Plasma Levels Of Growth Factor Research Articles

The Relationship between COVID-19 Severity and Plasma Levels of Vascular Endothelial Growth Factor (VEGF)

Background: This study aimed to assess the relationship between COVID-19 severity and the plasma levels of vascular endothelial growth factor. Methods: This cross-sectional study was conducted on 86 patients with COVID-19. A 5 ml venous blood sample was taken on the first day of hospitalization. VEGF was measured with the ELISA method using the Hangzhou East biopharm VEGF ELIZA Kit. Results: Although plasma VEGF levels were higher in the severe group than in the non-severe group, no significant relationship was found between the plasma level of VEGF and COVID-19 severity, which might be due to the small sample size. VEGF may be a valuable scientific marker, but in this study, it was not as useful as other markers in identifying COVID-19 severity. In addition, there was a direct and significant relationship between COVID-19 severity and the inflammatory markers LDH, neutrophil/lymph, and CRP. Therefore, measurement of inflammatory markers can assist in the early identification and prediction of severity and disease progression in COVID-19. Conclusion: Although plasma VEGF levels were higher in the severe group than in the non-severe group, no significant relationship was found between the plasma level of VEGF and COVID-19 severity, which might be due to the small sample size. VEGF may be a valuable scientific marker, but in this study, it was not as useful as other markers in identifying COVID-19 severity. In addition, there was a direct and significant relationship between COVID-19 severity and the inflammatory markers LDH, neutrophil/lymph, and CRP. Therefore, measurement of inflammatory markers can assist in the early identification and prediction of severity and disease progression in COVID-19.

Effect of Eight-week Selected Aerobic and Resistance Exercises on the Plasma Levels of Irisin, Follistatin, and Fibroblast Growth Factor 21 in Women Recovered from COVID-19

Background and Objectives Recently, performing regular sports activities has been considered an effective strategy for the rehabilitation of patients who have recovered from COVID-19. The present study aimed to assess the effect of eight weeks of selected aerobic and resistance exercises on the plasma levels of irisin, follistatin, and fibroblast growth factor 21 (FGF21) in women who recovered from COVID-19. Subjects and Methods A total of 33 women who recovered from COVID-19 were assigned to three groups, namely aerobic exercise, resistance, and control, after the general call and selection. Aerobic training with an intensity of 50%-70% of the reserve heart rate and resistance training with an intensity of 40%-75% of a maximum repetition was performed for eight weeks (three sessions per week). Irisin, follistatin, and FGF21 levels were measured using the ELISA method. The data were analyzed using the analysis of variance statistical test at the significant level of < 0.05. Results As illustrated by the results, selected aerobic and resistance exercises caused a significant increase in irisin, follistatin, and FGF21 levels. The results of the post hoc test demonstrated that this increase was significant in the aerobic and resistance groups compared to the control group. Moreover, within-group changes pointed to a significant increase in the mean before and after the intervention in the aerobic and resistance groups. Conclusion Carrying out selected aerobic and resistance exercises in women who recovered from COVID-19 boosts their physical strength and is effective in quick recovery by restoring some indicators of myokine profile.

Cloning, phylogenetic and expression analysis of two MyoDs in yellowtail kingfish (Seriola lalandi)

