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Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice., Methods: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated., Results: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates., Conclusion: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Coffee leaf rust, caused by the fungus Hemileia vastatrix, has become a major concern for coffee-producing countries. Additionally, there has been an increase in the resistance of certain races of the fungus to fungicides and breeding cultivars, making producers use alternative control methods. In this work, we transplanted the leaf surface microbiota of rust-resistant coffee species (Coffea racemosa and Coffea stenophylla) to Coffea arabica and tested whether the new microbiota would be able to minimize the damage caused by H. vastatrix. It was seen that the transplant was successful in controlling rust, especially from C. stenophylla, but the protection depended on the concentration of the microbiota. Certain fungi, such as Acrocalymma, Bipolaris, Didymella, Nigrospora, Setophaeosphaeria, Simplicillium, Stagonospora and Torula, and bacteria, such as Chryseobacterium, Sphingobium and especially Enterobacter, had their populations increased and this may be related to the antagonism seen against H. vastatrix. Interestingly, the relative population of bacteria from genera Pantoea, Methylobacterium and Sphingomonas decreased after transplantation, suggesting a positive interaction between them and H. vastatrix development. Our findings may help to better understand the role of the microbiota in coffee leaf rust, as well as help to optimize the development of biocontrol agents., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

The sample comprised 44 volunteers who had undergone some surgical procedure and were equally divided into four groups. G1 started the therapy 24 h after the surgical procedure with the device off. G2 followed the same time pattern, 24 h, but with the device turned on. G3 and G4 started therapy three days after the surgical procedure; in G3, the device was turned off, and in G4, the device remained on during therapy; each session lasted 30 min, using 660 nm (red), energy 180 J. For all groups, the therapy started with daily use for seven days and followed the interval use of three times a week until completed 21 days. The revaluation was performed after 7 and 21 days. The results found show changes in HR at rest, systolic and diastolic BP, and in peripheral oxygen saturation, which showed a significant difference in the groups that used on-therapy (p < 0.05). In the MCGILL Scale evaluation, the mean total score showed a more accentuated drop in the groups that used ILIB, (p < 0.05). ILIB may have prevented a more significant evolution of firosis levels; however, no changes were observed in the evaluation of sleep and anxiety. The application of the ILIB in patients undergoing plastic surgery was supported in terms of hemodynamics and pain; in addition, starting the ILIB application 24 h after the procedure proved to be more advantageous., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses., (© 2024. The Author(s).)

Leishmaniases, a group of diseases caused by the species of the protozoan parasite Leishmania, remains a significant public health concern worldwide. Host immune responses play a crucial role in the outcome of Leishmania infections, and several mediators that regulate inflammatory responses are potential targets for therapeutic approaches. Annexin A1 (AnxA1), an endogenous protein endowed with anti-inflammatory and pro-resolving properties, has emerged as a potential player. We have shown that during L. braziliensis infection, deficiency of AnxA1 exacerbates inflammatory responses but does not affect parasite burden. Here, we have investigated the role of AnxA1 in L. amazonensis infection, given the non-healing and progressive lesions characteristic of this infectious model. Infection of AnxA1 KO BALB/c mice resulted in increased lesion size and tissue damage associated with higher parasite burdens and enhanced inflammatory response. Notably, therapeutic application of the AnxA1 peptidomimetic Ac2-26 improves control of parasite replication and increases IL-10 production in vivo and in vitro, in both WT and AnxA1 KO mice. Conversely, administration of WRW4, an inhibitor of FPR2/3, resulted in larger lesions and decreased production of IL-10, suggesting that the effects of AnxA1 during L. amazonensis infection are associated with the engagement of these receptors. Our study illuminates the role of AnxA1 in L. amazonensis infection, demonstrating its impact on the susceptibility phenotype of BALB/c mice. Furthermore, our results indicate that targeting the AnxA1 pathway by using the Ac2-26 peptide could represent a promising alternative for new treatments for leishmaniasis., 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 Masson SAS.. All rights reserved.)

Bovine alpha herpesvirus-5 (BoAHV-5) is related to the development of meningoencephalitis in cattle. Very little is known about the molecular pathways involved in the central nervous system (CNS) damage associated with inflammation during BoHV-5 infection in mice. To better identify the specific immunological pathways triggered by BoAHV-5 infection in mice, we evaluated the mRNA expression of 84 genes involved in innate and adaptive immune responses. We compared gene expression changes in the cerebrum from noninfected and infected mice with BoHV-5 at a 1 × 107 TCID50. Then, we analyzed the association of these genes with neurological signs, neuropathology, and activation of glial cells in response to BoHV-5 infection. Three days after BoAHV-5 infection, increased expression of TNF, IL-2, CXCL10, CXCR3, CCR4, CCL5, IFN-γ, IL-10, IRF7, STAT1, MX1, GATA 3 C3, LIZ2, caspase-1 and IL-1b was found. We also observed the upregulated expression of the CD8a, TBX21 and CD40LG genes and the downregulated expression of the CD4 gene after BoAHV-5 infection. In addition, BoHV-5-infected animals showed higher levels of all the evaluated inflammatory mediators (TNF, IFN-γ and IL-10) on day 3 postinfection. BoAHV-5-infected animals showed neurological changes along with meningoencephalitis, neuropil vacuolation, hemorrhage and reactive gliosis. Astrogliosis and microgliosis, indicated by increased expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), were found throughout the neuropil in infected brains. Moreover, cleaved caspase-3 immunopositive glio-inflammatory cells were visualized around some blood vessels in areas of neuroinflammation in the cerebrum. In agreement on that we found higher cleaved caspase-3 and Iba-1 expression evaluated by western blot analysis in the brains of infected mice compared to control mice. In conclusion, our results revealed., Competing Interests: Declaration of Competing Interest All authors wish to confirm that there are no known conflicts of interest associated with this publication., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The plasminogen/plasmin (Plg/Pla) system, best known for its classical role in thrombolysis, has been recently highlighted as a regulator of other biological processes in mammals, including key steps involved in the resolution of inflammation. Inflammation resolution is a complex process coordinated by different cellular effectors, notably leukocytes, and active mediators, and is initiated shortly after the inflammatory response begins. Once the inflammatory insult is eliminated, an effective and timely engagement of proresolution programs prevents persistent inflammation, thereby avoiding excessive tissue damage, fibrosis, and the development of autoimmunity. Interestingly, recent studies demonstrate that Plg/Pla and their receptor, plasminogen receptor  KT (Plg-R KT ), regulate key steps in inflammation resolution. The number of studies investigating the involvement of the Plg/Pla system in these and other aspects of inflammation, including degradation of extracellular matrices, immune cell migration, wound healing, and skeletal growth and maintenance, highlights key roles of the Plg/Pla system during physiological and pathologic conditions. Here, we discuss robust evidence in the literature for the emerging roles of the Plg/Pla system in key steps of inflammation resolution. These findings suggest that dysregulation in Plg production and its activation plays a role in the pathogenesis of inflammatory diseases. Elucidating central mechanisms underlying the role of Plg/Pla in key steps of inflammation resolution either in preclinical models of inflammation or in human inflammatory conditions, can provide a rationale for the development of new pharmacologic interventions to promote resolution of inflammation, and open new pathways for the treatment of thromboinflammatory conditions., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

