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1.
JCI Insight ; 4(17)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31484831

RESUMO

`NK cell-mediated regulation of antigen-specific T cells can contribute to and exacerbate chronic viral infection, but the protective mechanisms against NK cell-mediated attack on T cell immunity are poorly understood. Here, we show that progranulin (PGRN) can reduce NK cell cytotoxicity through reduction of NK cell expansion, granzyme B transcription, and NK cell-mediated lysis of target cells. Following infection with the lymphocytic choriomeningitis virus (LCMV), PGRN levels increased - a phenomenon dependent on the presence of macrophages and type I IFN signaling. Absence of PGRN in mice (Grn-/-) resulted in enhanced NK cell activity, increased NK cell-mediated killing of antiviral T cells, reduced antiviral T cell immunity, and increased viral burden, culminating in increased liver immunopathology. Depletion of NK cells restored antiviral immunity and alleviated pathology during infection in Grn-/- mice. In turn, PGRN treatment improved antiviral T cell immunity. Taken together, we identified PGRN as a critical factor capable of reducing NK cell-mediated attack of antiviral T cells.

2.
J Oleo Sci ; 68(9): 909-922, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484903

RESUMO

The objective of this research was to evaluate the effect of wheat gluten on gut microbiota from hamsters and also analyse whether alterations in microbiota could result in wheat gluten's lipid-lowering properties. Four weeks male hamsters were divided into 3 groups (n=10). Two hypercholesterolemic groups were fed for 35 days with hypercholesterolemic diet, containing 20% (w/w) wheat gluten or casein. Wheat gluten significantly reduced serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) concentrations, and also decreased the liver total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE), triglycerides (TG) concentrations. Wheat gluten group had a higher fecal lipids, total cholesterol (TC) and bile acids (BA) than that of casein group (p < 0.05). Moreover, wheat gluten significantly increased total short-chain fatty acids (SCFA) concentrations in feces. Sequencing of 16S rRNA gene revealed that intake of wheat gluten decreased the relative abundances of Firmicutes and Erysipelotrichaceae, but to increased the relative abundances of Bateroidetes, Bacteroidales_S24-7_group and Ruminococcaceae. The lipid lowering properties of wheat gluten was associated with the lower ratio of Firmicutes/Bateroidetes, the lower of the bacterial taxa Erysipelotrichaceae and the higher of the bacterial taxa Bacteroidales_S24-7_group and Ruminococcaceae. These results suggest that wheat gluten modulate cholesterol metabolism by altering intestinal microflora.

3.
Bioelectrochemistry ; 131: 107349, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31476657

RESUMO

Several textile industry processes produce complex organics, azo dyes and sulfide streams that pose a severe challenge to environmental protection. In this work, single-chamber air cathode microbial fuel cells were used to investigate the interaction mechanisms among Congo red decolorization, sulfide oxidation and bioelectricity generation. The results showed that effective removal of sulfide (>98%) and azo dyes (>88%) was achieved at an initial sulfide/dye ratio of 0.9 under neutral conditions, accompanied by a maximum power output of approximately 23.50 mW m-2. In this study, biogenic sulfide played a major role in azo dye decolorization and power generation compared with the chemical sulfide. The results indicated that bulk reduction of sulfide and cell lysis products during biogenic sulfide production by sulfate-reduction bacteria could accelerate the chemical reduction of azo dyes. Moreover, S0, SO42- and S2O32- were identified as degradation products, and the intermediates primarily included 3,4-diaminonaphthalene-1-sulfonic acid, sodium 4-aminonaphthalene-1-sulfonate and 4, 4'-diamine biphenyl. Microbial community analysis showed that Proteobacteria (80.7%), Gammaproteobacteria (48.1%), and Dokdonella (29.5%) dominated at the phylum, class, and genus levels, respectively, of the anodic biofilm. This study offers a feasible option for the treatment of recalcitrant organics, azo dyes and sulfide pollutants using single-chamber air cathode MFCs.

4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(9): 882-885, 2019 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-31515781

RESUMO

OBJECTIVE: To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ. METHODS: GCDH gene variants was detected by Sanger sequencing among the three children and their family members. RESULTS: Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers. CONCLUSION: The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.

