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Objective To investigate the expression level of serine/threonine phosphoprotein phosphatase 4C(PPP4C)in gastric cancer,and analyze its relationship with prognosis and the underlying regulatory mechanism.Methods The clinical data of 104 gastric cancer patients admitted to the First Affiliated Hospital of Bengbu Medical College between January 2012 and August 2016 were collected.Immunohistochemical staining was employed to determine the expression levels of PPP4C and Ki-67 in the gastric cancer tissue.The gastric cancer cell lines BGC823 and HGC27 were cultured and transfected with the vector for PPP4C knockdown,the vector for PPP4C overexpression,and the lentiviral vector(control),respectively.The effects of PPP4C on the cell cycle and proliferation were analyzed and the possible regulatory mechanisms were explored.Results PPP4C was highly expressed in gastric cancer(P<0.001),and its expression promoted malignant progression of the tumor(all P<0.01).Univariate and Cox multivariate analysis clarified that high expression of PPP4C was an independent risk factor affecting the 5-year survival rate of gastric cancer patients(P=0.003).Gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis suggested that PPP4C may be involved in the cell cycle.The correlation analysis showed that the expression of PPP4C was positively correlated with that of Ki-67 in gastric cancer(P<0.001).The up-regulation of PPP4C expression increased the proportion of tumor cells in the S phase,alleviated the G2/M phase arrest,and promoted the proliferation of gastric cancer cells and the expression of cyclin D1 and cyclin-dependent kinase 6(CDK6)(all P<0.05).The down-regulation of PPP4C decreased the proportion of gastric cancer cells in the S phase,promoted G2/M phase arrest,and inhibited cell proliferation and the expression of cyclin D1,CDK6,and p53(all P<0.05).p53 inhibitors promoted the proliferation of BGC823 and HGC27 cells in the PPP4C knockdown group(P<0.001,P<0.001),while p53 activators inhibited the proliferation of BGC823 and HGC27 cells in the PPP4C overexpression group(P<0.001,P=0.002).Conclusions PPP4C is highly expressed in gastric cancer and affects the prognosis of the patients.It may increase the proportion of gastric cancer cells in the S phase and alleviate the G2/M phase arrest by inhibiting p53 signaling,thereby promoting cell proliferation.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Proteína Supressora de Tumor p53 , Fosfoproteínas/metabolismo , Antígeno Ki-67 , Linhagem Celular Tumoral , Prognóstico , Proliferação de Células , Fosfoproteínas Fosfatases/metabolismo , Treonina , SerinaRESUMO
Pyrolysis and activation processes are important pathways to utilize residues after lipid extraction from microalgae in a high-value way. The obtained microalgae-based nitrogen-doped activated carbon has excellent electrochemical performance. It has the advantage of nitrogen self-doping using high elemental nitrogen in microalgae. In this study, two kinds of microalgae, Nanochloropsis and Chlorella, were used as feedstock for lipid extraction. The microalgae residue was firstly pyrolyzed at 500 °C to obtain biochar. Then, nitrogen-doped activated carbons were synthesized at an activation temperature of 700-900 °C with different ratios of biochar and KOH (1:1, 1:2, and 1:4). The obtained carbon materials presented rich nitrogen functional groups, including quaternary-N, pyridine-N-oxide, pyrrolic-N, and pyridinic-N. The nitrogen content of microalgae-based activated carbon material was up to 2.62%. The obtained materials had a specific surface area of up to 3186 m2/g and a pore volume in the range of 0.78-1.54 cm3/g. The microporous pore sizes of these materials were distributed at around 0.4 nm. Through electrochemical testing such as cyclic voltammetry and galvanostatic charge-discharge of materials, the materials exhibited good reversibility and high charge-discharge efficiency. The sample, sourced from microalgae Chlorella residue at activation conditions of 700 °C and biochar/KOH = 1:4, exhibited excellent endurance of 94.1% over 5000 cycles at 2 A/g. Its high specific capacitance was 432 F/g at 1 A/g.
