METTL14 regulates inflammation in ulcerative colitis via the lncRNA DHRS4-AS1/miR-206/A3AR axis DOI Creative Commons

Weiyun Wu,

Xiaowen Li,

Zhuliang Zhou

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Nov. 11, 2024

As a chronic inflammatory bowel disease, the pathogenesis of ulcerative colitis (UC) has not been fully elucidated. N6-methyladenosine (m6A) modification, observed in various RNAs, is implicated diseases. Methyltransferase-like 14 (METTL14) major subunit methyltransferase complex catalyzing m6A modifications. Here, we designated to examine regulatory effects and mechanisms METTL14 on long non-coding RNA (lncRNA) during UC progression. knockdown decreased cell viability, promoted apoptosis, increased cleaved PARP Caspase-3 levels, while reducing Bcl-2 levels. also led significant increase NF-κB pathway activation cytokine production Caco-2 cells treated with TNF-α. Moreover, suppression aggravated colonic damage inflammation our dextran sulfate sodium (DSS)-induced murine model. silencing suppressed DHRS4-AS1 expression by modification transcripts. Furthermore, mitigated injury targeting miR-206/adenosine A3 receptor (A3AR) axis. overexpression counteracted enhancing impact TNF-α-induced cells. In conclusion, findings suggest that protects against via regulating DHRS4-AS1/miR-206/A3AR axis, thus representing potential therapeutic target for UC.

Language: Английский

Plasma Epstein-Barr Virus DNA load for diagnostic and prognostic assessment in intestinal Epstein-Barr Virus infection DOI Creative Commons
Chunxiang Ma, Mingshan Jiang, Jiaxin Li

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 7, 2025

The prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for loads in the diagnosis and outcome prediction infection, particularly cases primary lymphoproliferative diseases inflammatory bowel disease (IBD). Receiver operating characteristic (ROC) curves were examined determine suitable thresholds diagnosing predicting its prognosis. 108 patients retrospectively assigned test group, while 56 included validation group. Plasma significantly higher group compared non-intestinal (Median: 2.02 × 102 copies/mL, interquartile range [IQR]: 5.49 101-6.34×103 copies/mL versus 4.2×101 IQR: 1.07 ×101-6.08×101 copies/mL; P < 0.0001). at 9.21×101 6.77×101 proved beneficial identification prognostication respectively. Values 0.82 0.71 yielded by area under ROC curve (AUC) cohort, corresponding sensitivities 84.38% (95% confidence interval [95%CI]: 68.25%-93.14%) 87.5% (95%CI: 69%-95.66%), specificities 83.33% 64.15%-93.32%) 68.09% 53.83%-79.6%), positive predictive values (PPV) 87.1% 71.15%-94.87%) 58.33% 42.2%-72.86%), likelihood ratios (LR+) 5.06 2.74 Furthermore, 5.4×102 helped differentiate IBD with from EBV-positive disorders (PIEBV+LPDs), achieving an AUC 0.85 within well 85% sensitivity 63.96%-94.76%), 91.67% specificity 64.61%-99.57%), 94.44% PPV 74.24%-99.72%), LR+ 10.2 cohort. demonstrates notable potential distinguishing between different patient cohorts although requires further optimization clinical application.

Language: Английский

Citations

3

Epstein-Barr virus Infection Exacerbates Ulcerative Colitis by Driving Macrophage Pyroptosis via the Upregulation of Glycolysis DOI Creative Commons
Chunxiang Ma, Kexin Chen, Lili Li

et al.

Precision Clinical Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Epstein-Barr virus (EBV) infection is associated with clinical symptoms, treatment response, need for surgical intervention, and an enhanced likelihood of lymphoma among patients ulcerative colitis (UC). However, existing studies have primarily concentrated on the epidemiological associations between EBV UC, leaving mechanisms by which exacerbates poorly understood. Clinical specimens UC a mouse model dextran sulfate sodium-induced concurrent murine γ-herpesvirus 68 (MHV-68) were utilized to investigate relationship macrophage pyroptosis. In vivo, adoptive transfer MHV-68-induced macrophages depletion performed elucidate underlying mechanisms. vitro, myeloid leukemia mononuclear cells human (THP-1) derived from bone marrow (BMDMs) stimulated MHV-68, respectively, assess pyroptosis glycolysis. EBV-induced activation was positively correlated disease activity in patients. Furthermore, MHV-68 activated upregulating gasdermin D, NLRP3, interleukin-1β, interleukin-18 colonic tissues peritoneal mice colitis. also mediated THP-1 BMDMs, respectively. Additionally, BMDMs aggravated colitis, whereas attenuated intestinal injury. Mechanistically, promoted glycolysis, while glycolysis inhibitor, 2-deoxy-D-glucose, blocked this process vitro. driving through upregulation indicating potential therapeutic approach mitigate inflammation.

