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Purpose: To investigate serum levels of VEGF, IGF-1 and FGF-2, and relationships with several clinical characteristics in children and adolescents with autism spectrum disorder (ASD) with and without bipolar disorder (BD)., Method: 40 subjects with ASD + BD as study group, and 40 subjects with ASD as control group were included. Serum levels of VEGF, IGF-1, and FGF-2 were measured using commercial enzyme-linked immunosorbent assay kits., Results: The study group was significantly higher than the control group in terms of ASD severity, self-harming behavior and sleep disturbance. Serum VEGF and FGF-2 levels were significantly higher in the ASD + BD group than in the control group. There was no significant difference in serum IGF-1 levels between the two groups. There was no correlation between VEGF, IGF-1 and FGF-2 serum levels and ASD severity in the study group. However there was a negative correlation between VEGF levels and age at first diagnosis of BD, and a positive correlation between IGF-1 levels and the number of bipolar episodes in the study group., Conclusion: Growth factors like VEGF and FGF-2 may be potential biomarkers of bipolar disorder in young subjects with ASD. Given the difficulty of clinical management of BD in young subjects with ASD, potential biomarkers would help clinicians in the diagnosis and follow up of BD in this special population. Further research is needed whether VEGF and FGF-2 can be potential biomarkers in the clinical management of young subjects with ASD and BD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: 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., Methods: 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., Results: 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)., Conclusions: 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.

Background: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia., Methods: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)&#95;30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis., Results: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)&#95;30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2&#95;30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2&#95;30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2&#95;30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001)., Conclusions: Our results suggest that lower FGF2&#95;30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc)., Objectives: This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc., Material and Methods: This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer., Results: The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9)., Conclusions: The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.

Background: Various factors contribute to the pathogenesis of Multiple Sclerosis (MS), one of which is Fibroblast Growth Factor 2 (FGF2). The function of FGF2 is pleiotropic. The investigation of the role of this factor in the myelination has produced conflicting results., Objective: To investigate the serum levels of FGF2 in patients with MS., Subjects and Methods: Eighty patients with MS and eighty healthy volunteers with no history of inflammation or demyelinating disorders were included, and serum samples were collected to evaluate serum levels of FGF2 using the ELISA technique. Both groups had the same age and gender distribution. For analysis, the Mann-Whitney U test was used., Results: Patients with MS had considerably greater serum FGF2 levels than the control group (p = 0.005). There was no difference between the FGF2 level in men and women., Conclusion: Our data indicate that FGF2 levels may be related to the susceptibility of Iranian patients with MS. Further studies are required to analyze the involvement of FGF2 in enhancing the inflammatory process in MS.

Background: Children living with HIV frequently show high plasma levels of fibroblast growth factor-2 (FGF-2/bFGF). FGF-2 accelerates the progression of several experimental kidney diseases; however, the role of circulating FGF-2 in childhood HIV-chronic kidney diseases (HIV-CKDs) is unknown. We carried out this study to determine whether high plasma FGF-2 levels were associated with the development of HIV-CKDs in children., Methods: The plasma and urine FGF-2 levels were measured in 84 children (< 12 years of age) living with HIV during the pre-modern antiretroviral era, and followed for at least 3 years to determine the prevalence of proteinuria and HIV-CKDs. We also assessed the distribution of the kidney FGF-2 binding sites by autoradiography and Alcian blue staining, and explored potential mechanisms by which circulating FGF-2 may precipitate HIV-CKDs in cultured kidney epithelial and mononuclear cells derived from children with HIV-CKDs., Results: High plasma FGF-2 levels were associated with a high viral load. Thirteen children (~ 15%) developed HIV-CKDs and showed a large reservoir of FGF-2 low-affinity binding sites in the kidney, which can facilitate the recruitment of circulating FGF-2. Children with high plasma and urine FGF-2 levels had 73-fold increased odds (95% CI 9-791) of having HIV-CKDs relative to those with normal FGF-2 values. FGF-2 induced the proliferation and decreased the expression of APOL-1 mRNA in podocytes, and increased the attachment and survival of infected mononuclear cells cultured from children with HIV-CKDs., Conclusions: High plasma FGF-2 levels appear to be an additional risk factor for developing progressive childhood HIV-CKDs., (© 2021. IPNA.)

Objectives: To investigate whether inflammatory and growth factors (IGFs) were associated with incomplete device endothelialization (IDE) at 6 months after successful left atrial appendage closure (LAAC)., Background: IDE after LAAC is correlated with device-related thrombus (DRT) formation and subsequent thromboembolic events. However, biomarkers for early detection of IDE remain lacking., Methods: Plasma levels of IGFs including basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), stromal cell derived factor (SDF)-1a, transforming growth factor (TGF)-β 1 , vascular growth factor receptor-1 (VEGF-R 1 ) and von Willebrand factor (vWF) were determined using ELISA kits in 55 consecutive patients with atrial fibrillation (AF) at 6 months after LAAC with Watchman devices. The status of device endothelialization was assessed by transesophageal echocardiography and cardiac CT., Results: IDE and complete device endothelialization(CDE)were detected in 38 and 17 patients, respectively. Among the six IGFs, only plasma level of bFGF was significantly lower in patients with IDE compared to those with CDE (303.49 ± 246.84 vs. 556.31 ± 197.84 pg/ml, p < 0.001). C-statistics of plasma bFGF for discriminating patients with IDE from those with CDE was 0.785 (95 % CI: 0.663-0.907, p < 0.001), with a cut-off value of 440.52pg/ml (sensitivity 0.765; specificity 0.789). Multivariate logistic regression model showed that lower bFGF was an independent factor for IDE (OR: 11.752, 95 % CI: 2.869-48.144, P = 0.001). bFGF improved the classification of patients (NRI: 0.677,95 % CI: 0.320-1.033, p = 0.004)., Conclusions: Reduced plasma bFGF level confers an increased risk for IDE after LAAC. Further prospective studies are warranted to examine if bFGF could serve as a biomarker for IDE post LAAC.

Background: The prevalence of obesity has increased substantially in the last few decades. World Health Organization (2020) estimated that around 600 million obese adults worldwide were obese, and a further increase is expected in the future due to increased consumption of high-calorie diets and a sedentary lifestyle as per the evidence., Aim: To evaluate and compare the level of fibroblast growth factor platelet rich fibrin (A-PRF) in obese subject compare to healthy weight subject., Methods: Blood samples were collected from 23 volunteers, 15 obese subject (test group) and 8 non-obese (control group) at Riyadh Elm University. Considering the smaller sample size of our study, the results are to cautiously be interpreted for generalizability. Studies employing larger sample size are recommended to overcome this point. But considering the meticulous study procedure adhering to the study protocol and set criteria, the study pronounces greater internal validity in the sample chosen. The medical, dental histories, an interview and clinical examination was performed to check the eligibility of the participants to be involved in this study, Blood sample was collected in 10 ml syringe, then being processed using A-PRF centrifugation protocols. Ten milliliters of whole blood without anticoagulant was centrifuged at 1,300 rpm for 14 minutes., Results: The level of FGF-2 released from (A-PRF) concentration was significantly lower on obese which was measured on 4 different times (day 1, day 7, day 14 and day 28), compared to healthy., Conclusions: There was decrease in FGF-2 level released from (A-PRF) from obese compared to healthy., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (©2021 Pacini Editore SRL, Pisa, Italy.)

Background: Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis., Objectives: The aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis., Methods: 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay., Results: Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores., Conclusions: Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF., Competing Interests: The authors have declared that no competing interests exist.

