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

Tribulations and future opportunities for artificial intelligence in precision medicine DOI Creative Commons
Claudio Carini, Attila A. Seyhan

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

Published: April 30, 2024

Abstract Upon a diagnosis, the clinical team faces two main questions: what treatment, and at dose? Clinical trials' results provide basis for guidance support official protocols that clinicians use to base their decisions. However, individuals do not consistently demonstrate reported response from relevant trials. The decision complexity increases with combination treatments where drugs administered together can interact each other, which is often case. Additionally, individual's treatment varies changes in condition. In practice, drug dose selection depend significantly on medical protocol team's experience. As such, are inherently varied suboptimal. Big data Artificial Intelligence (AI) approaches have emerged as excellent decision-making tools, but multiple challenges limit application. AI rapidly evolving dynamic field potential revolutionize various aspects of human life. has become increasingly crucial discovery development. enhances across different disciplines, such medicinal chemistry, molecular cell biology, pharmacology, pathology, practice. addition these, contributes patient population stratification. need healthcare evident it aids enhancing accuracy ensuring quality care necessary effective treatment. pivotal improving success rates increasing significance discovery, development, trials underscored by many scientific publications. Despite numerous advantages AI, advancing Precision Medicine (PM) remote monitoring, unlocking its full requires addressing fundamental concerns. These concerns include quality, lack well-annotated large datasets, privacy safety issues, biases algorithms, legal ethical challenges, obstacles related cost implementation. Nevertheless, integrating medicine will improve diagnostic outcomes, contribute more efficient delivery, reduce costs, facilitate better experiences, making sustainable. This article reviews applications development sustainable, highlights limitations applying AI.

Language: Английский

Citations

34
The Artificial Intelligence-Driven Pharmaceutical Industry: A Paradigm Shift in Drug Discovery, Formulation Development, Manufacturing, Quality Control, and Post-Market Surveillance DOI Creative Commons
Kampanart Huanbutta,

Kanokporn Burapapadh,

Pakorn Kraisit

et al.

European Journal of Pharmaceutical Sciences, Journal Year: 2024, Volume and Issue: 203, P. 106938 - 106938

Published: Oct. 16, 2024

Language: Английский

Citations

13
NetSDR: Drug repurposing for cancers based on subtype-specific network modularization and perturbation analysis DOI
Bin Yang,

Wanshi Li,

Zhen Xu

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(3), P. 167688 - 167688

Published: Jan. 23, 2025

Language: Английский

Citations

1
Glyoxalase I Inhibitors Targeting Breast Cancer-Associated Endothelial Cells: An Integrated Network Pharmacology and Experimental Investigation DOI
Honglin Jiang, Lu Yang,

Qiuyue Sun

et al.

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141868 - 141868

Published: Feb. 1, 2025

Language: Английский

Citations

1
Architecting the metabolic reprogramming survival risk framework in LUAD through single-cell landscape analysis: three-stage ensemble learning with genetic algorithm optimization DOI Creative Commons
Xinti Sun, Min-Yu Nong, Fei Meng

et al.

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

Published: April 15, 2024

Abstract Recent studies have increasingly revealed the connection between metabolic reprogramming and tumor progression. However, specific impact of on inter-patient heterogeneity prognosis in lung adenocarcinoma (LUAD) still requires further exploration. Here, we introduced a cellular hierarchy framework according to malignant gene set, named & metabolism (MMR), reanalyze 178,739 single-cell reference profiles. Furthermore, proposed three-stage ensemble learning pipeline, aided by genetic algorithm (GA), for survival prediction across 9 LUAD cohorts ( n = 2066). Throughout pipeline developing three stage-MMR (3 S-MMR) score, double training sets were implemented avoid over-fitting; gene-pairing method was utilized remove batch effect; GA harnessed pinpoint optimal basic learner combination. The novel 3 S-MMR score reflects various aspects biology, provides new insights into precision medicine patients, may serve as generalizable predictor immunotherapy response. To facilitate clinical adoption developed an easy-to-use web tool risk scoring well therapy stratification patients. In summary, validated model within reprogramming, offering potential treatment effective approach prognostic models other diseases.

Language: Английский

Citations

5
Critical role of Oas1g and STAT1 pathways in neuroinflammation: insights for Alzheimer’s disease therapeutics DOI Creative Commons
Zhixin Xie, Linxi Li,

Weizhong Hou

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 14, 2025

Alzheimer's disease (AD) has a significant impact on an individual's health and places heavy burden society. Studies have emphasized the importance of microglia in progression development AD. Interferon responses Interferon-stimulated genes (ISGs) significantly function neuroinflammatory neurodegenerative diseases involving Therefore, further exploration relationship among microglia, ISGs, neuroinflammation AD is warranted. Microglia datasets from GEO database were retrieved, along with additional RNA-seq data laboratory mice. Weighted Correlation Network Analysis was used training dataset to identify gene co-expression networks. Genes black module intersected interferon-stimulated genes, differentially expressed (DEGs) identified. Machine learning algorithms applied DEGs, selected by both methods identified as hub ROC curves evaluate their diagnostic accuracy. Gene Set Enrichment performed reveal functional pathways closely relating genes. cells transfected siRNAs targeting Oas1g STAT1. Total RNA mouse brain tissues extracted, reverse-transcribed, analyzed via qRT-PCR. Proteins extracted cells, quantified, separated SDS-PAGE, transferred PVDF membranes, probed antibodies. fixed, permeabilized, blocked, stained antibodies for STAT1, then visualized photographed. Bioinformatics machine revealed that gene, AUC 0.812. associated interferon-related pathways. Expression validated models, where it upregulated after microglial activation. Knockdown experiments suggested siOas1g attenuated effect siSTAT1, expressions STAT1 p-STAT1 elevated. could reverse indicating potentially regulates ISGs through pathway. We demonstrated ISG can downregulate activation IFN-β reducing expression neuroinflammation. might be beneficial candidate prevention treatment

