Search

Wildland firefighters are exposed to metal(loid)s released during wildfires through vegetation combustion, which also promotes remobilization of accumulated anthropogenic metal(loid)s. Studies biomonitoring metal(loid)s exposure promoted exclusively by wildfire suppression activities are lacking. This work aimed to characterize, for the first time, the impact of real-life wildland firefighting operations on urinary levels of priority pollutant metal(loid)s [14 included in ATSDR, 11 in USEPA, and 4 in Human Biomonitoring for Europe Initiative priority lists] in firefighters. Spot urines were sampled pre-exposure (105 non-smokers, 76 smokers) and post-exposure to firefighting activities (20 non-smokers, 25 smokers); among those, paired samples were collected from 14 non-smoking and 24 smoking firefighters. Smokers displayed significantly higher baseline levels of zinc (28 %), lithium (29 %), cadmium (55 %), rubidium (13 %), and copper (20 %) than non-smokers. Following wildfire suppression, the concentration of the WHO potentially toxic metal(loid)s rose from 2 % to 3 % in smokers and 2 % to 5 % in non-smokers (up to 4 % for all firefighters and up to 5 % in paired samples). Levels of nickel (33-53 %), antimony (45-56 %), and cesium (40-47 %) increased significantly post-exposure in non-smokers (in all firefighters and in paired samples), whose urinary concentrations were generally more impacted by wildfire emissions than those of smokers. Arsenic (80 %) displayed the only significant increase post-exposure in smokers, being the best discriminant of exposure to wildfire emissions in these subjects. Significant positive correlations were found for age and/or career length with cadmium, lead, barium, strontium, and mercury, and for body mass index with arsenic. The reference/guidance values were exceeded for arsenic, zinc, cesium, nickel, antimony, cadmium, lead, thallium, mercury, copper, and cobalt in 1-90 % of firefighters suggesting augmented health risks due to wildfire combating and emphasizing the need of mitigation strategies. This study also provides biomonitoring data to help setting reference values for the occupationally exposed part of population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Mechanical perturbations of drug during solid pharmaceutical processing like milling can often generate crystal disorder posing serious implications to drug's stability. While physical changes like amorphization, recrystallization, polymorphism of the disordered drugs are extensively studied and reported in the literature, the propensities and inter-dependencies of recrystallization and degradation propensities of disordered drugs have seldom received deep attention. Previous investigations from our lab have explored some of these interplays, aiming to develop predictive stability models. As a follow-up, the implication of crystal disorder on the oxidative instability of Olanzapine (OLA) during accelerated storage is investigated in this work. Cryo-milling OLA at varied time intervals generated different extents of crystal disorder. The milled samples were characterized using calorimetry and infrared (IR) spectroscopy to examine the physical state, while their degradation was evaluated using ultra-performance liquid chromatographic methods. An X-ray amorphous OLA sample was generated by melt-cooling, and used as an amorphous reference. The crystallinity of the cryo-milled samples was quantified using a partial least square regression model based on ATR-FTIR spectroscopic data. The cryo-milled samples were exposed to different accelerated stability conditions along with crystalline (unmilled) and quench cooled (amorphous) samples, serving as controls. At periodic intervals, samples were removed from the stability storage, and analyzed using ATR-FTIR and UPLC methods to quantify the crystallinity- and degradation extents. A positive relation was witnessed between the initial degree of crystallinity and degradation kinetics of the disordered OLA samples during stability storage indicating a strong dependency of degradation on the disorder contents for such disordered solids. The results obtained in this study can potentially explain consequences of inter-batch variations of drugs during stability storage, in addition to enabling de-risking strategies towards eliminating solid drug instabilities in product development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Mitochondria are essential organelles that play crucial roles in various metabolic and signalling pathways. Proper neuronal function is highly dependent on the health of these organelles. Of note, the intricate structure of neurons poses a critical challenge for the transport and distribution of mitochondria to specific energy-intensive domains, such as synapses and dendritic appendages. When faced with chronic metabolic challenges and bioenergetic deficits, neurons undergo degeneration. Unsurprisingly, disruption of mitostasis, the process of maintaining cellular mitochondrial content and function within physiological limits, has been implicated in the pathogenesis of several age-associated neurodegenerative disorders. Indeed, compromised integrity and metabolic activity of mitochondria is a principal hallmark of neurodegeneration. In this review, we survey recent findings elucidating the role of impaired mitochondrial homeostasis and metabolism in the onset and progression of age-related neurodegenerative disorders. We also discuss the importance of neuronal mitostasis, with an emphasis on the major mitochondrial homeostatic and metabolic pathways that contribute to the proper functioning of neurons. A comprehensive delineation of these pathways is crucial for the development of early diagnostic and intervention approaches against neurodegeneration., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

The protein p53 is a transcription factor with several key roles in cells, including acting as a tumour suppressor. In most human cancers its tumour suppressor function is inactivated, either through inhibition by negative regulators or by mutation in the TP53 gene. Thus, there is a high interest in developing molecules able to activate p53 tumour suppressor activity. Tryptophanol-derived isoindolinones are known to act as wild-type and mutant p53 activators. Specifically, SLMP53-1 is a non-fluorescent wild-type and mutant p53 R280K reactivator, with potent in vivo anti-tumour activity in HCT116 and MDA-MB-231 mice xenograft models. With the aim of studying tryptophanol-derived isoindolinones intracellular localization by fluorescence microscopy, three SLMP53-1 based fluorescent probes were prepared. Here we report the design, synthesis, photophysical characterization, antiproliferative activity and cell localization studies of these fluorescent probes. The previously described structure-activity relationships of the SLMP53-1 scaffold set the basis for the design the fluorescent probes. The probes were prepared by connecting a small fluorophore (dansyl or 7-nitrobenzofurazan) to the indole nitrogen of the tryptophanol-derived oxazoloisoindolinone SLMP53-1 through two different linkers. The antiproliferative activity and cell localization studies of the three fluorescent probes were performed in HCT116 cells. The three probes showed enhanced internalization when compared with their fluorophore-linker intermediates, good photo-stability and high affinity for the endoplasmic reticulum, indicating the potential involvement of endoplasmic reticulum in the mechanism of action of tryptophanol-derived oxazoloisoindolinones., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tropane alkaloids (TAs) are toxic compounds with potent anticholinergic effects. Herbal infusions are among the most contaminated food commodities; however, the fate of TAs after ingestion remains poorly understood. This study presents a comprehensive investigation into the