Eggs are considered a high-quality protein source for their complete amino acid profile and digestibility. Therefore, this study aimed to compare the effects of whole egg (WE) v. egg white (EW) ingestion during 12 weeks of resistance training (RT) on the skeletal muscle regulatory markers and body composition in resistance-trained men. Thirty resistance-trained men (mean age 24·6 (sd 2·7) years) were randomly assigned into the WE + RT (WER, n 15) or EW + RT (EWR, n 15) group. The WER group ingested three WE, while the EWR group ingested an isonitrogenous quantity of six EW per d immediately after the RT session. Serum concentrations of regulatory markers and body composition were measured at baseline and after 12 weeks. Significant main effects of time were observed for body weight (WER 1·7, EWR 1·8 kg), skeletal muscle mass (WER 2·9, EWR 2·7 kg), fibroblast growth factor-2 (WER 116·1, EWR 83·2 pg/ml) and follistatin (WER 0·05, EWR 0·04 ng/ml), which significantly increased (P < 0·05), and for fat mass (WER -1·9, EWR -1·1 kg), transforming growth factor-β1 (WER -0·5, EWR -0·1 ng/ml), activin A (WER -6·2, EWR -4·5 pg/ml) and myostatin (WER -0·1, EWR -0·06 ng/ml), which significantly decreased (P < 0·05) in both WER and EWR groups. The consumption of eggs absent of yolk during chronic RT resulted in similar body composition and functional outcomes as WE of equal protein value. EW or WE may be used interchangeably for the dietary support of RT-induced muscular hypertrophy when protein intake is maintained.

Background: 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., Methods: 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., Results: 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., Conclusion: 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., Impact: 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.

Depletion of S-adenosyl methionine and 5-methyltetrahydrofolate; and elevation of total plasma homocysteine were documented in CAD patients, which might modulate the gene-specific methylation status and alter their expression. In this study, we have aimed to delineate CAD-specific epigenetic signatures by investigating the methylation and expression of 11 candidate genes i.e. ABCG1, LIPC, PLTP, IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66 and TGFBR3. The methylation-specific PCR and qRT-PCR were used to assess the methylation status and the expression of candidate genes, respectively. CAD patients showed the upregulation of IL-6, TNF-α, CDKN2A, CDKN2B, F2RL3, FGF2, P66, and TGFBR3. Hypomethylation of CDKN2A loci was shown to increase risk for CAD by 1.79-folds (95% CI 1.22-2.63). Classification and regression tree (CART) model of gene expression showed increased risk for CAD with F2RL3 > 3.4-fold, while demonstrating risk reduction with F2RL3 < 3.4-fold and IL-6 < 7.7-folds. This CAD prediction model showed the excellent sensitivity (0.98, 95% CI 0.88-1.00), specificity (0.91, 95% CI 0.86-0.92), positive predictive value (0.82, 95% CI 0.75-0.84), and negative predictive value (0.99, 95% CI 0.94-1.00) with an overall accuracy of 92.8% (95% CI 87.0-94.1%). Folate and B 12 deficiencies were observed in CAD cases, which were shown to contribute to hypomethylation and upregulation of the prime candidate genes i.e. CDKN2A and F2RL3. Early onset diabetes was associated with IL-6 and TNF-α hypomethylation and upregulation of CDKN2A. The expression of F2RL3 and IL-6 (or) hypomethylation status at CDKN2A locus are potential biomarkers in CAD risk prediction. Early epigenetic imprints of CAD were observed in early onset diabetes. Folate and B 12 deficiencies are the contributing factors to these changes in CAD-specific epigenetic signatures.

Objective: To identify potential biomarkers to distinguish adult-onset Still's disease (AOSD) from sepsis., Method: We recruited 70 patients diagnosed with AOSD according to the Yamaguchi criteria, 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the AOSD and sepsis groups in order to identify specific molecular networks. Further, multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by their importance and determine specific biomarkers for distinguishing AOSD from sepsis., Results: Seventeen of the 40 cytokines were found to be suitable for further analyses. The serum levels of eleven were significantly higher in patients with AOSD than healthy controls. Levels of serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and interleukin (IL)-18 were significantly elevated in patients with AOSD compared with those with sepsis, and cytokine clustering patterns differed between these two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both FGF-2 and IL-18 could distinguish AOSD from sepsis with high accuracy (cutoff value for FGF-2 = 36 pg/mL; IL-18 = 543 pg/mL, sensitivity 100%, specificity 72.2%, accuracy 93.8%)., Conclusion: Determination of FGF-2 and IL-18 levels in combination may represent a biomarker for the differential diagnosis of AOSD from sepsis, based on the measurement of multiple cytokines.

BACKGROUND Acute pancreatitis (AP) is a symptom of sudden pancreas inflammation, which causes patients severe suffering. In general, fibroblast growth factor (FGF) levels are increased and amylase and lipase activities are elevated during AP pathogenesis, but protein concentration are low. However, the mechanism through which FGF signaling regulates AP pathogenesis remains elusive. MATERIAL AND METHODS The concentrations of PGE2, TNF-alpha, sCRP, FGF1, and FGF2 in the serum samples of the AP group and healthy control group were detected by enzyme-linked immunosorbent assay. In addition, IkappaBalpha and p-IkappaBalpha levels were analyzed in the serum samples. Subsequently, the AP rat model was established, and FGF1, FGF2, anti-FGF1, and anti-FGF2 antibodies and Bay11-7082 were injected into AP rats. TNF-alpha, PAI-1 JNK, p-JNK, IkappaBalpha, and p-IkappaBalpha levels were also examined. RESULTS Results showed that levels of PGE2, TNF-alpha, sCRP, p-IkappaBalpha, FGF1, and FGF2, as well as amylase and lipase activity were increased in patients with AP compared with those in healthy people. In addition, protein concentrations were lower in patients with AP than in the healthy group. Activation of FGF signaling by injecting FGF1 or FGF2 also inhibited AP-induced inflammation response in the pancreas and increased amylase and lipase activities, as well as protein concentration. However, the injection of FGF1 and FGF2 antibodies accelerated AP-mediated inflammation responses in the serum. In addition, Bay11-7082 injection inhibited AP activation of inflammation response and amylase and lipase activities. Protein concentration were also increased in AP rats. CONCLUSIONS FGF signaling protects against AP-mediated damage by inhibition of AP-activating inflammatory responses.

Context: Osteosarcoma (OS) is a progressive primary bone tumor that originates from immature stromal spindle cells. After chemotherapy, the serum-related indexes which are related to the prognosis., Aims: The aim of this study is to investigate the correlation between changes in serum cyclooxygenase-2 (COX-2), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and tumor-specific growth factor (TSGF) levels and prognosis of patients with osteosarcoma (OS) before and after treatment., Settings and Design: Data of 75 patients with OS (observation group) and 55 healthy controls (control group) were retrospectively analyzed., Materials and Methods: Chemotherapy was administered to the observation group. Serum lactate dehydrogenase, alkaline phosphatase, and TSGF levels were measured before and after treatment. The observation group patients were classified as normal or abnormal according to the changes in serum COX-2, bFGF, VEGF, TGF-β, and TSGF levels after chemotherapy. Patients were followed up for 7.5 years, and the survival rate was determined., Statistical Analysis Used: Single-factor influencing prognosis was included in the Cox model, and independent factors influencing prognosis were analyzed., Results: After chemotherapy, the mean serum COX-2, bFGF, VEGF, and TSGF levels decreased significantly in the observation group but were still higher than those in the control group. Furthermore, serum TGF-β levels increased in the observation group but were still lower than those in the control group. The 5-year survival rate of patients with normal serum COX-2, bFGF, VEGF, and TSGF levels was significantly higher in the normal subgroup than in the abnormal subgroup. Cox analysis showed that the Enneking stage and COX-2 level after chemotherapy were independent prognostic factors., Conclusions: The serum COX-2, bFGF, VEGF, and TSGF levels of patients with OS significantly changed after chemotherapy, and the short-term survival rate of patients with normal levels of these biomarkers after chemotherapy was high., Competing Interests: None

Background: Fibroblast Growth Factor (FGF) 2 (also referred to as basic FGF) is a multifunctional growth factor that plays a pivotal role in the pro-survival, pro-migration and prodifferentiation of neurons., Method: Because alterations in FGF2 levels are suggested to contribute to the pathogenesis of schizophrenia, we investigated serum levels of FGF2 in the Gunn rat, a hyperbilirubinemia animal model of schizophrenic symptoms., Results: The enzyme-linked immunosorbent assay showed that the serum levels of FGF2 in Gunn rats were 5.09 ± 0.236 pg/mL, while those in the normal strain Wistar rats, serum levels were 11.90 ± 2.142 pg/mL. The serum FGF2 levels in Gunn rats were significantly lower than those in Wistar rats. We also measured serum levels of Unconjugated Bilirubin (UCB) and found a significant negative correlation between UCB and FGF2 in terms of serum levels in all the rats studied., Conclusion: Since it is known that FGF2 regulates dopaminergic neurons and have antineuroinflammatory effects, our finding suggests that low FGF2 levels may contribute to the pathogenesis of schizophrenia, in which imbalanced dopamin-ergic signaling and neuroinflammation are supposed to play certain roles., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Major depressive disorder (MDD) has a prevalence of 5% in adolescents. Several studies have described the association between the inflammatory response and MDD, but little is known about the relationship between MDD and growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF. It must be appointed that there are scarce reports on growth factors in adolescents with MDD and even fewer with a clinical follow-up. In this work, we evaluated the levels of growth factors (IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF) in MDD adolescents and the clinical follow-up during eight weeks of treatment with fluoxetine. Methods . All patients were diagnosed according to the DSM-IV-TR, and the severity of the symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS). Growth factors IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were quantified by cytometric bead array using serum samples from 22 adolescents with MDD and 18 healthy volunteers. Results . All patients showed clinical improvement since the fourth week of pharmacological treatment according to the HDRS. Considerably higher levels of IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were detected in MDD adolescents as compared to healthy volunteers. A significant but temporal decrease was detected in basic FGF, G-CSF, and GM-CSF at week four of fluoxetine administration. Conclusions . To the best of our knowledge, this is the first report to show alterations in the levels of growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF in MDD adolescents during eight weeks of clinical follow-up. These disturbances might be involved in the physiopathology of MDD since such growth factors have been proven to participate in the neural development and correct functioning of the CNS; therefore, subtle alterations in it may contribute to MDD., Competing Interests: The authors declare no conflicts of interest associated with the present manuscript., (Copyright © 2019 Enrique Becerril-Villanueva et al.)

Background/aim: FGF-2, HGF, MIF and PTN have been suggested as biomarkers for testicular germ cell cancer patients in earlier studies. Our study was designed to validate these potential novel tumor markers., Materials and Methods: Serum FGF-2, HGF, MIF and PTN levels were analysed using an ELISA technique in a screening cohort of 20 testicular germ cell cancer patients and 10 healthy men. MIF levels were measured in a validation cohort of 84 patients with testicular cancer, 24 with non-malignant testicular tumors and 64 healthy men., Results: Serum FGF-2, HGF and PTN levels did not differ in cancer patients and healthy males within the screening cohort, whereas MIF was significantly increased among cancer patients. Within the validation cohort, a modest but insignificant increase of serum MIF was observed in TGCT patients compared to healthy men. MIF levels were not correlated with adverse clinical-pathological parameters., Conclusion: FGF-2, HGF, MIF and PTN are not suitable as non-invasive biomarkers for testicular germ cell cancer patients., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Diosmin is a natural compound with a wide range of biological activity, e.g., it improves lymphatic drainage, supports microcirculation, and increases venous tone, and venous elasticity, hence, it is applied in the pharmacotherapy of chronic venous disorders (CVD). The aim of this study was to assess the correlation between diosmin administration (2 × 600 mg daily) in patients suffering from CVD and the levels of selected factors influencing angiogenesis, which are involved in CVD pathophysiology. Thirty-five CVD patients were examined. Levels of plasma tumor necrosis factor alpha (TNF alpha), vascular endothelial growth factor (VEGF-A and VEGF-C); angiostatin, interleukin 6 (IL-6), fibroblast growth factor 2 (FGF2); and plasminogen (PLG) were measured with an Elisa assay before and after three months of diosmin administration. The clinical symptoms of CVD were monitored using ultrasound images, echo Doppler assay, visual analogue scale (VAS), and measurement of the leg circumference. The average content of TNF alpha, VEGF-C, VEGF-A IL-6, and FGF2 decreased after the therapy with diosmin in a significant manner; with p < 0.001, p < 0.05, p < 0.05, p < 0.01, and p < 0.01, respectively, and a significant ( p < 0.05) increase in the plasma angiostatin level after the three-month treatment was found. A significant ( p < 0.05) decrease in edema and the average leg circumference of the patients was observed after the therapy. Diosmin influences the angiogenic and inflammatory mechanisms involved in the pathophysiology of edema presented in patients with a different class of CVD.

Purpose: Hepatokines are proteins produced by the liver and involved in regulating glucose and lipid metabolism. However, their role as the biomarkers of intrahepatic lipid content is not clear. The aim of the study was to evaluate the serum concentration of selected hepatokines: fibroblast growth factor-21 (FGF-21), selenoprotein P (SELENOP) and sex hormone-binding globulin (SHBG) in obese children., Patients and Methods: The cross-sectional study included 86 obese children with suspected liver disease. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in children with liver steatosis in ultrasound with elevated alanine aminotransferase (ALT) serum activity and excluded other liver diseases. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy ( 1 H-MRS)., Results: The concentration of FGF-21 and SELENOP was significantly higher and SHBG significantly lower in children with NAFLD compared to controls. Only FGF-21 level was significantly higher in NAFLD children than in obese patients without NAFLD. The significant positive correlation of FGF-21 with ALT, gamma glutamyltransferase (GGT), triglycerides, homeostatic model assessment-insulin resistance (HOMA-IR), the degree of liver steatosis in ultrasound and TILC in 1 H-MRS were found. The ability of serum FGF-21 to diagnose severe liver steatosis was significant., Conclusions: FGF-21 can be considered as a suitable biomarker in predicting TILC and fatty liver in obese children., (Copyright © 2019 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Context: Fibroblast growth factor (FGF)2 is an important stimulatory modulator of satellite cells in skeletal muscle. Satellite cells play a cardinal role in muscle growth and repair., Objective: We evaluated whether skeletal muscle expression of FGF2 and muscle growth and differentiation factors are reduced in patients with hypogonadotropic hypogonadism (HH) and whether testosterone replacement therapy results in their restoration., Design: This is a secondary analysis of a previously completed trial of testosterone replacement in men with type 2 diabetes and HH., Setting: Clinical Research Center at a university., Patients: Twenty-two men with HH and 20 eugonadal men were compared at baseline., Interventions: Twelve men with HH were treated with intramuscular injections of 250 mg testosterone every 2 weeks for 22 weeks, and 10 men received placebo injections. Quadriceps muscle biopsies and blood samples were obtained before and after testosterone therapy., Outcome Measures and Results: The expression of FGF2 and FGF receptor (FGFR)2 in skeletal muscle of men with HH was significantly lower than that in eugonadal men by 57% and 39%, respectively (P < 0.05). After 22 weeks of testosterone, the expression of FGF2 increased, whereas that of myogenic regulatory factor (MRF)4 and myostatin decreased significantly. There was no change in expression of FGFR2, myogenin, or myogenic differentiation protein in the skeletal muscle. Plasma FGF2 and IGF-1 concentrations increased after testosterone therapy., Conclusions: These data show that testosterone is a major modulator of FGF2, MRF4, and myostatin expression in skeletal muscle. These effects may contribute to the increase in muscle mass after testosterone therapy., (Copyright © 2019 Endocrine Society.)

