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1.
Sci Signal ; 15(729): eabm5011, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412849

RESUMO

Toll-like receptor (TLR) stimulation induces glycolysis and the production of mitochondrial reactive oxygen species (ROS), both of which are critical for inflammatory responses in macrophages. Here, we demonstrated that cyclin J, a TLR-inducible member of the cyclin family, reduced cytokine production in macrophages by coordinately controlling glycolysis and mitochondrial functions. Cyclin J interacted with cyclin-dependent kinases (CDKs), which increased the phosphorylation of a subset of CDK substrates, including the transcription factor FoxK1 and the GTPase Drp1. Cyclin J-dependent phosphorylation of FoxK1 decreased the transcription of glycolytic genes and Hif-1α activation, whereas hyperactivation of Drp1 by cyclin J-dependent phosphorylation promoted mitochondrial fragmentation and impaired the production of mitochondrial ROS. In mice, cyclin J in macrophages limited the growth of tumor xenografts and protected against LPS-induced shock but increased the susceptibility to bacterial infection. Collectively, our findings indicate that cyclin J-CDK signaling promotes antitumor immunity and the resolution of inflammation by opposing the metabolic changes that drive inflammatory responses in macrophages.


Assuntos
Imunidade Inata , Macrófagos , Animais , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Macrófagos/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
2.
Front Immunol ; 13: 824586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371015

RESUMO

Purpose: The development and progression of glioma are associated with the tumor immune microenvironment. Diffuse low-grade gliomas (LGGs) with higher immunosuppressive microenvironment tend to have a poorer prognosis. The study aimed to find a biological marker that can reflect the tumor immune microenvironment status and predict prognosis of LGGs. Methods: The target gene tenascin-C (TNC) was obtained by screening the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) databases. Then samples of LGGs were collected for experimental verification with immunohistochemistry, immunofluorescence, immunoblotting, quantitative real-time PCR. ELISA was employed to determine the content of TNC in serum and examine its relationship with the tumor immune microenvironment. Eventually, the sensitivity of immunotherapy was predicted on the basis of the content of TNC in LGGs. Results: In the high-TNC subgroup, the infiltration of immunosuppressive cells was increased (MDSC: r=0.4721, Treg: r=0.3154, etc.), and immune effector cells were decreased [NKT, γδT, etc. (p<0.05)], immunosuppressive factors were elevated [TGF-ß, IL10, etc. (p<0.05)], immunostimulatory factors, such as NKG2D, dropped (p<0.05), hypoxia scores increased (p<0.001), and less benefit from immunotherapy (p<0.05). Serum TNC level could be used to assess the status of tumor immune microenvironment in patients with grade II (AUC=0.8571; 95% CI: 0.6541-1.06) and grade III (AUC=0.8333; 95% CI: 0.6334-1.033) glioma. Conclusions: Our data suggested that TNC could serve as an indicator for the immunosuppressive microenvironment status and the prognosis of LGGs. Moreover, it could also act as a predictor for the effect of immunotherapy on LGG patients.


Assuntos
Neoplasias Encefálicas , Glioma , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico , Tenascina/genética , Microambiente Tumoral
3.
Sci Total Environ ; 821: 153534, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35101486

RESUMO

Recently, more and more cold flowing water aquaculture has been adopted, but its wastewater treatment is always ignored, which causes great pressure on the environment. In this study, a compound in-situ treatment system that applied hydroponic plants and biofilm was constructed to treat the wastewater produced by cold flowing water culture of sturgeon. The removal efficiency of the nutrients from culture and the microbial composition in water and biofilm were tested, the correlation between the water quality indexes and bacterium was analyzed, and the abundance of nitrogen and phosphorus cycling genes was quantified. The results show that the system respectively achieved 90%, 100%, 100%, 100% and 48% removal efficiency of NH4+-N, NO3--N, TN, TP and COD which were produced by experimental sturgeon culture. Chinese cabbage (Brassica rapa var. chinensis) and water dropwort (Oenanthe javanica) showed obvious growth in the four plants, which contributed to the removal of nutrients from wastewater. Besides, in the biofilm, Proteobacteria, Bacteroidetes and Verrucomicrobia became the top three dominant flora at the phylum level, and Flavobacterium, Rhodoferax, Sphaerotilus and Chitinimonas became the top four dominant flora at the genus level, which promoted the removal of nitrogen in the wastewater. The FAPROTAX analysis result shows that the highest functions within the carbon and nitrogen metabolisms were significantly identified in the biofilm, such as chemoheterotrophy, aerobic chemoheterotrophy and nitrate reduction. Further, the abundance of denitrifying genes (narG and napA) was higher than the nitrifying related genes (nxrB and amoA), indicating the more active denitrifying process. In summary, the compound in-situ treatment system efficiently removed nutrients from cold flowing water aquaculture. And the combined purification of hydroponic plants and biofilm which is rich in denitrifying bacterium plays an essential role in this process.


