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Journal of Jiangsu University(Medicine Edition)

	2024 Vol.34 Issue.01 Published 2024-01-23

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		2024 Vol. 34 (01): 0- [Abstract] ( 9 ) [HTML 1KB] [ PDF 738KB] ( 343 )

	1	hnRNPA2B1 enhances the resistance of pancreatic cancer cells to ferroptosis by inhibiting transferrin receptor
		LI Zheng1, LIU Yawen1, CHEN Jiaxi2, WANG Huizhi1, YU Zhengyue1, WANG Shunyu1, GONG Aihua1, XU Min3
		Objective： To investigate the role of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in ferroptosis of pancreatic cancer cells and its potential mechanisms. Methods： Three pancreatic cancer cell lines PaTu8988, MIA-paca2 and PANC1 were treated with different concentrations of Erastin for 3 days. The cell viability was detected by CCK8 method. The half inhibitory concentrations (IC50) of Erastin in three kinds of pancreatic cancer cell lines were calculated and their resistance capabilities to Erastin were compared; qRT-PCR and Western blotting were used to detect the relative expression levels of mRNA and protein of hnRNPA2B1 in pancreatic cancer cells. The differential expression of the hnRNPA2B1 in pancreatic cancer tissues and normal tissues was analyzed by GEPIA, and the survival prognosis of patients with differential expression of hnRNPA2B1 was analyzed from clinical data sets from GEO database. PaTu8988 cells was transfected with sh-Control and sh-hnRNPA2B1 plasmid, respectively, to knock down hnRNPA2B1; PANC1 cells was transfected with Vector and Flag-hnRNPA2B1 plasmid, respectively, to overexpress hnRNPA2B1; and the transfection efficiency was verfied by qRT-PCR and Western blotting, respectively; the effects of knockdown or overexpression of hnRNPA2B1 on the migration and invasion were detected by Transwell assay, and the effects on the proliferation of pancreatic cancer cells were detected by CCK8 assay. The cells in sh-Control, sh-hnRNPA2B1, Vector and Flag-hnRNPA2B1 group were treated with control (0 μmol/L Erastin) and Erastin (IC50 concentration), respectively, then flow cytometry was used to determine the lipid peroxidation level, and colorimetry was used to determine the malindialdehyde (MDA) and tissue iron concentration; in addition to Erastin, the sh-hnRNPA2B1 and Flag-hnRNPA2B1 groups were added with Ferrostatin-1, Necrostatin-1, ZVAD-FMK, respectively, the cells activity was detected by trypan blue dye exclusion. The relative expression levels of RNA and protein of transferrin receptor (TFRC), ferritin heavy chain, glutathione peroxidase 4 and solute carrier family 7 member 11 weredetected by qRT-PCR and Western blotting, respectively. Results： The resistance of three types of pancreatic cancer cells to Erastin from high to low were PaTu8988, MIA-paca2 and PANC1, corresponding Erastin IC50 was 18.020, 15.760 and 2.947 μmol/L, respectively (P<0.05). The relative expression level of hnRNPA2B1 was the highest in PaTu8988 cells, followed by MIA-paca2 cells and the lowest in PANC1 cells (P<0.05), which was the same with Erastin IC50. The expression level of hnRNPA2B1 in pancreatic cancer tissues was significantly higher than that in normol tissues, and the prognosis of patients with higher expression of hnRNPA2B1 was poor (P<0.05). Down-regulating the expression of hnRNPA2B1, the migration, invasion and proliferation ability of PaTu8988 cells were greatly reduced, while up-regulating was the opposite (P<0-05). Erastin-induced cell death was significantly restored by Ferrostatin-1 not by ZVAD-FMK or Necrostatin-1 (P<0.05); compared with sh-Control group, the level of lipid peroxidation, MDA and iron concentration in sh-hnRNPA2B1 group were significantly increased (P<0.05); compared with Vector group, Flag-hnRNPA2B1 group showed lower level of lipid peroxidation, MDA and ironconcentration (P<0.05). Upregulation of hnRNPA2B1 inhibited the expression of TFRC, while interference with hnRNPA2B1 produced the opposite effect (P<0.05). Conclusion： hnRNPA2B1 could inhibit t he intracelluar accumulation of iron by inhibiting the expression of TFRC, thus promoting the resistance of pancreatic cancer cells to ferroptosis.
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		2024 Vol. 34 (01): 1-10 [Abstract] ( 8 ) [HTML 1KB] [ PDF 2230KB] ( 427 )

