TFEB-mediated lysosomal exocytosis alleviates high-fat diet-induced lipotoxicity in the kidney.

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown.

Cyclin-dependent kinase 4-related tubular epithelial cell proliferation is regulated by Paired box gene 2 in kidney ischemia-reperfusion injury.

Paired box 2 (Pax2) is a transcription factor essential for kidney development and is reactivated in proximal tubular epithelial cells (PTECs) during recovery from kidney injury. However, the role of Pax2 in this process is still unknown. Here the role of Pax2 reactivation during injury was examined in the proliferation of PTECs using an ischemia-reperfusion injury (IRI) mouse model.

New Technique to Analyze the Breath Sound Spectrum in Children with Asthma.

Objective: Breath sound parameters have been reported as useful biomarkers for evaluating the airway condition.

Methods: The reliability of breath sound analysis using an improved method was investigated. Eighty-three asthmatic children were included in the present study.

A Lung Sound Analysis in Infants with Risk Factors for Asthma During Acute Respiratory Infection.

The parameters of lung sounds have been suggested as biomarkers of airway changes. Using a commercially available lung sound analyzer, we investigated the characteristics of the lung sounds in infants with acute respiratory infection (ARI). Infants with ARI who were 6 to 18 months of age were included in this study.

Eicosapentaenoic acid attenuates renal lipotoxicity by restoring autophagic flux.

Recently, we identified a novel mechanism of lipotoxicity in the kidney proximal tubular cells (PTECs); lipid overload stimulates macroautophagy/autophagy for the renovation of plasma and organelle membranes to maintain the integrity of the PTECs. However, this autophagic activation places a burden on the lysosomal system, leading to a downstream suppression of autophagy, which manifests as phospholipid accumulation and inadequate acidification in lysosomes. Here, we investigated whether pharmacological correction by eicosapentaenoic acid (EPA) supplementation could restore autophagic flux and alleviate renal lipotoxicity.

[EFFECT OF INSPIRATORY FLOW ON BREATH SOUND ANALYSIS IN CHILDREN WITH ASTHMA].

Background: In order to determine the optimal breathing method for childhood lung sound analyses, it is important to study the effect of airflow on the parameters of lung sounds.

Methods: Sixty-one well-controlled children with atopic asthma (median; 12 years) participated. After confirming that there was no wheezing or respiratory symptoms, the lung sound spectrums of the inspiratory flow before and after inhalation of a β stimulant were analyzed.

Guidelines for the medical management of pediatric vesicoureteral reflux.

Urinary tract infection is a bacterial infection that commonly occurs in children. Vesicoureteral reflux is a major underlying precursor condition of urinary tract infection, and an important disorder in the field of pediatric urology. Vesicoureteral reflux is sometimes diagnosed postnatally in infants with fetal hydronephrosis diagnosed antenatally.

Changes in the Breath Sound Spectrum with Bronchodilator Inhalation in Asthmatic Children with Long-term Management.

Objective: Using a commercially available breath sound analyzer, the airway reversibility in asthmatic children during healthy periods was investigated.

Methods: Fifty samples of 34 children with asthma (median age, 11 years; range, 6-16 years) who visited our hospital and whose lung function was normal were included. The breath sound parameters, the frequency limiting 99% of the power spectrum (F) and spectrum curve indices, the total area under the curve of the dBm data (A/A and B/A) and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF and RPF) were evaluated before and after β agonist inhalation.

Autophagy protects kidney from phosphate-induced mitochondrial injury.

Hyperphosphatemia is a common complication in patients with advanced chronic kidney disease (CKD) as well as an increased risk of cardiovascular mortality; however, the molecular mechanisms of phosphate-mediated kidney injury are largely unknown. Autophagy is a lysosomal degradation system, which plays protective roles against kidney diseases. Here, we studied the role of autophagy in kidney proximal tubular cells (PTECs) during phosphate overload.

Metabolic effects of RUBCN/Rubicon deficiency in kidney proximal tubular epithelial cells.

Macroautophagy/autophagy is a lysosomal degradation system which plays a protective role against kidney injury. RUBCN/Rubicon (RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein) inhibits the fusion of autophagosomes and lysosomes. However, its physiological role in kidney proximal tubular epithelial cells (PTECs) remains uncertain.

The Evaluation of Changes in the Breath Sound Spectrum with Bronchoconstriction and Bronchodilatation in Asthmatic Children.

Objective: Focusing on the relative-middle sound area of the breath sound spectrum, the relationship between airway changes and breath sounds in asthmatic children was investigated.

