Ground effect of an inverted double element wing diffuser on a sedan car.

The diffuser is a critical component in sports cars, enhancing aerodynamics by increasing downforce and reducing drag. Previous studies have focused on its dependence on diffuser incidence, height, and base pressure. The design of the car, particularly the rear end shape and the rear wing's presence, affect base pressure and the diffuser's performance.

Generative Artificial Intelligence in Patient Education: ChatGPT Takes on Hypertension Questions.

Introduction Uncontrolled hypertension significantly contributes to the development and deterioration of various medical conditions, such as myocardial infarction, chronic kidney disease, and cerebrovascular events. Despite being the most common preventable risk factor for all-cause mortality, only a fraction of affected individuals maintain their blood pressure in the desired range. In recent times, there has been a growing reliance on online platforms for medical information.

The effect of toxoplasmosis on renal function in hemodialysis patients.

Toxoplasma gondii is an obligate intracellular protozoan parasite; it spreads via the circulatory system during infection and causes chronic infection in various organs. Toxoplasmosis affects nearly one third of people worldwide, especially immunocompromised people. This study aimed to determine the effect of toxoplasmosis on renal function in hemodialysis patients.

Diagnosis of Oral in Patients under 12 Years: as a Marker of Molecular Characterization of .

has been found as the most abundant pathogenic yeast species under the group Candida-non-albicans. Despite this, it is taxonomically related to and has many of its pathogenic characteristics. Infection with is closely associated with many virulence factors encoded by multiple virulence genes.

Evaluation of some trace elements in sera of asthma patients: a case control study.

Introduction: Asthma is a chronic inflammatory disease of the airways characterized by recurrent respiratory symptoms of dyspnea, wheezing, chest tightness, and cough.

Aim: This study aims to investigate the concentrations of Cu, Zn, Mg, Mn, Fe, Cr, Ni, and Al in the serum of asthmatic patients.

Materials And Methods: An atomic absorption technique was used to determine the levels of trace elements.

The NPXXY Motif Regulates β-Arrestin Recruitment by the CB1 Cannabinoid Receptor.

Activation of signaling effectors by G-protein coupled receptors (GPCRs) depends on different molecular mechanisms triggered by conserved amino acid residues. Although studies have focused on the G-protein signaling state, the mechanism for β-arrestin signaling by CB1 is not yet well defined. Studies have indicated that transmembrane helix 7 (TMH7) and the highly conserved NPXXY motif can be subject to different conformational changes in response to biased ligands and could therefore participate in a molecular mechanism to trigger β-arrestin recruitment.

Anti-Inflammatory Properties of KLS-13019: a Novel GPR55 Antagonist for Dorsal Root Ganglion and Hippocampal Cultures.

KLS-13019, a novel devised cannabinoid-like compound, was explored for anti-inflammatory actions in dorsal root ganglion cultures relevant to chemotherapy-induced peripheral neuropathy (CIPN). Time course studies with 3 µM paclitaxel indicated > 1.9-fold increases in immunoreactive (IR) area for cell body GPR55 after 30 min as determined by high content imaging.

Contribution of G Protein-Coupled Receptor 55 to Periaqueductal Gray-Mediated Antinociception in the Inflammatory Pain.

The brain mechanism of inflammatory pain is an understudied area of research, particularly concerning the descending pain modulatory system. The G protein-coupled receptor 55 (GPR55) is a lysophosphatidylinositol-sensitive receptor that has also been involved in cannabinoid signaling. It is widely expressed throughout the central nervous system, including the periaqueductal gray (PAG), a brainstem area and key element of the descending pain modulatory system.

Nondestructive Determination of Strength of Concrete Incorporating Industrial Wastes as Partial Replacement for Fine Aggregate.

Schmidt rebound hammer test was employed in this study as a nondestructive test. This test method has been universally utilized due to its non-destructiveness for quick and easy assessment of material strength properties and quality of concrete of an existing structure. Industrial waste materials (air-dried alum sludge, treated alum sludge, limestone dust and quarry dust) were employed as replacement material for fine aggregates in this study.

Cannabinoid Cancer Biology and Prevention.

Plant-based, synthetic, and endogenous cannabinoids have been shown to control a diverse array of biological processes, including regulation of cell fate across cancers. Their promise as broad-based antitumor agents in preclinical models has led to the initiation of pilot clinical trials. Session 5 of the National Cancer Institute's Cannabis, Cannabinoids and Cancer Research Symposium provides an overview of this research topic.

CB1 Cannabinoid Receptor Signaling and Biased Signaling.

The CB1 cannabinoid receptor is a G-protein coupled receptor highly expressed throughout the central nervous system that is a promising target for the treatment of various disorders, including anxiety, pain, and neurodegeneration. Despite the wide therapeutic potential of CB1, the development of drug candidates is hindered by adverse effects, rapid tolerance development, and abuse potential. Ligands that produce biased signaling-the preferential activation of a signaling transducer in detriment of another-have been proposed as a strategy to dissociate therapeutic and adverse effects for a variety of G-protein coupled receptors.

Discovery of a Biased Allosteric Modulator for Cannabinoid 1 Receptor: Preclinical Anti-Glaucoma Efficacy.

