein, we describe an approach to accomplish multiplexed upconversion in vivo imaging through time-domain discrimination of tissue-penetrating NIR luminescence at 808 nm (from thulium ions) with a multitude of distinct lifetimes. A tetradomain nanostructure design enables one to regulate energy migration and upconverting processes within confined nanoscopic domains in defined ways, thus yielding high quantum yield upconversion luminescence (maximum ≈ 6.1%, 0.11 W/cm2) with precisely controlled lifetimes that span 2 orders of magnitude (from 78 to 2157 µs). Importantly, intravenous and subcutaneous administration of aqueous form UCNPs into a Kunming mouse demonstrates high-contrast lifetime-colored imaging of them in liver and two abdomen subcutis. Moreover, optical patterns of these UCNPs allow multicolour presentation of a series of deciphered images that are hued with precisely defined lifetimes. The described temporal multiplexed upconversion approach, demonstrated in in vivo imaging and multilevel anticounterfeiting, has implications for high-throughput biosensing, volumetric displays, and diagnosis and therapy.

8.
J Phys Chem A ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31951409

RESUMO

Quantum chemical calculations using ab initio methods at the CCSD(T) level with large basis sets and DFT calculations using the BP86 functional have been carried out for O22+ and N2. An energy decomposition analysis of the chemical bonds suggests that the shorter bond in O22+ compared with isoelectronic N2 is due to the weaker Pauli repulsion in the dication, which overcompensates the weakening of attractive interactions that are operative in N2. At the equilibrium distance of N2, the orbital (covalent) bonding in O22+ is weaker than in N2, and the attractive Coulomb interactions in the neutral diatomic system become repulsive in the dication, but the weakening of the Pauli repulsion caused by the shrinking of the orbitals in O22+ compensates for these forces and leads to a shortening of the bond. The results also show that the bond dissociation energy is not a reliable indicator for the strength of bond, which is more faithfully given by the (local) force constant.

9.
Theranostics ; 10(3): 1197-1212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938060

RESUMO

Objective: Vascular smooth muscle cells (VSMCs) undergo the phenotypic changes from contractile to synthetic state during vascular remodeling after ischemia. SIRT1 protects against stress-induced vascular remodeling via maintaining VSMC differentiated phenotype. However, the effect of smooth muscle SIRT1 on the functions of endothelial cells (ECs) has not been well clarified. Here, we explored the role of smooth muscle SIRT1 in endothelial angiogenesis after ischemia and the underlying mechanisms. Methods: We performed a femoral artery ligation model using VSMC specific human SIRT1 transgenic (SIRT1-Tg) and knockout (KO) mice. Angiogenesis was assessed in in vivo by quantification of the total number of capillaries, wound healing and matrigel plug assays, and in vitro ECs by tube formation, proliferation and migration assays. The interaction of HIF1α with circRNA was examined by using RNA immunoprecipitation, RNA pull-down and in situ hybridization assays. Results: The blood flow recovery was significantly attenuated in SIRT1-Tg mice, and markedly improved in SIRT1-Tg mice treated with SIRT1 inhibitor EX527 and in SIRT1-KO mice. The density of capillaries significantly decreased in the ischemic gastrocnemius of SIRT1-Tg mice compared with SIRT1-KO and WT mice, with reduced expression of VEGFA, which resulted in decreased number of arterioles. We identified that the phenotypic switching of SIRT1-Tg VSMCs was attenuated in response to hypoxia, with high levels of contractile proteins and reduced expression of the synthetic markers and NG2, compared with SIRT1-KO and WT VSMCs. Mechanistically, SIRT1-Tg VSMCs inhibited endothelial angiogenic activity induced by hypoxia via the exosome cZFP609. The cZFP609 was delivered into ECs, and detained HIF1α in the cytoplasm via its interaction with HIF1α, thereby inhibiting VEGFA expression and endothelial angiogenic functions. Meantime, the high cZFP609 expression was observed in the plasma of the patients with atherosclerotic or diabetic lower extremity peripheral artery disease, associated with reduced ankle-brachial index. Knockdown of cZFP609 improved blood flow recovery after hindlimb ischemia in SIRT1-Tg mice. Conclusions: Our findings demonstrate that SIRT1 may impair the plasticity of VSMCs. cZFP609 mediates VSMCs to reprogram endothelial functions, and serves as a valuable indicator to assess the prognosis and clinical outcomes of ischemic diseases.

