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1.
Plant Mol Biol ; 114(3): 51, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691187

RESUMO

Pomegranate (Punica granatum L.) which belongs to family Lythraceae, is one of the most important fruit crops of many tropical and subtropical regions. A high variability in fruit color is observed among different pomegranate accessions, which arises from the qualitative and quantitative differences in anthocyanins. However, the mechanism of fruit color variation is still not fully elucidated. In the present study, we investigated the red color mutation between a red-skinned pomegranate 'Hongbaoshi' and a purple-red-skinned cultivar 'Moshiliu', by using transcriptomic and metabolomic approaches. A total of 51 anthocyanins were identified from fruit peels, among which 3-glucoside and 3,5-diglucoside of cyanidin (Cy), delphinidin (Dp), and pelargonidin (Pg) were dominant. High proportion of Pg in early stages of 'Hongbaoshi' but high Dp in late stages of 'Moshiliu' were characterized. The unique high levels of Cy and Dp anthocyanins accumulating from early developmental stages accounted for the purple-red phenotype of 'Moshiliu'. Transcriptomic analysis revealed an early down-regulated and late up-regulated of anthocyanin-related structure genes in 'Moshiliu' compared with 'Hongbaoshi'. Alao, ANR was specially expressed in 'Hongbaoshi', with extremely low expression levels in 'Moshiliu'. For transcription factors R2R3-MYB, the profiles demonstrated a much higher transcription levels of three subgroup (SG) 5 MYBs and a sharp decrease in expression of SG6 MYB LOC116202527 in high-anthocyanin 'Moshiliu'. SG4 MYBs exhibited two entirely different patterns, LOC116203744 and LOC116212505 were down-regulated whereas LOC116205515 and LOC116212778 were up-regulated in 'Moshiliu' pomegranate. The results indicate that specific SG members of the MYB family might promote the peel coloration in different manners and play important roles in color mutation in pomegranate.


Assuntos
Antocianinas , Frutas , Regulação da Expressão Gênica de Plantas , Punica granatum , Transcriptoma , Frutas/genética , Frutas/metabolismo , Antocianinas/metabolismo , Antocianinas/genética , Punica granatum/genética , Punica granatum/metabolismo , Pigmentação/genética , Perfilação da Expressão Gênica , Cor , Metabolômica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Life Sci ; 335: 122230, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37952835

RESUMO

AIMS: Immunotherapy has shown remarkable effects on several malignancies; however, its impact on gastric cancers has been limited. Therefore, a novel strategy to overcome resistance to immunotherapy is required. In this study, we compared the gene expression profiles of two murine GC cell lines that exhibited different effects on tumor immunity. The functions of specific genes related to negative tumor immunity and the impact of a specific inhibitor were evaluated in syngeneic GC mouse models. MATERIALS AND METHODS: RT-PCR and Western blotting validated Gas6 and AXL expression in murine cell lines. RT-PCR compared YTN16 and YTN3 GC cell's impact on T cell activation. AXL, the receptor for GAS6 in YTN16, was validated by western blotting. Gas6 was inhibited in YTN16 cells using shRNA, and then the gene expression pattern, effects to T cell activation, and tumor growth were assessed. YTN16 cells were injected into mice and treated with CCB-3233, anti-PD-1 antibody, or both. Immunohistochemistry and flow cytometry evaluated tumor-infiltrating immune cells. KEY FINDINGS: YTN16 cells expressed more Gas6 and had reduced T cell activation compared to YTN3 cells. AXL activation was higher in YTN16. CCB-3233 reduced AXL phosphorylation. Knocking down Gas6 in YTN16 reduced immunosuppression-related genes and increased tumor-infiltrating T cells. Combined CCB-3233 and anti-PD-1 treatment reduced tumor growth and increased T-cell infiltration. Human GC data revealed a negative correlation between GAS6 and immune activation-related genes. SIGNIFICANCE: The GAS6/AXL pathway contributes to immunotherapy resistance in GC. Targeting this pathway may be a novel therapeutic strategy.


