Lipid Fraction from Agaricus brasiliensis as a Potential Therapeutic Agent for Lethal Sepsis in Mice.

Sepsis is a potentially fatal clinical condition that results from an immune imbalance in the host during an infection. It presents systemic alterations due to excessive activation of pro-inflammatory mediators that contribute to inflammation, formation of reactive species, and tissue damage. Anti-inflammatory mediators are then extensively activated to regulate this process, leading to immune exhaustion and, consequently, immunosuppression of the host. Considering the biological activities of the nutraceutical Agaricus brasiliensis (A. brasiliensis), such as immunomodulatory, antioxidant, and antitumor activities, the present study investigated the therapeutic potential of the lipid fraction of A. brasiliensis (LF) in a model of lethal sepsis in mice (Mus musculus), induced by cecal ligation and perforation (CLP). The results showed that treatment of septic animals with LF or LF associated with ertapenem (LF-Erta) reduced systemic inflammation, promoting improvement in clinical parameters and increased survival. The data show a reduction in pro-inflammatory and oxidative stress markers, regulation of the anti-inflammatory response and oxidizing agents, and increased bacterial clearance in the peritoneal cavity and liver. Thus, it can be concluded that LF as a treatment, and in conjunction with antibiotic therapy, has shown promising effects as a hepatoprotective, antioxidant, antimicrobial, and immunomodulatory agent.

Linalool-rich rosewood essential oil (Aniba rosaeodora Ducke) mitigates emotional and neurochemical impairments induced by ethanol binge-like exposure during adolescence in female rats.

Linalool-rich Rosewood oil (Aniba rosaeodora Ducke) is a natural compound widely used in perfumery industry. Evidence suggests that linalool exerts antidepressant and anxiolytic effects. Conversely, ethanol binge drinking (i.e., intermittent and episodic consumption) during adolescence elicits neurobehavioral alterations associated with brain damage. Here, we investigated whether linalool-rich Rosewood oil administration can improve the emotional and molecular impairments associated with ethanol binge-like exposure during adolescence in female rats. Rosewood oil was obtained by hydrodistillation and posteriorly analyzed. Adolescent female Wistar rats received four-cycles of ethanol binge-like pattern (3 g/kg/day, 3 days on/4 days off) and daily Rosewood oil (35 mg/kg, intranasally) for 28 days. Twenty-four hours after treatments, it was evaluated the impact of ethanol exposure and Rosewood oil treatment on the putative emotional impairments assessed on the splash and forced swimming tests, as well as the levels of brain-derived neurotrophic factor (BDNF), S100B, oxidative parameters, and inflammatory cytokines in prefrontal cortex and hippocampus. Results indicated that Rosewood oil intranasal administration mitigated emotional impairments induced by ethanol exposure accompanied by a marked increase in BDNF, S100B, glutathione (GSH), and antioxidant activity equivalent to Trolox (TEAC) levels in brain areas. Rosewood oil treatment also prevented the ethanol-induced increase of interleukin-1ß, interleukin-6, tumor necrosis factor α (TNF-α), and neurofilament light chain (NFL) levels. These findings provide the first evidence that Rosewood oil intranasal administration exerts protective effects against emotional and molecular impairments associated with adolescent ethanol binge-like exposure, possibly due to linalool actions triggering neurotrophic factors, rebalancing antioxidant status, and attenuating proinflammatory process.

NK Cytotoxicity Mediated by NK-92 Cell Lines Expressing Combinations of Two Allelic Variants for FCGR3.

