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1.
Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training.
Jerobin, J, Ramanjaneya, M, Bettahi, I, Parammal, R, Siveen, KS, Alkasem, M, Aye, M, Sathyapalan, T, Skarulis, M, Atkin, SL, et al
Lipids in health and disease. 2021;(1):34
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined. METHODS Ten PCOS and nine healthy subjects were studied at baseline status and after moderate-intensity chronic exercise training (1 h exercise, 3 times per week, 8 weeks). All participants were infused with 1.5 mL/min of saline or intralipids (20%) for 5 h, and during the last 2 h of saline or intralipids infusion hyperinsulinemic-euglycemic clamp (HIEC) was performed. CTRP-2, CTRP-9, GDF-8 and GDF-15 levels were measured at 0, 3 and 5 h. RESULTS Intralipids dramatically increased CTRP-2 levels in PCOS (P = 0.02) and control (P = 0.004) subjects, which was not affected by insulin infusion or by exercise. Intralipids alone had no effects on CTRP-9, GDF-8, or GDF-15. Insulin increased the levels of GDF-15 in control subjects (P = 0.05) during the saline study and in PCOS subjects (P = 0.04) during the intralipid infusion. Insulin suppressed CTRP9 levels during the intralipid study in both PCOS (P = 0.04) and control (P = 0.01) subjects. Exercise significantly reduced fasting GDF-8 levels in PCOS (P = 0.03) and control (P = 0.04) subjects; however, intralipids infusion after chronic exercise training increased GDF-8 levels in both PCOS (P = 0.003) and control (P = 0.05) subjects and insulin infusion during intralipid infusion reduced the rise of GDF-8 levels. CONCLUSION This study showed that exogenous lipids modulate CTRP-2, which might have a physiological role in lipid metabolism. Since chronic exercise training reduced fasting GDF-8 levels; GDF-8 might have a role in humoral adaptation to exercise. GDF-15 and CTRP-9 levels are responsive to insulin, and thus they may play a role in insulin responses.
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2.
An autologous protein gel for soft tissue augmentation: in vitro characterization and clinical evaluation.
Fedyakova, E, Pino, A, Kogan, L, Eganova, C, Troya, M, Anitua, E
Journal of cosmetic dermatology. 2019;(3):762-772
Abstract
BACKGROUND The aging process affects all organs of the body, but the skin is the most visible indicator with a great psychosocial impact. As a consequence, many skin anti-aging strategies have been developed to minimize, postpone, and even reverse the aging process. Growth factors have been widely studied in skin wound healing as these polypeptides play an essential role in the complex process of tissue regeneration. Recently, a novel 3D injectable gel based on the autologous technology platelet rich in growth factor has been described. OBJECTIVES In this study, a comparison between hyaluronic acid (HA, the gold standard for skin rejuvenation), and this novel autologous formulation has been conducted. METHODS Rheological and mechanical properties were determined. The in vitro biological capacity of both treatments on human dermal fibroblasts proliferation, migration, chemotaxis, and extracellular matrix synthesis was also assessed. Additionally, a clinical evaluation of the autologous platelet gel treatment was performed by macrophotographs, ultrasound analyses, and clinical and patient surveys. RESULTS The autologous gel outperformed the general biomechanical properties of HA and kept an optimal viscoelastic gel-like behavior for soft tissue augmentation. Both formulations stimulated cell chemotaxis, migration, and type I collagen synthesis. The autologous gel induced a statistically higher cell proliferation. After the autologous formulation treatment, a soft tissue augmentation effect was also noticed along with an overall skin quality improvement in terms of hydration, elasticity, wrinkle reduction, and general satisfaction scores. CONCLUSIONS This novel injectable formulation has desirable mechanical and bioactive properties for 3D tissue regeneration and might offer a safe and effective treatment for depressed areas of the skin.
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3.
Progranulin serum levels in human kidney transplant recipients: A longitudinal study.
Nicoletto, BB, Pedrollo, EF, Carpes, LS, Coloretti, NG, Krolikowski, TC, Souza, GC, Gonçalves, LFS, Manfro, RC, Canani, LH
PloS one. 2018;(3):e0192959
Abstract
BACKGROUND The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. OBJECTIVE To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. METHODS Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. RESULTS Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01) and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months), remaining significantly lower than before transplantation (p<0.01) (pover time<0.01). At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. CONCLUSION Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.
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4.
Circulating sclerostin and Dickkopf-1 levels in patients with nonalcoholic fatty liver disease.
Polyzos, SA, Anastasilakis, AD, Kountouras, J, Makras, P, Papatheodorou, A, Kokkoris, P, Sakellariou, GT, Terpos, E
Journal of bone and mineral metabolism. 2016;(4):447-56
Abstract
There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.1 ± 6.8) to SS (53.5 ± 6.4) and NASH (46.0 ± 8.1 pmol/l) patients (p = 0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p = 0.012). Although serum DKK-1 did not differ between groups (p = 0.135), there was a trend toward U-shaped distribution (controls 35.8 ± 2.8; SS 27.3 ± 2.9; NASH 36.8 ± 4.4 pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (≤33 %) than higher (>33 %) steatosis grade (27.7 ± 3.1 and 38.8 ± 4.7 pmol/l, respectively; p = 0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.
