Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease

Mitochondria has emerged as a critical ruler of metabolic reprogramming in immune responses and inflammation. In the context of colitogenic T cells and IBD, there has been increasing research interest in the metabolic pathways of glycolysis, pyruvate oxidation, and glutaminolysis. These pathways have been shown to play a crucial role in the metabolic reprogramming of colitogenic T cells, leading to increased inflammatory cytokine production and tissue damage. In addition to metabolic reprogramming, mitochondrial dysfunction has also been implicated in the pathogenesis of IBD. Studies have shown that colitogenic T cells exhibit impaired mitochondrial respiration, elevated levels of mROS, alterations in calcium homeostasis, impaired mitochondrial biogenesis, and aberrant mitochondria-associated membrane formation. Here, we discuss our current knowledge of the metabolic reprogramming and mitochondrial dysfunctions in colitogenic T cells, as well as the potential therapeutic applications for treating IBD with evidence from animal experiments

Examination of the Anaerobic Growth of Campylobacter concisus

Campylobacter concisus is an oral bacterium that is associated with intestinal diseases. C. concisus was previously described as a bacterium that requires H2-enriched microaerobic conditions for growth. The level of H2 in the oral cavity is extremely low, suggesting that C. concisus is unlikely to have a microaerobic growth there. In this study, the anaerobic growth of C. concisus was investigated. The growth of fifty-seven oral C. concisus strains and six enteric C. concisus strains under various atmospheric conditions including anaerobic conditions with and without H2 was examined. The atmospheric conditions were generated using commercially available gas-generation systems. C. concisus putative virulence proteins were identified using mass spectrometry analysis. Under anaerobic conditions, 92% of the oral C. concisus strains (52/57) and all six enteric strains grew without the presence of H2 and the presence of H2 greatly increased C. concisus growth. An oral C. concisus strain was found to express a number of putative virulence proteins and the expression levels of these proteins were not affected by H2. The levels of H2 appeared to affect the optimal growth of C. concisus. This study provides useful information in understanding the natural colonization site and pathogenicity of C. concisus

Elucidation of enteric virulence of Campylobacter concisus

Campylobacter concisus is a Gram-negative mobile oral bacterium that has been shown to be associatedwith human inflammatory bowel disease. Various experiments were conducted in this PhD project, aiming toelucidate the enteric virulence of C. concisus.The growth of oral C. concisus strains under different atmospheric conditions was examined. It was foundthat 92 % of strains grew under anaerobic conditions without H2. However, none of the strains grew undermicroaerobic conditions without H2. The presence H2 greatly increased the growth of C. concisus underanaerobic conditions and enabled C. concisus to grow under microaerobic conditions. The H2 had no effectson the expression of a number of putative virulence factors in C. concisus.The effects of formate and fumarate, on the production of H2S in oral C. concisus were investigated.Supplementation of formate and fumarate significantly increased the positivity of H2S production. Inaddition, the fumarate significantly increased C. concisus growth.Bioinformatics analysis was conducted to search for potential virulence factors encoded by prophages.Four prophage elements were identified in the genome of C. concisus strain 13826 with putative attachmentsites overlapping with tRNA. Each prophage elements contained a novel Xer phage integrase. It was foundthat CON_phi2 prophage encodes a Zot protein, and CON_phi3 encodes a Zot-like protein. Moreover, thephylogenetic analysis showed the horizontal gene transfer between Campylobacter species.Monoclonal antibody to C. concisus Zot was produced and verified. The impact of bile on the expressionof Zot was examined. It was found that a full length and a cleaved fragment of Zot were released from C.concisus in the presence of ox bile.Whether C. concisus strains affect actin in the intestinal epithelial cell line, Caco2 cells, was examined.Some C. concisus strains significantly reduced the levels of β-actin and caused the redistribution of F-actin inCaco2 cells.These findings show that the enteric virulence of C. concisus is determined by bacterial, host andenvironmental factors

A Deep Learning-Based Crop Disease Diagnosis Method Using Multimodal Mixup Augmentation

With the widespread adoption of smart farms and continuous advancements in IoT (Internet of Things) technology, acquiring diverse additional data has become increasingly convenient. Consequently, studies relevant to deep learning models that leverage multimodal data for crop disease diagnosis and associated data augmentation methods are significantly growing. We propose a comprehensive deep learning model that predicts crop type, detects disease presence, and assesses disease severity at the same time. We utilize multimodal data comprising crop images and environmental variables such as temperature, humidity, and dew points. We confirmed that the results of diagnosing crop diseases using multimodal data improved 2.58%p performance compared to using crop images only. We also propose a multimodal-based mixup augmentation method capable of utilizing both image and environmental data. In this study, multimodal data refer to data from multiple sources, and multimodal mixup is a data augmentation technique that combines multimodal data for training. This expands the conventional mixup technique that was originally applied solely to image data. Our multimodal mixup augmentation method showcases a performance improvement of 1.33%p compared to the original mixup method

MOESM2 of Zonula occludens toxins and their prophages in Campylobacter species

Additional file 2. Comparison of Campylobacter prophage proteins with known viral proteins. #Identity: Percentage of identical amino acids (number of identical amino acids divided by number of amino acids in proteins from Campylobacter species)

The effects of oral and enteric Campylobacter concisus strains on expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells.

