Conjugated bile acids alleviate acute pancreatitis through inhibition of TGR5 and NLRP3 mediated inflammation DOI Creative Commons
Ziyi Zhang,

Xiuliu Guo,

Jingtianyi Liu

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 20, 2024

Severe acute pancreatitis (SAP) is a crucial gastrointestinal disease characterized by systemic inflammatory responses and persistent multiple organ failure. The role of bile acids (BAs) in diverse diseases increasingly recognized as crucial, but the underlying BA conjugation remains elusive. Our study aim to investigate potential conjugated SAP reveal molecular mechanisms its regulatory effects. We hypothesized that taurochenodeoxycholic acid (TCDCA) glycochenodeoxycholic (GCDCA) could protect through inhibiting activation NLRP3 inflammasomes via TGR5 pathway macrophages. To test our hypothesis, we used BA-CoA: amino N-acyltransferase knockout (Baat−/−) mice established mouse models using caerulein- sodium taurocholate- induced. utilized range methods, including pathology sections, qRT-PCR, immunofluorescence, Western blotting, ELISA, identify regulation. Amino significantly exacerbated increasing pancreatic damage models. Moreover, serum TCDCA levels Baat−/− were lower than those wild-type (WT) with or without SAP, GCDCA showed stronger anti-inflammatory effects chenodeoxycholic (CDCA) vitro. treatment alleviated Takeda G protein-coupled receptor 5 NOD-like family, pyrin domain containing 3—dependent manner vivo. Reinforcing conclusions from study, clinical patients exhibited decreased content BAs, especially GCDCA, which was inversely correlated severity responses. Conjugated inhibit inflammasome activating pathway, thereby alleviating immunopathology. results provide new insights into variability outcomes paves way for developing more effective therapeutic interventions AP.

Language: Английский

Accurate prediction of drug combination risk levels based on relational graph convolutional network and multi-head attention DOI Creative Commons

Shihui He,

Lijun Yun, Hai-Cheng Yi

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: June 16, 2024

Abstract Background Accurately identifying the risk level of drug combinations is great significance in investigating mechanisms combination medication and adverse reactions. Most existing methods can only predict whether there an interaction between two drugs, but cannot directly determine their accurate level. Methods In this study, we propose a multi-class prediction model named AERGCN-DDI, utilizing relational graph convolutional network with multi-head attention mechanism. Drug-drug events varying levels are modeled as heterogeneous information graph. Attribute features nodes links learned based on compound chemical structure information. Finally, AERGCN-DDI proposed to heterogenous neural modules. Results To evaluate effectiveness method, five-fold cross-validation ablation study were conducted. Furthermore, compared its predictive performance baseline models other state-of-the-art benchmark datasets. Empirical studies demonstrated superior performances AERGCN-DDI. Conclusions emerges valuable tool for predicting combinations, thereby aiding clinical decision-making, mitigating severe side effects, enhancing patient prognosis.

Language: Английский

Citations

3
Repurposing lipid-lowering drugs on asthma and lung function: evidence from a genetic association analysis DOI Creative Commons
Yue Zhang,

Zichao Jiang,

Lingli Chen

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 3, 2024

Abstract Objective To explore the correlation between asthma risk and genetic variants affecting expression or function of lipid-lowering drug targets. Methods We conducted Mendelian randomization (MR) analyses using in several genes associated with medication targets: HMGCR (statin target), PCSK9 (alirocumab NPC1L1 (ezetimibe APOB (mipomersen ANGPTL3 (evinacumab PPARA (fenofibrate APOC3 (volanesorsen as well LDLR LPL. Our objective was to investigate relationship drugs through MR. Finally, we assessed efficacy stability MR analysis Egger inverse variance weighted (IVW) methods. Results The elevated triglyceride (TG) levels APOC3, LPL targets were found increase risk. Conversely, higher LDL-C driven by decrease Additionally, (driven APOB, targets) TG target) improved lung (FEV1/FVC). decreased Conclusion In conclusion, our findings suggest a likely causal drugs. Moreover, there is compelling evidence indicating that therapies could play crucial role future management asthma.

Language: Английский

Citations

2
Essential Protein Identification in Cancer: A Graph-Based Approach Integrating Topological and Biological Features in PPI Networks DOI
Trilochan Rout,

Anjali Mohapatra,

Madhabananda Kar

et al.