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Chlorella , Microalgas , Carvão Vegetal , Nitrogênio/química , Pirólise , LipídeosRESUMO
Zn-Mn batteries with two-electron conversion reactions simultaneously on the cathode and anode harvest a high voltage plateau and high energy density. However, the zinc anode faces dendrite growth and parasitic side reactions while the Mn2+/MnO2 reaction on the cathode involves oxygen evolution and possesses poor reversibility. Herein, a novel nanomicellar electrolyte using methylurea (Mu) has been developed that can encapsulate ions in the nanodomain structure to guide the homogeneous deposition of Zn2+/Mn2+ in the form of controlled release under an external electric field. Consecutive hydrogen bonding network is broken and a favorable local hydrogen bonding system is established, thus inhibiting the water-splitting-derived side reactions. Concomitantly, the solid-electrolyte interface protective layer is in situ generated on the Zn anode, further circumventing the corrosion issue resulting from the penetration of water molecules. The reversibility of the Mn2+/MnO2 conversion reaction is also significantly enhanced by regulating interfacial wettability and improving nucleation kinetics. Accordingly, the modified electrolyte endows the symmetric Znâ¥Zn cell with extended cyclic stability of 800 h with suppressed dendrites growth at an areal capacity of 1 mAh cm-2. The assembled Zn-Mn electrolytic battery also demonstrates an exceptional capacity retention of nearly 100% after 800 cycles and a superior energy density of 800 Wh kg-1 at an areal capacity of 0.5 mAh cm-2.
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Here, we report a "critical distance" method for the synthesis of 9 kinds of sub-5 nm rhodium (Rh)-based intermetallic catalysts. Enlarging the distance between intermetallic particles on high-surface-area carbon black supports could significantly suppress the metal sintering in high-temperature annealing. The prepared Rh2Sn intermetallic catalysts exhibited enhanced activity in catalyzing the hydrogenation of nitrobenzene.
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To understand the mitigation effects of melatonin on the chilling-induced photoinhibition in tomato, four groups of seedlings were labelled: NW (normal temperature + water), NM (normal temperature + melatonin), CW (chilling + water) and CM (chilling+ melatonin). We measured chlorophyll fluorescence, key photosynthetic parameters and the cycle efficiency for chloroplast ascorbic acid-glutathione (AsA-GSH). The results showed that, compared with the NW control, photosynthesis rate in CW was decreased by 50.3%-72.6%, chloroplast malondialdehyde content was decreased by 17.5%-132.7%, superoxide anion production was increased by 86.5%-235.9%, and H2O2 was increased by 96.6%-208.4%. These trends were significantly alleviated by exogenous melatonin, with photosynthetic rates in CM being increased by 22.7%-24.7% compared with in CW, malondialdehyde content being decreased by 16.6%-29.0%, the rate of superoxide anion production being decreased by 14.9%-22.7%, H2O2 content being decreased by 10.7%-27.1%. Compared with CW, the quantum yield of photochemical energy in PS â ¡ was increased by 15.8% in CM, the quantum yield of regulated non-photochemical energy loss was increased by 7.2%, the quantum yield of non-regulated non-photochemical energy loss was decreased by 24.7%, and the activities of key metabolic enzymes in the AsA-GSH cycle were increased to different degrees. We concluded that exogenous melatonin application could alleviate photoinhibition in tomato seedlings under chilling by balancing the partitioning of absorption energy in PS â ¡ and by enhancing the ROS scavenging efficiency of the AsA-GSH cycle in the chloroplast.
