Neuroblastomas are the most common extracranial solid tumors in children and have a unique feature of neuronal differentiation. Peroxisome proliferator-activated receptor (PPAR)-γ is reported to have neuroprotective effects in addition to having antitumor effects in various cancers. Thus, we aimed to clarify the role of PPAR-γ agonist and antagonist in malignant neuro­blastomas, which also possess neuronal features. In MYCN-amplified neuro­blastoma CHP212 cells, treatment with the PPAR-γ antagonist GW9662 induced growth inhibition in a dose-dependent manner. In addition, the PPAR-γ antagonist treatment changed cell morphology with increasing expression of the neuronal differentiation marker tubulin beta 3 (TUBB3) and induced G1 phase arrest and apoptosis in MYCN-amplified neuro­blastoma. Notably, the PPAR-γ antagonist treatment significantly decreased expression of NMYC, B-cell lymphoma 2 (BCL2) and bromodomain-containing protein 4 (BRD4). It is implied that BRD4, NMYC, BCL2 suppression by the PPAR-γ antagonist resulted in cell growth inhibition, differentiation, and apoptosis induction. In our in vivo study, the PPAR-γ antagonist treatment induced CHP212 cells differentiation and resultant tumor growth inhibition. Our results provide a deeper understanding of the mechanisms of tumor cell differentiation and suggest that PPAR-γ antagonist is a new therapeutic and prevention option for neuro­blastomas.

Fibrosis, induced by reactive oxygen species (ROS) production in neutrophils, has harmful effects on the liver and various other organs. However, little is known about the association between liver fibrosis and ROS levels in neutrophils in the general population. This large-scale epidemiological study aimed to determine the association between liver fibrosis and neutrophil-generated ROS levels according to age and sex in the general population. This cross-sectional study included 1,000 participants from a district health promotion project. Participants were grouped based on sex (male; female) and age (young, <65 years; old, ≥65 years). The four groups were as follows: male, young (n = 289); male, old (n = 100); female, young (n = 425); and female, old (n = 186). Liver fibrosis was assessed using the fibrosis 4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Basal and stimulated ROS were considered in the analysis. Multiple linear analyses showed (1) significant positive corre­lations between all liver fibrosis scores and basal ROS in the young groups, and (2) significant negative correlations between NFS and stimulated ROS in females. Preventing liver fibrosis through neutrophil-related immune system enhancement may avert the development of lifestyle-related diseases and infections.

Lysophosphatidic acid is composed of lysophosphatidic acid (LPA) molecules with varied chemical forms. The present cross-sectional study was conducted to investigate the associations of various LPA molecules with liver fibrosis. Forty-six patients affected by various types of liver disease who underwent an ultrasound-guided liver biopsy were recruited for this study. Liver fibrosis was evaluated using histological grading, as well as shear wave ‍velocity (Vs) and serum level of type IV collagen 7S (T4c7s). Serum levels of LPA molecules were determined using liquid-chromatography tandem mass-spectrometry (LC-MSMS). Total LPA showed a significant positive association with fibrosis severity evaluated based on histological grading, Vs, and T4c7s used as parameters, following adjustment for other confounding factors, including disease type, age, gender, body mass index, and high-sensitivity C-reactive protein. This association was replicated when 16:0-LPA was substituted for total LPA. In contrast, when 20:4-LPA was substituted for total LPA, no significant association with liver fibrosis was observed. In conclusion, the degree of association varied among the different LPA molecule chemical forms, suggesting different pathophysiological roles of individual LPA molecules, although total LPA concentration was shown to be ‍associated with liver fibrosis.

