AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepi...AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.展开更多
BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammato...BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.展开更多
Objective:The aim of this study is to investigate the effects of Hepatocyte Growth Factor(HGF)on the expression levels of IL-8,TNF-α,IL-4,and IL-21 in mice with liver injury induced by CCL_(4).Methods:An acute liver ...Objective:The aim of this study is to investigate the effects of Hepatocyte Growth Factor(HGF)on the expression levels of IL-8,TNF-α,IL-4,and IL-21 in mice with liver injury induced by CCL_(4).Methods:An acute liver injury mouse model was established using CCL_(4),and hepatocytes and white blood cells were separated by gradient density centrifugation.Different concentrations of HGF were added in vitro,and the expression levels of cytokines were detected using ELISA.Results:In the in vivo injury model,the hepatocyte experiment results showed that the expression level of IL-8 was reduced in the 10 ng/mL HGF group compared to the injured hepatocyte group(P<0.05),and increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.05).For IL-4,the expression levels were reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the injured hepatocyte group.The white blood cell experiment results showed that the expression levels of TNF-αwere reduced in both the 10ng/ml HGF group(P<0.05)and the 25 ng/mL HGF group(P<0.05)compared to the injured white blood cell group.In the in vitro injury model,hepatocyte experiment results showed that the expression levels of TNF-αwere reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the normal control group.For IL-4,the expression level was reduced in the 25 ng/mL HGF group compared to the normal control group(P<0.05).The white blood cell experiment results showed that the expression level of TNF-αwas increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.001);for IL-21,the expression levels were reduced in the CCL_(4) model group(P<0.05),10 ng/mL HGF group(P<0.05),25 ng/mL HGF group(P<0.05),and 50 ng/mL HGF group(P<0.05)compared to the normal control group.Conclusion:when the liver of mice is acutely damaged by CCL_(4),HGF can reduce the expression levels of inflammatory cytokines IL-8,TNF-α,IL-4 in hepatocytes,and TNF-αin liver white blood cells.展开更多
AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility wer...AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility were investigated in two human CCA cell lines,HuCCA-1 and KKU-M213,using Transwell in vitro assay.Levels of proteins of interest and their phosphorylated forms were determined by Western blotting.Localization of E-cadherin was analyzed by immunofluorescence staining and visualized under confocal microscope. Activities of matrix degrading enzymes were determined by zymography. RESULTS:Both CCA cell lines expressed higher Met levels than the H69 immortalized cholangiocyte cell line.HGF induced invasion and motility of the cell lines and altered E-cadherin from membrane to cytoplasm localization,but did not affect the levels of secreted matrix metalloproteinase(MMP) -2,MMP-9 andurokinase plasminogen activator,key matrix degrading enzymes involved in cell invasion.Concomitantly,HGF stimulated Akt and extracellular signal-regulated kinase(ERK) 1/2 phosphorylation but with slightly different kinetic profiles in the two cell lines.Inhibition of the phosphoinositide 3-kinase(PI3K) /Akt pathway by the PI3K inhibitor,LY294002,markedly suppressed HGFstimulated invasion of both CCA cell lines,and inhibition of the ERK pathway by U0126 suppressed HGF-induced invasion of the KKU-M213 cell line but had a moderate effect on HuCCA-1 cells. CONCLUSION:These data indicate that HGF promotes CCA cell invasiveness through dys-localization of E-cadherin and induction of cell motility by distinct signaling pathways depending on cell line type.展开更多
Summary: Angiogenic gene therapy and cell-based therapy for peripheral arterial disease (PAD) have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells (MSCs...Summary: Angiogenic gene therapy and cell-based therapy for peripheral arterial disease (PAD) have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells (MSCs)transplantation with ex vivo human hepatocyte growth factor (HGF) gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley (SD) rats were randomized to receive HGF gene-modified MSCs transplantation (HGF-MSC group), untreated MSCs transplantation (MSC group), or PBS injection (PBS group), respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.展开更多
This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property o...This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property of FK506. Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by bilateral transection of sciatic nerve 0.5 cm distal to piriform muscle. Then the treatment group received subcutaneous injection of FK506 (1 mg/kg) at the back of neck, while the injury group was given 0.9% saline. The L4-6 spinal cords were harvested at various time points after the surgery. Western blotting and immunofluorescent staining were used to detect the level and position of HGF in spinal cord. Immunofluorescent staining showed that HGF-positive neurons were located in anterior horn, intermediate zone and posterior horn of gray matter in normal spinal cord. Western blotting revealed that there was no significant difference in the expressions of HGF between the injury group and the normal group, while the expression of HGF was significantly higher in the treatment group than in the injury group 7 and 14 days after surgery. It is suggested that peripheral nerve injury does not result in up-regulation of the expression of HGF in spinal cord, while FK506 may induce high expression of endogenous HGF after injury thereby protecting neurons and promoting axonal outgrowth.展开更多
