The role of ayahuasca in cell viability and oxidative stress in gastric adenocarcinoma cell line.

Ayahuasca, a psychoactive beverage native to the Amazon, originally derived from Banisteriopsis caapi stem scrapings and Psychotria viridis leaves, exhibits hallucinogenic properties due to N,N-dimethyltryptamine. When combined with ß-carbolines, it enters the bloodstream and central nervous system, inhibiting monoamine oxidase-A. Over time, therapeutic effects have been associated to ayahuasca consumption. This study assessed the impact of extracts from three plant decoctions used in ayahuasca preparation on the gastric adenocarcinoma cell line (AGS). MTT reduction assays selected B. caapi, Mimosa hostilis, and Peganum harmala samples as most effective. Lactate dehydrogenase activity evaluated membrane integrity loss, while oxidative stress induction was measured using dihydroethidium and 2',7'-dichlorodihydrofluorescein diacetate probes. Results revealed apoptosis induction in AGS cells, with all three samples significantly reducing oxidative stress.

Portuguese Recommendations for the management of Raynaud's phenomenon and digital ulcers in systemic sclerosis and other connective tissue diseases.

OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological and pharmacological management of Raynaud's phenomenon (RP) and digital ulcers (DUs) in patients with systemic sclerosis and other immune-mediated connective tissue diseases (CTDs). METHODS: A task force comprising 21 rheumatologists, two surgeons (vascular and plastic), two nurses, and one patient representative was established. Following a systematic literature review performed to inform the recommendations, statements were formulated and discussed during two meetings (one online and one in-person). Levels of evidence, grades of recommendation (GoR), and level of agreement (LoA) were determined. RESULTS: Five overarching principles and 13 recommendations were developed. GoR ranged from A to D. The mean ± standard difference (SD) LoA with the overarching principles and recommendations ranged from 7.8±2.1 to 9.8±0.4. Briefly, the management of RP and DUs in patients with CTDs should be coordinated by a multidisciplinary team and based on shared decisions with patients. Nifedipine should be used as first-line therapy for RP and/or DUs. Sildenafil, tadalafil, and/or iloprost IV are second-line options for severe and/or refractory patients with RP and/or DUs. Sildenafil, tadalafil and/or Iloprost IV, should be prescribed for healing and prevention (also including bosentan) of DUs. In patients with RP and/or DUs, non-pharmacological interventions might be considered as add-ons, but there is limited quality and quantity of scientific evidence supporting their use. CONCLUSIONS: These recommendations will inform rheumatologists, specialist nurses, other healthcare professionals, and patients about a comprehensive and personalized management of RP and DUs. A research agenda was developed to address unmet needs, particularly for non-pharmacologic interventions.

The Role of Ayahuasca in Colorectal Adenocarcinoma Cell Survival, Proliferation and Oxidative Stress.

The psychedelic beverage ayahuasca is originally obtained by Banisteriopsis caapi (B. caapi) (BC) and Psychotria viridis (P. viridis) (PV). However, sometimes these plant species are replaced by others that mimic the original effects, such as Mimosa hostilis (M. hostilis) (MH) and Peganum harmala (P. harmala) (PH). Its worldwide consumption and the number of studies on its potential therapeutic effects has increased. This study aimed to evaluate the anticancer properties of ayahuasca in human colorectal adenocarcinoma cells. Thus, the maximum inhibitory concentration (IC50) of decoctions of MH, PH, and a mixture of these (MHPH) was determined. The activities of caspases 3 and 9 were evaluated, and the cell proliferation index was determined through immunocytochemical analysis (Ki-67). Two fluorescent probes were used to evaluate the production of oxidative stress and the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was also evaluated. It was demonstrated that exposure to the extracts significantly induced apoptosis in Caco-2 cells, while decreasing cell proliferation. MH and MHPH samples significantly reduced oxidative stress and significantly increased glutathione peroxidase activity. No significant differences were found in SOD activity. Overall, it was demonstrated that the decoctions have a potential anticancer activity in Caco-2 cells.

Characterisation of Cannabis-Based Products Marketed for Medical and Non-Medical Use Purchased in Portugal.

