The protective role of peroxisome proliferator-activated receptor gamma in lipotoxic podocytes.

Podocytes are specialized epithelial cells that maintain the glomerular filtration barrier. These cells are susceptible to lipotoxicity in the obese state and irreversibly lost during kidney disease leading to proteinuria and renal injury. PPARγ is a nuclear receptor whose activation can be renoprotective.

mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity.

Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment.

Assessment of Pre-operative Measurements of Tumor Size by MRI Methods as Survival Predictors in Wild Type IDH Glioblastoma.

We evaluate the performance of three MRI methods to determine non-invasively tumor size, as overall survival (OS) and Progression Free Survival (PFS) predictors, in a cohort of wild type, IDH negative, glioblastoma patients. Investigated protocols included bidimensional (2D) diameter measurements, and three-dimensional (3D) estimations by the ellipsoid or semi-automatic segmentation methods. We investigated OS in a cohort of 44 patients diagnosed with wild type IDH glioblastoma (58.

Assessment of Overall Survival in Glioma Patients as Predicted by Metabolomic Criteria.

We assess the efficacy of the metabolomic profile from glioma biopsies in providing estimates of postsurgical Overall Survival in glioma patients. Tumor biopsies from 46 patients bearing gliomas, obtained neurosurgically in the period 1992-1998, were analyzed by high resolution H magnetic resonance spectroscopy (HR- H MRS), following retrospectively individual postsurgical Overall Survival up to 720 weeks. The Overall Survival profile could be resolved in three groups; Short (shorter than 52 weeks, = 19), Intermediate (between 53 and 364 weeks, = 19) or Long (longer than 365 weeks, = 8), respectively.

ΔNp73 status in peritoneal and ovarian dissemination of appendicular adenocarcinoids (goblet cells).

Introduction: Goblet cell carcinoma (GCC) is an appendicular neoplasia representing less than 5% of all appendicular tumors, found in 0.3-0.9% of the appendectomies, 35-58% of all appendicular neoplasms, and less than 14% of malign appendix tumors.

Long-term caloric restriction ameliorates deleterious effects of aging on white and brown adipose tissue plasticity.

Age-related increased adiposity is an important contributory factor in the development of insulin resistance (IR) and is associated with metabolic defects. Caloric restriction (CR) is known to induce weight loss and to decrease adiposity while preventing metabolic risk factors. Here, we show that moderate 20% CR delays early deleterious effects of aging on white and brown adipose tissue (WAT and BAT, respectively) function and improves peripheral IR.

Maintenance of Kidney Metabolic Homeostasis by PPAR Gamma.

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear hormone receptors that control the transcription of specific genes by binding to regulatory DNA sequences. Among the three subtypes of PPARs, PPARγ modulates a broad range of physiopathological processes, including lipid metabolism, insulin sensitization, cellular differentiation, and cancer. Although predominantly expressed in adipose tissue, PPARγ expression is also found in different regions of the kidney and, upon activation, can redirect metabolism.

MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse.

In a Dutch consanguineous family with recessively inherited nonsyndromic hearing impairment (HI), homozygosity mapping combined with whole-exome sequencing revealed a MPZL2 homozygous truncating variant, c.72del (p.Ile24Metfs22).

The expression of oxidative stress response genes is modulated by a combination of resveratrol and N-acetylcysteine to ameliorate ototoxicity in the rat cochlea.

Aminoglycoside antibiotics are used widely in medicine despite their ototoxic side-effects. Oxidative stress and inflammation are key mechanisms determining the extent and severity of the damage. Here we evaluate the protective effect of a treatment with resveratrol plus N-acetylcysteine on the ototoxic actions of kanamycin and furosemide in the rat.

Phenotypic Variation in Patients with Homozygous c.1678G>T Mutation in EVC Gene: Report of Two Mexican Families with Ellis-van Creveld Syndrome.

BACKGROUND Ellis-van Creveld syndrome is an autosomal recessive chondro-ectodermal dysplasia characterized by disproportionate short stature, limb shortening, narrow chest, postaxial polydactyly and dysplastic nails and teeth. In addition, 60% of cases present congenital heart defects. Ellis-van Creveld syndrome is predominantly caused by mutations in the EVC or EVC2 (4p16) genes, with only a few cases caused by mutations in WDR35.

Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives.

The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases. Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically. Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.

Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations.

Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus.

Enhanced brain-derived neurotrophic factor delivery by ultrasound and microbubbles promotes white matter repair after stroke.

Ultrasound-targeted microbubble destruction (UTMD) has been shown to be a promising tool to deliver proteins to select body areas. This study aimed to analyze whether UTMD was able to deliver brain-derived neurotrophic factor (BDNF) to the brain, enhancing functional recovery and white matter repair, in an animal model of subcortical stroke induced by endothelin (ET)-1. UTMD was used to deliver BDNF to the brain 24 h after stroke.

