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.

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.

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.

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 fgfr1 caused different phenotypes displaying in different cells or specific organs and revealed some novel functions of FGFR1 in bone development.Fgfr1 mutation mainly induced 2 types of human skeletal diseases,craniosynostosis syndrome and dysplasias. Similar mutation of fgfr1 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.

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.

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.

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.

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.

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: Male 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 (SMA) occlusion. In groups R and A, the rats sustained for 45 min of SMA 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, SMA 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 RTPCR 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 P53and 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 P21WAF-1in A group were obviously lower than those in R group at6-12 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-1protein expression.

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.

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。

冠心病患者血清bFGF、sTLT-1水平与支架置入术后再狭窄的关系

目的探讨冠心病患者血清碱性成纤维细胞生长因子(bFGF)、可溶性髓样细胞触发受体样转录因子1(sTLT-1)水平与支架置入术后支架内再狭窄(ISR)的关系。方法收集2020年1月至2022年3月收治的冠心病行支架置入术患者450例。根据术后1年复查是否发生ISR分为ISR组(41例)、非ISR组(409例)。比较ISR组与非ISR组一般资料、实验室相关指标、血清bFGF、sTLT-1水平;Pearson法分析冠心病支架置入术后ISR患者血清bFGF、sTLT-1水平的相关性;Logistic回归分析冠心病患者支架置入术后发生ISR的影响因素;ROC曲线分析血清bFGF、sTLT-1水平诊断冠心病患者支架置入术后发生ISR的临床价值。结果ISR组狭窄程度、植入支架数量、术前Gensini评分、血清sTLT-1、CRP水平显著高于非ISR组,支架直径、血清bFGF、CysC水平显著低于非ISR组(P<0.05);Ⅲ级组血清bFGF水平显著高于Ⅳ级组(P<0.05),Ⅲ级组血清sTLT-1水平显著低于Ⅳ级组(P<0.05);冠心病支架置入术后发生ISR的患者血清bFGF与sTLT-1水平呈负相关(R=-0.648,P<0.001);sTLT-1、CRP是冠心病患者支架置入术后发生ISR的危险因素,bFGF、CysC是保护因素(P<0.05);血清bFGF、sTLT-1两者联合诊断冠心病患者支架置入术后发生ISR的AUC为0.901,优于各自单独诊断(Z二者联合-bFGF=3.086、Z二者联合-sTLT-1=2.754,P=0.002、P=0.030),联合诊断的敏感度为89.80%,特异性为76.12%。结论冠心病支架置入术后发生ISR的患者血清bFGF水平下调,sTLT-1水平上调,二者均是ISR的影响因素,且联合诊断冠心病患者支架置入术后ISR的发生具有较高效能。

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。

牛磺熊去氧胆酸通过调节内质网应激抑制转化生长因子β1所诱导的心肌成纤维细胞纤维化

目的探讨牛磺熊去氧胆酸(TUDCA)对转化生长因子β1(TGF-β1)所诱导的心肌成纤维细胞(CFs)活化的作用及相关机制,为TUDCA治疗糖尿病心肌纤维化提供新的治疗目标。方法提取原代SD乳鼠CFs和心肌细胞,通过免疫荧光法鉴定CFs的纯度。分别将高糖培养下的CFs用不同时间的TGF-β1干预,用Western blot检测内质网应激(ERS)通路相关蛋白和纤维化指标的表达,探讨TGF-β1对CFs活化及ERS相关通路的影响。用Western blot检测CFs和心肌细胞内同型半胱氨酸内质网应激泛素样结构域1(Herpud1)的表达情况。通过沉默Herpud1的表达及用Transwell和Western blot检测沉默Herpud1后CFs纤维化指标的表达,探讨Herpud1在TGF-β1诱导的CFs活化中的作用。用CCK-8检测不同浓度的TUDCA处理下CFs的活力。用免疫荧光和Western blot检测TUDCA对TGF-β1诱导的CFs中Herpud1、葡萄糖调节蛋白78(GRP78)、转录激活因子6(ATF6)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)和Ⅰ型胶原蛋白(CollagenⅠ)表达的影响。为进一步明确Herpud1在TUDCA抑制CFs活化中的作用,用Western blot检测过表达Herpud1后相关蛋白的表达情况。结果在成功构建CFs纤维化模型的基础上,TGF-β1能够诱导CFs活化及ERS通路相关蛋白的表达;Herpud1在CFs中的表达高于心肌细胞;敲除Herpud1可抑制TGF-β1所诱导的CFs活化;TUDCA能显著降低TGF-β1诱导的CFs中GRP78、ATF6、α-SMA、Vimentin和CollagenⅠ的表达水平;此外,过表达Herpud1还可逆转TUDCA对TGF-β1诱导的CFs活化的抑制。结论下调Herpud1基因的表达是TUDCA抑制TGF-β1诱导的CFs纤维化的机制之一。

