Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a ...Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.展开更多
BACKGROUND The prevalence of gestational diabetes mellitus(GDM)has been increasing worldwide and is associated with multiple adverse pregnancy outcomes.Despite standard screening,some cases remain undiagnosed.Fibrobla...BACKGROUND The prevalence of gestational diabetes mellitus(GDM)has been increasing worldwide and is associated with multiple adverse pregnancy outcomes.Despite standard screening,some cases remain undiagnosed.Fibroblast growth factor 21(FGF21)plays a role in modulating glucose metabolism.There is an ongoing controversy regarding the relevance of FGF21 to GDM.AIM To evaluate the association between early second trimester serum FGF21 levels and gestational diabetes,and its predictive potential for outcomes.METHODS This cross-sectional observational study was conducted at a tertiary medical center,Chiang Mai University,Thailand.It included 28 pregnant women diag-nosed with GDM and 81 pregnant women with normal glucose status.Blood samples were collected according to the study schedule,and pregnancy outcomes were recorded meticulously.Descriptive analysis was employed to evaluate the data.RESULTS Most participants in our study had no risk factors for GDM(body mass index<24 kg/m2,no first-degree relatives with diabetes,no history of GDM),normal baseline glucose status(fasting glucose<110 mg/dL),and no insulin resistance(homeostatic model assessment of insulin resistance<2).There was a trend of increased FGF21 levels in the insulin-treated GDM group compared with dietary-treated GDM and non-GDM(73.58 pg/mL vs 62.94 pg/mL vs 63.59 pg/mL,respectively,P=0.73).However,no significant association was found between FGF21 concen-trations and pregnancy outcomes based on quintiles of FGF21 levels.CONCLUSION FGF21 was not associated with GDM or pregnancy outcomes;however,due to the small sample size,larger clinical trials with a diverse population are suggested to confirm these results.展开更多
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 ...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.展开更多
Objective:To evaluate the therapeutic effect of recombinant bovine basic fibroblast growth factor(rbFGF)eye gel combined with tobramycin-dexamethasone(TOB-Dex)eye drops on dry eye syndrome(DES)after cataract surgery.M...Objective:To evaluate the therapeutic effect of recombinant bovine basic fibroblast growth factor(rbFGF)eye gel combined with tobramycin-dexamethasone(TOB-Dex)eye drops on dry eye syndrome(DES)after cataract surgery.Methods:86 patients with DES after cataract surgery,admitted from November 2021 to November 2023,were randomly divided into groups.The observation group included 43 patients treated with rbFGF eye gel combined with TOB-Dex eye drops.The reference group included 43 patients treated with TOB-Dex eye drops alone.Multiple indicators,including total effective rate and clinical symptom scores,were compared between the two groups.Results:The total effective rate in the observation group was higher than in the reference group(P<0.05).Before treatment,there were no differences in clinical symptom scores,serum factors,or disease severity scores between the two groups(P>0.05).Three weeks after treatment,the observation group had lower clinical symptom scores,serum factors,and disease severity scores compared to the reference group(P<0.05).The adverse reaction rate in the observation group was lower than in the reference group(P<0.05).Conclusion:rbFGF eye gel combined with TOB-Dex eye drops can improve the clinical efficacy for patients with DES after cataract surgery,alleviate disease symptoms,reduce inflammatory responses,and have fewer adverse reactions.展开更多
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 depri...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.展开更多
AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. MET...AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. METHODS： Hale rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group （R）, aFGF treatment group （A）, intestinal ischemia group （I）, and sham-operated control group （C）. In group I, the animals were killed after 45 min of superior mesenteric artery （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA occlusion and were treated with normal saline （0.15 mL） and aFGF （20 μg/kg, 0.15 mL）, then sustained at various times for up to 48 h after reperfusion. In group C, SHA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique （TUNEL）. Intestinal tissue samples were taken not only for RT- PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS： In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were （41.17±3.49）%, （42.83±5.23）%, and （53.33±6.92）% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points （50.67±6.95）%, （54.17±7.86）%, and （64.33±6.47）%, respectively, （P〈0.05））. The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group （P〈0.05） at 2-12 h after reperfusion, while the mRNA levels of P53 and P21VVAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion （P〈0.05）. CONCLUSION： P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.展开更多