absorption, and metabolism of five TAs (atropine, scopolamine, tropine, homatropine, and apoatropine) following the digestion of contaminated tea. In vitro human cell models were employed, including gastric (NCI-N87), intestinal (Caco-2:HT29-MTX), and hepatic (HEP-G2) cells. TAs were found to be highly absorbed in the intestinal epithelium, while gastric cells exhibited poor absorption. Metabolism was studied using a custom-made database, revealing that it occurs predominantly in intestinal cells, involving hydroxylation and methylation reactions. Cell metabolomics was conducted using annotation, fragment simulation, and statistical software platforms. Significant statistical differences were observed for 40 tentatively identified compounds. MetaboAnalyst 5.0 was employed to discern the most disturbed metabolic pathways, with amoniacids biosynthesis pathways and TCA cycles being the most affected. These pathways are involved in responses to cellular metabolic stress, neurotransmitter production, cellular energy generation, and the regulation of oxidative stress response. The findings of this study enhance our understanding of the fate of TAs after ingestion, their metabolization and their effects at the cellular level., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Antimicrobial peptides have been radiolabeled and investigated as molecular diagnostic probes due to their propensity to accumulate in infectious sites rather than aseptic inflammatory lesions. LyeTx I is a cationic peptide from the venom of Lycosa erythrognatha, exhibiting significant antimicrobial activity. LyeTx I mn∆K is a shortened derivative of LyeTx I, with an optimized balance between antimicrobial and hemolytic activities. This study reports the first 68 Ga-radiolabeling of the DOTA-modified LyeTx I mn∆K and primarily preclinical evaluations of [ 68 Ga]Ga-DOTA(K)-LyeTx I mn∆K as a PET radiopharmaceutical for infection imaging., Methods: DOTA(K)-LyeTx I mn∆K was radiolabeled with freshly eluted 68 Ga. Radiochemical yield (RCY), radiochemical purity (RCP), and radiochemical stability (in saline and serum) were evaluated using ascending thin-layer chromatography (TLC) and reversed-phase high-performance liquid chromatography (RP-HPLC). The radiopeptide's lipophilicity was assessed by determining the logarithm of the partition coefficient (Log P). Serum protein binding (SBP) and binding to Staphylococcus aureus (S. aureus) cells were determined in vitro. Ex vivo biodistribution studies and PET/CT imaging were conducted in healthy mice (control) and mice with infection and aseptic inflammation to evaluate the potential of [ 68 Ga]Ga-DOTA(K)-LyeTx I mn∆K as a specific PET radiopharmaceutical for infections., Results: [ 68 Ga]Ga-DOTA(K)-LyeTx I mn∆K was obtained with a high RCY (>90 %), and after purification through a Sep-Pak C18 cartridge, the RCP exceeded 99 %. Ascending TLC and RP-HPLC showed that the radiopeptide remained stable for up to 3.0 h in saline solution and up to 1.5 h in murine serum. [ 68 Ga]Ga-DOTA(K)-LyeTx I mn∆K exhibited hydrophilic characteristics (Log P = -2.4 ± 0.1) and low SPB (ranging from 23.3 ± 0.4 % at 5 min of incubation to 10.5 ± 1.1 % at 60 min of incubation). The binding of [ 68 Ga]Ga-DOTA(K)-LyeTx I mn∆K to S. aureus cells was proportional to bacterial concentration, with binding percentages of 8.8 ± 0.5 % (0.5 × 10 9  CFU . mL -1 ), 16.2 ± 1.4 % (1.0 × 10 9  CFU . mL -1 ), and 62.2 ± 0.6 % (5.0 × 10 9  CFU . mL -1 ). Ex vivo biodistribution studies and PET/CT images showed higher radiopeptide uptake at the infection site compared to the aseptic inflammation site; the latter was similar to the control group. Target-to-non-target (T/NT) ratios obtained by ex vivo biodistribution data were approximately 1.0, 1.3, and 3.0 at all investigated time intervals for the control, aseptic inflammation, and infection groups, respectively. Furthermore, T/NT ratios obtained from PET/CT images were 1.1 ± 0.1 for the control group and 1.4 ± 0.1 for the aseptic inflammation group. For the infection group, T/NT ratio was 5.0 ± 0.3, approximately 5 times greater compared to the former groups., Conclusions: The results suggest the potential of [ 68 Ga]Ga-DOTA(K)-LyeTx I mn∆K as a PET radiopharmaceutical for molecular imaging of infections., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Major Depressive Disorder (MDD) is a very complex disease, challenging to study and manage. The complexities of MDD require extensive research of its mechanisms to develop more effective therapeutic approaches. Crucial in the context of this disease is the role of brain-derived neurotrophic factor (BDNF) signaling pathway., Aim: This manuscript aims to explore the complex relationship between MDD and BDNF signaling pathway, focusing on how BDNF is modulated in response to oxidative stress and corticosterone, known to be altered in MDD and contributing to the pathology of the disorder, when treated with scopolamine and mirtazapine., Methods: To assess BDNF levels after the different treatment conditions, rat hippocampal slices and mice primary hippocampus and cortical cell culture were analyzed by immunofluorescence and Western blot., Key Findings: Both mirtazapine and scopolamine under stress conditions induced by hydrogen peroxide (H 2 O 2 ) and corticosterone, had a significant impact on BDNF levels, and this was distinct in different neuronal models. Mirtazapine, especially when combined with H 2 O 2 , altered BDNF expression. Scopolamine when combined with both stressors also altered BDNF levels. However, its effects varied depending on the specific neuronal model and stress condition. In accordance with BDNF results, phosphorylated tropomyosin receptor kinase B (pTrkB) presented increased activation when neuronal cells subjected to stress were treated with mirtazapine or scopolamine., Significance: Collectively, this study highlights the complex connection between these compounds, stress conditions, and BDNF/TrkB modulation, supporting the potential therapeutic effects of scopolamine and mirtazapine in modulating BDNF levels, even in stressful conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Propolis is a natural resinous mixture produced by honeybees with numerous biological activities. Considering the recently reported potential of propolis as an adjuvant in COVID-19 treatment, a methodology for the fractionation of the hexane extract of Brazilian green propolis (HEGP) was developed for the obtention of prenylated biomarkers by countercurrent chromatography. The inhibition of the interaction between the receptor binding domain (RBD) of spike and ACE2 receptor was evaluated by the Lumitᵀᴹ immunoassay. Fractionation of HEGP was performed by both normal (CCC1 and CCC2, with extended elution) and reversed (CCC3) phase elution-extrusion modes with the solvent system hexane-ethanol-water 4:3:1. The normal elution mode of CCC1 (471 mg HEGP in a 80 mL column volume, 1.6 mm id) was scaled-up (CCC5, 1211 mg HEGP in a 112 mL column volume, 2.1 mm id), leading to the isolation of 89.9 mg of artepillin C, 1; 52.7 mg of baccharin, 2; and 26.6 mg of chromene, with purities of 93 %, 83 % and 88 %, respectively, by HPLC-PDA. Among the isolated compounds, artepillin C, 1, and baccharin, 2, presented the best results in the Lumitᵀᴹ immunoassay, showing 67% and 51% inhibition, respectively, at the concentration of 10 μM. This technique proved to be of low operational cost and excellent reproducibility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The presence of plastic debris and organo-brominated compounds in the marine environment poses a concern to wildlife. Plastic can absorb and release chemical compounds, making their ingestion potentially harmful, while chemical compounds have become omnipresent, with a tendency to bioaccumulate in the food web. Seabirds are often used as indicators of marine plastic pollution, yet studies on the