A common observation in diabetic kidney disease is lipid accumulation, but the mechanism(s) underlying this pathology is unknown. Inhibition of Vascular endothelial growth factor B (VEGF-B) signaling was shown to prevent glomerular lipid accumulation and ameliorated diabetic kidney disease in experimental models. Here, we examined kidney biopsies from patients with Type 2 (84%) and Type 1 diabetes (16%), combined with data mining of RNA-seq dataset analyses in patients with diabetic kidney disease.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
September 2024
Keratin intermediate filaments form dynamic filamentous networks, which provide mechanical stability, scaffolding, and protection against stress to epithelial cells. Keratins and other intermediate filaments have been increasingly linked to the regulation of mitochondrial function and homeostasis in different tissues and cell types. While deletion of keratin 8 (K8) in mouse colon elicits a colitis-like phenotype, epithelial hyperproliferation, and blunted mitochondrial ketogenesis, the role of K8 in colonocyte mitochondrial function and energy metabolism is unknown.
View Article and Find Full Text PDFBackground: Polycystic ovary syndrome's (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead to changes in protein levels and biological function.
Methods: To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry, and analyzed gene expression and methylation.
When discussing glomerular function, one cell type is often left out, the mesangial cell (MC), probably since it is not a part of the filtration barrier per se. The MCs are instead found between the glomerular capillaries, embedded in their mesangial matrix. They are in direct contact with the endothelial cells and in close contact with the podocytes and together they form the glomerulus.
View Article and Find Full Text PDFObjective: To describe the successful restoration of superior eyelid function in a horse following traumatic avulsion using an advancement flap blepharoplasty and subdermal hyaluronic acid filler.
Animal Studied: A 21-year-old American Paint Horse stallion who was attacked by a fellow stallion resulting in numerous traumatic injuries including avulsion of approximately 75% of the left superior eyelid.
Procedures: With standing sedation and locoregional anesthesia, the superior eyelid wound was debrided and an advancement flap blepharoplasty (H-plasty) and temporary tarsorrhaphy were performed.
Introduction: Elevated phosphate (P) in urine may reflect a high intake of inorganic P salts from food additives. Elevated P in plasma is linked to vascular dysfunction and calcification.
Objective: To explore associations between P in urine as well as in plasma and questionnaire-estimated P intake, and incidence of cardiovascular disease (CVD).
Objectives: Performing pediatric otoscopy can be difficult secondary to patient compliance, which potentiates misdiagnosis and inaccurate treatment of acute otitis media. This study used a convenience sample to assess the feasibility of using a video otoscope for the examination of tympanic membranes in children presenting to a pediatric emergency department.
Methods: We obtained otoscopic videos using the JEDMED Horus + HD Video Otoscope.
Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis globally. Because of the heterogeneity of the disease prognostic biomarkers are highly needed.
Aim: To investigate associations between galactose-deficient IgA1 (Gd-IgA1) concentrations in plasma and urine and disease activity and progression in patients with IgAN.
Significance Statement: A tightly regulated actin cytoskeleton attained through balanced activity of RhoGTPases is crucial to maintaining podocyte function. However, how RhoGTPases are regulated by geranylgeranylation, a post-translational modification, has been unexplored. The authors found that loss of the geranylgeranylation enzyme geranylgeranyl transferase type-I (GGTase-I) in podocytes led to progressive albuminuria and foot process effacement in podocyte-specific GGTase-I knockout mice.
View Article and Find Full Text PDFDeciphering the pathophysiological mechanisms of primary podocytopathies that can lead to end-stage renal disease and increased mortality is an unmet need. Studying how microRNAs (miRs) interfere with various signaling pathways enables identification of pathomechanisms, novel biomarkers and potential therapeutic options. We investigated the expression of miR-200c in urine from patients with different renal diseases as a potential candidate involved in podocytopathies.
View Article and Find Full Text PDFKrabbe disease is a rare autosomal recessive neurodegenerative disease, caused by mutations in the GALC gene, which encodes for the lysosomal enzyme galactocerebrosidase. Typical clinical manifestations of Krabbe include psychomotor deterioration, visual loss, seizures, and spasticity, that result from central nervous system demyelination. We report a case of a 35-year-old male with Krabbe who presented in adulthood with isolated severe, upper extremity predominant demyelinating sensorimotor polyneuropathy and did not develop other distinguishing clinical or radiological features of Krabbe until the later stages of the disease.
