Novel roles of HIF-PHIs in chronic kidney disease : the link between iron metabolism, kidney function, and FGF23

Hanudel et al. investigated the effects of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) on iron metabolism in a chronic kidney disease (CKD) mouse model and showed that vadadustat, an HIF-PHI, exerted beneficial effects on anemia and iron disorders independently of erythroferrone. Vadadustat also inhibited the progression of CKD and the CKD-associated increase of plasma fibroblast growth factor 23 in CKD mice. This study provides new insights into the action of HIF-PIHs in CKD

The role of iron, a trace nutrient, on diabetes

The nutrient balance is an important factor to keep healthy state in the body. In various nutrients, iron is a most abundant trace metal element. Iron-deficient anemia is often seen in the iron-related disorders, therefore, lots of functional food, drink, and nutritional supplement are widely provided and used to prevent iron deficiency. On the other hand, over iron intake induces excess iron status, causing increased oxidative stress production via catalyzing Fenton reaction. Recent evidences suggest that iron involves the pathological conditions of non-iron accumulating diseases, and the role of iron is noticed again. Diabetes is associated with poor prognosis to develop a variety of complications such as cardiovascular disease and diabetic kidney disease（DKD）in addition to diabetic retinopathy and neuropathy. Moreover, patients with diabetes often present reduced skeletal muscle mass, and it causes more impaired insulin resistance by diminishing glucose uptake. Recent studies have shown that iron content is associated with diabetic and obese condition, and high iron intake increases diabetes risk. We have clarified the favorable effect of iron reduction on obesity and DKD through diminishing oxidative stress. In addition, excess iron caused skeletal muscle atrophy and it was ameliorated by an anti-oxidant drug. Thus, iron plays an important role in diabetes and its complication through oxidative stress production. Further studies are clarifying an important role of trace nutrient including iron and so on, contributing to the development of new therapeutic strategy

Novel role of the biometal element iron in the development of therapeutic strategies

Iron is the most abundant trace metal and indispensable for the biogenicity of living organisms. Iron deficiency anemia is often observed in iron-related disorders, and therefore, proactive iron intake is recommended. In contrast, iron causes oxidative stress by catalyzing the Fenton reaction. Recent evidence suggests that iron is involved in the pathophysiology of non-iron-accumulating diseases, and the role of iron has been revisited. In the last three decades, many studies have shown that iron content is associated with diabetes and that high iron intake increases the risk of diabetes onset. Iron reduction by phlebotomy or iron chelators ameliorates insulin sensitivity and secretion. Several studies have shown that high iron levels are also associated with obesity. Therefore, we speculate that iron reduction could exert a favorable effect on obesity. As expected, iron chelators mitigated obesity by inhibiting inflammatory cytokines and oxidative stress in KKAy mice. We advocate that “iron stress” is related to iron-dependent inflammation and oxidative stress, and have reported that iron stress is involved in kidney disease, sarcopenia, vascular dysfunction, and so on. However, non-specific iron reduction always causes iron-deficient adverse effects, such as anemia, and it is difficult to adopt a clinical application. Macrophage plays a critical role in chronic inflammation including obesity and diabetes. M1 inflammatory macrophages exhibit an iron-retention phenotype with elevated H-ferritin（ FTH） expression. Mice with macrophage-specific FTH deletion（FTHKO） showed reduced iron concentrations in macrophages, without anemia. HFD- induced obesity and diabetes were alleviated in FTHKO mice by inhibiting inflammation and oxidative stress in adipose tissue, similar to the effect of systemic iron reduction. Therefore, macrophages are the main source of iron stress, leading to new therapeutic strategies for controlling the iron levels in macrophages

