Pharmacological Reports最新文献

{"title":"Signs of antidepressant-like effects of temozolomide as measured in the forced-swim test in adult rats.","authors":"Laura Gálvez-Melero, M Julia García-Fuster","doi":"10.1007/s43440-026-00892-0","DOIUrl":"https://doi.org/10.1007/s43440-026-00892-0","url":null,"abstract":"<p><strong>Background: </strong>Temozolomide is the gold standard chemotherapeutic agent for glioblastoma multiforme. Yet its pharmacological use has been linked to the emergence of depressive- and/or anxiety-like behaviors, probably through the inhibition of hippocampal neurogenesis. Since prior studies reporting these negative effects were based on prolonged treatment paradigms (from 2 weeks to up to 6 months), and given the lack of studies including females, our approach aimed at further characterizing the behavioral effects induced by temozolomide (25 mg/kg, 1 or 2 cycles, 5 days/cycle) in a adult rats of both sexes.</p><p><strong>Methods: </strong>Rats were scored across time through specific behavioral tests that capture diverse manifestations of affective-like responses (forced-swim, open field, novelty-suppressed feeding, sucrose preference) or cognitive performance (Barnes maze). At the neurochemical level, we ascertained the effects of 2 cycles of temozolomide on an early stage of hippocampal neurogenesis (neural progenitors, NeuroD) and other potential neuroplasticity targets (mature BDNF, FADD).</p><p><strong>Results: </strong>Temozolomide induced signs of antidepressant-like responses as measured in the forced-swim test in a treatment-duration manner. It also decreased NeuroD and hippocampal FADD, a neuroplastic marker previously associated with the acute and repeated actions of most antidepressants. These results suggested that other mechanisms of action might be associated with temozolomide's behavioral effects besides hippocampal neurogenesis, such as the correlative one described through the neuroplastic molecule FADD.</p><p><strong>Conclusions: </strong>In conjunction with the prior data, our results suggested cycle- and/or length-dependent treatment effects in terms of temozolomide's antidepressant- vs. depressant-like profile, while proposing a novel biomarker related to treatment response.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875571","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":"The anti-CEACAM1 agonistic antibody CCM5.01 inhibits the growth of colon cancer cell lines in 2D and 3D models.","authors":"Shiran Niazov, Ilan Zaffran, Ofra Benny, Micha Ben-Zimra, Francesca Levi-Schaffer","doi":"10.1007/s43440-026-00891-1","DOIUrl":"https://doi.org/10.1007/s43440-026-00891-1","url":null,"abstract":"<p><strong>Background: </strong>Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is an inhibitory receptor expressed by multiple tumors, including colorectal cancer (CRC). CEACAM1 exists as a long isoform (L) containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a short isoform (S) lacking ITIMs. While microsatellite instability (MSI) CRCs respond to immunotherapy, microsatellite-stable (MSS) CRCs remain resistant, highlighting the need for alternative therapeutic targets. We previously developed an agonistic anti-CEACAM1 monoclonal antibody (mAb), CCM5.01, and demonstrated its CEACAM1-dependent inhibitory effects in melanoma. Here, we evaluated CCM5.01 inhibitory activity on CRC cell lines and related it to L/S ratio.</p><p><strong>Methods: </strong>CRC cell lines HT-29, LOVO, and HCT-116 were treated with CCM5.01 and analyzed by proliferation assays before and after transfection with L or S CEACAM1 isoforms. Transfected cells treated with CCM5.01 were analyzed for signaling and in 3D spheroid models.</p><p><strong>Results: </strong>CEACAM1-positive CRC cells showed dose-dependent inhibition in response to CCM5.01 treatment and were associated with L/S isoform expression. High CEACAM1-L expression induced growth inhibition and apoptosis, while CEACAM1-S promoted cellular activity. Similar isoform-dependent effects were observed in spheroid models.</p><p><strong>Conclusions: </strong>CEACAM1-mediated signaling in CRCs critically depends on the L/S isoform ratio, supporting CEACAM1-targeted activating therapy as a potential strategy in both MSI and immunotherapy-resistant MSS CRC.