Quantitative Biodistribution of OMVs Using SPECT/CT Imaging with HYNIC-Duramycin Radiolabeling.

Bacterial outer membrane vesicles (OMVs) are emerging as important players in the host-microbiome interaction, while also proving to be a promising platform for vaccine development and targeted drug delivery. The available methods for measuring their biodistribution, however, are limited. We aimed to establish a high-efficiency radiolabeling method for the treatment of OMVs.

Cardiovascular autonomic and peripheral sensory neuropathy in women with obesity.

Introduction: A higher incidence of neural dysfunction in people with obesity has been described. We determined the prevalence of neuropathic lesions in obese women and evaluated their potential association with anthropometric and laboratory parameters.

Patients And Methods: In our cross-sectional study, we enrolled female patients with obesity and without diabetes before obesity treatment.

Evaluation of NO and PN Emission in Relation to Actuator Control.

This study aimed to investigate the interrelationships between key harmful emission components, nitrogen oxides (NO), and particulate numbers (PNs) in diesel engine exhaust and the control actuators of diesel engines. This research involved conducting a series of experiments under fixed parameters within an engine brake laboratory environment to elucidate these correlations. The objectives of this study were to conduct a comprehensive review of the relevant emissions technology literature and a comparative assessment of particle measurement methods based on dilution ratios and develop innovative aerosol preparation principles tailored to condensation particle measurement.

Radiolabeling of Platelets with Tc-HYNIC-Duramycin for In Vivo Imaging Studies.

Following the in vivo biodistribution of platelets can contribute to a better understanding of their physiological and pathological roles, and nuclear imaging methods, such as single photon emission tomography (SPECT), provide an excellent method for that. SPECT imaging needs stable labeling of the platelets with a radioisotope. In this study, we report a new method to label platelets with Tc, the most frequently used isotope for SPECT in clinical applications.

Probing binding and occlusion of substrate in the human creatine transporter-1 by computation and mutagenesis.

In chordates, energy buffering is achieved in part through phosphocreatine, which requires cellular uptake of creatine by the membrane-embedded creatine transporter (CRT1/SLC6A8). Mutations in human slc6a8 lead to creatine transporter deficiency syndrome, for which there is only limited treatment. Here, we used a combined homology modeling, molecular dynamics, and experimental approach to generate a structural model of CRT1.

Molecular imaging of bacterial outer membrane vesicles based on bacterial surface display.

The important roles of bacterial outer membrane vesicles (OMVs) in various diseases and their emergence as a promising platform for vaccine development and targeted drug delivery necessitates the development of imaging techniques suitable for quantifying their biodistribution with high precision. To address this requirement, we aimed to develop an OMV specific radiolabeling technique for positron emission tomography (PET). A novel bacterial strain (E.

A questionnaire based survey among pharmacy practitioners to evaluate the level of knowledge and confidence towards antimicrobial stewardship.

Objective: Our study aimed to assess the knowledge, understanding and confidence of the practicing pharmacists in UAE as an antimicrobial Stewards. Antimicrobial resistance threatens the achievements of modern medicine globally, and it's highly required for the AMS principles to be implemented in our communities.

Methods: A cross-sectional online- questionnaire based survey was used among UAE pharmacy practitioners from different areas of practice who are holding pharmaceutical degrees and/or licensed pharmacists.

A questionnaire based survey among pharmacy practitioners to evaluate the level of knowledge and confidence towards antimicrobial stewardship.

Objective: Our study aimed to assess the knowledge, understanding and confidence of the practicing pharmacists in UAE as an antimicrobial Stewards. Antimicrobial resistance threatens the achievements of modern medicine globally, and it's highly required for the AMS principles to be implemented in our communities.

Methods: A cross-sectional online- questionnaire based survey was used among UAE pharmacy practitioners from different areas of practice who are holding pharmaceutical degrees and/or licensed pharmacists.

