A nonhuman primate model with Alzheimer's disease-like pathology induced by hippocampal overexpression of human tau.

Background: Alzheimer's disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys.

Establishing age-adjusted trabecular bone score curves using dual-energy X-ray absorptiometry in Chinese women and men: a cross-sectional study.

Background: Trabecular bone score (TBS) is a relatively new gray-level textural parameter that provides information on bone microarchitecture. TBS has been shown to be a good predictor of fragility fractures independent of bone density and clinical risk factors. Estimating the normal reference values of TBS in both sexes among the Chinese population is necessary to improve the clinical fracture risk assessment.

Age-related changes in lumbar bone mineral density measured using quantitative computed tomography in healthy female cynomolgus monkeys.

Background: Cynomolgus monkeys are widely used in studies related to osteoporosis, and there is no evidence of age-related changes in volumetric bone mineral density (vBMD) measured using quantitative computed tomography (QCT) in nonhuman primates. This study aimed to describe changes in the characteristics of lumbar vBMD with age, to analyze the relationship between lumbar vBMD and body composition, and to investigate the precision of QCT measurements in healthy female cynomolgus monkeys.

Methods: Age-related changes in lumbar vBMD were described using cubic regression models, and the accumulated bone loss rates (ABLR) of the lumbar spine were calculated.

Quantitative assessment of translocator protein (TSPO) in the non-human primate brain and clinical translation of [F]LW223 as a TSPO-targeted PET radioligand.

Objectives: Translocator protein 18 kDa (TSPO) positron emission tomography (PET) can be harnessed for the non-invasive detection of macrophage-driven inflammation. [F]LW223, a newly reported TSPO PET tracer which was insensitive to rs6971 polymorphism, showed favorable performance characteristics in a recent imaging study involving a rat myocardial infarction model. To enable quantitative neuroimaging with [F]LW223, we conducted kinetic analysis in the non-human primate (NHP) brain.

Easily automated radiosynthesis of [F]P10A-1910 and its clinical translation to quantify phosphodiesterase 10A in human brain.

Our previous work showed that [F]P10A-1910 was a potential radioligand for use in imaging phosphodiesterase 10A (PDE10A). Specifically, it had high brain penetration and specific binding that was demonstrated in both rodents and non-human primates. Here, we present the first automatic cGMP-level production of [F]P10A-1910 and translational PET/MRI study in living human brains.

Recent developments on the application of molecular probes in multiple myeloma: Beyond [F]FDG.

Multiple myeloma (MM) is a neoplastic plasma cell proliferative disorder characterized by various osteolytic bone destruction as a radiological morphological marker. Functional imaging, particularly nuclear medicine imaging, is a promising method to visualize disease processes before the appearance of structural changes by targeting specific biomarkers related to metabolism ability, tumor microenvironment as well as neoplastic receptors. In addition, by targeting particular antigens with therapeutic antibodies, immuno-PET imaging can support the development of personalized theranostics.

Discovery of a highly specific F-labeled PET ligand for phosphodiesterase 10A enabled by novel spirocyclic iodonium ylide radiofluorination.

As a member of cyclic nucleotide phosphodiesterase (PDE) enzyme family, PDE10A is in charge of the degradation of cyclic adenosine (cAMP) and guanosine monophosphates (cGMP). While PDE10A is primarily expressed in the medium spiny neurons of the striatum, it has been implicated in a variety of neurological disorders. Indeed, inhibition of PDE10A has proven to be of potential use for the treatment of central nervous system (CNS) pathologies caused by dysfunction of the basal ganglia-of which the striatum constitutes the largest component.

Positron Emission Tomography in the Neuroimaging of Autism Spectrum Disorder: A Review.

