Serum bFGF Research Articles

Knockdown the moyamoya disease susceptibility gene, RNF213, upregulates the expression of basic fibroblast growth factor and matrix metalloproteinase-9 in bone marrow derived mesenchymal stem cells.

Moyamoya disease (MMD) is a chronic, progressive cerebrovascular occlusive disease. Ring finger protein 213 (RNF213) is a susceptibility gene of MMD. Previous studies have shown that the expression levels of angiogenic factors increase in MMD patients, but the relationship between the susceptibility gene RNF213 and these angiogenic mediators is still unclear. The aim of the present study was to investigate the pathogenesis of MMD by examining the effect of RNF213 gene knockdown on the expression of matrix metalloproteinase-9 (MMP-9) and basic fibroblast growth factor (bFGF) in rat bone marrow-derived mesenchymal stem cells (rBMSCs). Firstly, 40 patients with MMD and 40 age-matched normal individuals (as the control group) were enrolled in the present study to detect the levels of MMP-9 and bFGF in serum by ELISA. Secondly, Sprague-Dawley male rat BMSCs were isolated and cultured using the whole bone marrow adhesion method, and subsequent phenotypic analysis was performed by flow cytometry. Alizarin red and oil red O staining methods were used to identify osteogenic and adipogenic differentiation, respectively. Finally, third generation rBMSCs were transfected with lentivirus recombinant plasmid to knockout expression of the RNF213 gene. After successful transfection was confirmed by reverse transcription-quantitative PCR and fluorescence imaging, the expression levels of bFGF and MMP-9 mRNA in rBMSCs and the levels of bFGF and MMP-9 protein in the supernatant of the culture medium were detected on the 7th and 14th days after transfection. There was no significant difference in the relative expression level of bFGF among the three groups on the 7th day. For the relative expression level of MMP-9, there were significant differences on the 7th day and 14th day. In addition, there was no statistically significant difference in the expression of bFGF in the supernatant of the RNF213 shRNA group culture medium, while there was a significant difference in the expression level of MMP-9. The knockdown of the RNF213 gene affects the expression of bFGF and MMP-9. However, further studies are needed to determine how they participate in the pathogenesis of MMD. The findings of the present study provide a theoretical basis for clarifying the pathogenesis and clinical treatment of MMD.

Assessment of serum levels and placental bed tissue expression of IGF-1, bFGF, and PLGF in patients with placenta previa complicated with placenta accreta spectrum disorders.

This study aims to detect the serum levels of IGF-1, bFGF, and PLGF and their expressions in placental bed tissues of patients with placenta previa complicated with PAS disorders. This case and control study included 40 multiparous pregnant women with complete placenta previa between 34 weeks and 38 weeks of gestation and they were divided into two groups: 25 patients with PAS (case group) and 15 patients without PAS (control group). The venous blood samples were collected 2 h before the cesarean section, and the placental bed tissues were taken intraoperatively at the placental implantation site and then were histologically examined to evaluate the gravity of the myometrial invasion of the placenta. According to FIGO PAS increasing grading, the 25 patients were also divided into three groups: PAS grade I group, PAS grade II group, and PAS grade III group. The concentrations of IGF-1, bFGF, and PLGF in serum were measured using ELISA, and the mean ratio of the relative mRNA expression of each biomarker in placental bed tissues was calculated using qRT-PCR. The staining intensity and the positive cells were quantitatively measured and expressed as means by using Image J software for IHC analysis. IGF-1 had low serum levels and high placental bed expression in placenta previa patients with PAS disorders compared to those without PAS (all p < 0.0001). PLGF had high serum levels (p = 0.0200) and high placental bed expression (p < 0.0001) in placenta previa patients with PAS disorders compared to those without PAS. IGF-1 serum levels decreased up to PAS grade II (means were 24.3 ± 4.03, 21.98 ± 3.29, and 22.03 ± 7.31, respectively for PAS grade I, PAS grade II, PAS grade III groups, p = 0.0006). PLGF serum levels increased up to PAS grade II (means were 12.96 ± 2.74, 14.97 ± 2.56, and 14.89 ± 2.14, respectively for the three groups, p = 0.0392). However, IGF-1 and PLGF mRNA placental bed expression increased up to PAS grade III. The relative expression of mRNA means for the three groups was 3.194 ± 1.40, 3.509 ± 0.63, and 3.872 ± 0.70, respectively for IGF-1; and 2.784 ± 1.14, 2.810 ± 0.71, and 2.869 ± 0.48, respectively for PLGF (all p < 0.0001). Their IHC (immunohistochemical) staining also had increasing trends, but p > 0.05. bFGF was not significantly expressed in placenta previa with PAS disorders in most of the analysis sections (p > 0.05). Low serum levels and high expression in placental bed tissues of IGF-1, or high serum levels and high expression in placental bed tissues of PLGF, may differentiate placenta previa patients with FIGO PAS grade I and PAS grade II from those without PAS disorders. However, they could not significantly predict the degree of placental invasiveness in FIGO PAS grades II and III.

