1.LOX-1 promotes hyperglycemia-induced phagocytosis dysfunction of BV2 microglia through the β-catenin/ATF6α pathway
Yajuan ZHANG ; Jing LIU ; Limin TIAN ; Na ZHANG ; Yanyan ZHANG ; Yaqian LIU ; Huiling SI ; Wenshu ZHAO ; Jumei QIU ; Qi ZHANG
Chinese Journal of Diabetes 2024;32(6):450-457
Objective To investigate the molecular mechanism of lectin-like oxidized low-density lipoprotein receptor 1(LOX-1)in the regulation of high glucose induced phagocytosis dysfunction of mouse microglia(BV2 microglia).Methods BV2 cells were cultured in vitro,lentivirus LOX-1RNAi vector(LV-LOX-1)and lentivirusempty vector(LV-Con)were constructed and divided into normal control(NC)group,HG group,LV-LOX-1 group and LV-Con group.After infecting BV2 cells with LV-LOX-1 and LV-Con,the cells were cultured with 25 mmol/L glucose for 24 h,and then divided into HG+LV-LOX-1 group and HG+LV-Con group.After treatment of HG+LV-LOX-1 and HG+LV-Con infected BV2 microglia with 15 μmol/L FH535(β-catenin inhibitor)and AEBSF(ATF6α inhibitor)for 24 h,respectively,they were denoted as HG+LV-LOX-1+FH535 group,HG+LV-Con+FH535 group,HG+LV-LOX-1+AEBSF group,and HG+LV-Con+AEBSF group.Transfection efficiency was determined by fluorescence microscopy,RT-PCR and Western blot.Cell viability was detected b CCK-8.RT-PCR and Western blot were used to detect the mRNA and protein expression of LOX-1,β-catenin,ATF6α and milk fat globular-surface growth factor Ⅷ(MFG-E8)in each group.Results After 72 h of LV-LOX-1 infection,the cells in LV-LOX-1 and LV-Con groups showed a lot of green fluorescence,but not in NC group.Compared with NC group,the mRNA and protein expression of LOX-1 and ATF6α were increased(P<0.05),while the mRNA and protein expression of MFG-E8 and β-catenin decreased in HG group(P<0.05).Compared with HG+LV-Con group,the mRNA and protein expression of LOX-1 and ATF6α were decreased(P<0.05),while the mRNA and protein expression of MFG-E8 and β-catenin increasedin HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,the mRNA and protein expressions of MFG-E8 and β-catenin were decreased(P<0.05),and the mRNA and protein expressions of ATF6α and p-β-catenin and p-ATF6α were increased in HG+LV-LOX-1+FH535 group(P<0.05).Compared with HG+LV-LOX-1 group,the mRNA and protein expression were increased(P<0.05),ATF6α mRNA and protein expression and p-ATF6α protein expression were decreased MFG-E8 in HG+LV-LOX-1+AEBSF group(P<0.05).Conclusions LOX-1,MFG-E8,β-catenin and ATF6α are involved in the regulation of phagocytosis of BV2 cells.LOX-1 promotes the phagocytosis dysfunction of BV2 microglia induced by high glucose through β-catenin/ATF6α signaling pathway.
2.Correlation of serum Metrnl levels with glycolipid metabolism and inflammatory status in patients with type 2 diabetes mellitus combined with abdominal obesity
Ziying WEN ; Jing LIU ; Jing YU ; Jumei QIU ; Fan YANG ; Ruixia YANG ; Qi ZHANG
Chinese Journal of Diabetes 2024;32(10):721-725
Objective To investigate the correlation between serum nickel-like protein(Metrnl)level and glycolipid metabolism and inflammatory state in patients with T2DM complicated with abdominal obesity.Methods One hundred and twenty-four T2DM patients and 140 non-diabetic controls who were hospitalized in Gansu Provincial People's Hospital from May to September 2022 were selected and divided into T2DM combined abdominal obesity group(T2DM+AO,n=81),T2DM group(n=43),abdominal obesity group(AO,n=69)and normal control group(NC,n=71)according to whether they suffered from T2DM and abdominal obesity.ELISA method was used to determine the levels of serum Metrnl,IL-4 and IL-13.The correlation between serum Metrnl and the indicators of glucose and lipid metabolism,WC,BMI,VFA,FPG,HbA1c,TC,TG,LDL-C,HDL-C and the indicators of inflammatory state,IL-4 and IL-13 were analyzed.Results Compared with NC group,serum Metrnl levels in T2DM group,AO and T2DM+AO group were decreased(P<0.05).Serum Metrnl was negatively correlated with WC,BMI,VFA,FPG,HbA1c,TG,IL-4,IL-13(P<0.01),and positively correlated with HDL-C(P<0.05).Age,WC,BMI and IL-4 were the influencing factors of Metrnl.WC,VFA,FPG and Metrnl were the influencing factors of T2DM combined with abdominal obesity.The ROC curve showed that serum Metrnl had a sensitivity of 82.5%and a specificity of 93.8%for the diagnosis of T2DM with abdominal obesity.Conclusions Serum Metrnl in T2DM patients with abdominal obesity is significantly reduced,and is closely related to glucose and lipid metabolism and inflammatory status.Serum Metrnl may be a novel biomarker factor for T2DM complicated with abdominal obesity.