Natural killer (NK) cells play an important role in the surveillance of viral infections and cancer. NK cell antibody-dependent cellular cytotoxicity (ADCC) and direct cytotoxicity are mediated by the recognition of antibody-coated target cells through the Fc gamma receptor IIIA (FcγRIIIa/CD16) and by ligands of activating/inhibitory NK receptors, respectively. Allelic variants of the FCGR3A gene include the high-affinity single-nucleotide polymorphism (SNP) rs396991 (V176F), which is associated with the efficacy of monoclonal antibody (mAb) therapies, and the SNP rs10127939 (L66H/R). The contribution of FCGR3A SNPs to NK cell effector functions remains controversial; therefore, we generated a panel of eight NK-92 cell lines expressing specific combinations of these SNPs and tested their cytotoxicities. NK-92 cells were stably transfected with plasmids containing different combinations of FCGR3A SNPs. Messenger RNA and FcγRIIIa/CD16 cell surface expressions were detected using new generation sequencing (NGS) and flow cytometry, respectively. All FcγRIIIa/CD16-transfected NK-92 cell lines exhibited robust ADCC against three different target cell lines with minor differences. In addition, enhanced direct NK cytotoxicity against K562 target cells was observed, suggesting a mechanistic role of FcγRIIIa/CD16 in direct NK cytotoxicity. In conclusion, we generated eight FcγRIIIa/CD16-transfected NK-92 cell lines carrying different combinations of two of the most studied FCGR3A SNPs, representing the major genotypes described in the European population. The functional characterization of these cell lines revealed differences in ADCC and direct NK cytotoxicity that may have implications for the design of adoptive cancer immunotherapies using NK cells and tumor antigen-directed mAbs.

Is there any association between the presence of biomarkers and apical periodontitis? A systematic review.

This systematic review aimed to verify whether there is evidence of an association between apical periodontitis and the presence of systemic biomarkers. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA. For this, the acronym PECO was used; population (P) of adult humans exposed (E) to the presence of apical periodontitis, compared (C) to adult humans without apical periodontitis, and the outcome (O) of the presence of biomarkers was observed. The articles were searched in PubMed, Scopus, Web of Science, LILACS, Cochrane Library, OpenGray, and Google Scholar grey databases. Subsequently, studies were excluded based on title, abstract, and full article reading, following the eligibility criteria. The methodological quality of the selected studies was evaluated using the Newcastle-Ottawa qualifier. After exclusion, 656 studies were identified, resulting in 17 final articles that were divided into case-control, cross-sectional, and cohort studies. Eight studies were considered to have a low risk of bias, one had a medium risk of bias, and eight had a high risk of bias. In addition, 12 articles evaluated biomarkers in blood plasma, four evaluated them in saliva, and only one evaluated them in gingival crevicular fluid. The results of these studies indicated an association between apical periodontitis and the systemic presence of biomarkers. These markers are mainly related to inflammation, such as interleukins IL-1, IL-2, and IL-6, oxidative markers, such as nitric oxide and superoxide anions, and immunoglobulins IgG and IgM. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42023493959).

Exploring BPA alternatives - Environmental levels and toxicity review.

Bisphenol A alternatives are manufactured as potentially less harmful substitutes of bisphenol A (BPA) that offer similar functionality. These alternatives are already in the market, entering the environment and thus raising ecological concerns. However, it can be expected that levels of BPA alternatives will dominate in the future, they are limited information on their environmental safety. The EU PARC project highlights BPA alternatives as priority chemicals and consolidates information on BPA alternatives, with a focus on environmental relevance and on the identification of the research gaps. The review highlighted aspects and future perspectives. In brief, an extension of environmental monitoring is crucial, extending it to cover BPA alternatives to track their levels and facilitate the timely implementation of mitigation measures. The biological activity has been studied for BPA alternatives, but in a non-systematic way and prioritized a limited number of chemicals. For several BPA alternatives, the data has already provided substantial evidence regarding their potential harm to the environment. We stress the importance of conducting more comprehensive assessments that go beyond the traditional reproductive studies and focus on overlooked relevant endpoints. Future research should also consider mixture effects, realistic environmental concentrations, and the long-term consequences on biota and ecosystems.

Climate-driven shifts in decapod larvae assemblages in a temperate estuary.

The study examines the complex impact of climatic patterns, driven by the North Atlantic Oscillation (NAO), on regional climate, hydrology, and sea surface temperatures. Focused on the period from 2003 to 2012, the research specifically investigates the influence of thermal variability on decapod larval communities. Monthly zooplanktonic sampling conducted at the Mondego Estuary, Portugal, entrance over a decade revealed the prevalence of Carcinus maenas, Diogenes pugilator, and Pachigrapsus marmoratus larvae. These assemblages displayed notable interannual and seasonal fluctuations, often corresponding with changes in sea surface temperatures. Significant system shifts around 2007, instigated by the large-scale NAO, led to subsequent modifications in sea surface temperature and decapod larvae communities' dynamics. Post-2007, there was an upward trajectory in both species' abundance and richness. Phenologically during the former period, the community exhibited two abundance peaks, with the earlier peak occurring sooner, attributed to heightened temperatures instead of the unique peak exhibited before 2007. The research further elucidated the occurrences of Marine Heatwaves (MHW) in the region, delving into their temporal progression influenced by the NAO. Although water temperature emerged as a crucial factor influencing decapod larvae communities annually and seasonally, the study did not observe discernible impacts of MHW events on these communities. These communities represent essential trophic links and are crucial for the survival success of adult decapods. Given the rapid pace of climate change and increasing temperatures, it is imperative to assess whether these environmental shifts, particularly in thermal conditions, affect these meroplanktonic communities.

