The role of glial cells missing 2 in induced pluripotent stem cell parathyroid differentiation.

Glial cells missing 2 (GCM2) has been identified as an essential factor for parathyroid differentiation, and GCM2 silencing in parathyroid cells decreases calcium-sensing receptor (CaSR) expression. However, the role of GCM2 in parathyroid differentiation from induced pluripotent stem cells (iPSCs) is unclear. Here, we investigated the role of GCM2 in parathyroid differentiation from iPSCs using the Tet-On 3 G system.

Long term outcome of C1-esterase inhibitor deficiency.

Hereditary angioedema (HAE) is a rare hereditary disorder characterized by episodic swelling and life-threatening airway obstruction caused by laryngeal angioedema. In most HAE patients, reduced level of serum C1-Inhibitor (type-I-HAE) or presence of aberrant C1-Inhibitor (type-II-HAE) result in the lost of regulation of the complementary system and contact activation system with downstream over-activation of bradykinin - the chief mediator leading to angioedema. Type-III HAE (HAE-nl-C1INH) is rare without deficient or dysfunction of C1-Inhibitor, often with genetic aberrant related to the contact activation system.

Citrin-deficient patient-derived induced pluripotent stem cells as a pathological liver model for congenital urea cycle disorders.

Citrin deficiency is a congenital secondary urea cycle disorder lacking useful disease models for effective treatment development. In this study, human induced pluripotent stem cells (iPSCs) were generated from two patients with citrin deficiency and differentiated into hepatocyte-like cells (HLCs). Citrin-deficient HLCs produced albumin and liver-specific markers but completely lacked citrin protein and expressed argininosuccinate synthase only weakly.

Efficient protocol for the differentiation of kidney podocytes from induced pluripotent stem cells, involving the inhibition of mTOR.

The mechanistic/mammalian target of rapamycin (mTOR) is involved in a wide range of cellular processes. However, the role of mTOR in podocytes remains unclear. In this study, we aimed to clarify the role of mTOR in podocyte differentiation from human induced pluripotent stem cells (hiPSCs) and to establish an efficient differentiation protocol for human podocytes.

The Induction of Parathyroid Cell Differentiation from Human Induced Pluripotent Stem Cells Promoted Via TGF-α/EGFR Signaling.

The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism.

Exposing intracellular molecular changes during the differentiation of human-induced pluripotent stem cells into erythropoietin-producing cells using Raman spectroscopy and imaging.

The objective of this study was to explore intracellular molecular changes during the differentiation of human-induced pluripotent stem cells (iPSCs) into erythropoietin (EPO)-producing cells using Raman spectroscopy and imaging. Raman imaging data of fixed cells at four stages of cell differentiation were analyzed by a partial least squares (PLS) regression model, and the variations in the intracellular molecular compositions with cell differentiation were investigated. As a result, three biomarkers characterizing the cell phases were identified: dimethyl sulfoxide (DMSO), fatty acids with a low grade of unsaturation, and glycoproteins.

Pre-stroke habitual prolonged sleep as a predictor for post-stroke sleep quality, stroke-related quality of life, and lifestyle values.

Background: Prolonged sleep is a higher stroke risk, but post-stroke prolonged sleep facilitates stroke recovery. No study has explored the relationship between pre- and post-stroke prolonged sleep and their involvement in stroke-related quality of life (QOL).This study aimed to clarify the role of pre- and post-stroke prolonged sleep in QOL and sleep quality during hospitalization.

Persistent or permanent atrial fibrillation is associated with severe cardioembolic stroke in patients with non-valvular atrial fibrillation.

Background: Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke severity in patients with CE stroke divided by the type of AF.

Methods: Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied.

Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells.

Erythropoietin (EPO) is a crucial hormone for erythropoiesis and produced by adult kidneys. Insufficient EPO production in chronic kidney disease (CKD) can cause renal anemia. Although hypoxia-inducible factors (HIFs) are known as a main regulator, the mechanisms of EPO production have not been fully elucidated.

CD140b and CD73 are markers for human induced pluripotent stem cell-derived erythropoietin-producing cells.

Renal anemia in chronic kidney disease is treated with recombinant human erythropoietin (rhEPO). However, some patients with anemia do not respond well to rhEPO, emphasizing the need for a more biocompatible EPO. Differentiation protocols for hepatic lineages have been modified to enable production from human induced pluripotent stem cell (hiPSC)-derived EPO-producing cells (EPO cells).

Failure to confirm a sodium-glucose cotransporter 2 inhibitor-induced hematopoietic effect in non-diabetic rats with renal anemia.

Aims/introduction: Clinical studies have shown that treatment with inhibitors of sodium-glucose cotransporter 2 (SGLT2) significantly increases the hematocrit in patients with type 2 diabetes. To investigate whether SGLT2 inhibitors directly promote erythropoietin production independently on blood glucose reduction, the hematopoietic effect of the specific SGLT2 inhibitor, luseogliflozin, was examined in non-diabetic rats with renal anemia.