Phosphatidylinositol 4,5-bisphosphate (PIP) facilitates norepinephrine transporter dimerization and modulates substrate efflux.

The plasmalemmal norepinephrine transporter (NET) regulates cardiovascular sympathetic activity by clearing extracellular norepinephrine in the synaptic cleft. Here, we investigate the subunit stoichiometry and function of NET using single-molecule fluorescence microscopy and flux assays. In particular, we show the effect of phosphatidylinositol 4,5-bisphosphate (PIP) on NET oligomerization and efflux.

Development and Functional Characterization of a Versatile Radio-/Immunotheranostic Tool for Prostate Cancer Management.

Due to its overexpression on the surface of prostate cancer (PCa) cells, the prostate stem cell antigen (PSCA) is a potential target for PCa diagnosis and therapy. Here we describe the development and functional characterization of a novel IgG4-based anti-PSCA antibody (Ab) derivative (anti-PSCA IgG4-TM) that is conjugated with the chelator DOTAGA. The anti-PSCA IgG4-TM represents a multimodal immunotheranostic compound that can be used (i) as a target module (TM) for UniCAR T cell-based immunotherapy, (ii) for diagnostic positron emission tomography (PET) imaging, and (iii) targeted alpha therapy.

Microglia modulate blood flow, neurovascular coupling, and hypoperfusion via purinergic actions.

Microglia, the main immunocompetent cells of the brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with cells in the neurovascular unit that shape CBF in both mice and humans.

Analysis of Three-Dimensional Cell Migration in Dopamine-Modified Poly(aspartic acid)-Based Hydrogels.

Several types of promising cell-based therapies for tissue regeneration have been developing worldwide. However, for successful therapeutical application of cells in this field, appropriate scaffolds are also required. Recently, the research for suitable scaffolds has been focusing on polymer hydrogels due to their similarity to the extracellular matrix.

Occlusion of the human serotonin transporter is mediated by serotonin-induced conformational changes in the bundle domain.

The human serotonin transporter (hSERT) terminates neurotransmission by removing serotonin (5HT) from the synaptic cleft, an essential process for proper functioning of serotonergic neurons. Structures of the hSERT have revealed its molecular architecture in four conformations, including the outward-open and occluded states, and show the transporter's engagement with co-transported ions and the binding mode of inhibitors. In this study, we investigated the molecular mechanism by which the hSERT occludes and sequesters the substrate 5HT.

Sodium Binding Stabilizes the Outward-Open State of SERT by Limiting Bundle Domain Motions.

The human serotonin transporter (hSERT) removes the neurotransmitter serotonin from the synaptic cleft by reuptake into the presynaptic nerve terminal. A number of neurologic diseases are associated with dysfunction of the hSERT, and several medications for their treatment are hSERT blockers, including citalopram, fluoxetine, and paroxetine. The substrate transport is energized by the high concentration of external NaCl.

In situ lymphoma imaging in a spontaneous mouse model using the Cerenkov Luminescence of F-18 and Ga-67 isotopes.

Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.

Thermal Unfolding of the Human Serotonin Transporter: Differential Effect by Stabilizing and Destabilizing Mutations and Cholesterol on Thermodynamic and Kinetic Stability.

Folding-deficient mutants of solute carrier 6 (SLC6) family members have been linked to human diseases. The serotonin transporter [(SERT)/SLC6A4] is an important drug target in the treatment of depression, anxiety, and obsessive-compulsive disorders and-with structural information in several conformational states-one of the best understood transporters. Here, we surmised that thermal unfolding offered a glimpse on the folding energy landscape of SLC6 transporters.

(2-Aminopropyl)benzo[β]thiophenes (APBTs) are novel monoamine transporter ligands that lack stimulant effects but display psychedelic-like activity in mice.