Yellowtail kingfish (Seriola lalandi) is a pelagic piscivore distributed circumglobally. Owing to its great market value, the growth mechanism of S. lalandi, including muscle development and growth, is a hot research topic. The myoblast determination protein (MyoD) gene has been shown to play an important role in formation of myoblasts and the function of somites in fish. The open reading frame (ORF) sequences of MyoD1 and MyoD2 in S. lalandi encoded 298 and 263 amino acids possessing three common characteristic domains, respectively, containing a myogenic basic domain, a bHLH domain, and a ser-rich region (helix III). S. lalandi MyoDs shared the highest identity with the MyoDs of S. dumerili. MyoDs are highly expressed in white muscle (P < 0.05) in S. lalandi. The expression level of MyoD1 mRNA was higher than that of MyoD2 mRNA during embryonic and early developmental stages, indicating that the two MyoD isoforms may have different roles in muscle formation. Moreover, the mRNA expression of MyoDs in the brain, pituitary, liver and muscle of endocrine growth axis were analyzed in the various sizes and ages stages. The expression levels of MyoDs in the different sizes and ages of S. lalandi showed that expression of both these genes was particularly high in 400-g fish and 2-year-old fish (P < 0.05). Moreover, the increases in the mRNA expression and plasma levels of growth hormone (GH) and insulin-like growth factor (IGF-I) were accompanied by an increase in mRNA expression of MyoDs, indicating the roles of GH and IGF-I in muscle development and growth of S. lalandi. Overall, the expression profiles of genes associated with muscle development are the first step taken towards deciphering fast growth mechanism in this important Seriola fish.

Oxidative Stress and the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Pathway in Multiple Sclerosis: Focus on Certain Exogenous and Endogenous Nrf2 Activators and Therapeutic Plasma Exchange Modulation.

The pathogenesis of multiple sclerosis (MS) suggests that, in genetically susceptible subjects, T lymphocytes undergo activation in the peripheral compartment, pass through the BBB, and cause damage in the CNS. They produce pro-inflammatory cytokines; induce cytotoxic activities in microglia and astrocytes with the accumulation of reactive oxygen species, reactive nitrogen species, and other highly reactive radicals; activate B cells and macrophages and stimulate the complement system. Inflammation and neurodegeneration are involved from the very beginning of the disease. They can both be affected by oxidative stress (OS) with different emphases depending on the time course of MS. Thus, OS initiates and supports inflammatory processes in the active phase, while in the chronic phase it supports neurodegenerative processes. A still unresolved issue in overcoming OS-induced lesions in MS is the insufficient endogenous activation of the Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) pathway, which under normal conditions plays an essential role in mitochondria protection, OS, neuroinflammation, and degeneration. Thus, the search for approaches aiming to elevate endogenous Nrf2 activation is capable of protecting the brain against oxidative damage. However, exogenous Nrf2 activators themselves are not without drawbacks, necessitating the search for new non-pharmacological therapeutic approaches to modulate OS. The purpose of the present review is to provide some relevant preclinical and clinical examples, focusing on certain exogenous and endogenous Nrf2 activators and the modulation of therapeutic plasma exchange (TPE). The increased plasma levels of nerve growth factor (NGF) in response to TPE treatment of MS patients suggest their antioxidant potential for endogenous Nrf2 enhancement via NGF/TrkA/PI3K/Akt and NGF/p75NTR/ceramide-PKCζ/CK2 signaling pathways.

Contemporaneous Perioperative Inflammatory and Angiogenic Cytokine Profiles of Surgical Breast, Colorectal, and Prostate Cancer Patients: Clinical Implications.

Surgery-induced tumor growth acceleration and synchronous metastatic growth promotion have been observed for decades. Surgery-induced wound healing, orchestrated through growth factors, chemokines, and cytokines, can negatively impact patients harboring residual or metastatic disease. We provide detailed clinical evidence of this process in surgical breast, prostate, and colorectal cancer patients. Plasma samples were analyzed from 68 cancer patients who had not received treatment before surgery or adjuvant therapy until at least four weeks post-surgery. The levels of plasma cytokines, chemokines, and growth factors were simultaneously quantified and profiled using multiplexed immunoassays for eight time points sampled per patient. The immunologic processes are induced immediately after surgery in patients, characterized by a drastic short-term shift in the expression levels of pro-inflammatory and angiogenic molecules and cytokines. A rapid and significant spike in circulating plasma levels of hepatocyte growth factor (HGF), interleukin-6 (IL-6), placental growth factor (PLGF), and matrix metalloproteinase-9 (MMP-9) after surgery was noted. The rise in these molecules was concomitant with a significant drop in transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF-AB/BB), insulin-like growth factor-1 (IGF-1), and monocyte chemoattractant protein-2 (MCP-2). If not earlier, each plasma analyte was normalized to baseline levels within 1-2 weeks after surgery, suggesting that surgical intervention alone was responsible for these effects. The effects of surgical tumor removal on disrupting the pro-inflammatory and angiogenic plasma profiles of cancer patients provide evidence for potentiating malignant progression. Our findings indicate a narrow therapeutic window of opportunity after surgery to prevent disease recurrence.

