Oxidized Low-Density Lipoproteins Trigger Hepatocellular Oxidative Stress with the Formation of Cholesteryl Ester Hydroperoxide-Enriched Lipid Droplets.

Oxidized low-density lipoproteins (oxLDLs) induce oxidative stress in the liver tissue, leading to hepatic steatosis, inflammation, and fibrosis. Precise information on the role of oxLDL in this process is needed to establish strategies for the prevention and management of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Here, we report the effects of native LDL (nLDL) and oxLDL on lipid metabolism, lipid droplet formation, and gene expression in a human liver-derived C3A cell line. The results showed that nLDL induced lipid droplets enriched with cholesteryl ester (CE) and promoted triglyceride hydrolysis and inhibited oxidative degeneration of CE in association with the altered expression of LIPE, FASN, SCD1, ATGL, and CAT genes. In contrast, oxLDL showed a striking increase in lipid droplets enriched with CE hydroperoxides (CE-OOH) in association with the altered expression of SREBP1, FASN, and DGAT1. Phosphatidylcholine (PC)-OOH/PC was increased in oxLDL-supplemented cells as compared with other groups, suggesting that oxidative stress increased hepatocellular damage. Thus, intracellular lipid droplets enriched with CE-OOH appear to play a crucial role in NAFLD and NASH, triggered by oxLDL. We propose oxLDL as a novel therapeutic target and candidate biomarker for NAFLD and NASH.

Dried and Fermented Powders of Edible Algae (Neopyropia yezoensis) Attenuate Hepatic Steatosis in Obese Mice.

Edible algae Neopyropia yezoensis is used as "Nori", its dried sheet product, in Japanese cuisine. Its lipid components reportedly improve hepatic steatosis in obese db/db mice. In this study, we prepared "Nori powder (NP)" and "fermented Nori powder (FNP)" to utilize the functional lipids contained in "Nori" and examined their nutraceutical effects in vivo. Male db/db mice were fed a basal AIN-76 diet, a 10% NP-supplemented diet, or a 10% FNP-supplemented diet for 4 weeks. We detected eicosapentaenoic acid (EPA) present in both NP and FNP in the serum and liver of db/db mice in a dose-dependent manner. The NP diet reduced hepatic triglyceride accumulation (by 58%) in db/db mice by modulating gene expression, which resulted in the inhibition of lipogenic enzyme activity. Additionally, NP intake significantly suppressed the expression of inflammatory genes in the liver and hepatic injury marker levels in the sera (by 26%) of db/db mice. The FNP diet also led to a marked reduction in hepatic triglyceride accumulation (by 50%) and hepatic injury (by 28%) in db/db mice, and the mechanism of these alleviative actions was similar to that of the NP diet. Although the EPA content of FNP was one-third that of NP, metabolomic analysis revealed that bioactive betaine analogs, such as stachydrine, betaine, and carnitine, were detected only in FNP. In conclusion, we suggest that (1) mechanical processing of "Nori" makes its lipid components readily absorbable by the body to exert their lipid-lowering effects, and (2) fermentation of "Nori" produces anti-inflammatory molecules and lipid-lowering molecules, which together with the lipid components, can exert hepatic steatosis-alleviating effects.

[Lung Transplantation at a Low Volume Center].

The number of lung transplantation performed in Japan is extremely low compared to other countries, whereas we have 10 facilities certified as cadaveric lung transplantation in Japan, meaning that there are low volume centers. By August 2021, we performed lung transplantation in 21 cases for 12 years, therefore, our facility should be considered as low volume center. Surgical outcomes at low volume centers are generally considered poor. However, the overall five-year survival rate of total cases was 84.8%, and that of cadaveric cases was 94.4% in our hospital. It was better than the average of about 73% of all facilities in Japan. These data suggested that the accreditation system in Japan is functioning well. On the other hand, there may be a disparity between facilities. At our facility, we are actively performing inverted lung transplantation so as not to lose the opportunity for transplantation, and we have performed it in three cases so far and have achieved good results.

Eicosapentaenoic acid-containing polar lipids from seaweed Susabinori (Pyropia yezoensis) alleviate hepatic steatosis in obese db/db mice.

