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1.
Dev Comp Immunol ; 126: 104226, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34348114

RESUMO

Although interleukin and interleukin analogues which play important immunomodulatory roles in mammals have not yet been reported in invertebrates, interleukin enhancer binding factor (IEBF) which acts as a transcription factor has been recently studied in several crustaceans and it may be involved in innate immune defence against pathogens. In this study, an IEBF 2 homologue was identified in the fresh water crayfish, Procambarus clarkii. The significantly changed expression levels of Pc-iebf 2 after bacterial challenge revealed the possibility of its participation in defence against bacterial infection. The results of an RNAi assay showed that the crayfish survival rate was obviously decreased after dsIEBF 2 injection, compared with the control groups. And S. aureus proliferation was obviously enhanced at 24 and 48 h post bacterial injection, when Pc-iebf 2 was knocked down. The possible molecular mechanisms for the innate immune regulation functions of Pc-IEBF 2 were also investigated. We speculated that Pc-IEBF 2 plays an important role in defending against bacterial infection in crayfish. It could regulate some innate immune responses by affecting the Toll signalling pathway, melanisation, and cell apoptosis.

2.
Front Neurosci ; 15: 797849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34955741

RESUMO

Although recent evidence indicates an association between gene co-expression and functional connectivity in human brain, specific association patterns remain largely unknown. Here, using neuroimaging-based functional connectivity data of living brains and brain-wide gene expression data of postmortem brains, we performed comprehensive analyses to dissect relationships between gene co-expression and functional connectivity. We identified 125 connectivity-related genes (20 novel genes) enriched for dendrite extension, signaling pathway and schizophrenia, and 179 gene-related functional connections mainly connecting intra-network regions, especially homologous cortical regions. In addition, 51 genes were associated with connectivity in all brain functional networks and enriched for action potential and schizophrenia; in contrast, 51 genes showed network-specific modulatory effects and enriched for ion transportation. These results indicate that functional connectivity is unequally affected by gene expression, and connectivity-related genes with different biological functions are involved in connectivity modulation of different networks.

3.
J Mech Behav Biomed Mater ; 124: 104859, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607301

RESUMO

Stereolithography (SL) 3D printing of ceramic materials is a promising forming technology to prepare denture with complex shape in the dental field. But the SL formed parts often have inferior mechanical properties than traditional forming method, and the debinding process is time assuming, limiting the clinical application of the technology. In this paper, a novel fluorapatite (FAp) glass-ceramics samples were fabricated through SL 3D printing based on self-made glass-ceramic powders. The effect of laser power and scanning speed on mechanical properties and tribological properties of FAp glass-ceramics were investigated. Phase compositions and microstructure of specimens were characterized by X-ray diffractometer and scanning electron microscope. The microhardness, flexural strength, elastic modulus and tribological performances of the SL samples were tested and compared with that of traditional dry pressing formed samples. The results showed that with the appropriate laser parameters and a relatively short debinding time, the SL formed glass-ceramics had microhardness, flexural strength, and elastic modulus of 772.05 Hv, 205.97 MPa, and 97.06 GPa, respectively, which exceeded that of traditional formed samples. The results reveal that it is possible to efficiently obtain FAp glass-ceramics with excellent mechanical and tribological performance by SL 3D printing process with appropriate parameters.


Assuntos
Cerâmica , Estereolitografia , Apatitas , Porcelana Dentária , Teste de Materiais , Propriedades de Superfície
4.
Front Neurosci ; 15: 639527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33958982

