Cells of the human intestinal tract mapped across space and time.

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.

A Change of Paradigm in the Management of Acute Psychiatric Episodes? A Retrospective Cohort Study on Trajectories of Use of Clinical Resources After the Implementation of Intensive Home-Treatment.

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (pBonf = 0.018) and with previous hospitalizations (pBonf < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (pBonf = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.

Synthesis and Anti-Inflammatory Evaluation of a Library of Chiral Derivatives of Xanthones Conjugated with Proteinogenic Amino Acids.

In recent decades, the relationship between drug chirality and biological activity has been assuming enormous importance in medicinal chemistry. Particularly, chiral derivatives of xanthones (CDXs) have interesting biological activities, including enantioselective anti-inflammatory activity. Herein, the synthesis of a library of CDXs is described, by coupling a carboxyxanthone (1) with both enantiomers of proteinogenic amino esters as chiral building blocks (2-31), following the chiral pool strategy. The coupling reactions were performed at room temperature with good yields (from 44 to 99.9%) and very high enantiomeric purity, with most of them presenting an enantiomeric ratio close to 100%. To afford the respective amino acid derivatives (32-61), the ester group of the CDXs was hydrolyzed in mild alkaline conditions. Consequently, in this work, sixty new derivatives of CDXs were synthetized. The cytocompatibility and anti-inflammatory activity in the presence of M1 macrophages were studied for forty-four of the new synthesized CDXs. A significant decrease in the levels of a proinflammatory cytokine targeted in the treatment of several inflammatory diseases, namely interleukin 6 (IL-6), was achieved in the presence of many CDXs. The amino ester of L-tyrosine (X1AELT) was the most effective in reducing IL-6 production (52.2 ± 13.2%) by LPS-stimulated macrophages. Moreover, it was ≈1.2 times better than the D-enantiomer. Indeed, enantioselectivity was observed for the majority of the tested compounds. Thus, their evaluation as promising anti-inflammatory drugs should be considered.

Microfluidic mixing system for precise PLGA-PEG nanoparticles size control.

In this study, a microfluidic device was employed to produce polymeric nanoparticles (NPs) with well-controlled sizes. The influence of several parameters in the synthesis process, namely, polymer concentration, flow rate and flow rate ratio between the aqueous and organic solutions was investigated. To evaluate the NPs size effect, three diameters were selected (30, 50 and 70 nm). Their cytocompatibility was demonstrated on endothelial cells and macrophages. Additionally, their efficacy to act as drug carriers was assessed in an in vitro inflammatory scenario. NPs loaded and released diclofenac (DCF) in a size-dependent profile (smaller sizes presented lower DCF content and higher release rate). Moreover, 30 nm NPs were the most effective in reducing prostaglandin E2 concentration. Therefore, this study demonstrates that microfluidics can generate stable NPs with controlled sizes, high monodispersity and enhanced batch-to-batch reproducibility. Indeed, NPs size is a crucial parameter for drug encapsulation, release and overall biological efficacy.

On the Bioactivity of Echinacea purpurea Extracts to Modulate the Production of Inflammatory Mediators.

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1ß, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.

Structural and elemental analysis of biochars in the search of a synthetic path to mimetize anthropic Amazon soils.

In this work, chemical and structural properties of various biochars were analyzed and compared with those from a highly stable anthropic soil, Terra Preta de Índio (TPI). TPI is believed to be responsible for the fertility of Amazonian soils and their stability; therefore, the production of a synthetic TPI would be of great interest for agricultural applications. Biochar produced from different raw biomasses were comprehensively characterized and, based on the obtained results, a preliminary study was performed testing three different routes of chemical activation using nitric acid, phosphoric acid, and potassium hydroxide as activating agents. After chemical activations, metal contents in the biochars decreased, as expected, and high degrees of carbonization were observed. In the case of the activation performed with HNO3, intense signals related to carboxylic groups in TG-MS analysis and in potentiometric titrations point out to a highly oxygenated biochar. Structural analysis showed that activations generated point defects in sp2-carbon structures of biochar, with the material obtained after KOH activation showing a high surface area (569 m2 g-1), an important feature for the use as soil amendment.

Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or ß-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and magnitude of the stimuli, may play a role in the development of an adaptive or maladaptive phenotype.

Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Molecular and serological surveillance of canine enteric viruses in stray dogs from Vila do Maio, Cape Verde.

