1.PARP-1 inhibitor reduces inflammation and oxidative stress in rats with chronic obstructive pulmonary disease by activating SIRT1-PGC-1α axis
Yaru HOU ; Xinle SHU ; Xia ZHANG ; Sen LI ; Wenmu YONG
Chinese Journal of Immunology 2023;39(12):2540-2544
Objective:To establish an experimental model of chronic obstructive pulmonary disease(COPD)in rats,and explore whether polyadenosine diphosphate ribose polymerase-1(PARP-1)inhibitors regulate Sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γ co-activator 1α(PGC-1α)to reduce inflammation and oxidative stress in COPD rats,and explore the possibility of SIRT1-PGC-1α axis as a new target of PARP-1 inhibitor.Methods:Twelve of 48 SD rats were randomly selected as healthy group,and the remaining rats were used to construct experimental models of COPD.Rats that were successfully modeled were randomly divided into model group,PARP-1 inhibitor treatment group and PARP-1 inhibitor+PGC-1α inhibitor group.HE staining was used to observe pathological changes of lung tissue,ELISA was used to detect levels of TNF-α,IL-6,IL-1β,malondialdehyde(MDA),superoxide dismutase(SOD)in rats lung tissue,fluorescence quantitative PCR was used to detect expression levels of SIRT1 and PGC-1α mRNA of rats in each group,Western blot was used to detect expressions of SIRT1 and PGC-1α proteins.Results:Lung tissue structure of rats in healthy group was complete,compared with healthy group,lung tissue of model group suffered structural damage,with a large number of inflammatory cells infiltrated,contents of TNF-α,IL-1β and IL-6 in alveolar lavage fluid were significantly increased,con-tent of MDA in serum was significantly increased,while content of SOD was significantly reduced,and expressions of SIRT1,PGC-1α mRNA and protein were significantly reduced;compared with model group,lung tissue structure of rats in PARP-1 inhibitor treatment group was recovered,and inflammatory cells were reduced,contents of TNF-α,IL-1β and IL-6 were significantly reduced,content of MDA in serum was significantly reduced,while content of SOD was significantly increased,and expressions of SIRT1,PGC-1α mRNA and protein were significantly increased;compared with PARP-1 inhibitor treatment group,the number of inflammatory cells in PARP-1 inhibitor+PGC-1α inhibitor group was increased,contents of TNF-α,IL-1β and IL-6 were significantly increased,content of MDA in serum was significantly increased,while content of SOD was significantly reduced,expressions of SIRT1,PGC-1α mRNA and protein were significantly reduced.Conclusion:PARP-1 inhibitors can alleviate inflammation and oxidative stress by activating SIRT1-PGC-1α axis,thereby effectively alleviating COPD.
2.Dynamic changes in Th17/Treg balance among children with seasonal allergic rhinitis
Qing MIAO ; Xi CHEN ; Yixin REN ; Yongge LIU ; Yan WANG ; Wei XU ; Zhen LI ; Hui GUAN ; Huijie HUANG ; Xiaoling HOU ; Kang ZHU ; Qi GAO ; Yaru WANG ; Li XIANG
Chinese Journal of Microbiology and Immunology 2017;37(5):355-360
Objective To investigate the levels and significance of Th17 cells and regulatory T cells (Treg) in peripheral blood of children with allergic rhinitis during pollen and non-pollen seasons.Methods Thirteen children with hay fever, 10 children with house dust mite(HDM)-allergic asthma and 10 healthy children were recruited into this study.Percentages of Th17 and Treg cells were detected by flow cytometry.Levels of IL-17, IL-10 and TGF-β in cell culture supernatants were measured by ELISA.Results (1) The percentages of Th17 cells in children with allergic rhinitis [(3.4±2.4)%] were significantly higher than those in HDM-allergic asthmatics [(2.1±1.6)%] and those in healthy children [(0.5±0.3)%] during pollen season (both P<0.05).The levels of Treg cells in allergic rhinitis group [(2.1±1.3)%] and in HDM-allergic asthma group [(3.6±1.9)%] were significantly lower than those in healthy control group [(5.5±2.8)%] (both P<0.05).The levels of Th17 cells [(3.0±1.9)% vs (3.4±2.4)%, P<0.05] and ratios of Th17/Treg cells [(1.4±1.0)% vs (1.7±1.5)%, P<0.05] in children with allergic rhinitis were significantly decreased during non-pollen season as compared with those during pollen season, but the levels of Treg cells were up-regulated [(2.4±1.6)% vs (2.1±1.3)%, P<0.05].(2) Correlation analysis revealed that the ratios of Th17/Treg cells were positively correlated with the concentrations of FeNO (fractional concentration of exhaled NO) (r=0.321, P<0.05) and the counts of circulating eosinophils (r=0.198, P<0.05) in children with allergic rhinitis during pollen season.Conclusion The imbalanced Th17 and Treg cells in children with allergic rhinitis during pollen season might play a vital role in the regulation of allergic airway inflammation.
