1,721,039 research outputs found
Recent advances on natriuretic peptide system: New promising therapeutic targets for the treatment of heart failure
No full textDo pentraxin 3 and neural pentraxin 2 have different facet function in hepatocellular carcinoma?
No full textThe long pentraxin (PTX) 3 and the neuronal pentraxin (NPTX) 2 has been found to exert pleiotropic roles in cancers due to their action in inflammation. However, the accurate clinical significance of PTX3 and NPTX2 in hepatocellular carcinoma (HCC), one of the commonest cancers in the world has not been well-defined. The aim of the study was to analyze the expression profile of PTX3 and NPTX2 in liver biopsies of HCV-positive HCC patients (liver recipients, LR, n = 14, age 59.4 ± 1.8 years) undergoing liver transplantation and in donors (LD, n = 14, age 62.1 ± 17.3 years), trying both to identify them as predictive biomarkers of clinical liver severity in HCC patients and to understand if they were mutually substitutable. The PTX3 and NPTX2 transcripts were significantly up regulated in HCC tissues (p = 0.004 and p = 0.02 LD vs. LR, respectively). Dividing patients following MELD score, PTX3 expression increased as a function of liver disease severity, while this trend was not observed for NPTX2, which mRNA level increased similarly in both MELD group, reaching the significance only in patients with MELD score < 9 (p = 0.01). A positive correlation was found between PTX3 and NPTX2 expression (p = 0.001; r = 0.69). This is the first study that concerns PTX3 and NPTX2 as a function of clinical severity from which emerged that both of them are unequivocally involved in HCC, but only PTX3 could be considered a staging marker in these HCV-related HCC patients, unlike NPTX2, which could only play a role as an inflammatory marker
Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity
No full textApelin, a peptide of 77 amino acids, and its endogenous ligand, angiotensin-like-receptor 1 (APJ), play a key role in the development of tumors by enhancing angiogenesis, metastasis, cell proliferation, development of cancer stem cells and drug resistance and inhibiting apoptosis of cancer cells. However, little is known about Apelin/APJ system involvement in hepatocellular carcinoma (HCC). The aim of this study was to evaluate Apelin and APJ expression in liver specimens, obtained from subjects with HCV-positive HCC who underwent liver transplantation, according to liver disease severity (liver recipients, LR, n = 14, age 59.4 ± 1.8) and in donors (liver donors, LD, n = 14, age 62.1 ± 17.3). Apelin/APJ axis, apoptotic and inflammatory markers were evaluated by Real-Time PCR analysis. The Apelin/APJ system expression resulted significantly higher in LR in comparison with LD (p < 0.05), in particular in those with more severe liver disease. The apoptotic (Bcl-2, BAX, NOTCH-1, Casp-3) and inflammatory (IL-6, TNF-α) markers were increased as a function of disease severity (p < 0.05). Multiple significant positive correlations were found between Apelin/APJ axis and the other markers. Although further investigations are needed to better understand the role of Apelin/APJ axis in HCC, our result indicated a potential role of this axis in its development and progression as well as in recognizing novel therapeutic targets opening a new avenue for treatment
Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression
No full textHepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. The study aimed to perform a data mining analysis of the expression and regulatory role of key genes in HCC to reveal novel potential biomarkers of diagnosis prognosis, or progression since their availability is still almost lacking. Starting from data of our cohort of patients (HCV-positive HCC pts undergoing liver transplantation (LR, n = 10) and donors (LD, n = 14), deeply analyzed previously, in which apelin, osteopontin, osteoprotegerin, NOTCH-1, CASP-3, Bcl-2, BAX, PTX3, and NPTX2 were analyzed, we applied statistical analysis and in-silico tools (Gene Expression Profiling Interactive Analysis, HCCDB database and GeneMania, UALCAN) to screen and identify the key genes. Firstly, we performed a stepwise regression analysis using our mRNA-datasets which revealed that higher expression levels of apelin and osteopontin were positively associated with the HCC and identified that the most consistently differentially expressed gene across multiple HCC expression datasets was only OPN. This comprehensive strategy of data mining evidenced that OPN might have a potential function as an important tumor marker-driven oncogenesis being associated with poor prognosis of HCC patients
Circulating levels of cardiac natriuretic hormones measured in women during menstrual cycle.
