Serum FGF23 Levels Research Articles

Tgr5-/- mice are protected from ethanol-induced metabolic alterations through enhanced leptin and Fgf21 signaling.

Alcohol-associated liver disease (ALD) is caused by chronic use of alcohol and ranges from hepatic steatosis to fibrosis and cirrhosis. Bile acids are physiological detergents that also regulate hepatic glucose and lipid homeostasis by binding to several receptors. One such receptor, Takeda G protein-coupled receptor 5 (TGR5), may represent a therapeutic target for ALD. Here, we used a chronic 10-day + binge ethanol-feeding model in mice to study the role of TGR5 in alcohol-induced liver injury. Female C57BL/6J wild-type mice and Tgr5-/- mice were pair-fed Lieber-DeCarli liquid diet with ethanol (5% v/v) or isocaloric control diet for 10 days followed by a gavage of 5% ethanol or isocaloric maltose control, respectively, to represent a binge-drinking episode. Tissues were harvested 9 hours following the binge, and metabolic phenotypes were characterized through examination of liver, adipose, and brain mechanistic pathways. Tgr5-/- mice were protected from alcohol-induced accumulation of hepatic triglycerides. Interestingly, liver and serum levels of Fgf21 were significantly increased during ethanol feeding in Tgr5-/- mice, as was phosphorylation of Stat3. Parallel to Fgf21 levels, increased leptin gene expression in white adipose tissue and increased leptin receptor in liver were detected in Tgr5-/- mice fed ethanol diet. Adipocyte lipase gene expression was significantly increased in Tgr5-/- mice regardless of diet, whereas adipose browning markers were also increased in ethanol-fed Tgr5-/- mice, indicating potential for enhanced white adipose metabolism. Lastly, hypothalamic mRNA targets of leptin, involved in the regulation of food intake, were significantly increased in Tgr5-/- mice fed ethanol diet. Tgr5-/- mice are protected from ethanol-induced liver damage and lipid accumulation. Alterations in lipid uptake and Fgf21 signaling, and enhanced metabolic activity of white adipose tissue, may mediate these effects.

Biomarkers for Bile Acid Malabsorption in Diarrhea-predominant Irritable Bowel Syndrome: A Systematic Review and Meta-analysis.

A clear relationship of biological indexes between bile acid malabsorption (BAM) and diarrhea-predominant irritable bowel syndrome (IBS-D) has not been well analyzed. This meta-analysis aimed to establish a more convenient method to diagnose BAM in IBS-D patients by comparing the differences in biomarkers between IBS-D patients and healthy people. Multiple databases were searched for relevant case-control studies. Indicators used to diagnose BAM included 75 Se-homocholic acid taurine (SeHCAT), 7α-hydroxy-4-cholesten-3-one(C4), fibroblast growth factor-19 and 48-hour fecal bile acid (48FBA). The rate of BAM (SeHCAT) was calculated by using a random-effect model. The levels of C4, FGF19, and 48FBA were compared, and the overall effect size was combined by a fixed effect model. The search strategy identified 10 relevant studies comprising 1034 IBS-D patients and 232 healthy volunteers. The pooled rate of BAM in IBS-D patients was 32% (according to SeHCAT; 95% CI: 24%-40%). The level of C4 in IBS-D patients was significantly higher than that in the control group (2.86ng/mL; 95% CI: 1.09, 4.63); The level of FGF19 was significantly lower than that in the control group (-33.97pg/mL; 95% CI: -51.13, -16.82); The level of 48FBA was significantly higher than that in the control group (0.059; 95% CI: 0.41, 0.77). The results mainly concluded serum C4 and FGF19 levels in IBS-D patients. Most of the studies have different normal cutoff points of serum C4 and FGF19 levels; the performance of each test should be further estimated. By comparing the levels of these biomarkers, BAM in patients with IBS-D could be identified more accurately, which would lead to more effective treatment.

The role of Klotho and FGF23 in cardiovascular outcomes of diabetic patients with chronic limb threatening ischemia: a prospective study

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.