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Melatonina , Solanum lycopersicum , Melatonina/farmacologia , Plântula/fisiologia , Superóxidos/metabolismo , Superóxidos/farmacologia , Peróxido de Hidrogênio , Fotossíntese , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Glutationa/metabolismo , Glutationa/farmacologia , Malondialdeído/metabolismoRESUMO
Objective: To investigate the prognostic value of the expression of myeloid leukemia factor 1-interacting protein (MLF1IP) in gastric cancer tissue and its regulatory role in tumor progression. Methods: Gene Expression Omnibus (GEO) database was used to analyze the expression level of MLF1IP in tumor tissues of gastric cancer patients. Kaplan-Meier Plotter database was used to analyze the relationship between MLF1IP expression level and patient prognosis. We conducted a retrospective analysis of 108 gastric cancer patients who had undergone radical surgery at our hospital between January 2015 and December 2015. The expression of MLF1IP in gastric cancer tissue and adjacent tissues was examined. We analyzed the relationship between MLF1IP and the clinicopathological parameters of gastric cancer patients and its impact on the long-term prognosis of gastric cancer patients. Univariate and multivariate regression analyses were done to identify the risk factors affecting the long-term prognosis of gastric cancer patients. The assessment value of MLF1IP for long-term prognosis of gastric cancer was analyzed with ROC curve. The effects of MLF1IP on the proliferation, migration, and invasion of gastric cancer cells were analyzed in vitro with gastric cancer cell line (MGC803). A xenograft tumor model was established with nude mice to analyze in vivo the effect of MLF1IP on tumor growth. Results: The results of the gastric cancer cohort GSE29272 of GEO database showed that the expression level of MLF1IP in gastric cancer tissues was significantly higher than that in normal tissues ( P<0.05). Analysis with Kaplan-Meier Plotter database indicated that high MLF1IP expression was correlated with poor prognosis in gastric cancer patients. Immunohistochemical analysis showed that the expression level of MLF1IP in gastric cancer tissues was higher than that in adjacent tissues ( P<0.05). Correlation analysis showed that the MLF1IP level in gastric cancer tissue was positively correlated with Ki67 ( r=0.609, P<0.01), peripheral blood carcinoembryonic antigen (CEA) ( r=0.572, P<0.01) and carbohydrate antigen 19-9 (CA19-9) ( r=0.623, P<0.01). Kaplan-Meier (K-M) survival analysis showed that the 5-year survival rate of patients in the MLF1IP high expression group was significantly lower than that in the MLF1IP low expression group ( P<0.01). Cox regression analysis showed that independent risk factors for 5-year survival after radical gastrectomy for gastric cancer included the expression of MLF1IP ( HR=2.508, 95% CI: 1.259-4.999), CEA≥5 µg/L ( HR=2.171, 95% CI: 1.152-4.092), CA19-9≥37 kU/L ( HR=2.401, 95% CI: 1.094-5.269), and T3-T4 stages ( HR=2.779, 95% CI: 1.049-7.358) and N2-N3 stages ( HR=2.072, 95% CI: 1.100-3.904). ROC analysis showed that the sensitivity, specificity, and accuracy of MLF1IP (the cut-off value was 3.00 relative protein expression level) in assessing the 5-year survival rate after radical gastrectomy for gastric cancer was 75.00%, 76.92%, and 76.2%, respectively ( P<0.05). CCK-8, Transwell assay, and scratch assays showed that in vitro knocking down of MLF1 IP gene expression significantly inhibited the proliferation, migration and invasion of gastric cancer cells. Subcutaneous tumor xenograft experiment in nude mice showed that knocking down MLF1 IP gene significantly inhibited tumor growth. Conclusion: Increased expression of MLF1IP in gastric cancer tissue, which may be involved in the malignant activities of proliferation, migration, and invasion of gastric cancer cells, has a certain predictive value for poor prognosis.
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Leucemia Mieloide , Neoplasias Gástricas , Animais , Camundongos , Humanos , Prognóstico , Antígeno Carcinoembrionário , Neoplasias Gástricas/patologia , Camundongos Nus , Estudos Retrospectivos , Antígeno CA-19-9RESUMO
Photocatalytic degradation of pollutants is an effective environment purification strategy. Metal-organic frameworks (MOFs) have attracted extensive attention in the field of photocatalysis owing to their structural diversity, uniform cavity, and large specific surface area. However, poor electrical conductivity, light absorption, and water stability restrict their development. The tailorable structure of MOFs may effectively overcome these limitations. Herein, three Cu-based MOFs (complexes 1-3) with one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D) structures, respectively, were successfully prepared by introducing different uncoordinated ligands and adjusting the ligand/metal salt ratio. Among them, complex 1 with a 1D chain was constructed as a typical J-type aggregation by π-π stacking interactions between adjacent naphthalene rings. This intermolecular aggregation mode enhances strong exciton coupling between conjugated rings, reduces the transition energy, expands the intrinsic light absorption edge, and provides a channel for electron transport, thus improving the charge-separation efficiency. As expected, complex 1 with a 1D chain structure exhibited excellent Fenton-like catalytic activity. The apparent reaction rates were 3.2 and 2.0 times higher than those of 2D and 3D MOFs, respectively.