	11	Expression and clinical significance of survivin and cell division cycle associated protein 5 in gastric cancer and gastric stromal tumor
		BAO Jie1, GAO Xiaojiao2, HAN Wei3, WANG Qinghua1
		Objective： To detect the expression of survivin and cell division cycle associated protein 5 (CDCA5) in gastric cancer and gastric stromal tumor, and analyze the correlation between them and their value in the evaluation of clinicopathological parameters. Methods： Firstly, the expression and correlation of survivin coding gene, BIRC5 (baculoviral IAP repeat containing 5) and CDCA5 in gastric cancer were analyzed by GEPIA database. Immunohistochemistry was used to detect the expression of survivin and CDCA5 in 76 cases of gastric cancer and 63 cases of gastric stromal tumor. Spearman′s rank correlation test was used to analyze the correlation between survivin and CDCA5 and clinicopathological features of the patients. Then, PROMO database was used to predict transcription factors that may act on their promoters. Finally, the interaction between survivin and CDCA5 was predicted by HDOCK. Results： GEPIA database analysis showed that the expressions of BIRC5 mRNA and CDCA5 mRNA in gastric cancer tissues were significantly higher than those in normal gastric tissues (P<0.01), and the expressions of BIRC5 mRNA and CDCA5 mRNA in gastric cancer tissues were positively correlated (r=0.79, P<0.01). Immunohistochemical results showed that the expression levels of survivin and CDCA5 were significantly higher than those of the corresponding paracancerous/paratumoral tissues (P<0.001), and the expressions of both were positively correlated in gastric cancer and gastric stromal tumor tissues (rgastric cancer=0.410，rgastric stromal tumor=0.347，both P<0.05). In gastric cancer, survivin was positively correlated with tumor size, lymphatic vessel invasion and TNM stage (all P<0.05); CDCA5 expression was negatively correlated with tumor differentiation (P<0.05) and positively correlated with TNM stage (P<0.05); and the copositive expression was closely related to tumor size, tumor differentiation lymphatic vessel invasion and TNM stage (all P<005). In gastric stromal tumors, survivin was positively correlated with mitosis and National Institute of Health (NIH) risk stratifications (P<0.05); CDCA5 was positively correlated with tumor size and NIH risk stratifications (P<0.05); and the copositive expression was positively correlated with tumor size, mitosis and NIH risk stratifications (P<0.05). In addition, PROMO identified 13 transcription factors that might regulate CDCA5 and BIRC5 promoters simultaneously. And HDOCK predicted that there were multiple pairs of interactions between survivin and CDCA5. Conclusion： Under the co-action of multiple transcription factors, survivin and CDCA5 were up-regulated in gastric cancer and gastric stromal tumour with a positive correlation. Both were related to some clinicopathological parameters of gastric cancer and gastric stromal tumor, and the clinical value of combined detection is greater than that of individual molecular detection.
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		2024 Vol. 34 (01): 11-18 [Abstract] ( 10 ) [HTML 1KB] [ PDF 5932KB] ( 361 )

