Endogenously produced hyaluronan contributes to the regulation of peritoneal adhesion development DOI Creative Commons
Anna Kocurková,

Michaela Kerberova,

Kristina Nešporová

et al.

BioFactors, Journal Year: 2023, Volume and Issue: 49(4), P. 940 - 955

Published: May 8, 2023

Abstract Peritoneal adhesions are postsurgical fibrotic complications connected to peritoneal inflammation. The exact mechanism of development is unknown; however, an important role attributed activated mesothelial cells (MCs) overproducing macromolecules extracellular matrix (ECM), including hyaluronic acid (HA). It was suggested that endogenously‐produced HA contributes the regulation different fibrosis‐related pathologies. However, little known about altered production in fibrosis. We focused on consequences increased turnover murine model adhesions. Changes metabolism were observed early phases adhesion vivo . To study mechanism, human MCs MeT‐5A and isolated from peritoneum healthy mice pro‐fibrotically by transforming growth factor β (TGFβ), attenuated two modulators carbohydrate metabolism, 4‐methylumbelliferone (4‐MU) 2‐deoxyglucose (2‐DG). attenuation mediated upregulation HAS2 downregulation HYAL2 lower expression pro‐fibrotic markers, fibronectin α‐smooth muscle actin (αSMA). Moreover, inclination form clusters also downregulated, particularly 2‐DG‐treated cells. effects 2‐DG, but not 4‐MU, changes cellular metabolism. Importantly, inhibition AKT phosphorylation after use both inhibitors. In summary, we identified endogenous as regulator fibrosis, just a passive player during this pathological process.

Language: Английский

Metabolism mechanism of glycosaminoglycans by the gut microbiota: Bacteroides and lactic acid bacteria: A review DOI

Jiahuan Dong,

Yanhua Cui,

Xiaojun Qu

et al.

Carbohydrate Polymers, Journal Year: 2024, Volume and Issue: 332, P. 121905 - 121905

Published: Feb. 5, 2024

Language: Английский

Citations

11
Biosynthetic production of anticoagulant heparin polysaccharides through metabolic and sulfotransferases engineering strategies DOI Creative Commons
Jian-Qun Deng, Yi Li,

Yu-Jia Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 4, 2024

Abstract Heparin is an important anticoagulant drug, and microbial heparin biosynthesis a potential alternative to animal-derived production. However, effectively using synthesis enzymes faces challenges, especially with recombinant expression of active heparan sulfate N -deacetylase/ -sulfotransferase. Here, we introduce the monosaccharide -trifluoroacetylglucosamine into Escherichia coli K5 facilitate sulfation modification. The Protein Repair One-Stop Service-Focused Rational Iterative Site-specific Mutagenesis (PROSS-FRISM) platform used enhance sulfotransferase efficiency, resulting in engineered NST-M8 enzyme significantly improved stability (11.32-fold) activity (2.53-fold) compared wild-type This approach can be applied engineering various sulfotransferases. multienzyme cascade reaction enables production from bioengineered heparosan, demonstrating anti-FXa (246.09 IU/mg) anti-FIIa (48.62 activities. study offers insights overcoming challenges modification, paving way for future development animal-free heparins cellular system-based semisynthetic strategy.

Language: Английский

Citations

7
Recent advances in molecular and nanoparticle probes for fluorescent bioanalysis DOI
Haowen Luo,

Lejie Tian,

Yaoming Zhang

et al.

Nano Research, Journal Year: 2024, Volume and Issue: 17(7), P. 6443 - 6474

Published: April 12, 2024

Language: Английский

Citations

5
Cytotoxicity and Genome Characteristics of an Emetic Toxin-Producing Bacillus cereus Group sp. Isolated from Raw Milk DOI Creative Commons
Jintana Pheepakpraw,

Chanita Sinchao,

Sawannee Sutheeworapong

et al.

