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Attention Deficit/Hyperactivity Disorder (ADHD) is a common behavioral syndrome that begins in childhood and affects 3.4% of children worldwide. Due to its etiological complexity, there are no consistent biomarkers for ADHD, however the high heritability presented by the disorder indicates a genetic/epigenetic influence. The main epigenetic mechanism is DNA methylation, a process with an important role in gene expression and in many psychiatric disorders. Thus, our study sought to identify epi-signatures biomarkers in 29 children clinically diagnosed with ADHD. After DNA extraction and bisulfite conversion, we performed methylation array experiment for differential methylation, ontological and biological age analysis. The biological response in ADHD patients was not sufficient to determine a conclusive epi-signature in our study. However, our results highlighted the interaction of energy metabolism and oxidative stress pathways in ADHD patients detected by differential methylation patterns. Furthermore, we were able to identify a marginal association between the DNAmAge and ADHD. Our study present new methylation biomarkers findings associated with energy metabolism and oxidative stress pathways, in addition to DNAmAge in ADHD patients. However, we propose that further multiethnic studies, with larger cohorts and including maternal conditions, are necessary to demonstrate a definitive association between ADHD and these methylation biomarkers. •There is still no conclusive episignature for ADHD.•Oxidative stress and energy metabolism play a crucial role in the pathophysiology of ADHD.•Biological methylation age (DNAmAge) acceleration has a marginal association with clinical status of ADHD.

Cri Du Chat syndrome, or 5p− syndrome, is characterized by a terminal or interstitial deletion on the short arm of chromosome 5 that causes variable clinical manifestations, including high-pitched cry in newborns, delayed growth, and global development. Different cytogenomic rearrangements, family history, and environmental factors may hinder the genotype–phenotype association. Thus, the phenotypic variability of this syndrome may not be limited only to variations in gene structure, such as deletions and duplications. It is possible that other mechanisms related to the activation or inactivation of promoters and/or exons of actively transcribed genes, such as DNA methylation are involved. Therefore, we studied the genome-wide methylation status profile of peripheral blood samples from fifteen patients with Cri du Chat Syndrome and nine control samples through the array method to look for Differentially Methylated Regions. We found that Differentially Methylated Regions outside the 5p region are mainly associated with regulating gene transcription, splicing, and chromatin remodeling. Most biological pathways are related to transcription, histone and chromatin binding, spliceosome and ribosomal complex, and RNA processing. Our results suggest that changes in the 5p region can cause an imbalance in other chromosomal regions capable of affecting gene modulation and thus explain the phenotypic differences in patients with 5p−.

The objective of this study was to evaluate the biological effects of roasted Cashew nuts consumption on biochemical and murinometric parameters in dyslipidemic rats receiving lipid supplementation. Young male rats were randomly assigned to three experimental groups (n = 10). The Control group (CONT) was treated with water, the Dyslipidemic group (DL) received a high fat content emulsion throughout the experiment, and the Dyslipidemic Cashew Nuts group (DLCN) received the same high fat content emulsion throughout the experiment, yet was treated with Cashew nuts. Body parameters, biochemical, hepatic and fecal fatty acid profiles were all evaluated. The levels of total cholesterol and triglycerides were higher in the DL and DLCN groups as compared to the control group. DLCN and CONT presented no difference in HDL levels. DLCN presented higher glycemia levels than the other groups. There was reduction of body fat in DLCN as compared to other groups, but with higher accumulations of liver fat. DLCN presented a reduction in saturated hepatic fatty acids of 20.8%, and an increase of 177% in relation to CONT; there was also a 21% in increase DL for ω9 fatty acids in comparison to CONT. As for fecal fatty acids, there was a lower concentration of polysaturates in DLCN as compared to the other groups. The data showed that the consumption of Cashew nuts by the dyslipidemic animals treated with a hyperlipidic diet induced greater accumulations of liver fat and worsened glycemic levels, despite having reduced visceral fats and increased fecal fat excretion.

