Search Results (6,239)

Oxidative stress is a central and well-established driver of cardiovascular disease, contributing to mitochondrial dysfunction, endothelial injury, inflammatory activation, and progressive myocardial and vascular remodeling. Although the major endogenous sources of cardiovascular reactive oxygen species (ROS), including NADPH oxidases, mitochondrial electron transport chain leakage, and uncoupled nitric oxide synthase, are well characterized, an additional and underappreciated contributor has recently emerged: cytochrome P450 2D6 (CYP2D6), an enzyme classically regarded as a hepatic drug-metabolizing protein. Accumulating evidence indicates that CYP2D6 is expressed extrahepatically in cardiac, vascular, and neural tissue, where uncoupled catalytic cycling is proposed to generate ROS independently of its canonical xenobiotic-metabolizing role, although direct experimental evidence for this pathway in human cardiac and vascular tissue remains limited. CYP2D6-derived oxidative processes may interact with mitochondrial respiratory function, endothelial nitric oxide bioavailability, and redox-sensitive inflammatory pathways, potentially contributing to cardiovascular vulnerability under specific genetic or pathological conditions. Critically, the magnitude of this oxidative contribution is not fixed: it is dynamically shaped by inherited CYP2D6 genetic variation, with poor and ultra-rapid metabolizer phenotypes exhibiting divergent oxidative burden and pharmacokinetic vulnerability, and is further amplified by polypharmacy, multimorbidity, and inflammation-driven phenoconversion, whereby clinically expressed CYP2D6 activity diverges from inherited genotype in ways that intensify redox imbalance. These dynamics are particularly relevant in East Asian populations, where the decreased-function CYP2D6*10 allele is highly prevalent. In this narrative, hypothesis-generating review, we integrate evidence from pharmacogenomics, redox biology, and cardiovascular pharmacology to propose a conceptual framework that reframes CYP2D6 as a genetically and pharmacologically tunable node within cardiovascular redox biology. We further examine emerging redox biomarkers, multi-omics platforms, and AI-assisted modeling as translational strategies for capturing this dynamic oxidative risk in real time. This framework supports a shift from static genotype-guided prescribing toward oxidative-risk-informed, adaptive cardiovascular precision medicine. Importantly, our focus on CYP2D6 should not be interpreted as evidence that it is a major cardiovascular CYP isozyme or an established driver of cardiovascular pathology. Rather, CYP2D6 is examined here as a deliberately hypothesis-generating candidate whose unusually strong pharmacogenetic variability, clinically important cardiovascular drug substrates, dynamic susceptibility to phenoconversion, extrahepatic expression, and mechanistically plausible links to endogenous substrate metabolism and CYP-associated ROS generation provide a convergent rationale for focused investigation. The mechanistic framework proposed in this review has not yet been experimentally and prospectively validated and should not be applied directly to clinical decision-making without supporting clinical data. Full article

