Serum Levels Of Growth Factors Research Articles

Hydrolyzed egg yolk powder promotes bone growth and development in rats: A multidimensional mechanistic study

Given the growing worldwide focus on bone health, exploring safe and effective interventions to maintain skeletal integrity is imperative. This study involved intragastrically administering hydrolyzed egg yolk powder (HEYP) to 3-week-old Sprague‒Dawley (SD) rats over a period of six weeks. The effects of HEYP on bone growth and the underlying mechanisms were comprehensively investigated by evaluating known bone growth parameters, bone microstructural features, serum biochemical parameters, the metabolome, and the gut microbiome. HEYP administration significantly increased longitudinal bone growth while concurrently increasing the serum levels of osteogenic growth factors. Subsequent metabolomic analyses revealed significant alterations in the serum levels of metabolites associated with bone metabolism, highlighting the profound impact of HEYP on amino acid metabolism. Additionally, gut microbiome analyses revealed HEYP-induced changes in the gut microbiota (GM), identifying key bacterial genera, including Blautia, Parasutterella, Marvinbryantia and Prevotella, that were potentially beneficial for bone formation and linked to bone growth. Correlation analyses further highlighted associations between significantly altered serum metabolites, distinct bacterial genera, and bone growth-related parameters. These findings emphasized that HEYP might promote bone growth through various pathways, offering insights into the potential development and application of functional foods that promote bone health and potentially aid in osteoporosis prevention.

Prognostic value of circulatory growth factors to predict responsiveness to chemotherapy and remission status of patients with acute myeloid leukemia

IntroductionTumor neovascularization, an essential requirement for malignant disease progression and metastasis, depends on the dysregulation of pro-angiogenic and anti-angiogenic activities. This study aimed to investigate the utilization of circulatory angiopoietins (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF-A and VEGF-C), and basic fibroblast growth factor (bFGF) as a prognostic tool for acute myeloid leukemia (AML).Material and methodsTwenty-four AML patients who were under chemotherapeutic intervention were included. Patients’ relapse status, responsiveness to chemotherapy, and remission status were obtained from their medical profiles. For comparative purposes, fifteen healthy subjects were included. Serum levels of growth factors were measured.ResultsAs compared to control subjects, AML patients had significantly lower average levels of Ang-1 (170.8 ±12.7 versus 59.2 ±12.5 ng/ml) and VEGF-A (56.0 ±13.1 versus 98.6 ±11.9 ng/dl) that coincide with a higher average level of Ang-2 (18.5 ±4.1 ng/ml versus 7.5 ±0.8 ng/ml). Spearman’s correlation analysis defined a significant association of sAng-1 and sAng-2 with patients’ response to chemotherapy ( = 0.488) and remission status ( = 0.476), respectively. According to the receiver operating characteristic (ROC) curve, downregulation of Ang-1 has good predictivity for poor responsiveness to chemotherapy (AUC = 0.781, p < 0.05) while upregulation of sAng-2 has good predictivity for failed remission status (AUC = 0.779, p < 0.05).ConclusionsIn the context of AML, dysregulated circulatory levels of Ang-1 and Ang-2 are suggested prognostic markers to provide useful predictivity of patients’ adverse responsiveness to chemotherapy and remission status, respectively.

Gene polymorphism and serum levels of some angiogenic growth factors and pro- and anti-inflammatory cytokines in patients with post-infarction cardiac remodeling

Gene polymorphism and serum levels of some angiogenic growth factors and pro- and anti-inflammatory cytokines in patients with post-infarction cardiac remodeling

Gender effect of glucose, insulin/glucagon ratio, lipids, and nitrogen-metabolites on serum HGF and EGF levels in patients with diabetes type 2.