We recently demonstrated that clindamycin exhibits activities in acute and chronic models of pain and inflammation. In the present study, we investigated the effects of clindamycin and a clindamycin acetylated derivative (CAD) in models of acute joint inflammation and in a microbiological assay. Joint inflammation was induced in mice by intraarticular (i.a.) injection of zymosan or lipopolysaccharide (LPS). Clindamycin or CAD were administered via the intraperitoneal route 1 h before zymosan or LPS. Paw withdrawal threshold, joint diameter, histological changes, neutrophil recruitment, tumor necrosis factor-α (TNF-α) production and phosphorylation of the IκBα and NF-κB/p65 were evaluated. In vitro assays were used to measure the antibacterial activity of clindamycin and CAD and also their effects on zymosan-induced TNF-α production by RAW264.7 macrophages. Clindamycin exhibited activity against Staphylococcus aureus and Salmonella Typhimurium ATCC® strains at much lower concentrations than CAD. Intraarticular injection of zymosan or LPS induced articular hyperalgesia, edema and neutrophil infiltration in the joints. Zymosan also induced histological changes, NF-κB activation and TNF-α production. Responses induced by zymosan and LPS were inhibited by clindamycin (200 and 400 mg/kg) or CAD (436 mg/kg). Both clindamycin and CAD inhibited in vitro TNF-α production by macrophages. In summary, we provided additional insights of the clindamycin immunomodulatory effects, whose mechanism was associated with NF-κB inhibition and reduced TNF-α production. Such effects were extended to a clindamycin derivative with reduced antibacterial activity, indicating that clindamycin derivatives should be investigated as candidates to drugs that could be useful in the management of inflammatory and painful conditions., 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 Elsevier B.V. All rights reserved.)

The immune and nervous systems can be thought of as cognitive and plastic systems, since they are both involved in cognition/recognition processes and can be architecturally and functionally modified by experience, and such changes can influence each other's functioning. The immune system can affect nervous system function depending on the nature of the immune stimuli and the pro/anti-inflammatory responses they generate. Here we consider interactions between the immune and nervous systems in homeostasis and disease, including the beneficial and deleterious effects of immune stimuli on brain function and the impact of severe and non-severe malaria parasite infections on neurocognitive and behavioral parameters in human and experimental murine malaria. We also discuss the effect of immunization on the reversal of cognitive deficits associated with experimental non-severe malaria in a model susceptible to the development of the cerebral form of the illness. Finally, we consider the possibility of using human vaccines, largely exploited as immune-prophylactics for infectious diseases, as therapeutic tools to prevent or mitigate the expression of cognitive deficits in infectious and chronic degenerative diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ethnopharmacological Relevance: Campomanesia lineatifolia Ruiz & Pavón (Myrtaceae), an edible species found in Brazilian Forest, possesses leaves that are traditionally used for the treatment of gastrointestinal disorders in Brazil. Extracts of C. lineatifolia are rich in phenolics and exhibit antioxidant, and gastric antiulcer properties. Furthermore, Campomanesia spp. have been described to possess anti-inflammatory properties, but studies related to chemical constituents of C. lineatifolia are scarce in the literature., Aim of the Study: This work aims to identify the chemical composition of the phenolic-rich ethanol extract (PEE) from C. lineatifolia leaves and evaluate the anti-inflammatory activity that could be related to its ethnopharmacological use., Materials and Methods: The high-speed countercurrent chromatography (HSCCC), using an isocratic and a step gradient elution method, and NMR, HPLC-ESI-QTOF-MS/MS were used to isolate and identify the chemicals of PEE, respectively. Lipopolysaccharide-(LPS)-stimulated THP-1 cells were used to evaluate the anti-inflammatory activities from PEE and the two majority flavonoids isolated by measure TNF-α and NF-κB inhibition assays., Results: Fourteen compounds were isolated from the PEE, further identified by NMR and HPLC-ESI-QTOF-MS/MS, twelve of them are new compounds, and two others are already known for the species. The PEE, quercitrin and myricitrin promoted a concentration-dependent inhibition of TNF-α, and PEE promoted an inhibition of NF-κB pathway., Conclusions: PEE from C. lineatifolia leaves demonstrated significant anti-inflammatory activity that may be related to the traditional use to treat gastrointestinal disorders., 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 Elsevier B.V. All rights reserved.)