RESUMO

Mapping gene expression profiles to neuroimaging phenotypes in the same anatomical space provides opportunities to discover molecular substrates for human brain functional properties. Here, we aimed to identify cell-type-specific gene modules associated with the regional homogeneity (ReHo) of spontaneous brain activity and their associations with brain disorders. Fourteen gene modules were consistently associated with ReHo in the three datasets, five of which showed cell-type-specific expression (one neuron-endothelial module, one neuron module, one astrocyte module and two microglial modules) in two independent cell series of the human cerebral cortex. The neuron-endothelial module was mainly enriched for transporter complexes, the neuron module for the synaptic membrane, the astrocyte module for amino acid metabolism, and microglial modules for leukocyte activation and ribose phosphate biosynthesis. In enrichment analyses of cell-type-specific modules for 10 common brain disorders, only the microglial module was significantly enriched for genes obtained from genome-wide association studies of multiple sclerosis (MS) and Alzheimer's disease (AD). The ReHo of spontaneous brain activity is associated with the gene expression profiles of neurons, astrocytes, microglia and endothelial cells. The microglia-related genes associated with MS and AD may provide possible molecular substrates for ReHo abnormality in both brain disorders.

5.
Am J Otolaryngol ; 42(3): 102900, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33454455

RESUMO

OBJECTIVE: To investigate the distribution of pathogenic bacteria in patients with tympanic membrane perforation after chronic suppurative otitis media (CSOM) in dry ear and its influence on the success rate of tympanoplasty and postoperative infection. METHODS: 740 patients with tympanic membrane perforation after CSOM underwent endoscopic tympanoplasty were selected. The mucosal surface secretion of middle-ear was collected for bacterial culture and drug sensitivity test. The patients were followed up several times from 1 week to 3 months after the surgery. RESULTS: 740 cases of ear secretions samples, raise the pathogens of 208 cases (28.1%), the success rate of surgery with microorganism grown and with no grown was 93.8% and 91.5%. fungus (14.6%) was the most species among the patients with the positive result, followed by methicillin-sensitive Staphylococcus aureus (4.1%), Pseudomonas (2.0%), Staphylococcus epidermidis (1.9%), methicillin-resistant Staphylococcus aureus (1.6%) and so on. There was no statistical difference in the proportion of perforation and infection in each group. There were no statistically significant differences in gender, age and duration of disease among the groups. CONCLUSION: There were still microbial colonization in patients with tympanic membrane perforation after CSOM in dry ear, include fungus, Staphylococcus aureus and Pseudomonas aeruginosa. Different microbial colonization had no influence on the success rate of tympanoplasty and postoperative infection.


Assuntos
Orelha Média/microbiologia , Endoscopia/métodos , Otite Média Supurativa/complicações , Otite Média Supurativa/microbiologia , Perfuração da Membrana Timpânica/microbiologia , Perfuração da Membrana Timpânica/cirurgia , Timpanoplastia/métodos , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pseudomonas/isolamento & purificação , Estudos Retrospectivos , Staphylococcus aureus/isolamento & purificação , Staphylococcus epidermidis/isolamento & purificação , Perfuração da Membrana Timpânica/etiologia
6.
Neurosci Bull ; 37(3): 287-297, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32975745

RESUMO

Subcortical vascular mild cognitive impairment (svMCI) is a common prodromal stage of vascular dementia. Although mounting evidence has suggested abnormalities in several single brain network metrics, few studies have explored the consistency between functional and structural connectivity networks in svMCI. Here, we constructed such networks using resting-state fMRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls. The functional networks were then parcellated into topological modules, corresponding to several well-defined functional domains. The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level (whole brain and modular level). We found no significant intergroup differences in the functional-structural coupling within the whole brain; however, there was significantly increased functional-structural coupling within the dorsal attention module and decreased functional-structural coupling within the ventral attention module in the svMCI group. In addition, the svMCI patients demonstrated decreased intramodular connectivity strength in the visual, somatomotor, and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network, mainly linking the visual, somatomotor, dorsal attention, ventral attention, and frontoparietal control modules. There was no significant correlation between the altered module-level functional-structural coupling and cognitive performance in patients with svMCI. These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.