Catalytic Transformation of Nitroarenes to Amines over Ba(1-x)SrxTiO3 (0 < x < 1) Perovskites in Water.

This work is focused on the application of lanthanide-free perovskite Ba1-xSrxTiO3 (0 < x < 1) in valorization of toxic pollutants as 4-nitrophenol (4-NPh). The series of perovskites were fabricated by facile, one-step solid-state preparation method and characterized via various techniques: elemental analysis (Inductively Coupled Plasma Optical Emission Spectrometry, ICP-OES), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR) and dielectric properties (impedance spectroscopy, IS). The methods confirmed the assumed composition, structure and high purity of the materials. The results showed that substitution of Ba2+ by Sr2+ in the perovskite crystal lattice influenced the dielectric properties of samples and the size of the grains. The absorption and catalytic properties of Ba(1-x)SrxTiO3 (0 < x < 1) series were evaluated in reduction of 4-NPh in water using NaBH4 as reducing agent. No adsorption of 4-NPh was found for all the materials during 180 min of contact (experiment without reducing agent), and the best catalytic performance was found for the Ba(1-x)SrxTiO3 (x = 0.3) sample. The catalytic transformation of 4-NPh to 4-APh follows a pseudo-first-order model, and the catalysts can be easily regenerated via mild annealing (300 °C).

Chagas Disease: A Silent Threat for Dogs and Humans.

Chagas disease (CD) is a vector-borne Neglected Zoonotic Disease (NZD) caused by a flagellate protozoan, Trypanosoma cruzi, that affects various mammalian species across America, including humans and domestic animals. However, due to an increase in population movements and new routes of transmission, T. cruzi infection is presently considered a worldwide health concern, no longer restricted to endemic countries. Dogs play a major role in the domestic cycle by acting very efficiently as reservoirs and allowing the perpetuation of parasite transmission in endemic areas. Despite the significant progress made in recent years, still there is no vaccine against human and animal disease, there are few drugs available for the treatment of human CD, and there is no standard protocol for the treatment of canine CD. In this review, we highlight human and canine Chagas Disease in its different dimensions and interconnections. Dogs, which are considered to be the most important peridomestic reservoir and sentinel for the transmission of T. cruzi infection in a community, develop CD that is clinically similar to human CD. Therefore, an integrative approach, based on the One Health concept, bringing together the advances in genomics, immunology, and epidemiology can lead to the effective development of vaccines, new treatments, and innovative control strategies to tackle CD.

Infectious Sacroiliitis as a Rare Postpartum Complication: A Case Report.

Infectious sacroiliitis is a rare and challenging diagnosis. Sacroiliac joint changes related to pregnancy and puerperium can predispose to this condition. However, its clinical presentation can often mimic common causes of lower back pain and delay the diagnosis. We report the case of a 31-year-old pregnant woman with twins who presented at 29 weeks of gestation with lower back and right buttock pain that radiated down to the thigh. Although initially interpreted as sciatica pain, the diagnosis of psoas hematoma complicated with infectious sacroiliitis was made. With this case, we aim to bring awareness to this condition in order to raise suspicion among clinicians for an earlier diagnosis.

Factors associated to mortality in children with critical COVID-19 and multisystem inflammatory syndrome in a resource-poor setting.

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo-18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2-28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3-202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4-13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization.

Potential Biotechnological Applications of Venoms from the Viperidae Family in Central America for Thrombosis.

Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent's total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.

Polychaete (Alitta virens) meal inclusion as a dietary strategy for modulating gut microbiota of European seabass (Dicentrarchus labrax).