Gouty arthritis (GA) is an inflammatory arthritis triggered by the deposition of monosodium urate monohydrate (MSU) crystals, causing pain, inflammation, and joint damage. Several drugs are currently employed to manage acute flares of GA, but they either have limited effectiveness or induce severe adverse reactions. Ouratea spectabilis is traditionally used in Brazil to treat gastric ulcers and rheumatism. The ethanolic extract of O. spectabilis stems (OSpC) and four biflavanones (ouratein A - D) isolated thereof were evaluated in a murine model of GA induced by the injection of MSU crystals. The underlying mechanism of action of ouratein D was investigated in vitro in cell cultures by measurement of IL-1 β levels by ELISA and Western blot analysis. The administration of OSpC (10, 30 or 100 mg/Kg, p. o.) reduced the migration of total inflammatory cells, monocytes, and neutrophils and diminished the levels of IL-1 β and CXCL1 in the synovial tissue. Among the tested compounds, only ouratein D (1 mg/Kg) reduced the migration of the inflammatory cells and it was shown to be active up to 0.01 mg/Kg (equivalent to 0.34 nM/Kg, p. o.). Treatment of pre-stimulated THP-1 cells (differentiated into macrophages) or BMDMs with ouratein D reduced the release of IL-1 β in both macrophage lines. This biflavanone reduced the activation of caspase-1 (showed by the increase in the cleaved form) in supernatants of cultured BMDMs, evidencing its action in modulating the inflammasome pathway. The obtained results demonstrate the anti-gout properties of O. spectabilis and point out ouratein D as the bioactive component of the assayed extract., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Non-HACEK Gram-negative bacilli (NGNB) infective endocarditis (IE) has a growing frequency. We aimed to describe cases of NGNB IE and find associated risk factors. Methods: We conducted a prospective observational study of consecutive patients with definitive IE according to the modified Duke criteria in four institutions in Brazil. Results: Of 1154 adult patients enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 years, males predominated, accounting for 25/38 (65.8%). Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). Worsening heart failure occurred in 18/38 (47.4%). Higher prevalence of embolic events was found (55,3%), mostly to the central nervous system 7/38 (18.4%). Vegetations were most commonly on aortic valves 17/38 (44.7%). Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38 (34.2%). Overall mortality was 19/38 (50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), hemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors for mortality. Conclusions: The rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with central venous catheters, prosthetic valves, intracardiac devices and hemodialysis and had a high mortality rate.

Macrophages are important effectors of inflammation resolution that contribute to the elimination of pathogens and apoptotic cells and restoration of homeostasis. Pre-clinical studies have evidenced the anti-inflammatory and pro-resolving actions of GILZ (glucocorticoid-induced leucine zipper). Here, we evaluated the role of GILZ on the migration of mononuclear cells under nonphlogistic conditions and Escherichia coli- evoked peritonitis. TAT-GILZ (a cell-permeable GILZ-fusion protein) injection into the pleural cavity of mice induced monocyte/macrophage influx alongside increased CCL2, IL-10 and TGF-β levels. TAT-GILZ-recruited macrophages showed a regulatory phenotype, exhibiting increased expression of CD206 and YM1. During the resolving phase of E. coli -induced peritonitis, marked by an increased recruitment of mononuclear cells, lower numbers of these cells and CCL2 levels were found in the peritoneal cavity of GILZ-deficient mice (GILZ -/- ) when compared to WT. In addition, GILZ -/- showed higher bacterial loads, lower apoptosis/efferocytosis counts and a lower number of macrophages with pro-resolving phenotypes. TAT-GILZ accelerated resolution of E. coli- evoked neutrophilic inflammation, which was associated with increased peritoneal numbers of monocytes/macrophages, enhanced apoptosis/efferocytosis counts and bacterial clearance through phagocytosis. Taken together, we provided evidence that GILZ modulates macrophage migration with a regulatory phenotype, inducing bacterial clearance and accelerating the resolution of peritonitis induced by E. coli .

Sepsis is a lethal syndrome characterized by systemic inflammation and abnormal coagulation. Despite therapeutic advances, sepsis mortality remains substantially high. Herein, we investigated the role of the plasminogen/plasmin (Plg/Pla) system during sepsis. Plasma levels of Plg were significantly lower in mice subjected to severe compared with nonsevere sepsis, whereas systemic levels of IL-6, a marker of sepsis severity, were higher in severe sepsis. Plg levels correlated negatively with IL-6 in both septic mice and patients, whereas plasminogen activator inhibitor-1 levels correlated positively with IL-6. Plg deficiency render mice susceptible to nonsevere sepsis induced by cecal ligation and puncture (CLP), resulting in greater numbers of neutrophils and M1 macrophages, liver fibrin(ogen) deposition, lower efferocytosis, and increased IL-6 and neutrophil extracellular trap (NET) release associated with organ damage. Conversely, inflammatory features, fibrin(ogen), and organ damage were substantially reduced, and efferocytosis was increased by exogenous Pla given during CLP- and LPS-induced endotoxemia. Plg or Pla protected mice from sepsis-induced lethality and enhanced the protective effect of antibiotics. Mechanistically, Plg/Pla-afforded protection was associated with regulation of NET release, requiring Pla-protease activity and lysine binding sites. Plg/Pla are important host-protective players during sepsis, controlling local and systemic inflammation and collateral organ damage.

Hepatocellular carcinoma often develops in the context of chronic liver disease. It is the sixth most frequently diagnosed cancer and the third most common cause of cancer-related mortality worldwide. Although the mainstay of therapy is surgical resection, most patients are not eligible because of liver dysfunction or tumor extent. Sorafenib was the first tyrosine kinase inhibitor that improved the overall survival of patients who failed to respond to local therapies or had advanced disease, and for many years, it was the only treatment approved for the first-line setting. However, in recent years, trials have demonstrated an improvement in survival with treatments based on immunotherapy and new targeting agents, thereby extending the treatment options. A phase III trial showed that a combination of immunotherapy and targeted therapy, including atezolizumab plus bevacizumab, improved survival in the first-line setting, and is now considered the new standard of care. Other agents and combinations are being tested, including the combination of nivolumab plus ipilimumab and tremelimumab plus durvalumab, and they reportedly have clinical benefits. The aim of this manuscript is to review the latest approved therapeutic options in first- and second-line settings for advanced HCC and discuss future perspectives.