Hepatocyte growth factor (HGF) exhibits potent growth-inducing properties across various tissues, while epidermal growth factor (EGF) acts as a molecular integration point for diverse stimuli. HGF plays a crucial role in hepatic metabolism, tissue repair, and offers protective effects on epithelial and non-epithelial organs, in addition to its involvement in reducing apoptosis and inflammation, underscoring its anti-inflammatory capabilities. The HGF-Met system is instrumental in hepatic metabolism and enhancing insulin sensitivity in animal diabetes models. Similarly, the EGF and its receptor tyrosine kinase family (EGFR) are critical in regulating cell growth, proliferation, migration, and differentiation in both healthy and diseased states, with EGF also contributing to insulin sensitivity. In this observational study, we aimed to identify correlations between serum levels of HGF and EGF, insulin, glucagon, glucose, and primary serum lipids in patients with type 2 diabetes mellitus (DM), taking into account the impact of gender. We noted differences in the management of glucose, insulin, and glucagon between healthy men and women, potentially due to the distinct influences of sexual hormones on the development of type 2 DM. Additionally, metabolites such as glucose, albumin, direct bilirubin, nitrites, and ammonia might influence serum levels of growth factors and hormones. In summary, our results highlight the regulatory role of insulin and glucagon in serum glucose and lipids, along with variations in HGF and EGF levels, which are affected by gender. This link is especially significant in DM, where impaired cell proliferation or repair mechanisms lead to metabolic changes. The gender-based differences in growth factors point to their involvement in the pathophysiology of the disease.

The effects of TRX suspension training on sarcopenic biomarkers and functional abilities in elderlies with sarcopenia: a controlled clinical trial

BackgroundSarcopenia is an age-related progressive loss of muscle mass and strength that can be modulated by resistance training. This study aimed to investigate the effects of TRX Suspension Training (TST) on serum levels of neuromuscular and growth factors and functional indices in elderly men with sarcopenia, an age-related condition characterized by progressive muscle mass and strength loss.MethodsNineteen sarcopenic elderly men (age = 74.87 ± 4.58 years) were randomly assigned into two groups, the TST group (n = 10) and the control group (n = 9). Serum concentrations of regulatory muscle markers, anthropometric and body composition indices, and functional tests were evaluated at baseline and after 8 weeks. The training protocol consisted of eight weeks of TRX exercises, with three weekly sessions.ResultsAfter 8 weeks of training, growth factors such as Follistatin (FST) (P = 0.001), 22 kDa C-terminal agrin fragment (CAF) (P = 0.031), and growth differentiation factor 15 (GDF15) (P = 0.049) increased significantly in the training group in comparison to the control group and Myostatin (MSTN) (P = 0.002) had a significant decrease. However, there was no significant difference in ASMM/m2 (P = 0.527), SMM/m2 (P = 0.621), or Body fat mass (P = 0.433) within or between groups. In addition, the TRX Suspension Training had a significant effect on the functional tests and improved gait speed (P = 0.037), chair stand (P = 0.016), and TUG (P = 0.016) as well as Handgrip strength (P = 0.035).ConclusionOur findings highlight the efficacy of TRX Suspension Training in enhancing the serum levels of muscle growth factors and functional capacities among elderly individuals with sarcopenia. Therefore, considering the ongoing COVID-19 pandemic, this protocol can prove beneficial for this demographic group.Trial registryIranian Registry of Clinical Trials identifier: IRCT20230727058944N1, prospectively registered 20-09-2023, https://en.irct.ir/trial/71635

Role of Vascular Endothelial Growth Factor as a Potential Biomarker in Congenital Heart Defects: A Systematic Review.

Several studies have investigated the role of vascular endothelial growth factor (VEGF) variants, serum levels, and correlations with other extrinsic factors in congenital heart defects (CHDs); however, the findings need confirmation. The present systematic review evaluates the association between CHDs and genetic polymorphisms and serum expressions. Relevant literature was searched through electronic databases using keywords and MeSH terms. VEGF activity was comparatively assessed between cyanotic and acyanotic CHDs, and the association between different polymorphisms and heart defects was evaluated. We ultimately evaluated 12 studies regarding the association between VEGF serum patterns and found that serum VEGF levels were upregulated or downregulated in correlation with hypoxia and hemoglobin levels and were significantly associated with cyanotic CHDs compared with acyanotic CHDs. Our results also showed a significant role for different single-nucleotide polymorphisms, including rs699947, rs2010963, and rs3025039. The findings of the current study suggested a significant association between CHDs and VEGF genetic polymorphisms or varied serum levels. Nevertheless, more comprehensive studies may provide conclusive results and valuable insights into the pathogenesis of CHDs and relevant treatment strategies.

Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study.

The aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients' MEWS scores was also assessed. The serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system. The study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-β, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity. MIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.

The effect of Nigella sativa on serum levels of insulin-like growth factor and its binding proteins in postmenopausal women with low bone density: A triple-blind randomized controlled trial

Animal studies have shown that Nigella sativa (NS) seed oil can increase Insulin-like growth factor (IGF-1) serum levels. This study aimed to investigate the effect of oral capsule NS on serum levels of IGF-1 and its binding proteins (IGFBP-1, IGFBP-3) in postmenopausal women with bone loss density. Sixty postmenopausal women of 50 to 65 years with bone loss density randomly received a soft capsule of NS oil 1000 mg or placebo once daily for six months with a 1:1 allocation ratio. DEXA method was used to measure bone density. Serum concentrations of IGF-1, IGFBP-1 and-3, ALT, AST, ALP, Cr, and urea were measured at baseline and after the intervention. There were no significant differences in serum levels of IGF1, IGFBP-1, urea, Cr, ALT, AST, and ALP between the two groups at the end of six months. However, a significant increase has been shown in IGFBP-3 between groups after the intervention (Adjusted mean difference: 95% CI: 1.65: 0.36 to 2.97; p=0.013). We observed a significant increase in IGFBP-3 serum levels without any side effects. Additional research with an increased number of participants may be needed for further clarification of its beneficial anabolic effects on the GH system.

Importance of Determining Vascular Endothelial Growth Factor Serum Levels in Children with Infantile Hemangioma.

Background and Objectives: A potential role of vascular endothelial growth factor (VEGF) in the pathophysiology of infantile hemangiomas (IH) is thought to be plausible. The primary objective of this study was to investigate the importance of determining VEGF serum levels at various stages of IH growth in children. Materials and Methods: A nested case-control study was conducted. For the purposes of the researched target group, samples of fifty (N = 50) children with IH without associated diseases at different stages of hemangioma growth (proliferative and involutional stages) were used. The control group consisted of one hundred (N = 100) healthy children comparable in terms of age and sex, in whom the existence of IH and vascular malformations was ruled out via clinical examination. An immunoassay (ELISA) was used to determine VEGF serum levels in hemangioma growth's proliferation and involution phases. Results: A comparison of serum levels of VEGF in the phases of proliferation and involution in the group of patients with IH did not show a statistically significant difference (p = 0.171). The control group had significantly higher serum VEGF levels than the patient group in both the proliferation phase (p = 0.009) and the involution phase (p = 0.019). In the proliferation phase, a multivariate regression model explained 15% of the variance in the dependent variable, without significant predictor variables, while in the involution phase, it explained 21% of the variance in the dependent variable, and the history of invasive prenatal procedures stood out as a significant predictor variable positively associated with serum VEGF levels (beta coefficient = 0.33; p = 0.043). Conclusions: Although IH is thought to be the result of the dysregulation of angiogenesis and vasculogenesis under the influence of angiogenic factors, especially VEGF, this study did not demonstrate that VEGF serum levels in the proliferation phase of hemangioma growth were higher than those in the involution phase, or in relation to the control group.

Angiopoietin-2 Is Associated with Aortic Stiffness in Diabetes Patients in Ghana: A Case-Control Study.