Assuntos
Desnitrificação , Águas Residuárias , Aquicultura , Biofilmes , Reatores Biológicos , Hidroponia , Nitrogênio/análise , Águas Residuárias/análise
4.
Anim Nutr ; 8(1): 235-248, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34988305

RESUMO

In recent years, high-fat diet (HFD) has been widely applied in aquaculture, which reduces the intestinal health of cultured fish. The current study evaluated the protective effects of nano-selenium (nano-Se) on intestinal health of juvenile grass carp (Ctenopharyngodon idella) fed with HFD. A total of 135 experimental fish were fed with a regular diet (Con), a HFD (HFD) and a HFD containing nano-Se at 0.6 mg/kg (HSe) for 10 weeks. The results showed that dietary nano-Se significantly improved the survival rate and feed efficiency which were reduced by HFD in juvenile grass carp (P < 0.05). Also, nano-Se (0.6 mg/kg) supplement alleviated intestinal damage caused by the HFD, thus maintaining the integrity of the intestine. Moreover, it significantly up-regulated the expression of genes related to tight junction (ZO-1, c laudin-3 and o ccludin), anti-oxidization (GPx4a andGPx4b), and the protein of ZO-1 in the intestine of juvenile grass carp, which were depressed by the HFD (P < 0.05). Furthermore, nano-Se supplementation significantly suppressed the expressions of genes related to the inflammation, including inflammatory cytokines (IL-8, IL-1ß, IFN-γ, TNF-α and IL-6), signaling molecules (TLR4, p38 MAPK and NF-κB p65), and protein expression of NF-κB p65 and TNF-α in the intestine of juvenile grass carp which were induced by the HFD (P < 0.05). Besides, dietary nano-Se normalized the intestinal microbiota imbalance of juvenile grass carp caused by the HFD through increasing the abundance of the beneficial bacteria, e.g., Fusobacteria. Finally, dietary nano-Se increased the production of short chain fatty acids (SCFA) in the intestine, especially for butyric acid and caproic acid, which were negatively related to the increase of intestinal permeability and inflammation. In summary, supply of nano-Se (0.6 mg/kg) in HFD could effectively alleviate intestinal injury of juvenile grass carp by improving intestinal barrier function and reducing intestinal inflammation and oxidative stress. These positive effects may be due to the regulation of nano-Se on intestinal microbiota and the subsequently increased beneficial SCFA levels.

5.
Sci Total Environ ; 809: 151113, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34688743

RESUMO

This study explored the performances, and associated mechanisms of biochar promoting volatile fatty acids (VFA) oxidation via extracellular electron transfer (EET) pathway. It was found that in a bioelectrochemical system, adding biochar suspension remarkably enhanced electricity generation whatever acetate or propionate used as an electron donor. The maximum current density in biochar-assisted groups reached 1.6-2.2 A/m2, which were 69.2-220.0% higher than that of control groups. The lower electrical resistance of anode in biochar-assisted groups was potentially attributed to the formed biofilm dominated by electro-active Geobacteraceae, and the electron donor type depending on dominant genus. In specific, with biochar assistance, Desulfuromonas enriched from 1.1% to 25.0% when acetate as an electron donor, and the relative abundance of Geobacter increased from 4.6% to 31.7% as dominant genus in propionate-added group. Electrochemical analysis uncovered that biochar hardly elevated sludge electrical conductivity, while the excellent redox-based electron exchange transfer capacity likely made biochar as a transient electron acceptor, which was more accessible than anode to support the metabolism of electroactive bacteria in the initial stage. Meanwhile, the porous surface area of biochar particle likely provided a "bridge" between suspended sludge and anode, to support a more directional evolution of electroactive bacteria on anode. This dual-function of biochar achieved a sustainable VFA oxidation via EET-based pathway.