Foods, Journal Year: 2025, Volume and Issue: 14(3), P. 485 - 485

Published: Feb. 3, 2025

The Bacillus cereus group frequently contaminates milk and dairy products. Some members of this can produce the heat-stable pre-formed toxin cereulide, which causes emetic foodborne intoxication. This study characterised B. isolates from raw cow’s in biochemical, genetic, toxigenic aspects. Of 158 derived 99 samples, 7 (4.43%) harboured cereulide synthetase A (cesA), encodes a associated with phenotype. Heat-treated culture filtrates cesA-positive demonstrated cytotoxicity to HepG2 Caco-2 cells, resulting cell viabilities 32.22–36.57% 44.41–47.08%, respectively. levels were comparable those reference strain, F4810/72 (alternately termed AH187). Genome analysis representative isolate, CSB98, revealed complete ces gene cluster additional virulence factors such as non-haemolytic enterotoxin, haemolysins phospholipases, suggesting that isolate could be both diarrhoeagenic. CSB98 exhibited closer relationship type strain paranthracis than sensu stricto (ATCC 14579). genomes AH187 indistinguishable through OrthoANI analysis, but 13 variants identified via SNP calling. These results affirm genetic conservation among traits.

Language: Английский

Citations

0
Genomic characterization of Bacillus cereus isolated from food poisoning cases revealed the mechanism of toxin production DOI Creative Commons

Qian Zhou,

Guanqiao Li, Yinshan Cui

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 12, 2024

Introduction Bacillus cereus is a ubiquitous opportunistic human pathogen that causes food intoxications worldwide. However, the genomic characteristics and pathogenic mechanisms of B. are still unclear. Methods Here, we isolated purified nine strains ( LY01-LY09 ) caused vomiting, diarrhea other symptoms from four foodborne outbreaks happened in Guizhou Province southwest China June to September 2021. After colony observation, Gram staining, microscopic examination biochemical test, they were identified as . The characteristics, phylogenetic relationships virulence factors analyzed at genome level. Genome sequencing, comparative analysis, secondary metabolite analysis quantitative PCR utilized give thorough exploration strains. Results We obtained maps found had complex interspecific relationship with anthracis thuringiensis also observed contraction gene families , contracted mainly associated prophage, which contributed species diversity Hsp20 family underwent rapid evolution facilitated adaptation adverse environmental conditions. Moreover, exhibited higher copy number non-ribosomal polypeptide synthetase (NRPS) genes carried complete cereulide ces cluster sequences. Considering NRPS system classical regulatory mechanism for emetic toxin synthesis, hypothesized could synthesize toxins through regulation clusters by system. Discussion These findings important further investigation into evolutionary between their related species, well underlying governing synthesis secretion bacterial toxins.

Language: Английский

Citations

3
Engineered Leukocyte Biomimetic Colorimetric Sensor Enables High-Efficient Detection of Tumor Cells Based on Bioorthogonal Chemistry DOI
Min Li,

Lanlan Jia,

Aihong Zhu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(28), P. 36106 - 36116

Published: July 2, 2024

Accurate detection of heterogeneous circulating tumor cells (CTCs) is critical as they can make more aggressive, drug-resistant, and metastasizing. Although the leukocyte membrane coating strategy promising in meeting challenge detecting CTCs due to its inherent antiadhesive properties, it still limited by reduction or loss expression known markers. Bioorthogonal glycol-metabolic engineering expected break down this barrier feeding with sugar derivatives a unique functional group establish artificial targets on surface cells. Herein, an engineered biomimetic colorimetric sensor was accordingly fabricated for high-efficient CTCs. Compared conventional coating, could covalently bound models fed Ac4ManNAz vitro through synergy bioorthogonal chemistry metabolic glycoengineering, ignoring phenotypic changes Meanwhile, sandwich structure composed layer/CTCs/MoS2 nanosheet formed visual HeLa low 10 mL–1. Overall, approach overcome dependence cell technology specific phenotypes provide new viewpoint highly efficiently detect

Language: Английский

Citations

3
Unraveling the intricacies of glycosaminoglycan biosynthesis: Decoding the molecular symphony in understanding complex polysaccharide assembly DOI

Zhi-Yuan Yao,

Jin-Song Gong,

Jiayu Jiang

et al.