Effects of Multiwall Carbon Nanotubes on Premature Kidney Aging: Biochemical and Histological Analysis.

Carbon nanotubes (CNTs) have gained much attention due to their superb properties, which make them promising options for the reinforcing composite materials with desirable mechanical properties. However, little is known about the linkage between lung exposure to nanomaterials and kidney disease. In this study, we compared the effects on the kidneys and aging for two different types of multiwall carbon nanotubes (MWCNTs): pristine MWCNTs (PMWCNTs) and acid-treated MWCNTs (TMWCNTs), with TMWCNTs being the preferred form for use as a composite material due to its superior dispersion properties. We used tracheal instillation and maximum tolerated dose (MTD) for both types of CNTs. MTD was determined as a 10% weight loss dose in a 3-month subchronic study, and the appropriate dosage for 1-year exposure was 0.1 mg/mouse. Serum and kidney samples were analyzed using ELISA, Western blot, and immunohistochemistry after 6 months and 1 year of treatment. PMWCNT-administered mice showed the activation of pathways for inflammation, apoptosis, and insufficient autophagy, as well as decreased serum Klotho levels and increased serum levels of DKK-1, FGF-23, and sclerostin, while TMWCNTs did not. Our study suggests that lung exposure to PMWCNTs can induce premature kidney aging and highlights a possible toxic effect of using MWCNTs on the kidneys in the industrial field, further highlighting that dispersibility can affect the toxicity of the nanotubes.

Liver-derived FGF21 is required for the effect of time-restricted feeding on high-fat diet-induced fatty liver in mice.

Nonalcoholic fatty liver disease (NAFLD), which leads to insulin resistance, steatosis, and even hepatocellular carcinoma, is the most common chronic liver disease worldwide, however, effective treatment is still lacking. This study determined the role of liver FGF21 and the mechanisms underlying the protective effects of time-restricted feeding (TRF) in NAFLD. FGF21 liver knockout (FGF21 LKO) mice and C57BL/6 wild-type (WT) mice were fed either a normal or a high-fat diet (HFD) for 16 weeks. Mice with diet-induced obesity (DIO) were also used. The mice were fed either ad libitum or in a time-restricted manner. Serum FGF21 levels were significantly increased after 16 weeks of TRF. TRF prevented body weight gain, improved glucose homeostasis, and protected against high-fat diet-induced hepatosteatosis and liver damage. The expression of genes related to liver lipogenesis and inflammation was reduced in TRF mice, but the expression of genes involved in fatty acid β-oxidation was increased. However, those beneficial effects of TRF were blunted in the FGF21 LKO mice. Moreover, TRF promoted improvements in insulin sensitivity and liver damage in DIO mice. Our data show that liver FGF21 signaling was involved in the effect of TRF on high-fat diet-induced fatty liver.

A potential link between fibroblast growth factor-23 and the progression of AKI to CKD

BackgroundPatients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear.MethodSerum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFβ/Smad and Wnt/β-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis.ResultsThe level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of β-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of β-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells.ConclusionThe increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-β and Wnt/β-catenin activation.

Lymphangioleiomyomatosis: circulating levels of FGF23 and pulmonary diffusion.

Lymphangioleiomyomatosis (LAM) is a rare, destructive disease of the lungs with a limited number of determinants of disease activity, which are a critical need for clinical trials. FGF23 has been implicated in several chronic pulmonary diseases. We aimed to determine the association between serum FGF23 levels and pulmonary function in a cohort of patients with LAM. This was a descriptive single-center study in which subjects with LAM and controls with unreported lung disease were recruited. Serum FGF23 levels were measured in all subjects. Clinical data, including pulmonary function testing, were retrospectively obtained from electronic medical records of LAM subjects. Associations between FGF23 levels and clinical features of LAM were explored via nonparametric hypothesis testing. The sample comprised 37 subjects with LAM and 16 controls. FGF23 levels were higher in the LAM group than in the control group. In the LAM group, FGF23 levels above the optimal cutoff point distinguished 33% of the subjects who had nondiagnostic VEGF-D levels. Lower FGF23 levels were associated with impaired DLCO (p = 0.04), particularly for those with isolated diffusion impairment with no other spirometric abnormalities (p = 0.04). Our results suggest that FGF23 is associated with pulmonary diffusion abnormalities in LAM patients and elicit novel mechanisms of LAM pathogenesis. FGF23 alone or in combination with other molecules needs to be validated as a biomarker of LAM activity in future clinical research.