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 st...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.展开更多
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...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.展开更多
[ Objective] This study aimed to investigate the expression of recombinant protein of fibroblast growth factor 21 （ FGF21 ） in Escherichia coli induced by lactose and explore the possibility of engineering productio...[ Objective] This study aimed to investigate the expression of recombinant protein of fibroblast growth factor 21 （ FGF21 ） in Escherichia coli induced by lactose and explore the possibility of engineering production. [ Method ] The effects of lactose concentration, induction duration, induction starting time, and induc- tion temperature on expression of the recombinant product were compared, and the optimal condition for lactose induction was determined with IPTG induction as a control. [ Result] As an induction agent, lactose plays an ideal rele in the production of recombinant FGF21. In addition, the expression level of lactose induction product is consistent with that of IPTG induction product. Induction in a 250 rrd flask containing 50 ml of medium at A600 0.8 - 1.0 using 0.5 g/L lactose at 35 ℃ for 6 h are the optimal condition. [ Conclusion] Lactose can induce the expression of FGF21 gene and achieve ideal results. This study provides experimental basis and reference for the industrial production of FGF21.展开更多
AIMS To explore the possible effects of basic fibrob- last growth factor (bFGF) on ischemic gut and liver in- juries after trauma. METHODS Animal model of super mesenteric artery (SMA) occlusion was used in this study...AIMS To explore the possible effects of basic fibrob- last growth factor (bFGF) on ischemic gut and liver in- juries after trauma. METHODS Animal model of super mesenteric artery (SMA) occlusion was used in this study. Seventy-two Wistar rats were divided into three groups of 24 rats each. Each animal in group 1 (bFGF treated) was in- jected with 4 μg of bFGF in 0.15 ml of normal saline solution containing 0.1%(w/v) heparin through the jugular vein at the onset of reperfusion. Animals in group 2 (saline treated) received the same vehicle, but without bFGF. Group 3 (sham-operated) ani- mals were treated with the same operations,but without SMA occlusion. Liver function parameters, serum TNFα,bacterial examination and pathological study were used to evaluate the results. RESULTS In group 1,the amounts of ALT and AST and serum TNFα were reduced significantly at 6,24 and 48 hours as compared with group 2. Bacterial ex- amination showed that the bacterial translocation from gut to liver,spleen and MLN in group 1 was much lower than that in group 2. The pathological results support the concept of significant protecting effects of bFGF. CONCLUSIONS Venous administration of bFGF may help reduce gut and liver injuries after ischemia and reperfusion. Its mechanism of action may involve the mitogenic and non-mitogenic effects of bFGF.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
Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survi...Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.展开更多
AIM: To investigate the interfering effect of Y-27632, a ROCK-I selective inhibitor, on the signal transduction pathway of transforming growth factor-beta 1 (TGF-beta 1) in ocular Tenon capsule fibroblasts (OTFS) in v...AIM: To investigate the interfering effect of Y-27632, a ROCK-I selective inhibitor, on the signal transduction pathway of transforming growth factor-beta 1 (TGF-beta 1) in ocular Tenon capsule fibroblasts (OTFS) in vitro. METHODS: After OTFS from passages 4 to 6 47 vitro were induced by TGF-beta 1 and then treated by Y-27632, the changes of the OTFS cell cycles were analyzed via flow cytometry, and the proteins expression of the alpha -smooth muscular actin (alpha -SMA), connective tissue growth factor (CTGF), collagen I were calculated by Western blot. After OTFS treated by the different concentrations of Y-27632, the expression levels of the alpha -SMA, CTGF and collagen I mRNA were assayed by RT-PCR. RESULTS: Y-27632 had no markedly effect on the OTFS cell cycles. After treated by TGF-beta 1, OTFS in G1 period significantly increased. The cell cycles distribution by both TGF-beta 1 and Y-27632 had no remarkable difference from that in control group. Y-27632 significantly inhibited the proteins expressions of both alpha -SMA and CTGF, while to some extent inhibited that of collagen I. TGF-beta 1 significantly promoted the proteins expressions of alpha -SMA, CTGF and collagen I. After OTFS treated by both TGF-beta 1 and Y-27632, of alpha -SMA, the protein expression was similar with that in control group (P=0.066>0.05), but the protein expression of CTGF or collagen I, respectively, was significantly different from that in control group (P=0.000<0.01). The differences of expressions of the alpha -SMA, CTGF and collagen I mRNA in 30, 150, 750 mu mol/L Y-27632 group were statistically significant, compared with those in control group, respectively (alpha -SMA, P=0.002, 0.000, 0.000; CTGF, P=0.014, 0.002, 0.001; collagen I,P=0.003, 0.002, 0.000). CONCLUSION: Blocking the Rho/ROCK signaling pathway by using of Y-27632 could inhibit the cellular proliferation and the expression of both CTGF and alpha -SMA whatever OTFS induced by TGF-beta 1 or not. Y-27632 suppressed the expression of collagen I mRNA without induction.展开更多