Impaired angiogenesis, measured as serum levels of angiogenic growth factors, may be among the mechanisms underlining aortic stiffness in diabetes patients. We studied the association between aortic stiffness and circulating angiogenic growth factors in type 2 diabetes (T2DM) patients without any organ damage. In a case-control design, aortic pulse wave velocity (PWV), augmentation index (AIx), and aortic blood pressures (BPs) were measured in 140 T2DM patients and 110 nondiabetic controls. Fasting blood samples were collected to measure the levels of angiopoietin- (Ang-) 1, Ang-2, and vascular endothelial growth factor-A (VEGF). Compared to nondiabetes participants, T2DM patients had increased PWV (8.7 ± 1.5 vs. 7.6 ± 1.3, p = 0.031), aortic pulse BP (58 ± 20 vs. 49 ± 17, p = 0.011), Ang-2 (838 (473-1241) vs. 597 (274-1005), p = 0.018), and VEGF (72.2 (28-201.8) vs. 48.4 (17.4-110.1), p = 0.025) but reduced levels of AIx (21.7 ± 13.8 vs. 34 ± 12.9, p < 0.001) and Ang-1 (33.1 (24.7-42.1) vs. 41.1 (30-57.3), p = 0.01). In all study participants, compared to those in the lower tertile, participants in the upper tertile of Ang-2 had increased odds of PWV (2.01 (1.17-3.84), p = 0.004), aortic systolic BP (1.24 (1.04-1.97), p = 0.011), and aortic pulse BP (1.19 (1.04-1.82), p = 0.041) but reduced odds of AIx (0.84 (0.71-0.96), p = 0.014) in multivariable-adjusted models. In our study population, increased circulating Ang-2 was associated with increased levels of aortic stiffness parameters.

Determinants of serum cytokines in a population sample of healthy subjects from Iran

IntroductionCytokines are synthesized and released by immune system cells and mediate critical immune responses. Aging is associated with increased serum levels of some pro-inflammatory cytokines . A positive correlation between the concentration of several cytokines and blood pressure has been reported; higher cytokine concentrations may be related to the underlying causes of hypertension through the effects of inflammatory responses or as an independent etiology for hypertension .To assess the relationship between the serum levels of inflammatory cytokines and growth factors, with biochemical and anthropometric characteristics in healthy Iranian subjects.Material and methodsAnthropometric measurements and blood sampling were performed in 103 healthy Iranian participants. Fasting blood glucose (FBG), hs-CRP and lipid profile were measured in these participants. 12 serum cytokines/growth factors (MCP-1, TNF-α, EGF, IFN-γ, VEGF, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10 were measured.ResultsFBG was positively associated with serum IL-2, IL-4 and IL-1α (P = 0.044, &lt; 0.001 and = 0.017, respectively). Serum EGF and IL-4 were positively associated with age (P &lt; 0.001). IL-8 was inversely associated with SBP (P = 0.002) and gender (P = 0.028). There was a positive association between VEGF and HDL (P = 0.007). The serum levels of IFN-γ and TNF-α were positively associated with serum TG (P = 0.018 and 0.006, respectively).ConclusionsThere are associations between various pro-and anti-inflammatory cytokines in serum and several anthropometric measurements.

Cytokines, chemokines, and cells growth factors in patients with mild to moderate SARS-CoV-2 infection: A case-control study.

Several biomarkers have been evaluated as predictors of severity or in directing the treatment of COVID-19, however there are no conclusive results. In this study, we evaluated serum levels of cytokines, chemokines, and cell growth factors in association with the pathobiology of mild to moderate SARS-CoV-2 infection. Serum levels of SARS-CoV-2 infected patients (n = 113) and flu symptoms individuals negative for SARS-CoV-2 (n = 58), tested by the RT-qPCR test-nasal swab were compared to healthy controls (n = 53). Results showed that the proinflammatory cytokines IL-1β, MCP-3, TNF-α, and G-CSF were increased in symptomatic patients and the cytokines IL-6 and IL-10 were associated with patients positive for SARS-CoV-2 when compared to healthy controls. Symptoms associated with COVID-19 were fever, anosmia, ageusia, and myalgia. For patients without SARS-CoV-2 infection, their major symptom was sore throat. The pathobiology of mild to moderate SARS-CoV-2 infection was associated with increasing proinflammatory cytokines and a pleiotropic IL-6 and anti-inflammatory IL-10 cytokines compared to healthy controls. Thus, knowledge about the pathophysiology and the involvement of biomarkers in the mild to moderate profile of the disease should be evaluated. Monitoring these biomarkers in patients with mild to moderate disease can help establish adequate treatment and prevention strategies for long-term COVID-19.