Background: Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) primarily participates in protein synthesis by binding aminoacyl-tRNA complexes to facilitate peptide chain elongation on ribosomes. Its expression and functional roles exhibit significant heterogeneity across various malignancies, exerting dual regulatory effects as both an oncogene and a tumor suppressor. This study aims to investigate the potential prognostic value and tumor-suppressive role of EEF1A1 in kidney renal clear cell carcinoma (KIRC). Methods: We analyzed the differential expression of EEF1A1 in KIRC and its correlation with patient prognosis based on the TCGA, GEO, and HPA databases. The STRING and GEPIA databases were utilized to perform functional enrichment analysis of its interacting proteins and co-expressed genes. The xCell algorithm was employed to assess the correlation between EEF1A1 and immune cell infiltration, immune checkpoints, and immunomodulatory molecules. Furthermore, drug sensitivity analysis was conducted to evaluate its clinical application potential. Finally, the expression of EEF1A1 in 786-0 and A498 cell lines was validated via qRT-PCR and Western blotting. Furthermore, CCK-8, wound healing, and Transwell migration/invasion assays were performed to evaluate cell proliferation, migration, and invasion, respectively. Results: EEF1A1 may function as a negative regulator of malignant behaviors in KIRC tissues and cell lines, and its expression level was closely associated with clinicopathological features and prognosis of patients. GO, KEGG, and GSEA enrichment analyses revealed that low EEF1A1 expression is closely linked to immunosuppressive pathways. Further immunological analysis confirmed significant correlations between EEF1A1 and various immune cell infiltrates, immune checkpoints, tumor-infiltrating lymphocytes, and immunomodulatory molecules. Moreover, cells with high EEF1A1 expression exhibited increased sensitivity to anti-tumor drugs, with expression levels negatively correlated with inhibitory activity (IC50). Finally, overexpression of EEF1A1 significantly inhibited the proliferation, migration, and invasion of clear cell renal cell carcinoma cells. Conclusions: EEF1A1 serves as a potential prognostic biomarker in KIRC and is associated with clinical progression, immune-related characteristics, metabolic pathways, and drug sensitivity. Functional validation further supports its role in regulating malignant phenotypes of KIRC cells. Full article

Tannic acid grafting provides a practical strategy for introducing bioactive phenolic functionality into microbial polysaccharides for multifunctional hydrogel design. Herein, tannic acid-modified succinoglycan (SG-TA) was prepared through an ascorbic acid/ H₂O₂-mediated free-radical process. Spectroscopic, thermal, and purification-control analyses were consistent with covalent incorporation of tannic acid-derived moieties into SG, while characteristic structural features of the SG framework remained evident after modification. SG-TA exhibited tannic acid-equivalent phenolic contents of up to 321.9 mg TAE/g and markedly enhanced antioxidant and antibacterial activities compared with native SG. SG-TA was subsequently incorporated into a poly(vinyl alcohol) (PVA)/borax network to form dynamic SG-TA/PVA/borax (STPB) hydrogels based on reversible interactions. The hydrogels exhibited composition-dependent viscoelasticity, rapid rheological recovery, macroscopic self-rejoining, enhanced deformability, antioxidant and antibacterial functionality, and preliminary cytocompatibility. Time-dependent phenolic release showed that SG-TA-derived phenolic species were partially released from the network, indicating contributions from both matrix-associated and releasable functionality. The reversible network also enabled pH- and glucose-responsive release of 5-fluorouracil as a model small-molecule drug. These findings demonstrate the potential of SG-TA as an intrinsically bioactive microbial polysaccharide for multifunctional, self-healing, and stimuli-responsive drug-delivery hydrogels. Full article

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), exposed critical gaps in global preparedness for rapidly evolving viral pandemics. Though current antiviral treatments have shown some efficacy in managing COVID-19, substantial limitations, such as inefficient targeted drug delivery, aberrant host immune responses, and inadequate preparedness for future viral pandemics, were also evident. These challenges underscore the urgent need for target-specific, precise and efficient therapeutic strategies to modulate viral entry and immune dysregulation. Extracellular vesicles (EVs), cell-released cargo-carrying nanoscale vesicles, can both facilitate and inhibit viral infection depending on their cargo composition. Thus, endogenous EVs can promote or inhibit COVID-19 pathogenesis by modulating critical pathways, including angiotensin-converting enzyme 2 (ACE2)-mediated viral entry, transmembrane protease serine 2 (TMPRSS2)- dependent spike protein activation, nuclear factor kappa B (NF-κB)-driven inflammatory signaling, and NLRP3 inflammasome activation. In contrast, engineered EVs, such as ACE2-expressing EVs, mesenchymal stem cell-derived EVs and microRNA-enriched EVs, have therapeutic potential as they can facilitate antiviral defense through immune modulation, viral neutralization and suppression of cytokine storm. Moreover, EV-associated nucleic acids, proteins and lipids can act as biomarkers for disease detection and severity stratification. A deeper understanding of EV-virus mechanistic insights can enhance preparedness for similar viral diseases. In this review, we provide a comprehensive analysis of the molecular mechanisms underlying EV-virus interactions highlighting the therapeutic and diagnostic potential of EVs in tackling COVID-19 and future viral pandemics. Full article