The analysis of large-scale sequence data has revealed that plants over time recruit certain microbes that are efficient colonizers of the rhizosphere. This enrichment phenomenon is especially seen in annual crops, but we suggest that there could have been some type of enrichment in perennial crops such as coffee plants. To verify this hypothesis, we performed a metagenomic and chemical analysis in rhizosphere with three different plant ages (young, mature, and old) and cultivated on the same farm. We verified that from mature to old plants, there was a decrease in diversity, particularly Fusarium and Plenodomus, while there was an increase in Aspergillus, Cladosporium, Metarhizium, and Pseudomonas. We also detected that the abundance of anti-microbials and ACC-deaminase grows as plants age, although denitrification and carbon fixation had reduced abundances. In summary, we detected an enrichment in the microbial community, especially in the great increase in the participation of Pseudomonas, passing from 50% of the relative abundance as the plants get older. Such enrichment can occur through the dynamics of nutrients such as magnesium and boron., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Preeclampsia is a hypertensive disease of pregnancy associated with intense inflammatory and pro-coagulant responses. Neuroserpin is a serine protease inhibitor that has been involved in neurological and immune processes and has not yet been investigated in preeclampsia. Herein, we evaluated neuroserpin levels in association with other inflammatory mediators (IL-17A, IL-33, and CXCL-16) during severe preeclampsia. The mediators' plasma levels were measured by immunoassays in 24 pregnant women with severe preeclampsia (early preeclampsia: N = 17, late preeclampsia: N = 7), 34 normotensive pregnant women, and 32 non-pregnant women. In general, pregnancy was associated with higher levels of neuroserpin, IL-17A, IL-33, and CXCL-16 than the non-pregnant state. However, this increase was attenuated in pregnancies complicated by severe preeclampsia. Although neuroserpin levels did not differ between normotensive pregnant women and pregnant women with severe preeclampsia, neuroserpin levels tended to be lower in early-onset than in late-onset severe preeclampsia. There were positive correlations between neuroserpin and IL-17A, neuroserpin and CXCL-16, and IL-17A and CXCL-16 levels in women with severe preeclampsia. In addition, although the risk for developing severe preeclampsia was higher in older women in this study, maternal age did not significantly influence the mediators' levels, nor their correlations in the preeclampsia group. In summary, our data suggest that neuroserpin might be a potential biomarker for early-onset severe preeclampsia and, that the imbalance among neuroserpin, IL-17A, IL-33, and CXCL-16 levels may be associated with the pathogenesis of preeclampsia, regardless of the maternal age., 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 Elsevier GmbH. All rights reserved.)

Malaria, an ancient infectious parasitic disease, is caused by protozoa of the genus Plasmodium, whose erythrocytic cycle is accompanied by fever, headache, sweating and chills and a systemic inflammation that can progress to severe forms of disease, including cerebral malaria. Approximately 25% of survivors of this syndrome develop sequelae that may include neurological, neurocognitive, behavioral alterations and poor school performance. Furthermore, some outcomes have also been recorded following episodes of non-severe malaria, which correspond to the most common clinical form of the disease worldwide. There is a body of evidence that neuroinflammation, due to systemic inflammation, plays an important role in the neuropathogenesis of malaria culminating in these cognitive dysfunctions. Preclinical studies suggest that vaccination with type 2 immune response elicitors, such as the tetanus-diphtheria (Td) vaccine, may exert a beneficial immunomodulatory effect by alleviating neuroinflammation. In this viewpoint article, vaccination is proposed as a therapy approach to revert or mitigate neurocognitive deficits associated with malaria., 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 Author(s). Published by Elsevier Inc. All rights reserved.)

Inflammation resolution is an active process that involves cellular events such as apoptosis and efferocytosis, which are key steps in the restoration of tissue homeostasis. Hepatocyte growth factor (HGF) is a growth factor mostly produced by mesenchymal-origin cells and has been described to act via MET receptor tyrosine kinase. The HGF/MET axis is essential for determining the progression and severity of inflammatory and immune-mediated disorders. Here, we investigated the effect of blocking the HGF/MET signalling pathway by PF-04217903 on the resolution of established models of neutrophilic inflammation. In a self-resolving model of gout induced by MSU crystals, HGF expression on periarticular tissue peaked at 12 h, the same time point that neutrophils reach their maximal accumulation in the joints. The HGF/MET axis was activated in this model, as demonstrated by increased levels of MET phosphorylation in neutrophils (Ly6G + cells). In addition, the number of neutrophils was reduced in the knee exudate after PF-04217903 treatment, an effect accompanied by increased neutrophil apoptosis and efferocytosis and enhanced expression of Annexin A1, a key molecule for inflammation resolution. Reduced MPO activity, IL-1β and CXCL1 levels were also observed in periarticular tissue. Importantly, PF-04217903 reduced the histopathological score and hypernociceptive response. Similar findings were obtained in LPS-induced neutrophilic pleurisy. In human neutrophils, the combined use of LPS and HGF increased MET phosphorylation and provided a prosurvival signal, whereas blocking MET with PF-04217903 induced caspase-dependent neutrophil apoptosis. Taken together, these data demonstrate that blocking HGF/MET signalling may be a potential therapeutic strategy for inducing the resolution of neutrophilic inflammatory responses., Competing Interests: Conflict of interest The authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Data recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of non-severe rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12 th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rosa-Gonçalves, de Sousa, Maia, Ribeiro-Gomes, Gress, Werneck, Souza, Almeida and Daniel-Ribeiro.)