	19	High expression of ONECUT2 mediates 5-FU chemotherapy resistance in patients with recurrent gastric cancer
		ZHU Haifeng1, CHEN Shu2, LONG Weiguo3, WANG Xu4
		Objective： To explore whether one cut domain family member 2 (ONECUT2) transcription factor could be a therapeutic target for 5-FU resistant gastric cancer (GC) relapsed patients. Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the expression level of ONECUT2 in GC patients and GC relapsed patients. Gene set enrichment analyses (GSEA) were performed using STAD patients from TCGA to explore the correlation between ONECUT2 and biological processes related to drug metabolism. CCK-8 cytotoxic assays were performed to evaluate the role of ONECUT2 knockdown or overexpression on 5-FU resistance in gastric cancer cell lines. 30 relapsed GC patients with previously resected tumor samples were recruited to analyze the correlation between ONECUT2 expression level and 5-FU treatment efficacy. Results: According to the results of TCGA data analysis, in GC patients with chemotherapeutic treatment and cancer reoccurrence events, higher ONECUT2 level contributed to shorter disease-free interval. GSEA results suggested that upregulated ONECUT2 was positively correlated with xenobiotic drug metabolism, and which was related to drug resistance in GC patients. ONECUT2 knockdown reduced IC50 value of 5-FU in GC cells in vitro; on the contrast, ONECUT2 overexpression increased IC50 value of 5-FU in GC cells in vitro. The sensitivity of 5-FU treatment was negatively correlated with ONECUT2 mRNA level of tumor samples derived from 30 GC patients who relapsed after surgical resection. Conclusion: Relapsed GC patients had a higher expression of ONECUT2, and higher ONECUT2 expression level was positively related to 5-FU resistance in relapsed GC patients. These results provided a potential therapeutic target for GC treatment.
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		2024 Vol. 34 (01): 19-24 [Abstract] ( 12 ) [HTML 1KB] [ PDF 3577KB] ( 316 )

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		2024 Vol. 34 (01): 25-29 [Abstract] ( 10 ) [HTML 1KB] [ PDF 2198KB] ( 306 )

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		2024 Vol. 34 (01): 30-36 [Abstract] ( 11 ) [HTML 1KB] [ PDF 827KB] ( 450 )

	37	Oxidative damage to human umbilical vein endothelial cells caused by di(2-ethylhexyl) phthalate and the repairing effect of resveratrol
		WANG Zixuan1, LIU Wei1, LIN Bohan1, LI Tao1, YANG Qin2, YU Qiwen1, SUN Xiaochun1
		Objective： To investigate the oxidative damage of human umbilical vein endothelial cells HUVEC induced by di-2-ethylhexyl phthalate (di-2-ethylhexyl phthalate, DEHP), and the repairing effect of resveratrol on this damage. Methods： The ranges of damage concentration of DEHP and the repair concentration of resveratrol were screened by CCK8 experiment. The different levels of malondialdehyde (MDA) and superoxide dismutase （SOD） activity in HUVEC were detected by chemical spectrophotometry. The content of reactive oxygen species （ROS） in HUVEC was detected by fluorescent probe of reactive oxygen species. The mitochondrial membrane potential (MMP) of different HUVEC groups was detected by JC-1 kit. CCK8 experiment, Transwell experiment and scratch healing experiment were applied to observe the changes of various cell capacities of HUVEC. The apoptosis of HUVEC were detected by cell flow cytometry experiment and Western blotting. Results： After treated with 80 μmol/L DEHP for 24 hours, the cell proliferation ability was significantly reduced (P<0.01), and 40 μmol/L resveratrol had no obvious toxicity to the cells; The MDA level and SOD activity of the cells in the injury group were significantly higher than those in the control group (all P<0.01), compared with the damage group, the repair group were significantly decreased (all P<0.05); the expression of ROS in the damage group was significantly higher than that in the control group (P<0.01), the repair group was significantly lower than the damage group (P<0.01); the MMP of the damage group was significantly lower than that of the control group (P<0.01), and the repair group was significantly higher than the damage group (P<0.01); Compared with the control group, the proliferation, migration, and tube-forming abilities of the cells were significantly decreased (all P<0.05), and the repair group was significantly increased compared with the damage group (all P<0.05); the apoptosis level of the damage group was significantly higher than that of the control group (P<0.05), the repair group was significantly lower than the damage group (P<0.05). Conclusion： DEHP can inhibit the proliferation, migration, and tube-forming abilities of HUVEC through oxidative stress pathway and induce its apoptosis, while resveratrol can effectively repair the damage.
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		2024 Vol. 34 (01): 37-43 [Abstract] ( 7 ) [HTML 1KB] [ PDF 2985KB] ( 342 )