Assuntos
Receptores Proteína Tirosina Quinases , Neoplasias Gástricas , Humanos , Camundongos , Animais , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tirosina Quinase Axl , Neoplasias Gástricas/patologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Microambiente Tumoral , Imunoterapia
3.
J Biol Eng ; 17(1): 25, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36998087

RESUMO

BACKGROUND: Human induced pluripotent stem cells (hiPSCs) provide an in vitro system to identify the impact of cell behavior on the earliest stages of cell fate specification during human development. Here, we developed an hiPSC-based model to study the effect of collective cell migration in meso-endodermal lineage segregation and cell fate decisions through the control of space confinement using a detachable ring culture system. RESULTS: The actomyosin organization of cells at the edge of undifferentiated colonies formed in a ring barrier differed from that of the cells in the center of the colony. In addition, even in the absence of exogenous supplements, ectoderm, mesoderm, endoderm, and extraembryonic cells differentiated following the induction of collective cell migration at the colony edge by removing the ring-barrier. However, when collective cell migration was inhibited by blocking E-cadherin function, this fate decision within an hiPSC colony was altered to an ectodermal fate. Furthermore, the induction of collective cell migration at the colony edge using an endodermal induction media enhanced endodermal differentiation efficiency in association with cadherin switching, which is involved in the epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that collective cell migration can be an effective way to drive the segregation of mesoderm and endoderm lineages, and cell fate decisions of hiPSCs.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-994255

RESUMO

Objective:To evaluate the relationship between mitochondrial calcium uniporter protein (MCU)-mediated mitochondrial dynamics and intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Twenty-four wild-type adult male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (S group), intestinal I/R group (IIR group), sham operation+ MCU inhibitor Ru360 group (S+ Ru360 group) and intestinal I/R + Ru360 group (IIR+ Ru360 group). The mouse model of intestinal I/R injury was prepared by clamping the root of the superior mesenteric artery for 45 min followed by 2 h of reperfusion in anesthetized animals. Small intestinal tissues were obtained at the end of reperfusion for examination of the intestinal mucosal injury which was scored according to Chiu and for determination of the content of malondialdehyde (MDA) (TBA method), activity of superoxide dismutase (SOD) (WST-8 method), content of lactic dehydrogenase (LDH) (colorimetric method), and expression of MCU, dynamin-related protein 1 (Drp1), recombinant human mitochondrial fission 1 protein (Fis1), mitofusin-1 (Mfn1) and Mfn2 (by Western blot). Results:Compared with S and S+ Ru360 groups, the Chiu′s score and contents of MDA and LDH were significantly increased, the activity of SOD was decreased, the expression of MCU, Drp1 and Fis1 was up-regulated, and the expression of Mfn1 and Mfn2 was down-regulated in IIR and IIR+ Ru360 groups ( P<0.05). Compared with IIR group, the Chiu′s score and contents of MDA and LDH were significantly decreased, the activity of SOD was increased, the expression of MCU, Drp1 and Fis1 was down-regulated, and the expression of Mfn1 and Mfn2 was up-regulated in IIR+ Ru360 group ( P<0.05). Conclusions:The mechanism underlying intestinal I/R injury may be related to MCU-induced promotion of mitochondrial fission, reduction of mitochondrial fusion and mediation of imbalance in mitochondrial dynamics in mice.

5.
Biomolecules ; 12(12)2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36551269

RESUMO

Halogenation of bioactive peptides via incorporation of non-natural amino acid derivatives during chemical synthesis is a common strategy to enhance functionality. Bacterial tyrptophan halogenases efficiently catalyze regiospecific halogenation of the free amino acid tryptophan, both in vitro and in vivo. Expansion of their substrate scope to peptides and proteins would facilitate highly-regulated post-synthesis/expression halogenation. Here, we demonstrate novel in vitro halogenation (chlorination and bromination) of peptides by select halogenase enzymes and identify the C-terminal (G/S)GW motif as a preferred substrate. In a first proof-of-principle experiment, we also demonstrate chemo-catalyzed derivatization of an enzymatically chlorinated peptide, albeit with low efficiency. We further rationally derive PyrH halogenase mutants showing improved halogenation of the (G/S)GW motif, both as a free peptide and when genetically fused to model proteins with efficiencies up to 90%.