Background/Objectives: Despite the clinical efficacy of cannabidiol (CBD) in treating certain epilepsies, its in vivo neuropharmacological mechanisms remain incompletely understood. This Phase 1 clinical trial aimed to evaluate the acute effects of a single oral dose of highly purified CBD (GWP42003-P) on cortical excitability. Transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) and electromyography (TMS-EMG) were utilized as assessment tools. Methods: In a randomized, double-blind, placebo-controlled crossover trial, 15 healthy male participants received a single 1500 mg dose of GWP42003-P or placebo. Cortical activity metrics, including resting and active motor thresholds (RMT, AMT), short intracortical inhibition (SICI), TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP), and inter-trial phase clustering (ITPC), were recorded pre-dose and at 1, 4, and 6 h post-dose. Results: RMT and AMT significantly decreased over time following CBD administration, though without a significant Condition × Time interaction. While primary analyses showed no condition-driven alterations for SICI, TEPs, or TRSP, secondary longitudinal modeling revealed a transient reduction in beta-band desynchronization 1 h post-dose, aligning with peak plasma concentration. The drug condition also exhibited a qualitative, non-significant trend toward increased alpha ITPC and decreased delta ITPC at 4 and 6 h post-dose compared to placebo. Conclusions: A single acute 1500 mg dose of GWP42003-P did not produce statistically significant alterations in widespread cortical excitability in healthy adult males. However, the transient blunting of beta desynchronization at peak concentration may reflect CBD’s distinct, non-classical neuromodulatory profile. Overall, these largely null findings suggest that acute CBD administration lacks a robust, direct modulatory effect on cortical networks. Capturing its precise neuropharmacological mechanisms will likely require future investigations utilizing chronic dosing paradigms or clinical patient populations. Full article

Background/Objectives: Programmed cell death protein 1 (PD-1) is a key immune checkpoint that suppresses anti-tumor T-cell responses and is an established target for cancer immunotherapy. UDIZ-007 is a fully human anti-PD-1 antibody that blocks PD-1/PD-L1 and PD-1/PD-L2 interactions and eradicates MC38-hPD-L1 colon tumors in B-hPD-1 transgenic mice. This study further characterized the pharmacokinetics (PK), immunogenicity, and safety of UDIZ-007 to support its clinical development. Methods: UDIZ-007 was produced in a stable Chinese hamster ovary (CHO) cell line, and its biophysical and in vitro functional profiles were assessed. PK, immunogenicity, and safety were evaluated in mice and cynomolgus macaques. Results: UDIZ-007 showed biophysical and in vitro functional properties consistent with therapeutic antibodies and demonstrated potent, dose-dependent anti-tumor activity against MC38-hPD-L1 colon tumors engrafted in B-hPD-1 transgenic mice. Single-dose PK studies in mice at 10 and 100 mg/kg and in cynomolgus macaques at 10, 50, and 101.2 mg/kg showed a trend toward dose-proportional exposure. In cynomolgus macaques, UDIZ-007 had a prolonged half-life of approximately 12 days. Repeated intravenous administration at 10, 50, or 101.2 mg/kg in cynomolgus macaques was generally well tolerated, with no major treatment-related toxicities. Accordingly, the no-observed-adverse-effect level (NOAEL) was established at the highest tested dose, 101.2 mg/kg. Anti-drug antibodies (ADAs) were detected in some animals and were associated with expected PK variability but not with adverse effects. Tissue cross-reactivity studies across 32 human and cynomolgus macaque tissues showed binding primarily restricted to lymphoid tissues known to express PD-1. Conclusions: UDIZ-007 demonstrated robust anti-tumor activity, favorable PK and safety profiles, as well as selective binding to PD-1-expressing tissues, supporting its clinical development as a potential cancer immunotherapy. Full article

