Plasmodium vivax blood-stage invasion into reticulocyte is critical for parasite development. Thus, validation of novel parasite invasion ligands is essential for malaria vaccine development. ...Recently, we demonstrated that EBP2, a Duffy binding protein (DBP) paralog, is antigenically distinct from DBP and could not be functionally inhibited by anti-DBP antibodies. Here, we took advantage of a small outbreak of P.vivax malaria, located in a non-malarious area of Brazil, to investigate for the first time IgM/IgG antibodies against EBP2 and DEKnull-2 (an engineering DBPII vaccine) among individuals who had their first and brief exposure to P.vivax (16 cases and 22 non-cases). Our experimental approach included 4 cross sectional surveys at 3-month interval (12-month follow-up). The results demonstrated that while a brief initial P.vivax infection was not efficient to induce IgM/ IgG antibodies to either EBP2 or DEKnull-2, IgG antibodies against DEKnull-2 (but not EBP2) were boosted by recurrent blood-stage infections following treatment. Of interest, in most recurrent P. vivax infections (4 out of 6 patients) DEKnull-2 IgG antibodies were sustained for 6 to 12 months. Polymorphisms in the ebp2 gene does not seem to explain EBP2 low immunogenicity as the ebp2 allele associated with the P.vivax outbreak presented high identity to the original EBP2 isolate used as recombinant protein. Although EBP2 antibodies were barely detectable after a primary episode of P.vivax infection, EBP2 was highly recognized by serum IgG from long-term malaria-exposed Amazonians (range from 35 to 92% according to previous malaria episodes). Taken together, the results showed that individuals with a single and brief exposure to P.vivax infection develop very low anti-EBP2 antibodies, which tend to increase after long-term malaria exposure. Finally, the findings highlighted the potential of DEKnull-2 as a vaccine candidate, as in non-immune individuals anti-DEKnull-2 IgG antibodies were boosted even after a brief exposure to P.vivax blood stages.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is ...part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.
Bacterial cellulose (BC) is a versatile material produced by microorganisms in the form of a hydrogel film with high water retention capacity, porosity, and mechanical strength. BC can incorporate ...and release substances, making it an interesting polymer for use in the cosmetic and biomedical industries. The aim of the present study was to evaluate the use of a bacterium for the production of cellulose films in which propolis extract was added in situ and ex situ (during and after membrane production, respectively) with promising use as a skincare product. The bacterium Gluconacetobacter hansenii was grown in standard Hestrin–Schramm (HS) medium as well as HS medium with propolis extract for 7 days. A radiolytic process with 60Co was investigated as a safe sterilization method. The average yield was 120.55 ± 2.40 g of cellulose/L. The polymeric system exhibited antioxidant activity (15.16% inhibition of oxidant activity) and high water‐retention capacity (98.01 ± 0.17%). In conclusion, natural additives can provide the antioxidant characteristics of BC. Moreover, gamma irradiation proved to be an effective sterilization method, while maintaining the properties of the material.
Bacterial cellulose characteristics from Gluconacetobacter hansenii were investigated and propolis extract was added to the polymer via ex situ. The polymer blend was sterilized with 60Co irradiation. The obtained polymer blend showed an antioxidant activity content of 15.16%.
Twenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) click chemistry between ...4-azido-7-chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 μM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 μM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained.
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•Synthesis of 7-chloroquinolinotriazoles via click reaction.•All compounds were evaluated for in vitro antimalarial activity and cytotoxicity.•Most of them were non-cytotoxic and five compounds disclosed antimalarial activity.•SAR studies allowed to understanding the antimalarial activity profile.•Promising hits for the development of antimalarial quinolinotriazoles.
The present study describes the development of a polymeric matrix based on bacterial cellulose (BC) additivated with grape skin residue extract by in situ and ex situ methods, to obtain a material ...with antioxidant and moisturizing characteristics for possible cosmetic applications. The samples developed by the different methods showed antioxidant activity, and this property was intensified with the increase of the extracted content used. Among the samples added by the in situ method, the produced with a fermentation medium containing only pure grape skin residue extract (100%v/v—G100) presented the highest value of antioxidant activity 35.6%. While for the produced by the ex situ method (HSG“ex situ”) the value was approximately 30.3%. Both antioxidant activity results were close to those found for the pure extract (38.5%), emphasizing its stability even after incorporation into the membrane. In addition, it was observed that other properties, such as high water retention capacities (around 98%), high porosity (around 85%), and low crystallinity, favor the development of cosmetic products, because they increase the moisturizing effect and the ability to incorporate active compounds. In addition, the use of residue from the grape juice extraction process is valuable inputs for BC additive with antioxidant properties.
The graphic shows the three main stages of the research: Production of bacterial cellulose in situ and ex situ; structural Characterizations: morphological and thermal; absorption and release study of the antioxidant additive in water.
The novel coronavirus SARS-CoV-2 has been affecting the world, causing severe pneumonia and acute respiratory syndrome, leading people to death. Therefore, the search for anti-SARS-CoV-2 compounds is ...pivotal for public health. Natural products may present sources of bioactive compounds; among them, flavonoids are known in literature for their antiviral activity.
Siparuna
species are used in Brazilian folk medicine for the treatment of colds and flu. This work describes the isolation of 3,3′,4′-tri-
O
-methyl-quercetin, 3,7,3′,4′-tetra-
O
-methyl-quercetin (retusin), and 3,7-di-
O
-methyl-kaempferol (kumatakenin) from the dichloromethane extract of leaves of
Siparuna cristata
(Poepp. & Endl.) A.DC., Siparunaceae, using high-speed countercurrent chromatography in addition to the investigation of their inhibitory effect against SARS-CoV-2 viral replication. Retusin and kumatakenin inhibited SARS-CoV-2 replication in Vero E6 and Calu-3 cells, with a selective index greater than lopinavir/ritonavir and chloroquine, used as control. Flavonoids and their derivatives may stand for target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.
