1.Protective effect of protein kinase C inhibitor on rat renal vascular endothelial injury induced by lipopolysaccharide.
Lan LIN ; Bing HE ; Yanyang CHENG ; Weiping CHEN ; Zhiliang XU
Chinese Critical Care Medicine 2019;31(3):346-349
OBJECTIVE:
To investigate the protective effect of protein kinase C (PKC) inhibitor rottlerin on rat renal vascular endothelial injury induced by lipopolysaccharide (LPS).
METHODS:
Rat renal microvascular endothelial cells cultured for 3-6 generations were divided into three groups according to random number table: blank control group in which cells were not challenged, LPS group in which cells were only stimulated by LPS 10 mg/L for 24 hours, and PKC inhibitor group in which cells were treated with PKC inhibitor rottlerin 2 μmol/L 30 minutes before LPS stimulation. The levels of tumor necrosis factor-α (TNF-α) and interleukins (IL-1β, IL-8) were determined by enzyme-linked immunosorbent assay (ELISA). Monolayer permeability was determined by Transwell assay. The expressions of PKC, RhoA and vascular endothelial-cadherin (VE-cadherin) were detected by Western Blot. The morphological characteristic and distribution of F-actin was measured by laser confocal fluorescence microscope.
RESULTS:
Compared with blank control group, the levels of inflammatory cytokines at 24 hours after 10 mg/L LPS stimulation were significantly increased in LPS group [TNF-α (ng/L): 397.3±25.4 vs. 46.8±8.9, IL-1β (ng/L): 76.7±11.2 vs. 12.6±3.2, IL-8 (ng/L): 574.5±31.4 vs. 73.2±9.6, all P < 0.05], the permeability of endothelial cells was significantly increased (A value: 1.32±0.03 vs. 0.36±0.02, P < 0.05), while the expressions of PKC and RhoA were significantly up-regulated (PKC/β-actin: 0.88±0.02 vs. 0.61±0.03, RhoA/β-actin: 0.96±0.01 vs. 0.49±0.03, both P < 0.05), VE-cadherin expression was significantly down-regulated (VE-cadherin/β-actin: 0.51±0.01 vs. 0.72±0.04, P < 0.05), and the F-actin distribution disorder had obvious stress fiber formation. Compared with LPS group, the levels of inflammatory cytokines were significantly lowered in PKC inhibitor group [TNF-α (ng/L): 127.4±14.6 vs. 397.3±25.4, IL-1β(ng/L): 43.2±7.8 vs. 76.7±11.2, IL-8 (ng/L): 212.7±18.2 vs. 574.5±31.4, all P < 0.05], the permeability of endothelial cells was significantly decreased (A value: 0.81±0.02 vs. 1.32±0.03, P < 0.05), the expressions of PKC and RhoA were significantly down-regulated (PKC/β-actin: 0.44±0.03 vs. 0.88±0.02, RhoA/β-actin: 0.63±0.05 vs. 0.96±0.01, both P < 0.05), the VE-cadherin expression was significantly up-regulated (VE-cadherin/β-actin: 0.69±0.03 vs. 0.51±0.01, P < 0.05), and the F-actin remodeling and stress fiber formation were significantly reduced.
CONCLUSIONS
PKC inhibitor could significantly attenuate the damage of vascular endothelial barrier induced by LPS, and plays an important role in endothelial cell barrier.
Acute Kidney Injury/prevention & control*
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Animals
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Endothelium, Vascular/drug effects*
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Interleukin-1beta
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Lipopolysaccharides/toxicity*
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Protein Kinase C/antagonists & inhibitors*
;
Protein Kinase Inhibitors/pharmacology*
;
Random Allocation
;
Rats
2.Analysis of survival time and benefits of postoperative radiotherapy in resected small cell lung cancer patients
Yanyang WANG ; Xiaolong DING ; Xuehong BAI ; Liang YU ; Jinxi HE ; Ren ZHAO
Chinese Journal of Radiation Oncology 2023;32(3):201-206
Objective:To analyze the survival time, prognostic factors and the value of postoperative thoracic radiotherapy in resected small cell lung cancer (SCLC) patients.Methods:Clinic opathological data of SCLC patients who received surgical treatment in Cancer Hospital & General Hospital of Ningxia Medical University from April 2014 to September 2021 were enrolled in this retrospective study. All patients were subject to follow-up. The survival time of SCLC patients was evaluated by Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed by Cox proportional hazard model.Results:A total of 64 patients with SCLC were enrolled in the study. The 5-year overall survival (OS) rate was 43.5%. Univariate analysis showed that TNM staging ( P=0.027), postoperative neutrophil-lymphocyte ratio (NLR) ( P=0.039) and adjuvant thoracic radiotherapy ( P=0.041) were the prognostic factors. Multivariate analysis showed that TNM staging ( P=0.038) and adjuvant thoracic radiotherapy ( P=0.022) were the prognostic factors in patients with SCLC. The 5-year OS rates of patients with and without adjuvant thoracic radiotherapy were 71.6% and 35.4% ( P=0.028), respectively. There was a statistically significant difference in the 5-year OS rates between pathological stage N 2 SCLC patients with or without adjuvant thoracic radiotherapy (75.0% vs. 0%, P=0.030). Conclusions:TNM staging and postoperative adjuvant thoracic radiotherapy are prognostic factors in patients with SCLC undergoing surgical treatment. Pathological stage N 2 SCLC patients can benefit from adjuvant thoracic radiotherapy.