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866010","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":"Effects of lovastatin on cortical excitability, E/I balance, and antioxidant markers in a case series of patients with drug-resistant epilepsy: a proof-of-concept study.","authors":"Sulaiman I Abuhaiba, Isabel Catarina Duarte, Francisco Sales, Miguel Castelo-Branco","doi":"10.1007/s43440-026-00890-2","DOIUrl":"https://doi.org/10.1007/s43440-026-00890-2","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant epilepsy (DRE) remains a major clinical challenge, with neuroinflammation and excitatory/inhibitory (E/I) imbalance being implicated in its pathophysiology. This proof-of-concept case series aimed to investigate the neurochemical and neurophysiological effects of a short course of lovastatin in individuals with DRE.</p><p><strong>Methods: </strong>Five participants with drug-resistant temporal lobe epilepsy completed a double-blind, placebo-controlled, crossover protocol involving oral administration of lovastatin (60 mg/day) and placebo for three consecutive days. Post-intervention assessments included: (1) magnetic resonance spectroscopy (MRS) in the visual cortex to quantify gamma-aminobutyric acid (GABA+), Glutamate (Glx), and Glutathione (GSH); (2) resting-state electroencephalogram (EEG) to measure the frequency of interictal epileptiform discharges (IEDs); and (3) event-related potentials (ERPs) during a facial recognition task.</p><p><strong>Results: </strong>Compared to placebo, lovastatin administration was associated with a statistically significant reduction in the GABA+/Glx ratio (p = 0.041) and IED frequency (p = 0.04), alongside a statistically significant increase in GSH concentration (p = 0.039). Lovastatin also modulated visual processing ERPs, statistically significantly delaying the P100 latency (p = 0.04) and reducing the absolute N170 peak amplitude (p = 0.04).</p><p><strong>Conclusion: </strong>This study demonstrates that a short course of lovastatin can modulate key in vivo biomarkers of E/I balance, redox state, and cortical excitability in patients with DRE. These preliminary findings provide a mechanistic rationale for further, larger studies to explore the potential of statins as a novel strategy for modifying pathological brain activity.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831534","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":"preSCRIPT: Large-scale prescription search and annotation engine for pharmacogenomic studies.","authors":"Maria Pieczarka, Paweł Pieńkowski, Paula Konowalska, Sylwia Grubarek, Jacek Hajto, Dżesika Hoinkis, Marcin Piechota, Małgorzata Borczyk, Michał Korostyński","doi":"10.1007/s43440-026-00889-9","DOIUrl":"https://doi.org/10.1007/s43440-026-00889-9","url":null,"abstract":"<p><strong>Background: </strong>Pharmacogenetics (PGx) has traditionally focused on a small number of high-impact variants affecting drug response due to the fact that PGx studies are labor-intensive and therefore low-throughput. Population biobanks linked to electronic health records (EHRs), including the UK Biobank (UKB) with prescription data for ~ 230,000 individuals offer opportunities to scale PGx research. This, however, comes with a challenge as EHRs do not provide direct treatment response outcomes. One way to overcome this is to draw indirect drug response phenotypes from prescription records.</p><p><strong>Methods: </strong>Here, we propose preSCRIPT, a framework to filter and annotate raw prescriptions from the UKB to derive phenotypes for analyses which includes an algorithm to distinguish short prescription gaps from true dose changes. As a proof of concept, we applied preSCRIPT to warfarin, paracetamol, codeine, amitriptyline, simvastatin, aspirin, and amlodipine and derived therapy length and median daily doses. We tested associations for those seven drugs and two phenotypes across single-nucleotide polymorphisms (SNPs), cytochrome P450 (CYP) genes, and human leukocyte antigen (HLA) alleles.</p><p><strong>Results: </strong>We recovered known associations such as CYP2D6 variants with amitriptyline therapy length and dose, CYP2C9/CYP4F2/CYP2C19 with warfarin dose, and CYP2D6 with codeine dose. For drugs without formal PGx guidelines, we identified an association between CYP2D6 enzyme activity and aspirin therapy length and several SNPs, including rs62471929 (CYP3A5), a variant for amlodipine dose, which reached nominal significance in an independent hold-out set.</p><p><strong>Conclusions: </strong>Overall, preSCRIPT provides a scalable framework for prescription-based discovery in pharmacogenomics. As a proof of concept it recovers established PGx associations and nominates novel, hypothesis-generating candidate loci.