Prognostic Values of Tissue and Serum Angiogenic Growth Factors Depend on the Phenotypic Subtypes of Colorectal Cancer.

We classified colorectal cancer (CRC) patients into four phenotypic subgroups and investigated the prognostic value of angiogenic growth factors across subgroups. Preoperative serum concentrations and tissue expressions of VEGF, bFGF, and PDGF-bb were determined among 322 CRC patients. We classified patients into phenotypic subgroups (immune, canonical, metabolic, and mesenchymal) according to a method described in our earlier work. Among the metabolic subgroup, patients with high serum concentrations of VEGF, bFGF, or PDGF-bb exhibited a significantly improved prognosis. Moreover, those with high VEGF tissue expressions exhibited a significantly improved prognosis among patients in the metabolic subgroup. Among immune patients, a high VEGF serum expression is associated with a worse prognosis. A high serum bFGF concentration is associated with a favorable prognostic factor among patients with a canonical tumor phenotype. A high PDGF-bb tissue expression is associated with non-metastasized disease and with the immune, canonical, and metabolic subtypes. To our knowledge, this is the first study to show that the prognostic value of angiogenic growth factors differs between phenotypic subtypes.

Dan-Deng-Tong-Nao softgel capsule promotes angiogenesis of cerebral microvasculature to protect cerebral ischemia reperfusion injury via activating HIF-1α-VEGFA-Notch1 signaling pathway

BackgroundA proprietary Chinese herbal product called Dan-Deng-Tong-Nao softgel capsule (DDTNC) is used to treat ischemic stroke. However, the preventive mechanisms of DDTNC against cerebral ischemia reperfusion injury (CIRI) haven not been characterized. ObjectiveTo explore the mechanisms of protective effects of DDTNC against CIRI from both internal and external levels. MethodsChemical characterization was performed using UPLC. The potential protective mechanisms of DDTNC against CIRI were predicted using network pharmacology. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in rats. An model of brain microvascular endothelial cells (BMECs) induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was also established. We evaluated neurological deficits, cerebral infarct volume, cortical neuron damage, and mitochondrial swelling in vivo. We evaluated the expression of VEGFR2, VEGFA, HIF-1α, CD31, and CD34 in ischemic cortex, and VEGF, bFGF, BDNF, angiostatin, and endostatin in serum of rats and in BMEC supernatants. We also evaluated cell viability, cytotoxicity, intracellular ROS, apoptosis, and migration ability in vitro. ResultsSeven components were detected in DDTNC. KEGG enrichment analysis showed that DDTNC may modulate angiogenesis via the HIF-1 signaling pathway. DDTNC treatment reduced neurological score and infarct volume, and improved cell morphology of damaged neurons. Transmission electron microscopy showed that DDTNC reduced mitochondria swelling in cortical neurons. Furthermore, DDTNC reduced intracellular ROS and inhibited apoptosis. DDTNC boosted the expression of CD31, CD34, VEGFR2, VEGFA and HIF-1α, highlighting its involvement in angiogenesis, according to immunofluorescence studies. Furthermore, DDTNC enhanced tube formation and migration of BMECs in vitro. ELISA and western blotting indicated that DDTNCCSF induced the expression of VEGF, BDNF and bFGF, reduced the level of angiostatin and endostatin, increased the protein expression of VEGFA, Notch1 and HIF-1α in vitro and in vivo. ConclusionsDDTNC promoted angiogenesis to protect brain tissue against MCAO/R, and exerted protective effects against OGD/R in BMECs via activating HIF-1α-VEGFA-NOTCH1 signal transduction pathway.

