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Objective:To investigate the diagnostic value of Flt3 ligand (Flt3L) and growth arrest specific protein 6 (Gas6) in post-chemotherapy infection of patients with non-Hodgkin′s lymphoma.Methods:A total of 94 NHL patients admitted to Wuhan No.1 Hospital for chemotherapy from July 2019 to October 2020 were collected, and divided into infection group ( n=40) and non-infection group ( n=54). Fifty healthy subjects at the same period were selected as the control group to analyze the expression levels of Flt3L, Gas6 and general inflammatory indicators among the three groups. The relationship between Flt3L, Gas6 and general inflammatory indicators were analyzed. The predictive value of Flt3L and Gas6 for post-chemotherapy infection in NHL patients was analyzed by ROC curve. Kaplan-Meier curve was used to analyze the infection status of NHL chemotherapy patients with serum Flt3L and Gas6 levels. Results:The levels of serum Flt3L [807.80(215.10-1 232.00) pg/ml] and Gas6 [20.04(13.14-27.52) ng/ml] in the infection group were higher than those in the non-infection group and the control group, and the differences were statistically significant (all P<0.05);The levels of serum Flt3L[887.3(321.60-1 367.00) pg/ml] and Gas6[25.24(17.61-42.86) ng/ml] in the severely infection group were higher than those in the mildly infection group, and the differences were statistically significant (all P<0.05). serum Flt3L was negatively correlated with WBC and positively correlated with IL-6;serum Gas6 was negatively correlated with WBC.ROC curve analysis showed that the AUC and 95% CI of Flt3L and Gas6 were 0.814 (0.718-0.909) and 0.644 (0.523-0.765), respectively. The combined application of serum Flt3L with hsCRP, PCT and IL-6 significantly improved the diagnostic efficiency, and the area under the curve was 0.956, 0.923 and 0.865, respectively. Kaplan-Meier curve analysis showed that when serum Flt3L≥649.80 pg/ml and serum Gas6≥21.50 ng/ml in NHL chemotherapy patients, the infection rate was significantly increased ( P all<0.05). Conclusion:Serum Flt3L and Gas6 levels in post chemotherapy-infection of NHL patients were significantly increased and correlated with the severity of infection. Early detection of serum Flt3L levels is helpful to predict the diagnosis of infection in NHL patients after chemotherapy.
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Growth arrest specific protein 6 (GAS6) plays an important role in the occurrence and development of tumors, and its signal transduction is involved in cell proliferation, adhesion and migration, but its related functions and molecular mechanisms in endometriosis (EMs) are still unclear. In this study, we searched and downloaded the transcriptome datasets of EMs from GEO database and performed GEO online analysis, and then screened out the differentially expressed genes and performed cluster analysis based on GO and KEGG pathway. The mRNA levels of the differentially expressed genes shared by more than three datasets were verified by qRT-PCR in the endometrium of ten women with no endometriosis and no clear disease and the ectopic endometrium of 11 patients with ovarian chocolate cysts. Immunohistochemistry and qRT-PCR were used to verify the expression of GAS6 and epithelial mesenchymal transition (EMT) marker genes, and immunofluorescence was used to co-label GAS6 and E-cadherin in endometriosis clinical samples. In this study, a total of 47 differentially expressed genes were screened out of the four transcriptome datasets, which were mainly enriched in processes such as cell migration and related signal pathways such as MAPK, PI3K-AKT, and tight junction. The mRNA levels of the nine differentially expressed genes shared by more than three datasets in endometriosis patients were consistent with the results of bioinformatics analysis. GAS6 expression levels in ectopic endometrium of EMs patients are higher than the control group (P < 0. 05), and EMs patients have the characteristics of EMT in the ectopic endometrial tissue, that is, the expression of E-cadherin is down-regulated (P < 0. 05) and the expression of vimentin is up-regulated (P < 0. 01). The expression of E-cadherin in the ectopic endometrial glandular epithelial cells of EMs patients is low while the expression of GAS6 is up-regulated, suggesting that GAS6 may mediate the EMT process in endometriosis. In conclusion, this study reveals that GAS6 is highly expressed in endometriosis patients and may mediate the EMT process to participate in the occurrence and development of endometriosis, providing a potential target for clinical treatment of endometriosis.