Assuntos
Halogenação , Oxirredutases , Oxirredutases/metabolismo , Proteínas de Bactérias/metabolismo , Peptídeos/metabolismo , Aminoácidos/metabolismo
6.
Front Cardiovasc Med ; 9: 1057195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582736

RESUMO

Introduction: A contactless multiscale cardiac motion measurement method is proposed using impulse radio ultra-wideband (IR-UWB) radar at a center frequency of 7.29 GHz. Motivation: Electrocardiograph (ECG), heart sound, and ultrasound are traditional state-of-the-art heartbeat signal measurement methods. These methods suffer from defects in contact and the existence of a blind information segment during the cardiogram measurement. Methods: Experiments and analyses were conducted using coarse-to-fine scale. Anteroposterior and along-the-arc measurements were taken from five healthy male subjects (aged 25-43) when lying down or prone. In every measurement, 10 seconds of breath-holding data were recorded with a radar 55 cm away from the body surface, while the ECG was monitored simultaneously as a reference. Results: Cardiac motion detection from the front was superior to that from the back in amplitude. In terms of radar detection angles, the best cardiac motion information was observed at a detection angle of 120°. Finally, in terms of cardiac motion cycles, all the ECG information, as well as short segments of cardiac motion details named blind ECGs segments, were detected. Significance: A contactless and multiscale cardiac motion detection method is proposed with no blind detection of segments during the entire cardiac cycle. This paves the way for a potentially significant method of fast and accurate cardiac disease assessment and diagnosis that exhibits promising application prospects in contactless online cardiac monitoring and in-home healthcare.

7.
Front Bioeng Biotechnol ; 10: 1032707, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36588932

RESUMO

Biocatalytic C-H halogenation is becoming increasingly attractive due to excellent catalyst-controlled selectivity and environmentally benign reaction conditions. Significant efforts have been made on enzymatic halogenation of industrial arenes in a cost-effective manner. Here we report an unprecedented enzymatic halogenation of a panel of industrially important indole, azaindole and anthranilamide derivatives using a thermostable RebH variant without addition of any external flavin reductase enzyme. The reactions were catalyzed by the RebH variant 3-LSR enzyme with the help of a co-purified E. coli reductase identified as alkyl hydroperoxide reductase F (AhpF).

8.
Chinese Journal of Burns ; (6): 301-305, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-936010

RESUMO

Skin and soft tissue expansion can provide skin tissue similar to the recipient area in color and texture, which is one of the ideal methods in the repair of superficial defects. However, due to the long treatment cycle and relatively high complications rate in pediatric patients, expansion still faces many challenges. Based on the clinical practice and the current progress in skin and soft tissue expansion, this paper briefly discusses the change of skin after expansion, and the application, prevention and treatment of complications in the application of expansion in pediatric patients, aiming to provide reference for expansion in pediatric patients.


Assuntos
Criança , Humanos , Procedimentos de Cirurgia Plástica , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Expansão de Tecido , Resultado do Tratamento
9.
Materials (Basel) ; 14(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34501052

RESUMO

Here, we compare two different transparent conducting oxides (TCOs), namely indium tin oxide (ITO) and indium zinc tin oxide (IZTO), fabricated as transparent conducting films using processes that require different temperatures. ITO and IZTO films were prepared at 230 °C and at room temperature, respectively, on glass and polyethylene terephthalate (PET) substrates using reactive magnetron sputtering. Electrochromic WO3 films deposited on ITO-based and IZTO-based ECDs using vacuum cathodic arc plasma (CAP) were investigated. IZTO-based ECDs have higher optical transmittance modulation, ΔT = 63% [from Tbleaching (90.01%) to Tcoloration (28.51%)], than ITO-based ECDs, ΔT = 59%. ECDs consisted of a working electrochromic electrode (WO3/IZTO/PET) and a counter-electrode (Pt mesh) in a 0.2 M LiClO4/perchlorate (LiClO4/PC) liquid electrolyte solution with an active area of 3 cm × 4 cm a calculated bleaching time tc of 21.01 s and a coloration time tb of 4.7 s with varying potential from -1.3 V (coloration potential, Vc) to 0.3 V (bleaching potential, Vb).

