Synthesis and bioevaluation of a new Ga-labelled niraparib derivative that targets PARP-1 for tumour imaging.

Poly ADP-ribose polymerase (PARP) inhibitors prevent the repair of DNA single-strand breaks in cancer cells with abnormal homologous recombination, producing a synthetic lethal effect. Thus, PARP inhibitors have become clinically effective anticancer drugs. Labelling with radionuclides may extend the use of PARP inhibitors as tracers in nuclear medicine diagnostics, helping to stratify patients.

Scoping Review: The Effects of Interrupted Onabotulinumtoxin A Treatment for Chronic Migraine Prevention During the COVID-19 Pandemic.

Objective: To systematically examine the literature on the clinical consequences of inadvertent delays in scheduled onabotulinumtoxin A (OTA) therapy for chronic migraine during the COVID-19 pandemic and assess recommendations when access to OTA is limited.

Background: The coronavirus (COVID-19) pandemic was unprecedented in its impact on the global medical community. Most healthcare institutions in the United States (US) and the world had begun significantly limiting elective procedures, undermining management of many debilitating chronic conditions.

Current Status and Perspectives of Novel Radiopharmaceuticals with Heterologous Dual-targeted Functions: 2013-2023.

Radiotracers provide molecular- and cellular-level information in a noninvasive manner and have become important tools for precision medicine. In particular, the successful clinical application of radioligand therapeutic (RLT) has further strengthened the role of nuclear medicine in clinical treatment. The complicated microenvironment of the lesion has rendered traditional single-targeted radiopharmaceuticals incapable of fully meeting the requirements.

Synthesis and Evaluation of Tc-Labeled l-Aspartic Acid as a EuK Polymer Linker for Targeting PSMA to a Novel SPECT Tumor Tracer.

The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating Tc with various coligands.

Spinal Cord Stimulator Complication Rates: A Single-Institution, 22-Year Study (1999-2021).

Background: Since the initial introduction in 1967 of spinal cord stimulation (SCS) in the field of neuromodulation, SCS has been utilized to treat a multitude of chronic pain disorders refractory to both conservative and surgical management. Although efficacious when indicated, SCS has associated risks.

Objectives: The goals of this study are to explore the trend of rates of SCS complications in 2 approximately equally sized cohorts (1999-2015 and 2016-2021) within a single institution over a 22-year period.

Development of a Novel Tc-Labeled Folate Derivative Containing Phenyl Isonitrile to Target Folate Receptor with Reduced Renal Uptake.

The folate receptor has attracted much attention in the field of radiolabeled imaging agents due to the significant difference in its expression levels between tumor cells and most normal cells. However, the development of folate-based imaging agents has been limited by their high uptake in the kidney. In this study, to reduce the high renal uptake of radiolabeled folate-based tracers, a phenyl-isonitrile folate derivative (CNMBFA) was designed and labeled with technetium-99m.

Validation of thoracolumbar injury classification and Severity Score in the management of acute and subacute Osteoporotic vertebral compression fractures - A pilot study and a suggested modification.

Objective: To retrospectively assess the Thoracolumbar Injury Classification and Severity Score (TLICS) in patients with osteoporotic vertebral compression fractures (OVCF) and compare the treatment given with that predicted by the TLICS score.

Methods: All medical records of patients presenting from January 2014 to November 2017 for acute atraumatic or low impact OVCF were screened, and eligible patients were retrospectively reviewed. The TLICS score was determined based upon magnetic resonance imaging (MRI) findings and clinical records.

Synthesis and Evaluation of Tc-Labeled Pro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many Tc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these Tc-labeled tracers is a common problem that limits their clinical application.

Novel Tc-Labeled Mannose Derivative as a Highly Promising Single Photon Emission Computed Tomography Probe for Tumor Imaging.

F-2-fluoro-2-deoxy-d-glucose ([F]FDG) has been the most used positron emission tomography imaging agent for clinical applications. Single photon emission computed tomography (SPECT) imaging is cheaper and used more widely for diagnostic use, but there is no SPECT tumor imaging agent for clinical applications comparable to [F]FDG. Mannose is a C2 epimer of glucose and can also be transported into tumor cells via glucose transporters (GLUTs).

Preparation and Evaluation of a Novel Tc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [Tc]Tc-CNPN complex with high radiochemical purity (>95%).

Geniposidic acid alleviates osteoarthritis progression through inhibiting inflammation and chondrocytes ferroptosis.

Osteoarthritis is one of the common diseases that seriously affects the quality of life of middle-aged and elderly people worldwide. Geniposidic acid (GPA) is extracted from Eucommia ulmoides that exhibits various pharmacological effects. This study investigated the function of GPA on osteoarthritis (OA) in IL-1β-stimulated mouse chondrocytes and mouse OA model.

Literature Review: Mechanism, Indications, and Clinical Efficacy of Peripheral Nerve Stimulators in Lower Extremity Pain.

Purpose Of Review: Lower extremity pain is deemed by Center for Disease Control and Prevention (CDC) to be a significant source of chronic pain in adults. If not appropriately managed, patients are subjected to risks of prolonged musculoskeletal dysfunction, disruption to quality of life, and elevated healthcare expenditures. Peripheral nerve stimulation (PNS) has shown great potential in recent years demonstrating efficacy in multiple diagnoses ranging from acute post-surgical pain to complex regional pain syndrome (CRPS).

