scholarly journals CRANAD-28: A Robust Fluorescent Compound for Visualization of Amyloid Beta Plaques

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 863 ◽  
Author(s):  
Kathleen Ran ◽  
Jing Yang ◽  
Anil V. Nair ◽  
Biyue Zhu ◽  
Chongzhao Ran
Keyword(s):  
Amyloid Beta ◽  
Ex Vivo ◽  
Significant Negative Correlation ◽  
Future Research ◽  
Fluorescent Compound ◽  
Number Count ◽  
Interesting Insight ◽  
Imaging Tool ◽  
Low Toxicity

CRANAD-28, a difluoroboron curcumin analogue, has been demonstrated in earlier reports to successfully label amyloid beta (Aβ) plaques for imaging both ex vivo and in vivo. CRANAD-28’s imaging brightness, ability to penetrate the blood brain barrier, and low toxicity make the compound a potentially potent imaging tool in Alzheimer’s research. In this study, the Aβ-labeling ability of CRANAD-28 was investigated in further detail using histological staining to assess different criteria, including stained Aβ plaque brightness, Aβ plaque size, and Aβ plaque number count. The results of this study demonstrated CRANAD-28 to be superior across all criteria assessed. Furthermore, CRANAD-28 and IBA-1 antibody were used to label Aβ-plaques and microglia respectively. Statistical analysis with Spearman regression revealed a statistically significant negative correlation between the size of labeled Aβ plaques and surrounding microglia density. This finding provides interesting insight into Aβ plaque and microglia dynamism in AD pathology and corroborates the findings of previous studies. In addition, we found that CRANAD-28 provided distinct spectral signatures for Aβs in the core and periphery of the plaques. Based on the study’s results, CRANAD-28 could be considered as an alternative standard for imaging Aβ-plaques in future research studies.

scholarly journals Effect of Processing on Fish Protein Antigenicity and Allergenicity

Foods ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 969
Author(s):  
Xingyi Jiang ◽  
Qinchun Rao
Keyword(s):  
Fish Species ◽  
Protein Denaturation ◽  
Ex Vivo ◽  
Protein Solubility ◽  
Future Research ◽  
Food Protein ◽  
In Vivo Evaluation ◽  
Fish Allergy

Fish allergy is a life-long food allergy whose prevalence is affected by many demographic factors. Currently, there is no cure for fish allergy, which can only be managed by strict avoidance of fish in the diet. According to the WHO/IUIS Allergen Nomenclature Sub-Committee, 12 fish proteins are recognized as allergens. Different processing (thermal and non-thermal) techniques are applied to fish and fishery products to reduce microorganisms, extend shelf life, and alter organoleptic/nutritional properties. In this concise review, the development of a consistent terminology for studying food protein immunogenicity, antigenicity, and allergenicity is proposed. It also summarizes that food processing may lead to a decrease, no change, or even increase in fish antigenicity and allergenicity due to the change of protein solubility, protein denaturation, and the modification of linear or conformational epitopes. Recent studies investigated the effect of processing on fish antigenicity/allergenicity and were mainly conducted on commonly consumed fish species and major fish allergens using in vitro methods. Future research areas such as novel fish species/allergens and ex vivo/in vivo evaluation methods would convey a comprehensive view of the relationship between processing and fish allergy.

scholarly journals Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET

2021 ◽  
Vol 22 (4) ◽  
pp. 1645
Author(s):  
Daniel Gündel ◽  
Masoud Sadeghzadeh ◽  
Winnie Deuther-Conrad ◽  
Barbara Wenzel ◽  
Paul Cumming ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ex Vivo ◽  
Specific Binding ◽  
Monocarboxylate Transporters ◽  
Binding Potential ◽  
Kidney Cortex ◽  
Binding Studies ◽  
Imaging Tool ◽  
Pre Treatment

The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [18F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [18F]FACH in healthy mice and piglets. We measured the [18F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [18F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a KD of 118 ± 12 nM and Bmax of 6.0 pmol/mg wet weight. The specificity of [18F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC0–60min after pre-treatment with α-CCA-Na in mice (−47%) and in piglets (−66%). [18F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [18F]FACH binding potential (BPND) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [18F]FACH uptake was confirmed by displacement studies in 4T1 cells. [18F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

scholarly journals Non-Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo

2020 ◽  
Author(s):  
Ozgun Kocabiyik ◽  
Valeria Cagno ◽  
Paulo Jacob Silva ◽  
Yong Zhu ◽  
Laura Sedano ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Ex Vivo ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
New Class ◽  
Influenza Strain ◽  
Low Toxicity