Cannabis-based products have gained attention in recent years for their perceived therapeutic benefits (with cannabinoids such as THC and CBD) and widespread availability. However, these products often lack accurate labelling regarding their cannabinoid content. Our study, conducted with products available in Portugal, revealed significant discrepancies between label claims and actual cannabinoid compositions. A fully validated method was developed for the characterisation of different products acquired from pharmacies and street shops (beverages, herbal samples, oils, and cosmetic products) using high-performance liquid chromatography coupled with a diode array detector. Linearity ranged from 0.4 to 100 µg/mL (0.04-10 µg/mg) (THC, 8-THC, CBD, CBG, CBDA, CBGA), 0.1-100 µg/mL (0.01-10 µg/mg) (CBN), 0.4-250 µg/mL (0.04-25 µg/mg) (THCA-A), and 0.8-100 µg/mL (0.08-10 µg/mg) (CBCA). Among sampled beverages, none contained detectable cannabinoids, despite suggestive packaging. Similarly, oils often differed from the declared cannabinoid compositions, with some containing significantly higher CBD concentrations than labelled. These inconsistencies raise serious concerns regarding consumer safety and informed decision-making. Moreover, our findings underscore the need for stringent regulation and standardised testing protocols to ensure the accuracy and safety of cannabis-based products.

Comparative study of sample preparation procedures to determine the main compounds in ayahuasca beverages by QuEChERS and high-performance liquid chromatography analysis.

INTRODUCTION: Ayahuasca is a psychoactive drink originally consumed by indigenous people of the Amazon. The lack of regulation of this drink leads to uncontrolled consumption, and it is often consumed in religious contexts. OBJECTIVE: The aim of this work is to compare three miniaturised extraction techniques for extracting the main ayahuasca compounds from beverages. METHODOLOGY: Three sample pretreatment techniques were evaluated (dispersive liquid-liquid microextraction [DLLME], microextraction by packed sorbent [MEPS] and QuEChERS [Quick, Easy, Cheap, Effective, Rugged and Safe]) for the simultaneous extraction of N,N-dimethyltryptamine (DMT), tetrahydroharmine (THH), harmine, harmaline, harmol and harmalol from ayahuasca beverage samples. Then, the most promising technique (QuEChERS) was chosen to pre-concentrate the analytes, subsequently detected by high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD). RESULTS: The procedure was optimised, with the final conditions being 500 µL of extractor solvent, 85 mg of primary secondary amine (PSA) and 4 s of vortexing. The analytical method was validated, showing to be linear between 0.16 and 10 µg/mL for ß-carbolines and between 0.016 and 1 µg/mL for DMT, with coefficients of determination (R2) between 0.9968 and 0.9993. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 0.16 µg/mL for all compounds, except for DMT (0.016 µg/mL) and extraction efficiencies varied between 60.2% and 88.0%. CONCLUSION: The analytical methodology proved to be accurate and precise, with good linearity, LODs and LLOQs. This method has been fully validated and successfully applied to ayahuasca beverage samples.

Midwives' practices on perineal protection and episiotomy decision-making: A qualitative and descriptive study.

INTRODUCTION: Perineal trauma is associated with both short- and long-term morbidity which in turn relates to the degree of trauma. The objective of this study was to understand midwives' practices regarding perineal protection during the second phase of labor, emphasizing decision-making to perform an episiotomy. METHODS: A descriptive and explanatory study was conducted with an intentional sample of twenty-two midwives working in the labor ward of a tertiary hospital in a metropolitan location and in the public service, in Portugal. A semi-open interview was applied to collect the data from 5 to 15 January 2019. The computer software package, NVivo version 10, was used to perform the thematic analysis. RESULTS: Four main themes arose from the midwives' data: 1) Factors affecting the application of perineal protection techniques', 2) Birth position, 3) Techniques for perineal protection, and 4) Episiotomy. The reasons for performing an episiotomy were the presence of tense perineum, large weight baby, previous obstetric anal sphincter injury, and Kristeller maneuver. CONCLUSIONS: Midwives' practices regarding perineal protection techniques and reasons for performing an episiotomy were not all in line with the evidence. Perineal massage was not mentioned as a perineal protection technique.

Circadian ABCG2 Expression Influences the Brain Uptake of Donepezil across the Blood-Cerebrospinal Fluid Barrier.