Autism spectrum disorder (ASD) is a basket term for neurodevelopmental disorders characterized by marked impairments in social interactions, repetitive and stereotypical behaviors, and restricted interests and activities. Subtypes include (A) disorders with known genetic abnormalities including fragile X syndrome, Rett syndrome, and tuberous sclerosis and (B) idiopathic ASD, conditions with unknown etiologies. Positron emission tomography (PET) is a molecular imaging technology that can be utilized for dynamic and quantitative research, and is a valuable tool for exploring pathophysiological mechanisms, evaluating therapeutic efficacy, and accelerating drug development in ASD.

Localizing Epileptic Foci Before Surgery in Patients With MRI-Negative Refractory Epilepsy Using Statistical Parameter Mapping and Three-Dimensional Stereotactic Surface Projection Based on F-FDG PET.

Patients with refractory epilepsy are not only free of seizures after resecting epileptic foci, but also experience significantly improved quality of life. Fluorine-18-fluorodeoxyglucose positron-emission tomography (F-FDG PET) is a promising avenue for detecting epileptic foci in patients with magnetic resonance imaging (MRI)-negative refractory epilepsy. However, the detection of epileptic foci by visual assessment based on F-FDG PET is often complicated by a variety of factors in clinical practice.

Recent developments on PET radiotracers for TSPO and their applications in neuroimaging.

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD).

F-Box Gene D5RF Is Regulated by Agrobacterium Virulence Protein VirD5 and Essential for Agrobacterium-Mediated Plant Transformation.

We previously reported that the virulence protein VirD5 possesses transcriptional activation activity, binds to a specific DNA element D5RE, and is required for -mediated stable transformation, but not for transient transformation. However, direct evidence for a role of VirD5 in plant transcriptional regulation has been lacking. In this study, we found that the Arabidopsis gene (coding for VirD5 response F-box protein, ) is regulated by VirD5.

Light-activatable cannabinoid prodrug for combined and target-specific photodynamic and cannabinoid therapy.

Cannabinoids are emerging as promising antitumor drugs. However, complete tumor eradication solely by cannabinoid therapy remains challenging. In this study, we developed a far-red light activatable cannabinoid prodrug, which allows for tumor-specific and combinatory cannabinoid and photodynamic therapy.

Combined CB2 receptor agonist and photodynamic therapy synergistically inhibit tumor growth in triple negative breast cancer.

Triple negative breast cancer (TNBC) is the deadliest form of breast cancer because it is more aggressive, diagnosed at later stage and more likely to develop local and systemic recurrence. Many patients do not experience adequate tumor control after current clinical treatments involving surgical removal, chemotherapy and/or radiotherapy, leading to disease progression and significantly decreased quality of life. Here we report a new combinatory therapy strategy involving cannabinoid-based medicine and photodynamic therapy (PDT) for the treatment of TNBC.

Synthesis and Evaluation of a Tetra[6,7]quinoxalinoporphyrazine-based Near Infrared Photosensitizer.

Here we report a near infrared, water-soluble, functional and dendrimeric photosensitizer (PS) based on quinoxalinoporphyrazine structure. The photophysical properties and photodynamic therapy results suggest that this quinoxalinoporphyrazine-based dendrimer may serve as an efficient near infrared (NIR) PS platform.

VirD5 is required for efficient Agrobacterium infection and interacts with Arabidopsis VIP2.

During Agrobacterium (Agrobacterium tumefaciens) infection, the translocated virulence proteins (VirD2, VirE2, VirE3, VirF and VirD5) play crucial roles. It is thought that, through protein-protein interactions, Agrobacterium uses and abuses host plant factors and systems to facilitate its infection. Although some molecular functions have been revealed, the roles of VirD5 still need to be further elucidated.

Multilayer photodynamic therapy for highly effective and safe cancer treatment.

Unlabelled: Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes.

