A5029372617- Aldose Reductase and Taurine
- Acute Kidney Injury Research
- Mesenchymal stem cell research
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Cancer, Hypoxia, and Metabolism
- Chronic Kidney Disease and Diabetes
- Eicosanoids and Hypertension Pharmacology
- Extracellular vesicles in disease
- Parathyroid Disorders and Treatments
- Cancer-related Molecular Pathways
- Clusterin in disease pathology
- Renal and related cancers
- Heme Oxygenase-1 and Carbon Monoxide
- Cardiac Ischemia and Reperfusion
- Tissue Engineering and Regenerative Medicine
- Cancer Risks and Factors
- Trace Elements in Health
- Dialysis and Renal Disease Management
- Lipid metabolism and disorders
- Pancreatitis Pathology and Treatment
- Neonatal Respiratory Health Research
- Renal and Vascular Pathologies
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
Universidad de Los Andes, Chile
2015-2025
National Institutes of Health
2004-2009
Universidad de Los Andes
2009
National Heart Lung and Blood Institute
2008-2009
University of Chile
1996-2006
Wilfrid Laurier University
2000
Therapeutic approaches for CKD (chronic kidney disease) have been able to reduce proteinuria, but not diminish the disease progression. We demonstrated beneficial effects by injection of BM (bone marrow)-derived MSCs (mesenchymal stem cells) from healthy donors in a rat model with CKD. However, it has recently reported that BM-MSCs derived uraemic patients failed confer functional protection similar model. This suggests autologous are suitable treatment In present study, we explored...
Introduction Preeclampsia is a maternal hypertensive disorder with uncertain etiology and leading cause of fetal mortality worldwide, causing nearly 40% premature births delivered before 35 weeks gestation. The first stage preeclampsia characterized by reduction utero-placental blood flow which reflected in high pressure proteinuria during the second half pregnancy. In human placenta androgens derived from adrenal glands are converted into estrogens enzymatic action placental aromatase. This...
High NaCl activates the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP), resulting in increased of several protective genes, including glycine betaine/gamma-aminobutyric acid transporter (BGT1). damages DNA, and DNA damage ataxia telangiectasia mutated (ATM) kinase through autophosphorylation on Ser-1981. TonEBP/OREBP contains ATM consensus phosphorylation sites at Ser-1197, Ser-1247, Ser-1367. The present studies test whether is...
CKD (chronic kidney disease) has become a public health problem. The therapeutic approaches have been able to reduce proteinuria, but not successful in limiting disease progression. In this setting, cell therapies associated with regenerative effects are attracting increasing interest. We evaluated the effect of MSC (mesenchymal stem cells) on progression and expression molecular biomarkers effects. Adult male Sprague-Dawley rats subjected 5/6 NPX (nephrectomy) received single intravenous...
Background/Objectives: Pain management in colorectal cancer is influenced by genetic variability opioid receptor genes (OPRM1 and OPRD1), potentially affecting efficacy adverse drug reactions (ADRs). This study evaluated the association of OPRM1 (rs1799971 rs510769) OPRD1 (rs2236861) polymorphisms with pain severity, efficacy, ADRs Chilean patients. Methods: The genotypes clinical data from 69 patients were analyzed. Associations between genotypes, ADRs, severity (maximum Visual Analog...
High NaCl causes DNA double-strand breaks and activates the transcription factor, TonEBP/OREBP, resulting in increased of several protective genes, including those involved accumulation compatible organic osmolytes. Several kinases are known to contribute signaling activation ATM, which is a member phosphatidylinositol 3-kinase (PI3K)-like kinase family activated by breaks. The purpose present studies was investigate possible role PI3K Class IA (PI3K-IA). We found that high increases PI3K-IA...
Tubular damage has a role in Diabetic Kidney Disease (DKD). We evaluated the early tubulointerstitial biomarkers type-1 Diabetes Mellitus (T1DM) pediatric participants and studied correlation with classical DKD parameters.Thirty-four T1DM fifteen healthy were enrolled. Clinical biochemical parameters [Glomerular filtration Rate (GFR), microalbuminuria (MAU), albumin/creatinine ratio (ACR), glycated hemoglobin A1c (HbA1c)] evaluated. Neutrophil gelatinase-associated lipocalin (NGAL),...
To assess the role of several genetic factors in combination with an environmental factor as modulators prostate cancer risk. We focus on allele variants low-penetrance genes associated cell control, detoxification processes and smoking.In a case-control study we compared people carrying p53cd72 Pro allele, CYP1A1 M1 GSTM1 null genotypes their risk.The joint risk for smokers Pro* M1*, GSTM1null or M1* was significantly higher (odds ratio [OR]: 13.13, 95% confidence interval [CI]: 2.41-71.36;...
