Potentially inappropriate prescriptions and potential prescription omissions in older people living with HIV.

OBJECTIVES: This study aimed to determine the prevalence of potentially inappropriate prescriptions (PIPs) and potential prescription omissions (PPOs) in a Spanish cohort of people living with HIV (PLWH) aged ≥65 years and to identify risk factors for the presence of PIPs and PPOs. METHODS: This retrospective cross-sectional study was conducted across 10 public hospitals in the Autonomous Community of Madrid, Spain. Clinical and demographic data were cross-checked against hospital and community pharmacy dispensation registries. PIPs and PPOs were assessed using the American Geriatrics Society (AGS)/Beers and Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert Doctors to Right Treatment (START) criteria. Risk factors for PIPs and PPOs and agreement between AGS/Beers and STOPP/START criteria were statistically analysed. RESULTS: This study included 313 PLWH (median age 72 years), of whom 80.5% were men. PIP prevalence rates were 29.4% and 44.4% based on the AGS/Beers and STOPP criteria, respectively. The concordance between AGS/Beers and STOPP criteria was moderate. Benzodiazepines and proton pump inhibitors were the chronic comedications most commonly involved in PIPs. PPOs were observed in 61.4% of the patients. The leading omissions were insufficient influenza and pneumococcal vaccine coverage and inadequate bone health-related treatments. The number of chronic comedications, female sex, neuropsychiatric disorders, and cancer diagnosis were risk factors for PIPs, whereas osteopenia and osteoporosis were risk factors for PPOs. CONCLUSIONS: A high prevalence of PIPs and PPOs was observed in our cohort of older PLWH. These findings emphasize the importance of comprehensive medication reviews in this population to reduce inappropriate medication use and address their specific and underserved therapeutic needs.

Lichen Depsidones with Biological Interest.

Depsidones are some of the most abundant secondary metabolites produced by lichens. These compounds have aroused great pharmacological interest due to their activities as antioxidants, antimicrobial, and cytotoxic agents. Hence, this paper aims to provide up-to-date knowledge including an overview of the potential biological interest of lichen depsidones. So far, the most studied depsidones are fumarprotocetraric acid, lobaric acid, norstictic acid, physodic acid, salazinic acid, and stictic acid. Their pharmacological activities have been mainly investigated in in vitro studies and, to a lesser extent, in in vivo studies. No clinical trials have been performed yet. Depsidones are promising cytotoxic agents that act against different cell lines of animal and human origin. Moreover, these compounds have shown antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungi, mainly Candida spp. Furthermore, depsidones have antioxidant properties as revealed in oxidative stress in vitro and in vivo models. Future research should be focused on further investigating the mechanism of action of depsidones and in evaluating new potential actions as well as other depsidones that have not been studied yet from a pharmacological perspective. Likewise, more in vivo studies are prerequisite, and clinical trials for the most promising depsidones are encouraged.

Lichen Extracts from Cetrarioid Clade Provide Neuroprotection against Hydrogen Peroxide-Induced Oxidative Stress.

Oxidative stress is involved in the pathophysiology of many neurodegenerative diseases. Lichens have antioxidant properties attributed to their own secondary metabolites with phenol groups. Very few studies delve into the protective capacity of lichens based on their antioxidant properties and their action mechanism. The present study evaluates the neuroprotective role of Dactylina arctica, Nephromopsis stracheyi, Tuckermannopsis americana and Vulpicida pinastri methanol extracts in a hydrogen peroxide (H2O2) oxidative stress model in neuroblastoma cell line "SH-SY5Y cells". Cells were pretreated with different concentrations of lichen extracts (24 h) before H2O2 (250 µM, 1 h). Our results showed that D. arctica (10 µg/mL), N. stracheyi (25 µg/mL), T. americana (50 µg/mL) and V. pinastri (5 µg/mL) prevented cell death and morphological changes. Moreover, these lichens significantly inhibited reactive oxygen species (ROS) production and lipid peroxidation and increased superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) levels. Furthermore, they attenuated mitochondrial membrane potential decline and calcium homeostasis disruption. Finally, high-performance liquid chromatography (HPLC) analysis revealed that the secondary metabolites were gyrophoric acid and lecanoric acid in D. artica, usnic acid, pinastric acid and vulpinic acid in V. pinastri, and alectoronic acid in T. americana. In conclusion, D. arctica and V. pinastri are the most promising lichens to prevent and to treat oxidative stress-related neurodegenerative diseases.

