Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea

Microbiome, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 4, 2025

Disorder in bile acid (BA) metabolism is known to be an important factor contributing diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear. The colonic pool and microbiota between health piglets diarrheal were compared. Fecal transplantation various cell experiments further indicated that chenodeoxycholic (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which main cause Non-targeted metabolomics uncovered inhibition glucuronidation by Lactobacillus reuteri (L. reuteri) through deriving indole-3-carbinol (I3C). In vitro, gene involved reduction induced-diarrhea screened RNA transcriptomics sequencing, activation pathway FXR-SIRT1-LKB1 alleviate P53-mediated apoptosis proposed vitro multifarious siRNA interference, CO-IP, immunofluorescence, so on, mechanism was also verified a variety mouse models. Here, we reveal for first time core derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, reaction mediated host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) necessary induced Mechanistically, L. activates aryl hydrocarbon receptor decrease UGT1A4 transcription CDCA-3β-glucuronide content, thereby upregulating signal. LKB1 binds with P53 based on protein interaction, ultimately resists Moreover, assists attain ameliorative effects FXR diarrhea, reversion abnormal pathway, improving outcomes supplement. These findings uncover crucial interplay epithelial cells microbes, highlighting UGT1A4-mediated conversion as key target ameliorating

Language: Английский

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Omics technologies in allergy and asthma research: An EAACI position paper

Allergy, Journal Year: 2022, Volume and Issue: 77(10), P. 2888 - 2908

Published: June 17, 2022

Allergic diseases and asthma are heterogenous chronic inflammatory conditions with several distinct complex endotypes. Both environmental genetic factors can influence the development progression of allergy. Complex pathogenetic pathways observed in allergic disorders present a challenge patient management successful targeted treatment strategies. The increasing availability high-throughput omics technologies, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics allows studying biochemical systems pathophysiological processes underlying responses. Additionally, techniques clinical applicability by functional identification validation biomarkers. Therefore, finding molecules or patterns characteristic for immune-inflammatory endotypes, subsequently its development, progression, treatment. There is great potential to further increase effectiveness single approaches integrating them other omics, nonomics data. Systems biology aims simultaneously longitudinally understand multiple layers multifactorial disease, allergy, several, separated data sets generating complete molecular profile condition. With use sophisticated biostatistics machine learning techniques, these provide in-depth insight into individual biological will allow efficient customized healthcare approaches, called precision medicine. In this EAACI Position Paper, Task Force "Omics technologies research" broadly reviewed current advances research, focus on methodology analysis, aiming researchers (basic clinical) desk reference field. strategies understanding disease pathophysiology key tools reach unmet needs allergy medicine, patients' stratification, accurate prognosis, prediction efficacy prevention measures highlighted.

Language: Английский

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Toxicity identification evaluation for hydraulic fracturing flowback and produced water during shale gas exploitation in China: Evidence from tissue residues and gene expression

Water Research, Journal Year: 2023, Volume and Issue: 241, P. 120170 - 120170

Published: June 3, 2023

Language: Английский

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A single-cell characterised signature integrating heterogeneity and microenvironment of lung adenocarcinoma for prognostic stratification

EBioMedicine, Journal Year: 2024, Volume and Issue: 102, P. 105092 - 105092

Published: March 28, 2024

The high heterogeneity of tumour and the complexity microenvironment (TME) greatly impacted development prognosis cancer in era immunotherapy. In this study, we aimed to portray single cell-characterised landscape lung adenocarcinoma (LUAD), develop an integrated signature incorporating both TME for stratification.

Language: Английский

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Heterogeneity of tumor immune microenvironment of EGFR/ALK-positive tumors versus EGFR/ALK-negative tumors in resected brain metastases from lung adenocarcinoma

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(3), P. e006243 - e006243

Published: March 1, 2023

Previous studies found that lung adenocarcinomas (LUAD) with EGFR-positive and ALK-positive were less responsive to immunotherapy, which may be associated a suppressive tumor immune microenvironment (TIME). Given the discordance in TIME between primary cancer brain metastasis, it is urgent explore patients EGFR/ALK-positive LUAD metastases (BMs).The transcriptome feature of formalin-fixed paraffin-embedded samples BMs paired from 70 was illustrated by RNA-sequencing. Six them available for sample analysis. Then, after excluding 3 co-occurring patients, we divided 67 into 41 26 EGFR/ALK-negative patients. The differences profiling two groups analyzed three dimensions: TIME, T-cell receptor repertoire, immunohistochemistry. Finally, survival data 55 collected.Compared LUAD, present an immunosuppressed manifested as: inhibition immune-related pathways; low expression checkpoint; decreased infiltration CD8+T cells cytotoxic lymphocyte; increased proportion M2 macrophages. In different subgroups based on EGFR/ALK gene variation status, both tumors relatively immunosuppressive microenvironment, but heterogeneity undergo mechanisms. showed regulatory T (Treg) cells, while Moreover, TCGA-LUAD cohort, reduced cell infiltrations (p<0.001) borderline significantly higher Tregs than (p=0.072). parallel, had median macrophages (p=0.175), although there no statistical significance. Collectively, similar milieu BMs. analysis uncovered CD8A expression, lymphocyte infiltration, scores better prognosis groups.This study LUAD-derived exhibited revealed characteristics. Meanwhile, EGFR-negative potential benefit immunotherapy. These findings boost molecular clinical understanding