AbstractInfluenza is one of the most widespread viral infections worldwide and represents a major public health problem. The risk that one of the next pandemics is caused by an influenza strain is very high. It is very important to develop broad-spectrum influenza antivirals to be ready for any possible vaccine shortcomings. Anti-influenza drugs are available but they are far from ideal. Arguably, an ideal antiviral should target conserved viral domains and be virucidal, i.e. irreversibly inhibit viral infectivity. Here, we describe a new class of broad-spectrum anti-influenza macromolecules that meets these criteria and displays exceedingly low toxicity. These compounds are based on a cyclodextrin core modified on its primary face with long hydrophobic linkers terminated in 6’sialyl-N-acetyllactosamine (6’SLN) or 3’SLN. SLN enables nanomolar inhibition of the viruses while the hydrophobic linkers confer irreversibility to the inhibition. The combination of these two properties allows for efficacy in vitro against several human or avian influenza strains, as well as against a 2009 pandemic influenza strain ex vivo. Importantly, we show that, in mice, the compounds provide therapeutic efficacy when administered 24h post-infection allowing 90% survival as opposed to no survival for the placebo and oseltamivir..

scholarly journals Brain mGluR5 in mice with amyloid beta pathology studied with in vivo [11C]ABP688 PET imaging and ex vivo immunoblotting

2017 ◽  
Vol 113 ◽  
pp. 293-300 ◽  
Author(s):  
Xiaotian T. Fang ◽  
Jonas Eriksson ◽  
Gunnar Antoni ◽  
Ulrika Yngve ◽  
Linda Cato ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Pet Imaging ◽  
Ex Vivo

scholarly journals Adenosine A2AReceptors in Substance Use Disorders: A Focus on Cocaine

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1372 ◽  
Author(s):  
Karolina Wydra ◽  
Dawid Gawliński ◽  
Kinga Gawlińska ◽  
Małgorzata Frankowska ◽  
Dasiel O. Borroto-Escuela ◽  
...  
Keyword(s):  
Substance Use ◽  
Substance Use Disorders ◽  
Current Knowledge ◽  
Ex Vivo ◽  
D2 Receptors ◽  
Future Research ◽  
Receptor Complexes ◽  
Abused Drugs ◽  
The Brain

Several psychoactive drugs can evoke substance use disorders (SUD) in humans and animals, and these include psychostimulants, opioids, cannabinoids (CB), nicotine, and alcohol. The etiology, mechanistic processes, and the therapeutic options to deal with SUD are not well understood. The common feature of all abused drugs is that they increase dopamine (DA) neurotransmission within the mesocorticolimbic circuitry of the brain followed by the activation of DA receptors. D2 receptors were proposed as important molecular targets for SUD. The findings showed that D2 receptors formed heteromeric complexes with other GPCRs, which forced the addiction research area in new directions. In this review, we updated the view on the brain D2 receptor complexes with adenosine (A)2A receptors (A2AR) and discussed the role of A2AR in different aspects of addiction phenotypes in laboratory animal procedures that permit the highly complex syndrome of human drug addiction. We presented the current knowledge on the neurochemical in vivo and ex vivo mechanisms related to cocaine use disorder (CUD) and discussed future research directions for A2AR heteromeric complexes in SUD.

scholarly journals Endomicroscopy of the Pancreaticobiliary System

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Shajan Peter ◽  
Ji Young Bang ◽  
Klaus Mönkemuller ◽  
Shyam Varardarajulu ◽  
C. Mel Wilcox
Keyword(s):  
Imaging Techniques ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Future Research ◽  
Imaging Tool ◽  
Long Term Impact ◽  
Improved Accuracy ◽  
Precise Interpretation