exposure of tropical communities to plastic contamination are still scarce. In this study we monitored the amounts of plastics in faeces and organo-brominated compounds ingested/assimilated in feathers by adults and chicks of Cape Verde shearwaters and Bulwer's petrels from Cabo Verde. Anthropogenic pollutants, polybrominated diphenyl ethers (PBDEs), and naturally generated methoxylated-PBDEs (MeO-PBDEs) were among the probed compounds. The frequency of plastic debris ingestion was similar in both species' adults and chicks, although, the characteristics of the ingested plastic differed. Frequency and number of microplastics increased throughout the nestling season for chicks from both species. All species and age groups showed the presence of PBDEs and MeO-PBDEs. Among PBDEs, Bulwer's petrels exhibited higher concentrations than Cape Verde shearwaters, and chicks had higher concentration profiles than adults. Specifically, Bulwer's petrel chicks showed higher concentrations than Cape Verde shearwater chicks. On the contrary, Cape Verde shearwater adults exhibited higher occurrence and concentrations of MeO-PBDEs when compared to Cape Verde shearwater chicks. We found no effect of plastic loadings or loadings of organohalogen contaminants on body condition or size, although harmful effects may be hidden or reveal themselves in a medium- to long-term. Feather samples from both adults and chicks were shown to be useful for comparing intraspecific contamination levels and appear suitable for the long-term assessment of organohalogen contaminants in seabirds. Species-specific foraging and feeding strategies are likely the drivers of the observed variation in organochlorine contamination burdens among seabird species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Photosensitization reactions caused by ultraviolet and visible radiation (UV-vis) absorbing chemicals can induce DNA damage through direct and indirect mechanisms. In this context, the investigation of phototoxicity is an essential part of the toxicological assessment programs for drugs, cosmetics and other chemicals that may be exposed to UV-vis light. The current battery of photosafety assessment tests includes an initial investigation of their photoreactive potential followed by in vitro phototoxicity testing. The in vitro 3T3 Neutral Red Uptake (NRU) and the Reconstructed Human Epidermis phototoxicity methods are currently the only validated and recognized tests for this purpose. However, they are not suitable for detecting the photogenotoxic potential of compounds, as they are based on photocytotoxicity measurement. Although there are adaptations of genotoxicity assays in the presence of UV-vis irradiation, these methods are not validated and standardized, and their biomodels have limitations. Additionally, even though computational toxicology is an already implemented strategy for human health hazard assessment, in silico photosafety models also have limitations. The currently available in silico models are based on the 3T3 NRU assay, thus limiting their ability to reliably predict photogenotoxicity. There is evidence of chemicals that present negative results in 3T3 NRU-based in vitro and in silico tests, yet exhibit photogenotoxic potential. This is exemplified by the agrochemical glyphosate, whose photomutagenic effect was recently reported using a promising yeast-based method as a New Approach Methodology. Therefore, the need to implement a battery of phototoxicity tests, including in vitro and/or in silico photogenotoxicity assessments, to complement the existing photocytotoxicity tests should be re-discussed. Otherwise, photosafety is not completely guaranteed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Patient prioritization is a effective strategy to identify high risk patients for targeted Clinical Pharmacy Service (CPS) in hospital pharmacy. However, there is a paucity of patient prioritization tool to use in clinical practice., Objectives: Describe the development, content validation and standardization of an adult patient prioritization tool for hospital CPS named, PrioFarClinH., Methods: The tool was developed using a stepwise design multi: Scoping Review to identify prioritization criteria/sub-criteria; Delphi technique to obtain consensus under the identified criteria/sub-criteria; Survey with pharmacists evaluating applicability of the criteria/sub-criteria obtained from Delphi; Definition of criteria/sub-criteria to be included in PrioFarClinH attribution of scores. Content validation was performed by a panel of experts evaluating relevance, feasibility, clarity and adequacy of the score. Content Validity Index (CVI) was calculated. Standardization occurred through a retrospective observational study carried out at 24 and 72 h and median of the patient's hospital stay. An intragroup norm was performed, determining percentile ranks of the instrument's total scores. Patients with a P90 score were classified with a high level of prioritization for CPS., Results: PrioFarClinH is divided into three sections, with prioritization criteria for health issues; therapeutic classes; laboratory parameters. It comprises 51 criteria with specific scores with simple total calculation. None of the criteria presented CVI <0.78, maintaining the items from the initial version of PrioFarClinH. The scores were adjusted per suggestions from the panel of judges. Data were collected from 393 patients. The P90 percentile in the three hospitalization stages (24 h, 72 h, and median) was found, respectively, in the following scores: 18.0, 20.0, and 22.6., Conclusions: PrioFarClinH is a comprehensive tool to target and to prioritize adults patients most likely to benefit from CPS. Evidence for adequate content validity was provided. However, further validation of this tool is necessary to establish tool performance., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Zinc plays a crucial role both in the immune system and endocrine processes. Zinc restriction in the diet has been shown to lead to degeneration of the endocrine pancreas, resulting in hormonal imbalance within the β-cells. Proteostasismay vary depending on the stage of a pathophysiological process, which underscores the need for tools aimed at directly analyzing biological status. Among proteomics methods, MALDI-ToF-MS can serve as a rapid peptidomics tool for analyzing extracts or by histological imaging. Here we report the optimization of MALDI imaging mass spectrometry analysis of histological thin sections from mouse pancreas. This optimization enables the identification of the major islet peptide hormones as well as the major accumulated precursors and/or proteolytic products of peptide hormones. Cross-validation of the identified peptide hormones was performed by LC-ESI-MS from pancreatic islet extracts. Mice subjected to a zinc-restricted diet exhibited a relatively lower amount of peptide intermediates compared to the control group. These findings provide evidence for a complex modulation of proteostasis by micronutrients imbalance, a phenomenon directly accessed by MALDI-MSI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Hypertension is the chronic disease that most affects the elderly population worldwide and is the main modifiable risk factor for cardiovascular diseases. In hypertensive elderly patients, health literacy emerges as a key component for achieving better clinical outcomes., Objective: This study aims to describe the health literacy strategies used for elderly patients with arterial hypertension., Methods: A review of the scientific literature was conducted in accordance with recommendations from the Joanna Briggs Institute and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. Three databases were used to identify relevant studies which were then assessed for eligibility, extracted, and categorized., Results: A total of 6442 articles were identified in