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Because hepatic steatosis is an early pathogenesis of NAFLD, the discovery of food components that could ameliorate hepatic steatosis is of interest. Susabinori (Pyropia yezoensis) is recognized as one of the most delicious edible brown algae, and we prepared lipid component of susabinori (SNL), which is rich in eicosapentaenoic acid (EPA)-containing polar lipids. In this study, we tested whether feeding SNL to db/db mice protects them from developing obesity-induced hepatic steatosis. After four weeks of feeding, hepatomegaly, hepatic steatosis, and hepatic injury were markedly alleviated in SNL-fed db/db mice. These effects were partly attributable to the suppression of activities and mRNA expressions of lipogenic enzymes and enhanced levels of adiponectin due to the SNL diet. Additionally, mRNA expression of monocyte chemoattractant protein-1, an inflammatory chemokine, was markedly suppressed, and the mRNA levels of PPARδ, the anti-inflammatory transcription factor, were strongly enhanced in the livers of db/db mice by the SNL diet. We speculate that the development and progression of obesity-induced hepatic steatosis was prevented by the suppression of chronic inflammation due to the combination of bioactivities of EPA, phospholipids, and glycolipids in the SNL diet.

Risk Factors for Cardiac Adverse Events in Infants and Children with Complex Heart Disease Scheduled for Bi-ventricular Repair: Prognostic Value of Pre-operative B-Type Natriuretic Peptide and High-Sensitivity Troponin T.

Few reports have described the prognostic value of measuring both B-type natriuretic peptides (BNP) and high-sensitivity troponin T (hs-TnT) in pediatric patients with complex congenital heart disease (CHD) undergoing surgery. We assessed demographic, hemodynamic, and laboratory data, including BNP and hs-TnT levels, for the prediction of cardiac adverse events in 85 patients. Cardiac adverse events were defined as death, cardiac arrest, worsening heart failure requiring inotropic agents and/or respiratory support, and unscheduled surgery/intervention either within or after 12 months of surgery. There were 17 cardiac adverse events. Of the demographic variables, low birth weight (< 2500 g: Odds ratio [OR], 5.97; 95% confidential interval [CI] 1.48-24.0; p = 0.001) and Ross/New York Heart Association [NYHA] class (≥ 2.0) (OR 12.7; 95% CI 3.08-52.7; p = 0.0004) were strongly association with cardiac adverse events. Among hemodynamic and laboratory variables, preoperative BNP (OR 14.04; 95% CI 2.15-91.7; p = 0.001) and hs-TnT levels (OR 16.66; 95% CI 2.27-122; p = 0.002) were found to be independent risk factors. Receiver operating characteristic analysis determined BNP and hs-TnT levels of 60.9 pg/mL and 0.025 ng/mL, respectively, to be markers of high risk. Kaplan-Meier analysis demonstrated significant differences in the freedom from cardiac adverse events between Group A (BNP or hs-TnT elevated, n = 26) and Group B (both biomarkers elevated, n = 19; log-rank, p < 0.001). In conclusion, low birth weight (< 2500 g) and Ross/NYHA class ≥ 2.0 are strongly associated with cardiac adverse events. Preoperative BNP and hs-TnT also provide prognostic information in patients with complex CHD scheduled for surgery. Using both markers in combination predicts cardiac adverse events better than using either separately.

Development of suction force during early diastole from the left atrium to the left ventricle in infants, children, and adolescents.