cis -Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus , a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis -aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis -aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1 β levels in periarticular tissue. cis -Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis -aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis -Aconitic acid reduced in vitro the release of TNF- α and phosphorylation of I κ B α in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis -aconitic acid-induced anti-inflammatory effects. In conclusion, cis -aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Many Pseudomonas species promote plant growth and colonize a wide range of environments. The annotation of a Coffea arabica ESTs database revealed a considerable number of Pseudomonas sequences. To evaluate the genomic and physiology of Pseudomonas that inhabit coffee plants, fluorescent Pseudomonas from C. arabica root environment were isolated. Two of them had their genomes sequenced; one from rhizospheric soil, named as MNR3A, and one from internal part of the root, named as EMN2. In parallel, we performed biochemical and physiological experiments to confirm genomic analyses results. Interestingly, EMN2 has achromobactin and aerobactin siderophore receptors, but does not have the genes responsible for the production of these siderophores, suggesting an interesting bacterial competition strategy. The two bacterial isolates were able to degrade and catabolize plant phenolic compounds for their own benefit. Surprisingly, MNR3A and EMN2 do not contain caffeine methylases that are responsible for the catabolism of caffeine. In fact, bench experiments confirm that the bacteria did not metabolize caffeine, but were resistant and chemically attracted to it. Furthermore, both bacteria, most especially MNR3A, were able to increase growth of lettuce plants. Our results indicate MNR3A as a potential plant growth promoting bacteria., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: Pseudomonas spp. promotes plant growth and colonizes a wide range of environments. During the annotation of a Coffea arabica ESTs database, we detected a considerable number of contaminant Pseudomonas sequences, specially associated with leaves. The genome of a Pseudomonas isolated from coffee leaves was sequenced to investigate in silico information that could offer insights about bacterial adaptation to coffee phyllosphere. In parallel, several experiments were performed to confirm certain physiological characteristics that could be associated with phyllospheric behavior. Finally, in vivo and in vitro experiments were carried out to verify whether this isolate could serve as a biocontrol agent against coffee rust and how the isolate could act against the infection.  RESULTS: The isolate showed several genes that are associated with resistance to environmental stresses, such as genes encoding heat/cold shock proteins, antioxidant enzymes, carbon starvation proteins, proteins that control osmotic balance and biofilm formation. There was an increase of exopolysaccharides synthesis in response to osmotic stress, which may protect cells from dessication on phyllosphere. Metabolic pathways for degradation and incorporation into citrate cycle of phenolic compounds present in coffee were found, and experimentally confirmed. In addition, MN1F was found to be highly tolerant to caffeine. The experiments of biocontrol against coffee leaf rust showed that the isolate can control the progress of the disease, most likely through competition for resources., Conclusion: Genomic analysis and experimental data suggest that there are adaptations of this Pseudomonas to live in association with coffee leaves and to act as a biocontrol agent., (© 2022. The Author(s).)

The ISTH London 2022 Congress is the first held (mostly) face-to-face again since the COVID-19 pandemic took the world by surprise in 2020. For 2 years we met virtually, but this year's in-person format will allow the ever-so-important and quintessential creativity and networking to flow again. What a pleasure and joy to be able to see everyone! Importantly, all conference proceedings are also streamed (and available recorded) online for those unable to travel on this occasion. This ensures no one misses out. The 2022 scientific program highlights new developments in hemophilia and its treatment, acquired and other inherited bleeding disorders, thromboinflammation, platelets and coagulation, clot structure and composition, fibrinolysis, vascular biology, venous thromboembolism, women's health, arterial thrombosis, pediatrics, COVID-related thrombosis, vaccine-induced thrombocytopenia with thrombosis, and omics and diagnostics. These areas are elegantly reviewed in this Illustrated Review article. The Illustrated Review is a highlight of the ISTH Congress. The format lends itself very well to explaining the science, and the collection of beautiful graphical summaries of recent developments in the field are stunning and self-explanatory. This clever and effective way to communicate research is revolutionary and different from traditional formats. We hope you enjoy this article and will be inspired by its content to generate new research ideas., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Coffee is one of the most important commodities in the global market. Of the 130 species of Coffea , only Coffea arabica and Coffea canephora are actually cultivated on a large scale. Despite the economic and social importance of coffee, little research has been done on the coffee tree microbiome. To assess the structure and function of the rhizosphere microbiome, we performed a deep shotgun metagenomic sequencing of the rhizospheres of five different species, C. arabica, C. canephora, Coffea stenophylla, Coffea racemosa, and Coffea liberica. Our findings indicated that C. arabica and C. stenophylla have different microbiomes, while no differences were detected between the other Coffea species. The core rhizosphere microbiome comprises genera such as Streptomyces, Mycobacterium, Bradyrhizobium, Burkholderia, Sphingomonas, Penicillium, Trichoderma, and Rhizophagus, several of which are potential plant-beneficial microbes. Streptomyces and mycorrhizal fungi dominate the microbial communities. The concentration of sucrose in the rhizosphere seems to influence fungal communities, and the concentration of caffeine/theobromine has little effect on the microbiome. We also detected a possible relationship between drought tolerance in Coffea and known growth-promoting microorganisms. The results provide important information to guide future studies of the coffee tree microbiome to improve plant production and health. IMPORTANCE The microbiome has been identified as a fundamental factor for the maintenance of plant health, helping plants to fight diseases and the deleterious effects of abiotic stresses. Despite this, in-depth studies of the microbiome have been limited to a few species, generally with a short life cycle, and perennial species have mostly been neglected. The coffee tree microbiome, on the other hand, has gained interest in recent years as Coffea trees are perennial tropical species of enormous importance, especially for developing countries. A better understanding of the microorganisms associated with coffee trees can help to mitigate the deleterious effects of climate change on the crop, improving plant health and making the system more sustainable.

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac 2-26 for analysis. In addition, the effect of Ac 2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease., Competing Interests: VC, MS, JH, CB, CQ, MG, JC, TG, GL, JB, IP, CM, TM, KB, RM, MO, MA, LS, DS, HS, MT No competing interests declared, MP is on the Scientific Advisory Board of ResoTher Pharma AS, which is interested in developing Annexin A1-derived peptides for cardiovascular settings, (© 2022, Costa et al.)

Annexin-A1 (AnxA1) and its N-terminal derived peptide Ac2-26 regulate the inflammatory response in several experimental models of disorders. This study evaluated the effect of endogenous AnxA1 and its N-terminal peptide Acetyl 2-26 (Ac2-26) on allergic asthma triggered by house dust mite (HDM) extract in mice. ANXA 1 -/- and wildtype (WT) mice were exposed to intranasal instillation of HDM every other day for 3 weeks, with analyses performed 24 h following the last exposure. Intranasal administration of peptide Ac2-26 was performed 1 h before HDM, beginning 1 week after the initial antigen application. ANXA 1 -/- mice stimulated with HDM showed marked exacerbations of airway hyperreactivity (AHR), eosinophil accumulation, subepithelial fibrosis, and mucus hypersecretion, all parameters correlating with overexpression of cytokines (IL-4, IL-13, TNF-α, and TGF-β) and chemokines (CCL11/eotaxin-1 and CCL2/MCP-1). Intranasal treatment with peptide Ac2-26 decreased eosinophil infiltration, peribronchiolar fibrosis, and mucus exacerbation caused by the allergen challenge. Ac2-26 also inhibited AHR and mediator production. Collectively, our findings show that the AnxA1-derived peptide Ac2-26 protects against several pathological changes associated with HDM allergic reaction, suggesting that this peptide or related AnxA1-mimetic Ac2-26 may represent promising therapeutic candidates for the treatment of allergic asthma.