The Genus Cetraria s. str.-A Review of Its Botany, Phytochemistry, Traditional Uses and Pharmacology.

The genus Cetraria s. str. (Parmeliaceae family, Cetrarioid clade) consists of 15 species of mostly erect brown or greenish yellow fruticose or subfoliose thallus. These Cetraria species have a cosmopolitan distribution, being primarily located in the Northern Hemisphere, in North America and in the Eurasia area. Phytochemical analysis has demonstrated the presence of dibenzofuran derivatives (usnic acid), depsidones (fumarprotocetraric and protocetraric acids) and fatty acids (lichesterinic and protolichesterinic acids). The species of Cetraria, and more particularly Cetraria islandica, has been widely employed in folk medicine for the treatment of digestive and respiratory diseases as decoctions, tinctures, aqueous extract, and infusions. Moreover, Cetraria islandica has had an important nutritional and cosmetic value. These traditional uses have been validated in in vitro and in vivo pharmacological studies. Additionally, new therapeutic activities are being investigated, such as antioxidant, immunomodulatory, cytotoxic, genotoxic and antigenotoxic. Among all Cetraria species, the most investigated by far has been Cetraria islandica, followed by Cetraria pinastri and Cetraria aculeata. The aim of the current review is to update all the knowledge about the genus Cetraria covering aspects that include taxonomy and phylogeny, morphology and distribution, ecological and environmental interest, phytochemistry, traditional uses and pharmacological properties.

Pharmacological Update Properties of Aloe Vera and its Major Active Constituents.

Aloe vera has been traditionally used to treat skin injuries (burns, cuts, insect bites, and eczemas) and digestive problems because its anti-inflammatory, antimicrobial, and wound healing properties. Research on this medicinal plant has been aimed at validating traditional uses and deepening the mechanism of action, identifying the compounds responsible for these activities. The most investigated active compounds are aloe-emodin, aloin, aloesin, emodin, and acemannan. Likewise, new actions have been investigated for Aloe vera and its active compounds. This review provides an overview of current pharmacological studies (in vitro, in vivo, and clinical trials), written in English during the last six years (2014-2019). In particular, new pharmacological data research has shown that most studies refer to anti-cancer action, skin and digestive protective activity, and antimicrobial properties. Most recent works are in vitro and in vivo. Clinical trials have been conducted just with Aloe vera, but not with isolated compounds; therefore, it would be interesting to study the clinical effect of relevant metabolites in different human conditions and pathologies. The promising results of these studies in basic research encourage a greater number of clinical trials to test the clinical application of Aloe vera and its main compounds, particularly on bone protection, cancer, and diabetes.

Lichens of Parmelioid Clade as Promising Multitarget Neuroprotective Agents.

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are multifactorial disorders which are increasing in incidence and prevalence over the world without existing effective therapies. The search for new multitarget compounds is the latter therapeutic strategy to address these pathological conditions. Lichens have an important and unknown therapeutic value attributed to their unique secondary metabolites. The aim of this study is to evaluate for the first time the in vitro neuroprotective activities and molecular mechanisms underlying methanol extracts of lichens of the parmelioid clade and to characterize major bioactive secondary metabolites responsible for their pharmacological actions. Of the 15 parmelioid lichen species, our results showed that Parmotrema perlatum and Hypotrachyna formosana methanol extracts exhibited high antioxidant activity as evidenced in ORAC, DPPH, and FRAP assays. Then, SH-SY5Y cells were pretreated with methanol extracts (24 h) followed by Fenton reagent exposure (2 h). Pretreatments with these two more antioxidant methanol lichen extracts increased cell viability, reduced intracellular ROS, prevented oxidative stress biomarkers accumulation, and upregulated antioxidant enzyme (CAT, SOD, GR, and GPx) activity compared to Fenton reagent cells. The neuroprotective activity was much higher for H. formosana than for P. perlatum, even equal to or higher than Trolox (reference compound). Moreover, H. formosana extracts inhibited both AChE and BuChE activities in a concentration dependent manner, and P. perlatum only showed concentration dependent activity against AChE. Finally, chemical composition analysis using TLC and HPLC methods revealed that physodic acid, lividic acid, and lichexanthone are major secondary metabolites in H. formosana and stictic acid and constictic acid are in P. perlatum. These results demonstrated that P. perlatum and, specially, H. formosana are promising multitargeted neuroprotective agents due to their antioxidant and AChE and BuChE inhibition activities.