the databases, out of which 1486 were duplicates and were removed. Based on titles and abstracts, 4887 articles were excluded, and 59 were eliminated through full-text analysis for not meeting the eligibility criteria. Ten studies were included in this scoping review. The identified strategies included face-to-face group educational sessions, face-to-face individual educational sessions, use of written educational materials, educational sessions through electronic devices and/or computers, individual counseling, physical exercise, and personal health diary. The most addressed topics were the nature of hypertension, nutrition, and physical exercise. The study environments highlighted the importance of involving a multidisciplinary team in health literacy strategies for elderly individuals whith hypertension., Conclusions: Interventions with mixed measures were commonly used by the authors and encouraged disease self-management. Access to information and the promotion of critical thinking allowed patients to have better disease control. However, studies linking health literacy and elderly individuals with arterial hypertension are still scarce, indicating the need for further research., Competing Interests: Declarations of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Integral health encompasses the way individuals live, considering their quality of life. An inadequate lifestyle can harm human health, increasing the risk of developing chronic non-communicable diseases, which represent 71% of the causes of death worldwide and 54.7% in Brazil. The COVID-19 pandemic has led to impacts on quality of life, resulting from lifestyle changes, especially among health professionals. This constitutes an important factor in the health-disease relationship and the core of the healthcare approach embraced by Ayurveda. The present study evaluated the role of daily Ayurvedic practices in improving the quality of life of health professionals working in the Family Health Strategy of SUS in Paty do Alferes/RJ, Brazil. Ayurveda practices based on Trayopastamba were introduced to 30 health professionals through lectures and guided activities from July to October 2021, spanning three months. Quality of life was assessed using the WHOQOL-BREF questionnaire before and after the intervention. An improvement in perceived quality of life was observed in the physical, psychological, and environmental domains (p > 0.05), while the social domain did not show statistically significant results. The physical domain demonstrated the most substantial score increase (10.95). Conversely, the social domain displayed the smallest rise in scores (5.83). In conclusion, the daily Ayurvedic practices demonstrated the potential to enhance the quality of life in this group, contributing to health promotion in a practical and economically accessible manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Siderophores are small molecules of organic nature, released by bacteria to chelate iron from the surrounding environment and subsequently incorporate it into the cytoplasm. In addition to iron, these secondary metabolites can complex with a wide variety of metals, which is why they are commonly studied in the environment. Heavy metals can be very toxic when present in large amounts on the planet, affecting public health and all living organisms. The pollution caused by these toxic metals is increasing, and therefore it is urgent to find practical, sustainable, and economical solutions for remediation. One of the strategies is siderophore-assisted bioremediation, an innovative and advantageous alternative for various environmental applications. This research highlights the various uses of siderophores and metallophores in the environment, underscoring their significance to ecosystems. The study delves into the utilization of siderophores and metallophores in both marine and terrestrial settings (e.g. bioremediation, biocontrol of pathogens, and plant growth promotion), such as bioremediation, biocontrol of pathogens, and plant growth promotion, providing context for the different instances outlined in the existing literature and highlighting their relevance in each field. The study delves into the structures and types of siderophores focusing on their singular characteristics for each application and methodologies used. Focusing on recent developments over the last two decades, the opportunities and challenges associated with siderophores and metallophores applications in the environment were mapped to arm researchers in the fight against environmental pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Elevated levels of prostaglandin E 2 have been implicated in the pathophysiology of various diseases. Anti-inflammatory drugs that act through the inhibition of cyclooxygenase enzymatic activity, thereby leading to the suppression of prostaglandin E 2 , are often associated with several side effects due to their non-specific inhibition of cyclooxygenase enzymes. Consequently, the targeted suppression of prostaglandin E 2 production with innovative molecules and/or mechanisms emerges as a compelling therapeutic strategy for the treatment of inflammatory-related diseases. Therefore, in this study, a systematic analysis of 28 pyrazole derivatives was conducted to explore their potential mechanisms for reducing prostaglandin E 2 levels. In this context, the evaluation of these derivatives extended to examining their capacity to reduce prostaglandin E 2 in vitro in human whole blood, inhibit cyclooxygenase-1 and cyclooxygenase-2 enzymes, modulate cyclooxygenase-2 expression, and suppress oxidative burst in human leukocytes. The results enabled the establishment of significant structure-activity relationships, elucidating key determinants for their activities. In particular, the 4-styryl group on the pyrazole moiety and the presence of chloro substitutions were identified as key determinants. Pyrazole 8 demonstrated the capacity to reduce prostaglandin E 2 levels by downregulating cyclooxygenase-2 expression, and pyrazole-1,2,3-triazole 18 emerged as a dual-acting agent, inhibiting human leukocytes' oxidative burst and cyclooxygenase-2 activity. Furthermore, pyrazole 26 demonstrated effective reduction of prostaglandin E 2 levels through selective cyclooxygenase-1 inhibition. These results underscore the multifaceted anti-inflammatory potential of pyrazoles, providing new insights into the substitutions and structural frameworks that are beneficial for the studied activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Thrombosis is currently among the major causes of morbidity and mortality in the World. New prevention and therapy alternatives have been increasingly sought in medicinal plants. In this context, we have been investigating parsley, Petroselinum crispum (Mill.) Nym, an aromatic herb with two leaf varieties. We report here the in vitro, in vivo, and ex vivo anti-hemostatic and antithrombotic activities of a parsley curly-leaf variety. Aqueous extracts of aerial parts (PCC-AP), stems (PCC-S), and leaves (PCC-L) showed significant in vitro antiplatelet activity. PCC-AP extract exhibited the highest activity (IC 50 2.92 mg/mL) when using ADP and collagen as agonists. All extracts also presented in vitro anticoagulant activity (APTT and PT) and anti-thrombogenic activity. PCC-S was the most active, with more significant interference in the factors of the intrinsic coagulation pathway. The oral administration of PCC-AP extract in rats caused a greater inhibitory activity in the deep vein thrombi (50%; 65 mg/kg) than in arterial thrombi formation (50%; 200 mg/kg), without cumulative effect after consecutive five-day administration. PCC-AP extract was safe in the induced bleeding time test. Its anti-aggregating profile was similar in ex vivo and in vitro conditions but was more effective in the extrinsic pathway when compared to in vitro results. Apiin