Background and aim: Recent evidence suggests that growth factors might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The aim of this study was to determine whether serum levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), nerve growth factor (NGF), fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) were altered in children with ADHD. Methods: Serum levels of BDNF, GDNF, NT-3, NGF, VEGF and FGF-2 were analyzed in 49 treatment- naive children with ADHD and age, gender matched 36 healthy controls using enzyme-linked immunosorbent assay. ADHD symptoms were scored by Du Paul ADHD Rating Scale and Strengths and Difficulties Questionnaire. Results: We found that serum VEGF levels were significantly lower ( p  < 0.001) and GDNF levels were significantly higher in ADHD group compared to control group ( p  = 0.003). However, we found no correlations between ADHD symptoms and serum VEGF or GDNF levels. Furthermore, we observed no significant alterations in serum BDNF, NT-3, NGF, FGF-2 levels in children with ADHD. Conclusion: To our knowledge, the present study is the first to examine serum VEGF and FGF-2 levels in children with ADHD. Our results indicate that VEGF and GDNF might be involved in the etiology of ADHD. Further studies are required to determine the role of growth factors in the etiology and consequently in the treatment of ADHD.

Background: Although several pharmacological treatment options for depression are currently available, a large proportion of patients still do not achieve a complete remission or respond adequately to the initial antidepressant prescribed for reasons that remain relatively unknown. This study explored the application of serum biomarkers to the predict the efficacy of escitalopram for treating depression, to guide clinical drug selection., Method: In this study, 306 patients suffering from depression were treated with escitalopram (10 mg) for 6 weeks. After 6 weeks of treatment, the patients were divided into an escitalopram-sensitive group (ES, n = 172) and an escitalopram-insensitive group (EIS, n = 134) according their HAMD-24 scores after 6 weeks of treatment. Serum samples from all participants were collected on the first day, and 10 different serum biomarkers were analysed. Data from 100 patients in the ES group and 100 patients in the EIS group were then used to build a logistic regression model, and a receiver operating characteristic (ROC) curve was drawn. To validate the accuracy of our model, another 72 patients in the ES group and 34 patients in the EIS group were studied., Results: Of the 10 selected serum biomarkers, 4 were screened to build the regression model. BDNF, FGF-2, TNF-α and 5-HT. The regression equation was Z = 1/[1 + e -(-5.065+0.145 (BDNF)+0.029 (FGF-2)-0.368 (TNF-α)+0.813 (5-HT)) ], and the 4 biomarkers-combined detection achieved an AUC (area under the ROC curve) of 0.929 and a predictive accuracy of 88.70%., Limitation: Decision support tools based on our combined biomarker prediction models hold comparatively great promises; however, they need to be validated on a much larger scales than current studies provide., Conclusion: The logistic regression model and ROC curves based of the serum biomarkers used in this study provide a more reliable means to predict the efficacy of escitalopram in patients with depression, and provide clinical evidence for drug selection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To determine the effect of ultrasonic debridement on serum inflammatory factors of procalcitonin (PCT), highsensitivity C-reactive protein (hs-CRP), red blood cell deposition rate (ESR) content, and expression levels of wound tissue basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)., Study Design: An experimental study., Place and Duration of Study: Department of Emergency, Dongguan People's Hospital, China, from February 2016 to February 2018., Methodology: A total of 80 patients with limb flap repair were randomly divided into a control group and an observation group, with 40 cases in each group. Control group was treated with conventional surgical debridement, and the observation group was treated with ultrasound debridement technique. The effect was compared between two groups., Results: On the 1st, 3rd, and 7th days after flap repair, Numeric Rating Scale (NRS) scores in observation group were lower than those in control group (all p <0.001). On the 7th day after the flap repair, serum levels of PCT, hs-CRP, and ESR were lower in observation group than those in control group (all p <0.001). On the 7th and 12th day after flap repair, expression levels of bFGF and EGF protein in the wound tissue of observation group were higher than those in control group (all p <0.001). Infection with sinus tract formed after the flap repair in observation group was lower than that in control group (p=0.048)., Conclusion: Compared with conventional surgical debridement, ultrasound debridement technique can more effectively reduce postoperative inflammatory reactions, reduce postoperative wound infection, relieve pain in patients, promote the bFGF and EGF expression in the wound tissue.

Huntington's disease (HD) is a hereditary disorder that typically manifests in adulthood with a combination of motor, cognitive and psychiatric problems. The pathology is caused by a mutation in the huntingtin gene which results in the production of an abnormal protein, mutant huntingtin (mHtt). This protein is ubiquitously expressed and known to confer toxicity to multiple cell types. We have recently reported that HD brains are also characterised by vascular abnormalities, which include changes in blood vessel density/diameter as well as increased blood-brain barrier (BBB) leakage., Objectives: Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells., Methods: We assessed the functional status of platelets by performing ELISA, western blot and RNA sequencing in a cohort of 71 patients and 68 age- and sex-matched healthy control subjects. We further performed haemostasis and platelet depletion tests in the R6/2 HD mouse model., Results: Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis., Conclusion: Taken together, our results provide a better understanding for the impact of mHtt on platelet function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Epidermal growth factor (EGF) and Fibroblast Growth Factor-2 (FGF-2) are growth factors involved neuronal growth and synaptic plasticity. These markers have been implicated in neuropsychiatric disorders, including major depression. However, no particular studies of EGF and FGF-2 have been conducted in older adults with major depressive disorder (MDD). In this study, we aim to investigate the plasma levels of EGF and FGF-2 in elderly with MDD. We included 89 older adults with MDD and 51 older (healthy control, HC) adults. The cognitive performance was evaluated by the Mattis Dementia Rating Scale (MDRS). The EGF and FGF-2 were measured by using multiplex assay for LUMINEX platform. There were also no significant differences between the patient group in terms of plasma levels of EGF and FGF-2 when compared to the HC group. There were not any significant correlations between plasma levels of EGF or FGF2 and MDRS total or individual scores in patient group and HC. There were significant correlations between plasma levels of EGF and FGF2 in both patient group and HC. Further study on plasma levels of EGF and FGF2 should be implemented in larger samples in elderly with MDD., (Copyright © 2018. Published by Elsevier B.V.)

Takayasu arteritis (TAK) and giant cell arteritis (GCA) are two major variants of large vessel vasculitis, and age is a major factor in their differential diagnosis. We sought to determine whether the two diseases exist on the same spectrum. We compared the serum levels of multiple cytokines and chemokines in 25 patients with TAK, 20 patients with GCA, and sex- and age-matched healthy donors for either condition (HD-TAK and HD-GCA). To evaluate the effects of age on the levels of cytokines and chemokines, we performed multiple logistic regression analysis using the least absolute shrinkage and selection operator (LASSO) method. The levels of IL-1RA, IL-10, GM-CSF, G-CSF, FGF-2, eotaxin, and IP-10 were significantly different between TAK and GCA, but no differences were found in the levels of IL-6, IL-12(p40), IL-17, IFN-γ, and TNF-α. Significant differences in the levels of IL-1RA, IL-10, GM-CSF, eotaxin, and IP-10 were observed between the HD-TAK and HD-GCA groups. Multiple logistic regression analysis demonstrated that only FGF-2 and IP-10 could significantly distinguish the diseases when added to age. Multiple logistic analysis using factors selected by the LASSO method revealed that FGF-2 was the only significant factor to distinguish the diseases when added to age. Among numerous cytokines and chemokines analyzed, only FGF-2 could be used together with age at diagnosis to differentiate TAK and GCA. Our results suggested the importance of considering the effects of age on serum cytokines.