Donepezil (DNPZ) is a cholinesterase inhibitor used for the management of Alzheimer's disease (AD) and is dependent on membrane transporters such as ABCG2 to actively cross brain barriers and reach its target site of action in the brain. Located in the brain ventricles, the choroid plexus (CP) forms an interface between the cerebrospinal fluid (CSF) and the bloodstream, known as the blood-CSF barrier (BCSFB). Historically, the BCSFB has received little attention as a potential pathway for drug delivery to the central nervous system (CNS). Nonetheless, this barrier is presently viewed as a dynamic transport interface that limits the traffic of molecules into and out of the CNS through the presence of membrane transporters, with parallel activity with the BBB. The localization and expression of drug transporters in brain barriers represent a huge obstacle for drug delivery to the brain and a major challenge for the development of therapeutic approaches to CNS disorders. The widespread interest in understanding how circadian clocks modulate many processes that define drug delivery in order to predict the variability in drug safety and efficacy is the next bridge to improve effective treatment. In this context, this study aims at characterizing the circadian expression of ABCG2 and DNPZ circadian transport profile using an in vitro model of the BCSFB. We found that ABCG2 displays a circadian pattern and DNPZ is transported in a circadian way across this barrier. This study will strongly impact on the capacity to modulate the BCSFB in order to control the penetration of DNPZ into the brain and improve therapeutic strategies for the treatment of AD according to the time of the day.

Extraction of Antioxidants from Brown Macroalgae Fucus spiralis.

In this study, different extraction methods and conditions were used for the extraction of antioxidants from brown macroalgae Fucus spiralis. The extraction methodologies used were ultrasound-assisted extraction (ultrasonic bath and ultrasonic probe), extraction with a vortex, extraction with an Ultra-Turrax® homogenizer, and high-pressure-assisted extraction. The extracts were analyzed for their total phenolic content (TPC) and their antioxidant activity, and evaluated through the 2,2-difenil-1-picrilhidrazil (DPPH) free radical scavenging method and ferric reducing antioxidant power (FRAP) assay. Ultrasonic probe-assisted extraction yielded the highest values of TPC (94.78-474.16 mg gallic acid equivalents/g extract). Regarding the antioxidant activity, vortex-assisted extraction gave the best DPPH results (IC50 1.89-16 µg/mL), while the highest FRAP results were obtained using the Ultra-Turrax® homogenizer (502.16-1188.81 µmol ascorbic acid equivalents/g extract). For each extraction method, response surface methodology was used to analyze the influence of the experimental conditions "extraction time" (t), "biomass/solvent ratio" (R), "solvent" (S, water % in water/ethanol mixture), and "pressure" (P) on TPC, DPPH, and FRAP of the F. spiralis extracts. In general, higher TPC content and higher antioxidant capacity (lower IC50 and higher FRAP) were obtained with higher R, t, and P, and lower S (higher ethanol %). The model regarding the combined effects of independent variables t, R, and S on the FRAP response values for vortex-assisted extractions best fitted the experimental data (R2 0.957), with optimal extraction conditions of t = 300 s, R = 50 g, and S = 25%.

Molecular characterization of cetacean poxviruses along the coast of mainland Portugal.

Cetacean poxvirus (CePV) is the causative agent of tattoo skin disease (TSD) in dolphins, porpoises and whales, a condition characterized by pinhole, ring-like lesions or generalized tattoo-like skin lesions. This study genetically characterized cetacean poxviruses from stranded animals along mainland Portugal. Samples from skin lesions compatible with TSD were obtained from 4 odontocete species (Delphinus delphis, Stenella coeruleoalba, Phocoena phocoena, and Tursiops truncatus) and analyzed using a conventional PCR assay targeting the DNA polymerase gene partially. Among the positive samples (n = 29, 65.9%), a larger DNA polymerase gene fragment was obtained, allowing a robust phylogenetic analysis. Nineteen samples (43.2%) were successfully amplified and sequenced using Sanger sequencing. By combining 11 of these sequences with those from public databases, a maximum likelihood phylogenetic tree was constructed, revealing high heterogeneity within the group. These findings contribute to a better understanding of the genetic diversity, epidemiology, phylogenetics, and evolution of CePV.

How temperature modulates the expression of pathogenesis-related molecules of the cross-kingdom pathogen Lasiodiplodia hormozganensis.

