Biology subjects

Terai, S.

Publications and source records attributed to Terai, S..

5 recordsLinked to original sources

bioRxiv2025

Regulatory T cell stability determines the efficiency of bile duct regeneration during cholangitis.

Background and AimsCholangiopathies such as Primary Sclerosing Cholangitis (PSC) cause damage to the bile ducts and fibrosis with no effective cure. A reduction and impairment in the function of regulatory T cells (Tregs) occurs in PSC. Yet, it is currently unknown what consequence this has on bile duct regeneration. We investigate whether Tregs regulate bile duct regeneration and the dynamics of Tregs turnover during bile duct injury. Approach and ResultsWe used the transgenic Foxp3GFPDTR model to mimic reduced Tregs infiltration to the liver during bile duct injury and showed that reduced intrahepatic Tregs limits bile duct regeneration. Fate mapping of Tregs (Foxp3CreERTAi14) showed that Tregs acquire a pro-inflammatory phenotype within the inflammatory microenvironment, even after IL2 mediated Tregs expansion. Ox40L expression correlates with fibrosis in PSC patients. In the 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine (DDC)-diet mouse model of experimental cholangiopathy, combining IL2-complex administration and blocking Ox40L decreases periportal fibrosis level, increases Treg number and reduces the pro-inflammatory phenotype of Tregs. ConclusionsThese results indicate that Tregs mediate cholangiocyte response to biliary injury, and Tregs downregulate Foxp3 and acquire an inflammatory phenotype in an inflammatory microenvironment. Enhancing Treg numbers through IL2 complex administration and blocking Ox40 signalling simultaneously suppress the inflammatory phenotype of Tregs and reduces bile duct damage and fibrosis.

immunology↗

bioRxiv2024

Bioinformatic evaluation of the potential oral-gut translocation of periodontal pathogens in patients with colorectal polyps

ObjectiveThis study aimed to characterize the profiles of the oral and gut microbiota of patients with colorectal polyps using 16S rRNA gene sequencing and bioinformatic approaches. BackgroundPrevious studies have shown microbial translocation from the oral cavity to the gut, implying pathogenic impacts on gastroesophageal disease, including colorectal cancer (CRC). However, its details remain unclear. MethodsTwenty patients scheduled for endoscopic colorectal polypectomy were enrolled in this study. Oral samples (saliva and subgingival dental plaque) and intestinal samples (feces and swab of intestinal mucosa) were collected during preoperative and 6-month-postoperative reassessment periods. After sequencing the V3-V4 region of the bacterial 16S rRNA gene, several bioinformatic analyses (bacterial composition, diversity, core microbiome, and shared ASV) were performed on pre- and postoperative samples for each subject. ResultsThe bacterial composition was dominated by Bacteroides, Streptococcus, Fusobacterium, Veillonella, and Prevotella_7 in all four samples. Beta diversity analysis using weighted UniFrac distance distinctly segregated the samples between oral and intestinal environments in the principal coordinate analysis plot. Core microbiome analysis revealed that Streptococcus and Porphyromonas were dominantly shared in intra-oral environments. Additionally, alongside Streptococcus, periodontitis-related bacteria, such as Veillonella, Fusobacterium, Porphyromonas, Prevotella_7, Haemophilus, and Prevotella, were identified as shared genera between oral and intestinal environments. Finally, shared ASV analysis demonstrated that Streptococcus was shared in the oral and intestinal environments of most patients, while periodontal pathogens were shared in some patients. ConclusionsThe core microbiome and shared ASV analyses revealed that several genes are shared between oral and intestinal environments in patients with colorectal polyps, indicating the oral-gut translocation of periodontitis-related bacteria. Further large-scale studies are needed to elucidate their involvement in CRC.

bioinformatics↗

bioRxiv2022

Analysis of genetic relatedness between gastric and oral H. pylori in patients with early gastric cancer using multilocus sequence typing