Despite the availability of effective vaccines, yellow fever outbreaks persist, highlighting the need for antiviral drugs. Background/Objectives: This study investigated Hippeastrum puniceum (Amaryllidaceae) as a potential source of antiviral compounds against wild-type yellow fever virus (wt-YFV). Methods/Results: The crude bulb extract of H. puniceum exhibited 58% protection against wt-YFV. Bioassay-guided fractionation of the extract by UHPLC-HRMS led to the annotation of six alkaloids (bulbisine, cathinone, trigonelline, tetrahydroharman-3-carboxylic acid, and 2,7-dimethoxyhomolycorine or 3-O-acetylnarcissidine) in active fractions, along with the amino acids arginine, asparagine, tryptophan, and glutamic acid. In silico ADMET analyses predicted favorable pharmacokinetic and toxicological profiles, supporting their potential as drug candidates. Six of the annotated compounds were evaluated in vitro for cytotoxicity and antiviral activity against wt-YFV. However, none showed significant antiviral activity when tested individually, suggesting that the observed antiviral effect may result from synergistic interactions between two or more compounds within active fractions. Conclusions: Our results underscore the importance of further investigations in vitro, particularly assays exploring the synergy among the annotated compounds against YFV. The integration of bioassay-guided fractionation of active plant extracts with computational analyses emerges as a promising strategy for the discovery of natural products with therapeutic potential against yellow fever, a reemerging disease.

Background: The Biological Isolation and Containment Unit (BICU) is a subunit of the Teaching Hospital of the Faculty of Veterinary Medicine of the University of Lisbon, Portugal, for the admission of animals with confirmed infectious diseases or under clinical suspicion and waiting for a diagnosis. As a high-risk environment for the transmission of infectious agents, it is extremely important to implement programs for the surveillance of nosocomial microorganisms in these facilities. The purpose of this study was to evaluate the level of bacterial contamination of the BICU environmental surfaces and to implement corrective actions on disinfection protocols. Swab samples were collected from selected environmental surfaces in 3 different areas of the BICU (isolation, work, and preparatory rooms) to evaluate the total aerobic bacterial load and investigate the presence of 4 nosocomial microorganisms: vancomycin-resistant Enterococcus spp., methicillin-resistant Staphylococcus aureus, 3rd-generation cephalosporin-resistant Escherichia coli, and carbapenem-resistant Pseudomonas aeruginosa. Bacterial quantification was performed by using non-selective media, while specific selective media were used for the isolation of the target microorganisms. Isolates were identified based on their macro and microscopic characteristics and their biochemical profile. Subsequently, new disinfection protocols were implemented, and their effectiveness evaluated. Results: The surfaces with the highest bacterial load in the isolation, preparatory, and worker’s rooms were the cages, hand-held sponge, and telephone, respectively. Regarding the 4 pathogens investigated, Enterococcus spp. were the most frequently isolated (11.3%), followed by E. coli (1.5%) and P. aeruginosa (1.5%). One of the P. aeruginosa isolates obtained was resistant to imipenem. In the end, new disinfection protocols were implemented, which proved to be effective in reducing bacterial counts by 99.99% in cages and the sponge, and by 90 to 99% on the telephone. Conclusions: This study allows to conclude that the cages and the human contact surfaces were the most contaminated in the isolation rooms. Nevertheless, the new disinfection strategies seemed to be effective in reducing environmental contamination, including by some potentially nosocomial agents, although more samples must be analyzed for definitive conclusions. These results may contribute to highlight the importance of infection prevention and control measures, as fundamental tools to reduce the spread of infectious agents in the hospital environment.

Objectives This randomized, triple-blind, crossover clinical trial aimed to evaluate the efficacy, onset, length of pulp and soft tissue anesthesia, and pain during injection of 2% buffered articaine and 4% non-buffered articaine solutions. Methods Each volunteer received two maxillary supraperiosteal anesthesia infiltrations in canine area. The infiltrations were performed at two different sessions using a different local anesthetic solution for each session, and the anesthetic injection speed was always 1 mL/min. The assessment of the onset and length of pulpal and soft tissue anesthesia was performed with the pulp electrical test “pulp tester” and the esthesiometer kit, respectively. Volunteers marked pain during injection on a visual analog scale (VAS). The anesthetics solutions pH was evaluated through the pH meter equipment. Results There was no difference between the two anesthetic solutions (onset of soft tissue anesthesia, p = 0.5386; length of soft tissue anesthesia, p = 0.718; onset of pulpal anesthesia, p = 0.747; length of pulpal anesthesia, p = 0.375), except for pain during the injection which was lower when buffered 2% articaine was used ( p = 0.001) and the pH. The pH analysis revealed that the solutions differed from one another ( p < 0.01). Conclusion The 2% buffered articaine solution provided the same anesthetic properties then 4% unbuffered articaine with a great reduction in pain during injection. Clinical relevance The possibility of use 2% buffered articaine solution instead of 4% articaine maintaining the same anesthetic properties with a great reduction in pain during injection and half of the anesthetic salt concentration.

