Pharmacological Reports最新文献

{"title":"Selective non-nuclear estrogen receptor activation with PaPE-1 evokes neuroprotection involving mTOR/MEK in an in vitro model of hypoxic/ischemic injury.","authors":"Andrzej Łach, Bernadeta A Pietrzak-Wawrzyńska, Karolina Przepiórska-Drońska, Agnieszka Wnuk","doi":"10.1007/s43440-026-00866-2","DOIUrl":"10.1007/s43440-026-00866-2","url":null,"abstract":"<p><strong>Background: </strong>Hypoxic/ischemic brain injuries, including ischemic stroke and perinatal asphyxia, remain major causes of mortality and long-term neurological disability, establishing a demand for therapeutic strategies suitable against the multifactorial nature of underlying mechanisms. Estrogen receptors (ERs) signaling is known to exert neuroprotective effects, however, genomic ER activation is associated with serious adverse effects, including carcinogenesis and thromboembolisms. Pathway Preferential Estrogen-1 (PaPE-1), a compound that selectively activates the non-nuclear subset of ERs, may provide neuroprotection, thereby overcoming the deleterious effects. The aim of this study was to elucidate the molecular mechanisms underlying the neuroprotective effects of PaPE-1 in an in vitro model of hypoxic-ischemic neuronal injury, with particular emphasis on non-nuclear estrogen receptor signaling and its downstream pathways.</p><p><strong>Methods: </strong>Primary mouse cortical neuronal cells were subjected to 6 hours of experimental hypoxic/ischemic injury, followed by 18 hours of post-treatment with PaPE-1. Subsequently, a variety of biochemical assessments were conducted, including measurements of neuronal viability, cell death, and formation of autophagy-related vesicles. Moreover, the influence of PaPE-1 was assessed with molecular methods, encompassing measurements of gene and protein expression level and a set of epigenetic-related parameters, for instance, assessment of global DNA/RNA methylation and locus-specific methylation of genes and miRNA expression. To dissect signaling pathways, selective pharmacological inhibitors targeting mTOR/MEK1/2 and autophagy regulators were applied. ER subtype involvement was examined using ER-selective antagonists and specific siRNA silencing.</p><p><strong>Results: </strong>Non-nuclear ER activation with PaPE-1 attenuated maladaptive autophagy, RNA/DNA oxidative stress damage, and neuronal degeneration while contributing to the regulation of gene expression and epigenetic processes. Evocation of robust neuroprotection involved modulation of mTOR and MEK1/2 signaling, predominantly mediated by estrogen receptor 1 (ESR1).</p><p><strong>Conclusion: </strong>In conclusion, PaPE-1 exhibits a multitarget mode of action that provides broad-spectrum protection against hypoxic/ischemic neuronal injuries. Considering its complexity of action and confirmed strong, neuroprotective activity, this compound holds promise for broader evaluation across different brain cell types and in vivo models.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1145-1178"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPA receptor modulation in depression: from molecular mechanisms of plasticity to therapeutic translation.","authors":"Wojciech Ziemichód, Natalia Kajka, Klaudia Kister, Karolina Kasprzak, Kaja Karakuła, Dariusz Juchnowicz","doi":"10.1007/s43440-026-00871-5","DOIUrl":"10.1007/s43440-026-00871-5","url":null,"abstract":"<p><p>The glutamatergic system, particularly N-methyl-D-aspartate (NMDA) receptors, has long been a significant focus of research into new strategies for treating depression, and the clinical success of ketamine, an NMDA receptor antagonist, has been a significant breakthrough. In parallel, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, another key component of the glutamatergic system, have been studied for decades, and renewed interest stems from evidence linking their activation to the rapid antidepressant effects and synaptic plasticity observed after ketamine administration. Among pharmacological agents targeting AMPA receptors, the class of positive allosteric modulators, AMPAkines, has attracted particular interest. These compounds act by prolonging AMPA receptor channel open time, thereby enhancing excitatory neurotransmission and upregulating brain-derived neurotrophic factor (BDNF) expression. Preclinical studies consistently