Methods: In Study 1, 77 children (6-16 years old) were included. The breath sound parameters, the ratio of the second area to the third area of the power spectrum (A/A) and the ratio of the third area to the fourth area (B/B) were evaluated 3 times, before and just after methacholine inhalation and after β agonist inhalation.

Podocyte Injury Augments Intrarenal Angiotensin II Generation and Sodium Retention in a Megalin-Dependent Manner.

We have previously shown that podocyte injury increases the glomerular filtration of liver-derived Agt (angiotensinogen) and the generation of intrarenal Ang II (angiotensin II) and that the filtered Agt is reabsorbed by proximal tubules in a manner dependent on megalin. In the present study, we aimed to study the role of megalin in the generation of renal Ang II and sodium handling during nephrotic syndrome. We generated proximal tubule-specific megalin KO (knockout) mice and crossed these animals with NEP25 mice, in which podocyte-specific injury can be induced by injection of the immunotoxin LMB2.

Objective measurement of nocturnal cough in infants with acute bronchiolitis.

Objectives: The objective measurement of the cough severity and the assessment of the pattern of nocturnal coughing could be useful in the treatment of respiratory diseases in children.

Study Design: In children with respiratory syncytial virus (RSV)-induced acute bronchiolitis, coughs were recorded using our original system with a microphone and accelerometer, and analyzed using our customized software program. The number of coughs in every 30-minute interval was measured in patients with acute bronchiolitis (n = 20), and their results were compared with those of infants with asthma exacerbation (n = 16).

Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes.

Background: Evidence of a protective role of autophagy in kidney diseases has sparked interest in autophagy as a potential therapeutic strategy. However, understanding how the autophagic process is altered in each disorder is critically important in working toward therapeutic applications.

Methods: Using cultured kidney proximal tubule epithelial cells (PTECs) and diabetic mouse models, we investigated how autophagic activity differs in type 1 versus type 2 diabetic nephropathy.

Adipocytes do not significantly contribute to plasma angiotensinogen.

Recently, it has been reported that 25% of plasma angiotensinogen (Agt) is derived from fat. Meanwhile, liver-specific Agt knockout (KO) mice have markedly low plasma Agt, which may be due to reduced fat mass. To study the contribution of the fat to plasma Agt, we tested whether increasing fat mass can elevate plasma Agt and blood pressure in liver- Agt KO mice.

Lipophagy maintains energy homeostasis in the kidney proximal tubule during prolonged starvation.

Macroautophagy/autophagy is a self-degradation process that combats starvation. Lipids are the main energy source in kidney proximal tubular cells (PTCs). During starvation, PTCs increase fatty acid (FA) uptake, form intracellular lipid droplets (LDs), and hydrolyze them for use.

En Bloc Cadaver Kidney Transplantation From a 9-Month-Old Donor to an Adult Recipient: Maturation of Glomerular Size and Podocyte in the Recipient.

Background: Favorable outcomes of en bloc pediatric donor kidney transplantation to adult recipients are attributed primarily to grafting of twice the nephron mass of a single kidney.

Methods: The kidneys of a 9-month-old male infant were transplanted en bloc in a 56-year-old man. Biopsies were performed 1 hour postreperfusion, 6 months and 3.

Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules.

Advanced glycation end products (AGEs) are involved in the progression of diabetic nephropathy. AGEs filtered by glomeruli or delivered from the circulation are endocytosed and degraded in the lysosomes of kidney proximal tubular epithelial cells (PTECs). Autophagy is a highly conserved degradation system that regulates intracellular homeostasis by engulfing cytoplasmic components.

Losartan attenuates the coronary perivasculitis through its local and systemic anti-inflammatory properties in a murine model of Kawasaki disease.

Background: Kawasaki disease is a common systemic vasculitis that leads to coronary artery lesions. Besides its antihypertensive effects, losartan can modulate inflammation in cardiovascular disease. We examined whether losartan can attenuate coronary inflammation in a murine model of Kawasaki disease.

Distinct neural mechanisms for the control of thirst and salt appetite in the subfornical organ.

Body fluid conditions are continuously monitored in the brain to regulate thirst and salt-appetite sensations. Angiotensin II drives both thirst and salt appetite; however, the neural mechanisms underlying selective water- and/or salt-intake behaviors remain unknown. Using optogenetics, we show that thirst and salt appetite are driven by distinct groups of angiotensin II receptor type 1a-positive excitatory neurons in the subfornical organ.

High-Fat Diet-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney.

Excessive fat intake contributes to the progression of metabolic diseases cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs).