Acta Pharmaceutica最新文献

Sedation is crucial for managing mechanically ventilated intensive care unit (ICU) patients, but agents differ in their effects. Propofol, benzodiazepines and α₂-agonists are commonly used, yet their comparative impact remains unclear. This review searched OVID MEDLINE and Embase from January 2006 to June 2025 for randomised controlled trials in adult ICU patients. The primary outcome was duration of mechanical ventilation; secondary outcomes were ICU length of stay, delirium and mortality. Twenty-six trials (N = 4,993) were included. Dexmedetomidine significantly shortened mechanical ventilation (mean difference [MD] -0.60 days; 95 % CI -0.89 to -0.31), with larger effects versus midazolam (MD -1.25 days) and mixed comparators (MD -1.23 days), but not versus propofol (MD -0.34 days). ICU stay was also reduced (MD -0.94 days; 95 % CI -1.49 to -0.39). Delirium risk decreased (odds ratio [OR] 0.58; 95 % CI 0.38-0.87). No mortality difference was found. Dexmedetomidine is therefore associated with a modest but clinically meaningful reduction in ventilation time, ICU stay and delirium, particularly when compared with benzodiaze-pines, though benefits over propofol are less certain.

Umbilical cord mesenchymal stem cells (UC-MSCs) have shown therapeutic potential in renal diseases due to their homing ability. This study compared the effects of three administration routes (intravenous, local renal injection, and interventional injection) on UC-MSC distribution in kidney tissue. Eighteen New Zealand rabbits were assigned to the three groups (n = 6 each), and DiI-labelled UC-MSCs were tracked using confocal microscopy to evaluate their distribution in the kidney, lung, and brain. Local renal injection led to high MSC concentrations at the injection site, but distribution to the contralateral kidney was minimal and comparable to that of intravenous injection. Intravenous delivery via the marginal ear vein was simple and convenient but resulted in limited renal homing (< 1 %) and no significant difference between kidneys. Interventional injection achieved the highest delivery efficiency (12.4 %) and a more uniform renal distribution. Notably, inflammatory cytokine levels (IL-6, TNF-α, IL-10) were significantly elevated in the local injection group (p < 0.05). These results indicated that the choice of administration route critically affects MSC targeting and therapeutic potential, and interventional injection may offer the most effective strategy for precise UC-MSC delivery in renal therapy.

This study assessed the gastrointestinal (GI) safety profiles of tigecycline, omadacycline, and eravacycline through a retrospective disproportionality analysis of reports submitted to the FDA Adverse Event Reporting System (FAERS) between the second quarter of 2005 and the first quarter of 2024. Among 3,261 adverse event reports associated with these agents, 809 (24.8 %) involved gastrointestinal disorders, with tigecycline accounting for the largest proportion (588 reports), followed by omadacycline (197) and eravacycline (24). Disproportionality analysis revealed that gastrointestinal disorders ranked among the top three system organ classes for all three drugs, with positive signals observed for tigecycline (ROR = 1.63), omadacycline (ROR = 3.04), and eravacycline (ROR = 1.79), the strongest association being with omadacycline. While most GI events were consistent with known safety information, several unexpected signals were identified, including gastrointestinal haemorrhage, melena, small-intestinal obstruction, tongue discolouration, and intestinal perforation for tigecycline, as well as lip swelling and tongue discolouration for omadacycline. The median onset times of GI events were 4, 0, and 2.5 days for tigecycline, omadacycline, and eravacycline, respectively, with nearly half of the events occurring within three days of treatment initiation. These findings reveal distinct GI safety patterns among newer tetracycline-derived antibiotics and underscore the importance of early and route-specific monitoring in clinical practice.

Cell division cycle 20 homologue (Cdc20), a key regulator of the anaphase-promoting complex/cyclosome (APC/C), is frequently overexpressed in human cancers and represents a promising therapeutic target. However, monotherapy targeting Cdc20 has shown limited efficacy, partly due to compensatory activation of cyclin-dependent kinase 1 (Cdk1). In this study, we investigated the combinatorial potential of the pan-Cdk inhibitor ZK304709 with the Cdc20 inhibitor apcin in HeLa cervical cancer cells. Transcriptomic analysis revealed that both CDC20 and CDK1 are upregulated in cervical cancer tissues. Mechanistically, apcin treatment induced cyclin B1 accumulation and enhanced Cdk1 phosphorylation at Thr161, suggesting feedback activation. In contrast, ZK304709 reduced p-Cdk1(T161) levels and suppressed Cdc20 expression at both protein and mRNA levels. Functionally, the combination of apcin and ZK304709 synergistically inhibited cell proliferation and induced G2/M phase arrest in HeLa cells. These findings demonstrate that dual inhibition of Cdk1 and Cdc20 disrupts compensatory signalling pathways and enhances antitumour efficacy in HeLa cells, providing a rational strategy for combination therapy in cervical cancer.