demonstrated antidepressant-like effects of low-impact AMPAkines, which offer a favorable safety profile in contrast to high-impact compounds that carry seizure risk. Although preliminary clinical trials support these findings, their limited scope highlights persistent translational challenges. These include a narrow therapeutic window, suboptimal pharmacokinetic properties, and the limited predictive validity of animal models. AMPAkines thus represent a potentially promising class of rapid-acting antidepressants, although significant translational hurdles remain. This narrative review aims to synthesize evidence on the role of AMPA receptors in neuroplasticity, the therapeutic potential of AMPA receptor modulators (AMPAkines) in influencing neuroplasticity, and their potential therapeutic applications in depression.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1045-1057"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148227302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kisspeptin-10 regulates glycosaminoglycan and decorin content in human cardiac fibroblast cultures.","authors":"Paulina Radwańska, Maciej Olkiewicz, Lucyna Piera, Jacek Drobnik","doi":"10.1007/s43440-026-00870-6","DOIUrl":"10.1007/s43440-026-00870-6","url":null,"abstract":"<p><strong>Background: </strong>Cardiac fibroblasts play a key role in extracellular matrix (ECM) remodelling through the synthesis of glycosaminoglycans and proteoglycans (PGs), such as decorin; however, the effects of kisspeptin-10 (KiSS-10) on these components in the heart remain unknown. The aim of this study was to determine the influence of KiSS-10 on glycosaminoglycan and decorin content in human cardiac fibroblast cultures and identify its mechanism.</p><p><strong>Methods: </strong>The effects of KiSS-10 on glycosaminoglycans and decorin were assessed in human cardiac fibroblast cell line, with or without signalling inhibitor. Glycosaminoglycan levels were determined by the Farndale method, decorin secretion by enzyme-linked immunosorbent assay (ELISA), and decorin expression by quantitative polymerase chain reaction (qPCR).</p><p><strong>Results: </strong>KiSS-10 treatment caused a dose-dependent increase in glycosaminoglycan content in both cells and medium. This stimulatory effect was abolished by blocking G-protein-coupled receptor 54 (GPR54) with peptide 234 or focal adhesion kinase (FAK) with FAK inhibitor 14 (FAKi). Combining KiSS-10 with phospholipase C inhibitor (D609) did not alter the glycosaminoglycan level compared to KiSS-10 alone. KiSS-10 increased decorin secretion but not expression. Combining peptide 234 with KiSS-10 did not alter media decorin level compared to KiSS-10 alone.</p><p><strong>Conclusions: </strong>KiSS-10 significantly elevated glycosaminoglycan and decorin accumulation in human cardiac fibroblast cultures. This regulatory effect on glycosaminoglycan level appears to be dependent on GPR54 activation and FAK signalling, but not on phospholipase C function. Hence, KiSS-10 may be involved in ECM remodelling in the heart.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1179-1191"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147974388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A discovery-based proteomic approach of epidermal growth factor and growth hormone-releasing peptide-6 in a model of acute ischemic stroke.","authors":"Arielis Rodríguez-Ulloa, Nelvys Subirós-Martínez, Luis Javier González, Daniela Risco-Acevedo, Gerardo E Guillén-Nieto, Vladimir Besada, Diana García-Del-Barco-Herrera","doi":"10.1007/s43440-026-00872-4","DOIUrl":"10.1007/s43440-026-00872-4","url":null,"abstract":"<p><strong>Background: </strong>Combined therapy with epidermal growth factor (EGF) and growth hormone-releasing peptide 6 (GHRP6) has demonstrated neuroprotective effects in models of global and focal brain ischemia. Clinical studies in ischemic stroke patients have confirmed the safety and preliminary efficacy of this combined treatment. This study aimed to elucidate the molecular mechanisms underlying the effects of EGF+GHRP6 co-administration.</p><p><strong>Methods: </strong>Male Wistar rats were subjected to endothelin-1 (ET-1)-induced middle cerebral artery (MCA) occlusion and randomly assigned to three experimental groups: EGF+GHRP6‑treated ischemic, vehicle‑treated ischemic, and sham-operated controls (n = 12 per group). Label-free quantitative proteomic analysis of the ischemic penumbra was performed at 3 and 24 h post-treatment. Functional enrichment and pathway analysis of differentially modulated proteins were performed using bioinformatics tools.