Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Vertebral artery–posterior inferior cerebellar artery bypass using a radial artery graft for hemorrhagic dissecting vertebral artery aneurysms: surgical technique and report of 2 cases

Endovascular occlusion of hemorrhagic dissecting aneurysms of the vertebral artery (VA) is not possible when the posterior inferior cerebellar artery (PICA) originates from the dissecting aneurysm or when the contralateral VA provides inadequate collateral blood flow to the distal basilar circulation. The authors introduce a VA-PICA bypass with radial artery interposition graft and aneurysm trapping as an alternative approach and describe 2 cases in which this bypass was used to treat hemorrhagic dissecting VA aneurysms. The VA-PICA bypass is performed via a standard far lateral approach. An end-to-side anastomosis between the radial artery graft and the PICA at the level of the caudal loop is performed first, and an end-to-side anastomosis is performed between the V(3) segment and the proximal end of the radial artery graft. A 56-year-old woman harbored a hemorrhagic dissecting VA aneurysm incorporating the origin of the PICA. Endovascular treatment failed, with aneurysm refilling on follow-up angiography. A 65-year-old man had a hemorrhagic dissecting VA aneurysm and a hypoplastic contralateral VA. Both patients were treated with the VA-PICA bypass and aneurysm trapping, with adequate filling of the PICA territory in the first patient and both the PICA territory and the basilar circulation in the second patient. Vertebral artery-PICA bypass with radial artery interposition graft and subsequent trapping of the dissected VA segment is an alternative to occipital artery-PICA and PICA-PICA bypass for the treatment of hemorrhagic dissecting VA aneurysms that are not suitable for endovascular occlusion

Distal Middle Cerebral Artery Aneurysms - Endovascular Treatment Results With Literature Review

Intracranial aneurysms of the distal intracranial arteries are uncommon lesions which are difficult to treat with surgical techniques. Distal middle cerebral artery (MCA) aneurysms constitute approximately 5% of all MCA aneurysms. We report the results of our coil embolization for the treatment of distal MCA aneurysms. Eleven patients (four men and seven women, average age 37 years) with distally located MCA aneurysms were treated. Four of the aneurysms were fusiform in shape and the remainder were saccular. Seven of the aneurysms were in the dominant hemisphere. Four of the seven patients who had saccular aneurysms were treated with selective aneurysm embolization. The remaining seven patients were treated with aneurysmal sac and parent artery coiling. All patients had good retrograde flow into the peripheral branches of the occluded artery. All the procedures were completed successfully without any additional neurological deficits. Coil embolization is a safe and effective technique for the treatment of distal MCA aneurysms. If the parent artery cannot be preserved, pial collaterals can supply adequate blood to prevent neurological deficits.Wo