Language: Английский

Citations

2

Diagnosis and management of inflammatory bowel disease DOI
Lili Li, Rui Cheng,

Yushan Wu

et al.

Journal of Evidence-Based Medicine, Journal Year: 2024, Volume and Issue: 17(2), P. 409 - 433

Published: June 1, 2024

Abstract Inflammatory bowel disease (IBD) is a chronic and relapsing immune‐mediated of the gastrointestinal tract with gradually increasing global incidence prevalence. A prolonged course IBD leads to decline in patient quality life creation substantial economic burden on society. Owing lack specific diagnostic markers, diagnosis still needs gold standard based combination clinical manifestations, imaging, laboratory, endoscopic results. Accordingly, current goals treatment are alleviate symptoms reduce recurrence rates. Therefore, it imperative develop set procedures diagnose treat IBD. In this review, we summarize prominent emerging studies, outline classical contemporary approaches diagnosing managing IBD, integrate multiple guidelines. Furthermore, propose possibility establishing an early comprehensive workflow personalized management strategy future. We aim enhance standardization for

Language: Английский

Citations

14

Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation DOI Creative Commons
Liping Chen, Zhenghao Ye, Junhua Li

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 13, 2025

The conversion of primary bile acids to secondary by the gut microbiota has been implicated in colonic inflammation. This study investigated role related acid metabolism inflammation both patients with inflammatory bowel disease (IBD) and a murine model dextran sulfate sodium (DSS)-induced colitis. Bile fecal samples from IBD DSS-induced colitis mice, without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS). composition DSS-colitis mice was characterized via Illumina MiSeq sequencing bacterial 16S rRNA gene V3-V4 region. Metagenomic profiling further identified metabolism-related signatures stool mice. Histological analysis, quantitative PCR (qPCR) Western Blotting conducted on assess inflammation, mucosal barrier integrity, associated signaling pathways. multivariate analysis Soft Independent Modelling Class Analogy (SIMCA, Umetrics, Sweden). relation between relative abundance specific phyla/genera concentration through Spearman's correlation analyses. Finally, lithocholic (LCA), key acid, administered gavage evaluate its effect integrity. In IBD, altered. Moreover, changes modulate intestine. As continues shift, profile undergoes additional alterations. aforementioned alterations also observed revealed dysbiosis modifications acids, notably LCA Through as that significantly affects integrity barrier. Subsequent experiments confirmed supplementation effectively mitigated inhibitory effects progression primarily activation sphingosine-1-phosphate receptor 2 (S1PR2)/NF-κB p65 pathway. Analysis microbiome metagenomic data microbiota, an increased unclassified genus within family Prevotellaceae Furthermore, positive biosynthesis pathways, well level. These findings suggest positively correlated bacteria, Prevotellaceae, are closely intestinal Targeting may involve inhibiting members potential therapeutic strategies.

Language: Английский

Citations

0

Antibacterial activity and impact on keratinocyte cell growth of Cutibacterium acnes bacteriophages in a Cutibacterium acnes IA1- colonized keratinocyte model DOI Creative Commons

Juan C Farfán-Esquivel,

María Victoria Gutiérrez,

Alejandro Ondo-Méndez

et al.

Current Research in Microbial Sciences, Journal Year: 2025, Volume and Issue: unknown, P. 100356 - 100356

Published: Jan. 1, 2025

Language: Английский

Citations

0

Inflammation and cancer: molecular mechanisms and clinical consequences DOI Creative Commons
Hikmet Akkız, Cem Şimşek, Deniz Balcı

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 17, 2025

Inflammation, a hallmark of cancer, has been associated with tumor progression, transition into malignant phenotype and efficacy anticancer treatments in cancer. It affects all stages from the initiation carcinogenesis to metastasis. Chronic inflammation induces immunosup-pression, providing an environment conducive carcinogenesis, whereas acute antitumor immune response, leading suppression. Solid tumors have inflammatory microenvironment (TME) containing cancer cells, stromal soluble molecules, which plays key role progression therapy response. Both cells TME are highly plastic constantly change their phenotypic functional properties. Cancer-associated inflammation, majority consists innate important cell plasticity, development drug resistance. Today, combined used advanced technologies, such as single-cell RNA sequencing spatial molecular imaging analysis, pathways linking chronic largely elucidated. In this review article, we highlighted cellular mechanisms involved cancer-associated its effects on treatment We also comprehensively setting GI cancers.