10.
Environ Sci Technol ; 55(17): 11557-11567, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34431667

RESUMO

The lockdown due to COVID-19 created a rare opportunity to examine the nonlinear responses of secondary aerosols, which are formed through atmospheric oxidation of gaseous precursors, to intensive precursor emission reductions. Based on unique observational data sets from six supersites in eastern China during 2019-2021, we found that the lockdown caused considerable decreases (32-61%) in different secondary aerosol components in the study region because of similar-degree precursor reductions. However, due to insufficient combustion-related volatile organic compound (VOC) reduction, odd oxygen (Ox = O3 + NO2) concentration, an indicator of the extent of photochemical processing, showed little change and did not promote more decreases in secondary aerosols. We also found that the Chinese provinces and international cities that experienced reduced Ox during the lockdown usually gained a greater simultaneous PM2.5 decrease than other provinces and cities with an increased Ox. Therefore, we argue that strict VOC control in winter, which has been largely ignored so far, is critical in future policies to mitigate winter haze more efficiently by reducing Ox simultaneously.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Oxigênio , Material Particulado/análise , SARS-CoV-2
11.
Chembiochem ; 22(18): 2791-2798, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34240527

RESUMO

Activating industrially important aromatic hydrocarbons by installing halogen atoms is extremely important in organic synthesis and often improves the pharmacological properties of drug molecules. To this end, tryptophan halogenase enzymes are potentially valuable tools for regioselective halogenation of arenes, including various industrially important indole derivatives and similar scaffolds. Although endogenous enzymes show reasonable substrate scope towards indole compounds, their efficacy can often be improved by engineering. Using a structure-guided semi-rational mutagenesis approach, we have developed two RebH variants with expanded biocatalytic repertoires that can efficiently halogenate several novel indole substrates and produce important pharmaceutical intermediates. Interestingly, the engineered enzymes are completely inactive towards their natural substrate tryptophan in spite of their high tolerance to various functional groups in the indole ring. Computational modelling and molecular dynamics simulations provide mechanistic insights into the role of gatekeeper residues in the substrate binding site and the dramatic switch in substrate specificity when these are mutated.


Assuntos
Proteínas de Bactérias/metabolismo , Indóis/química , Oxirredutases/metabolismo , Triptofano/metabolismo , Actinobacteria/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Sítios de Ligação , Biocatálise , Halogenação , Indóis/metabolismo , Simulação de Dinâmica Molecular , Mutagênese Sítio-Dirigida , Oxirredutases/química , Oxirredutases/genética , Especificidade por Substrato , Triptofano/química
12.
Huan Jing Ke Xue ; 42(6): 2648-2658, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34032064

RESUMO

Oxygenated volatile organic compounds (OVOCs) are important intermediates in the troposphere and the most important sources of ozone. Proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS) was used to measure VOCs in the Chengdu Plain, Southwestern China. The diurnal variations, photochemical reactivity, O3 formation potential, and sources were also investigated. The mixing ratios of ten kinds of VOCs (acetaldehyde, acetone, isoprene, Methyl ethyl ketone, Methyl vinyl ketone and Methacrolein, benzene, toluene, styrene, C8 aromatics, and C9 aromatics) were (10.97±4.69)×10-9. The concentrations of OVOCs, aromatic hydrocarbons, and biogenic VOCs were (8.54±3.44)×10-9, (1.53±0.93)×10-9, and (0.90±0.32)×10-9, respectively. Isoprene, acetaldehyde, and m-xylene were the top three photochemically active species with the greatest O3 formation potentials. The dominant three OVOCs species (acetaldehyde, acetone, and MEK) were mainly derived from local biogenic sources and anthropogenic secondary sources, and acetone had a strong regional background level, indicating that pollution in this area is significantly affected by regional transmission. This study deepens the understanding of regional O3 formation mechanisms in southwest China and provides a basis for the scientifically informed control of O3 pollution.

