Fibroblast growth factor 15,induced by elevated bile acids,mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy

BACKGROUND Fibroblast growth factor(FGF)15/19,which is expressed in and secreted from the distal ileum,can regulate hepatic glucose metabolism in an endocrine manner.The levels of both bile acids(BAs)and FGF15/19 are elevated after bariatric surgery.However,it is unclear whether the increase in FGF15/19 is induced by BAs.Moreover,it remains to be understood whether FGF15/19 elevations contribute to improvements in hepatic glucose metabolism after bariatric surgery.AIM To investigate the mechanism of improvement of hepatic glucose metabolism by elevated BAs after sleeve gastrectomy(SG).METHODS By calculating and comparing the changes of body weight after SG with SHAM group,we examined the weight-loss effect of SG.The oral glucose tolerance test(OGTT)test and area under the curve of OGTT curves were used to assess the anti-diabetic effects of SG.By detecting the glycogen content,expression and activity of glycogen synthase as well as the glucose-6-phosphatase(G6Pase)and phosphoenolpyruvate carboxykinase(Pepck),we evaluated the hepatic glycogen content and gluconeogenesis activity.We examined the levels of total BA(TBA)together with the farnesoid X receptor(FXR)-agonistic BA subspecies in systemic serum and portal vein at week 12 post-surgery.Then the histological expression of ileal FXR and FGF15 and hepatic FGF receptor 4(FGFR4)with its corresponding signal pathways involved in glucose metabolism were detected.RESULTS After surgery,food intake and body weight gain of SG group was decreased compare with the SHAM group.The hepatic glycogen content and glycogen synthase activity was significantly stimulated after SG,while the expression of the key enzyme for hepatic gluconeogenesis:G6Pase and Pepck,were depressed.TBA levels in serum and portal vein were both elevated after SG,the FXR-agonistic BA subspecies:Chenodeoxycholic acid(CDCA),lithocholic acid(LCA)in serum and CDCA,DCA,LCA in portal vein were all higher in SG group than that in SHAM group.Consequently,the ileal expression of FXR and FGF15 were also advanced in SG group.Moreover,the hepatic expression of FGFR4 was stimulated in SG-operated rats.As a result,the activity of its corresponding pathway for glycogen synthesis:FGFR4-Ras-extracellular signal regulated kinase pathway was stimulated,while the corresponding pathway for hepatic gluconeogenesis:FGFR4-cAMP regulatory element-binding protein-peroxisome proliferator-activated receptorγcoactivator-1αpathway was suppressed.CONCLUSION Elevated BAs after SG induced FGF15 expression in distal ileum by activating their receptor FXR.Furthermore,the promoted FGF15 partly mediated the improving effects on hepatic glucose metabolism of SG.

Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

Effects of hepatocyte growth factor on MMP-2 expression in scleral fibroblasts from a guinea pig myopia model

AIMTo investigate the effects of hepatocyte growth factor (HGF) on MMP-2 expression in scleral fibroblasts from guinea pig with LIM.

Emodin regulating excision repair cross-complementation group 1 through fibroblast growth factor receptor 2 signaling

AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.

Synergistic Effects of Activin A and Fibroblast Growth Factor 2 in the Modulation of Insulin Expression

Diabetes is the most prevalent and serious metabolic disease, and the number of diabetic patients worldwide is increasing. The reduction of insulin biosynthes is in pancreatic E-cells is closely associated with the onset and progression of diabetes, therefore, it is important to search for ways to induce insulin-producing cells in non-E-cells. In the present study, it has been reported that activin A and a basic fibroblast growth factor 2 （ FGF2）, can synergistically increase the insulin mRNA level, in both mouse El4 striatal primary cell cultures and the hippocampal neuronal cell line HT22. Activin A and FGF2 can jointly stimulate the nuclear translocation of Smad3 and specifically activate ERK1/2. It is interesting to note that a specific inhibitor for MEK, U0126, can efficiently block the induction of an insulin promoter activity by activin A and FGF2. This indicates that activin A collaborates with FGF2, giving a signal to induce the insulin gene through selective activation of the ERK-type MAP kinase and Smad3 in mouse striatal and HT22 cells. These data suggest that activin A may act in concert with FGF2 for the development of insulin -positive neurons

Fibroblast growth factor 21 in dairy cows:current knowledge and potential relevance

Fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress conditions.Dairy cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early lactation.It has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of lactation.This finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or humans.However,the role of FGF21 in dairy cows has been less investigated so far.Following a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy cows.The first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy cows.In the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is addressed.In the third part,findings of exogenous FGF21 application on metabolism in dairy cows are reported.Finally,the potential relevance of FGF21 in dairy cows is discussed.It is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy cows.However,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.

Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

There is evidence that the expression of members of the fibroblast growth factor （FGF） protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 （FGF2） and fibroblast growth factor receptor-1 （FGFR1） protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

Effect of basic fibroblast growth factor and danshen on bcl-2 and p53 mRNA expression in the brain of rats exposed to repeated, high, positive acceleration (+Gz)

BACKGROUND： Both animal experiments and clinical studies have shown that basic fibroblast growth factor （bFGF） and danshen （Salvia miltiorrhiza） can exhibit protective effects on ischemia-reperfusion cerebral injury. OBJECTIVE： To test whether bFGF and danshen can protect cerebral injury induced by exposure to repeated, high, positive acceleration （＋Gz） in an animal model and to analyze the possible mechanisms. DESIGN, TIME AND SETTING： Randomized controlled animal study. The experiment was performed at the Research Center for Molecular Biology, Air-force General Hospital of Chinese PLA from April to August 2000. MATERIALS： A total of 20 clean grade, healthy, Sprague Dawley rats of both genders, weighing （200 ± 15） g, were provided by our experimental animal center. Rats were randomly divided into 5 groups： the control group, ＋Gz exposure group, bFGF group, danshen group, and saline group, with 4 animals per group. bFGF （Beijing Bailuyuan Biotechnology Co. Ltd.） and danshen solution （Shanghai Zhongxi Pharmaceutical Co. Ltd.） were used. METHODS： All rats were fixed on a rotary arm of a centrifugal apparatus （2 m in radius） with their heads oriented towards the center of the apparatus. Except for rats in the control group, the value of ＋Gz exposure was ＋14 Gz with an acceleration rate of 1.5 G/s. The peak force lasted for 45 seconds. ＋Gz exposure was performed three times with intervals of 30 minutes. Rats in the control group received the same ＋Gz procedure, but the G value was ＋1 Gz. Rats in bFGF group and danshen group were intraperitoneally injected with 100 μg/kg bFGF or 15 g/kg danshen solution, respectively, at 30 minutes prior to centrifugation and immediately after centrifugation. Rats in saline group were injected with the same volume of saline. Six hours after exposure, rats were decapitated. One hemisphere was preserved in liquid nitrogen for RNA extraction and the other was processed for apoptosis detection. MAIN OUTCOME MEASURES： mRNA levels of bcl-2 and p53 were measured by semi-quantitative reverse-transcription polymerase chain reaction. Apoptotic cell death was detected by terminal deoxynuleotidyl transferase-mediated dUTP nick end labeling. RESULTS： Changes in mRNA expression of bcl-2 and p53 and apoptotic cells were observed in rat brain six hours after repeated ＋Gz exposures, bFGF and danshen were able block the changes of bcl-2 and p53 expression and inhibit apoptotic cell death. CONCLUSION： The data suggest that apoptosis and changes in bcl-2 and p53 expression in the rat brain can be induced by repeated ＋Gz exposures. Apoptosis is, therefore, one of the molecular mechanisms of brain damage induced by repeated ＋Gz exposures, bFGF and danshen were of the equal potency in preventing brain injury induced by repeated ＋Gz exposures.

RNA interference affects tumorigenicity and expression of insulin-like growth factor-1,insulin-like growth factor-1 receptor,and basic fibroblast growth factor-2 in rat C6 glioma cells

