Eur J Hum Genet. 2025 Apr 25. doi: 10.1038/s41431-025-01851-8. Online ahead of print.

NO ABSTRACT

PMID:40281080 | DOI:10.1038/s41431-025-01851-8

Int J Infect Dis. 2025 Apr 23:107913. doi: 10.1016/j.ijid.2025.107913. Online ahead of print.

ABSTRACT

Diffuse panbronchiolitis (DPB) is a chronic inflammatory disease predominantly affecting East Asians. It is characterized by persistent Pseudomonas aeruginosa colonization and progressive respiratory failure. Lung transplantation (LTx) serves as a definitive treatment option for advanced cases, but post-transplant recurrence poses significant challenges. This report describes a Japanese woman who experienced DPB recurrence after bilateral LTx. Persistent P. aeruginosa colonization and recurrent respiratory symptoms were managed with off-label tobramycin solution for inhalation (TSI), which is commonly used in cystic fibrosis. TSI treatment led to significant clinical and radiological improvements, clearance of P. aeruginosa from sputum cultures, and no further hospitalizations during six months of therapy. This case suggests the potential of TSI as a therapeutic approach for managing recurrent DPB and indicates its role in stabilizing post-transplant outcomes. Further studies may clarify its efficacy and expand its application in broader DPB management strategies.

PMID:40280231 | DOI:10.1016/j.ijid.2025.107913

AAPS PharmSciTech. 2025 Apr 25;26(5):113. doi: 10.1208/s12249-025-03112-9.

ABSTRACT

In this study, a quercetin-loaded liposome system modified with collagenase was developed to increase QU penetration in the ECM and improve IPF treatment. Quercetin-loaded long circulation liposome (QU-LP) and quercetin-loaded liposome modified with collagenase type I (QU-CLP) were prepared, followed by characterization of the encapsulation efficiency, particle size, morphology, and in vitro drug release. Their effect on the cytotoxicity of A549 cells was detected by the Cell Counting Kit-8, and the cellular uptake was investigated using cellular fluorescence imaging and flow cytometry. TGF-β1 induced A549 cell model was established to mimic pulmonary fibrosis to explore further the anti-pulmonary fibrosis effect of QU-CLP by CCK8 experiment. QU-CLP significantly improves the solubility and bioavailability of QU by encapsulating it in the internal cavity with a high encapsulation efficiency (EE%) of 92.86 ± 1.03%. Liposomes alleviate the influence of QU on normal A549 cell growth. Enhanced fluorescence intensity was observed in A549 cells treated with coumarin 6-labeled and collagenase-modified nanoliposomes (C6-CLP) after 4 h of incubation on the collagen matrix, confirming that collagenase-loaded liposomes could penetrate the collagen barrier and cells internalized more hydrophobic drug. The mean fluorescence intensity (MFI) of the C6-CLP group was 2.88 times that of the C6-labeled nanoliposomes (C6-LP). Moreover, QU-CLP significantly (**P < 0.01) inhibited the proliferation of A549 cells stimulated by TGF-β1. QU-CLP has excellent potential for delivering QU with enhanced bioavailability, high cellular uptake efficiency, and improved therapeutic efficacy in IPF.

PMID:40281247 | DOI:10.1208/s12249-025-03112-9

Lung. 2025 Apr 25;203(1):57. doi: 10.1007/s00408-025-00811-9.

ABSTRACT

PURPOSE: Combined lung-liver transplant (CLLT) is a complex yet life-saving procedure for patients with simultaneous end-stage lung and liver disease. Given the geographical allocation change to the lung allocation score (LAS) in 2017 and the recent SARS-CoV-2 outbreak in 2019, we aim to provide an updated analysis of the patient selection and outcomes of CLLTs.

METHODS: The UNOS registry was used to identify all patients who underwent CLLT between January 2014 and June 2023. To account for the changes made to LAS in 2017, baseline characteristics and outcomes were compared between era 1 (before 2017) and era 2 (after 2017). Risk factors for mortality were analyzed using the Cox regression hazard models. Recipient survival of up to 3 years was analyzed using the Kaplan-Meier method.

