BIOLOGICAL ACTIVITIES AND PHENOLIC COMPOSITION OF WASHINGTONIA FILIFERA SEEDS

Plant materials represent a great source of antioxidant and bioactive compounds which are different in their chemical composition and biological properties. There has been a remarkable increment on research of antioxidant molecules because of their protective action against oxidative stress. It causes serious cell and tissue damage leading it to be the major cause of aging process and the pathogenesis of several diseases like diabetes and neurodegenerative diseases. The chemical composition and the biological properties of fruits of the palm Washingtonia filifera (Lindl.) H.Wendl. is poorly studied. Therefore, the aim of this thesis was to investigate the potential bioactivity of W. filifera fruit extracts and relate them with the phenolic profile. The phenolic composition, antioxidant capacity and the inhibitory activity on different enzymes implicate in several disease were evaluated. In particular, W. filifera seed extracts appeared to be a good source of phenolics and showed a significant antioxidant activity. The phenolic composition mainly consisted of procyanidin dimers B1–B4. Alcoholic seed extracts displayed interesting xanthine oxidase, butyrylcholinesterase, elastase, collagenase, α-amylase and α-glucosidase inhibitory activity. Docking studies were also performed to predict the binding sites of the main compounds identified within enzymes structure. All in all, W. filifera seeds appear as a promising natural source for the purification of bioactive compounds with antioxidant and biological properties

Euphorbia characias: Phytochemistry and Biological Activities

The aim of this review is to summarize all the compounds identified and characterized from Euphorbia characias, along with the biological activities reported for this plant. Euphorbia is one of the greatest genera in the spurge family of Euphorbiaceae and includes different kinds of plants characterized by the presence of milky latex. Among them, the species Euphorbia characias L. is an evergreen perennial shrub widely distributed in Mediterranean countries. E. characias latex and extracts from different parts of the plant have been extensively studied, leading to the identification of several chemical components such as terpenoids, sterol hydrocarbons, saturated and unsaturated fatty acids, cerebrosides and phenolic and carboxylic acids. The biological properties range between antioxidant activities, antimicrobial, antiviral and pesticidal activities, wound-healing properties, anti-aging and hypoglycemic properties and inhibitory activities toward target enzymes related to different diseases, such as cholinesterases and xanthine oxidase. The information available in this review allows us to consider the plant E. characias as a potential source of compounds for biomedical research

Hydroxy-3-Phenylcoumarins as Multitarget Compounds for Skin Aging Diseases: Synthesis, Molecular Docking and Tyrosinase, Elastase, Collagenase and Hyaluronidase Inhibition, and Sun Protection Factor

Skin aging is a progressive biological process of the human body, and it is not only time-dependent. Differently substituted 3-phenylcoumarins proved to efficiently inhibit tyrosinase. In the current work, new substitution patterns have been explored, and the biological studies were extended to other important enzymes involved in the processes of skin aging, as elastase, collagenase and hyaluronidase. From the studied series, five compounds presented inhibitory activity against tyrosinase, one compound against elastase, eight compounds against collagenase and two compounds against hyaluronidase, being five compounds dual inhibitors. The 3-(4 '-Bromophenyl)-5,7-dihydroxycoumarin (1) and 3-(3 '-bromophenyl)-5,7-dihydroxycoumarin (2) presented the best profiles against tyrosinase (IC50 = 1.05 mu M and 7.03 mu M) and collagenase (IC50 = 123.4 mu M and 110.4 mu M); the 3-(4 '-bromophenyl)-6,7-dihydroxycoumarin (4) presented a good inhibition against tyrosinase and hyaluronidase; the 3-(3 '-bromophenyl)-6,7-dihydroxycoumarin (5) showed an effective tyrosinase and elastase inhibition; and 6,7-dihydroxy-3-(3 '-hydroxyphenyl)coumarin (11) presented a dual profile inhibition against collagenase and hyaluronidase. Furthermore, considering the overall activities tested, compounds 1 and 2 proved to be the most promising anti-aging compounds. These compounds also showed to have a photo-protective effect, without being cytotoxic to human skin keratinocyte cells. To predict the binding site with the target enzymes, computational studies were also carried out

Design, Synthesis, and in Vitro Evaluation of 4-(4-Hydroxyphenyl)piperazine-Based Compounds Targeting Tyrosinase

Melanin biosynthesis is enzymatically regulated by tyrosinase (TYR, EC 1.14.18.1), which is efficiently inhibited by natural and synthetic phenols, demonstrating potential therapeutic application for the treatment of several human diseases. Herein we report the inhibitory effects of a series of (4-(4-hydroxyphenyl)piperazin-1-yl)arylmethanone derivatives, that were designed, synthesised and assayed against TYR from Agaricus bisporus (AbTYR). The best inhibitory activity was predominantly found for compounds bearing selected hydrophobic ortho-substituents on the aroyl moiety (IC50 values in the range of 1.5–4.6 μM). They proved to be more potent than the reference compound kojic acid (IC50=17.8 μM) and displayed competitive mechanism of inhibition of diphenolase activity of AbTYR. Docking simulation predicted their binding mode into the catalytic cavities of AbTYR and the modelled human TYR. In addition, these compounds displayed antioxidant activity combined with no cytotoxicity in MTT tests. Notably, the best inhibitor affected tyrosinase activity in α-MSH-stimulated B16F10 cells, thus demonstrating anti-melanogenic activity