The role of iron in obesity and diabetes

Iron is an essential trace metal for all life, but excess iron causes oxidative stress through catalyzing the toxic hydroxy-radical production via the Fenton reaction. The number of patients with obesity and diabetes has been increasing worldwide, and their onset and development are affected by diet. In both clinical and experimental studies, a high body iron content was associated with obesity and diabetes, and the reduction of body iron content to an appropriate level can ameliorate the status and development of obesity and diabetes. Macrophages play an essential role in the pathophysiology of obesity and diabetes, and in the metabolism and homeostasis of iron in the body. Recent studies demonstrated that macrophage polarization is related to adipocyte hypertrophy and insulin resistance through their capabilities of iron handling. Control of iron in macrophages is a potential therapeutic strategy for obesity and diabetes

The role of iron, a trace nutrient, on diabetes

The nutrient balance is an important factor to keep healthy state in the body. In various nutrients, iron is a most abundant trace metal element. Iron-deficient anemia is often seen in the iron-related disorders, therefore, lots of functional food, drink, and nutritional supplement are widely provided and used to prevent iron deficiency. On the other hand, over iron intake induces excess iron status, causing increased oxidative stress production via catalyzing Fenton reaction. Recent evidences suggest that iron involves the pathological conditions of non-iron accumulating diseases, and the role of iron is noticed again. Diabetes is associated with poor prognosis to develop a variety of complications such as cardiovascular disease and diabetic kidney disease（DKD）in addition to diabetic retinopathy and neuropathy. Moreover, patients with diabetes often present reduced skeletal muscle mass, and it causes more impaired insulin resistance by diminishing glucose uptake. Recent studies have shown that iron content is associated with diabetic and obese condition, and high iron intake increases diabetes risk. We have clarified the favorable effect of iron reduction on obesity and DKD through diminishing oxidative stress. In addition, excess iron caused skeletal muscle atrophy and it was ameliorated by an anti-oxidant drug. Thus, iron plays an important role in diabetes and its complication through oxidative stress production. Further studies are clarifying an important role of trace nutrient including iron and so on, contributing to the development of new therapeutic strategy

COVID-19と心疾患

Coronavirus disease-2019（COVID-19） induces of multi-organs damage including heart, vessels, and lung neurological systems in addition to respiratory disorders, causing subsequent complications. Patients with cardiovascular damage induced by COVID-19 show ischemic heart disease, arrhythmias, and venous thromboembolism, resulting in death. Patients with a medical history of hypertension, diabetes, and coronary artery disease are associated with an increased rate of aggravation and mortality. It is very important to prevent the onset of cardiovascular complications caused by COVID-19, however, there are no therapeutics for them and new treatments and therapeutic agents need to be developed. Kampo medicine is a traditional Japanese herbal medicine and has been attracting attention in the treatment of COVID-19. This article outlines the pathophysiological findings of COVID-19-related cardiovascular complications and the potential effect of Kampo as supportive care against it

Thermodynamic study of gap structure and pair-breaking effect by magnetic field in the heavy-fermion superconductor CeCu2Si2

This paper presents the results of specific-heat and magnetization measurements, in particular their field-orientation dependence, on the first discovered heavy-fermion superconductor CeCu$_2$Si$_2$ ($T_{\rm c} \sim 0.6$ K). We discuss the superconducting gap structure and the origin of the anomalous pair-breaking phenomena, leading e.g., to the suppression of the upper critical field $H_{\rm c2}$, found in the high-field region. The data show that the anomalous pair breaking becomes prominent below about 0.15 K in any field direction, but occurs closer to $H_{\rm c2}$ for $H \parallel c$. The presence of this anomaly is confirmed by the fact that the specific-heat and magnetization data satisfy standard thermodynamic relations. Concerning the gap structure, field-angle dependences of the low-temperature specific heat within the $ab$ and $ac$ planes do not show any evidence for gap nodes. From microscopic calculations in the framework of a two-band full-gap model, the power-law-like temperature dependences of $C$ and $1/T_1$, reminiscent of nodal superconductivity, have been reproduced reasonably. These facts further support multiband full-gap superconductivity in CeCu$_2$Si$_2$.Comment: 10 pages, 8 figures, published in Phys. Rev.