View Article and Find Full Text PDFKeratin intermediate filaments convey mechanical stability and protection against stress to epithelial cells. Keratins are essential for colon health, as seen in keratin 8 knockout (K8) mice exhibiting a colitis phenotype. We hypothesized that keratins support the nuclear envelope and lamina in colonocytes.
View Article and Find Full Text PDFObjective: To evaluate if previously found associations between low serum bilirubin concentration and kidney function decline is independent of hemoglobin and other key confounders.
Research Design And Methods: Clinical trial data from the SAVOR-TIMI 53 trial as well as the UK primary care electronic healthcare records, Clinical Practice Research Datalink (CPRD), were used to construct three cohorts of patients at risk of chronic kidney disease (CKD). The randomized clinical trial (RCT) cohort from the subset of SAVOR-TIMI 53 trial consisted of 10,555 type-2 diabetic patients with increased risk of cardiovascular disease.
Diabetic kidney disease is a consequence of hyperglycemia and other complex events driven by early glomerular hemodynamic changes and a progressive expansion of the mesangium. The molecular mechanisms behind the pathophysiological alterations of the mesangium are yet to be elucidated. This study aimed at investigating whether lipid signaling might be the missing link.
View Article and Find Full Text PDFFood is an important source of perfluoroalkyl acid (PFAA) exposure for the general adult population, but few data exist for adolescents. Healthy food habits established during adolescence may positively influence health later in life. Associations between serum PFAA concentrations and a healthy eating index (SHEIA15), as well as a diet diversity score (RADDS), were determined in a nationally representative adolescent population from Sweden (Riksmaten Adolescents 2016-2017, RMA).
View Article and Find Full Text PDFThe glomerulus is the functional unit for filtration of blood and formation of primary urine. This intricate structure is composed of the endothelium with its glycocalyx facing the blood, the glomerular basement membrane and the podocytes facing the urinary space of Bowman's capsule. The mesangial cells are the central hub connecting and supporting all these structures.
View Article and Find Full Text PDFPurpose: Simple renal cysts are common benign lesions that arise from the renal parenchyma. Cyst growth can lead to confusion as well as concern from patients and referring providers about the need for imaging follow-up or additional evaluation. The purpose of this study was to evaluate the natural history of simple renal cysts and determine the best metric to characterize cyst evolution.
View Article and Find Full Text PDFPER: and polyfluoroalkyl substances (PFAS) may affect adolescent health, yet factors related to PFAS concentrations in serum are poorly understood. We studied demographic, life-style and physiological determinants of serum PFAS concentrations in Swedish adolescents from a nation-wide survey, Riksmaten Adolescents 2016-17 (RMA, age 10-21 years, n = 1098). Serum samples were analyzed for 42 PFAS, using liquid chromatography-tandem mass spectrometry.
View Article and Find Full Text PDFObjectives: This study aimed to define the proportion of children who seek assistance for poorly controlled fracture pain, identify factors associated with requesting help, and explore caregivers' opioid preferences.
Methods: We enrolled 251 children and their caregivers in the orthopedic surgery clinic of a tertiary care children's hospital. Children 5 to 17 years old presenting within 10 days of injury for follow-up for a single-extremity, nonoperative long bone fracture(s) were eligible.
Rationale & Objective: Immunoglobulin A nephropathy (IgAN) is a common glomerular disease, with mesangial cell proliferation as a major feature. There is no disease-specific treatment. Platelet-derived growth factor (PDGF) contributes to the pathogenesis of IgAN.
View Article and Find Full Text PDFInflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes.
View Article and Find Full Text PDFAll capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and damage to the ESL coupled to proteinuria is seen for example in diabetic kidney disease (DKD). We used the principles of ion exchange chromatography in vivo to elute the highly negatively charged components of the ESL with a 1 M NaCl solution in rats.
View Article and Find Full Text PDFThe purpose of this article is to evaluate interobserver, intraobserver, and interplatform variability and compare the previously established association between texture metrics and tumor histologic subtype using three commercially available CT texture analysis (CTTA) software platforms on the same dataset of large (> 7 cm) renal cell carcinomas (RCCs). CT-based texture analysis was performed on contrast-enhanced MDCT images of large (> 7 cm) untreated RCCs in 124 patients (median age, 62 years; 82 men and 42 women) using three different software platforms. Using this previously studied cohort, texture features were compared across platforms.
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