Effect of non-anticoagulant N-desulfated heparin on expression of vascular endothelial growth factor, angiogenesis and metastasis of orthotopic implantation of human gastric carcinoma

AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor (VEGF) of ortho- topic implantation of human gastric carcinoma in male severe combined immune deficiency (SCID) mice.? METHODS: Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SCID mice.? The mice were randomly divided into normal saline group and N-desulfated heparin group.? One week after operation, the mice in N-desulfated heparin group re- ceived i.?v.? injections of N-desulfated heparin (SShhaanngghhaaii Institute of Cell Biology, Chinese Academy of Sciences, 10 mg/kg.?d)) ttwwiiccee wweeeekkllyy ffoorr ???? wwkk..?? ??hhee mmiiccee iinn nnoorrmmaall saline group received i.?v.? injections of normal saline (100 μL) twice weekly for ?? wk.? ?he mice were sacrificed six weeks after implantation.? ?umor metastasis was evalu- ated histologically for metastasis under microscope.? In- tratumoral microvessel density (MVD) and VEGF expres- sion were evaluated immuohistochemically.? VVVEEEGGGFFF mmmRR?NNNAAA expression in gastric tissue of SCID mice was detected by real time PC?.? RESULTS: The tumor metastasis rate was 80% in nor- mal saline group and 20% in N-desulfated heparin group (P ???? 00..??00??))..?? MMVVDD wwaass ??..??00 ???? ????..??11 iinn nnoorrmmaall ssaalliinnee ggrroouupp and 4.??? ?? 1.?? in N-desulfated heparin group (P ???? 00..??00??))..?? VEGF positive immunostaining was found in cytoplasmof cancer cells.? ?he rate of VEGF positive expression was higher in normal saline group than in N-desulfated hepa- rin treated group (90% vs 20%, P ???? 00..??00??))..?? VVEEGGFF mm??NNAA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group (Ct value 19.??1 ?? 1.?01 vs 22.??? ?? 1.???6, P ???? 00..??00??))..?? NN--ddeessuullffaatteedd hheeppaarriinn ssiiggnniiffii- cantly inhibited the expression of VEGF mRNA in can- cer cells.? No bleeding occurred in N-desulfated heparin group.? CONCLUSION: N-desulfated heparin can inhibit me- tastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious anticoagulant activity.?

Effects of Heparin on Transforming Growth Factor-β_1 and Extracellular Matrix Components in the Glomeruli of Diabetic Rats

The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n=8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β 1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β 1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β 1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β 1 expression.

In vitro Studies on Binding and Release of Vascular Endothelial Growth Factor in Heparinized Bovine Pericardiums

Objective: To investigate binding and release of vascular endothelial growth factor (VEGF) and its effect on adhesion and proliferation of endothelial cells (ECs) in acellular fresh specimens of bovine pericardiums, which were modified by heparinization. Methods: Cross-linked acellular fresh specimens of bovine pericardiums were heparinized by three methods: (1) heparinized N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) treated acellular tissue samples; (2) heparinized poly(ethyleneimine) (PEI) treated acellular tissue samples; (3) heparinized EDC-PEI treated acellular tissue samples. Controlled release of VEGF and its effect on adhesion and proliferation of ECs was evaluated. Results: In the present study, binding and release of VEGF had better performance in heparinized EDC-PEI treated group, compared with heparinized EDC-alone treated group and heparinized PEI-alone group. We could observe enhanced ability to adhesion and proliferation via modest moisture and effective controlled binding and release of VEGF. Conclusion: Binding of VEGF in heparinized EDC treated group was stable, while release of VEGF in heparinized treated group was adjusted freely. Interestingly, controlled binding and release of VEGF could exert beneficial effect on adhesion and proliferation of ECs in heparinized EDC-PEI treated group.

Forkhead Box q1 promotes invasion and metastasis in colorectal cancer by activating the epidermal growth factor receptor pathway

BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.