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813689","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":"Regulator of G protein signaling 6 (RGS6) controls the effect of cannabinoids on intestinal tract motility and visceral pain sensation in mice.","authors":"Mikołaj Świerczyński, Adam Makaro, Maria Jaczyńska, Marta Sobalska-Kwapis, Michał Seweryn, Zuzanna Kasprzak, Aleksandra Tarasiuk-Zawadzka, Maciej Sałaga","doi":"10.1007/s43440-026-00887-x","DOIUrl":"https://doi.org/10.1007/s43440-026-00887-x","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal (GI) tract diseases cause symptoms that significantly affect the quality of life. A promising direction in the search for novel therapeutic options in this field is the investigation of G protein-coupled receptors (GPCRs), whose activity is modulated by their regulator proteins (RGS). In this study, we examined RGS6 involvement in GI inflammation and functional disorders and its effect on cannabinoid (CB), opioid, and serotonin receptor (5HTR)-targeting compounds, METHODS: Using quantitative PCR, western blot, and ELISA assays, we characterized RGS6 expression in the mouse GI tract and measured GPCR-related secondary messenger expression upon stimulation with GPCR agonists in vitro in Caco-2 cells, both wild type (WT) and RGS6 knock-out (KO). Then, in vivo in a dextran sulfate sodium (DSS) mouse model of colitis using WT, global and tissue-specific RGS6 KO mice, inflammation, antinociceptive effects, and GI motility were examined.</p><p><strong>Results: </strong>In Caco-2 cells, we found that RGS6 KO increased extracellular signal-regulated kinase phosphorylation, which was blocked by CB agonist WIN 55,212-2. Moreover, incubation with WIN 55,212-2 significantly reduced cyclic adenosine monophosphate (cAMP) levels in RGS6 KO but not WT cells. In DSS-induced, acute and chronic-relapsing mouse models of colitis, RGS6 KO resulted in resistance to stress-induced GI hypermotility. WIN 55,212-2 (1 mg/kg ip) substantially prolonged GI transit time and displayed antinociceptive properties that were stronger in the absence of RGS6. Epithelial -specific RGS6 KO did not affect the action of WIN 55,212-2.</p><p><strong>Conclusions: </strong>RGS6 exerts crucial effects on GI physiology by acting on CB signaling in the enteric and/or central nervous system.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760495","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":"The course of platinum-based chemotherapy is associated with the risk of hematological complications during poly(ADP-ribose) polymerase (PARP) inhibitor therapy in patients with ovarian cancer.","authors":"Cezary Miedziarek, Aleksandra Gładych-Macioszek, Michał Potograbski, Aleksandra Kapłon, Ewa Nowak-Markwitz, Mikołaj Piotr Zaborowski","doi":"10.1007/s43440-026-00888-w","DOIUrl":"10.1007/s43440-026-00888-w","url":null,"abstract":"<p><strong>Background: </strong>Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is a standard treatment in selected ovarian cancer patients. However, hematological toxicity remains a clinical problem. The study aimed to identify predictors of early hematologic toxicity during PARP inhibitor maintenance therapy in high-grade serous ovarian cancer.</p><p><strong>Methods: </strong>We retrospectively analyzed 130 patients receiving PARP inhibitors (niraparib, 49; olaparib, 81). Blood counts from first-line platinum chemotherapy and from the first 3 months of PARP inhibitor therapy were assessed. Adverse events were graded using the Common Terminology Criteria for Adverse Events v5.0. Weekly changes and minimal values for neutrophils, hemoglobin, and platelets were calculated (excluding post-intervention values).</p><p><strong>Results: </strong>Thrombocytopenia was mainly related to niraparib treatment, and anemia was mainly related to olaparib treatment. During niraparib therapy, higher human epididymis protein 4 (He4) at diagnosis correlated with greater platelet decline and lower platelet nadir. In multivariable linear regression, higher body weight (β = 1.86, 95% CI 0.05 to 3.67, p = 0.044) and higher minimal hemoglobin during chemotherapy (β = 67.41, 95% CI 16.39 to 118.43, p = 0.011) were independently associated with higher minimal platelet count during niraparib treatment. In multivariable logistic regression, higher minimal neutrophil count during chemotherapy (OR = 4.51, 95% CI 1.47 to 17.96, p = 0.015) and lower minimal platelet count during chemotherapy (OR = 0.975, 95% CI 0.958 to 0.989, p = 0.001) were independently associated with grade 3 or 4 thrombocytopenia during niraparib treatment. In the olaparib cohort, lower minimal neutrophil count during chemotherapy (β = -0.414, 95% CI -0.755 to -0.074, p = 0.018) and higher hemoglobin concentration at qualification for PARP inhibitor therapy (β = 0.533, 95% CI 0.042 to 1.024, p = 0.034) were independently associated with higher minimal hemoglobin during treatment.