Lasiodiplodia hormozganensis, initially recognized as a fungal plant pathogen, is recognized now acknowledged as a potential threat to humans. However, our understanding of the pathogenesis mechanisms of Lasiodiplodia species remains limited, and the impact of temperature on its pathogenicity is unclear. This study aims to elucidate the effects of temperature on the biology of L. hormozganensis, focusing on the expression of pathogenesis-related molecules and its ability to function as a cross-kingdom pathogen. We conducted experiments at two different temperatures, 25 and 37 °C, analyzing the proteome and transcriptome of L. hormozganensis. Using strain CBS339.90, initially identified as L. theobromae but confirmed through ITS and tef1-α sequence analysis to be L. hormozganensis, we aimed to understand the fungus's protein expression under varying temperature conditions. Results from the functional analysis of the secretome at 25 °C showed a noteworthy presence of proteins related to carbohydrate metabolism, catabolism, plant cell wall degradation, and pathogenesis. However, when grown at 37 °C, the fungus exhibited an increased production of stress response and pathogenesis-related proteins. Our findings identified various pathways crucial for pathogenesis in both plants and humans, suggesting that L. hormozganensis possesses the genetic foundation to infect both hosts. Specific pathogenesis-related proteins, including the phytotoxin snodprot1, aspartic protease aspergillopepsin, and virulence protein SSD1, were also identified. Concluding, we propose a possible mechanism of how L. hormozganensis adapts to different temperatures. The shift in temperature results in the expression of genes that favor human related pathogenesis molecules.

A Low Transition Temperature Mixture-based viscosupplementation complemented with celecoxib for osteoarthritis treatment.

Viscosupplementation consists of hyaluronic acid (HA) intra-articular injections, commonly applied for osteoarthritis treatment while non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered for pain relief. Here, HA and a NSAID (celecoxib) were combined in a formulation based on a low transition temperature mixture (LTTM) of glycerol:sorbitol, reported to increase celecoxib's solubility, thus rendering a potential alternative viscosupplement envisioning enhanced therapeutic efficiency. The inclusion of glucosamine, a cartilage precursor, was also studied. The developed formulations were assessed in terms of rheological properties, crucial for viscosupplementation: the parameters of crossover frequency, storage (G') and loss (G'') moduli, zero-shear-rate viscosity, stable viscosity across temperatures, and shear thinning behaviour, support viscoelastic properties suitable for viscosupplementation. Additionally, the gels biocompatibility was confirmed in chondrogenic cells (ATDC5). Regarding drug release studies, high and low clearance scenarios demonstrated an increased celecoxib (CEX) release from the gel (6 to 73-fold), compared to dissolution in PBS. The low clearance setup presented the highest and most sustained CEX release, highlighting the importance of the gel structure in CEX delivery. NMR stability studies over time demonstrated the LTTM+HA+CEX (GHA+CEX) gel as viable candidate for further in vivo evaluation. In sum, the features of GHA+CEX support its potential use as alternative viscosupplement.

The Role of Parental Adherence to the Mediterranean Diet and Family Time Together in Children's Weight Status: The BeE-School Project.

The family context has been associated with children's weight status. This study aims to investigate the association of parents' adherence to the Mediterranean diet and family time with the weight status of children. The research is part of BeE-school, a cluster-randomized trial implemented in primary schools located in socially vulnerable contexts. A total of 735 children (380 boys and 355 girls) aged 6 to 10 participated in the study. Anthropometrics were assessed during school time, and weight status was categorized, while parents self-reported sociodemographic variables, adherence to the Mediterranean diet (MEDAS questionnaire), and family time. Children from families with higher education levels whose parents have a high adherence to the Mediterranean diet have lower odds of overweight/obesity (odds ratio (OR) 0.301, 95% CI 0.143-0.634, p = 0.002). Also, children from families with lower education levels who have more time together with their family have lower odds of overweight/obesity (OR 0.731, 95% CI 0.573-0.934, p = 0.012). The family environment, mainly family time together and adherence to the Mediterranean diet, exerts a significant influence on children's weight status. Professionals working in children's health should consider the family when fostering health-promoting behaviors.

A Novel Collagen Aerogel with Relevant Features for Topical Biomedical Applications.

