BMC Geriatr. 2025 Mar 28;25(1):205. doi: 10.1186/s12877-025-05851-7.

ABSTRACT

BACKGROUND: Globally, falls are considered a serious healthcare problem for aged care residents. Fall-risk-increasing drugs (FRIDs) are medications that can increase the risk of falling, given their adverse effects. Medication reviews are advocated to identify potentially inappropriate use of FRIDs. However, their impact on clinical and resident-centered outcomes is unclear. This study explored aged care residents' use of FRIDs and the content of medication review reports concerning these.

METHODS: A retrospective cross-sectional study of medication review reports completed between 1st July 2021 and 30th June 2022 was conducted. Statistical descriptive analysis was used to examine the use of FRIDs (defined as medications listed in the Screening Tool of Older Persons Prescriptions in older adults with high fall risk (STOPPFall)). The resident's medicine experience, identified drug-related problems (DRPs), and related recommendations concerning FRIDs were explored via content analysis. For recommendations to deprescribe FRIDs, clinical situations detailed in the reports were compared to those presented in STOPPFall.

RESULTS: Medication review reports relating to 966 residents were analysed. Of these residents, 83.2% (n = 804) used FRIDs, with 31.2% (n = 301) taking three or more FRIDs. In total, pharmacists made recommendations concerning 2635 identified DRPs, of which 19.7% (n = 520) were the potentially inappropriate use of FRIDs and deprescribing was recommended. The clinical situation for which deprescribing was most frequently recommended was the use of a FRID for an indication of limited clinical benefit 37.9% (n = 197). The clinical situation was not detailed for 130 (25.0%) recommendations to deprescribe FRIDs, and only three reports included the resident's viewpoint on deprescribing.

CONCLUSIONS: FRID use was found to be highly prevalent among aged care residents. Pharmacists frequently identified opportunities to deprescribe FRIDs. However, reports often omitted resident viewpoints and the clinical grounds for deprescribing. Using resident-centered communication in medication review reports could improve their impact on FRID use and resident outcomes.

PMID:40155803 | DOI:10.1186/s12877-025-05851-7

Biomedicines. 2025 Mar 13;13(3):707. doi: 10.3390/biomedicines13030707.

ABSTRACT

Backgroung/objectives: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of malignant lymphoma and is a heterogeneous disease with various gene and chromosomal abnormalities. The development of novel therapeutic treatments has improved DLBCL prognosis, but patients with early relapse or refractory disease have a poor outcome (with a mortality of around 40%). Metabolic reprogramming is a hallmark of cancer cells. Fatty acid (FA) metabolism is frequently altered in cancer cells and recently emerged as a critical survival path for cancer cell survival. Methods: We first performed the metabolic characterization of an extended panel of DLBCL cell lines, including lipid droplet content. Then, we investigated the effect of drugs targeting FA metabolism on DLBCL cell survival. Further, we studied how the combination of drugs targeting FA and either mitochondrial metabolism or mTOR pathway impacts on DLBCL cell death. Results: Here, we reveal, using a large panel of DLBCL cell lines characterized by their metabolic status, that targeting of FA metabolism induces massive DLBCL cell death regardless of their OxPhos or BCR/glycolytic subtype. Further, FA drives resistance of DLBCL cell death induced by mitochondrial stress upon treatment with either metformin or L-asparaginase, two FDA-approved antimetabolic drugs. Interestingly, combining inhibition of FA metabolism with that of the mTOR oncogenic pathway strongly potentiates DLBCL cell death. Conclusion: Altogether, our data highlight the central role played by FA metabolism in DLBCL cell survival, independently of their metabolic subtype, and provide the framework for the use of drugs targeting this metabolic vulnerability to overcome resistance in DLBCL patients.

PMID:40149683 | PMC:PMC11940118 | DOI:10.3390/biomedicines13030707

Cancer Lett. 2025 Mar 26:217660. doi: 10.1016/j.canlet.2025.217660. Online ahead of print.