Assuntos
Elétrons , Ácidos Graxos Voláteis , Carvão Vegetal , Condutividade Elétrica , Eletrodos , Oxirredução
6.
Bioresour Technol ; 346: 126352, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34798251

RESUMO

This study explored the influence of biochar (BC) on anaerobic digestion (AD) of swine manure under various tetracycline (TC) pressures. It was found that both low (0.5 mg/L) and high (50 mg/L) TC pressures inhibited AD performance, while BC mitigated it in multi-facets. Under high TC pressure, BC accelerated syntrophic methanogenesis by boosting direct interspecies electron transfer pathway. The TC removal efficiencies were enhanced by 24.3-158.2% with BC assistance, which was attributed to the enhanced biological degradation rather than BC's physiochemical adsorption. Moreover, BC possibly acted as a protective role to alleviate intensive extracellular polymeric substances secretion under TC pressures. Integrated microbial community, metabolic function predicting, and antibiotic resistance genes (ARG) analysis revealed that BC addition not only enriched Anaerolineceae, which likely responsible for the 24.2-41.9% higher level expression of organics metabolic pathways and xenobiotics biodegradation, but also reduced ARG abundance by controlling the potential ARG host (Firmicutes) proliferation.


Assuntos
Carvão Vegetal , Esterco , Anaerobiose , Animais , Antibacterianos/farmacologia , Digestão , Suínos , Tetraciclina
7.
Artigo em Inglês | MEDLINE | ID: mdl-34954089

RESUMO

Our previous study has found that selenium (Se) can alleviate lipid accumulation caused by high-fat diet (HFD) in fish. This study aims to explore the selenoproteins (SePs) in grass carp Ctenopharyngodon idella by characterizing cDNAs of nine SeP genes (SELENOF, SELENOM, SELENOS, SELENOP1, SELENOP2, SELENOE, SELENOL, SELENOU1a and SELENOU1b) and measuring their transcriptional activity in response to HFD and HFD supplemented with 0.3 mg/Kg and 0.6 mg/Kg of Se (HSe 0.3 and HSe 0.6). Firstly, the nine SeP genes in grass carp encoded proteins with conserved functional protein regions in fish and other vertebrates. Secondly, the nine SeP genes except SELENOS showed high expression levels in the hepatopancreas, but in the adipose tissue, only SELENOS, SELENOE and SELENOU1b showed high expression levels. Further, HFD significantly up-regulated the expressions of SELENOF and SELENOS in the hepatopancreas and SELENOM in the adipose tissue of grass carp (P < 0.05), but significantly down-regulated the expressions of SELENOU1b in the hepatopancreas, SELENOP2, SELENOE, SELENOL and SELENOU1a in the adipose tissue and SELENOM in the muscle of grass carp (P < 0.05). In addition, for the hepatopancreas, the expressions of SELENOS in the HSe 0.3 group and SELENOF, SELENOM and SELENOP2 in the HSe 0.6 group significantly decreased compared with the HFD group (P < 0.05). For the adipose tissue, the expressions of SELENOF, SELENOP2, SELENOL, SELENOU1a and SELENOU1b in the HSe 0.3 group and SELENOP2, SELENOE, SELENOU1a and SELENOU1b in the HSe 0.6 group significantly increased compared with the HFD group (P < 0.05). In summary, the transcriptional activities of the nine SeP genes were regulated by the HFD and HFD supplemented with Se, indicating the potential role of these genes in the Se regulated lipid metabolism processes in grass carp, which is worthy of in-depth study.


Assuntos
Carpas , Doenças dos Peixes , Selênio , Ração Animal/análise , Animais , Carpas/genética , Carpas/metabolismo , Dieta , Dieta Hiperlipídica , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Selênio/farmacologia , Selenoproteínas/genética , Selenoproteínas/metabolismo , Distribuição Tecidual
8.
Front Bioeng Biotechnol ; 9: 641130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33842445

RESUMO

Design an implant similar to the human bone is one of the critical problems in bone tissue engineering. Metal porous scaffolds have good prospects in bone tissue replacement due to their matching elastic modulus, better strength, and biocompatibility. However, traditional processing methods are challenging to fabricate scaffolds with a porous structure, limiting the development of porous scaffolds. With the advancement of additive manufacturing (AM) and computer-aided technologies, the development of porous metal scaffolds also ushers in unprecedented opportunities. In recent years, many new metal materials and innovative design methods are used to fabricate porous scaffolds with excellent mechanical properties and biocompatibility. This article reviews the research progress of porous metal scaffolds, and introduces the AM technologies used in porous metal scaffolds. Then the applications of different metal materials in bone scaffolds are summarized, and the advantages and limitations of various scaffold design methods are discussed. Finally, we look forward to the development prospects of AM in porous metal scaffolds.