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Objective To investigate the expression and prognostic significance of mediator complex subunit 8 (MED8) in gastric cancer and its impact on the cell cycle.Methods The expression of MED8 in gastric cancer and adjacent tissues and its correlation with patients' prognosis were analyzed using public databases.A validation cohort of 104 patients who underwent radical resection for gastric cancer in the First Affiliated Hospital of Bengbu Medical College from June 2012 to July 2017 was included.The receiver operating characteristic curve was established to evaluate the predictive value of MED8 for postoperative 5-year survival.Bioinformatics tools were used to predict the biological roles of MED8 in gastric cancer.The effect of the MED8 level on the G1/S phase transition of gastric cancer cells (MGC-803) was analyzed via lentivirus transduction and flow cytometry.Western blotting was carried out to assess the impact of MED8 expression on the protein levels of cyclin-dependent kinase 4(Cdk4) and G1/S-specific cyclin-D1(CyclinD1) in MGC-803 cells.Results The high expression of MED8 in the gastric cancer tissue was associated with poor prognosis (P<0.001) and had prognostic significance (area under curve=0.733,P<0.001).Gene enrichment analysis suggested that MED8 may participate in the cell cycle process.Flow cytometry results revealed that the upregulation of MED8 expression promoted the transition of MGC-803 cells from the G1 phase to the S phase (P<0.001),while the downregulation of MED8 had the opposite effect (P<0.001).Western blotting showed increases in the protein levels of Cdk4 and CyclinD1 in MGC-803 cells with upregulated MED8 expression (all P<0.001),and decreases in the cells with downregulated MED8 expression (all P<0.001).Conclusion MED8 is highly expressed in gastric cancer and may affect its progression and prognosis by regulating the G1/S phase transition of gastric cancer cells.
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Neoplasias Gástricas , Humanos , Prognóstico , Proliferação de Células , Ciclo Celular , Complexo Mediador/metabolismo , Linhagem Celular TumoralRESUMO
Supported ordered intermetallic compounds exhibit superior catalytic performance over their disordered alloy counterparts in diverse reactions. But the synthesis of intermetallic compounds catalysts often requires high-temperature annealing that leads to the sintering of metals into larger crystallites. Herein, we report a small molecule-assisted impregnation approach to realize the general synthesis of a family of intermetallic catalysts, consisting of 18 binary platinum intermetallic compounds supported on carbon blacks. The molecular additives containing heteroatoms (that is, O, N, or S) can be coordinated with platinum in impregnation and thermally converted into heteroatom-doped graphene layers in high-temperature annealing, which significantly suppress alloy sintering and insure the formation of small-sized intermetallic catalysts. The prepared optimal PtCo intermetallics as cathodic oxygen-reduction catalysts exhibit a high mass activity of 1.08 A mgPt-1 at 0.9 V in H2-O2 fuel cells and a rated power density of 1.17 W cm-2 in H2-air fuel cells.
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Objective: To investigate the effects of aerobic versus resistance exercise on soleus muscle contractile properties and the expressions of MuRF1, PGC-1α and FNDC5 in amyotrophic rats after unloading, and the possible molecular biological mechanisms. Methods: Male Wistar rats were randomly divided into recovery group (CT), aerobic exercise group (A), resistance exercise group (R) and control group (C), with 6 rats in each group. The control group did not receive any treatment. The other three groups underwent tail suspension for 2 weeks, and then the recovery group recovered quietly. The aerobic group and the resistance group underwent a 2-week exercise intervention. Exercise plan: the aerobic group rats were treated with treadmill speed corresponding to 65% maximum oxygen uptake (VO2max), 60 min/d, 5 d/w; the rats in the resistance group were allowed to climb the ladder with 65% of the maximum voluntary weight-bearing (MVCC) for 3 times, with a total of 5 sets. Each time had a rest of 1 min, with an interval of 2 min among sets, and 5 d/w. Fasting for 24 hours after the last exercise, the soleus muscle samples were collected to observe the histological changes, test the contractility, and detect MuRF1 and PGC-1α and FNDC5 expressions. Results: compared with the control group, the body weight, soleus muscle wet weight, average cross-sectional area of muscle fibers and muscle contractility of the recovery group were decreased significantly(P<0.01), and the expression of MuRF1 was increased significantly(P<0.01). Compared with the recovery group, the body weight, wet weight of soleus muscle, the average cross-sectional area of muscle fiber and muscle contractility of rats in aerobic group and resistance group were increased (P<0.01), the expression of PGC-1α/FNDC5 was increased (P<0.01) and the expression of MuRF1 was decreased significantly (P<0.01). Compared with the aerobic group, the expression of PGC-1α in soleus muscle of rats in the resistance group was increased (P<0.05), while the expression of MuRF1 was decreased (P<0.05). Conclusion: Aerobic and resistance exercise can significantly improve muscle contractility, upregulate the expression of PGC-1α/FNDC5, and inhibit the expression of MuRF1, indicating that the molecular mechanisms of aerobic and resistance exercise to improve unloaded muscular atrophy may be related to PGC-1α and MuRF1.