Synthesis and Preclinical Evaluation of Novel Tc-Labeled FAPI-46 Derivatives with Significant Tumor Uptake and Improved Tumor-to-Nontarget Ratios.

Fibroblast activation protein (FAP), which is expressed on the cell membranes of fibroblasts in most solid tumors, has become an important target for tumor diagnosis and treatment. However, previously reported Tc-labeled FAPI-04 complexes have high blood uptake, limiting their use in the clinic. In this work, six Tc-labeled FAPI-46 derivatives with different linkers (different amino acids, peptides, or polyethylene glycol) were prepared and evaluated.

Radiosynthesis and Bioevaluation of Tc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging.

To develop a novel Tc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, = 5-9) with different carbon linkers were designed, synthesized and radiolabeled with the [Tc]Tc(I) core, [Tc][Tc(I)(CO)(HO)] core and [Tc][Tc(V)N] core. All the complexes are hydrophilic, maintain good stability and specifically bind in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [Tc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio.

Exosome microRNA-22 inhibiting proliferation, migration and invasion through regulating Twist1/CADM1 axis in osteosarcoma.

This study aims to the function of miR-22 original mesenchymal stem cells (MSC) on osteosarcoma (OS) proliferation, migration and invasion. Bio-informatics analysis including GEO2R analysis, Gene Ontology analysis, integration analysis were used to confirmed the target genes (miR-22, Twist1, CADM1) in OS. RT-qPCR and western blotting confirmed the different expression of miR-22, Twist1, CADM1 in OS tissues, MG63 and Saos cell lines.

Ruscogenin attenuates cartilage destruction in osteoarthritis through suppressing chondrocyte ferroptosis via Nrf2/SLC7A11/GPX4 signaling pathway.

Osteoarthritis (OA) is a common joint degenerative disease, and chondrocyte injury is the main pathological and physiological change. Ruscogenin (Rus), a bioactive compound isolated from Radix Ophiopogon japonicus, exhibits various pharmacological effects. The aim of this research was to test the role and mechanism of Rus on OA both in vivo and in vitro.

Comparative Descriptive Analysis of Physician Versus Patient-Directed Gabapentin Usage In Chronic Pain - A Preliminary Report.

Background: Gabapentin is one of the most common medications employed in Pain Medicine, specifically targeting the management of neuropathic pain. We are most familiar with the incremental dosing strategy where a ceiling dose is eventually attained guided by efficacy and patient tolerance, after which a fixed dosing regimen is prescribed. We propose that autonomous short-term dose variations per patient could have rapid clinically significant effects in the management of chronic pain.

Synthesis and Evaluation of Tc-Labelled 2-Nitroimidazole Derivatives with Different Linkers for Tumour Hypoxia Imaging.

When developing novel radiopharmaceuticals, a linker moiety between the chelator and targeting vector can have a crucial influence on adjusting the affinity of the tracer and its biodistribution in organisms. To develop novel Tc-labelled hypoxia imaging radiotracers, in this study, five isocyanide-containing 2-nitroimidazole derivatives with different linkers (L1, L2, L3, L4 and L5) were synthesised and radiolabelled with technetium-99m to obtain five stable Tc-complexes ([Tc]Tc-L1, [Tc]Tc-L2, [Tc]Tc-L3, [Tc]Tc-L4 and [Tc]Tc-L5). Corresponding rhenium analogues of [Tc]Tc-L1 were synthesised and suggested the structures of these Tc-complexes would be a monovalent cation with a technetium (I) core surrounded by six ligands.

Kukoamine A protects mice against osteoarthritis by inhibiting chondrocyte inflammation and ferroptosis via SIRT1/GPX4 signaling pathway.

Aims: Osteoarthritis (OA) is one of the common chronic degenerative joint diseases, characterized by cartilage damage, subchondral bone changes, osteophyte formation, and synovitis. Kukoamine A (KuKA) is a bioactive compound isolated from Lycium chinense which is known as its anti-inflammatory activity. In this study, we detected the regulatory role of KuKA on OA both in vivo and in vitro.

Brevilin A attenuates cartilage destruction in osteoarthritis mouse model by inhibiting inflammation and ferroptosis via SIRT1/Nrf2/GPX4 signaling pathway.

Osteoarthritis (OA) is a serious orthopedic disease that affects people's quality of life. Although there are many treatment methods, the treatment effect is still not good. Brevilin A is a bioactive compound isolated from the medicinal herbCentipeda minima.

Preparation and Bioevaluation of a Novel Tc-Labeled Glucose Derivative Containing Cyclohexane as a Promising Tumor Imaging Agent.

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [Tc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without purification, [Tc]Tc-CNMCHDG had a high radiochemical purity of over 95% and great in vitro stability and hydrophilicity (log P = -3.

A Simple Kit Formulation for Preparation and Exploratory Human Studies of a Novel Tc-Labeled Fibroblast Activation Protein Inhibitor Tracer for Imaging of the Fibroblast Activation Protein in Cancers.

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a Tc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic Tc-labeled complex ([Tc]Tc-DP-FAPI) was obtained by kit formulation.