3.Influence of adaptive statistical iterative reconstruction-V on image quality and radiation dose of abdominal CT in phantom
Yaru CHAI ; Jingjing XING ; Jianbo GAO ; Peijie LYU ; Ping HOU ; Suya WANG ; Jie LIU
Chinese Journal of Medical Imaging Technology 2018;34(1):118-122
Objective To evaluate the influence of preset adaptive statistical iterative reconstruction-V (ASIR-V) techniques on image quality and radiation dose reduction of abdominal CT in phantom,and to investigate the optimal ASIR-V level.Methods Abdominal anthropomorphic phantom was scanned using Revolution CT,when noise index (NI) were set as 6,8,10,12 and 14,respectively.Then 0-100% ASIR-V and conventional scan was performed and 55 sets of images were obtained.CT value,noise,subjective score and radiation dose were recorded,and the optimal ASIR-V was obtained.Subjective scores of images in each group were compared using rank sum test,and CT value,noise and radiation dose were compared with one way ANOVA and paired t test.Results The image subjective score unchanged when NI was 6,8 or 10,slightly increased when NI was 12 and 14 with 0-40% ASIR-V,and decreased above 50% ASIR-V at all NI.When NI was 6,8 or 10,more than 70% ASIR-V image subjective score fell below 3 points.When NI was 12 or 14 group,more than 60% ASIR V subjective score fell below 3 points.The image quality score of conventional scan had no difference with 40% ASIR-V when NI was 6,8 or 10,respectively (P=0.626,0.915,0.514),and inferior to 40% ASIR-V when NI was 12 or 14 (P=0.041,0.036),while in all NI group,image quality score of conventional scan was superior to 60% ASIR-V (P=0.021,0.012,0.015,0.014,0.007).CT values and image noises had no significant differences in different parts in all NI groups (all P>0.05).CT dose index volume (CTDIvol) continuing decreased with ASIR-V.Compared with that of conventional scan,at 40%,50% and 60% ASIR-V,CTDIvol reduced by 49.82%,62.51% and 71.63%,respectively.Conclusion Preset ASIR-V can reduce radiation dose obviously while maintaining the overall image quality,and 40%-60% ASIR-V can be recommended for abdominal CT in clinical application.
4.Value of spectral CT imaging in the differential diagnosis of benign and malignant ovarian tumors
Dandan GUO ; Zhixu ZHANG ; Ping HOU ; Yaru CHAI ; Jiayin LI ; Yang LIU ; Jianbo GAO
Journal of Practical Radiology 2018;34(3):398-400,451
Objective To investigate the CT spectral imaging features of benign and malignant ovarian tumors and to assess the value of spectral CT in differentiating between benign and malignant ovarian tumors.Methods This study was granted by the institutional review board with a waiver for informed consent.34 patients with ovarian tumor(11 benign tumors and 23 malignant tumors)underwent preoperative CT scanning that included arterial phase (AP)and venous phase (VP)with GSI mode.Measurements were performed on the GSI viewer.The iodine concentration (IC,100 ug/cm3)was saved,and the normalized iodine concentration (NIC)and the spectral curve(spectral Hounsfield unit curve)were recorded.The slope of the curve was calculated as the formula:(CT attenuation (40 keV)-CT attenuation(100 keV))/60.The CT value was measured at 70 keV in Mono image.CT values,the slope of the spectral curve,the iodine concentration and NIC were compared between the two groups by using independent sample t-test with software SPSS 2 1.0.Receiver operating characteristic (ROC)was used to determine the threshold of slope of the spectral curve,the iodine concentration and NIC for differentiating benign and malignant ovarian tumors in VP.Results The slope of the spectral curve,the iodine concentration and NIC of malignant ovarian tumors in VP were 1.72±0.77,14.50±6.44 (100 μg/cm3),and 0.33±0.12.The slope of the spectral curve,the iodine concentration and NIC of benign ovarian tumors in VP were 1.05±0.48,8.86±4.04 (100 μg/cm3),and 0.22±0.13.Significant differences were found between the slope of spectral curve,the iodine concentration and NIC of the malignant ovarian tumors and those of the benign ovarian tumors in VP (P=0.01).CT values in double phases revealed no difference between these two groups (P>0.05).Conclusion There is a significant difference between the solid component of benign ovarian tumors and that of malignant ovarian tumors in spectral CT.GSI scan mode can provide more information for the differential diagnosis of benign and malignant ovarian tumors.