The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal c...The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen＇s method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. Immu- nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fi- broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through gene related peptide and acetylcholinesterase cord. attenuating the decreased expression of calcitonin n anterior horn motor neurons of the injured spinal展开更多
Metabolic disorders are increasingly leading to non-alcoholic fatty liver disease,subsequent steatohepatitis,cirrhosis and hepatocellular carcinoma.Fibroblast growth factors and their receptors play an important role ...Metabolic disorders are increasingly leading to non-alcoholic fatty liver disease,subsequent steatohepatitis,cirrhosis and hepatocellular carcinoma.Fibroblast growth factors and their receptors play an important role in maintaining metabolic homeostasis also in the liver and disorders in signaling have been identified to contribute to those pathophysiologic conditions leading to hepatic lipid accumulation and chronic inflammation.While specific and well tolerated inhibitors of fibroblast growth factor receptor activity are currently developed for(non-liver)cancer therapy,treatment of non-alcoholic fatty liver disease and nonalcoholic steatohepatitis is still limited.Fibroblast growth factor-mimicking or restoring approaches have recently evolved as a novel therapeutic option and the impact of such interactions with the fibroblast growth factor receptor signaling network during non-alcoholic fatty liver disease/non-alcoholic steatohepatitis development is reviewed here.展开更多
The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differen...The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.展开更多
Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We review...Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received com-bined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with anti-biotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. Results: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). Conclusion: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair.展开更多
AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorp...AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P = 0.020), well differentiated (log rank χ 2 = 12.798, P = 0.000), T1 or T2 stage (log rank χ 2 = 4.745, P = 0.029), without lymph node involvement (log rank χ 2 = 6.647, P = 0.010), and at an early clinical stage (log rank χ 2 = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.展开更多
BACKGROUND： Spleen deficiency in traditional Chinese medicine refers to the functional disorder of spleen, pancreas, intestines, and nervous system in modern medicine. OBJECTIVE; To test whether electro-acupuncture c...BACKGROUND： Spleen deficiency in traditional Chinese medicine refers to the functional disorder of spleen, pancreas, intestines, and nervous system in modern medicine. OBJECTIVE; To test whether electro-acupuncture could alter basic fibroblast growth factor （bFGF） protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats. DESIGN, TIME AND SETTING： The randomized, controlled, in vivo animal experiment was performed at the National LeveI-B Laboratory of Clinical Cell Molecule and Biology in Shenzhen Hospital of Traditional Chinese Medicine, between March and November in 2008. MATERIALS： Reserpine injection was produced by Guangdong Bangmin Pharmaceutical Co. Rhubarb extract granule preparation was produced by Guangdong Yifang Pharmaceutical. Huanqiu Brand sterile acupuncture pin was provided by Suzhou Acupuncture Supplies, China. Huatuo Brand electroacupuncture instrument （type SDZ-II） was purchased from Suzhou Medical Appliance Factory, China. METHODS： A total of 96 male Sprague Dawley rats were randomly assigned to control （n = 32） and induction （n = 64） groups. Spleen deficiency was induced via intraperitoneal injection of reserpine and intragastric administration of rhubarb. The successful models were randomized into two groups： model and electro-acupuncture, with 32 rats in each group. Electro-acupuncture was administered at Zusanfi （ST 36） and Sanyinjiao （SP 6） acupoints using a condensation wave and rarefaction （condensation wave 15 Hz） at a strength of 6-15 V for 20 minutes, once per day. The appearance of a slight shiver in the corresponding locus was taken as the standard. According to electro- acupuncture time points, each group was assigned to four subgroups at 7, 14, 28, and 49 days, respectively, with eight rats in each subgroup. Immunohistochemical staining, image analysis, and reverse-transcription polymerase chain reaction were performed at different time points. MAIN OUTCOME MEASURES： bFGF protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats. RESULTS： After 7 days of electro-acupuncture therapy, bFGF protein and mRNA expression significantly increased compared with the model and control groups （P 〈 0.05）. After 14 days, bFGF protein and mRNA expression decreased until 28 days, where levels were then equal to the model group and greater than the control group （P 〈 0.05）. After 49 days, the above indices remained increased in the electro-acupuncture group compared to the model and control groups （P 〈 0.05）. CONCLUSION： Continuous electro-acupuncture maintained a high level of bFGF protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats.展开更多