RESULTS: 117 CLLTs were performed (77.8% in era 2). Donor organs experienced significantly longer ischemic times (p = 0.039) and traveled longer distances (p = 0.025) in era 2. However, recipient (p = 0.79) and graft (p = 0.41) survival remained comparable at up to 3 years post-transplant between eras. CLLTs demonstrated similar long-term survival to isolated lung transplants (p = 0.73). Higher recipient LAS was associated with an increased mortality risk (HR 1.14, p = 0.034). Recipient diagnosis of idiopathic pulmonary fibrosis carried a 5.03-fold risk of mortality (p = 0.048) compared to those with cystic fibrosis.

CONCLUSION: In the post-2017 LAS change era, CLLTs are increasingly performed with comparable outcomes to isolated lung transplants. A careful, multidisciplinary approach to patient selection and management remains paramount to optimizing outcomes for this rare patient population.

PMID:40281222 | DOI:10.1007/s00408-025-00811-9

Sci Rep. 2025 Apr 25;15(1):14448. doi: 10.1038/s41598-025-97037-9.

ABSTRACT

To investigate the molecular mechanisms underlying idiopathic pulmonary fibrosis (IPF), we analyzed the GSE173355 and GSE173356 datasets obtained from the NCBI-GEO database. We identified differentially expressed genes (DEGs) and differentially methylated sites. Functional enrichment analysis was conducted for both DEGs and differentially methylated sites. Functional enrichment analysis was performed for both DEGs and differentially methylated sites, alongside an examination of immune-related scores, proportions, and GSVA enrichment scores of immune cells in IPF versus control samples. An integrated gene-methylation association analysis revealed 8 genes with expression levels negatively influenced by methylation. The Rap1 pathway, Focal adhesion, and Axon guidance were significantly enriched among both DEGs and differentially methylated sites. Immune-related scores were notably lower in the IPF group compared to the control group, with marked differences in immune cell proportions and GSVA enrichment scores. Screening of DEGs identified 361 differentially expressed immune-related genes (IRGs). Protein-protein interaction (PPI) network analysis using the STRING database and Cytoscape software unveiled 10 key genes and 3 core subnetworks. RT-qPCR validation in bleomycin-induced IPF mouse model and A549 EMT model confirmed the reliability of most findings. These results provide new insights into IPF pathogenesis and potential therapeutic strategies, necessitating further functional validation.

PMID:40280949 | DOI:10.1038/s41598-025-97037-9

Free Radic Biol Med. 2025 Apr 23:S0891-5849(25)00244-8. doi: 10.1016/j.freeradbiomed.2025.04.034. Online ahead of print.

ABSTRACT

Mitochondrial oxidative damage-mediated dysfunction is implicated in pulmonary pathogenesis, yet the molecular mechanisms linking redox imbalance to pulmonary fibrosis remain elusive. In this study, we demonstrate that DNA methyltransferase 3A (DNMT3A) drives fibroblast activation and pulmonary fibrosis by epigenetically repressing superoxide dismutase 2 (SOD2), a critical antioxidant enzyme. Using fibroblast-specific DNMT3A-deficient mice and bleomycin-induced pulmonary fibrosis models, we observed that DNMT3A ablation significantly attenuated mitochondrial oxidant overproduction, restored mitochondrial membrane potential (MMP), and reduced fibrotic progression. Mechanistically, DNMT3A directly bound to the SOD2 promoter, inducing hypermethylation and transcriptional silencing, which exacerbated oxidative stress and fibroblast proliferation. Conversely, AAV6-mediated SOD2 overexpression or DNMT3A knockdown rescued SOD2 expression, suppressed mitochondrial oxidative burden, and ameliorated fibrosis. Clinically, idiopathic pulmonary fibrosis (IPF) patient tissues exhibited elevated DNMT3A levels, diminished SOD2 expression, and marked mitochondrial dysfunction, corroborating our experimental findings. These results unveil a novel DNMT3A/SOD2 axis as an epigenetic regulator of mitochondrial redox dysregulation-driven fibrosis, providing a potential therapeutic avenue for targeting oxidative damage in pulmonary fibrotic disorders.