Recent research has revealed the significant impact of novel feed ingredients on fish gut microbiota, affecting both the immune status and digestive performance. As a result, analyzing the microbiota modulatory capabilities may be a useful method for assessing the potential functionality of novel ingredients. Therefore, this study aimed to evaluate the effects of dietary polychaete meal (PM) from Alitta virens on the autochthonous and allochthonous gut microbiota of European seabass (Dicentrarchus labrax). Two diets were compared: a control diet with 25% fishmeal (FM) and a diet replacing 40% of fishmeal with PM, in a 13-week feeding trial with juvenile fish (initial weight of 14.5 ± 1.0 g). The feed, digesta, and mucosa-associated microbial communities in fish intestines were analyzed using high-throughput sequencing of the 16S rRNA gene on the Illumina MiSeq platform. The results of feed microbiota analyses showed that the PM10 feed exhibited a higher microbial diversity than the FM diet. However, these feed-associated microbiota differences were not mirrored in the composition of digesta and mucosal communities. Regardless of the diet, the digesta samples consistently exhibited higher species richness and diversity than the mucosa samples. Overall, digesta samples were characterized by a higher abundance of Firmicutes in PM-fed fish. In contrast, at the gut mucosa level, the relative abundances of Mycobacterium, Taeseokella and Clostridium genera were lower in the group fed the PM10 diet. Significant differences in metabolic pathways were also observed between the FM and PM10 groups in both mucosa and digesta samples. In particular, the mucosal pathways of caffeine metabolism, phenylalanine metabolism, and sulfur relay system were significantly altered by PM inclusion. The same trend was observed in the digesta valine, leucine, and isoleucine degradation and secretion pathways. These findings highlight the potential of PM as an alternative functional ingredient in aquafeeds with microbiota modulatory properties that should be further explored in the future.

Granulomatosis With Polyangiitis: The Complexity of Clinical Manifestations, Therapeutic Challenges, and Complications of a Severe Multisystemic Case.

We report a case of a 34-year-old male with severe multisystemic involvement (including the testis, musculoskeletal system, skin, upper respiratory tract, ocular system, peripheral nerves, abdomen, and kidney) due to granulomatosis with polyangiitis (GPA) and a high proteinase 3 (PR3)-antineutrophil cytoplasmic antibodies (PR3ANCA) titer. A renal biopsy showed pauci-immune glomerulonephritis (GN). Systemic corticotherapy combined with cyclophosphamide was chosen for induction therapy. During the induction phase, clinical deterioration occurred in the form of severe alveolar hemorrhage, leading to admission to the intensive care unit (ICU). Influenza A (H1N1) was detected in the respiratory tract. Furthermore, blood sampling revealed an invasive Klebsiella pneumoniae infection that persisted despite multiple antibiotic regimens. A CT scan showed splenic vascular compromise, assumed to be the primary source of the infection, with sustained improvement after splenectomy. Maintenance therapy included a tapering dose of corticotherapy for 36 months and azathioprine 100mg daily for five years, which achieved full and sustained remission. The patient has been in full remission for nine years, with mild renal sequelae, including proteinuria and secondary hypertension.

Serotonin Syndrome: An Emerging Reality in the Emergency Department.

Serotonin syndrome (SS) is an entity caused by interference with the serotonin metabolism and/or by medications that act as serotonin receptor agonists. The signs and symptoms are nonspecific, making the diagnosis challenging. Treatment depends on the severity of the manifestations. In mild to moderate cases, it typically resolves within the first 24 hours after initiating therapy and discontinuation of the serotoninergic medications. A 42-year-old woman with a previous history of depression was admitted to the hospital due to the voluntary ingestion of multiple tablets of escitalopram 10 mg and venlafaxine 75 mg. Physical examination showed a hyperthermic and diaphoretic patient. Tremor, agitation, bilateral ocular clonus, and spontaneous inferior limb clonus were also present. Hunter's criteria were applied, and the diagnosis of SS was assumed. Supportive and symptomatic treatments were initiated. The evolution was benign, with symptomatic remission in the first 24 hours. In the last decades, a large increase in the use of antidepressants was noted, and, as such, defining SS as rare is no longer appropriate. Delaying the treatment can dictate an increase in morbidity and mortality. It is important to highlight that the diagnosis is mainly clinical as diagnostic criteria may miss out on some cases. As such, clinical awareness of SS's multiplicity of presentations is of utmost importance.

Investigating differences in young- and late-onset progressive supranuclear palsy.