This review systematically elucidates the rapidly evolving field of biomimetic coacervate coatings, bridging the fundamental thermodynamic principles of liquid–liquid phase separation (LLPS) with advanced biomedical translations. While conventional surface modifications for medical implants frequently fail to maintain structural and functional integrity within dynamic, wet physiological environments, biomimetic coacervation inspired by natural underwater adhesive mechanisms offers a highly versatile, conformable, and robust interfacial strategy. Here, we analyze the critical physicochemical driving forces governing coacervate formation, emphasizing the synergistic interplay of electrostatic, hydrophobic, hydrogen-bonding, and cation–$\pi$ interactions. We comprehensively discuss diverse macromolecular design principles utilizing marine-derived biopolymers, synthetic or recombinant polypeptides, and hybrid organic–inorganic condensates, alongside key architectural orchestration methodologies including direct deposition, in situ triggerable coacervation, and layer-by-layer (LbL) assembly. Furthermore, we evaluate multi-functional clinical translations, highlighting breakthroughs in wet tissue sealing, bone repair, localized stimuli-responsive drug or nucleic acid delivery, anti-biofouling medical device coatings, and regenerative cell–material interfaces. Ultimately, this review underscores the profound potential of biomimetic coacervates as a cornerstone platform for next-generation multifunctional medical devices and personalized regenerative medicine. Full article

Cervical cancer remains a major cause of cancer-related mortality worldwide, highlighting the need for strategies that may improve responses to conventional chemotherapeutics. Epigallocatechin gallate (EGCG), a green-tea polyphenol with diverse biological activities, has been investigated as a potential chemosensitizing agent. This study evaluated the interaction between EGCG and doxorubicin (DOX) in HeLa cervical cancer cells, with HaCaT keratinocytes included as a non-malignant comparator. Cell viability and drug interactions were assessed using the CCK-8 assay and Chou–Talalay combination index (CI) analysis. Complementary assays evaluated membrane integrity, wound closure, apoptosis, cell-cycle distribution, intracellular DCF-associated fluorescence with or without N-acetylcysteine (NAC) pretreatment, caspase-3 immunoreactivity, and EGFR, FOXP3, CASP3, and CASP7 mRNA expression. Network-based analyses were additionally used to identify candidate molecular associations and pathways. CI analysis demonstrated synergistic EGCG–DOX interactions in HeLa cells under the tested conditions, whereas additive or antagonistic interactions predominated in HaCaT cells. Combined treatment produced the greatest reduction in viable cells, increased apoptosis, altered cell-cycle distribution, and reduced wound closure. It also produced the highest viability-normalized DCF-associated fluorescence, which was attenuated by NAC pretreatment, indicating an antioxidant-sensitive change in intracellular oxidative status without establishing a causal role in cytotoxicity. Combined treatment was further associated with increased total caspase-3 immunoreactivity and altered EGFR, FOXP3, CASP3, and CASP7 transcript levels. Overall, EGCG and DOX exhibited synergistic interactions and multiple treatment-associated cellular and transcriptional responses in HeLa cells under the present in vitro conditions. These findings do not establish cancer-specific selectivity or a definitive molecular mechanism but provide a basis for validation in additional cervical cancer models and at clinically relevant exposures. Full article