Language: Английский

Citations

0

Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease DOI Creative Commons

Yushan Wu,

Rui Cheng, Hao Lin

et al.

BMC Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 26, 2025

Language: Английский

Citations

0

Neue und aktuelle Therapieziele bei chronisch entzündlichen Darmerkrankungen DOI

Raul Lande,

Irina Blumenstein

DMW - Deutsche Medizinische Wochenschrift, Journal Year: 2025, Volume and Issue: 150(08), P. 427 - 432

Published: March 31, 2025

Chronic inflammatory bowel diseases (IBD), such as Crohn's disease (MC) and ulcerative colitis (CU), are serious immune-mediated that affect the gastrointestinal tract represent a considerable burden for patients. In recent decades, treatment of IBD has shifted from symptomatic control to more precise, long-term goals. Advances in research have led therapy goals having been redefined expanded order achieve complete inflammation prevent complications long term.An important component modern therapeutic approaches is definition specific markers serve indicators achievement these These enable objective monitoring success thus offer clear approach controlling therapy. The present article focuses on new discusses role target clinical practice.A central goal endoscopic healing, i.e. macroscopic healing intestinal mucosa. practice this includes particular an ulcer-free contrast remission alone, provides assessment state correlates strongly with improved prognosis.The histologic goes beyond aims no longer detect signs at microscopic level. This particularly relevant results show patients who histological even lower recurrence rate better than those only or remission.Even though curative currently exists, cure remains ultimate research. current practice, still unattainable but progress genetic immunological offers hope. term, aim innovative gene editing immunotherapy disease. could mean not free symptoms, also freed term.

Language: Английский

Citations

0

Akkermansia muciniphila Protects Against Trinitrobenzene Sulfonic Acid Induced Colitis by Inhibiting IL6/STAT3 Pathway DOI
Mingshan Jiang,

Yongbin Jia,

Chunxiang Ma

et al.

Inflammatory Bowel Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Background Inflammatory bowel disease is a long-standing inflammatory disorder that influences the intestinal tract. The intent of this research to explore whether relative abundance Akkermansia muciniphila related IL6/STAT3 pathway and fundamental molecular mechanisms A. on trinitrobenzene sulfonic acid (TNBS)-induced enteritis mouse model, including expression cytokines proteins in signaling pathway. Methods association between was investigated by using mucosal biopsies fecal samples. TNBS-induced colitis models were performed elucidate underlying mechanisms. alteration microbiota organized 16s rRNA sequencing. Results In Crohn’s patients, level STAT3 IL-6 presented negative relationship with muciniphila. IL-6, p-STAT3, downregulated A.m+TNBS group, indicating may inhibit vivo. To investigate potential defensive role supplementation vivo enteritis, 16S sequencing analyze changes composition. results revealed marked increase microbial diversity within muciniphila-treated suggesting beneficial modulation gut microbiome associated supplementation. Conclusions Our findings declared alleviates gastrointestinal inflammation through IL-6/STAT3 This protective effect mediated downregulation STAT3, highlighting mechanism which modulates responses. work disclosed demonstrates influence against vivo, proposing it qualified as unique therapeutic focusing modulating or p-STAT3 treatment colitis.

Language: Английский

Citations

0

SIRT1 Stabilizes β-TrCP1 to Inhibit Snail1 Expression in Maintaining Intestinal Epithelial Integrity to Alleviate Colitis DOI Creative Commons
Liang Wang, Jinsong Li, Mingshan Jiang

et al.

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: 18(2), P. 101354 - 101354

Published: Jan. 1, 2024

DSS-induced mouse colitis is caused by the inhibition of SIRT1, leading to β-TrCP1 degradation and Snail1 stabilization, resulting in disruption cell adhesion tight junction, accompanied integrity loss epithelial barrier increased inflammation, which can be alleviated NMN.

Language: Английский

Citations

3