Although the suction force that moves blood into the left ventricle during early diastole is thought to play an important role in diastolic function, there have been a few studies of this phenomenon in normal children. Suction force is measured as the intraventricular pressure difference (IVPD) and intraventricular pressure gradient (IVPG), which is calculated as IVPD divided by left ventricular length. The purpose of this study was to determine the suction force in infants, children, and adolescents using IVPD and IVPG. We included 120 normal children categorized into five groups based on age: G1 (0-2 years), G2 (3-5 years), G3 (6-8 years), G4 (9-11 years), and G5 (12-16 years). The total, basal, and mid-apical IVPD and IVPG were calculated using color M-mode Doppler imaging of the mitral valve inflow using the Euler equation. The total IVPD increased with age from G1 to G5 (1.75 + 0.51 vs. 2.95 + 0.72 mmHg, respectively; p < 0.001), due to an increase in mid-apical IVPD with constant basal IVPD. Although total IVPG was constant, mid-apical IVPG was larger in G5 than in G1 (0.21 + 0.06 vs. 0.16 + 0.07 mmHg/cm, respectively; p = 0.006). Total, basal, and mid-apical IVPDs were significantly correlated with age and the parameters of heart size and mitral annular e'. Mid-apical IVPG correlated with age and e' positively, but basal IVPG did with age negatively and did not with e'. The suction force increased at the mid-apical segment, correlating with increasing heart size and developing left ventricular relaxation, even after adjustment for left ventricular length.

[Infective Endocarditis in Right Ventricle( RV)-Pulmonary Artery( PA) Conduit Late after the Ross Procedure;Report of a Case].

Ross procedure has been found to have a lower incidence of infective endocarditis compared to other aortic replacement procedure using prosthetic valves. We report a case of 25-year-old man who underwent Ross procedure for congenital aortic stenosis and regurgitation when he was 7 years old. He presented with fever and was highly suspected of infective endocarditis. All sets of blood cultures were positive for Heamophilus parainfluenzae. Autologous pericardial pulmonary valve was severely stenotic and computed tomography (CT) scan and radio isotope (RI) scan revealed infection at the stenotic valve. We performed right ventricle (RV)-pulmonary artery (PA) conduit replacement and he was discharged after completion of intravenous antibiotic treatment. We experienced a rare case of infective endocarditis in a patient late after Ross procedure. Prophylaxis against infective endocarditis is mandatory even in patients with infection resistant Ross procedure.

Measurement of Aortic Valve Coaptation and Effective Height Using Echocardiography in Patients with Ventricular Septal Defects and Aortic Valve Prolapse.

Decreased coaptation height in adults has been identified as a marker of early valve failure. We evaluated aortic valve coaptation and effective height in healthy children and in children with a ventricular septal defect (VSD) with aortic cusp prolapse (ACP), using echocardiography. We included 45 subjects with VSD with ACP, 27 did not develop aortic regurgitation (AR) by ACP and 18 developed AR by ACP, and 83 healthy children as controls. Aortic root anatomy was estimated using the parasternal long-axis view. We measured the diameter of aortic valve (AV), coaptation height (CH), and effective height (EH) of the aortic valve. We defined the ACH (CH/AV ratio) and AEH (EH/AV ratio) indices as follows: [Formula: see text]. There were significant differences in ACH and AEH between the groups (control vs VSD with ACP vs VSD with ACP and AR, median ACH [%], 35.1 vs 32.0 vs 22.1; median AEH [%], 52.0 vs 48.0 vs 34.4, respectively; P < 0.01]). Intra-cardiac repair (ICR) was performed in 15 cases. Significant increases were observed in ACH and AEH before and after ICR (median ACH [%], before: 27.0, after: 32.7, P < 0.05; median AEH (%), before 38.5, after 45.8, P < 0.05). Measurement of ACH and AEH may allow direct and non-invasive assessment of the severity of VSD with ACP, which could aid clinicians in determining the need and timing for surgical intervention.

Soybean ß-conglycinin improves carbohydrate and lipid metabolism in Wistar rats.

The effects of dietary soybean ß-conglycinin on lipid metabolism and energy consumption were studied in Wistar adult rats. Rats were fed, a diet containing casein (control group) or ß-conglycinin (ß-conglycinin group), for 4 weeks. Carbohydrate consumption was higher and fat consumption was lower in the ß-conglycinin group than in the control group, whereas the total energy consumption was the same between the two groups. Serum adiponectin was higher in the ß-conglycinin group than in the control group. Serum triacylglycerol levels in the ß-conglycinin group were significantly lower than those in the control group. The secretion rate of triacylglycerols from the liver after the administration of tyloxapol, an inhibitor of lipolysis, was significantly lower in the ß-conglycinin group than in the control group. These results suggest the possibility that ß-conglycinin exerts hypolipidemic effects through an acceleration in carbohydrate consumption associated with an increase in adiponectin in rats.