基金supported by grants from Jiangsu Commission of Health,No.Z2021086(to XL)Science and Technology Program of Suzhou,Nos.SYSD2020008(to XL),SKYD2022012(to XL)+1 种基金Suzhou Municipal Health Commission,No.KJXW2020058(to XL)Science and Technology Program of Zhangjiagang,No.ZKS2018(to XL)。
文摘Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury.Fibroblast growth factor 21 can inhibit ferro ptosis and promote neurofunctional recovery,while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis.The relationship between heme oxygenase-1and ferroptosis remains controve rsial.In this study,we used a spinal co rd injury rat model to show that the levels of fibroblast growth factor 21 in spinal co rd tissue decreased after spinal cord injury.In addition,there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury.Furthe r,heme oxygenase-1 aggravated fe rroptosis after spinal cord injury,while fibroblast growth factor 21 inhibited fe rroptosis by downregulating heme oxygenase-1.Thus,the activation of fibroblast growth factor 21 may provide a potential treatment for spinal co rd injury.These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.
基金Supported by The Faculty of Medicine Research Fund,Chiang Mai University,Thailand,No.017/2564.
文摘BACKGROUND The prevalence of gestational diabetes mellitus(GDM)has been increasing worldwide and is associated with multiple adverse pregnancy outcomes.Despite standard screening,some cases remain undiagnosed.Fibroblast growth factor 21(FGF21)plays a role in modulating glucose metabolism.There is an ongoing controversy regarding the relevance of FGF21 to GDM.AIM To evaluate the association between early second trimester serum FGF21 levels and gestational diabetes,and its predictive potential for outcomes.METHODS This cross-sectional observational study was conducted at a tertiary medical center,Chiang Mai University,Thailand.It included 28 pregnant women diag-nosed with GDM and 81 pregnant women with normal glucose status.Blood samples were collected according to the study schedule,and pregnancy outcomes were recorded meticulously.Descriptive analysis was employed to evaluate the data.RESULTS Most participants in our study had no risk factors for GDM(body mass index<24 kg/m2,no first-degree relatives with diabetes,no history of GDM),normal baseline glucose status(fasting glucose<110 mg/dL),and no insulin resistance(homeostatic model assessment of insulin resistance<2).There was a trend of increased FGF21 levels in the insulin-treated GDM group compared with dietary-treated GDM and non-GDM(73.58 pg/mL vs 62.94 pg/mL vs 63.59 pg/mL,respectively,P=0.73).However,no significant association was found between FGF21 concen-trations and pregnancy outcomes based on quintiles of FGF21 levels.CONCLUSION FGF21 was not associated with GDM or pregnancy outcomes;however,due to the small sample size,larger clinical trials with a diverse population are suggested to confirm these results.
文摘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.
文摘Objective:To evaluate the therapeutic effect of recombinant bovine basic fibroblast growth factor(rbFGF)eye gel combined with tobramycin-dexamethasone(TOB-Dex)eye drops on dry eye syndrome(DES)after cataract surgery.Methods:86 patients with DES after cataract surgery,admitted from November 2021 to November 2023,were randomly divided into groups.The observation group included 43 patients treated with rbFGF eye gel combined with TOB-Dex eye drops.The reference group included 43 patients treated with TOB-Dex eye drops alone.Multiple indicators,including total effective rate and clinical symptom scores,were compared between the two groups.Results:The total effective rate in the observation group was higher than in the reference group(P<0.05).Before treatment,there were no differences in clinical symptom scores,serum factors,or disease severity scores between the two groups(P>0.05).Three weeks after treatment,the observation group had lower clinical symptom scores,serum factors,and disease severity scores compared to the reference group(P<0.05).The adverse reaction rate in the observation group was lower than in the reference group(P<0.05).Conclusion:rbFGF eye gel combined with TOB-Dex eye drops can improve the clinical efficacy for patients with DES after cataract surgery,alleviate disease symptoms,reduce inflammatory responses,and have fewer adverse reactions.
