Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model

Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1−/− mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1−/− mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1−/− mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target

Deletion of angiotensin II type I receptor reduces hepatic steatosis

Background/Aims: A distinct subgroup of angiotensin II type I receptor (AT1R) blockers (ARBs) have been reported to suppress the development of hepatic steatosis. These effects were generally explained by selective peroxisome proliferator-activated receptor (PPAR) gamma modulating properties of ARBs, independent of their AT1R blocking actions. Here, we provide genetic evidence of the direct role for AT1R in hepatic steatosis. Methods: The effect of AT1R deletion on steatohepatitis was investigated in AT1a(-/-) mice. Furthermore, the influence of AT1R inhibition by telmisartan as well as gene silencing of AT1R by siRNA was assessed in an in vitro experiment using HepG2 cells. Results: Compared to wild-type (WT), A T1a(-/-) mice fed methionine-choline deficient (MCD) diet resulted in negligible lipid accumulation in the liver with marked induction of PPAR alpha mRNA. In vitro experiments also demonstrated reduced cellular lipid accumulation by telmisartan and AT1R knockdown following exposure of long chain fatty acids. This is pre-sumably explained by the observation that the expression of PPAR alpha and its target genes were significantly up-regulated in specific siRNA treated HepG2 cells. Conclusions: Our data indicate, in addition to pharmacological effect of ARBs on PPAR gamma activation, a key biological role for AT1R in the regulation of hepatic lipid metabolism

The Exopolysaccharide Produced by Lactobacillus paracasei IJH-SONE68 Prevents and Ameliorates Inflammatory Responses in DSS–Induced Ulcerative Colitis

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract. IBD includes Crohn’s disease (CD) and ulcerative colitis (UC). CD can occur in any part of the gastrointestinal tract, whereas UC mainly occurs in the colon and rectum. We previously demonstrated that a novel exopolysaccharide (EPS) produced by a plant-derived bacterium, Lactobacillus paracasei IJH-SONE68, prevents and improves the inflammation in contact dermatitis model mice via oral administration. To evaluate the preventive effect of the EPS against other inflammatory diseases, in the present study, we employed dextran sulfate sodium (DSS)-induced UC model mice. The stool consistency, hematochezia, and colonic atrophy of the mice were improved by the orally administered EPS. We also evaluated the cytokine transcription. Overexpression of the mouse macrophage inflammatory protein 2 mRNA in the colon as a functional homolog of human interleukin-8 was decreased by the orally administered EPS. However, the expression of interleukin-10, which is known as an anti-inflammatory cytokine, was stimulated in the EPS-administrated group. Based on these results, we conclude that the IJH-SONE68-derived EPS is a promising lead material for the development of drugs useful in treating inflammatory diseases such as UC

Plant-Derived Lactobacillus paracasei IJH-SONE68 Improves the Gut Microbiota Associated with Hepatic Disorders: A Randomized, Double-Blind, and Placebo-Controlled Clinical Trial

Our previous clinical study has shown that the exopolysaccharide (EPS) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, improves chronic allergy status in humans. In addition, an inhibition of visceral fat accumulation was observed following the intake of EPS during animal experimentation. In the present study, we have further evaluated the health-promoting effects of a spray-dried powder of pineapple juice that is fermented with the IJH-SONE68 strain. This was conducted in a double-blind, randomized, placebo-controlled, parallel-group clinical trial at Hiroshima University from May 2019 to July 2021. Eighty healthy volunteers at range of ages 23–70, with a body mass index between 25 and 29.99, were enrolled. After the 12 weeks of the experimental period were complete, although the average visceral fat area in both groups similarly decreased, there was no significant difference in the content of visceral fat area or in the obesity-related physical parameters in both groups. Further, we found that the serum liver function indices (AST and ALT) in the test group decreased within a statistically determined trend (p = 0.054). The fecal microflora analysis revealed, in the test group, a statistically significant increase in the relative abundance changes within Anaerostipes, which has been reported to help suppress hepatic inflammation

The Exopolysaccharide Produced by <i>Lactobacillus paracasei</i> IJH-SONE68 Prevents and Ameliorates Inflammatory Responses in DSS–Induced Ulcerative Colitis

