Maqui and Omega 3: effects on lipid profile, oxidative stress levels and psycho-physical items in human subjects

Aims: to assess short-term efficacy of supplementation with Maqui (Aristotelia Chilensis (Mol.Stuntz)), a polyphenol with antioxidant power, and EPA/DHA concerning metabolism, oxidative stress and mental/physical state. Patients and Methods: a pilot prospective observational clinical/laboratory study was performed on 17 apparently healthy subjects (8 males and 9 females, mean age 47 years). All subjects received for two months: a) Maqui 600 mg per day and b) 360 mg of EPA and 240 mg of DHA (salmon oil) daily. At day 0 and day 60 all subjects underwent nine laboratory tests related to inflammation, metabolism (lipid profile mainly) and oxidative stress parameters. Pre-post treatment weight and BMI was calculated. A few physical and mental parameters were assessed by means of Short-Form 12 questionnaire. Statistical analysis was applied to the resulting data through Wilcoxon test and t-paired test. Results: laboratory results before and after Maqui + EPA/DHA supplementation were respectively (mean and p-value for the comparison): total cholesterol 228.8/199.8 mg/dl, p=0.23; low density lipoproteins 127.4/122.1 mg/dl, p=0.13; high density lipoproteins 59.1/57.6 mg/dl, p=0.25; Reactive C Protein 0.18/0.09 mg/dl, p=0.32; triglycerides 106.1/91.1 mg/dl p=0.09, glycemia 92.9/92.8 mg/dl p= 0.92; total free radicals 338.0/303.6 U.Carr., p=0.002; serum anti-oxidant capacity 2075/2190 umol/l, p= 0.04; oxidized lipoproteins 641.8/553.1 uEq/l, p=0.10. SF12 physical and mental items (mean values and SD) were 51.2 (+/- 6.2) and 41.2 (+/- 3,3) at day 0 and 54.6 (+/- 11.6) and 47.2 (+/- 9.7) at day 60 respectively. One case of transient constipation was recorded. Conclusions: daily supplementation with Maqui 600 mg + Omega 3 fatty acids (EPA 360 mg + DHA 240 mg) in apparently healthy middle-aged subjects resulted in a statistically significant improvement of oxidative stress parameters. An overall (non statistically significant) improvement of dysmetabolism biomarkers was achieved. Mental and physical parameters have mildly improved

Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers

Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring

CoMFA and CoMSIA analyses on 1,2,3,4-tetrahydropyrrolo[3,4-b]indole and benzimidazole derivatives as selective CB2 receptor agonists.

Novel classes of cannabinoid 2 receptor (CB2) agonists based on 1,2,3,4-tetrahydropyrrolo[3,4-b]indole and benzimidazole scaffolds have shown high binding affinity toward CB2 receptor and good selectivity over cannabinoid 1 receptor (CB1). A computational study of comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed, initially on each series of agonists, and subsequently on all compounds together, in order to identify the key structural features impacting their binding affinity. The final CoMSIA model resulted to be the more predictive, showing cross-validated r2 (rcv 2) = 0.680, non crossvalidated r2 (rncv 2) = 0.97 and test set r2 r2 pred \ubc 0:93. The study provides useful suggestions for the design of new analogues with improved affinity

CoMFA and CoMSIA analyses on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine derivatives as selective CB2 receptor agonists

Novel classes of CB2 agonists based on 4-oxo- 1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine scaffolds have shown high binding affinity toward CB2 receptor and good selectivity over CB1. A computational study of comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed, in order to identify the key structural features impacting their binding affinity. The final CoMSIA model resulted to be the more predictive, showing r2ncv= 0,84, r2cv=0,619,SEE=0,369, and r2pred= 0,75. The study provides useful suggestions for the synthesis of new selective analogues with improved affinity

Computational studies of the binding mode and 3D-QSAR analyses of symmetric formimidoester disulfides: a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors

Symmetric formimidoester disulfides (DSs) have recently been identified as a new class of potent nonnucleoside HIV-1 reverse transcriptase (RT) inhibitors. Given that three geometric isomers for DSs are possible, a computational strategy based on molecular docking studies, followed by comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was used in order to identify the most probable DS isomer interacting with RT, to elucidate the atomic details of the RT/DS interaction, and to identify key features impacting DS antiretroviral activity. The CoMFA model was found to be the more predictive, with values of r2 ncv \ubc 0:95, r2 cv \ubc 0:482, SEE=0.264, F=80, and r2 pred \ubc 0:73

Acylthiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: docking studies and ligand-based CoMFA and CoMSIA analyses

Acylthiocarbamates (ATCs) have been identified as a class of potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies followed by comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was used to identify the most important features impacting ATC antiretroviral activity. The CoMSIA model proved to be the more predictive, with r2 ncv=0.89, rcv 2=0.38, standard error of estimate (SEE)= 0.494, F=84, and r2 pred=0.81. The results of these studies will be useful in designing new ATCs with improved potency, also against clinically relevant resistant mutants

Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses

Thiocarbamates (TCs) have been recently identified as a new class of potent non-nucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses, has been used to elucidate the atomic details of the RT/TC interactions and to identify the most important features impacting the TC antiretroviral activity. The CoMFA model resulted to be the more predictive, and gave r2= 0.93, rcv2 = 0.53, SEE= 0.292, F =180, and rtest2= 0.70. The 3D-QSAR field contributions and the structural features of the RT binding site showed a good correlation. These studies will be useful to design new TCs with improved potency also against clinically relevant resistant mutants

Exploring the QSAR of pyrazolo[3,4-b]pyridine, pyrazolo[3,4-b]pyridone and pyrazolo[3,4-b]pyrimidine derivatives as antagonists for A1 adenosine receptor.

Pyrazolo[3,4-b]pyridines have been recently presented as a novel class of adenosine A1 receptor antagonists. Depending on substitutions on some key positions of their scaffold they show selectivity towards A1, A2A or A3 receptors, which results in a variety of therapeutic potentialities of these ligands. In this work, we present a QSAR study on these analogues as antagonists for adenosine A1 receptors. Using the MOE software we identified a pool of descriptors that numerically describes the ligand features impacting the affinity at adenosine A1 receptors. The obtained information is useful to understand the main structural features that strongly correlate with the A1 antagonism in this class of compounds and will be used for the rational design of more potent and selective pyrazolo[3,4-b]pyridine derivatives