Ovarian cancer remains a major cause of gynecological cancer-related mortality, highlighting the need for novel therapeutic strategies capable of enhancing antitumor activity while targeting multiple mechanisms involved in tumor progression. Everolimus, an inhibitor of the mammalian target of rapamycin pathway, and carboplatin are established antineoplastic agents with distinct mechanisms of action, whereas astaxanthin is a bioactive carotenoid with antioxidant, anti-inflammatory, and potential anticancer properties. This study compared the individual and pairwise combination effects of carboplatin, everolimus, and astaxanthin on cell viability, migratory capacity, and inflammatory and tumor-associated biomarkers in SKOV3 ovarian cancer cells. Human SKOV3 ovarian cancer cells were cultured under standard conditions and exposed to different concentrations of carboplatin, everolimus, and astaxanthin, either individually or as pairwise two-drug combinations, for 24–72 h. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Cell migration was evaluated using a scratch wound-healing assay. Based on the experimental treatment protocol, 100 nM everolimus, 100 μM carboplatin, and 100 μM astaxanthin, alone and in combination, were further evaluated for their effects on β-defensin 1, β-defensin 2, α-defensin 1, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels. Biomarker concentrations were determined by ELISA. Experiments were independently performed in triplicate. Everolimus, carboplatin, and astaxanthin produced concentration- and time-dependent alterations in SKOV3 cell viability, with more pronounced cytotoxic effects generally observed following prolonged exposure. The pairwise combination treatments also substantially affected cell viability, particularly at later experimental time points. Assessment of migratory capacity demonstrated significant differences in wound closure among treatment groups at 24, 48, and 72 h (p = 0.0224, p = 0.0155, and p = 0.0028, respectively), indicating a time-dependent inhibitory effect on SKOV3 cell migration. Treatment with carboplatin, everolimus, and astaxanthin, individually or in pairwise combinations, also significantly modulated β-defensin 1, β-defensin 2, α-defensin 1, TNF-α, and IL-1β levels compared with control cells, with the magnitude and direction of these changes varying according to treatment regimen and exposure duration. Everolimus, carboplatin, and astaxanthin exerted significant time- and treatment-dependent effects on the viability and migratory behavior of SKOV3 ovarian cancer cells and markedly modulated defensin and pro-inflammatory cytokine responses. The findings demonstrate distinct treatment- and time-dependent responses to the individual agents and their pairwise combinations in SKOV3 ovarian cancer cells. These observations represent preliminary comparative in vitro effects rather than evidence of pharmacological synergy or therapeutic benefit. Further mechanistic studies using additional ovarian cancer cell lines, formal drug interaction analyses, and in vivo models are required to establish the biological and potential therapeutic relevance of these treatment combinations. Full article

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by chronic inflammation, insulin resistance, and reproductive dysfunction. Although empagliflozin, a sodium-glucose cotransporter-2 inhibitor, has demonstrated anti-inflammatory and metabolic benefits, its molecular mechanisms in PCOS remain poorly understood. This study investigated the anti-inflammatory mechanisms of empagliflozin in PCOS using network pharmacology, molecular docking, and molecular dynamics simulations. Potential drug targets were identified using SwissTargetPrediction and SuperPred, while PCOS- and inflammation-related genes were obtained from GeneCards. Overlapping targets were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein–protein interaction network, and hub gene analyses. Molecular docking and 50 ns molecular dynamics simulations were performed to evaluate binding affinity and complex stability. Key inflammatory targets identified included TNF, IL6, IL1B, TLR4, STAT3, and PTGS2, with significant enrichment in cytokine-mediated signaling, TNF signaling, and NF-κB pathways. Empagliflozin showed strong binding affinities for PTGS2 (−9.0 kcal/mol) and TLR4 (−8.8 kcal/mol), while molecular dynamics simulations demonstrated stable protein–ligand complexes throughout the simulation. These findings suggest that empagliflozin may alleviate PCOS-associated inflammation by modulating the TLR4/NF-κB/PTGS2 signaling axis, supporting its potential as a repurposed therapeutic agent for PCOS and providing a foundation for future experimental validation. Full article

