Formyl peptide receptors in bone research.

PURPOSE/AIM OF THE STUDY: The formyl peptide receptor (FPR) participates in the immune response, with roles in infection and inflammation. In this review article, we summarize the current literature on these roles before discussing the function of FPRs in the pathogenesis of musculoskeletal disorders including osteoarthritis (OA), degenerative disc disease (DDD), and rheumatoid arthritis (RA). Additionally, we discuss the potential diagnostic and therapeutic roles of FPRs in these domains. METHODS: PubMed and Ovid MEDLINE searches were performed from 1965 through March 2022. Keywords included "FPR, tissue expression, inflammation, infection, musculoskeletal disorder, bone, rheumatoid arthritis, osteoarthritis, degenerative disc disease, mitochondria." RESULTS: Sixty-nine studies were included in this review article. FPRs appear to be ubiquitous in the pathogenesis, diagnosis, and treatment of common musculoskeletal disorders. They can potentially be utilized for the earlier diagnosis of OA and DDD. They may be employed with mesenchymal stem cells (MSCs) to reverse OA and DDD pathologies. With anti-inflammatory, anti-osteolytic, and pro-angiogenic functions, they may broaden treatment options in RA. CONCLUSIONS: FPRs appear to be heavily involved in the pathogenesis of common musculoskeletal conditions, including arthritis, degenerative disc disease, and rheumatoid arthritis. Furthermore, they demonstrate much promise in the diagnosis and treatment of these conditions. Their roles should continue to be explored.

Molecular profiling of neuroendocrine tumours to predict response and toxicity to peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) is a type of radiotherapy that targets peptide receptors and is typically used for neuroendocrine tumours (NETs). Some of the key challenges in its use are the prediction of efficacy and toxicity, patient selection, and response optimisation. In this Review, we assess current knowledge on the molecular profile of NETs and the strategies and tools used to predict, monitor, and assess the toxicity of PRRT. The few mutations in tumour genes that can be evaluated (eg, ATM and DAXX) are limited to pancreatic NETs and are most likely not informative. Assays that are transcriptomic or based on genes are effective in the prediction of radiotherapy response in other cancers. A blood-based assay for eight genes (the PRRT prediction quotient [PPQ]) has an overall accuracy of 95% for predicting responses to PRRT in NETs. No molecular markers exist that can predict the toxicity of PRRT. Candidate molecular targets include seven single nucleotide polymorphisms (SNPs) that are susceptible to radiation. Transcriptomic evaluations of blood and a combination of gene expression and specific SNPs, assessed by machine learning with algorithms that are tumour-specific, might yield molecular tools to enhance the efficacy and safety of PRRT.

Theranostic systems assembled in situ on demand by host-guest chemistry.

Theranostic systems have been explored extensively for a diagnostic therapy in the forms of polymer conjugates, implantable devices, and inorganic nanoparticles. In this work, we report theranostic systems in situ assembled by host-guest chemistry responding to a request. As a model theranostic system on demand, cucurbit[6]uril-conjugated hyaluronate (CB[6]-HA) was synthesized and decorated with FITC-spermidine (spmd) and/or formyl peptide receptor like 1 (FPRL1) specific peptide-spmd by simple mixing in aqueous solution. The resulting (FITC-spmd and/or peptide-spmd)@CB[6]-HA was successfully applied to the bioimaging of its target-specific delivery to B16F1 cells with HA receptors and its therapeutic signal transduction with elevated Ca(2+) and phosphor-extracellular signal-regulated kinase (pERK) levels in FPRL1-expressing human breast adenocarcinoma (FPRL1/MCF-7) cells. Finally, we could confirm in vitro and in vivo stability of the highly specific host-guest interaction. The on-demand theranostic platform technology using host-guest chemistry can be exploited for various bioimaging, biosensing, drug delivery, and tissue engineering applications.