5.
Biosens Bioelectron ; 143: 111599, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31476600

RESUMO

The reliable quantitative analysis of tumor biomarkers in circulating blood is crucial for cancer early screening, therapy monitoring and prognostic prediction. Herein, a novel biosensor combing surface-enhanced Raman spectroscopy (SERS) and surface molecularly imprinted polymer (SMIP) technology was developed for quantitative detection of carcinoembryonic antigen (CEA) that is closely related to several common cancers. Owing to the use of SMIP, recognition sites with high affinity to the target of interest can be well imprinted on the surface of SERS substrate, leading to a more stable and specific capture ability. In addition, two layers of core-shell nanoparticles were integrated to this SERS substrate to form highly efficient electromagnetic enhancement for SERS measurement via the generation of lots of "hot spot". Besides, a unique Raman reporter (CC) with silent Raman signals at 2024 cm-1 was capsulated in the nanoparticles to avoid the optical noises originating from endogenous molecules at fingerprint region (300-1800 cm-1). Meanwhile, we employed an internal standard molecular (CN) to real time correct the fluctuating signals of Raman reporter when performing the quantitative analysis. Due to these features, a limit of detection (LOD) of 0.064 pg mL-1 with the detection range of 0.1 pg mL-1 - 10 µg mL-1 can be achieved by this assay. Excitingly, this technology even showed wonderful performances for CEA detection in real blood from cancer patients, demonstrating great potential for biomarker-based cancer screening.

6.
Langmuir ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31475530

RESUMO

For the wide application of nanoparticles (NPs) (e.g., in nanotribology), it is of fundamental and practical importance to understand the self-assembly and lubrication behavior of confined NPs. In this work, a systematic study was conducted to probe the assembly and associated surface forces of spherical gold nanoparticles (Au NPs, diameter ∼5 nm) confined between pairs of mica (negatively charged) and (3-aminopropyl)triethoxysilane modified mica (APTES-mica, positively charged) surfaces using a surface forces apparatus (SFA) under aqueous conditions. It is observed that Au NPs were squeezed out of the confined gap between two mica surfaces during the loading process, resulting from the repulsive electric-double layer force. In contrast, multilayers of Au NPs were confined between two APTES-mica surfaces because of the attractive double-layer force between oppositely charged Au NPs and APTES-mica. Interestingly, the interaction between Au NPs and APTES-mica is stronger than the interactions between Au NPs, resulting in the rearrangement of the confined Au NPs under shearing. Importantly, a large friction coefficient (µ > 0.7) with unexpected nonlinear stick-slip friction was observed when sliding two APTES-mica surfaces with thin layers of Au NPs (∼20 nm) confined in between. The observed stick-slip motion could be explained by the velocity-dependent friction model where a critical shear velocity was required for transiting from stick-slip to smooth sliding. Our study provides useful information on the assembly and interaction forces of confined nanoparticles on charged surfaces, with implications for predicting the behaviors of NPs under confinement in various engineering applications.

7.
Math Biosci Eng ; 16(5): 4908-4922, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499696

RESUMO

Steganography poses a serious challenge to forensics because investigators cannot identify even traces of secret messages embedded using a steganographer. Contrarily, the objective of locating steganalysis is to locate the embedded message, which should help extract the secret message. In this paper, a methodology of locating steganalysis using quantitative steganalysis is presented for multiple stego images with embedded messages along the same embedding path. Three typical quantitative steganalysis methods are applied to the methodology to locate the messages embedded using LSB re-placement. Experimental results show that the presented methods can reliably estimate the embedding positions, which verifies the validity of the presented methodology. The presented methodology points out a new use of quantitative steganalysis, and further demonstrates that it is necessary to design more precise quantitative steganalysis methods.

