esearch consolidates its efficacy.Introduction The sigma-1 receptor (S1R) is attracting much attention for disease-modifying therapies in neurodegenerative diseases. It is a conserved protein, present in plasma and endoplasmic reticulum (ER) membranes and enriched in mitochondria-associated ER membranes (MAMs). It modulates ER-mitochondria Ca2+ transfer and ER stress pathways. Mitochondrial and MAM dysfunctions contribute to neurodegenerative processes in diseases such as Alzheimer, Parkinson, Huntington or Amyotrophic Lateral Sclerosis. Interestingly, the S1R can be activated by small druggable molecules and accumulating preclinical data suggest that S1R agonists are effective protectants in these neurodegenerative diseases.Area covered In this review, we will present the data showing the high therapeutic potential of S1R drugs for the treatment of neurodegenerative diseases, focusing on pridopidine as a potent and selective S1R agonist under clinical development. Of particular interest is the bi-phasic (bell-shaped) dose-response effect, representing a common feature of all S1R agonists and described in numerous preclinical models in vitro, in vivo and in clinical trials.Expert opinion S1R agonists modulate inter-organelles communication altered in neurodegenerative diseases and activate intracellular survival pathways. Research will continue growing in the future. The particular cellular nature of this chaperone protein must be better understood to facilitate the clinical developement of promising molecules.
  Little is known about right ventricular dysfunction in non-advanced idiopathic pulmonary fibrosis (IPF) patients without hypoxemia at rest. We evaluated it at rest and during exercise.
 
  123 IPF patients were evaluated, and 27met all the following criteria Gender-Age-Physiology Index score ≤5, modified Medical Research Council dyspnea score ≤3, peripheral oxygen saturation ≥92% at rest, and no history of oxygen therapy. They were submitted to two-dimensional speckle-tracking echocardiography at rest and during cardiopulmonary exercise to analyze right ventricular global longitudinal strain.
 
  Abnormal speckle-tracking echocardiography findings were identified in 10/27 patients (37%), indicating right ventricular (RV) dysfunction. No patients had abnormalities observed in conventional echocardiographic parameters. Significant differences in mPAP were observed between patients with RV dysfunction and those without dysfunction (at rest 26.0±4.8 vs. 19.1±4.2mmHg, 
  =0.001; during exercise 51.3±6.4 vs. 36.9±14.7mmHg, 
  =0.002).
 
  RV dysfunction was detected in 37% of non-advanced IPF patients and early recognition was only possible using speckle-tracking echocardiography. Special attention should be given to these patients as RV dysfunction is suggestive of worse prognosis. These patients could benefit from new specific drugs or even oxygen therapy for transitory hypoxia.
 RV dysfunction was detected in 37% of non-advanced IPF patients and early recognition was only possible using speckle-tracking echocardiography. Special attention should be given to these patients as RV dysfunction is suggestive of worse prognosis. These patients could benefit from new specific drugs or even oxygen therapy for transitory hypoxia.
  Heterozygous familial hypercholesterolemia (heFH) is a common metabolic disease associated with increased cardiovascular risk. Despite treatment with the currently available lipid-lowering agents (statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors), a substantial proportion of patients with heFH does not achieve low-density lipoprotein cholesterol (LDL-C) targets.
 
  The PubMed database was reviewed for relevant papers published up to August 2020. The safety and efficacy of novel agents, namely inclisiran and bempedoic acid, that lower LDL-C levels and might be useful in the management of patients with heFH are discussed.
 
  The prolonged lipid-lowering effect of inclisiran might improve adherence to treatment in patients with heFH. Bempedoic acid provides additional reductions in LDL-C levels in patients on high-intensity statin treatment; oral administration of this agent might be attractive to some patients. However, it is important to evaluate the effects of these agents on cardiovascular morbidity before they are incorporated in the management of heFH. The cost/benefit of treatment should also be considered, given the increasing complexity of lipid-lowering treatment.
 The prolonged lipid-lowering effect of inclisiran might improve adherence to treatment in patients with heFH. Bempedoic acid provides additional reductions in LDL-C levels in patients on high-intensity statin treatment; oral administration of this agent might be attractive to some patients.  https://www.selleckchem.com/products/pepstatin-a.html  However, it is important to evaluate the effects of these agents on cardiovascular morbidity before they are incorporated in the management of heFH. The cost/benefit of treatment should also be considered, given the increasing complexity of lipid-lowering treatment.Vicinal diols and its derivatives can be exploited as model compounds for the investigation of radiation-induced free-radical transformations of hydroxyl-containing biomolecules such as carbohydrates, phospholipids, ribonucleotides, amino acids, and peptides. In this paper, for the first time, the prospects of isotope reinforcement approach in inhibiting free-radical transformations of hydroxyl-containing compounds in aqueous solutions are investigated on the example of radiolysis of 1,2-propanediol and 1,2-propanediol-2-d1 aqueous solutions. At an absorbed dose rate of 0.110 ± 0.003 Gy·s-1 a profound kinetic isotope effect (KIE) is observed for the non-branched chain formation of acetone, which is a final dehydration product of predominant carbon-centred radicals CH3·C(OH)CH2OH. In 0.1 and 1 M deaerated solutions at pH 7.00 ± 0.01, the values of KIE are 8.9 ± 1.7 and 15.3 ± 3.1, respectively. A rationale for the fact that a strong KIE takes place only in the case of chain processes, which may occur during free-radical transformations of vicinal diols, is also provided herein based on the results of 2-propanol and 2-propanol-2-d1 indirect radiolysis. Lastly, the lack of KIE is shown in the case of 2-butanone formation from 2,3-butanediol or 2,3-butanediol-2,3-d2. This indicates that the type (primary, secondary) of the β-carbonyl radicals formed as a result of CH3·C(OH)CH(OH)R (R = H, CH3) dehydration determines the manifestation of the effect.