PMID:40280315 | DOI:10.1016/j.freeradbiomed.2025.04.034

Biochem Pharmacol. 2025 Apr 23:116959. doi: 10.1016/j.bcp.2025.116959. Online ahead of print.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is a disease that includes inflammation and scarring of the lung tissues. Cyclin-dependent kinase 8 (CDK8) is a target of interest due to its role in inflammatory pathways. CDK8 can also modulate the TGF-β/Smad signaling associated with IPF. Herein, a structure-based virtual screening (SBVS) campaign led to the identification of three CDK8 inhibitors. Testing of candidate inhibitors in protein and cellular assays confirmed CDK8 inhibition, with the most potent inhibitor producing an IC50 value of 398.8 nM. Computational analysis identified pharmacological interactions that lead to CDK8 inhibition. No significant cytotoxicity was observed when the inhibitor was treated in vitro. Further results showed that the inhibitor can disrupt proteins associated with the epithelial-mesenchymal transition (EMT) and reduce cell migration. Additionally, the inhibitor can disrupt the TGF- β1/Smad signaling axis in the nucleus, potentially impacting the transcription of IPF related protein expression, when treated in cells at 5 µM. Comparisons to structures of known CDK8 inhibitors showed the identified inhibitor to be structurally novel. When tested against a panel of kinases at 1 µM, the most potent inhibitor demonstrated a favorable CDK8 selectivity profile. The identification of the CDK8 inhibitors in this study can be used in future drug design studies and as CDK8 probes to explore alternative therapeutics for IPF.

PMID:40280247 | DOI:10.1016/j.bcp.2025.116959

BMC Cancer. 2025 Apr 25;25(1):780. doi: 10.1186/s12885-025-14193-x.

ABSTRACT

BACKGROUND: This study aimed to classify dysplastic and healthy oral epithelial histopathological images, according to WHO and binary grading systems, using the Vision Transformer (ViT) deep learning algorithm-a state-of-the-art Artificial Intelligence (AI) approach and compare it with established Convolutional Neural Network models (VGG16 and ConvNet).

METHODS: A total of 218 histopathological slide images were collected from the Department of Oral and Maxillofacial Pathology at Tehran University of Medical Sciences archive and combined with two online databases. Two oral pathologists independently labeled the images based on the 2022 World Health Organization (WHO) grading system (mild, moderate and severe), the binary grading system (low risk and high risk), including an additional normal tissue class. After preprocessing, the images were fed to the ViT, VGG16 and ConvNet models.

RESULTS: Image preprocessing yielded 2,545 low-risk, 2,054 high-risk, 726 mild, 831 moderate, 449 severe, and 937 normal tissue patches. The proposed ViT model outperformed both CNNs with the accuracy of 94% (VGG16:86% and ConvNet: 88%) in 3-class scenario and 97% (VGG16:79% and ConvNet: 88%) in 4-class scenario.

CONCLUSIONS: The ViT model successfully classified oral epithelial dysplastic tissues with a high accuracy, paving the way for AI to serve as an adjunct or independent tool alongside oral and maxillofacial pathologists for detecting and grading oral epithelial dysplasia.

PMID:40281456 | DOI:10.1186/s12885-025-14193-x

BMC Plant Biol. 2025 Apr 25;25(1):544. doi: 10.1186/s12870-025-06563-1.

ABSTRACT

BACKGROUND: Plasma-activated water (PAW) is a recently developed cutting-edge technology that is increasingly gaining interest for its applications in medicine, food industry and agriculture. In plant biology, PAW has been shown to enhance seed germination, plant growth, and plant resilience against biotic and abiotic stresses. Despite increasing knowledge of the beneficial effects exerted by PAW on plants, little information is currently available about how this emerging technology may affect mutualistic plant-microbe interactions in the rhizosphere.