13.
Chinese Journal of Digestion ; (12): 43-49, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-885731

RESUMO

Objective:To analyze the change rules of quantitative parameters of magnetic resonance-perfusion weighted imaging (MR-PWI) in cynomolgus monkeys with different degrees of liver fibrosis, and to explore the best parameter of MR-PWI in evaluating the severity of liver fibrosis.Methods:Liver fibrosis models of twenty-two cynomolgus monkeys were successfully established by subcutaneous injection of carbon tetrachloride and feeding with high-fat food. Among them, 15 cynomolgus monkeys developed into early liver cirrhosis (stage S4 of liver fibrosis). Compatibility group design was adopted, the comparative study on MR-PWI of exchange double blood supply model of liver was carried out in these 15 cynomolgus monkeys with a complete development process of liver fibrosis. The quantitative parameters of MR-PWI included endothelial transfer constant ( ktrans), reflux rate constant ( kep), extravascular extracellular space fractional volume ( ve), fractional plasma volume ( vp) and hepatic artery perfusion index (HPI). The change rules of the above parameters and their correlation with the severity of hepatic fibrosis were analyzed. The best parameter of MR-PWI was explored. Compatibility group design (randomized block design), analysis of variance, SNK- q test, Spearman rank correlation analysis and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. Results:ktrans and kep of MR-PWI of cynomolgus monkeys decreased along with the progress of hepatic fibrosis, and the differences were statistically significant ( F=685.228, 99.718, both P<0.01). There were statistically significant differences between each stage of hepatic fibrosis (S1 to S4) and normal liver tissue (S0) ((0.527±0.038), (0.479±0.035), (0.432±0.032) and (0.387±0.031) mL/min vs.(0.584±0.044) mL/min, all P<0.01; (2.193±0.307), (1.997±0.301), (1.624±0.174) and (1.532±0.130) mL/min vs. (2.565±0.482) mL/min, all P<0.01). There were statistically significant in ktrans and kep between stage S3, S4 severe liver fibrosis and stage S1 mild liver fibrosis, stage S2 moderate liver fibrosis (all P<0.01), however there were no statistically significant differences between stage S3 and stage S4 liver fibrosis, between stage S1 and stage S2 liver fibrosis (all P>0.05). Along with the development of the severity of liver fibrosis, HPIs increased gradually, and the differences were statistically significant ( F=839.883, P<0.01). The HPIs of stage S0 to S4 were 0.244±0.022, 0.317±0.035, 0.421±0.046, 0.546±0.043 and 0.651±0.058, respectively, and there were statistically significant differences between groups (all P<0.01). Along with the progression of the severity of liver fibrosis, vp decreased while ve increased gradually, but there were no statistically significant differences among groups (all P>0.05). The results of Spearman rank correlation analysis indicated that ktrans and kep were negatively correlated with the severity of liver fibrosis ( rs=-0.875 and -0.797, both P<0.01), however HPI was positively correlated with the severity of liver fibrosis ( rs=0.959, P<0.01). The results of ROC curve analysis showed that area under curves (AUCs) of ktrans, kep and HPI in the diagnosis of early cirrhosis were 0.852 (95% CI 0.767 to 0.937), 0.799 (95% CI 0.700 to 0.897) and 0.967 (95% CI 0.932 to 1.002), respectively. The best cut-off values were 0.395 mL/min, 1.561 mL/min and 0.590, respectively. The sensitivity was 86.7%, 79.6% and 97.4%, respectively and the specificity was 77.4%, 71.9% and 93.1%, respectively. The thresholds of HPI in the diagnosis of liver fibrosis at stage S1, stage S2, stage S3 and stage S4 were 0.291, 0.376, 0.503 and 0.590, respectively; the sensitivity was 95.7%, 93.8% and 94.4% and 97.4%, respectively and the specificity was 89.5%, 84.7%, 91.3% and 92.7%, respectively. Conclusions:The parameters of MR-PWI change regularly with the development of liver fibrosis in the cynomolgus monkey model, among which HPI is the best parameter for quantitative evaluation of the severity of liver fibrosis.