Immunological signature of patients with thymic epithelial tumors and Good syndrome: Correlation with clinical outcome.

e20648 Background: Thymic epithelial tumors (TETs) are extremely rare and heterogenous neoplasms, associated with immune dysregulation. Recognized prognostic factors are TNM stage and the Masaoka-Koga classification. To the best of our knowledge, no study has been conducted to investigate the correlation between immunophenotype, level of cytokines, chemochines and clinical outcome in TETs patients. The aim of this study was to evaluate the correlation of immunological signature and long-term outcome in patients with TETs and Good Syndrome (GS). Methods: From May 2019 to October 2022, consecutive patients with TETs and GS, referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR) of Federico II of Naples, were enrolled. The immunophenotype of monocytes, neutrophils, eosinophils, CD4+ T cells, CD8 + T cells, B-cells, NK cells and NKT-cells, T regulatory cells, and the evaluation of serum levels of cytokines, chemokines and growth factors were assessed using the 8-color immunophenotyping kit, Treg detection kit and pre-formed Kits by Bioplex multiplex, respectively. D’Agostino-Pearson normality test was used to evaluate whether the continuous data were normally distributed, and a two-tailed t-test for independent samples was used. Overall survival (OS) analysis was performed generating Kaplan-Meier curves and Cox Univariate models for the considered categorical stratifications. p-values &lt; 0.05 were considered statistically significant. Results: A total of 24 consecutive TETs patients were included in the study: 13 (54.17%) patients were male and 11 (48.83%) were female, with a median age of 54.96 ± 9.6 years. Tumor histology included 20 thymoma, and 4 thymic carcinoma. Autoimmune diseases were found in 13 patients all of whom had thymoma. At the time of this analysis, 5 (20.83%) patients had no evidence of disease (NED) by imaging and were in follow-up, 17 (70.83%) patients were still alive. The analysis of leucocytes did not show statistically significant association with clinical outcome of TETs patients. On the contrary, a statistically significant correlation between serum concentration of IL-6 and OS was found with lower levels of IL-6 associated with poorer prognosis (HR: 9.654; p = 0.016). In addition, we found a statistically significant reduction of IL-2 (p = 0.04), IL-15 (p = 0.048), IL-5 (p = 0.03) and VEGF (p = 0.01) serum levels in patients with evidence of disease, as compared to NED patients. Conclusions: Overall, these findings suggest that measurement of IL-6 levels may be a useful parameter for identifying TETs patients with GS who have more aggressive diseases. Our preliminary data may be useful in the clinical management of this complex disease. Further studies are needed to better understand the pathophysiology and clinical implications of immunophenotype alterations in TETs patients.

Association of vascular endothelial growth factor serum levels with ankylosing spondylitis in Egyptian patients

BackgroundAnkylosing spondylitis (AS) is one of inflammatory rheumatic diseases which result in wide range of manifestations on the musculoskeletal system and axial joint specifically. Endothelial cell migration and proliferation, as well as subsequent neoangiogenesis and remodelling in autoimmune disorders, are pathogenic mechanisms that are fundamental to inflammation activation and angiogenesis. The development of advanced lesions is thought to involve vascular proliferation as well as vascular endothelial growth factor (VEGF), which serves a regulatory role. It was found that AS patients had increased serum levels of VEGF, which were linked to the disease activity.Aim of the workThe purpose of this study is to measure serum VEGF levels in Egyptian AS patients and assess their relation to disease-related variables, including radiographic findings.ResultsVEGF serum levels showed a highly significant positive correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) and modified Stroke Ankylosing Spondylitis Spinal Score (MSASS) (p < 0.001); also, there was a significant correlation between the VEGF values and the Ankylosing Spondylitis Disease Activity Index (ASDAS) and the New York x-ray sacroiliac score.ConclusionsThese findings and data illustrate the strong relationship between ASDAS and VEGF and the radiographic score in AS patients. ASDAS combined with VEGF not only is considered a tool for determining the level of disease activity only but also is considered as an indicator for the assessment of the syndesmophytes formation, which performs a crucial role in the prognosis and outcome in AS patients.