We aimed to determine the chemical profile and unveil Anadenanthera colubrina (Vell.) Brenan standardized extract effects on inflammatory cytokines expression and key proteins from immunoregulating signaling pathways on LPS-induced THP-1 monocyte. Using the RT-PCR and Luminex Assays, we planned to show the gene expression and the levels of IL-8, IL-1β, and IL-10 inflammatory cytokines. Key proteins of NF-κB and MAPK transduction signaling pathways (NF-κB, p-38, p-NF-κB, and p-p38) were detected by Simple Western. Using HPLC-ESI-MS n (High-Performance Liquid-Chromatography) and HPLC-HRESIMS, we showed the profile of the extract that includes an opus of flavonoids, including the catechins, quercetin, kaempferol, and the proanthocyanidins. Cell viability was unaffected up to 250 µg/mL of the extract (LD 50  = 978.7 µg/mL). Thereafter, the extract's impact on the cytokine became clear. Upon LPS stimuli, in the presence of the extract, gene expression of IL-1β and IL-10 were downregulated and the cytokines expression of IL-1β and IL-10 were down an upregulated respectively. The extract is involved in TLR-4-related NF-κB/MAPK pathways; it ignited phosphorylation of p38 and NF-κB, orchestrating a reduced signal intensity. Therefore, Anadenanthera colubrina 's showed low cytotoxicity and profound influence as a protector against the inflammation, modulating IL-1β and IL-10 inflammatory cytokines gene expression and secretion by regulating intracellular NF-κB and p38-MAPK signaling pathways.

Biodiversity data, particularly species occurrence and abundance, are indispensable for testing empirical hypothesis in natural sciences. However, datasets built for research programmes do not often meet FAIR (findable, accessible, interoperable and reusable) principles, which raises questions about data quality, accuracy and availability. The 21 st century has markedly been a new era for data science and analytics and every effort to aggregate, standardise, filter and share biodiversity data from multiple sources have become increasingly necessary. In this study, we propose a framework for refining and conforming secondary biodiversity data to FAIR standards to make them available for use such as macroecological modelling and other studies. We relied on a Darwin Core base model to standardise and further facilitate the curation and validation of data related including the occurrence and abundance of multiple taxa of a region that encompasses estuarine ecosystems in an ecotonal area bordering the easternmost Amazonia. We further discuss the significance of feeding standardised public data repositories to advance scientific progress and highlight their role in contributing to the biodiversity management and conservation.

Sepsis is a life-threatening condition characterized by organ dysfunction resulting from a dysregulated host response to infection. Sepsis induces systemic inflammation and increases adhesion molecule expression and activation, promoting leukocyte adhesion to the endothelium. In addition, sepsis leads to the disruption of vascular integrity with fluid leakage and migration of leukocytes across the compromised endothelial barrier, leading to organ damage. Bioactive food compounds such as DHA, an essential omega 3 polyunsaturated fatty acid (PUFA) in the Mediterranean Diet (MedDiet), are known for their anti-inflammatory and pro-resolving properties. Thus, the supplementation of DHA may affect sepsis development, protecting the host. To investigate the role of DHA in neutrophil function, we conducted flow chamber assays using isolated neutrophils from mice and humans treated with DHA. To assess whether similar effects occur , we performed intravital microscopy of the TNF-stimulated cremaster muscle. Finally, we employed the cecal ligation and puncture (CLP) model to evaluate the therapeutic potential of DHA in experimental sepsis, and we applied intravital microscopy to assess cerebral vascular perfusion and the cerebral microcirculation in septic mice. We found a significant reduction in neutrophil rolling and adhesion in DHA-treated neutrophils compared to controls in flow chamber assays, which can be mechanistically explained by a substantial reduction in adhesion markers, such as PSGL-1, CD11a, and CXCR4. Next, we employed intravital microscopy in the mouse cremaster muscle, stimulating it with tumor necrosis factor, and found a significant reduction in leukocyte rolling and adhesion in DHA-treated mice, confirming the flow chamber results. We also used a CLP model of sepsis. We found that DHA treatment ameliorated CLP-related sepsis parameters, including mortality, clinical score, total leukocyte and neutrophil transmigration, cytokine levels in peritoneal exudate, plasma, and brain tissue, and lactate levels. DHA treatment also improved cerebral microcirculatory perfusion and exhibited anti-inflammatory and pro-resolving effects, reflected by increased plasma and brain tissue resolving D1 and D2 levels. Together, we identify DHA as a promising anti-inflammatory therapeutic agent that mitigates sepsis-related vascular dysfunction and prevents organ failure.

[This corrects the article DOI: 10.3389/fphar.2025.1708348.].