Impact of fasting time on hepatic lipid metabolism in nutritional animal studies.

Many animal studies on improvement of lipid metabolism, using dietary components, fast the animals on the final day of the feeding. Although fasting has a significant impact on lipid metabolism, its time-dependent influence is not fully understood. We examined the effects of several fasting times on lipid metabolism. Rats fed with a semisynthetic diet for 2 wk were killed after 0 (9:00 am), 6 (7:00 am-1:00 pm), 9 (0:00 am-9:00 am), and 13 h (8:00 pm-9:00 am) of fasting. Compared to the 0 h group, marked reduction of liver weight and hepatic triacylglycerol content was observed in the 9 and 13 h groups. Activities of hepatic enzymes involved in fatty acid synthesis gradually decreased during fasting. In contrast, drastic time-dependent reduction of gene expression, of the enzymes, was observed. Expression of carnitine palmitoyltransferase mRNA was higher in the fasting groups than in the 0 h group. Our study showed that fasting has a significant impact on several parameters related to lipid metabolism in rat liver.

Time-Course Metabolomic Analysis: Production of Betaine Structural Analogs by Fungal Fermentation of Seaweed.

Betaine structural analogs are compounds characterized by the presence of positive and negative charges in a single molecule and have been reported to have physiological properties, such as anti-inflammatory activities. In this study, we performed a metabolomic analysis of metabolite composition changes during the fermentation of Neopyropia yezoensis, an edible red alga, with Aspergillus oryzae for 72 h. The results indicated that three specific betaine structural analogs (betaine, stachydrine, and carnitine) exhibited significant changes in production by the end of the 72 h fermentation period. Time-course analysis suggested that betaine was generated from the precursor choline at 12-24 h during the late stage of fungal growth, while stachydrine was generated from the precursor-related compound glutamic acid at 48-72 h during the sporulation stage. However, the contribution of the precursor lysine to the increased production of carnitine during the 12-72 h period was unclear. This study provides useful information on the efficient production of betaine structural analogs by the fungal fermentation of seaweed as well as various other food materials.

Ozonated Olive Oil Intake Attenuates Hepatic Steatosis in Obese db/db Mice.

Chronic inflammation and insulin resistance lead to metabolic syndrome and there is an urgent need to establish effective treatments and prevention methods. Our previous study reported that obese model Zucker (fa/fa) rats fed with ozonated olive oil alleviated fatty liver and liver damage by suppressing inflammatory factors. However, differences among animal species related to the safety and efficacy of ozonated olive oil administration remain unclear. Therefore, this study investigated the effects of oral intake of ozonated olive oil on lipid metabolism in normal mice and mice in the obesity model. C57BL/6J and db/db mice were fed the following AIN-76 diets for four weeks: the mice were either fed a 0.5% olive oil diet (Control diet) or 0.5% ozonated olive oil diet (Oz-Olive diet) in addition to 6.5% corn oil. The results indicated that four weeks of Oz-Olive intake did not adversely affect growth parameters, hepatic lipids or serum parameters in normal C57BL/6J mice. Subsequent treatment of db/db mice with Oz-Olive for four weeks reduced the levels of hepatic triglycerides, serum alkaline phosphatase, and serum insulin. These effects of Oz-Olive administration might be due to suppression of fatty acid synthesis activity and expression of lipogenic genes, as well as suppression of inflammatory gene expression. In conclusion, this study confirmed the safety of Oz-Olive administration in normal mice and its ability to alleviate hepatic steatosis by inhibiting fatty acid synthesis and inflammation in obese mice.

Effects of heat-killed Lactobacillus pentosus S-PT84 on postprandial hypertriacylglycerolemia in rats.