Assuntos
Disfunção Cognitiva , Demência Vascular , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Imagem de Tensor de Difusão , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem
7.
Small ; 17(9): e1903663, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31729163

RESUMO

Bismuth ferrite (BiFeO3 ) has recently become interesting as a room-temperature multiferroic material, and a variety of prototype devices have been designed based on its thin films. A low-cost and simple processing technique for large-area and high-quality BiFeO3 thin films that is compatible with current semiconductor technologies is therefore urgently needed. Development of BiFeO3 thin films is summarized with a specific focus on the chemical solution route. By a systematic analysis of the recent progress in chemical-route-derived BiFeO3 thin films, the challenges of these films are highlighted. An all-solution chemical-solution deposition (AS-CSD) for BiFeO3 thin films with different orientation epitaxial on various oxide bottom electrodes is introduced and a comprehensive study of the growth, structure, and ferroelectric properties of these films is provided. A facile low-cost route to prepare large-area high-quality epitaxial BFO thin films with a comprehensive understanding of the film thickness, stoichiometry, crystal orientation, ferroelectric properties, and bottom electrode effects on evolutions of microstructures is provided. This work paves the way for the fabrication of devices based on BiFeO3 thin films.

8.
Front Neurosci ; 15: 738913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34987355

RESUMO

The purpose of this study was to analyze microstructural alterations in cerebral gray matter using non-Gaussian diffusion kurtosis imaging (DKI) in neuromyelitis optica spectrum disorder (NMOSD) patients with optic neuritis (NMOSD-ON). DKI was performed in 14 NMOSD-ON patients and 22 normal controls (NCs). DKI-derived metrics, including mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), fractional anisotropy (FA), and mean diffusivity (MD), were voxel-wisely compared by two-sample t-tests with gaussian random field (GRF) correction between the two groups. The correlations between altered DKI metrics and clinical features were analyzed. Compared with NCs, NMOSD-ON patients showed significantly decreased MK and RK both in the left inferior temporal gyrus (ITG), and decreased AK in the bilateral calcarine (CAL). While increased MD in the left fusiform gyrus (FFG), right CAL, and right hippocampus (HIP)/parahippocampal gyrus (PHG) were found. Furthermore, correlation analysis showed that mean deviation was negatively correlated with AK values of bilateral CAL and positively correlated with MD values of right CAL (q < 0.05, false discovery rate (FDR) corrected). For NMOSD-ON patients, microstructural abnormalities in the occipital visual cortex are correlated with clinical disability. These findings may provide complementary information to understand the neuropathological mechanisms underlying the impairments of cerebral gray matter in NMOSD-ON.

9.
Psychol Med ; : 1-10, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33121546

RESUMO

BACKGROUND: Major depressive disorder (MDD) is a common debilitating disorder characterized by impaired spontaneous brain activity, yet little is known about its alterations in dynamic properties and the molecular mechanisms associated with these changes. METHODS: Based on the resting-state functional MRI data of 65 first-episode, treatment-naïve patients with MDD and 66 healthy controls, we compared dynamic regional homogeneity (dReHo) of spontaneous brain activity between the two groups, and we investigated gene expression profiles associated with dReHo alterations in MDD by leveraging transcriptional data from the Allen Human Brain Atlas and weighted gene co-expression network analysis. RESULTS: Compared with healthy controls, patients with MDD consistently showed reduced dReHo in both fusiform gyri and in the right temporal pole and hippocampus. The expression profiles of 16 gene modules were correlated with dReHo alterations in MDD. These gene modules were enriched for various biological process terms, including immune, synaptic signalling, ion channels, mitochondrial function and protein metabolism, and were preferentially expressed in different cell types. CONCLUSIONS: Patients with MDD have reduced dReHo in brain areas associated with emotional and cognitive regulation, and these changes may be related to complex polygenetic and polypathway mechanisms.