BACKGROUND: Infections caused by canine parvovirus, canine distemper virus and canine coronavirus are an important cause of mortality and morbidity in dogs worldwide. Prior to this study, no information was available concerning the incidence and prevalence of these viruses in Cape Verde archipelago. RESULTS: To provide information regarding the health status of the canine population in Vila do Maio, Maio Island, Cape Verde, 53 rectal swabs were collected from 53 stray dogs during 2010 and 93 rectal swabs and 88 blood samples were collected from 125 stray dogs in 2011. All rectal swabs (2010 n = 53; 2011 n = 93) were analysed for the presence of canine parvovirus, canine distemper virus and canine coronavirus nucleic acids by quantitative PCR methods. Specific antibodies against canine distemper virus and canine parvovirus were also assessed (2011 n = 88).From the 2010 sampling, 43.3% (23/53) were positive for canine parvovirus DNA, 11.3% (6/53) for canine distemper virus RNA and 1.9% (1/53) for canine coronavirus RNA. In 2011, the prevalence values for canine parvovirus and canine coronavirus were quite similar to those from the previous year, respectively 44.1% (41/93), and 1.1% (1/93), but canine distemper virus was not detected in any of the samples analysed (0%, 0/93). Antibodies against canine parvovirus were detected in 71.6% (63/88) blood samples and the seroprevalence found for canine distemper virus was 51.1% (45/88). CONCLUSIONS: This study discloses the data obtained in a molecular and serological epidemiological surveillance carried out in urban populations of stray and domestic animals. Virus transmission and spreading occurs easily in large dog populations leading to high mortality rates particularly in unvaccinated susceptible animals. In addition, these animals can act as disease reservoirs for wild animal populations by occasional contact. Identification of susceptible wildlife of Maio Island is of upmost importance to evaluate the risk of pathogen spill over from domestic to wild animals in Cape Verde and to evaluate the associated threat to the wild susceptible species.

Green and Hawksbill Sea turtles of Eastern Atlantic: New insights into a globally important rookery in the Gulf of Guinea.

Sea turtles are critical components of marine ecosystems, and their conservation is important for Ocean Governance and Global Planet Health. However, there is limited knowledge of their ecology in the Gulf of Guinea. To fill this knowledge gap, this study presents the first integrative assessment of green and hawksbill turtles in the region, combining nesting surveys over 9 years and telemetry data, to offer insights into these population dynamics, and behaviours, including nesting preferences, morphological and reproductive parameters, diving patterns and inter-nesting core-use areas. Both green and hawksbill turtles are likely making a recovery on São Tomé, potentially driven by sustained conservation efforts. There are preliminary indications of recovery, but we interpret this cautiously. Coupled with satellite tracking, this study estimated that 482 to 736 green turtles and 135 to 217 hawksbills nest on the beaches of São Tomé. Their movements overlap significantly with a proposed Marine Protected Area (MPA), which suggests they may be well placed for conservation if managed appropriately. However, the presence of artisanal fisheries and emerging threats, such as sand mining and unregulated tourism, highlight the urgent need for robust management strategies that align global conservation objectives with local socioeconomic realities. This study significantly enhances our understanding of the ecology and conservation needs of the green and hawksbill turtles in the Gulf of Guinea. The insights gleaned here can contribute to the development of tailored conservation strategies that benefit these populations and the ecosystem services upon which they depend.

Metal accumulation in female green sea turtles (Chelonia mydas) from Eastern Atlantic affects their egg quality with potential implications for embryonic development.

Sea turtles, with their global distribution and complex life cycle, often accumulate pollutants such as metals and metalloids due to their extended lifespan and feeding habits. However, there are limited studies exploring the impact of metal pollution on the reproductive health of female sea turtles, specifically focusing on the quality of their eggs, which has significant implications for the future generations of these charismatic animals. São Tomé Island, a crucial nesting and feeding habitat for green sea turtles, underscores the urgent need for comprehensive research in this ecologically significant area. This study aimed to investigate whether metals and metalloids in the blood of nesting female green sea turtles induce genotoxic effects in their erythrocytes and affect their egg morphometric characteristics and the composition of related compartments. Additionally, this study aimed to evaluate whether the quality of energetic reserves for embryo development (fatty acids in yolk's polar and neutral lipids) is influenced by the contamination status of their predecessors. Results revealed correlations between Cu and Hg levels and increased "lobed" erythrocytes, while As and Cu negatively influenced shell thickness. In terms of energy reserves, both polar and neutral lipid fractions contained primarily saturated and monounsaturated fatty acids, with prevalent 18:1n-9, 18:0, 16:0, 14:0, and 12:0 fatty acids in yolk samples. The yolk polar fraction was more susceptible to contaminant levels in female sea turtles, showing consistent negative correlations between pollution load index and essential n3 fatty acids, including linolenic, eicosatrienoic, eicosapentaenoic, and docosapentaenoic acids, crucial for embryonic development. These metals accumulation, coupled with the reduced availability of these key fatty acids, may disrupt the eicosanoid and other important pathways, affecting reproductive development. This study reveals a negative correlation between metal contamination in female sea turtles' blood and egg lipid reserves, raising concerns about embryonic development and the species' future generations.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth in vitro and in vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic lethal targeting of WRN in MSI cancer and tools to dissect WRN biology. Significance: We report the discovery and characterization of potent, selective WRN helicase inhibitors for MSI cancer treatment, with biomarker analysis and evaluation of efficacy in vivo and in immunotherapy-refractory preclinical models. These findings pave the way to translate WRN inhibition into MSI cancer therapies and provide tools to investigate WRN biology. See related commentary by Wainberg, p. 1369.