</p><p><strong>Results: </strong>Proteomic profiling validated the ischemic model and revealed 40 and 223 proteins differentially modulated by EGF+GHRP6 at 3 and 24 h, respectively. Proteins involved in neurotransmitter transport were consistently overrepresented in the EGF+GHRP6-regulated proteome at both time points. At 24 h post-treatment, proteins associated with reactive oxygen species (ROS) detoxification, heat shock factor 1 (HSF1) activation, and negative regulation of cellular hypoxia response were significantly modulated. Additionally, anti-apoptotic and mitochondrial proteins were modulated in the ischemic penumbra, supporting the neuroprotective effects of EGF+GHRP6. Notably, proteins known to attenuate brain damage after stroke were up-regulated, while those promoting ischemic injury were down-regulated following the combined treatment.</p><p><strong>Conclusions: </strong>These findings provide molecular evidence supporting the neuroprotective mechanism of action of EGF+GHRP6 co-administration and reinforce its potential as a therapeutic strategy for ischemic stroke.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1087-1101"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocholesterolemic agents and the gut microbiota: a review of interactions and modulatory activity.","authors":"Manuel Mântua E Garcia, Virginie Xavier, Ricardo C Calhelha, Sandrina A Heleno","doi":"10.1007/s43440-026-00874-2","DOIUrl":"10.1007/s43440-026-00874-2","url":null,"abstract":"<p><p>Hypercholesterolemia is a major risk factor that contributes to the development and/or aggravation of cardiovascular diseases. High cholesterol levels are frequently managed with hypocholesterolemic agents, either synthetic or natural. Beyond their cholesterol-lowering effects, these compounds can also affect the host's gut microbiota. This review examined the extent and quality of the modulatory activity of selected hypocholesterolemic agents (n = 11) on the gut microbiota profile, based on a comprehensive literature search and analysis of interactions between the gut microbiota and distinct cholesterol-lowering compounds. With a few exceptions, anti-cholesterol interventions were associated with changes in gut microbiota β-diversity and a decrease in the Bacillota/Bacteroidota ratio. Further analyses at family and genus levels revealed patterns of modulation that clustered by molecular target and bioavailability. Overall, gut microbiota shifts favoured short-chain fatty acid (SCFA)-producing bacteria over inflammation-promoting taxa. Furthermore, for some anti-cholesterol compounds, microbial metabolism and the concomitant release of bioactive metabolites suggested partially microbiota-dependent cholesterol-lowering effects. These findings may inform new strategies for cholesterol management from a gut-health perspective; however, further research is needed to establish causality and draw robust conclusions regarding medication-microbiota relationships.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"981-1004"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The onset of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) with the use of decongestant agents: a European pharmacovigilance analysis.","authors":"Antonietta Anatriello, Andrea Cantone, Ciro Pentella, Maria Giovanna Vastarella, Annamaria Mascolo, Annalisa Capuano, Concetta Rafaniello","doi":"10.1007/s43440-026-00877-z","DOIUrl":"10.1007/s43440-026-00877-z","url":null,"abstract":"<p><strong>Background: </strong>On December 1st, 2023, the Pharmacovigilance Risk Assessment Committee (PRAC) published a safety warning against using pseudoephedrine in patients with severe or uncontrolled hypertension and severe acute or chronic kidney disease for the risk of developing posterior reversible encephalopathy syndrome (PRES) or reversible cerebral vasoconstriction syndrome (RCVS). Based on this consideration and the availability of other decongestants with the same mechanism of action as pseudoephedrine in the European market, we decided to conduct a safety study to evaluate cases of RCVS or PRES reported with other decongestants.