The amounts of Reactive oxygen species (ROS) become higher by strenuous exercises which consume larger amounts of oxygen in active muscles. Since these ROS directly injured muscles, the high ROS concentration involves muscle fatigue. Thus, an immediate ROS scavenging system in the muscle is desired. Since Monascus pigment (MP) involves physiologically active substances which scavenge ROS, it may be a clue to save the muscle injury. However, there are no reports examining MP effects on oxidative stress in skeletal muscle. In this study, we investigated the effect and mechanism of MP on skeletal muscle cells damaged by oxidative stress. The ability to directly eliminate ROS was evaluated by mixing MP solutions with ^・OH and O₂^・−, a type of ROS. The effect of peroxidation in C2C12 cells was evaluated by cell viability assay or western blotting. MP scavenges ^・OH and O₂^・−. MP treatment increases the survival rate under oxidative stress. At that time, the expression of catalase, an antioxidant enzyme, was increased: the enzyme change H₂O₂ into H₂O to rescue the cells under oxidative stress. We conclude that monascus pigment suppressed myotube damage under oxidative stress by both non-enzymatic ROS scavenging and up-regulation of catalase expression.

Coronavirus disease 2019 (COVID-19) vaccines are highly effective; however, vaccine-related adverse events, including autoimmunity, have been reported. Case reports describing relapse or new-onset of ulcerative colitis (UC) after COVID-19 mRNA vaccination are available. However, the molecular mechanisms underlying the development of colonic inflammation associated with COVID-19 mRNA vaccination are poorly understood. Furthermore, it is unclear whether the relapse of UC after COVID-19 vaccination is driven by unique cytokine responses that differ from those of UC not associated with vaccination. mRNAs derived from COVID-19 vaccines are potent inducers of type I IFN response. We encountered three cases of UC relapse after COVID-19 vaccination. mRNA expressions of IFN-α, IFN-β, IL-1β, and IL-12/23p40 showed higher tendency in the colonic mucosa of patients with UC associated with vaccination compared with those not associated with vaccination. In contrast, the expressions of C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 were comparable. Immunofluorescence analyses also showed higher expression of IFN-α in the colonic mucosa of patients with UC associated with COVID-19 vaccination than in those not associated with vaccination. Taken together, these data suggest that the colonic mucosa of patients with UC who relapsed after COVID-19 vaccination was characterized by enhanced type I IFN responses.

Several beneficial effects of poly-γ-glutamic acid (γ-PGA) have been reported. To test whether natto, a fermented soy food rich in γ-PGA, can improve intestinal microbiota content and lipid metabolism in a high-fat diet, we compared the intestinal microbiota content, plasma, liver, and fecal contents, and changes in gene expression in the livers and large intestines of a group of mice fed a high-fat diet supplemented with cooked soybeans (SC group) and a group fed a high-fat diet supplemented with natto (NA group) for 42 days; high-fat diet-fed mice were used as a control (Con group). Hepatic lipid levels were significantly lower, the fecal bile acid and lipid levels were significantly greater, and the Bacteroidetes/Firmicutes ratio was significantly higher in the SC and NA groups as compared to Con group. Additionally, plasma glucose and triglyceride levels, the expression of liver fatty acid synthase, and the relative abundance of Turicibacteraceae, Streptococcaceae, Clostridiaceae, and Peptococcaceae were significantly lower while the relative abundance of Lactobacillaceae was significantly higher in the NA group than in the Con group. Although both natto and cooked soybeans impacted the metabolic response to a high-fat diet, the addition of natto had a greater effect on glucose and lipid metabolism. γ-PGA may play an important role in natto functionality.

The molecular mechanism of aging, which has been a “black box” for many years, has been elucidated in recent years, and the nematode C. elegans, which is a model animal for aging research, has played a major role in its elucidation. From the analysis of C. ‍elegans longevity-related mutant genes, many signal trans­duction systems, with the insulin/insulin-like growth factor signal transduction system at the core, have emerged. It has become clear that this signal transduction system is greatly affected by external nutrients and is involved in the downstream regulation of oxidative stress, which is considered to be one of the main causes of aging.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of potent lipid-lowering drugs. Oxidized low-density lipoprotein (ox-LDL) is the key pathogenic factor leading to atherosclerosis. However, its effect on ox-LDL levels has not been clinically reported. For the very high-risk Atherosclerotic cardiovascular disease (ASCVD) patients, guidelines propose stricter blood lipid control targets to reduce the recurrence of cardiovascular events.