Collagen-based aerogels have great potential for topical biomedical applications. Collagen's natural affinity with skin, biodegradability, and gelling behavior are compelling properties to combine with the structural integrity of highly porous matrices in the dry form (aerogels). This work aimed to produce a novel collagen-based aerogel and to perform the material's solid-state and physicochemical characterization. Aerogels were obtained by performing different solvent exchange approaches of a collagen-gelled extract and drying the obtained alcogels with supercritical CO2. The resulting aerogels showed a sponge-like structure with a relatively dense mesoporous network with a specific surface area of 201-203 m2/g, a specific pore volume of 1.08-1.15 cm3/g, and a mean pore radius of ca. 14.7 nm. Physicochemical characterization confirmed that the obtained aerogels are composed of pure collagen, and the aerogel production process does not impact protein tertiary structure. Finally, the material swelling behavior was assessed at various pH values (4, 7, and 10). Collagen aerogels presented a high water uptake capacity up to ~2700 wt. %, pH-dependent stability, and swelling behavior in aqueous media. The results suggest that this collagen aerogel could be a promising scaffold candidate for topical biomedical applications.

Acoustic imaging of stable double diffusion in the Madeira abyssal plain.

Sub-mesoscale and mesoscale (i.e., 1-10 km and 10-200 km, respectively) ocean processes are highly relevant for the understanding of global circulation, mixing of water masses and energy exchange between ocean layers. However, the processes happening at these scales are hard to be characterized using direct measurements of temperature and salinity. Direct measurements are obtained from vertical probes and/or autonomous vehicles, which, despite their high vertical resolution, are sparsely located in space and therefore unable to capture spatial details at these scales. Seismic oceanography (SO) data have been successfully used to imaging and characterize the ocean at these spatial scales. These data represent indirect measurements of the ocean temperature and salinity along kilometric transects with high horizontal resolution (i.e., a near-synaptic view of the system under investigation), but lower vertical resolution when compared with direct observations. Despite its complex oceanographic setting, the Madeira Abyssal Plain is still largely uncharacterized due to the lack of direct observations. We show for the first time a comprehensive processing, modelling and interpretation of three 2-D seismic oceanography sections from this region. The data show coherent seismic reflection in space, depth and time and shed light into this oceanographic setting with an unprecedent horizontal resolution. The SO modelling and interpretation are combined with existing direct measurements and a quantitative method to correlate thermohaline staircases interpreted from conductivity-temperature-depth casts and seismic reflections is proposed. The results show the relatively stable presence of thermohaline staircases in simultaneously time and space between 1200 and 2000 m of water depth and their spatial variability and contribute to the generalization of SO in physical oceanography.

Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.

Eyebrow Lift: Open-Book ROOF Transposition and Orbicularis-Frontalis Sliding Maneuver.

This article delves into innovative surgical techniques, the open-book ROOF (retro-orbicularis oculi fat) transposition technique (OBRoof) and the orbicularis-frontalis sliding maneuver (OFS), designed for eyebrow and upper eyelid rejuvenation in the aging process. Emphasis is placed on understanding the dynamic changes occurring within the forehead and eyebrow envelope's five layers and their intrinsic relationships as well as the impact of the ROOF ptosis causing upper eyelid hooding. The OBRoof technique is highlighted for its effectiveness in addressing ptotic volume, offering a rejuvenated appearance by relocating volume to the supraciliary region.In the OFS, we explore the concept of extensive dissection above the upper border of the eyebrow to allow for free repositioning of the eyebrow. The stabilization is based on deep-plane facelift concepts, as the orbicularis oculi muscle corresponds to the superficial muscular aponeurotic system, and it is anchored to the deep layers (periosteum) by passing through the frontal muscle.In summary, this article provides a comprehensive exploration of innovative and minimally invasive techniques for eyebrow and upper eyelid rejuvenation, shedding light on their anatomical foundations, procedural intricacies, and the potential for achieving natural and lasting outcomes.

The European livestock resistome.