10.
Clin Neuropharmacol ; 43(1): 15-19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31895151

RESUMO

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare disease, whose etiology and risk factors remain unclear and need investigation. METHODS: We collected 7 CIE cases from 2646 patients injected with ioversol and 5 CIE cases from 526 patients injected with iopromide, all of whom underwent neurointervention surgery in our regional centers. The incidence of CIE, its characteristics, and risks were analyzed in both groups. RESULTS: The overall incidence of CIE was 0.38%, specifically 0.95% and 0.26% in the iopromide and ioversol groups, respectively; the former incidence was significantly higher than the latter (P = 0.029). The risk of CIE with iopromide was 3.567 to 3.618 times higher than that with ioversol (single-factor analysis odds ratio [OR], 3.618; 95% confidence interval [CI], 1.144-11.443; P = 0.029; multifactor analysis OR, 3.567 (95% CI, 0.827-15.379); P = 0.088). Moreover, acute cerebral infarction was an independent risk factor for CIE (OR, 4.024; 95% CI, 1.137-14.236; P = 0.031). Contrast-induced encephalopathy could occur within 5 minutes after injecting contrast media. The CIE characteristics differed according to the medium. In the ioversol group, the most common characteristic was visual disorder (71.43%), whereas in the iopromide group, the most common characteristic was delirium (100%). CONCLUSIONS: Compared with ioversol, iopromide appeared more likely to lead to CIE. Acute cerebral infarction was an independent risk factor for CIE. The earliest CIE onset was within 5 minutes after injecting contrast. The characteristics of CIE varied significantly for different contrast media.

11.
Chem Commun (Camb) ; 56(14): 2167-2170, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31970366

RESUMO

One-electron oxidation of 1,3-digerma-2,4-dipnictacyclobutadiene [LHGeE]2 (LH = CH[CHNDipp]2, dipp = 2,6-iPr2C6H3; 1: E = P; 2: E = As) with Ag[Al(ORF)4] (RF = C(CF3)3) afforded the stable radical cation salts 1˙+·[Al(ORF)4]- and 2˙+·[Al(ORF)4]-, respectively. The radical cation salts have been fully characterized, in conjunction with theoretical calculations. The EPR spectroscopic studies and DFT calculations reveal that the spin density mainly resides at the heavy pnictogen atoms, rather than delocalizes over the Ge2E2 ring. They represent the first structurally characterized cyclic radical species composed of both heavy group 14 and 15 elements.

12.
Anal Chem ; 92(1): 1097-1105, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31814401

RESUMO

Chemical cross-linking combined with mass spectrometry (CXMS) has emerged as a powerful tool to study protein structure, conformation, and protein-protein interactions (PPIs). Until now, most cross-linked peptides were generated by using commercial cross-linkers, such as DSS, BS3, and DSSO, which react with the primary amino groups of the lysine residues of proteins. However, trypsin, the most commonly used proteolytic enzyme, cannot cleave the C-terminus of a linked lysine, making the obtained cross-linked peptides longer than common peptides and unfavorable for MS identification and data searching. Herein, we propose an in situ sequential digestion strategy using enzymes with distinct cleavage specificity, named as smart cutter, to generate cross-linked peptides with suitable length so that the identification coverage could improve. Through the application of such a strategy to DSS cross-linked E. coli lysates, additional cross-linked sites (1.3-fold increase) obtained in comparison with those obtained by trypsin-trypsin digestion (2879 vs 1255). Among the different digestion combinations, AspN-trypsin performed the best, with 64% (673/1059) of the cross-linked sites complementary to trypsin-trypsin digestion, which is beneficial to ensure the depth for studying protein structure and PPIs. Taking the 60 kDa chaperonin protein as an example, more than twice the cross-linked sites (30 vs 14) were identified to enrich the protein structure information. In addition, compared to the published protein interaction network for E. coli ( http://www.bacteriome.org ), 91 potential PPIs were discovered with our strategy, of which 65 have not covered by trypsin-trypsin digestion. Therefore, these results illustrate the great significance of smart-cutter-based CXMS for the revelation of protein structure as well as finding new PPIs.