Objective To investigate the effects of hepatocyte growth factor(HGF)on vascular endothelial cells apoptosis induced by advanced glycation end products(AGEs)and its possible mechanism. Methods Human umbilical vein end...Objective To investigate the effects of hepatocyte growth factor(HGF)on vascular endothelial cells apoptosis induced by advanced glycation end products(AGEs)and its possible mechanism. Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and intervened by different concentrations of AGEs and HGF.The cell inhibitory rates of each group with different culture time(12, 24, 48, and 72 hours)were measured by methyl thiazolyl tetrazolium(MTT)assay. The early stage apoptosis was detected by flow cytometry with Annexin V-FITC/PI double staining, morphology of cell apoptosis was observed by hoechst 33258 fluorescence staining, and the expression of apoptosis-associated genes Bax and Bcl-2 were determined by Western blotting.The activity of caspase-3 was detected by enzyme-linked immunosorbent assay (ELISA).Results Morphological observation indicated that high concentration of AGEs induced characteristic apoptotic changes in HUVECs.Within a certain concentration range, HUVECs apoptosis inducing rates by AGEs were in both dose- and time-dependent manners.HGF significantly inhibited the apoptosis of HUVECs induced by AGEs (P< 0.05).AGEs significantly promoted expression of Bax protein, but not Bcl-2.Whereas HGF significantly promoted the expression of Bcl-2(P<0.01)and decreased the activity of caspase-3(P<0.05)without affecting Bax level.Conclusions AGEs can induce the apoptosis of endothelial cells in vitro.HGF may effectively attenuate AGEs-induced endothelial cells apoptosis through upregulating Bcl-2 gene expression and inhibiting caspase-3 activation.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertensi...BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertension(GH)in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses.Currently,the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests,and blood pressure test is usually used for the screening and diagnosis of hypertension.However,these criteria might not anticipate or detect all GDM or GH cases.Therefore,new specific predictive and diagnostic tools should be evaluated for this population.This study selected three biomarkers of osteoprotegerin(OPG),interleukin(IL)and hepatocyte growth factor(HGF)for GDM and GH predication and diagnosis.AIM To explore the feasibility of changes in placental and serum OPG,IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women.METHODS From January 2018 to January 2019,44 pregnant women with GDM and GH were selected as an observation group,and 44 healthy pregnant women were selected as a control group in the same period.Serum OPG,IL and HGF were compared between the two groups.RESULTS The levels of OPG and HGF in the observation group were lower than in the control group,and the level of IL-1βwas higher in the observation group than in the control group(all P<0.05).Furthermore,OPG and HGF were negatively associated with gestational diabetes and gestational hypertension,while IL-1βwas positively associated with GDM complicated with GH(all P<0.05).CONCLUSION The evaluation of serum OPG,HGF and IL-1βlevels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.展开更多
BACKGROUND: Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new...BACKGROUND: Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new vessels and form collateral circulation. OBJECTIVE: To observe histopathological changes in the femoral and intramuscular nerve three months after intramuscular injection of hepatocyte growth factor (HGF) into the peripheral skeletal muscle in a canine model of lower limb ischemia. DESIGN: Randomized occlusion modelled and verification animal study. SETTING: Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA. MATERIALS: This study was performed at Animal Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from September to November 2006. A total of eight male mongrel dogs, weighing 12–15 kg and 1.5–3 years of age, were selected for this study. This experimental study was in accordance with local ethics standards. Recombinant plasmid carrying HGF (pUDKH) and occlusion model plasmid (pUDK) were provided by the Third Laboratory of Radiation Medical Institute, Academy of Military Medical Sciences of PLA. METHODS: Grouping and model establishment: under anesthesia, complete vascular occlusion models were established on the left lower extremities. The experimental dogs were randomly divided into a model group and a pUDKH treatment group, with four dogs in each group. Dogs in the pUDKH group were injected with 0.15 mg/kg pUDKH. Ten minutes later, intramuscular injections were performed at three spots into the peripheral skeletal muscle of the left hind limb, as well as lateral injections at two spots. The injection volume at each spot was 0.2 mL. Dogs in the model group were injected with pUDK, and dosage and injection method were identical to the treatment group. MAIN OUTCOME MEASURES: Histopathological changes in the femoral nerve, as well as internal and external intramuscular nerve tissues in the hind limb of dogs three months after plasmid injection under optic microscope. RESULTS: (1) Histopathological changes in the femoral nerve: tiny nerves from the femoral nerve to the intramuscular nerve exhibited marked degeneration in the model group. The degenerating features included neurites, myelin sheaths, and Schwann cell nuclei. Neuropathy in the pUDKH treatment group was not detected. (2) Histopathological changes of the intramuscular nerve: large and irregular vacuoles were present on several longitudinal sections of intramuscular nerve fibers in the model group, as well as annular-shaped blank regions on transverse sections of peripheral neurites. In the pUDKH treatment group, large, blank regions were present in several segments of partial nerve fibers of the longitudinal intramuscular nerve region, but only a few nerve fibers exhibited annular-shaped blank regions on the transverse section of peripheral neurites. CONCLUSION: Local pUDKH injection may relieve or block femoral and intramuscular nerve tissue injury in a canine mocel of lower limb ischemia.展开更多