3.Application of acute physiology and chronic health evaluation Ⅱ score in the timing of noninvasive ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease
Jumei CHEN ; Wei WANG ; Wanrong QIU ; Qionge FU ; Cimei ZENG
Chinese Critical Care Medicine 2020;32(5):581-584
Objective:To explore the application of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score in the timing and nursing of noninvasive ventilation for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:106 AECOPD patients admitted to Haikou People's Hospital from January 2018 to October 2019 were selected as the study objects. According to the method of random number table, the patients were divided into observation group and control group, with 53 patients in each group. The control group selected the timing of noninvasive ventilation treatment according to the standards of Mechanical ventilation (second edition), weaned according to Clinical practice of mechanical ventilation, and received routine nursing in intensive care unit (ICU), including creating comfortable indoor environment, reasonable diet, condition monitoring, psychological nursing and complications nursing. On the basis of the control group, the patients in the observation group were given noninvasive ventilation when APACHE Ⅱ score was more than 10, and were weaned when APACHE Ⅱ score was less than or equal to 10. According to APACHE Ⅱ score < 10, 10-14, 15-19 and ≥ 20, the patients were given level-3 care, level-2 care, level-1 care and intensive care. The pulmonary function before and 3 days after the noninvasive ventilation treatment was monitored, and the duration of mechanical ventilation, the length of ICU stay, endotracheal intubation rate, incidence of complication [ventilator associated pneumonia (VAP)] and ICU mortality were recorded. The self-designed questionnaire of nursing satisfaction was used to evaluate the patients' nursing satisfaction. Results:There was no significant difference in general data such as gender or age between the two groups. After 3 days of noninvasive ventilation, the forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio of the two groups were increased significantly as compared with those before treatment, especially in the observation group, with statistical significances as compared with the control group [FEV1 (L): 3.02±0.22 vs. 2.54±0.19, FVC (L): 3.01±0.32 vs. 2.13±0.28, FEV1/FVC ratio: 0.89±0.08 vs. 0.79±0.08, all P < 0.05]. Compared with the control group, the duration of mechanical ventilation and length of ICU stay in the observation group were significantly shortened [duration of mechanical ventilation (days): 4.32±0.73 vs. 8.42±1.94, length of ICU stay (hours): 32.23±10.22 vs. 38.52±9.85, both P < 0.01]. The intubation rate, incidence of VAP and ICU mortality in the observation group were significantly lower than those in the control group [intubation rate: 1.9% (1/53) vs. 13.2% (7/53), incidence of VAP: 1.9% (1/53) vs. 15.1% (8/53), ICU mortality: 1.9% (1/53) vs. 13.2% (7/53), all P < 0.05]. The nursing satisfaction of patients in the observation group was significantly higher than that in the control group [96.2% (51/53) vs. 75.5% (40/53), P < 0.01]. Conclusions:APACHE Ⅱ score can be used to guide the choice of noninvasive ventilation treatment opportunity and nursing intervention measures for AECOPD patients. It can significantly improve the pulmonary function of patients, improve the treatment effect, reduce the incidence of complications, and improve the satisfaction of patients with nursing, which is effective in clinical application.
4.Lectin-like oxidized low-density lipoprotein receptor-1 regulates cardiac fibroblasts fibrosis induced by high glucose through glycogen synthase kinase-3β/signal transducer and activator of transcription 3 pathway
Yaqian LIU ; Jing LIU ; Limin TIAN ; Zhihong WANG ; Huiling SI ; Yajuan ZHANG ; Jumei QIU ; Qidang DUAN ; Yanyan ZHANG ; Na ZHANG ; Wenshu ZHAO ; Xia WANG ; Qi ZHANG
Chinese Journal of Diabetes 2024;32(5):373-379
Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.