Importance of Renal Dietitians in Nutritional Counselling and Dietary Interventions in The Early Stages of Chronic Kidney Disease

Chronic kidney disease (CKD) is becoming a public-health problem, at a global level. In CKD, patients progressively lose the ability to excrete phosphorus. Several observational studies have determined hyperphosphatemia emerging as an independent cardiovascular risk factor in CKD-Mineral and Bone Disorder (CKD-MBD). In early CKD, serum Klotho declines and fibroblast growth factor-23 (FGF‐23) starts increasing which coincides with its effects on augmenting urinary phosphate excretion with reduced serum phosphate reabsorption and decreased levels of calcitriol. The Klotho/FGF23 axis should be a novel target for renal clinicians being pathogenic contributors to CKD progression and cardiovascular disease (CVD) development. The high phosphorous load has been found to increase serum FGF-23 levels in the early stages of CKD which further leads to CVD and increased mortality. To control hyperphosphatemia, a potentially simple and effective approach of dietary phosphate control should be incorporated to reduce the early clinical consequences of CKD-MBD. Along with the amount of dietary phosphorus intake, its type (organic vs. inorganic), its source (animal vs. plant derived), phosphorus-to-protein ratio and preparation of food by boiling should also be made aware to patients which is likely a neglected aspect of dietary counselling in CKD. A kidney-friendly diet plan is needed to protect kidneys from further damage which is rather an arduous period for making patients follow a phosphate-restricted diet. Here, the role of the renal dietitian appears mandatory in counselling and educating the patients to effectively integrate dietary interventions into the therapeutic approach of CKD-MBD.

Serum and Urinary Soluble α-Klotho as Markers of Kidney and Vascular Impairment.

This study was designed to investigate the controversy on the potential role of sKlotho as an early biomarker in Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), to assess whether sKlotho is a reliable marker of kidney α-Klotho, to deepen the effects of sKlotho on vascular smooth muscle cells (VSMCs) osteogenic differentiation and to evaluate the role of autophagy in this process. Experimental studies were conducted in CKD mice fed a normal phosphorus (CKD+NP) or high phosphorus (CKD+HP) diet for 14 weeks. The patients' study was performed in CKD stages 2-5 and in vitro studies which used VSMCs exposed to non-calcifying medium or calcifying medium with or without sKlotho. The CKD experimental model showed that the CKD+HP group reached the highest serum PTH, P and FGF23 levels, but the lowest serum and urinary sKlotho levels. In addition, a positive correlation between serum sKlotho and kidney α-Klotho was found. CKD mice showed aortic osteogenic differentiation, together with increased autophagy. The human CKD study showed that the decline in serum sKlotho is previous to the rise in FGF23. In addition, both serum sKlotho and FGF23 levels correlated with kidney function. Finally, in VSMCs, the addition of sKlotho prevented osteogenic differentiation and induced autophagy. It can be concluded that serum sKlotho was the earliest CKD-MBD biomarker, a reliable indicator of kidney α-Klotho and that might protect against osteogenic differentiation by increasing autophagy. Nevertheless, further studies are needed to investigate the mechanisms of this possible protective effect.

