Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

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.

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.

Interference of Y-27632 on the signal transduction of transforming growth factor beta type 1 in ocular Tenon capsule fibroblasts

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.

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.

The hypoxia-inducible factor-1α activates ectopic production of fibroblast growth factor 23 in tumor-induced osteomalacia

Tumor-induced osteomalacia （TIO） is a rare paraneoplastic syndrome in which ectopic production of fibroblast growth factor 23 （FGF23） by non-malignant mesenchymal tumors causes phosphate wasting and bone fractures. Recent studies have implicated the hypoxia-inducible factor-la （HIF-la） in other phosphate wasting disorders caused by elevated FGF23, including X-linked hypophosphatemic rickets and autosomal dominant hypophosphatemia. Here we provide evidence that HIF-la mediates aberrant FGF23 in TIO by transcriptionally activating its promoter. Immunohistochemical studies in phosphaturic mesenchymal tumors resected from patients with documented TIO showed that HIF-la and FGF23 were co-localized in spindle- shaped cells adjacent to blood vessels. Cultured tumor tissue produced high levels of intact FGF23 and demonstrated increased expression of HIF-la protein. Transfection of MC3T3-E1 and Saos-2 cells with a HIF-la expression construct induced the activity of a FGF23 reporter construct. Prior treatment of tumor organ cultures with HIF-la inhibitors decreased HIF-la and FGF23 protein accumulation and inhibited HIF-la-induced luciferase reporter activity in transfected cells. Chromatin immunoprecipitation assays confirmed binding to a HIF-la consensus sequence within the proximal FGF23 promoter, which was eliminated by treatment with a HIF-la inhibitor. These results show for the first time that HIF-la is a direct transcriptional activator of FGF23 and suggest that upregulation of HIF-la activity in TIO contributes to the aberrant FGF23 production in these patients.

Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1 in Human Meningiomas

The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1. The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.

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.

Effects of Tanshinone ⅡA on Transforming Growth Factor β1-Smads Signal Pathway in Renal Interstitial Fibroblasts of Rats

The effects of tanshinone ⅡA （TSN） on transforming growth factor β1 （TGFβ1） signal transduction in renal interstitial fibroblasts of rats were studied in order to investigate its mechanism in prevention of renal interstitial fibrosis. Rat renal fibroblasts of the line NRK/49F were cultured in vitro, stimulated with 5 ng/mL TGFβ1 and pretreated with 10-6, 10-5, 10-4 mol/L TSN respectively. The mRNA levels of fibronectin （FN） were examined by RT-PCR. The protein expression of FN and Smads was detected by Western blot. TGFβ1 induced the expression of FN mRNA and Smads in a time-dependent manner in a certain range. Compared with pre-stimulation, the FN mRNA and protein levels were increased by 1.1 times and 1.5 times respectively （P〈0.01, P〈0.01）, and the protein expression of phosphorylated Smad2/3 （p-Smad2/3） increased by 7 times at the end of TGFβ1 stimulation （P〈0.01）. TSN pretreatment may down-regulate the FN and p-Smad2/3 expression in a dose-dependent manner. 10-6 mol/L TSN pretreatment had no effect on the FN and p-Smad2/3 expression （both P〉0.05）. After pretreatment with 10-5 and 10-4 mol/L TSN, the FN mRNA levels were decreased by 28.1% and 43.8% respectively （P〈0.05, P〈0.01）, the FN protein levels were decreased by 40% and 44% respectively （P〈0.05, P〈0.05）, and the p-Smad2/3 protein expression were decreased by 40% and 65% respectively （P〈0.05, P〈0.01）. The inhibitory effect of TSN on renal interstitial fibrosis may be related to its blocking effect on TGFβ1-Smads signal pathway in renal intersti- tial fibroblasts.

Role of fibroblast growth factor receptor 1 in the bone development and skeletal diseases

Accumulating data suggest that FGFs/FGFR1 plays essential roles in the bone development and human skeletal diseases. Conditional inactivation of fgfrl caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development. Fgfrl mutation mainly induced 2 types of human skeletal diseases, craniosynostosis syndrome and dysplasias. Similar mutation of fgfrl in mouse model just mimicked the phenotype that happened in human. These fa- cilitate the investigation on the underlying mechanism of the diseases. Here we mainly focused on the ad- vance of FGFR1 function in the bone development and its mutation caused skeletal diseases.