We apply the magic methyl effect to improve the potency/efficacy of GAT211, the prototypic 2-phenylindole-based cannabinoid type-1 receptor (CB1R) agonist-positive allosteric modulator (ago-PAM). Introducing a methyl group at the α-position of nitro group generated two diastereomers, the greater potency and efficacy of , (±)- vs , (±)- constitutes the first demonstration of diastereoselective CB1R-allosteric modulator interaction. Of the (±)- enantiomers, (-)-(,)- evidenced improved potency over GAT211 as a CB1R ago-PAM, whereas (+)-(,)- was a CB1R allosteric agonist biased toward G protein- vs β-arrestin1/2-dependent signaling.

GPR55 in the brain and chronic neuropathic pain.

There is a clear need for novel and improved therapeutic strategies for alleviating chronic neuropathic pain, as well as a need for better understanding of brain mechanisms of neuropathic pain, which are less understood than spinal and peripheral mechanisms. The G protein-coupled receptor 55 (GPR55), is a lysophosphatidylinositol (LPI)-sensitive receptor that has also been involved in cannabinoid signaling. It is expressed throughout the central nervous system, including the periaqueductal gray (PAG), a brainstem area and key element of the descending pain control system.

Biodegradation of low viscosity spindle oil causing environmental pollution.

Three hydrocarbon degrading microorganisms were isolated from the soil samples collected from the storage sites of low viscosity spindle oil containers and identified on the basis of morphological and biochemical characteristics as Aeromonas hydrophila, Bacillus subtilis and Staphylococcus aureus. The study has revealed high ability of these microorganisms for oil biodegradation. The results have indicated that all isolates had the potential to breakdown the hydrocarbon.

Application of Fluorine- and Nitrogen-Walk Approaches: Defining the Structural and Functional Diversity of 2-Phenylindole Class of Cannabinoid 1 Receptor Positive Allosteric Modulators.

Cannabinoid 1 receptor (CB1R) allosteric ligands hold a far-reaching therapeutic promise. We report the application of fluoro- and nitrogen-walk approaches to enhance the drug-like properties of GAT211, a prototype CB1R allosteric agonist-positive allosteric modulator (ago-PAM). Several analogs exhibited improved functional potency (cAMP, β-arrestin 2), metabolic stability, and aqueous solubility.

Acute cocaine administration alters permeability of blood-brain barrier in freely-moving rats- Evidence using miniaturized fluorescence microscopy.

Background: Cocaine has a variety of negative effects on the central nervous system, including reports of decreased barrier function of brain microvascular endothelial cells. However, few studies have directly shown the effects of cocaine on blood-brain barrier (BBB) function in vivo. The miniature integrated fluorescence microscope (i.

GPR55-mediated effects on brain microvascular endothelial cells and the blood-brain barrier.

GPR55, an atypical cannabinoid receptor activated by lysophosphatidylinositol (LPI) has been involved in various physiological and pathological processes. We examined the effect of GPR55 activation on rat brain microvascular endothelial cells (RBMVEC), an essential component of the blood-brain barrier (BBB). GPR55 was detected in RBMVEC by western blot and immunocytochemistry.

Choline Is an Intracellular Messenger Linking Extracellular Stimuli to IP-Evoked Ca Signals through Sigma-1 Receptors.

Sigma-1 receptors (Sig-1Rs) are integral ER membrane proteins. They bind diverse ligands, including psychoactive drugs, and regulate many signaling proteins, including the inositol 1,4,5-trisphosphate receptors (IPRs) that release Ca from the ER. The endogenous ligands of Sig-1Rs are unknown.

Understanding the endocannabinoid system as a modulator of the trigeminal pain response to concussion.

Post-traumatic headache is the most common symptom of postconcussion syndrome and becomes a chronic neurological disorder in a substantial proportion of patients. This review provides a brief overview of the epidemiology of postconcussion headache, research models used to study this disorder, as well as the proposed mechanisms. An objective of this review is to enhance the understanding of how the endogenous cannabinoid system is essential for maintaining the balance of the CNS and regulating inflammation after injury, and in turn making the endocannabinoid system a potential modulator of the trigeminal response to concussion.

Effects of Platelet-Activating Factor on Brain Microvascular Endothelial Cells.

Platelet-activating factor (PAF) is a potent phospholipid mediator that exerts various pathophysiological effects by interacting with a G protein-coupled receptor. PAF has been reported to increase the permeability of the blood-brain barrier (BBB) via incompletely characterized mechanisms. We investigated the effect of PAF on rat brain microvascular endothelial cells (RBMVEC), a critical component of the BBB.

Novel analogs of PSNCBAM-1 as allosteric modulators of cannabinoid CB1 receptor.

In this work, we explored the molecular framework of the known CB1R allosteric modulator PSNCBAM-1 with the aim to generate new bioactive analogs and to deepen the structure-activity relationships of this type of compounds. In particular, the introduction of a NH group between the pyridine ring and the phenyl nucleus generated the amino-phenyl-urea derivative SN15b that behaved as a positive allosteric modulator (PAM), increasing the CB1R binding affinity of the orthosteric ligand CP55,940. The functional activity was evaluated using serum response element (SRE) assay, which assesses the CB1R-dependent activation of the MAPK/ERK signaling pathway.

Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus.

Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation.

CB and CB Receptor Pharmacology.

The CB and CB cannabinoid receptors (CBR, CBR) are members of the G protein-coupled receptor (GPCR) family that were identified over 20 years ago. CBRs and CBRs mediate the effects of Δ-tetrahydrocannabinol (Δ-THC), the principal psychoactive constituent of marijuana, and subsequently identified endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonoyl glycerol. CBRs and CBRs have both similarities and differences in their pharmacology.