To describe trends in dispensing of medications used for ADHD in Norway through two complementary analyses: a national dispensing analysis and a methylphenidate product analysis. The national dispensing analysis used public Norwegian Institute of Public Health statistics for all ages during 2005–2025 to describe annual recipient counts overall and by active substance. The methylphenidate product analysis used a commissioned aggregated extract covering ages ≥ 6 years during 2005–2022 to describe product-specific user counts by product category and release profile. Product-specific user counts overlapped across products. Diagnoses and treatment indications were unavailable in both analyses. In the national dispensing analysis, the number of individuals dispensed at least one included medication increased from 16,578 in 2005 to 124,420 in 2025, corresponding to 0.36
Falls are a major geriatric syndrome associated with substantial morbidity, functional decline, and loss of independence. Although sodium–glucose cotransporter 2 (SGLT2) inhibitors provide well-established cardiovascular and renal benefits, their association with falls in older adults remains uncertain because of limited and inconsistent evidence. Therefore, this study primarily aimed to investigate the association between SGLT2 inhibitor use and recurrent falls in older adults undergoing comprehensive geriatric assessment (CGA), and secondarily to compare these findings with those for other medication classes, including established fall-risk-increasing drugs. This retrospective cross-sectional study included 1,069 adults aged ≥ 65 years who underwent CGA. Recurrent falls were defined as ≥ 2 falls during the previous year. Participants were categorised as fallers or non-fallers. Demographic characteristics, comorbidities, medication use including SGLT2 inhibitors, laboratory findings, and CGA parameters were recorded. Logistic regression analyses were performed to identify medication groups associated with recurrent falls after sequential adjustment for confounding factors. A total of 1,069 older adults were included, of whom 298 (27.9
Polyethylene terephthalate microplastics (PET-MPs) are widespread emerging environmental pollutants, yet their pathogenic role in recurrent pregnancy loss (RPL) has not been clarified. This study intended to uncover key molecular targets and mechanisms mediating the connection between PET-MP exposure and RPL. We collected PET-related targets and RPL differentially expressed genes from dataset GSE165004, then performed enrichment and protein-protein interaction analyses on overlapping genes. Machine learning selected hub genes, followed by immune infiltration assessment and molecular docking verification. Decidual single-cell RNA sequencing, YWHAZ virtual knockout, and in vitro PET-MP treatment of trophoblast and endometrial stromal cells were implemented. Thirty-five intersecting genes were screened. Four hub genes (YWHAZ, SRC, CYP1A2, PAK2) had promising diagnostic capacity and correlated with immune cell infiltration. Molecular docking revealed stable binding of PET to all four hub proteins. YWHAZ was downregulated in multiple decidual cell subsets of RPL patients, and its knockout disturbed immune pathways. In vitro, PET-MPs suppressed cell viability and YWHAZ protein expression in trophoblast and endometrial stromal cells. This exploratory integrated study suggests that PET-MP exposure may contribute to RPL through immune and signaling dysfunction. YWHAZ is identified as a candidate PET-responsive mediator and a potential diagnostic biomarker for RPL. This study provides exploratory mechanistic insights and candidate biomarkers for microplastic‑associated reproductive toxicity.
Teriflunomide, the active metabolite of leflunomide, has attracted interest as a candidate for cancer repurposing because, in addition to inhibiting dihydroorotate dehydrogenase (DHODH), it may also modulate non-canonical signalling pathways implicated in tumour growth and survival. This study investigated the anticancer effects of teriflunomide in luminal and triple-negative breast cancer models and examined whether its downstream molecular effects differ according to subtype. Luminal MCF-7 and triple-negative MDA-MB-231 breast cancer cells were treated with teriflunomide and analysed using cell viability, clonogenicity, migration assays, label-free proteomics, KEGG pathway analysis, and phospho-kinase profiling. Treated cancer cells were also compared with untreated counterparts and with non-tumorigenic MCF-10 A cells to evaluate treatment-associated proteomic remodelling. Teriflunomide reduced tumour-cell fitness in both models, but downstream molecular responses were subtype dependent. In MCF-7 cells, treatment was associated with a clearer shift in protein abundance and suppression of growth-related phospho-signalling, particularly within the PI3K/AKT/mTOR/p70S6K/RSK axis. In contrast, MDA-MB-231 cells showed a more limited abundance-level proteomic shift but broader activation of phospho-signalling involving EGFR/Src/STAT3, MAPK, and AKT-related pathways, consistent with adaptive rewiring under drug-induced stress. Integration of proteomic and phospho-kinase data showed that changes in kinase abundance were often uncoupled from changes in activation state. Proteomic analysis identified MFF, TOMM20, CSNK1A1, DKC1, ANPEP, and DDAH1 as notable regulated markers. TCGA-based validation showed that most top-regulated proteins differed between breast cancer and normal tissue, while only a subset varied across pathological stages, supporting their relevance as potential combination-strategy candidates. Teriflunomide exerts subtype-dependent anticancer effects in breast cancer cells and reshapes signalling networks in a context-specific manner. These findings support further evaluation of teriflunomide in subtype-informed combination strategies targeting adaptive kinase and metabolic pathways.
Myocardial ischemia causes cardiomyocyte death and cardiac dysfunction. While vascular regeneration to restore blood supply is key for heart failure management, it often triggers myocardial ischemia-reperfusion injury (MIRI). Icariin (ICA), a bioactive compound from Epimedium brevicornu Maxim., exhibits cardioprotective effects, but its role in MIRI remains unclear. Cardiac microvascular endothelial cells (CMECs) subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were treated with ICA. Cell viability was evaluated via CCK-8 assay, while wound-healing and tube formation assays assessed migratory and angiogenic capacities. Network pharmacology integrated TCMSP, SwissTargetPrediction and GeneCards databases to construct drug-target-disease networks. STRING 11.5 analyzed protein-protein interactions (PPI), with DAVID performing GO and KEGG enrichment. Molecular docking (MD) and molecular dynamics simulation (MDs) validated ligand-receptor binding, and Western blotting verified protein expression modulated by ICA. ICA exerted dose-dependent cytoprotection against OGD/R injury, significantly enhancing CMECs migration and tube formation (P < 0.05). Network analysis identified 12 key targets intersecting ICA’s pharmacological profile and MIRI pathogenesis. Enrichment analysis highlighted involvement in AGE-RAGE, sphingolipid, and VEGF signaling pathways. MD confirmed strong binding of ICA to PKCA (-8.79 kcal/mol), PKCB (-7.13 kcal/mol) and PTGS2 (-4.17 kcal/mol). Western blotting showed that ICA restored PKCA, PKCB and PTGS2 expression, while pharmacological inhibition of PKC signaling attenuated the functional protective effects of ICA. MDs revealed that ICA binding promoted PKCA structural compactness and reduced regional flexibility. This study demonstrates ICA attenuates MIRI by promoting CMECs angiogenesis through PKC-mediated signaling. Not applicable. Lcariin protects CMECs from OGD/R injury in a dose-dependent manner, enhancing cell viability, migration and angiogenesis. Network pharmacology identifies 12 key targets and signaling pathways like AGE-RAGE, sphingolipid and VEGF involved in ICA’s action. Molecular docking shows strong binding of ICA to PKCA, PKCB and PTGS2, with MDs revealing ICA induces PKCA structural compactness.