BACKGROUND： Human gliomas are more likely to express basic fibroblast growth factor-2 （FGF-2） insulin-like growth factor-1（IGF-1）, and IGF-1 receptor （IGF-1R） than normal brain tissue. These factors activate signal transduction systems of Ras/MAPK and PI3K/Akl, which promote glioma growth. OBJECTIVE： To utilize RNA interference （RNAi） technique to down-regulate FGF-2, IGF-1, and IGF-1R gene expression, and to investigate the effects of these genes on rat C6 glioma cells, as well as the feasibility of RNAi for treating glioma. DESIGN, TIME AND SETTING： This neurooncological, randomized, controlled, in vivo and in vitro experiment, which used RNAi methodology, was performed at the Laboratory of Molecular Biology, Institute of Biochemistry, Chinese Academy of Sciences between August 2005 and February 2008. MATERIALS： Rat C6 cell lines were purchased from Shanghai Institute of Cellular Biology Affiliated to Chinese Academy of Sciences. Small interfering RNA （siRNA） was synthesized by Shanghai GenePharma. Anti-IGF-1, anti-IGF-1R, anti-FGF-2, anti-mouse and anti-rabbit IgG G1-HRP antibodies were provided by Santa Cruz Biotechnology, USA. Four to six week-old BALB/c nude mice were purchased from the Laboratory Animal Center, Chinese Academy of Sciences. METHODS： C6 glioma cells were transfected with siRNA, which was chemically synthesized in vitro to correspond to endogenous FGF-2, IGF-1, and IGF-1R genes. The inhibition ratio of targeting mRNA expression was detected by semiquantitative RT-PCR, and protein expression was determined by Western blot analysis. C6 glioma cell proliferation was observed using a growth curve C6 glioma cell apoptosis rate and cell cycle were detected by flow cytometry. C6 glioma cell growth regression was observed by transwell migration assay. In addition, nude mouse subcutaneous tumor models were used in this study. For studying the anti-tumor effects of IGF-1 and IGF-1R siRNA, two blank control groups, with six mice each, were set up： A （2.5 μg siRNA was injected one week after C6 cells were inoculated, Le., when tumor volume reached 8 mm × 8 mm） and B （siRNA was injected at the same time with C6 cells were inoculated. To study the effects of FGF-2 siRNA, the groups consisted of a blank control group, negative control group, 2.6 μg siRNA group, 4 μg siRNA group, and 5.3 μg siRNA group, with six mice each. MAIN OUTCOME MEASURES： mRNA and protein inhibition ratio of FGF-2, IGF-1, and IGF-1 R; C6 glioma cell proliferation, apoptosis, and cycle growth arrest; C6 glioma cell growth regression and subcutaneous tumorigenicity rates. RESULTS： All siRNA constructs proved to be effective. After 48 hours, transfection of 200 nmol/L siRNA resulted in a FGF-2 or IGF-1R gene inhibition ratio 〉 80% and an IGF-1 gene inhibition ratio of approximately 70%. Protein expression levels for FGF-2, IGF-1, and IGF-1R decreased in a dose-dependent manner following siRNA transfection, with an inhibition rate 〉 85%, 60%, and 50%, respectively. C6 glioma cell proliferation and apoptosis rates increased in proportion to siRNA. The apoptosis rate of C6 glioma cells induced by FGF-2, IGF-1, and IGF-1R siRNA was 39.96%, 15.07% and 22.47%, respectively （P 〈 0.01）. Transfection of 200 nmol/L IGF or IGF-1R siRNA for 48 hours suppressed C6 glioma cell migration. At 30 days after intratumoral injection of 2.6, 4, and 5.3 tJg FGF-2 siRNA, tumor growth regression rate of FGF-2 siRNA was 56%, 67%, and 86%, respectively. The tumor growth regression rate was 71.88% and 45.71%, respectively, when IGF-1 or IGF-1R siRNA was intratumorally injected 1 week after C6 glioma cell transplantation. When IGF-1 or IGF-1 R siRNA was intratumorally injected during C6 glioma cell transplantation, the tumor growth regression rate was 78.13% and 74.29%, respectively. CONCLUSION： siRNA transfection downregulated gene expression of FGF-2, IGF-1, and IGF-1R In addition, siRNA treatment markedly suppressed glioma cell proliferation, growth, and migration, and concomitantly reduced subcutaneous tumorigenicity.