Graphical abstract
Plasmodium vivax blood-stage invasion into reticulocyte is critical for parasite development. Thus, validation of novel parasite invasion ligands is essential for malaria vaccine development. ...Recently, we demonstrated that EBP2, a Duffy binding protein (DBP) paralog, is antigenically distinct from DBP and could not be functionally inhibited by anti-DBP antibodies. Here, we took advantage of a small outbreak of P.vivax malaria, located in a non-malarious area of Brazil, to investigate for the first time IgM/IgG antibodies against EBP2 and DEKnull-2 (an engineering DBPII vaccine) among individuals who had their first and brief exposure to P.vivax (16 cases and 22 non-cases). Our experimental approach included 4 cross sectional surveys at 3-month interval (12-month follow-up). The results demonstrated that while a brief initial P.vivax infection was not efficient to induce IgM/ IgG antibodies to either EBP2 or DEKnull-2, IgG antibodies against DEKnull-2 (but not EBP2) were boosted by recurrent blood-stage infections following treatment. Of interest, in most recurrent P. vivax infections (4 out of 6 patients) DEKnull-2 IgG antibodies were sustained for 6 to 12 months. Polymorphisms in the ebp2 gene does not seem to explain EBP2 low immunogenicity as the ebp2 allele associated with the P.vivax outbreak presented high identity to the original EBP2 isolate used as recombinant protein. Although EBP2 antibodies were barely detectable after a primary episode of P.vivax infection, EBP2 was highly recognized by serum IgG from long-term malaria-exposed Amazonians (range from 35 to 92% according to previous malaria episodes). Taken together, the results showed that individuals with a single and brief exposure to P.vivax infection develop very low anti-EBP2 antibodies, which tend to increase after long-term malaria exposure. Finally, the findings highlighted the potential of DEKnull-2 as a vaccine candidate, as in non-immune individuals anti-DEKnull-2 IgG antibodies were boosted even after a brief exposure to P.vivax blood stages. Author summary Vaccines might be a crucial component of the current efforts to malaria control and elimination, and much of the vaccine-related research on P. vivax has been focused on region II of the Duffy binding protein (DBPII), a ligand for human blood-stage infection. Recently, the newly described Erythrocyte binding protein 2 (EBP2), a P.vivax DBP paralog that it is antigenically distinct from DBP, was identified as potential vaccine targets. To date, scarce data are available about the naturally acquired immunity to EBP2. In a small outbreak of P.vivax malaria, located in a non-malarious area, we investigated whether a first P.vivax exposure induces antibodies against EBP2 that could be boosted by P.vivax recurrent infections. In parallel, we included an engineered DBPII vaccine (named DEKnull-2) whose antibody response were previously associated with broadly neutralizing P.vivax antibodies. This study shows EBP2, compared with DEKnull-2, was poorly immunogenic among individuals who experienced their first blood-stage P. vivax malaria infection. However, EBP2 was highly immunogenic in long-term malaria exposed individuals, reinforcing its potential as a P. vivax blood-stage vaccine candidate. Finally, our results reinforce that multiple blood-stage antigens should be targeted for the development of efficient vaccines against P. vivax.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lupeol, a triterpene frequently found in Asteraceae plant species, showed moderate to low activity in different strains of Plasmodium falciparum, the most virulent malaria etiological agents. In this ...work, lupeol was isolated from Parahancornia fasciculata, a plant that is used to treat malaria in the Amazonia region. In the search of more activity lupeol derivatives, five new 1,2,3-triazole hybrid molecules were synthetized by copper-catalyzed azide-alkyne cycloaddition. The antiplasmodial activity of the semi-synthetic compounds were evaluated by the lactate dehydrogenase assay; the lupeol propargyl ether was the only one to disclosing increased activity (half maximal inhibitory concentration-IC50-62.0 ± 1.92 µmol L-1) in relation to lupeol (IC50 117.00 µmol L-1). Therefore, this work revealed a new class of interesting lupeol derivatives that can be obtained by linking electron donors to the hydroxy group at C-3.
Purpose
To compare lung ultrasound (US) and computed tomography (CT) in the assessment of pregnant women with COVID‐19.
Methods
Prospective study comprising 39 pregnant inpatients with COVID‐19 who ...underwent pulmonary assessment with CT and US with a maximum span of 48 h between the exams. The thorax was divided into 12 regions and assessed in terms of the following: the presence of B‐lines (>2), coalescent B‐lines, consolidation on US; presence of interlobular thickening, ground glass, consolidation on CT. The two methods were scored by adding up the scores from each thoracic region.
Results
A significant correlation was found between the scores obtained by the two methods (rICC = 0.946; p < 0.001). They were moderately in agreement concerning the frequency of altered pulmonary regions (weighted kappa = 0.551). In US, a score over 15, coalescent B‐lines, and consolidation were predictors of the need for oxygen, whereas the predictors in CT were a lung score over 16 and consolidation. The two methods, US (p < 0.001; AUC = 0.915) and CT (p < 0.001; AUC = 0.938), were fairly accurate in predicting the need for oxygen.
Conclusion
In pregnant women, lung US and chest CT are of similar accuracy in assessing lungs affected by COVID‐19 and can predict the need for oxygen.
Lung ultrasound may be satisfactorily incorporated into the obstetricians' clinical practice to evaluate pregnant women with COVID‐19. It is an alternative method which is more accessible, less expensive, faster to learn, which can be used at the bedside and repeatedly without running the risk of exposing the fetus to radiation.
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