ABSTRACT

Medulloblastoma (MB) represents the most common malignant central nervous system tumor in childhood. The nervous system plays a critical role in the progression of MB, with interactions between the nervous system and cancer significantly influencing oncogenesis, tumor growth, invasion, stemness, and metabolism. These interactions also regulate angiogenesis, metastatic dissemination, the tumor immune microenvironment, and drug resistance. Investigating the nervous system-MB axis holds promise for identifying diagnostic markers, prognostic biomarkers, and therapeutic targets. It also provides insights into the molecular mechanisms underlying MB and informs the development of novel therapeutic strategies. This review summarizes the latest advancements in understanding the interplay between the nervous system and MB, including the role of glial cells in MB and the potential of drug repurposing targeting nervous system components for MB treatment. These findings underscore promising diagnostic and therapeutic opportunities for MB management. Additionally, we outline future research directions in neurosciences that may pave the way for innovative therapeutic approaches and deepen our understanding of this complex disease.

PMID:40154912 | DOI:10.1016/j.canlet.2025.217660

Ann Pharm Fr. 2025 Mar 26:S0003-4509(25)00047-1. doi: 10.1016/j.pharma.2025.03.005. Online ahead of print.

ABSTRACT

OBJECTIVES: The key objective of present research is to effectively treat lung cancer with repurposed celecoxib while overcoming challenges such as solubility, bioavailability, non-selectivity, and negative effects by delivering celecoxib through nanostructured lipid carriers via the parenteral route.

METHODS: Celecoxib-laden nanostructured lipid carriers were manufactured by melt-emulsification ultrasonication approach and optimized through Box-Behnken Design. The celecoxib nanostructured lipid carriers were examined for particle size, % entrapment efficiency, zeta potential, in vitro release, cytotoxicity, stability, etc. Results: The optimized celecoxib nanostructured lipid carriers displayed a % entrapment efficiency of 91.69±4.9% and particle size of 132.1±6.8 nm with a polydispersity index of 0.41±0.06, and a zeta potential of -39.1 ± 3.0 mV. Notably, celecoxib nanostructured lipid carriers exhibited better and controlled celecoxib release at phosphate buffer solution pH 6.8 than pH 7.4, revealing the tumor-targeting potential of nanostructured lipid carriers. Also, the release of celecoxib from nanostructured lipid carriers was controlled for 48 h, indicating reduced chances of systemic toxicity. The in vitro cytotoxicity against A549 cells of celecoxib nanostructured lipid carriers was 1.5-fold greater than that of pure celecoxib, confirming significant anti-lung cancer effectiveness. Further, the celecoxib-loaded nanostructured lipid carriers remained stable for twelve weeks at cold and ambient temperatures.

CONCLUSION: Thus, the given research concludes that parenteral administration of nanostructured lipid carriers could be a harmless, efficient, and novel choice to treat lung cancer using repurposed celecoxib.

PMID:40154777 | DOI:10.1016/j.pharma.2025.03.005

Cell Genom. 2025 Mar 21:100820. doi: 10.1016/j.xgen.2025.100820. Online ahead of print.

ABSTRACT

Most variants identified from genome-wide association studies (GWASs) are non-coding and regulate gene expression. However, many risk loci fail to colocalize with expression quantitative trait loci (eQTLs), potentially due to limited GWAS and eQTL analysis power or cellular heterogeneity. Population-scale single-cell RNA-sequencing (scRNA-seq) datasets are emerging, enabling mapping of eQTLs in different cell types (sc-eQTLs). Compared to eQTL data from bulk tissues (bk-eQTLs), sc-eQTL datasets are smaller. We propose a joint model of bk-eQTLs as a weighted sum of sc-eQTLs (JOBS) from constituent cell types to improve power. Applying JOBS to One1K1K and eQTLGen data, we identify 586% more eQTLs, matching the power of 4× the sample sizes of OneK1K. Integrating sc-eQTLs with GWAS data creates an atlas for 14 immune-mediated disorders, colocalizing 29.9% or 32.2% more loci than using sc-eQTL or bk-eQTL alone. Extending JOBS, we develop a drug-repurposing pipeline and identify novel drugs validated by real-world data.

PMID:40154479 | DOI:10.1016/j.xgen.2025.100820

J Infect Public Health. 2025 Mar 19;18(6):102763. doi: 10.1016/j.jiph.2025.102763. Online ahead of print.

ABSTRACT

BACKGROUND: Leprosy and tuberculosis caused by Mycobacterium leprae and Mycobacterium tuberculosis, respectively, are chronic infections with significant public health implications. While leprosy affects the skin and peripheral nerves and tuberculosis primarily targets the lungs, both diseases involve systemic immune responses. This study integrates transcriptomic analysis cheminformatics and molecular dynamics simulations to identify molecular mechanisms and potential therapeutic targets.

