Hypoxic Human Microglia Promote Angiogenesis Through Extracellular Vesicle Release.

Microglia, the brain-resident immune cells, orchestrate neuroinflammatory responses and are crucial in the progression of neurological diseases, including ischemic stroke (IS), which accounts for approximately 85% of all strokes worldwide. Initially deemed detrimental, microglial activation has been shown to perform protective functions in the ischemic brain. Besides their effects on neurons, microglia play a role in promoting post-ischemic angiogenesis, a pivotal step for restoring oxygen and nutrient supply.

Perioperative Marinobufagenin (MBG) Measurement May Improve Acute Kidney Injury Risk Assessment in Patients Undergoing Major Cardiac Surgery: A Proof-of-Concept Study.

Acute kidney injury (AKI) remains a significant complication following major cardiac surgery. Marinobufagenin (MBG), a cardiotonic steroid involved in sodium balance and blood pressure regulation, has been linked to organ damage after ischemia-reperfusion events. This pilot, prospective study investigates the utility of circulating MBG to improve AKI risk assessment in cardiac surgery patients as a stand-alone biomarker and after inclusion in a validated risk model (STS-AKI score).

Selenoprotein P-1 (SEPP1) as an Early Biomarker of Myocardial Injury in Patients Undergoing Cardiopulmonary Bypass.

: Biomarkers development for prognostication or prediction of perioperative myocardial disease is critical for the evolution of treatment options in patients undergoing cardiac surgery. The aim of our prospective monocentric study was to investigate the role of selenoprotein 1 (SEEP 1) as a potential biomarker for assessing the risk of myocardial injury after cardiac surgery. : Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by enzyme-linked immunosorbent assay (ELISA); (3) : circulating SEPP-1 levels measured 4 h after surgery were strongly correlated with CK-MB levels measured at 48 h (R = 0.

Role of kidney function on Nrf2 mRNA levels in type 2 diabetes.

Introduction: Diabetic kidney disease (DKD) is a major complication in patients with diabetes and the main contributor to the chronic kidney disease (CKD) global burden. Oxidative stress is a crucial factor in DKD pathogenesis but the role of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and its molecular regulators has been poorly investigated in man.

Research Design And Methods: In this case-control study, we analyzed the roles of Nrf2, a transcription factor shielding cells from oxidative stress, its repressor Kelch-like ECH-associated protein 1 (Keap1) and six microRNAs (miRNAs) that potentially suppress Nrf2.

Role of Gut Microbiota in Overweight Susceptibility in an Adult Population in Italy.

Although the gut microbiota is known to affect body weight, its relationship with overweight/obesity is unclear. Our aim was to characterize microbiota composition in a cohort from the southernmost area of Italy. We investigated whether an altered gut microbiota could play an etiological role in the pathogenesis of overweight/obesity.

SMCHD1 and LRIF1 converge at the FSHD-associated D4Z4 repeat and LRIF1 promoter yet display different modes of action.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic derepression of the 4q-linked D4Z4 macrosatellite repeat resulting in inappropriate expression of the D4Z4 repeat-encoded DUX4 gene in skeletal muscle. In 5% of FSHD cases, D4Z4 chromatin relaxation is due to germline mutations in one of the chromatin modifiers SMCHD1, DNMT3B or LRIF1. The mechanism of SMCHD1- and LRIF1-mediated D4Z4 repression is not clear.

Prevalence and detection rate of celiac disease in Italy: Results of a SIGENP multicenter screening in school-age children.

Background: Celiac disease is a common lifelong disorder. Recent studies indicate that the number of clinically detected cases has increased over the last decades, however little is known about changes in the prevalence and the detection rate of celiac disease.

Aim: To evaluate the current prevalence and detection rate of celiac disease in Italy by a multicenter, mass screening study on a large sample of school-age children.

Selenoprotein P-1 (SEPP1) as an Early Biomarker of Acute Kidney Injury in Patients Undergoing Cardiopulmonary Bypass.

