Etrinabdione (VCE-004.8), a B55α activator, promotes angiogenesis and arteriogenesis in critical limb ischemia.

Background: Vasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.

AMPK Activation by Extract Ze 450 Is Associated with Metabolic Effects and Cellular Resilience against Age-Related Pathologies in Different Tissue Cell Types.

extracts (CREs) have gained well-established use for the treatment of menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical effects of CREs have been well documented, the mechanisms underlying these effects are largely unknown. More recently, the metabolic effects of the CRE Ze 450 were demonstrated in cultured cells in vitro and in mouse models of obesity in vivo.

The Cannabigerol Derivative VCE-003.2 Exerts Therapeutic Effects in 6-Hydroxydopamine-Lesioned Mice: Comparison with The Classic Dopaminergic Replacement Therapy.

(1) Background: A cannabigerol aminoquinone derivative, so-called VCE-003.2, has been found to behave as a neuroprotective agent (administered both i.p.

Open, Laparoscopic, and Robotic Approaches to Treat Colorectal Cancer: A Comprehensive Review of Literature.

Surgery is usually required to treat colorectal cancer (CRC). Medical technology has advanced, providing various approaches to tackle this disease. Different surgeries are available, such as laparoscopic surgery, single-incision laparoscopic surgery, natural orifice transluminal endoscopic surgery, and robotic surgery.

Carotid Artery Stenosis: A Look Into the Diagnostic and Management Strategies, and Related Complications.

Carotid stenosis (CS) is a buildup of atherosclerotic plaque within the artery leading to a wide range of symptoms, from mild symptoms, including blurred vision and confusion, to much more life-threatening presentations, including paralysis due to stroke. The presentation is insidious, with symptoms exhibiting predominantly at severe stenosis; hence the emphasis is placed on the importance of early diagnosis, treatment, and lifestyle modifications. CS is seen undergoing almost the same pathogenesis of any atherosclerotic plaque formation, from endothelial damage of the artery lumen to the formation of a fibrous cap with a foam cell, lipid-filled core.

VCE-005.1, an hypoxia mimetic betulinic acid derivative, induces angiogenesis and shows efficacy in a murine model of traumatic brain injury.

One of the main global causes of mortality and morbidity is traumatic brain injury (TBI). Neuroinflammation and brain-blood barrier (BBB) disruption play a pivotal role in the pathogenesis of acute and chronic TBI onset. The activation of the hypoxia pathway is a promising approach for CNS neurodegenerative diseases, including TBI.

High-performance asymmetric supercapacitor based on a CdCO/CdO/CoO composite supported on Ni foam - part II: a three-electrode electrochemical study.

A binder-free CdCO/CdO/CoO compound with a micro-cube-like morphology on a nickel foam (NF) made a facile two-step hydrothermal + annealing procedure has been developed. The morphological, structural and electrochemical behavior of both the single compounds constituting this final product and the final product itself has been studied. The synergistic contribution effect of the single compounds in the final compounded resulting specific capacitance values are presented and discussed.

Neuroprotection by the cannabidiol aminoquinone VCE-004.8 in experimental ischemic stroke in mice.

Synthetic cannabidiol (CBD) derivative VCE-004.8 is a peroxisome proliferator-activated receptor gamma (PPARγ) and cannabinoid receptor type 2 (CB) dual agonist with hypoxia mimetic activity. The oral formulation of VCE-004.

Cation Co-intercalation in Potassium Copper(II) Hexacyanoferrates.

The cation-insertion solid state electrochemistry of a potassium copper(II) hexacyanoferrate in contact with LiClO /DMSO, NaPF /DMSO, and KPF /DMSO electrolytes has been theoretically and experimentally studied using the voltammetry of immobilized particles methodology. Voltammetric data, combined with SEM/EDS analysis permit to determine a K Cu Fe [Fe Fe (CN) ] stoichiometry for the synthesized solid. Separation of electronic and ionic contributions to Gibbs energy changes can be made based on cyclic voltammetric and open circuit potential measurements.

Neuroprotective Effects of Betulinic Acid Hydroxamate in Intraventricular Hemorrhage-Induced Brain Damage in Immature Rats.

Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. We aimed to study in an IVH model in immature rats the neuroprotective effect of betulinic acid hydroxamate (BAH), a B55α/PP2A activator that inhibits the activity of the hypoxia-inducing factor prolyl-hydroxylase type 2. IVH was induced in 1-day-old (P1) Wistar rats by the left periventricular injection of Clostridial collagenase.

Cannabidiol markedly alleviates skin and liver fibrosis.

Cannabidiol (CBD) has been suggested as a potential therapy for inflammatory and fibrotic diseases. Cannabidiol was demonstrated to reduce alcohol-induced liver inflammation and steatosis but its specific activity on the fibrotic process was not investigated. Herein, the antifibrotic effects of cannabidiol in the skin were analysed using NIH-3T3 fibroblasts and human dermal fibroblasts and using the bleomycin-induced model of skin fibrosis.

Minor Phytocannabinoids: A Misleading Name but a Promising Opportunity for Biomedical Research.

Despite the very large number of phytocannabinoids isolated from Cannabis ( L.), bioactivity studies have long remained focused on the so called "Big Four" [Δ-THC (), CBD (), CBG () and CBC ()] because of their earlier characterization and relatively easy availability via isolation and/or synthesis. Bioactivity information on the chemical space associated with the remaining part of the cannabinome, a set of ca 150 compounds traditionally referred to as "minor phytocannabinoids", is scarce and patchy, yet promising in terms of pharmacological potential.

Rotational constriction of curcuminoids impacts 5-lipoxygenase and mPGES-1 inhibition and evokes a lipid mediator class switch in macrophages.

Polypharmacological targeting of lipid mediator networks offers potential for efficient and safe anti-inflammatory therapy. Because of the diversity of its biological targets, curcumin (1a) has been viewed as a privileged structure for bioactivity or, alternatively, as a pan-assay interference (PAIN) compound. Curcumin has actually few high-affinity targets, the most remarkable ones being 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase (mPGES)-1.

A cannabidiol aminoquinone derivative activates the PP2A/B55α/HIF pathway and shows protective effects in a murine model of traumatic brain injury.

Background: Traumatic brain injury (TBI) is characterized by a primary mechanical injury and a secondary injury associated with neuroinflammation, blood-brain barrier (BBB) disruption and neurodegeneration. We have developed a novel cannabidiol aminoquinone derivative, VCE-004.8, which is a dual PPARγ/CB agonist that also activates the hypoxia inducible factor (HIF) pathway.

High-performance asymmetric supercapacitor based on CdCO/CdO/CoO composite supported on Ni foam.

A CdCO/CdO/CoO composite has been prepared on nickel foam through a combined hydrothermal-annealing method. An asymmetric hybrid supercapacitor (SC) device was assembled with this composite as the positive electrode and activated carbon was the negative electrode. The SC exhibited a high specific capacitance of 84 F g @ 1 mA cm, a maximum energy density of 26.

Neuroprotective Efficacy of Betulinic Acid Hydroxamate, a B55α/PP2A Activator, in Acute Hypoxia-Ischemia-Induced Brain Damage in Newborn Rats.

There is an increasing evidence of the neuroprotective effects of hypoxia inducing factor prolyl-hydroxylase inhibitors (HIF-PHDi) after hypoxic-ischemic (HI) brain damage (HIBD). We studied the neuroprotective effects of betulinic hydroxamate (BAH), a novel B55α/PP2A activator that dephosphorylates and inhibits PHD2 activity, in a rat model of neonatal HIBD. Seven-day-old (P7) Wistar rats were exposed to hypoxia after left carotid artery electrocoagulation and then received vehicle (HI + VEH) or BAH 3 mg/kg i.

A Nrf-2 Stimulatory Hydroxylated Cannabidiol Derivative from Hemp ().

A phytochemical analysis of mother liquors obtained from crystallization of CBD from hemp (), guided by LC-MS/MS and molecular networking profiling and completed by isolation and NMR-based characterization of constituents, resulted in the identification of 13 phytocannabinoids. Among them, anhydrocannabimovone (), isolated for the first time as a natural product, and three new hydroxylated CBD analogues (1,2-dihydroxycannabidiol, , 3,4-dehydro-1,2-dihydroxycannabidiol, , and hexocannabitriol, ) were obtained. Hexocannabitriol () potently modulated, in a ROS-independent way, the Nrf2 pathway, outperforming all other cannabinoids obtained in this study and qualifying as a potential new chemopreventive chemotype against cancer and other degenerative diseases.

Functional Selectivity of Coumarin Derivates Acting via GPR55 in Neuroinflammation.

Anti-neuroinflammatory treatment has gained importance in the search for pharmacological treatments of different neurological and psychiatric diseases, such as depression, schizophrenia, Parkinson's disease, and Alzheimer's disease. Clinical studies demonstrate a reduction of the mentioned diseases' symptoms after the administration of anti-inflammatory drugs. Novel coumarin derivates have been shown to elicit anti-neuroinflammatory effects via G-protein coupled receptor GPR55, with possibly reduced side-effects compared to the known anti-inflammatory drugs.

Preclinical Investigation in Neuroprotective Effects of the GPR55 Ligand VCE-006.1 in Experimental Models of Parkinson's Disease and Amyotrophic Lateral Sclerosis.

Cannabinoids act as pleiotropic compounds exerting, among others, a broad-spectrum of neuroprotective effects. These effects have been investigated in the last years in different preclinical models of neurodegeneration, with the cannabinoid type-1 (CB) and type-2 (CB) receptors concentrating an important part of this research. However, the issue has also been extended to additional targets that are also active for cannabinoids, such as the orphan G-protein receptor 55 (GPR55).

Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells.

An emerging number of studies address the involvement of neuroinflammation and oxidative stress in the pathophysiology of central nervous system (CNS) disorders such as depression, schizophrenia, anxiety, and neurodegenerative diseases. Different cytokines and molecules, such as prostaglandin (PG) E, are associated with neuroinflammatory processes. The active acetaminophen metabolite AM404 has been shown to prevent inflammation and neuroinflammation in primary microglia and organotypic hippocampal slice cultures.

Agathadiol, a labdane diterpenoid from juniper berries, is a positive allosteric modulator of CBR.

The neutral fraction of a juniper (Juniperus communis L.) berries acetone extract could positively modulate the activity of type 1 - cannabinoid receptor (CBR). Bioactivity-directed fractionation identified the labdane diterpenoid agathadiol (4) as a positive allosteric modulator of CBR, while closely related analogues were inactive.