1.The impact of obstructive sleep apnea on cardiac structure and function in elderly patients with type 2 diabetes mellitus
Sha SHA ; Zeyu SHU ; Tingting DU ; Jin TAN ; Qiang ZHANG
Chinese Journal of Geriatrics 2021;40(6):695-700
Objective:To investigate the impact of obstructive sleep apnea(OSA)on cardiac structure and function in elderly patients with type 2 diabetes mellitus(T2DM).Methods:This was a case-control study.Elderly patients with T2DM aged 65 years and above at the Department of Geriatrics of Tianjin Medical University General Hospital were consecutively enrolled in this study, and eventually 61 patients with complete general information were included.All patients were examined with polysomnography(PSG). They were divided into the T2DM group and the T2DM+ OSA group based on whether there was concurrent OSA.Differences in cardiac structure and function were compared between the two groups and between patients with mild OSA and those with moderate-severe OSA.The correlation of OSA with cardiac structure and function in T2DM patients was analyzed by using Pearson correlation and multiple linear regression analysis.Results:The left ventricular ejection fraction(LVEF)was lower in the T2DM+ OSA group than in the T2DM group(52.38±4.70 % vs.56.34±5.92%, t=2.892, P=0.005). The anteroposterior diameter of the right ventricle, inter-ventricular septum thickness and left ventricular posterior wall thickness increased in the T2DM+ OSA group compared with the T2DM group(21.50±1.49 mm vs.20.55±1.05 mm, 10.21±0.88 mm vs.9.52±1.04 mm, 10.42±0.83 mm vs.9.83±0.83 mm, t=-2.670, -2.770 and -2.716, P=0.010, 0.007 and 0.009). LVEF was lower in patients with moderate-severe OSA than in those with mild OSA group(50.58±3.55% vs.55.83±4.83%, t=3.813, P=0.001). The anteroposterior diameter of the right ventricle, inter-ventricular septum thickness and left ventricular posterior wall thickness were greater in patients with moderate-severe OSA than in those with mild OSA(21.86±1.39 mm vs.20.79±1.46 mm, 10.48±0.82 mm vs.9.69±0.75 mm, 10.68±0.80 mm vs.9.92±0.64 mm, t=-2.231, -2.871 and -2.943, P=0.032, 0.007 and 0.006). Pearson correlation analysis showed that the Apnea Hypopnea Index(AHI)was correlated with LVEF, the anteroposterior diameter of the right ventricle, inter-ventricular septum thickness and left ventricular posterior wall thickness( r=-0.425, 0.340, 0.458 and 0.473, P=0.001, 0.007, <0.001 and <0.001). After adjusting for age, body mass index, systolic blood pressure and triglycerides, multiple linear regression analysis showed that AHI was also correlated with LVEF, the anteroposterior diameter of the right ventricle, inter-ventricular septum thickness and left ventricular posterior wall thickness( β=-0.385, 0.520, 0.604 and 0.388, P=0.036, 0.011, 0.001 and 0.039). Conclusions:OSA aggravates cardiac remodeling and systolic insufficiency in T2DM patients and may be related to the severity of intermittent hypoxia.