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

BACKGROUND The importance of early diagnosis of alcoholic liver disease underscores the need to seek better and especially non-invasive diagnostic procedures.Leukocyte cellderived chemotaxin-2(LECT2)has been widely studied to determine its usefulness in monitoring the course of non-alcoholic fatty liver disease but not for alcoholic liver cirrhosis(ALC).AIM To determine the concentration of LECT2 in the blood serum of patients in relation to progressive stages of ALC,its relation to fibroblast growth factor 1(FGF-1)and FGF-21,and to examine the possible wider use of LECT2 in diagnosing ALC.METHODS A retrospective case-control study was conducted with 69 ALC cases and 17 controls with no ALC.Subjects were recruited from the region of Lublin(eastern Poland).Liver cirrhosis was diagnosed based on clinical features,history of heavy alcohol consumption,laboratory tests,and abdominal ultrasonography.The degree of ALC was evaluated according to Pugh-Child criteria(the Pugh-Child score).Blood was drawn and,after centrifugation,serum was collected for analysis.LECT2,FGF-1,and FGF-21 were determined using enzyme-linked immunosorbent assay kits.RESULTS The LECT2 Levels in the control group were 18.99±5.36 ng/mL.In the study groups,they declined with the progression of cirrhosis to 11.06±6.47 ng/mL in one group and to 8.06±5.74 ng/mL in the other(P<0.0001).Multiple comparison tests confirmed the statistically significant differences in LECT2 Levels between the control group and both test groups(P=0.006 and P<0.0001).FGF-21 Levels were 44.27±64.19 pg/mL in the first test group,45.4±51.69 pg/mL in the second(P=0.008),and 13.52±7.51 pg/mL in the control group.The difference between the control group and the second test group was statistically significant(P=0.007).CONCLUSION We suggest that LECT2 may be a non-invasive diagnostic factor for alcoholinduced liver cirrhosis.The usefulness of LECT2 for non-invasive monitoring of alcohol-induced liver cirrhosis was indirectly confirmed by the multiple regression model developed on the basis of our statistical analysis.

Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice

BACKGROUND Fibroblast growth factor 21(FGF21),primarily secreted by the pancreas,liver,and adipose tissues,plays a pivotal role in regulating glucose and lipid metabolism.Acute pancreatitis(AP)is a common inflammatory disease with specific clinical manifestations.Many patients with diabetes present with concurrent inflammatory symptoms.Diabetes exacerbates intestinal permeability and intestinal inflammation,thus leading to the progression to AP.Our previous study indicated that FGF21 significantly attenuated susceptibility to AP in mice.AIM To investigate the potential protective role of FGF21 against AP in diabetic mice.METHODS In the present study,a mouse model of AP was established in diabetic(db)/db diabetic mice through ceruletide injections.Thereafter,the protective effects of recombinant FGF21 protein against AP were evaluated,with an emphasis on examining serum amylase(AMS)levels and pancreatic and intestinal inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-alpha(TNF-),and intestinal IL-1β].Additionally,the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with AP.An antibiotic(Abx)cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, thePhylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformaticssoftware package, was used to predict different pathways between the groups and to explore the potentialmechanisms by which the gut microbiota influenced the protective effect of FGF21.RESULTSThe results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P < 0.01)and inflammatory factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ±0.051, P < 0.01), and IL-1β (1.377 ± 0.069 vs 0.3328 ± 0.02542, P < 0.01) in diabetic mice with AP. Moreover, notablesigns of recovery were observed in the pancreatic structure of the mice. The histologic evidence of inflammation inthe small intestine, including edema and villous damage, was significantly alleviated. FGF21 also significantlyaltered the composition of the gut microbiota, reestablishing the Bacteroidetes/Firmicutes ratio. Upon treatment withan Abx cocktail to deplete the gut microbiota, the FGF21 + Abx group showed lower levels of serum AMS (0.9328 ±0.075 vs 0.2249 ± 0.023, P < 0.01) and inflammatory factors (1.083 ± 0.12 vs 0.2799 ± 0.032, p < 0.01) than the FGF21group. Furthermore, the FGF21 + Abx group exhibited diminished injury to the pancreatic and small intestinaltissues, accompanied by a significant decrease in blood glucose levels (17.50 ± 1.1 vs 9.817 ± 0.69 mmol/L, P <0.001). These findings underscored the superior protective effects of the combination therapy involving an Abxcocktail with FGF21 over the FGF21 treatment alone in diabetic mice with AP. The gut microbiota compositionacross different groups was further characterized, and a differential expression analysis of gene functions wasundertaken using the PICRUSt2 prediction method. These findings suggested that FGF21 could potentially confertherapeutic effects on diabetic mice with AP by modulating the sulfate reduction I pathway and the superpathwayof n-acetylceramide degradation in the gut microbiota.CONCLUSION This study reveals the potential of FGF21 in improving pancreatic and intestinal damage recovery, reducing bloodglucose levels, and reshaping gut microbiota composition in diabetic mice with AP. Notably, the protective effectsof FGF21 are augmented when combined with the Abx cocktail.