Potent immunosuppressive and regenerative properties of mesenchymal stem cells (MSCs) position them as a novel therapy for autoimmune diseases. This research examines the therapeutic effect MSCs administration at different disease stages in experimental encephalomyelitis (EAE). Classical atypical scores EAE, associated with Th1 Th17 response, respectively, also Treg lymphocytes, were evaluated. onset (EAE+MSC ) induced an important amelioration clinical signs less lasting peak EAE ). No was...
Recently, it has been observed that mesenchymal stem cells (MSCs) can modulate their immunoregulatory properties depending on the specific in-vitro activation of different Toll-like receptors (TLR), such as TLR3 and TLR4. In present study, we evaluated effect polyinosinic:polycytidylic acid (poly(I:C)) lipopolysaccharide (LPS) pretreatment immunological capacity MSCs in vitro vivo.C57BL/6 bone marrow-derived were pretreated with poly(I:C) LPS for 1 hour immunomodulatory was evaluated. T-cell...
The current hypothesis postulates that NFAT5 activation in the kidney's inner medulla is due to hypertonicity, resulting cell protection. Additionally, renal hypoxic (10–18 mmHg); however there no information about effect of hypoxia on NFAT5. Using vivo and vitro models, we evaluated reducing partial pressure oxygen (PO2) activity. We found 1) Anoxia increased expression nuclear translocation primary cultures IMCD cells from rat kidney. 2) transcriptional activity HEK293 cells. 3)...
Hypertonicity (e.g., high NaCl) activates the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP), increasing of protective genes. In present studies, by stably expressing amino acids 1-547 TonEBP/OREBP in HEK 293 cells and immunoprecipitating it plus associated proteins from nuclei exposed to NaCl, we identify 14 that are physically with TonEBP/OREBP. The fall into several classes: 1) DNA-dependent kinase, both its catalytic subunit...
Tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP) is a Rel that activates transcription of osmoprotective genes at high extracellular NaCl. Other proteins NFAT1–4 and NF-κB complex with activator protein-1 (AP-1) to transactivate target through interaction composite NFAT/NF-κB·AP-1 sites. TonEBP/OREBP commonly have one or more conserved AP-1 binding sites near cognate elements (OREs). Also, the c-Fos c-Jun are all activated by We now find, using an ORE·AP-1...
High NaCl elevates activity of the osmoprotective transcription factor TonEBP/OREBP by increasing its phosphorylation, transactivating activity, and localization to nucleus. We investigated possible role in this activation phospholipase C-γ1 (PLC-γ1), which has a predicted binding site at TonEBP/OREBP-phospho-Y143. find following. ( i ) Activation transcriptional high is reduced PLC-γ1 null cells HEK293 knocked down specific siRNA. ii increases phosphorylation Y143. iii Wild-type...
Oxidative stress produces macromolecules dysfunction and cellular damage. Renal ischemia-reperfusion injury (IRI) induces oxidative stress, inflammation, epithelium endothelium damage, cessation of renal function. The IRI is an inevitable process during kidney transplantation. Preliminary studies suggest that aminoguanidine (AG) antioxidant compound. In this study, we investigated the effects AG (50 mg/kg, intraperitoneal) its association with molecular pathways activated by (30 min/48 h) in...
High NaCl activates the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP) by increasing its abundance and transactivation, latter signaled a variety of kinases. In addition, high causes TonEBP/OREBP to translocate into nucleus, but little is known about signals directing this translocation. The result increased protective genes, including those involved in accumulation organic osmolytes. also damages DNA, DNA damage ataxia...
Chronic kidney disease (CKD) is characterized by loss of renal function. The pathological processes involved in the progression this condition are already known, but molecular mechanisms have not been completely explained. Recent reports shown intrinsic capacity to undergo repair after acute injury through reexpression repairing proteins (Villanueva S, Cespedes C, Vio CP. Am J Physiol Regul Integr Comp 290: R861–R870, 2006). Stimulation with basic fibroblast growth factor (bFGF) could...
Fibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes FGF23 levels regulatory factors children on peritoneal dialysis (PD).FGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D parathyroid hormone (PTH) plasma concentrations were measured during 1 year follow-up PD children. Anthropometric dialytical...
During gestation, low oxygen environment is a major determinant of early placentation process, while persistent placental hypoxia leads to pregnancy-related complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). PE affects 5%-8% all pregnancies worldwide cause maternal fetal morbidity mortality. development, due poor trophoblast invasion reduced uteroplacental perfusion endothelial dysfunction clinical manifestation PE. Here we hypothesized that nuclear factor...