Relationship between serum fibroblast growth factor 19 and vascular endothelial growth factor and soluble klotho protein in type 1 diabetic children

BackgroundFibroblast growth factor 19 (FGF19) takes part in maintaining the balance of glycolipids and may be involved in complications of type 1 diabetes(T1D) in children. This study aimed at at evaluating the relationship among the levels of serum FGF19 and vascular endothelial growth factor(VEGF)and soluble klotho protein(sklotho) in type 1 diabetic children.MethodsIn a cross-section single center study samples were obtained from 96 subjects: 66 T1D and 30 healthy children.Serum FGF19 and VEGF and sklotho concentrations were measured by ELISA. And 66 type 1 diabetes participants were divided into two groups according to T1D duration or three groups according to HbA1c.Furthermore,we compared the serum levels of FGF19 and VEGF and sklotho in different groups.ResultsThe concentration of FGF19 was lower in T1D than in the controls(226.52 ± 20.86pg/mu vs.240.08 ± 23.53 pg/L, p = 0.03),while sklotho was also lower in T1D than in the controls (2448.67 ± 791.92pg/mL vs. 3083.55 ± 1113.47pg/mL, p = 0.011). In contrast, VEGF levels were higher in diabetic patients than in controls (227.95 ± 48.65pg/mL vs. 205.92 ± 28.27 pg/mL, p = 0.016). In T1D, FGF19 and VEGF and sklotho was not correlated with the duration of diabetes. FGF19 and VEGF and sklotho were correlated with HbA1c (r=-0.349, p = 0.004 and r = 0.302, p = 0.014 and r=-0.342, p = 0.005, respectively), but not with blood glucose and lipid. Among subjects in the T1D group, concentrations of FGF19,VEGF and sklotho protein were different between different groups according to the degree of HbA1c(P < 0.005).Furthermore, there was a positive correlation between the serum FGF19 concentration and sklotho levels (r = 0.247,p = 0.045), and a negative correlation between the serum FGF19 concentration and VEGF level(r=-0.335,P = 0.006). Conclusions: The serum FGF19 levels have a close relation with serum VEGF levels and sklotho levels among T1D subjects. FGF19 may be involved in the development of complications in children with type 1 diabetes through interaction with VEGF and sklotho.

Mechanical loading modulates phosphate related genes in rat bone.

Mechanical loading determines bone mass and bone structure, which involves many biochemical signal molecules. Of these molecules, Mepe and Fgf23 are involved in bone mineralization and phosphate homeostasis. Thus, we aimed to explore whether mechanical loading of bone affects factors of phosphate homeostasis. We studied the effect of mechanical loading of bone on the expression of Fgf23, Mepe, Dmp1, Phex, Cyp27b1, and Vdr. Twelve-week old female rats received a 4-point bending load on the right tibia, whereas control rats were not loaded. RT-qPCR was performed on tibia mRNA at 4, 5, 6, 7 or 8 hours after mechanical loading for detection of Mepe, Dmp1, Fgf23, Phex, Cyp27b1, and Vdr. Immunohistochemistry was performed to visualise FGF23 protein in tibiae. Serum FGF23, phosphate and calcium levels were measured in all rats. Four-point bending resulted in a reduction of tibia Fgf23 gene expression by 64% (p = 0.002) and a reduction of serum FGF23 by 30% (p<0.001), six hours after loading. Eight hours after loading, Dmp1 and Mepe gene expression increased by 151% (p = 0.007) and 100% (p = 0.007). Mechanical loading did not change Phex, Cyp27b1, and Vdr gene expression at any time-point. We conclude that mechanical loading appears to provoke both a paracrine as well as an endocrine response in bone by modulating factors that regulate bone mineralization and phosphate homeostasis.

Insights into the Molecular and Hormonal Regulation of Complications of X-Linked Hypophosphatemia

X-linked hypophosphatemia (XLH) is characterized by mutations in the PHEX gene, leading to elevated serum levels of FGF23, decreased production of 1,25 dihydroxyvitamin D3 (1,25D), and hypophosphatemia. Those affected with XLH manifest impaired growth and skeletal and dentoalveolar mineralization as well as increased mineralization of the tendon–bone attachment site (enthesopathy), all of which lead to decreased quality of life. Many molecular and murine studies have detailed the role of mineral ions and hormones in regulating complications of XLH, including how they modulate growth and growth plate maturation, bone mineralization and structure, osteocyte-mediated mineral matrix resorption and canalicular organization, and enthesopathy development. While these studies have provided insight into the molecular underpinnings of these skeletal processes, current therapies available for XLH do not fully prevent or treat these complications. Therefore, further investigations are needed to determine the molecular pathophysiology underlying the complications of XLH.