9.
Materials (Basel) ; 13(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899150

RESUMO

For the multi-layer and multi-pass welding process of the heavy plate, the hydrogen diffusion behavior was numerically simulated to study the effect of solid-state phase transition (SSPT) on the hydrogen diffusion in the thickness direction, and the influence of the residual stress-induced diffusion after SSPT. The calculation results were compared with the experimental results. The comparison shows that the distribution of hydrogen concentration in the direction of thickness was in good agreement. The position with the most severe cold cracking sensitivity was located at a 20-30 mm depth from the top surface in this article. After welding, the hydrogen concentration in this position was kept at a high level for a long time under the effect of the size-constraint effect of the heavy plate and the existence of welding residual stress gradient. In addition, the SSPT reduced the residual stress level of weld metal (WM) significantly, increased that of the heat affected zone (HAZ), and the hydrogen was redistributed under the influence of stress. In the process of phase transformation, the parameters of hydrogen diffusion property of the material changed dramatically in a short time, the hydrogen diffusion coefficient increased in order of magnitude, and the solubility decreased in order of magnitude. This directly led to the upward diffusion of hydrogen in WM, and produced a self-gathering effect. For a welded joint of heavy plate, the self-gathering effect between passes was effective in the short-range and ineffective in the long-range.

10.
Bioresour Technol ; 314: 123777, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32665106

RESUMO

In this review, progress in the potential mechanisms of biochar amendment for AD performance promotion was summarized. As adsorbents, biochar was beneficial for alleviating microbial toxicity, accelerating refractory substances degradation, and upgrading biogas quality. The buffering capacity of biochar balanced pH decreasing caused by volatile fatty acids accumulation. Moreover, biochar regulated microbial metabolism by boosting activities, mediating electron transfer between syntrophic partners, and enriching functional microbes. Recent studies also suggested biochar as potential useful additives for membrane fouling alleviation in anaerobic membrane bioreactors (AnMBR). By analyzing the reported performances based on different operation models or substrate types, debatable issues and associated research gaps of understanding the real role of biochar in AD were critically discussed. Accordingly, Future perspectives of developing biochar-amended AD technology for real-world applications were elucidated. Lastly, with biochar-amended AD as a core process, a novel integrated scheme was proposed towards high-efficient energy-resource recovery from various bio-wastes.


Assuntos
Reatores Biológicos , Carvão Vegetal , Anaerobiose , Biocombustíveis , Metano
11.
J Nanobiotechnology ; 18(1): 61, 2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32306970

RESUMO

Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe2+ are more abundant in peri-hematomal tissue than in healthy tissue because of red blood cell lysis, we developed a metal ion-responsive nanocarrier based on a phosphonated calix[4]arene derivative in order to deliver the neuroprotective agent dauricine (DRC) specifically to sites of primary and secondary brain injury. The potential of the dauricine-loaded nanocarriers for ICH therapy was systematically evaluated in vitro and in mouse models of autologous whole blood double infusion. The nanocarriers significantly reduced brain water content, restored blood-brain barrier integrity and attenuated neurological deficits by inhibiting the activation of glial cells, infiltration by neutrophils as well as production of pro-inflammatory factors (IL-1ß, IL-6, TNF-α) and matrix-metalloprotease-9. These results suggest that our dauricine-loaded nanocarriers can improve neurological outcomes in an animal model of ICH by reducing inflammatory injury and inhibiting apoptosis and ferroptosis.