10.
Fish Shellfish Immunol ; 104: 517-526, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32589929

RESUMO

In invertebrates, innate immunity was the crucial defending pattern against pathogenic microorganisms. For the past few years, Toll or Toll like receptors (TLRs) signaling pathway was studied extensively in crustaceans. Among the components of Toll or Toll like receptors (TLRs) signaling pathway, tumor necrosis factor receptor-associated factor 6 (TRAF6) acted as an important cytoplasmic adaptor, which was conserved from Drosophila to human. In this study, a new traf6 like gene was cloned from hepatopancreas of P. clarkii. After challenged respectively by S. aureus or E. ictaluri, the expression profiles were studied. And the results showed that the mRNA transcript of Pc-traf6 like gene was up-regulated significantly in the hemocytes, hepatopancreas, gills, and intestine of crayfish. After Pc-traf6 like gene was knocked down, the expression levels of transcription factor (Dorsal) and some crucial immunity effectors (ALF 3, Lysozyme 1, Lectin 1, and Crustin 2) in TLRs signaling pathway were dramatically suppressed. Simultaneously, the survival rate of crayfish challenged respectively by S. aureus or E. ictaluri was significantly decreased in RNAi assay. All these results indicated that Pc-traf6 like gene played an important role in regulating the expression of downstream effectors in the TLRs signaling pathway of crayfish.


Assuntos
Astacoidea/genética , Astacoidea/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/imunologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Sequência de Bases , Edwardsiella ictaluri/fisiologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/veterinária , Perfilação da Expressão Gênica , Filogenia , Alinhamento de Sequência , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/veterinária , Staphylococcus aureus/fisiologia , Fator 6 Associado a Receptor de TNF/química
11.
Pharm Res ; 37(6): 102, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32440783

RESUMO

PURPOSE: To model absolute neutrophil count (ANC) suppression in response to acute radiation (AR) exposure and evaluate ANC time course as a predictor of overall survival (OS) in response to AR exposure with or without treatment with granulocyte colony-stimulating factor in nonhuman primates. METHODS: Source data were obtained from two pivotal studies conducted in rhesus macaques exposed to 750 cGy of whole body irradiation on day 0 that received either placebo, daily filgrastim, or pegfilgrastim (days 1 and 8 after irradiation). Animals were observed for 60 days with ANC measured every 1 to 2 days. The population model of ANC response to AR and the link between observed ANC time course and OS consisted of three submodels characterizing injury due to radiation, granulopoiesis, and a time-to-event model of OS. RESULTS: The ANC response model accurately described the effects of AR exposure on the duration of neutropenia. ANC was a valid surrogate for survival because it explained 76% (95% CI, 41%-97%) and 73.2% (95% CI, 38.7%-99.9%) of the treatment effect for filgrastim and pegfilgrastim, respectively. CONCLUSION: The current model linking radiation injury to neutropenia and ANC time course to OS can be used as a basis for translating these effects to humans.


Assuntos
Filgrastim/administração & dosagem , Modelos Biológicos , Neutropenia/prevenção & controle , Neutrófilos , Polietilenoglicóis/administração & dosagem , Lesões Experimentais por Radiação/prevenção & controle , Animais , Estudos de Viabilidade , Feminino , Contagem de Leucócitos , Leucopoese/efeitos dos fármacos , Leucopoese/efeitos da radiação , Macaca mulatta , Masculino , Neutropenia/sangue , Neutropenia/etiologia , Neutropenia/mortalidade , Lesões Experimentais por Radiação/sangue , Lesões Experimentais por Radiação/mortalidade , Fatores de Tempo
12.
J Mech Behav Biomed Mater ; 102: 103523, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31877524

RESUMO

Dental glass-ceramics with main crystal of fluorapatite are usually employed as veneering porcelain. However, failure of the porcelain happens clinically in the form of fracture or excessive wear. The aims of the study were to evaluate the influence of microstructures of a SiO2-Al2O3-K2O-CaO-P2O5 fluorapatite glass-ceramic on its mechanical properties and tribological behaviors, and to improve the comprehensive performance by adjusting content and sintering process. The glass-ceramics were fabricated by sintering method with different CaO contents and heat treatment regimes. Phase compositions and crystal length of specimens were characterized by X-ray diffractometer and scanning electron microscope. Combined with mechanical properties, friction and wear behaviors in both dry and artificial saliva lubrication conditions were investigated. The results show that different content of CaO and heat treatment temperature could change crystallinity of main fluorapatite crystal. Larger crystallinity improves the mechanical properties, significantly influencing friction and wear behaviors. The specimens with 6.0 wt % CaO and sintered at 1100 °C have the best comprehensive performance, which show excellent mechanical properties and wear resistance.


