Basic & Clinical Pharmacology & Toxicology最新文献

{"title":"Bruceine A Inhibits Cell Proliferation by Targeting the USP13/PARP1 Signalling Pathway in Multiple Myeloma","authors":"Mengjie Guo,&nbsp;Han Meng,&nbsp;Yi Sun,&nbsp;Lianxin Zhou,&nbsp;Tingting Hu,&nbsp;Tianyi Yu,&nbsp;Haowen Bai,&nbsp;Yuanjiao Zhang,&nbsp;Chunyan Gu,&nbsp;Ye Yang","doi":"10.1111/bcpt.70027","DOIUrl":"https://doi.org/10.1111/bcpt.70027","url":null,"abstract":"<p>Multiple myeloma (MM) is an incurable hematologic malignancy, driving significant interest in the discovery of novel therapeutic strategies. Bruceine A (BA), a tetracyclic triterpene quassinoid derived from <i>Brucea javanica</i>, has shown anticancer properties by modulating multiple intracellular signalling pathways and exhibiting various biological effects. However, the specific pharmacological mechanisms by which it combats MM remain unclear. In this study, we identified USP13 as a potential target of BA. We observed a significant increase in USP13 expression in patients with MM, which was strongly associated with a poorer prognosis. Furthermore, enhanced USP13 expression can stimulate MM cell proliferation both in vitro and in vivo. Mass spectrometry analysis, combined with co-immunoprecipitation and in vitro ubiquitination experiments, revealed PARP1 as a critical downstream target of USP13. USP13 can stabilize PARP1 protein through deubiquitination, promoting PARP1-mediated DNA damage repair (DDR) and facilitating MM progression. Notably, we utilized MM cell lines, an MM Patient-Derived Tumour Xenograft model, and a 5TMM3VT mouse model to determine the anticancer effects of BA on MM progression, revealing its potential to target USP13/PARP1 signalling and disrupt DDR in MM cells. In conclusion, these findings suggest that BA inhibiting USP13/PARP1-mediated DDR might be a promising therapeutic strategy for MM.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cells of the Vasculature: Advances in the Regulation of Vascular Tone in the Brain and Periphery","authors":"Luke S. Dunaway,&nbsp;William A. Mills III,&nbsp;Ukpong B. Eyo,&nbsp;Brant E. Isakson","doi":"10.1111/bcpt.70023","DOIUrl":"https://doi.org/10.1111/bcpt.70023","url":null,"abstract":"<p>The vasculature is a complex tissue in which multiple cell types coordinate the regulation of tissue perfusion in response to hemodynamic and biochemical signals. Advances in this field are continuing to deepen our understanding of the relative importance of these cell types through the body. In the peripheral vasculature, tone is generated primarily by smooth muscle cells and regulated by endothelial cells, and neurons. In the brain parenchyma, unique cell types including pericytes, perivascular astrocytes and microglia, also contribute to the regulation of arterial and capillary tone. Here, we provide a cell-by-cell review of the regulation of vascular tone and highlight recent advances in the regulation of vascular tone in both the periphery and cerebral vasculature.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase","authors":"Riham Rafea,&nbsp;Mauro Siragusa,&nbsp;Ingrid Fleming","doi":"10.1111/bcpt.70029","DOIUrl":"https://doi.org/10.1111/bcpt.70029","url":null,"abstract":"<p>Nitric oxide (NO) generated by the endothelial NO synthase (eNOS) plays an essential role in the maintenance of vascular homeostasis and the prevention of vascular inflammation. There are a myriad of mechanisms that regulate the activity of the enzyme that may prove to represent interesting therapeutic opportunities. In this regard, the kinases that phosphorylate the enzyme and regulate its activity in situations linked to vascular disease seem to be particularly promising. Although the actions of NO were initially linked mainly to the activation of the guanylyl cyclase and the generation of cyclic GMP in vascular smooth muscle cells and platelets, it is now clear that NO elicits the majority of its actions via its ability to modify redox-activated cysteine residues in a process referred to as <i>S</i>-nitrosylation. The more wide spread use of mass spectrometry to detect <i>S</i>-nitrosylated proteins has helped to identify just how large the NO sphere of influence is and just how many cellular processes are affected. It may be an old target, but the sheer impact of eNOS on vascular health really justifies a revaluation of therapeutic options to maintain and protect its activity in situations associated with a high risk of developing cardiovascular disease.