Functional metabolomics revealed the dual-activation of cAMP-AMP axis is a novel therapeutic target of pancreatic cancer

Liu, Jingjing; Jing, Wanghui; Wang, Tianyu; Hu, Zhe; Lü, Haitao

doi:10.1016/j.phrs.2022.106554

Cited by 7 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The heatmaps were drawn via TBtools [30]. The PCoA, correlation heatmaps, and RDA analysis were performed on Omicshare Tools (https://www.omicshare.com/tools/, accessed on 10 December 2023) [31,32].…”

Section: Discussionmentioning

confidence: 99%

Metagenomic Insight into the Effect of Probiotics on Nitrogen Cycle in the Coilia nasus Aquaculture Pond Water

Mang,

Gao,

et al. 2024

Microorganisms

View full text Add to dashboard Cite

Recently, probiotics have been widely applied for the in situ remediation of aquatic water. Numerous studies have proved that probiotics can regulate water quality by improving the microbial community. Nitrogen cycling, induced by microorganisms, is a crucial process for maintaining the balance of the aquatic ecosystem. Nevertheless, the underlying mechanisms by which probiotics enhance water quality in aquatic systems remain poorly understood. To explore the water quality indicators and their correlation with nitrogen cycling-related functional genes, metagenomic analysis of element cycling was performed to identify nitrogen cycling-related functional genes in Coilia nasus aquatic water between the control group (C) and the groups supplemented with probiotics in feed (PF) or water (PW). The results showed that adding probiotics to the aquatic water could reduce the concentrations of ammonia nitrogen (NH4+-N), nitrite (NO2−-N), and total nitrogen (TN) in the water. Community structure analysis revealed that the relative abundance of Verrucomicrobiota was increased from 30 d to 120 d (2.61% to 6.35%) in the PW group, while the relative abundance of Cyanobacteria was decreased from 30 d to 120 d (5.66% to 1.77%). We constructed a nitrogen cycling pathway diagram for C. nasus aquaculture ponds. The nitrogen cycle functional analysis showed that adding probiotics to the water could increase the relative abundance of the amoC_B and hao (Nitrification pathways) and the nirS and nosZ (Denitrification pathways). Correlation analysis revealed that NH4+-N was significantly negatively correlated with Limnohabitans, Sediminibacterium, and Algoriphagus, while NO2−-N was significantly negatively correlated with Roseomonas and Rubrivivax. Our study demonstrated that adding probiotics to the water can promote nitrogen element conversion and migration, facilitate nitrogen cycling, benefit ecological environment protection, and remove nitrogen-containing compounds in aquaculture systems by altering the relative abundance of nitrogen cycling-related functional genes and microorganisms.

show abstract

Section: Discussionmentioning

confidence: 99%

Metagenomic Insight into the Effect of Probiotics on Nitrogen Cycle in the Coilia nasus Aquaculture Pond Water

Mang,

Gao,

et al. 2024

Microorganisms

View full text Add to dashboard Cite

show abstract

“…Finally, it was verified that the accumulation of AMP and cAMP induced by gemcitabine can, respectively, activate the downstream kinases AMP-activated protein kinase and protein kinase A, leading to tumor growth inhibition through the overexpression of growth arrest and DNA damage-inducible protein 45A. The dual activation of the AMP-cAMP axis represents a potential new target for PC treatment [ 63 ].…”

Section: Classical Multi-omics Integration Methodsmentioning

confidence: 99%

Advances in Integrated Multi-omics Analysis for Drug-Target Identification

Du,

Fan,

Zhang

et al. 2024

Biomolecules

View full text Add to dashboard Cite

As an essential component of modern drug discovery, the role of drug-target identification is growing increasingly prominent. Additionally, single-omics technologies have been widely utilized in the process of discovering drug targets. However, it is difficult for any single-omics level to clearly expound the causal connection between drugs and how they give rise to the emergence of complex phenotypes. With the progress of large-scale sequencing and the development of high-throughput technologies, the tendency in drug-target identification has shifted towards integrated multi-omics techniques, gradually replacing traditional single-omics techniques. Herein, this review centers on the recent advancements in the domain of integrated multi-omics techniques for target identification, highlights the common multi-omics analysis strategies, briefly summarizes the selection of multi-omics analysis tools, and explores the challenges of existing multi-omics analyses, as well as the applications of multi-omics technology in drug-target identification.

show abstract

“… 15 Besides their role as biomarkers, small‐molecule metabolites can directly interact with drugs to coordinate therapeutic strategies or bind with proteins to regulate various physiological functions, alter disease‐related signaling pathways, and affect disease progression. 16 , 17 , 18 , 19 Previous research has also underscored the potential of metabolites to regulate neuroinflammation and the post‐injury microenvironment following SCI. According to the research by Zeng et al., there is a disruption in purine metabolism after SCI, with significant changes in multiple genes and metabolites, which may participate in processes such as inflammation, apoptosis, and axonal regeneration following SCI.…”

Section: Introductionmentioning

confidence: 99%

“…In early breast cancer, metabolites like glutamine, tyrosine, proline, histidine, alanine, and citrate have been associated with proliferating tumor cells 15 . Besides their role as biomarkers, small‐molecule metabolites can directly interact with drugs to coordinate therapeutic strategies or bind with proteins to regulate various physiological functions, alter disease‐related signaling pathways, and affect disease progression 16–19 . Previous research has also underscored the potential of metabolites to regulate neuroinflammation and the post‐injury microenvironment following SCI.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury

Zhang,

Shao,

Zhang

et al. 2024

CNS Neurosci Ther

View full text Add to dashboard Cite

AimWe aimed to confirm the inhibitory effect of nicotinamide on fibrotic scar formation following spinal cord injury in mice using functional metabolomics.MethodsWe proposed a novel functional metabolomics strategy to establish correlations between gene expression changes and metabolic phenotypes using integrated multi‐omics analysis. Through the integration of quantitative metabolites analysis and assessments of differential gene expression, we identified nicotinamide as a functional metabolite capable of inhibiting fibrotic scar formation and confirmed the effect in vivo using a mouse model of spinal cord injury. Furthermore, to mimic fibrosis models in vitro, primary mouse embryonic fibroblasts and spinal cord fibroblasts were stimulated by TGFβ, and the influence of nicotinamide on TGFβ‐induced fibrosis‐associated genes and its underlying mechanism were examined.ResultsAdministration of nicotinamide led to a reduction in fibrotic lesion area and promoted functional rehabilitation following spinal cord injury. Nicotinamide effectively downregulated the expression of fibrosis genes, including Col1α1, Vimentin, Col4α1, Col1α2, Fn1, and Acta2, by repressing the TGFβ/SMADs pathway.ConclusionOur functional metabolomics strategy identified nicotinamide as a metabolite with the potential to inhibit fibrotic scar formation following SCI by suppressing the TGFβ/SMADs signaling. This finding provides new therapeutic strategies and new ideas for clinical treatment.

show abstract

Functional metabolomics revealed the dual-activation of cAMP-AMP axis is a novel therapeutic target of pancreatic cancer

Cited by 7 publications

References 47 publications

Metagenomic Insight into the Effect of Probiotics on Nitrogen Cycle in the Coilia nasus Aquaculture Pond Water

Metagenomic Insight into the Effect of Probiotics on Nitrogen Cycle in the Coilia nasus Aquaculture Pond Water

Advances in Integrated Multi-omics Analysis for Drug-Target Identification

Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury

Contact Info

Product

Resources

About