A derivative of the natural compound kakuol affects DNA relaxation of topoisomerase IB inhibiting the cleavage reaction.

Topoisomerases IB are anticancer and antimicrobial targets whose inhibition by several natural and synthetic compounds has been documented over the last three decades. Here we show that kakuol, a natural compound isolated from the rhizomes of Asarum sieboldii, and a derivative analogue are able to inhibit the DNA relaxation mediated by the human enzyme. The analogue is the most efficient one and the inhibitory effect is enhanced upon pre-incubation with the enzyme. Analysis of the different steps of the catalytic cycle indicates that the inhibition occurs at the cleavage level and does not prevent DNA binding. Molecular docking shows that the compound preferentially binds near the active site at the bottom of the catalytic residue Tyr723, providing an atomistic explanation for its inhibitory activity.

Antioxidant and Anti-Inflammatory Activities of Stellera chamaejasme L. Roots and Aerial Parts Extracts.

Natural products, mainly plants, have a crucial role in folk medicine. Particularly, Stellera chamaejasme L. has been traditionally used in Mongolian medicine to treat various diseases, including chronic tracheitis, tuberculosis, and psoriasis. In this study, ethanol (EtOH) and dichloromethane (DCM) extracts of its roots (R) and aerial parts (AP) were evaluated for their antioxidant and anti-inflammatory activities. Thin-layer chromatography demonstrated the presence of flavonoids, namely kaempferol and quercetin-3-O-glucopyranoside, only in the EtOH-AP. Conversely, it showed that kaempferol, quercetin-3-O-glucopyranoside, coumarin, luteolin, rutin, morin, and riboflavin were not present in the other three extracts. The S. chamaejasme extracts exhibited strong antioxidant activity. In addition, the roots extracts presented the highest antioxidant activity against peroxyl radicals, with the EtOH-R being the most potent (IC50 = 0.90 ± 0.07 µg/mL). S. chamaejasme extracts also efficiently inhibited the production of one of the main pro-inflammatory cytokines, interleukin (IL)-6, in a dose-dependent manner by lipopolysaccharide-stimulated macrophages. Particularly, DCM-R was the strongest extract, reducing ≈ 91.5% of the IL-6 production. Since this extract was the most effective, gas chromatography-mass spectrometry (GC-MS) analyses were performed and demonstrated the presence of two fatty acids (palmitic acid and 9-octadecenoic acid), one fatty alcohol (1-hexadecanol), and one triterpenoid (squalene) that can contribute to the observed bioactivity. Herewith, S. chamaejasme extracts, mainly DCM-R, exhibit antioxidant and anti-inflammatory activities that could be applied as new and innovative natural formulations for the treatment of chronic inflammatory diseases.

Echinacea purpurea Fractions Represent Promising Plant-Based Anti-Inflammatory Formulations.

Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1/2, STAT 3, and/or NF-κB signaling pathways, and/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases.

Base editing screens map mutations affecting interferon-γ signaling in cancer.

Interferon-γ (IFN-γ) signaling mediates host responses to infection, inflammation and anti-tumor immunity. Mutations in the IFN-γ signaling pathway cause immunological disorders, hematological malignancies, and resistance to immune checkpoint blockade (ICB) in cancer; however, the function of most clinically observed variants remains unknown. Here, we systematically investigate the genetic determinants of IFN-γ response in colorectal cancer cells using CRISPR-Cas9 screens and base editing mutagenesis. Deep mutagenesis of JAK1 with cytidine and adenine base editors, combined with pathway-wide screens, reveal loss-of-function and gain-of-function mutations, including causal variants in hematological malignancies and mutations detected in patients refractory to ICB. We functionally validate variants of uncertain significance in primary tumor organoids, where engineering missense mutations in JAK1 enhanced or reduced sensitivity to autologous tumor-reactive T cells. We identify more than 300 predicted missense mutations altering IFN-γ pathway activity, generating a valuable resource for interpreting gene variant function.