Changes in serum basic fibroblast growth factor concentration following intracordal injection.

Although many studies have reported improvements in voice outcomes with intracordal trafermin injection, there is a lack of data documenting its changes in serum basic fibroblast growth factor (bFGF) blood concentration. This study examined whether serum bFGF concentrations change after intracordal trafermin injection. This retrospective study was conducted at Tokyo Voice Center. We investigated serum bFGF concentrations before and after injection in 40 patients who underwent intracordal trafermin injection. There were 26 males and 14 females, with an age ranging from 13 to 88 years (average 53.25 years). They were diagnosed with paralysis (15 patients), atrophy (15 patients), sulcus (8 patients), and others (2 patients: scar and functional), presenting with severe hoarseness that interfered with daily life. The mean pre- and post-injective serum bFGF concentration of the 40 patients was 6.689 and 4.658 pg/mL, respectively. The difference in mean serum bFGF concentration between pre- and post-injective was -2.031 pg/mL. The Pearson correlation coefficient was calculated to evaluate the correlation between dosage of trafermin and post-injective serum bFGF concentration, and a moderate correlation was found at r = 0.52. Generalized linear model regression analysis was performed for the purpose of adjusting for confounding among variables. The only variable that showed a statistically predominant association with post-injective serum bFGF concentrations was the dosage of trafermin, with an estimated regression coefficient of 0.048. In this study, the dosage of trafermin we injected and post-injective serum bFGF concentrations were dose-dependent but the amount of changes in the serum bFGF concentration was negligible within the physiological range. Therefore, as with subcutaneous and wound administration, intracordal trafermin injections may be safe. Level IV.

Efficacy of lenvatinib combined with sequential transarterial chemoembolization for primary hepatocellular carcinoma and the effects on serum basic fibroblast growth factor and vascular endothelial growth factor.

Objective: The aim of this research was to investigate the therapeutic efficacy of lenvatinib combined with sequential transarterial chemoembolization (TACE) on primary hepatocellular carcinoma (HCC) and the effects on serum basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Method: A total of 104 patients with primary HCC, admitted to People's Hospital of Leshan from April 2018 to January 2021, were selected as the study subjects and were divided into the TACE-LEN group (n = 53) who were treated with lenvatinib combined with sequential TACE and the TACE group (n = 51) who were treated with TACE alone, according to the appropriate treatment modalities. The clinical efficacy 8weeks after treatment; the serum levels of total bilirubin, conjugated bilirubin, and alanine aminotransferase (ALT); the prothrombin time (PT); the indocyanine green retention rate at 15min (ICGR15); and the serum bFGF and VEGF levels before treatment and at 8weeks after treatment were compared between the two groups. The incidence of adverse events and the survival rates at 18 months were also recorded for both groups. COX regression analysis was used to analyze the risk factors affecting the survival of patients. Results: Eight weeks after treatment, the objective response rate was higher in the TACE-LEN group than in the TACE group (77.36% vs. 56.36%, p < 0.05), but there were no statistically significant differences in the bilirubin and ALT levels, the PT, and the ICGR15 between the two groups (p > 0.05). The serum bFGF and VEGF levels post-therapeutic were lower in the TACE-LEN group than in the TACE group (p < 0.05). The differences in the incidence of postoperative adverse events and the survival rate within 6months were not statistically significant between the two groups (p > 0.05). In addition, the survival rates within 12 and 18months after treatment were higher in the TACE-LEN group than in the TACE group than in the TACE group (81.1% vs. 64.7%, 69.8% vs. 49.1%, p < 0.05). ICG-R15 and treatment regimen are risk factors for survival. Conclusion: The worse the liver reserve is, the worse the prognosis is. The combination of TACE and lenvatinib showed better efficacy and longer survival than TACE monotherapy for HCC patients and reduced the levels of bFGF and VEGF.