P022 A correlation of serum Fibroblast Growth Factor 21 level with inflammatory markers and indicators of nutritional status in patients with Inflammatory Bowel Disease

Abstract Background Fibroblast Growth Factor 21 (FGF21) is an endocrine hormone produced mostly in the liver, adipose tissue, and the pancreas. Main inducers of the FGF21 secretion include fasting state, overfeeding, inflammation, and physical activity. FGF21 is involved in the metabolism of lipids, carbohydrates, and proteins. It also participates in body weight regulation. Previous studies have shown that serum FGF21 level is increased in animal model of colitis and patients with Inflammatory Bowel Disease (IBD) (Liu et al. Gastroenterol Res Pract 2017). The aim of this study was to assess the correlation between serum FGF21 level and inflammatory markers as well as indicators of nutritional status in IBD patients. Methods Fasting serum FGF21 level was measured using ELISA test in 67 patients with IBD (38 patients with Crohn’s disease and 29 patients with ulcerative colitis) and 10 control subjects. Among IBD patients, 24 subjects were in remission and 43 in acute phase of the disease. Fecal calprotectin, serum CRP, albumin and cholesterol levels were tested in all patients. BMI was also assessed. The Spearman rank correlation coefficient (R) was calculated to evaluate associations between the variables. Results No significant differences were found in serum FGF21 level between four studied groups: all IBD patients, IBD patients with remission, IBD patients with exacerbation and healthy controls. However, a positive correlation was observed in IBD patients between serum FGF21 and fecal calprotectin levels (R= 0.39, p= 0.003). There was also a trend toward a positive correlation between FGF21 and CRP levels (R= 0.24, p= 0.053). Moreover, an inverse correlation was found in IBD patients between FGF21 level and nutritional status indicators: BMI (R= –0.36, p= 0.003), albumin level (R= –0.38, p= 0.001), and cholesterol level (R= –0.30, p= 0.014). Conclusion The intensity of intestinal inflammation is related to FGF21 level, which correlates negatively with nutritional status indicators in the course of IBD. The disturbances in FGF21 secretion may contribute to the multifactorial pathogenesis of malnutrition and weight loss in IBD patients.

Carotid Intima-media Thickness is a Sequel of Elevated FGF-23 Levels in CKD!

International Journal of Medicine and Public Health,2022,12,4,165-168.DOI:10.5530/ijmedph.2022.4.30Published:January 2023Type:Original ArticleCarotid Intima-media Thickness is a Sequel of Elevated FGF-23 Levels in CKD!Upma Narain, Arvind Gupta, and Seema Pandey Upma Narain1,*, Arvind Gupta2, Seema Pandey3 1Microbiologist and Immunologist, Tejas Microdiagnostics, Prayagraj, Uttar Pradesh, INDIA. 2Department of Nephrology, MLN Medical College, Prayagraj, Uttar Pradesh, INDIA. 3Department of Radio Diagnosis, MLN Medical College, Prayagraj, Uttar Pradesh, INDIA. Abstract:Background: FGF-23 regulates phosphate homeostasis and has a correlation with morbidity and mortality due to cardiovascular episodes and chronic renal conditions. The risk of subclinical atherosclerosis can be predicted by measurements of the intima-media thickness of the carotid artery. The objective of this studyisto study therelation between serum FGF-23 levels and Carotid intima-media thickness in the early stages of CKD. Materials and Methods: This study was conducted at MLN Medical College, SRN Hospital, Prayagraj and Tejas Microdiagnostics. The study design adopted was prospective and observational. A total of 270 newly diagnosed CKD patients were enrolled as cases while 90 patients without CKD were taken as control. Highresolution ultrasonography was utilised to measure Carotid artery intima-media thickening. Serum FGF-23 levels were performed at the beginning of study, along with other baseline investigations and were repeated on 6th and 9th months respectively. Results: Among the case group of CKD, the mean age was 54.8+2.1 years with male to female proportions representing 62% and 38%, respectively of the control group consisted mean age distribution of 51.0 + 2.1 years a and male-female proportion of 58% and 42%, respectively. It was observed that FGF-23 levels and Carotid intima-media thickness measurements were high in patients than in controls. A statistically significant correlation at 0.01 levels was observed between FGF-23 and the Carotid intima-media thickness. Conclusion: Our study clearly establishes a strong correlation between FGF-23 and CIMT indicating that FGF-23 plays an important role in the development of vascular calcifications in early stages of CKD. Subclinical atherosclerosis in CKD patients can be predicted by monitoring of their FGF-23 and CIMT level. Keywords:Association, Carotid intima-media thickness, CKD, FGF-23View:PDF (347.97 KB)