Assuntos
Benzilisoquinolinas/química , Calixarenos/química , Hemorragia Cerebral/patologia , Portadores de Fármacos/química , Metais/química , Nanoestruturas/química , Fármacos Neuroprotetores/química , Fenóis/química , Tetra-Hidroisoquinolinas/química , Animais , Benzilisoquinolinas/administração & dosagem , Benzilisoquinolinas/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Hemorragia Cerebral/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Interleucina-1beta/metabolismo , Íons/química , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Organofosfonatos/química , Espécies Reativas de Oxigênio/metabolismo , Tetra-Hidroisoquinolinas/administração & dosagem , Tetra-Hidroisoquinolinas/farmacologia
12.
J Nutr ; 149(12): 2247-2254, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31373375

RESUMO

BACKGROUND: Brain iron deposition is a feature of Alzheimer disease and may contribute to its development. However, the relative contribution of dietary iron remains unclear. OBJECTIVES: We investigated the impact of high dietary iron on brain pathological changes and cognitive function in adult wild-type (WT) mice and amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice. METHODS: Male WT mice and APP/PS1 mice aged 10 wk were fed either a control diet (66 mg Fe/kg) (WT-Ctrl and APP/PS1-Ctrl) or a high iron diet (14 g Fe/kg) (WT-High Fe and APP/PS1-High Fe) for 20 wk. Iron concentrations in brain regions were measured by atomic absorption spectrophotometry. Brain iron staining and amyloid-ß (Aß) immunostaining were performed. Protein expressions in the hippocampus were determined by immunoblotting. Superoxide dismutase (SOD) activity and malondialdehyde concentration were examined. Cognitive functions were tested with the Morris water maze system. RESULTS: In the hippocampus, APP/PS1-High Fe mice had significantly higher iron concentration (2.5-fold) and ferritin (2.0-fold) than APP/PS1-Ctrl mice (P < 0.001), and WT-High Fe mice had significantly higher ferritin (2.0-fold) than WT-Ctrl mice (P < 0.001). Interestingly, APP/PS1 mice had significantly higher iron concentration (2-3-fold) and ferritin (2-2.5-fold) than WT mice fed either diet (P < 0.001). Histological analysis indicated that iron accumulated in the hippocampal dentate gyrus region in APP/PS1 mice, consistent with the pattern of Aß deposition. For both mouse strains, iron treatment induced Aß and phospho-τ expression (1.5-3-fold) in the hippocampus, but had little impact on oxidative stress and cognitive function. Furthermore, APP/PS1 mice had significantly lower SOD activity and higher malondialdehyde concentration than WT mice in the hippocampus (P < 0.0001), paralleled by apparent cognitive dysfunction. CONCLUSIONS: Dietary iron overload induces iron disorder and Aß and phospho-τ expression in the hippocampus of adult WT and APP/PS1 transgenic mice.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Hipocampo/metabolismo , Homeostase , Ferro/administração & dosagem , Ferro/metabolismo , Presenilina-1/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/genética , Animais , Dieta , Crescimento , Masculino , Camundongos , Camundongos Transgênicos , Estresse Oxidativo , Fosforilação , Proteínas tau/genética
13.
Sci Rep ; 9(1): 9437, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31263155

RESUMO

Accumulation of iron has been associated with the pathobiology of various disorders of the central nervous system. Our previous work has shown that hephaestin (Heph) and ceruloplasmin (Cp) double knockout (KO) mice induced iron accumulation in multiple brain regions and that this was paralleled by increased oxidative damage and deficits in cognition and memory. In this study, we enriched astrocytes and oligodendrocytes from the cerebral cortex of neonatal wild-type (WT), Heph KO and Cp KO mice. We demonstrated that Heph is highly expressed in oligodendrocytes, while Cp is mainly expressed in astrocytes. Iron efflux was impaired in Cp KO astrocytes and Heph KO oligodendrocytes and was associated with increased oxidative stress. The expression of Heph, Cp, and other iron-related genes was examined in astrocytes and oligodendrocytes both with and without iron treatment. Interestingly, we found that the expression of the mRNA encoding ferroportin 1, a transmembrane protein that cooperates with CP and HEPH to export iron from cells, was positively correlated with Cp expression in astrocytes, and with Heph expression in oligodendrocytes. Our findings collectively demonstrate that HEPH and CP are important for the prevention of glial iron accumulation and thus may be protective against oxidative damage.