METHODS: Transcriptomic datasets were analyzed to identify dysregulated genes and pathways. Pathway enrichment tissue-specific and bulk RNA-seq expression analyses provided biological context. System biology networks revealed regulatory hub genes and molecular docking studies evaluated CHEMBL compounds as potential therapeutics. Molecular dynamics (MD) simulations assessed the stability of top ligand-protein complexes through RMSD RMSF and MM-GBSA free energy calculations.

RESULTS: Gene expression analysis identified 13 core dysregulated genes, including HSP90AA1 MAPK8IP3 and ZMPSTE24. Tissue-specific expression localized pivotal genes to lung tissues and immune cells with HSP90AA1 highly expressed in alveolar macrophages and epithelial cells. HSP90AA1 gene emerged as a central hub gene with 96 interactions involved in stress response pathways. Docking studies identified CHEMBL3653862 and CHEMBL3653884 with strong binding affinities (-10.16 to -12.69 kcal/mol) interacting with Asp93 and Tyr139. MD simulations confirmed binding stability with RMSD fluctuations within 2.1-3.5 Å and MM-GBSA energy values supporting ligand-protein stability.

CONCLUSION: This study identifies HSP90AA1 as a potential drug target in leprosy and tuberculosis. Findings support host-directed therapy approaches and highlight the importance of computational modeling in accelerating drug discovery. The study provides a foundation for future experimental validation, including in vitro and in vivo testing to advance drug repurposing strategies for these chronic infections.

PMID:40153981 | DOI:10.1016/j.jiph.2025.102763

Bull Cancer. 2025 Mar;112(3S1):3S107-3S116. doi: 10.1016/S0007-4551(25)00164-X.

ABSTRACT

In Europe, a rare cancer is defined as having an incidence rate of less than 6/100,000. Rare lung cancers encompass many entities defined by the 2021 WHO classification of thoracic tumors, and represent around 10% of all lung cancers. Rare lung cancers involve several histological types (carcinoma, sarcoma and lymphoma), each of which comprises several entities. The management of these patients with rare cancers requires specific medical expertise at every level (diagnosis, treatment and follow-up). These patients should therefore be referred to expert centers affiliated with national networks, giving them appropriate care and better access to innovative treatments. The deployment of systematic molecular characterization of these tumors has allowed for the identification and better characterization of specific entities. Some entities are specific to the lung, while others are more commonly found in other organs. In this review, we will only consider malignant lung tumors with an incidence of less than 1%.

PMID:40155070 | DOI:10.1016/S0007-4551(25)00164-X

J Pharm Sci. 2025 Mar 26:103772. doi: 10.1016/j.xphs.2025.103772. Online ahead of print.

ABSTRACT

OATP2B1, encoded by SLCO2B1, is a drug transporter expressed widely throughout the body in tissues such as the intestine and liver. Genetic variation of this transporter may lead to altered disposition of OATP2B1 substrate drugs, but especially the effects of rare variants are poorly understood. The aim of this study was to characterize the effects of naturally occurring missense single nucleotide variants of SLCO2B1 (c.601G>A, c.935G>A, c.953C>T, c.1175C>, c.1457C>T, c.1559G>C, c.1596C>A, and the c.601G>A + c.935G>A haplotype) on the in vitro functionality of OATP2B1. To characterize transport activity, cellular uptake of dibromofluorescein, 5-carboxyfluorescein, estrone sulfate, and rosuvastatin was compared in OATP2B1 reference- and variant-expressing HEK293 cells. The abundance of OATP2B1 variants in HEK293 crude membrane preparations was quantified with LC-MS/MS-based quantitative targeted absolute proteomics analysis. Variant c.1559G>C impaired OATP2B1-mediated uptake of all tested substrates almost completely, but protein abundance was not reduced to the same extent. Other studied variants had comparable or only modestly reduced protein abundance and transport function compared to reference OATP2B1. These results can be utilized to understand findings from clinical pharmacogenetic studies. More importantly, the results can aid in predicting the consequences of rare variants, such as the loss-of-function variant c.1559G>C, which can be difficult to detect in clinical studies.

PMID:40154787 | DOI:10.1016/j.xphs.2025.103772

Semin Cancer Biol. 2025 Mar 26:S1044-579X(25)00051-3. doi: 10.1016/j.semcancer.2025.03.002. Online ahead of print.

ABSTRACT

Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.