Ginger polysaccharide UGP1 suppressed human colon cancer growth via p53, Bax/Bcl-2, caspase-3 pathways and immunomodulation

In previous study, we got a purified ginger polysaccharide UGP1 and verified its significant antitumor activities on colon cancer HCT116 cells. In this article, we aimed to illustrate the underlying mechanism of UGP1 exerted antitumor activities on colon cancer by using in vitro cell models and in vivo animal models. The results demonstrated that UGP1 could induce S-phase cell cycle arrest, up-regulate the expression of Bax and p53, down-regulate the expression of Bcl-2, and activate the downstream protein caspase-9 and caspase-3, which was related to intrinsic apoptosis pathway on HCT116 cells. Moreover, UGP1 significantly stimulated RAW264.7 cell proliferation and secretion activity. Similarly, UGP1 inhibited tumor proliferation on tumor-bearing mice, increased the expression of p53 and the ratio of Bax/Bcl-2, enhanced the secretion of pro-inflammatory cytokines TNF-α, IL-2, IL-6 and decreased the secretion of pro-tumor cytokines TGF-β and bFGF in serum. In conclusion, it indicated that the UGP1 could suppress human colon cancer growth by inducing apoptosis via the regulation of p53, caspase-3, and Bax/Bcl-2 ratio-dependent pathway and regulating immune system activity. This investigation provided basic theoretical mechanism of ginger polysaccharide-exerted antitumor activities, and contributed to develop a possible functional food or adjuvant agent for prevention or treatment of colon cancer.

Effects of Infrared Combined with Methylcobalamin on the Vibratory Sensory Threshold and Nerve Conduction Velocity of the Lower Extremity in Patients with Diabetic Foot Treatment.

Objective To investigate the effect of infrared combined with methylcobalamin on the vibratory sensory threshold and lower limb nerve conduction velocity of patients with diabetic foot. Methods One hundred and six patients with diabetic foot in our hospital from February 2018 to December 2020 were enrolled and divided into the study and control groups. The patients in the control group were given methylcobalamin, and the patients in the research group were treated with infrared light on the basis of the control group. The therapeutic effect, vibration sensory threshold, lower limb nerve conduction velocity, and related biochemical index levels before and after treatment in the two groups were counted. Result The total effective rate of the study group (94.34%) was significantly higher than that of the control group (81.13%). The left/right lower limb vibration sensation threshold decreased in both groups after treatment, and the study group was lower than that of the control group (P < 0.05). The conduction velocity of the left/right common peroneal nerve and tibial nerve increased in both groups after treatment, and the study group was larger than that of the control group (P < 0.05). The bFGF, VEGF, and APN increased in both groups after treatment. VEGF and APN increased and IL-6 and TNF-α decreased in both groups after treatment, and the study group was better than the control group (P < 0.05). Conclusion Infrared and methylcobalamin combined treatment of diabetic foot can effectively improve lower extremity nerve conduction velocity and vibration sensory threshold, regulate serum bFGF and VEGF levels, reduce the degree of inflammatory response, and help improve the overall treatment effect.

S-adenosyl-L-methionine improves ventricular remodeling after myocardial infarction by regulating angiogenesis and fibrosis

Purpose: To investigate the effect of S-adenosyl-L-methionine (SAM) on angiogenesis and fibrosis in the heart of rats with myocardial infarction (MI), and to determine the mechanism of action.Methods: Sprague Dawley rats with MI received SAM treatment (15 mg/kg) intraperitoneally. The cumulative survival (%) of rats was recorded to determine their rate of survival. Hematoxylin-eosin staining, echocardiography, and hemodynamics were also performed. In addition, the effects of SAM vascular regeneration in the rats were analyzed by determining the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hypoxia-inducible factor 1-α (HIF1-α) in rats.Results: The 8-week survival rate of the MI group was significantly lower than that of the sham group, while SAM significantly improved the survival rate of the rats. In addition, SAM improved the contractile and diastolic heart function in the rats and also increased the ventricular pressure change. Furthermore, SAM elevated the expressions of VEGF, bFGF and HIF1-α in rat myocardium and serum. In myocardial tissues of SAM-treated rats, the expressions of collagen I, collagen III and α-sma were reduced, indicating that SAM inhibited myocardial fibrosis. In addition, SAM promoted cardiac angiogenesis by activating Jagged1/Notch1 signaling pathway.Conclusion: SAM promotes angiogenesis of the myocardium by activating Jagged1/Notch1 signaling pathway and inhibiting fibrosis in rat myocardium. Therefore, SAM effectively inhibits ventricular remodeling in rats after MI, thereby improving the rats’ heart structure and function. The results may provide new targets for the treatment of myocardial infarction.