Objective: To study the amelioration effect of AdenovirusS-mediated human hepatocyte growth factor (AdsHGF) on postinfarction heart failure in the swine myocardial infarction model. Methods: Twelve SuZhong young s...Objective: To study the amelioration effect of AdenovirusS-mediated human hepatocyte growth factor (AdsHGF) on postinfarction heart failure in the swine myocardial infarction model. Methods: Twelve SuZhong young swine were randomly divided into 2 groups with 6 swine in each group: Ad5-HGF-treated group and null-Ad5 group. Four weeks after ligation at left anterior descending coronary artery in swine hearts, Ad5-HGF was transferred to the swine myocardium. Simultaneously, Gated myocardial perfusion imaging was performed to evaluate cardiac perfusion and heart function. After three weeks, Gated myocardial perfusion imaging was performed again, then the hearts were harvested and sectioned to examine the expression of HGF through ELISA. Results: High expression of human HGF was observed in the myocardium of Ad5-HGF-treated group. From 4 weeks to 7 weeks after operation, Left ventricular ejection fraction was increased in Ad5-HGF-treated group. The improvement in LVEF was greater in Ad5-HGF-treated group than that in null-Ad5 group at 7 weeks after operation. Cardiac perfusion was significantly improved in the Ad5-HGF-treated group. Conclusion: High expression of human HGF was observed in the myocardium through intracoronary transfection, which suggests that HGF can ameliorate heart function in swine with postinfarction heart failure.展开更多
The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of t...The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF.Herein,this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGF^(K119Q) and hbFGF^(K119E),respectively.The mutants were produced by BL21(DE3)/pET3c expression system...展开更多
Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reporte...Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reported a female patient who suffered wound rupture due to early post-operation mobilization and weight-bearing. The wound dehiscence was successfully managed by applying recombinant basic fibroblast growth factor-2 and anti-infective treatment without removing prosthetic joint.展开更多
Human hepatocyte growth factor can be used to treat cerebral infarction, administered by lateral ventricular, cerebellomedullary cistern or subarachnoid injections. However, the target gene ex-pression product is scar...Human hepatocyte growth factor can be used to treat cerebral infarction, administered by lateral ventricular, cerebellomedullary cistern or subarachnoid injections. However, the target gene ex-pression product is scarcely found in the ischemic penumbra, but extensively distributes in other regions, increasing the risks of gene therapy. The present study directly transfected hepatocyte growth factor gene into the ischemic penumbra of rats with transient middle cerebral artery occlusion. Immunohistochemical analysis revealed that infarct volume was significantly decreased, hepatocyte growth factor protein expression level and vessel quantity in the ischemic penumbra were significantly increased, and learning and memory were significantly improved.展开更多
Objective To research whether serum hepatocyte growth factor(HGF)level increases in ischemic stroke and hemorrhagic stroke,and explore the relationship between the serum HGF level and stroke recurrence.Methods We stud...Objective To research whether serum hepatocyte growth factor(HGF)level increases in ischemic stroke and hemorrhagic stroke,and explore the relationship between the serum HGF level and stroke recurrence.Methods We studied a total of 92 consecutive acute stroke patients who had been admitted to hospital within 24h of onset from 6 participating hospitals in Xi’an from January 2000 to May 2004.All patients were divided into ischemic stroke group and hemorrhagic stroke group according to the results of brain computed tomography(CT)scan or MRI on admission.Patients in stroke groups were divided into recurrent group and non-recurrent group.Healthy volunteers or patients without cerebrovascular diseases comprised the control group.Stroke and control groups were strictly matched with 1∶1 ratio.The patients were followed up for 4 years.Serum HGF was tested with enzyme-linked immunosorbent assay(ELISA).Results Serum HGF of stroke patients was significantly higher than that of control group(P<0.05).The serum HGF level in recurrent group was higher than that in non-recurrent group of ischemic patients,and there was no significant difference in hemorrhagic ones.Conclusion These results indicate that serum HGF may be used as a diagnostic marker for stroke,and serum HGF level is helpful in predicting the recurrence of ischemic stroke.展开更多
