A molecular explanation of cardiovascular protection through abnormal cannabidiol: Involving the dysfunctional ß-adrenergic and ATP-sensitive K+ channel activity in cardiovascular compromised preterm infants.

Growing cannabis efficacy, usage frequency, legal supply, and declining awareness of danger recently led to expanded United States cannabis exposure. In turn, cannabis use among elderly people over 50 has more than tripled in a decade and has contributed toward a positive association of cannabis use with pathological conditions, which include type II diabetes, metabolic syndrome, neurovascular and cardiovascular disease. Remarkably, all these outcome results are mediated by the involvement of the ATP-sensitive K+ channel. Cardiovascular compromise is a common syndrome in preterm infants that leads to incidence and death and has been distinguished by poor systemic flow or hypotension. Conditions of cardiovascular compromise include vasodysregulation and myocardial malfunction through dysfunctional ß-adrenergic activity. To avoid organ hypoperfusion progressing to tissue hypoxia-ischemia, inotropic drugs are used. Many premature children, however, respond insufficiently to inotropic activity with adrenergic agonists. The clinical disturbance including myocardial dysfunction through the activation of the ATP-sensitive K+ channel is often involved and the comparative efficacy of the nonpsychotropic cannabinoid, abnormal cannabidiol (Abn-CBD) is not yet known. Therefore, our primary aim was to investigate the molecular exploration of the cannabinoid system specifically Abn-CBD in cardiovascular protection involving dysregulated KATP.

The emerging potential of SIRT-3 in oxidative stress-inflammatory axis associated increased neuroinflammatory component for metabolically impaired neural cell.

People suffering from conditions like epilepsy, where there is an excess of neuron excitement, stroke, and cardiac arrest, where there are oxygen and glucose deprivation, Alzheimer, Parkinson, and Huntington's disease that causes metabolic and also oxidative stress-inflammatory axis; are known to be more vulnerable to disturbances in the metabolism, and there is a lot of inadequacy in defining the inflammation's mechanistic connections, as well as neurodegeneration and the bioenergetic deficiencies in the CNS. We retrieved relevant studies from PubMed/ScienceDirect/Medline/Public library of science/Mendeley/Springer link as well as Google Scholar. We used various keywords both individually and in combination with the literature search. 'Epidemiology of neurodegenerative disorders', 'neurodegenerative diseases associated hyper inflammation', 'Mechanism of inflammation in neuronal cell', 'Involvement of SIRTin inflammation', 'Pathogenesis of mitochondrial associated metabolic impairment in neurons', 'Reactive oxygen species-mediated mitochondrial dysfunction' were a few of the keywords used for the search. PINCH, which is a chronic neuro-inflammatory component that cannot be detected in matured neurons which are healthy, though expressed in oxidative stress inflammatory axis related tauopathy and diseases that cause neurodegeneration. We attempted to study the regulatory mechanisms that cause changes in the bioenergetics and its neuronal defects and mitochondrial subcellular localization that are PINCH protein-mediated on the other handSIRT1, the most intensively studied sirtuin, in oxidative stress-mediated inflammatory consequence for many diseases but very few research data explore the role of SIRT-3 for correction of the chronic neuroinflammatory component. Thus, in this review, we investigate the very recently identified molecules involving in the pathogenesis during stimulated oxidative stress-inflammatory axis in the excitatory neuronal cell which changes brain metabolism. Simultaneously, in CNS neurons of diseases with a component of chronic neuroinflammation which exhibit neuroprotective response, the consequences (mechanistic and biological) of SIRT-3, could be emerging future targets for neurodegenerative disorder treatment with impaired metabolisms.

Vardenafil and cilostazol can improve vascular reactivity in rats with diabetes mellitus and rheumatoid arthritis co-morbidity.

Endothelial dysfunction and vascular reactivity defects secondary to metabolic and immunological disorders carry risk of serious cardiovascular complications. Here, the effects of the phosphodiesterase (PDE) inhibitors vardenafil and cilostazol were examined against rheumatoid arthritis (RA)/diabetes mellitus (DM)-co-morbidity-induced endothelial dysfunction and vascular reactivity defects. After setting of RA/DM-co-morbidity model, rats were divided into a normal control group, an RA/DM-co-morbidity group, and two treatment groups receiving oral vardenafil (10 mg/kg/day) and cilostazol (30 mg/kg/day) for 21 days after RA/DM-co-morbidity induction. Aorta was isolated for biochemical estimations of the pro-inflammatory vasoconstrictor molecules angiotensin-II (Ang-II) and endothelin-1 (ET-1), the adhesion molecules P-selectin and vascular cell adhesion molecule-1 (VCAM-1), the energy sensor adenosine-5'-monophosphate-activated protein kinase (AMPK), and the vasodilator anti-inflammatory molecule vasoactive intestinal peptide (VIP) using enzyme-linked immunosorbent assay (ELISA) and western blot analysis. Immunohistochemical estimations of endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 were performed coupled with histopathological examination using routine hematoxylin and eosin (H&E) and special Masson trichrome staining. The in vitro study was conducted using aortic strips where cumulative concentration response curves were done for the endothelium-dependent relaxing factor acetylcholine and the endothelium-independent relaxing factor sodium nitroprusside after submaximal contraction with phenylephrine. Vardenafil and cilostazol significantly improved endothelial integrity biomarkers in vivo supported with histopathological findings in addition to improved vasorelaxation in vitro. Apart from their known PDE inhibition, up-regulation of vascular AMPK and eNOS coupled with down-regulation of Ang-II, ET-1, P-selectin, VCAM-1 and MMP-2 may explain vardenafil and cilostazol protective effect against RA/DM-co-morbidity-induced endothelial dysfunction and vascular reactivity defects.