文摘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.
基金Supported by the National Natural Science Foundation of China,No. 30400172, 30230370the National Basic Science and Development programme (973 programme, 2005 CB 522603)
文摘AIM： To detect the effect of acid fibroblast growth factor （aFGF） on P53 and P21WAF-1 expression in rat intestine after ischemia-reperfusion （I-R） injury in order to explore the protective mechanisms of aFGF. METHODS： Hale rats were randomly divided into four groups, namely intestinal ischemia-reperfusion group （R）, aFGF treatment group （A）, intestinal ischemia group （I）, and sham-operated control group （C）. In group I, the animals were killed after 45 min of superior mesenteric artery （SHA） occlusion. In groups R and A, the rats sustained for 45 min of SHA occlusion and were treated with normal saline （0.15 mL） and aFGF （20 μg/kg, 0.15 mL）, then sustained at various times for up to 48 h after reperfusion. In group C, SHA was separated, but without occlusion. Apoptosis in intestinal villi was determined with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling technique （TUNEL）. Intestinal tissue samples were taken not only for RT- PCR to detect P53 and P21WAF-1 gene expression, but also for immunohistochemical analysis to detect P53 and P21WAF-1 protein expression and distribution. RESULTS： In histopathological study, ameliorated intestinal structures were observed at 2, 6, and 12 h after reperfusion in A group compared to R group. The apoptotic rates were （41.17±3.49）%, （42.83±5.23）%, and （53.33±6.92）% at 2, 6, and 12 h after reperfusion, respectively in A group, which were apparently lower than those in R group at their matched time points （50.67±6.95）%, （54.17±7.86）%, and （64.33±6.47）%, respectively, （P〈0.05））. The protein contents of P53 and P21WAF-1 were both significantly decreased in A group compared to R group （P〈0.05） at 2-12 h after reperfusion, while the mRNA levels of P53 and P21VVAF-1 in A group were obviously lower than those in R group at 6-12 h after reperfusion （P〈0.05）. CONCLUSION： P53 and P21WAF-1 protein accumulations are associated with intestinal barrier injury induced by I-R insult, while intravenous aFGF can alleviate apoptosis of rat intestinal cells by inhibiting P53 and P21WAF-1 protein expression.
基金Supported by the Grant from the Medical University of Lublin,No. DS 507/2013–2015
文摘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.
基金the 2022 Zhejiang Provincial Health Science and Technology Plan,No.2022KY1216.
文摘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.
基金Supported by Science and Technology Development Fund of Jilin Province(20090949,20116044)Student Research Fund from Jilin Medical College([2010]No.09)
文摘[ Objective] This study aimed to investigate the expression of recombinant protein of fibroblast growth factor 21 （ FGF21 ） in Escherichia coli induced by lactose and explore the possibility of engineering production. [ Method ] The effects of lactose concentration, induction duration, induction starting time, and induc- tion temperature on expression of the recombinant product were compared, and the optimal condition for lactose induction was determined with IPTG induction as a control. [ Result] As an induction agent, lactose plays an ideal rele in the production of recombinant FGF21. In addition, the expression level of lactose induction product is consistent with that of IPTG induction product. Induction in a 250 rrd flask containing 50 ml of medium at A600 0.8 - 1.0 using 0.5 g/L lactose at 35 ℃ for 6 h are the optimal condition. [ Conclusion] Lactose can induce the expression of FGF21 gene and achieve ideal results. This study provides experimental basis and reference for the industrial production of FGF21.
基金Supported by the National Natural Science Foundation of China (No.39470706).