Local inhibition of matrix metalloproteinases reduced M2 macrophage activity and impeded recovery in spinal cord transected rats after treatment with fibroblast growth factor-1 and nerve grafts

Alternatively activated macrophages （M2 macrophages） promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited more M2 macrophages and improved partial functional recovery in spinal cord transected rats. The migration of macrophages is matrix metalloproteinase （MMP） dependent. We used a general inhibitor of MMPs to influence macrophage migration, and we examined the migration of macrophage populations and changes in spinal function. Rat spinal cords were completely transected at Ts, and 5 mm of spinal cord was removed （group T）. In group R, spinal cord-transected rats received treatment with fibroblast grow th factor- 1 and peripheral nerve grafts. In group RG, rats received the same treatment as group R with the addition of 200 μM GM6001 （an MMP inhibitor） to the fibrin mix. We found that MMP-9, but not MMP- 2, was upregulated in the graft area of rats in group R. Local application of the MMP inhibitor resulted in a reduction in the ratio of arginase-1 （M2 macrophage subset）/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was applied at 8 weeks postoperation, the partial functional recovery observed in group R was lost. This effect was accompanied by a decrease in brain-derived neurotrophic factor levels in the nerve graft. These results suggested that the arginase-1 positive population in spinal cord transected rats is a migratory cell population rather than the phenotypic conversion of early iNOS^＋ cells and that the migration of the arginase-1^＋ population could be regulated locally. Simultaneous application of MMP in- hibitors or promotion of MMP activity for spinal cord injury needs to be considered if the coadministered treatment involves M2 recruitment.

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.

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.

Are there fibroblast growth factor receptor 1 mutations in a Chinese Kallmann syndrome family?

The present study examined 58 members of a Kallmann syndrome family and investigated whether there are fibroblast growth factor receptor 1 （FGFR1） gene mutations in this family. Genomic DNA from the proband and family members was subjected to PCR to amplify 18 exons of FGFR1, and the amplified products were sequenced to identify potential mutations. MRI of the olfactory bulb region was performed on suspected subjects. The patient and his father were diagnosed with Kallmann syndrome. A polymorphic site was found at 39542, with the proband and his parents being heterozygous （guanine ＋ cytosine）. However, healthy controls and the other members of this family were homozygous for guanine at this position.

EXPRESSION AND SIGNIFICANCE OF BASIC FIBROBLAST GWOWTH FACTOR AND FIBROBLAST GROWTH FACTOR RECEPTOR-1 IN OVARIAN EPITHELIAL NEOPLASM

Objective To study the relevance of expression of basic fibroblast growth factor (bFGF), fibroblast growth factor receptor 1 (FGFR 1) and carcinogenesis and progression of ovarian epithelial neoplasm. Methods Ten cases of normal ovarian tissues and 75 cases of ovarian epithelial neoplasm tissues were detected by immunohistochemical methods: S P for bFGF, FGFR 1,double immunohistochemistry Lab SA for Ki 67 antigen and bFGF. Results The expression level of bFGF, FGFR 1in ovarian epithelium and ovarian epithelial neoplasm showed a step wise increase in the following order:normal <benign <borderline <malignant; The expression level and intensity of bFGF and FGFR 1 were increased with the decrease of differentiation degree and increase of clinical stage in ovarian carcinoma; There was no statistical difference between the expression of bFGF, FGFR 1 in serous cystadenocarcinoma and that of mucinous cystadenocarcinoma; The expression of bFGF was correlated with that of FGFR 1 in neoplastic tissues; There were positive expression rates of bFGF and Ki 67 antigen in ovarian epithelial neoplasm. Conclusion As an important proliferative factor, bFGF plays an important role in carcinogenisis and progression of ovarian epithelial neoplasm.

Exogenous acid fibroblast growth factor inhibits ischemia-reperfusion-induced damage in intestinal epithelium via regulating P53 and P21WAF-1 expression

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.

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.

儿童慢性粒细胞白血病慢性期红细胞参数及血清bFGF、TGF-β1、VEGF表达变化分析

目的探究儿童慢性粒细胞白血病(CML)慢性期红细胞参数及血清碱性成纤维细胞生长因子(bFGF)、转化生长因子β1(TGF-β1)及血管内皮生长因子(VEGF)表达变化。方法前瞻性选取2020年1月至2023年1月在首都医科大学附属北京儿童医院进行治疗的54例CML慢性期患儿为研究组,另随机抽取46名同期在本院进行体检的健康儿童为健康对照组。研究组给予酪氨酸激酶抑制剂治疗。比较两组间红细胞参数及血清bFGF、TGF-β1、VEGF表达变化,并比较研究组治疗前后红细胞参数及血清bFGF、TGF-β1、VEGF表达水平。结果研究组的RBC、血红蛋白、红细胞压积(HCT)及平均红细胞血红蛋白浓度(MCHC)水平分别为(3.45±0.04)×10^(12)/L、(102.33±1.15)g/L、(32.03±0.61)%、322.15±2.58,均显著低于对照组[(4.98±0.03)×10^(12)/L、(149.78±1.88)g/L、(44.33±0.31)%、334.12±0.77],平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)及红细胞体积分布宽度(RDW)水平分别为(91.44±0.77)fL、(33.15±2.55)pg、(17.55±0.12)%,均显著高于对照组[(89.88±0.34)fL、(30.24±0.16)pg、(12.66±0.11)%],差异均有统计学意义(P<0.05)。研究组的血清bFGF、VEGF水平分别为(30.66±9.66)、(128.68±30.58)pg/mL,均显著高于对照组[(5.26±1.54)、(70.66±11.26)pg/mL],TGF-β1水平为(38.22±8.06)μg/L,显著低于对照组[(78.66±8.13)μg/L],差异均有统计学意义(P<0.05)。治疗后,研究组患儿的RBC、血红蛋白、HCT、MCV及MCH水平均较治疗前显著降低,MCHC及RDW水平均较治疗前显著升高,差异均有统计学意义(P<0.05)。研究组治疗后的血清bFGF、VEGF水平均较治疗前显著降低,TGF-β1水平较治疗前显著升高,差异均有统计学意义(P<0.05)。结论在儿童CML慢性期患儿中可见血细胞参数明显异常,血清bFGF、VEGF水平显著升高,TGF-β1水平显著降低。酪氨酸激酶抑制剂治疗CML慢性期能有效改善患儿红细胞形态及功能,抑制肿瘤细胞生长,临床疗效显著,值得临床推广使用。

