1.Relationship between the expression levels of PMS-2 and PGP protein and clinicopathological features,prognosis and immune function in gastric cancer
Yunbo NIE ; Tangchun CHI ; Nanlin WU ; Tingting HENG
Immunological Journal 2025;41(10):743-749
Objective To analyze the relationship between the expression levels of post-meiosis isolated protein 2(PMS-2)and p-glycoprotein(PGP)in gastric cancer tissues and clinicopathological characteristics,prognosis and immune function.Methods The clinical data of 100 patients with gastric cancer who visited the hospital from May 2018 to February 2022 were selected for retrospective analysis.All patients received radical surgical treatment.The expression levels of PGP and PMS-2 proteins in adjacent tissues and cancer tissues were determined by immunohistochemistry,and the correlations between the expression of PGP and PMS-2 proteins in cancer tissues and the clinicopathological characteristics and immune function of patients with gastric cancer were analyzed.The patients were followed up for 3 years after the operation to analyze the influencing factors of prognosis in patients with gastric cancer,as well as the correlation between the protein expressions of PGP and PMS-2 in cancer tissues and prognosis.Results The positive expression rates of PGP and PMS-2 proteins in cancer tissues were higher than those in adjacent tissues(P<0.05).Positive expression of PMS-2 and PGP protein was significantly associated with advanced clinical stage(stage Ⅲ),presence of lymph node metastasis,and poorer tumor differentiation(P<0.05).However,their expression showed no significant correlation with age,gender,Lauren classification,vascular invasion,or tumor diameter(P>0.05).The preoperative CD4+/CD8+levels of gastric cancer patients with positive expression of PMS-2 and PGP proteins were respectively lower than those of patients with negative expression of PMS-2 and PGP proteins(P<0.05).Cox multivariate regression analysis showed that clinical stage Ⅲ,degree of differentiation,distant metastasis,lymph node metastasis,positive expression of PMS2 protein,positive expression of PGP protein,and preoperative CD4+/CD8+were all influencing factors for the prognosis of patients with gastric cancer(P<0.05).After a 3-year follow-up,the survival curves of gastric cancer patients with negative expressions of PMS2 and PGP protein were respectively higher than those of patients with positive expressions of PMS-2 and PGP protein(P<0.05).Conclusion The expressions of PMS-2 and PGP proteins in gastric cancer tissues are closely associated with clinical stage,presence or absence of lymph node metastasis,degree of tumor differentiation,prognosis and preoperative CD4+/CD8+level.Moreover,patients with positive expressions of PMS-2 and PGP proteins have a worse prognosis.
2.Mechanistic study of endothelial cell division cycle protein 42 in pulmo-nary vascular barrier injury during acute lung injury
Wen XU ; Jiafei LI ; Fang WANG ; Nanlin WU ; Lilong QIN
Chinese Journal of Pathophysiology 2025;41(4):704-713
AIM:This study aims to investigate the potential mechanism of cell division cycle protein 42(Cdc42)in acute lung injury(ALI).METHODS:(1)The levels of Cdc42 and IQ motif-containing GTPase-activating protein 1(IQGAP1)in ALI were analyzed using the Gene Expression Omnibus(GEO)database.(2)The plasma samples were collected from 30 patients diagnosed with ALI and 30 healthy controls between January 2022 and December 2023.The bronchoalveolar lavage fluid(BALF)from ALI patients was also collected.Eighteen male C57BL/6 mice were ran-domly divided into control(CON)group,lipopolysaccharide(LPS)group,and LPS+ML141(Cdc42 inhibitor)group,with 6 mice in each group.After 72 h,the mice were euthanized,and the BALF was collected for analysis,including cell enumeration and protein concentration determination using the bicinchoninic acid method.Enzyme-linked immunosorbent assay was used to measure the levels of Cdc42 and inflammatory cytokines[interleukin-6(IL-6),IL-1β and tumor necro-sis factor α(TNF-α)]in human plasma and mouse BALF.Lung damage in mouse tissue sections was evaluated by HE staining.(3)Mouse pulmonary microvascular endothelial cells(PMVECs)were isolated by magnetic bead-based cell sorting and were divided into CON,LPS and LPS+ML141 groups.Vascular ring formation assay was conducted to assess the an-giogenic potential of PMVECs,and calcium ion imaging technology was employed to measure calcium ion concentrations in PMVECs.The levels of reactive oxygen species(ROS)were assessed using a ROS detection kit.Western blot was uti-lized to analyze the protein levels of Cdc42,VE-cadherin,intercellular adhesion molecule-1(ICAM-1),myosin light chain(MLC),phosphorylated MLC(p-MLC)and IQGAP1 in PMVECs.RESULTS:(1)The GEO database analysis re-vealed significant up-regulation of Cdc42 expression in ALI model(P<0.01).(2)Clinical assessments showed markedly elevated plasma levels of Cdc42 and pro-inflammatory cytokines(IL-6,IL-1β and TNF-α)in ALI patients(P<0.01),with subsequent reductions after treatment(P<0.05).Neutrophil counts in the BALF of ALI patients were significantly in-creased.In ALI animal models,cell count,protein concentration and inflammatory mediator levels in BALF,and lung tis-sue damage scores were significantly elevated(P<0.01),all of which were notably reduced after treatment with Cdc42 in-hibitor ML141(P<0.05).(3)The PMVECs in LPS group exhibited significant increases in Cdc42,ICAM-1,p-MLC,IQGAP1,ROS,and calcium ion concentrations(P<0.01),alongside significant decreases in VE-cadherin expression and angiogenic capacity(P<0.01).All parameters were significantly improved after ML141 treatment(P<0.05).CON-CLUSION:The Cdc42 may influence IQGAP1 by modulating calcium levels in PMVECs,playing a critical role in pulmo-nary vascular barrier injury during ALI.