Methods: The clinical data of 290 very high-risk ASCVD patients diagnosed in the First Affiliated Hospital of Zhengzhou University from May 2022 to October 2022 were collected retrospectively. According to whether evolocumab (a PCSK9 inhibitor) was used after percutaneous coronary intervention (PCI), they were divided into evolocumab group (153 cases) and statin monotherapy group (137 cases). At hospital admission, ox-LDL, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteinA1 (apoA1), apolipoprotein B-100 (apoB), lipoprotein (a) (Lp(a)), and high-sensitivity reactive protein (hs-CRP) levels were collected and used as baseline data. The above-mentioned indexes were collected from the outpatient chart approximately 2 weeks after discharge. We compared the lipid profiles and inflammatory markers between baseline and two weeks later.

Results: After two weeks of treatment, TC, TG, LDL-C, apoB, and ox-LDL in the evolocumab group and statin monotherapy group were significantly lower than those before treatment (p<0.05). The decrease of TC, TG, LDL-C, apoB, and ox-LDL in the evolocumab group was more than in the stain monotherapy group (p<0.05). In the evolocumab group, the LDL-C levels decreased by approximately 64.49%. The ox-LDL levels also decreased by 68.09%. The levels of TC and TG decreased 54.49% and 17.60%, respectively. The ApoB levels decreased 51.04%. However, the HDL-C and ApoA1 levels were not significantly different, regardless of evolocumab administration. hs-CRP level in each group was higher than the baseline and the difference was statistically significant.

Conclusion: PCSK9 inhibitors reduce ox-LDL levels in very high-risk ASCVD patients in a short time.

Quercetin is a natural flavonol and has various health beneficial functions. Our pervious study demonstrated that long-term feeding (13 weeks) of quercetin and its glycosides, isoquercitrin, rutin, and enzymatically modified isoquercitrin (EMIQ), which is a mixture of quercetin monoglycoside and its oligoglycosides, prevented hyperglycemia and adiposity in mice fed a high-fat diet but not standard diet. It is, however, unclear whether a single administration of these compounds prevent postprandial hyperglycemia or not. In the present study, we estimated their prevention effect on acute hyperglycemia by an oral glucose tolerance test in ICR mice and investigated its mechanism. It was found that quercetin glycosides, but not the aglycone, suppressed acute hyperglycemia and isoquercitrin showed the strongest effect among the glycosides. As the underlying mechanism, quercetin glycosides promoted translocation of glucose transporter 4 (GLUT4) to the plasma membrane of skeletal muscle of mice through phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its upstream Ca²⁺/calmodulin-dependent protein kinase kinase β (CAMKKβ) without activating the insulin- and JAK/STAT-signal pathways. In conclusion, single oral administration of quercetin glycosides prevented a blood sugar spike by promoting GLUT4 translocation through activating the CAMKKβ/AMPK signaling pathway.

Vitamin D insufficiency, milder than deficiency, is common, and a risk of various diseases. Since vitamin D exert diverse actions, both skeletal and non-skeletal, its insufficiency is a risk of various diseases including osteoporosis, sarcopenia, cardiovascular disease, cancer, and even mortality. Regarding the association of vitamin D status and disease risk, a marked discrepancy exists between the results from the observational studies and intervention studies, mostly yielding the positive and negative results in the former and latter, respectively. Such inconsistency probably arises from methodological problems, of which the baseline vitamin D status would be the most important. Vitamin D intervention would be effective in the deficient/insufficient subjects, but not in sufficient subjects. Since the elderly subjects, especially the institutionalized people, are mostly vitamin D deficient/insufficient, they are likely to benefit from improvement of vitamin D status.

Vitamin insufficiency is a risk of various diseases, and correcting the vitamin status alone would reduce the risk of many diseases, and favorable to avoid the undesirable consequences of polypharmacy in the elderly. Additionally, disease prevention by nutritional improvement is cheap and free from side effects, and suited for the primary prevention of diseases.