SN Computer Science, Journal Year: 2024, Volume and Issue: 5(7)

Published: Oct. 9, 2024

Language: Английский

Citations

1
Integrated edge information and pathway topology for drug-disease associations DOI Creative Commons
Xianbin Li, Xiangzhen Zan, Tao Liu

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(7), P. 110025 - 110025

Published: May 18, 2024

Drug repurposing is a promising approach to find new therapeutic indications for approved drugs. Many computational approaches have been proposed prioritize candidate anticancer drugs by gene or pathway level. However, these methods neglect the changes in interactions at edge To address limitation, we develop drug method (iEdgePathDDA) based on information and topology. First, identify drug-induced disease-related edges (the interactions) within pathways using Pearson correlation coefficient. Next, calculate inhibition score between edges. Finally, candidates according all Case studies show that our successfully identifies drug-disease pairs CTD database. Compared state-of-the-art approaches, results demonstrate has superior performance terms of five metrics across colorectal, breast, lung cancer datasets.

Language: Английский

Citations

0
Exploring cutting-edge strategies for drug repurposing in female cancers – An insight into the tools of the trade DOI
Kshreeraja S. Satish,

Ganesan Rajalekshmi Saraswathy,

Ritesh Giri

et al.

Progress in molecular biology and translational science, Journal Year: 2024, Volume and Issue: unknown, P. 355 - 415

Published: Jan. 1, 2024

Language: Английский

Citations

0
A weighted Bayesian integration method for predicting drug combination using heterogeneous data DOI Creative Commons
Tingting Li,

Long Xiao,

Haigang Geng

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 28, 2024

Language: Английский

Citations

0
Repurposed Drugs: Current Trends in Drug Discovery DOI Creative Commons
G. Srikanth,

Durga Prasad Beda,

Niggula Praveen Kumar

et al.

IntechOpen eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 9, 2024

Drug repurposing is a drug discovery strategy that involves identifying new therapeutic uses for existing drugs. relies on the idea limited number of genes or gene products mediate biological processes and several entities—such as transcripts, proteins, genes—have pleiotropic effects similar tasks. Recently, has gained attention different approach looks novel previously approved rejected commercial medications to address conditions other than those they were designed for. It offers numerous benefits, such faster development timelines, reduced costs, established safety profiles, potential treatments unmet medical needs. This chapter explains current trends in future perspectives repurposed

Language: Английский

Citations

0
Conjugated bile acids alleviate acute pancreatitis through inhibition of TGR5 and NLRP3 mediated inflammation DOI Creative Commons
Ziyi Zhang,

Xiuliu Guo,

Jingtianyi Liu

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 20, 2024

Severe acute pancreatitis (SAP) is a crucial gastrointestinal disease characterized by systemic inflammatory responses and persistent multiple organ failure. The role of bile acids (BAs) in diverse diseases increasingly recognized as crucial, but the underlying BA conjugation remains elusive. Our study aim to investigate potential conjugated SAP reveal molecular mechanisms its regulatory effects. We hypothesized that taurochenodeoxycholic acid (TCDCA) glycochenodeoxycholic (GCDCA) could protect through inhibiting activation NLRP3 inflammasomes via TGR5 pathway macrophages. To test our hypothesis, we used BA-CoA: amino N-acyltransferase knockout (Baat−/−) mice established mouse models using caerulein- sodium taurocholate- induced. utilized range methods, including pathology sections, qRT-PCR, immunofluorescence, Western blotting, ELISA, identify regulation. Amino significantly exacerbated increasing pancreatic damage models. Moreover, serum TCDCA levels Baat−/− were lower than those wild-type (WT) with or without SAP, GCDCA showed stronger anti-inflammatory effects chenodeoxycholic (CDCA) vitro. treatment alleviated Takeda G protein-coupled receptor 5 NOD-like family, pyrin domain containing 3—dependent manner vivo. Reinforcing conclusions from study, clinical patients exhibited decreased content BAs, especially GCDCA, which was inversely correlated severity responses. Conjugated inhibit inflammasome activating pathway, thereby alleviating immunopathology. results provide new insights into variability outcomes paves way for developing more effective therapeutic interventions AP.

Language: Английский

Citations

0