脑脊液IGF-1、β_(2)-MG、HBP与儿童化脓性脑膜炎发生发展的相关性

目的探究脑脊液中胰岛素样生长因子-1(IGF-1)、β_(2)微球蛋白(β_(2)-MG)、肝素结合蛋白(HBP)水平与儿童化脓性脑膜炎疾病发生发展的相关性。方法选取2021年2月至2023年2月郑州大学第一附属医院儿科收治的86例化脓性脑膜炎患儿为研究组,另选取86例非中枢神经系统感染患儿为对照组,比较两组脑脊液IGF-1、β_(2)-MG、HBP水平,探究其与研究组患儿病情严重程度及预后的相关性。结果研究组脑脊液中IGF-1、β_(2)-MG、HBP水平均高于对照组(P<0.05),且对化脓性脑膜炎具有较高的诊断价值,其曲线下面积分别为0.925、0.930、0.850;重度组脑脊液IGF-1、β_(2)-MG、HBP水平高于轻度组(P<0.05);预后不良组脑脊液IGF-1、β_(2)-MG、HBP水平高于预后良好组(P<0.05),且对化脓性脑膜炎预后不良具有较高的预测价值,其曲线下面积分别为0.879、0.854、0.822。结论监测化脓性脑膜炎患儿脑脊液中IGF-1、β_(2)-MG、HBP的水平对于早期诊断、判断病情严重程度以及预测疾病预后具有重要价值。

Effects of heparin on growth factor-induced mitogenic and proliferative responses of rat pulmonary a

目的：探讨肝素是否能抑制生长因子诱导的大鼠肺动脉平滑肌细胞（ＰＡＳＭＣ）分裂和增殖．方法：应用含１０％ＦＢＳ的Ｍ１９９培养液培养大鼠ＰＡＳＭＣ．细胞分裂及细胞增殖分别用［ｍｅｔｈｙｌ３Ｈ］ＴｄＲ和细胞计数监测．结果：ＦＢＳ（１０％），以及ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联合应用均能增加大鼠ＰＡＳＭＣ分裂．肝素（１００ｍｇ·Ｌ－１）抑制１０％ＦＢＳ诱导的大鼠ＰＡＳＭＣ增殖（２８％±６％）和胸腺嘧啶摄取反应（２７％±７％），抑制ＦＢＳ（１％）与ＰＤＧＦ（５０μｇ·Ｌ－１），ＦＧＦ（５０μｇ·Ｌ－１），或ＩＬ１α（１００ｎｇ·Ｌ－１）联用诱导的大鼠ＰＡＳＭＣ增殖（２５％±６％，２７％±７％，２０％±４％），以及胸腺嘧啶摄取反应（２３％±７％，２６％±６％，２０％±６％）．结论：肝素抑制生长因子诱导的大鼠ＰＡＳＭＣ的分裂与增殖．