Leucine-rich repeat kinase 2 (LRRK2) plays an important role in a variety of inflammatory diseases, as well as peripheral and central immune responses. At present, there are few reports about the role of LRRK2 in lung cancer, and need to be further explored. The main purpose of this study is to explore the role and mechanism of LRRK2 in lung cancer. The results revealed that the expression of LRRK2 was increased in the tissues of lung cancer patient and lung cancer cells. Further studies found that interference with LRRK2 expression significantly induced the apoptosis, and promoted the expression of caspase-3, caspase-9 and Bax. More importantly, si-LRRK2 inhibited the expression of VEGF and P-gp, indicating inhibition of cell proliferation and drug resistance. What’s more, LRRK2 regulated TLR4/NF-κB signaling pathways and NLRP3 inflammasome, and TLR4/NF-κB pathways was involved in the molecular mechanism of LRRK2 on lung cancer cells. In conclusion, this study suggested that the mechanism of si-LRRK2 inhibiting the progression of lung cancer is to regulate the TLR4/NF-κB signaling pathways and NLRP3 inflammasome.

Clinical studies had found that hydrogen/oxygen mixed inhalation was beneficial to ameliorate the respiratory symptoms in the adjuvant treatment of patients with COVID-19. We aimed to explore the efficacy of Hydrogen/oxygen therapy in favoring the recovery of Omicron SARS-CoV-2 Variant Infection. There were 64 patients who randomly assigned to receive Hydrogen/Oxygen inhalation (32 patients) and Oxygen inhalation (32 patients). The average shedding duration of Omicron in Hydrogen/oxygen group was shorter than Oxygen group. The trend of cumulative negative conversion rate of Omicron increased gradually after the third day. The IL-6 levels in Hydrogen/oxygen group decreased by 22.8% compared with the baseline. After Hydrogen/oxygen mixed gas inhalation, the lymphocyte count increased to 61.1% of the baseline on the 3rd day in the Hydrogen/oxygen group. More patients in the Hydrogen/oxygen group had resolution of pulmonary lesions. Our study showed the beneficial trends of molecular hydrogen in treating patients with COVID-19, which may offer a prospective solution to adjuvant therapy for COVID-19 Patients.

We conducted a retrospective case-control study to assess the efficacy of personalized health guidance interventions provided by public health nurses on individuals with type 2 diabetes mellitus and obesity who sought medical checkups. A selection was made of individuals who had made regular visits (two or more times) to the Takagi Hospital for medical checkups between January 1, 2017, and October 31, 2021. Two hundred eight subjects (cases) who received health guidance intervention were divided into two groups: one group without pharmacotherapy for diabetes mellitus in medical institutions (n = 92) and another group with pharmacotherapy (n = 116). Cases were provided with individual health guidance interventions by public health nurses for a duration of 30 minutes, in accordance with the Japanese clinical guidelines for the prevention of lifestyle-related diseases. Sex- and age-matched controls were chosen from individuals with diabetes mellitus who did not receive any health guidance. The health guidance intervention for cases without pharmacotherapy resulted in improvements in various health indicators, including body weight, body mass index, waist circumference, diastolic blood pressure, serum triglyceride levels, and γ-glutamyl trans-peptidase. Conversely, these positive effects were not observed in the control group who did not receive any health guidance. The therapeutic effects of health guidance were observed in cases where pharmacotherapy was administered. In conclusion, the implementation of individual health guidance interventions may prove to be effective for individuals with type 2 diabetes mellitus and obesity who regularly attend medical checkups.