The effect of Lactobacillus pentosus strain S-PT84 (S-PT84) on postprandial hypertriacylglycerolemia was investigated in rats. S-PT84 dose-dependently inhibited the hydrolysis of triacylglycerols by pancreatic lipase in vitro. Intragastric administration of S-PT84 significantly reduced the lymphatic recovery of (3)H-trioleoylglycerol up to 8 h. The oral administration of a fat emulsion, with or without S-PT84, resulted in the concentration of plasma triacylglycerol 2 h and 3 h after administration being significantly lower in the S-PT84 group than in the group without S-PT84 (control group). These results suggest that S-PT84 alleviated postprandial hypertriacylglycerolemia by delaying triacylglycerol absorption in the intestine through the inhibition of pancreatic lipase.

Effect of Mukitake mushroom (Panellus serotinus) on the pathogenesis of lipid abnormalities in obese, diabetic ob/ob mice.

BACKGROUND: Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries, and several compounds that modulate the immune system, lower blood lipid levels, and inhibit tumor and viral action have been isolated. The fruiting body of Panellus serotinus (Mukitake) is recognized in Japan as one of the most delicious edible mushrooms, and previous studies have demonstrated that the dietary intake of powdered whole Mukitake or Mukitake extracts prevents the development of non-alcoholic fatty liver disease (NAFLD) in leptin-resistant db/db mice. In the present study, we evaluated the effect of the Mukitake diet on the pathogenesis of metabolic disorders in leptin-deficient ob/ob mice. RESULTS: After 4 weeks of feeding, hepatomegaly, hepatic lipid accumulation, and elevated hepatic injury markers in the serum were markedly alleviated in Mukitake-fed ob/ob mice compared with control mice. Moreover, the mild hyperlipidemia in control ob/ob mice was attenuated and the elevated atherogenic index was reduced in Mukitake-fed ob/ob mice. These effects were partly attributable to the suppression of hepatic lipogenic enzyme activity due to the Mukitake diet. CONCLUSION: The current results showed that Mukitake supplementation is beneficial for the alleviation of NAFLD and dyslipidemia in obese, diabetic ob/ob mice.

Protective effects of fractional extracts from Panellus serotinus on non-alcoholic fatty liver disease in obese, diabetic db/db mice.

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialised countries. Various mushrooms have been used in Eastern folk medicine for the treatment of lifestyle diseases. We previously found that the dietary intake of powdered whole Panellus serotinus (Mukitake) alleviates NAFLD in obese, diabetic db/db mice. In the present study, we investigated the influence of Mukitake fractional extracts on the development of NAFLD in db/db mice. A significant reduction in the hepatic TAG content, macrovesicular hepatocytes and activities of key enzymes for de novo synthesis of the fatty acid was observed in both the water-soluble Mukitake extract (WE) diet and the ethanol-soluble Mukitake extract (EE) diet groups compared with the control diet group of the db/db mice. The serum level of monocyte chemoattractant protein-1 (MCP-1), which is known to exacerbate insulin resistance, was significantly decreased in the WE group. On the other hand, the serum level of adiponectin, which plays a protective role against the metabolic syndrome, was significantly increased in the EE group. Additionally, differential analysis between Mukitake and Shiitake, mycelia from the same family, using liquid chromatography time-of-flight MS technology revealed that only seven and five compounds exist in WE and EE from Mukitake, respectively. In conclusion, the present study demonstrated that Mukitake displays at least two different physiological actions that alleviate NAFLD: one through the reduction in inflammatory damage by its suppression in MCP-1 production and the other through an increase in level of serum adiponectin and the prevention of visceral fat accumulation.

SHRSP/Izm and WKY/NCrlCrlj rats having a missense mutation in Abcg5 deposited plant sterols in the body, but did not change their biliary secretion and lymphatic absorption-comparison with Jcl:Wistar and WKY/Izm rats.