Background: Acute Kidney Injury (AKI) is a frequent, dangerous complication in patients undergoing cardiopulmonary bypass (CPB) with oxidative stress playing a crucial role. In this pilot study we evaluated the possible role of the selenoprotein-p1 (SEPP1), a circulating, anti-oxidant selenium transporter, as a predictive biomarker of AKI in this population setting.

Methods: Circulating SEPP1 was measured in the blood of 45 patients before surgery and at 4 h, 8 h and 12 h after CPB by Enzyme-Linked Immunosorbent Assay (ELISA).

Effectiveness of Apremilast in Real Life in Patients with Psoriasis: A Longitudinal Study.

Apremilast is an oral selective phosphodiesterase-4 inhibitor developed recently for psoriasis treatment. The aim of this study is to assess the real-life outcomes of use of apremilast in patients with psoriasis in everyday clinical practice. A total of 159 adult patients (90 males) with plaque psoriasis were included in the study.

Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described.

Long-term blood pressure monitoring by office and 24-h ambulatory blood pressure in renal transplant patients: a longitudinal study.

Background: Renal transplant patients have a high prevalence of nocturnal hypertension, and hypertension misclassification by office blood pressure (BP) is quite common in these patients. The potential impact of hypertension misclassification by office BP on hypertension management in this population has never been analysed.

Methods: We performed a longitudinal study in a cohort of 260 clinically stable renal transplant patients.

The sirtuin1 gene associates with left ventricular myocardial hypertrophy and remodeling in two chronic kidney disease cohorts: a longitudinal study.

Background: Oxidative stress and inflammation are major drivers of myocardial hypertrophy in chronic kidney disease (CKD). The silent information regulator gene 1 (Sirt1) is a fundamental mediator of the response to oxidative stress and inflammation and promotes myocardial growth under stress conditions; therefore, it may contribute to myocardial hypertrophy and concentric remodeling of the left ventricle (LV) in CKD.

Methods: We investigated the cross-sectional and longitudinal relationship between three candidate polymorphisms in the Sirt1 gene and LV parameters in two cohorts of CKD patients including 235 stage G5D patients and 179 stages G1-5 patients, respectively.

Office, standardized and 24-h ambulatory blood pressure and renal function loss in renal transplant patients.

Objectives: Hypertension is a risk factor for renal function loss in kidney transplant patients but there are still no longitudinal studies focusing on the relationship between ambulatory blood pressure (BP) monitoring (ABPM) and the glomerular filtration rate (GFR) evolution over time in these patients.

Methods: In a cohort of 260 renal transplant patients, we investigated the longitudinal relationship between repeated office BP measurements and simultaneous GFR measurements (on average 35 paired measurements per patient) and the relationship between baseline ABPM with the same outcome measure (by linear mixed models). Furthermore, we tested the prediction power of baseline ABPM and standardized BP measurements for a combined renal end point (GFR loss >30%, end-stage kidney disease or death) over a 3.

A polymorphism in a major antioxidant gene (Kelch-like ECH-associated protein 1) predicts incident cardiovascular events in chronic kidney disease patients: an exploratory study.

Objective: Oxidative stress is considered a major pathway conducive to cardiovascular disease in chronic kidney disease (CKD) patients. However, observational studies and clinical trials testing this relationship are controversial. The Nuclear factor-erythroid-2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) system is a major system regulating antioxidant mechanisms in living organisms.

Association of IL-6 and a functional polymorphism in the IL-6 gene with cardiovascular events in patients with CKD.

Background And Objectives: High serum IL-6 is a major risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patients with CKD, but it is still unknown whether the link between IL-6 and CVD in CKD is causal in nature.

Design, Setting, Participants, & Measurements: In a cohort of 755 patients with stages 2-5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up±SD, 31±10 months) and used the functional polymorphism (-174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal.

Joint effect of insulin signaling genes on all-cause mortality.

Objective: We have previously reported the combined effect of SNPs perturbing insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on insulin resistance (IR), type 2 diabetes (T2D) and cardiovascular events. We here investigated whether such a combined effect affects also all-cause mortality in a sample of 1851 Whites of European ancestry.

Methods: We investigated a first sample of 721 patients, 232 deaths, 3389 person-years (py).

A genetic marker of uric acid level, carotid atherosclerosis, and arterial stiffness: a family-based study.