Correlation of Serum FGF23 and Chronic Kidney Disease-Mineral and Bone Abnormality Markers With Cardiac Structure Changes in Maintenance Hemodialysis Patients.

CKD-MBD is a mineral and bone metabolism syndrome caused by chronic kidney disease. FGF23 is an important factor regulating phosphorus and is the main influencer in the CKD-MBD process. In this study, we observed the correlation among serum FGF23 and calcium, phosphorus and parathyroid hormone, and the correlation between FGF23 levels and cardiac structural changes in MHD patients. We examined serum FGF23 concentrations in 107 cases of MHD patients using the ELISA method, recorded demographic information and biochemical data, and analyzed the correlation between serum FGF23 levels and blood calcium and blood phosphorus and PTH levels. All patients were evaluated by cardiac color ultrasound, and we finally analyzed the association between the FGF23 level and cardiac structural changes. In 107 cases of MHD patients, serum FGF23 levels were linearly associated with serum calcium (r = 0.27 P < 0.01) and parathyroid hormone levels (r = 0.25, P < 0.05). FGF 23 was negatively correlated with age (r = -0.44, P < 0.01).Serum FGF23 levels were correlated with right atrial hypertrophy in HD patients (P < 0.05). No correlation was found among FGF23, left ventricular hypertrophy/enlargement, and valve calcification stenosis (P > 0.05). Serum FGF23 showed a positive correlation among blood calcium levels and PTH levels in hemodialysis patients, and FGF23 levels can affect the incidence of right atrial hypertrophy in MHD patients.

Effects of the Foam Massage Roller on VEGF-A and FGF-2 Blood Levels in Young Men.

Angiogenesis induced in muscles or massaged tissue is thought to support their regeneration and performance. Therefore, different methods that could promote angiogenesis are investigated. The aim of this study was to examine whether the use of the foam roller massager for lower limb muscles affects VEGF-A and FGF-2 levels in young men. The study group included 60 healthy young men attending Military University of Land Forces, Wroclaw, Poland. The participants were randomly divided into two groups. The experimental group included 40 individuals who performed self-massage of the lower limbs using a foam roller. The control group comprised 20 individuals who did not perform massage. Massage was applied to lower limb muscles four times a week for seven weeks. Blood was collected before the experiment and after weeks 1, 3, 5, and 7. ELISA was used to determine changes in VEGF-A and FGF-2 levels in blood serum. The results of the study demonstrated a significant increase in VEGF-A serum levels in the group of individuals who underwent massage each week compared to VEGF-A concentrations before the experiment. The increase in VEGF-A levels in the experimental group was observed throughout the experiment compared to the control group. No significant changes in serum FGF-2 levels were found. The use of a foam massage roller increased VEGF-A serum levels, which may indicate stimulation of angiogenesis.