13.
J Comput Chem ; 41(4): 279-289, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31713268

RESUMO

Density functional theory (DFT) calculations were performed to gain insight into the mechanism of the nickel-catalyzed hydrocyanation of terminal alkynes with Zn(CN)2 and water to exclusively generate the branched nitrile with excellent Markovnikov selectivity. After precatalyst activation to give the LNi(0) active species, the transformation proceeds via the following steps: (1) oxidative addition of H2 O to the LNi(0) provides the intermediate LNi(II)H(OH); (2) ligand exchange of LNi(II)H(OH) with Zn(CN)2 gives the intermediate LNi(II)H(CN); (3) alkyne insertion to the LNi(II)H(CN) forms the alkenyl nickel complex, followed by the reductive elimination step reaching the final product. This mechanism is kinetically and thermodynamically more favorable than that of the experimental proposed ones. On the basis of the experimental observations, more water molecules cannot further improve the reaction as it has also been rationalized. Furthermore, the origin of the high regioselectivity of the product, the variable effectiveness of the metal mediator as function of ligands, as well as the high yield of the alkyl-substituted alkynes substrates, is analyzed in detail. © 2019 Wiley Periodicals, Inc.

14.
J Gene Med ; 22(1): e3144, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31742830

RESUMO

BACKGROUND: The hepatobiliary tract may be a valuable administration site for gene delivery. We demonstrated the role of temporary biliary obstruction for gene transfection by retrograde intrabiliary infusion. METHODS: Male Sprague-Dawley rats received intrabiliary infusion of luciferase plasmid via an artificial common bile duct, with temporary biliary obstruction for 0 minutes (NO group), 30 minutes (30 min group) and 24 hours (24 h group), respectively (n = 4 for each group). Gene expression levels were evaluated by luciferase bioluminescence on postoperative days (POD) 1, 2 and 7. Serum and livers were collected on POD 1 and 14 for liver biochemistry, hematoxylin and eosin staining, and immunohistochemistry. RESULTS: On POD 1, luciferase chemoluminescence was significantly higher in the 24 h group than in the NO group (p = 0.002) and the 30 min group (p = 0.002). However, it decreased rapidly after reversal of the obstruction in the 24 h group (POD 1 versus POD 2, p = 0.002; POD 1 versus POD 7, p = 0.002). Liver biochemistry was changed on POD 1, but no significant differences were detected after 14 days of recovery (p > 0.05). Similar histological changes were found in the three groups, with no unwanted proliferation of biliary epithelial cells. The obstruction did not cause serious liver damage. CONCLUSIONS: Temporary biliary obstruction for 24 hours facilitated the safe, feasible and effective transfection of plasmid DNA into the liver via the hepatobiliary tract. In the future, endoscopic retrograde cholangiopancreatography and its dilation balloon could be used to create biliary obstruction and allow the direct gene delivery into the liver. More research is necessary for achieving stable gene expression, as well as in terms of weighing its benefits against potential complications.