脓毒症患者血清VitD、FRT、HB-EGF表达情况与预后预测价值探讨

目的 探讨分析脓毒症患者血清维生素D(VitD)、铁蛋白(FRT)、肝素结合性表皮生长因子(HB-EGF)表达情况与预后预测价值。方法 选取2021年1月—2022年1月某院重症监护病房收治的86例脓毒症患者作为病例组,并选择重症监护病房中60例非脓毒症患者作为对照组。根据脓毒症患者1个月后预后情况,将患者分为存活组和死亡组。入院时采集患者血清,检测血清VitD、FRT、HB-EGF水平,分析其表达水平与脓毒症患者预后的相关性,并采用受试者工作特征曲线下面积(AUC)评估其对预后的预测价值。结果 病例组脓毒症患者白细胞计数、C反应蛋白(CRP)、降钙素原(PCT)、肿瘤坏死因子(TNF-α)、白细胞介素(IL)-6、IL-1β、FRT水平高于对照组非脓毒症患者,VitD、HB-EGF水平低于对照组非脓毒症患者,差异均有统计学意义(均P<0.05)。随访脓毒症患者1个月后预后情况,55例存活,31例死亡。死亡组患者APACHEⅡ评分、SOFA评分、PCT、TNF-α、IL-1β、FRT高于存活组患者,而VitD、HB-EGF低于存活组患者,差异均有统计学意义(均P<0.05)。Pearson相关性分析结果显示,VitD与APACHEⅡ评分、SOFA评分、白细胞计数、CRP、PCT、TNF-α呈负相关关系(均P<0.05);HB-EGF与APACHEⅡ评分、CRP、PCT、TNF-α、IL-6、IL-1β呈负相关关系(均P<0.05);FRT与APACHEⅡ评分、CRP、PCT、TNF-α、IL-6、IL-1β呈正相关关系(均P<0.05)。血清VitD、FRT、HB-EGF联合检测预测脓毒症患者预后的AUC为0.82(95%CI:0.72~0.86),灵敏度为84.39%,特异度为69.35%。结论 脓毒症患者血清VitD、HB-EGF水平较低,FRT水平较高,其表达水平与患者预后密切相关,对预测脓毒症患者预后具有较好预测价值。

川芎嗪联合低分子肝素钙对妊娠期子痫前期孕妇sFlt-1、VEGF、PLGF、ET-1水平及妊娠结局的影响

目的:探讨妊娠期子痫前期孕妇采用川芎嗪联合低分子肝素钙治疗对其血清可溶性FMS样酪氨酸激酶-1(Soluble fms-like tyrosine kinase-1,sFlt-1)、血管内皮细胞生长因子(Vascular endothelial growth factor,VEGF)、胎盘生长因子(Placental growth factor,PLGF)、内皮素-1(Endothelin-1,ET-1)水平及妊娠结局的影响。方法:选取2022年1月至2023年1月我院收治的102例妊娠期子痫前期孕妇开展前瞻性研究,将102例孕妇随机分为参照组(51例)、联合组(51例)。参照组采用低分子肝素钙治疗,联合组采用低分子肝素钙+川芎嗪治疗。对比两组治疗前后舒张压、收缩压、平均动脉压、24 h尿蛋白定量、血浆D-二聚体(D-dimer,D-D)、纤维蛋白原(Fibrinogen,FIB)、凝血酶时间(Thrombin time,TT)、凝血酶原时间(Prothrombin time,PT)、血清sFlt-1、VEGF、PLGF、ET-1水平,以及两组终止妊娠孕周、新生儿体质量、Apgar评分、新生儿窒息占比。结果:治疗后联合组舒张压、收缩压、平均动脉压、24 h尿蛋白定量、血浆D-D、FIB、血清sFlt-1、ET-1水平低于治疗前、参照组,血浆TT、PT、血清VEGF、PLGF水平高于治疗前、参照组;联合组终止妊娠孕周长于参照组,新生儿体质量、Apgar评分高于参照组(P<0.05);两组新生儿窒息占比差异无统计学意义。结论:川芎嗪联合低分子肝素钙治疗可降低妊娠期子痫前期孕妇血压水平,减少尿蛋白,改善凝血功能,减轻内皮损伤,从而延长孕周、提高新生儿体质量、Apgar评分,可为临床治疗妊娠期子痫前期提供参考依据。