Metagenomic sequencing has proven to be a powerful tool in the monitoring of antimicrobial resistance (AMR). Here, we provide a comparative analysis of the resistome from pigs, poultry, veal calves, turkey, and rainbow trout, for a total of 538 herds across nine European countries. We calculated the effects of per-farm management practices and antimicrobial usage (AMU) on the resistome in pigs, broilers, and veal calves. We also provide an in-depth study of the associations between bacterial diversity, resistome diversity, and AMR abundances as well as co-occurrence analysis of bacterial taxa and antimicrobial resistance genes (ARGs) and the universality of the latter. The resistomes of veal calves and pigs clustered together, as did those of avian origin, while the rainbow trout resistome was different. Moreover, we identified clear core resistomes for each specific food-producing animal species. We identified positive associations between bacterial alpha diversity and both resistome alpha diversity and abundance. Network analyses revealed very few taxa-ARG associations in pigs but a large number for the avian species. Using updated reference databases and optimized bioinformatics, previously reported significant associations between AMU, biosecurity, and AMR in pig and poultry farms were validated. AMU is an important driver for AMR; however, our integrated analyses suggest that factors contributing to increased bacterial diversity might also be associated with higher AMR load. We also found that dispersal limitations of ARGs are shaping livestock resistomes, and future efforts to fight AMR should continue to emphasize biosecurity measures.IMPORTANCEUnderstanding the occurrence, diversity, and drivers for antimicrobial resistance (AMR) is important to focus future control efforts. So far, almost all attempts to limit AMR in livestock have addressed antimicrobial consumption. We here performed an integrated analysis of the resistomes of five important farmed animal populations across Europe finding that the resistome and AMR levels are also shaped by factors related to bacterial diversity, as well as dispersal limitations. Thus, future studies and interventions aimed at reducing AMR should not only address antimicrobial usage but also consider other epidemiological and ecological factors.

Modeling Lysosomal Storage Disorders in an Innovative Way: Establishment and Characterization of Stem Cell Lines from Human Exfoliated Deciduous Teeth of Mucopolysaccharidosis Type II Patients.

Among the many lysosomal storage disorders (LSDs) that would benefit from the establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on the establishment and characterization of two MPS II patient-derived stem cell line(s) from deciduous baby teeth. To the best of our knowledge, this is the first time a stem cell population has been isolated from LSD patient samples obtained from the dental pulp. Taking into account our results on the molecular and biochemical characterization of those cells and the fact that they exhibit visible and measurable disease phenotypes, we consider these cells may qualify as a valuable disease model, which may be useful for both pathophysiological assessments and in vitro screenings. Ultimately, we believe that patient-derived dental pulp stem cells (DPSCs), particularly those isolated from human exfoliated deciduous teeth (SHEDs), may represent a feasible alternative to induced pluripotent stem cells (iPSCs) in many labs with standard cell culture conditions and limited (human and economic) resources.

How Can Deep Eutectic Systems Promote Greener Processes in Medicinal Chemistry and Drug Discovery?

Chemists in the medicinal chemistry field are constantly searching for alternatives towards more sustainable and eco-friendly processes for the design and synthesis of drug candidates. The pharmaceutical industry is one of the most polluting industries, having a high E-factor, which is driving the adoption of more sustainable processes not only for new drug candidates, but also in the production of well-established active pharmaceutical ingredients. Deep eutectic systems (DESs) have emerged as a greener alternative to ionic liquids, and their potential to substitute traditional organic solvents in drug discovery has raised interest among scientists. With the use of DESs as alternative solvents, the processes become more attractive in terms of eco-friendliness and recyclability. Furthermore, they might be more effective through making the process simpler, faster, and with maximum efficiency. This review will be focused on the role and application of deep eutectic systems in drug discovery, using biocatalytic processes and traditional organic chemical reactions, as new environmentally benign alternative solvents. Furthermore, herein we also show that DESs, if used in the pharmaceutical industry, may have a significant effect on lowering production costs and decreasing the impact of this industry on the quality of the environment.

Selective Depletion of Staphylococcus aureus Restores the Skin Microbiome and Accelerates Tissue Repair after Injury.

Our skin is home to a diverse community of commensal microorganisms integral to cutaneous function. However, microbial dysbiosis and barrier perturbation increase the risk of local and systemic infection. Staphylococcus aureus is a particularly problematic bacterial pathogen, with high levels of antimicrobial resistance and direct association with poor healing outcome. Innovative approaches are needed to selectively kill skin pathogens, such as S aureus, without harming the resident microbiota. In this study, we provide important data on the selectivity and efficacy of an S aureus-targeted endolysin (XZ.700) within the complex living skin/wound microbiome. Initial cross-species comparison using Nanopore long-read sequencing identified the translational potential of porcine rather than murine skin for human-relevant microbiome studies. We therefore performed an interventional study in pigs to assess the impact of endolysin administration on the microbiome. XZ.700 selectively inhibited endogenous porcine S aureus in vivo, restoring microbial diversity and promoting multiple aspects of wound repair. Subsequent mechanistic studies confirmed the importance of this microbiome modulation for effective healing in human skin. Taken together, these findings strongly support further development of S aureus-targeted endolysins for future clinical management of skin and wound infections.