Pneumonia is a leading cause of morbidity and mortality. While inflammation is a host protective response that ensures bacterial clearance, a finely regulated response is necessary to prevent bystander tissue damage. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a GC-induced protein with anti-inflammatory and proresolving bioactions, yet the therapeutical role of GILZ in infectious diseases remains unexplored. Herein, we investigate the role and effects of GILZ during acute lung injury (ALI) induced by LPS and Streptococcus pneumoniae infection. GILZ deficient mice (GILZ -/- ) presented more severe ALI, characterized by increased inflammation, decreased macrophage efferocytosis and pronounced lung damage. In contrast, pulmonary inflammation, and damage were attenuated in WT mice treated with TAT-GILZ fusion protein. During pneumococcal pneumonia, TAT-GILZ reduced neutrophilic inflammation and prevented the associated lung damage. There was also enhanced macrophage efferocytosis and bacterial clearance in TAT-GILZ-treated mice. Mechanistically, TAT-GILZ enhanced macrophage phagocytosis of pneumococcus, which was lower in GILZ -/- macrophages. Noteworthy, early treatment with TAT-GILZ rescued 30% of S. pneumoniae -infected mice from lethal pneumonia. Altogether, we present evidence that TAT-GILZ enhances host resilience and resistance to pneumococcal pneumonia by controlling pulmonary inflammation and bacterial loads leading to decreased lethality. Exploiting GILZ pathways holds promise for the treatment of severe respiratory infections.

Leishmania spp. infection outcomes are dependent on both host and parasite factors. Manipulation of host signaling pathways involved in the generation of immune responses is thought to be one of the most common mechanisms used by parasites for persistence within the host. Considering the diversity of pathologies caused by different Leishmania spp., it is plausible that significant differences may exist in the mechanisms of host cell manipulation by each parasite species, which may have implications when developing new vaccine or treatment strategies. Here we show that in L. braziliensis -infection in BALB/c mice, a model of resistance, activation of ERK1/2 coincides with the peak of inflammatory responses and resolution of tissue parasitism. In contrast, in the susceptibility model of L. amazonensis -infection, an early silent phase of infection is observed, detected solely by quantification of parasite loads. At this early stage, only basal levels of P-ERK1/2 are observed. Later, after a brief shutdown of ERK1/2 phosphorylation, disease progression is observed and is associated with increased inflammation, lesion size and tissue parasitism. Moreover, the short-term down-regulation of ERK1/2 activation affected significantly downstream inflammatory pathways and adaptive T cell responses. Administration of U0126, a MEK/ERK inhibitor, confirmed this phenomenon, since bigger lesions and higher parasite loads were seen in infected mice that received U0126. To investigate how kinetics of ERK1/2 activation could affect the disease progression, U0126 was administered to L. amazonensis -infected animals earlier than the P-ERK1/2 switch off time-point. This intervention resulted in anticipation of the same effects on inflammatory responses and susceptibility phenotype seen in the natural course of infection. Additionally, in vitro inhibition of ERK1/2 affected the phagocytosis of L. amazonensis by BMDMs. Collectively, our findings reveal distinct temporal patterns of activation of inflammatory responses in L. braziliensis and L. amazonensis in the same animal background and a pivotal role for a brief and specific shutdown of ERK1/2 activation at late stages of L. amazonensis infection. Since activation of inflammatory responses is a crucial aspect for the control of infectious processes, these findings may be important for the search of new and specific strategies of vaccines and treatment for tegumentary leishmaniasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Oliveira, Souza-Testasicca, Ricotta, Vago, dos Santos, Crepaldi, Lima, Queiroz-Junior, Sousa and Fernandes.)

Nonphlogistic migration of macrophages contributes to the clearance of pathogens and apoptotic cells, a critical step for the resolution of inflammation and return to homeostasis. Angiotensin-(1-7) [Ang-(1-7)] is a heptapeptide of the renin-angiotensin system that acts through Mas receptor (MasR). Ang-(1-7) has recently emerged as a novel proresolving mediator, yet Ang-(1-7) resolution mechanisms are not fully determined. Herein, Ang-(1-7) stimulated migration of human and murine monocytes/macrophages in a MasR-, CCR2-, and MEK/ERK1/2-dependent manner. Pleural injection of Ang-(1-7) promoted nonphlogistic mononuclear cell influx alongside increased levels of CCL2, IL-10, and macrophage polarization toward a regulatory phenotype. Ang-(1-7) induction of CCL2 and mononuclear cell migration was also dependent on MasR and MEK/ERK. Of note, MasR was upregulated during the resolution phase of inflammation, and its pharmacological inhibition or genetic deficiency impaired mononuclear cell recruitment during self-resolving models of LPS pleurisy and E. coli peritonitis. Inhibition/absence of MasR was associated with reduced CCL2 levels, impaired phagocytosis of bacteria, efferocytosis, and delayed resolution of inflammation. In summary, we have uncovered a potentially novel proresolving feature of Ang-(1-7), namely the recruitment of mononuclear cells favoring efferocytosis, phagocytosis, and resolution of inflammation. Mechanistically, cell migration was dependent on MasR, CCR2, and the MEK/ERK pathway.