Assuntos
Cerâmica , Dióxido de Silício , Porcelana Dentária , Fricção , Vidro , Teste de Materiais , Microscopia Eletrônica de Varredura
13.
Membranes (Basel) ; 9(9)2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484439

RESUMO

Air separation is very important from the viewpoint of the economic and environmental advantages. In this work, defect-free facilitated transport membranes based on poly(amide-12-b-ethylene oxide) (Pebax-2533) and tetra(p-methoxylphenyl)porphyrin cobalt chloride (T(p-OCH3)PPCoCl) were fabricated in systematically varied compositions for O2/N2 separation. T(p-OCH3)PPCoCl was introduced as carriers that selectively and reversibly interacted with O2 and facilitated O2 transport in the membrane. The T(p-OCH3)PPCoCl had good compatibility with the Pebax-2533 via the hydrogen bond interaction and formed a uniform and thin selective layer on the substrate. The O2 separation performance of the thin film composite (TFC) membranes was improved by adding a small amount of the T(p-OCH3)PPCoCl and decreasing the feed pressure. At the pressure of 0.035 MPa, the O2 permeability and O2/N2 selectivity of the 0.6 wt % T(p-OCH3)PPCoCl/Pebax-2533 was more than 3.5 times that of the Pebax-2533 TFC membrane, which reached the 2008 Robeson upper bound. It provides a candidate membrane material for O2/N2 efficient separation in moderate conditions.

14.
Lipids ; 54(10): 651-663, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31463983

RESUMO

Vitamin D deficiency has been frequently reported in chronic liver disease. However, its influence on hepatic lipid accumulation in alcoholic liver disease remains unclear. The present study investigated the effects of vitamin D deficiency on acute alcohol-induced hepatic lipid metabolism in mice. Mice were fed with vitamin D deficient diet, in which vitamin D was depleted for 12 weeks to establish an animal model of vitamin D deficiency. Some mice were administered a single gavage of alcohol (4 g/kg bodyweight) before they were euthanized. Results show that feeding mice with vitamin D deficient diet did not induce hepatic lipid accumulation. In contrast, vitamin D deficiency markedly reduced alcohol-induced triacylglycerol (TAG) content and prevented hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated alcohol-induced sterol-regulated element-binding protein (SREBP)-1c activation, which regulates genes for hepatic fatty acid (FA) and TAG synthesis, and the expression of its target genes fatty acid synthase (Fasn) and acetyl-coenzyme- A carboxylase (Acc). In addition, vitamin D deficiency alleviated alcohol-induced downregulation of hepatic nuclear peroxisome proliferator-activated receptor (PPAR)α, which governs FA transport and ß-oxidation, and the expression of Carnitine palmitoyltransferase (Cpt)-1α, cytochrome P450, family 4, subfamily a, polypeptide (Cyp4a)10, and Cyp4a14, which are key enzymes for hepatic fatty acids ß-oxidation and ω-oxidation. Taken together, these results suggest that vitamin D deficiency is not a direct risk factor for hepatic lipid accumulation. Vitamin D deficiency alleviates acute alcohol-induced hepatic lipid accumulation through inhibiting hepatic de novo fatty acid syntheses and promoting fatty acid ß-oxidation and ω-oxidation.


Assuntos
Intoxicação Alcoólica/metabolismo , Metabolismo dos Lipídeos , Hepatopatias Alcoólicas/metabolismo , Deficiência de Vitamina D/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR
15.
Artigo em Inglês | MEDLINE | ID: mdl-31221017

RESUMO

Antibiotic resistance genes (ARGs), as emerging environmental contaminants, have become a threat to human health. Here, we use the combined process of powdered activated carbon (PAC) and ultrafiltration (UF) to investigate the removal of ARGs, the class I integron (intI1), 16S rDNA and dissolved organic carbon (DOC) in wastewater effluent. Additionally, the removal mechanisms of ARGs by PAC-UF were investigated. Our results show that a higher PAC concentration might increase DOC and ARGs removal. The maximum removal of DOC and ARGs was 63.2% and 1.35-log-3.35-log, respectively. At the same time, the ARGs are positively correlated with DOC, intI1 and 16S rDNA, indicating that reducing their concentration would contribute to the reduction of ARGs. We also found that the optimal PAC dose could effectively increase membrane flux, reduce membrane fouling resistance and alleviate membrane fouling. This study demonstrates that the PAC-UF process is a potential deep water purification process and control technology for reducing ARGs risk.