and coumaric acid derivatives are the main compounds in PCC-AP according to the HPLC-DAD-ESI-MS/MS profile. We demonstrated for the first time that extracts from different parts of curly parsley have significant antiplatelet, anticoagulant, and antithrombotic activity without inducing hemorrhage, proving its potential as a source of antithrombotic compounds., Competing Interests: Declaration of competing interest none., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cutaneous leishmaniasis (CL) is a vector-borne disease characterized by skin lesions that can evolve into high-magnitude ulcerated lesions. Thus, this study aimed to develop an innovative nanoemulsion (NE) with clove oil, Poloxamer® 407, and multiple drugs, such as amphotericin B (AmB) and paromomycin (PM), for use in the topical treatment of CL., Methods: Droplet size, morphology, drug content, stability, in vitro release profile, in vitro cytotoxicity on RAW 264.7 macrophages, and antileishmanial activity using axenic amastigotes of Leishmania amazonensis were assessed for NEs., Results: After optimizing the formulation parameters, such as the concentration of clove oil and drugs, using an experimental design, it was possible to obtain a NE with an average droplet size of 40 nm and a polydispersion index of 0.3, and these parameters were maintained throughout the 365 days. Furthermore, the NE showed stability of AmB and PM content for 180 days under refrigeration (4 °C), presented a pH compatible with the skin, and released modified AmB and PM. NE showed the same toxicity as free AmB and higher toxicity than free PM against RAW 264.7 macrophages. The same activity as free AmB, and higher activity than free PM against amastigotes L. amazonensis., Conclusion: It is possible to develop a NE for the treatment of CL; however, complementary studies regarding the antileishmanial activity of NE should be carried out., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Rare diseases are characterized by substantial unmet need mostly because the majority have limited, or no treatment options and a large number also affect children. Since the inception of EU orphan regulation in 2000 the European Medicines Agency Committee for Orphan Medicinal Products has received several applications for paediatric rare neuromuscular diseases (PERAN) however treatment options remain limited. Here we discuss the results form an observational, retrospective, cross-sectional study to characterize the currently authorised orphan medicinal products (OMP) and orphan designations (OD) given to products for PERAN in the last two decades. In the EU about half of PERAN diseases have at least one active OD approved since 2000, and about half of these are for Duchenne muscular dystrophy (DMD). The large majority of PERAN diseases do not have an authorised medicine with only 6 OMP currently authorised for Spinal muscular atrophy (3); DMD (1) and Myasthenia gravis (2). One in five products have inactive or discontinued regulatory development but clinical trials are ongoing for the vast majority of PERAN diseases, and more than half are in the final stage of clinical research with significantly more products with medical plausibility based in clinical data reaching advanced stages in clinical development., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, 3D-printing based on fused-deposition modeling (FDM) was employed as simple and cost-effective strategy to fabricate a novel format of rotating-disk sorptive devices. As proof-of-concept, twenty organochlorine and organophosphorus pesticides were determined in water samples through rotating-disk sorptive extraction (RDSE) using honeycomb-like 3D-printed disks followed by gas chromatography coupled to mass spectrometry (GC-MS). The devices that exhibited the best performance were comprised of polyamide + 15 % carbon fiber (PA + 15 % C) with the morphology being evaluated through X-ray microtomography. The optimized extraction conditions consisted of 120 min of extraction using 20 mL of sample at stirring speed of 1100 rpm. Additionally, liquid desorption using 800 µL of acetonitrile for 25 min at stirring speed of 1100 rpm provided the best response. Importantly, the methodology also exhibited high throughput since an extraction/desorption platform that permitted up to fifteen simultaneous extractions was employed. The method was validated, providing coefficients of determination higher than 0.9706 for all analytes; limits of detection (LODs) and limits of quantification (LOQs) ranged from 0.15 to 3.03 μg L -1 and from 0.5 to 10.0 μg L -1 , respectively. Intraday precision ranged from 4.01 to 18.73 %, and interday precision varied from 4.83 to 20.00 %. Accuracy was examined through relative recoveries and ranged from 73.29 to 121.51 %. This method was successfully applied to analyze nine groundwater samples from monitoring wells of gas stations in São Paulo. Moreover, the greenness was assessed through AGREEprep metrics, and an overall score of 0.69 was obtained indicating that the method proposed can be considered sustainable., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC 50 values of 1.23 and 1.39 μM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC 50 values of 0.45 μM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Effective and timely detection is vital for mitigating the severe impacts of Sexually Transmitted Infections (STI), including syphilis and HIV. Cyclic Voltammetry (CV) sensors have shown promise as diagnostic tools for these STI, offering a pathway towards cost-effective solutions in primary health care settings., Objective: This study aims to pioneer the use of Fourier Descriptors (FDs) in analyzing CV curves as 2D closed contours, targeting the simultaneous detection of syphilis and HIV., Methods: Raw CV signals are filtered, resampled, and transformed into 2D closed contours for FD extraction. Essential shape characteristics are captured through selected coefficients. A complementary geometrical analysis further extracts features like curve areas and principal axes lengths from CV curves. A Mahalanobis Distance Classifier is employed for differentiation between patient and control groups., Results: The evaluation of the proposed method revealed promising results with classification performance metrics such as Accuracy and F1-Score consistently achieving values rounded to 0.95 for syphilis and 0.90 for HIV. These results underscore the potential efficacy of the proposed approach in differentiating between patient and control samples for STI detection., Conclusion: By integrating principles from biosensors, signal processing, image processing, machine learning, and medical diagnostics, this study presents a comprehensive approach to enhance the detection of both syphilis and HIV. This setts the stage for advanced and accessible STI diagnostic solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Zika virus (ZIKV), the causative agent of Zika fever, is a flavivirus transmitted by mosquitoes of the Aedes genus. Zika virus infection has become an international concern due to its association with severe neurological complications such as fetal microcephaly. Viral infection can induce the release of ATP in the extracellular environment, activating receptors sensitized by extracellular nucleotides, such as the P2X7 receptor. This receptor is the primary purinergic receptor involved in neuroinflammation, neurodegeneration, and immunity. In this work, we investigated the role of ATP-P2X7 receptor signaling in Zika-related brain abnormalities. Wild-type mice (WT) and P2X7 receptor-deficient (P2X7 -/- ) C57BL/6 newborn mice were subcutaneously inoculated with 5 × 10 6 plaque-forming units of ZIKV or mock solution. P2X7 receptor expression increased in the brain of Zika virus-infected mice compared to the mock group. Comparative analyses of the hippocampi from WT and P2X7 -/- mice revealed that