Although oral cavity is the second most colonized site after the stomach, the association between gastric and oral Helicobacter pylori remains unclear. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer by multilocus sequence typing (MLST) analysis using seven housekeeping genes. Gastric biopsy specimens and oral samples, including saliva, supragingival dental biofilm, and superficial layers of the tongue, were collected from 21 patients positive for H. pylori by a fecal antigen test. The number of H. pylori allelic profiles of seven loci obtained from oral and gastric samples ranged from zero to seven since the yield of DNA was small even when the nested PCR was performed. The alleles of seven loci from both collection sites were determined from only one patient, and two out of seven alleles matched between oral and gastric samples. MLST analysis revealed that only one sample had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in two patients was markedly similar to gastric H. pylori, implying that the the origins of two strains may be the same, and the stomach and the oral cavity may be infected at the same time. In brief, although different genotypes of H. pylori exist in the oral cavity independently of H. pylori present in the stomach, there are rare cases in which the same H. pylori is present in the stomach and the oral cavity. It is necessary to establish a culture method for oral H. pylori for elucidating whether the oral cavity will act as the source of the gastric infection, as our analysis was based on a limited number of allele sequences. Author summaryHericobacter pylori is a clinically important pathogen that causes chronic gastritis and peptic ulcers, which are associated with gastric carcinoma. Oral H. pylori DNA has also been detected in a range of oral specimens, including saliva, supra- or sub-gingival biofilm, dentin caries, dental pulp, infected root canal, and coating of the tongue. Thus, researchers speculate that the main route of transmission of gastric H. pylori infections is via the oral cavity, however, there is inadequate evidence to support this suggestion. This study aimed to investigate if the oral and gastric H. pylori have the same origin using multilocus sequence typing. The results of this study provided some insight into the role of oral cavity as the source of H. pylori infections in stomach.

microbiology↗

bioRxiv2021

The impact of PNPLA3 and TM6SF2 in cirrhosis related complications

Patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6-superfamily member 2 (TM6SF2) polymorphisms have major impact for fibrosis due to steatohepatitis. However, there are scant data about correlations between cirrhosis-related complications and the polymorphisms of these genes. Therefore, we aimed to determine the role of the PNPLA3 and TM6SF2 polymorphisms in fibrosis progression for patients with liver cirrhosis. A multicenter study was performed at six hospitals in Japan enrolling 400 patients with liver cirrhosis caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33). These cirrhotic patients included those with complications of variceal bleeding, hepatic ascites, and/or hepatic encephalopathy and those without. To assess the role of the PNPLA3 and TM6SF2 polymorphisms in patients with cirrhosis related complications, we calculated the odds ratio and relative risk for the rs738409 and rs58542926 polymorphisms. We also accessed whether or not the interaction between these two polymorphisms contributed to cirrhosis related complications. As a result, the odds ratio for complications in the NAFLD group significantly increased in the presence of the rs738409 GG genotype when the CC genotype was used as the reference. There were no significant risks between complications and the presence of the rs738409 G allele in the virus or alcohol groups. There were no significant risks of complications in the frequency of the rs58542926 T polymorphism regardless of the etiology of liver cirrhosis. The interaction between the rs738409 and rs58542926 polymorphisms had the highest odds ratio of 2.415 for complications in the rs738409 GG + rs58542926 (CT+TT) group when rs738409 (CC+CG) + TM6SF2 CC was used as the reference in the NAFLD group although there was no statistically interaction between these gene polymorphisms (P=0.085).

genetics↗

bioRxiv2019

Autophagy controls lipid droplet formation by fine-tuning NCoR1 levels

Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, such as following a meal. LDs serve as an energy reservoir during fasting and have a buffering capacity that prevents lipotoxicity. Autophagy and the autophagic machinery have been proposed to play a role in LD biogenesis but the underlying molecular mechanism remains unclear. Here, we show that when nuclear receptor co-repressor 1 (NCoR1), which inhibits the transactivation of nuclear receptors, accumulates due to autophagy suppression, LD biogenesis is blocked. Ablation of ATG7, a gene essential for autophagy, suppressed the expression of gene targets of liver X receptor (LXR), a nuclear receptor responsible for fatty acid and triglyceride synthesis in an NCoR1-dependent manner. LD biogenesis in response to fasting and after hepatectomy was hampered by the suppression of autophagy. These results indicate that autophagy controls physiological hepatosteatosis by fine-tuning NCoR1 protein levels.

cell biology↗