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Molecular and Clinical Impact of Atorvastatin Exposure on Paclitaxel Neurotoxicity in Sensory Neurons and Cancer Patients","authors":"Emma Simonsen,&nbsp;Christina Mortensen,&nbsp;Cathrine Lundgaard Riis,&nbsp;Karina Dahl Steffensen,&nbsp;Morten Olesen,&nbsp;Martin Thomsen Ernst,&nbsp;Tore Bjerregaard Stage,&nbsp;Anton Pottegård","doi":"10.1111/bcpt.70022","DOIUrl":"https://doi.org/10.1111/bcpt.70022","url":null,"abstract":"<p>Recent evidence suggests that atorvastatin exacerbates paclitaxel neurotoxicity via P-glycoprotein inhibition. We used a translational approach to investigate if atorvastatin or simvastatin exacerbates (i) paclitaxel neurotoxicity in human sensory neurons and (ii) paclitaxel-induced peripheral neuropathy (PIPN) in cancer patients. Paclitaxel neurotoxicity was assessed by quantifying neuronal networks of human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) with and without atorvastatin or simvastatin exposure. We estimated the odds ratio (OR) of early paclitaxel discontinuation due to PIPN in a nationwide cohort of paclitaxel-treated women (2014–2018), comparing atorvastatin users to simvastatin users and nonusers of statins. Only the highest concentration of atorvastatin (100 nM) significantly exacerbated paclitaxel neurotoxicity in iPSC-SNs (<i>p</i> &lt; 0.05). Among 576 paclitaxel-treated women, atorvastatin use was not significantly associated with early paclitaxel discontinuation due to PIPN, with adjusted ORs of 0.80 [95% confidence interval (CI) 0.34–1.88] compared with simvastatin, and 1.24 [95% CI 0.44–3.53] compared with nonuse. Supplementary analyses showed varying but statistically nonsignificant results. Our in vitro findings suggest that atorvastatin, not simvastatin, significantly worsens paclitaxel neurotoxicity. However, no link was found between atorvastatin use and early paclitaxel discontinuation due to PIPN. Larger, well-designed studies are required to clarify the discrepancy between in vitro and clinical data and the inconsistencies with previous clinical evidence.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pathobiology of Cerebrovascular Lesions in CADASIL Small Vessel Disease","authors":"Anne Joutel","doi":"10.1111/bcpt.70028","DOIUrl":"https://doi.org/10.1111/bcpt.70028","url":null,"abstract":"<p>Cerebral small vessel disease (cSVD) is a significant global health issue, accounting for approximately 25% of ischemic strokes and 20% of all dementia cases. CADASIL, the most common monogenic form of cSVD, is caused by stereotyped mutations in the NOTCH3 receptor that alter the number of cysteine residues in its extracellular domain (Notch3^ECD). The two hallmark features of CADASIL are the loss of arterial smooth muscle cells (SMCs) and the abnormal accumulation of Notch3^ECD, without associated accumulation of its transmembrane intracellular domain. Notably, cysteine-altering mutations in NOTCH3 are prevalent in the general population, and although they are not directly associated with classical CADASIL disease, they are still linked to an elevated risk of stroke and dementia. NOTCH3 is predominantly expressed in the mural cells of small blood vessels and plays an essential role in the development, maintenance, function and survival of arterial SMCs. Recent research has challenged the loss-of-function hypothesis, instead implicating Notch3^ECD aggregation, involving both mutant and wild-type NOTCH3, as the primary driver of vascular pathology in CADASIL. Consequently, therapeutic strategies targeting the reduction of Notch3^ECD levels in brain arteries, such as antisense therapies, are considered highly promising for clinical development.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalin Ameliorates L-Glutamate-Induced Hippocampal Oxidative Stress Injury and Apoptosis in Mice by Regulating Nrf2/HO-1 Signalling Pathway","authors":"Feng Li,&nbsp;Zishan Huang,&nbsp;Huanyu Gou,&nbsp;Jiarui Zheng,&nbsp;Mingjiang Yao","doi":"10.1111/bcpt.70024","DOIUrl":"10.1111/bcpt.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the effect and mechanism of baicalin on L-glutamate-induced oxidative stress injury in the hippocampus of mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty mice were divided into five groups:Sham, model, N-acetyl-L-cysteine (NAC) and baicalin (BA-7.5 mg/kg and BA-15 mg/kg). A model of excitatory amino acid toxicity with oxidative stress injury was induced by injecting L-glutamate into the lateral ventricle. Drugs were administered intraperitoneally post-modelling. Six hours later, behavioural tests were performed. Brain lesions were observed via HE staining, and neuronal apoptosis was evaluated using TUNEL staining. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined using biochemical methods. Fluorescent staining was employed to detect the expression of reactive oxygen species (ROS). The expression of Cytochrome C (CytC) was assessed by immunohistochemistry. The levels of Nrf2, HO-1, SOD2 and catalase (Cat) were detected by qPCR and WB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The behavioural tests showed that the motion distance and pain threshold were reduced in the model group. MDA, ROS and CytC were increased, while SOD and Cat were decreased after modelling. The CA3 region of the hippocampus exhibited pathological changes, and the rate of TUNEL-positive increased. Baicalin could reverse these changes, especially BA-7.5 mg/kg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Baicalin can reduce the injury induced by L-glutamate, and the mechanism might be related to the activation of the Nrf2/HO-1 pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Arterial Oxygen Saturation With Partial Pressure of Oxygen Using a Turnover Model in Volunteers","authors":"Jung-Min Yi,&nbsp;Ji-Yeon Bang,&nbsp;Kyung Mi Kim,&nbsp;Eun-Kyung Lee,&nbsp;Byung-Moon Choi","doi":"10.1111/bcpt.70019","DOIUrl":"https://doi.org/10.1111/bcpt.70019","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The relational equation for predicting arterial oxygen saturation (SaO₂) with a partial pressure of oxygen (PaO₂) has been described and used in clinical settings. However, the equation has limitations as it was derived empirically. This study aimed to assess the relationship between PaO₂ and SaO₂ using a turnover model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>In a controlled desaturation study to assess the accuracy of a pulse oximeter, volunteers (<i>n</i> = 12) breathed hypoxic gas mixtures via a mouthpiece. Various target SaO₂ values were achieved within the range of 70%–100%. PaO₂ and SaO₂ were measured using a CO-oximeter. A turnover model was fitted to PaO₂–SaO₂ pair data. The performance of the two SaO₂ prediction methods (conventional formula and turnover model) was evaluated using additional volunteer data not used in the model-building process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The pharmacodynamic parameters were as follows: <i>k</i>_out (1/min) = 4.45 for Asians, 0.93 for Africans, <i>I</i>_max = 0.837 and IC₅₀ (mmHg) = 79.2%, <i>γ</i> = 5.24. PaCO₂ and pH were not significant covariates. The median prediction and median absolute prediction error were 5.6% and 5.7%, respectively, for the conventional formula, and 0.1% and 1.2%, respectively, for the turnover model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The relationship between PaO₂ and SaO₂ was better explained by the turnover model than by the conventional formula within the 70%–100% SaO₂ range.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Demographic Patterns in Medication use During Pregnancy: A Nationwide Register Study","authors":"Mette Østergaard Thunbo,&nbsp;Julie Hauer Vendelbo,&nbsp;Daniel R. Witte,&nbsp;Agnete Larsen,&nbsp;Lars Henning Pedersen","doi":"10.1111/bcpt.70020","DOIUrl":"https://doi.org/10.1111/bcpt.70020","url":null,"abstract":"<p>In recent years, medication use during pregnancy has increased, yet its association with maternal characteristics remains unclear. To address this gap, we aimed to investigate how maternal age, pre-gestational body mass index (BMI), smoking, parity, ethnic origin and employment status relate to medication use during pregnancy. We conducted a nationwide Danish registry study, including 698 447 clinically recognised pregnancies with a gestational age of at least 10 weeks, spanning from 2008 to 2018. Medication use was estimated based on prescription redemptions during pregnancy and stratified by the demographic factors of interest. Overall, 60.3% of pregnant women redeemed at least one prescription, while 28.9% redeemed multiple medications. Notably, higher usage was observed among women aged 35 or older, those with a BMI of 30 kg/m² or more, smokers, multipara, Black women, and early retirees. Medication combination patterns differed with the demographic subgroups. These findings highlight notable differences in medication use among demographic groups during pregnancy, underscoring the need for tailored healthcare strategies during pregnancy.