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PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation.
J Nucl Med
January 2025
Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland;
Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)--(thiophen-2-ylmethyl)pyrimidin-4-amine ([C]MC1) to detect COX-2 density in a healthy human brain. The specificity of [C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents.
View Article and Find Full Text PDFReconstructing prehistoric lifeways using multi-Isotope analyses of human enamel, dentine, and bone from Legaire Sur, Spain.
PLoS One
January 2025
Archaeology, Environmental Changes and Geo-Chemistry, Vrije Universiteit Brussel, Belgium.
Megalithism has been repetitively tied to specialised herding economies in Iberia, particularly in the mountainous areas of the Basque Country. Legaire Sur, in the uplands of Álava region, is a recently excavated passage tomb (megalithic monument) that held a minimum number of 25 individuals. This study analysed the carbon, nitrogen, oxygen, and strontium isotope ratios of 18 individuals, in a multi-tissue sampling study (successional tooth enamel sampling, incremental dentine sampling, and bulk bone collagen sampling).
View Article and Find Full Text PDFAn orally available P1'-5-fluorinated M inhibitor blocks SARS-CoV-2 replication without booster and exhibits high genetic barrier.
PNAS Nexus
January 2025
Department of Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.
View Article and Find Full Text PDFConstruction of a Vero cell line expression human KREMEN1 for the development of CVA6 vaccines.
Virol J
January 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen, 361102, PR China.
Coxsackievirus A6 (CVA6) has emerged as a major pathogen causing hand, foot and mouth disease (HFMD) outbreaks worldwide. The CVA6 epidemic poses a new challenge in HFMD control since there is currently no vaccine available against CVA6 infections. The Vero cell line has been widely used in vaccine production, particularly in the preparation of viral vaccines, including poliovirus vaccines and EV71 vaccines.
View Article and Find Full Text PDFNose to brain strategy coupled to nano vesicular system for natural products delivery: Focus on synaptic plasticity in Alzheimer's disease.
J Pharm Anal
December 2024
Laboratory of Neuropharmacology, EBRI Rita Levi-Montalcini Foundation, Rome, 00161, Italy.
A wide number of natural molecules demonstrated neuroprotective effects on synaptic plasticity defects induced by amyloid-β (Aβ) in and Alzheimer's disease (AD) models, suggesting a possible use in the treatment of this neurodegenerative disorder. However, several compounds, administered parenterally and orally, are unable to reach the brain due to the presence of the blood-brain barrier (BBB) which prevents the passage of external substances, such as proteins, peptides, or phytocompounds, representing a limit to the development of treatment for neurodegenerative diseases, such as AD. The combination of nano vesicular systems, as colloidal systems, and nose to brain (NtB) delivery depicts a new nanotechnological strategy to overtake this limit and to develop new treatment approaches for brain diseases, including the use of natural molecules in combination therapy for AD.
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