Polypropylene nanoplastic exposure leads to lung inflammation through p38-mediated NF-κB pathway due to mitochondrial damage.

Background: Polypropylene (PP) is used in various products such as disposable containers, spoons, and automobile parts. The disposable masks used for COVID-19 prevention mainly comprise PP, and the disposal of such masks is concerning because of the potential environmental pollution. Recent reports have suggested that weathered PP microparticles can be inhaled, however, the inhalation toxicology of PP microparticles is poorly understood.

Chalcones and Five-Membered Heterocyclic Isosteres Bind to Alpha Synuclein Fibrils in Vitro.

A series of chalcone and heterocyclic isosteres, in which the enone moiety was replaced with an isoxazole and pyrazole ring system, was synthesized and their affinities for alpha synuclein (Asyn), amyloid beta (Aβ), and tau fibrils were measured in vitro. The compounds were found to have a modest affinity and selectivity for Asyn versus Aβ fibrils and low affinity for tau fibrils. Insertion of a double bond to increase the extendable surface area resulted in an increase in affinity and improvement in selectivity for Asyn versus Aβ and tau fibrils.

Alpha Synuclein Fibrils Contain Multiple Binding Sites for Small Molecules.

The fibrillary aggregation of the protein alpha synuclein (Asyn) is a hallmark of Parkinson's disease, and the identification of small molecule binding sites on fibrils is essential to the development of diagnostic imaging probes. A series of molecular modeling, photoaffinity labeling, mass spectrometry, and radioligand binding studies were conducted on Asyn fibrils. The results of these studies revealed the presence of three different binding sites within fibrillar Asyn capable of binding small molecules with moderate to high affinity.

Bacterial infection imaging with [F]fluoropropyl-trimethoprim.

There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [F]fluoropropyl-trimethoprim, or [F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (, , and ) relative to controls.

Quantitative PET Reporter Gene Imaging with [C]Trimethoprim.

There is a need for improved methods to image genetically engineered cells, including immune cells used for cell-based therapy. Given the genetic manipulation inherent to gene therapy, the use of a reporter protein is a logical solution and positron emission tomography (PET) can provide the desired sensitivity and spatial localization. We developed a broadly applicable PET imaging strategy based on the small bacterial protein E.

Dexmedetomidine for sedation in pediatric patients who received more than 20 sessions of radiation therapy: two cases report.

Dexmedetomidine is a highly selective α-adrenoceptor agonist that demonstrates anxiolytic and analgesic properties without inducing respiratory compromise, which makes it a suitable agent for procedural sedation and imaging studies. In our current case reports, intravenous dexmedetomidine infusion was used to provide sedation to 2 pediatric patients over more than 20 sessions of radiation therapy. On both occasions, dexmedetomidine provided adequate sedation without respiratory depression.

Comparative evaluation of 4 and 6-carbon spacer conformationally flexible tetrahydroisoquinolinyl benzamide analogues for imaging the sigma-2 receptor status of solid tumors.

Introduction: Nine novel analogues were synthesized including a 6-carbon spacer analogue of ISO-1 (7). They have moderate binding affinity for sigma-2 (σ) receptors and high selectivity for σ receptors relative to sigma-1 (σ) receptors.

Methods: ([F]7) was synthesized and evaluated as a candidate ligand for positron emission (PET) imaging of the σ receptor in tumors.

Evaluation of the angiogenesis inhibitor KR-31831 in SKOV-3 tumor-bearing mice using (64)Cu-DOTA-VEGF(121) and microPET.

KR-31831 ((2R,3R,4S)-6-amino-4-[N-(4-chloropheyl)-N-(1H-imidazol-2ylmethyl)amino]-3-hydroxyl-2-methyl-2-dimethoxymethyl-3,4-dihydro-2H-1-benzopyran), an angiogenesis inhibitor, was evaluated in tumor-bearing mice using molecular imaging technology. Pre-treatment microPET images were acquired on SKOV-3 cell-implanted nude mice after injection with (64)Cu-DOTA-VEGF(121). KR-31831 (50 mg/kg) was then injected intraperitoneally into the treatment group (n=3), while injection vehicle was injected into the control (n=4) and blocking (n=3) groups.

Synthesis and evaluation of ¹⁸F-labeled styryltriazole and resveratrol derivatives for β-amyloid plaque imaging.

In the present study, a styryltriazole and four resveratrol derivatives were synthesized as candidates for β-amyloid (Aβ) plaque imaging. On the basis of their binding affinities to Aβ(1-42) aggregates, the styryltriazole (1, K(i) = 12.8 nM) and one resveratrol derivative (5, K(i) = 0.

Synthesis and evaluation of 1-(4-[¹⁸F]fluoroethyl)-7-(4'-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging.

Alzheimer's disease is characterized by the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed [(18)F]fluoropropylcurcumin ([(18)F]FP-curcumin), which demonstrated excellent binding affinity (K(i)=0.07 nM) for Aβ(1-40) aggregates and good pharmacokinetics in normal mouse brains.

16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium.

We synthesized 16-cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid (99mTc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.

2-[methyl-(11)C]methoxyestradiol: synthesis, evaluation and pharmacokinetics for in vivo studies on angiogenesis.

2-Methoxyestradiol (1) is an endogenous metabolite of estradiol that has been shown to inhibit cell proliferation and angiogenesis. In this study, 2-[methyl-(11)C]methoxyestradiol ([(11)C]1) was synthesized and evaluated for in vivo studies on angiogenesis. Radiotracer [(11)C]1 was synthesized at a decay-corrected radiochemical yield of 25-34% from [(11)C]CH(3)I with a specific activity of 34-38 GBq/micromol.

Synthesis and evaluation of radioiodine-labelled CP-118,954 for the in-vivo imaging of acetylcholinesterase.

Objectives: Alzheimer's disease (AD) is characterized by reduced acetylcholinesterase (AChE) activity in the post-mortem tissues of AD patients. Therefore, AChE has been an attractive target for the diagnosis of AD. In the present study, 5,7-dihydro-3-[2-(1-(phenylmethyl)-4-piperidinyl)ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one (CP-118,954), a potent AChE inhibitor, was labelled with radioiodine and evaluated as an AChE imaging agent for SPECT.