Nicotinamide ameliorates podocyte injury and albuminuria in adriamycin-induced nephropathy.

Podocytes are key components of the glomerular filtration barrier, and their injury leads to proteinuria, chronic kidney disease (CKD), and nephrotic syndrome. Effective treatments for these conditions are not well established, and prevention of podocyte injury is a crucial challenge. Nicotinamide (NAM), a form of vitamin B3, has been reported to exert beneficial effects in various renal disease models due to its antioxidant and anti-inflammatory properties and its ability to replenish nicotinamide adenine dinucleotide (NAD).

Hemodialysis employing molecular hydrogen (H) enriched dialysis solution may improve dialysis related fatigue through impact on energy metabolism.

Hemodialysis employing molecular hydrogen (H)-enriched dialysis solution rendered by water electrolysis (E-HD), has been reported to alleviate dialysis-related fatigue, but its association with metabolic profiles remains unclear. Eighty-one patients undergoing standard HD were classified into 3 groups [Group A (n = 25, 30.9%): fatigue with activity reduction-subgroups A1: chronic persistent fatigue (n = 11), A2: fatigue only on dialysis days (n = 14); Group B: fatigue without activity reduction (n = 24, 29.

Generation of thiyl radicals in a spatiotemporal controlled manner by light: Applied for the cis to trans isomerization of unsaturated fatty acids/phospholipids.

Thiyl radicals are important reactive sulfur species and can cause cis to trans isomerization on unsaturated fatty acids. However, biocompatible strategies for the controlled generation of thiyl radicals are still lacking. In this work, we report the study of a series of naphthacyl-derived thioethers as photo-triggered thiyl radical precursors.

Conjugated fatty acids drive ferroptosis through chaperone-mediated autophagic degradation of GPX4 by targeting mitochondria.

Conjugated fatty acids (CFAs) have been known for their anti-tumor activity. However, the mechanism of action remains unclear. Here, we identify CFAs as inducers of glutathione peroxidase 4 (GPX4) degradation through chaperone-mediated autophagy (CMA).

Impacts of low birthweight on kidney development and intergenerational growth of the offspring.

Low birthweight (LBW) increases the risk of adult-onset diseases, including kidney diseases, with intergenerational consequences; however, the underlying mechanisms and effective interventions are unclear. To examine the cross-generational effects of LBW, we established an LBW mouse model through reduced uterine perfusion pressure (RUPP) and investigated the therapeutic potential of tadalafil, a phosphodiesterase 5 inhibitor, on LBW-associated consequences. RUPP-pups (R1) had lower fetal and birth weights, delayed renal development, and fewer glomeruli than Sham-pups.

Industrially produced trans-fatty acids are potent promoters of DNA damage-induced apoptosis.

trans-Fatty acids (TFAs) are unsaturated fatty acids harboring at least one carbon-carbon double bond in trans configuration, which are categorized into two groups according to their origin: industrial and ruminant TFAs, hereafter called iTFAs and rTFAs, respectively. Numerous epidemiological studies have shown a specific link of iTFAs to various diseases, such as cardiovascular and neurodegenerative diseases. However, there is little evidence for underlying mechanisms that can explain the specific toxicity of iTFAs, and how to mitigate their toxicity.

A comprehensive toxicological analysis of trans-fatty acids (TFAs) reveals a pro-apoptotic action specific to industrial TFAs counteracted by polyunsaturated FAs.

trans-Fatty acids (TFAs) are unsaturated fatty acids containing at least one carbon-carbon double bond in trans configuration, which are classified into two groups according to their food source: industrial TFAs (iTFAs) and ruminant TFAs (rTFAs). Previous epidemiological evidence has demonstrated a preferential association of iTFAs, rather than rTFAs, with various diseases including cardiovascular diseases. However, it is still unknown how iTFAs exert their specific toxicity and what effective treatments are available to mitigate their toxicity.