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@#[Abstract] Objective: To investigate the effects and molecular mechanism of lncRNA GAS6-AS2 on the proliferation, migration and invasion of lung cancer A549 cells and its sensitivity to paclitaxel (PTX). Methods: qPCR was used to detect the levels of GAS6-AS2 and miR-125a-3p in lung cancer A549 and A549/PTX cells. Si-NC, si-GAS6-AS2, miR-NC, miR-125A-3p, pcDNA, PCDNA-GAS6-AS2, si-GAS6-AS2+anti-miR-GAS6-AS2 and si-GAS6-AS2+anti-miR-125A-3p were transfected into A549/PTX cells by liposomal transfection.A549 and A549/PTX cells were treated with PTX of different concentrations (1 nmol/L, 5 nmol/L, 10 nmol/L, 20 nmol/L, 40 nmol/L). WB was used to detect the expression levels of proliferation, migration and invasion related proteins (cyclin D1, p21, MMP2 and MMP9). MTT assay was used to determine the inhibitory effect of PTX on A549/PTX cell proliferation. Transwell assay was applied to detect cell migration and invasion ability of cells. Dual-luciferase reporter gene system was performed to verify the relationship between GAS6-AS2 and miR-125a-3p. Results: The expression level of GAS6-AS2 in A549/PTX cells was significantly higher than that in A549 cells (P<0.01), and the expression level of miR-125a-3p in A549/PTX cells was significantly lower than that in A549 cells (P<0.01). The inhibitory rates of PTX at different concentrations on A549/PTX cells were significantly lower than that on A549 cells (P<0.01), in a concentration-dependent manner. GAS6-AS2 knockdown or miR-125a-3p over-expression combined with PTX treatment could inhibit A549/PTX cell migration and invasion, enhance inhibition rate of PTX on cell proliferation, promote the expression of p21 protein, and suppress the expressions of cyclin D1, MMP2 and MMP9 (all P<0.01). GAS6-AS2 targeted and negatively regulated the expression of miR-125a-3p. Interfering miR-125a-3p reversed the effects of GAS6-AS2 knockdown on proliferation, migration, invasion and PTX sensitivity of A549/PTX cells (all P<0.01). Conclusion: GAS6-AS2 knockdown inhibits proliferation, migration and invasion of A549/PTX cells and enhances sensitivity of cells to PTX by targeting miR-125a-3p; thus, it can be used as a potential molecular target for lung cancer.
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@#AIM:To investigate the expression changes and clinical significances of Gas6, SDF-1α and SDF-1β in serum in patients with diabetic retinopathy(DR). <p>METHODS: Totally 113 patients with DR were divided into proliferative group(<i>n</i>=45)and nonproliferative group(<i>n</i>=68). In the same period, 49 cases of patients with non-contracted DR diabetes were selected as the diabetic group and 42 cases of healthy subjects were selected. The indexes of blood glucose, blood lipids and hs-CRP were detected. The expressions of Gas6, SDF-1α and SDF-1β genes in serum were detected by using real-time PCR technology. <p>RESULTS: The HOMA-IR, TG and hs-CRP in the diabetic group, nonproliferative group and proliferative group gradually increased, the differences were statistically significant(<i>F</i>=39.672, 81.625, 99.872, all <i>P</i><0.05). The LDL-C in the nonproliferative group and proliferative group were higher than the diabetic group and healthy subjects, while the HDL-C were lower than the diabetic group and the healthy subjects, the differences were statistically significant(<i>F</i>=51.974, 43.824, all <i>P</i><0.05). The relative expression levels of Gas6 mRNA in proliferative group, nonproliferative group and diabetic group were higher than the healthy subjects; the relative expression levels of SDF-1α mRNA in proliferative group were higher than the nonproliferative group, diabetic group and healthy subjects. The relative expression levels of SDF-1β mRNA in proliferative group and nonproliferative group were higher than the diabetic group and healthy subjects, and the proliferative group were higher than the nonproliferative group, the differences were statistically significant(<i>F</i>=15.381, 21.589, 38.942, all <i>P</i><0.05). Pearson correlation analysis showed that the relative expression levels of Gas6 mRNA in serum in patients with DR were positively correlated with TG, TC and LDL-C(<i>r</i>=0.228, 0.241, 0.209, all <i>P</i><0.05), and the relative expression levels of SDF-1α mRNA and SDF-1β mRNA in serum were positively correlated with hs-CRP(<i>r</i>=0.297 and 0.325, all <i>P</i><0.05). <p>CONCLUSION: The expression levels of Gas6, SDF-1α and SDF-1β genes in serum in patients with DR are elevated. They might be related to abnormal blood lipid metabolism and inflammatory response.
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Objective@#To investigate the modulation role of Gas6 in silica-induced inflammatory effect on human macrophages.@*Methods@#Differentiated THP-1 macrophages were exposed to different concentrations of silica for 6 h and 24 h. Additionally, silica-activated macrophages were treated with different concentrations of recombine human Gas6 and Gas6 antibody respectively. Cell viabilities were determined by CCK-8 kit. Expression levels of Gas6 and inflammatory cytokines (TNF-α, IL-1β and IL-6) were measured by ELISA assay kits.@*Results@#Silica particles induced clear dose-dependent decreases of cell viability and Gas6 expression at both 6 h and 24 h. The cell viability of 24 h is lower than 6 h at the same concentration of silica (P<0.05). Furthermore, silica activated macrophages treated with Gas6 antibody induced significant decreases of Gas6 both at 6 h and 24 h (P<0.05). After pretreated with various concentrations of Gas6 antibody, silica induced higher expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6) in dose-dependent manners at two time points. Addition of exoge-nous Gas6 significantly suppressed silica-induced inflammatory cytokines concentrations mentioned above in the cell culture supernatants in clear dose-dependent manners.@*Conclusion@#Exogenous Gas6 could inhibit the secre-tion of inflammatory cytokines in macrophages, while the block of Gas6 might enhance this inflammation.
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Objective To investigate the expression level of Gas6 in patients with Immune Thrombocytopenia (ITP) and its clinical significance.Methods The experimental group was peripheral blood samples collected from 35 cases diagnosed with ITP in hematology department of Changhai Hospital in Shanghai from October 2013 to December 2015.Control group was peripheral blood from 35 healthy examined individuals at the same time.After separating plasm from the two group samples,the protein level of Gas6,IFN-α,IL-4,IFN-γ and IL-17 were measured by Enzyme-linked immunosorbent assay (ELISA),comparison of expressional level of the two groups was measured by t test.Pearson correlation analysis was used to decide the relation between Gas6 and cytokines such as IFN-α.Results The expression level of Gas6 in experimental and control groups was 27.28±7.56 ng/ml vs 20.51±5.39 ng/ml (t=4.314,P＜0.000 1);IFN-γ was 221.67±57.64 pg/ml vs 45.32 ±16.79 pg/ml (t=17.38,P＜0.000 1);IL-4 was 113.86±26.48 pg/ml vs 49.87±14.98 pg/ml (t=12.44,P＜0.000 1);IL-17 was 168.96±47.88 pg/ml vs 109.56±28.97 pg/ml (t=6.28,P＜0.000 1);IFN-α was 34.83±8.12 pg/ml vs 29.89 ± 5.76 pg/ml (t=2.936,P=0.004 5),all with statistical differences (P＜0.05).Pearson analysis showed that Gas6 was positively related with IL-17,IL-4,IFN γ (r=0.564,0.486,0.449,P＜0.05) and there was difference statistically,but Gas6 was not correlated with IFN-α.Conclusion Gas6 may participate in the disease formation of ITP through affection on cytokines secreted by Th cell subsets,and it was the potential therapeutic and predicted target for this disease clinically.