文摘AIMS To explore the possible effects of basic fibrob- last growth factor (bFGF) on ischemic gut and liver in- juries after trauma. METHODS Animal model of super mesenteric artery (SMA) occlusion was used in this study. Seventy-two Wistar rats were divided into three groups of 24 rats each. Each animal in group 1 (bFGF treated) was in- jected with 4 μg of bFGF in 0.15 ml of normal saline solution containing 0.1%(w/v) heparin through the jugular vein at the onset of reperfusion. Animals in group 2 (saline treated) received the same vehicle, but without bFGF. Group 3 (sham-operated) ani- mals were treated with the same operations,but without SMA occlusion. Liver function parameters, serum TNFα,bacterial examination and pathological study were used to evaluate the results. RESULTS In group 1,the amounts of ALT and AST and serum TNFα were reduced significantly at 6,24 and 48 hours as compared with group 2. Bacterial ex- amination showed that the bacterial translocation from gut to liver,spleen and MLN in group 1 was much lower than that in group 2. The pathological results support the concept of significant protecting effects of bFGF. CONCLUSIONS Venous administration of bFGF may help reduce gut and liver injuries after ischemia and reperfusion. Its mechanism of action may involve the mitogenic and non-mitogenic effects of bFGF.
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.
基金Supported by KAKENHI(partiallyGrant-in-Aid for Scientific ResearchNo.23390329)
文摘Fibroblast growth factor receptors(FGFRs) regulate a variety of cellular functions, from embryogenesis to adult tissue homeostasis. FGFR signaling also plays significant roles in the proliferation, invasion, and survival of several types of tumor cells. FGFR-induced alterations, including gene amplification, chromosomal translocation, and mutations, have been shown to be associated with the tumor initiation and progression of gastric cancer, especially in diffuse-type cancers. Therefore, the FGFR signaling pathway might be one of the therapeutic targets in gastric cancer. This review aims to provide an overview of the role of FGFR signaling in tumorigenesis, tumor progression, proliferation, and chemoresistance. We also discuss the accumulating evidence that demonstrates the effectiveness of using clinical therapeutic agents to inhibit FGFR signaling for the treatment of gastric cancer.
基金Shaanxi Province Science and Technology Gongguan Program, China (No.2011-K14-02-03)
文摘AIM: To investigate the interfering effect of Y-27632, a ROCK-I selective inhibitor, on the signal transduction pathway of transforming growth factor-beta 1 (TGF-beta 1) in ocular Tenon capsule fibroblasts (OTFS) in vitro. METHODS: After OTFS from passages 4 to 6 47 vitro were induced by TGF-beta 1 and then treated by Y-27632, the changes of the OTFS cell cycles were analyzed via flow cytometry, and the proteins expression of the alpha -smooth muscular actin (alpha -SMA), connective tissue growth factor (CTGF), collagen I were calculated by Western blot. After OTFS treated by the different concentrations of Y-27632, the expression levels of the alpha -SMA, CTGF and collagen I mRNA were assayed by RT-PCR. RESULTS: Y-27632 had no markedly effect on the OTFS cell cycles. After treated by TGF-beta 1, OTFS in G1 period significantly increased. The cell cycles distribution by both TGF-beta 1 and Y-27632 had no remarkable difference from that in control group. Y-27632 significantly inhibited the proteins expressions of both alpha -SMA and CTGF, while to some extent inhibited that of collagen I. TGF-beta 1 significantly promoted the proteins expressions of alpha -SMA, CTGF and collagen I. After OTFS treated by both TGF-beta 1 and Y-27632, of alpha -SMA, the protein expression was similar with that in control group (P=0.066>0.05), but the protein expression of CTGF or collagen I, respectively, was significantly different from that in control group (P=0.000<0.01). The differences of expressions of the alpha -SMA, CTGF and collagen I mRNA in 30, 150, 750 mu mol/L Y-27632 group were statistically significant, compared with those in control group, respectively (alpha -SMA, P=0.002, 0.000, 0.000; CTGF, P=0.014, 0.002, 0.001; collagen I,P=0.003, 0.002, 0.000). CONCLUSION: Blocking the Rho/ROCK signaling pathway by using of Y-27632 could inhibit the cellular proliferation and the expression of both CTGF and alpha -SMA whatever OTFS induced by TGF-beta 1 or not. Y-27632 suppressed the expression of collagen I mRNA without induction.