</p><p><strong>Methods: </strong>A European, retrospective, post-marketing surveillance study was conducted to describe individual case safety reports (ICSRs) of RCVS and PRES reported with decongestants and to compare the likelihood of reporting these events among decongestants. Data were retrieved from the EudraVigilance database from January 1st, 2001, to December 31st, 2025.</p><p><strong>Results: </strong>A total of 65 ICSRs reported PRES or RCVS with decongestants, most of which referred to female patients aged 18-64 years. A disproportionate reporting of RCVS was found for xylometazoline (reporting odds ratio, ROR: 3.39; 95% confidence interval, CI: 1.94-5.93) and phenylephrine (ROR: 2.00; 95% CI: 1.11-3.61), and a disproportionate reporting of PRES for ephedrine (ROR: 6.44; 95% CI: 1.80-23.10) and phenylephrine (ROR: 3.47; 95% CI: 1.22-9.88) compared to all other decongestants.</p><p><strong>Conclusion: </strong>Our results suggest that all decongestants should be used with caution, and attention should be paid to signs and symptoms of PRES and RCVS when taking these medicines.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1264-1274"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical latanoprost acid for female androgenetic alopecia: a pilot proof-of-concept trial with mechanistic evidence of prostaglandin F2α receptor activation.","authors":"Adriana Rakowska, Małgorzata Dutkiewicz, Oliwia Zegrocka-Stendel, Dorota Dymkowska, Grzegorz Huszcza, Maciej Wierzbicki, Jarosław Walczak, Lidia Rudnicka, Katarzyna Koziak","doi":"10.1007/s43440-026-00876-0","DOIUrl":"10.1007/s43440-026-00876-0","url":null,"abstract":"<p><strong>Background: </strong>Prostaglandin F2α receptor (FP receptor) signaling is a plausible target for promoting hair growth, but clinical data on topical latanoprost acid (the active free-acid FP agonist) in hair loss are lacking. This study aimed to evaluate the clinical efficacy, safety, and mechanistic basis of topical latanoprost acid in women with female androgenetic alopecia.</p><p><strong>Methods: </strong>In this investigator-initiated, randomized, double-blind, single-center, dose-ranging pilot trial, 29 adult women with hair loss predominantly consistent with female androgenetic alopecia were randomized to vehicle (n = 2) or topical latanoprost acid 0.01% (n = 8), 0.05% (n = 13), or 0.1% (n = 6), applied once daily for 6 months. The primary endpoint was within-participant change in target-area hair count (TAHC, hairs/cm²) from baseline to month 6; trichoscopic activity markers (yellow dots) and follicular-unit (FU) remodeling were secondary and exploratory outcomes. Human hair dermal papilla cells (HHDPCs) were assessed for FP receptor-linked signaling (intracellular Ca²⁺ flux) and DNA synthesis by 5-ethynyl-2'-deoxyuridine (EdU) incorporation after exposure to latanoprost acid versus equimolar latanoprost.</p><p><strong>Results: </strong>An increase in TAHC was observed across all active treatment arms (mean ± SEM ΔTAHC: 17.8 ± 4.3, 23.5 ± 6.1, and 16.5 ± 6.5 hairs/cm² in the latanoprost acid 0.01%, 0.05%, and 0.1% arms, respectively). No significant between-arm differences were detected. Secondary and exploratory trichoscopic analyses showed reductions in yellow-dot counts, a decrease in single-hair FUs, and an increase in triple-hair FUs. Safety was favorable, with no serious adverse events. In mechanistic assays, latanoprost acid triggered rapid, concentration-dependent Ca²⁺ flux, whereas equimolar latanoprost produced delayed signals; neither compound altered EdU incorporation.</p><p><strong>Conclusions: </strong>In this pilot proof-of-concept trial, topical latanoprost acid showed a coherent clinical-trichoscopic bioactivity signal, supported by FP receptor-linked signaling in HHDPCs. These findings require confirmation in larger randomized pharmacokinetic/pharmacodynamic-integrated trials designed to optimize dose, confirm efficacy, and further characterize long-term safety.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT07412587; registered on February 2, 2026.