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Unraveling the dynamics of B7-H3-targeting therapeutic antibodies in cancer through PET imaging and antibody pharmacokinetics.
J Control Release
January 2025
Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
B7-H3, an immunomodulatory protein overexpressed in many cancers, is associated with tumor aggressiveness and poor prognosis, making it a crucial target for imaging to elucidate its role in cancer progression and guide therapeutic interventions. This study employed PET imaging to investigate the in vivo delivery and pharmacokinetics of two anti-B7-H3 antibodies, Ab-1 and Ab-2, in mouse xenograft models with varying B7-H3 expression levels. The antibodies were radiolabeled with [Zr]Zr and evaluated through PET imaging, biodistribution studies, and in vitro assays to assess binding, tumor uptake, and retention.
View Article and Find Full Text PDFUnexpected cardiovascular risks of glucagon-like peptide-1 receptor agonist and aspirin co-administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study.
Diabetes Obes Metab
January 2025
Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan.
Aims: To examine the cardiovascular safety of combining glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D).
Materials And Methods: This propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP-1 RA plus aspirin versus those receiving GLP-1 RA alone, for both diabetic and non-diabetic individuals.
Berberine ameliorates seizure activity and cardiac dysfunction in pentylenetetrazol-kindling seizures in rats: Modulation of sigma1 receptor, Akt/eNOS signaling, and ferroptosis.
Neuropharmacology
January 2025
Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Pharmacology and Toxicology Department, Faculty of Pharmacy, King Salman International University (KSIU), South Sinai 46612, Egypt.
Seizures can lead to cardiac dysfunction. Multiple pathways contribute to this phenomenon, of which the chaperone sigma-1 receptor (S1R) signaling represents a promising nexus between the abnormalities seen in both epilepsy and ensuing cardiac complications. The study explored the potential of Berberine (BER), a promising S1R agonist, in treating epilepsy and associated cardiac abnormalities in a pentylenetetrazol (PTZ) kindling rat model of epilepsy.
View Article and Find Full Text PDFProgressive central cardiorespiratory rate downregulation and intensifying epilepsy lead to sudden unexpected death in epilepsy in mouse model of the most common human ATP1A3 mutation.
Epilepsia
January 2025
Division of Pediatric Neurology and Developmental Medicine, Department of Pediatrics, Duke University, Durham, North Carolina, USA.
Objective: This study was undertaken to test the following hypotheses in the Atp1a3 mouse (which carries the most common human ATP1A3 (the major subunit of the neuronal Na/K-adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death in epilepsy (SUDEP) occurs during seizures and is due to terminal apneas in some and due to lethal cardiac arrhythmias in others; and Atp1a3 mice have central cardiorespiratory dysregulation and abnormal respiratory drive.
Methods: Comparison was made of littermate wild-type and Atp1a3 groups using (1) simultaneous in vivo video-telemetry recordings of electroencephalogram, electrocardiogram, and breathing; (2) whole-body plethysmography; and (3) hypoglossal nerve recordings.
Results: In Atp1a3 mice, (1) SUDEP consistently occurred during seizures that were more severe than preterminal seizures; (2) seizure clustering occurred in periods preceding SUDEP; (3) slowing of breathing rate (BR) and heart rate was observed preictally before preterminal and terminal seizures; and (4) the sequence during terminal seizures was as follows: bradypnea with bradycardia/cardiac arrhythmias, then terminal apnea, followed by terminal cardiac arrhythmias.
Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.
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