宫颈高危型HPV感染对阴道微生态失衡及HB-EGF和EGFR表达的影响

目的探讨宫颈高危型人乳头瘤病毒(HPV)感染患者血清肝素结合性表皮生长因子(HB-EGF)、表皮生长因子受体(EGFR)表达水平以及患者阴道微生态失衡情况。方法选取2020年4月至2022年5月于河北省石家庄市人民医院就诊的169例宫颈炎患者作为研究对象,根据患者是否感染高危型HPV分为实验组(感染高危型HPV)88例、对照组(未感染高危型HPV)81例,收集整理所有患者的临床资料。检测实验组高危型HPV感染亚型,检测并比较两组患者阴道菌群分布状态和微生态平衡状态,检测两组血清HB-EGF和EGFR表达水平并进行比较,采用Spearman相关性分析高危型HPV感染与血清HB-EGF、EGFR水平及阴道微生态的相关性,采用Logisitic回归分析高危型HPV感染的影响因素。结果高危型HPV感染检测结果显示,HPV16检出率最高,其次是HPV18;实验组患者血清HB-EGF、EGFR表达水平显著高于对照组(t=12.653、9.208,P<0.05);实验组衣原体、细菌性阴道炎、解脲脲原体、乳酸杆菌异常和阴道微生态失衡所占比例显著高于对照组(χ^(2)=6.396、5.581、8.025、4.254、9.433,P<0.05);高危型HPV感染与血清HB-EGF及EGFR表达水平、衣原体、乳酸杆菌异常、细菌性阴道炎、解脲脲原体均呈正相关(r=0.382、0.417、0.376、0.516、0.449、0.391,P<0.05);乳酸杆菌异常、EGFR表达水平、HB-EGF表达水平是高危型HPV感染的影响因素(P<0.05)。结论高危型HPV感染患者血清HB-EGF、EGFR水平上调,高危型HPV感染会加重阴道微生态失衡,增加宫颈病变的风险。

大豆异黄酮对先兆流产模型大鼠的保胎作用及机制研究

目的 研究大豆异黄酮对先兆流产大鼠的保胎作用及可能机制。方法 取雌鼠促情,与雄鼠交配、妊娠后随机分为正常组(纯化水灌胃,n=10)、模型组(纯化水灌胃,n=9)、阳性对照药组(黄体酮4 mg/kg,肌内注射,n=9)和大豆异黄酮低、中、高剂量组(25、50、100 mg/kg灌胃,n=10)。除正常组外,其余各组大鼠均于孕8 d以米非司酮+米索前列醇灌胃建立先兆流产模型。各组大鼠分别于孕1~7 d、孕9~12 d给药/纯化水,每天1次。孕14 d时,计算各组大鼠的保胎率,检测大鼠血清中β-人绒毛膜促性腺激素(β-HCG)、孕酮(P)水平,观察大鼠胎盘与蜕膜组织病理形态学变化并检测其细胞凋亡指数,检测胎盘组织中凋亡相关因子(Fas)、凋亡相关因子配体(FasL)、增殖细胞核抗原(PCNA)和肝素结合表皮生长因子(HB-EGF) mRNA及其蛋白表达,检测蜕膜组织中Fas、PCNA和HB-EGF mRNA及其蛋白表达。结果 模型组大鼠胎盘组织充血扩张明显,血管较少且形态不规则,可见大量严重基质水肿、炎症细胞浸润和铁胆黄素沉积。与模型组比较,大豆异黄酮各剂量组大鼠的保胎率,血清β-HCG、P水平,胎盘与蜕膜组织中PCNA、HB-EGF mRNA及其蛋白表达水平均显著升高(P<0.05),病理学变化显著改善;胎盘与蜕膜组织细胞凋亡指数,胎盘组织中Fas、FasL mRNA及其蛋白表达水平,蜕膜组织中Fas mRNA及其蛋白表达水平均显著降低(P<0.05),且大豆异黄酮的上述作用呈剂量依赖性(P<0.05)。结论 大豆异黄酮对先兆流产模型大鼠有保胎作用;其作用机制可能与下调母-胎界面Fas、FasL mRNA及其蛋白表达,上调PCNA、HB-EGF mRNA及其蛋白表达有关。