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Consumo de Oxigênio , Oxigênio , Animais , Masculino , Ratos , Peso Corporal , Fibronectinas , Fibras Musculares Esqueléticas , Atrofia Muscular , Ratos Wistar , Fatores de TranscriçãoRESUMO
Size control of supported Pd-based intermetallic nanoparticles (i-NPs) remains a major challenge because the required high-temperature annealing for atomic diffusion and ordering easily causes metal sintering. Here, we described a pentacoordinate Al3+ site (Al3+penta) anchoring approach for the preparation of Pd-based i-NPs with controlled size, which takes advantage of the strong chemical interaction between Al3+penta sites and Pd-based i-NPs to realize size control. We synthesized six types of Pd-based i-NPs, and four of them can remain an average particle size of <6 nm. Furthermore, one of our prepared Pd-based i-NPs (that is, Pd3Pb) demonstrated outstanding performance in catalyzing the semihydrogenation of phenylacetylene.
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Luminescent metal-organic frameworks (LMOFs) have been widely developed in the field of chemical sensing owing to their outstanding photoluminescence performance, high selectivity, anti-interference, high sensitivity, and fast response, and have become one of the research hotspots of emerging functional materials. However, in practical applications, many tests are carried out in the water environment, and fragile water stability greatly limits the application of MOFs in the field. Therefore, it is important to develop a method to enhance the water stability of MOFs. Herein, a new complex {[Zn(L)]·CH3CN} n (Zn-MOF, H2L = 5-(benzimidazol-1-yl) isophthalic acid) with a superior photophysical property has been synthesized first. Its water stability was highly enhanced by the doping of CuII ions by the one-pot method. In addition, the detection performances of doping material Cu0.1/Zn-MOF for sixteen metal ions and thirteen antibiotics were well studied. It was found that Cu0.1/Zn-MOF displays high sensitivity, fast response, lower detection limit, and long-term stability for the detection of Fe3+, NFT, NFZ, FZD, and TC in the aqueous medium.
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Supported bimetallic nanoparticle catalysts with small size have attracted wide research attention in catalysis but are difficult to synthesize because high-temperature annealing required for alloying inevitably accelerates metal sintering and leads to larger particles. Here, we report a simple and scalable "critical interparticle distance" method for the synthesis of a family of bimetallic nanocluster catalysts with an average particle size of only 1.5 nm by using large-surface-area carbon black supports at high temperatures, which consist of 12 diverse combinations of 3 noble metals (Pt, Ru, and Rh) and 4 other metals (Cr, Fe, Zr, and Sn). In this strategy, high-temperature treatments ensure the formation of alloyed bimetallic nanoparticles and enlargement of the interparticle distance on high-surface-area supports significantly suppresses metal sintering. The prepared ultrafine Pt2Sn and RuSn nanocluster catalysts exhibited enhanced performance in catalyzing the synthesis of aromatic secondary amines and the selective hydrogenation of furfural, respectively.
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Catalytic biomass conversions are sustainable processes to produce value-added fuels and chemicals but need stable catalysts that can tolerate harsh hydrothermal conditions. Herein, we report a hydrothermally stable catalyst by alloying Pt with a high-melting-point metal Nb. The Pt/Nb alloy catalysts are prepared by H2 reduction at a high temperature of 900 °C with a high-surface-area carbon black support, which can suppress metal sintering at high temperatures and thus lead to small-sized alloyed Pt/Nb particles of only 2.2 nm. Taking the advantages of surface acid property provided by the Nb sites and the size effect, the prepared C-supported small-sized Pt/Nb alloy catalysts exhibit attractive activities for the hydrogenation of levulinic acid into γ-valerolactone and the water-gas shift reaction. More significantly, benefiting from the inherent stability of high-melting-point Nb, the Pt/Nb alloy catalysts show much enhanced hydrothermal stability compared to commercial Pt/C and Ru/C catalysts.