Background: Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis., Methods: Blood and bone marrow plasma levels of Ang-2, FGF-2, HGF, VEGF, PDGF-β, IL-8, TNF-α, TIMP-1, and TIMP-2 were determined at diagnosis in MM patients enrolled in the GIMEMA MM0305 randomized controlled trial by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with the type of therapy and patients' characteristics and with a group of non-MM patients as controls., Results: No significant differences were detected between the blood and bone marrow plasma levels of angiogenic cytokines. A cutoff for each CAF was established. The therapeutic response of patients with blood plasma levels of CAFs lower than the cutoff was better than the response of those with higher levels in terms of percentage of responding patients and quality of response., Conclusion: FGF-2, HGF, VEGF, and PDGF-β plasma levels at diagnosis have predictive significance for response to treatment. The stratification of patients based on the levels of CAFs at diagnosis and their variations after therapy is useful to characterize different risk groups concerning outcome and response to therapy., Trial Registration: Clinical trial information can be found at the following link: NCT01063179.

Preclinical and clinical studies suggest that brain-derived neurotrophic factor and nerve growth factor are involved in the pathogenesis of schizophrenia (SCZ). However, the roles of other neurotrophic factors in SCZ remain unclear. The aim of this study was to investigate the blood levels of FGF2 and ADNP in first-episode, drug-free SCZ patients compared with healthy control subjects. 20 SCZ patients, and 20 age and sex matched controls were recruited in this study. Serum FGF2 and ADNP protein levels were measured by ELISA assay, and the results showed that FGF2 levels were significantly increased in patients with SCZ when compared with controls, whereas ADNP protein levels did not significantly associated with SCZ. However, we found that blood ADNP mRNA levels were significantly increased in the patients with SCZ when compared with controls. In addition, subgroup analyses suggested that FGF2 levels were significantly increased in female patients of SCZ, but not in male patients of SCZ. Correlation analyses suggested that age and disease severity (PANSS score) did not have moderating effects on the serum FGF2 levels. Taken together, our results for the first time demonstrated that blood FGF2 was up-regulated in first-episode, drug free-SCZ patients, therefore enhancing the knowledge of neurotrophic factor profile in patients with SCZ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: This study aimed to assess whether neutrophil gelatinase-associated lipocalin (NGAL) and fibroblast growth factor 23 (FGF23) could be reliable biomarkers for early diagnosis of contrast-induced nephropathy (CIN)., Methods: 202 patients who underwent percutaneous coronary intervention (PCI) were included in the research. All subjects were divided into CIN group and non-CIN group. Serum NGAL and FGF23 were evaluated before and 0, 1, and 2 days after PCI. Serum levels of these two markers were compared intra-group and among groups. Receiver-operating characteristic (ROC) analysis and logistic regression models were conducted to assess the diagnostic performance of NGAL and FGF23 in detecting CIN., Results: When compared with baseline values, serum levels of both NGAL and FGF23 in all subjects increased after PCI, and the values peaked 1 day after PCI, but the changing was greater in CIN group. There were obvious differences between two groups in serum NGAL after 1, 2 days, and similar differences present in serum FGF23 after 1 day. ROC analysis showed that the area under the curve (AUC) of relative values (percent change from the baseline) in NGAL after 1 day was 0.899 (95% CI: 0.834-0.964, p = .000), the optimum cutoff was 49% (sensitivity = 80%, specificity = 92.4%). And the AUC in FGF23 was 0.814 (95% CI: 0.733-0.894, p = .000), the optimum cutoff was 20% (sensitivity = 73.3%, specificity = 87.6%). Both serum NGAL and serum FGF23 could improve the clinical models in identifying CIN., Conclusions: NGAL and FGF23 may have certain value in early diagnosis of CIN.

Introduction: The aim of the present study was to assess the circulating levels of vascular endothelial growth factor (VEGF) and other suggested therapeutic growth factors with the degree of ischemia in patients with different clinical manifestations of peripheral arterial disease (PAD) according to the Rutherford grades., Methods: The study cohort consists of 226 consecutive patients admitted to a Department of Vascular Surgery for elective invasive procedures. PAD patients were grouped according to the Rutherford grades after a clinical assessment. Ankle-brachial pressure indices (ABI) and absolute toe pressure (TP) values were measured. Serum levels of circulating VEGF, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF) were measured from serum and analysed against Rutherford grades and peripheral hemodynamic measurements., Results: The levels of VEGF (P = 0.009) and HGF (P < 0.001) increased significantly as the ischaemic burden became more severe according to the Rutherford grades. PDGF behaved in opposite manner and declined along increasing Rutherford grades (P = 0.004). A significant, inverse correlations between Rutherford grades was detected as follows; VEGF (Pearson's correlation = 0.183, P = 0.004), HGF (Pearson's correlation = 0.253, P < 0.001), bFGF (Pearson's correlation = 0.169, P = 0.008) and PDGF (Pearson's correlation = 0.296, P < 0.001). In addition, VEGF had a clear direct negative correlation with ABI (Pearson's correlation -0.19, P = 0.009) and TP (Pearson's correlation -0.20, P = 0.005) measurements., Conclusions: Our present observations show that the circulating levels of VEGF and other suggested therapeutic growth factors are significantly increased along with increasing ischemia. These findings present a new perspective to anticipated positive effects of gene therapies utilizing VEGF, HGF, and bFGF, because the levels of these growth factors are endogenously high in end-stage PAD., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: The liver's capability to completely regenerate after injury is a unique phenomenon in which cytokines are of particular interest. Here, we aimed to assess the release patterns and prognostic relevance of liver regeneration-related cytokines in the setting of living-donor liver transplant., Materials and Methods: Eleven cytokines related to liver regeneration (hepatocyte growth factor, interleukin 6, insulin-like growth factor-1, tumor necrosis factor alpha, transforming growth factor beta, granulocyte colony-stimulating factor, stem cell factor, chemokine (C-X-C motif) ligand 12, angiogenin, fibroblast growth factor-2, and vascular endothelial growth factor) were compared in 13 living-donor liver transplant recipients and their corresponding donors before and daily (10 days) after transplant. Patients and donors were stratified by clinical outcomes (early graft loss within 4 weeks after transplant vs beneficial outcome)., Results: Most cytokines tested (especially tumor necrosis factor alpha and stem cell factor) were elevated in recipients versus donors. Many cytokines were also increased in recipients with graft loss (especially CXCL12) and in donors of recipients with beneficial outcomes (especially fibroblast growth factor 2). Fibroblast growth factor 2 levels were also correlated positively with serum gamma-glutamyltransferase, and higher preoperative concentrations in donors were associated with recipients having beneficial outcomes, indicating an improved regenerative capacity. In contrast, elevated CXCL12 levels in recipients before and after LDLT predicted graft loss and were linked to ongoing liver damage., Conclusions: In living-donor liver transplant, there are distinct differences between donors and recipients regarding the release of liver regeneration-related cytokines. Moreover, fibroblast growth factor 2 and CXCL12 may be of diagnostic value in a complementary way to describe or even predict the possible outcomes after transplant. These results may be of clinical interest not only for living-donor liver transplant but also for acute liver failure.

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10 -4 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10 -5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10 -7 ), TGF-α (p = 4.08 × 10 -5 ), fractalkine (p = 1.12 × 10 -3 ), monocyte chemotactic protein-3 (p = 1.36 × 10 -4 ), macrophage inflammatory protein 1-alpha (p = 4.6 × 10 -4 ) and vascular endothelial growth factor (p = 4.23 × 10 -5 ). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth-factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL., (© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The study demonstrates significant variety of neovascularization degree and vessel diameter in the carotid atherosclerotic plaque. It is suggested that the increase in the number of vessels with a diameter <20 μ can be indicative of increased atherosclerosis activity, while the increase in the number of vessels with a diameter ≥40 μ indicates "reparative potential" of plaques. Duplex contrast-enhanced ultrasound scanning allows characterization of the localization and number of vessels with a diameter of ≥30 μ in the plaque, while even slight elevation of plasma concentration of basic fibroblast growth factor attests, first of all, to increased content of small vessels <30 μ in the plaque. The level of fibroblast growth factor >1.5 pg/ml is a reliable marker of increased number of both small and large vessels in the plaque.