FGF−21、IMA、MCP−1与急性心肌梗死患者预后的关系

目的 研究成纤维细胞生长因子-21 (fibroblast growth factor 21,FGF-21)、缺血修饰白蛋白(ischemia modified albumin,IMA)、单核细胞趋化蛋白-1 (monocyte chemotactic protein-1,MCP-1)与急性心肌梗死(acute myocardial Infarction,AMI)患者预后的关系。方法 选择本院2017年5月-2020年7月诊治的110例AMI患者,根据患者预后情况分为预后不良组和预后良好组,收集患者临床资料,分析其血清FGF-21、IMA、MCP-1水平与AMI患者预后的关系以及诊断主要不良心血管事件(major adverse cardiovascular event,MACE)发生的效能。结果 预后良好组患者血清FGF-21、IMA、MCP-1水平低于预后不良组,差异有统计学意义(P<0.05);血清FGF-21、IMA、MCP-1水平3者联合预测预后的ROC曲线下面积(area under curve,AUC)以及敏感度最高(P<0.05);不同血清FGF-21、IMA、MCP-1水平患者MACE发生率比较,差异有统计学意义(P<0.05);Cox单因素以及多因素分析结果显示,FGF-21>150.12 ng/L、IMA> 75.78 U/mL、MCP-1> 49.67 pg/mL、肌酸激酶-同工酶(CK-MB)> 35 U/L以及心肌肌钙蛋白Ⅰ(cTnⅠ)> 75.78 U/mL均是影响AMI患者预后不良的独立危险因素(P<0.05)。结论 血清FGF-21、IMA、MCP-1水平均可较好地预测AMI患者预后不良的发生,且三者联合预测效能更高,同时血清FGF-21、IMA、MCP-1水平增高与MACE的发生密切相关,是AMI患者预后不良的危险因素。

血清血管生成抑制蛋白-1成纤维生长因子-23联合尿β2-微球蛋白对DN的诊断价值

目的探究血清血管生成抑制蛋白-1(VASH-1)、成纤维生长因子-23(FGF23)联合尿β2-微球蛋白(β2-MG)对糖尿病肾病(DN)的诊断价值。方法选取2022年1月至2023年5月在焦作煤业(集团)有限责任公司中央医院进行治疗的115例DN患者作为DN组,选取同时期本院60例健康体检者为对照组。根据24 h尿清蛋白排泄率(URER),将DN组分为单纯糖尿病组(A组,35例)、微量清蛋白尿组(B组,41例)和大量清蛋白尿组(C组,39例);比较受试者血清VASH-1、FGF-23水平、尿素、肌酐含量、尿β2-MG水平;采用Pearson法对血清VASH-1、FGF-23水平与尿素、肌酐含量、尿β2-MG水平进行相关性分析;采用多因素logistic回归分析DN发生的影响因素;受试者工作特征(ROC)曲线分析血清VASH-1、FGF-23联合尿β2-MG对DN的诊断价值。结果DN组血清VASH-1、FGF-23、尿素、肌酐含量、尿β2-MG水平均高于对照组(P<0.05);C组患者血清VASH-1、FGF-23、尿素、肌酐含量、尿β2-MG水平均高于B组和A组(P<0.05);DN患者血清VASH-1、FGF-23水平与尿素、肌酐含量、尿β2-MG水平均呈正相关(P<0.05);血清VASH-1、FGF-23、尿素、肌酐含量、尿β2-MG水平均为影响DN发生的危险因素(P<0.05);血清VASH-1、FGF-23、尿β2-M联合诊断DN价值高于单独诊断(Z_(三者联合-VASH-1)=4.389、P<0.001,Z_(三者联合-FGF-23)=3.117、P=0.002,Z_(三者联合-β2-MG)=4.556、P<0.001)。结论DN患者血清VASH-1、FGF-23、尿β2-MG水平与疾病的发生发展有关,且三者联合诊断效果较好,有望为DN的诊断提供一定的临床诊断价值。