PMID:40154652 | DOI:10.1016/j.semcancer.2025.03.002

J Biol Chem. 2025 Mar 26:108460. doi: 10.1016/j.jbc.2025.108460. Online ahead of print.

ABSTRACT

Activation of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl‒ channel requires PKA phosphorylation at the regulatory (R) domain to relieve inhibition of ATP-dependent channel activity. This study aimed to identify the primary inhibitory site that prevents channel activation. CFTR mutants with deletion of residues 760-783 (ΔR760-783) elicited constitutive macroscopic and single-channel Cl‒ currents in the presence of ATP before PKA phosphorylation, suggesting that protein segment R760-783 in the R domain blocks CFTR activation. With the background of ΔR760-835, further deletion of R708-759 led to fully active channels in the presence of ATP, but absence of PKA, suggesting that R708-759 prevents the activation of ΔR760-835-CFTR. R760-783 peptides were unstructured in buffered solutions in circular dichroism spectroscopy and the N771P mutation that interrupts the α-helix formation induced no apparent constitutive current before PKA phosphorylation. These data suggest that interpeptide interactions by α-helices likely contribute trivially to the blocking effect of R760-783. CFTR mutants with small deletions or alanine replacements containing any one of residues R766 and S768 in a PKA consensus sequence and M773 and T774 generated PKA-independent CFTR Cl‒ currents. Similarly, introducing the mutations Q767C or T774C into a control CFTR construct produced constitutive CFTR Cl‒ currents by positively charged MTSET modification of target cysteines. Moreover, PKA-independent single-channel activity was evidently observed in R766K-, S768K- and T774K-CFTR mutants. Therefore, the four residues R766, S768, M773 and T774 may form an inhibitory module that precludes CFTR activation through side-chain interactions. This inhibitory mechanism might be emulated by other PKA-dependent proteins.

PMID:40154618 | DOI:10.1016/j.jbc.2025.108460

Eur Respir J. 2025 Mar 28:2402249. doi: 10.1183/13993003.02249-2024. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with severe COVID-19 may develop lung fibrosis. Pirfenidone is an anti-fibrotic drug approved for idiopathic pulmonary fibrosis. The efficacy and safety of pirfenidone in patients with fibrotic interstitial lung changes after recovery from severe COVID-19 pneumonia was evaluated.

METHODS: Phase 2, double-blind, placebo-controlled, Spanish multicenter clinical trial randomized to receive pirfenidone or placebo (2:1) for 24-weeks. The primary endpoint was the proportion of patients that improved, considered when percent change in forced vital capacity (FVC) was ≥10% and/or any reduction in the fibrotic score chest high-resolution computed tomography (HRCT). Secondary endpoints included health-related quality of life (HRQoL), exercise capacity, and drug safety profile.

RESULTS: From 119 eligible patients, 113 were randomized and 103 were analyzed (pirfenidone n=69, placebo n=34). Most patients were male (73.5%) and were receiving low-dose prednisone; mean age was 63.7 years and body-mass index was 29 kg·m-2. The percentage of patients that improved was similar in the pirfenidone and placebo groups (79.7% versus 82.3%, respectively). The mean predicted FVC (%) increased 12.74 (20.6) with pirfenidone and 4.35 (22.3) with placebo (p=0.071), and the HRCT (%) fibrotic score reduced 5.44 (3.69) with pirfenidone and 2.57 (2.59) with placebo (p=0.52). Clinically meaningful improvement in HRQoL was not statistically different (55.2% in pirfenidone and 39.4% in placebo group, respectively). Exercise capacity, adverse events and hospitalizations were similar between groups. No deaths were reported.

CONCLUSIONS: The overall improvement in lung function and the HRCT fibrotic score after 6 months with pirfenidone was not significantly different than placebo.

PMID:40154560 | DOI:10.1183/13993003.02249-2024

Cancer Cell. 2025 Mar 20:S1535-6108(25)00108-4. doi: 10.1016/j.ccell.2025.03.007. Online ahead of print.