Objective:To construct the adenoviral expression vector system containing human hepatocyte growth factor (hHGF) cDNA, and to further study the transduction efficiency and the expression of HGF in mesenchymal stem c...Objective:To construct the adenoviral expression vector system containing human hepatocyte growth factor (hHGF) cDNA, and to further study the transduction efficiency and the expression of HGF in mesenchymal stem cells (MSCs). Methods:The HGF cDNA was amplificated from the expression plasmid pCMV-HGF, and was subcloned into the adenovirus shuttle plasmid pDC316-IRESEGFP vector containing a green fluorescence protein (GFP) reporter gene. Virus Ad-HGF was produced by homologous recombination in HEK293 package cells. Bone marrow derived MSCs were harvested and cultured, and then were transduced with Ad-HGF. The efficiency of Ad-HGF transduction was assessed by FACS analysis using GFP gene expression. And HGF/MSCs were generated. The HGF concentrations in supernatants of HGF/MSCs were determined by ELISA using anti-human HGF monoclonal antibody. Results: The recombinant, named pDC316-HGF-IRES-eGFP, was digested with restriction enzyme, and the DNA sequencing of HGF was identical to the report in Genebank and did not reveal any mutation. GFP expression could be observed on the second day after packing of the linearized pAd-HGF in HEK293 cells and 7.15 × 10^10pfu/ml titer of Ad-HGF was obtained. Forty-eight hours after transduction, 96.89% of HGF/MSCs were GFP positive. Peak concentration levels of hHGF(103ng/mL) in the cultured supernatants were detected on day 2 post-transduction, and the adenovirus-mediated expression of HGF by MSCs was maintained for at least 2 weeks in vivo. Conclusion:Our data demonstrated that the adenovirus expression'vector system pDC316-HGF-IRES-EGFP has been constructed successfully, and their effective expressions also have been obtained in MSCs. This will provide material basis for the next study on liver regeneration after small-for-size liver transplantation.展开更多
<b><span style="font-family:Verdana;">Background: </span></b><span style="font-family:Verdana;">Hepatocellular carcinoma is the third leading cause of tumor </span&...<b><span style="font-family:Verdana;">Background: </span></b><span style="font-family:Verdana;">Hepatocellular carcinoma is the third leading cause of tumor </span><span style="font-family:Verdana;">related mortality and develops mostly in patients with chronic liver disease and</span><span style="font-family:;" "=""> <span style="font-family:Verdana;">liver cirrhosis. Human hepatocyte growth factor (HGF) is produced in various</span> <span style="font-family:Verdana;">organs of the body and is characterized as a multifunctional factor with vari</span><span style="font-family:Verdana;">ous biologic activities. </span><b><span style="font-family:Verdana;">Aim:</span></b><span style="font-family:Verdana;"> Our aim was to investigate the predictive factors of </span><span style="font-family:Verdana;">recurrence specially the role of HGF in patients with HCC treated with TACE. </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> one hundred HCC patients treated by TACE who </span><span style="font-family:Verdana;">achieved complete response were included and divided into two groups a</span><span style="font-family:Verdana;">ccording to disease free survival (DFS) status at 1 year: the non</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">early recurrence</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> (NER) group (1) and the early recurrence (ER) group (2). Univariate binary logistic regression analysis for the possible risk factors of recurrence showed that AFP, multinodularity and HGF level were significant. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> high </span><span style="font-family:Verdana;">AFP, multinodularity and high HGF were inter-related possible risk factor</span></span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> for</span><span style="font-family:Verdana;"> 1-year recurrence of HCC in patients with initial remission following TACE</span><span style="font-family:Verdana;">.</span>展开更多
Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Method...Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Methods: Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60 Co, with the absorption dose rate of 0. 56 Gy/min, then treated with saline (0.2 ml/ mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expres-sion level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. Results: The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P<0.05 or P<0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P<0.05 or P < 0.01). Conclusion:By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of hemopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.Original article on CJITWM (Chin) 2004;24(5):439展开更多
Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, su...Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.展开更多
AIM To study the changes of endogenoustransforming growth factor β(TGFβ)and basicfibroblast growth factor(bFGF)in lung followingintestinal ischemia and reperfusion injury andtheir effects on lung injury and repair.M...AIM To study the changes of endogenoustransforming growth factor β(TGFβ)and basicfibroblast growth factor(bFGF)in lung followingintestinal ischemia and reperfusion injury andtheir effects on lung injury and repair.METHODS Sixty Wistar rats were divided intofive groups,which underwent sham-operation,ischemia(45 minutes),and reperfusion(6,24and 48 hours,respectively)after ischemia(45minutes).Immunohistochemical method wasused to observe the localization and amounts ofboth growth factors.RESULTS Positive signals of both growthfactors could be found in normal lung,mainly inalveolar cells and endothelial cells of vein.Afterischemia and reperfusion insult,expressions ofboth growth factors were increased and theiramounts at 6 hours were larger than those ofnormal control or of 24 and 48 hours after insult.CONCLUSION The endogenous bFGF and TGF βexpression appears to be up-regulated in thelung following intestinal ischemia andreperfusion,suggesting that both growth factorsmay be involved in the process of lung injury andrepair.展开更多
基金the Natural Science Foundation of Shaanxi Province(No.2022JM-521)the Science and Technology Plan Project of Xi’an(No.21YXYJ0031).
文摘AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.
文摘BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.