Association of plasma NRP2 and VEGF-C levels with prostate cancer disease severity.

Neuropilin 2 (NRP2) expression in tissue is an independent prognostic factor for aggressive prostate cancer. Since the NRP2 pathway activation is thought to occur in part through secondary resistance, quantification of NRP2 in initial tissue biopsy specimens collected at diagnosis may have limited utility in identifying patients at highest risk for morbidity and mortality. Given that metastatic tissue is only occasionally obtained for analysis, there is a need for development of a plasma biomarker indicative of NRP2 pathway activation to potentially inform prostate cancer prognosis. Therefore, we investigated if plasma levels of NRP2 or vascular endothelial growth factor C (VEGF-C), a known soluble ligand of NRP2, are prognostic for prostate cancer. We hypothesized that plasma NRP2 and VEGF-C would be associated with more advanced disease or relapsed disease. NRP2 and VEGF-C levels were quantified by enzyme-linked immunoassay in plasma samples obtained from 145 prostate cancer patients in an opportunistic biobank. These patients were either (1) newly diagnosed (N = 28), (2) in remission (N = 56), or (3) relapsed disease (N = 61). Plasma samples from 15 adult males without known malignancy served as a comparator cohort. Statistical analysis was performed to investigate the association of plasma NRP2/VEGF-C with patient outcomes, adjusting for age, race, prostate-specific antigen (PSA), Gleason score, and tumor stage at diagnosis. Neither NRP2 nor VEGF-C levels were significantly different in cancer patients compared to noncancer controls. We observed no clear association between plasma NRP2 and disease severity. Increased plasma VEGF-C was significantly associated with disease remission and correlated with Stage I/II and intermediate-risk Gleason score. Neither NRP2 nor VEGF-C correlated with PSA level. Although tissue NRP2 expression correlates with severe disease, this was not observed for plasma NRP2. Plasma NRP2 levels did not correlate with disease severity or relapse. VEGF-C was highest in patients in remission and with less severe disease. Future investigation is needed to identify noninvasive methods to assess tumor NRP2 status.

Plasma VEGF-D and sFLT-1 are potential biomarkers of hemodynamics and congestion in heart failure and following heart transplantation

BackgroundInflammation and tyrosine-kinases are known mediators in the pathobiology of cardiovascular disease. Plasma biomarkers reflecting these systems may provide a non-invasive complement reflecting haemodynamics, aiding in clinical decision-making. We therefore aimed to investigate the plasma levels of vascular and inflammatory proteins, and their associations with invasive haemodynamics in advanced heart failure (HF) before, and at multiple follow-ups after heart transplantation (HT). MethodsUsing multiplex sandwich immunoassays, absolute plasma concentrations of nine vascular and inflammatory proteins were assessed in 26 patients with advanced HF, before-HT, and at four-weeks, six-months, and one-year after-HT. Right heart catheterization (RHC) haemodynamics were assessed at the time of blood sampling. Repeated measures correlations were performed to evaluate the overall intra-individual development of plasma protein levels in relation to haemodynamics’ development over time. ResultsOut of nine proteins included initially, in advanced HF, elevated plasma levels of vascular endothelial growth factor D (VEGF-D) and soluble fms-like tyrosine kinase-1 (sFlt-1) decreased most markedly, at four-weeks (p<0.0001), and decreased further at six-months (p<0.05) and at the one-year follow-ups after-HT (p<0.05). Over time, plasma VEGF-D correlated strongest with haemodynamic parameters including pulmonary arterial wedge pressure (PAWP) (rmr= 0.75, 95% bootstrapped confidence interval (CI) 0.61-0.84, p<0.0001), followed by mean right atrial pressure (MRAP) (rmr= 0.74, 95% CI 0.61-0.82, p<0.0001), and mean pulmonary arterial pressure (mPAP) (rmr= 0.74, 95% CI 0.58-0.82, p<0.0001). Plasma sFlt-1 correlated also with multiple haemodynamic parameters including PAWP (rmr= 0.66, 95% CI 0.58-0.79, p<0.0001), MRAP (rmr= 0.64, 95% CI 0.58-0.81, p<0.0001), and mPAP (rmr= 0.61, 95% CI 0.51-0.76, p<0.0001). ConclusionsIn advanced HF, elevated plasma VEGF-D and sFlt-1 levels decrease early, already within four weeks after HT, and further throughout the first year postoperatively. Our findings support that high plasma VEGF-D and sFlt-1 concentrations before HT are related to congestion, and overall haemodynamic improvement. Plasma VEGF-D and sFlt-1 may consequently be potential non-invasive biomarkers for monitoring hemodynamic deterioration and congestion in HF, and surveillance after HT.