老年重症肺炎合并呼吸衰竭患者血清DcR3、GDF-15、HBP水平及其对病情、预后的影响

目的 探究老年重症肺炎(SP)合并呼吸衰竭(RF)患者血清诱骗受体3(DcR3)、生长分化因子-15(GDF-15)、肝素结合蛋白(HBP)水平及其对病情、预后的影响。方法 选取2020年9月—2022年2月在本院就诊治疗的老年SP合并RF患者128例为观察组研究对象,根据病情严重程度将其分为低危组42例、中危组54例和高危组32例,再根据预后情况将其分为生存组98例和死亡组30例;另选取同期在本院就诊治疗的未合并RF的老年SP患者128例为对照组研究对象。采用酶联免疫吸附法(ELISA)测定血清DcR3、GDF-15、HBP、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平;采用Pearson分析老年SP合并RF患者血清DcR3、GDF-15、HBP与TNF-α、IL-6、APACHEⅡ评分的相关性;采用多因素logistic回归分析老年SP合并RF患者死亡的影响因素;采用受试者工作特征(ROC)曲线评价血清DcR3、GDF-15、HBP水平在预测老年SP合并RF患者预后中的应用价值。结果 观察组血清DcR3、GDF-15、HBP水平较对照组均显著升高(P<0.05);老年SP合并RF患者血清DcR3、GDF-15、HBP水平随患者病情严重程度加重而呈现逐渐升高趋势(P<0.05);死亡组老年SP合并RF患者血清DcR3、GDF-15、HBP、TNF-α、IL-6水平以及APACHEⅡ评分较生存组均显著升高(P<0.05);Pearson相关分析显示,老年SP合并RF患者血清DcR3、GDF-15、HBP水平与TNF-α、IL-6、APACHEⅡ评分均呈正相关(P<0.05);多因素Logistic回归分析显示,高水平DcR3、GDF-15、HBP均为老年SP合并RF患者死亡的独立危险因素(P<0.05);ROC曲线分析显示,血清DcR3、GDF-15、HBP水平预测老年SP合并RF患者死亡的曲线下面积(AUC)分别为0.843、0.841、0.804,三者联合预测的AUC为0.943,均优于其单独预测(Z=2.258、2.303、2.653,P<0.05)。结论 老年SP合并RF患者血清DcR3、GDF-15、HBP水平均显著升高,且随其病情严重程度加重而升高,三者联合在预测老年SP合并RF患者预后中具有重要价值。

Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor

The ability to maintain functional hepatocytes has important implications for bioartificial liver development,cell-based therapies,drug screening,and tissue engineering.Several approaches can be used to restore hepatocyte function in vitro,including coating a culture substrate with extracellular matrix(ECM),encapsulating cells within biomimetic gels(Collagen-or Matrigel-based),or co-cultivation with other cells.This paper describes the use of bioactive heparin-based core-shell microcapsules to form and cultivate hepatocyte spheroids.These microcapsules are comprised of an aqueous core that facilitates hepatocyte aggregation into spheroids and a heparin hydrogel shell that binds and releases growth factors.We demonstrate that bioactive microcapsules retain and release endogenous signals thus enhancing the function of encapsulated hepatocytes.We also demonstrate that hepatic function may be further enhanced by loading exogenous hepatocyte growth factor(HGF)into microcapsules and inhibiting transforming growth factor(TGF)-β1 signaling.Overall,bioactive microcapsules described here represent a promising new strategy for the encapsulation and maintenance of primary hepatocytes and will be beneficial for liver tissue engineering,regenerative medicine,and drug testing applications.

低分子肝素钠联合拉贝洛尔治疗妊娠期高血压疾病的效果

目的探讨低分子肝素钠联合拉贝洛尔治疗妊娠期高血压疾病的效果。方法选取本院收治的60例妊娠期高血压疾病患者为研究对象,按照随机数字表法分为两组,各30例。对照组应用拉贝洛尔治疗,试验组应用低分子肝素钠联合拉贝洛尔治疗,比较两组治疗前后的妊娠期高血压相关指标、子宫血流动力学指标及胎盘生长因子水平。结果治疗后,试验组平均动脉压、血尿素氮、尿酸、收缩压、舒张压水平均低于对照组,差异有统计学意义(P<0.05);治疗后,试验组搏动指数、阻力指数、脐动脉收缩压与舒张压比值均低于对照组,差异有统计学意义(P<0.05);治疗后,试验组妊娠相关血浆蛋白A水平低于对照组,血管内皮细胞生长因子、胎盘生长因子水平高于对照组,差异有统计学意义(P<0.05)。结论低分子肝素钠联合拉贝洛尔治疗妊娠期高血压疾病,可有效改善患者的血压相关指标、子宫血流动力学指标及胎盘生长因子水平,值得推广。

成纤维细胞生长因子2和尿肝素结合蛋白在产后尿路感染诊断中的应用价值及影响因素分析

目的:分析成纤维细胞生长因子2(FGF2)和尿肝素结合蛋白(U-HBP)在产后尿路感染诊断中的应用价值及影响因素。方法:选取2021年3月—2023年8月临海市中医院收治的210例产妇为研究对象,根据是否发生产后尿路感染将其分为尿路感染组(n=36)和非尿路感染组(n=174)。比较两组临床资料,分析影响产后尿路感染的因素,采用受试者工作特征(ROC)曲线分析FGF2、U-HBP早期诊断产后尿路感染的价值。结果:尿路感染组患者体质量指数、既往患尿路感染、患妊娠期糖尿病、FGF2、U-HBP水平高于非尿路感染组,差异有统计学意义(P<0.05)。Logistic回归分析结果显示,体质量指数、妊娠期糖尿病、FGF2、U-HBP是影响产后尿路感染的主要因素(P<0.05)。FGF2、U-HBP以及两者联合检测早期诊断产后尿路感染的ROC曲线下面积分别为0.713、0.930、0.952。结论:FGF2、U-HBP是产后尿路感染的危险因素,可作为早期诊断产后尿路感染的生物学标志物。

Low molecular weight heparin suppresses lymphatic endothelial cell proliferation induced by vascular endothelial growth factor C in vitro

Background Pancreatic cancer is one of the most aggressive human malignancies. Lymphangiogenesis plays an important role in lymph node metastasis of many solid tumors. It is well known that low molecular weight heparins （LMWHs） can inhibit cell growth, cell invasion and angiogenesis, which are key processes in tumor progression. Methods We measured the expression of vascular endothelial growth factor C （VEGF-C） in pancreatic cancer cells （PANC-1） using reverse transcription-polymerase chain reaction （RT-PCR） and Western blotting. We used an in vitro assay to evaluate the anti-lymphangiogenic effect of an LMWH, Fragmin, on human lymphatic endothelial cell （HLEC） proliferation. Results Fragmin at a low concentration can effectively inhibits HLEC proliferation induced by VEGF-C. VEGF-C secreted by PANC-1 cells stimulated HLEC proliferation. Low concentration LMWH suppressed HLEC proliferation induced by VEGF-C but did not affect proliferation or VEGF-C expression of PANC-1 cells, whereas high concentrations of LMWH inhibited PANC-1 cell proliferation. Conclusions These results suggest that VEGF-C released by cancer cells plays an important role in promoting HLEC proliferation. The LMWH Fragmin has anti-lymphangiogenic effects and may inhibit lymphatic metastasis in pancreatic cancer.

Binding of EGF1 Domain Peptide in Coagulation Factor Ⅶ with Tissue Factor and Its Implications for the Triggering of Coagulation

The binding function of EGF1 domain peptide with tissue factor(TF)and its ability of triggering coagulation were explored.The TF expression model in vitro was established by lipopolysaccha-ride induction.The affinity of EGFP-EGF1 and TF expressing cells was analyzed by fluorescence microscopy and flow cytometry(FCM).The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface plasmon resonance(SPR).The ability of EGFP-EGF1 in triggering coagulation was tested by prothrombin time assay.The FCM res...