In vitro neuroprotective potential of the monoterpenes α-pinene and 1,8-cineole against H2O2-induced oxidative stress in PC12 cells.

Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Natural products are considered as therapeutically useful antioxidant agents against reactive oxygen species (ROS). We have evaluated the antioxidant and protective potential of the monoterpenes 1,8-cineole and α-pinene against H2O2-induced oxidative stress in PC12 (rat pheochromocytoma) cells. Pretreatment with these monoterpenes was found to attenuate the loss of cell viability and the changes in cell morphology. Moreover, they inhibited the intracellular ROS production and markedly enhanced the expression of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and heme-oxygenase 1 (HO-1). In addition, they were able to decrease apoptosis as is evident from reduced capase-3 activity. The mechanisms of their antioxidant action appear to involve ROS scavenging and induction of the nuclear Nrf2 factor. This study demonstrates the potential beneficial therapeutic effect of these common monoterpenes on the oxidant/antioxidant balance in diseases of the nervous system.

Kaurane diterpenes as mitochondrial alterations preventive agents under experimental oxidative stress conditions.

CONTEXT: Foliol, linearol, and sidol are the most common diterpenes found in Sideritis L. spp. (Lamiaceae) with a wide range of demonstrated properties including anti-inflammatory, antioxidant, and anti-apoptotic effects. OBJECTIVE: For the first time, the present work was studied for the potential protective role of these kaurane-type diterpenes on mitochondrial oxidative stress induced by H2O2 in the human astrocytoma U373-MG cell line and in the rat adrenal pheochromocytoma PC12 cell line. MATERIALS AND METHODS: Mitochondrial protection was assayed at 5 and 10 µM concentrations for 24 h (for kaurane diterpenes) and H2O2 as oxidative stress inducer (0.1 mM for PC12 cells and 1 mM for U373-MG, for 30 min). ATP concentration was determined by high-performance liquid chromatography (HPLC), and changes in mitochondrial membrane potential, caspase-3 activity as well as in cytosolic and mitochondrial calcium levels were assessed by fluorometric techniques, by using specific fluorescent probes. RESULTS: Pretreatments for 24 h with linearol and sidol, prior to H2O2 exposure, acted as mitochondrial alterations preventive agents by increasing membrane potential (over 40-60% in PC12 cells and over 10-20% in U373-MG), restoring both cytosolic and mitochondrial calcium homeostasis (linearol at 10 µM caused a 3.5-fold decrease in cytosolic calcium concentration in PC12 cells), decreasing caspase-3 activity (over 1.25-1.5-fold for linearol and sidol) and avoiding ATP depletion (linearol increased over 20% ATP level in both cell types). CONCLUSION: Our results suggest that linearol and sidol could provide protective activity by targeting mitochondria in response to the deleterious changes induced by H2O2.

Risk of dementia among antidepressant elderly users: A population-based cohort analysis in Spain.