基金Natural Science Foundation of Hainan Province(No.821QN0893)Natural Science Project of Hainan Provincial Department of Education(No.Hnky2022-38)Innovation and Entrepreneurship Training Program for College Students of Hainan Medical College(No.S202211810034)。
文摘Objective:The aim of this study is to investigate the effects of Hepatocyte Growth Factor(HGF)on the expression levels of IL-8,TNF-α,IL-4,and IL-21 in mice with liver injury induced by CCL_(4).Methods:An acute liver injury mouse model was established using CCL_(4),and hepatocytes and white blood cells were separated by gradient density centrifugation.Different concentrations of HGF were added in vitro,and the expression levels of cytokines were detected using ELISA.Results:In the in vivo injury model,the hepatocyte experiment results showed that the expression level of IL-8 was reduced in the 10 ng/mL HGF group compared to the injured hepatocyte group(P<0.05),and increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.05).For IL-4,the expression levels were reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the injured hepatocyte group.The white blood cell experiment results showed that the expression levels of TNF-αwere reduced in both the 10ng/ml HGF group(P<0.05)and the 25 ng/mL HGF group(P<0.05)compared to the injured white blood cell group.In the in vitro injury model,hepatocyte experiment results showed that the expression levels of TNF-αwere reduced in both the 25 ng/mL HGF group(P<0.05)and the 50 ng/mL HGF group(P<0.05)compared to the normal control group.For IL-4,the expression level was reduced in the 25 ng/mL HGF group compared to the normal control group(P<0.05).The white blood cell experiment results showed that the expression level of TNF-αwas increased in the 50 ng/mL HGF group compared to the 10 ng/mL HGF group(P<0.001);for IL-21,the expression levels were reduced in the CCL_(4) model group(P<0.05),10 ng/mL HGF group(P<0.05),25 ng/mL HGF group(P<0.05),and 50 ng/mL HGF group(P<0.05)compared to the normal control group.Conclusion:when the liver of mice is acutely damaged by CCL_(4),HGF can reduce the expression levels of inflammatory cytokines IL-8,TNF-α,IL-4 in hepatocytes,and TNF-αin liver white blood cells.
基金Supported by Mahidol University,Thailand and Thailand Research Fund(Suthiphongchai T)Strategic Consortia for Capacity Building of University Faculties and Staff Scholarship,Commission on Higher Education,Ministry of Education,Thailand(Menakongka A)
文摘AIM:To investigate the role of hepatocyte growth factor(HGF) in cholangiocarcinoma(CCA) cell invasiveness and the mechanisms underlying such cellular responses. METHODS:Effects of HGF on cell invasion and motility were investigated in two human CCA cell lines,HuCCA-1 and KKU-M213,using Transwell in vitro assay.Levels of proteins of interest and their phosphorylated forms were determined by Western blotting.Localization of E-cadherin was analyzed by immunofluorescence staining and visualized under confocal microscope. Activities of matrix degrading enzymes were determined by zymography. RESULTS:Both CCA cell lines expressed higher Met levels than the H69 immortalized cholangiocyte cell line.HGF induced invasion and motility of the cell lines and altered E-cadherin from membrane to cytoplasm localization,but did not affect the levels of secreted matrix metalloproteinase(MMP) -2,MMP-9 andurokinase plasminogen activator,key matrix degrading enzymes involved in cell invasion.Concomitantly,HGF stimulated Akt and extracellular signal-regulated kinase(ERK) 1/2 phosphorylation but with slightly different kinetic profiles in the two cell lines.Inhibition of the phosphoinositide 3-kinase(PI3K) /Akt pathway by the PI3K inhibitor,LY294002,markedly suppressed HGFstimulated invasion of both CCA cell lines,and inhibition of the ERK pathway by U0126 suppressed HGF-induced invasion of the KKU-M213 cell line but had a moderate effect on HuCCA-1 cells. CONCLUSION:These data indicate that HGF promotes CCA cell invasiveness through dys-localization of E-cadherin and induction of cell motility by distinct signaling pathways depending on cell line type.
基金supported by a grant from the National Natural Science Foundation of China(No.30470457)
文摘Summary: Angiogenic gene therapy and cell-based therapy for peripheral arterial disease (PAD) have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells (MSCs)transplantation with ex vivo human hepatocyte growth factor (HGF) gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley (SD) rats were randomized to receive HGF gene-modified MSCs transplantation (HGF-MSC group), untreated MSCs transplantation (MSC group), or PBS injection (PBS group), respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.
文摘This study is to investigate the effect of FK506 on expression of hepatocyte growth factor (HGF) in rats' spinal cord following peripheral nerve injury and to elucidate the mechanisms for neuroprotective property of FK506. Fifty male rats were randomly divided into normal group, injury group and treatment group. Models of peripheral nerve injury were established by bilateral transection of sciatic nerve 0.5 cm distal to piriform muscle. Then the treatment group received subcutaneous injection of FK506 (1 mg/kg) at the back of neck, while the injury group was given 0.9% saline. The L4-6 spinal cords were harvested at various time points after the surgery. Western blotting and immunofluorescent staining were used to detect the level and position of HGF in spinal cord. Immunofluorescent staining showed that HGF-positive neurons were located in anterior horn, intermediate zone and posterior horn of gray matter in normal spinal cord. Western blotting revealed that there was no significant difference in the expressions of HGF between the injury group and the normal group, while the expression of HGF was significantly higher in the treatment group than in the injury group 7 and 14 days after surgery. It is suggested that peripheral nerve injury does not result in up-regulation of the expression of HGF in spinal cord, while FK506 may induce high expression of endogenous HGF after injury thereby protecting neurons and promoting axonal outgrowth.