Real role of growth factor receptor-binding protein 10:Linking lipid metabolism to diabetes cardiovascular complications

Cardiovascular complications of patients with type 2 diabetes mellitus(T2DM)threaten the health and life of numerous individuals.Recently,growth factor receptor-binding protein 10(GRB10)was found to play a pivotal role in vascular complications of T2DM,which participates in the regulation of lipid metabolism of T2DM patients.The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM.The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.

lncRNA-BBOX1-2通过调控成纤维细胞生长因子受体1促进胃癌的发生和发展

目的探讨长链非编码RNA(long non-coding RNA,lncRNA)BBOX1-2通过调控成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)对胃癌的发生发展机制的影响。方法回顾性选取2017年4月至2019年1月于上海交通大学医学院附属瑞金医院卢湾分院接受胃癌根治术30例病人肿瘤组织及癌旁相应正常组织作为研究对象,采用实时定量PCT(real-time PCR,RT-PCR)检测lncRNA-BBOX1-2和FGFR1表达;si-linc-BBOX1-2转染SGC-7901细胞后,通过蛋白质印迹法/细胞存活率分析(MTT)、细胞迁移和侵袭(Transwell)实验、细胞划痕、平板克隆一系列生物学功能实验,检测肿瘤细胞生物学功能及FGFR1表达的变化。结果胃癌组织中的lncRNA-BBOX1-2(3.68±0.58比1.15±0.11)和FGFR1(4.26±0.71比1.19±0.18)表达显著高于癌旁正常组织(P<0.05);si-linc-BBOX1-2转染SGC-7901细胞后,FGFR1表达下调,细胞活力、迁移、侵袭和生存能力明显下降。结论LincRNA-BBOX1-2可通过调控FGFR1的表达介导胃癌细胞的增殖、凋亡、迁移和侵袭,可能为胃癌的治疗提供了新的靶点和潜在的生物学标志物。

Effects of 530 nm monochromatic light on basic fibroblast growth factor and transforming growth factor-β1 expression in Müller cells

AIMTo expose rat retinal M&#x000fc;ller cells to 530 nm monochromatic light and investigate the influence of varying light illumination times on basic fibroblast growth factor (bFGF) and transforming growth factor-&#x003b2;1 (TGF-&#x003b2;1) expression.METHODSThree groups of rat retinal M&#x000fc;ller cells cultured in vitro under a 530 nm monochromatic light were divided into 6, 12 and 24h experimental groups, while cells incubated under dark conditions served as the control group. The bFGF and TGF-&#x003b2;1 mRNA expression, protein levels and fluorescence intensity of the M&#x000fc;ller cells were analyzed.RESULTSThe bFGF mRNA expression and protein levels were significantly upregulated in M&#x000fc;ller cells in all three experimental groups compared with the control group (P&#x0003c;0.05), while that of TGF-&#x003b2;1 was downregulated (P&#x0003c;0.05). Also, bFGF expression was positively correlated, but TGF-&#x003b2;1 expression was negatively correlated with illumination time. The largest changes for both cytokines were seen in the 24h group. The changes in bFGF and TGF-&#x003b2;1 fluorescence intensity were highest in the 24h group, and significant differences were observed among the experimental groups (P&#x0003c;0.05).CONCLUSIONThe expressions of bFGF and TGF-&#x003b2;1 changed in a time-dependent manner in M&#x000fc;ller cells exposed to 530 nm monochromatic light with 250 lx illumination intensity. M&#x000fc;ller cells might play a role in the development of myopia by increasing bFGF expression or decreasing TGF-&#x003b2;1 expression. Changes in cytokine expression in retinal M&#x000fc;ller cells may affect monochromatic light-induced myopia.