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by chronic inflammation of the gastrointestinal tract. IBD includes Crohn’s disease (CD) and ulcerative colitis (UC). CD can occur in any part of the gastrointestinal tract, whereas UC mainly occurs in the colon and rectum. We previously demonstrated that a novel exopolysaccharide (EPS) produced by a plant-derived bacterium, Lactobacillus paracasei IJH-SONE68, prevents and improves the inflammation in contact dermatitis model mice via oral administration. To evaluate the preventive effect of the EPS against other inflammatory diseases, in the present study, we employed dextran sulfate sodium (DSS)-induced UC model mice. The stool consistency, hematochezia, and colonic atrophy of the mice were improved by the orally administered EPS. We also evaluated the cytokine transcription. Overexpression of the mouse macrophage inflammatory protein 2 mRNA in the colon as a functional homolog of human interleukin-8 was decreased by the orally administered EPS. However, the expression of interleukin-10, which is known as an anti-inflammatory cytokine, was stimulated in the EPS-administrated group. Based on these results, we conclude that the IJH-SONE68-derived EPS is a promising lead material for the development of drugs useful in treating inflammatory diseases such as UC

Plant-Derived <i>Lactobacillus paracasei</i> IJH-SONE68 Improves Chronic Allergy Status: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

We have recently demonstrated that the exopolysaccharides (EPSs) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, prevent and ameliorate allergic reaction on contact in dermatitis model mice. In the present study, we conducted a clinical trial using a capsule containing spray-dried powder from pineapple juice broth fermented with the LAB strain as an experimental diet. The clinical trial was conducted as a double-blind and placebo-controlled randomized comparative study from May 2019 to July 2021. Males and females between the ages of 21 and 70 who experience chronic allergies participated in the study. Sixty subjects were instructed to orally take a capsule containing the IJH-SONE68 powder or placebo, every day for 12 weeks. After the clinical trial was over, the scores based on subjects’ self-assessment of allergic status were significantly improved in the intervention group, as compared with the placebo group. Some serum biochemicals associated with inflammation response were also significantly improved by intake of the experimental diet. In conclusion, the IJH-SONE68-derived EPS improves chronic allergy status in humans and is expected to decrease their inconvenience

Development of Microfluidic Plasma Counting System for Small Animal Molecular Imaging Using PET - Principle Validation for Blood Transportation System

2009 World Molecular Imaging Congres

Development of Microfluidic Plasma Counting System for Small Animal Molecular Imaging Using PET --- Measurement of Small Radioactivity Concentration

[Introduction] The system for uL-ordered blood sampling and plasma radioactiveconcentration measurement, Microfluidic Mouse Plasma Counting System (uFmPC, patent pending), isdeveloping. uFmPC should measure very small radioactivity concentration, from several to hundreds Bq/uL.This study aimed to investigate the accuracy on such small radioactivity concentration. [Method] In uFmPC,blood was sampled using microfluidic technique, and it was stocked in channels on a plastic disc (CD-Well).The blood was then separated by rotating the disc. Because the channels had exact cross-sectional area of0.067 mm2, the volumes of blood and separated plasma could be derived by measurement of the lengthusing a flatbed scanner. The amount of radioactivity was acquired by a storage phosphor screen. In theexperiments, one and three uL of FDG solutions containing the radioactivity ranging from 4 to 128 Bq/uLwere introduced in the channels. The radioactivity was measured using Imaging Plate (IP) and BAS-5000(Fujifilm Corp., Japan) with 120-minute exposure. CD-Well was also scanned by GT-X970 scanner (SeikoEPSON, Japan) in 2400 dpi in order to measure the volume of solution. The activity concentration of givenFDG was compared with a photo-stimulated luminescence value (PSL) derived from uFmPC. [Results andDiscussion] Measured images were shown in Fig. 1: a scanned image (A) and an image from IP (B). Theposition of introduced FDG was detected as shown in (C) with black thick curves, and it was applied to theIP image to read out an amount of radioactivity. (D) was a superimposed image. From 120-minute exposure,the PSL was correlated with the given concentration well (y = 1.8x + 4.4 for 1 uL case and y = 2.1x + 6.6 for3 uL case. r2=1.00 for both cases). We can conclude that the concept of uFmPC had potential to measuresmall radioactivity concentration.2009 World Molecular Imaging Congres