Low-Molecular-Weight Heparin and Protamine-Based Polyelectrolyte Nano Complexes for Protein Delivery (A Review Articles)

We produced low-molecular-weight heparin/protamine micro (nano) particles (LMW-H/P MPs·NPs) as a carrier for heparin-binding growth factors (GFs), such as fibroblast growth factor (FGF)-2 and various GFs in platelet-rich plasma (PRP). A mixture of LMW-H (MW: approximately 5000 Da, 6.4 mg/ml) and protamine (MW: approximately 3000 Da, 10 mg/ml) at a ratio of 7:3 (vol:vol) yields a dispersion of micro (nano) particles (200 nm - 3 μm in diameter). The diluted LMW-H solution in saline (0.32 mg/ml) mixed with diluted protamine (0.5 mg/ml) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (approximately 100 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/ml dextran (MW: 178-217 kDa) and remained soluble after lyophilization of dialyzed LMW-H /P NPs solution. The LMW-H/P MPs·NPs adsorb GFs, control their release, protect GFs and activate their biological activities. Furthermore, administration of GFs-containing F/P MPs·NPs exhibited significantly higher inductions of vascularization and fibrous tissue formation in vivo than GFs alone. LMW-H/P MPs·NPs can also efficiently bind to tissue culture plates and retain the binding of GFs. The LMW-H/P MPs·NP-coated matrix with various GFs or cytokines provided novel biomaterials that could control cellular activity such as proliferation and differentiation. Thus, LMW-H/P MPs·NPs are an excellent carrier for GFs and are a functional coating matrix for various kinds of cell cultures.

脓毒症患者肝素结合性表皮生长因子、降钙素原、血管性血友病因子、高迁移率族蛋白B1表达及与病情进展及预后关系

目的探讨肝素结合性表皮生长因子(HB-EGF)、降钙素原(PCT)、血管性血友病因子(vWF)、高迁移率族蛋白B1(HMGB1)在脓毒症患者中的表达,及4种因子与脓毒症病情发展和预后的关系。方法选取自2020年9月至2022年4月收治的150例脓毒症患者为研究对象,基于脓毒症严重程度分为脓毒症组(n=74)与脓毒症休克组(n=76),且依据不同预后将脓毒症患者分为存活组(n=107)与死亡组(n=43);同时,随机选取同期行常规体检的75例健康者为健康组。分析各组HB-EGF、PCT、vWF、HMGB1表达水平,观察脓毒症两组急性生理学与慢性健康状况评分系统(APACHEⅡ)和序贯器官衰竭(SOFA)评分;分析HB-EGF、PCT、vWF、HMGB1与APACHEⅡ及SOFA的相关性;分析HB-EGF、PCT、vWF、HMGB1及联合检测对脓毒症的诊断价值;二元Logistic方程分析脓毒症患者死亡的影响因素。结果健康组HB-EGF水平显著高于脓毒症两组,且脓毒症休克组HB-EGF水平最低,PCT、vWF、HMGB1水平健康组最低,脓毒症休克组明显高于脓毒症组;存活组HB-EGF水平显著高于死亡组,但PCT、vWF、HMGB1水平明显低于死亡组;健康组、脓毒症组及脓毒症休克组APACHEⅡ及SOFA均依次降低,差异均有统计学意义(P<0.05)。HB-EGF与APACHEⅡ及SOFA均呈负相关,PCT、vWF、HMGB1与APACHEⅡ及SOFA均呈正相关。HB-EGF、PCT、vWF、HMGB1及联合检测对脓毒症的诊断敏感度分别为76.52%、67.79%、70.44%、69.54%、93.56%,特异度分别为68.99%、77.32%、71.76%、72.96%、88.78%。HB-EGF、PCT、vWF、HMGB1与APACHEⅡ均为脓毒症患者死亡的独立危险因素(P<0.05)。结论HB-EGF、PCT、vWF、HMGB1在不同脓毒症患者中均有不同表达,且与预后具有一定相关性;同时,HB-EGF、PCT、vWF、HMGB1指标对脓毒症均有一定诊断价值,但四者联合诊断价值更高。