The relationship of fibroblast growth factor 23 with calcification of the thoracic aorta according to the results of multislice computed tomography in patients with resistant arterial hypertension

Objective: to evaluate the incidence and severity of thoracic aortic calcification, the relationship with endothelial dysfunction and fibroblast growth factor in patients with resistant arterial hypertension.Materials and methods: the study involved 92 patients with resistant hypertension. Daily monitoring of blood pressure (ABPM) was performed, the functional state of the endothelium was assessed in a sample with reactive hyperemia, the calcium index (CI) of the thoracic aorta was determined using MSCT, and the serum level of FGF-23 was determined using enzyme immunoassay.Results: based on ABPM, patients were divided into groups 1st-controlled (n=44) and 2nd-uncontrolled (n=48) resistant AH. In the 2nd group, a more pronounced dysfunction of the endothelium was revealed in the sample with reactive hyperemia and changes in the velocity parameters of blood flow. FGF23 levels and CI were higher in individuals with uncontrolled resistant hypertension. According to the results of correlation-regression analysis, CI was associated with the value of pulse pressure (r=0.49, p=0.007), the duration of hypertension (r=0.68, p=0.04) and the duration of regular antihypertensive therapy (r = −0 .33, p=0.02). FGF- 23 was found to be associated with PA hemodynamic parameters: with Ved (r=0.42, p=0.003), PI (r=0.43, p=0.041) and RI (r=0.46, p=0.025), as well as with CI (r=0.76, p=0.006).Conclusion: patients with uncontrolled resistant hypertension showed a more pronounced decrease in brachial artery EVR and an increase in vascular resistance indices in the test with reactive hyperemia, which was statistically significantly associated with the level of FGF23. In patients with resistant hypertension, excessive calcification of the thoracic aorta was found according to the results of MSCT. Calcium index values are higher in patients with high pulse BP, longer duration of hypertension and high levels of FGF23.

Serum ANGPTL4 and FGF2, energy-related blood biochemicals, cytokine responses and oxidative stress in dairy cows with subclinical ketosis

In this study, it was aimed to investigate the serum levels of ANGPTL4, FGF21, IL-1β, IL-6, SOD, MDA, and serum biochemical and hematological parameters in cows with subclinical ketosis. The mean serum β-hydroxybutyric acid (BHB) level was 1.37 ± 0.04 mmol/L in 10 dairy cows aged 3-5 years that were &amp;lt;21 days postpartum and diagnosed with subclinical ketosis. The mean serum BHB level was 0.40 ± 0.08 mmol/L in 10 healthy dairy cows in the same period and in the same age range. An increase in serum AST (P&amp;lt;0.001) and a decrease in serum albumin levels (P&amp;lt;0.05) indicated altered liver functions. An increase in serum non-esterified fatty acid (P&amp;lt;0.001) and decreases in serum HDL, triglyceride, and total cholesterol levels (P&amp;lt;0.05) were interpreted as indicators of increased metabolic pathology risk due to negative energy balance. Increases in serum ANGPTL4, FGF2, IL-1β, IL-6, and MDA (P&amp;lt;0.001) and SOD levels (P&amp;lt;0.05) were evaluated as indicators of the development of effective metabolic, inflammatory, and oxidative stress.It was concluded that significant increases in serum ANGPTL4, FGF2, IL-1β, IL-6, and MDA and SOD levels in dairy cows with subclinical ketosis were associated with negative energy balance, effective cytokine responses, and oxidative stress.