15.
Arch Virol ; 165(1): 137-143, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745718

RESUMO

Canine circovirus (canine CV) is an etiological agent associated with diarrhea, hemorrhagic gastroenteritis and vasculitis. Although canine CV has been identified and characterized in southern China in recent years, its epidemiology in other regions of China and its precise molecular characteristics have not been examined. In this study, we examined 141 fecal specimens collected from domestic dogs with or without diarrhea in Heilongjiang province, Northeastern China, during 2014 to 2016. A total of 18 out of 141 samples were found to be positive for canine CV by real-time quantitative PCR. In the diarrhea samples, canine CV was detected in coinfections with canine parvovirus 2. More importantly, two different canine CV strains were detected in one sample. Five canine CV genomes were successfully amplified. Sequence analysis showed that there were two unique amino acid changes in the Rep protein (N39S in the K1 strain, and T71A in the XF16 strain). Phylogenetic analysis indicated that canine CV could be divided into four genotypes, and specific nucleotide mutations could be used for confirming the four genotypes. Moreover, recombination analysis revealed that a total of eight recombination events were found in five genomic sequences. Molecular evolution analysis showed that the canine CV has been under purifying selection. This study provides evidence that at least three genotypes of canine CV are co-circulating in China. Continuous epidemiological surveillance is therefore necessary to understand their importance for the evolution of canine CV.


Assuntos
Circovirus/classificação , Diarreia/veterinária , Doenças do Cão/virologia , Mutação , Parvovirus Canino/isolamento & purificação , Animais , China , Circovirus/genética , Diarreia/virologia , Cães , Evolução Molecular , Fezes/virologia , Parvovirus Canino/genética , Filogenia , Proteínas Virais/genética , Sequenciamento Completo do Genoma
16.
Surg Endosc ; 34(1): 417-428, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30972622

RESUMO

BACKGROUND: Submucosal tunneling endoscopic resection (STER) and endoscopic submucosal excavation (ESE) were recently introduced to cure submucosal tumors (SMTs) originating from the muscularis propria (MP) layer. This study aimed to compare clinical performance and safety of STER and ESE in treating esophageal SMTs originating from the MP layer. METHODS: From January 2011 to December 2017, retrospective data collection and follow-up were applied for all STER or ESE cases with esophageal SMTs originating from the MP layer in our endoscopy center, including clinical characteristics, procedure success, efficacy, and adverse events. Subgroup analysis was further done based on tumor size and origin. RESULTS: 90 STER and 77 ESE were enrolled in this study. There were no significant difference for patient characteristics, procedure performance, and complications for ESE and STER intervention (P > 0.05). STER was faster than ESE (3.90 mm2/min vs 2.82 mm2/min, P < 0.05). For large tumors (≥ 20 mm), both techniques had the similar performance (P > 0.05), while STER led to the shorter hospitalization (4.0d vs 7.0d, P < 0.05) and lower postoperative complication (16.3% vs 45.5%, P < 0.05). For small tumors (< 20 mm), STER achieved faster operation (STER vs ESE, 2.57 mm2/min vs 1.83 mm2/min, P < 0.05). Regardless of tumor origin, there were no significant difference for both techniques, but STER resulted in short hospitalization for SMTs from the deep MP layer (STER vs ESE, 5.0d vs 7.0d, P < 0.05). During the follow-up, 2 residual and 4 recurrence occurred in the STER group, as well as 1 residual and 2 recurrence in the ESE group. CONCLUSIONS: Both STER and ESE were effective for treating esophageal SMTs originating from the MP layer. STER might be better due to its faster operation, less complications, and shorter hospitalization.

