To seek significant features of systemic lupus erythematosus (SLE) by utilizing bioinformatics analysis.
Method
Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was used to quantify lysine crotonylation (Kcr) and lysine 2-hydroxyisobutyrylation (Khib) in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients and normal controls.
Results
Seventy-six differentially modified proteins (DMPs) dually modified by Kcr and Khib were identified between SLE patients and healthy people. GO enrichment analysis prompted significant enrichment of seventy-six DMPs in MHC class II protein complex binding and leukocyte migration. KEGG pathways were enriched in antigen processing and presentation pathway and leukocyte transendothelial migration pathway. Six DMPs (CLTC, HSPA1B, HSPA8, HSP90AB1, HSPD1, and PDIA3) were identified in antigen processing and presentation pathway, of which HSPA8 was the core protein. Significant changes of Kcr and Khib in HSPA8 may increase ATP hydrolysis and promote antigen binding to MHC II molecule. In leukocyte transendothelial migration pathway, 7 DMPs (ACTN1, ACTN4, EZR, MSN, RAC1, RHOA, and VCL) were identified. MSN was the protein with the most modification sites in this pathway. In amino terminal ferm region of MSN, Kcr and Khib expression change may lead to the adhesion between leukocytes and endothelial cells, which was an important step of leukocyte migration.
Conclusion
Kcr and Khib may promote the antigen presentation and jointly regulate the tissue damage mediated by leukocyte migration in SLE patients, which may play key roles in the pathogenesis of SLE probably.
Key Points
• Antigen processing and presentation and leukocyte transendothelial migration may play key roles in the pathogenesis of SLE.
To dissect the role of vascular endothelial growth factor receptor-2 (VEGFR2) in Müller cells and its effect on neuroprotection in diabetic retinopathy (DR), we disrupted VEGFR2 in mouse Müller glia and determined its effect on Müller cell survival, neuronal integrity, and trophic factor production in diabetic retinas. Diabetes was induced with streptozotocin. Retinal function was measured with electroretinography. Müller cell and neuronal densities were assessed with morphometric and immunohistochemical analyses. Loss of VEGFR2 caused a gradual reduction in Müller glial density, which reached to a significant level 10 months after the onset of diabetes. This observation was accompanied by an age-dependent decrease of scotopic and photopic electroretinography amplitudes and accelerated loss of rod and cone photoreceptors, ganglion cell layer cells, and inner nuclear layer neurons and by a significant reduction of retinal glial cell line–derived neurotrophic factor and brain-derived neurotrophic factor. Our results suggest that VEGFR2-mediated Müller cell survival is required for the viability of retinal neurons in diabetes. The genetically altered mice established in this study can be used as a diabetic animal model of nontoxin-induced Müller cell ablation, which will be useful for exploring the cellular mechanisms of neuronal alteration in DR. 相似文献
BACKGROUND Neuroblastoma(NB) is the most common type of extracranial solid tumour in children. The overall prognosis of NB is poor, but at the same time, NB shows significant clinical diversity. NB can demonstrate spontaneous regression or can differentiate into benign ganglioneuroma.CASE SUMMARY This study retrospectively analyzed the clinical data of a patient with spontaneous regression of stage Ⅲ NB who was admitted in May 2015. Studies of the spontaneous regression of NB published from October 1946 to September 2019 were retrieved through Pub Med. The clinical manifestations, diagnosis,treatment, and follow-up results were analysed.CONCLUSION Spontaneous regression of stage Ⅲ NB is rare in the clinic. The report of this case is an important supplement to the study of the spontaneous regression of NB. 相似文献
Therapeutic hypothermia is often used for traumatic brain injury because of its neuroprotective effect and decreased secondary brain injury. However, this procedure lacks clinical evidence supporting its efficacy, and adverse outcomes have been reported during general anesthesia. A 61-year-old man with a history of percutaneous coronary intervention (PCI) was admitted with traumatic brain injury. Immediately after admission, he underwent mild therapeutic hypothermia with a target temperature of 33.0°C for neuroprotection. During general anesthesia for emergency surgery because he developed a mass effect, hypothermic cardiac arrest occurred following an additional decrease in the core body temperature. Moreover, myocardial infarction caused by restenosis of the previous PCI lesion also contributed to the cardiac arrest. Although the patient recovered spontaneous circulation after an hour-long cardiopulmonary resuscitation with rewarming, he eventually died of subsequent repetitive cardiac arrests. When anesthetizing patients undergoing therapeutic hypothermia, caution is required to prevent adverse outcomes that can be caused by unintentional severe hypothermia and exacerbation of underlying heart disease. 相似文献
The aim was to study the characteristics of lateral mandibular horizontal deviations during opening–closing movements and their association with TMJ sounds of the clicking type. Subjects were 28 healthy volunteers and 38 patients diagnosed with MRI imaging as having TMJ disc dysfunction, 22 with disc displacement without (DD) and 16 as having disc displacement with reduction (DDR). TMJ sounds were recorded with miniature microphones placed in the ear canals, and jaw movements were documented with a kinesiograph. A sign, unbalanced lateral deviation (ubd) was defined as a rapid, short duration, change in jaw movement direction from, and back to, a smooth deviation path in the horizontal plane. The hypotheses were that degrees of maximal deviations, proportions of unbalanced deviation (ubd) and such deviation associated with TMJ sounds (ubdS), differ between healthy subjects and patients with DD or DDR. Comparisons between groups were made using one‐way anova and chi‐square analysis, as appropriate. No differences were found between groups regarding degree of lateral deviation per se. The proportions of ubd and ubdS were significantly higher in patients with DDR than in healthy subjects and than in patients with DD (P < 0·001), but no such differences were found between healthy subjects and patients with DD. For prediction of DDR, the sensitivity and specificity of the sign ubdS were found to be 68·8% and 89·3%, respectively. For the sign ubd, they were 100·0% and 64·3%. This indicates that the sign ubdS has diagnostic value in screening for DDR. 相似文献