8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(7): 757-766, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31413213

RESUMO

OBJECTIVE: To investigate the effect of miR-30a/HMGA2-mediated autophagy in osteosarcoma cells on apoptosis induced by chemotherapeutics. 
 Methods: A total of 30 osteosarcoma tissues of sensitive and resistant to chemotherapeutics were divided into a chemotherapy-sensitive group and a chemotherapy-resistant group. The mRNA expression levels of miR-30a and high mobility group protein A2 (HMGA2) in the chemotherapy-sensitive group and the chemotherapy-resistant group, and the mRNA expression levels of miR-30a in osteosarcoma U2-OS cells treated by cisplatin, doxorubicin and methotrexate at different concentrations were detected by real-time PCR. The expression levels of autophagy related protein Beclin 1, microtubule associated protein 1 light chain 3B (LC3B) and autophagy factor P62 were detected by Western blotting. The osteosarcoma U2-OS cells were transfected with miR-30a mimics and miR-30a inhibitors to construct a miR-30a high expression group, a miR-30a low expression group and a control group. The expression levels of Beclin 1, LC3B and P62 in osteosarcoma U2-OS cells after treatment of cisplatin and doxorubicin in these 3 groups were detected by Western blotting; the level of autophagy was detected by monodansylcada (MDC) staining; the level of ROS was detected by dihydroethidium (DHE); the level of cell surviving rate was detected by cell counting kit-8 (CCK-8); the level of apoptosis was detected by annexin APC/PI double staining; the level of mitochondria oxidative damage was detected by mitochondrial membrane potential assay kit with JC-1 (JC-1 method). The interaction between miR-30a and HMGA2 was detected by dual luciferase reporter assay. The osteosarcoma U2-OS cells were transfected with HMGA2 mimics and HMGA2-shRNA to construct a high HMGA2 group, a low HMGA2 group, and a control group. The expression levels of Beclin 1, LC3B and P62 in osteosarcoma U2-OS cells after the treatment of cisplatin were detected by Western blotting.
 Results: The level of miR-30a in the chemotherapy-resistant tissues was significantly lower than that in the chemotherapy-sensitive tissues (P<0.05), and the expression of HMGA2 was opposite comparing to that of miR-30a (P<0.05). After the treatment by low concentration (5 µmol/L) of chemotherapeutics, the level of miR-30a was down-regulated in osteosarcoma U2-OS cells, accompanied with up-regulation of Beclin 1 and LC3B (P<0.01) and down-regulation of P62 (P<0.01). Compared with the control group, the expression levels of Beclin 1 and LC3B were significantly decreased (P<0.05), and the expression level of P62 was significantly increased (P<0.05) in the miR-30a high expression group, which was opposite in the miR-30a low expression group. In the miR-30a high expression group treated by chemotherapeutics, the level of autophagy and the cell survival rate were lower than those in group with low expression of miR-30a, while the levels of ROS, the mitochondrial oxidative damage and the apoptosis were higher than those in group with low expression of miR-30a (all P<0.05). The targeting interaction between HMGA2 and miR-30a were verified by dual luciferase reporter assay. Compared with the control group, the expression levels of Beclin 1 and LC3B were significantly increased (P<0.05), and the expression level of P62 was significantly decreased (P<0.05) in the HMGA2 high expression group, which was opposite in the HMGA2 low expression group.
 Conclusion: Suppression of miR-30a/HMGA2-mediated autophagy in osteosarcoma cells is likely to enhance the therapeutic effect of chemotherapeutics.


Assuntos
Autofagia , Neoplasias Ósseas , Proteína HMGA2/metabolismo , MicroRNAs/genética , Osteossarcoma , Apoptose , Proteínas Reguladoras de Apoptose , Proteína Beclina-1 , Linhagem Celular Tumoral , Humanos
9.
Fish Shellfish Immunol ; 93: 711-719, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31419532