Materials And Methods: Renal anemia was induced by treatment with adenine (200 or 600 mg/kg/day, orally for 10 days) in non-diabetic Wistar-Kyoto or Wistar rats, respectively.

The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity.

The EMPA-REG OUTCOME study revealed that a sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, can remarkably reduce cardiovascular (CV) mortality and heart failure in patients with high-risk type 2 diabetes. Recently, the CANVAS program also showed that canagliflozin, another SGLT2 inhibitor, induces a lower risk of CV events. However, the precise mechanism by which an SGLT2 inhibitor elicits CV protective effects is still unclear.

Low Body Mass Index is a Poor Prognosis Factor in Cardioembolic Stroke Patients with NonValvular Atrial Fibrillation.

Background: The relationship between body mass index (BMI) and the severity of cardioembolic stroke (CES) remains poorly understood.

Method: A total of 419 consecutive CES patients with nonvalvular atrial fibrillation (NVAF), and with a modified Rankin Scale (mRS) score of 0 or 1 before onset admitted within 48hours after onset to the Hirosaki Stroke and Rehabilitation Center were studied. The patients were divided into three groups, low BMI (L-BMI; n = 36, BMI < 18.

A sodium-glucose cotransporter 2 inhibitor attenuates renal capillary injury and fibrosis by a vascular endothelial growth factor-dependent pathway after renal injury in mice.

Multiple large clinical trials have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors reduce the risk of renal events. However, the mechanism responsible for this outcome remains unknown. Here we investigated the effects of the SGLT2 inhibitor luseogliflozin on the development of renal fibrosis after renal ischemia/reperfusion injury in non-diabetic mice.

Effect of a SGLT2 inhibitor on the systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats.

We aimed to examine the effects of a sodium glucose co-transporter 2 (SGLT2) inhibitor on systemic and intrarenal renin-angiotensin system (RAS) in subtotally nephrectomized non-diabetic rats, a model of chronic kidney disease (CKD). Oral administration of the selective SGLT2 inhibitor, TA-1887 (10 mg/kg/day), for 10 weeks induced glycosuria. However, plasma renin activity, plasma angiotensinogen levels, kidney angiotensin II contents and renal injury were not significantly affected by TA-1887.

A novel approach to adenine-induced chronic kidney disease associated anemia in rodents.

To date, good experimental animal models of renal anemia are not available. Therefore, the purpose of this study was to establish a novel approach to induce chronic kidney disease (CKD) with severe anemia by oral administration of adenine in rodents. Adenine was administered to 6-week-old male C57BL/6 mice (25 and 50 mg/kg body weight) by oral gavage daily for 28 days.

Hypertension with diabetes mellitus complications.

Chronic diabetic complications are classified as microvascular or macrovascular and contribute to mortality and loss of quality of life. Hyperglycemia plays a critical role in the pathogenesis of microvascular complications, such as diabetic retinopathy, incipient nephropathy, and neuropathy, while atherosclerosis contributes to the pathogenesis of macrovascular complications. Diabetes mellitus and hypertension are frequently present together.

A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy.

The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy.

Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.

The production of erythropoietin (EPO) by the kidneys, a principal hormone for the hematopoietic system, is reduced in patients with chronic kidney disease (CKD), eventually resulting in severe anemia. Although recombinant human EPO treatment improves anemia in patients with CKD, returning to full red blood cell production without fluctuations does not always occur. We established a method to generate EPO-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols.

Responses of renal hemodynamics and tubular functions to acute sodium-glucose cotransporter 2 inhibitor administration in non-diabetic anesthetized rats.

The aim of this study is to examine the effects of acute administration of luseogliflozin, the sodium-glucose cotransporter 2 (SGLT2) inhibitor, on renal hemodynamics and tubular functions in anesthetized non-diabetic Sprague Dawley (SD) rats and 5/6 nephrectomized (Nx) SD rats. Renal blood flow (RBF), mean arterial pressure (MAP), and heart rate (HR) were continuously measured and urine was collected directly from the left ureter. Intraperitoneal injection of luseogliflozin (0.

IBMX protects human proximal tubular epithelial cells from hypoxic stress through suppressing hypoxia-inducible factor-1α expression.

Hypoxia predisposes renal fibrosis. This study was conducted to identify novel approaches to ameliorate the pathogenic effect of hypoxia. Using human proximal tubular epithelial cells we showed that a pan-phosphodiesterase (PDE) inhibitor, 3-isobutyl-1-methylxanthine (IBMX) dose and time dependently downregulated hypoxia-inducible factor 1α (HIF-1α) mRNA expression, which was further augmented by addition of a transcriptional inhibitor, actinomycin D.