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Objective To investigate the effect of long intergenic non-coding RNA COX2 (lincRNA-COX2) on apoptosis and polarization of Listeria monocytogenes (Lm)-infected RAW264.7 cells. Methods RAW264.7 cells were cultured and divided into control group (uninfected cells), Lm infection group, negative control of small interfering RNA (si-NC) group, si-NC and Lm infection group, small interfering RNA of lincRNA-COX2 (si-lincRNA-COX2) group, si-lincRNA-COX2 and Lm infection group. RAW264.7 cells were infected with MOI=10 Lm for 6 hours, and then the inhibition efficiency of siRNA transfection was detected by fluorescence microscope and quantitative real-time PCR (qRT-PCR). The expression levels of cleaved-caspase-3(c-caspase-3), caspase-3, B-cell lymphoma-2 (Bcl2), Bcl2 associated X protein (BAX), arginase 1 (Arg1), inducible nitric oxide synthase (iNOS) were detected by Western blot analysis. Results c-caspase-3/caspase-3, BAX/Bcl2 and iNOS were significantly up-regulated, while the level of Arg1 was down-regulated in Lm-infected RAW264.7 cells compared with control group. LincRNA-COX2 knockdown inhibited the increase of protein levels for BAX/Bcl2, c-caspase-3/caspase-3 and iNOS in Lm-infected RAW264.7 cells, while the level of Arg1 in Lm-infected RAW264.7 cells was up-regulated. Conclusion Knockdown of lincRNA-COX2 can inhibit cell apoptosis and suppress the macrophage polarization into M1 type in Lm-infected RAW264.7 cells.
Subject(s)
Animals , Mice , Apoptosis/genetics , bcl-2-Associated X Protein/metabolism , Caspase 3/metabolism , Cyclooxygenase 2/metabolism , Listeria monocytogenes/pathogenicity , Macrophages/microbiology , RNA, Long Noncoding/metabolism , RNA, Small Interfering/geneticsABSTRACT
Objective:To investigate the relationship between the expression level of circular RNA_0005414 and islet cell function in type 2 diabetes patients.Methods:A total of 110 patients with type 2 diabetes and 106 cases of normal glucose tolerance (control group) in Uygur populations, 64 cases of type 2 diabetes mellitus and 63 cases of normal glucose tolerance (control group) in Han populations were enrolled in the study. All subjects underwent oral glucose tolerance test chemistry panel. Homeostasis model assessment for insulin resistance (HOMA-IR) and β cell function (HOMA-β) were evaluated by homeostasis model as islet cell function indexes. The differentially expressed circular RNAs were screened using RNA sequencing from the peripheral blood monocytes of 5 Uygur patients with type 2 diabetes mellitus and matched controls. The expression level of a significantly up-regulated circular RNA_0005414 was detected and verified, and the relationship between the expression level of circular RNA_0005414 and islet cell function was analyzed.Results:Differential expression profiles of circular RNAs were found in Uygur type 2 diabetic patients . The expression level of circular RNA_0005414 in Uygur type 2 diabetic group was higher than that in Uygur control group ( P<0.01), the expression level of circular RNA_0005414 in Han type 2 diabetic group was higher than that in Han control group ( P<0.01), the expression level of circular RNA_0005414 in Uygur type 2 diabetes group was higher than that in Han type 2 diabetes group, but the difference was not statistically significant ( P>0.05). In the Uyghur and Han groups, Spearman correlation analysis showed that the expression level of circular RNA_0005414 was positively correlated with fasting blood glucose, 2 h plasma glucose after glucose loading, HbA 1C, total cholesterol, fasting insulin, HOMA-IR ( P<0.05) and negatively correlated with HOMA-β ( P<0.01). Partial correlation analysis showed that circular RNA_0005414 expression level was positively correlated with fasting blood glucose, HbA 1C, and HOMA-IR ( P<0.01). Multivariate linear regression analysis showed that circular RNA_0005414 was the only factor affecting HOMA-β in Uygur patients with type 2 diabetes. Conclusion:The expression level of circular RNA_0005414 was closely related to islet cell function in Uygur type 2 diabetes patients, the up-regulation of circular RNA_0005414 may be involved in the occurrence and development of type 2 diabetes in Uygur.
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Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.
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Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.
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OBJECTIVE：To evaluate the economic value of dapagliflozin combined with metformin in the treatment of type 2 diabetes mellitus （T2DM）. METHODS ：Based on related literatures and phase 3 randomized controlled clinical trial （RCT）of metformin alone or combined with dapagliflozin for T2DM，Markov model was built to simulate the dynamic changes of 3 schemes such as 5 mg dapagliflozin combined with metformin ，10 mg dapagliflozin combined with metformin or metformin alone （the dose of metformin were all 1 500 mg）in the treatment of T 2DM patients without or with complications and death . Quality adjusted life years（QALYs）was used as a health output indicator and the threshold of willingness-to-pay was 3 times of GDP in 2019. Cohort simulation in Markov model was applied to obtain long-term effect and cost of 3 schemes in the treatment of T 2DM. The incremental cost-effectiveness ratio （ICER）was analyzed ；the sensitivity of cost ，utility and discount was analyzed to check the stability of the analysis result. RESULTS ：According to the results of Markov model cohort simulation ，after 10 years of disease progression，compared with metformin alone ，ICER of 5 mg dapagliflozin combined with metformin was 41 259.17 yuan/QALYs， and that of 10 mg dapagliflozin combined with metformin was 92 824.85 yuan/QALYs. Compared with 5 mg dapagliflozin combined with metformin ，ICER of 10 mg dapagliflozin combined with metformin was 1 209 525.95 yuan/QALYs. Extension of termination time to 20 or 30 years had no effect on results. According to the sensitivity analysis ，the change of key parameters in the set range did not affect the model results ，indicating the result was stable. CONCLUSIONS ：For T 2DM，5 mg dapagliflozin combined with metformin is more cost-effective .
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OBJECTIVE：To understand the situation of healthcar e workers’occupational exposure of hazardous drugs （chemotherapeutic drugs and antiviral drug ）and relative cognition level ，and to provide reference for improving the level of occupational protection. METHODS ：During Oct. 2018 to Mar. 2019，healthcare workers from 12 hospitals of different levels and different departments in Shaanxi province were selected as respondents to conduct a self-designed questionnaire survey. Information we surveyed contained baseline characteristics ，hazardous drugs exposure ，physical health status ，and occupational protection. Valid questionnaires were collected and analyzed statistically. RESULTS ：A totally of 1 848 questionnaires were sent out ，and 1 767 questionnaires were collected ，including 95 were pharmacists ，100 were physicians ，and 1 572 were nurses. The frequency of diarrhea and menstrual disorders in healthcare workers with long-term exposure to antiviral drugs （antiviral drug exposure group ） and cross-exposure to antiviral drugs and chemotherapeutic drugs （cross-exposure group ）were significantly higher than unexposed group （P＜0.05）. The incidence of routine blood abnormalities in cross-exposure group ，antiviral drug exposure group and healthcare workers with long-term exposure to chemotherapy drugs （chemotherapy drug exposure group ） was higher than unexposed group by 9.13％，5.50％ and 12.34％，respectively. 84.7％ of the respondents had little knowledge of hazardous drugs ， and 8.15％ of the respondents had never received occupational protection training. Additionally ，the ratio of healthcare workers receiving occupational protection training in the cross-exposure group was significantly higher than unexposed group （P＜0.05）， and the ratio of healthcare workers receiving occupational protection training in antiviral drug exposure group were significantly lower than unexposed group （P＜0.05）. CONCLUSIONS ：Long-term exposure to hazardous drugs will cause certain occupational hazards to healthcare workers. It is necessary to improve healthcare workers ’awareness of self-protection ，increase the input of hospitals in occupational protection training and establish occupational protection standards in order to improve the current situation of occupational protection of healthcare workers.
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Objective@#To observe the infection status and the distribution of the gene subtypes of human papillomavirus (HPV) in Huzhou.@*Methods@#Cervical exfoliated cells were collected from the women who attended the physical examination and the cervical HPV examination from June 2017 to December 2017 in Huzhou Maternal and Child Health-Care hospital. A total of 2 830 women were tested for 21 HPV genotypes (including HPV-16, 18, 31, 59, 66, 53, 33, 58, 45, 56, 52, 35, 68, 51, 39, 82, 26, 73, 6, 11, 81), using real-time polymerase chain reaction (RT-PCR), investigated the infection status and subtype distribution.@*Results@#Among the 2 830 women, 269 were positive for HPV, the total infection rate was 9.51% (269/2 830). The infection rate of single gene and double gene was 86.99% (234/269) and 11.90% (32/269), respectively. The infection rate of high-risk subtypes was 9.11% among the detected women (258/2 830), accounting for 83.77% of HPV gene detections (258/308). The HPV-58, 16, 52 were the most commonly found gene subtypes among the high-risk HPV. The rate of HPV infection and high-risk subtypes of HPV infection in women was the highest in the 56-60 year old group, and the lowest in the 31-35 year old group. In different age groups, the difference in high-risk HPV infection rate was statistically significant, the total infection rate had no statistical significance.@*Conclusions@#In Huzhou area, the HPV infection rate of women found through normal physical examination was 9.51%, the high risk type was 58, 16 and 52, and the 56-60 year old group was the high incidence group. This study provides the HPV infection status and HPV gene subtype distribution characteristics in women in Huzhou, which has important guiding value for the vaccine development and application, and for prevention of HPV infection.
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<p><b>OBJECTIVE</b>To assess the value of whole-genome amplification (WGA) and next generation sequencing (NGS) for the pre-implantation screening of discarded embryos.</p><p><b>METHODS</b>In total 476 discarded embryos were collected. After continued culture, 23 high-quality blastocysts were obtained. Blastocysts graded as 4BC or above based on Gardner classification were subjected for blastula biopsy. Five to ten nourish ectoderm cells were hatched with a biopsy needle. Following WGA and NGS, deletion and/or duplication of chromosomal fragments and numerical chromosomal aberrations were analyzed.</p><p><b>RESULTS</b>In total 148 trophoblast cells were obtained from the 23 blastocysts. Following WGA, 60 amplification products were selected for NGS. The results showed that there were 39 abnormal chromosomes derived from 14 blastocysts, which gave an abnormal rate of blastocyst of 60.87% (14/23).</p><p><b>CONCLUSION</b>WGA combined with NGS can enable pre-implantation genetic screening for discarded embryos, which may improve the efficacy of in vitro fertilization as well as reduce the risk for birth defects.</p>