RESUMO

In the present study, we aimed to screen the potential probiotic Bacillus subtilis isolated from the gut of healthy fish using in vitro assays and to evaluate its effect on Dabry's sturgeon (Acipenser dabryanus) using in vivo feeding experiments. Among the isolates, B. subtilis BSth-5 and BSth-19 exhibited antimicrobial effect against four sturgeon-pathogenic bacteria, including Aeromonas hydrophila, A. veronii, A. media, and Streptococcus iniae. The cell number of B. subtilis BSth-5 and BSth-19 changed little after 2 h of exposure to pH 3.0 or fresh Dabry's sturgeon bile at 2.5% and 5.0%. Meanwhile, B. subtilis BSth-5 and BSth-19 produced extracellular protease, cellulose, and lipase. And it was proved that B. subtilis BSth-5 and BSth-19 were harmless after injection of Dabry's sturgeon. One group of Dabry's sturgeon was fed a control diet and two groups were fed experimental diets containing 2.0 × 108 CFU/g BSth-5 (T1 group) or BSth-19 (T2 group) for 8 weeks. No significant differences in final weight, weight gain rate, and special growth rate were observed in the T1 and T2 groups compared to the control group (P > 0.05), but a significant improvement in survival rate was detected after 4 and 8 weeks of feeding (P < 0.05). After 8 weeks, serum total antioxidant capacity, total superoxide dismutase activity, and IgM levels were significantly higher in the T1 and T2 groups compared to the control group (P < 0.05). Moreover, serum lysozyme activity was significantly higher in the T1 group relative to the control group during the whole experiment period (P < 0.05); however, the differences were not significant between the T2 and control groups (P > 0.05). Serum malondialdehyde levels in the T1 and T2 groups were significantly lower than those in the control group after 4 weeks (P < 0.05). Sturgeons in the T1 and T2 groups showed a higher survival rate after Aeromonas hydrophila infection. To summarize, dietary supplementation with BSth-5 and BSth-19 could enhance the survival rate, antioxidant activity, serum immunity, and disease resistance in A. dabryanus.

10.
Talanta ; 205: 120121, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450457

RESUMO

The amine decorated carbon quantum dots (NH2-CQDs) were synthesized through ultrasonic method from graphite rods derived CQDs and ammonia hydroxide and utilized as the sensing probes for cobalt (II) ions and nucleic acids. The sensing technique was investigated to be the fluorescence quenching effect, which demonstrated linear relationship between cobalt (II) ions concentration and the emission intensity deviation ratio in the concentration range of 50 nM to 40 µM with the detection limit of 12 nM. In brief, this sensitive and selective detection method was confirmed to demonstrate high potential in cobalt (II) ions detection in real samples and nucleic acid sensing in biological cells.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31464658

RESUMO

A strictly aerobic, Gram-stain-negative, rod-shaped, yellow, non-spore-forming bacterial strain, designated P-25T, was isolated from soil collected in Yantai, Shandong Province, PR China. The temperature, pH and NaCl concentration ranges for the growth of strain P-25T were 10-37 °C (optimum, 28-30 °C), pH 6.0-9.0 (optimum, pH 7.5-8.0) and 0-4 % (w/v) (optimum, 1 % w/v), respectively. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain P-25T was most closely related to Pedobacter xixiisoli S27T (98.1 % 16S rRNA gene sequence similarity), followed by Pedobacter chitinilyticus CM134L-2T (97.2 %) and Pedobacter ureilyticus THG-T11T (97.1 %). The genomic DNA G+C content of strain P-25T based on its draft genome sequence was 38.1 %. MK-7 was the major respiratory quinone, and iso-C15 : 0, C16 : 1ω7c and/or C16 : 1ω6c (summed feature 3) and iso-C17 : 0 3-OH were the major fatty acids. The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid, one unidentified phospholipid, two unidentified lipids, five unidentified aminolipids and two unidentified glycolipids. Average nucleotide identity values for the draft genomes between strain P-25T and strains S27T, CM134L-2T and THG-T11T were 81.8, 77.6 and 81.2 %, respectively, and the digital DNA-DNA hybridization (dDDH) values were 30.0, 19.2 and 27.6 %, respectively. Based on their phylogenetic and phenotypic characteristics, chemotaxonomic data, and dDDH results, strain P-25T is considered to represent a novel species of the genus Pedobacter, for which the name Pedobacter helvus sp. nov. is proposed; the type strain is strain P-25T (KCTC 62821T=CCTCC AB 2018185T).