	44	Purification of ELP-SOD fusion protein and liposome encapsulation
		ZHU Yuerong1, CHEN Xingyu2, FENG Jiaoyan2, ZHOU Ben2, FAN Yanrong2
		Objective： The ELP-SOD fusion protein was expressed by recombinant E.coli cells, and purified ELP-SOD enzyme with high activity was obtained by three rounds of inverse transition cycling (ITC). ELP-SOD liposomes with long halflife and enzyme activity were prepared by liposome encapsulation technology, which laid a foundation for the application of recombinant human SOD in medical, health care, cosmetics and other fields. Methods： The purity of ELP-SOD was evaluated by SDS-PAGE, Tanon3500 gel imaging system and Image studio software; the enzyme activity of SOD fusion protein was measured using an improved pyrogallol autooxidation method (325 nm method); by adjusting different pH values and temperature gradients, the pH and thermal stability of the fusion protein were assessed; adding Cu2+/Zn2+ increased ELP-SOD enzyme activity; in vivo half-life experiments was simulated using rat plasma; cytotoxicity was evaluated by incubating HUVEC and L929 cells with different concentrations of ELP-SOD in culture media; preparation of ELP-SOD liposomes by thin film hydration method and determination of their encapsulation efficiency; mouse skin in vitro was prepared and in vitro release experiments were conducted using TP-6 transdermal diffusion apparatus. By using Franz diffusion cell the transdermal efficiency of ELP-SOD liposomes was to be investigated in carrying ELP-SOD. Results： The highest expression level of ELPSOD fusion protein was 10 mg/L, with a purity of 978% and an enzyme specific activity of 4 894.5 U/mg; its stability was higher at pH 5.0-8.0 and temperatures below 60 ℃; the access of ELP had a certain extension effect on the half-life of SOD and has good biosafety; the encapsulation efficiency of ELP-SOD liposomes reaches over 80%, which could further prolong the half-life of ELP-SOD, and its transdermal efficiency was significantly higher than that of ELP-SOD. Conclusion： The purification process of ELP-SOD fusion protein was simplified through reversible thermal denaturation technology, and combined with lipid preparation technology, the biological half-life of the enzyme protein was extended and its bioavailability was improved.
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		2024 Vol. 34 (01): 44-51 [Abstract] ( 10 ) [HTML 1KB] [ PDF 2372KB] ( 327 )

	52	Predictive value of neutrophil-to-lymphocyte ratio for ischemic strokeassociated pneumonia
		ZHANG Tingting, YU Ming
		Objective： To explore the risk factors of stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) and its clinical significance. Methods： Patients with AIS admitted to the Department of Neurology, Affiliated Hospital of Jiangsu University from February 2021 to June 2022 were selected. According to whether patients had SAP, they were divided into SAP group and nonSAP group. The clinicopathological parameters of the two groups were compared, and the risk factors related to SAP were analyzed by multivariate logistic regression. Receiver operating characteristic (ROC) curve was used to evaluate the value of neutrophil to lymphocyte ratio (NLR) in predicting SAP. Results： Compared with the non-SAP group, patients in the SAP group were older, stayed in hospital longer (P<0.01), had higher NIHSS score, NLR and fasting blood glucose (all P<0.01), had a higher proportion of atrial fibrillation, disturbance of consciousness and dysphagia on admission (P＜0.01). Multiple logistic regression analysis showed that age, length of stay, NLR, NIHSS score and dysphagia were independent risk factors for SAP (P＜0.05). ROC curve analysis revealed that the area under the curve predicted by NLR for SAP was 0.758 (P＜0.05). The optimal cut-off value was 3.962, the sensitivity was 0.699, and the specificity was 0.770. Conclusion： The occurrence of SAP in acute ischemic stroke patients is associated with multiple risk factors, among which high NLR is an independent risk factor and has a certain predictive value for the occurrence of SAP.
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		2024 Vol. 34 (01): 52-55 [Abstract] ( 9 ) [HTML 1KB] [ PDF 1037KB] ( 433 )