基金supported by a grant from the Hunan Provincial Science and Technology Ministry in China, No. 2012SK3222Funding for New Teachers by the Ministry of Education in China, No. 200805331166
文摘The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage following spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Allen＇s method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also well recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additionally, anterior tibial muscle fibers slowly, but progressively, atrophied. Immu- nohistochemical staining showed that the absorbance values of calcitonin gene related peptide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fi- broblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related peptide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through gene related peptide and acetylcholinesterase cord. attenuating the decreased expression of calcitonin n anterior horn motor neurons of the injured spinal
文摘Metabolic disorders are increasingly leading to non-alcoholic fatty liver disease,subsequent steatohepatitis,cirrhosis and hepatocellular carcinoma.Fibroblast growth factors and their receptors play an important role in maintaining metabolic homeostasis also in the liver and disorders in signaling have been identified to contribute to those pathophysiologic conditions leading to hepatic lipid accumulation and chronic inflammation.While specific and well tolerated inhibitors of fibroblast growth factor receptor activity are currently developed for(non-liver)cancer therapy,treatment of non-alcoholic fatty liver disease and nonalcoholic steatohepatitis is still limited.Fibroblast growth factor-mimicking or restoring approaches have recently evolved as a novel therapeutic option and the impact of such interactions with the fibroblast growth factor receptor signaling network during non-alcoholic fatty liver disease/non-alcoholic steatohepatitis development is reviewed here.
基金supported by the National Natural Science Foundation of China,No.81070614the Key Project of the Natural Science Foundation of Hubei Province of China,No. 2008CDA044the Natural Science Foundation of Hubei University of Medicine,No.2011QDZR-2
文摘The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor, fibroblast growth factor receptor-3, in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro. Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo. Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence. Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro. Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain, namely the substantia nigra, compact part, dorsal tier, substantia nigra and reticular part, but was not detected in the forebrain comprising the caudate putamen and striatum. Unusual results were obtained in retrosplenial locations of adult rat brain. We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses. We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8, a secretory factor. Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells. In contrast, addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons. Our study may help delineate the important roles of fibroblast growth factor-8 in brain activities and neural stem/progenitor cell differentiation.
文摘Objective: To evaluate the efficacy and the indication of basic fibroblast growth factor (bFGF) in the treatment of exposure of orbital implants. Design: Retrospective and observational case series. Methods: We reviewed 41 patients (41 eyes) suffering exposure of orbital implants from Jan. 2000 to June 2006. The study group patients with mild exposure received com-bined treatment with bFGF and antibiotic drops, and while the control group patients with mild exposure were treated with anti-biotic drops only. The study group patients with moderate and severe exposure received combined treatment with bFGF and antibiotic drops, and after 2 months they were subjected to amniotic membrane transplantation, while the control group patients with moderate and severe exposure underwent amniotic membrane transplantation after using antibiotic drops. Observation of the growth of conjunctival epithelium and comparison of the healing rate of the two groups. Results: The healing rates of the mild, moderate and severe exposure study group were 100% and 92.3%. The healing rates of the mild, moderate and severe exposure control group were 55.6% and 66.7% respectively. The difference of the healing rates of the mild exposure study group and the control group was significant (P=0.033). And the difference of the healing rates of the moderate and severe exposure study group and the control group was not significant (P=0.167). Conclusion: bFGF may promote obviously the healing of orbital implant exposure, particularly it can be the first choice for the treatment of mild degree exposure. For the moderate and severe cases, it can be administered before surgical repair to enhance neovascularization and will tend to increase the success rate of surgical repair.
