Graphislactone A, a Fungal Antioxidant Metabolite, Reduces Lipogenesis and Protects against Diet-Induced Hepatic Steatosis in Mice.

Graphislactone A (GPA), a secondary metabolite derived from a mycobiont found in the lichens of the genus Graphis, exhibits antioxidant properties. However, the potential biological functions and therapeutic applications of GPA at the cellular and animal levels have not yet been investigated. In the present study, we explored the therapeutic potential of GPA in mitigating non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms through a series of experiments using various cell lines and animal models.

Deletion of gene causes early growth retardation and insulin resistance in mice.

Single-nucleotide polymorphisms in the human juxtaposed with another zinc finger protein 1 () gene have repeatedly been associated with both type 2 diabetes (T2D) and height in multiple genome-wide association studies (GWAS); however, the mechanism by which JAZF1 causes these traits is not yet known. To investigate the possible functional role of JAZF1 in growth and glucose metabolism in vivo, we generated knockout (KO) mice and examined body composition and insulin sensitivity both in young and adult mice by using H-nuclear magnetic resonance and hyperinsulinemic-euglycemic clamp techniques. Plasma concentrations of insulin-like growth factor 1 (IGF-1) were reduced in both young and adult KO mice, and young KO mice were shorter in stature than age-matched wild-type mice.

Gut bacteria-derived 3-phenylpropionylglycine mitigates adipocyte differentiation of 3T3-L1 cells by inhibiting adiponectin-PPAR pathway.

Background: Gut microbiota provide numerous types of metabolites that humans cannot produce and have a huge influence on the host metabolism. Accordingly, gut bacteria-derived metabolites can be employed as a resource to develop anti-obesity and metabolism-modulating drugs.

Objective: This study aimed to examine the anti-adipogenic effect of 3-phenylpropionylglycine (PPG), which is a glycine conjugate of bacteria-derived 3-phenylpropionic acid (PPA).

Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer.

Background: The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established.

Bone morphogenic protein 9 is a novel thermogenic hepatokine secreted in response to cold exposure.

Objective: Maintaining a constant core body temperature is essential to homeothermic vertebrate survival. Adaptive thermogenesis in brown adipose tissue and skeletal muscle is the primary mechanism of adjustment to an external stimulus such as cold exposure. Recently, several reports have revealed that the liver can play a role as a metabolic hub during adaptive thermogenesis.

Mechanisms linking gut microbial metabolites to insulin resistance.

Insulin resistance is the rate-limiting step in the development of metabolic diseases, including type 2 diabetes. The gut microbiota has been implicated in host energy metabolism and metabolic diseases and is recognized as a quantitatively important organelle in host metabolism, as the human gut harbors 10 trillion bacterial cells. Gut microbiota break down various nutrients and produce metabolites that play fundamental roles in host metabolism and aid in the identification of possible therapeutic targets for metabolic diseases.

Deletion of KLF10 Leads to Stress-Induced Liver Fibrosis upon High Sucrose Feeding.

Liver fibrosis is a consequence of chronic liver injury associated with chronic viral infection, alcohol abuse, and nonalcoholic fatty liver. The evidence from clinical and animal studies indicates that transforming growth factor-β (TGF-β) signaling is associated with the development of liver fibrosis. Krüppel-like factor 10 (KLF10) is a transcription factor that plays a significant role in TGF-β-mediated cell growth, apoptosis, and differentiation.

Allogeneic transplant can abrogate the risk of relapse in the patients of first remission acute myeloid leukemia with detectable measurable residual disease by next-generation sequencing.

In patients with acute myeloid leukemia (AML) consolidation treatment options are between allogeneic hematopoietic stem cell transplantation (HCT) and chemotherapy, based on disease risk at the time of initial presentation and age. Measurable residual disease (MRD) following induction chemotherapy could be incorporated as a useful parameter for treatment decisions. The present study evaluated treatment outcomes according to the next-generation sequencing (NGS)-based MRD status and the type of consolidation therapy in patients with normal karyotype (NK)-AML.

Revisiting the Bacterial Phylum Composition in Metabolic Diseases Focused on Host Energy Metabolism.

Over a hundred billion bacteria are found in human intestines. This has emerged as an environmental factor in metabolic diseases, such as obesity and related diseases. The majority of these bacteria belong to two dominant phyla, Bacteroidetes and Firmicutes.

The essential role of fructose-1,6-bisphosphatase 2 enzyme in thermal homeostasis upon cold stress.

Skeletal muscle is a major organ for glucose disposal and thermogenesis. While hepatic fructose-1,6-bisphosphatase is well known as a key enzyme for gluconeogenesis, the role of muscle fructose-1,6-bisphosphatase 2 (Fbp2) in glucose disposal and thermogenesis is unknown. Here, using Fbp2 knockout (KO) mice, we assessed the physiological role of Fbp2 in energy and glucose metabolism and thermogenesis.