ABSTRACT

Myeloid cancers such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) remain resistant to standard of care (SOC) and targeted therapies. In this study, we demonstrate that responsiveness to therapy is associated with activation of β-catenin-JAG1 in osteoblastic cells of patients treated with all-trans-retinoic acid (ATRA). ATRA suppresses β-catenin activity in patients and leukemic mice. Consequently, it inhibits the growth and survival of MDS/AML cells from patients with active β-catenin-JAG1 signaling and promotes their differentiation. This occurs independently of cytogenetics and mutational profile. ATRA also improves disease outcome in mice with no evidence of relapse and a superior safety profile to SOC. A human anti-JAG1 antibody improves efficacy in leukemic mice and patient-derived MDS/AML cells. β-catenin activation provides an explanation for the differential response to ATRA and a mechanistic biomarker for ATRA repurposing in myeloid malignancies, potentially evading relapse and extending across a broad range of cancers.

PMID:40154481 | DOI:10.1016/j.ccell.2025.03.007

J Immunother Cancer. 2025 Mar 28;13(3):e011273. doi: 10.1136/jitc-2024-011273.

ABSTRACT

INTRODUCTION: Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors, but they also commonly cause immune-related adverse events (irAEs). The predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Given the similarities between irAEs and autoimmune diseases, we sought to investigate the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs.

METHODS: The Genetics of immune-related adverse events and Response to Immunotherapy (GeRI) cohort comprises 1302 patients with non-small cell lung cancer (NSCLC) who received ICI therapy between 2009 and 2022 at four academic medical centers. We used a published polygenic risk score for autoimmune diseases (PRSAD) in the general population and validated it in the All of Us. We then assessed the association between PRSAD and cessation of ICI therapy due to irAEs in the GeRI cohort, using cause-specific and Fine-Gray subdistribution hazard models. To further understand the differential effects of type of therapy on the association between PRSAD and cessation of ICI due to irAEs, we conducted a stratified analysis by type of ICI therapy.

RESULTS: Using a competing risk model, we found an association between PRSAD and ICI cessation due to irAEs (HR per SD=1.24, p=0.004). This association was particularly strong in patients who had ICI cessation due to irAEs within 3 months of therapy initiation (HR per SD=1.40, p=0.005). Individuals in the top quintile of PRSAD had 4.8% ICI discontinuation for irAEs by 3 months, compared with 2% discontinuation by 3 months among patients in the bottom quintile (log-rank p=0.03). In addition, among patients who received combination programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte associated protein 4 (CTLA4) inhibitors, ICI discontinuation for irAEs by 3 months occurred in 4 of the 13 patients (30.8%) with high PRSAD genetic risk (top quintile) versus 3 of 21 patients (14.3%) with low PRSAD genetic risk (bottom quintile).

CONCLUSIONS: We demonstrate an association between a polygenic risk score for autoimmune disease and early ICI discontinuation for irAEs. Our results suggest that germline genetics may be used as an adjunctive tool for risk stratification around ICI clinical decision-making in solid tumor oncology.

PMID:40154961 | DOI:10.1136/jitc-2024-011273

PLoS One. 2025 Mar 28;20(3):e0304540. doi: 10.1371/journal.pone.0304540. eCollection 2025.

ABSTRACT

The primary objective is to identify which observational research methods have been used in the last 5 years in rare disease drug evaluation and how they are applied to generate adequate evidence regarding the real-world effectiveness or safety of rare disease drugs. Rare disease is an umbrella term for a condition which affects < 200,000 people each year and despite the rarity of these conditions, collectively they encompass approximately 7000 different conditions. With the striking number of rare conditions, many pharmaceutical manufacturers are introducing an increased number of drugs to treat them. However, due to small patient populations, heterogeneity and other factors related to rare diseases, there are feasibility concerns regarding the generation of adequate efficacy and safety evidence using conventional randomized controlled trials (RCTs). Recently, real-world evidence generated through observational (or real-world) studies has been proposed to address some of the feasibility concerns with RCTs by measuring drug effectiveness or safety in the real-world setting. However, there remain methodological concerns due to a lack of randomization/masking. This proposed scoping review aims to identify which observational research methods in the last 5 years are used in rare disease drug evaluation to address methodological concerns and how they are applied to generate evidence on drug effectiveness or safety. Articles must be primary observational or real-world studies reporting rare disease drug effectiveness or safety published within the five years preceding this review. Literature reviews, meta-analyses, randomized control trials, case series, case reports, opinion pieces, conference abstracts, and studies with unavailable full-text articles will be excluded. The search strategy will combine the following key search concepts: rare disease, drugs for rare disease and observational/real-world studies. The search will be conducted in MEDLINE and EMBASE. Review registration number: Open Science Framework, https://osf.io/f3wpv.