文摘AIM: To investigate the contribution of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism as a genetic risk factor for gastric cancer (GC) and to investigate any associations between this polymorphism and clinicopathological parameters and survival. METHODS: Tumors and matched adjacent non-cancer tissues were collected from 304 GC patients, and 5 mL of venous blood was collected from 62 GC patients and 392 ageand sex-matched healthy controls without cancer history from the same ethnic population. DNA was extracted, and direct sequencing analyses were performed to genotype the FGFR4 Gly388Arg polymorphism in all the samples. Differences in the genotype frequencies of the FGFR4 Gly388Arg polymorphism between GC patients and healthy controls were estimated using the χ 2 test. Binary logistic regression was used for all analysis variables to estimate risk as the ORs with 95%CIs. The relationships between the FGFR4 genotype and clinicopathological parameters were tested with the χ 2 test. The Kaplan-Meier product-limit method, the log-rank test, and the Cox regression model were applied to evaluate the effect of the FGFR4 genotype on the overall survival of patients with GC. RESULTS: In the present GC cohort, 118 patients (38.8%) were homozygous for the Gly388 allele, 124 patients (40.8%) were heterozygous, and 62 patients (20.4%) were homozygous for the Arg388 allele. The frequencies of the Gly/Gly, Gly/Arg, and Arg/Arg genotypes in the healthy controls were 33.6%, 48.0%, and 18.4%, respectively. The distributions of genotypes (χ 2 = 3.589, P = 0.166) and alleles (χ 2 = 0.342, P = 0.559) of the FGFR4 Gly388Arg polymorphism were not different between the GC patients and the healthy controls. Although we observed no correlation between the FGFR4 Gly388Arg polymorphism and clinicopathological parameters or survival in the total cohort of GC patients, the presence of the Arg388 allele was associated with shorter survival time in patients with GC if the tumor was small (log rank χ 2 = 5.449, P = 0.020), well differentiated (log rank χ 2 = 12.798, P = 0.000), T1 or T2 stage (log rank χ 2 = 4.745, P = 0.029), without lymph node involvement (log rank χ 2 = 6.647, P = 0.010), and at an early clinical stage (log rank χ 2 = 4.615, P = 0.032). CONCLUSION: Our results suggest that the FGFR4 Gly388Arg polymorphism is not a risk factor for GC cancer initiation but that it is a useful prognostic marker for GC patients when the tumor is relatively small, well differentiated, or at an early clinical stage.
基金Science and Technology Plan Program of Social Development of Guangdong Science and Technology Department in 2007,No.73127
文摘BACKGROUND： Spleen deficiency in traditional Chinese medicine refers to the functional disorder of spleen, pancreas, intestines, and nervous system in modern medicine. OBJECTIVE; To test whether electro-acupuncture could alter basic fibroblast growth factor （bFGF） protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats. DESIGN, TIME AND SETTING： The randomized, controlled, in vivo animal experiment was performed at the National LeveI-B Laboratory of Clinical Cell Molecule and Biology in Shenzhen Hospital of Traditional Chinese Medicine, between March and November in 2008. MATERIALS： Reserpine injection was produced by Guangdong Bangmin Pharmaceutical Co. Rhubarb extract granule preparation was produced by Guangdong Yifang Pharmaceutical. Huanqiu Brand sterile acupuncture pin was provided by Suzhou Acupuncture Supplies, China. Huatuo Brand electroacupuncture instrument （type SDZ-II） was purchased from Suzhou Medical Appliance Factory, China. METHODS： A total of 96 male Sprague Dawley rats were randomly assigned to control （n = 32） and induction （n = 64） groups. Spleen deficiency was induced via intraperitoneal injection of reserpine and intragastric administration of rhubarb. The successful models were randomized into two groups： model and electro-acupuncture, with 32 rats in each group. Electro-acupuncture was administered at Zusanfi （ST 36） and Sanyinjiao （SP 6） acupoints using a condensation wave and rarefaction （condensation wave 15 Hz） at a strength of 6-15 V for 20 minutes, once per day. The appearance of a slight shiver in the corresponding locus was taken as the standard. According to electro- acupuncture time points, each group was assigned to four subgroups at 7, 14, 28, and 49 days, respectively, with eight rats in each subgroup. Immunohistochemical staining, image analysis, and reverse-transcription polymerase chain reaction were performed at different time points. MAIN OUTCOME MEASURES： bFGF protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats. RESULTS： After 7 days of electro-acupuncture therapy, bFGF protein and mRNA expression significantly increased compared with the model and control groups （P 〈 0.05）. After 14 days, bFGF protein and mRNA expression decreased until 28 days, where levels were then equal to the model group and greater than the control group （P 〈 0.05）. After 49 days, the above indices remained increased in the electro-acupuncture group compared to the model and control groups （P 〈 0.05）. CONCLUSION： Continuous electro-acupuncture maintained a high level of bFGF protein and mRNA expression in the hippocampal dentate gyrus of spleen deficiency rats.