Assuntos
Antibacterianos/análise , Carvão Vegetal/química , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Ultrafiltração/métodos , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Incrustação Biológica/prevenção & controle , Membranas Artificiais , Águas Residuárias/química , Águas Residuárias/microbiologia
16.
Clin Transl Sci ; 12(4): 371-378, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30884170

RESUMO

This trial (20010168) studied how body weight (BW) and body mass index (BMI) influenced the pharmacokinetics (PK) of anakinra. Subjects (n = 32) were assigned to four groups (n = 8) according to BW and BMI. Randomization was according to a four-treatment, four-period, four-sequence crossover design. The four anakinra injections were 100, 150, and 300 mg s.c. and 100 mg i.v. Plasma samples were measured by enzyme-linked immunosorbent assay and noncompartmental PK parameters estimated. BW demonstrated the following effects: after i.v. administration, significant effects (P < 0.05) were observed for exposure (area under the concentration-time curve from zero to infinity (AUC0-∞ )), peak plasma concentration (Cmax ), volume of distribution at steady state, and clearance; whereas after s.c. administration, significant effects (P < 0.05) were observed for Cmax , AUC0-∞ , terminal half-life, and estimated apparent clearance. Mean AUC was reduced 24% and 33% for heavier (BW ≥ 100 kg) vs. lighter subjects (BW ≤ 90 kg) after i.v. and s.c. administration, respectively. BMI increased clearance for heavier subjects. For example, mean (SD) plasma clearance of i.v. anakinra increased from 1.17 ± 0.29 to 1.62 ± 0.24 mL/minute/kg (P < 0.05) for larger (> 100 kg) obese (BMI > 36) vs. larger (> 100 kg) less obese (BMI < 35) subjects, respectively. Similarly, results following s.c. supported those after i.v. administration. Derived half-lives increased with higher BW and higher BMI ranging from 3.63 hour for less obese, lighter-weight subjects to 7.62 hour for obese, heavier-weight subjects. Absolute bioavailability ranged from 80-92% and was unrelated to BW or BMI. Anakinra exposure is statistically significantly related to BW and to a lesser extent BMI.


Assuntos
Peso Corporal , Proteína Antagonista do Receptor de Interleucina 1/farmacocinética , Adulto , Idoso , Área Sob a Curva , Vias de Administração de Medicamentos , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
17.
Redox Biol ; 20: 451-457, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439686

RESUMO

Metabolic reprogramming is a feature of cancer cells and crucial for tumor growth and metastasis. Interferon-γ (IFNγ) is a cytokine that plays a pivotal role in host antitumor immunity. However, little is known about the roles of metabolic reprogramming in immune responses. Here, we show that colon cancer cells reprogram metabolism to coordinate proper cellular responses to IFNγ by downregulating mitochondrial pyruvate carrier (MPC)1 and 2 via STAT3 signaling. Forced overexpression of MPC promote the production of reactive oxygen species and enhance the apoptosis induced by IFNγ in colon cancer cells. Moreover, inhibiting STAT3 sensitize the antitumor efficacy of IFN-γ against colon cancer cells. Our findings present a previously unrecognized mechanism that colon cancer manipulate to resist IFNγ mediated antitumor immunity that have implications for targeting a unique aspect of this disease.