PMID:40153394 | DOI:10.1371/journal.pone.0304540

Am J Respir Crit Care Med. 2025 Mar 28. doi: 10.1164/rccm.202409-1792OC. Online ahead of print.

ABSTRACT

RATIONALE: Mycobacteroides abscessus infections affect immunocompromised patients and those with underlying pulmonary disease. Conventional imaging cannot distinguish M. abscessus infections from underlying pulmonary disease or sterile inflammation, requiring invasive procedures for definitive diagnosis.

OBJECTIVE: We evaluated 11C-para-aminobenzoic acid (11C-PABA), a chemically identical radioanalog of PABA, to detect and localize infections due to M. abscessus.

METHODS: In vitro uptake assays were performed to test the metabolism and accumulation of PABA into M. abscessus reference and clinical isolates. Dynamic 11C-PABA positron emission tomography (PET) was performed in a mouse model of M. abscessus pulmonary infection and in a patient with microbiologically-confirmed M. abscessus pulmonary infection (NCT05611905).

MAIN RESULTS: 11C-PABA was intracellularly metabolized by M. abscessus to 11C-7,8-dihydropteroate. Additionally, and the reference and all thirteen randomly chosen clinical isolates, including three resistant to trimethoprim-sulfamethoxazole, rapidly accumulated PABA. No PABA accumulation was noted by heat-inactivated bacteria or mammalian cells. Dynamic 11C-PABA PET in a mouse model of M. abscessus pulmonary infection rapidly distinguished infection from sterile inflammation and also accurately monitored response to antibiotic treatment. Finally, dynamic 11C-PABA PET in a 33-year-old female with cystic fibrosis and microbiologically confirmed M. abscessus pulmonary infection was safe and demonstrated significantly higher and sustained PET uptake in the affected lesions.

CONCLUSIONS: 11C-PABA PET is an innovative, clinically-translatable, noninvasive, bacteria-specific diagnostic to differentiate M. abscessus infections from underlying pulmonary disease in patients. This tool could also help in monitoring treatment responses and enable precision medicine approaches for patients with complicated infections. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

PMID:40153540 | DOI:10.1164/rccm.202409-1792OC

J Proteome Res. 2025 Mar 28. doi: 10.1021/acs.jproteome.4c00827. Online ahead of print.

ABSTRACT

Intercellular communication is important for host immunity in response to bacterial infections. Nontuberculous mycobacterium (NTM), such as Mycobacterium abscessus (M. ab), is a group of environmental bacteria that can cause severe lung infections in individuals with pre-existing lung conditions, including cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). There is limited knowledge understanding the interaction between airway epithelial cells and immune cells during NTM infections. In this study, we characterized microvesicles (MVs) released from uninfected and M. ab-infected human bronchial epithelial cells and investigated the effect of these MVs on the activation and polarization of THP-1-derived macrophages in cell culture. Our results indicate that MVs released by M. ab-infected human bronchial epithelial cells stimulated the activation of M2-polarized macrophages in cell culture when compared to MVs released by uninfected cells. Additionally, the proteomic analysis for isolated MVs showed that the proteins involved in the cell adhesion pathway were enriched in MVs from M. ab-infected human bronchial epithelial cells compared to MVs from uninfected cells. Among those, the cell surface protein, intercellular adhesion molecule 1 (ICAM-1), regulated the uptake of MVs released by M. ab-infected human bronchial epithelial cells by recipient macrophages in cell culture. In conclusion, our data suggest that in response to M. ab infection, human airway epithelial cells release MVs to modulate the activation of macrophages, which are key cells for mycobacterial intracellular survival in the host.

PMID:40153482 | DOI:10.1021/acs.jproteome.4c00827

Lung. 2025 Mar 28;203(1):55. doi: 10.1007/s00408-025-00806-6.

ABSTRACT

PURPOSE: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to multisystemic complications, particularly in the lungs. CFTR dysfunction results in altered ion transport, chronic inflammation, and progressive lung damage. The triple therapy elexacaftor/tezacaftor/ivacaftor (ETI) has demonstrated significant improvements in pulmonary function and quality of life. This study aimed to evaluate the anti-inflammatory effects of ETI by analysing systemic cytokine profiles over 12 months.