14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-884621

RESUMO

Objective:To construct a prognostic model of hepatocellular carcinoma (HCC) with differential expression of autophagy genes.Method:Autophagy genes expression data of HCC and normal liver tissues were obtained from The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) database respectively. The gene expression data from different platforms is normalized into log 2(FPKM value + 1). Differentially expressed autophagy-related genes of HCC were identified by using R program limma package from the TCGA-GTEx combined data set, the criteria of |logFC| > 1 and FDR < 0.05 was deemed to be of statistically significance. The Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by using R program clusterProfiler package, as criteria of P<0.05. Univariate and multivariate Cox proportional hazards regression analyses were performed by using R program survival package to identify the HCC potential prognostic differentially expressed autophagy-related genes. Furthermore, the statistically significant ( P<0.05) autophagy genes in the univariate Cox regression analysis were included in the multivariate Cox regression analysis, and the expression of each differentially expressed autophagy gene and the corresponding regression coefficient coef value based on this, the autophagy gene prognosis model of HCC was constructed: expmRNA1×βmRNA1+ expmRNA2×βmRNA2+ …+ expmRNAn×βmRNAn (exp: gene expression level; β: regression coefficient coef of multivariate Cox regression analysis). Draw the receiver operating characteristic (ROC) curve of the predictive model and calculate the area under curve (AUC) to evaluate the predictive value of the model. Results:The genes expression data and clinical information of 374 HCC samples and 160 normal liver tissue samples were obtained from TCGA and GTEx databases. Total 205 autophagy genes expression data was obtained from the TCGA-GTEx combined sequence. Among them, SPNS1, DIRAS3, TMEM74, NRG2, NRG1, IRGM, IKBKE, NKX2-3, BIRC5, CDKN2A, TP73 are differentially expressed autophagy genes that meet the screening criteria. GO analysis mainly enriched in "regulation of protein serine/threonine kinase activity" , "ErbB 2 signaling pathway" , "protein kinase regulator activity" and "kinase regulator activity" ; KEGG analysis enriched frequently in "EGFR tyrosine kinase inhibitor resistance" , "Hippo signaling pathway" . After integrating and deleting samples with missing survival information, a total of 418 sample expressions were included in the Cox regression analysis. After univariate and multivariate Cox risk regression analysis, the two autophagy genes NRG1 ( HR=1.5565, 95% CI: 1.1793-2.0543) and IKBKE ( HR=1.7502, 95% CI: 1.2093-2.5330) were screened out and a prognostic prediction model was established: (0.44247 × NRG1 expression level) + (0.55977 × IKBKE expression level). The ROC of the prognosis model shows that the AUC of the overall seven-year survival is 0.711. Conclusion:The prognosis model of HCC based on NRG1 and IKBKE has high predictive value for the long-term survival rate of hepatocellular carcinoma patients.

15.
Acta Pharmaceutica Sinica B ; (6): 1315-1328, 2021.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-881201

RESUMO

Bcr-Abl threonine 315 to isoleucine 315 (T315I) gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia (CML). Chemical degradation of Bcr-Abl

16.
Chin J Integr Med ; 26(11): 819-824, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32915425

RESUMO

OBJECTIVE: To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism. METHODS: The H22 liver cancer ascites lump model was established in male Kunming mice by injecting intraperitoneally (i.p.) with 5 × 106/mL H22 cells per mouse. Fifty tumor-bearing mice were divided into the control, model, pifithrin-α, GEG, and GEG+pifithrin-α groups using a random number table, 10 mice in each group. CTX (100 mg/kg i.p.) was administrated to mice from day 1 to day 3 (d1-d3) continuously except for the control group. The mice in the pifithrin-α, GEG and GEG+pifithrin-α groups were treated with pifithrin-α (2.2 mg/(kg·d) i.p.) for 6 consecutive days (d4-d9), GEG (9.5 g/(kg·d) i.p.) for 9 consecutive days (d1-d9), and GEG plus pifithrin-α, respectively. HSCs were collected after 9-d drug treatment. The anti-aging effect of GEG was studied by cell viability, cell cycle, and ß -galactosidase (ß -gal) assays. The mRNA and protein expressions of cyclin-dependent kinase 2 (CDK2), CDK4, inhibitor of cyclin-dependent kinase 4a encoding the tumor suppressor protein p16 (p16INK4a), p21Cip1/Waf1, p53, and phosphorylated retinoblastoma (pRb) were evaluated by quantitative real-time reverse transcription-polymerase chain reaction and semi-quantitative Western blot, respectively. RESULTS: Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced ß -gal expression. Furthermore, GEG significantly decreased the expressions of p16INK4a, p53 and p21Cip1/Waf1 proteins, and increased the expressions of CDK2, CDK4 and pRb proteins compared with the model group (P<0.05 or P<0.01). CONCLUSION: GEG can alleviate CTX-induced HSCs senescence in mice, and the p16INK4a-Rb signaling pathway might be the underlying mechanism.


Assuntos
Medula Óssea/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Ciclofosfamida/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Animais , Antineoplásicos Alquilantes/efeitos adversos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Camundongos
17.
Sci Rep ; 10(1): 8430, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32439890