Background: Until now, there are few studies evaluating serum levels of angiogenic cytokines in dermatomyositis (DM). Therefore, the aims of the present study were: (a) to analyze systematically and simultaneously serum levels of angiogenin (ANG), angiopoietin (ANGPT)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1 and - 2, platelet derived growth factor (PDGF)-AA and -BB in DM; (b) to correlate the serum level of these cytokines with the DM clinical and laboratory features., Methods: This is a cross sectional study, in which 48 patients with DM aged 18 to 45 years were gender-, age- and ethnicity-matched with 48 healthy individuals (control group). The serum levels of cytokines analyses were performed by multiplex immunoassay. The parameters of DM activity were based on the scores established by the International Myositis Assessment & Clinical Studies Group., Results: The mean ages, gender frequencies and ethnicities were comparable between the patients with DM and the control group. A significantly higher serum FGF-1 and FGF-2 levels (P < 0.001 and P < 0.001, respectively), lower VEGF and PDGF-AA levels (P = 0.009 and P = 0.022), and comparable ANG, ANGPT-1 and PDGF-BB levels were observed in DM patients compared to controls. There was a tendency for cytokines (with the exceptions of VEGF and PDGF-BB) to correlate positively with the DM activity parameters, whereas FGF-2 correlated inversely. Moreover, FGF-1 strongly correlated with DM cutaneous manifestations., Conclusions: The present data provide the relevance of different serum angiogenic cytokines in patients with DM. Additional studies will be needed to validate the data obtained in this work.

Background: Propranolol has become the treatment of choice for infantile hemangiomas (IH). Neither the pathogenesis of IH nor the mechanism of action of propranolol on them are well understood. Possible explanations include the inhibition of angiogenesis by decreasing vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), induction of vascular endothelial cell apoptosis and vasoconstriction., Objectives: The aim of the study was to assess serum concentrations of VEGF and bFGF in the course of propranolol therapy of IH in children, and to assess their clinical implications., Material and Methods: The study included 51 children with IH treated with propranolol. The participants were assessed before, during and after the therapy with Hemangioma Activity Score (HAS), Doppler ultrasound (US) of the lesions, as well as VEGF and bFGF serum concentrations., Results: All children showed clinical improvement measured in the HAS. A complete involution of the IH was reported in 32 (63%) children at the time of decision of the gradual withdrawing of propranolol, and in 28 (61%) patients at the end of the treatment (out of 46 patients present at the follow up after 1.5 months). Doppler US at the follow-up showed a complete disappearance of the blood flow in the lesion in 24 (52%) children and its reduction in 12 (26%) children. There was a significant decrease in VEGF and bFGF during and after treatment compared to pretreatment values. There was a correlation between the outcome of the Doppler US and changes in bFGF during and after treatment. Changes in VEGF during treatment did not correlate with changes in the Doppler US., Conclusions: Serum concentrations of VEGF and bFGF decreased during the propranolol treatment of IH, which may indicate the effect of propranolol on both. However, the statistical analysis showed their low prognostic value as biochemical markers of propranolol treatment. Clinical evaluation combined with Doppler US is the most valuable method of monitoring the therapy.

Few preliminary reports studied the utility of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) for differentiation between infantile hemangiomas (IHs) and vascular malformations. The aim of this study was to investigate the role of serum VEGF and bFGF levels in differentiating IHs from vascular malformations and identifying the stage and clinical course of IHs. Serum levels of VEGF and bFGF were assessed in 60 infants and children with various cutaneous vascular anomalies defined in 3 groups: proliferating IHs (n = 25), involuting IHs (n = 23), and vascular malformations (n = 12), in comparison with their levels in 40 healthy matched control. Serum levels of VEGF and bFGF were significantly elevated in all groups as compared to control ( P < .001, respectively). Both proliferating and involuting IHs had comparable levels of both markers ( P > .05, respectively) that were significantly higher in comparison with vascular malformations ( P < .05, respectively). Significantly lower VEGF levels were found in IHs that had regressed spontaneously (n = 11) compared to those regressed by treatment (n = 37), ( P < .05); meanwhile, bFGF showed no significant difference between both groups ( P > .05). Using receiver operating characteristic curves, a combined use of VGEF and bFGF yielded a sensitivity of 85.42% and a specificity of 100% for differentiating IHs from vascular malformations. Serum VEGF and/or bFGF levels are increased in cutaneous vascular anomalies and can differentiate IHs from vascular malformations. None of these markers could help in identifying the stage of IHs. Low VEGF is associated with spontaneous regression of IHs.

Background and Objectives: Atherosclerosis is highly prevalent in CKD. The rate of progression of atherosclerosis is associated with cardiovascular events. Fibroblast growth factor 2 (FGF-2) is a member of the FGF family with potentially both protective and deleterious effects in the development of atherosclerosis. The role of circulating FGF-2 levels in the progression of atherosclerosis in CKD is unknown., Design, Setting, Participants, & Measurements: We used a multicenter, prospective, observational cohorts study of 481 patients with CKD. We determined the presence of atheroma plaque in ten arterial territories by carotid and femoral ultrasounds. Progression of atheromatosis was defined as an increase in the number of territories with plaque after 24 months. Plasma levels of FGF-2 were measured by multiplex analysis. A multivariable logistic regression analysis was performed to determine whether plasma FGF-2 levels were associated with atheromatosis progression., Results: Average age of the population was 61 years. The percentage of patients in each CKD stage was 51% in stage 3, 41% in stages 4-5, and 8% in dialysis. A total of 335 patients (70%) showed plaque at baseline. Atheromatosis progressed in 289 patients (67%). FGF-2 levels were similar between patients with or without plaque at baseline (79 versus 88 pg/ml), but lower in patients with atheromatosis progression after 2 years (78 versus 98 pg/ml; P <0.01). In adjusted analyses, higher plasma FGF-2 was associated with lower risk of atheromatosis progression (odds ratio [OR], 0.86; 95% confidence interval [95% CI], 0.76 to 0.96; per 50 pg/ml increment). Analysis of FGF-2 in tertiles showed that atheroma progression was observed for 102 participants in the lowest tertile of FGF-2 (reference group), 86 participants in the middle tertile of FGF-2 (adjusted OR, 0.70; 95% CI, 0.40 to 1.20), and 74 participants in the lowest tertile of FGF-2 (adjusted OR, 0.48; 95% CI, 0.28 to 0.82)., Conclusions: Low FGF-2 levels are independently associated with atheromatosis progression in CKD., (Copyright © 2018 by the American Society of Nephrology.)