17.
Basic Clin Pharmacol Toxicol ; 126(2): 166-180, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31483925

RESUMO

Sorafenib, a multi-kinase inhibitor, is recommended as a new standard therapy for advanced hepatocellular carcinoma (HCC); however, it also exhibits severe cardiotoxicity and the toxicity mechanisms are not completely elucidated. Recent studies suggested that sorafenib-enhanced ROS may partially contribute to its anti-HCC effect, which implies that redox mechanism might also be involved in sorafenib's cardiotoxicity. In this study, we aimed to investigate if sorafenib is able to induce oxidative stress and how this may impair cellular functions in cardiomyocyte, ultimately accounting for its cardiotoxicity. Our results showed that in isolated rat hearts, sorafenib caused ventricular arrhythmias and left ventricular dysfunction, which were alleviated by the antioxidant N-(2-mercaptopropionyl)-glycine (MPG). In isolated ventricular myocytes, sorafenib increased diastolic intracellular Ca2+ levels, decreased Ca transients and the occurrence of Ca2+ waves. These changes were eliminated by MPG, CaMKII inhibitor KN-93 and the mitochondrial permeability transition pore (mPTP)inhibitor cyclosporin A (CsA). Moreover, the levels of oxidized and phosphorylated CaMKII were significantly increased. Sorafenib elevated ROS levels, which was reversed by CsA and MPG; additionally, sorafenib reduced the activity of mitochondrial complex III and augmented mitochondrial ROS production. In vivo rats treated with sorafenib exhibited a reduction of antioxidant defence and abnormal histological alterations including hypertrophy, increased fibrosis, disordered myofibrils and damaged mitochondria, which were protected by MPG. We conclude that sorafenib induces the disruption of Ca2+ homoeostasis and cardiac injury via enhanced ROS potentially through inhibiting mitochondrial complex III, the opening of mPTP and overactivating CaMKII. These results provide a potential strategy for preventing or reducing cardiotoxicity of sorafenib.

18.
ACS Appl Mater Interfaces ; 12(2): 2362-2369, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31846290

RESUMO

As a green, pollution-free, and renewable clean energy source, photocatalytic H2 production has attracted great attention. Here, epitaxial growth of pyramidal CdS-Cd nanoparticles on S-doped MoO2 nanosheets (CdS-Cd/S-MoO2) was prepared by one-step co-sublimation of CdS and MoO3. The photogenerated electrons of CdS as a photocatalyst are transferred to Cd and S-MoO2 as co-catalysts for H2 production, which is observed by surface photovoltage (SPV) under visible light irradiation. At last, the obtained CdS-Cd/S-MoO2 presented an efficient photocatalytic performance under the visible light (>420 nm) with a prominent H2 generation rate of as high as 24.98 µmol h-1 mg-1, which is 11 times higher than that of the CdS-Cd nanoparticles (2.26 µmol h-1 mg-1), and it is superior than that of the CdS (1.51 µmol h-1 mg-1).

19.
Dig Liver Dis ; 52(2): 233, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31843254
20.
Eur J Radiol ; 123: 108791, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31884189

RESUMO

PURPOSE: To investigate the utility of basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) for the diagnosis of vertebrobasilar artery lesions. METHOD: From October 2017-November 2018, 105 consecutive patients with abnormal configuration of the vertebrobasilar artery on time-of-flight magnetic resonance angiography (TOF-MRA) were enrolled. Conventional high-resolution MRI combined with TOF-MRA were performed to diagnose lesions and were used as the standard for sensitivity and specificity determination. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were calculated. The consistencies between the two methods were evaluated by kappa test. RESULTS: Of the 105 patients, 45 were diagnosed with arteriosclerosis, 46 with vertebral artery dysplasia, 11 with artery dissection or dissecting aneurysm, and 3 as simple dilatation. Results Compared with conventional high-resolution MRI combined with TOF-MRA, for vertebrobasilar arteriosclerosis, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of BPAS-MRI combined with TOF-MRA were 95.6 %, 95.0 %, 93.5 %, 96.6 % and 95.2 %, respectively and kappa value was 0.903. For vertebral artery dysplasia, they were 100 %, 96.6 %, 95.8 %, 100 %, and 98.1 %, respectively and kappa value was 0.961. For vertebrobasilar artery dissection or dissection aneurysm, they were 81.8 %, 96.8 %, 97.8 %, 75.0 % and 95.2 %, respectively and kappa value was 0.756. CONCLUSIONS: BPAS-MRI can show the outer contour of the vertebrobasilar artery system. Combined with TOF-MRA, it may be used to differentiate among vertebrobasilar artery abnormalities, and be used in hospitals where conventional high-resolution MRI is not feasible.

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