Effect of charge at an amino acid of basic fibroblast growth factor on its mitogenic activity

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...

Wnt pathway in the formation of ischemic brain injury Interventional pathway of basic fibroblast growth factor

BACKGROUND： Basic fibroblast growth factor （bFGF） can reduce neuronal apoptosis following ischemia/reperfusion （I/R） injury. Mechanism of the phenomenon should be elucidated.OBJECTIVE： The goal of this study was to observe the effect of bFGF on the expressions of Dickkopf-1（DKK-1） and β-catenin in the Wnt pathway in hippocampal tissue of rats following brain I/R injury, in order to investigate the role of Wnt pathway in the formation ofischemic brain injury.DESIGN： Randomized controlled experiment.SETTING： Shenyang Medical College.MATERIALS： Thirty healthy 3 months old male Wistar rats, weighing 300 - 350 g, were provided by the Experimental Animal Center of Shenyang Medical College. Thirty rats were randomized into sham-operation group, model group and treatment group. Goat anti-rat monoclonal antibody β-catenin was purchased from SANTA CRUZ Company. BFGF was developed by Beijing SL Pharmaceutical Co., Ltd.METHODS： This experiment was carried out in the Shenyang Medical College between November 2005 and May 2006. ①Focal brain I/R by suture-occluded method was modeled in rats in the treatment group and model group. Their middle cerebral artery was occluded 1 hour and reperfused for 24 hours. While in the sham-operation group, only the right common carotid artery and external carotid artery of rats were occluded for 90 minutes. ② The rats in the treatment group were intraperitoneally injected with 10 μg/kg bFGF,and those in the other groups were intraperitoneally injected with the same amount of saline.MAIN OUTCOME MEASURES： Following I/R 48 hours, the expressions of β-catenin and Dickkopf-1 mRNA in the neurons of hippocampal CA1 region by immunohistochemical SABC and RT-PCR.RESULTS： Following I/R 48 hours, the expressions of β-catenin and Dickkopf-1 mRNA in the neurons of hippocampal CA1 region was evaluated by means of immunohistochemical SABC and RT-PCR. ① Expression of DKK-1 mRNA in the sham-operation group was at low level, it was significantly higher in the model group compared to the sham-operation group; Expression of DKK-1 mRNA in the treatment group was significantly lower than that in the model group. ②Expression of β-catenin in the cerebral cortex and hippocampal cytoplasm of rats： The mean gray scale of β-catenin of model group was significantly lower than that of sham-operation group （74.27±2.65 vs. 111.36±5.39, P 〈 0.05）; The mean gray scale of β -catenin of treatment group was significantly higher than that of model group （86.18±7.41 vs. 74.27±2.65, P〈0.05）.CONCLUSION： bFGF may influence Wnt pathway by participating in the regulation of DKK-1 mRNA and β-catenin expressions, and thereby protect neurons.