the P2X7 receptor increased hippocampal damage in CA1/CA2 and CA3 regions. Doublecortin expression decreased significantly in the brains of ZIKV-infected mice. WT ZIKV-infected mice showed impaired motor performance compared to P2X7 -/- infected mice. WT ZIKV-infected animals showed increased expression of glial markers GFAP (astrocytes) and IBA-1 (microglia) compared to P2X7 -/- infected mice. Although the P2X7 receptor contributes to neuronal loss and neuroinflammation, WT mice were more efficient in controlling the viral load in the brain than P2X7 receptor-deficient mice. This result was associated with higher induction of TNF-α, IFN-β, and increased interferon-stimulated gene expression in WT mice than P2X7 -/- ZIKV-infected. Finally, we found that the P2X7 receptor contributes to inhibiting the neuroprotective signaling pathway AKT/mTOR while stimulating the caspase-3 activation, possibly two distinct pathways contributing to neurodegeneration. These findings suggest that ATP-P2X7 receptor signaling contributes to the antiviral response in the brain of ZIKV-infected mice while increasing neuronal loss, neuroinflammation, and related brain abnormalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management., Methods: To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4 + T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period., Results: The subject presented controlled viremia and low CD4 + counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal., Conclusion: Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Parasitic diseases are still a major public health problem especially among individuals of low socioeconomic status in underdeveloped countries. In recent years it has been demonstrated that parasites can release extracellular vesicles that participate in the host-parasite communication, immune evasion, and in governing processes associated with host infection. Extracellular vesicles are membrane-bound structures released into the extracellular space that can carry several types of biomolecules, including proteins, lipids, nucleic acids, and metabolites, which directly impact the target cells. Extracellular vesicles have attracted wide attention due to their relevance in host-parasite communication and for their potential value in applications such as in the diagnostic biomarker discovery. This review of the literature aimed to join the current knowledge on the role of extracellular vesicles in host-parasite interaction and summarize its molecular content, providing information for the acquisition of new tools that can be used in the diagnosis of parasitic diseases. These findings shed light to the potential of extracellular vesicle cargo derived from protozoan parasites as novel diagnostic tools., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

The presence of endocrine-disrupting compounds (EDCs) in water poses a significant threat to human and animal health, as recognized by regulatory agencies throughout the world. The Yeast Estrogen Screen (YES) assay is an excellent method to evaluate the presence of these compounds in water due to its simplicity and capacity to assess the bioaccessible forms/fractions of these compounds. In the presence of a compound with estrogenic activity, Saccharomyces cerevisiae cells, containing a lacZ reporter gene encoding the enzyme β-galactosidase, are induced, the enzyme is synthesised, and released to the extracellular medium. In this work, a YES-based approach encompassing the use of a lacZ reporter gene modified strain of S. cerevisiae, microcarriers as solid support, and a fluorescent substrate, fluorescein di-β-d-galactopyranoside, is proposed, allowing for the assessment of EDCs' presence after only 2 h of incubation. The proposed method provided an EC50 of 0.17 ± 0.03 nM and an LLOQ of 0.03 nM, expressed as 17β-estradiol. The assessment of different EDCs provided EC50 values between 0.16 and 1.2 × 10 3  nM. After application to wastewaters, similar results were obtained for EDCs screening, much faster, compared to the conventional 45 h spectrophotometric procedure using a commercial kit, showing potential for onsite high-throughput screening of environmental contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chronic Chagas cardiomyopathy (CCC) is responsible for the highest morbidity and worst prognosis in Chagas disease patients. However, predicting factors that correlate with disease progression, morbidity, and mortality is challenging. It is necessary to have simple, quantitative, and economical risk biomarkers that add value to conventional methods and assist in the diagnosis and prognosis of patients with CCC or in evolution., Objectives: We evaluated molecules related to cardiac remodeling and fibrosis, such as MMP-2, MMP-9, TIMP-2, TIMP-1, PICP, CTXI, and Gal-3, and correlated these biomarkers with echocardiographic variables (LVDD, LVEF, and E/e' ratio)., Methods: Blood samples from Chagasic patients without apparent cardiopathy (WAC), CCC patients, and healthy individuals were used to perform plasma molecule dosages using Luminex or ELISA., Results: MMP-2 and TIMP-2 presented higher levels in CCC; in these patients, the inhibitory role of TIMP-2 over MMP-2 was reinforced. The ratio of MMP-2/TIMP-2 in WAC patients showed a bias in favor of the gelatinase pathway. MMP-9 and TIMP-1 showed higher levels in Chagas patients compared to healthy subjects. PICP and CTXI are not associated with cardiac deterioration in Chagas disease. Increased levels of Gal-3 are associated with worse cardiac function in CCC. Receiver operating characteristic (ROC) curve analysis identified Gal-3 and TIMP-2 as putative biomarkers to discriminate WAC from cardiac patients., Conclusions: Among the molecules evaluated, Gal-3 and TIMP-2 have the potential to be used as biomarkers of cardiac remodeling and progressive myocardial fibrosis in Chagas disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The lack of human resources for disease prevention and control is evident in times of health crisis, such as the COVID-19 pandemic. In public health emergencies, the capacity for adequate assistance and guaranteed access to pharmacological treatment are fundamental and contribute to impact reduction. We aimed to analyze the profile, performance, and characteristics related to the self-perception of preparedness among pharmacists who responded to the COVID-19 pandemic in Brazil., Method: A cross-sectional study was conducted in two stages: content validation of a questionnaire and its application to a representative sample of pharmacists in Rio de Janeiro. The snowball technique was used to recruit participants. A logistic regression model was adjusted to determine the effects of the factors on the probability of a pharmacist feeling prepared to act during the pandemic., Results: Six experts approved and validated the questionnaire, and 376 pharmacists were included in the study, 60.6 % of whom were in places specially designated by health authorities to diagnose and treat COVID-19. Professionals participated in various activities related to pandemic demands, including medication management and population guidance. Postgraduate degrees increased the odds of participants feeling prepared to act during the pandemic. Furthermore, pharmacists who worked in reference facilities were more likely to feel ready than those who worked in other places. Professionals who knew treatment guidelines were almost three times more likely to feel prepared than the ones without the knowledge of treatment guidelines. Training or guidance on how to act during the pandemic increased pharmacists' odds of feeling prepared by 2.58 times., Conclusion: Pharmacists actuated from diagnosis to treatment and participated in the health activities required during the pandemic. Factors contributing to the self-perception of preparedness were identified. Such factors can be targets for