The use of antidepressants with anticholinergic effects has been associated with an increased risk of dementia. However, the results published are contradictory. The aim of the study is to compare the risk of developing dementia in elderly who were prescribed tricyclic antidepressants (TCA) versus those who were prescribed selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OA). A prospective population-based cohort study was performed using the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) data (from 2005 to 2018). The cohort study included 62,928 patients age ≥ 60 without dementia and with antidepressant long-term monotherapy. Patients were divided into exposure antidepressant groups based on ATC system [TCA, SSRIs users and OAs users]. The risk of dementia was calculated by Cox regression models, providing hazard ratios (HR) and 95 % confidence intervals. The Kaplan-Meier model was used for survival analysis. Chi2 test was used as association test. The results showed SSRI users had higher dementia risk than TCA users (HR = 1.864; 95%CI = 1.624-2.140). Moreover, OA users had also significant risk of dementia (HR = 2.103; 95%CI = 1.818-2.431). Several limitations are the variation of the trend in the prescription of antidepressants, the small number of patients that use some antidepressants, the lack of information related to the dose, or socioeconomic characteristics, the use of antidepressant drugs for other indications, or the therapeutic compliance. Our findings showed that older users of SSRI and OA have more risk of developing dementia than TCA elderly users. However, additional studies would be needed.

Mitochondrial-targeted protective properties of isolated diterpenoids from sideritis spp. in response to the deleterious changes induced by H2O2.

Mitochondrial impairment and oxidative stress are considered widely to be central events in many forms of neurodegenerative disease. The current study has evaluated for the first time the potential protective role of three diterpenoids [andalusol (1), conchitriol (2), and lagascatriol (3)] in response to the deleterious H2O2-induced changes on mitochondrial function. U373-MG human astrocytoma cells and PC12 rat adrenal pheochromocytoma cells were used as models for evaluating the cytoprotective potential of these compounds. In the absence of diterpenoids 1-3, H2O2 compromised mitochondrial function, decreasing mitochondrial membrane potential and ATP levels, increasing caspase-3 activity, and disrupting cytosolic and mitochondrial calcium homeostasis. However, treatment with the diterpenoids, prior to H2O2, prevented these mitochondrial perturbations. In particular, 1 and 3 were the most effective compounds in protecting mitochondrial function against H2O2-induced oxidative stress in U373-MG, whereas all three diterpenoids studied were significantly active against PC12 cells. Since consistent evidence has demonstrated the contribution of H2O2 on both progression and pathological development of several human diseases associated with mitochondrial function and oxidative stress responses, compounds 1-3 are worthy of further investigation.

In vitro permeability study of CNS-active diterpenes from Sideritis spp. using cellular models of blood-brain barrier.

The major diterpenes andalusol, conchitriol, foliol, lagascatriol, linearol, and sidol, isolated from Sideritis spp., have been recently identified as neuroprotective agents. In this study, the blood brain-barrier permeability characteristics of these natural compounds were investigated for the first time using in silico and in vitro (RBE4 monocultures and ECV304/C6 co-cultures) methods. Computational tools revealed that these diterpenes have a favorable permeability profile to pass across the blood brain-barrier. In the RBE4 cell model, used for uptake studies, all compounds were taken up in a concentration and time-dependent manner. A bidirectional transport of diterpenes was observed across the ECV304/C6 co-culture model, with Papp values in the range of 3.7 × 10(-6) cm/sec and 9.5 × 10(-6) cm/sec for foliol and andalusol, respectively. Andalusol and lagascatriol were the most efficiently in being taken up and transported across the established blood brain-barrier in vitro model. These findings suggest that the investigated compounds from Sideritis spp. may predominantly move across the blood brain-barrier by passive diffusion. The observations have implications for understanding how CNS-active diterpenes enter the brain endothelium and traverse the blood brain-barrier, and thus exert their neuroprotective actions.

Lichen Depsides and Tridepsides: Progress in Pharmacological Approaches.