3.Relationship between the expression levels of PMS-2 and PGP protein and clinicopathological features,prognosis and immune function in gastric cancer
Yunbo NIE ; Tangchun CHI ; Nanlin WU ; Tingting HENG
Immunological Journal 2025;41(10):743-749
Objective To analyze the relationship between the expression levels of post-meiosis isolated protein 2(PMS-2)and p-glycoprotein(PGP)in gastric cancer tissues and clinicopathological characteristics,prognosis and immune function.Methods The clinical data of 100 patients with gastric cancer who visited the hospital from May 2018 to February 2022 were selected for retrospective analysis.All patients received radical surgical treatment.The expression levels of PGP and PMS-2 proteins in adjacent tissues and cancer tissues were determined by immunohistochemistry,and the correlations between the expression of PGP and PMS-2 proteins in cancer tissues and the clinicopathological characteristics and immune function of patients with gastric cancer were analyzed.The patients were followed up for 3 years after the operation to analyze the influencing factors of prognosis in patients with gastric cancer,as well as the correlation between the protein expressions of PGP and PMS-2 in cancer tissues and prognosis.Results The positive expression rates of PGP and PMS-2 proteins in cancer tissues were higher than those in adjacent tissues(P<0.05).Positive expression of PMS-2 and PGP protein was significantly associated with advanced clinical stage(stage Ⅲ),presence of lymph node metastasis,and poorer tumor differentiation(P<0.05).However,their expression showed no significant correlation with age,gender,Lauren classification,vascular invasion,or tumor diameter(P>0.05).The preoperative CD4+/CD8+levels of gastric cancer patients with positive expression of PMS-2 and PGP proteins were respectively lower than those of patients with negative expression of PMS-2 and PGP proteins(P<0.05).Cox multivariate regression analysis showed that clinical stage Ⅲ,degree of differentiation,distant metastasis,lymph node metastasis,positive expression of PMS2 protein,positive expression of PGP protein,and preoperative CD4+/CD8+were all influencing factors for the prognosis of patients with gastric cancer(P<0.05).After a 3-year follow-up,the survival curves of gastric cancer patients with negative expressions of PMS2 and PGP protein were respectively higher than those of patients with positive expressions of PMS-2 and PGP protein(P<0.05).Conclusion The expressions of PMS-2 and PGP proteins in gastric cancer tissues are closely associated with clinical stage,presence or absence of lymph node metastasis,degree of tumor differentiation,prognosis and preoperative CD4+/CD8+level.Moreover,patients with positive expressions of PMS-2 and PGP proteins have a worse prognosis.