2型糖尿病合并甲状腺功能亢进患者血清Sema 5A、IGFBP-3水平与糖代谢指标的相关性分析

目的分析2型糖尿病合并甲状腺功能亢进(以下简称甲亢)患者血清信号素5A(Sema 5A)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平与糖代谢指标的相关性。方法选取2021年6月至2022年6月邯郸市中心医院收治的73例2型糖尿病合并甲亢患者作为合并组,56例单纯2型糖尿病患者作为糖尿病组,另选取同期在邯郸市中心医院体检的68例健康者作为对照组。比较对照组、糖尿病组、合并组血清Sema 5A、IGFBP-3水平,比较糖尿病组、合并组临床资料[体质量指数、糖尿病病程、空腹血糖(FBG)、餐后2 h血糖(2 h PG)、胰岛素(FIN)、甘油三酯、总胆固醇、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA1c)、三碘甲腺原氨酸(T_(3))、甲状腺素(T_(4))、游离三碘甲腺原氨酸(FT_(3))、游离甲状腺素(FT_(4))、促甲状腺素(TSH)、促甲状腺激素受体抗体(TRAB)及甲状腺过氧化物酶抗体(TPOAB)、胰岛素抵抗指数(HOMA-IR)]。采用多因素Logisitic回归分析2型糖尿病并发甲亢的危险因素,采用Pearson相关分析2型糖尿病合并甲亢患者血清Sema 5A、IGFBP-3水平与糖代谢指标的相关性,绘制受试者工作特征(ROC)曲线分析血清Sema 5A、IGFBP-3对2型糖尿病合并甲亢的诊断价值。结果合并组血清Sema 5A、IGFBP-3水平高于对照组和糖尿病组,且糖尿病组高于对照组,差异均有统计学意义(P<0.05)。合并组糖尿病病程长于糖尿病组,血清HOMA-IR、FIN、HbA1c、T_(3)、T_(4)、FT_(3)、FT_(4)、TRAB、TPOAB水平高于糖尿病组,TSH水平低于糖尿病组,差异均有统计学意义(P<0.05)。多因素Logisitic回归分析结果显示,HOMA-IR、TPOAB、Sema 5A、IGFBP-3水平升高,TSH水平降低为2型糖尿病并发甲亢的危险因素(P<0.05)。Pearson相关分析结果显示,2型糖尿病并发甲亢患者血清Sema 5A、IGFBP-3水平与HOMA-IR、FBG、2 h PG、FIN、HbA1c、HDL-C水平均呈正相关(P<0.05)。2型糖尿病并发甲亢患者血清Sema 5A、IGFBP-3水平与LDL-C水平呈负相关(P<0.05)。ROC曲线分析结果显示,血清Sema 5A、IGFBP-3诊断2型糖尿病合并甲亢的曲线下面积(AUC)分别为0.854、0.804,2项指标联合诊断的AUC为0.900,且2项指标联合诊断的AUC高于Sema 5A、IGFBP-3单独诊断的AUC(Z联合-Sema 5A=2.156,P=0.043;Z联合-IGFBP-3=2.873,P=0.004)。结论2型糖尿病合并甲亢患者血清Sema 5A、IGFBP-3水平升高,且二者与糖代谢指标密切相关。

血清FGF2和FGFR1对子痫前期患者不良妊娠结局的预测价值

目的 探讨血清成纤维细胞生长因子2(FGF2)和成纤维细胞生长因子受体1(FGFR1)与子痫前期(PE)患者妊娠结局的关系。方法 选取2021年1月—2022年12月河南省妇幼保健院PE患者82例(PE组)和健康孕妇82名(健康对照组)。收集所有研究对象的临床资料,并检测血清FGF2和FGFR1水平。根据PE患者的妊娠结局分为结局良好组(44例)和结局不良组(38例)。采用Pearson相关分析评估PE患者血清FGF2与FGFR1的相关性。采用Logistic回归分析评估PE患者发生不良妊娠结局的影响因素。采用受试者工作特征(ROC)曲线评价血清FGF2和FGFR1判断PE患者发生不良妊娠结局的效能。结果 PE组血清FGF2和FGFR1水平均低于健康对照组(P<0.05)。结局不良组血清FGF2和FGFR1水平均低于结局良好组(P<0.05),早发型PE和重度PE所占比例高于结局良好组(P<0.05),其他临床资料2个组之间差异均无统计学意义(P>0.05)。PE患者血清FGF2与FGFR1呈正相关(r=0.524,P<0.05)。早发型PE、重度PE是PE患者发生不良妊娠结局的危险因素[比值比(OR)值分别为3.682、4.029,95%可信区间(CI)分别为1.054~12.858、1.086~14.951,P<0.05],FGF2、FGFR1升高为保护因素(OR值分别为0.491、0.586,95%CI分别为0.293~0.822、0.382~0.898,P<0.05)。血清FGF2、FGFR1单项检测和联合检测判断PE患者发生不良妊娠结局的曲线下面积(AUC)分别为0.81、0.82、0.92。结论 PE患者血清FGF2和FGFR1水平显著降低,2项指标联合检测对PE患者发生不良妊娠结局有较高的预测效能。