Analysis of the Correlation of Basic Fibroblast Growth Factor in Serum of Patients with Diffuse Large B-Cell Lymphoma with Clinicopathological Efficacy and International Prognostic Index.

The correlation of basic fibroblast growth factor (bFGF) in serum of patients with diffuse large B-cell lymphoma (DLBCL) with clinicopathological efficacy and International Prognostic Index (IPI) is analyzed. 115 DLBCL patients admitted to our hospital for treatment from June 2020 to June 2021 are selected as the DLBCL patient group, 65 healthy subjects who received physical examination in our hospital during the same period are selected as the healthy control group, and the serum bFGF levels of DLBCL group and healthy control group are observed before treatment. The experimental results show that the serum bFGF expression of DLBCL patients is decreased significantly after chemotherapy, and the serum bFGF expression of DLBCL patients is closely related to the treatment effect, disease progression, tumor invasion, and prognosis, which has important clinical significance for judging the disease, treatment effect, and prognosis of patients.

Ozone improved the wound healing in type 2 diabetics via down-regulation of IL- 8, 10 and induction of FGFR expression.

Background and aim:We aimed to investigate the effect of ozonated autohaemotherapy (OA) on the wound healing, serum values of interleukin (IL) - 6, 8, 10, tumor necrosis factor-alpha (TNF-α), basic fibroblast growth factor (bFGF) and local expression of fibroblast growth factor receptors (FGFR) in type 2 diabetics with the acute soft-tissue infections.Methods:Patients in the first cohort (n-30) received a basic comprehensive treatment (BCT-group), and the second (n=28) also received OA (OA-group). Blood samples for ELISA and tissue specimens for the immunohistochemical examinations were collected at admission (day 0) and at the 9th day of inpatient treatment.Results:The additional using of OA has accelerated the timing of a single and the complete wound granulation and the timing to marginal epithelization, compared with the results of the standard treatment. The use of OA has significantly reduced the production of IL-8, 10 at 9th day. OA-group patients were characterized by consistently high levels of bFGF production in contrast to the BCT-group, where the decreasing in the serum bFGF level was observed. The maximum number of bFGFR - immunopositive labels was observed in OA-group out to 9th day (319,45 (249,90-348,43) versus baseline 192,65 (171,93-207,72), versus BCT-group 123,30 (105,23- 141,10), p<0,001).Conclusions:Application of OA in the complex treatment of the acute soft-tissue infections in diabetics makes it possible to achieve the significant reductions in the duration of the wound inflammation and regeneration phases by eliminating of overproduction of IL- 8, 10 and induction of expression of bFGF and its receptors. (www.actabiomedica.it)

Correlations of Serum MMP-9, TIMP-1, TGF-β and bFGF Levels with Atrial Fibrillation in Patients without Structural Heart Disease

ABSTRACT The researchers aimed in highlighting the correlations of serum MMP-9, TIMP-1, TGF-β1 and bFGF levels with atrial fibrillation (AF) within diseased persons showing no structural heart ailment. A total of 236 eligible diseased persons had been categorized within AF category (n=168) and non-AF category (n=68). Left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) had been measured through cardiac ultrasonography. Comparing concerning non-AF category, AF class had larger LAD and smaller LVEF (P&lt;0.01). MMP-9 and TGF-β1 levels had been higher while TIMP-1 level remained less within AF class as compared to non-AF class (P&lt;0.01). Age, LVEF and left atrial MMP-9/TIMP-1 remained free correlative factors of AF (P&lt;0.01). MMP-9/TIMP-1 remained definitely correlated concerning LAD within AF class (r=0.509, P&lt;0.01). Left atrial MMP-9/TIMP-1 remained higher within diseased persons regarding persistent AF (P&lt;0.01). Left atrial MMP-9/TIMP-1 is correlated with AF within diseased persons having no structural heart ailment, particularly in the case of persistent AF.