Background: Hyperuricemia associates with atherosclerosis complications, but it is uncertain whether this relationship is causal in nature. The urate transporter GLUT9 (encoded by the SLC2A9 gene) is a major genetic determinant of serum uric acid level in humans. Because polymorphisms are distributed randomly at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and atherosclerosis.

A polymorphism in the major gene regulating serum uric acid associates with clinic SBP and the white-coat effect in a family-based study.

Objectives: Hyperuricemia associates with hypertension, but it is uncertain whether this relationship is causal in nature. Glucose transporter 9 (GLUT9) gene is a major genetic determinant of plasma uric acid levels in humans. Since polymorphisms are randomly distributed at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and hypertension.

Association of a polymorphism in a gene encoding a urate transporter with CKD progression.

Background And Objectives: Hyperuricemia predicts a high risk for CKD progression but there is no large clinical trial in humans indicating that this relationship is causal in nature. The rs734553 single-nucleotide polymorphism (SNP) of the GLUT9 urate transporter gene was strongly associated with uric acid (UA) levels in a large meta-analysis.

Design, Setting, Participants, & Measurements: This prospective study adopted the Mendelian randomization approach.

The fat-mass and obesity-associated gene (FTO) predicts mortality in chronic kidney disease of various severity.

Background: Polymorphisms in the FTO (fat-mass and obesity-associated) gene have been associated with the body mass index, cancer, type 2 diabetes and hypertension.

Methods: We investigated the relationship between 17 tag single-nucleotide polymorphisms (SNPs) and all-cause mortality in three cohorts of dialysis patients (CREED-1, North Apulian and CREED-2 cohorts; n = 783) and in one cohort of stage 2-5 CKD patients (n = 757).

Results: We first explored the association between the 17 tag SNPs and all-cause mortality in the CREED-1 cohort and found that patients with the A allele of the FTO rs708259 polymorphism had an elevated risk of mortality (hazard ratio, HR: 1.

Joint effect of insulin signaling genes on cardiovascular events and on whole body and endothelial insulin resistance.

Objective: Insulin resistance (IR) and cardiovascular disease (CVD) share a common soil. We investigated the combined role of single nucleotide polymorphisms (SNPs) affecting insulin signaling (ENPP1 K121Q, rs1044498; IRS1 G972R, rs1801278; TRIB3 Q84R, rs2295490) on CVD, age at myocardial infarction (MI), in vivo insulin sensitivity and in vitro insulin-stimulated nitric oxide synthase (NOS) activity.

Design And Setting: 1.

Tissue inhibitor of metalloproteinases (TIMP-1), genetic markers of insulin resistance and cardiomyopathy in patients with kidney failure.

Background: Left ventricular hypertrophy (LVH) is a major cardiovascular (CV) complication in patients with kidney failure, and an association between polymorphisms in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene, a genetic marker of insulin resistance, and LVH and Left ventricular (LV) concentric remodelling has been recently documented in these patients. Aims. Since myocardial fibrosis is a prominent feature in LVH induced by insulin resistance, we tested the hypothesis that the interaction between ENPP1 rs1974201 and rs9402349 polymorphisms and the tissue inhibitor of metalloproteinases (TIMP-1)--a pro-fibrotic protein which inhibits extracellular matrix degradation--is implicated in concentric LVH and diastolic dysfunction in a cohort of 223 dialysis patients.

eNOS and caveolin-1 gene polymorphisms interaction and intima media thickness: a proof of concept study in ESRD patients.

Background: Caveolae are a prominent microdomain in endothelial cells and appropriate localization in caveolae is fundamental for endothelial nitric oxide synthase (eNOS) activity. Since the Glu298Asp variant in the eNOS gene alters caveolar localization of the corresponding enzyme, we tested the interaction between this variant and the rs4730751 polymorphism of the caveolin-1 (CAV-1) gene as related to arterial remodeling in end-stage renal disease (ESRD) patients.

Methods: One hundred and thirty-three ethnically homogeneous ESRD patients underwent carotid ultrasonographic studies to measure intima-media thickness (IMT) and carotid cross-sectional area (CSA).