No full textAlterations in fluid and electrolyte balance represent a common complaint by women during different stages of the menstrual cycle; however, conflicting results concerning the possible role of plasma Atrial Natriuretic Peptide (ANP) modifications during the menstrual cycle have been reported. This may be due to differences in assay methods or in the clinical protocol adopted. Moreover, possible variations in plasma Brain Natriuretic Peptide (BNP) levels during the menstrual cycle have not been studied. We measured the plasma levels of ANP and BNP by means of two highly sensitive and specific immunoradiometric assay (IRMA) methods in 19 normal women without premenstrual symptoms, in order to evaluate whether significant modifications of these hormones are present during the menstrual cycle. Because it is well-known that circulating levels of cardiac hormones show great variations in normal subjects due to their rapid plasma half lives, blood samples were collected at 2.5-min intervals over a 15-min period on the 5th and 24th days of the cycle. The mean (+/-SD) values of ANP (follicular phase=15.1+/-8.7 pg/ml; luteal phase=14.8+/-9.5 pg/ml) and of BNP (follicular phase=13.0+/-15.0 pg/ml; luteal phase=11.2+/-11.4 pg/ml) did not show significant variations during the menstrual cycle. Moreover, the variability of ANP values (CV=24.8+/-13.2%) was significantly higher (p=0.0318) than that of BNP values (CV=16.5+/-8.9%), and a significant correlation was found between the mean ANP and BNP values of the individual women studied (R=0.407, p=0.0437). The values of estradiol, progesterone, LH, FSH and prolactin did not correlate with the ANP or BNP values. In conclusion, our results indicate that circulating levels of cardiac hormones do not show any significant modifications during the menstrual cycle in healthy women
Pacing-induced regional differences in adenosine receptors mRNA expression in a Swine model of dilated cardiomyopathy.
Full text linkThe adenosinergic system is essential in the mediation of intrinsic protection and myocardial resistance to insult; it may be considered a cardioprotective molecule and adenosine receptors (ARs) represent potential therapeutic targets in the setting of heart failure (HF). The aim of the study was to test whether differences exist between mRNA expression of ARs in the anterior left ventricle (LV) wall (pacing site: PS) compared to the infero septal wall (opposite region: OS) in an experimental model of dilated cardiomyopathy. Cardiac tissue was collected from LV PS and OS of adult male minipigs with pacing-induced HF (n = 10) and from a control group (C, n = 4). ARs and TNF-α mRNA expression was measured by Real Time-PCR and the results were normalized with the three most stably expressed genes (GAPDH, HPRT1, TBP). Immunohistochemistry analysis was also performed. After 3 weeks of pacing higher levels of expression for each analyzed AR were observed in PS except for A1R (A1R: C = 0.6±0.2, PS = 0.1±0.04, OS = 0.04±0.01, p<0.0001 C vs. PS and OS respectively; A2AR: C = 1.04±0.59, PS = 2.62±0.79, OS = 2.99±0.79; A2BR: C = 1.2±0.1, PS = 5.59±2.3, OS = 1.59±0.46; A3R: C = 0.76±0.18, PS = 8.40±3.38, OS = 4.40±0.83). Significant contractile impairment and myocardial hypoperfusion were observed at PS after three weeks of pacing as compared to OS. TNF-α mRNA expression resulted similar in PS (6.3±2.4) and in OS (5.9±2.7) although higher than in control group (3.4±1.5). ARs expression was mainly detected in cardiomyocytes. This study provided new information on ARs local changes in the setting of LV dysfunction and on the role of these receptors in relation to pacing-induced abnormalities of myocardial perfusion and contraction. These results suggest a possible therapeutic role of adenosine in patients with HF and dyssynchronous LV contraction
Bone morphogenetic protein-4 system expression in human coronary artery endothelial and smooth muscle cells under dynamic flow: effect of medicated bioresorbable vascular scaffolds at low and normal shear stress.
No full textEndothelial and smooth muscle cell dysfunction is an early event at the onset of atherosclerosis, a heterogeneous and multifactorial pathology of the vascular wall. Bone morphogenetic protein (BMP)-4, a mechanosensitive autocrine cytokine, and BMPR-1a, BMPR-1b, BMPR2 specific receptors play a key role in atherosclerotic plaque formation and vascular calcification, and BMP4 is regarded as a biomarker of endothelial cell activation. The study aimed to examine the BMP4 system expression by Real-Time PCR in Human Coronary Artery Endothelial (HCAECs) and Smooth Muscle Cells (HCASMCs) under different flow rates determining low or physiological shear stress in the presence/absence of medicated Bioresorbable Vascular Scaffold (BVS). The HCAEC and HCASMC were subjected to 1-10-20 dyne/cm2 shear stress in a laminar-flow bioreactor system, with/without BVS+Everolimus (600 nM).