RESULTS: In this work we investigated the impact of irrigation with PAW, generated by a plasma torch, on arbuscular mycorrhizal (AM) symbiosis. Roots of the model legume Lotus japonicus expressing the bioluminescent Ca2+ reporter aequorin responded to treatment with PAW 5' (obtained by 5 min water exposure to plasma) with the immediate induction of cytosolic and nuclear Ca2+ signals, indicating that Ca2+-mediated signalling is one of the earliest cellular responses to PAW. The long-lasting elevations in intracellular Ca2+ levels were not found to alter cell viability. Quantitative analyses of AM fungal accommodation in the host plant roots along with phosphate accumulation in leaves, as well as chemical analysis of N, C, S in shoots, showed that treatments with PAW play a modulatory role on plant AM symbiotic performance, in a manner dependent on the time interval of water exposure to the plasma and on the duration of plant treatment with PAW. In particular, irrigation with PAW 5' increased fungal colonization after 4 weeks, leading to a significant increase in leaf phosphate content after 7 weeks.

CONCLUSIONS: Our findings reveal that PAW enhances AM symbiosis by facilitating early fungal accommodation in roots and subsequently increasing phosphate content in leaves at later stages. A better understanding of the mechanisms underlying the effects of PAW on the plant microbiome may drive research towards a fine-tuning of this novel green technology to maximize its beneficial effects in the context of a more sustainable agriculture.

PMID:40281400 | DOI:10.1186/s12870-025-06563-1

Sci Rep. 2025 Apr 25;15(1):14484. doi: 10.1038/s41598-025-98463-5.

ABSTRACT

The tumour microenvironment is composed of a complex cellular network involving cancer, stromal and immune cells in dynamic interactions. A large proportion of this network relies on direct physical interactions between cells, which may impact patient responses to clinical therapy. Doublets in scRNA-seq are usually excluded from analysis. However, they may represent directly interacting cells. To decipher the physical interaction landscape in relation to clinical prognosis, we inferred a physical cell-cell interaction (PCI) network from 'biological' doublets in a scRNA-seq dataset of approximately 18,000 cells, obtained from 7 treatment-naive ovarian cancer patients. Focusing on cancer-stromal PCIs, we uncovered molecular interaction networks and transcriptional landscapes that stratified patients in respect to their clinical responses to standard therapy. Good responders featured PCIs involving immune cells interacting with other cell types including cancer cells. Poor responders lacked immune cell interactions, but showed a high enrichment of cancer-stromal PCIs. To explore the molecular differences between cancer-stromal PCIs between responders and non-responders, we identified correlating gene signatures. We constructed ligand-receptor interaction networks and identified associated downstream pathways. The reconstruction of gene regulatory networks and trajectory analysis revealed distinct transcription factor (TF) clusters and gene modules that separated doublet cells by clinical outcomes. Our results indicate (i) that transcriptional changes resulting from PCIs predict the response of ovarian cancer patients to standard therapy, (ii) that immune reactivity of the host against the tumour enhances the efficacy of therapy, and (iii) that cancer-stromal cell interaction can have a dual effect either supporting or inhibiting therapy responses.

PMID:40280979 | DOI:10.1038/s41598-025-98463-5

Nat Commun. 2025 Apr 25;16(1):3873. doi: 10.1038/s41467-025-58907-y.

ABSTRACT

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Even among carriers of the same genetic variant, duodenal phenotypes vary, indicating that additional factors, such as the local immune system, play a role. We observe an increase in duodenal IL-17A(+)NKp44(-) innate lymphoid type 3 cell (ILC3) in FAP, localized near the epithelium and enriched in adenomas and carcinomas. Elevated IL1B, IL23A, and DLL4 transcript levels correlate with IL-17A(+)NKp44(-)ILC3 accumulation, and in vitro studies with duodenal organoids confirmed this relationship. Bulk RNA sequencing reveals upregulated Reactive oxygen species (ROS)-inducing enzymes DUOX2 and DUOXA2 in FAP adenomas. IL-17A-stimulated FAP organoids show increased DUOX2/DUOXA2 expression, Duox2 protein, and ROS production, leading to DNA damage, suggesting a mechanism by which these immune cells promote tumorigenesis. These findings suggest IL-17A(+)NKp44(-)ILC3s may contribute to a local environment that makes the epithelium more submissive for oncogenic transformation in FAP.

