Single cell transcriptional and chromatin accessibility profiling redefine cellular heterogeneity in the adult human kidney

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 13, 2021

Abstract The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding heterogeneity. We performed nucleus ATAC (snATAC-seq) RNA (snRNA-seq) sequencing to generate paired, cell-type-specific transcriptional profiles the adult human kidney. demonstrate that snATAC-seq is comparable snRNA-seq in assignment identity can further refine our functional heterogeneity nephron. majority differentially accessible regions are localized promoters significant proportion closely associated with expressed genes. Cell-type-specific enrichment transcription factor binding motifs implicates activation NF-κB promotes VCAM1 expression drives transition between subpopulation proximal tubule epithelial cells. Our multi-omics approach improves ability detect unique states within kidney redefines cellular thick ascending limb.

Language: Английский

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A comprehensive review on the potential of microbial enzymes in multipollutant bioremediation: Mechanisms, challenges, and future prospects

Journal of Environmental Management, Journal Year: 2023, Volume and Issue: 334, P. 117532 - 117532

Published: Feb. 20, 2023

Language: Английский

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Genetic modification of flavone biosynthesis in rice enhances biofilm formation of soil diazotrophic bacteria and biological nitrogen fixation

Plant Biotechnology Journal, Journal Year: 2022, Volume and Issue: 20(11), P. 2135 - 2148

Published: July 23, 2022

Improving biological nitrogen fixation (BNF) in cereal crops is a long-sought objective; however, no successful modification of showing increased BNF has been reported. Here, we described novel approach which rice plants were modified to increase the production compounds that stimulated biofilm formation soil diazotrophic bacteria, promoted bacterial colonization plant tissues and improved with grain yield at limiting contents. We first used chemical screening identify plant-produced induced nitrogen-fixing bacteria demonstrated apigenin other flavones BNF. then CRISPR-based gene editing targeting breakdown rice, increasing contents root exudation. When grown conditions, displayed yield. Biofilm also microbiome structure, favouring enrichment recruitment. Our results support manipulation flavone biosynthetic pathway as feasible strategy for induction cereals reduction use inorganic fertilizers.

Language: Английский

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Parallel gene expansions drive rapid dietary adaptation in herbivorous woodrats

Science, Journal Year: 2025, Volume and Issue: 387(6730), P. 156 - 162

Published: Jan. 9, 2025

How mammalian herbivores evolve to feed on chemically defended plants remains poorly understood. In this study, we investigated the adaptation of two species woodrats ( Neotoma lepida and N. bryanti ) creosote bush Larrea tridentata ), a toxic shrub that expanded across southwestern United States after Last Glacial Maximum. We found creosote-adapted have elevated gene dosage multiple biotransformation enzyme families. These duplication events occurred independently substantially increase expression genes, especially within glucuronidation pathway. propose increased resulting from is an important mechanism by which animals initially adapt novel environmental pressures.

Language: Английский

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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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Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression

British Journal of Cancer, Journal Year: 2020, Volume and Issue: 122(9), P. 1277 - 1287

Published: Feb. 12, 2020

Abstract The best-known role of UDP-glucuronosyltransferase enzymes (UGTs) in cancer is the metabolic inactivation drug therapies. By conjugating glucuronic acid to lipophilic drugs, UGTs impair biological activity and enhance water solubility these agents, driving their elimination. Multiple clinical observations support an expanding for as modulators response mediating resistance numerous types. However, accumulating evidence also suggests influence UGT pathway on progression. Dysregulation expression has been associated with progression several cancers, arguing possible mediators oncogenic pathways and/or disease accelerators a drug-naive context. consequences altered tumour biology are incompletely understood. They might be perturbed levels bioactive endogenous metabolites such steroids lipids that inactivated by or through non-enzymatic mechanisms, thereby eliciting signalling cascades. This review highlights supporting dual roles pathway, affecting resistance. Pharmacogenomic testing profiles patients development therapeutic options actions could provide useful prognostic predictive biomarkers efficacy anti-cancer drugs.