Investigating the impact of Platelet-Rich Plasma Infusion

Objective: To investigate the impact of Platelet-rich plasma infusion on performance enhancing growth factors and find molecular markers to distinguish athletes treated with such infusions. Study Design: Prospective, Double-blind, Randomized controlled study. Place and Duration: Department of Dental Education and Research, Altamash Institute of Dental Medicine, Karachi from 15th January 2022 to 20th June, 2022. Methodology: The ergogenic growth factors FGF-2 that are basal fibroblast growth factor, vascular endothelial growth factor, IGF-1 (insulin-like growth factor), IGFBP-3 (insulin-like growth factor binding protein-3), and platelet-derived growth factor-BB (PDGF-BB) WADA are tracked that were measured in 25 patients before (baseline) and 0.25, 3, 24, 48, 72, and 97 hours after the test. Patients under observation were prohibited from any movement or any food intake three hours prior to the exam. The change from each participant's baseline was calculated using an enzyme-linked immunosorbent assay to assess growth factors. Results: Total sample size was 23. Platelet-Rich Plasma had considerably higher levels of PDGF-BB (67% higher than standard 392 pg/ml), vascular endothelial growth factor (6.04% higher than standard 236 pg/ml), and bFGF (45% higher than standard 5 pg/ml), than serum, while IGF-1 and hGH levels were unchanged. IGF-1, bFGF, and vascular endothelial growth factor serum levels all significantly rose 24 and 48 hours after Platelet-Rich Plasma injection, as well as 3, 24, 48, 72, and 96 hours afterwards. Additionally, all 23 patients who had Platelet-Rich Plasma therapy had higher levels of vascular endothelial growth factor and success rate is 100% luckily. Conclusion: Serum levels of PDGF-BB, vascular endothelial growth factor, and bFGF significantly increase after Platelet-Rich Plasma injection, suggesting that Platelet-Rich Plasma have ergogenic effects. Following Platelet-Rich Plasma, the IGFBP-3 3 IGF-1 product, an indirect biomarker of hGH doping, significantly rose. All Platelet-Rich Plasma patients exhibited elevated vascular endothelial growth factor. Keywords: PRP Injection, Platelet-Rich Plasma, Human Growth Hormone, Growth Factors, Ergogenic Growth Factors, Insulin Growth Factor, Vascular Endothelial Growth Factor How to Cite This: Rizvi SH, Asphandiar DC, Arshad T, Hashmi FA. Investigating the impact of Platelet-Rich Plasma Infusion. Isra Med J. 2022; 14(3): 121-126. DOI: https://doi.org/10.55282/imj.oa1330