Campylobacter concisus, a Gram-negative bacterium that colonizes the human oral cavity, has been shown to be associated with inflammatory bowel diseases (IBD). The effects of different C. concisus strains on intestinal epithelial expression of Toll like receptors (TLR) have not been investigated. This study examined the effects of C. concisus strains isolated from patients with IBD and controls on expression of TLR4, its co-receptor myeloid differentiation factor (MD)-2; TLR2, TLR5, cyclooxygenase-2 (COX-2) and interleukin (IL)-8 in HT-29 cells.Fourteen oral and enteric C. concisus strains isolated from patients with IBD and healthy controls were co-incubated with HT-29 cells. Expression of TLR4, MD-2, TLR2, TLR5 and COX-2 in HT-29 cells in response to C. concisus infection was examined by Western blot, flow cytometry analysis and immunofluorescent staining visualized by confocal microscope. Production of IL-8 was evaluated by enzyme-linked immunosorbent assay.Both oral and enteric C. concisus strains upregulated expression of TLR4 in HT-29 cells. The levels of glycosylated TLR4 (Gly-TLR4) and surface TLR4 induced by C. concisus strains isolated from patients with IBD were significantly higher than those induced by C. concisus strains isolated from the healthy controls. Four C. concisus strains isolated from patients with IBD induced more than two-fold increase of surface expression of MD-2. C. concisus did not affect expression of TLR2 and TLR5. All C. concisus strains induced production of IL-8 and COX-2 in HT-29 cells.This study shows that some C. concisus strains, most from patients with IBD, upregulate surface expression of TLR4 and MD-2 in HT-29 cells. These data suggest that a potential role of specific C. concisus strains in modulating the intestinal epithelial responses to bacterial LPS needs to be investigated

MOESM4 of Zonula occludens toxins and their prophages in Campylobacter species

Additional file 4. Comparison of Zot proteins from Campylobacter species, N. meningitidis and V. cholerae. * indicates identical amino acids (shaded in red). : indicates conservative mutations (shaded in blue). .indicates semi-conservative mutations. Transmembrane domains are underlined. Walker A and walker B motifs in the N-terminus of Campylobacter Zot proteins were identified and boxed. Walker A has a sequence of GxxxxGK[S/T], where x is any residue. Walker B motif has a sequence of hhhh[D/E], where h is a hydrophobic residue [25]

MOESM1 of Zonula occludens toxins and their prophages in Campylobacter species

Additional file 1. Protein identities between prophages in other Campylobacter species and C. concisus CON_phi2 and CON_phi3. Zot proteins are in bold. Integrase proteins are underlined #Identity: Percentage of identical amino acids (number of identical amino acids divided by number of amino acids in proteins from C. concisus 13826)

Examination of the Anaerobic Growth of Campylobacter concisus Strains

Campylobacter concisus is an oral bacterium that is associated with intestinal diseases. C. concisus was previously described as a bacterium that requires H 2 -enriched microaerobic conditions for growth. The level of H 2 in the oral cavity is extremely low, suggesting that C. concisus is unlikely to have a microaerobic growth there. In this study, the anaerobic growth of C. concisus was investigated. The growth of fifty-seven oral C. concisus strains and six enteric C. concisus strains under various atmospheric conditions including anaerobic conditions with and without H 2 was examined. The atmospheric conditions were generated using commercially available gas-generation systems. C. concisus putative virulence proteins were identified using mass spectrometry analysis. Under anaerobic conditions, 92% of the oral C. concisus strains (52/57) and all six enteric strains grew without the presence of H 2 and the presence of H 2 greatly increased C. concisus growth. An oral C. concisus strain was found to express a number of putative virulence proteins and the expression levels of these proteins were not affected by H 2 . The levels of H 2 appeared to affect the optimal growth of C. concisus. This study provides useful information in understanding the natural colonization site and pathogenicity of C. concisus

Detection of COX-2 by Western blot in HT-29 cells infected with <i>C. concisus</i> strains.

<p>HT-cells 29 were lysed following incubation with <i>C. concisus</i> strains for 24 hours. Expression of COX-2 in HT-29 cells was detected by Western blot. The intensity of COX-2 band of each sample was normalized to the intensity of the internal control α-Tubulin of the same sample. The level of COX-2 was expressed as the fold change of the normalized band intensity of a sample relative to the normalized band intensity of the negative control (HT-29 cells without <i>C. concisus</i> infection). A: Representative Western blot of COX-2 (70 kD) and α-Tubulin (55 kD). B: Levels of COX-2 induced by different <i>C. concisus</i> strains; data were the average of triplicate experiments ± standard error. N: negative control. H2O1-H6O1: <i>C. concisus</i> strains isolated from healthy controls. The remaining nine <i>C. concisus</i> strains were from patients with IBD. The average level of COX-2 induced by <i>C. concisus</i> strains from patients with IBD was significantly higher than that induced by <i>C. concisus</i> strains from healthy controls (<i>P</i><0.05).</p