Therapeutic Plasma Exchange and Multiple Sclerosis Dysregulations: Focus on the Removal of Pathogenic Circulatory Factors and Altering Nerve Growth Factor and Sphingosine-1-Phosphate Plasma Levels.

Multiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions. Thus, their removal along with the modulation of certain bioactive molecules to improve neuroprotection using therapeutic plasma exchange (TPE) becomes of utmost importance. Recently, it has been proposed to determine the levels and precise effects of both beneficial and harmful components in the serum of MS patients undergoing TPE to serve as markers for appropriate TPE protocols. In this review we discuss some relevant examples, focusing on the removal of pathogenic circulating factors and altering the plasma levels of nerve growth factor and sphingosine-1-phosphate by TPE. Altered plasma levels of the reviewed molecular compounds in response to TPE reflect a successful reduction of the pro-inflammatory burden at the expense of an increase in anti-inflammatory potential in the circulatory and CNS compartments.

Soluble biomarkers of HIV-1-related systemic immune activation are associated with high plasma levels of growth factors implicated in the pathogenesis of Kaposi sarcoma in adults.

Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi's sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8. Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, Cameroon. CD3+/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25/IL-2Rα, and sCD40/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method. Overall, 20.2% (20/99) of HIV-1 infected and 20% (12/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25/IL-2Rα, sCD40/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P <0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (rs = 0.58, P =0.0067) and sCD40/TNFRSF5 (rs = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (rs = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (rs =0.25, P = 0.03 and rs = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (rs = 0.5, P <0.0001 and rs = 0.55, P <0.0001 respectively) and sCD40/TNFRSF5 (rs = 0.7, P <0.0001 and rs = 0.59, P <0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (rs = 0.39, P = 0.012 and rs = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (rs = 0.81, P <0.0001 and rs = 0.44, P = 0.0045 respectively). Our findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients' viremic status.

The potential immuno-stimulating effect of curcumin, piperine, and taurine combination in hepatocellular carcinoma; a pilot study