Objectives: The previously observed inverse association between hog farming and risk of lung cancer in the Agricultural Health Study (AHS) has been attributed to endotoxin exposure, the levels of which are particularly high in industrial hog confinement facilities. We conducted an investigation to explore the potential biological mechanisms underlying this association, as well as other immunological changes associated with hog farming., Methods: Serum immune marker levels were measured using a multiplexed bead-based assay in 61 active hog farmers and 61 controls matched on age, phlebotomy date and raising cattle. Both groups comprised non-smoking male AHS participants from Iowa. We compared natural log-transformed marker levels between hog farmers and controls using multivariate linear regression models., Results: Circulating levels of macrophage-derived chemokine (CCL22), a chemokine previously implicated in lung carcinogenesis, were reduced among hog farmers (17% decrease; 95% CI -28% to -4%), in particular for those with the largest operations (>6000 hogs: 26% decrease; 95% CI -39% to -10%; p trend =0.002). We also found that hog farmers had elevated levels of other immune markers, including macrophage inflammatory protein-3 alpha (MIP-3A/CCL20; 111% increase, 95% CI 19% to 273%), basic fibroblast growth factor (FGF-2; 93% increase, 95% CI 10% to 240%) and soluble interleukin-4 receptor (12% increase, 95% CI 1% to 25%), with particularly strong associations for MIP-3A/CCL20 and FGF-2 in winter., Conclusions: These results provide insights into potential immunomodulatory mechanisms through which endotoxin or other exposures associated with hog farming may influence lung cancer risk, and warrant further investigation with more detailed bioaerosol exposure assessment., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Degeneration of central neurons and fibers has been observed in postmortem brains of heroin dependent patients. However, there are no biomarkers to predict the severity of neurodegeneration related to heroin dependence. A correlation has been reported between inflammatory C-C motif chemokine ligand 11 (CCL11, or eotaxin-1) and neurodegeneration in Alzheimer's disease., Methods: Three-hundred-forty-four heroin dependent, Taiwanese patients under methadone maintenance treatment (MMT) were included with clinical assessment and genomics information. Eighty-seven normal control subjects were also recruited for comparison., Results: Using receiver operating characteristics curve analyses, CCL11 showed the strongest sensitivity and specificity in correlation with age by a cut-off at 45 years (AUC = 0.69, P < 0.0001) in MMT patients, but not normal controls. Patients 45 years of age or older had significantly higher plasma levels of CCL11, fibroblast growth factor 2 (FGF-2), nicotine metabolite cotinine, and a longer duration of addiction. Plasma level of CCL11 was correlated with that of FGF-2 (partial r 2  = 0.24, P < 0.0001). Carriers with the mutant allele of rs1129844, a functional single nucleotide polymorphism (Ala23Thr) in the CCL11 gene, showed a higher plasma level of Aß42, ratio of Aß42/Aß40, and insomnia side effect symptom score than the GG genotype carriers among MMT responders with morphine-negative urine results., Conclusions: The results suggest possible novel mechanisms mediated through CCL11 involving neurotoxicity in heroin dependent patients., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Autologous platelet-rich plasma (PRP) is widely used for a variety of clinical applications. However, clinical outcome studies have not consistently shown positive effects. The composition of PRP differs based on many factors. An improved understanding of factors influencing the composition of PRP is important for the optimization of PRP use., Hypothesis: Age and sex influence the PRP composition in healthy patients., Study Design: Controlled laboratory study., Methods: Blood from 39 healthy patients was collected at a standardized time and processed into leukocyte-poor PRP within 1 hour of collection using the same laboratory centrifuge protocol and frozen for later analysis. Eleven female and 10 male patients were "young" (aged 18-30 years), while 8 male and 10 female patients were "older" (aged 45-60 years). Thawed PRP samples were assessed for cytokine and growth factor levels using a multiplex assay and enzyme-linked immunosorbent assay. The platelet count and high-sensitivity C-reactive protein levels were measured. Two-way analysis of variance determined age- and sex-based differences., Results: Platelet and high-sensitivity C-reactive protein concentrations were similar in PRP between the groups ( P = .234). Male patients had higher cytokine and growth factor levels in PRP compared with female patients for inflammatory cytokines such as interleukin-1 beta (IL-1β) (9.83 vs 7.71 pg/mL, respectively; P = .008) and tumor necrosis factor-alpha (TNF-α) (131.6 vs 110.5 pg/mL, respectively; P = .048); the anti-inflammatory IL-1 receptor antagonist protein (IRAP) (298.0 vs 218.0 pg/mL, respectively; P < .001); and growth factors such as fibroblast growth factor-basic (FGF-basic) (237.9 vs 194.0 pg/mL, respectively; P = .01), platelet-derived growth factor (PDGF-BB) (3296.2 vs 2579.3 pg/mL, respectively; P = .087), and transforming growth factor-beta 1 (TGF-β1) (118.8 vs 92.8 ng/mL, respectively; P = .002). Age- but not sex-related differences were observed for insulin-like growth factor-1 (IGF-1) ( P < .001). Age and sex interaction terms were not significant. While mean differences were significant, there was also substantial intragroup variability., Conclusion: This study in healthy patients shows differences in the composition of PRP between men and women, with sex being a greater factor than age. There was also proteomic variability within the groups. These data support a personalized approach to PRP treatment and highlight the need for a greater understanding of the relationships between proteomic factors in PRP and clinical outcomes., Clinical Relevance: Variability in the proteomic profile of PRP may affect tissue and clinical responses to treatment. These data suggest that clinical studies should account for the composition of PRP used.

The aim of our study was to determine the blood levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2, and platelet-derived growth factor (PDGF)-AB in different stages of pulmonary sarcoidosis. There were 92 patients in sarcoidosis stages I + II, III, and IV enrolled into the study. All the patients underwent lung diffusing capacity and blood sampling. We found that VEGF levels differed significantly between the stage groups with the peak VEGF concentrations in stage III. TGF-β1 levels were similar in stages I + II and III, and tended to be lower in stage IV. The analysis of the subgroups showed increased VEGF and FGF-2, and reduced TGF-β1 concentration in stages I + II patients with relevantly reduced lung diffusing capacity or increased sarcoidosis activity compared to patients with normal lung diffusing capacity or inactive sarcoidosis. A tendency towards increased VEGF, PDGF-AB and TGF-β1 levels was observed in the analogical subgroup analysis within the stage III. We conclude that proangiogenic VEGF, and profibrotic FGF-2 and PDGF-AB may contribute to the progression of sarcoidosis, whereas TGF-β1, with its dual anti-inflammatory and profibrotic actions, may play a dichotomous protective or deleterious role. Reduced diffusing capacity and active sarcoidosis are associated with an unfavorable constellation of the markers studied, which predicts a progressive disease course.

Arterial embolization, aimed at the mechanical occlusion of tumor-feeding vessels, represents a satisfactory palliative therapy for bone metastases. In this study, we evaluated if the circulating levels of three factors related to the metastatic process change in response to embolization. Seven patients who underwent embolization of a single skeletal metastasis from carcinomas were analyzed prospectively. Circulating levels of Vascular Endothelial Growth Factor A (VEGF-A), Fibroblast Growth Factor 2 (FGF-2), and Tartrate-Resistant Acid Phosphatase-5b Isoform (TRACP5b) were evaluated before and after embolization at 1, 3, and 6 months. According to morphological and clinical evaluations, all the embolizations were successful. VEGF-A and TRACP5b did not show significant changes after the treatment. On the contrary, FGF-2 signifi- cantly decreased 1 month after the treatment. FGF-2 appears as a promising candidate for monitoring the efficacy of emboli- zation in patients with osteolytic metastases.