Infectious diseases, once believed to be an eradicable public health threat, still represent a leading cause of death worldwide. Environmental and social changes continuously favor the emergence of new pathogens and rapid dissemination around the world. The limited availability of anti-viral therapies and increased antibiotic resistance has made the therapeutic management of infectious disease a major challenge. Inflammation is a primordial defense to protect the host against invading microorganisms. However, dysfunctional inflammatory responses contribute to disease severity and mortality during infections. In recent years, a few studies have examined the relevance of resolution of inflammation in the context of infections. Inflammation resolution is an active integrated process transduced by several pro-resolving mediators, including Annexin A1 and Angiotensin-(1-7). Here, we examine some of the cellular and molecular circuits triggered by pro-resolving molecules and that may be beneficial in the context of infectious diseases., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Phosphoinositide-3-kinases (PI3Ks) are enzymes involved in signalling and modification of the function of all mammalian cells. These enzymes phosphorylate the 3-hydroxyl group of the inositol ring of phosphatidylinositol, resulting in lipid products that act as second messengers responsible for coordinating many cellular functions, including activation, chemotaxis, proliferation and survival. The identification of the functions that are mediated by a specific PI3K isoform is complex and depends on the specific cell type and inflammatory context. In this chapter we will focus on the role of PI3K isoforms in the context of innate immunity, focusing on the mechanisms by which PI3K signalling regulates phagocytosis, the activation of immunoglobulin, chemokine and cytokines receptors, production of ROS and cell migration, and how PI3K signalling plays a central role in host defence against infections and tissue injury., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

COVID-19 is a multisystem disease caused by SARS-CoV-2 and is associated with an imbalance between the coagulation and fibrinolytic systems. Overall, hypercoagulation, hypofibrinolysis and fibrin-clot resistance to fibrinolysis predispose patients to thrombotic and thromboembolic events. In the lungs, the virus triggers alveolar and interstitial fibrin deposition, endothelial dysfunction, and pulmonary intravascular coagulation, all events intrinsically associated with the activation of inflammation and organ injury. Adding to the pathogenesis of COVID-19, there is a positive feedback loop by which local fibrin deposition in the lungs can fuel inflammation and consequently dysregulates coagulation, a process known as immunothrombosis. Therefore, fibrinolysis plays a central role in maintaining hemostasis and tissue homeostasis during COVID-19 by cleaning fibrin clots and controlling feed-forward products of coagulation. In addition, components of the fibrinolytic system have important immunomodulatory roles, as evidenced by studies showing the contribution of Plasminogen/Plasmin (Plg/Pla) to the resolution of inflammation. Herein, we review clinical evidence for the dysregulation of the fibrinolytic system and discuss its contribution to thrombosis risk and exacerbated inflammation in severe COVID-19. We also discuss the current concept of an interplay between fibrinolysis and inflammation resolution, mirroring the well-known crosstalk between inflammation and coagulation. Finally, we consider the central role of the Plg/Pla system in resolving thromboinflammation, drawing attention to the overlooked consequences of COVID-19-associated fibrinolytic abnormalities to local and systemic inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The dataset presented in this article contains information about marine Area-Based Management Tools (ABMTs) used to assess their contribution to the United Nations 2030 Sustainable Development Goals. Following the scope of the analysis, ABMTs were identified by scrutinizing international and regional legal sources related to ocean management in the fields of marine conservation, fisheries, deep sea bed mining, underwater natural and cultural heritage, environmental conservation, and marine spatial planning. Legal sources were screened to depict the following characteristics of individual ABMTs: i) management objectives; ii) authorities responsible for delivering such objectives; iii) the system of management and planning entailed in the ABMT including the zoning type; and iv) the specific spatial scope and domain each ABMT refer to in vertical depth and horizontal domain. Data were generated through an internal expert elicitation. Experts, initially trained in the data analysis and related protocol, contributed to the data production because of their specific knowledge and experience in ocean management. This dataset represents a unique source of information for advancing research about monitoring and assessment of the achievement of sustainable development goals that encompasses different types of ABMTs., Competing Interests: 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., (© 2021 Published by Elsevier Inc.)

Objectives: We carried out a longitudinal study to compare leukotriene B4 (LTB4), lipoxin A4 (LXA4), and resolvin D1 (RvD1) levels in pregnant women with risk factors for PE - who did (N = 11) or did not develop (N = 17) this clinical condition., Design & Methods: For both groups, plasma levels of the lipid mediators were measured using immunoassays at 12-19, 20-29, and 30-34 weeks of gestation., Results: LTB4 tended to be upregulated throughout gestation in women who developed PE. Moreover, this increase was significant at 30-34 weeks. Although LXA4 levels also tended to be higher in the PE group, this difference was not significant for the evaluated gestational periods. Pregnant women with PE had lower RvD1 levels and a low RvD1/LTB4 ratio at 30-34 weeks, compared to those in the normotensive pregnant women. Contrarily, RvD1 levels increased at weeks 12-19 in pregnant women who developed PE. Particularly, LXA4 and RvD1 levels were higher at 30-34 weeks than those at 20-29 weeks considering both groups of women. We observed an interaction between the gestational outcome and the gestational period in case of RvD1., Conclusions: The imbalance among LTB4, LXA4, and RvD1 levels in these preeclamptic women is consistent with the excessive inflammation that underlies the pathogenesis of PE. Although our data highlight the potential for the use of these lipid mediators as clinical markers for PE development, future longitudinal studies must be carried out to confirm these findings., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective/background: Sleep disorders in cystic fibrosis may be present before daytime clinical manifestations, regardless of lung function impairment, affecting quality of life and disease progression. This study investigated the prevalence of obstructive sleep apnea in children and adolescents with cystic fibrosis and preserved lung function or mild impairment, and evaluated its association with clinical variables., Methods: A systematic review with meta-analysis of prevalence was conducted, including observational studies with polysomnographies in patients with cystic fibrosis who presented mean lung function values > 60% predicted. The methodological quality of the studies was analyzed, and a meta-analysis was performed to assess the prevalence of obstructive sleep apnea., Results: Of the 2318 studies identified, 7 were included in the systematic review and 6 in the meta-analysis of prevalence. The confounding factors and strategies identified were the items with greatest weakness in the methodological quality assessment. Most studies were cross-sectional, and sample size ranged from 9 to 67 individuals. The most frequent criterion for defining obstructive sleep apnea was apnea-hypopnea index (AHI) > 1 per hour. The prevalence found ranged from 32.3 to 100% and the pooled prevalence was 65% (I 2  = 53.4%), considering AHI>1, and 52% (I 2  = 89.4%) for AHI>2 per hour. It was not possible to verify the association between obstructive sleep apnea and clinical variables., Conclusions: A high prevalence of obstructive sleep apnea in children and adolescents with cystic fibrosis was found, regardless of age and lung function impairment, reinforcing the importance of investigating sleep-disordered breathing during clinical visits even when lung function is not yet compromised., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The study of microbes associated with the coffee tree has been gaining strength in recent years. In this work, we compared the leaf mycobiome of the traditional crop Coffea arabica with wild species Coffea racemosa and Coffea stenophylla using ITS sequencing for qualitative information and real-time PCR for quantitative information, seeking to relate the mycobiomes with the content of caffeine and chlorogenic acid in leaves. Dothideomycetes , Wallemiomycetes , and Tremellomycetes are the dominant classes of fungi. The core leaf mycobiome among the three Coffea species is formed by Hannaella , Cladosporium , Cryptococcus , Erythrobasidium, and Alternaria . A network analysis showed that Phoma , an important C. arabica pathogen, is negatively related to six fungal species present in C. racemosa and C. stenophylla and absent in C. arabica . Finally, C. arabica have more than 35 times the concentration of caffeine and 2.5 times the concentration of chlorogenic acid than C. stenophylla and C. racemosa . The relationship between caffeine/chlorogenic acid content, the leaf mycobiome, and genotype pathogen resistance is discussed.