BackgroundThis is a phase II clinical trial to investigate the immunotherapeutic effect of Curcumin, Piperine, and Taurine (CPT) combination in hepatocellular carcinoma (HCC).MethodsTwenty-six HCC patients aged (50–80 years) were recruited for administration of a daily dose of 5 g of curcumin, 50 mg of piperine, and 500 mg of taurine divided into three doses for successive 3 months. The three components (CPT) were prepared in one capsule. Patients were assessed after each month (cycle) for the plasma levels of CD4, CD8, CD25, Interleukins-2 (IL-2), IL-6, IL-12, Interferon-gamma (IFN- γ), Lactate dehydrogenase (LDH), and Vascular endothelial growth factor (VEGF), FOXP3 mRNA, and miRNA 21.ResultsThere was a significant increase in the plasma levels of CD4 and CD8, while a significant decrease in the CD25 level after the second and third cycles compared to the baseline level [P < 0.001 for both]. Also, there was a significant increase in the plasma levels of IL-2, IL-12, and IFN-γ [ P = 0.001, P = 0.006, and P = 0.029; respectively], while there was a significant decrease in IL-6, VEGF-α, LDH, and Alpha-fetoprotein (AFP) after CPT administration compared to the baseline levels [P < 0.001, P < 0.001, P = 0.020, and P = 0.004; respectively].The expression level of miRNA-21 was significantly decreased after CPT administration compared to the baseline level [5.5±0.88, 4.1±0.78, 3±0.75, and 2.5±0.76; respectively, P<0.001]. Though there was a noticeable decrease in the FOXP3 expression after each cycle, however, it didn’t reach a significant level [5.3±0.8, 4.2±0.76, 3.2±0.67, and 2.5±0.79; respectively, P=0.184].ConclusionCPT could exhibit a potential immune-stimulating effect in HCC patients. The current trial had been registered at the National Hepatology and Tropical Medicine Research Institute (NHTMRI), with a registration number of NHTMRI-IRB 2-21 on 5th January 2021.

Circulating levels of inflammatory cytokines and angiogenesis-related growth factors in patients with osteoarthritis after COVID-19.

The disease COVID-19, caused by SARS-CoV-2 infection, has a systemic effect and is associated with a number of pathophysiological mechanisms that mobilize a wide range of biomolecules. Cytokines and growth factors (GFs) are critical regulators of tissue damage or repair in osteoarthritis (OA) and are being recognized as key players in the pathogenesis of COVID-19. A clear understanding of the long-term consequences of SARS-CoV-2 infection, especially in patients with concomitant chronic diseases, is limited and needs to be elucidated. The study aimed to evaluate the degree of inflammation and levels of pro-angiogenic and hypoxic factors, as well as heat shock proteins HSP60 and HSP70 in plasma, of patients with OA after recovery from COVID-19. The research involved patients of an orthopedic specialty clinic aged 39 to 80 diagnosed with knee OA. All examined patients were divided into three groups: the Control group included conditionally healthy donors, group OA included patients with knee OA mainly stage II or III and the group of OA and COVID-19 included patients with OA who had COVID-19. The plasma levels of pro-inflammatory molecules IL-1β, IL-6, TNF-α, NF-κB, angiogenic factors VEGF, FGF-2, PDGF, hypoxic factor HIF-1α and molecular chaperones HSP60 and HSP70 were measured by enzyme-linked immunosorbent assay. The study showed that in both groups of patients, with OA and convalescent COVID-19, there was an increase in the plasma level of IL-1β and a decrease in TNF-α and NF-κB levels when compared to healthy controls. Systemic deregulation of the cytokine profile was accompanied by reduction in plasma levels of pro-angiogenic growth factors, most pronounced in cases of VEGF and PDGF. This analysis did not reveal any significant difference in the plasma level of HIF-1α. A decrease in the level of stress protein HSP60 in the blood of patients with OA, as well as those patients who have had SARS-CoV-2 infection, has been established. The results suggest the potential role pro-inflammatory cytokines and angiogenesis-related growth factors in pathogenesis of both joint pathologies and long-term systemic post-COVID-19 disorders.

Hyperbaric Oxygen Therapy Reduces Oxidative Stress and Inflammation, and Increases Growth Factors Favouring the Healing Process of Diabetic Wounds.