</p><p><strong>Conclusions: </strong>Early, severe cytopenias during PARP inhibitor therapy can be predicted using clinical data. Platinum-related side effects and parameters for disease diagnosis and eligibility for PARP inhibitor therapy identify high-risk patients, supporting risk-adapted monitoring and proactive dose optimization. These findings should be considered hypothesis-generating and require external validation before implementation in clinical decision-making.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725478","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":"The MEG3-miRNA regulatory axis could potentially modulate response to biological therapies in psoriatic arthritis.","authors":"Giada De Benedittis, Chiara Morgante, Andrea Latini, Arianna D'Antonio, Eneida Cela, Benedetta Monosi, Paola Conigliaro, Cinzia Ciccacci, Giuseppe Novelli, Maria Sole Chimenti, Paola Borgiani","doi":"10.1007/s43440-026-00884-0","DOIUrl":"https://doi.org/10.1007/s43440-026-00884-0","url":null,"abstract":"<p><strong>Background: </strong>The long non-coding RNA - microRNA (lncRNA-miRNA) regulatory axis is a key modulator of immune and inflammatory pathways, and growing evidence supports its contribution to therapeutic response variability. In our previous study, we identified the lncRNA MEG3 as potentially involved in the response to biological drugs, specifically TNFα- and IL17A-inhibitors, in psoriatic arthritis (PsA).</p><p><strong>Methods: </strong>To further characterize its role, we performed a bioinformatic analysis to identify MEG3-targeted miRNAs, followed by an exploratory expression profiling analysis using qRT-PCR in a cohort of 54 PsA patients at baseline (T0) and after 12 months of therapy (T12), compared with 15 healthy controls (CTRLs).</p><p><strong>Result: </strong>We identified four candidate miRNA targets: hsa-miR-21-5p, hsa-miR-19b-3p, hsa-miR-19a-3p, and hsa-miR-17-5p. Among these, hsa-miR-17-5p was significantly upregulated in PsA patients at T0 versus CTRLs. Most importantly, we found a significant decrease in hsa-miR-17-5p and hsa-miR-19b-3p levels in Responder patients at 12-month follow-up. We then explored whether MEG3 genetic variability contributes to miRNA modulation. First, we observed that the MEG3 rs941576 genetic variant appears to influence the expression levels of hsa-miR-19a-3p and hsa-miR-19b-3p. Next, in silico analyses indicated that this variant lies within an immune-active enhancer, altering the binding affinity for the transcription factors HIF1A/ARNT2, and suggested a link between MEG3 enhancer activity and hypoxia-responsive regulation of these miRNAs. Lastly, pathway enrichment analysis highlighted that both hsa-miR-17-5p and hsa-miR-19b-3p converge on the TGF-β signalling pathway.</p><p><strong>Conclusion: </strong>Our findings suggest the involvement of a specific MEG3-miRNA network in modulating the response to biological therapies in PsA.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148707451","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":"Pre-treatment with 2-mercaptoethanol attenuates ferroptosis-associated redox imbalance and inflammatory responses, but not tubulointerstitial fibrosis, in unilateral ureteral obstruction.","authors":"Daeun Moon, Jinu Kim","doi":"10.1007/s43440-026-00881-3","DOIUrl":"https://doi.org/10.1007/s43440-026-00881-3","url":null,"abstract":"<p><strong>Background: </strong>Unilateral ureteral obstruction (UUO) induces oxidative stress, inflammation, ferroptosis, and progressive fibrotic remodeling. Whether pharmacological modulation of ferroptosis-related redox imbalance attenuates obstructive kidney injury remains unclear. In this study, we investigated the effects of the thiol-containing antioxidant 2-mercaptoethanol (2-ME) in a mouse UUO model.</p><p><strong>Methods: </strong>Mice subjected to UUO received either pre-treatment or delayed treatment with 2-ME. Ferroptosis-related markers, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), the ratio of reduced to oxidized glutathione (GSH/GSSG), and lipid hydroperoxides, as well as inflammatory mediators, F4/80-positive macrophage infiltration, Havcr1 mRNA expression, and fibrotic parameters were evaluated using molecular and histological analyses.