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5.
Stanniocalcin-2 (STC2): A potential lung cancer biomarker promotes lung cancer metastasis and progression.
Na, SS, Aldonza, MB, Sung, HJ, Kim, YI, Son, YS, Cho, S, Cho, JY
Biochimica et biophysica acta. 2015;(6):668-76
Abstract
The homodimeric glycoprotein, stanniocalcin 2 (STC2) is previously known to be involved in the regulation of calcium and phosphate transport in the kidney and also reported to play multiple roles in several cancers. However, its function and clinical significance in lung cancer have never been reported and still remain uncertain. Here, we investigated the possibility of STC2 as a lung cancer biomarker and identified its potential role in lung cancer cell growth, metastasis and progression. Proteomic analysis of secretome of primary cultured lung cancer cells revealed higher expression of STC2 in cancers compared to that of adjacent normal cells. RT-PCR and Western blot analyses showed higher mRNA and protein expressions of STC2 in lung cancer tissues compared to the adjacent normal tissues. Knockdown of STC2 in H460 lung cancer cells slowed down cell growth progression and colony formation. Further analysis revealed suppression of migration, invasion and delayed G0/G1 cell cycle progression in the STC2 knockdown cells. STC2 knockdown also attenuated the H202-induced oxidative stress on H460 cell viability with a subsequent increase in intracellular ROS levels, which suggest a protective role of STC2 in redox regulatory system of lung cancer. These findings suggest that STC2 can be a potential lung cancer biomarker and plays a positive role in lung cancer metastasis and progression. This article is part of a Special Issue entitled: Medical Proteomics.
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6.
Implications of C1q/TNF-related protein-3 (CTRP-3) and progranulin in patients with acute coronary syndrome and stable angina pectoris.
Choi, KM, Hwang, SY, Hong, HC, Choi, HY, Yoo, HJ, Youn, BS, Baik, SH, Seo, HS
Cardiovascular diabetology. 2014;:14
Abstract
BACKGROUND C1q/TNF-related protein-3 (CTRP-3), an adiponectin paralog, and progranulin were recently identified as novel adipokines which may link obesity with glucose dysregulation and subclinical inflammation. We analyzed the relationship between CTRP-3, progranulin and coronary artery disease (CAD) in Korean men and women. METHODS Circulating CTRP-3 and progranulin levels were examined in 362 Korean adults with acute coronary syndrome (ACS, n = 69), stable angina pectoris (SAP, n = 85), and control subjects (n = 208) along with various kinds of cardiometabolic risk factors. RESULTS CTRP-3 concentrations were significantly decreased in patients with ACS or SAP compared to control subjects (P <0.001, respectively), whereas progranulin and adiponectin levels were similar. Correlation analysis adjusted for age and gender exhibited that CTRP-3 levels showed significant negative relationship with glucose (r = -0.110, P = 0.041) and high sensitive C-reactive protein (hsCRP) levels (r = -0.159, P = 0.005), and positive relationship with HDL-cholesterol (r = 0.122, P = 0.025) and adiponectin levels (r = 0.194, P <0.001). In a multivariate logistic regression analysis, the odds ratio for CAD risk was 5.14 (95% CI, 1.83-14.42) in the second, and 9.04 (95% CI, 2.81-29.14) in the first tertile of CTRP-3 levels compared to third tertile after adjusting for other cardiometabolic risk variables. CONCLUSIONS Patients with ACS or SAP had significantly lower circulating CTRP-3 concentrations compared to control subjects, although progranulin levels were not different. These results suggest the possibility that CTRP-3 might be useful for assessing the risk of CAD. TRIAL REGISTRATION (Clinical trials No.: NCT01594710).
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7.
The relationship between apelin and cardiac parameters in patients on peritoneal dialysis: is there a new cardiac marker?
Karadag, S, Ozturk, S, Gursu, M, Gurdal, A, Basinoglu, F, Yigit, S, Aydin, Z, Uzun, S, Sumnu, A, Oflaz, H, et al
BMC nephrology. 2014;:18
Abstract
BACKGROUND Many markers have been proposed for CVD risk assessment in dialysis population. Apelin is a peptide that has roles in cardiovascular functions and volume regulation namely vasodilation, decreased blood pressure (BP), positive inotropic effect and inhibition of antidiuretic hormone release. The aim of this study was to examine relationship of apelin levels with echocardiographic findings and laboratory parameters related with cardiovascular function and bone mineral metabolism among peritoneal dialysis (PD) patients. METHODS This is a cross-sectional study in which chronic PD patients aged between 18 and 80 without active cardiac, infectious or malignant diseases and hypervolemia have been included. Apelin-36 levels and echocardiographic findings were recorded as well as clinical and laboratory data. RESULTS Of the 53 patients, the mean age and female/male ratio was 52.8 ± 15.3 years and 30/23, respectively. Mean apelin level was 1.45 ± 0.37 ng/ml. Gender, drugs (renin-angiotensin-aldosteron inhibitors, statins), presence of left ventricular hypertrophy, diabetes mellitus, hypertension, hyperlipidemia and significant residual renal function did not affect apelin-36 levels. Apelin-36 was correlated negatively with age and left atrium diameter; and positively with diastolic BP, ejection fraction (EF), total cholesterol, LDL-cholesterol, HDL-cholesterol, parathyroid hormone and alkaline phosphatase (ALP) levels. Diastolic BP, LDL-cholesterol, ALP and EF were found to be the independent determinants of apelin-36 levels with linear regression analysis. CONCLUSIONS Apelinergic system has important roles in volume regulation, cardiovascular functions, lipid metabolism and bone mineral disorders in PD patients. Prospective studies with large population are required.