12.
Artigo em Inglês | MEDLINE | ID: mdl-31436521

RESUMO

A Gram-stain-negative bacterial strain, designated JW-3T, was isolated from a soil sample collected from farmland in Yantai, Shandong Province, PR China. Cells of strain JW-3T are motile rods and strictly aerobic, showing catalase- and oxidase-positive reactions. Strain JW-3T could grow at 16-37 °C (optimum, 30 °C), at pH 6.0-9.0 (pH 7.0) and in the presence of 0-1 % (w/v) NaCl (0.5 %, in Luria-Bertani broth). The major fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c; 35.5 %), iso-C16 : 0 (16.7 %) and C12 : 0 (10.8 %). The major respiratory quinone was ubiquinone-8 (Q8). The polar lipids of strain JW-3T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, four unidentified phospholipids, two unidentified lipids, two unidentified glycolipids and a partial unidentified aminophospholipid. Strain JW-3T was most closely related to Steroidobacter agariperforans KA5-BT with 97.67 % 16S rRNA gene sequence similarity. Results of phylogenetic analyses, based on 16S rRNA gene sequencing, showed that strain JW-3T forms a distinct phylogenic lineage within the genus Steroidobacter of the family Sinobacteraceae. The DNA G+C content of strain JW-3T was 62.57 mol%, based on its draft genome sequence. Average nucleotide identity values and digital DNA-DNA hybridization values for draft genomes, between strain JW-3T and strain KA5-BT, were 84.54 and 30.80 %, respectively. Based on its phenotypic, chemotaxonomic and molecular features, and DNA-DNA hybridization results, strain JW-3T represents a novel species of the genus Steroidobacter, for which the name Steroidobactersoli sp. nov. is proposed. The type strain is JW-3T (=CCTCC AB 2018184T=KCTC 62820T).

13.
Sci Total Environ ; 691: 1072-1081, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31466189

RESUMO

Sulfonamides and their corresponding antibiotic resistance genes (ARGs) are widespread in the environment, which leads to a major threat to global health crisis. Biodegradation plays a major role in sulfonamides removal in soil ecosystem, but the degradation dynamics and the associated functional bacteria in situ remain unclear. In this study, aerobic degradation of sulfadiazine (SDZ) at two dosages (1 and 10 mg/kg) was explored for up to 70 days in two different agricultural soils. The removal of SDZ in all treatments followed first-order multi-compartment model with half-life times of 0.96-2.57 days, and DT50 prolonged with the increase of initial dosage. A total of seven bacterial genera, namely Gaiella, Clostrium_sensu_stricto_1, Tumebacillus, Roseiflexus, Variocorax, Nocardioide and Bacillus, were proposed as the potential SDZ-degraders. sadA gene was for the first time detected in soil samples, but other functional genes might also participate in SDZ degradation. The enrichment of sulfonamide resistance genes was found after 70 days' incubation, which might result in the spread of ARGs in soil. This study can add some new insights towards SDZ degradation in soil ecosystem and provide a potential resource for the bioremediation of SDZ-contaminated soil.

14.
Water Res ; 163: 114907, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369921

RESUMO

Chrome mist suppressants are key chemicals used in the chrome plating industry to reduce exposure of workers by inhalation to airborne chromic acid pollution. Perfluoroalkyl sulfonated compounds are excellent mist suppressants, thanks to their chemical stability and surface activity. Therefore, despite mounting evidence for their persistence, bioaccumulation and toxicity, it is likely that such chemicals will continue to be used for the foreseeable future because of their importance and lack of alternatives. The present study is aimed at assessing the feasibility of advanced reduction as an effective technology to treat chrome plating industry wastewater. In particular, wastewater containing a chlorinated polyfluorinated ether sulfonate (i.e. F-53B), an alternative to perfluorooctanesulfonate (PFOS) used to prepare chrome mist suppressant in China, was treated by UV-activated sulfite. Results demonstrates that in ultrapure water F-53B can be easily degraded within 1 min-much faster than PFOS. Stoichiometric fluoride recovery was also achieved, confirming significant defluorination of the pollutant. Such superior reducibility was due to the presence of chlorine atoms, as corroborated by quantum chemical calculations. F-53B degradation was also achieved in chrome plating industrial wastewater, which yielded results were slower than those achieved in the laboratory nonetheless obtained complete abatement within 60 min. These results suggest that the proposed advanced reduction process is one of the safest options to control PFAS discharge in the environment and reduce the related risks to ecosystems.