Depsides and tridepsides are secondary metabolites found in lichens. In the last 10 years, there has been a growing interest in the pharmacological activity of these compounds. This review aims to discuss the research findings related to the biological effects and mechanisms of action of lichen depsides and tridepsides. The most studied compound is atranorin, followed by gyrophoric acid, diffractaic acid, and lecanoric acid. Antioxidant, cytotoxic, and antimicrobial activities are among the most investigated activities, mainly in in vitro studies, with occasional in silico and in vivo studies. Clinical trials have not been conducted using depsides and tridepsides. Therefore, future research should focus on conducting more in vivo work and clinical trials, as well as on evaluating the other activities. Moreover, despite the significant increase in research work on the pharmacology of depsides and tridepsides, there are many of these compounds which have yet to be investigated (e.g., hiascic acid, lassalic acid, ovoic acid, crustinic acid, and hypothamnolic acid).

Engineering 3D-Printed Advanced Healthcare Materials for Periprosthetic Joint Infections.

The use of additive manufacturing or 3D printing in biomedicine has experienced fast growth in the last few years, becoming a promising tool in pharmaceutical development and manufacturing, especially in parenteral formulations and implantable drug delivery systems (IDDSs). Periprosthetic joint infections (PJIs) are a common complication in arthroplasties, with a prevalence of over 4%. There is still no treatment that fully covers the need for preventing and treating biofilm formation. However, 3D printing plays a major role in the development of novel therapies for PJIs. This review will provide a deep understanding of the different approaches based on 3D-printing techniques for the current management and prophylaxis of PJIs. The two main strategies are focused on IDDSs that are loaded or coated with antimicrobials, commonly in combination with bone regeneration agents and 3D-printed orthopedic implants with modified surfaces and antimicrobial properties. The wide variety of printing methods and materials have allowed for the manufacture of IDDSs that are perfectly adjusted to patients' physiognomy, with different drug release profiles, geometries, and inner and outer architectures, and are fully individualized, targeting specific pathogens. Although these novel treatments are demonstrating promising results, in vivo studies and clinical trials are required for their translation from the bench to the market.

Mental health and drug use in college students: Should we take action?

BACKGROUND: College students are vulnerable to suffering from anxiety and depression. Moreover, mental disorders can contribute to drug consumption or inappropriate use of prescribed drugs. Studies on this topic in Spanish college students are limited. This work analyses anxiety and depression and psychoactive drug intake pattern in the post-COVID era in college students. METHODS: An online survey was conducted among college students from UCM (Spain). The survey collected data including demographic, academic student perception, GAD-7 and PHQ-9 scales, and psychoactive substances consumption. RESULTS: A total of 6798 students were included; 44.1 % (CI95%: 42.9 to 45.3) showed symptoms of severe anxiety and 46.5 % (CI95%: 45.4 to 47.8) symptoms of severe or moderately severe depression. The perception of these symptoms did not change after returning to face-to-face university classes in the post-COVID19 era. Despite the high percentage of cases with clear symptoms of anxiety and depression, most students never had a diagnosis of mental illnesses [anxiety 69.2 % (CI95%: 68.1 to 70.3) and depression 78.1 % (CI95%: 77.1 to 79.1)]. Regarding psychoactive substances, valerian, melatonin, diazepam, and lorazepam were the most consumed. The most worrying issue was the consumption of diazepam, 10.8 % (CI95%: 9.8 to 11.8), and lorazepam, 7.7 % (CI95%: 6.9 to 8.6) without medical prescription. Among illicit drugs, cannabis is the most consumed. LIMITATIONS: The study was based on an online survey. CONCLUSIONS: The high prevalence of anxiety and depression aligned with poor medical diagnosis and high intake of psychoactive drugs should not be underestimated. University policies should be implemented to improve the well-being of students.

The cytotoxicity effect of 7-hydroxy-3,4-dihydrocadalene from Heterotheca inuloides and semisynthetic cadalenes derivates towards breast cancer cells: involvement of oxidative stress-mediated apoptosis.