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Vegetation phenology is a comprehensive indictor for the responses of terrestrial ecosystem to climatic and environmental changes. Remote sensing spectrum has been widely used in the extraction of vegetation phenology information. However, there are many differences between phenology extracted by remote sensing and site observations, with their physical meaning remaining unclear. We selected one tile of MODIS data in northeastern China (2000-2014) to examine the SOS and EOS differences derived from the normalized difference vegetation index (NDVI) and the simple ratio vegetation index (SR) based on both the red and near-infrared bands. The results showed that there were significant differences between NDVI-phenology and SR-phenology. SOS derived from NDVI averaged 18.9 days earlier than that from SR. EOS derived from NDVI averaged 19.0 days later than from SR. NDVI-phenology had a longer growing season. There were significant differences in the inter-annual variation of phenology from NDVI and SR. More than 20% of the pixel SOS and EOS derived from NDVI and SR showed the opposite temporal trend. These results caused by the seasonal curve characteristics and noise resistance differences of NDVI and SR. The observed data source of NDVI and SR were completely consistent, only the mathematical expressions were different, but phenology results were significantly different. Our results indicated that vegetation phenology monitoring by remote sensing is highly dependent on the mathematical expression of vegetation index. How to establish a reliable method for extracting vegetation phenology by remote sensing needs further research.
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Ecossistema , Tecnologia de Sensoriamento Remoto , China , Monitoramento Ambiental , Estações do AnoRESUMO
BACKGROUND: In the battle against Crohn's disease, autophagy stimulation is a promising therapeutic option-one both new and newly rediscovered. In experimental models, docosahexaenoic acid (DHA)-a long-chain polyunsaturated fatty acid-has been demonstrated to be useful in the treatment of inflammatory bowel disease through inhibition of the nuclear factor-κB pathway. However, the impact of DHA on autophagy in the colon remains unclear. METHODS: Mice were divided into 3 groups: wild type (placebo), the interleukin 10 knockout group (IL-10-/-, placebo), and the DHA group (IL-10-/-, DHA). DHA was administered to IL-10-/- mice by gavage at a dosage of 35.5 mg/kg/d for 2 weeks. The severity of colitis, expression of proinflammatory cytokines, expression/distribution of LC3B, and mTOR signaling pathway were evaluated in the proximal colon tissues collected from all mice at the end of the experiment. RESULTS: DHA administration ameliorated experimental colitis in the IL-10-/- mice, as demonstrated by decreased proinflammatory cytokines (TNF-α and IFN-γ), reduced infiltration of inflammatory cells, and lowered histologic scores of the proximal colon mucosa. Moreover, in the DHA-treated mice, enhanced autophagy was observed to be associated with (1) increased expression and restoration of the distribution integrity of LC3B in the colon and (2) inhibition of the mTOR signaling pathway. CONCLUSION: This study showed that DHA therapy could attenuate experimental chronic colitis in IL-10-/- mice by triggering autophagy via inhibition of the mTOR pathway.
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Autofagia/efeitos dos fármacos , Colite/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/farmacologia , Interleucina-10/deficiência , Serina-Treonina Quinases TOR/genética , Animais , Doença Crônica , Colo/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-10/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/sangue , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Secreted frizzled related protein 5 (SFRP5), an anti-inflammatory adipokine, is relevant to the adipocyte differentiation. In order to clarify its role in regulating intramuscular fat (IMF) deposition in Tibetan chicken, the full-length sequence of the Tibetan chicken SFRP5 gene was cloned. The relative expression of SFRP5 gene was detected using quantitative RT-PCR in various tissues of 154 days old Tibetan chicken, as well as in breast muscle, thigh muscle, and adipose tissue at different growth stages. The results showed that SFRP5 gene was expressed in all examined tissues but highly enriched in adipose tissue. Temporal expression profile showed that the expression of SFRP5 was gradually decreased in breast muscle, but was fluctuated in thigh muscle and adipose tissue with the growth of Tibetan chicken. Furthermore, correlation analysis demonstrated that the expression of SFRP5 in breast muscle, thigh muscle and adipose tissue was correlated with IMF content at different levels. The results indicated that Tibetan chicken SFRP5 is involved in IMF deposition.