Language: Английский

Citations

0
Revolutionizing Biomedical Research: Unveiling the Power of Microphysiological Systems with Advanced Assays, Integrated Sensor Technologies, and Real-Time Monitoring DOI Creative Commons

Anupama Samantasinghar,

Naina Sunildutt,

Faheem Ahmed

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(10), P. 9869 - 9889

Published: March 10, 2025

The limitation of animal models to imitate a therapeutic response in humans is key problem that challenges their use fundamental research. Organ-on-a-chip (OOC) devices, also called microphysiological systems (MPS), are devices containing lining living cells grown under dynamic flow recapitulate the important features human physiology and pathophysiology with high precision. Recent advances microfabrication tissue engineering techniques have led wide adoption OOC next-generation experimental platforms. This review presents comprehensive analysis systems, categorizing them by types (single-pass multipass), operational mechanisms (pumpless pump-driven), configurations (single-organ multiorgan systems), along respective advantages limitations. Furthermore, it explores integration qualitative quantitative assay techniques, providing comparative evaluation without sensor integration. aims fill essential knowledge gaps, driving progress development paving way for breakthroughs biomedical research, pharmaceutical innovation, engineering.

Language: Английский

Citations

0
A comprehensive review on coating techniques to suppress the dendrites issue and improve the performance of lithium-ion batteries DOI
Wajid Ali, Kyungtae Ko, Faheem Ahmed

et al.

Journal of Coatings Technology and Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

Citations

0
Multi-transcriptomics reveals niche-specific expression programs and endothelial cells in glioblastoma DOI Creative Commons
James C. Hu,

Xiaohan Sa,

Yue Yang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 15, 2025

Glioblastoma (GBM) is a highly lethal malignant intracranial tumor, distinguished from low-grade glioma by histopathological hallmarks such as pseudopalisading cells around necrosis (PAN) and microvascular proliferation (MVP). To date the spatial organization of molecular cellular components these specific features has not been fully elucidated. Here, using bulk RNA sequencing, transcriptomic single cell sequencing (scRNA-seq) data GBM patients, we identified niche-specific transcriptional programs characterized differences in expression between PAN MVP. Notably, discovered spatially distinct domains within tumor core signatures: NDRG1 EPAS1, specifically expressed MVP regions. The clustering results showed two phenotypes endothelial (ECs) were enriched regions, respectively. PAN-associated exhibit copy number variations similar to those cells. Single trajectory analysis reveals pseudotime trajectory, indicating differentiation glioblastoma stem (GSCs) toward ECs. Necrosis cores which are surrounded hypoxic perivascular niches area microenvironment, have considered standardized morphological indicators aggressive GBM. Our findings provide insights into progression.

Language: Английский

Citations

0
Comprehensive Analysis of the Multi‐Target Binding Mechanism of Doxorubicin: Integrating Protein Microarray Screening, Molecular Docking, and Molecular Dynamics Simulation DOI
Wentao Wang,

Yanfei Cai,

Yun Chen

et al.

Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(5)

Published: May 1, 2025

ABSTRACT Understanding the mechanisms through which anticancer drugs interact with multiple protein targets is crucial for optimizing drug design and enhancing efficacy of chemotherapy. This study focuses on doxorubicin, a broad‐spectrum recognized its multi‐target action. We initially screened 363 doxorubicin‐binding proteins using microarrays; these, 166 known PDB (Protein Data Bank) structures were selected molecular docking to evaluate their binding energies. The energy distribution residue enrichment analyses revealed that doxorubicin preferentially binds specific residues at sites, including serine, glycine, arginine, glutamic acid, lysine, aspartic leucine. These stabilize hydrogen bonds, hydrophobic interactions, electrostatic interactions. In addition, RUVBL1 (RuvB‐like AAA ATPase 1) exhibited highest integrated score from microarray analyses. Furthermore, PPI (protein–protein interaction) network analysis centrality calculations identified key potential regulatory roles, MAPK1 (mitogen‐activated kinase exhibiting betweenness in network. Finally, dynamics simulations RUVBL1‐ MAPK1‐doxorubicin complexes conducted mechanisms. residues, Ile56, Lys59, Leu87, Pro296, Ile326 Asp88, Ile89, Pro93, Phe354, Ala92 mediate stable interactions doxorubicin. presents comprehensive analytical approach investigating between targets, providing reference framework understanding future similar data sets.

Language: Английский

Citations

0