Assuntos
Ceruloplasmina/genética , Ferro/metabolismo , Proteínas de Membrana/genética , Estresse Oxidativo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Ceruloplasmina/deficiência , Proteínas de Membrana/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligodendroglia/citologia , Oligodendroglia/metabolismo , Estresse Oxidativo/genética
14.
Front Pharmacol ; 10: 769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354485

RESUMO

Curcumin (CCM) has many potential uses in anticancer chemotherapy, but its low water solubility poses a major problem, preventing its translation into clinical use. TPGS is a water-soluble derivative of vitamin E that acts as a surfactant with the ability to form micellar nanoparticles in water. More importantly, TPGS acts as a potent antioxidant that can neutralize intracellular reactive oxygen species (ROS). In this study, we solubilized CCM with TPGS using thin-film rehydration to prepare aqueous formulations containing CCM at clinically relevant concentrations. We found that the minimal TPGS:CCM ratio for producing nanoparticles was 5:1 (w/w): at or above this ratio, stable nanoparticles formed with an average particle diameter of 12 nm. CCM was released from TPGS/CCM micelles in simulated colonic and gastric fluids. These TPGS/CCM nanoparticles were shown to decrease intracellular ROS levels and apoptosis and inhibited migration of HT-29 human colon cancer cells more potently than free CCM. Pharmacokinetic analysis showed TPGS/CCM to be more bioavailable than free CCM after oral administration to rats. Our results suggest that TPGS/CCM may increase therapeutic efficacy of CCM against colon cancer and merits further investigation in a clinical setting.

15.
Exp Ther Med ; 17(1): 603-612, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30651841

RESUMO

Neuroimaging techniques have been used to investigate idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) and different studies employing these methods have produced varying results. However, there have been few studies exploring diffusional kurtosis imaging (DKI) and regional homogeneity (ReHo) techniques in patients with IGE-GTCS. In the current study, resting-state functional magnetic resonance imaging (fMRI) and DKI data were collected from 28 patients with IGE-GTCS and 28 healthy controls. The ReHo method and tract-based spatial statistical (TBSS) analysis were performed to compare differences between the groups. Compared with healthy controls, patients with IGE-GTCS exhibited markedly increased ReHo in the bilateral putamen, the thalamus, right pallidum, right supplementary motor area and the bilateral paracentral lobules. Compared with healthy controls, patients with IGE-GTCS also exhibited markedly decreased ReHo in the posterior cingulate/precuneus, left angular gyrus and dorsolateral prefrontal cortex. In patients with IGE-GTCS, DKI revealed lower fractional anisotropy in the left anterior/superior corona radiata, left superior longitudinal fasciculus and genu/body of the corpus callosum. Higher mean diffusivity was detected in the bilateral anterior corona radiata, left superior corona radiata, left cingulum, and genu/body/splenium of the corpus callosum. Furthermore, reduced mean kurtosis values were identified over the bilateral superior/posterior corona radiate, left anterior corona radiata, right superior longitudinal fasciculus, left posterior thalamic radiation and the genu/body/splenium of the corpus callosum. Therefore, the results of the current study revealed abnormalities in spontaneous activity in the gray and white matter tracts in patients with IGE-GTCS. These results suggest that novel MRI technology may be useful to help determine the pathogenesis of IGE-GTCS.

16.
Redox Biol ; 17: 432-439, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29883959

RESUMO

Little is known about the iron efflux from the pancreas, but it is likely that multicopper ferroxidases (MCFs) are involved in this process. We thus used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout mice and Heph/Cp double-knockout mice to investigate the roles of MCFs in pancreatic iron homeostasis. We found that both HEPH and CP were expressed in the mouse pancreas, and that ablation of either MCF had limited effect on the pancreatic iron levels. However, ablation of both MCFs together led to extensive pancreatic iron deposition and severe oxidative damage. Perls' Prussian blue staining revealed that this iron deposition was predominantly in the exocrine pancreas, while the islets were spared. Consistent with these results, plasma lipase and trypsin were elevated in Heph/Cp knockout mice, indicating damage to the exocrine pancreas, while insulin secretion was not affected. These data indicate that HEPH and CP play mutually compensatory roles in facilitating iron efflux from the exocrine pancreas, and show that MCFs are able to protect the pancreas against iron-induced oxidative damage.


Assuntos
Ceruloplasmina/genética , Ferro/metabolismo , Proteínas de Membrana/genética , Estresse Oxidativo/genética , Animais , Ceruloplasmina/metabolismo , Homeostase/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Oxirredução , Oxirredutases/genética , Oxirredutases/metabolismo , Pâncreas Exócrino/metabolismo , Pâncreas Exócrino/patologia
17.
FEBS Lett ; 592(3): 394-401, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29355933

RESUMO

Little is known about the iron efflux mechanism in adipocytes. Here, we used hephaestin (Heph) and ceruloplasmin (Cp) single-knockout (KO) mice and Heph/Cp double-KO mice to investigate the roles of multicopper ferroxidases (MCFs) in this process. We show that both HEPH and CP are expressed in subcutaneous adipose tissue. Ablation of either MCF leads to a compensatory increase in the other, which contributes to the balance of iron status. However, ablation of both MCFs together induces severe iron deposition in adipocytes which is associated with decreased adiponectin and leptin mRNA expression. Furthermore, Heph/Cp KO mice display disordered carbohydrate metabolism characterized as type 2 diabetes. Together, these results demonstrate the protective roles of HEPH and CP in preventing iron overload in adipocytes.