	57	Effect of PECAM-1 and SMA on the prognosis of keloid after comprehensive treatment
		YANG Yifei1,2, XU hui1,2, LONG Weiguo3, LI Yumei1,2
		Objective： To explore the effect of the expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and smooth muscle actin (SMA) in the blood vessels of keloid on the prognosis of comprehensive treatment of keloid. Methods： From August 2020 to June 2022, a total of 61 patients with keloids diagnosed and treated in the Department of Dermatology, Affiliated Hospital of Jiangsu University were retrospectively analyzed, with a total of 69 keloids. All patients received comprehensive treatment of surgical resection and 90Sr isotope application. Immunohistochemical staining was used to detect the expression levels of PECAM-1 and SMA in blood vessels of surgically resected keloid specimens. All patients were followed up for 6 months by telephone and outpatient service. Results： A total of 19 (27.5%) keloids recurred within 6 months, and 11 (15.9%) had adverse reactions after 90Sr isotope application. The high expression rates of PECAM-1 and SMA in the recurrence group were higher than those in the non-relapse group (χ2=7.496, P=0.006; χ2=5.197, P=0.023); the incidence of adverse reactions after treatment had no significant association with the expression levels of PECAM-1 and SMA (χ2=0.172, P=0.935; χ2=1.110, P=0.484). Conclusion： The expression levels of PECAM-1 and SMA in keloid blood vessels were negatively correlated with the prognosis of comprehensive treatment, and they may be potential indicators for judging the prognosis of keloid.
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		2024 Vol. 34 (01): 57-60 [Abstract] ( 9 ) [HTML 1KB] [ PDF 1385KB] ( 349 )

	61	The value of dual-energy CT in cervical intervertebral disc degeneration and herniation
		LI Neng, ZHANG Yehua, KONG Lingling, ZHAO Guangshun, DENG Xiaoyi
		Objective： To assess the feasible of Rho/Z value derived from dual-energy computed tomography (DECT) in cervical disc degeneration (CDD) and herniation. Methods： MRI and DECT imaging data of 50 patients with neck back pain were included. All discs were classified on the basis of Pfirrmann grading system. Rho value of nucleus pulposus were measured and the variances in different grades and different disc level were analyzed with one-way ANOVA test. Correlations between Rho value and grades were analyzed with Spearman correlation test. MRI as the reference standard, the sensitivity, specificity, PPV, NPV and accuracy of conventional grayscale CT images and dual-energy color-coded reconstructed images in the detection of cervical disc herniation were compared. Results： The Rho value of nucleus pulposus in cervical intervertebral disc increased with the increase of Pfirrmann grade and decreased with the decrease of segmental position, and the difference was statistically significant (P<0.001). There was a moderate positive correlation between Rho value of nucleus pulposus and Pfirrmann grades (r=0.584, P<0.05). Dual-energy color-coded reconstructed images had higher overall sensitivity (86.7% vs 74.3%), specificity (90.2% vs 79.3%), PPV (96.7% vs 92.3%), NPV (66.9% vs 48.0%) and accuracy (87.5% vs 75.5%) in detecting cervical disc herniation compared conventional grayscale CT images. Conclusions： The color-coded reconstruction image of DECT can significantly improve the diagnostic accuracy of cervical disc herniation, and the Rho value of nucleus pulposus is associated with the degree of intervertebral disc degeneration.
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		2024 Vol. 34 (01): 61-66 [Abstract] ( 10 ) [HTML 1KB] [ PDF 4178KB] ( 310 )