Purpose: Endothelial barrier dysfunction is a hallmark of sepsis, and is at least partially mediated by pathways that regulate endothelial barrier assembly during angiogenesis. Not surprisingly, increased levels of key angiogenic proteins such as VEGF-A and Angiopoietin-2 have been described in sepsis. The purpose of this study was to investigate if additional pathways that regulate endothelial barrier integrity during angiogenesis could also be involved in the host response of sepsis., Material and Methods: We evaluated circulating levels of four proteins involved in angiogenesis, not previously studied in sepsis, in a cohort of 50 patients with severe sepsis and septic shock., Results: Circulating levels of BMP-9 and FGF-2 were similar in patients and healthy volunteers. In contrast, patients with septic shock presented 1.5-fold higher levels of endoglin (P=0.004), and 2-fold lower levels of Heparin-Binding EGF-like growth factor (HB-EGF) (P=0.002) when compared to healthy individuals. Of note, HB-EGF deficiency has been recently demonstrated to be detrimental to survival in a murine model of sepsis., Conclusions: Endoglin and HB-EGF could be involved in the host response of sepsis. Additional studies are warrant to investigate their role as biomarker or therapeutic targets in sepsis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Heart failure (HF) has a significant effect on the prognosis of the patients with atrial fibrillation (AF), and also it is an important risk factor for overall mortality. High molecular weight fibroblast growth factor-2 (Hi-FGF-2) is emerging as a prognostic marker with HF and AF. The aim of this study was to prove that Hi-FGF-2 would predict occurrence of HF in the patients with AF. Subjects diagnosed with paroxysmal AF (Group paAF), persistent AF (Group peAF) and sinus rhythm (Group SR) were enrolled in the study. Serum Hi-FGF-2 concentration was measured by ELISA at baseline. Multivariable logistic models and receiver operating characteristic (ROC) curve analysis were established to predict the prognosis of AF subjects. 260 patients were enrolled in the study: 104 (40.0%) admitted for sinus rhythm (Group SR) and 156 (60.0%) with AF (Group paAF and Group peAF). The Hi-FGF-2 levels were much lower in the Group SR (58.2 ± 27.1 ng/L) than in the Group AF. Furthermore, the Group peAF (84.3 ± 34.1 ng/L) had higher Hi-FGF-2 levels than the Group paAF (72.9 ± 35.8 ng/L). Serum Hi-FGF-2 levels were classified into trisection in the multivariable logistic model (T1 < 57.3 ng/L, 57.3 < T2 < 86.5 ng/L, and T3 > 86.5 ng/L). Hi-FGF-2 showed good predictive ability for new-onset HF in the patients with AF. The occurrence of HF was associated significantly with increased tertile of serum Hi-FGF-2 levels (T2: OR 5.922, 95% CI 1.109-31.626, P = 0.037 and T3: OR 8.262, 95% CI 1.735-39.343, P = 0.008). ROC curve analysis showed that the area under curves for Hi-FGF-2 were 0.720 (P < 0.0001). Hi-FGF-2 has a significant meaning in AF subjects. Further to this, higher circulating Hi-FGF-2 was highly related to persistent AF, and Hi-FGF-2 may be an independent risk factor of occurrence HF in AF subjects.

Background: The main clinical forms of paracoccidioidomycosis (PCM) are the acute/subacute form (AF) and the chronic form (CF), and they both display considerable clinical variability. The immune responses of PCM patients, during and after treatment, remain neglected, mainly in the case of CF patients, due to the high prevalence of pulmonary sequelae., Objective: To evaluate the distribution of whole blood T cell subsets, serum cytokines, and biomarkers of pulmonary fibrosis in PCM patients, according to the clinical form and at different time points, during the antifungal therapy., Methods: Eighty-seven PCM patients, from an endemic area in Brazil, were categorised into groups, according to the clinical form (AF or CF) and the moment of treatment. The peripheral blood T lymphocyte subsets of these patients were analysed using fluorescence-activated cell sorting. The serum levels of cytokines, basic fibroblast growth factor and surfactant protein-D (SP-D) were also analysed., Findings: In the CF patients, an expansion of the peripheral blood TCD4+ cells was observed during the treatment, and this persisted even after two years of antifungal treatment. In addition, these patients showed high serum levels of SP-D., Conclusion: Our findings highlight the immunological changes CF patients undergo, during and after treatment, possibly due to the hypoxia triggered by pulmonary fibrosis and emphysema.

The neurodevelopment and functioning of the central nervous system, and especially the cerebral cortex, have basic importance to understand neuropsychiatric disorders like autism. Fibroblast growth factor-2 (FGF-2) plays a very important role in the development and functioning of the cortex. FGF-2 is related to developmental processes in the central nervous system such as neurogenesis, migration, differentiation and survival. This study researched the serum FGF-2 levels in children with autism spectrum disorder (ASD). With this aim, 60 ASD children and 40 healthy controls were compared. We applied a sociodemographic form and the Childhood Autism Rating Scale (CARS) to each subject with their family to assess the severity of autism. Additionally, all subjects had routine laboratory tests performed. Serum samples were studied with ELISA. The results found that serum FGF-2 levels were statistically significantly low in the patient group compared to the healthy control group (p value 0.003). Additionally there was a statistically significant negative correlation identified between serum FGF-2 levels and CARS score for all subjects (r = -0.300; p = 0.02). In conclusion, FGF-2 may contribute to the etiopathogenesis of ASD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Hippocampal concentrations of the neurotrophic factor fibroblast growth factor 2 (FGF2) are negatively associated with the expression of fear following conditioning in rats. Heightened conditioned fear expression may be a prospective risk factor for the development of human anxiety and trauma disorders. However, the relationship between conditioned fear expression and FGF2 is yet to be established in humans., Methods: Using a cross-species approach, we first investigated the relationship between serum concentrations of FGF2 and individual differences in conditioned fear expression in rats (n = 19). We then subjected 88 human participants, who were recruited from university and community advertisements, to a differential fear conditioning procedure and assessed the relationship between salivary concentrations of FGF2 and fear expression to a conditioned stimulus (CS) (a stimulus paired with a shock) and a CS that was never paired with shock., Results: Rats with low serum levels of FGF2 exhibited significantly more freezing than rats with high serum levels of FGF2. Similarly, relative to those with high salivary FGF2, human participants with low salivary FGF2 exhibited significantly heightened skin conductance responses to the CS without shock during fear conditioning and to both the CS with shock and CS without shock during fear recall., Conclusions: These studies establish that peripheral markers of FGF2 concentrations are negatively associated with fear expression in both rats and humans. To the extent that conditioned fear expression predicts anxiety and trauma disorder vulnerability, FGF2 may be a clinically useful biomarker in the prediction and eventual prevention of these disorders., (Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Delay in the diagnosis of multiple sclerosis (MS) stems from the lack of specific clinical and analytical markers to assist in the early diagnosis and prediction of progressive course. We propose a decision-tree model that better defines early at onset MS patients and those with the progressive form by analysing a 12-biomarkers panel in serum and CSF samples of patients with MS, other neurological diseases (OND) and healthy contols. Thus, patients at onset of neurological disease were first classified by serum IL-7 levels <141pg/ml (OR=6.51, p<0.001). Combination of IL-7 and CXCL10 indicated risk for a specific MS clinical form, where IL-7<141 and CXCL10<570pg/ml were associated with the highest risk for PP-MS (OR=22, p=0.01). Unexpectedly, both PP-MS and RR-MS patients shared significantly decreased prototypical biomarkers of inflammation and tissue regeneration in CSF than OND suggesting a defective intrinsic immune response playing a role at the beginning of the disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Angiogenesis is the process of new vessel formation originating from the existing vascular network. It plays an important role in the growth and spread of malignancies, including brain tumors. The process of angiogenesis is characterized by increased expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and by the release of their soluble forms into circulation., Objectives: The aim of the study was to evaluate serum levels of VEGF and bFGF in children with malignant and benign brain tumors., Material and Methods: The study group (group N) included 106 children diagnosed with brain tumors. The children in group N were classified according to tumor pathology into 3 subgroups: N1 (n = 63): patients with malignant tumors, excluding anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM); N2 (n = 25): patients with benign tumors; and N3 (n = 18): patients with high grade gliomas (AA and GBM). VEGF and bFGF were determined by ELISA in blood samples before the initiation of chemotherapy. VEGF and bFGF levels were compared within the subgroups in relation to tumor grading and the extent of surgery., Results: The median VEGF in patients with brain tumors was significantly higher than in the control group. The median levels of VEGF and bFGF in subgroup N1 were significantly higher than in the control group. The differences in VEGF and bFGF concentrations between the subgroups in relation to the extent of tumor resection were not significant., Conclusions: Significantly higher plasma VEGF levels in children with brain neoplasms may reflect enhanced angiogenesis in the tumors.