Discovery of N-((1-(4-(3-(3-((6,7-Dimethoxyquinolin-3-yl)oxy)phenyl)ureido)-2-(trifluoromethyl)phenyl)piperidin-4-yl)methyl)propionamide (CHMFL-KIT-8140) as a Highly Potent Type II Inhibitor Capable of Inhibiting the T670I "Gatekeeper" Mutant of cKIT Kinase.

cKIT kinase inhibitors, e.g., imatinib, could induce drug-acquired mutations such as cKIT T670I that rendered drug resistance after chronic treatment.

Ex Vivo Imaging, Biodistribution, and Histological Study in Addition to In Vivo Imaging.

In addition to in vivo fluorescence imaging, ex vivo evaluations including ex vivo imaging, biodistribution, and histological study are often conducted to further investigate the biological behavior of fluorescent probes. These studies can further confirm the localization of fluorescent probes at the target sites and demonstrate the probe distribution in various organs and tissues. Such studies can also be extended to cellular level for biochemical analysis.

Before In Vivo Imaging: Evaluation of Fluorescent Probes Using Fluorescence Microscopy, Multiplate Reader, and Cytotoxicity Assays.

Fluorescent probes are widely utilized for noninvasive fluorescence imaging. Continuing efforts have been made in developing novel fluorescent probes with improved fluorescence quantum yield, enhanced target-specificity, and lower cytotoxicity. Before such probes are administrated into a living system, it is essential to evaluate the subcellular uptake, targeting specificity, and cytotoxicity in vitro.

Imaging Agents in Targeting Tumor Hypoxia.

Tissue hypoxia may occur in many diseases, specifically during the occurrence and growth of malignant solid-tumors. Targeting hypoxia is one of the most significant characteristics of tumors in diagnosis, monitoring, and treatment. This review summarizes the current oxygen-sensitive imaging agents used to target tumor hypoxia, including positron-emission computed tomography/single photon-emission computed tomography radionuclide labeled tracers, magnetic resonance imaging contrast agents for hypoxia detection, and hypoxia-sensitive optical imaging probes.

Tumor mitochondria-targeted photodynamic therapy with a translocator protein (TSPO)-specific photosensitizer.

Unlabelled: Photodynamic therapy (PDT) has been proven to be a minimally invasive and effective therapeutic strategy for cancer treatment. It can be used alone or as a complement to conventional cancer treatments, such as surgical debulking and chemotherapy. The mitochondrion is an attractive target for developing novel PDT agents, as it produces energy for cells and regulates apoptosis.

Synthesis of a reactive oxygen species responsive heterobifunctional thioketal linker.

A new heterobifunctional reactive oxygen species (ROS) responsive thioketal linker and its synthesis are described. This linker allows for developing new ROS-responsive agents with two distinct functionalities using universal bioconjugation methods. The reaction kinetics of the thioketal cleavage in the presence of ROS is also described.

In vivo inflammation imaging using a CB2R-targeted near infrared fluorescent probe.

Chronic inflammation is considered as a critical cause of a host of disorders, such as cancer, rheumatoid arthritis, atherosclerosis, and neurodegenerative diseases, although the exact mechanism is yet to be explored. Imaging tools that can specifically target inflammation are therefore important to help reveal the role of inflammation in disease progression, and allows for developing new therapeutic strategies to ultimately improve patient care. The purpose of this study was to develop a new in vivo inflammation imaging approach by targeting the cannabinoid receptor type 2 (CB2R), an emerging inflammation biomarker, using a unique near infrared (NIR) fluorescent probe.

A novel near-infrared fluorescence imaging probe that preferentially binds to cannabinoid receptors CB2R over CB1R.

The type 2 cannabinoid receptors (CB2R) have gained much attention recently due to their important regulatory role in a host of pathophysiological processes. However, the exact biological function of CB2R and how this function might change depending on disease progression remains unclear and could be better studied with highly sensitive and selective imaging tools for identifying the receptors. Here we report the first near infrared fluorescence imaging probe (NIR760-XLP6) that binds preferentially to CB2R over the type 1 cannabinoid receptors (CB1R).