Editorial: The CB2 cannabinoid system: A new strategy in neurodegenerative disorder and neuroinflammation

Editorial for Frontiers journal without abstrac

Sigma-2 Receptors as Potential Novel Biomarkers During the Progression of Benign Prostatic Hypertrophy (BPH) into Prostate Cancer

Abstract: BPH could be considered the most common benign tumor for men between 60 and 75 years of age. PSA is an unsatisfactory biomarker to define BPH progression to cancer. Recently, sigma-2 receptors have been recognized in several prostate cancer cell lines such as PC-3, DU-145 and LNCaP. It is reported that, in some cases, BPH could progress to malignancy and this progression can not easily be monitored by biomarkers such as PSA. In this paper we investigated 10 specimens from TURP, finding overexpression of sigma-2 receptors in two of these specimens (specimen 1 and 2) accompanied by 4 ng/mL PSA values. We hypothesize that the presence of sigma-2 receptors is related to a BPH progressing in prostate cancer. A possible correlation between sigma-2 receptors and PSA values could be useful to identify this pathological progression

Induced expression of P-gp and BCRP transporters on brain endothelial cells using transferrin functionalized nanostructured lipid carriers:A first step of a potential strategy for the treatment of Alzheimer's disease

P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are two transporters expressed in human neural stem/progenitor cells and at the Blood-Brain Barrier (BBB) level with decreased activity in the early stage of Alzheimer's disease (AD). Both proteins, have a protective role for the embryonic stem cells in the early developmental step, maintaining them in an undifferentiated state, and limit the access of exogenous and endogenous agents to the brain. Recently, MC111 selected from a P-gp/BCRP ligands library was investigated as multitarget strategy for AD treatment, considering its ability to induce the expression and activity of both proteins. However, MC111 clinical use could be limited for the ubiquitous physiological expression of efflux transporters and its moderate toxicity towards endothelial cells. Therefore, a selective MC111 delivery system based on nanostructured lipid carriers (NLC) functionalized with transferrin were developed. The results proved the formation of NLC with average size about 120 nm and high drug encapsulation efficiency (EE% greater than 50). In vitro studies on hCMEC/D3 cells revealed that the MC111 was selectively released by NLC at BBB level and then inducing the activity and expression of BCRP and P-gp, involved in the clearance of amyloid p peptide on brain endothelial cells

Sugar-based bactericides targeting phosphatidylethanolamine-enriched membranes

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6242839/Anthrax is an infectious disease caused by Bacillus anthracis, a bioterrorism agent that develops resistance to clinically used antibiotics. Therefore, alternative mechanisms of action remain a challenge. Herein, we disclose deoxy glycosides responsible for specific carbohydrate-phospholipid interactions, causing phosphatidylethanolamine lamellar-to-inverted hexagonal phase transition and acting over B. anthracis and Bacillus cereus as potent and selective bactericides. Biological studies of the synthesized compound series differing in the anomeric atom, glycone configuration and deoxygenation pattern show that the latter is indeed a key modulator of efficacy and selectivity. Biomolecular simulations show no tendency to pore formation, whereas differential metabolomics and genomics rule out proteins as targets. Complete bacteria cell death in 10 min and cellular envelope disruption corroborate an effect over lipid polymorphism. Biophysical approaches show monolayer and bilayer reorganization with fast and high permeabilizing activity toward phosphatidylethanolamine membranes. Absence of bacterial resistance further supports this mechanism, triggering innovation on membrane-targeting antimicrobials.The European Union is gratefully acknowledged for the support of the project “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP, GA 612347. We thank the Management Authorities of the European Regional Development Fund and the National Strategic Reference Framework for the support of the Incentive System - Research and Technological Development Co-Promotion FACIB Project number 21457. Fundação para a Ciência e a Tecnologia is also acknowledged for the support of projects UID/Multi/00612/2013, FCT/UID/ Multi/04046/2013, IF/00808/2013/CP1159/CT0003, PTDC/BBBBQB/6071/2014, as well as for the post-doc grant SFRH/BPD/42567/2007 (A.M.), the Ph.D. grants SFRH/BDE/51998/2012 (C.D.), and SFRH/BDE/51957/2012 (J.P.P.), both co-sponsored by CIPAN, and also for the Ph.D. grant SFRH/BD/116614/2016 (R.N.).info:eu-repo/semantics/publishedVersio

New Strategies to Overcome Resistance to Chemotherapy and Immune System in Cancer

MultiDrug resistance (MDR) is a complex phenomenon responsible for multiple cross-resistance towards structurally unrelated drugs and it characterizes almost 70% of solid and haematological tumours at the diagnosis [...

Editorial: Molecular modulators of GPCRs signal transduction

GPCRs; molecular modulators; oligomerization; probe design; signal transduction