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1236-1249"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the interaction between aryl hydrocarbon receptor and methotrexate: implications for treatment resistance in rheumatoid arthritis patients.","authors":"Anna Wajda, Gabriela Filipowicz, Yana Kaliberda, Barbara Stypińska, Tomasz Kmiołek, Ewa Kuca-Warnawin, Małgorzata Jarończyk, Agata Matusiewicz, Bożena Jaszczyk, Małgorzata Stasiek, Anna Felis-Giemza, Katarzyna Bazała, Adam Ejma-Multański, Diana Bogucka, Ewa Modzelewska, Marzena Olesińska, Agnieszka Paradowska-Gorycka","doi":"10.1007/s43440-026-00875-1","DOIUrl":"10.1007/s43440-026-00875-1","url":null,"abstract":"<p><strong>Background: </strong>The aryl hydrocarbon receptor (AHR) plays a key role in immune regulation and drug metabolism, potentially influencing methotrexate (MTX) treatment outcomes in patients with rheumatoid arthritis (RA). This exploratory study investigated the relationship between AHR activity and MTX responsiveness, and examined whether combination therapy with tocilizumab (TCZ), an interleukin (IL)-6 receptor inhibitor, could influence MTX resistance and treatment response.</p><p><strong>Methods: </strong>We employed in silico docking to assess MTX binding to the AHR Per-Arnt-Sim (PAS)-B domain. Ex vivo and in vitro models using peripheral blood mononuclear cells (PBMCs) from RA patients and healthy donors were also used. Flow cytometry was used to analyze AHR expression across immune cell subtypes. Additionally, HepG2 cells served as a pharmacological model to study the interaction of MTX and TCZ with AHR and the expression of drug transporter genes.</p><p><strong>Results: </strong>AHR expression was significantly higher in monocytes from good responders to MTX than in those from poor responders and MTX-intolerant patients, suggesting that monocytes were the PBMC subset most strongly associated with AHR-related patterns of MTX response. In silico analysis supported the binding of MTX to the PAS-B domain of AHR. The in vitro model confirmed that monocytes were the most responsive subset in the context of AHR-related changes. Treatment with TCZ tended to reduce the proportion of AHR-positive monocytes, whereas co-treatment with MTX shifted AHR toward a pattern comparable to that in good responders or under control conditions.</p><p><strong>Conclusions: </strong>Our findings underscore the complexity of MTX pharmacodynamics and highlight AHR as a potential biomarker for predicting treatment response in RA patients. The combination of MTX and TCZ modulated AHR activity and could inform personalized therapeutic strategies, especially in patients exhibiting MTX resistance or intolerance. While preliminary, this multi-layered investigation-combining patient samples, 3D cultures, and molecular docking-supports further research into AHR-modulating therapies in RA.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1217-1235"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148296148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Italian regional data and oropharyngeal adverse events to drugs and vaccines: insights from a 3-year spontaneous reporting (2022-2024).","authors":"Liberata Sportiello, Mario Gaio, Alessia Zinzi, Gaetano La Mantia, Vera Panzarella, Giuseppe Colella, Paola Martina Marra, Laura Sottosanti, Simona Potenza, Giacomo Oteri, Martina Coppini, Giuseppe Seminara, Rodolfo Mauceri, Ilaria Morreale, Vittorio Fusco, Giuseppina Campisi, Annalisa Capuano","doi":"10.1007/s43440-026-00873-3","DOIUrl":"10.1007/s43440-026-00873-3","url":null,"abstract":"<p><strong>Background: </strong>Oropharyngeal adverse events (O-AEs) represent a potential safety concern associated with several drugs and/or vaccines. Although often underestimated, these events may provide valuable insights into a patient's overall clinical condition, appearing initially mild but later worsening. Therefore, this study aimed to analyze O-AEs related to drugs and/or vaccines using structured safety data.</p><p><strong>Methods: </strong>Safety reports from three Italian regions were retrieved from the national pharmacovigilance database (rete nazionale di farmacovigilanza, RNF) and analyzed for the period 2022-2024. All reports were structured and analyzed according to the International Council of Harmonisation (ICH) E2B (R3) format. Additionally, reporting odds ratios (RORs) were calculated to compare the likelihood of O-AEs being reported by different categories of reporters (e.g., physicians, other healthcare professionals, or patients).