interventions to promote the preparedness of the workforce for future health emergencies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Bisphenol A (BPA), an endocrine disruptor widely used in food contact materials, has been linked to a worse health profile. This study intends to estimate the association between BPA exposure and cardiometabolic patterns at adolescence., Methods and Results: Data from the Portuguese population-based birth cohort Generation XXI at the age of 13 were used (n = 2386 providing 3-day food diaries and fasting blood samples). BPA exposure was measured in 24-h urine from a subsample (n = 206) and then predicted in all participants using a random forest method and considering dietary intake from diaries. Three cardiometabolic patterns were identified (normal, modified lipid profile and higher cardiometabolic risk) using a probabilistic Gaussian mixture model. Multinomial regression models were applied to associate BPA exposure (lower, medium, higher) and cardiometabolic patterns, adjusting for confounders. The median BPA exposure was 1532 ng/d, corresponding to 29.4 ng/kg/d. Adolescents higher exposed to BPA (compared to medium and lower levels) had higher BMI z-score (kg/m 2 ) (0.68 vs. 0.39 and 0.52, respectively; p = 0.008), higher levels of body fat (kg) (16.3 vs. 13.8 and 14.6, respectively; p = 0.002), waist circumference (76.2 vs. 73.7 and 74.9, respectively; p = 0.026), insulinemia (ug/mL) (14.1 vs. 12.7 and 13.1, respectively; p = 0.039) and triglyceridemia (mg/dL) (72.7 vs. 66.1 and 66.5, respectively; p = 0.030). After adjustment, a significant association between higher BPA and a higher cardiometabolic risk pattern was observed (OR: 2.55; 95%CI: 1.41, 4.63)., Conclusion: Higher BPA exposure was associated with a higher cardiometabolic risk pattern in adolescents, evidencing the role of food contaminants in health., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance (PVR), right ventricular (RV) failure and premature death. Compounds with vasodilatory characteristics, such as β-caryophyllene, could be promising therapeutics for PAH. This study aimed to determine the effects of free and nanoemulsified β-caryophyllene in lung oxidative stress and heart function in PAH rats. Male Wistar rats (170 g, n = 6/group) were divided into four groups: control (CO), monocrotaline (MCT), monocrotaline + β-caryophyllene (MCT-Bcar) and monocrotaline + nanoemulsion with β-caryophyllene (MCT-Nano). PAH was induced by MCT (60 mg/kg i.p.), and 7 days later, treatment with β-caryophyllene, either free or in a nanoemulsion (by gavage, 176 mg/kg/day) or vehicle was given for 14 days. Echocardiographic and hemodynamic measurements were performed, and after, the RV was collected for morphometry and the lungs for evaluation of oxidative stress, antioxidant enzymes, total sulfhydryl compounds, nitric oxide synthase (NOS) activity and endothelin-1 receptor expression. RV hypertrophy, increased PVR and RV systolic and diastolic pressures (RVSP and RVEDP, respectively) and increased mean pulmonary arterial pressure (mPAP) were observed in the MCT group. Treatment with both free and nanoemulsified β-caryophyllene reduced RV hypertrophy, mPAP, RVSP and lipid peroxidation. The reduction in RVSP was more pronounced in the MCT-Nano group. Moreover, RVEDP decreased only in the MCT-Nano group. These treatments also increased superoxide dismutase, catalase and NOS activities and decreased endothelin-1 receptors expression. Both β-caryophyllene formulations improved mPAP, PVR and oxidative stress parameters. However, β-caryophyllene in a nanoemulsion was more effective in attenuating the effects of PAH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with Leishmania (Leishmania) amazonensis. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (∼40%) and lymph nodes (∼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The economic burden of chronic wounds, the complexity of the process of tissue repair and the possibility of resistant bacterial infections, have triggered a significant research interest in the application of natural alternative therapies for wound healing. Biomolecules are intrinsically multi-active, as they affect multiple mechanisms involved in tissue repair phenomenon, including immunomodulatory, anti-inflammatory, cell proliferation, extra cellular matrix remodeling and angiogenesis. Chitosan features a unique combination of attributes, including intrinsic hemostatic, antimicrobial, and immunomodulatory properties, that make it an exceptional candidate for wound management, in the development of wound dressings and scaffolds. In this study, we produced nanoemulsions (NE) loaded with SFO, characterized them, and evaluated their tissue repairing properties. Dynamic light scattering (DLS) analysis confirmed the formation of a nanoemulsion with a droplet size of 21.12 ± 2.31 nm and a polydispersity index (PdI) of 0.159, indicating good stability for up to 90 days. To investigate the potential wound healing effects, SFO-loaded NE were applied on male C57BL/6 mice for seven consecutive days, producing a significantly higher wound closure efficiency (p < 0.05) for the group treated with SFO-loaded NE compared to the control group treated with the saline solution. This finding indicates that the SFO-loaded NE exhibits therapeutic properties that effectively promote wound healing in this experimental model. Then, SFO-loaded NE were incorporated into chitosan:polyvinyl alcohol (PVA)-based films. The inclusion of NE into the polymer matrix resulted in increased lipophilicity reflected by the contact angle results, while decreasing moisture absorption, water solubility, and crystallinity. Moreover, FTIR analysis confirmed the formation of new bonds between SFO-NE and the film matrix, which also impacted on porosity properties. Thermal analysis indicated a decrease in the glass transition temperature of the films due to the presence of SFO-NE, suggesting a plasticizing role of NE, confirmed by XRD results, that showed a decrease in the crystallinity of the blend films upon the addition of SFO-NE. AFM images showed no evidence of NE droplet aggregation in the Chitosan:PVA film matrix. Moisture absorption and water content decreased upon incorporation of SFO-loaded NE. Although the inclusion of NE increased hydrophobicity and water contact angle, the values remained within an acceptable range for wound healing applications. Overall, our results emphasize the significant tissue repairing properties of SFO-loaded NE and the potential of Chitosan:PVA films containing nanoencapsulated SFO as effective formulations for wound healing with notable tissue repairing properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leprosy is a chronic infectious disease caused by the intracellular bacillus Mycobacterium leprae (M. leprae), which is known to infect skin macrophages and Schwann cells. Although adipose tissue is a recognized site of Mycobacterium tuberculosis infection, its role in the histopathology of leprosy was, until now, unknown. We analyzed the M. leprae capacity to infect and persist inside adipocytes, characterizing the induction of a lipolytic phenotype in adipocytes, as well as the effect of these infected cells on macrophage recruitment. We evaluated 3T3-L1-derived adipocytes, inguinal adipose tissue of SWR/J mice, and subcutaneous adipose tissue biopsies of leprosy patients. M. leprae was able to infect 3T3-L1-derived adipocytes in vitro, presenting a strong lipolytic profile after infection, followed by significant cholesterol efflux. This lipolytic phenotype was replicated in vivo by M. leprae injection into mice inguinal adipose tissue. Furthermore, M. leprae was detected inside crown-like structures in the subcutaneous adipose tissue of multibacillary patients. These data indicate that subcutaneous adipose tissue could be an important site of infection, and probably persistence, for M. leprae, being involved in the modulation of the innate immune control in leprosy via the release of cholesterol, MCP-1, and adiponectin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