BACKGROUND: The impact of age of onset on the presentation of progressive supranuclear palsy phenotypes is not well studied. We hypothesized that there is difference in presentation and phenotype between young- and late-onset PSP. OBJECTIVES: Our aim was to compare phenotypes and rate of change in disability between young-onset PSP (YOPSP) and late-onset PSP (LOPSP). METHODS: Retrospective data of patients seen in the Rossy PSP Centre from March 2014 to April 2022 with clinical diagnosis of PSP as per the MDS 2017 diagnostic criteria were examined. We used cut-off age of 65 years to categorize the patients into YOPSP and LOPSP. We compared the prevalence of phenotypes, presenting symptoms, and MDS core criteria between the two groups. The severity of disease between the two groups was measured using PSP-RS. RESULTS: We found 107 patients with clinical diagnosis of PSP as per MDS criteria, a third were defined as YOPSP. PSP speech/language (SL) phenotype was more prevalent in YOPSP (18% vs 0%, p < 0.001). Aphasia was significantly higher in YOPSP (16% vs 1.4%, p = 0.03). The speech and language dysfunction (C1) core criteria were more prevalent in YOPSP (33.3% vs 12.2%, p = 0.05). Longitudinal analysis of PSP-RS showed worsening of bulbar total score at 6 months in YOPSP (t (38) = 2.87; p = 0.05). CONCLUSION: Our study revealed that YOPSP are more likely to present with a speech and language variant. Our results highlight that age of onset may predict PSP phenotypes, which holds both clinical and prognostic importance.

Caffeic Acid-Zinc Basic Salt/Chitosan Nanohybrid Possesses Controlled Release Properties and Exhibits In Vivo Anti-Inflammatory Activities.

Caffeic acid (CA) exhibits a myriad of biological activities including cardioprotective action, antioxidant, antitumor, anti-inflammatory, and antimicrobial properties. On the other hand, CA presents low water solubility and poor bioavailability, which have limited its use for therapeutic applications. The objective of this study was to develop a nanohybrid of zinc basic salts (ZBS) and chitosan (Ch) containing CA (ZBS-CA/Ch) and evaluate its anti-edematogenic and antioxidant activity in dextran and carrageenan-induced paw edema model. The samples were obtained by coprecipitation method and characterized by X-ray diffraction, Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and UV-visible spectroscopy. The release of caffeate anions from ZBS-CA and ZBS-CA/Ch is pH-dependent and is explained by a pseudo-second order kinetics model, with a linear correlation coefficient of R2 ≥ 0.99 at pH 4.8 and 7.4. The in vivo pharmacological assays showed excellent anti-edematogenic and antioxidant action of the ZBS-CA/Ch nanoparticle with slowly releases of caffeate anions in the tissue, leading to a prolongation of CA-induced anti-edematogenic and anti-inflammatory activities, as well as improving its inhibition or sequestration antioxidant action toward reactive species. Overall, this study highlighted the importance of ZBS-CA/Ch as an optimal drug carrier.

Diploid Nuclei Occur throughout the Life Cycles of Pucciniales Fungi.

Within Eukaryotes, fungi are the typical representatives of haplontic life cycles. Basidiomycota fungi are dikaryotic in extensive parts of their life cycle, but diploid nuclei are known to form only in basidia. Among Basidiomycota, the Pucciniales are notorious for presenting the most complex life cycles, with high host specialization, and for their expanded genomes. Using cytogenomic (flow cytometry and cell sorting on propidium iodide-stained nuclei) and cytogenetic (FISH with rDNA probe) approaches, we report the widespread occurrence of replicating haploid and diploid nuclei (i.e., 1C, 2C and a small proportion of 4C nuclei) in diverse life cycle stages (pycnial, aecial, uredinial, and telial) of all 35 Pucciniales species analyzed, but not in sister taxa. These results suggest that the Pucciniales life cycle is distinct from any cycle known, i.e., neither haplontic, diplontic nor haplodiplontic, corroborating patchy and disregarded previous evidence. However, the biological basis and significance of this phenomenon remain undisclosed. IMPORTANCE Within Eukaryotes, fungi are the typical representatives of haplontic life cycles, contrasting with plants and animals. As such, fungi thus contain haploid nuclei throughout their life cycles, with sexual reproduction generating a single diploid cell upon karyogamy that immediately undergoes meiosis, thus resuming the haploid cycle. In this work, using cytogenetic and cytogenomic tools, we demonstrate that a vast group of fungi presents diploid nuclei throughout their life cycles, along with haploid nuclei, and that both types of nuclei replicate. Moreover, haploid nuclei are absent from urediniospores. The phenomenon appears to be transversal to the organisms in the order Pucciniales (rust fungi) and it does not occur in neighboring taxa, but a biological explanation or function for it remains elusive.