RESUMO

Nanoporous structures have proven as an effective way for enhanced electrochromic performance by providing a large surface area can get fast ion/electron transfer path, leading to larger optical modulation and fast response time. Herein, for the first time, application of vacuum cathodic arc plasma (CAP) deposition technology to the synthesis of WO3/NiO electrode films on ITO glass for use in fabricating complementary electrochromic devices (ECDs) with a ITO/WO3/LiClO4-Perchlorate solution/NiO/ITO structure. Our objective was to optimize electrochromic performance through the creation of electrodes with a nanoporous structure. We also examined the influence of WO3 film thickness on the electrochemical and optical characteristics in terms of surface charge capacity and diffusion coefficients. The resulting 200-nm-thick WO3 films achieved ion diffusion coefficients of (7.35 × 10-10 (oxidation) and 4.92 × 10-10 cm2/s (reduction)). The complementary charge capacity ratio of WO3 (200 nm thickness)/NiO (60 nm thickness) has impressive reversibility of 98%. A demonstration ECD device (3 × 4 cm2) achieved optical modulation (ΔT) of 46% and switching times of 3.1 sec (coloration) and 4.6 sec (bleaching) at a wavelength of 633 nm. In terms of durability, the proposed ECD achieved ΔT of 43% after 2500 cycles; i.e., 93% of the initial device.

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-869873

RESUMO

Objective:To evaluate the role of autophagy in ischemia postconditioning (IPO)-induced attenuation of intestinal ischemia-reperfusion (I/R) injury in mice.Methods:Thirty-two SPF healthy adult male C57BL/6J mice, aged 9-12 weeks, weighing 25-29 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group (group S), intestinal I/R group (group IIR), group IPO and IPO plus 3-methyladenine (3-MA) group (group IPO+ 3-MA). The model of intestinal I/R was established by occlusion of superior mesenteric artery for 45 min followed by 2-h reperfusion in anesthetized animals.The mice underwent 3 cycles of 30-s reperfusion followed by 30-s ischemia before restoration of reperfusion in group IPO.Blood samples from the femoral artery were collected at 2 h of reperfusion for determination of concentrations of serum diamine oxidase (DAO), D-lactate (D-LA) and intestinal fatty acid binding protein (I-FABP). The animals were then sacrificed and intestinal tissues were removed for microscopic examination of the pathologic changes which were scored according to Chiu and for determination of the expression of autophagy-related proteins Beclin-1 and p62 (by Western blot). The water content of intestinal tissues was calculated. Results:Compared with group S, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly increased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in IIR, IPO and IPO+ 3-MA groups ( P<0.05). Compared with group IIR, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, water content of intestinal tissues, and LC3Ⅱ/LC3Ⅰ ratio were significantly decreased, Beclin-1 expression was up-regulated, and p62 expression was down-regulated in group IPO ( P<0.05). Compared with group IPO, the Chiu′s score, concentrations of serum DAO, D-LA and I-FABP, and water content of intestinal tissues were significantly increased, LC3Ⅱ/LC3Ⅰratio was decreased, Beclin-1 expression was down-regulated, and p62 expression was up-regulated in group IPO+ 3-MA ( P<0.05). Conclusion:Autophagy is involved in ischemia postconditioning-induced attenuation of intestinal I/R injury in mice.

19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-880540

RESUMO

OBJECTIVE@#To evaluate the effect of Guilu Erxian Glue (, GEG) on cyclophosphamide (CTX)-induced bone marrow hematopoietic stem cells (HSCs) senescence in mice and explore the underlying mechanism.@*METHODS@#The H@*RESULTS@#Compared with the model group, GEG increased cell viability as well as proliferation (P<0.05 or P<0.01) and reduced β -gal expression. Furthermore, GEG significantly decreased the expressions of p16@*CONCLUSION@#GEG can alleviate CTX-induced HSCs senescence in mice, and the p16

20.
Medicine (Baltimore) ; 98(8): e14519, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813154

RESUMO

To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (n = 1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3 km of living residence (odds ratio [OR] = 8.73, 95% CI: 1.42-53.74, P = .019), living in a newly decorated house/apartment (OR = 25.37, 95% CI: 4.44-144.81, P < .001), vegetarian diet (OR = 131.60, 95% CI: 3.45-5020.16, P = .009), preference of sugar (OR = 89.38, 95% CI: 7.22-1106.44, P < .001), preference of oily food (OR = 55.68, 95% CI: 5.12-605.26, P = .001), drinking lake water or pond water (OR = 58.05, 95% CI: 3.21-1049.81, P < .001), habit of staying up late (OR = 11.87, 95% CI: 3.43-41.02, P < .001), infection history (OR = 10.08, 95% CI: 2.75-36.93, P < .001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.


Assuntos
Anemia Aplástica/etiologia , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Anemia Aplástica/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Comportamentos Relacionados com a Saúde/etnologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
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