PMID:40280932 | DOI:10.1038/s41467-025-58907-y

BMC Plant Biol. 2025 Apr 25;25(1):535. doi: 10.1186/s12870-025-06493-y.

ABSTRACT

BACKGROUND: Plants must continuously adapt to environmental fluctuations, which significantly influence their photosynthetic performance and overall metabolism. The sucrose cycling system within plant cells plays a critical regulatory role during stress conditions. This study employed a systems biology approach to analyze system stabilities mathematically under various regulatory conditions impacting sucrose cycling dynamics. We investigated the effects of mutations within this cycle, specifically HEXOKINASE1 (Arabidopsis thaliana gin2-1), alongside high-light exposure. Finally, we confirmed the modeling output in vitro by enzyme assays.

RESULTS: The implementation of experimental subcellular metabolite data into a Structural Kinetic Model (SKM) enabled exploration of regulatory responses and system stabilities within a three-compartment model. Within system instabilities, gin2-1 was more instable than its wild type. The gin2-1 mutation particularly was destabilized when fructokinase function was impaired by phosphorylated sugars. Additionally, we confirmed that phosphorylated sugars serve as stronger activators of sucrose-phosphate synthase (SPS) than glucose. Interestingly, models with fructose SPS activation exhibited a similar stability pattern. Consequently, we proposed and confirmed in silico a triple activation of SPS by highly activating phosphorylated sugars and lower activating non-phosphorylated hexoses. Additionally, we biochemically confirmed the previously unknown, but now predicted, activation of SPS by fructose in vitro.

CONCLUSION: In summary, our study highlights the essential role of sucrose cycling in plant cells under stress conditions. The in silico findings reveal that phosphorylated sugars are stronger activators of SPS than glucose and introduce a previously unknown activation mechanism by fructose. These potential activation capacities were confirmed in vitro through SPS enzyme activity assays, underscoring the efficiency of our systems biology approach. Overall, this research provides valuable insights into carbohydrate metabolism regulation and paves the way for future investigations to deepen our understanding of the complexities involved in sucrose cycling and biosynthesis in plants.

PMID:40281434 | DOI:10.1186/s12870-025-06493-y

NPJ Precis Oncol. 2025 Apr 25;9(1):120. doi: 10.1038/s41698-025-00818-8.

ABSTRACT

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation; this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs.

PMID:40281242 | DOI:10.1038/s41698-025-00818-8

Trends Ecol Evol. 2025 Apr 24:S0169-5347(25)00073-4. doi: 10.1016/j.tree.2025.03.010. Online ahead of print.

ABSTRACT

Biological invasions alter ecosystems by disrupting ecological processes that can degrade biodiversity, harm human health, and cause massive economic burdens. Existing frameworks to classify the ecological impacts either miss many types of impact or conflate mechanisms (causes) with the impacts themselves (consequences). We propose a comprehensive typology of 19 types of ecological impact across six levels of ecological organisation. This allows more accurate diagnosis of the cause of impact and can help triage management options to tackle each impact-mechanism combination. We integrated the typology with broad ecological concepts such as energy, mass, and information flow and storage. By highlighting cascading effects across multiple levels, this typology provides a clearer framework for documenting, and communicating invasion impacts, thereby improving management and research.

PMID:40280812 | DOI:10.1016/j.tree.2025.03.010

J Hazard Mater. 2025 Apr 21;493:138345. doi: 10.1016/j.jhazmat.2025.138345. Online ahead of print.