The emergence of life-threatening zoonotic diseases caused by betacoronaviruses, including the ongoing coronavirus disease 19 (COVID-19) pandemic, has highlighted the need for developing preclinical models mirroring respiratory and systemic pathophysiological manifestations seen in infected humans. Here, we showed that C57BL/6J wild-type mice intranasally inoculated with the murine betacoronavirus murine hepatitis coronavirus 3 (MHV-3) develop a robust inflammatory response leading to acute lung injuries, including alveolar edema, hemorrhage, and fibrin thrombi. Although such histopathological changes seemed to resolve as the infection advanced, they efficiently impaired respiratory function, as the infected mice displayed restricted lung distention and increased respiratory frequency and ventilation. Following respiratory manifestation, the MHV-3 infection became systemic, and a high virus burden could be detected in multiple organs along with morphological changes. The systemic manifestation of MHV-3 infection was also marked by a sharp drop in the number of circulating platelets and lymphocytes, besides the augmented concentration of the proinflammatory cytokines interleukin 1 beta (IL-1β), IL-6, IL-12, gamma interferon (IFN-γ), and tumor necrosis factor (TNF), thereby mirroring some clinical features observed in moderate and severe cases of COVID-19. Importantly, both respiratory and systemic changes triggered by MHV-3 infection were greatly prevented by blocking TNF signaling, either via genetic or pharmacologic approaches. In line with this, TNF blockage also diminished the infection-mediated release of proinflammatory cytokines and virus replication of human epithelial lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Collectively, results show that MHV-3 respiratory infection leads to a large range of clinical manifestations in mice and may constitute an attractive, lower-cost, biosafety level 2 (BSL2) in vivo platform for evaluating the respiratory and multiorgan involvement of betacoronavirus infections. IMPORTANCE Mouse models have long been used as valuable in vivo platforms to investigate the pathogenesis of viral infections and effective countermeasures. The natural resistance of mice to the novel betacoronavirus SARS-CoV-2, the causative agent of COVID-19, has launched a race toward the characterization of SARS-CoV-2 infection in other animals (e.g., hamsters, cats, ferrets, bats, and monkeys), as well as adaptation of the mouse model, by modifying either the host or the virus. In the present study, we utilized a natural pathogen of mice, MHV, as a prototype to model betacoronavirus-induced acute lung injure and multiorgan involvement under biosafety level 2 conditions. We showed that C57BL/6J mice intranasally inoculated with MHV-3 develops severe disease, which includes acute lung damage and respiratory distress that precede systemic inflammation and death. Accordingly, the proposed animal model may provide a useful tool for studies regarding betacoronavirus respiratory infection and related diseases.

The main goal of this study was to identify the prevalence of alcohol use and associations with selected variables among clients in a primary healthcare setting. A quantitative, cross-sectional study was carried out using structured questionnaires to measure the pattern of alcohol consumption, quality of life and common mental disorders. The results showed that men, people between 18 and 40 years old, with income between $300.00 and 1200.00 and smokers were at a higher risk of problematic alcohol use. Healthcare professionals should include alcohol screening questions to identify the hazardous consumption of alcohol at an early stage and prevent negative consequences., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Malaria is a life-threatening disease caused by Plasmodium and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by Plasmodium infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by Plasmodium berghei ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during Plasmodium infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of Plasmodium -infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Nayara Kauffmann et al.)

I report here the genome sequences of a Bacillus paranthracis strain isolated from book page surface. The presented data show a new study field for this species, which is frequently encountered in several environment, including soil, rhizosphere and notably human samples. I provide some insights about genomic content of Bacillus paranthracis, for example the presence of multiple antibiotic resistance genes, genes for polyhydroxybutyrate metabolism, 120 genes related to stress resistance and pathogenicity-related genes such as phospholipase C, metalloprotease and a cluster for non-hemolytic enterotoxin. In vitro tests showed that this isolate has motility, ability to produce biofilm, cytotoxic and enterotoxic ability, which makes this isolate a potential pathogen., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The immune system plays a role in the maintenance of healthy neurocognitive function. Different patterns of immune response triggered by distinct stimuli may affect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the effect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria. We show that immune modulation induced by a specific combination of immune stimuli that induce a type 2 immune response can enhance long-term recognition memory in healthy adult mice subjected to novel object recognition task (NORT) and reverse a lack of recognition ability in NORT and anxiety-like behaviour in a light/dark task that result from a single episode of mild Plasmodium berghei ANKA malaria. Our findings suggest a potential use of immunogens for boosting and recovering recognition memory that may be impaired by chronic and infectious diseases and by the effects of ageing., (© 2021. The Author(s).)