The polymeric immunoglobulin receptor (pIgR) mediates trans cytosis of IgA, a pivotal anti-inflammatory player of the mucosal immune system. Transcytosis mediated by pIgR entails protein effectors of vesicle-mediated transport involved in signal pathway activation that lead to the sorting of pIgR-IgA complexes from the basolateral to apical membrane. Each step of pIgR transport encompasses multiple targets for regulation, but the role of cholinergic system components, i.e. acetylcholine (ACh), the ligand of nicotinic (nAChR) and muscarinic (mAChR) receptors, is unclear. This study evaluated the effect of the cholinergic system on pIgR at transcriptional and protein levels. Accordingly, lipopolysaccharide (LPS)-primed Caco-2 cells were treated with nicotine (nAChR agonist) and/or mecamylamine (nAChR antagonist) or with muscarine (mAChR agonist) and/ or atropine (mAChR antagonist), and then pIgR was analysed in situ by immunofluorescence and by RT-qPCR. In general terms, cholinergic antagonists counteracted the upmodu latory outcome of both cholinergic agonists on both pIgR cellular location and mRNA levels. These findings suggest that the cholinergic system plays a key role in the regulation of epithelial immunity by modulating pIgR expression. The study provides insights into the interaction between the cholinergic system and intestinal immune mechanisms for future research in mucosal immunity and possible therapeutic strategies.

Scutellarin has a good myocardial protective effect. However, the underlying mechanism of scutellarin on cardiomyocyte pyroptosis remains unclear. In this study, we elucidated the mechanism of scutellarin to protect the injured myocardium. The molecular docking technique was used to predict the targets of scutellarin in protecting against myocardial injury. H9c2 cell pyroptosis was induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Then, the activities of CK and LDH were measured through a colourimetric assay. The level of cTnI was quantified by ELISA. mRNA expressions of NLRP3, cysteine-dependent aspartate-specific protease-1 (caspase-1), gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were analyzed using RT-qPCR. Protein expressions of NLRP3, caspase-1, and GSDMD were detected by the immunofluorescence technique. Protein expression of NLRP3 was analysed by using Western blotting. Scutellarin had a good binding affinity with NLRP3, caspase-1, and GSDMD. Compared with LSP and ATP-treated cells, concentrations of 25, 50, and 100 µmol L-1 scutellarin reduced CK and LDH activities and the level of cTnI, decreased the mRNA expression of NLRP3, caspase-1, and GSDMD. In the mechanism study, scutellarin decreased mRNA expressions of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18, and reduced the fluorescence expressions of NLRP3, caspase-1, and GSDMD. Scutellarin reduced the protein expression of NLRP3. Scutellarin inhibits myocardial cell pyroptosis induced by LPS and ATP, and the mechanism is related to the NLRP3/caspase-1/GSDMD signalling pathway.

Selumetinib (SEL) is a recently approved medication for paediatric patients who have neurofibromatosis type 1. It is the first approved therapy for this rare, debilitating, and disfiguring disease. Development of proper analytical platforms for SEL analysis in its marketed pharmaceutical formulation (Koselugo^® capsules) and blood plasma is highly warranted. Availability of such analytical tools would ensure SEL capsules' quality and effective therapy. This study introduces, for the first time, the development of two label-free and sensitive platforms for SEL quantification in capsules and human plasma. These platforms are microwave-assisted with an ultraviolet absorbance microplate reader (MW-UV) and reverse-phase high-performance liquid chromatography with a photodiode-array detector (HPLC-PDA). Both platforms employed the SEL native UV absorption as an analytical signal. The MW-UV measured the UV absorption in 96-well transparent plates at 255 nm. The HPLC-PDA involved chromatographic separation of SEL and tozasertib (TOZ), internal standard, on a C18 column both were detected at 255 nm. The optimum procedures of both platforms were established and validated following the ICH guidelines. The linearity ranges were 15-500 µg mL^-1 and 0.8-100 µg mL-1, with limits of quantification of 15.3 and 3.5 µg mL^-1, for MW-UV and HPLC-PDA, resp. Both platforms displayed high precision with relative standard deviation values ≤ 1.8 %, and high accuracy with recovery ranging from 98.3 to 102.3 %. The platforms were successfully applied to quantify SEL in bulk form, Koselugo^® capsules, and were preliminarily applied to human plasma analysis. Eco-friendliness assessment confirmed the adherence of both platforms to green analytical approaches. MW-UV and HPLC-PDA are simple and fast, enabling high-throughput analysis, thus introducing valuable tools for routine use in quality control and clinical laboratories for SEL quantification.

