Hemophilia

CCDC6, a ferroptosis-related gene, modulates stemness features of pancreatic cancer cells in vitro.

OBJECTIVE: Pancreatic cancer (PC) poses a significant threat to patient quality of life. Ferroptosis, a novel form of non-apoptotic cell death, is implicated in pancreatic tumorigenesis and therapy resistance. This study aims to identify key ferroptosis-related genes (FRGs) as prognostic biomarkers, to construct a risk model for predicting patient outcomes, and to explore the underlying biological...

Integrating AI in Medicinal Chemistry for Accelerated Drug Discovery: A Comprehensive SAR (CSAR) Optimization Strategy and Discovery of Potent ALDH3A1 Inhibitors.

Developing potent, selective small-molecule inhibitors remains a major challenge in drug discovery. ALDH3A1, a detoxifying aldehyde dehydrogenase isoform implicated in cancer and neurodegeneration, is a promising yet underexplored therapeutic target. To accelerate inhibitor optimization, we developed an AI-guided, reaction-based hit-to-lead workflow combining sequential reaction enumeration, pharm...

An integrated computational-experimental approach identifies Malate Synthase G as therapeutic target to disrupt carbon metabolism in chronic Pseudomonas aeruginosa infection.

Pseudomonas aeruginosa is a leading cause of nosocomial infections, particularly in individuals with a compromised immune system. Due to its strong ad...

Turning failure into success: how artificial intelligence can help personalize therapies and re-use patient data.

Despite robust preclinical evidence, many clinical trials, including several that targeted the purinergic system, fail to demonstrate efficacy in huma...

Cyclosporine in hematological disorders: mechanisms, clinical practice and emerging advances.

Cyclosporine A (CsA) functions as a calcineurin inhibitor that perturbs T cell activation via calcineurin-nuclear factor of activated T cells (CaN-NFA...

Network toxicology and bioinformatics reveal potential molecular links between cadmium exposure and pancreatic cancer.

BACKGROUND: Environmental cadmium (Cd) pollution poses a severe threat to human health due to its strong bioaccumulation and high carcinogenicity. Alt...

Review of systemic therapy in HCC with an approach to response assessment in clinical practice.

Systemic therapy for hepatocellular carcinoma (HCC) has undergone rapid transformation over the past decade, significantly expanding treatment options...

Machine learning models for predicting metabolic syndrome to support clinical decision-making in ART-treated adults living with HIV.

BACKGROUND: Metabolic syndrome (MetS) is an emerging complication among people living with HIV (PLHIV) receiving long-term antiretroviral therapy (ART...

Advances in immune checkpoint inhibitor therapy for microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) colorectal cancer: Insights from the tumor immune microenvironment.

This review systematically analyzes the relationship between the immune microenvironment characteristics of microsatellite instability-high (MSI-H) or...

When Trees Guide Molecules: Multiobjective Search in de Novo Drug Design.

Seen as a problem of guided exploration with multiple objectives, molecular design requires carefully elaborated decision-tree-based strategies for tr...

Predicting immune checkpoint inhibitor cardiotoxicity using machine learning: a systematic review of model performance and methodological quality.

BACKGROUND: Immune checkpoint inhibitors (ICIs) significantly improve cancer outcomes but can cause rare, potentially fatal cardiotoxicity, including ...

A Multistage Virtual Screening Strategy Integrating Molecular Similarity, Deep Learning Scoring, and Molecular Docking toward the Discovery of Novel LRRK2 Inhibitors.

Leucine-rich repeat kinase 2 (LRRK2) has emerged as an attractive molecular target for Parkinson's disease therapeutics. To discover novel and potent ...

Beyond target lesions: Prognostic value of longitudinal AI-derived whole-body [1⁸F]FDG PET/CT metrics in metastatic melanoma.

PURPOSE: To investigate the prognostic value of an artificial intelligence (AI)-based semi-automated tool for longitudinal whole-body quantification o...

Enterotype-specific microbial biomarkers of immune checkpoint inhibitor response revealed by large-scale integrated metagenomic analysis.

The gut microbiota appears to play a critical role in modulating antitumor immune responses and influencing the efficacy of cancer immunotherapy drugs...

AI-driven multi-omics drug repurposing nominates AZD7762 as a multitarget inhibitor of IL22RA1 and FAM221A in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with limited targeted treatment options and poor clinical outcomes. We developed...

AI-based histopathology analysis predicts checkpoint inhibitor response in advanced melanoma and identifies patterns associated with response.

INTRODUCTION: Readily available predictive biomarkers for immune checkpoint inhibitor (ICI) response in advanced melanoma are limited. This study eval...

Advances in quantum dot-based fluorescent biosensors for enzyme detection: mechanistic insights and applications in disease.

It is imperative to develop precise detection tools for enzymes, as key biomarkers in disease pathogenesis, to fuel progress in clinical diagnostics a...

Transcriptional states define dependencies and therapeutic vulnerabilities in head and neck cancer.

Molecular heterogeneity in head and neck squamous cell carcinoma (HNSCC) is well recognized, yet existing subtype frameworks remain largely descriptiv...

Multi-region proteomic mapping identifies FTL1 and SERPINA3K as protective factors in cardiac aging.

Aging is a well-recognized risk factor in cardiovascular diseases (CVDs), primarily due to its association with the gradual decline in cardiac functio...

Integrated multi-stage screening assisted discovery and optimization of spirooxindole MDM2 inhibitors.

The rational design of novel MDM2 inhibitors with superior biochemical properties represents the most consequential outcome of contemporary computer-a...