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Axl belongs to the family of receptor tyrosine kinase. Axl and its ligand Gas6 are aberrantly over-expressed in numerous human cancers. The binding of Gas6 and Axl could activate multiple signaling pathways, which take part in the development and progression of cancer, including cell survival, migration, invasion, and angiogenesis. In recent years, Axl and Gas6 have been considered as a promising novel target for cancer therapeutics. Several Axl inhibitors, including small-molecule tyrosine kinase inhibitors and anti-Axl monoclonal antibodies are currently under research. In this paper, we review the development of Axl-targeting drugs in tumor therapy.
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OBJECTIVE:To investigate the effects of Shenmai injection combined with sodium ferulate on infarct size and relat-ed indicators of patients with acute myocardial infarction. METHODS:110 patients with acute myocardial infarction were randomly divided into control group(55 patients) and observation group(55 patients). Patients in the control group received oxygen inhala-tion,coronary expansion by nitrates,water and electrolyte regulation and acid-base balance regulation,thrombolytic fibrinolytic agent utilization,sedation and analgesia by analgesics and other conventional treatments. Meanwhile,50 ml Shenmai injection was given to the control group,dissolved in 200 ml 5% Glucose injection,intravenously,twice a day;observation group was addition-ally given 0.2 g Sodium ferulate for injection,dissolved in 200 ml 5% Glucose injection,intravenously,twice a day. The treat-ment course for both groups was 14 d. Clinical efficacy in 2 groups was observed,myocardial infarction size before and after treat-ment was recorded,hemorheology indexes(whole blood viscosity,fibrinogen and erythrocyte aggregation index),catdiac enzymes index homocysteine(Hcy),and growth arrest-specific gene product 6(Gas6)before and after treatment together with the incidence of adverse reactions were detected. RESULTS:The total effective rate in observation group was significantly higher than it in con-trol group. The difference was statistically significant(P0.05). After treatment,the myocardial infarct size in 2 groups was reduced,hole blood viscosity,fibrinogen and erythro-cyte aggregation indexes were reduced,and these in observation group were lower than in control group;in the 8 day during the treatment,serum level of Hcy in observation group was reduced;in the 15 day,blood level of Hcy and Gas6 in observation groups was reduced,serum level of Hcy in control group was reduced,and these in observation group was lower than in control group. The differences were statistically (P<0.05). And there were no obvious adverse reactions during treatment. CONCLU-SIONS:Based on conventional treatment,Shenmai injection combined with sodium ferulate shows significant efficacy in the treat-ment of acute myocardial infarction,and can reduce blood level of Hcy and Gas6,improve hemorheology indexes and narrow the myocardial infarct size.
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Axl belongs to the family of receptor tyrosine kinase. Axl and its ligand Gas6 are aberrantly over-expressed in numerous human cancers. The binding of Gas6 and Axl could activate multiple signaling pathways,which take part in the development and progression of cancer,including cell survival,migration,invasion,and angiogenesis. In recent years,Axl and Gas6 have been considered as a promising novel target for cancer therapeutics. Several Axl inhibitors,including small-molecule tyrosine kinase inhibi?tors and anti-Axl monoclonal antibodies are currently under research. In this paper ,we review the development of Axl-targeting drugs in tumor therapy.
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OBJECTIVE:To investigate the effect of intravitreal injection of ranibizumab on visual acuity and GAS6,SDF-1 and VEGF levels in serum of patients with proliferative diabetic retinopathy lesions. METHODS:56 patients diagnosed as prolifera-tive diabetic retinopathy in our hospital during Mar. 2012 to Mar. 2014 were analyzed retrospectively and divided into simple lateral eyes group(29 cases)and bilateral eyes group(27 cases). All patients received single intravitreal injection of ranibizumab. The se-rum levels of GAS6,SDF-1 and VEGF were detected before treatment and 1,4 and 8 weeks after treatment. The visual acuity of patients were detected before treatment and 1 week after treatment. RESULTS:1,4 and 8 weeks after treatment,the serum levels of GAS6,SDF-1 and VEGF in 2 groups were decreased significantly,with statistical significance(P0.05). 1 week after treatment,the number of letter which had been seen by patient’s BC-VA were increased,compared to before treatment,with statistical significance(P0.05). CONCLUSIONS:Intravitreal injection of ranibizumab can improve visual acuity of patients with pro-liferative diabetic retinopathy.