文摘Objective To investigate the effects of hepatocyte growth factor(HGF)on vascular endothelial cells apoptosis induced by advanced glycation end products(AGEs)and its possible mechanism. Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and intervened by different concentrations of AGEs and HGF.The cell inhibitory rates of each group with different culture time(12, 24, 48, and 72 hours)were measured by methyl thiazolyl tetrazolium(MTT)assay. The early stage apoptosis was detected by flow cytometry with Annexin V-FITC/PI double staining, morphology of cell apoptosis was observed by hoechst 33258 fluorescence staining, and the expression of apoptosis-associated genes Bax and Bcl-2 were determined by Western blotting.The activity of caspase-3 was detected by enzyme-linked immunosorbent assay (ELISA).Results Morphological observation indicated that high concentration of AGEs induced characteristic apoptotic changes in HUVECs.Within a certain concentration range, HUVECs apoptosis inducing rates by AGEs were in both dose- and time-dependent manners.HGF significantly inhibited the apoptosis of HUVECs induced by AGEs (P< 0.05).AGEs significantly promoted expression of Bax protein, but not Bcl-2.Whereas HGF significantly promoted the expression of Bcl-2(P<0.01)and decreased the activity of caspase-3(P<0.05)without affecting Bax level.Conclusions AGEs can induce the apoptosis of endothelial cells in vitro.HGF may effectively attenuate AGEs-induced endothelial cells apoptosis through upregulating Bcl-2 gene expression and inhibiting caspase-3 activation.
基金Supported by Hainan Province Major Program of Science and Technology Projects 2017,No.ZDKJ2017007.
文摘BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertension(GH)in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses.Currently,the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests,and blood pressure test is usually used for the screening and diagnosis of hypertension.However,these criteria might not anticipate or detect all GDM or GH cases.Therefore,new specific predictive and diagnostic tools should be evaluated for this population.This study selected three biomarkers of osteoprotegerin(OPG),interleukin(IL)and hepatocyte growth factor(HGF)for GDM and GH predication and diagnosis.AIM To explore the feasibility of changes in placental and serum OPG,IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women.METHODS From January 2018 to January 2019,44 pregnant women with GDM and GH were selected as an observation group,and 44 healthy pregnant women were selected as a control group in the same period.Serum OPG,IL and HGF were compared between the two groups.RESULTS The levels of OPG and HGF in the observation group were lower than in the control group,and the level of IL-1βwas higher in the observation group than in the control group(all P<0.05).Furthermore,OPG and HGF were negatively associated with gestational diabetes and gestational hypertension,while IL-1βwas positively associated with GDM complicated with GH(all P<0.05).CONCLUSION The evaluation of serum OPG,HGF and IL-1βlevels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.
基金the Foundation of High-Tech Key Project of the National 863 Program, No. 2001AA217061
文摘BACKGROUND: Recent advancements in gene therapy have provided new methodology for treating ischemia in lower extremities. Gene transfer of angiogenic factors to ischemic tissues may promote local proliferation of new vessels and form collateral circulation. OBJECTIVE: To observe histopathological changes in the femoral and intramuscular nerve three months after intramuscular injection of hepatocyte growth factor (HGF) into the peripheral skeletal muscle in a canine model of lower limb ischemia. DESIGN: Randomized occlusion modelled and verification animal study. SETTING: Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA. MATERIALS: This study was performed at Animal Experimental Center, Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA from September to November 2006. A total of eight male mongrel dogs, weighing 12–15 kg and 1.5–3 years of age, were selected for this study. This experimental study was in accordance with local ethics standards. Recombinant plasmid carrying HGF (pUDKH) and occlusion model plasmid (pUDK) were provided by the Third Laboratory of Radiation Medical Institute, Academy of Military Medical Sciences of PLA. METHODS: Grouping and model establishment: under anesthesia, complete vascular occlusion models were established on the left lower extremities. The experimental dogs were randomly divided into a model group and a pUDKH treatment group, with four dogs in each group. Dogs in the pUDKH group were injected with 0.15 mg/kg pUDKH. Ten minutes later, intramuscular injections were performed at three spots into the peripheral skeletal muscle of the left hind limb, as well as lateral injections at two spots. The injection volume at each spot was 0.2 mL. Dogs in the model group were injected with pUDK, and dosage and injection method were identical to the treatment group. MAIN OUTCOME MEASURES: Histopathological changes in the femoral nerve, as well as internal and external intramuscular nerve tissues in the hind limb of dogs three months after plasmid injection under optic microscope. RESULTS: (1) Histopathological changes in the femoral nerve: tiny nerves from the femoral nerve to the intramuscular nerve exhibited marked degeneration in the model group. The degenerating features included neurites, myelin sheaths, and Schwann cell nuclei. Neuropathy in the pUDKH treatment group was not detected. (2) Histopathological changes of the intramuscular nerve: large and irregular vacuoles were present on several longitudinal sections of intramuscular nerve fibers in the model group, as well as annular-shaped blank regions on transverse sections of peripheral neurites. In the pUDKH treatment group, large, blank regions were present in several segments of partial nerve fibers of the longitudinal intramuscular nerve region, but only a few nerve fibers exhibited annular-shaped blank regions on the transverse section of peripheral neurites. CONCLUSION: Local pUDKH injection may relieve or block femoral and intramuscular nerve tissue injury in a canine mocel of lower limb ischemia.