	67	The causal relationship between inflammatory bowel disease and osteoporosis fracture based on a Mendelian randomization
		CHEN Shangtong1, CHEN Yueping2, SONG Shilei1, HUANG Chuanhong1
		Objective： To investigate the causal relationship between inflammatory bowel disease and osteoporotic fracture by using the two-sample Mendelian randomization (MR) method. Methods: The pooled data from GenomeWide Association Studies (GWAS) were analyzed. Samples from Crohn′s disease and ulcerative colitis were selected for further analysis, where GWAS summary data for Crohn′s disease and ulcerative colitis were obtained from the European IEU database, 20 883 for Crohn′s disease, 47 745 for ulcerative colitis, and GWAS summary data for osteoporotic fractures from the FinnGen database, 173 619. Single nucleotide polymorphisms (SNPs), which are closely associated with Crohn′s disease and ulcerative colitis, were used as instrumental variables (IVs), and the inverse variance weighting method (IVW), the MR-Egger regression method, the Weighted Median method (WME), Simple Mode method and the Weighted Mode method were used to evaluate the causal relationship by means of odds ratio (OR). The Cochran Q heterogeneity test was performed by IVW and MR-Egger method, horizontal pleiotropy analysis by MR_pleiotropy_test function and MR PRESSO pleiotropy test, sensitivity analysis by MR_leaveoneout_plot function, and F values were calculated to evaluate the presence of weak IVs bias. Results: A total of 52 SNPs closely related to Crohn′s disease were obtained as IVs, IVW result ［OR(95%CI): 1.12(1.03-1.22), P=0.006］, WME result ［OR(95%CI) 1.15(1.01-1.32), P=0.02］, MREgger results ［OR(95%CI) 1.16(0.94-1.44), P=0.15］. Simple Mode results ［OR(95%CI): 1.15(0.88-1.50), P=0.28］ and Weighted Mode results ［OR(95%CI): 1.16(0.97-1.39), P=0.10］ suggested a positive causal relationship between Crohn′s disease and osteoporotic fracture. In total, 88 SNPs closely associated with ulcerative colitis were obtained as IVs, IVW result ［OR(95%CI) 1.15(1.03-1.28), P=0.009］, MREgger result ［OR(95%CI): 1.35(1.03-1.75), P=0.02］, WME result ［OR(95%CI): 1.18(1.01-1.37), P=0.02］, Simple Mode result ［OR(95%CI): 1.15(0.86-1.55), P=0.32］ and Weighted Mode results ［OR(95%CI): 1.19(0.96-1.47), P=0.10］ suggested a positive causal relationship between ulcerative colitis and osteoporotic fracture. The results of the heterogeneity test in Crohn′s disease-osteoporotic fractures were P=0.55 and P=0.52, respectively, suggesting the absence of heterogeneity. The MR_pleiotropy_test function result was P=0.69, and the MR PRESSO method result was P=0.55, indicating the absence of pleiotropy, and the sensitivity analysis showed stable results. The heterogeneity tests of ulcerative colitis-osteoporotic fractures were P=0.23 and P=0.25, respectively, suggesting the absence of heterogeneity. The MR_pleiotropy_test function result was P=0.20, and the MR PRESSO method result was P=0.24, indicating the absence of pleiotropy, and the sensitivity analysis showed stable results. All F values were greater than 10, suggesting that there was no weak IVs bias. Conclusion: Inflammatory bowel disease may increase the risk of osteoporotic fractures.
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		2024 Vol. 34 (01): 67-73 [Abstract] ( 11 ) [HTML 1KB] [ PDF 8340KB] ( 307 )