ABSTRACT

Butyl xanthate (BuX) is an emerging pollutant due to wide use as flotation collector, posing a serious threat to ecosystem health in mining areas. Here we develop a combinational plant-microbe remediation strategy for restoration of BuX-contaminated mining areas. A novel bacterial strain that completely degraded up to 1000 mg/L of BuX within 12 h was isolated and identified as Pseudomonas monteilii W50. It was found to harbor good tolerance to extreme environmental conditions and multiple plant growth-promoting traits such as phosphate and potassium solubilization, indole-3-acetic acid and gibberellin production, and cellulose degradation. This strain can colonize in the rhizosphere of an emergent macrophyte Cyperus alternifolius, improving removal of BuX and chemical oxygen demand (COD) from simulated wastewater. Compared to the phytoremediation alone, the removal of BuX and COD increased from 70 % to 98 % and from 21 % to 46 % respectively in the combined remediation The strain W50 protected the macrophyte from the phytotoxicity of BuX and the macrophyte provided it with a suitable habitat for return, benefiting each other. Compared to the individual treatment using C. alternifolius or strain W50, the combinational treatment significantly improved the plant growth and the residence of inoculated bacteria. Overall, C. alternifolius and strain W50 are the perfect combination for efficient and sustainable remediation of BuX-contaminated mine wastewater, overcoming the constraints of individual phytoremediation or bioaugmentation methods.

PMID:40280067 | DOI:10.1016/j.jhazmat.2025.138345

J Hazard Mater. 2025 Apr 21;493:138350. doi: 10.1016/j.jhazmat.2025.138350. Online ahead of print.

ABSTRACT

Microbial metal resistance, a trait that enables microorganisms to withstand high levels of toxic metals, has been studied for over a century. The significance of uncovering these mechanisms goes beyond basic science as they have implications for human health through their connection to microbial pathogenesis, metal bioremediation, and biomining. Recent advances in analytical chemistry and molecular biology have accelerated the discovery and understanding of genetic mechanisms underlying microbial metal resistance, identifying specific metal resistance genes and their operons. The emergence of omics tools has further propelled research towards a comprehensive understanding of how cells respond to metal stress at the systemic level, revealing the complex regulatory networks and evolutionary dynamics that drive microbial adaptation to metal-rich environments. In this article, we present a historical overview of the evolving understanding of the genetic determinants of metal resistance in microbes. Through multiple narrative threads, we illustrate how our knowledge of microbial metal resistance and genetics has interacted with genetic tools and concept development. This review also discusses how our understanding of microbial metal resistance has progressed from the Mendelian perspective to the current systems biology viewpoint, particularly as omics approaches have considerably enhanced our understanding. This system-level understanding has opened new possibilities for genetically engineered microorganisms to regulate metal homeostasis.

PMID:40280066 | DOI:10.1016/j.jhazmat.2025.138350

Comput Biol Med. 2025 Apr 24;192(Pt A):110157. doi: 10.1016/j.compbiomed.2025.110157. Online ahead of print.

ABSTRACT

It is known that microbiome and health are related, in addition, recent research has found that microbiome has potential clinical uses. These facts highlight the importance of the microbiome in actual science. However, microbiome data has some characteristics that makes its statistical study challenging. In recent years, longitudinal and non-longitudinal methods have been designed to analyze the microbiota and knowing more about the bacterial behavior. In this article in the form of a review we summarize the characteristics of microbiome data and the statistical methods most widespread to analyze it. We have taken into account if the strategies are longitudinal or not. We also classify the methods based on their specific analytical objectives and based on their mathematical characteristics. The methods are structured according to their biological goals and mathematical features, ensuring that the insights provided are both relevant and accessible to professionals in biology and statistics. We present this review as a reference for the most widely used methods in microbiome data analysis and as a foundation for identifying potential areas for future research. We want to point out that this review can be particularly useful to remark the importance of the methodology designed in order to study microbiome longitudinal datasets.

PMID:40279974 | DOI:10.1016/j.compbiomed.2025.110157

Hum Genomics. 2025 Apr 25;19(1):44. doi: 10.1186/s40246-025-00753-6.

ABSTRACT

BACKGROUND: Statins are essential for managing cardiovascular disease (CVD), but adverse effects often lead to treatment discontinuation and non-adherence, underscoring the need for personalized approaches. This study aimed to evaluate the influence of pharmacogenomic (PGx) variants and demographic factors on statin-associated adverse effects in a multiethnic cohort from the United Arab Emirates (UAE).