549: ANALYSIS OF NEUROPROTECTIVE COLD SHOCK PROTEINS IN A MULTICENTER STUDY OF PEDIATRIC CARDIAC ARREST

Introduction: The efficacy of hypothermic neuroprotection varies by age. Cold exposure stimulates production of cold stress hormones (CSHs) which trigger thermogenesis and may be neuroprotective. FGF21 is a neuroprotective CSH that requires the Beta-klotho (KLB) co-receptor to signal. KLB is abundant in the newborn brain, decreases with age, and is virtually absent in adults. Thus, infants and young children may uniquely benefit from FGF21/KLB mediated neuroprotection. In vitro studies revealed that FGF21 upregulates the powerful neuroprotectant RNA-Binding Motif-3 (RBM3) in developmentally immature neurons (but not mature neurons). We sought to characterize FGF21 and RBM3 serum levels in children after cardiac arrest (CA) and evaluate their interdependence. Methods: Secondary analysis of serum samples collected in a multi-institutional prospective observational study evaluating biomarkers after pediatric CA. We measured FGF21 (Luminex) and RBM3 (ELISA) levels. All patients with serum from at least two timepoints (0-24h, 24-48h, 48-72h) were included. We also included serum from healthy controls. FGF21 and RBM3 levels at each timepoint were compared to controls (Wilcoxon-Ranksum); the relationship between FGF21/RBM3 at each timepoint was also evaluated (Spearman). Results: A total of 296 samples from 111 post-arrest patients were analyzed, and 20 samples from controls. Median age of the post-arrest cohort was 31.3 months (IQR: 6.9-129.9); 37.3 months (IQR: 18.6-63.6) for controls. Median FGF21 levels in the controls was 282pg/mL (IQR: 64-736), and did not differ significantly at 0-24h, 24-48h, and 48-72h (383 [IQR: 72-867], 723 [IQR: 167-1,688] and 552 [IQR: 210-1,225], respectively, P>0.05). Median control RBM3 was 2,944pg/mL (IQR: 969-8,241), and did not differ significantly at 0-24h, 24-48h, and 48-72h (1,538 [IQR: 757-4,146], 1,454 [625-3,543] and 1,526 [IQR: 613-3,591], respectively, P>0.05). FGF21 and RBM3 were correlated at 0-24h and 48-72h (Spearman’s coefficient of 0.384 and 0.223, respectively; P< 0.05 for both). Conclusions: After pediatric CA, serum FGF21 levels trend upward and RBM3 levels downward and correlate at early and late timepoints. Ongoing studies are examining their relationship to age, demographics, CA endophenotype, use of hypothermia, other serum biomarkers, and outcomes.

Myocardial remodeling and fibroblast growth factor in patients with resistant hypertension

Aim. To study the prevalence and severity of left ventricular hypertrophy (LVH), its relationship with fibroblast growth factor (FGF23) in patients with resistant hypertension (RH) depending on the effectiveness of multiagent antihypertensive therapy.Material and methods. The study included 92 patients diagnosed with RH. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, general laboratory tests, and the serum FGF23 level was determined.Results. According to ABPM results, patients were divided into following groups: 1st — controlled RH (n=44) and 2nd — uncontrolled (n=48) RH. The groups were comparable in sex, age, main clinical and anthropometric parameters. In group 2, the main parameters of ABPM were higher. There were no differences in general laboratory tests, In the group of uncontrolled RH, the level of FGF23 was higher — 11,7 [8,5; 15,4] pmol/ml vs 9,2 [7,1; 11,6] pmol/ml in the 1st group (p=0,0036). According to echocardiography, a comparable violation of left ventricular (LV) diastolic function, an increase in left atrial size, LV mass (LVM) and LVM index were found. In patients of the 2nd group, large values of interventricular septal thickness were revealed — 1,3 [1,2; 1,4] cm vs 1,2 [1,1; 1,3] cm in the 1st group (p=0, 0043) and relative LV wall thickness (LVWT) — 0,50 [0,48; 0,53] vs, 0,45 [0,43; 0,50] in the 1st group (p&lt;0,0001). In the 1st and 2nd groups, concentric LVH was more common (18 (41%) patients in the 1st and 26 (54,1%) in the 2nd (p=0,044) groups) than eccentric LVH (15 (34,1%) and 13 (27,1%) patients in the 1st and 2nd groups, respectively). Correlation analysis revealed a positive relationship between pulse pressure and HTN duration (r=48, p=0,02) and FGF23 level (r=0,62, p=0,004). The LVM index was positively associated with the diastolic pressure-time index (BP) (r=51, p=0,02). A positive correlation was found between relative LVWT and pulse pressure (r=0,64, p=0,02) and a negative relationship with the duration of regular antihypertensive therapy (r=47, p=0,04), A strong relationship was found between LVEF and FGF23 levels (r=0,75, p=0,005).Conclusion. For patients with uncontrolled resistant hypertension, an increase in pulse pressure and myocardial remodeling in the form of concentric hypertrophy are more characteristic. FGF23 is significantly higher in uncontrolled RH and is positively associated with pulse pressure and relative LVWT.