Background: Heterotheca inuloides, traditionally employed in Mexico, has demonstrated anticancer activities. Although it has been proven that the cytotoxic effect is attributed to cadinane-type sesquiterpenes such as 7-hydroxy-3,4-dihydrocadalene, the mechanism of action by which these agents act in tumor lines and their regulation remain unknown. This study was undertaken to investigate for first time the cytotoxic activity and mechanism of action of 7-hydroxy-3,4-dihydrocadalene and two semi-synthetic cadinanes derivatives towards breast cancer cells. Methods: Cell viability and proliferation were assayed by thiazolyl blue tetrazolium bromide (MTT) assay and Trypan blue dye exclusion assay. Cell migration measure was tested by wound-healing assay. Moreover, the reactive oxygen species (ROS) and lipid peroxidation generation were measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay and thiobarbituric acid reactive substance (TBARS) assay, respectively. Furthermore, expression of caspase-3, Bcl-2 and GAPDH were analyzed by western blot. Results: The results showed that 7-hydroxy-3,4-dihydrocadalene inhibited MCF7 cell viability in a concentration and time dependent manner. The cytotoxic potency of semisynthetic derivatives 7-(phenylcarbamate)-3,4-dihydrocadalene and 7-(phenylcarbamate)-cadalene was remarkably lower. Moreover, in silico studies showed that 7-hydroxy-3,4-dihydrocadalene, and not so the semi-synthetic derivatives, has optimal physical-chemical properties to lead a promising cytotoxic agent. Further examination on the action mechanism of 7-hydroxy-3,4-dihydrocadalene suggested that this natural product exerted cytotoxicity via oxidative stress as evidenced in a significantly increase of intracellular ROS levels and in an induction of lipid peroxidation. Furthermore, the compound increased caspase-3 and caspase-9 activities and slightly inhibited Bcl-2 levels. Interestingly, it also reduced mitochondrial ATP synthesis and induced mitochondrial uncoupling. Conclusion: Taken together, 7-hydroxy-3,4-dihydrocadalene is a promising cytotoxic compound against breast cancer via oxidative stress-induction.

The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through #INPST hashtag analysis.

BACKGROUND: The development of digital technologies and the evolution of open innovation approaches have enabled the creation of diverse virtual organizations and enterprises coordinating their activities primarily online. The open innovation platform titled "International Natural Product Sciences Taskforce" (INPST) was established in 2018, to bring together in collaborative environment individuals and organizations interested in natural product scientific research, and to empower their interactions by using digital communication tools. METHODS: In this work, we present a general overview of INPST activities and showcase the specific use of Twitter as a powerful networking tool that was used to host a one-week "2021 INPST Twitter Networking Event" (spanning from 31st May 2021 to 6th June 2021) based on the application of the Twitter hashtag #INPST. RESULTS AND CONCLUSION: The use of this hashtag during the networking event period was analyzed with Symplur Signals (https://www.symplur.com/), revealing a total of 6,036 tweets, shared by 686 users, which generated a total of 65,004,773 impressions (views of the respective tweets). This networking event's achieved high visibility and participation rate showcases a convincing example of how this social media platform can be used as a highly effective tool to host virtual Twitter-based international biomedical research events.

Diterpenoids isolated from Sideritis species protect astrocytes against oxidative stress via Nrf2.

Andalusol (1), conchitriol (2), and lagascatriol (3) are diterpenoids produced by Sideritis species. Hydrogen peroxide-induced oxidative stress in U373-MG cells was used as an in vitro model to evaluate the cytoprotective potential, based on antioxidant properties, of these isolated compounds and to investigate the underlying mechanisms. Experimental results revealed that pretreatment with compounds 1 and 3 restored H2O2-induced oxidative changes by increasing cell viability, attenuating morphological changes, inhibiting intracellular ROS production and lipid peroxidation, and enhancing the antioxidant defense system. Furthermore, nuclear factor E2-related factor 2 (Nrf2) signaling was involved in the protective mechanisms of 1-3. The present findings suggest that two of the compounds studied (1 and 3) might play a preventive role in neurodegenerative diseases associated with oxidative stress.

Phytochemical Characterization and Pharmacological Properties of Lichen Extracts from Cetrarioid Clade by Multivariate Analysis and Molecular Docking.