</p><p><strong>Results: </strong>Over three years, 47,664 reports were collected, of which 1,740 (3.6%) contained at least one suspected O-AE. Most patients were female (65.7%) with a median age of 55 years (IQR 38-66). The majority of reports described non-serious events (66.7%), and outcomes were favorable in most cases (75.9%). The safety reports related to drugs (90.5%) were largely more than those related to vaccines (9.5%). A total of 129 cases of medication-related osteonecrosis of the jaw (MRONJ) were identified, most of which were serious and had unfavorable outcomes. Disproportionality analysis revealed that physicians were less likely to report O-AEs than patients (ROR=0.72; 0.62-0.84; P<<0.05) and more likely than nurses (ROR=1.34; 0.98-1.87; P<0.05). Compared with 2019-2021, the main difference was the lower proportion of vaccine-related reports, which declined from 47.8% to 9.5% in 2022-2024.</p><p><strong>Conclusions: </strong>Only a small proportion of safety reports involved O-AEs. These findings highlight the importance of enhancing awareness among physicians (particularly dentists) regarding O-AEs, and of fostering a collaborative pharmacovigilance culture across healthcare providers, thereby improving patient safety through more timely and reliable reporting.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1275-1291"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of gadolinium doping on physicochemical properties and neuroprotective activity of polyacrylic acid conjugated cerium oxide nanoparticles - in vitro study of potential theranostics for neurodegenerative diseases.","authors":"Rugmani Meenambal, Tomasz Kruk, Piotr Warszyński, Natalia Łopuszyńska, Władysław P Węglarz, Katarzyna Stan-Głowińska, Joanna Wojewoda-Budka, Krzysztof Jasiński, Aleksandra Mąsior, Danuta Jantas","doi":"10.1007/s43440-026-00863-5","DOIUrl":"10.1007/s43440-026-00863-5","url":null,"abstract":"<p><strong>Background: </strong>Cerium oxide nanoparticles (CeO NPs) are showing neuroprotective effects in various experimental models of neurodegeneration. Doping of nanoparticles with magnetic resonance imaging (MRI) contrast agents (e.g., gadolinium) could enable simultaneous diagnosis and treatment of neurodegenerative diseases, a technology called theranostics that is used primarily in oncology but can also be successfully applied in the diagnosis and treatment of neurodegenerative diseases.</p><p><strong>Methods: </strong>In this study, we doped polyacrylic acid conjugated cerium oxide nanoparticles with gadolinium (Gd-CeO) to create a theranostic agent with MRI capabilities and neuroprotective properties. These nanoparticles were evaluated for their physicochemical characteristics, magnetic resonance imaging potential, biosafety profile, cellular uptake, and neuroprotective effects compared to CeO nanoparticles (CeO) in a human neuronal model of Parkinson's disease employing undifferentiated and retinoic acid-differentiated SH-SY5Y cells.</p><p><strong>Results: </strong>The synthesized Gd-CeO nanoparticles showed good stability, concentration-dependent T₁ and T₂ contrast features, and were not cytotoxic. The Gd-CeO nanoparticles were rapidly taken by cells and maintained neuroprotective potency against hydrogen peroxide (H₂O₂)- and 6-hydroxydopamine (6-OHDA)-induced cell damage to a similar extent as did CeO nanoparticles without Gd doping. Moreover, we demonstrated a protective effect of Gd-CeO and CeO nanoparticles on mitochondrial membrane potential, DNA fragmentation, and the number of necrotic cells in both models of cell injury, whereas at the level of caspase-3 activity, we showed an inhibitory effect of the studied NPs only in the 6-OHDA model. Finally, the protection mediated by Gd-CeO and CeO nanoparticles against H₂O₂ was confirmed in mouse primary cortical neurons.</p><p><strong>Conclusions: </strong>Since the developed Gd-CeO nanoparticles showed promising contrast features, as well as maintaining biosafety and neuroprotective properties similar to those of nanoparticles without Gd doping, they could be further investigated as a potential theranostic probe for neurodegenerative diseases, including Parkinson's disease.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1119-1144"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13437749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147863719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}