</p><p><strong>Results: </strong>UUO markedly decreased the expression of GPX4 and SLC7A11, reduced the GSH/GSSG ratio, and elevated lipid hydroperoxide levels. These changes were accompanied by increased tubular injury scores, infiltration of F4/80-positive macrophages, and extracellular matrix accumulation. Pre-treatment with 2-ME increased GPX4 and SLC7A11 expression, improved the GSH/GSSG balance, reduced lipid hydroperoxide levels, and attenuated inflammatory activation. Additionally, 2-ME pre-treatment significantly reduced tubular injury scores and Havcr1 mRNA expression. However, 2-ME did not consistently suppress collagen deposition or the expression of fibrosis-related genes. Delayed administration of 2-ME failed to significantly alter antioxidant, inflammatory, or fibrotic markers.</p><p><strong>Conclusions: </strong>Pre-treatment with 2-ME attenuates ferroptosis-associated redox imbalance and inflammatory responses in UUO but does not consistently suppress tubulointerstitial fibrosis. These findings suggest that 2-ME can serve as a pharmacological tool to modulate thiol-dependent redox balance and inflammatory activation during UUO, whereas fibrosis progression likely involves additional mechanisms.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670352","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":"Association between elemental concentrations and chemotherapy-related acute adverse events in patients with nasopharyngeal carcinoma.","authors":"Xi Chen, Tian-Rui Gao, Li-Xia Peng, Wei Hu, Hu Liang, Ze-Jiang Zhan, Ying Deng, Chi-Xiong Liang, Jia-Yu Zhou, Lu-Lu Zhang, Hao-Yang Huang, Xiang Guo, Xiao-Jiang Tang, Chao-Nan Qian, Xing Lv","doi":"10.1007/s43440-026-00865-3","DOIUrl":"10.1007/s43440-026-00865-3","url":null,"abstract":"<p><strong>Background: </strong>While environmental exposure to toxic elements, such as cadmium (Cd) and chromium (Cr), is known to impair general organ function, its specific impact on patients' tolerance to platinum (Pt)-based chemotherapy remains largely unexplored. This study aimed to determine whether pretreatment accumulation of specific trace elements is associated with the occurrence of acute adverse events (AEs) in patients with nasopharyngeal carcinoma (NPC) receiving platinum (Pt)-based chemotherapy.</p><p><strong>Methods: </strong>A single-center, prospective, longitudinal study was conducted on 140 patients with NPC. Elemental concentrations measured before the initiation of chemotherapy (hereafter referred to as \"pretreatment concentrations\") of 13 elements (arsenic (As), calcium (Ca), Cd, cobalt (Co), Cr, copper (Cu), mercury (Hg), magnesium (Mg), nickel (Ni), lead (Pb), platinum (Pt), selenium (Se), and zinc (Zn)) and acute AEs for each chemotherapy cycle were recorded. Elemental concentrations were measured in blood (B) and urine (U) using inductively coupled plasma mass spectrometry (ICP-MS). Univariate and multivariate logistic regression analyses were performed to evaluate the associations between element levels and chemotherapy-related acute adverse events (AEs).</p><p><strong>Results: </strong>The study enrolled 140 patients with stage II (n = 2, 1.4%), III (n = 76, 54.3%), and IVA (n = 62, 44.3%) NPC. Moderate positive correlations (Spearman's correlation coefficients ranging from 0.2 to 0.7, p < 0.05) were observed between the concentrations of individual elements (such as Cd, Pb, and Cr) measured in paired whole blood and urine samples. NPC patients with high urinary Cr, blood Cd, and urinary Pb concentrations were more likely to experience higher incidences of thrombocytopenia (5% vs. 23%, p = 0.002), hepatotoxicity (40% vs. 60%, p = 0.028), and dysglycemia (46% vs. 74%, p < 0.001), respectively. In the multivariate adjusted logistic regression, blood Cd (OR = 3.65, 95% CI 1.38-9.64; p = 0.009) and urinary Cr (OR = 3.34, 95% CI 1.60-19.87; p = 0.007) were identified as independent predictors of hepatotoxicity and thrombocytopenia in NPC patients receiving Pt-based chemotherapy.</p><p><strong>Conclusions: </strong>Pretreatment elevation of specific elements, particularly blood Cd and urinary Cr, was independently associated with a significantly increased risk of chemotherapy-related acute AEs. Specifically, blood Cd and urinary Cr were independent predictors of hepatotoxicity and thrombocytopenia in NPC patients undergoing Pt-based chemotherapy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"1250-1263"},"PeriodicalIF":4.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148043297","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":"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}