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8.
Serum preadipocyte factor-1 concentrations in females with obesity and type 2 diabetes mellitus: the influence of very low calorie diet, acute hyperinsulinemia, and fenofibrate treatment.
Kavalkova, P, Touskova, V, Roubicek, T, Trachta, P, Urbanova, M, Drapalova, J, Haluzikova, D, Mraz, M, Novak, D, Matoulek, M, et al
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2013;(11):820-6
Abstract
Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients.
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9.
Growth factor release from platelet concentrates: analytic quantification and characterization for clinical applications.
Durante, C, Agostini, F, Abbruzzese, L, Toffola, RT, Zanolin, S, Suine, C, Mazzucato, M
Vox sanguinis. 2013;(2):129-36
Abstract
BACKGROUND AND OBJECTIVES Clinical use of plasma rich in growth factors requires biochemical product control. We aimed to measure and modulate concentrations of growth factors in solutions deriving from platelet apheresis or whole blood. MATERIALS AND METHODS Growth factor concentrations were measured 5', 10', 20', 30', 60' after CaCl2 was added at 40°C to platelet-apheresis products (n = 39) or after 60' in platelet concentrates from whole blood (n = 13). Growth factor release was also obtained in platelet apheresis a) by incubation at 22°C or 40°C for 10' or 30' (n = 4); b) by repeated freeze-thaw (n = 9). RESULTS Fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) isoforms AA and AB and transforming growth factor beta (TGF-β) concentrations (pg/10(9 ) plt) were 25-60% higher in growth factors solutions from whole blood compared to platelet apheresis. Vascular endothelial growth factor (VEGF), TGF-β and PDGF isoforms were released early (5-10') during incubation: TGF-β concentration increased also at 30'. FGF and epidermal growth factor (EGF) were released only after 30'. Incubation at 40°C/10' increased VEGF (+70%) and decreased EGF (-30%) and PDGF-BB (-50%) versus 22°C/30'. Shock significantly increased TGF-β (1.6-fold), EGF (1.5-fold), FGF (4.5-fold) and lowered PDGF isoforms (0.2- to 0.5-fold) versus prolonged incubation at 40°C. CONCLUSION Platelets from platelet apheresis and whole-blood release all investigated growth factors. The release can be regulated controlling incubation time and/or temperature and performing cell lysis.
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10.
LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia.
Tasci, I, Erdem, G, Ozgur, G, Tapan, S, Dogru, T, Genc, H, Acikel, C, Ozgurtas, T, Sonmez, A
Atherosclerosis. 2009;(1):222-8
Abstract
Apelin, a relatively newer adipokine with various actions in cardiovascular system, was recently reported to decrease in dyslipidemia. The present study addresses whether plasma apelin increases after hypolipidemic intervention either through therapeutic life style change (TLC) or statin treatment. A total of 134 patients were subjected to treatment with a TLC intervention for 12 weeks. Of these, 116 successfully completed the period, and LDL-cholesterol level decreased to target level (<160 mg/dL) in 54 (46.5%) individuals. The remaining 62 patients were treated with rosuvastatin for 12 weeks, and 56 of them finished the study. Circulating apelin, adiponectin, leptin, TNF-alpha, hsCRP and insulin levels were determined both at baseline and after TLC intervention and statin treatment. There was no significant change in plasma apelin concentration in patients unresponsive to TLC (p=0.110). LDL-cholesterol lowering either through TLC or statin treatment was accompanied by an increase in plasma apelin (p=0.000, p=0.020) and adiponectin (p=0.001, p=0.011). Serum leptin decreased after successful TLC (p=0.042/male, p=0.023/female) but not after statin treatment (p=0.959/male, p=0.134/female). Serum TNF-alpha (p=0.902) and plasma hsCRP (p=0.135) levels remained unchanged after TLC intervention but decreased after statin treatment (p=0.000, p=0.023, respectively). Plasma insulin and homeostasis model assessment scores decreased after TLC (p=0.000 for both) but not rosuvastatin treatment (p=0.865, p=0.722, respectively). In conclusion, independent of the type of treatment, reduction in LDL-cholesterol levels in otherwise healthy people with isolated dyslipidemia results in an increase in plasma apelin concentration. More experiments may show a substantial role for this peptide in the mechanism of atherosclerosis.