This study investigates the development and characterisation of niosome-based delivery systems for olanzapine, an antipsychotic drug. Niosomes were prepared using various grades of Span surfactants (Span 60, Span 40, and Span 20) in combination with cholesterol at different ratios. The formulations were characterised in terms of particle size, polydispersity index, zeta potential, and encapsulation efficiency. Results showed an inverse relationship between surfactant hydrophilic-lipophilic balance (HLB) values and niosome size, with Span 60 producing the smallest vesicles. Optimal formulations were achieved with a 1:1 ratio of surfactant to cholesterol. Span 60 niosomes exhibited the highest encapsulation efficiency (up to 81 ± 2.5 %) and the most negative zeta potential, indicating superior stability. In vitro release studies demonstrated sustained release profiles for all niosomal formulations compared to the free drug, with Span 60 formulations showing the slowest release rates. Release kinetics analysis revealed a Fickian diffusion-controlled mechanism best described by the Korsmeyer-Peppas model. These findings suggest that niosomal formulations, particularly those based on Span 60, offer a promising approach for improving olanzapine delivery, potentially enhancing its bioavailability and therapeutic efficacy in the treatment of psychiatric disorders.

This study aimed to investigate the anticancer effects and underlying mechanisms of an ethanolic extract of Lavandula stoechas L. flowers (LsHE) on colorectal cancer. The extract demon strated high phenolic content (230.31 ± 11.28 mg GAE g^-¹ dm) and strong antioxidant activity. HPLC analysis identified rosmarinic acid and quercetin as major constituents. HT-29 colorectal carcinoma cells and HEK-293 healthy kidney epithelial cells were treated with LsHE for 48 h. The concentration of LsHE required to inhibit 50 % of HT-29 cell viability was found to be 86.37 ± 3.07 µg mL^-1, whereas a higher concentration of 131.30 ± 9.33 µg mL^-1 was observed for HEK-293 cells. In HT-29 cells, flow cytometry analysis revealed increased early (9.7 %) and late (6.8 %) apoptotic populations following LsHE treatment (p < 0.0001). qRT-PCR analysis showed significant upregulation of TP53 and CASP3 compared to the untreated group (p < 0.05 and p < 0.01, resp.), while BAX expression was unexpectedly downregulated. These findings suggest that LsHE may trigger caspase-3-dependent apoptosis through a p53-mediated mechanism, potentially independent of the BAX/BCL-2 pathway. In conclusion, the present in vitro study highlights the potential of LsHE as a natural agent that still exerts some cytotoxicity toward normal epithelial cells and pro-apoptotic activity in colorectal cancer cells. Our findings provide a molecular basis for further in vivo studies to evaluate the possible therapeutic potential and mechanistic relevance of LsHE in CRC chemoprevention.

The quality of chamomile (Matricaria recutita) is largely determined by its content of essential oils and flavonoids, the main pharmacologically active constituents. In this study, the phyto-chemical profiling of 22 commercially available chamomile flower tea samples was aided by chemometrics, comparing loose teas of whole heads with tea bags containing comminuted flowers. Principal component analysis (PCA) and agglomerative hierarchical clustering (AHC), which included both essential oil and flavonoid constituents, showed that chamomile teas can be well-differentiated and categorised into two groups that are closely related to the pharmaceutical form and largely explain the influence of processing. Multivariate analyses of the phytochemical data matrix showed clear differences between loose chamomile tea and tea bags, with the former having a more consistent composition and an overall higher quality. The essential oil content varied widely (0.75-5.34 mL kg^-1), with only five loose teas exceeding the minimum content specified in the European Pharmacopoeia (≥ 4 mL kg^-1), while most tea bag samples did not fulfil this requirement. GC-MS analyses of essential oils revealed sesquiterpenes as predominant constituents, assigning all samples to the bisabolol oxide-rich chemotype. The total flavonoid content determined by UV/Vis spectrophotometry ranged from 0.17 to 0.55 %, whereas RP-HPLC/DAD analysis revealed that the levels of apigenin-7-glucoside in tea bag samples often did not meet pharmacopoeial standards. Partial least squares-discriminant analysis (PLS-DA) yielded a robust and statistically significant model, showing for the first time that the quality differences between loose teas and tea bags can be explained by at least four key components. These results highlight the utility of chemometric tools in chamomile quality assessment and emphasise the need for improved standardisation that supports the preference for whole flower teas to ensure therapeutic efficacy.