Coarse-grained molecular dynamics simulation of water diffusion in the presence of carbon nanotubes.

Computational modeling of the translational diffusion of water molecules in anisotropic environments entails vital relevance to understand correctly the information contained in the magnetic resonance images weighted in diffusion (DWI) and of the diffusion tensor images (DTI). In the present work we investigated the validity, strengths and weaknesses of a coarse-grained (CG) model based on the MARTINI force field to simulate water diffusion in a medium containing carbon nanotubes (CNTs) as models of anisotropic water diffusion behavior. We show that water diffusion outside the nanotubes follows Ficḱs law, while water diffusion inside the nanotubes is not described by a Ficḱs behavior.

White matter injury restoration after stem cell administration in subcortical ischemic stroke.

Introduction: Despite its high incidence, nerve fiber (axon and myelin) damage after cerebral infarct has not yet been extensively investigated. The aim of this study was to investigate white matter repair after adipose-derived mesenchymal stem cell (ADMSC) administration in an experimental model of subcortical stroke. Furthermore, we aimed to analyze the ADMSC secretome and whether this could be implicated in this repair function.

Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity, and insulin resistance.

Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance, which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and nonalcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Because adult hepatocytes fail to induce COX-2 expression regardless of the proinflammatory stimuli used, we have evaluated whether this lack of expression under mild proinflammatory conditions might constitute a permissive condition for the onset of insulin resistance.

Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke.

Background And Purpose: Translational research is beginning to reveal the importance of trophic factors as a therapy for cellular brain repair. The purpose of this study was to analyze whether brain-derived neurotrophic factor (BDNF) administration could mediate oligodendrogenesis and remyelination after white matter injury in subcortical stroke.

Methods: Ischemia was induced in rats by injection of endothelin-1.

Interaction between PARP-1 and HIF-2α in the hypoxic response.

Hypoxia-inducible factors (HIFs) mediate the transcriptional adaptation of hypoxic cells. The extensive transcriptional programm regulated by HIFs involves the induction of genes controlling angiogenesis, cellular metabolism, cell growth, metastasis, apoptosis, extracellular matrix remodeling and others. HIF is a heterodimer of HIF-α and HIF-β subunits.

Insulin receptor substrate 2 (IRS2)-deficient mice show sensorineural hearing loss that is delayed by concomitant protein tyrosine phosphatase 1B (PTP1B) loss of function.

The insulin receptor substrate (IRS) proteins are key mediators of insulin and insulinlike growth factor 1 (IGF-1) signaling. Protein tyrosine phosphatase (PTP)-1B dephosphorylates and inactivates both insulin and IGF-1 receptors. IRS2-deficient mice present altered hepatic insulin signaling and β-cell failure and develop type 2-like diabetes.

Transgenic mice expressing cyclooxygenase-2 in hepatocytes reveal a minor contribution of this enzyme to chemical hepatocarcinogenesis.

Cyclooxygenase-2 (COX-2) has been associated with cell growth regulation, tissue remodeling, and carcinogenesis. Ectopic expression of COX-2 in hepatocytes constitutes a nonphysiological condition ideal for evaluating the role of prostaglandins (PGs) in liver pathogenesis. The effect of COX-2-dependent PGs in chronic liver disease, hepatitis, fibrosis, and chemical hepatocarcinogenesis, has been investigated in transgenic (Tg) mice that express human COX-2 in hepatocytes and in Tg hepatic human cell lines.

Imaging tumor hypoxia by magnetic resonance methods.

Tumor hypoxia results from the negative balance between the oxygen demands of the tissue and the capacity of the neovasculature to deliver sufficient oxygen. The resulting oxygen deficit has important consequences with regard to the aggressiveness and malignancy of tumors, as well as their resistance to therapy, endowing the imaging of hypoxia with vital repercussions in tumor prognosis and therapy design. The molecular and cellular events underlying hypoxia are mediated mainly through hypoxia-inducible factor, a transcription factor with pleiotropic effects over a variety of cellular processes, including oncologic transformation, invasion and metastasis.

The redox switch/redox coupling hypothesis.

We provide an integrative interpretation of neuroglial metabolic coupling including the presence of subcellular compartmentation of pyruvate and monocarboxylate recycling through the plasma membrane of both neurons and glial cells. The subcellular compartmentation of pyruvate allows neurons and astrocytes to select between glucose and lactate as alternative substrates, depending on their relative extracellular concentration and the operation of a redox switch. This mechanism is based on the inhibition of glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase by NAD(+) limitation, under sufficiently reduced cytosolic NAD(+)/NADH redox conditions.