妊娠期糖尿病患者血清Ficolin-3、Omentin-1、FGF19 水平检测及其对发生GDM的预测价值

目的探讨妊娠期糖尿病(GDM)患者血清纤维凝胶蛋白-3(Ficolin-3)、网膜素-1(Omentin-1)、成纤维细胞生长因子19(FGF19)水平检测及意义,以期为临床早期制订干预方案、降低GDM发生率提供参考。方法选取2020年9月至2022年9月于该院孕24~28周行口服葡萄糖耐量试验且结果为阳性的96例孕妇作为GDM组,同期96例孕24~28周行口服葡萄糖耐量试验且结果为阴性孕妇作为对照组。比较两组孕11~13周(孕早期)一般资料及检测指标[年龄、体质量指数(BMI)、孕次、产次、孕周、收缩压(SBP)、舒张压(DBP)、空腹血糖(FBG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)];比较两组孕早期血清Ficolin-3、Omentin-1、FGF19水平;采用Pearson相关分析孕早期血清Ficolin-3、Omentin-1、FGF19水平与BMI、FBG、HbA1c、TC、TG、LDL-C水平的相关性;采用受试者工作特征(ROC)曲线分析孕早期血清Ficolin-3、Omentin-1、FGF19联合检测对孕早期发生GDM的预测价值。结果孕早期GDM组BMI、FBG、HbA1c、TC、TG、LDL-C水平均高于对照组,差异均有统计学意义(P<0.05)。孕早期GDM组血清Ficolin-3水平高于对照组,Omentin-1、FGF19水平均低于对照组,差异均有统计学意义(P<0.05)。孕早期血清Ficolin-3水平与BMI、FBG、HbA1c、TC、TG、LDL-C水平均呈正相关(P<0.05);血清Omentin-1、FGF19水平与BMI、FBG、HbA1c、TC、TG、LDL-C水平均呈负相关(P<0.05)。孕早期血清Ficolin-3水平升高及血清Omentin-1、FGF19水平降低为孕早期发生GDM的危险因素(P<0.05)。孕早期血清Ficolin-3、Omentin-1、FGF19联合检测预测发生GDM的曲线下面积为0.930,灵敏度、特异度分别为89.58%、81.25%。结论血清Ficolin-3、Omentin-1、FGF19与GDM的发生具有明显相关性,可为临床早期预测GDM提供参考依据,以便针对性给予干预措施,降低GDM的发生风险,改善母婴结局。

Mechanisms by which fibroblast growth factor 20 improves motor performance in a mouse model of Parkinson’s disease

Genome-wide studies have reported that Parkinson's disease is associated with abnormal expression of various growth factors. In this study, male C57BL/6 mice aged 10 weeks were used to establish Parkinson's disease models using an intraperitoneal injection of 60 mg/kg 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine. 28 days later, 10 or 100 ng fibroblast growth factor 20 was injected intracerebroventricularly. The electrophysiological changes in the mouse hippocampus were recorded using a full-cell patch clamp. Expression of Kv4.2 in the substantia nigra was analyzed using a western blot assay. Serum malondialdehyde levels were analyzed by enzyme-linked immunosorbent assay. The motor coordination of mice was evaluated using the rotarod test. The results showed that fibroblast growth factor 20 decreased A-type potassium current in neurons of the substantia nigra, increased long-term potentiation amplitude in the hippocampus, and downregulated Kv4.2 expression. A high dose of fibroblast growth factor 20 reduced serum malondialdehyde levels and enhanced the motor coordination of mice. These findings confirm that fibroblast growth factor 20 has a therapeutic effect on the toxicity induced by l-methyl-4-phenyl-l,2,3s6-tetrahydropyridine, and its mechanism of action is associated with the inhibition of A-type K^+ currents and Kv4.2 expression. All animal procedures were approved by the Animal Care and Use Committee of Qilu Hospital of Shandong University, China in 2017 (approval No. KYLL-2017-0012).

硫酸氨基葡萄糖联合美洛昔康对膝骨关节炎患者血清FGF-2、TGF-β、IGF-1水平及膝关节运动功能的影响

目的 探究硫酸氨基葡萄糖联合美洛昔康对膝骨关节炎患者血清成纤维细胞生长因子-2(fibroblast growth factor-2, FGF-2)、转化生长因子-β(transforming growth factor-β, TGF-β)、胰岛素样生长因子-1(insulin-like growth factor-1, IGF-1)水平及膝关节运动功能的影响。方法 选择2021年6月-2023年6月就诊的膝骨关节炎114例,以随机数字表法分为联合组和美洛昔康组各57例。美洛昔康组予美洛昔康片治疗,联合组在美洛昔康组基础上加用硫酸氨基葡萄糖胶囊治疗,均治疗6周后观察疗效,比较2组治疗前、治疗6周后膝关节运动功能、炎性因子、生长因子水平及治疗期间安全性。结果 治疗6周后,联合组总有效率为91.23%(52/57)高于美洛昔康组的73.68%(42/57)(P<0.05)。治疗6周后,2组5次坐立试验、2.4 m起立行走试验所需时间短于治疗前,且联合组短于美洛昔康组(P<0.05,P<0.01);西安大略和麦克马斯特大学骨关节炎指数评分及血清前列腺素E2、白细胞介素-17、基质金属蛋白酶-3水平低于治疗前,且联合组低于美洛昔康组(P<0.05,P<0.01)。治疗6周后,2组血清FGF-2、TGF-β、IGF-1水平均高于治疗前,且联合组高于美洛昔康组(P<0.05,P<0.01)。2组治疗期间总不良反应发生率比较差异无统计学意义(P>0.05)。结论 硫酸氨基葡萄糖联合美洛昔康可有效升高膝骨关节炎患者血清FGF-2、TGF-β、IGF-1水平,延缓软骨退行性病变,控制机体炎症反应,进而有效改善患者膝关节运动功能,疗效显著,安全性良好。