We previously reported that chromatin licensing and DNA replication factor 1 (CDT1) expression was associated with the extent of proliferation of atypical hepatocytes and the time to postoperative recurrence in cases of hepatocellular carcinoma (HCC). This study aimed to clarify the clinical significance or pathogenesis of CDT1 expression in non-cancerous and cancerous liver cases with HCC. We investigated the association between the expression of CDT1 in non-cancerous or cancerous liver tissues and long-term outcome, histologic findings or biochemical examination results in 62 cases. We also examined the dual localization between CDT1 and ki-67, FbxW7, P57kip2, P53 and c-Myc by confocal laser scanning microscopy. CDT1 mRNA expression was significantly higher in cancerous liver than in non-cancerous liver (P<0.0001). High CDT1 mRNA expression reveals the strong degree of inflammatory cell infiltration in lobules, high levels of serum transaminase, to show hepatic spare decline and poor long-term prognosis. CDT1 mRNA was highly expressed in a group of poorly differentiated cancer cells. CDT1 co-localized with Ki-67, P57kip2, Fbwx7, P53 and c-Myc in the nucleus or cytoplasm of hepatocytes and cancer cells. We found that CDT1 mRNA expression could represent the degree of hepatic spare ability and the high carcinogenic state.

We have previously reported that chromatin licensing and DNA replication factor 1 (CDT1) is associated with the postoperative recurrence of hepatocellular carcinoma (HCC). Based on this fact, we verified whether CDT1 mRNA expression is also associated with HCC development from chronic hepatitis C (CHC) and liver cirrhosis (LC). There were 142 cases with CHC or LC who underwent liver biopsy. Detection of CDT1 mRNA in liver was performed by RT–qPCR using frozen liver biopsy tissues. We examined the association between the CDT1 mRNA expression and clinical conditions and long-term outcome. We then examined the association between serum cytokine/chemokine levels and CDT1 mRNA expression in 58 cases. The cumulative incidence rates of HCC development in cases with CDT1 mRNA in the low expression group showed significantly lower than those in the high expression group (P=0.0391). A significant correlation was found between CDT1 mRNA expression and the extent of proliferation of atypical hepatocytes in hematoxylin and eosin-stained sections (P<0.0001). CDT1 mRNA expression has been associated with cytokines involved in tumorigenesis in experimental and human cancers. We found that cases with high CDT1 mRNA expression were at risk for developing HCC, even if they were CHC or LC.

BACKGROUND: Post-intensive care syndrome (PICS) is an emerging issue in critically ill patients. The impact of nutrition therapy in the acute phase on PICS remains unclear. METHODS: We conducted a multicenter prospective study on adult patients with COVID-19 who required mechanical ventilation for more than three days and were discharged from the intensive care unit. The questionnaire for the PICS evaluation was mailed after hospital discharge. Physical PICS, defined as less than 90 points on the Barthel Index (BI), was assigned as the primary outcome. We examined the types of nutrition therapy in the first week that affected PICS components. RESULTS: 269 eligible patients were evaluated 10 months after discharge. Supplemental parenteral nutrition (SPN) >400 kcal/day correlated with a lower occurrence of physical PICS (10% vs 21.92%, p=0.042) and a higher BI and visual analogue scale scores for physical condition, whereas the amounts of energy and protein provided, early enteral nutrition, and a gradual increase in nutrition delivery did not, and none correlated with cognitive or mental PICS components. A multivariable regression analysis revealed that SPN had an independent impact on physical PICS (odds ratio 0.33, 95%CI 0.12-0.92, p=0.034), even after adjustments for age, sex, body mass index, and Sequential Organ Failure Assessment scores. Protein provision ≥1.2 g/kg/day was associated with a lower occurrence of physical PICS (odds ratio 0.42, 95%CI 0.16-1.08, p=0.071). CONCLUSIONS: SPN at an appropriate dose in the acute phase had a positive impact on physical PICS in critical care for ventilated patients with COVID-19.