Margaritaria nobilis L.f. (Phyllanthaceae) Ethanolic Extract: Low Acute Oral Toxicity and Antinociceptive Activity.

Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf's ethanolic extract is determined by ultra-performance liquid chromatography-high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals' consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.

An emergent treat: Marine heatwaves - Implications for marine decapod crustacean species - An overview.

Anthropogenic-mediated climate change severely affects the oceans. The most common definition of a Marine heatwave (MHW) considers that water temperatures rise above the 90th percentile threshold values, based on the last 30 years' average of temperature records for a particular location, and remains this high for five or more days. The current review addresses the evolution of definitions used, as well as the current understanding of the driving mechanisms of MHWs. The collected information shows that the study of MHW is recent and there is a growing interest among the scientific community on this topic, motivated largely by the impacts that pose to marine ecosystems. Further, a more in-depth analysis was carried out, addressing the impacts of MHW events on marine decapod crustacean species. The investigation of such impacts has been carried out using three main methodological approaches: the analysis of in situ records, observed in 33 studies; simulating MHW events through mesocosm experiments, found in 6 studies; and using computational predictive models, detected in 1 study. From the literature available it has been demonstrated that consequences are serious for these species, from altered expansion ranges to alterations of assemblages' abundances. Still, studies addressing the impacts of these extreme events on the decapod communities are scarce, often only limited to adult life forms of commercially relevant species, neglecting non-commercial ones and meroplanktonic life stages. Despite the severe impacts on the health of ecosystems, repercussions on socioeconomic human activities, like fisheries and aquaculture, are also a reality. Overall, this review aims to raise scientific and public awareness of these marine events, which are projected to increase in intensity and frequency in the coming decades. Therefore, there is a growing need to better understand and predict the mechanisms responsible for these extreme events and the impacts on key species, like decapod crustaceans.

Endotoxin tolerance and low activation of TLR-4/NF-κB axis in monocytes of COVID-19 patients.

Higher endotoxin in the circulation may indicate a compromised state of host immune response against coinfections in severe COVID-19 patients. We evaluated the inflammatory response of monocytes from COVID-19 patients after lipopolysaccharide (LPS) challenge. Whole blood samples of healthy controls, patients with mild COVID-19, and patients with severe COVID-19 were incubated with LPS for 2 h. Severe COVID-19 patients presented higher LPS and sCD14 levels in the plasma than healthy controls and mild COVID-19 patients. In non-stimulated in vitro condition, severe COVID-19 patients presented higher inflammatory cytokines and PGE-2 levels and CD14 + HLA-DRlow monocytes frequency than controls. Moreover, severe COVID-19 patients presented higher NF-κB p65 phosphorylation in CD14 + HLA-DRlow, as well as higher expression of TLR-4 and NF-κB p65 phosphorylation in CD14 + HLA-DRhigh compared to controls. The stimulation of LPS in whole blood of severe COVID-19 patients leads to lower cytokine production but higher PGE-2 levels compared to controls. Endotoxin challenge with both concentrations reduced the frequency of CD14 + HLA-DRlow in severe COVID-19 patients, but the increases in TLR-4 expression and NF-κB p65 phosphorylation were more pronounced in both CD14 + monocytes of healthy controls and mild COVID-19 patients compared to severe COVID-19 group. We conclude that acute SARS-CoV-2 infection is associated with diminished endotoxin response in monocytes. KEY MESSAGES: Severe COVID-19 patients had higher levels of LPS and systemic IL-6 and TNF-α. Severe COVID-19 patients presented higher CD14+HLA-DRlow monocytes. Increased TLR-4/NF-κB axis was identified in monocytes of severe COVID-19. Blunted production of cytokines after whole blood LPS stimulation in severe COVID-19. Lower TLR-4/NF-κB activation in monocytes after LPS stimulation in severe COVID-19.