Immune Dysregulation in Human Telomere Diseases

Germline variants in a diversity of genes involved in telomere maintenance result in premature telomere shortening and cause clinical conditions that are collectively called telomeropathies, which range from mucocutaneous findings (skin hypopigmentation, nail dystrophy and oral leukoplakia) to bone marrow failure, myeloid neoplasms, pulmonary fibrosis and cirrhosis. Even though pulmonary fibrosis and liver cirrhosis develop in up to a quarter of patients with telomeropathies, the exact mechanisms promoting the fibrotic pathology remain unclear. Considering that the hematopoietic compartment is particularly sensitive to telomere erosion, we aimed to investigate whether the immune response may play a role on the development of fibrotic lesions in a murine model, and to evaluate immunological biomarkers in patients diagnosed with telomere diseases. To assess the effects of telomere attrition on the development of liver fibrosis and immune response, G3 Terc-/- and Tert-/- mice (background C57BL/6J) and wild-type (WT) mice were infected with S. mansoni cercariae and euthanized after 12 weeks. Telomere length (TL) was determined by qPCR in leukocytes and liver sections and confirmed to be shorter in both knockout (KO) models in comparison to WT animals (p≤0.01). Collagen deposition in liver tissue was quantified with Picro Sirius Red staining and showed larger fibrotic areas in WT mice (14 ± 5,2%) when compared to Terc-/- (7,2 ± 4,3%; p≤0.05) and Tert-/- (6,3 ± 2,4%; p≤0.05). Macrophage infiltration was evaluated by immunostaining using antibodies against F4/80, CD206 and iNOS, and revealed less positive cells within the liver of Terc-/- and Tert-/- mice in comparison to WT (p≤0.001). We studied the ability of bone marrow-derived macrophages (BMDMs) to be polarized towards M1 and M2-like phenotypes ex vivo, upon stimulation with either LPS or IL-4, respectively. Expression of TNF-alpha, IL-6 and MMP9 demonstrated that the classical activation of Terc-/- and Tert-/- BMDMs was impaired in a similar fashion, and these cells did not exhibit the M1-like phenotype as observed in the WT BMDMs. Conversely, CD206 and ARG1 were significantly upregulated in KOs stimulated with IL-4, suggesting that telomerase-null BMDMs are skewed towards an M2 polarization. We also evaluated 18 patients with telomere diseases (median age, 33.9 years; range, 12.8-62.5 years; male/female, 9/9; marrow failure, 15; pulmonary manifestations, 5; hepatic manifestations, 5) and 10 healthy individuals (median age, 32.1; range, 13.9-56.3 years; male/female, 5/5) for their immune profile. Eight patients had very short TL (<1st percentile) and ten had short TL (<10th percentile). All healthy individuals had TL >10th percentile. We measured serum levels of cytokines, chemokines and growth factors using a customized Luminex panel to assess 32 analytes in a single assay. Spearman's correlation coefficient was used to analyze associations between TL z-scores and the variables of interest. Analysis showed significant correlations (p≤0.05) with angiopoietin-1, IL-1α, IL-1β, IL-1RA, IL-3, IL-4, IL-7, IL-23, IL-27, MCP-1, M-CSF, MIP-3α and PDGF-BB and, in all cases, Spearman's rho was positive, indicating that shorter telomeres were correlated with decreased protein serum levels. In order to study the maturation of T- and B-cells, T-cell receptor excision circles (TRECs) and kappa-deleting excision circles (KRECs) were quantified by qPCR in dried blood spot samples from ten patients with short telomeres and ten age-matched healthy individuals. Both biomarkers were significantly reduced in patients (p≤0.05), showing that production and/or maturation of T- and B-lymphocytes is impaired. TRECs were negatively correlated to age in the control group, (rs = -0.66; p = 0.043), but not in patients (p>0.05), suggesting that TRECs do not follow the same pattern of age-dependent decrease in short telomere syndromes. Altogether, the results demonstrate that telomere erosion contributes to impaired immune responses and T- and B-cell maturation, which may contribute to the pathophysiology of several clinical manifestations in telomeropathies. Further studies are necessary to deeply characterize innate and adaptative immune response in telomere syndromes and better understand how it correlates to fibrosis development. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

HbA1c and Serum Level of VEGF in Diabetic Retinopathy Patients

Objective: This study aims to determine whether HbA1c level has a correlation with vascular endothelial growthfactor (VEGF) serum level in diabetic retinopathy (DR) patients.Methods: This is an analytical cross-sectional study of patients with DR due to type 2 diabetes, with a purposivesampling technique. Patients were grouped into non-proliferative DR (NPDR) and proliferative DR (PDR). HbA1cand VEGF serum levels were assessed by taking the patient’s venous blood.Results: A total of 82 samples were included, in which the mean HbA1c levels were 8.17% ± 1.91% and the medianVEGF levels were 85.78 ng/L (range 38.23-149.43 ng/L). A total of 23 out of 35 NPDR patients were female (65.7%),while 29 out of 47 PDR patients were male (61.7%). Approximately 61.7% of PDR patients had a DM duration ofmore than 10 years, while 62.9% of NPDR patients had DM duration of less than 10 years. There was an increasein the mean of HbA1c levels in the PDR group compared to NPDR, although it was not statistically significant (p =0.214), and there was no difference in the median VEGF levels of the two groups. Spearman’s correlation analysisrevealed no correlation between HbA1 and VEGF levels in diabetic retinopathy, in both the NPDR and PDRgroups (correlation coefficient 0.183 and -0.022 respectively).Conclusion: No statistically significant correlation was found between HbA1c and VEGF serum levels in diabeticretinopathy patients. In this study poor glycemic control were not proven for their implications for VEGFprogression. VEGF serum levels may not be used as a marker of DR severity.

Serum soluble mediator waves and networks along healthy ageing.