It is often difficult to accurately differentiate between benign and malignant pancreaticobiliary strictures, and some are interpreted as indeterminate despite ERCP, EUS, or radiological imaging techniques, thereby making it difficult for the clinician to make appropriate management decisions. Probe-based confocal laser endomicroscopy (pCLE) is an innovative imaging tool integrating real-time in vivo imaging of these difficult-to-interpret strictures in the pancreaticobiliary system during endoscopy. Recent studies of endomicroscopy have shown a promising role with improved accuracy in distinguishing these lesions, thus paving the way for future research addressing improving precise interpretation, training, and long long-term impact.

scholarly journals FLAME: Macroscopic imaging with microscopic resolution. Optical biopsy of human skin

2020 ◽  
Author(s):  
Alexander Fast ◽  
Akarsh Lal ◽  
Amanda F. Durkin ◽  
Christopher B. Zachary ◽  
Anand K. Ganesan ◽  
...  
Keyword(s):  
Human Skin ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Counting ◽  
Optical Biopsy ◽  
Large Area ◽  
Time Resolved ◽  
Distribution Maps ◽  
Imaging Tool

AbstractWe introduce a compact, fast large area multiphoton exoscope (FLAME) system with enhanced molecular contrast for macroscopic imaging of human skin with microscopic resolution. A versatile imaging platform with multiple modes of operation for comprehensive analysis of live or resected thick human skin tissue, it produces 3D images that encompass sub-mm2 to cm2 scale areas of tissue within minutes. The FLAME imaging platform, which expands on a design recently introduced by our group, features deep learning, additional scanning hardware elements and time-resolved single photon counting detection to uniquely allow fast discrimination and 3D virtual staining of melanin. We demonstrate its performance and utility by fast ex vivo and in vivo imaging of human skin. With the ability to provide rapid access to depth resolved images of skin over cm2 area and to generate 3D distribution maps of key sub-cellular skin components such as melanocytic dendrites and melanin, FLAME represents a promising imaging tool for enhancing diagnosis accuracy, guiding therapy and understanding skin biology.

scholarly journals Nanotechnology Approaches for Chloroplast Biotechnology Advancements

2021 ◽  
Vol 12 ◽  
Author(s):  
Gregory M. Newkirk ◽  
Pedro de Allende ◽  
Robert E. Jinkerson ◽  
Juan Pablo Giraldo
Keyword(s):  
Synthetic Biology ◽  
Plant Species ◽  
Targeted Delivery ◽  
Current Knowledge ◽  
Ex Vivo ◽  
Future Research ◽  
Agricultural Field ◽  
Diverse Plant Species ◽  
Diverse Plant

Photosynthetic organisms are sources of sustainable foods, renewable biofuels, novel biopharmaceuticals, and next-generation biomaterials essential for modern society. Efforts to improve the yield, variety, and sustainability of products dependent on chloroplasts are limited by the need for biotechnological approaches for high-throughput chloroplast transformation, monitoring chloroplast function, and engineering photosynthesis across diverse plant species. The use of nanotechnology has emerged as a novel approach to overcome some of these limitations. Nanotechnology is enabling advances in the targeted delivery of chemicals and genetic elements to chloroplasts, nanosensors for chloroplast biomolecules, and nanotherapeutics for enhancing chloroplast performance. Nanotechnology-mediated delivery of DNA to the chloroplast has the potential to revolutionize chloroplast synthetic biology by allowing transgenes, or even synthesized DNA libraries, to be delivered to a variety of photosynthetic species. Crop yield improvements could be enabled by nanomaterials that enhance photosynthesis, increase tolerance to stresses, and act as nanosensors for biomolecules associated with chloroplast function. Engineering isolated chloroplasts through nanotechnology and synthetic biology approaches are leading to a new generation of plant-based biomaterials able to self-repair using abundant CO2 and water sources and are powered by renewable sunlight energy. Current knowledge gaps of nanotechnology-enabled approaches for chloroplast biotechnology include precise mechanisms for entry into plant cells and organelles, limited understanding about nanoparticle-based chloroplast transformations, and the translation of lab-based nanotechnology tools to the agricultural field with crop plants. Future research in chloroplast biotechnology mediated by the merging of synthetic biology and nanotechnology approaches can yield tools for precise control and monitoring of chloroplast function in vivo and ex vivo across diverse plant species, allowing increased plant productivity and turning plants into widely available sustainable technologies.