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Adipocinas , Tecido Adiposo/metabolismo , Proteínas Aviárias , Galinhas , Músculo Esquelético/metabolismo , Adipocinas/química , Adipocinas/genética , Adipocinas/metabolismo , Animais , Proteínas Aviárias/química , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Diferenciação Celular/genética , Galinhas/genética , Galinhas/metabolismo , Galinhas/fisiologia , Clonagem Molecular , Feminino , Masculino , Filogenia , Via de Sinalização Wnt/genéticaRESUMO
A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10(-/-)) at 16 weeks of age with established colitis were treated with DHA (i.g. 35.5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10(-/-) mice by improving the intestinal epithelial barrier function.
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Colite/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/administração & dosagem , Interleucina-10/genética , Intestinos/efeitos dos fármacos , Animais , Apoptose , Colite/patologia , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interferon gama/metabolismo , Interleucina-10/deficiência , Interleucina-17/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , Ocludina/genética , Ocludina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
BACKGROUND: Celastrol had been proved effective in the treatment for IBD, probably with the modulation of oxidative stress, inflammatory cytokines and intestinal homeostasis. This study was aimed to investigate whether celastrol could ameliorate the inflammation of IL-10 deficient mice, a murine model of Crohn's disease (CD) with the induction of autophagy. MATERIAL AND METHODS: The mice included were divided into four groups, ##WT group, IL-10(-/-) group, Cel group and Control group (celastrol+3-Methyladenine). Celastrol (2 mg/kg) treatment by gavage was administered to mice daily over one week. 3-Methyladenine (autophagy inhibitors) was administered at a dose of 30 mg/kg by intraperitoneal injection. The histological evaluation of the colon, tissue myeloperoxidase (MPO), and colon inflammation of mice in the four groups was evaluated and compared. Furthermore, the PI3K/Akt/mTOR pathway and the status of autophagy in intestine affected by celastrol were also assessed. RESULTS: The one-week administration of celastrol ameliorated established colitis in IL-10 deficient mice, associated with a reduction of marked histological inflammation, a decreased colon MPO concentration and suppression of colonic proinflammatory cytokine. Furthermore, the decreased neutrophil infiltration in proximal colon and improvement of inflammation in the Cel group was much more obvious than that in the Control group. The Western blotting analysis of the PI3K/Akt/mTOR pathway and autophagy showed that celastrol treatment up-regulated the autophagy of colon tissue by suppressing the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: Celastrol ameliorates experimental colitis in IL-10 deficient mice via the up-regulation of autophagy by suppressing the PI3K/Akt/mTOR signaling pathway.
Assuntos
Anti-Inflamatórios/uso terapêutico , Autofagia/efeitos dos fármacos , Colo/efeitos dos fármacos , Doença de Crohn/tratamento farmacológico , Interleucina-10/deficiência , Triterpenos/uso terapêutico , Animais , Anti-Inflamatórios/administração & dosagem , Western Blotting , Colo/imunologia , Colo/patologia , Doença de Crohn/imunologia , Doença de Crohn/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Interleucina-10/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Triterpenos Pentacíclicos , Peroxidase/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Triterpenos/administração & dosagemRESUMO
AIM: To investigate the impact of enteral nutrition (EN) on the body composition and metabolism in patients with Crohn's disease (CD). METHODS: Sixty-one patients diagnosed with CD were enrolled in this study. They were given only EN (enteral nutritional suspension, TPF, non-elemental diet) support for 4 wk, without any treatment with corticosteroids, immunosuppressive drugs, infliximab or by surgical operation. Body composition statistics such as weight, body mass index, skeletal muscle mass (SMM), fat mass, protein mass and inflammation indexes such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and CD activity index (CDAI) were recorded before and after EN support. RESULTS: The 61 patients were divided into three groups according to CDAI before and after EN support: A (active phase into remission via EN, n=21), B (remained in active phase before and after EN, n=19) and C (in remission before and after EN, n=21). Patients in group A had a significant increase in SMM (22.11±4.77 kg vs 23.23±4.49 kg, P=0.044), protein mass (8.01±1.57 kg vs 8.44±1.45 kg, P=0.019) and decrease in resting energy expenditure (REE) per kilogram (27.42±5.01 kcal/kg per day vs 22.62±5.45 kcal/kg per day, P<0.05). There was no significant difference between predicted and measured REE in active CD patients according to the Harris-Benedict equation. There was no linear correlation between the measured REE and CRP, ESR or CDAI in active CD patients. CONCLUSION: EN could decrease the hypermetabolism in active CD patients by reducing the inflammatory response.