Introduction: Lichens, due to the presence of own secondary metabolites such as depsidones and depsides, became a promising source of health-promoting organisms with pharmacological activities. However, lichens and their active compounds have been much less studied. Therefore, the present study aims to evaluate for the first time the antioxidant capacity and enzyme inhibitory activities of 14 lichen extracts belonging to cetrarioid clade in order to identify new natural products with potential pharmacological activity. Materials and Methods: In this study, an integrated strategy was applied combining multivariate statistical analysis (principal component analysis and hierarchical cluster analysis), phytochemical identification, activity evaluation (in vitro battery of antioxidant assays FRAP, DPPH, and ORAC), and enzyme inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and molecular profiling with in silico docking studies of the most promising secondary metabolites. Results. Among fourteen lichen samples, Dactylina arctica stands out for its higher antioxidant capacities, followed by Nephromopsis stracheyi, Tuckermannopsis americana, Vulpicida pinastri, and Asahinea scholanderi. Moreover, Asahinea scholanderi and Cetraria cucullata extracts were the best inhibitors of AChE and BuChE. The major secondary metabolites identified by HPLC were alectoronic acid and α-collatolic acid for Asahinea scholanderi and usnic acid and protolichesterinic acid for Cetraria cucullata. Molecular docking studies revealed that alectoronic acid exhibited the strongest binding affinity with both AChE and BuChE with and without water molecules. Conclusions: Our results concluded that these species could be effective in the treatment of neurodegenerative diseases, being mandatory further investigation in cell culture and in vivo models.

A New Cryptic Lineage in Parmeliaceae (Ascomycota) with Pharmacological Properties.

We used molecular data to address species delimitation in a species complex of the parmelioid genus Canoparmelia and compare the pharmacological properties of the two clades identified. We used HPLC_DAD_MS chromatography to identify and quantify the secondary substances and used a concatenated data set of three ribosomal markers to infer phylogenetic relationships. Some historical herbarium specimens were also examined. We found two groups that showed distinct pharmacological properties. The phylogenetic study supported the separation of these two groups as distinct lineages, which are here accepted as distinct species: Canoparmelia caroliniana occurring in temperate to tropical ecosystems of a variety of worldwide localities, including America, Macaronesia, south-west Europe and potentially East Africa, whereas the Kenyan populations represent the second group, for which we propose the new species C. kakamegaensis Garrido-Huéscar, Divakar & Kirika. This study highlights the importance of recognizing cryptic species using molecular data, since it can result in detecting lineages with pharmacological properties previously overlooked.

Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers.

Antifungal drugs such as amphotericin B (AmB) interact with lipids and phospholipids located on fungal cell membranes to disrupt them and create pores, leading to cell apoptosis and therefore efficacy. At the same time, the interaction can also take place with cell components from mammalian cells, leading to toxicity. AmB was selected as a model antifungal drug due to the complexity of its supramolecular chemical structure which can self-assemble in three different aggregation states in aqueous media: monomer, oligomer (also known as dimer) and poly-aggregate. The interplay between AmB self-assembly and its efficacy or toxicity against fungal or mammalian cells is not yet fully understood. To the best of our knowledge, this is the first report that investigates the role of excipients in the supramolecular chemistry of AmB and the impact on its biological activity and toxicity. The monomeric state was obtained by complexation with cyclodextrins resulting in the most toxic state, which was attributed to the greater production of highly reactive oxygen species upon disruption of mammalian cell membranes, a less specific mechanism of action compared to the binding to the ergosterol located in fungal cell membranes. The interaction between AmB and sodium deoxycholate resulted in the oligomeric and poly-aggregated forms which bound more selectively to the ergosterol of fungal cell membranes. NMR combined with XRD studies elucidated the interaction between drug and excipient to achieve the AmB aggregation states, and ultimately, their diffusivity across membranes. A linear correlation between particle size and the efficacy/toxicity ratio was established allowing to modulate the biological effect of the drug and hence, to improve pharmacological regimens. However, particle size is not the only factor modulating the biological response but also the equilibrium of each state which dictates the fraction of free monomeric form available. Tuning the aggregation state of AmB formulations is a promising strategy to trigger a more selective response against fungal cells and to reduce the toxicity in mammalian cells.