Language: Английский

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Transcriptomic analysis reveals zinc-mediated virulence and pathogenicity in multidrug-resistant Acinetobacter baumannii

Advances in protein chemistry and structural biology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 21

Published: Jan. 1, 2024

Language: Английский

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Transcriptome and MicroRNA Analysis of Juglans regia in Response to Low-Temperature Stress

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1401 - 1401

Published: Feb. 7, 2025

Walnuts are among the globally significant woody food and oil tree species. At high latitudes, they frequently experience late-frost damage, inducing low-temperature stress, which significantly affects walnut seedlings. The aim of this study was to investigate physiological biochemical alterations in seedlings under (LT) stress along with its underlying molecular mechanisms. Physiological indices were determined, transcriptome miRNA sequenced by sampling leaves (0 h, 6 12 24 48 h) two-month-old live walnuts treated a low temperature 4 °C. results indicated that LT induced an increase electrical conductivity malondialdehyde content while simultaneously causing reduction Fv/Fm. From comparison between control groups, total 12,566 differentially expressed genes (DEGs) identified, consisting 6829 up-regulated 5737 down-regulated genes. Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment analyses revealed DEGs primarily enriched polysaccharide metabolic processes, responses abscisic acid phenylpropanoid biosynthesis pathways. Furthermore, database identified 1052 miRNAs response walnuts; these found target 7043 predicted Through integration analysis data, 244 differential identified. Following GO KEGG genes, we regulate pathways involved starch sucrose metabolism, glyoxylate dicarboxylate glycerophospholipid biosynthesis, as well phenylalanine, tyrosine, tryptophan stress. Additionally, conducted in-depth associations microRNAs (DEMs) within metabolism pathway. Real-time fluorescent quantitative PCR (qRT-PCR) validation expression patterns subset confirmed accuracy data. This unveils potential mechanisms walnut’s providing valuable genetic resources for future research on cold tolerance damage.

Language: Английский

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Utility of a Large Series of B‐Cell Precursor Acute Lymphoblastic Leukemia Cell Lines as a Model System

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(5)

Published: March 1, 2025

ABSTRACT Background In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), chromosomal translocations are strongly associated with prognoses. RNA sequencing (RNA‐seq) is a powerful technology that reveals close correlation between types of translocation and patterns gene expression in clinical samples BCP‐ALL. Cancer cell lines research tools, thus, we built larger series BCP‐ALL performed RNA‐seq analysis to confirm their utility as model system. Methods We total 94 lines, including 80 8 representative translocations. Results the UMAP visualization, association was confirmed fusion genes expression. cluster profile, each type showed clear profile top 51 variable genes. Of importance, majority also significant samples. When an 125 cycle‐related percentage S G2/M phases 67 evaluated, positive cycle progression 10 ( HDAC2 , CDC23 YWHAG MAD2L1 CCNH ANAPC7 CDC6 ANAPC5 ORC3 RBX1 ). Moreover, upregulation downregulation 40 genes, respectively, were observed established at relapse compared those diagnosis. Four SP6 CCNE1 HIST1H2BH DECR2 ) two EVI2B SYN1 these significantly higher lower, than Conclusion Large tool for studying mechanisms leukemogenesis disease

Language: Английский

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Hypobaric hypoxia exposure alters transcriptome in mouse testis and impairs spermatogenesis in offspring

Gene, Journal Year: 2022, Volume and Issue: 823, P. 146390 - 146390

Published: March 4, 2022

Language: Английский

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T proliferating cells derived autophagy signature associated with prognosis and immunotherapy resistance in a pan-cancer analysis

iScience, Journal Year: 2023, Volume and Issue: 27(1), P. 108701 - 108701

Published: Dec. 8, 2023

Despite autophagy modulating tumor immunity in the microenvironment (TME), immunotherapeutic efficacy and potential mechanism of signature was not explicit. We manually curated an gene set defined a pan-cancer by comparing malignant tissues normal The Cancer Genome Atlas (TCGA) cohort. derived from T proliferating cells as demonstrated multiple single-cell RNA sequencing (scRNA-seq) datasets. could influence cell-cell interactions TME predict responsiveness immune checkpoint inhibitors (ICIs) metastatic renal cell carcinoma, non-small lung cancer, bladder melanoma cohorts. Metabolism inactivation accompanied with dysregulation investigated transcriptomic proteomic data. predictive role regulation validated in-house Our study provides valuable insights into mechanisms ICI resistance.

Language: Английский

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