基金The Medical Key Personproject of the 135 Projects of Jiangsu Province(R2002043)
文摘Objective: To study the amelioration effect of AdenovirusS-mediated human hepatocyte growth factor (AdsHGF) on postinfarction heart failure in the swine myocardial infarction model. Methods: Twelve SuZhong young swine were randomly divided into 2 groups with 6 swine in each group: Ad5-HGF-treated group and null-Ad5 group. Four weeks after ligation at left anterior descending coronary artery in swine hearts, Ad5-HGF was transferred to the swine myocardium. Simultaneously, Gated myocardial perfusion imaging was performed to evaluate cardiac perfusion and heart function. After three weeks, Gated myocardial perfusion imaging was performed again, then the hearts were harvested and sectioned to examine the expression of HGF through ELISA. Results: High expression of human HGF was observed in the myocardium of Ad5-HGF-treated group. From 4 weeks to 7 weeks after operation, Left ventricular ejection fraction was increased in Ad5-HGF-treated group. The improvement in LVEF was greater in Ad5-HGF-treated group than that in null-Ad5 group at 7 weeks after operation. Cardiac perfusion was significantly improved in the Ad5-HGF-treated group. Conclusion: High expression of human HGF was observed in the myocardium through intracoronary transfection, which suggests that HGF can ameliorate heart function in swine with postinfarction heart failure.
基金supported by grants from the Natural Science Foundation of China(No.30973671)the Natural Science Foundation of Guangdong Province of China(No.9151064001000031)
文摘The amino acid at the 119th position of human basic fibroblast growth factor(hbFGF),lysine(K119),is a critical component for its mitogenic activity.However,little is known about the effects of the characteristics of this residue including charge on the mitogenic activity of hbFGF.Herein,this basic residue was replaced with neutral glutamine residue and acidic glutamic acid residue to construct mutants hbFGF^(K119Q) and hbFGF^(K119E),respectively.The mutants were produced by BL21(DE3)/pET3c expression system...
文摘Wound complications are estimated to be affected in about 9% of TKA patients, which may increase the risk of deep periprosthetic infection and results in re-operation, joint fusion, or amputation. Here we have reported a female patient who suffered wound rupture due to early post-operation mobilization and weight-bearing. The wound dehiscence was successfully managed by applying recombinant basic fibroblast growth factor-2 and anti-infective treatment without removing prosthetic joint.
基金the Out-standing Middle-aged and Young Talents, Education Department of Hubei Province, No. Q20082403
文摘Human hepatocyte growth factor can be used to treat cerebral infarction, administered by lateral ventricular, cerebellomedullary cistern or subarachnoid injections. However, the target gene ex-pression product is scarcely found in the ischemic penumbra, but extensively distributes in other regions, increasing the risks of gene therapy. The present study directly transfected hepatocyte growth factor gene into the ischemic penumbra of rats with transient middle cerebral artery occlusion. Immunohistochemical analysis revealed that infarct volume was significantly decreased, hepatocyte growth factor protein expression level and vessel quantity in the ischemic penumbra were significantly increased, and learning and memory were significantly improved.
基金the branch project of Research of Stroke Risk Factor in China973 Program of National Science & Technology Board(G2000056901)
文摘Objective To research whether serum hepatocyte growth factor(HGF)level increases in ischemic stroke and hemorrhagic stroke,and explore the relationship between the serum HGF level and stroke recurrence.Methods We studied a total of 92 consecutive acute stroke patients who had been admitted to hospital within 24h of onset from 6 participating hospitals in Xi’an from January 2000 to May 2004.All patients were divided into ischemic stroke group and hemorrhagic stroke group according to the results of brain computed tomography(CT)scan or MRI on admission.Patients in stroke groups were divided into recurrent group and non-recurrent group.Healthy volunteers or patients without cerebrovascular diseases comprised the control group.Stroke and control groups were strictly matched with 1∶1 ratio.The patients were followed up for 4 years.Serum HGF was tested with enzyme-linked immunosorbent assay(ELISA).Results Serum HGF of stroke patients was significantly higher than that of control group(P<0.05).The serum HGF level in recurrent group was higher than that in non-recurrent group of ischemic patients,and there was no significant difference in hemorrhagic ones.Conclusion These results indicate that serum HGF may be used as a diagnostic marker for stroke,and serum HGF level is helpful in predicting the recurrence of ischemic stroke.
基金supported by National Natural Science Foundation of China(No.30671992)a grant from the"135"Foundation of Jiangsu Province(No.135-10).
文摘Objective:To construct the adenoviral expression vector system containing human hepatocyte growth factor (hHGF) cDNA, and to further study the transduction efficiency and the expression of HGF in mesenchymal stem cells (MSCs). Methods:The HGF cDNA was amplificated from the expression plasmid pCMV-HGF, and was subcloned into the adenovirus shuttle plasmid pDC316-IRESEGFP vector containing a green fluorescence protein (GFP) reporter gene. Virus Ad-HGF was produced by homologous recombination in HEK293 package cells. Bone marrow derived MSCs were harvested and cultured, and then were transduced with Ad-HGF. The efficiency of Ad-HGF transduction was assessed by FACS analysis using GFP gene expression. And HGF/MSCs were generated. The HGF concentrations in supernatants of HGF/MSCs were determined by ELISA using anti-human HGF monoclonal antibody. Results: The recombinant, named pDC316-HGF-IRES-eGFP, was digested with restriction enzyme, and the DNA sequencing of HGF was identical to the report in Genebank and did not reveal any mutation. GFP expression could be observed on the second day after packing of the linearized pAd-HGF in HEK293 cells and 7.15 × 10^10pfu/ml titer of Ad-HGF was obtained. Forty-eight hours after transduction, 96.89% of HGF/MSCs were GFP positive. Peak concentration levels of hHGF(103ng/mL) in the cultured supernatants were detected on day 2 post-transduction, and the adenovirus-mediated expression of HGF by MSCs was maintained for at least 2 weeks in vivo. Conclusion:Our data demonstrated that the adenovirus expression'vector system pDC316-HGF-IRES-EGFP has been constructed successfully, and their effective expressions also have been obtained in MSCs. This will provide material basis for the next study on liver regeneration after small-for-size liver transplantation.