In this study we found that endocrine disrupting chemicals (EDCs) were omnipresent in a tropical seabird community comprising diverse ecological guilds and distinct foraging and trophic preferences. Because EDCs tend to bioaccumulate within the food web and microplastics can absorb and release harmful chemical compounds, our findings draw attention to the potential threats to wildlife. Thus, the goal of this study was to investigate the role of plastic ingestion, trophic and foraging patterns (δ 15 N and δ 13 C) of five tropical seabird species breeding in sympatry, on the exposure to EDCs, namely Polybrominated diphenyl ethers (PBDEs), methoxylated polybrominated diphenyl ethers (MeO-PBDEs) and personal care products (PCPs, e.g., musk fragrances and UV-filters). Results indicated that microplastics occurrence and EDCs detection frequency varied among species. Microplastics occurrence was higher in species with dual and coastal foraging strategies. Preen oil had higher levels of MeO-PBDEs and PCPs, while serum had higher levels of PBDEs. In brown boobies, the correlation between microplastics and ∑PBDEs levels was significant, suggesting that microplastics ingestion is a key PBDEs route. Trophic position (δ 15 N) plays a key role in PBDEs accumulation, particularly in Bulwer's petrel, which occupies a high trophic position and had more specialized feeding ecology than the other species. MeO-PBDEs were linked to foraging habitat (δ 13 C), although the link to foraging locations deserves further investigation. Overall, our findings not only fill key gaps in our understanding of seabirds' exposure to microplastics and EDCs, but also provide an essential baseline for future research and monitoring efforts. These findings have broader implications for the marine wildlife conservation and pollution management in sensitive environments, such as the tropical regions off West Africa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Macrophages switch among different activation phenotypes according to distinct environmental stimuli, varying from pro-inflammatory (M1) to alternative (also named resolutive; M2) activation forms. M1-and M2-activated macrophages represent the two extremes of the activation spectrum involving multiple species, which vary in terms of function and the cytokines secreted. The consensus is that molecular characterization of the distinct macrophage population and the signals driving their activation will help in explaining disease etiology and formulating therapies. For instance, myeloid cells residing in the tumor microenvironment are key players in tumor progression and usually display an M2-like phenotype, which help tumor cells to evade local inflammatory processes. Therefore, these specific cells have been proposed as targets for tumor therapies by changing their activation profile. Furthermore, M2 polarized macrophages are phagocytic cells promoting tissue repair and wound healing and are therefore potential targets to treat different diseases. We have already shown that clotrimazole (CTZ) decreases tumor cell viability and thus tumor growth. The mechanism by which CTZ exerts its effects remains to be determined, but this drug is an inhibitor of the PI3K/AKT/mTOR pathway. In this study, we show that CTZ downregulated M2-activation markers in macrophages polarized to the M2 profile. This effect occurred without interfering with the expression of M1-polarized markers or pro-inflammatory cytokines and signaling. Moreover, CTZ suppressed NFkB pathway intermediates and disrupted PI3K/AKT/mTOR signaling. We concluded that CTZ reverses macrophage M2 polarization by disrupting the PI3K/AKT/mTOR pathway, which results in the suppression of NFkB induction of M2 polarization. In addition, we find that CTZ represents a promising therapeutic tool as an antitumor agent., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Trichomoniasis is a common sexually transmitted infection that poses significant complications for women. Challenges in treatment include adverse effects and resistance to standard antimicrobial agents. Given this context, a sesame seed oil nanoemulsion (SONE) was developed and showed anti-Trichomonas vaginalis activity. To facilitate the local application of SONE, a polysaccharide film was developed using xanthan gum (XG) and κ-carrageenan gum (CG). A blend of XG and CG (at 2 %, ratio 1:3) plasticized with glycerol produced a more promising film (XCF) than using the gums individually. The film containing SONE (SONE-XCF) was successfully obtained by replacing the aqueous solvent with SONE via solvent evaporation technique. The hydrophilic SONE-XCF exhibited homogeneity and suitable mechanical properties for vaginal application. Furthermore, SONE-XCF demonstrated mucoadhesive properties and high absorption capacity for excessive vaginal fluids produced in vaginitis. It also had a disintegration time of over 8 h, indicating long retention at the intended site of action. Hemolysis and chorioallantoic membrane tests confirmed the safety of the film. Therefore, SONE-XCF is a biocompatible film with a natural composition and inherent activity against T. vaginalis, possessing exceptional characteristics that make it appropriate for vaginal application, offering an interesting alternative for trichomoniasis treatment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leticia Cruz reports was provided by Federal University of Santa Maria. Leticia Cruz reports a relationship with Federal University of Santa Maria that includes: employment. The authors declare no conflit of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The development of carrier-based delivery systems for oral administration of retinoic acid (RA), that provides its release and absorption at intestinal level, is of major relevance in the treatment of acute promyelocytic leukemia. The aim of this work was to evaluate RA bioaccessibility and intestinal transport on ethyl cellulose (EC)- and EC + polyethylene glycol (ECP)-based microparticles and to understand the impact of meal co-ingestion by applying in vitro assays. RA-loaded microparticles were produced by spray-drying with an encapsulation efficiency higher than 90 % for both formulations. The gastric bioaccessibility of RA (after in vitro static digestion of RA-loaded particles) was lower than 3 % for both types of microparticles, with and without meal co-ingestion. Whereas after intestinal digestion, RA bioaccessibility was significantly higher and affected by the type of microparticles and the presence of meal. The digestion of EC- and ECP-based microparticles without diet enabled a significantly higher bioaccessibility of RA when compared to the one recorded for the co-digestion of these microparticles with diet. Herein, RA bioaccessibility decreased from 84 ± 1 to 24 ± 6 % (p < 0.0001) for microparticles EC and 54 ± 4 to 25 ± 5 % (p < 0.001) for microparticles ECP. Moreover, comparing both types of microparticles, RA bioaccessibility was significantly higher for EC-based microparticles digested without diet (p < 0.0001). At last, the bioaccessibility of RA was similar among EC- and ECP-based microparticles when co-digested with diet. Intestinal transport experiments performed in Caco-2 monolayers evidenced that after 2 h of transport the amount of RA retained in the apical compartment was higher than the amount that reached the basolateral compartment evidencing a slow transport at intestinal level that was higher when RA is spiked in the blank of digestion and the meal digestion samples compared to RA dissolved in HBSS (44 ± 6 (p < 0.01) and 38 ± 1 (p < 0.05) vs 26 ± 2 %, respectively)., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2023. Published by Elsevier B.V.)