An observation of the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen in treating acute spinal cord injury.

Objective:To examine the clinical efficacy of combining Riluzole with mannitol and hyperbaric oxygen therapy in treating thoracolumbar vertebral fracture-induced acute spinal cord injury (ASCI).Methods:From June 2015 to May 2018, 80 patients with thoracolumbar fractures and ASCI who were treated at Baoding First Central Hospital were selected. All patients underwent posterior laminectomy and screw fixation, and they were randomly divided into two groups using a random number table method. The control group received conventional postoperative treatment, while the experimental group was treated with riluzole combined with mannitol and hyperbaric oxygen on the basis of conventional treatment. The recovery of nerve function which included motor function and sensory function, and the changes of serum IL-6, CRP, BDNF, BFGF and other factors before treatment and four weeks after treatment of the two groups of patients were observed and evaluated.Results:After treatment, the motor function scores and sensory function scores of the two groups of patients were improved compared with those before treatment (p<0.05). Compared with the control group, the experimental group improved significantly, and the difference was statistically significant (p<0.05). The levels of IL-6, BDNF and NFGF in the experimental group were significantly lower than those in the control group (p<0.05).Conclusions:For patients with thoracolumbar fractures and ASCI undergoing laminar decompression and fixation, the comprehensive treatment plan of riluzole combined with mannitol and hyperbaric oxygen has certain advantages. Compared with the conventional therapy, it may significantly improve the movement and sensory functions of patients, relieve the inflammatory response of spinal cord, and promote recovery from the injury.

The Relationship Between the Imaging Characteristics of Tumor Angiogenesis and the Expression of Serum Cytokines in Lung Cancer

Objective: As for the lung cancer patients, their imaging characteristics of CT and DSA are evaluated, so as to analyze the relationship between the degree of angiogenesis and the expression of cytokines. Method: Firstly, the CT and DSA data of 40 lung cancer patients who are confirmed by pathology and received intravascular interventional therapy are collected. 5 mL venous blood of patients is extracted and serum samples are extracted. The levels of matrix metalloproteinase-2 (MMP-2) as well as basic fibroblast growth factor (bFGF) in 40 patients with lung cancer are detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the contents of MMP-2 and bFGF in serum of 40 healthy people are collected as normal control group. Normal distribution, t-test and F-test are used to verify the correlation between the image features of lung cancer and the expression levels of MMP-2 and bFGF in serum. Results: Firstly, the levels of MMP-2 and bFGF in lung cancer group are obviously higher than those in the control group, and the difference was statistically significant. P values were 0.002 and 0, respectively (P &lt; 0.01). In addition, a positive correlation exists between MMP-2 and bFGF in the group of lung cancer as well as control, and the correlation coefficients are 0.602 as well as 0.712, respectively. Secondly, DSA of lung cancer shows that MMP-2 and bFGF of different types of blood supply lung cancer are different. The P value of intra group and inter group comparison was 0, and the difference is statistically significant. Thirdly, on the image, the lung cancer has necrotic cavity. The P value of MMP-2 and bFGF are 0.046 and 0.005 respectively. The P value of MMP-2 and bFGF are 0.001 and 0.001 respectively with the burr sign on the image. The P value of serum MMP-2 and bFGF are 0 and 0.001 with the deep lobulated sign on the image, both of which are statistically significant. There is no correlation between the size and location of lung cancer focus, whether there is peripheral obstructive pneumonia and the level of MMP-2 and bFGF. Conclusion: The DSA blood supply of lung cancer is related to the expression of MMP-2 as well as bFGF in serum, which can reflect the angiogenic state of tumor and be used as the basis of anti-angiogenic therapy. Whether the CT image of lung cancer shows necrotic cavity, burr sign and deep lobulated sign has a correlation with the expression of MMP-2 as well as bFGF in the serum. The combination of the two is helpful for the accurate assessment of the disease.