血清HB-EGF和SAA水平对高血压患者颈动脉粥样硬化的诊断价值

[目的]研究血清肝素结合性表皮生长因子(HB-EGF)、血清淀粉样蛋白A(SAA)对高血压患者颈动脉粥样硬化(CAS)的诊断价值。[方法]选取高血压患者100例,根据颈动脉内膜中膜厚度(CIMT)诊断结果将其分为高血压组(n=42)、高血压CAS组(n=58);另选取同期体检的健康受试者50例,设为健康对照组。比较健康对照组、高血压组和高血压CAS组血清HB-EGF、SAA水平及CIMT;采用Pearson相关分析法分析100例高血压患者血清HB-EGF、SAA水平与CIMT的相关性;采用Logistic回归分析法分析CAS的危险因素;采用ROC曲线分析血清HB-EGF、SAA水平对高血压患者CAS的诊断价值。[结果]与健康对照组比较,高血压组和高血压CAS组血清HB-EGF、SAA水平显著升高(P<0.05),CIMT显著增加(P<0.05)。与高血压组比较,高血压CAS组血清HB-EGF、SAA水平显著升高(P<0.05),CIMT显著增加(P<0.05)。Pearson相关分析显示,血清HB-EGF、SAA水平与CIMT均表现为正相关(r=0.807,95%CI:0.7257~0.8662,P<0.001;r=0.765,95%CI:0.6688~0.8357,P<0.001)。Logistic回归分析显示,高HB-EGF、高SAA均是高血压患者发生CAS的危险因素(P<0.05)。ROC曲线分析显示,血清HB-EGF、SAA水平诊断CAS的最佳截断点分别为19.84μg/L、8.97 mg/L,两者单独及联合诊断CAS的AUC分别为0.811、0.810、0.875,两者联合诊断的价值高于单独诊断。[结论]血清HB-EGF、SAA水平在高血压CAS患者中显著升高,两者与CIMT均为正相关,且对高血压CAS具有较高的诊断效能。

血清肝素结合表皮生长因子mRNA与急性冠脉综合征的关系

目的 观察分析血清肝素结合表皮生长因子(HB-EGF)信使核糖核酸(mRNA)与急性冠脉综合征(ACS)的关系,探讨血清HB-EGF mRNA对ACS发病的预测价值及发病早期的诊断价值。方法 收集青海省人民医院急诊科2019年12月至2022年3月收治的经冠脉造影(CAG)确诊为ACS患者113例,分为急性心肌梗死(AMI)组58例和不稳定型心绞痛(UA)组55例,以同期在门急诊或体检时经CAG或冠脉CT检查无狭窄并有含高血压、糖尿病或吸烟的人群51例为对照组。采用实时荧光定量聚合酶链式反应(RT-qPCR)检测ACS患者血清HB-EGF mRNA的表达水平。运用多元有序Logistic回归分析HB-EGF mRNA与ACS的关系。根据Gensini不同评分将ACS患者分为低分组(n=34)、中分组(n=56)和高分组(n=23),比较三组患者血清HB-EGF mRNA水平,并分析两组ACS患者血清HB-EGF mRNA与冠脉病变程度之间的相关性。应用ROC曲线下面积(AUC)评估血清HB-EGF mRNA对ACS患者的诊断价值。结果 多元有序Logistic回归分析显示,HB-EGF mRNA是ACS的危险因素(OR=10.994, 95%CI4.005~30.182,P<0.001)。血清HB-EGF mRNA水平低分组<中分组<高分组(P<0.05)。UA组(r_(s)=0.667,P<0.001)和AMI组(r_(s)=0.857,P<0.001)血清HB-EGF mRNA与冠脉病变程度呈正相关。UA组和AMI组血清HB-EGF mRNA的AUC分别为0.911和0.979(P值均<0.001),以约登指数最大值所对应的值为最佳截断值,得到最佳工作点(optimal operating point, OOP)分别为1.68和2.14。结论 血清HB-EGF mRNA升高与ACS有关,HB-EGF mRNA在动脉粥样硬化的发生、发展中可作为一个独立的危险因子。