Obesity increases the risk of arterial hypertension in young adults and favors an early-onset cardiomyopathy by generating oxidative stress. In this sense, indiscriminate consumption of sucrose and fructose sweetened beverages from early ages causes obesity, however its consequences on the heart when there is a genetic predisposition to develop hypertension are not clear. We compared the effects of sucrose, fructose, and their combination in weanling male spontaneously hypertensive rats to determine the relationship between genetic hypertension, obesity, and consumption of these sugars on the degree of cardiac hypertrophy, oxidative stress and Ca²⁺/calmodulin dependent protein kinase II delta oxidation. Histological, biochemical, and western blot studies were performed 12 weeks after treatment initiation. We found that chronic consumption of sucrose or fructose leads to obesity, exacerbates genetic arterial hypertension-induced metabolic alterations, and increases cardiac oxidative stress, Ca²⁺/calmodulin dependent protein kinase II delta oxidation and cardiac hypertrophy. Nonetheless, when sucrose and fructose are consumed together, metabolic alterations worsen and are accompanied by dilated cardiomyopathy. These data suggest that sucrose and fructose combined consumption starting from maternal weaning in rats with genetic predisposition to arterial hypertension accelerates the progression of cardiomyopathy resulting in an early dilated cardiomyopathy.

The aim of this study was to analyze the effect of heme synthesis inhibition on cytoglobin expression and its correlation with keloid fibroblast viability and proliferation. The study was conducted on primary culture of keloid fibroblasts. Heme synthesis in keloid fibroblasts was inhibited using succinyl acetone. We measured ALAD enzyme activity using a colorimetric method; cytoglobin mRNA expression using qRT-PCR; cytoglobin protein expression using ELISA and immunocytochemistry; fibroblast viability using the MTT test; and fibroblast proliferation using BrdU test. The results showed that the ALAD enzyme activity level was lower in the keloid fibroblasts treated with SA (1, 2.5, and 5 mM) than in the control. The CYGB mRNA and protein expressions level were significantly lower in the keloid fibroblasts cultured with 2.5 mM and 5 mM SA than in the control and 1 mM SA. The viability and proliferation of the keloid fibroblasts decreased when the SA concentration was increased. In conclusion, the use of succinyl acetone at a concentration of 1; 2.5; and 5 mM caused decrease ALAD enzyme activity which indicated the inhibition of the heme synthesis. Inhibition of heme synthesis can affect cytoglobin expression, which correlates with the viability and proliferation of keloid fibroblasts.

Reactive oxygen species (ROS) and highly reactive oxygen species (hROS) secreted by leukocytes are crucial to innate immunity; however, they pose a risk of oxidative stress. To monitor their balance in daily health check-ups, optical technologies for the simultaneous measurement of ROS (superoxide radicals) and hROS (hypochlorite ions) that utilize only a few microliters of whole blood have been developed. The aim of this study was to clarify whether this system could assess the effects of fat ingestion on postprandial oxidative status. Eight healthy young Japanese women ingested a beverage containing oral fat tolerance test cream. Blood samples were collected before and 0.5, 1, 2, 4, and 6 h after fat ingestion. Blood ROS and hROS levels, oxidative stress markers, and biochemical markers were monitored. Consistent with previous studies, triglyceride levels significantly increased at 4 h (p < 0.01) and returned to near-baseline levels 6 h after ingestion. ROS levels peaked significantly at 2 h (p < 0.05), and hROS levels peaked significantly at 1 (p < 0.05) and 2 h (p < 0.01) after ingestion. This study offers an insight into the acute effects of fat ingestion on leukocyte activity and provides a methodology for monitoring postprandial oxidative status.

Simplifying the diagnostic criteria for sarcopenia is key to establishing effective interventions. Herein, we aimed to clarify novel diagnostic factors. We calculated novel fat indices (total fat index [TFI] and limb fat index [LFI]) and clarified factors leading to pre-sarcopenia and sarcopenia in 594 enrolled older adults. Physical measurements (height, weight, body mass index [BMI], gait speed, grip strength, and skeletal muscle mass) were performed. Sarcopenia was determined using established diagnostic criteria (pre-sarcopenia, n=102; sarcopenia, n=42). Age was associated with sarcopenia status. BMI, TFI, and LFI were lower in patients with pre-sarcopenia and sarcopenia. Logistic regression analysis showed the following odds ratios (ORs) for pre-sarcopenia: BMI (OR:0.787, 95% confidence interval [CI]:0.7-0.885), LFI (OR:0.589, 95% CI:0.402-0.863), and age (OR:1.06, 95% CI:1.02-1.1). ORs for sarcopenia (vs. pre-sarcopenia) were as follows: LFI (OR:50.6, 95% CI:10.2-250.0), age (OR:1.1, 95% CI:1.0-1.2), and BMI (OR:0.418, 95% CI:0.28-0.608). Our findings contribute to informing medical guidelines.