We had previously found plant sterols deposited in the bodies of stroke-prone spontaneously hypertensive rats (SHRSP)/Sea and Wistar Kyoto (WKY)/NCrlCrlj rats that had a missense mutation in the Abcg5 cDNA sequence that coded for ATP-binding cassette transporter (ABC) G5. We used SHRSP/Izm, WKY/NCrlCrlj, and WKY/Izm rats in the present study to determine the mechanisms for plant sterol deposition in the body. Jcl:Wistar rats were used as a control strain. A diet containing 0.5% plant sterols fed to the rats resulted in plant sterol deposition in the body of SHRSP/Izm, but not in WKY/Izm or Jcl:Wistar rats. Only a single non-synonymous nucleotide change, G1747T, resulting in a conservative cysteine substitution for glycine at amino acid 583 (Gly583Cys) in Abcg5 cDNA was identified in the SHRSP/Izm and WKY/NCrlCrlj rats. However, this mutation was not found in the WKY/Izm or Jcl:Wistar rats. No significant difference in the biliary secretion or lymphatic absorption of plant sterols was apparent between the rat strains with or without the missense mutation in Abcg5 cDNA. Our observations suggest that plant sterol deposition in rat strains with the missense mutation in Abcg5 cDNA can occur, despite there being no significant change in the biliary secretion or lymphatic absorption of plant sterols.

[Arterial switch operation for transposition of the great arteries with situs inversus and mirror image dextrocardia].

We report a successful arterial switch operation for complete transposition of great arteries with atrial and visceral situs inversus totalis and mirror image dextrocardia in a 12-day-old infant girl. The aorta was located left side-by-side to the pulmonary trunk with a single coronary artery (mirror image of 1RLCx). After French maneuver, the posterior circumference of the neo-aorta was reconstructed. Then the coronary button was transplanted into the neo-aorta with a trap door technique carefully avoiding any twist and over-stretch. The neo-pulmonary trunk was reconstructed with an autologous pericardial patch and sutured to the longitudinal incision made into the left central pulmonary artery. The baby was discharged from hospital and has been doing well without any morbidity relating myocardial ischemia.

Profiling of lysophosphatidylethanolamine molecular species in human serum and in silico prediction of the binding site on albumin.

Lysophosphatidylethanolamine (LPE) is a major lysophospholipid produced by phospholipids and binds to human serum albumin (HSA). LPEs may play various roles in vivo depending on the differences in their acyl chains. However, only few reports have been published on the biological functions of LPEs. Hence, we determined the exact relative abundance of the major LPEs in the serum of healthy participants (n = 8) using liquid chromatography-tandem mass spectrometry. Consequently, LPE 18:2 (24.1 ± 5.2%) was found to be the most abundant in serum. To understand the distribution of LPEs, the serum separated via gel-filtration high-performance liquid chromatography was subjected to quantitative measurement. LPEs were more observed in the albumin fraction than the lipoprotein fraction. We also performed a fluorescence displacement assay and an in silico molecular docking experiment using AutoDock to confirm the affinity and binding sites of the LPEs on HSA. The binding affinities of the LPEs for drug sites 1 and 2 on HSA were relatively low, with Ki values of approximately 11 and 3.8 µM, respectively. AutoDock analysis revealed the conformation of the LPEs bound to drug sites and the possibility of LPEs binding to other HSA sites. These findings could help to elucidate the biological and pathological functions of LPEs.

Lysophosphatidylethanolamine Affects Lipid Accumulation and Metabolism in a Human Liver-Derived Cell Line.

The physiological functions of lysophosphatidylethanolamine (lysoPE) have not been fully elucidated. In this study, the effects of lysoPE on lipogenesis and lipolysis were investigated in a cultured human liver-derived cell line. The intracellular lipid profile was investigated in detail using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to better understand the underlying mechanism. The expression of genes related to lipid metabolism and catabolism was analyzed using real-time PCR. LysoPE supplementation induced cellular lipid droplet formation and altered triacylglycerol (TAG) profiles. Furthermore, lysoPE downregulated expression of the TAG hydrolyzation regulation factor ATGL, and reduced the expression of fatty acid biosynthesis-related genes SREBP1 and SCD1. LC-MS/MS-based lipidomic profiling revealed that the addition of lysoPE 18:2 increased the PE species containing linoleic acyl, as well as the CE 18:2 species, likely due to the incorporation of linoleic acyl from lysoPE 18:2. Collectively, these findings suggest that lysoPE 18:2 is involved in lipid droplet formation by suppressing lipolysis and fatty acid biosynthesis. Thus, lysoPE might play a pathological role in the induction of fatty liver disease.