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。

血清DKK1、FGF19联合CT在原发性肝癌患者介入治疗疗效评估中的应用价值

目的探讨血清Dickkopf-1(DKK1)、成纤维细胞生长因子19(FGF19)联合计算机断层扫描(CT)对原发性肝癌(PHC)患者经导管动脉栓塞化疗(TACE)的疗效评估价值。方法分别纳入2022年1月-2023年2月本院136例PHC患者,TACE治疗2个月后依据疗效分为灭活组(59例)与残留组(77例)。双抗体夹心法检测血清DKK1、FGF19水平,并对患者进行CT扫描。ROC曲线获取血清DKK1、FGF19诊断PHC患者TACE治疗后疗效的最佳截断值。以数字减影血管造影检查(DSA)为金标准,探讨血清DKK1、FGF19联合CT扫描对TACE治疗后疗效的诊断价值。采用Kappa检验分析血清DKK1、FGF19联合CT诊断PHC疗效与DSA结果一致性。结果残留组患者血清DKK1、FGF19水平分别为(2.41±0.33)ng/mL、(206.72±21.60)pg/mL,明显高于灭活组的(1.87±0.29)ng/mL、(169.57±18.45)pg/mL,差异有统计学意义(P<0.05)。ROC曲线显示,血清DKK1、FGF19水平诊断PHC患者TACE治疗后疗效的曲线下面积分别为0.925、0.916,敏感度为83.12%、84.42%,特异度为91.52%、94.92%。CT扫描评估PHC患者TACE治疗疗效与DSA结果一致性高,Kappa值=0.766(P<0.05)。血清DKK1、FGF19联合CT扫描诊断疗效的准确度为93.38%,敏感度、特异度为96.10%、89.83%,且联合检测的敏感度明显优于单独DKK1、FGF19、CT扫描(P<0.05)。结论血清DKK1、FGF19联合CT扫描对PHC患者TACE治疗后疗效有一定诊断价值。

经钻孔引流术治疗慢性硬膜下血肿患者血清TSP1、TSP2、bFGF、VEGF、S-100β水平变化及其临床意义

目的探讨经钻孔引流术治疗慢性硬膜下血肿患者血清血小板反应蛋白1(TSP1)、血小板反应蛋白2(TSP2)、碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子(VEGF)、中枢神经特异蛋白(S-100β)水平变化及其临床意义。方法选取江苏省中医院2019年1月~2023年6月收治的慢性硬膜下血肿患者142例作为病例组,均进行钻孔引流术;另选取同期健康体检人员146例作为健康对照组,比较两组不同脑损伤、手术前后、不同复发情况的血清TSP1、TSP2、bFGF、VEGF、S-100β水平,分析血清TSP1、TSP2、bFGF、VEGF、S-100β水平与慢性硬膜下血肿患者脑损伤程度的相关性。结果与健康对照组比较,病例组血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对更高;与轻度脑损伤组进行比较,中度脑损伤组、重度脑损伤组血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对更高,且重度脑损伤组高于中度脑损伤组;与术前进行比较,术后7 d慢性硬膜下血肿患者血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对较低;与复发组进行比较,未复发组血清TSP1、TSP2、bFGF、VEGF、S-100β水平均相对较低(P<0.05)。Pearson相关分析结果显示,慢性硬膜下血肿患者血清TSP1、TSP2、bFGF、VEGF、S-100β水平与GCS评分均呈负相关关系(r=-0.655、-0.674、-0.711、-0.689、-0.705,P<0.05)。结论慢性硬膜下血肿患者经钻孔引流术后血清TSP1、TSP2、bFGF、VEGF、S-100β水平均降低,并与患者脑损伤程度、转归具有高度相关性,临床上可通过检测慢性硬膜下血肿患者上述各项血清学指标的变化情况,以便及时判断慢性硬膜下血肿患者的脑损伤程度。