METHODS: This sub-analysis of the EmHeart Study included 675 patients using rosuvastatin or atorvastatin. Patients were genotyped for SLCO1B1 and ABCG2 actionable variants using real-time PCR. Data on demographics, comorbidities, and statin use were extracted from electronic health records. Adverse events, including statin-associated muscle symptoms (SAMS) and liver enzyme elevation, were tracked over 12 months. Associations were analyzed using chi-square tests and logistic regression.

RESULTS: Rosuvastatin users carrying the ABCG2 rs2231142 variant had a threefold increased risk of liver enzyme elevation, particularly among East Asian patients (P < 0.005). Atorvastatin users with the SLCO1B1 rs4149056 variant exhibited a twofold increased risk of SAMS, with higher rates observed in females and Arabs (P < 0.05). The combination of rosuvastatin with ezetimibe further exacerbated risks of SAMS and liver enzyme elevation.

CONCLUSION: This study highlights the importance of genetic testing and demographic factors, such as ethnicity and gender, in tailoring statin therapy to minimize adverse effects. Despite extensive research on PGx-guided statin prescribing, clinical implementation remains limited. Integrating PGx testing into routine practice and enhancing physician awareness of genetic and demographic risk factors can improve the safety, efficacy, and adherence of lipid-lowering therapies in diverse populations.

PMID:40281622 | DOI:10.1186/s40246-025-00753-6

Alzheimers Res Ther. 2025 Apr 25;17(1):92. doi: 10.1186/s13195-025-01735-5.

ABSTRACT

A recent paper published a lecanemab analysis with data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. While the authors mention the limitations of FAERS, such as "voluntary (underreporting), the inability to establish causality, reporting bias, data quality issues, and the absence of a denominator, which precludes calculating incidence rates", they proceed with generalizations, clinical conclusions, and even treatment recommendations based on the crude disproportionality analysis. Consideration of post-marketing safety reports, including those found in the FAERS database, is an essential component of pharmacovigilance. However, FDA guidance [2, 3] highlights that: (1) "Rates of occurrence cannot be established with reports," (2) "Documenting one or more of these outcomes in a report does not necessarily mean that the suspect product(s) named in the report was the cause of the outcomes," and (3) "Importantly, the FAERS data by themselves are not an indicator of the safety profile of the drug." The FAERS database includes reports from many sources, including reports by companies, as well as from health care professionals and consumers. The reports in the FDA database have significant limitations, including submission of incomplete, inaccurate, untimely, duplicate, relatedness to drug uncertainty, and/or unverified information. Therefore, broader generalizations, clinical conclusions, and treatment recommendations should not be made based solely on FAERS databases analyses.

PMID:40281605 | DOI:10.1186/s13195-025-01735-5

IEEE J Biomed Health Inform. 2025 Apr 25;PP. doi: 10.1109/JBHI.2025.3564360. Online ahead of print.

ABSTRACT

Drug repositioning (DR) has emerged as an effective method of identifying new indications for existing drugs. Many DR methods have demonstrated superior performance. However, most of them utilize a limited number of biological entities, ignoring the critical role of other entities in addressing data sparsity as well as improving model generalization capabilities. In addition, fully capturing high-order information of biological data still needs to be fully explored. To address above issues, a model based on transformer and enhanced multi-view contrastive learning (TEMCL) is proposed for predicting drug-disease associations (DDAs). Firstly, transformer is employed to obtain high-order features of nodes from similarity information. Secondly, based on similarity matrices and association matrices of nodes, two different types of views are constructed, i.e., homogeneous hypergraphs and heterogeneous association graphs. Among them, to alleviate sparsity problem existing in heterogeneous graphs, protein nodes as well as meta-path enhancement strategy are introduced. Thirdly, hypergraph convolutional network and heterogeneous graph transformer are used to extract node features on above two types of views, respectively. Contrastive learning is applied to obtain more representative features. Finally, multilayer perceptron (MLP) is used for predicting DDAs. Experiments show that TEMCL outperforms existing methods on DR task, exhibiting superior performance. In addition, case studies further demonstrate the effectiveness of this model. TEMCL provides new insights for identifying novel DDAs.

PMID:40279215 | DOI:10.1109/JBHI.2025.3564360