	74	Predictive value of systemic inflammatory markers for the onset of sarcopenia in patients with lower extremity arteriosclerosis obliterans
		NIE Lu1,2, YANG Qifan3, ZHENG Weimiao1,2, XU Qiang1,2
		Objective： To assess the predictive value of systemic inflammatory indicators, including systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and C-reactive protein (CRP), for the onset of sarcopenia in patients with lower extremity arteriosclerosis obliterans (ASO). Methods： A total of 251 ASO patients from the Wujin Hospital Affiliated with Jiangsu University and the Second People′s Hospital Affiliated with Nanjing Medical University were included in the study. Patients were classified into sarcopenia and non-sarcopenia groups based on the psoas muscle index (PMI) of the third lumbar vertebra. Relevant blood indicators of the patients were collected, and SII, PLR, NLR, and LMR were calculated. Binary Logistic regression analysis was used to identify the risk factors for sarcopenia, and the predictive performance of each indicator was assessed by using the receiver operating characteristic (ROC) curve. Results： Among the 251 ASO patients, there were 98 (39.0%) in the sarcopenia group and 153 (61.0%) in the non-sarcopenia group. Compared with the non-sarcopenia group, the age of patients in the sarcopenia group was significantly increased (P<0.001), and the levels of SII, PLR, NLR and CRP were significantly increased (P<0.01), and the levels of BMI and LMR were significantly decreased (P<0.01). Multivariate Logistic analysis revealed that advanced age, low BMI, elevated SII were independent risk factors for sarcopenia. The ROC curve further confirmed the predictive value of these indicators for sarcopenia, with the area under the curve (AUC) of age, BMI, SII, and combined prediction of 3 indicators for the onset of sarcopenia being 0.674, 0.678, 0.644, and 0.746 respectively (all P<0.001). Conclusion： Age, BMI, and systemic inflammatory indicators such as SII have predictive value for the onset of sarcopenia in ASO patients.
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		2024 Vol. 34 (01): 74-78 [Abstract] ( 11 ) [HTML 1KB] [ PDF 1697KB] ( 286 )

	79	Preliminary construction and evaluation of a phosphatidylserine-modified extracellular vesicles nano-drug delivery system for inflammation therapy
		YAN Jie, CHANG Tian, ZHANG Jing, GE Guangrong, CHEN Jiuyuan, HUO Qiang, CHENG Xiu
		］Objective： Preliminarily to construct and evaluate phosphatidylserine (PS)-modified macrophage-derived extracellular vesicles (EVs) nanocarriers (PS-EVs@Que) for delivering quercetin (Que) and study the role of PS-EVs@Que in the treatment of inflammation. Methods： EVs were isolated from macrophages by ultracentrifugation, Que was loaded into EVs by ultrasonication (EVs@Que), and finally PSEVs@Que was prepared by incubating PS into EVs@Que solution, the morphology, particle size, drug loading capacity and encapsulation efficiency of formulations were also evaluated; cellular uptake of EVs and PS-modified EVs were determined by immunofluorescence. Macrophages were treated with LPS, LPS+EVs@Que, LPS+PSEVs@Que and control group respectively, and the expression of iNOS, a marker on the surface of macrophages, were detected by Western Blotting; the expression of inflammatory factors TNF-α and IL-6 were detected by Enzyme-Linked Immunosorbent Assay (ELISA). Results： The prepared PS-EVs@Que presented a circular-like vesicle structure with an average particle size of (118.45±0.97) nm, drug loading capacity of (8.59±0.16)% and encapsulation efficiency of (20.08±0.52)%. The uptake results showed that the modification of PS resulted in better phagocytosis of EVs by macrophages and enhanced the uptake of EVs by macrophages. Macrophage iNOS protein expression reduced in the PS-EVs@Que group compared with other groups (P<0.01), and the expression of inflammatory factors TNF-α and IL-6 were significantly inhibited (P<0.01). Conclusion： In this study, we successfully constructed and evaluated a nanomedicine delivery system, which improved the bioavailability of Que, inhibited the polarization of pro-inflammatory phenotype (M1 type) of macrophages, and reduced the pro-inflammatory factors, providing a reference for novel nanomedicines treatment of inflammatory diseases.
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		2024 Vol. 34 (01): 79-83 [Abstract] ( 12 ) [HTML 1KB] [ PDF 4042KB] ( 361 )

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		2024 Vol. 34 (01): 84-92 [Abstract] ( 9 ) [HTML 1KB] [ PDF 858KB] ( 483 )

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