Assuntos
Neoplasias do Colo/metabolismo , Interferon gama/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Piruvatos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Transporte Biológico , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Mitocôndrias/genética , Modelos Biológicos , Oxirredução , Pró-Proteína Convertase 1/genética , Pró-Proteína Convertase 1/metabolismo , Pró-Proteína Convertase 2/genética , Pró-Proteína Convertase 2/metabolismo
18.
Chem Commun (Camb) ; 54(90): 12671-12685, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30357137

RESUMO

It is imperative to develop efficient, reversible and economic technologies for separating CO2 which mainly comes from flue gas, natural gas and syngas. Membranes based on functionalized ionic liquids (ILs) have attracted much attention from researchers in recent years, and have been considered as a very promising technology. This feature article focuses on the research progress in CO2 separation using functionalized IL membranes. The recent advances in the preparation, separation performance, and separation mechanism of supported IL membranes (SILMs), pure poly(ionic liquid) (PIL) membranes, PIL-copolymer membranes, PIL-IL composite membranes and polymer-IL composite membranes for CO2 separation have been reviewed. In addition, the future directions and prospects for CO2 separation using functionalized IL membranes are given.

19.
J Exp Clin Cancer Res ; 37(1): 259, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373678

RESUMO

BACKGROUND: Lysosome-associated agents have been implicated as possible chemo-sensitizers and immune regulators for cancer chemotherapy. We investigated the potential roles and mechanisms of hydroxychloroquine (HCQ) in combination with chemotherapy in lung cancer treatment. METHODS: The effects of combined treatment on non-small cell lung cancer (NSCLC) were investigated using cell viability assays and animal models. The influence of HCQ on lysosomal pH was evaluated by lysosomal sensors and confocal microscopy. The effects of HCQ on the tumour immune microenvironment were analysed by flow cytometry. RESULTS: HCQ elevates the lysosomal pH of cancer cells to inactivate P-gp while increasing drug release from the lysosome into the nucleus. Furthermore, single HCQ therapy inhibits lung cancer by inducing macrophage-modulated anti-tumour CD8+ T cell immunity. Moreover, HCQ could promote the transition of M2 tumour-associated macrophages (TAMs) into M1-like macrophages, leading to CD8+ T cell infiltration into the tumour microenvironment. CONCLUSIONS: HCQ exerts anti-NSCLC cells effects by reversing the drug sequestration in lysosomes and enhancing the CD8+ T cell immune response. These findings suggest that HCQ could act as a promising chemo-sensitizer and immune regulator for lung cancer chemotherapy in the clinic.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Células A549 , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Hidroxicloroquina/farmacologia , Neoplasias Pulmonares/patologia , Lisossomos/química , Lisossomos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Water Sci Technol ; 77(1-2): 211-219, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29339620

RESUMO

The combined processes of powdered activated carbon/biological powdered activated carbon- ultrafiltration (PAC/BPAC-UF) were used to treat secondary effluent. In this study, the effect of PAC and BPAC on membrane flux, membrane resistance and the removal of different molecular weight organic compounds were investigated. In addition, the structure characteristics of the microorganisms of the BPAC were analyzed. The results showed that the optimum dosage of PAC and BPAC was 10 mg/L and 40 mg/L respectively. The reversible membrane fouling resistance of BPAC-UF was higher than that of PAC-UF, and the two processes had the least irreversible resistance at the best dosage. The biodegradation of BPAC increased the concentration of small molecular weight organic matter up to 10,000 Da in the membrane effluent. So the dissolved organic carbon (DOC) removal effect of BPAC-UF process worsened. Microorganisms such as Proteobacteria, Bacteroidetes, Planctomycetes and other microorganisms on the surface of the BPAC enhanced the removal of organic matter in water. The results of scanning electron microscopy (SEM) scans showed that there was net mucus membrane on the UF membrane surface before the backwashing of the BPAC-UF process which increased the proportion of reversible pollution resistance. The physical flushing effect of BPAC-UF was better than that of direct UF and PAC-UF processes.


Assuntos
Incrustação Biológica , Carvão Vegetal/química , Membranas Artificiais , Ultrafiltração/métodos , Águas Residuárias/química , Águas Residuárias/microbiologia , Purificação da Água/métodos , Biodegradação Ambiental , Incrustação Biológica/prevenção & controle , Peso Molecular , Compostos Orgânicos , Propriedades de Superfície , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química
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