Dysbiosis resulting from a high fat/high sucrose diet (HFHSD) causes sarcopenia by decreasing the production of short-chain fatty acids (SCFAs). This study investigated the effects of miso, a traditional fermented soybean food in Japan, on muscle mass atrophy. Eight week old male C57BL/6J mice were fed HFHSD with or without miso for 12 weeks. A miso diet increased soleus muscle weights (p <0.05) and reduced intraperitoneal glucose tolerance and insulin tolerance (p <0.05). The miso diet downregulated the Tnfα and Ccl2 expression, related to inflammation, and Trim63 and Fbxo32 expression, related to muscle atrophy, in the soleus muscle (p <0.05). The miso diet increased SCFA levels, including acetic, propanoic, and butanoic acids, in the feces, serum, and soleus muscle (p <0.05). According to the LEfSe analysis, the miso diet increased family Prevotellaceae, family Christensenellaceae, family Dehalobacterium, family Desulfitibacter; family Deferribacteraceae, order Deferribacterales, class Deferribacteres; and family Gemmatimonadaceae, order Gemmatimonadetes, and class Gemmatimonadales, whereas the miso diet decreased family Microbacteriaceae, order Micrococcales, class Actinobacteria, and family Lactobacillaceae. Miso suppressed HFHSD induced impaired glucose tolerance, low muscle strength, and muscle atrophy by improving dysbiosis and increasing SCFA production and provides new insights into the preventive effects of fermented foods on sarcopenia.

Disorder of phosphate metabolism is a common pathological condition in chronic kidney disease patients. Excessive intake of dietary phosphate deteriorates chronic kidney disease and various complications including cardiovascular and infectious diseases. Recent reports have demonstrated that gut microbiome disturbance is associated with both the etiology and progression of chronic kidney disease. However, the relationship between dietary phosphate and gut microbiome remains unknown. Here, we examined the effects of excessive intake of phosphate on gut microbiome. Five-week-old male C57BL/6J mice were fed either control diet or high phosphate diet for eight weeks. Analysis of the gut microbiota was carried out using MiSeq next generation sequencer, and short-chain fatty acids were determined with GC-MS. In analysis of gut microbiota, significantly increased in Erysipelotrichaceae and decreased in Ruminococcaceae were observed in high phosphate diet group. Furthermore, high phosphate diet induced reduction of microbial diversity and decreased mRNA levels of colonic tight junction markers. These results suggest that the excessive intake of dietary phosphate disturbs gut microbiota and affects intestinal barrier function.

Hyperphosphatemia is an independent and non-classical risk factor of cardiovascular disease and mortality in patients with chronic kidney disease (CKD). Increased levels of extracellular inorganic phosphate (Pi) are known to directly induce vascular calcification, but the detailed underlying mechanism has not been clarified. Although serum Pi levels during the growth period are as high as those observed in hyperphosphatemia in adult CKD, vascular calcification does not usually occur during growth. Here, we have examined whether the defence system against Pi-induced vascular calcification can exist during the growth period using mice model. We found that calcification propensity of young serum (aged 3 weeks) was significantly lower than that of adult serum (10 months), possibly due to high fetuin-A levels. In addition, when the aorta was cultured in high Pi medium in vitro, obvious calcification was observed in the adult aorta but not in the young aorta. Furthermore, culture in high Pi medium increased the mRNA level of tissue-nonspecific alkaline phosphatase (TNAP), which degrades pyrophosphate, only in the adult aorta. Collectively, our findings indicate that the aorta in growing mouse may be resistant to Pi-induced vascular calcification via a mechanism in which high serum fetuin-A levels and suppressed TNAP expression.