15.
Sci Total Environ ; 694: 133711, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400687

RESUMO

A case study was implemented to investigate the seasonal and spatial variations of 43 kinds of pharmaceuticals and personal care products (PPCPs) in the water supply system of Changzhou in China. The source water, water samples in each unit along the drinking water treatment process, as well as the drinking water product in both urban and rural area in different seasons have been included. The total concentrations of detected PPCPs range from 6.37 ng/L to 809.28 ng/L, the level of which is higher than other reports in China. In summer, more kinds of PPCPs were at higher concentrations in drinking water in urban area in spite of that fewer kinds of PPCPs were detected in raw water than in winter. It mainly because some kinds of PPCPs, which can be still detected under higher temperature and stronger irradiation in summer, were hardly removed by the drinking water treatment plant (DWTP). Therefore, people are at relatively higher health risk by PPCPs exposure through the intake of drinking water during summer than winter. The advanced treatment which applied GAC (granular activated carbon) filtration improved 2% to 46% of removal efficiency on PPCPs compared with conventional process, for which advanced treatment processes should be advocated in more DWTPs in China. In rural private wells, the situation is more worrying. Twelve more kinds of PPCPs were detected in rural drinking water than in urban, of which the max concentration reached 107 ng/L. The total concentrations of PPCPs in drinking water in rural area were obviously higher than in urban area, which lead to risk quotient (RQ) values of 4-6 times higher.

16.
Gut ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409605

RESUMO

OBJECTIVE: The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease. DESIGN: Mice lacking Fmr1 gene expression were used to study the role of FMRP during tumour necrosis factor (TNF)-induced liver damage in disease model systems. Liver damage and mechanistic studies were performed using real-time PCR, Western Blot, staining of tissue sections and clinical chemistry. RESULTS: Fmr1null mice exhibited increased liver damage during virus-mediated hepatitis following infection with the lymphocytic choriomeningitis virus. Exposure to TNF resulted in severe liver damage due to increased hepatocyte cell death. Consistently, we found increased caspase-8 and caspase-3 activation following TNF stimulation. Furthermore, we demonstrate FMRP to be critically important for regulating key molecules in TNF receptor 1 (TNFR1)-dependent apoptosis and necroptosis including CYLD, c-FLIPS and JNK, which contribute to prolonged RIPK1 expression. Accordingly, the RIPK1 inhibitor Necrostatin-1s could reduce liver cell death and alleviate liver damage in Fmr1null mice following TNF exposure. Consistently, FMRP-deficient mice developed increased pathology during acute cholestasis following bile duct ligation, which coincided with increased hepatic expression of RIPK1, RIPK3 and phosphorylation of MLKL. CONCLUSIONS: We show that FMRP plays a central role in the inhibition of TNF-mediated cell death during infection and liver disease.

17.
Life Sci ; 234: 116771, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31421084

RESUMO

AIMS: We aimed to elucidate the effects and mechanisms of MAT1 in the progression of osteosarcoma, especially for its lung metastasis. MAIN METHODS: CCK-8 and flow cytometry assays were carried out to detect the proliferation and apoptosis of osteosarcoma cells. Wound healing and transwell assays were used to determine cell migration and invasion abilities. Real time quantitative PCR (RT-PCR) and western blot technologies were applied to detect the expression levels of RNA and protein, respectively. KEY FINDS: The results showed that both the mRNA and protein expression levels of MAT1 were elevated in osteosarcoma tissues with lung metastasis and metastatic lung tissues, particularly in the metastatic lung tissues, as compared to the osteosarcoma tissues without lung metastasis. High expression level of MAT1 in osteosarcoma patients showed a negative association with the overall survival. In addition, upregulation of MAT1 induced significant increases in cell growth, migration and invasion and an obvious inhibition in cell apoptosis in osteosarcoma MG63 and 143B cells, as well as elevated AKT1 expression level. Moreover, knockdown of AKT1 obviously impaired MAT1-mediated promotions in cell migration and invasion in vitro, as well as repressed tumor growth and reduced the number of metastatic lung tumors in xenografted nude mice. SIGNIFICANCE: This study reveals that high expression of MAT1 closely related to the poor prognosis and malignant clinical process of osteosarcoma patients. MAT1 serves as a promoter in the lung metastasis of osteosarcoma through increasing AKT1 expression. Our study may provide a potent therapeutic target for the lung metastasis of osteosarcoma.

18.
Mol Med Rep ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31432144

RESUMO

The inflammatory response is one of the most important factors in the occurrence and development of acute lung injury (ALI). Hypoxia­inducible factor­1α (HIF­1α) and the NOD­like receptor 3 (NLRP3) inflammasome have been demonstrated to serve an important role in the pathogenesis of ALI. The objective of the present study was to investigate whether HIF­1α could regulate activation of the NLRP3 inflammasome and its potential function and specific mechanism in bleomycin (BLM)­induced ALI. Activation of the NLRP3 inflammasome and secretion of IL­1ß were detected following silencing of HIF­1α or NF­κB, respectively, in BLM­treated A549 and RLE­6TN cells. The results demonstrated that the NLRP3 inflammasome could be activated after BLM treatment. HIF­1α and NF­κB expression significantly increased in the BLM group. The levels of NF­κB­ and NLRP3 inflammasome­associated proteins, including NLRP3, apoptosis­associated speck­like protein containing CARD and caspase­1, markedly decreased after treating A549 and RLE­6TN cells with HIF­1α small interfering RNA. Activation of the NLRP3 inflammasome was also inhibited after silencing NF­κB. Furthermore, the levels of IL­1ß markedly decreased in the cellular culture supernatants following inhibition of HIF­1α and NF­κB. Therefore, the present study indicated that HIF­1α could modulate the activation of the NLRP3 inflammasome and the secretion of IL­1ß through NF­κB signaling in BLM­induced ALI. The current results improve understanding of the mechanism of ALI and may provide new ideas for identifying therapeutic targets of ALI.

19.
Phys Chem Chem Phys ; 21(35): 19529-19537, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31463497

RESUMO

In spite of the widespread applications of amorphous silica-aluminas (ASAs) in many important industrial chemical processes, their high-resolution structures have remained largely elusive. Specifically, the lack of long-range ordering in ASA precludes the use of diffraction methods while NMR spectroscopy has been limited by low sensitivity. Here, we use conventional as well as DNP-enhanced 29Si-29Si, 27Al-27Al, and 29Si-27Al solid-state NMR experiments to shed light on the ordering of atoms in ASAs prepared by flame-spray-pyrolysis. These experiments, in conjunction with a novel Monte Carlo-based approach to simulating RESPDOR dephasing curves, revealed that ASA materials obey Loewenstein's rule of aluminum avoidance. 3D 17O{1H} and 2D 17O{1H,27Al} experiments were developed to measure site-specific O-H and HO-Al distances, and show that the Brønsted acid sites originate predominantly from the pseudo-bridging silanol groups.

20.
Food Chem ; 301: 125271, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31376690

RESUMO

Mature endosperm was separated regionally into different parts in three rice cultivars, Te-qing (TQ), Wu-xiang 9915 (WX9915) and Guang-ling-xiang-nuo (GLXN), and their transgenic lines with inhibition of starch branching enzyme I and IIb (SBEI/IIb-). Within the three wild-type cultivars, starches from endosperm different regions showed similar molecular and crystalline structures. However, in rices with inhibition of SBEs, amylopectin short branch-chain content and branching degree gradually decreased, but amylopectin B3+ chain content and average chain length increased gradually from the interior to exterior of endosperm. The amylose content gradually increased from the interior to exterior of endosperm in TQ- and WX9915-SBEI/II- lines. From the interior to exterior of endosperm, starch changed gradually from CC- to CB-type in TQ-SBEI/II- line and from CA- to CC-type in GLXN-SBEI/II- line, and remained CA-type in WX9915-SBEI/II- line. These results provided some information for quality breeding and utilizations of rice with inhibition of SBE.

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