5.Changes in percentage and function of CD4+CD25+regulatory T cells in peripheral blood of patients with hay fever
Qing MIAO ; Wei XU ; Kang ZHU ; Xiaoling HOU ; Huijie HUANG ; Yaru WANG ; Yongge LIU ; Yan WANG ; Hui GUAN
Chinese Journal of Microbiology and Immunology 2017;37(9):659-665
Objective To investigate the changes in percentage and function of CD4+CD25+regu-latory T cells ( Tregs) in peripheral blood of patients with hay fever. Methods A total of 20 patients with hay fever, 20 patients with house dust mite-induced allergic asthma and 20 healthy subjects were enrolled in this study. Peripheral blood samples were collected from all subjects to isolate PBMCs. Percentages of Tregs in PBMCs were measured by flow cytometry. CD4+CD25+ Tregs and CD4+CD25-T cells ( Teffs) were isola-ted by immunomagnetic cell sorting. Effects of CD4+CD25+Tregs on the proliferation of Teffs were evaluated by MTT assay. Expression of Foxp3 and TGF-β1 at mRNA level was analyzed by RT-PCR. Results During the pollen season, the percentage of circulating Tregs in patients with hay fever [(1. 82+0. 82)%] was sig-nificantly lower than that in patients with house dust mite-induced allergic asthma [(2. 96±1. 34)%] and health subjects [(5. 78±2. 29)%] (both P<0. 05). Expression of Foxp3 at mRNA level was significantly reduced in patients with hay fever (0. 46±0. 25) as compared with that of the house dust mite-induced aller-gic asthma (0. 64±0. 31) and healthy control (1. 04±0. 21) groups (both P<0. 05). Expression of TGF-β1 at mRNA level in both hay fever (0. 34±0. 27) and house dust mite-induced allergic asthma (0. 43±0. 31) groups was lower than that of the healthy control group (0. 99±0. 34). Treg-mediated suppression of Teff proliferation was significantly decreased in patients with hay fever [(17. 1±8. 4)%] as compared with that in patients with house dust mite-induced allergic asthma [(21. 4±9. 1)%]) and healthy subjects [(36. 0± 13. 9)%] (P<0. 05). Conclusion Decreased percentage and defective function of Tregs might be one of the major causes for the occurrence and development of hay fever in children during the pollen season.
6.Optimization of unnatural amino acid incorporation in collagen and the cross-linking through thioether bond.
Yaru HOU ; Meng ZHANG ; Fei XU
Chinese Journal of Biotechnology 2021;37(9):3231-3241
The source of recombinant collagen is clean, and it has the advantages of flexible sequence design, high yield and high purity, so it has a wide application prospect as biomaterials in tissue engineering and other fields. However, how to promote the cross-linking of recombinant collagen molecules and make them form a more stable spatial structure is the difficulty to be overcome in the design of recombinant collagen nanomaterials. Unnatural amino acid O-(2-bromoethyl)-tyrosine was incorporated into collagen by two-plasmid expression system. The results showed that high-purity collagen incorporated with unnatural amino acid could be obtained by induction with final concentration of 0.5 mmol/L IPTG and 0.06% arabinose at 25 °C for 24 hours. The intermolecular cross-linking through thioether bond was formed between collagen molecule incorporated with unnatural amino acid and collagen molecule with cysteine mutation in pH 9.0 NH4HCO3 buffer, which formed aggregates with the largest molecular size up to 1 micrometre. The results pave the way for the design of recombinant collagen biomaterials.
Amino Acids
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Biocompatible Materials
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Collagen/genetics*
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Sulfides