Hyperbaric oxygen therapy (HBOT) is the clinical application of oxygen at pressures higher than atmospheric pressure. HBOT has been effectively used to manage diverse clinical pathologies, such as non-healing diabetic ulcers. The aim of the present study was to analyse the effects of HBOT on the plasma oxidative and inflammation biomarkers and growth factors in patients with chronic diabetic wounds. The participants received 20 HBOT sessions (five sessions/week), and blood samples were obtained at sessions 1, 5 and 20, before and 2 h after the HBOT. An additional (control) blood sample was collected 28 days after wound recovery. No significant differences were evident in haematological parameters, whereas the biochemical parameters progressively decreased, which was significant for creatine phosphokinase (CPK) and aspartate aminotransferase (AST). The pro-inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β), progressively decreased throughout the treatments. Biomarkers of oxidative stress--plasma protein levels of catalase, extracellular superoxide dismutase, myeloperoxidase, xanthine oxidase, malondialdehyde (MDA) levels and protein carbonyls--were reduced in accordance with wound healing. Plasma levels of growth factors--platelet-derived growth factor (PDFG), transforming growth factor β (TGF-β) and hypoxia-inducible factor 1-alpha (HIF-1α)-- were increased as a consequence of HBOT and reduced 28 days after complete wound healing, whereas matrix metallopeptidase 9 (MMP9) progressively decreased with the HBOT. In conclusion, HBOT reduced oxidative and pro-inflammatory mediators, and may participate in activating healing, angiogenesis and vascular tone regulation by increasing the release of growth factors.

High Plasma Levels of Fibroblast Growth Factor 23 Are Associated with Increased Risk of COVID-19 in End-Stage Renal Disease Patients on Hemodialysis: Results of a Prospective Cohort.

We performed a prospective cohort of ESRD patients in hemodialysis who had measurements of plasma intact FGF23 in 2019. We determined COVID-19 infections, hospitalizations, and mortality between January 2020 and December 2021. We evaluated 243 patients. Age: 60.4 ± 10.8 years. Female: 120 (49.3%), diabetes: 110 (45.2%). During follow-up, 45 patients developed COVID-19 (18.5%), 35 patients were hospitalized, and 12 patients died (mortality rate: 26.6%). We found that patients with higher FGF23 levels (defined as equal or above median) had a higher rate of SARS-CoV-2 infection versus those with lower levels (18.8% versus 9.9%; Hazard ratio: 1.92 [1.03-3.56], p = 0.039). Multivariate analysis showed that increased plasma FGF23 was independently associated with SARS-CoV-2 infection and severe COVID-19. Our results suggest that high plasma FGF23 levels are a risk factor for developing COVID-19 in ESRD patients. These data support the potential immunosuppressive effects of high circulating FGF23 as a factor implicated in the association with worse clinical outcomes. Further data are needed to confirm this hypothesis.

Reduced Angiopoietin Factor 2 Levels Are Correlated with Better Cardiac Function and Prognosis in Valvular Heart Disease.

There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients - but not NYHA III/IV patients - was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

Regulators of angiogenesis in chemotherapy-induced peripheral neuropathy

Background: Chemotherapy-induced peripheral polyneuropathy is a major neurotoxicity of treatment for acute lymphoblastic leukemia (ALL) in children. Pathophysiological mechanisms of the injury of peripheral neural system are not fully investigated; however, some studies have shown the involvement of vascular endothelial growth factors.&#x0D; Aim: To evaluate plasma levels of angiogenic growth factors in children with ALL and to identify their association with the development of vincristine-induced peripheral polyneuropathy.&#x0D; Materials and methods: This single center prospective study included 41 patients with ALL aged 3 to 17 years. All patients were given the ALL-MB 2015 chemotherapy regimen. Depending on the vincristine-induced peripheral polyneuropathy, the patients were divided into two groups: the main group (n = 22) comprised of the patients with neurological signs and symptoms of peripheral neuropathy and the control group (n = 19), those without clinical signs of the peripheral nervous system involvement. The levels of angiogenic growth factors (VEGF-A, VEGF-D, PlGF-1, and PDGF-BB) were measured in plasma by multiparameter immunofluorescent analysis.&#x0D; Results: During 3 months of the follow up the chemotherapy-induced signs of peripheral polyneuropathy developed in 53.6% (n = 22) of the children. In 72.7% (n = 16) of the patients the chemotherapy-induced peripheral polyneuropathy was characterized by a combination of neurologic abnormalities with prevailing motor symptoms. The comparative analysis of plasma angiogenic growth factors in children with ALL depending on the presence or absence of the vincristine-induced peripheral polyneuropathy showed that there was a significant decrease of the VEGF-A in those with chemotherapy-induced peripheral polyneuropathy, compared to those without (Me [Q1; Q3]: 178.20 [138.40; 228.45] and 558.50 [160.10; 650.0], respectively, p 0.017). This parameter had diagnostic sensitivity of 77.7% and specificity of 76.9%.&#x0D; Conclusion: We have shown a high clinical value of plasma vascular endothelial growth factor (VEGF-A) level, which makes it possible to consider it as a significant biological marker of neurotoxicity in vincristine-induced peripheral polyneuropathy.

The search for systemic biomarkers for monitoring degenerative lumbar spinal disorders

ObjectivesIn our previous study, we reported that low back pain (LBP) severity and disability significantly correlate with body composition and several blood biochemical factors. Herein, we tested the hypothesis that these covariates are associated with anatomical deformations of the lumbar spine, in particular, radiographic facet joint osteoarthritis (FJOA) and lumbar disc degeneration (LDD) features important contributors to LBP. MethodsCT and MRI images of the lumbar spine were obtained from 200 individuals suffering from LBP-sciatica. We examined the FJOA and total LDD score - the sum of the scores of the three radiographic features (intervertebral disc herniation, osteophythosis and spondylolisthesis) at the L1 - S1 vertebral levels. By implementing a bioelectrical impedance analysis, we assessed the participants for body composition, specifically, extracellular water (ECW). Plasma levels of growth and differentiation factor 15 (GDF-15) and visceral adipose tissue-derived serine protease inhibitor (vaspin), were detected by ELISA. ResultsBy conducting a series of multivariable regression analyses, we report that the circulating levels of GDF-15, vaspin, and ECW are significantly and independently associated with FJOA scores [βGDF15 ​= ​0.38 ​± ​0.08, p ​= ​0.0001; βVASPIN ​= ​0.36 ​± ​0.07, p ​= ​0.000004; βECW ​= ​0.24 ​± ​0.07, p ​= ​0.002]. The levels of GDF-15 (β ​= ​0.30 ​± ​0.10, p ​= ​0.007) and ECW (β ​= ​0.20 ​± ​0.09, p ​= ​0.03) were also found significantly associated with the LDD scores. ConclusionThe obtained new data suggest that GDF-15, vaspin and ECW may serve as biomarkers for FJOA and LDD phenotypes.

Targeting angiopoietin-2 as a novel treatment option for kidney fibrosis

Kidney fibrosis is a hallmark of chronic kidney disease yet is poorly treated. Chang etal. determined that plasma and kidney levels of the vascular growth factor, angiopoietin-2, were elevated in patients with chronic kidney disease and mice with kidney disease. Angiopoietin-2 inhibited the renoprotective effects of angiopoietin-1 and promoted CC chemokine ligand 2-mediated kidney damage, endothelial cell apoptosis, vascular rarefaction, inflammation, fibrosis, and kidney dysfunction. Hence, therapeutically inhibiting angiopoietin-2 may represent a novel means of treating these chronic kidney disease-associated pathologies.

Sodium-Glucose Cotransporter-2 Inhibition Exacerbates Hepatic Encephalopathy in Biliary Cirrhotic Rats.