FGF2和BMP-2对Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后的预测价值

目的探讨成纤维细胞生长因子2(FGF2)和骨形态发生蛋白-2(BMP-2)对Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后的预测价值。方法前瞻性选取2020年1月—2021年12月在新疆医科大学第一附属医院住院治疗的105例Ⅲ、Ⅳ型慢性骨髓炎患者作为研究对象,均接受病灶清除联合封闭负压引流治疗,按不同治疗预后分为疗效好组75例(71.4%)和疗效差组30例(28.6%)。比较两组患者的临床资料、血清炎症因子、FGF2及BMP-2表达水平;采用多因素Logistic回归分析影响患者预后的独立危险因素,分析FGF2及BMP-2与预后的关系;构建相关列线图模型,绘制受试者工作特征(ROC)曲线和决策曲线,分析FGF2、BMP-2及联合预测模型的预测效能和净收益率。结果疗效差组Ⅳ型Cierny-Mader分型及窦道形成患者占比高于疗效好组(P<0.05)。疗效差组患者术前红细胞沉降率(ESR)、C反应蛋白(CRP)及肿瘤坏死因子-α(TNF-α)水平均高于疗效好组(P<0.05),疗效差组患者术前FGF2及BMP-2水平均低于疗效好组(P<0.05)。多因素Logistic回归分析结果显示,Cierny-Mader分型[O^R=5.036(95%CI:1.369,9.894)]、窦道形成[O^R=2.987(95%CI:1.156,7.247)]、FGF2[O^R=0.446(95%CI:0.129,0.735)]和BMP-2[O^R=0.485(95%CI:0.212,0.738)]为影响Ⅲ、Ⅳ型慢性骨髓炎患者预后的危险因素(P<0.05)。基于FGF2、BMP-2构建预测预后的列线图模型,校准曲线显示,Ⅲ、Ⅳ型慢性骨髓炎患者治疗疗效的预测值与实际观测值十分接近;ROC曲线分析结果显示,Cierny-Mader分型、窦道形成、FGF2及BMP-2预测预后的曲线下面积分别为0.783(95%CI:0.754,0.875)、0.752(95%CI:0.761,0.893)、0.823(95%CI:0.789,0.885)及0.811(95%CI:0.797,0.875),FGF2及BMP-2的最佳截断值分别为18.9 ng/L和113.5 ng/L,4者联合预测的曲线下面积为0.952(95%CI:0.896,0.991);决策曲线分析结果显示,Cierny-Mader分型、窦道形成、FGF2及BMP-2预测预后均具有良好的净收益率,并且联合预测的总体净收益率高于单一指标。结论基于Cierny-Mader分型、窦道形成、FGF2及BMP-24个指标构建的列线图模型能准确预测Ⅲ、Ⅳ型慢性骨髓炎患者病灶清除联合封闭负压引流治疗预后。

老年2型糖尿病合并骨质疏松患者血清IL-34、LCN2、FGF23水平及临床意义

目的探讨血清白细胞介素-34(IL-34)、脂质运载蛋白2(LCN2)、成纤维细胞生长因子23(FGF23)在2型糖尿病合并骨质疏松患者中的水平及意义。方法选取2020年6月至2022年7月该院收治的82例老年2型糖尿病合并骨质疏松患者为观察组,另选择同期82例老年2型糖尿病合并骨量减少患者为骨量减少组,82例在该院体检的健康者为对照组。根据骨质疏松严重程度将观察组患者分为轻度骨质疏松组和严重骨质疏松组。检测所有研究对象血清IL-34、LCN2、FGF23水平。采用受试者工作特征(ROC)曲线分析血清IL-34、LCN2、FGF23对2型糖尿病合并骨质疏松的诊断价值。结果与对照组比较,观察组和骨量减少组血清IL-34、FGF23水平均升高,且观察组高于骨量减少组,差异均有统计学意义(P<0.05)。与对照组比较,观察组和骨量减少组LCN2水平均降低,且观察组低于骨量减少组,差异均有统计学意义(P<0.05)。轻度骨质疏松组有48例患者,严重骨质疏松组有34例患者。严重骨质疏松组血清IL-34、FGF23水平均高于轻度骨质疏松组,严重骨质疏松组LCN2水平低于轻度骨质疏松组,差异均有统计学意义(P<0.05)。ROC曲线分析结果显示,IL-34、LCN2、FGF23单项及3项指标联合检测诊断2型糖尿病合并骨质疏松的曲线下面积(AUC)分别为0.867、0.796、0.717、0.949。结论血清IL-34、LCN2及FGF23联合检测对2型糖尿病合并骨质疏松具有较高的诊断价值,可为临床制订科学治疗方案提供参考依据。