What's New in the Molecular Mechanisms of Diabetic Kidney Disease: Recent Advances.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease, including end-stage kidney disease, and increases the risk of cardiovascular mortality. Although the treatment options for DKD, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists, have advanced, their efficacy is still limited. Thus, a deeper understanding of the molecular mechanisms of DKD onset and progression is necessary for the development of new and innovative treatments for DKD.

Myeloid cell-derived coagulation tissue factor is associated with renal tubular damage in mice fed an adenine diet.

Patients with chronic kidney disease (CKD) commonly exhibit hypercoagulability. Increased levels of uremic toxins cause thrombogenicity by increasing tissue factor (TF) expression and activating the extrinsic coagulation cascade. TF is induced in monocytes and macrophages under pathological conditions, such as inflammatory diseases.

Effect of uremic toxins on hippocampal cell damage: analysis in vitro and in rat model of chronic kidney disease.

One third of the patients with chronic kidney disease (CKD) develop cognitive impairment, which is also an independent risk factor for mortality. However, the concise mechanism of cerebro-renal interaction has not been clarified. The present study examines the effects of uremic toxins on neuronal cells and analyzes the pathological condition of the brain using mouse hippocampal neuronal HT-22 cells and adenine-induced CKD model rats.

Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease.

Nicotinamide adenine dinucleotide (NAD) supplies energy for deoxidation and anti-inflammatory reactions fostering the production of adenosine triphosphate (ATP). The kidney is an essential regulator of body fluids through the excretion of numerous metabolites. Chronic kidney disease (CKD) leads to the accumulation of uremic toxins, which induces chronic inflammation.

Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet.

Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet.

The effect of aldosterone on adiposity - The role of glucose absorption in the small intestine.

We have previously demonstrated that manipulation of the renin angiotensin system (RAS) has large effects on digestive efficiency. However, the effects of aldosterone on body weight, adiposity, and glucose absorption in the intestine remains unknown. We here demonstrated that lack of aldosterone synthase (ASKO) in mice did not affect adiposity.

Protease-activated receptor 2 contributes to placental development and fetal growth in mice.

Background: Protease-activated receptor 2 (PAR2) is activated by serine proteases such as coagulation tissue factor/VIIa complex, factor Xa or trypsin and is pro-angiogenic in several disease models. Impaired angiogenesis in placenta causes placental dysfunction and fetal growth restriction. PAR2 is expressed in the placenta trophoblast.

Metabolomics of a mouse model of preeclampsia induced by overexpressing soluble fms-like tyrosine kinase 1.

Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model.

Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease.

Protease-activated receptors (PARs) are coagulation protease targets, and they increase expression of inflammatory cytokines and chemokines in various diseases. Of all PARs, previous reports have shown that PAR1 or PAR2 inhibition is protective against diabetic glomerular injury. However, how PAR1 and PAR2 cooperatively contribute to diabetic kidney disease (DKD) pathogenesis and whether dual blockade of PARs is more effective in DKD remain elusive.

Effects of the oral adsorbent AST-120 on fecal p-cresol and indole levels and on the gut microbiota composition.

In chronic kidney disease, elevated levels of circulating uremic toxins are associated with a variety of symptoms and organ dysfunction. Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are microbiota-derived metabolites and representative uremic toxins. We have previously shown that the oral adsorbent AST-120 profoundly reduced pCS compared to IS in adenine-induced renal failure in mice.

Drugs Repurposed as Antiferroptosis Agents Suppress Organ Damage, Including AKI, by Functioning as Lipid Peroxyl Radical Scavengers.

Background: Ferroptosis, nonapoptotic cell death mediated by free radical reactions and driven by the oxidative degradation of lipids, is a therapeutic target because of its role in organ damage, including AKI. Ferroptosis-causing radicals that are targeted by ferroptosis suppressors have not been unequivocally identified. Because certain cytochrome P450 substrate drugs can prevent lipid peroxidation obscure mechanisms, we evaluated their antiferroptotic potential and used them to identify ferroptosis-causing radicals.