Promising inhibition of diabetes-related enzymes and antioxidant properties of Ptilostemon casabonae leaves extract

Type 2 diabetes (T2D) is a progressive metabolic disorder of glucose metabolism. One of the therapeutic approaches for the treatment of T2D is reducing postprandial hyperglycaemia through inhibition of the digestive enzymes α-glucosidase and α-amylase. In this context, aimed at identifying natural products endowed with anti-T2D potential, we focused on Ptilostemon casabonae (L.) Greuter, a species belonging to Asteraceae family. Enzymatic inhibition, antioxidant activity, phenolic composition and cellular assays were performed. This study revealed that the P. casabonae hydroalcoholic extract exerts a potent inhibitory activity against α-glucosidase. This activity is supported by an antioxidant effect, preventing ROS formation in a stressed cellular system. HPLC-PDA-MS/MS analysis, revealed a complex polyphenolic fraction. Among the tested pure compounds, 1,5-dicaffeoylquinic acid, apigenin and rutin displayed good α-glucosidase inhibitory activity. Our study suggested new potential of P. casabonae encouraging us to further testing the possible therapeutic potential of this extract

Incidence and Clinical Features of Cerebrovascular Disease Among HIV-Infected Adults in the Southeastern United States

With aging of the HIV-infected population, non-AIDS conditions such as cardiovascular disease (CVD) now account for substantial mortality and morbidity. While myocardial infarction is the major outcome of interest in the field of HIV and CVD, cerebrovascular disease remains understudied, especially in the Southeastern United States. We determined the incidence and clinical features of cerebrovascular events (CVE) in a large HIV clinical cohort in North Carolina (NC). A total of 2,515 HIV-infected adults contributed a median of 4.5 years (IQR: 2.0, 7.8) of follow-up. Fifty-three CVEs were adjudicated for an incidence rate of 3.87 per 1,000 person-years (95% CI: 2.90, 5.06). The ischemic stroke incidence was 2.26 per 1,000 person-years (95% CI: 1.53, 3.21), approximately 1.5 times the rate of a population-based cohort in NC. At the time of CVE, the median age was 48 years (IQR: 42, 55). Of ischemic strokes 76% resulted from large artery atherosclerosis or small vessel (lacunar) disease. In multivariable analyses, age, hypertension, dyslipidemia, recent CD4+ cell count ≤200 cells/mm3, and recent HIV RNA >400 copies/ml were associated with an increased risk of CVE. Antiretroviral therapy (ART) was not associated with the risk of CVE. We concluded that in the post-ART era, HIV-infected individuals appear to be at moderately increased risk of stroke. Prevention of CVEs in this population will require modification of traditional CVD risk factors and early, effective treatment of HIV infection

Effects of Combination Antiretroviral Therapies on the Risk of Myocardial Infarction Among HIV Patients

Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating a randomized controlled trial comparing initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI

Validation of Medicaid Claims-based Diagnosis of Myocardial Infarction Using an HIV Clinical Cohort

In non-experimental comparative effectiveness research using healthcare databases, outcome measurements must be validated to evaluate and potentially adjust for misclassification bias. We aimed to validate claims-based myocardial infarction algorithms in a Medicaid population using an HIV clinical cohort as the gold standard

Identification of Cellular Infiltrates during Early Stages of Brain Inflammation with Magnetic Resonance Microscopy

A comprehensive view of brain inflammation during the pathogenesis of autoimmune encephalomyelitis can be achieved with the aid of high resolution non-invasive imaging techniques such as microscopic magnetic resonance imaging (μMRI). In this study we demonstrate the benefits of cryogenically-cooled RF coils to produce μMRI in vivo, with sufficient detail to reveal brain pathology in the experimental autoimmune encephalomyelitis (EAE) model. We could visualize inflammatory infiltrates in detail within various regions of the brain, already at an early phase of EAE. Importantly, this pathology could be seen clearly even without the use of contrast agents, and showed excellent correspondence with conventional histology. The cryogenically-cooled coil enabled the acquisition of high resolution images within short scan times: an important practical consideration in conducting animal experiments. The detail of the cellular infiltrates visualized by in vivo μMRI allows the opportunity to follow neuroinflammatory processes even during the early stages of disease progression. Thus μMRI will not only complement conventional histological examination but will also enable longitudinal studies on the kinetics and dynamics of immune cell infiltration

Evaluating expert-based habitat suitability information of terrestrial mammals with GPS-tracking data

Aim Macroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species. Location Worldwide. Time period 1998-2021. Major taxa studied Forty-nine terrestrial mammal species. Methods Using GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types. Results IUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively. Main conclusions We show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data