A protective mechanism of probiotic Lactobacillus against hepatic steatosis via reducing host intestinal fatty acid absorption.

The gut microbiome has been known to contribute up to ~30% of the energy absorption of the host. Although various beneficial mechanisms of probiotics have been suggested for non-alcoholic fatty liver disease (NAFLD), whether and which probiotics impact the host's intestinal energy absorption have not yet been quantitatively studied. Here, we suggest a novel mechanism of probiotics against NAFLD, in which Lactobacillus rhamnosus GG, the most common probiotic, shares intestinal fatty acids and prevents the development of diet-induced hepatic steatosis.

Intrinsic expression of viperin regulates thermogenesis in adipose tissues.

Viperin is an interferon (IFN)-inducible multifunctional protein. Recent evidence from high-throughput analyses indicates that most IFN-inducible proteins, including viperin, are intrinsically expressed in specific tissues; however, the respective intrinsic functions are unknown. Here we show that the intrinsic expression of viperin regulates adipose tissue thermogenesis, which is known to counter metabolic disease and contribute to the febrile response to pathogen invasion.

Plasma CRABP2 as a Novel Biomarker in Patients with Non-Small Cell Lung Cancer.

Background: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC).

Corrigendum: Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance.

[This corrects the article DOI: 10.1038/ncomms14477.].

Adipocyte-Specific Deficiency of De Novo Sphingolipid Biosynthesis Leads to Lipodystrophy and Insulin Resistance.

Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes.

Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.

We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice.

Feasibility of Modified FOLFOX in Elderly Patients Aged ≥80 Years with Metastatic Gastric Cancer or Colorectal Cancer.

Objective: The aim of this study was to assess the feasibility of a modified FOLFOX regimen as first-line treatment in elderly patients with metastatic gastric cancer (GC) or colorectal cancer (CRC).

Methods: We included chemotherapy-naïve patients over 80 years old with metastatic GC or CRC in our study. From September 2008 to November 2014, 28 consecutive patients were enrolled and treated with modified FOLFOX.

A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer.

Objectives: More than half of cases of gastric cancer (GC) are diagnosed in elderly patients (≥70years). While doublet combination with fluoropyrimidines and platinum is currently considered standard first-line chemotherapy in advanced GC, the main goal of chemotherapy remains palliation.

Materials And Methods: In a multi-center phase III trial, patients with chemotherapy-naïve, metastatic GC, aged 70years or older were randomized 1:1 to receive X monotherapy (capecitabine 1000mg/m bid po on days one to fourteen) or XELOX (X plus oxaliplatin 110mg/m iv on D1).

Phospholipase D1 deficiency in mice causes nonalcoholic fatty liver disease via an autophagy defect.

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides (TG) as lipid droplets in the liver. Although lipid-metabolizing enzymes are considered important in NAFLD, the involvement of phospholipase D1 (PLD1) has not yet been studied. Here, we show that the genetic ablation of PLD1 in mice induces NAFLD due to an autophagy defect.

What factors determine the need for lumbar puncture in patients with fever and headache?

Introduction: We performed this study to find clinical features and laboratory parameters that could facilitate the process of selecting patients who should receive lumbar punctures from among those who present with headache and fever.

Methods: We selected patients aged ≥ 16 years who presented to and received lumbar puncture in the emergency department of Kangwon National University Hospital, South Korea, between 2011 and 2013. Patients who received lumbar punctures were divided into two groups - those who were diagnosed with viral meningitis and those who were not.

Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis.

Oxidative stress is important for the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a chronic disease that ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1 (Nrf2-Keap1) pathway is essential for cytoprotection against oxidative stress. In this study, we found that oxidative stress or inflammatory biomarkers and TUNEL positive cells were markedly increased in NASH patients compared to normal or simple steatosis.

Effect of ischemic preconditioning on the expression of c-myb in the CA1 region of the gerbil hippocampus after ischemia/reperfusion injury.

Objectives: In the present study, we investigated the effect of ischemic preconditioning (IPC) on c-myb immunoreactivity as well as neuronal damage/death after a subsequent lethal transient ischemia in gerbils.

Materials And Methods: IPC was subjected to a 2 min sublethal ischemia and a lethal transient ischemia was given 5 min transient ischemia. The animals in all of the groups were given recovery times of 1 day, 2 days and 5 days and we examined change in c-myb immunoreactivity as well as neuronal damage/death in the hippocampus induced by a lethal transient ischemia.

Difference in transient ischemia-induced neuronal damage and glucose transporter-1 immunoreactivity in the hippocampus between adult and young gerbils.

Objectives: The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1)-immunoreactive microvessels in their ischemic hippocampal CA1 region.

Materials And Methods: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries.