A lipidome landscape of aging in mice.

Understanding the molecular mechanisms of aging is crucial for enhancing healthy longevity. We conducted untargeted lipidomics across 13 biological samples from mice at various life stages (2, 12, 19 and 24 months) to explore the potential link between aging and lipid metabolism, considering sex (male or female) and microbiome (specific pathogen-free or germ-free) dependencies. By analyzing 2,704 molecules from 109 lipid subclasses, we characterized common and tissue-specific lipidome alterations associated with aging.

Genetic deletion of Cyp4f18 disrupts the omega-3 epoxidation pathway and results in psoriasis-like dermatitis.

Cyp4f18 catalyzes the conversion of n-3 polyunsaturated fatty acids (PUFAs) into omega-3 epoxides, such as 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) and 19,20-epoxydocosapentaenoic acid (19,20-EpDPE) from eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), respectively. Cyp4f18-deficient mice spontaneously develop psoriasis-like dermatitis. A significant increase in the number of IL-17A-positive gamma delta (γδ) T cells in the skin and enlargement of draining lymph nodes was observed.

Eosinophils promote corneal wound healing via the 12/15-lipoxygenase pathway.

Lipid mediators play important roles in regulating inflammatory responses and tissue homeostasis. Since 12/15-lipoxygenase (12/15-LOX)-derived lipid mediators such as lipoxin A (LXA ) and protectin D1 (PD1) protect against corneal epithelial cell damage, the major cell types that express 12/15-LOX and contribute to the corneal wound healing process are of particular interest. Here, we found that eosinophils were the major cell type expressing 12/15-LOX during the corneal wound healing process.

Successful Kidney Transplantation Alone With Severe Left Ventricular Systolic Dysfunction of Ejection Fraction 14%: A Case Report.

It is well known that correction of uremia by kidney transplantation alone (KTA) improves left ventricular systolic dysfunction (LVSD). However, for kidney transplant candidates with extremely severe LVSD, KTA is considered to be contraindicated because of the high risk of peri-operative management. We report a case of successful kidney transplantation with severe LVSD with an ejection fraction (EF) of 14% and low systolic blood pressure (SBP) of approximately 65 to 80 mm Hg.

Cell-free and Concentrated Ascites Reinfusion Therapy for Refractory Ascites in Cirrhosis in Post-marketing Surveillance and the Role of Tolvaptan.

Objective Ascites becomes refractory to diuretics in cirrhotic patients, who then require repeated large-volume paracentesis or cell-free and concentrated ascites reinfusion therapy (CART). The objective of this study was to confirm the safety and efficacy of CART, evaluate the actual situations with respect to the prescription of diuretics and determine the role of diuretics after the introduction of CART. Patients and Methods We recruited 34 cirrhotic patients who received CART with concomitant diuretics using furosemide (76.

Anatomical Variations of the Left Renal Vein During Laparoscopic Donor Nephrectomy.

Objectives: The aim of this study is to investigate the outcome of laparoscopic donor nephrectomy with vascular anomalies of the left renal vein.

Patients And Methods: Between August 2010 and September 2018, a total of 120 laparoscopic donor nephrectomies were performed at Kagoshima University. Among them, we experienced 7 cases of donors with anomalous left renal vein (circumaortic left renal vein n = 5, retroaortic left renal vein n = 1, left renal vein drainage into hemiazygos vein n = 1).

Omega-3 fatty acid-derived mediators that control inflammation and tissue homeostasis.

Omega-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosapentaenoic acid and docosahexaenoic acid, display a wide range of beneficial effects in humans and animals. Many of the biological functions of PUFAs are mediated via bioactive metabolites produced by fatty acid oxygenases such as cyclooxygenases, lipoxygenases and cytochrome P450 monooxygenases. Liquid chromatography-tandem mass spectrometry-based mediator lipidomics revealed a series of novel bioactive lipid mediators derived from omega-3 PUFAs.

Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study.

Background: Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease worldwide and is characterized by insulin resistance, hepatic steatosis and often prediabetes or diabetes. Canagliflozin, a selective sodium glucose cotransporter 2 inhibitor, is a new oral anti-diabetic drug that reduces hyperglycaemia by promoting urinary glucose excretion. Glycosuria produced by canagliflozin is associated with weight loss, mainly due to reduced fat volume and improve insulin resistance.

Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid.

The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of highest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood.

Protective and therapeutic effect of felodipine against bleomycin-induced pulmonary fibrosis in mice.

Idiopathic pulmonary fibrosis (IPF) involves alveolar epithelial injury and abnormal collagen production caused by activated fibroblasts; transforming growth factor (TGF)-β1 is implicated in this activation. In this study, we screened for chemicals capable of inhibiting TGF-β1-induced collagen production in cultured fibroblasts from medicines already in clinical use. We selected felodipine based on its extent of collagen production inhibition, clinical safety profile, and other pharmacological activity.

Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in refractory ascites: Post-marketing surveillance results.

We performed post-marketing surveillance to evaluate the safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART sessions in 147 patients at 22 centers were performed. The most common primary disease was cancer (128 cases, 300 sessions).

Identification of approved drugs that inhibit the binding of amyloid β oligomers to ephrin type-B receptor 2.

Ephrin type-B receptor 2 (EphB2) is a member of the receptor tyrosine kinase family and plays an important role in learning and memory functions. In patients with Alzheimer's disease (AD) and in mouse models of AD, a reduction in the hippocampal EphB2 level is observed. It was recently reported that normalization of the EphB2 level in the dentate gyrus rescues memory function in a mouse model of AD, suggesting that drugs that restore EphB2 levels may be beneficial in the treatment of AD.

Usefulness of Levocarnitine and/or Branched-Chain Amino Acids during Invasive Treatment for Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy.

Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma.

Here, we found that members of the microRNA-29 family (miR-29a/b/c; "miR-29s") were significantly reduced in clear cell renal cell carcinoma (ccRCC) tissues, suggesting that they functioned as tumour suppressors. Restoration of all mature members of the miR-29 family inhibited cancer cell proliferation, migration and invasion. LOXL2 was a direct target gene of miR-29s, as shown by genome-wide gene expression analysis and luciferase reporter assay.

Elevation of branched-chain amino acid levels in diabetes and NAFL and changes with antidiabetic drug treatment.

Diabetes mellitus (DM), non-alcoholic fatty liver (NAFL), and obesity are associated with elevated branched-chain amino acid (BCAA) levels, but the mechanism and significance of this has not been elucidated. Eighty-four subjects were enrolled including 43 with DM. Serum BCAA levels were positively correlated with waist-hip ratio and ALT.

Encapsulation of beraprost sodium in nanoparticles: analysis of sustained release properties, targeting abilities and pharmacological activities in animal models of pulmonary arterial hypertension.

Prostaglandin I2 (PGI2) and its analogues (such as beraprost sodium, BPS) are beneficial for the treatment of pulmonary arterial hypertension (PAH). The encapsulation of BPS in nanoparticles to provide sustained release and targeting abilities would improve both the therapeutic effect of BPS on PAH and the quality of life of patients treated with this drug. BPS was encapsulated into nanoparticles prepared from a poly(lactic acid) homopolymer and monomethoxy poly(ethyleneglycol)-poly(lactide) block copolymer.

Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer.

Recent clinical trials of chemotherapeutics for advanced bladder cancer (BC) have shown limited benefits. Therefore, new prognostic markers and more effective treatment strategies are required. One approach to achieve these goals is through the analysis of RNA networks.

Discovery of Novel SPAK Inhibitors That Block WNK Kinase Signaling to Cation Chloride Transporters.

Upon activation by with-no-lysine kinases, STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) phosphorylates and activates SLC12A transporters such as the Na(+)-Cl(-) cotransporter (NCC) and Na(+)-K(+)-2Cl(-) cotransporter type 1 (NKCC1) and type 2 (NKCC2); these transporters have important roles in regulating BP through NaCl reabsorption and vasoconstriction. SPAK knockout mice are viable and display hypotension with decreased activity (phosphorylation) of NCC and NKCC1 in the kidneys and aorta, respectively. Therefore, agents that inhibit SPAK activity could be a new class of antihypertensive drugs with dual actions (i.

Development of biodegradable nanoparticles for liver-specific ribavirin delivery.

Ribavirin is an antiviral drug used for the treatment of chronic hepatitis C. However, ribavirin induces severe side effects such as hemolytic anemia. In this study, we prepared biodegradable nanoparticles as ribavirin carriers to modulate the pharmacokinetics of the drug.

Expression of the tumor suppressive miRNA-23b/27b cluster is a good prognostic marker in clear cell renal cell carcinoma.

Purpose: We observed abnormal expression of the microRNA-23b/27b (miR-23b/27b) cluster in our previous study of miRNA expression signatures. However, the relationship between aberrant miRNA expression and clear cell renal cell carcinoma is not well established. We investigated the functional significance of the miR-23b/27b cluster in clear cell renal cell carcinoma cells and evaluated these miRNAs as biomarkers to predict the risk of clear cell renal cell carcinoma.

Tumour-suppressive microRNA-24-1 inhibits cancer cell proliferation through targeting FOXM1 in bladder cancer.

Here, we found that microRNA-24-1 (miR-24-1) is significantly reduced in bladder cancer (BC) tissues, suggesting that it functions as a tumour suppressor. Restoration of mature miR-24-1 inhibits cancer cell proliferation and induces apoptosis. Forkhead box protein M1 (FOXM1) is a direct target gene of miR-24-1, as shown by genome-wide gene expression analysis and luciferase reporter assay.

Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities.

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and airflow limitations. We recently proposed that the muscarinic antagonist mepenzolate bromide (mepenzolate) would be therapeutically effective against COPD due to its muscarinic receptor-dependent bronchodilatory activity as well as anti-inflammatory properties. Mepenzolate has an asymmetric carbon atom, thus providing us with the opportunity to synthesize both of its enantiomers ((R)- and (S)-mepenzolate) and to examine their biochemical and pharmacological activities.