TAp73 depletion accelerates aging through metabolic dysregulation

Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging.     

Caval replacement strategy in pediatric retroperitoneal tumors encasing the vena cava: a single-center experience and review of literature

Background

Complete encasement of the inferior vena cava by retroperitoneal tumors is rare. Although replacement of the vena cava has been considered for various conditions in adults, it is rarely used in children except for challenging resections and as a last chance approach – often aiming more at debulking than cure.

BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumors

Although discussed using variable terminology, cutaneous BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumor (BIMT) has been considered a discrete diagnostic entity since 2011. Here, we review the initial genomic studies that identified these distinct melanocytic tumors and the clinical and histopathological features that define these tumors. These epithelioid, predominantly dermal, and melanocytic tumors present as erythematous nodules and histopathologically have features that may overlap with Spitz nevi and nevoid melanoma. There is no sex predilection, and cutaneous BIMTs can appear at any age; however, in most familial (germline mutant) cases patients have multiple cutaneous tumors with a first diagnosis in the second or third decade of life; ocular melanoma and other tumors are increasingly identified in these kindreds with germline BAP1 mutation. These tumors have been described with a myriad of terms including: Wiesner nevus, nevoid melanoma‐like melanocytic proliferation (NEMMP), BAP1 mutant Spitz nevus, BAP1 mutant nevoid melanoma, cutaneous BAPoma, and most recently cutaneous BIMT.     

Baboon‐Like Syndrome in Children

Baboon syndrome is a combination of diffuse symmetrical erythema on the major flexural areas and V‐shaped erythema on both upper anteromedial thighs. Infectious agents have been described as possible triggers. We describe for the first time baboon syndrome in a child induced by a coinfection with Epstein‐Barr virus and cytomegalovirus.     

Measurement of Novel Biomarkers to Predict Chronic Heart Failure Outcomes and Left Ventricular Remodeling

Myocardial remodeling is pivotal in the progression and complication of chronic heart failure (HF). We assessed serial measurement of five biomarkers with biologic links to remodeling (biglycan, secreted frizzled-related protein 3, endostatin, insulin-like growth factor binding protein 7 [IGFBP7], mimecan) in 142 patients with HF followed through 882 office visits. IGFBP7 and mimecan were most associated with events; in fully adjusted models, lower IGFBP7 concentrations across visits independently predicted fewer events (odds ratio [OR]?=?0.83; 95 % confidence interval [CI]?=?0.73–0.95, p?=?0.01). Subjects with rising mimecan had greater decrease in left ventricular end diastolic (p?=?0.07) and systolic (p?=?0.01) volumes, greater increase in ejection fraction (p?=?0.02), and had lowest event rates. Statistical models suggested several HF medications might lead to changes in both IGFBP7 and mimecan values. The results suggest serial measurement of IGFBP7 provides prognostic information, while changes in mimecan provide unique information regarding myocardial remodeling.     

Left ventricular longitudinal systolic dysfunction is an independent marker of cardiovascular risk in patients with hypertension

BackgroundTo explore the prognostic value of left ventricular (LV) longitudinal systolic dysfunction in patients with hypertension.MethodsIn 156 hypertensive subjects, LV longitudinal systolic function was assessed by echocardiographic measurement of M-mode left atrioventricular plane displacement (AVPD) and Tissue Doppler (TD)-derived mitral annulus peak systolic velocity (S(m)). Patients were followed for development of the following cardiovascular events: congestive heart failure requiring hospitalization, new-onset angina, nonfatal myocardial infarction, coronary revascularization procedures, transient ischemic attack, nonfatal stroke, and cardiovascular death.ResultsOver a follow-up of 23.3 +/- 5.4 months, 24 patients had 29 events. Both longitudinal systolic indices were predictive of outcome (hazard ratios: AVPD, 0.24, P < 0.001; S(m), 0.22; P < 0.001). AVPD 相似文献   

A study on the action of vitamin E supplementation on plasminogen activator inhibitor type 1 and platelet nitric oxide production in type 2 diabetic patients

Background and aimType 2 diabetic (T2DM) patients show decreased fibrinolysis, mainly linked to high plasminogen activator inhibitor type 1 (PAI-1) production, together with a reduced bioavailability of nitric oxide and an impairment in Na⁺/K⁺-ATPase activity possibly involved in increased cardiovascular risk. Vitamin E is the major natural lipid-soluble antioxidant in human plasma. The present work was conducted in order to measure PAI-1, ICAM and VCAM-1 plasma levels, platelet nitric oxide production and membrane Na⁺/K⁺-ATPase activity in type 2 diabetic subjects treated with vitamin E (500 IU/day) for 10 weeks and then followed for other 20 weeks.Methods and resultsThirty-seven T2DM patients (24 males and 13 females) were studied. None of them were affected by any other disease or diabetic complications. Significant differences were detected for PAI-1 antigen (p < 0.001), PAI-1 activity (p < 0.001), nitric oxide (NO) production (p < 0.001), and Na⁺/K⁺-ATPase activity (p < 0.001) among the 4 phases of the study. A significant decrease both in ICAM and VCAM-1 plasma levels was also found at the 10th week compared with baseline (respectively p < 0.001 and p < 0.05).ConclusionOur data suggest that vitamin E counteracts endothelial activation in T2DM patients possibly representing a new tool for endothelial protection.