The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3Yrs to >70Yrs). A broad increase in serum soluble mediators was observed at 6-10Yrs with subsequent decline at 11-20Yrs and 21-30Yrs followed by a second round of upregulation starting at 31-40Yrs, with a large increase at 51-60Yrs and a marked decline at age >70Yrs. Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6-10Yrs and a second wave around 61-70Yrs. A universal decline was observed later at age >70Yrs. In males, the second wave started earlier at 31-40Yrs with a peak at 51-60Yrs and a further smooth decline towards >70Yrs. Conversely, in females, the first peak extended from 3-5Yrs to 6-10Yrs and the second wave starting around 41-50Yrs with a peak at 61-70Yrs followed by a sharp decline at >70Yrs. Overall, CCL11, CXCL8, IL-1β, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31-40Yrs) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3-5Yrs, with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11-20Yrs, 51-60Yrs and >70Yrs) than in males (at 21-30Yrs, 61-70Yrs). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes.

Serum vascular endothelial growth factor as a marker for tubal pregnancy.

SUMMARYOBJECTIVE:The objective of this study was to evaluate whether a single measurement of vascular endothelial growth factor could distinguish between intrauterine pregnancy and ectopic pregnancy and to correlate the levels of vascular endothelial growth factor with serum levels of progesterone andβ-human chorionic gonadotropin in each subgroup.METHODS:Ninety patients with a positive human chorionic gonadotropin test and either abdominal pain or vaginal bleeding were selected; pregnancies were singletons, spontaneously conceived, 42–56 days of gestational age. All patients had a transvaginal ultrasound examination and were divided into three subgroups: abnormal intrauterine pregnancy, tubal pregnancy, and normal intrauterine pregnancy. Tubal pregnancies were surgically treated and histologically confirmed. Blood samples were collected for the determination of β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor and their concentrations were compared in each subgroup. Receiver operating characteristic curve was calculated by comparing the subgroup of tubal pregnancy to the other groups. A Fisher discriminant function analysis was performed. The level of significance was 5%.RESULTS:One-way analysis of variance revealed a significant correlation between the different subgroups and β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor serum levels (p<0.001). Vascular endothelial growth factor concentration was significantly higher for patients with tubal pregnancy than for other subgroups (p<0.05). β-Human chorionic gonadotropin and progesterone levels were higher in the subgroup with normal intrauterine pregnancies compared with the subgroups with tubal and abnormal intrauterine pregnancies (p<0.05). Serum vascular endothelial growth factor level >188.7 ng/mL predicted tubal pregnancy with 96.7% sensitivity, 95.0% specificity, 90.6% positive predictive value, and 98.3% negative predictive value.CONCLUSIONS:Serum vascular endothelial growth factor could be a marker in discriminating intrauterine pregnancy from tubal pregnancy; its levels are increased in women with ectopic pregnancy compared with women with normal and abnormal intrauterine pregnancies.

Evaluating serum level of granulocyte, macrophage and granulocyte-macrophage colony-stimulating factors in patients with breast tumor

Colony-stimulating factors (CSFs) are glycoproteins that stimulate the proliferation and differentiation of hematopoietic progenitor cells in the bone marrow. But numerous studies have shown that these factors can stimulate the proliferation of non-hematopoietic cells, including cancer cells. Hence, in this study, Macrophage-CSF (M-CSF), macrophage-granulocyte CSF (GM-CSF), and granulocyte-SCF (G-CSF) were evaluated in the serum of patients with breast tumors and their relationship with pathological and paraclinical parameters of the disease. In this study, 62 patients with breast cancer who had not received any treatment and 54 healthy women who matched the age group with the patient group were included as a control group. After obtaining informed consent, 5ml of peripheral blood was taken from both groups, and their serum was isolated. Serum levels of the studied cytokines were measured by the cytokine-bead array method. Data were analyzed using SPSS18 software and a significance level of 0.05. The mean serum levels of M-CSF, G-CSF, and GM-CSF growth factors in patients with breast cancer were 63.48, 16.13, and 6.11pg/ml, respectively. Although the statistical analysis did not show a significant difference between serum levels of these growth factors in the patient and control groups (p <0.05), further studies showed that with increasing disease stages from I to III, serum levels of GM-CSF significantly. Decreases (p = 0.016). Overall, the results of this study indicated the antitumor role of GM-CSF in breast cancer. However, confirmation of these results requires more complete studies with larger sample sizes.