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in PET Imaging of α7 Nicotinic Receptors: From Radioligand Development to CNS Applications","authors":"Janus H. Magnussen","doi":"10.1111/bcpt.70025","DOIUrl":"https://doi.org/10.1111/bcpt.70025","url":null,"abstract":"<p>Positron emission tomography (PET) has significantly advanced our understanding of the brain by enabling non-invasive imaging and quantification of molecular processes, including receptor binding. In this review, we explore the development and application of PET radioligands targeting the α7 nicotinic acetylcholine receptor (α7 nAChR), a receptor implicated in various central nervous system (CNS) diseases, such as Alzheimer's disease, schizophrenia and cognitive disorders. Despite challenges associated with the low density of α7 nAChRs and difficulties in achieving adequate brain penetration, several promising radioligands have been developed, including ¹¹C-(<i>R</i>)-MeQAA, ¹¹C-NS14492 and ¹⁸F-ASEM. These radioligands facilitate the evaluation of the ‘three pillars of survival’ in drug development: tissue accessibility, target engagement and downstream pharmacology. PET imaging offers critical insights into drug distribution across the blood–brain barrier, receptor occupancy and the pharmacodynamic effects of α7 nAChR–targeted therapies. By reviewing current radioligands and their applications, we highlight the potential of PET imaging to deepen our understanding of α7 nAChR–mediated signalling pathways and its implications for CNS drug discovery. Future innovations in radioligand development, including more selective and brain-penetrant compounds, will be key to fully realizing the potential of PET imaging in α7 nAChR–targeted research and treatment.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pregnancy Outcomes After Semaglutide Exposure","authors":"Line Kolding,&nbsp;Jakob Nørgaard Henriksen,&nbsp;Eva Aggerholm Sædder,&nbsp;Per Glud Ovesen,&nbsp;Lars Henning Pedersen","doi":"10.1111/bcpt.70021","DOIUrl":"https://doi.org/10.1111/bcpt.70021","url":null,"abstract":"&lt;p&gt;Semaglutide, a GLP1 agonist, is used for glycemic control in Type 2 diabetes and weight management [&lt;span&gt;1&lt;/span&gt;]. In animals (mice, rats and rabbits), GLP1 agonists is associated with embryofetal mortality, structural abnormalities and growth disturbances concerning delayed ossification and skeletal variants [&lt;span&gt;2&lt;/span&gt;]. A recent cohort study on the potential risk of malformations included GLP-1 receptor agonists but did not provide specific estimates for semaglutide [&lt;span&gt;3&lt;/span&gt;]. Except for case reports, there are no studies on other pregnancy outcomes [&lt;span&gt;1, 4, 5&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Unintentional use of semaglutide in pregnancy is rapidly increasing. Women who experience such exposure are difficult to advise due to the lack of human data. We report pregnancy and neonatal outcomes of pregnancies exposed to semaglutide based on data from a cohort of over 100 000 pregnancies.&lt;/p&gt;&lt;p&gt;The study population included all singleton pregnancies surviving the first trimester in the Central Denmark Region, which accounts for one fifth of Denmark's population. This encompassed pregnancies from a gestational age (GA) of 12 + 0/7 weeks onwards, with conception dates ranging from 1 June 2016 to 22 June 2023, regardless of foetal survival. In Denmark, there is universal access to healthcare free of charge.&lt;/p&gt;&lt;p&gt;Data were collected from the electronic charts from all hospitals in the region and linked on the individual level, including exact mother–child linkage, via a unique identifier from the Danish Civil Registration System.&lt;/p&gt;&lt;p&gt;Exposure to semaglutide (ATC A10BJ06) and/or insulin (ATC A10B) in first trimester (from the estimated conceptiondate to 70 days after, corresponding to GA 12 + 0/7), pregnancy and neonatal outcomes and informations regarding diabetes were collected from the electronic patient record.&lt;/p&gt;&lt;p&gt;Major malformations were classified according to EUROCAT classification including both prenatal (ultrasound data) and postnatal registered malformations as previously reported, with a deviation with reverse registration of congenital malformations (DQ) diagnoses found later in life (until June 2024) [&lt;span&gt;6&lt;/span&gt;]. The neonatal outcomes of respiratory distress syndrome (RDS), hypoglycemia and jaundice were identified using ICD10 codes (RDS DP220, 228, 229/hypoglycemia DP703, 704/jaundice DP550, 551, 558-560, 569, 570, 578-585, 588-593, 598, and 599). The outcomes of semaglutide-exposed pregnancies were compared to pregnancies exposed to either insulin or no diabetes medication.&lt;/p&gt;&lt;p&gt;Statistical analyses were performed with Stata (Stata Corp, College Station, TX, United States).&lt;/p&gt;&lt;p&gt;Wilcoxon ranksum test was used for numerical data and Fishers exact test for dichotomous data.&lt;/p&gt;&lt;p&gt;Access to the data was approved according to Danish legislation (Sundhedsloven §46, permission [1-45-70-88-22, 5 April 2024]), and data were stored according to the EU GDPR rules.&lt;/p&gt;&lt;p&gt;The study was conducted in accordance with the Basic &amp; Clinic","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"136 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}