Derivatives of (2-aminopropyl)indole (API) and (2-aminopropyl)benzofuran (APB) are new psychoactive substances which produce stimulant effects in vivo. (2-Aminopropyl)benzo[β]thiophene (APBT) is a novel sulfur-based analog of API and APB that has not been pharmacologically characterized. In the current study, we assessed the pharmacological effects of six APBT positional isomers in vitro, and three of these isomers (3-APBT, 5-APBT, and 6-APBT) were subjected to further investigations in vivo.

Digital variance angiography allows about 70% decrease of DSA-related radiation exposure in lower limb X-ray angiography.

Our aim was to investigate whether the previously observed higher contrast-to-noise ratio (CNR) and better image quality of Digital Variance Angiography (DVA) - compared to Digital Subtraction Angiography (DSA) - can be used to reduce radiation exposure in lower limb X-ray angiography. This prospective study enrolled 30 peripheral artery disease patients (mean ± SD age 70 ± 8 years) undergoing diagnostic angiography. In all patients, both normal (1.

Digital Variance Angiography in Selective Lower Limb Interventions.

Purpose: To evaluate the potential benefits of digital variance angiography (DVA) in selective lower limb angiography and to compare the performance of 2 DVA algorithms (conventional DVA1 and the recently developed DVA2) to that of digital subtraction angiography (DSA).

Materials And Methods: From November 2019 to May 2020, 112 iodinated contrast media (ICM) and 40 carbon dioxide (CO) angiograms were collected from 15 and 13 peripheral artery disease patients, respectively. The DVA files were retrospectively generated from the same unsubtracted source file as DSA.

The novel piperazino-enaminone JOAB-40 reduced colitis severity in mice via inhibition tumor necrosis factor-α and interleukin-1β.

Brief Introduction: The synthetic compound enaminone E121 has an established role as a potent anti-tussive, bronchodilator and anti-inflammatory agent in asthma, cough, and colitis induced animal models. The addition of an N-alkylated piperazine motif to the terminal end of E121 lead to the generation of various analogues such as JOAB-40. JOAB-40 was shown to be more potent than the lead compound E121 in inhibiting the expression of the chemokine receptor CCR2, ERK1/2 phosphorylation, and the release of pro-inflammatory cytokines in vitro.

Investigating the Mechanism of Sodium Binding to SERT Using Direct Simulations.

The serotonin transporter (SERT) terminates neurotransmission by transporting serotonin from the synapse into the pre-synaptic nerve terminal. Altered SERT function leads to several neurological diseases including depression, anxiety, mood disorders, and attention deficit hyperactivity disorders (ADHD). Accordingly SERT is the target for their pharmacological treatments, but also targeted by multiple drugs of abuse.

Intraperitoneal Glucose Transport to Micrometastasis: A Multimodal In Vivo Imaging Investigation in a Mouse Lymphoma Model.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes.

The safety, efficacy and pharmaceutical quality of male enhancement nutraceuticals bought online: Truth versus claim.

Objective: Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural.

The Bile Salt Export Pump: Molecular Structure, Study Models and Small-Molecule Drugs for the Treatment of Inherited BSEP Deficiencies.

The bile salt export pump (BSEP/ABCB11) is responsible for the transport of bile salts from hepatocytes into bile canaliculi. Malfunction of this transporter results in progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2) and intrahepatic cholestasis of pregnancy (ICP). Over the past few years, several small molecular weight compounds have been identified, which hold the potential to treat these genetic diseases (chaperones and potentiators).

Initial evidence of a 50% reduction of contrast media using digital variance angiography in endovascular carotid interventions.

Purpose: In previous clinical studies Digital Variance Angiography (DVA) provided higher signal-to-noise ratio (SNR) and better image quality than Digital Subtraction Angiography (DSA). Our aim was to investigate whether this quality reserve of DVA provides an opportunity for the reduction of iodinated contrast media (ICM) in carotid X-ray angiography (CXA).

Method: Our prospective study enrolled 26 patients (67.