Standard pharmacotherapy for mental disorders, including depression and anxiety, is supported by extensive clinical validation and international treatment guidelines. However, it is frequently associated with limitations such as adverse side effects, low patient adherence, and the risk of relapse. Conventional approaches rely primarily on antidepressants, anxiolytics, mood stabilizers, neuroleptics, and stimulants, which modulate monoaminergic, GABAergic, and dopaminergic neurotransmission. Recently, preclinical and emerging clinical studies have suggested that selected natural substances—specifically mushroom-derived compounds and well-established medicinal plants—may offer complementary therapeutic pathways. This narrative review critically evaluates the pharmacological efficacy, mechanisms of action, and safety profiles of selected natural compounds, including psilocybin-related tryptamines, Hericium erinaceus, ibotenic acid/muscimol from Amanita muscaria, ergothioneine, as well as notable botanical agents (e.g., Hypericum perforatum, Valeriana officinalis). We systematically distinguish between robust human clinical data (e.g., psilocybin-assisted therapy) and preliminary in vitro/in vivo findings. Particular attention is paid to their neurotrophic, anti-inflammatory, and neuromodulatory properties, while emphasizing substantial safety concerns, including intoxication risks associated with isoxazole derivatives, and potentially severe cytochrome P450-mediated drug–drug interactions. Ultimately, while certain natural compounds show promise as adjunctive interventions, most remain strictly investigational and cannot replace evidence-based conventional pharmacotherapy without further long-term, large-scale randomized controlled trials. Full article

The growing accumulation of microplastics in marine ecosystems, coupled with the presence of emerging contaminants such as pharmaceuticals, represents an environmental problem that has received little attention to date. The present study evaluates the potential of microplastics to act as transport vectors for pharmaceuticals through their adsorption onto two plastic polymers widely used today: polyethylene terephthalate (PET) and medium-density polyethylene (MDPE) in seawater. As a control, the same experiments were conducted in ultrapure water (Milli-Q). Both plastics were exposed to a mixture of 29 pharmaceuticals belonging to different therapeutic classes over a 28-day period, with sampling conducted at various time intervals. The identification, quantification, and characterization of the compounds were performed using ultra-high-performance liquid chromatography coupled with mass spectrometry detection. Statistical analysis was performed using R-Studio software. Outcomes reveal that the type of polymer significantly influences adsorption, with MDPE being more efficient than PET. In contrast, the type of water and the therapeutic class of the drugs were not identified as determining factors. Furthermore, a positive, albeit moderate, correlation was observed between the hydrophobicity of the pharmaceutical and its adsorption efficiency on MDPE. These findings suggest that hydrophobic interactions play a key role in the adsorption of drugs onto microplastics, providing a solid foundation for future research, such as predictive models or mitigation strategies in aquatic ecosystems. Full article

Background: In this study, two cocrystals of diclofenac acid (DCA) with the coformers theophylline (THEO) and isonicotinamide (ISNT) were prepared. Subsequently, nanococrystals were generated from these cocrystals using a top-down wet media milling approach. Methods: Critical process parameters such as milling time, milling volume, drug loading percentage, bead volume, and dispersion media were optimized to achieve the desired particle size distribution. The nanococrystals were characterized using dynamic light scattering (DLS), polarized light microscopy (PLM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Results: In vitro dissolution studies revealed that nanococrystals of DCA-ISNT (DE_0–120 = 22.5% at pH 1.2 and DE_0–120 = 58.7% at pH 4.5) and DCA-THEO (DE_0–120 = 18.5% at pH 1.2 and DE_0–120 = 48.2% at pH 4.5) exhibited superior dissolution performance compared to DCA nanocrystals (DE_0–120 = 12.5% at pH 1.2 and DE_0–120 = 39.0% at pH 4.5), with the dissolution advantage decreasing as the pH of the medium increased. The improved dissolution behaviour was a complex interplay of factors including particle size distribution, surface wetting kinetics, exposure of hydrophilic/hydrophobic functional groups during dissolution, nanococrystal microenvironmental pH, DCA’s ionization behaviour, lattice energy, and intermolecular interaction strengths. Additionally, nanococrystals exhibited a significantly higher flux rate in simultaneous gastric transfer dissolution and flux studies compared with DCA, likely due to higher apparent solubility and superior diffusion through the unstirred water layer (UWL). Pharmacokinetic studies confirmed that nanococrystals DCA-ISNT NCC (AUC_0–∞ = 3062.65 ± 526.91 ng/mL·h) outperformed DCA nanocrystals (AUC_0–∞ = 2352.53 ± 537.78 ng/mL·h), DCA-THEO NCC (AUC_0–∞ = 2222.96 ± 151.19 ng/mL·h) and the cocrystals in terms of pharmacokinetic performance. Conclusions: The findings indicate that DCA-ISNT NCC exhibited superior pharmacokinetic performance and, together with the enhanced dissolution and flux properties of the nanococrystals, demonstrates their potential for enhanced therapeutic efficacy. Full article