Assuntos
Adipócitos/metabolismo , Ceruloplasmina/genética , Diabetes Mellitus Tipo 2/metabolismo , Ferro/metabolismo , Proteínas de Membrana/genética , Adiponectina/genética , Animais , Ceruloplasmina/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/veterinária , Técnicas de Inativação de Genes , Leptina/genética , Masculino , Proteínas de Membrana/metabolismo , Camundongos
18.
Eur J Radiol ; 93: 16-23, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28668411

RESUMO

BACKGROUND AND PURPOSE: Cognitive impairment is a common non-motor complication of Parkinson's disease (PD). To investigate cognitive-related changes of gray matter (GM) structure and function in PD using voxel-based morphometry (VBM) and resting state functional connectivity (RSFC). MATERIALS AND METHODS: Resting state functional magnetic resonance imaging (rs-fMRI) and 3D-T1-weighted MRI scans were obtained from 21 PD patients with mild cognitive impairment (PD-MCI), 11 PD patients with normal cognitive function (PD-NC), and 21 healthy controls (HC). Functional connectivity (FC) was analyzed by defining the posterior cingulated cortex (PCC) as the seed region. VBM was performed to assess patterns of GM atrophy. RESULTS: In PD-NC versus HC, results indicated decreased PCC-FC in the right temporal gyrus(TG) and increased PCC-FC in the left medial temporal lobe(MTL), bilateral precuneus(Pcu), and parieto-occipital junction(POJ), as well as GM atrophy in the bilateral prefrontal-striatal circuit(pFTSC), TG and Pcu. In PD-MCI versus PD-NC, decreased PCC-FC was found in the bilateral prefrontal cortex(PFC), left POJ, and right TG. In addition, PCC-FC of the bilateral Pcu and GM volume of the left MTL, bilateral TG, and PFC were positively associated with cognitive score. CONCLUSIONS: Structural and functional damage of the PFC and temporal lobe are associated with subtle cognitive decline in PD, while functional enhancement of the MTL and POJ is involved in normal cognitive function of PD. In addition, the combined application of rs-fMRI and VBM analysis might become an effective means to investigate cognitive impairment-related GM abnormalities in PD-MCI patients prior to development of dementia.


Assuntos
Disfunção Cognitiva/complicações , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Disfunção Cognitiva/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Sci Rep ; 6: 39470, 2016 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-27991585

RESUMO

Multicopper ferroxidases (MCFs) play an important role in cellular iron homeostasis. However, the role of MCFs in renal metabolism remains unclear. We used Hephaestin (Heph) and Ceruloplasmin (Cp) single or double (Heph/Cp) knockout (KO) mice to study the roles of MCFs in the kidney. Renal iron levels and the expression of iron metabolism genes were examined. The non-heme iron content both in the renal cortex and medulla of Heph/Cp KO mice was significantly increased. Perls' Prussian blue staining showed iron accumulation on the apical side of renal tubular cells in Heph/Cp KO mice. A significant increase in ferritin protein expression was also observed in the renal medulla and cortex of Heph/Cp KO mice. Both DMT1 and TfR1 protein expression were significantly decreased in the renal medulla of Heph/Cp KO mice, while the expression of DMT1 protein was significantly increased in the renal cortex of these animals. Significant increase in proteinuria and total urinary iron was observed in the double knockout mice, and this was associated with compromised structural integrity. These results suggest that KO of both the HEPH and CP genes leads to kidney iron deposition and toxicity, MCFs could protect kidney against a damage from iron excess.


Assuntos
Ceruloplasmina/genética , Ceruloplasmina/metabolismo , Ferro/metabolismo , Rim/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Animais , Cobre/química , Ferritinas/metabolismo , Ferrocianetos , Genótipo , Homeostase , Córtex Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
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