3.Value of 3D printing combined with intraoperative electrophysiological monitoring in excision of cerebellopontine angle tumor
Guowen WANG ; Yanyang HE ; Bo WANG ; Shanshan XIE ; Tenglong JIN ; Yazhou WANG ; Bingshui SHAO ; Kun GAO ; Kai LI ; Minli ZHANG ; Hongyu ZHAO
Chinese Journal of Neuromedicine 2021;20(7):700-704
Objective:To investigate the value of 3D printing combined with intraoperative electrophysiological monitoring in excision of cerebellopontine angle (CPA) tumor.Methods:The clinical data of 43 patients with CPA tumor, admitted to our hospital from October 2016 to October 2019, were collected and analyzed. These patients were voluntarily divided into ordinary group ( n=27) and optimized group ( n=16). Patients in the ordinary group were operated microscopically, and those in the optimized group were operated microscopically with 3D printing combined with intraoperative electrophysiological monitoring. The degrees of tumor resection and neurological functions (facial and auditory nerve function, swallowing function, limb activity) improvements were compared between the two groups. Results:The degrees of tumor resection of the optimized group were significantly higher than those of the ordinary group ( P<0.05), and the improvement of facial and auditory nerve function in the optimized group was significantly better than that in the ordinary group ( P<0.05). There was no significant difference in improvements of swallowing function and limb activity between the two groups ( P>0.05). Conclusion:The 3D printing combined with intraoperative electrophysiological monitoring can improve the resection rate of CPA tumor, protect the facial auditory nerve, and improve the quality of life of patients after surgery.
4.Current status and future of treatment of pulmonary fibrosis by mesenchymal stem cells and extracellular vesicles
Yanyang WANG ; Chan LIU ; Limei YU ; Zhixu HE
Chinese Journal of Tissue Engineering Research 2024;28(25):4079-4086
BACKGROUND:Despite a series of clinical treatment measures,the treatment of pulmonary fibrosis still faces challenges.In recent years,mesenchymal stem cells and their extracellular vesicles have attracted extensive attention as an emerging therapeutic strategy and are considered to be a promising means of treating pulmonary fibrosis. OBJECTIVE:To systematically review the application of mesenchymal stem cells and their extracellular vesicles in the treatment of pulmonary fibrosis,to comprehensively understand their therapeutic mechanism,efficacy evaluation and problems,and provide reference and guidance for further research and clinical application in the future. METHODS:Using Chinese and English search terms"mesenchymal stem cells","mesenchymal stem cell extracellular vesicles","pulmonary fibrosis",we searched the CNKI and PubMed electronic journal databases.By means of manual reading and eliminating duplicate articles,112 articles were selected,but 58 Chinese and English articles were finally included for summary. RESULTS AND CONCLUSION:(1)Mesenchymal stem cells and their extracellular vesicles have shown great potential in the treatment of pulmonary fibrosis,such as regulating inflammatory responses,inhibiting fibroblast proliferation,and promoting damaged tissue repair.Preliminary results from clinical trials have also shown some effects of the treatment,including improved lung function and quality of life in patients.(2)However,mesenchymal stem cells and extracellular vesicles in the treatment of pulmonary fibrosis still face some challenges.During treatment,technical challenges such as cell migration and intrachistological localization need to be addressed for it to accurately reach the damaged lung tissue.Furthermore,its long-term safety also needs to be further studied and improved.For translational medicine development,standardized procedures such as cell collection,cell isolation,cell culture,cell harvesting,and cell identification need to be refined.(3)Despite these challenges,through the joint efforts of scientific researchers and medical personnel,these problems are expected to be gradually solved.In the future,we can further improve treatment outcomes by optimizing treatment regimens and exploring individualized treatments.At the same time,in-depth research on the therapeutic mechanism of stem cells and their extracellular vesicles is expected to develop more efficient and safe therapeutic strategies.