文摘<b><span style="font-family:Verdana;">Background: </span></b><span style="font-family:Verdana;">Hepatocellular carcinoma is the third leading cause of tumor </span><span style="font-family:Verdana;">related mortality and develops mostly in patients with chronic liver disease and</span><span style="font-family:;" "=""> <span style="font-family:Verdana;">liver cirrhosis. Human hepatocyte growth factor (HGF) is produced in various</span> <span style="font-family:Verdana;">organs of the body and is characterized as a multifunctional factor with vari</span><span style="font-family:Verdana;">ous biologic activities. </span><b><span style="font-family:Verdana;">Aim:</span></b><span style="font-family:Verdana;"> Our aim was to investigate the predictive factors of </span><span style="font-family:Verdana;">recurrence specially the role of HGF in patients with HCC treated with TACE. </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> one hundred HCC patients treated by TACE who </span><span style="font-family:Verdana;">achieved complete response were included and divided into two groups a</span><span style="font-family:Verdana;">ccording to disease free survival (DFS) status at 1 year: the non</span></span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">early recurrence</span><span style="font-family:;" "=""><span style="font-family:Verdana;"> (NER) group (1) and the early recurrence (ER) group (2). Univariate binary logistic regression analysis for the possible risk factors of recurrence showed that AFP, multinodularity and HGF level were significant. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> high </span><span style="font-family:Verdana;">AFP, multinodularity and high HGF were inter-related possible risk factor</span></span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> for</span><span style="font-family:Verdana;"> 1-year recurrence of HCC in patients with initial remission following TACE</span><span style="font-family:Verdana;">.</span>
文摘Objective: To study the expressions of basic fibroblast growth factor (bFGF) and its receptor (bFGFR) in bone marrow of mice with acute radiation injury, and to evaluate the effect of Ligustrazine (Lt) on them. Methods: Fifty-six Kunming mice of clean grade were randomly divided into 3 groups, the normal group, the control group and the Lt group. Mice in the latter two groups were once homogeneously systemic irradiated with 6.0 Gy of 60 Co, with the absorption dose rate of 0. 56 Gy/min, then treated with saline (0.2 ml/ mice) or Lt (2 mg/mice) respectively, twice a day through gastrogavage for successive 13 days. Mice were sacrificed in batch on the 3rd, 7th and 14th day by cervical dislocation to collect the bilateral femoral bone marrow for preparing bone marrow mono-nuclear cell (BMMNC) suspension. The bFGFR expression on surface of BMMNC was determined by flow cytometry; and the bFGF expres-sion level in one side of femoral bone marrow tissue was detected by immunohistochemistry with SABC-AP assay. Results: The bFGF expression in bone marrow of mice on the 3rd, 7th and 14th day after acute radiation injury all were significantly lower than that of the normal mice (P<0.05 or P<0.01). The expressions of bFGF and bFGFR in the Lt group detected were significantly higher than that in the control group detected at the corresponding time points (P<0.05 or P < 0.01). Conclusion:By way of enhancing bFGF expression in bone marrow and bFGFR expression on surface of BMMNC to accelerate the repairing of hemopoietic micro-environment in bone marrow might be one of the mechanisms of Lt in promoting hemopoietic function reconstitution after acute radiation injury.Original article on CJITWM (Chin) 2004;24(5):439
文摘Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.
基金the National Grant for Outstanding Young Researchers of China,No.39525024
文摘AIM To study the changes of endogenoustransforming growth factor β(TGFβ)and basicfibroblast growth factor(bFGF)in lung followingintestinal ischemia and reperfusion injury andtheir effects on lung injury and repair.METHODS Sixty Wistar rats were divided intofive groups,which underwent sham-operation,ischemia(45 minutes),and reperfusion(6,24and 48 hours,respectively)after ischemia(45minutes).Immunohistochemical method wasused to observe the localization and amounts ofboth growth factors.RESULTS Positive signals of both growthfactors could be found in normal lung,mainly inalveolar cells and endothelial cells of vein.Afterischemia and reperfusion insult,expressions ofboth growth factors were increased and theiramounts at 6 hours were larger than those ofnormal control or of 24 and 48 hours after insult.CONCLUSION The endogenous bFGF and TGF βexpression appears to be up-regulated in thelung following intestinal ischemia andreperfusion,suggesting that both growth factorsmay be involved in the process of lung injury andrepair.