scholarly journals Teicoplanin potently blocks the cell entry of 2019-nCoV

2020 ◽  
Author(s):  
Junsong Zhang ◽  
Xiancai Ma ◽  
Fei Yu ◽  
Jun Liu ◽  
Fan Zou ◽  
...  
Keyword(s):  
Virus Infection ◽  
Ebola Virus ◽  
Ex Vivo ◽  
Cathepsin L ◽  
Specific Treatment ◽  
Inhibitory Effect ◽  
Cell Entry ◽  
The Public ◽  
Low Toxicity

AbstractSince December 2019, the outbreak of a new coronavirus, named 2019-nCoV, has greatly threatened the public health in China and raised great concerns worldwide. No specific treatment for this infection is currently available. We previously reported that teicoplanin, a glycopeptide antibiotic which has routinely been used in the clinic to treat bacterial infection with low toxicity, significantly inhibits the invasion of cells by Ebola virus, SARS-CoV and MERS-CoV, via specifically inhibiting the activity of cathepsin L. Here, we tested the efficacy of teicoplanin against 2019-nCoV virus infection and found that teicoplanin potently prevents the entrance of 2019-nCoV-Spike-pseudoviruses into the cytoplasm, with an IC50 of 1.66 μM. Although the inhibitory effect upon the replication of wildtype viruses ex vivo and in vivo remains to be determined, our preliminary result indicates that the potential antiviral activity of teicoplanin could be applied for the treatment of 2019-nCoV virus infection.

scholarly journals Increased soluble amyloid-beta causes early aberrant brain network hypersynchronisation in a mature-onset mouse model of amyloidosis

2019 ◽  
Author(s):  
Inès R.H. Ben-Nejma ◽  
Aneta J. Keliris ◽  
Jasmijn Daans ◽  
Peter Ponsaerts ◽  
Marleen Verhoye ◽  
...  
Keyword(s):  
Mouse Model ◽  
Postnatal Development ◽  
Amyloid Beta ◽  
Resting State ◽  
Ex Vivo ◽  
Fold Increase ◽  
Brain Network ◽  
Resting State Networks ◽  
The Impact

ABSTRACTBackgroundAlzheimer’s disease (AD) is the most common form of dementia in the elderly population. Currently, no effective cure is available for AD. According to the amyloid hypothesis, the accumulation and deposition of the amyloid-beta (Aβ) peptides plays a key role in AD pathology. Soluble Aβ (sAβ) oligomers were shown to be synaptotoxic and involved in pathological hypersynchronisation of brain resting-state networks in different transgenic developmental-onset mouse models of amyloidosis. However, the impact of protein overexpression during brain postnatal development may cause additional phenotypes unrelated to AD. To address this concern, we investigated sAβ effects on functional resting-state networks in transgenic mature-onset amyloidosis Tet-Off APP (TG) mice.MethodsTG mice and control littermates were raised on doxycycline (DOX) diet from 3d up to 3m of age to suppress transgenic Aβ production. Thereafter, longitudinal resting-state functional MRI was performed on a 9.4T MR-system starting from week 0 (3m old mice) up to 28w post DOX treatment. Ex vivo immunohistochemistry and ELISA analysis (additional mice cohort) was performed to address the development of amyloid pathology.ResultsFunctional Connectivity (FC) analysis demonstrated early abnormal hypersynchronisation in the TG mice compared to the controls at 8w post DOX treatment. This effect was observed particularly across regions of the default mode-like network, known to be affected in AD. Ex vivo analyses performed at this time point confirmed a 20-fold increase in total sAβ levels and the absence of Aβ plaques in the TG mice compared to the controls. On the contrary at week 28, TG mice showed an overall hypoconnectivity, coinciding with a widespread deposition of Aβ plaques in the brain.ConclusionsBy preventing developmental influence of APP and/or sAβ during brain postnatal development, we demonstrated FC abnormalities driven by sAβ synaptotoxicity on resting state neuronal networks in mature-induced TG mice. Thus, the Tet-Off APP mouse model could be a powerful tool while used as a mature-onset model to shed light into amyloidosis mechanisms in AD. Therefore, this inducible APP expression model used in combination with early non-invasive in vivo rsfMRI readout for sAβ synaptotoxicity sets the stage for future Aβ targeting preventative treatment studies.

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