4.Mechanistic study of endothelial cell division cycle protein 42 in pulmo-nary vascular barrier injury during acute lung injury
Wen XU ; Jiafei LI ; Fang WANG ; Nanlin WU ; Lilong QIN
Chinese Journal of Pathophysiology 2025;41(4):704-713
AIM:This study aims to investigate the potential mechanism of cell division cycle protein 42(Cdc42)in acute lung injury(ALI).METHODS:(1)The levels of Cdc42 and IQ motif-containing GTPase-activating protein 1(IQGAP1)in ALI were analyzed using the Gene Expression Omnibus(GEO)database.(2)The plasma samples were collected from 30 patients diagnosed with ALI and 30 healthy controls between January 2022 and December 2023.The bronchoalveolar lavage fluid(BALF)from ALI patients was also collected.Eighteen male C57BL/6 mice were ran-domly divided into control(CON)group,lipopolysaccharide(LPS)group,and LPS+ML141(Cdc42 inhibitor)group,with 6 mice in each group.After 72 h,the mice were euthanized,and the BALF was collected for analysis,including cell enumeration and protein concentration determination using the bicinchoninic acid method.Enzyme-linked immunosorbent assay was used to measure the levels of Cdc42 and inflammatory cytokines[interleukin-6(IL-6),IL-1β and tumor necro-sis factor α(TNF-α)]in human plasma and mouse BALF.Lung damage in mouse tissue sections was evaluated by HE staining.(3)Mouse pulmonary microvascular endothelial cells(PMVECs)were isolated by magnetic bead-based cell sorting and were divided into CON,LPS and LPS+ML141 groups.Vascular ring formation assay was conducted to assess the an-giogenic potential of PMVECs,and calcium ion imaging technology was employed to measure calcium ion concentrations in PMVECs.The levels of reactive oxygen species(ROS)were assessed using a ROS detection kit.Western blot was uti-lized to analyze the protein levels of Cdc42,VE-cadherin,intercellular adhesion molecule-1(ICAM-1),myosin light chain(MLC),phosphorylated MLC(p-MLC)and IQGAP1 in PMVECs.RESULTS:(1)The GEO database analysis re-vealed significant up-regulation of Cdc42 expression in ALI model(P<0.01).(2)Clinical assessments showed markedly elevated plasma levels of Cdc42 and pro-inflammatory cytokines(IL-6,IL-1β and TNF-α)in ALI patients(P<0.01),with subsequent reductions after treatment(P<0.05).Neutrophil counts in the BALF of ALI patients were significantly in-creased.In ALI animal models,cell count,protein concentration and inflammatory mediator levels in BALF,and lung tis-sue damage scores were significantly elevated(P<0.01),all of which were notably reduced after treatment with Cdc42 in-hibitor ML141(P<0.05).(3)The PMVECs in LPS group exhibited significant increases in Cdc42,ICAM-1,p-MLC,IQGAP1,ROS,and calcium ion concentrations(P<0.01),alongside significant decreases in VE-cadherin expression and angiogenic capacity(P<0.01).All parameters were significantly improved after ML141 treatment(P<0.05).CON-CLUSION:The Cdc42 may influence IQGAP1 by modulating calcium levels in PMVECs,playing a critical role in pulmo-nary vascular barrier injury during ALI.
5.Correlation and clinical significance of Survivin and Caspase-9 gene expression in Uygur breast cancer patients with different HER-2 phenotypes
Wenlong SHI ; Jiang WU ; Bingjun LI ; Nanlin LI ; Rui LING ; Jianghao CHEN
The Journal of Practical Medicine 2018;34(10):1589-1593,1597
Objective To detect the expression of Survivin and Caspase-9 gene in Uygur breast cancer pa-tients with different HER-2 phenotypes,to find out the difference and association of the two genes and to find out the potential roles of the two genes breast cancer pathogenesis. Methods We selected 72 Uygur patients diag-nosed as breast cancer initially and they were divided into group A with HER-2 positive(n = 39)and group B with HER-2 negative(n = 33). Another 40 Uygur patients with benign breast were involved as the controls. Immunohis-tochemistry and real-time RT-PCR were used to detect the two genes,and analyze the differences and association of each gene between the groups. Results (1)The expression of Survivin gene in group A and B were higher than that in the control group. Further analysis showed that the expression of Survivin gene was enhanced in group A when compared with that in group B(P < 0.05);while even the expression of Survivin gene in group B was higher than that in the control group but no statistical difference was found(P > 0.05).(2)The expression of Caspase-9 gene in group A and B were lower than that in the control group. Real-time RT-PCR showed that the expression of Caspase-9 gene of group A was decreased when compared with that in group B(P < 0.05);While the expression of Caspase-9 gene of group B was slightly lower that of the control group but it showed no statistical significance (P > 0.05). Immunohistochemical results showed there were no statistical differences of expression of Caspase- 9 gene in group A and B and control group(all P > 0.05). The expression of Survivin and Caspase-9 gene was nega-tively associated in group A and B(P < 0.01;P < 0.05). Conclusions In Uygur patients with HER-2 positive breast cancer,the expression of Survivin gene is enhanced but that of caspase-9 gene is decreased,and they are negatively associated. Through inhabiting caspase-9 gene,Survivin gene may potentially lead to the occurrence of HER-2 positive breast cancer.

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