METHODS: A prospective study included 32 CF patients ≥ 18 years with at least one delF508 mutation, undergoing ETI therapy. Clinical stability was ensured prior to therapy initiation. Demographic data, BMI (Body Mass Index), FEV1% (Forced expiratory Volume in the first second), VR/TLC (residual volume/total lung capacity) and sweat chloride concentrations were recorded at baseline, 6 months and 12 months. Inflammatory markers, including fibrinogen, C-reactive protein (CRP), and a panel of 8 cytokines, were measured using multiplex bead-based immunoassays and electrochemiluminescence. Longitudinal changes were analysed using mixed-effects models and statistical tests, with significance set at p < 0.05.

RESULTS: During a 12-month follow-up, the neutrophils number and proinflammatory biomarkers analyzed, fibrinogen, CRP, GM-CSF, IFN- γ, IL-1 α, IL-1 β, IL-8 (CXCL8), IL-12p70, IL-17A (CTLA-8), and TNF-α, significantly decreased, while eosinophils remained stable. Mixed-effects models confirmed the significant association of inflammatory biomarkers with FEV1, BMI, sweat chloride levels, and VR/TLC highlighting the role of inflammation in the progression of CF.

CONCLUSIONS: ETI demonstrated marked anti-inflammatory effects in CF patients, reducing systemic inflammation and improving clinical parameters.

PMID:40153049 | DOI:10.1007/s00408-025-00806-6

PLoS One. 2025 Mar 28;20(3):e0321409. doi: 10.1371/journal.pone.0321409. eCollection 2025.

ABSTRACT

[This corrects the article DOI: 10.1371/journal.pone.0312112.].

PMID:40153338 | DOI:10.1371/journal.pone.0321409

IEEE Trans Pattern Anal Mach Intell. 2025 Mar 28;PP. doi: 10.1109/TPAMI.2025.3556133. Online ahead of print.

ABSTRACT

Recent years have witnessed significant advances in image deraining due to the progress of effective image priors and deep learning models. As each deraining approach has individual settings (e.g., training and test datasets, evaluation criteria), how to fairly evaluate existing approaches comprehensively is not a trivial task. Although existing surveys aim to thoroughly review image deraining approaches, few of them focus on unifying evaluation settings to examine the deraining capability and practicality evaluation. In this paper, we provide a comprehensive review of existing image deraining methods and provide a unified evaluation setting to evaluate their performance. Furthermore, we construct a new high-quality benchmark named HQ-RAIN to conduct extensive evaluations, consisting of 5,000 paired high-resolution synthetic images with high harmony and realism. We also discuss existing challenges and highlight several future research opportunities worth exploring. To facilitate the reproduction and tracking of the latest deraining technologies for general users, we build an online platform to provide the off-the-shelf toolkit, involving the large-scale performance evaluation. This online platform and the proposed new benchmark are publicly available at http://www.deraining.tech/.

PMID:40153286 | DOI:10.1109/TPAMI.2025.3556133

IEEE J Biomed Health Inform. 2025 Mar 28;PP. doi: 10.1109/JBHI.2025.3555813. Online ahead of print.

ABSTRACT

Electroencephalography (EEG) data is easily contaminated by various sources, significantly affecting subsequent analyses in neuroscience and clinical applications. Therefore, effective artifact removal is a key step in EEG preprocessing. While current deep learning methods have demonstrated notable efficacy in EEG denoising, single-channel approaches primarily focus on temporal features and neglect inter-channel correlations. Meanwhile, multi-channel methods mainly prioritize spatial features but often overlook the unique temporal dependencies of individual channels. A common limitation of both single-channel and multi-channel methods is their strict requirements on the input channel setting, which restricts their practical applicability. To address these issues, we design a flexible architecture named Artifact removal Spatio-Temporal Integration Network (ASTI-Net), a dual-branch denoising model capable of handling arbitrary EEG channel settings. ASTI-Net utilizes spatio-temporal attention weighting with dual branches that capture inter-channel spatial characteristics and intra-channel temporal dependencies. Its architecture incorporates deformable convolutional operations and channel-wise temporal processing, accommodating varying numbers of EEG channels and enhancing applicability across diverse clinical and research settings. By integrating features from both branches through a fusion reconstruction module, ASTI-Net effectively restores clean multi-channel EEG. Extensive evaluation on two semi-simulated datasets, along with qualitative assessment on real task-state EEG data, validates that ASTI-Net outperforms existing artifact removal methods.

PMID:40153283 | DOI:10.1109/JBHI.2025.3555813