A Panel of Eight miRNAs Is Deregulated in HTLV-2 Infected PBMCs and BJABGu Cell Line

Despite human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 being retroviruses closely related at a genomic level, HTLV-2 differs from HTLV-1 in terms of pathogenicity in both single infection and coinfection contexts. Moreover, the HTLV-2 association with clinical outcomes is still debated and several mechanisms underlying HTLV-2 infection remain unexplored as well. Cellular miRNAs are key factors in the post-transcriptional regulation of gene expression and they are known to be potential targets for several pathogens to control the host microenvironment and, in particular, escape immune responses. Here, we identified a HTLV-2-related signature of eight miRNAs (miR-125a-3p, miR-381-3p, miR-502-5p, miR-708-5p, miR-548d-5p, miR-548c-5p, miR-1-3p, and miR-511-5p) in both HTLV-2 infected PBMC and BJABGu cell lines. Altered miRNA expression patterns were correlated with the impairment of Th cell differentiation and signaling pathways driven by cytokines and transcriptional factors such as the Runt-related transcription factor (RUNX) family members. Specifically, we demonstrated that the RUNX2 protein was significantly more expressed in the presence of Tax-2 compared with Tax-1 in an in vitro cell model. To the best of our knowledge, these data represent the first contribution to elucidating the HTLV-2 mediated alteration of host cell miRNA profiles that may impact on HTLV-2 replication and persistent infection

PCSK9 Expression in Epicardial Adipose Tissue : Molecular Association with Local Tissue Inflammation

Epicardial adipose tissue (EAT) has the unique property to release mediators that nourish the heart in healthy conditions, an effect that becomes detrimental when volume expands and proinflammatory cytokines start to be produced. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a proinflammatory mediator involved in atherosclerosis, is also produced by visceral fat. Due to the correlation of inflammation with PCSK9 and EAT enlargement, we evaluated whether PCSK9 was expressed in EAT and associated with EAT inflammation and volume. EAT samples were isolated during surgery. EAT thickness was measured by echocardiography. A microarray was used to explore EAT transcriptoma. The PCSK9 protein levels were measured by Western Blot in EAT and ELISA in plasma. PCSK9 was expressed at both the gene and protein levels in EAT. We found a positive association with EAT thickness and local proinflammatory mediators, in particular, chemokines for monocytes and lymphocytes. No association was found with the circulating PCSK9 level. The expression of PCSK9 in EAT argues that PCSK9 is part of the EAT secretome and EAT inflammation is associated with local PCSK9 expression, regardless of circulating PCSK9 levels. Whether reducing EAT inflammation or PCSK9 local levels may have beneficial effects on EAT metabolism and cardiovascular risk needs further investigations

Usefulness of glycated albumin as a biomarker for glucose control and prognostic factor in chronic kidney disease patients on dialysis (CKD-G5D)

In chronic kidney disease patients on dialysis (CKD-G5D) accurate assessment of glycemic control is vital to improve their outcome and survival. The best glycemic marker for glucose control in these patients is still debated because several clinical and pharmacological factors may affect the ability of the available biomarkers to reflect the patient's glycemic status properly. This review discusses the role of glycated albumin (GA) both as a biomarker for glucose control and as a prognostic factor in CKD-G5D; it also looks at the pros and cons of GA in comparison to the other markers and its usefulness in hemodialysis and peritoneal dialysis

Soluble receptor for advanced glycation end products : a protective molecule against intramyocardial lipid accumulation in obese Zucker rats?

Most of the obesity-related complications are due to ectopic fat accumulation. Recently, the activation of the cell-surface receptor for advanced glycation end products (RAGE) has been associated with lipid accumulation in different organs. Nevertheless, the role of RAGE and sRAGE, the soluble form that prevents ligands to activate RAGE, in intramyocardial lipid accumulation is presently unknown. To this aim, we analyzed whether, in obesity, intramyocardial lipid accumulation and lipid metabolism-related transcriptome are related to RAGE and sRAGE. Heart and serum samples were collected from 10 lean (L) and 10 obese (OB) Zucker rats. Oil red staining was used to detect lipids on frozen heart sections. The lipid metabolism-related transcriptome (84 genes) was analyzed by a specific PCR array. Heart RAGE expression was explored by real-time RT-PCR and Western blot analyses. Serum levels of sRAGE (total and endogenous secretory form (esRAGE)) were quantified by ELISA. Genes promoting fatty acid transport, activation, and oxidation in mitochondria/peroxisomes were upregulated in OB hearts. Intramyocardial lipid content did not differ between OB and L rats, as well as RAGE expression. A slight increase in epicardial adipose tissue was observed in OB hearts. Total sRAGE and esRAGE concentrations were significantly higher in OB rats. sRAGE may protect against obesity-induced intramyocardial lipid accumulation by preventing RAGE hyperexpression, therefore allowing lipids to be metabolized. EAT also played a protective role by working as a buffering system that protects the myocardium against exposure to excessively high levels of fatty acids. These observations reinforce the potential role of RAGE pathway as an interesting therapeutic target for obesity-related complications, at least at the cardiovascular level

Evaluation of circulating sRAGE in osteoporosisaccording to BMI, adipokines and fracture risk: a pilot observational study

Background: Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism. Results: Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism. Conclusions: The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis

Neutrophil gelatinase-associated lipocalin and acute kidney injury in endovascular aneurysm repair or open aortic repair: a pilot study

Introduction: Acute kidney injury (AKI) occurs frequently after abdominal aortic surgery and there is currently no effective marker able to detect early onset. The aim of this study is to evaluate the ability of neutrophil gelatinase-associated lipocalin (NGAL) to early identify the development of acute renal damage in patients undergoing endovascular aneurysm repair (EVAR) or open aortic repair (OAR). Materials and methods: Serial samples of blood and urine were obtained from 25 patients undergoing both EVAR and OAR. Seven male subjects with AKI and 18 subjects with no-AKI (17 males, 1 female) were included in the study. We determined concentrations of serum creatinine (sCr) and urinary, serum and whole blood NGAL (uNGAL, sNGAL, bNGAL) collected at baseline, and after 4 and 18 hours. AKI was defined according to the RIFLE criteria (risk, injury, failure, loss of kidney function, and end-stage kidney disease): increase by 50% in sCr or reduction of at least 25% of estimated glomerular filtration rate (eGFR) from baseline. Results: Seven patients developed AKI in the stage Risk. There was no significant difference in sNGAL concentrations in the AKI group as compared to no-AKI group. However, the uNGAL/uCreatinine ratio and bNGAL concentrations were significantly higher after 18 hours in the AKI group (no-AKI 1.69 (0.91 - 2.47) vs AKI 3.2 (2.08 - 5.92) ng/mg for uNGAL/uCreatinine ratio, P = 0.036; and no-AKI 83 (59 - 131) vs AKI 164 (126 – 263) ng/mL for bNGAL, P = 0.029). Conclusions: Our results suggest that uNGAL, sNGAL and bNGAL, after abdominal aortic surgery, are not suitable as early biomarkers of AKI