Antimicrobial resistance is a growing global health challenge, highlighting the need for new bioactive compounds from medicinal plants. Vepris nobilis is traditionally used in East Africa for treating infections and respiratory disorders; however, its essential oil (EO) composition and antimicrobial mechanisms remain poorly characterized. This study investigated the chemical composition and antimicrobial activity of V. nobilis EO, along with an in silico evaluation of its major constituent, germacrene D. The EO was extracted by hydrodistillation and analyzed using gas chromatography-mass spectrometry (GC–MS). Its antimicrobial activity was evaluated against 26 bacterial and 4 fungal strains using disc diffusion, broth microdilution, and MBC/MFC (Minimum Bactericidal Concentration/Minimum Fungicidal Concentration) assays. Germacrene D showed stronger activity than the EO, particularly against both multidrug resistant (MDR) and non-MDR Gram-negative bacterial strains (MIC = 10 µg/mL), with bactericidal and fungicidal effect. Molecular docking of germacrene D against two clinically relevant enzymes—dehydrosqualene synthase (CrtM) from Staphylococcus aureus and SWISS-modeled sterol 14-α-demethylase (CYP51) from Penicillium funiculosum—suggested potential interactions with both targets, with a favorable predicted binding affinity for CrtM (−7.654 kcal/mol) and for CYP51 (−5.898 kcal/mol). These findings provide preliminary insights into a possible antimicrobial mechanism, although experimental validation is needed to confirm this hypothesis. ADMET analysis suggested favorable drug-like properties despite limited solubility. These findings provide scientific support for the traditional use of V. nobilis leaves in the treatment of respiratory infections and highlight germacrene D as a promising lead compound for further antimicrobial development. Full article

Chronic kidney disease (CKD) affects more than 10% of the global population and represents one of the leading causes of mortality. This study aimed to assess the pharmacotherapy of hospitalized patients aged ≥ 65 years with CKD, focusing on the prevalence of polypharmacy, potentially inappropriate medications (PIMs), potentially clinically significant drug–drug interactions (DDIs), the use of renal-risk drugs (RRDs). A prospective observational study was conducted at the Department of Nephrology and Dialysis of University Hospital Dubrava, including 100 participants. A clinical pharmacist obtained the Best Possible Medication History (BPMH) within 24 h of hospital admission. A total of 1324 comorbidities were recorded (median 12 per patient), along with 985 prescribed medications. Polypharmacy (5–9 drugs) was observed in 43% of patients, while excessive polypharmacy (≥10 drugs) was present in 48%. A total of 258 PIMs were identified, with 89% of patients having at least one PIM (mean 2.6 per patient). Nearly 94% of patients had significantly impaired renal function (G3–G5), and 82% were exposed to inappropriately prescribed RRDs. Contraindicated medications based on renal function were identified in 62% of patients, while 52% had at least one medication prescribed at an unadjusted dose. A total of 1097 potentially clinically significant DDIs were identified, with a mean of 10.9 interactions per patient. The results indicate a high prevalence of polypharmacy, PIMs, potentially clinically significant DDIs and inappropriately prescribed RRDs among older hospitalized patients with CKD, increasing the risk of adverse events and unfavorable treatment outcomes. The findings highlight the importance of the 24 h period following hospital admission as an early opportunity for identifying medication-related problems and optimizing pharmacotherapy in highly vulnerable patients, such as elderly patients with CKD. The study also emphasizes the importance of early involvement of a clinical pharmacist in the pharmacotherapy review and obtaining the BPMH. Full article