2.Knockdown of SMARCA4 leads to ferroptosis of HT1080 cells through inhibition of cholesterol synthesis
Rongjinlei ZHANG ; Zeyu QIU ; Yuanlong GE ; Zhenyu JU ; Shu WU
Chinese Journal of Pathophysiology 2024;40(3):420-430
AIM:To investigate the role and molecular mechanisms of SMARCA4(SWI/SNF-related,matrix-associated,actin-dependent regulator of chromatin,subfamily A,member 4)in ferroptosis.METHODS:(1)Human fi-brosarcoma HT1080 cells were treated with dimethyl sulfoxide(DMSO)and different concentrations(31.25,62.5 and 125 nmol/L)of Ras-selective lethal small molecule 3(RSL3;ferroptosis inducer).Each treatment had 3 replicate wells of cells.The protein levels of SMARCA4 were detected by Western blot.(2)Two small interfering RNAs(siSMARCA4-1 and siSMARCA4-2)were constructed according to the SMARCA4 gene sequence.After SMARCA4 knockdown,each treat-ment had 3 replicate wells of cells,and the protein levels of SMARCA4 were determined by Western blot.Effects of DMSO,necrostatin 2 racemate(Nec-1s;necroptosis inhibitor),Z-VAD(OMe)-FMK(Z-VAD,pan-caspase inhibitor/apoptosis inhibitor)and ferrostatin-1(Fer-1,ferroptosis inhibitor)on cell viability were assessed using high-content analy-sis.The levels of ferroptosis indicators,including prostaglandin-endoperoxide synthase 2(PTGS2)transcription,lipid peroxidation,reactive oxygen species(ROS),labile iron pool(LIP)and glutathione,were determined by RT-qPCR and flow cytometry.The mRNA expression levels of pivotal iron metabolism genes,ferroptosis-related ROS regulatory genes,and cholesterol synthesis-related genes were measured using RT-qPCR.Impact of cholesterol on the cell viability were as-sessed using high-content analysis.(3)Common differential gene analysis and gene ontology(GO)enrichment analysis were performed on published online data.RESULTS:(1)Treatment with RSL3 significantly reduced the protein level of SMARCA4(P<0.05).(2)Knockdown of SMARCA4 resulted in ferroptosis.(3)Knockdown of SMARCA4 did not induce ferroptosis by modulating the LIP and the transcription levels of ROS-related genes.(4)Knockdown of SMARCA4 affected the pathways associated with the cell membrane,lipid raft,and cholesterol synthesis.(5)Addition of cholesterol to cell culture medium rescued the ferroptosis induced by SMARCA4 knockdown(P<0.01).CONCLUSION:Treatment with RSL3 reduces the protein level of SMARCA4 in human fibrosarcoma HT1080 cells,and inhibition of cholesterol synthesis by SMARCA4 knockdown leads to the ferroptosis of HT1080 cells.
3.Lumbar facet joint degeneration contributes to degenerative lumbar scoliosis induced by asymmetric stress in rabbits.
Jiye ZHANG ; Yonghui SHU ; Quan ZHU ; Zeyu ZHANG ; Wangji LI ; Pingying SHA ; Shuai ZHENG
Journal of Southern Medical University 2019;39(8):993-997
OBJECTIVE:
To investigate the role of lumbar facet joint degeneration in the development of degenerative lumbar scoliosis caused by asymmetric stress.
METHODS:
Thirty-six New Zealand white rabbits were randomly divided into 3 groups (n=12): Group A with aspiration of the nucleus pulposus to induce disc degeneration; Group B with removal of the left capsule from the facet joints at L3/4 to L5/6 to induce degeneration; and Group C with both treatments. Springs were deployed on the left adjacent facets at L3/4, L5/6 and L5/6 to stress the facet joints. Serial radiographs were taken at 3 and 6 months, and the facet joint tissues were sampled at 6 months for Safranin O-fast green staining to assess the severity of cartilage degeneration based on the Mankin score.
RESULTS:
The Cobb angle differed significantly among the 3 groups (=24.865, =0.000). In all the groups, the Cobb angles at 6 months increased significantly as compared with that at 3 months ( <0.05). The Cobb angles were significantly greater in group C than in the other 2 groups at both 3 and 6 months ( <0.05) but showed no significant difference between Groups A and B (>0.05). The severity of facet joint degeneration also differed significantly among the 3 groups (= 22.009, =0.000), and was the most severe in group C ( <0.05); facet joint degeneration was more severe in group B than in group A ( <0.05).
CONCLUSIONS
Facet joint degeneration is an important factor that contributes to the development of degenerative lumbar scoliosis. Disc degeneration and facet joints degeneration can lead to lumbar scoliosis, which in turn aggravates disc degeneration, facet joints degeneration and asymmetric stress, thus forming a vicious circle to further exacerbate lumbar scoliosis.
Animals
;
Intervertebral Disc Degeneration
;
Lumbar Vertebrae
;
Lumbosacral Region
;
Rabbits
;
Scoliosis
;
Stress, Physiological
;
Zygapophyseal Joint