In HCAECs without BVS, the BMP4 expression was similar at 1,20 dyne/cm2, decreasing at 10 dyne/cm2, while adding BVS+Everolimus, it decreased both at 1,10 compared to 20 dyne/cm2. In HCASMCs without BVS+Everolimus, the BMP4 system mRNA expression was significantly reduced at 1,10 dyne/cm2 compared to 20 dyne/cm2, while in the presence of BVS+Everolimus, higher BMP4 mRNA levels were observed at 10 compared to 1,20 dyne/cm2. In HCAECs and HCASMCs, BMPRs were expressed in all experimental conditions except for BMPR-1a at 1 dyne/cm2 in HCAEC. Significant correlations were found between BMP4 and BMPRs.
The more negligible effect on BMP4 expression due to low shear stress in HCAEC compared to HCASMC and its reduction in the presence of BVS+Everolimus at low shear stress highlighted the protection BMP4-mediated against endothelial dysfunction and neo-atherogenesis
C-type natriuretic peptide plasma levels and whole blood mRNA expression show different trends in adolescents with different degree of endothelial dysfunction
No full textC-type natriuretic peptide (CNP) is an endogenous adipogenesis regulator whose plasma levels in childhood are known, while no data are available on its expression. Our aim was to evaluate both CNP plasma levels and CNP system expression in whole blood obtained from normal-weight (N, n = 24) and obese (O, n = 16) adolescents (age:13.5 ± 0.4 years). Endothelial function was assessed measuring reactive hyperemia index (RHI). CNP plasma levels, evaluated with specific RIA, resulted significantly lower in O than in N (6.1 ± 0.8 vs.15.2 ± 1.3 pg/mL; p < 0.0001), while CNP/NPR-B/NPR-C mRNA, measured by Real-Time PCR, resulted similar in N (4.1 ± 1.7; 5.0 ± 1.6; 2.2 ± 0.9) and in O (4.3 ± 1.6; 3.5 ± 1.1; 2.3 ± 0.8). RHI was significantly lower in O than in N (1.4 ± 0.08 vs.2.1 ± 0.04, p < 0.0001). Dividing all subjects according to the RHI median value, irrespective of the presence or absence of obesity (Group 1 > 1.9, n = 23, Group 2 < 1.9, n = 17), CNP plasma concentrations resulted significantly (p = 0.014) higher in Group 1 (14.6 ± 1.6) than in Group 2 (7.5 ± 1.0), showing a significant correlation with RHI (p = 0.0026), while CNP mRNA expression was, surprisingly, higher in Group 2 (7.0 ± 2.3) than in Group 1 (1.8 ± 0.4; p = 0.02). NPR-B mRNA resulted similar in both Groups (4.3 ± 1.6; 4.7 ± 1.3) and NPR-C significantly higher in Group 2 (p = 0.02). Our data suggest different trends between CNP plasma levels and expression, assessed for the first time in whole blood, that could reflect changes occurring both at CNP transcriptional level in activated leukocytes due to inflammation, and at circulating levels, due to CNP paracrine/autocrine activities. This could represent an interesting area for new therapies able to modulate endothelial dysfunction
Adenosine Receptor mRNA Expression in Normal and Failing Minipig Hearts
No full textBackground: Chronic heart failure (HF) results in possibly beneficial endogenous adenosina accumulation. The final biological action of adenosine in a particular organ or cell population may depend on the relative expression level and signaling efficiency of the individual adenosine receptor (AR) subtypes.
Aim: To determine myocardial expression of ARs, in the different chambers of failing compared to normal minipig hearts.
Materials and Methods: Cardiac tissue (left and right atrium, left and right ventricle) was collected from male adult minipigs without (control, C, n=5) and with pacing-induced HF (n=5). ARs mRNA expression was evaluated by RT-PCR together with TNF– mRNA expression.
Results: A1R, A2AR, A2BR and A3R were expressed in all cardiac regions analyzed and, after 3 weeks of pacing, in left ventricle mRNA of each ARs resulted more expressed that in controls (A3R/gapdh: C=0.2±0.07 vs. HF: 1.4±0.5 p=0.03). TNF– mRNA expression resulted significantly higher in left ventricle of HF pig (p=0.009). We also observed a significant correlation between TNF– mRNA expression and A1R (r=0.6 p=0.0002), A2AR (r=0.8 p<0.0001), A2BR (r=0.9 p<0.0001), A3R (r=0.7 p<0.0001).
Conclusion: ARs mRNA espression were characterized simultaneously in all cardiac chambers of normal and HF animals. All ARs, and expecially AR3 subtype, are expressed in all cardiac chambers and, compared to controls, overexpressed in left ventricle
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