In liver cirrhosis, hepatic inflammation and abundant portal-systemic collaterals are indicated for the development of hepatic encephalopathy. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a type of anti-diabetic agent which exert pleiotropic and anti-inflammatory effects. Diabetes and chronic liver disease often coexist, but the influence of SGLT-2 inhibition on liver cirrhosis and hepatic encephalopathy remains unknown. This study investigated the effect of SGLT-2 inhibition on cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats via common bile duct ligation. A total of two weeks of treatment with the SGLT-2 inhibitor, empagliflozin 30 mg/kg/d, was applied. The motor activities, hemodynamics, biochemistry parameters, plasma levels of vascular endothelial growth factor (VEGF), and the severity of portal-systemic collateral shunts were measured. The hepatic histopathology and protein expressions were examined. We found that empagliflozin treatment did not affect hemodynamics, liver biochemistry, or blood glucose levels in cirrhotic rats. Empagliflozin did not affect hepatic inflammation and fibrosis. The protein expression of factors related to liver injury were not influenced by empagliflozin. However, empagliflozin decreased motor activities in cirrhotic rats and increased portal-systemic collateral shunts and VEGF plasma levels. In summary, SGLT-2 inhibition by empagliflozin did not ameliorate portal hypertension and hepatic inflammation in cirrhotic rats. In contrast, it exacerbated hepatic encephalopathy, which was evidenced by a decrease in motor activity. A possible mechanism could be an increase of portal-systemic shunts related to VEGF upregulation. Therefore, empagliflozin use should be cautious in cirrhotic patients regarding the development of hepatic encephalopathy. SIGNIFICANCE STATEMENT: Sodium-glucose cotransporter-2 inhibition by empagliflozin did not ameliorate portal hypertension and hepatic inflammation in cirrhotic rats. In contrast, it exacerbated hepatic encephalopathy through increased portal-systemic shunts related to VEGF up-regulation.

Рotential Laboratory Markers of Vincristine-Induced Peripheral Neuropathy

New chemotherapy agents of haematological malignancies in children often lead to adverse drug reactions, including vincristine-induced peripheral neuropathy (VIPN). The incidence of this pathology ranges from 22 to 72%. The clinic and instrumental evaluation of children with VPN, including questionaries, scales, electrodiagnostic examinations, do not provide an opportunity for prognosis and early detection of chemotherapy-related neurologic complications. Consequently, identifying biomarkers associated with VIPN is urgently warranted that discussed in this review. PubMed and Scopus were browsed based on the keywords that allowed us to select 55 articles (4 systemic reviews, 14 scientific reviews, 37 original articles) between 2017 and 2021. Reports from the included studies clearly emphasize that vincristine-induced peripheral neuropathy is associated with changes in plasma and cerebrospinal fluid (CSF) levels of the nerve growth factor (NGF) light chains of neurofilaments (NfL) and brain derived neurotrophic factor (BDNF) that are biomarkers of axonal damage. However, none of them do have criterion validity sensitivity and specificity. One of the most promising prognostic biomarkers is CХCL10 and CXCL12 that detect children with or without VIPN (sensitivity 79%, specificity 78%). The next task is finding an optimal profile of these cytokines. These cytokines together with axonal biomarkers can be used for the diagnosis and prevention of chemotherapy-induced neurotoxicity in children.

Plasma apelin and vascular endothelial growth factor levels in preterm infants: relationship to neonatal respiratory distress syndrome

Aim The study aimed to determine the association between cord plasma levels of apelin and vascular endothelial growth factor (VEGF) with respiratory distress syndrome (RDS) in preterm infants. Methods This case-control study included 120 preterm infants admitted to the neonatal intensive care unit of our hospital between January 2019 and January 2020. The infants were divided into RDS (n = 60) and non-RDS groups (n = 60). The cord plasma apelin and VEGF levels, perinatal characteristics, and neonatal complications were compared between the two groups. Results The plasma apelin levels in the RDS group were significantly higher than in the non-RDS group (158.9 ± 24.8 vs. 125.2 ± 18.2 pg/mL, respectively), whereas VEGF levels in the non-RDS group were significantly higher than in the RDS group (187.4 ± 28.5 vs. 245.1 ± 44.8 pg/mL, respectively) (both p < .001). Infants with more severe RDS had higher plasma apelin levels and lower plasma VEGF levels. In the receiver operating characteristic curve analysis for the prediction of RDS, a cutoff of 148.4 pg/mL for apelin level yielded a sensitivity of 63.3% and a specificity of 95.0%, whereas a cutoff of 214.2 pg/mL for VEGF level showed a sensitivity of 86.7% and a specificity of 75.0%. Apelin levels were negatively correlated with VEGF levels in infants with RDS (r = 0.84, p < .001). Conclusion Differences in cord plasma apelin and VEGF levels may aid in the early diagnosis and treatment of RDS in preterm infants.