Biotechnology Advances, Journal Year: 2024, Volume and Issue: 75, P. 108416 - 108416

Published: July 20, 2024

Language: Английский

Citations

2
Harnessing and Mimicking Bacterial Features to Combat Cancer: From Living Entities to Artificial Mimicking Systems DOI
Peng Gao, Zhenyu Duan, Gang Xu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: Aug. 1, 2024

Bacterial-derived micro-/nanomedicine has garnered considerable attention in anticancer therapy, owing to the unique natural features of bacteria, including specific targeting ability, immunogenic benefits, physicochemical modifiability, and biotechnological editability. Besides, bacterial components have also been explored as promising drug delivery vehicles. Harnessing these features, cutting-edge biotechnologies applied attenuated tumor-targeting bacteria with properties or functions for potent effective cancer treatment, strategies gene-editing genetic circuits. Further, advent bacteria-inspired micro-/nanorobots mimicking artificial systems furnished fresh perspectives formulating developing highly efficient systems. Focusing on advantages this review delves into advances bacteria-derived treatment recent years, which experienced a process from living entities Meanwhile, summary relative clinical trials is provided primary challenges impeding their application are discussed. Furthermore, future directions suggested combat cancer.

Language: Английский

Citations

2
Selective Glycan Labeling of Mannose-Containing Glycolipids in Mycobacteria DOI
So Young Lee, Victoria M. Marando, Stephanie R. Smelyansky

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 146(1), P. 377 - 385

Published: Dec. 19, 2023

Mycobacterium tuberculosis (Mtb) is one of history's most successful human pathogens. By subverting typical immune responses, Mtb can persist within a host until conditions become favorable for growth and proliferation. Virulence factors that enable mycobacteria to modulate systems include suite mannose-containing glycolipids: phosphatidylinositol mannosides, lipomannan, lipoarabinomannan (LAM). Despite their importance, tools covalent capture, modification, imaging are limited. Here, we describe chemical biology strategy detect visualize these glycans. Our approach, biosynthetic incorporation, synthesize lipid-glycan precursor be incorporated at late-stage step in glycolipid biosynthesis. We previously demonstrated selective mycobacterial arabinan modification by incorporation using an exogenous donor. This report reveals labeling general selective: it allows cell surface without nonspecific mannosylated glycoproteins. Specifically, employed azido-(Z,Z)-farnesyl phosphoryl-β-d-mannose probes took advantage the strain-promoted azide–alkyne cycloaddition label directly localization dynamics glycolipids. studies highlight generality utility as probe structure directs distinct The disclosed agents allowed direct tracking target immunomodulatory cellulo. anticipate will facilitate investigating diverse biological roles

Language: Английский

Citations

6
Cell-Based Assay Approaches for Glycosaminoglycan Synthase High-Throughput Screening: Development and Applications DOI
Hong‐Yu Hu, Jian-Qun Deng,

Yu-Jia Wang

et al.

ACS Chemical Biology, Journal Year: 2023, Volume and Issue: 18(7), P. 1632 - 1641

Published: July 10, 2023

Glycosaminoglycan synthases have immense potential in applications involving synthesis of oligosaccharides, using enzymatic approaches and construction cell factories that produce polysaccharides as critical metabolic components. However, the use high-throughput activity assays to screen for evolution these enzymes can be challenging because there are no significant changes fluorescence or absorbance associated with glycosidic bond formation. Here, incorporation azido-labeled N-acetylhexosamine analogs into bacterial capsule via metabolism bioorthogonal chemistry, fluorophores were specifically introduced onto surfaces. Furthermore, correlations between detectable signals polysaccharide-synthesizing capacity individual bacteria established. Among 10 candidate genes, 6 members chondroitin synthase family quickly identified a recombinant Bacillus subtilis host strain. Additionally, directed heparosan was successfully performed fluorescence-activated sorting Escherichia coli O10:K5(L):H4, yielding several mutants increased activity. Cell-based selectively detect presence absence within an colony cells, well their level activity, broad exploration engineering glycosaminoglycan synthases. These also support creation novel strategies screening enzyme based on systems.

Language: Английский

Citations

3