Basic fibroblast growth factors as a biomarker of focal segmental glomerulosclerosis in HIV-positive and HIV-negative children

Background. HIV infection can lead to the development of HIV-associated nephropathy (HIVAN) with the majority of patients progressing to end-stage kidney disease. Previous studies have recognised basic fibroblast growth factor (bFGF) as a biomarker for HIVAN, since significant levels of bFGF low-affinity receptors have been found in the kidneys of HIV-infected children. Objective. To assess the association between bFGF and kidney disease in the development of focal segmental glomerulosclerosis (FSGS) in HIV-positive and negative children. Methods. The study group consisted of 31 children; HIVAN ( n =11) and idiopathic FSGS ( n =20). The control group consisted of both HIV-positive ( n =20) and HIV-negative ( n =20) children with no kidney disease. Serum samples from all patients in both the study and control groups were analysed for bFGF. Results . The concentration of bFGF was higher, in comparison with idiopathic FSGS children, in HIVAN children ( p =0.0167). There was also a significant elevation of serum bFGF levels in children with HIVAN when compared with HIV-positive ( p =0.0288) and HIV-negative ( p =0.0043) control groups. Conclusion. This study demonstrated statistically significant differences between bFGF levels in children with HIVAN and a control group, although it failed to distinguish significant differences in bFGF levels between HIVAN and idiopathic FSGS children.

Diagnostic Value of Basic Fibroblast Growth Factor and Platelet-Derived Growth Factor-AB Circulating Levels in Hepatitis C Virus-Associated Hepatocellular Carcinoma

Abstract Background: As a hypervascular tumor, Hepatocellular Carcinoma (HCC) is characterized by neovascularization which plays an important role in its growth and progression. Basic Fibroblast Growth Factor (bFGF) is a potent endothelial cell mitogen and angiogenic factor that was found to be elevated in different cancers. Platelet-Derived Growth Factor-AB (PDGF-AB) is another factor implicated in enhanced proliferation and migration of pericytes and is a potent stim-ulator of angiogenesis in many tumors. Aim of Study: This study aimed to evaluate the circulating levels of bFGF and PDGF-AB and to examine their diagnostic significance in Hepatitis C Virus (HCV)-associated HCC. Methods: This study included one hundred subjects divided into healthy controls (n=25), HCV patients (n=25), and HCV-associated HCC patients (n=50). The levels of bFGF, PDGF-AB, and Alpha-Fetoprotein (AFP) in addition to the activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase as well as total bilirubin and albumin concentrations were determined in sera of the enrolled subjects. Results: Levels of bFGF and PDGF-AB were higher in HCC patients compared to controls and HCV patients and were found to be associated with increased susceptibility to HCV-associated HCC. Additionally, the diagnostic values of bFGF and PDGF-AB to distinguish HCC patients from non-cancerous patients were good, although they are still inferior to that of AFP. However, the combination of bFGF and PDGF-AB with AFP enhanced the efficacy of the latter. Conclusion: Serum bFGF and PDGF-AB may contribute to the pathogenesis of HCV-associated HCC, and they seem to be good diagnostic biomarkers of HCC along with AFP.

2149-PUB: The Changes in the Panel of Circulating Cytokines Associated with Chronic Kidney Disease in Patients with Type 2 Diabetes

Aim: To estimate the differences in the panel of circulating cytokines mediating low-grade inflammation and fibrosis in patients with type 2 diabetes (T2D) and chronic kidney disease.Methods: We examined 130 patients with T2D duration ≥10 years. Among them, 65 individuals had reduced estimated glomerular filtration rate (eGFR; 15-59 ml/min/1.73 m2) and 64 patients had increased albuminuria. Thirty healthy subjects were acted as control. Serum IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17A, bFGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-BB, RANTES, TNF-α, and VEGF were assessed by multiplex analysis. Urinary nephrin and podocin, as podocyte injury markers, and WFDC-2, a marker of tubulointerstitial fibrosis, were assessed by ELISA. Results: Patients with T2D and reduced eGFR had increased levels of IL-1ra, IL-8, IL-13 and decreased IL-7, IL-9 and IL-15 concentrations when compared to those with preserved renal function and control (all p&amp;lt;0.05). Excretion of WFDC-2, but not podocyte markers, was increased in these patients (p≤0.02). The elevation of albuminuria was associated with enhanced excretion of nephrin and podocin (p&amp;lt;0.0001), but no differences were found in the levels of all measured cytokines between patients with normal and elevated albuminuria. The levels of IL-2, IL-4, IL-5, IL-17A, bFGF, G-CSF, IP-10 and MIP-1α correlated negatively with eGFR. No correlations were found between measured cytokines and glomerular markers. There was positive correlation between WFDC-2 and MIP-1α. The levels of IL-10 and IL-15, two anti-inflammatory cytokines, correlated negatively with WFDC-2. Conclusion: The obtained results demonstrate that decreased eGFR and increased urinary excretion of WFDC-2, a marker of tubulointerstitial fibrosis, are associated with a predominance of pro-inflammatory and fibrogenic molecules in the panel of circulating cytokines in T2D subjects. Disclosure A.I. Korbut: None. O. Fazullina: None. V. Klimontov: None.