A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.

Stress response markers in the blood of São Tomé green sea turtles (Chelonia mydas) and their relation with accumulated metal levels.

Metals are persistent worldwide being harmful for diverse organisms and having complex and combined effects with other contaminants in the environment. Sea turtles accumulate these contaminants being considered good bioindicator species for marine pollution. However, very little is known on how this is affecting these charismatic animals. São Tomé and Príncipe archipelago harbours important green sea turtle (Chelonia mydas) nesting and feeding grounds. The main goal of this study was to determine metal and metalloid accumulation in the blood of females C. mydas nesting in São Tomé Island, and evaluate the possible impacts of this contamination by addressing molecular stress responses. Gene expression analysis was performed in blood targeting genes involved in detoxification/sequestration and metal transport (mt, mtf and fer), and in antioxidant and oxidative stress responses (cat, sod, gr, tdx, txrd, selp and gclc). Micronuclei analysis in blood was also addressed as a biomarker of genotoxicity. Present results showed significant correlations between different gene expressions with the metals evaluated. The best GLM models and significant relationships were found for mt expression, for which 78% of the variability was attributed to metal levels (Al, Cu, Fe, Hg, Pb and Zn), followed by micronuclei count (65% - Cr, Cu, Fe, Hg, Mn and Zn), tdx expression (52% - Cd, Fe, Mn, Pb and Se), and cat expression (52% - As, Fe, Se and Cd x Hg). Overall, this study demonstrates that these green sea turtles are trying to adapt to the oxidative stress and damage produced by metals through the increased expression of antioxidants and other protectors, which raises concerns about the impacts on these endangered organisms' fitness. Furthermore, promising biomarker candidates associated to metal stress were identified in this species that may be used in future biomonitoring studies using C. mydas' blood, allowing for a temporal follow-up of the organisms.

Fishroesomes as carriers with antioxidant and anti-inflammatory bioactivities.

The great diversity of marine habitats and organisms renders them a high-value source to find/develop novel drugs and formulations. Therefore, herein, sardine (Sardina pilchardus) roe was used as a lipidic source to produce liposomes. This fish product presents high nutritional value, being its lipidic content associated with important health benefits. Consequently, it can be advantageously used to produce therapeutically active delivery devices. Roe lipids were extracted using the Matyash method. After lipid film hydration and extrusion, sardine roe-derived large unilamellar liposomes (LUVs), designated as fishroesomes, presented a size of ≈330 nm and a significant negative surface charge (≈-27 mV). Radical scavenging assays demonstrated that fishroesomes efficiently neutralized peroxyl, hydroxyl and nitric oxide radicals. Moreover, fishroesomes significantly reduced the expression of pro-inflammatory cytokines and chemokines by LPS-stimulated macrophages at non-toxic concentrations for L929 and THP-1 cells. Consequently, the developed liposomes exhibit unique properties as bioactive drug carriers for inflammatory diseases treatment.

Encapsulation of essential oils using cinnamic acid grafted chitosan nanogel: Preparation, characterization and antifungal activity.

Chemical modifications in the chitosan structure may result in obtaining a new material with improved chemical properties, such as an ability to encapsulate lipophilic compounds. This study aimed to synthesize cinnamic acid grafted chitosan nanogel to encapsulate the essential oils of Syzygium aromaticum and Cinnamomum ssp., in order to develop a material to be applied in the control of dermatophytosis caused by the fungus Microsporum canis. The cinnamic acid graft in chitosan was verified by the Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Solid State Nuclear Magnetic Resonance of the 13C Nucleus (13C SSNMR) and Thermal analysis coupled to mass spectrometry (TG-MS) techniques. The nanogel obtained showed affinity for the essential oils of S. aromaticum and Cinnamomum, with encapsulation efficiencies equal to 74% and 89%, respectively. When in an aqueous medium the nanogel with the encapsulated essential oils was able to form stable nanoparticles with average sizes of 176.0 ± 54.3 nm and 263.0 ± 81.4 nm. The cinnamic acid grafted chitosan nanogel showed antifungal activity in vitro against M. canis, inhibiting up to 53.96% of its mycelial growth. Complete inhibition of mycelial growth was achieved by the nanogel with encapsulated essential oils. The results found in this work demonstrated the development of a material with potential application in the control of dermatophytosis caused by the fungus M. canis.