Language: Английский

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Xenobiotic metabolism and transport in Caenorhabditis elegans

Journal of Toxicology and Environmental Health Part B, Journal Year: 2021, Volume and Issue: 24(2), P. 51 - 94

Published: Feb. 17, 2021

Caenorhabditis elegans has emerged as a major model in biomedical and environmental toxicology. Numerous papers on toxicology pharmacology C. have been published, this species now adopted by investigators academic toxicology, pharmacology, drug discovery labs. also attracted the interest of governmental regulatory agencies charged with evaluating safety chemicals. However, major, fundamental aspect toxicological science remains underdeveloped elegans: xenobiotic metabolism transport processes that are critical to understanding toxicokinetics toxicodynamics, extrapolation other species. The aim review was initially briefly describe history trajectory use pharmacological studies. Subsequently, physical barriers chemical uptake role worm microbiome transformation were described. Then what is not known regarding classic Phase I, II, III performed. In addition, following discussed (1) regulation metabolism; (2) published for specific chemicals; (3) genetic diversity these elegans. Finally, placed an evolutionary context; key areas future research highlighted; implications extrapolating toxicity results discussed.

Language: Английский

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Structure, synthesis, biosynthesis, and activity of the characteristic compounds fromGinkgo bilobaL.

Natural Product Reports, Journal Year: 2021, Volume and Issue: 39(3), P. 474 - 511

Published: Sept. 28, 2021

Covering: 1928-2021Ginkgo biloba L. is one of the most distinctive plants to have emerged on earth and has no close living relatives. Owing its phylogenetic divergence from other plants, G. contains many compounds with unique structures that served broaden chemical diversity herbal medicine. Examples such include terpene trilactones (ginkgolides), acylated flavonol glycosides (ginkgoghrelins), biflavones (ginkgetin), ginkgotides ginkgolic acids. The extract leaf used prevent and/or treat cardiovascular diseases, while ginkgo-derived are currently at various stages preclinical clinical trials worldwide. global annual sales products estimated total US$10 billion. However, content purity active isolated by traditional methods usually low subject varying environmental factors, making it difficult meet huge demand international market. This highlights need develop new strategies for preparation these characteristic biloba. In this review, we provide a detailed description bioactivities summarize recent research development synthesis, biosynthesis, biotechnological production terpenoids, flavonoids, alkylphenols/alkylphenolic acids Our aim an important point reference all scientists who ginkgo-related medicinal or purposes.

Language: Английский

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Glycosyltransferase GT1 family: Phylogenetic distribution, substrates coverage, and representative structural features

Computational and Structural Biotechnology Journal, Journal Year: 2020, Volume and Issue: 18, P. 1383 - 1390

Published: Jan. 1, 2020

Highlights•The phylogenetic distribution of GT1 family enzymes showed domain-dependent pattern.•The characterized GTs distinct substrates spectrum.•Two regions that discriminate the from different domains were identified.Graphical abstractAbstractGlycosyltransferases (GTs) are responsible for transferring glycosyl moieties activated sugar donors to certain acceptors, among which have been known their outstanding glycosylation capacities toward diverse natural products, such as glycolipids, flavonoids and macrolides etc. However, there still lacks a systematic collation this important members. In minireview, all sequences phylogenetically analyzed, grouping proteins exhibited taxonomic life pattern, revealing many untapped clades GTs. The further analysis facilitated classification coverage domains, whereby bacteria can tolerate wider spectrum chemical skeletons substrates, showing higher promiscuity than those other domains. Furthermore, sequence sizes compared understand selectivity. Based on multiple alignments 28 representative with crystal structures, two critical located in N-terminal identified, most variable essential binding and/or catalysis. key roles these validated by enumerating influential residues interacted structures plants. atlas terms phylogeny, selectivity, length, motifs provides clues exploration unknown GT1s rational engineering enzymes, synthesizing novel promising glycoconjugates pharmaceutical application.

Language: Английский

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Drug metabolism and drug transport of the 100 most prescribed oral drugs

Basic & Clinical Pharmacology & Toxicology, Journal Year: 2022, Volume and Issue: 131(5), P. 311 - 324

Published: Aug. 16, 2022

Safe and effective use of drugs requires an understanding metabolism transport. We identified the 100 most prescribed in six countries conducted a literature search on vitro data to assess contribution Phase I II enzymes drug transporters Eighty-nine undergo or are known substrates for transporters. involved 67 drugs, while mediate 18 drugs. CYP3A4/5 is important enzyme 43 followed by CYP2D6 (23 drugs), CYP2C9 CYP2C19 (22 CYP1A2 (14 drugs) CYP2C8 (11 drugs). More than half (54 P-glycoprotein (P-gp) be transport 30 breast cancer resistance protein (BCRP) facilitates 11 A considerable proportion subject combination metabolism, and/or conclude that majority frequently depend Thus, variability remains priority.

Language: Английский

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