Serum cytokine profiles in infants with infantile hemangiomas on oral propranolol treatment: VEGF and bFGF, potential biomarkers predicting clinical outcomes.

Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment. For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter ≥2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays. Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-α, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-α, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. MMP-2, VEGF-α, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol. We found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.

Huayu Wan Prevents Lewis Lung Cancer Metastasis in Mice via the Platelet Pathway.

Objective To study the mechanism of Huayu Wan on the metastasis of Lewis lung cancer in mice via the platelet pathway. Method Construction of the lung metastasis model by injection of Lewis cells through the tail vein. The next day, 72 mice were randomly divided into the Huayu Wan group (HYW), the aspirin group, the control group, and the normal group . Treatment was given for 5 days per week for a total of 16 days. The size and distribution of lung metastases were observed. Thromboelastography was used to detect platelet function, flow cytometry was used to analyze platelet activation, and ELISA was used to detect platelet tumor metastasis-related factor expression. Result Lung weight in the control group was significantly higher than that in the HYW group (P < 0.05). The distribution of lung metastases in the control group was obviously more than that in the HYW group. The thromboelastogram showed that the R value of the control group was significantly lower than the normal group, while the R values of the HYW and aspirin groups were higher than the control group (P < 0.05). Flow cytometry analysis showed that the expression of CD62P in platelet-rich plasma in the control group was significantly higher than that in the normal group, while the expression of CD62P in the HYW and aspirin groups was lower than that in the control group (P < 0.05). In addition, ELISA showed that the expression of VEGF, bFGF, and CD62P in serum of the HYW group was significantly decreased than the control group (P < 0.05), and the expression of VEGF and bFGF in serum of the aspirin group was significantly decreased than the control group (P < 0.05). Conclusion The mechanism of Huayu Wan inhibiting the metastasis of lung cancer in mice may be related to the improvement of blood hypercoagulability, the inhibition of platelet activation, and the expression of VEGF, bFGF, and CD62P.

Concentration of proinflammatory cytokines in patients with ulcers as a complication of type 2 diabetes mellitus.

IntroductionDifficult healing of chronic wounds is a serious problem for modern medicine. It leads to ulceration, especially in conditions such as diabetic foot syndrome or chronic venous insufficiency. This may be a result of chemical, physical, thermal or biological factors, among others. Analysis of mediators and molecular factors released by the abovementioned structure helps to better understand the mechanism of healing of chronic wounds and the formation of ulcers.AimTo assess excretion of selected cytokines in patients with ulcerations as a complication of diabetes mellitus type 2.Material and methodsSeventeen patients aged 68–87 took part in the assessment of wound healing in patients with ulceration in the course of diabetes mellitus type 2. The control group consisted of 21 healthy patients aged 32–62. In the blood serum bFGF, TNF-α, IL-4, TGF-β1, TGF-β2 and TGF-β3 were determined.ResultsA significant difference was found in bFGF, IL-4, TGF-β1, TGF-β2, and TGF-β3 levels. Concentration of bFGF was 12% lower in patients with ulcers than in the non-ulcerated control group (p = 0.013). IL-4 concentration was 46% lower in patients with ulcers than in the non-ulcerated control group (p = 0.002). TGF-β1, TGF-β2 and TGF-β3 concentrations were also lower in the group of patients with ulcers compared to those in the non-ulcerated control group.ConclusionsReduced concentrations of selected cytokines and growth factors may indicate abnormal activity of the cells that secrete them and affect the healing process of chronic wounds, hindering and delaying the healing process.