Pyrazolones are heterocyclic compounds with interesting biological properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cyclic AMP (cAMP), ...which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan
, the etiological agent of Chagas disease (CD), a major neglected tropical disease.
phenotypic screening identified a 4-bromophenyl-dihydropyrazole dimer as an anti-
hit and 17 novel pyrazolone analogues with variations on the phenyl ring were investigated in a panel of phenotypic laboratory models. Potent activity against the intracellular forms (Tulahuen and Y strains) was obtained with 50% effective concentration (EC
) values within the 0.17 to 3.3 μM range. Although most were not active against bloodstream trypomastigotes, an altered morphology and loss of infectivity were observed. Pretreatment of the mammalian host cells with pyrazolones did not interfere with infection and proliferation, showing that the drug activity was not the result of changes to host cell metabolism. The pyrazolone NPD-227 increased the intracellular cAMP levels and was able to sterilize
-infected cell cultures. Thus, due to its high potency and selectivity
, and its additive interaction with benznidazole (Bz), NPD-227 was next assessed in the acute mouse model. Oral dosing for 5 days of NPD-227 at 10 mg/kg + Bz at 10 mg/kg not only reduced parasitemia (>87%) but also protected against mortality (>83% survival), hence demonstrating superiority to the monotherapy schemes. These data support these pyrazolone molecules as potential novel therapeutic alternatives for Chagas disease.
This study evaluated the anthocyanin stability and the formation characteristics of microencapsulated blueberry extract produced by a spray-drying method using maltodextrin DE20 and hi-maize wall ...materials as the standard formulation (S); the other treatments were combined with inulin (T1), gum arabic (T2), and inulin and gum arabic (T3). The characteristics of microcapsule formation and the stability were evaluated at different storage temperatures during 60 days of analysis. The microcapsules showed encapsulation efficiency that ranged from 96.80 to 98.83%. Of all the treatments, T3 presented the lowest anthocyanin loss at all the storage conditions (5.94% at room temperature, 5.82% at refrigeration, and 4.45% at freezing temperature) and, the longest half-life (679.81 days at room temperature, 693.32 days at refrigeration, and 913.41 days at freezing temperature). The combination of wall materials resulted in substantially improved stability, as well as the protection of anthocyanin compounds under the simulated gastrointestinal conditions, which was possibly due to synergistic action. These results are important findings regarding the preservation and increased shelf-life of anthocyanin compounds, given the instability of these compounds, and they increase the possibility of using them as functional ingredients by the food industry.
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•T3 treatment showed the highest anthocyanins concentration and lowest loss during the storage.•T3 treatment displayed the longest half-life (913.41 days) at freezing temperature.•The microcapsules showed the lowest loss of anthocyanin at lower temperature storage.•Combination of wall materials properly increased anthocyanin protection.
PurposeThe purpose of the article is to analyze the influence of output control, autonomous motivation and controlled motivation on task performance of public servants at home office owing to the ...COVID-19 pandemic.Design/methodology/approachA survey was conducted based on the perception of 236 public servants, and structural equation modeling (SEM) technique was used for data analysis.FindingsBoth autonomous motivation and output control are positively and significantly related to task performance.Research limitations/implicationsThe present study expands the literature with information about individual performance and management control, which can be related to the control, motivation and task performance of public servants at home office in a pandemic context.Practical implicationsThe results could offer a basis for understanding how managers can deal with the challenges while at home office. They can also provide managers with information that they can use to build management strategies to foster the performance of public servants at home office.Social implicationsHome office can decrease commuting to a central workplace, alleviate traffic problems and reduce car pollution. It also allows for business continuity in the face of storms and pandemics.Originality/valueMost studies about home office, COVID-19 and task performance have addressed personal, professional and organizational characteristics. However, little is known about the analysis of combinations of the following constructs: output control, autonomous and controlled motivations, and how both affect task performance of public servants.
•Fast and accurate patulin extraction, without the need for specific cleaning.•Sequential mass spectrometry with high selectivity potential.•The method covered validation requirements and was ...confirmed with the FAPAS® Test.
Patulin (PAT) is a potent mycotoxin commonly found in apples and apple-based products such as juice, thus affecting global food safety. Therefore, development of fast and simple analytical methods to effectively control its contamination is of great importance. This study developed and validated a technique for the analysis of PAT in samples of industrialized apple juice based on liquid–liquid extraction and using acetonitrile as the extraction solvent. Detection via mass spectrometry was performed after Atmospheric Pressure Chemical Ionization (APCI). Mean recoveries of 97.5, 92.49 and 96.92% were reached for 4, 8 and 20 μg/L of PAT, respectively. The analyte was monitored with an APCI source in negative ion mode to identify its fragments. The 24 analyzed samples presented PAT levels below the limit of quantification. It may be concluded that the method fulfilled all of the validation criteria, thus being appropriate for routine surveillance of PAT in apple juice.
The treatment of severe musculoskeletal injuries, such as loss of bone tissue and consolidation disorders, requires bone transplantation, and the success of this bone reconstruction depends on the ...grafts transplant's osteogenic, osteoconductive, and osteoinductive properties. Although the gold standard is autograft, it is limited by availability, morbidity, and infection risk. Despite their low capacity for osteoinduction and osteogenesis, decellularized bone allografts have been used in the search for alternative therapeutic strategies to improve bone regeneration. Considering that bone marrow stromal cells (BMSCs) are responsible for the maintenance of bone turnover throughout life, we believe that associating BMSCs with allograft could produce a material that is biologically similar to autologous bone graft. For this reason, this study evaluated the osteogenic potential of bone allograft cellularized with BMSCs. First, BMSC was characterized and allograft decellularization was confirmed by histology, scanning electron microscopy, and DNA quantification. Subsequently, the BMSCs and allografts were associated and evaluated for adhesion, proliferation, and in vitro and in vivo osteogenic potential. We demonstrated that, after 2 hours, BMSCs had already adhered to the surface of allografts and remained viable for 14 days. In vitro osteogenic assays indicated increased osteogenic potential of allografts compared with beta-tricalcium phosphate (β-TCP). In vivo transplantation assays in immunodeficient mice confirmed the allograft's potential to induce bone formation, with significantly better results than β-TCP. Finally, our results indicate that allograft can provide structural support for BMSC adhesion, offering a favorable microenvironment for cell survival and differentiation and inducing new bone formation. Taken together, our data indicate that this rapid methodology for cellularization of allograft with BMSCs might be a new therapeutic alternative in regenerative medicine and bone bioengineering.
Extracellular proteolytic enzymes are produced by a variety of pathogenic microorganisms, and contribute to host colonization by modulating virulence. Here, we present a first characterization of ...leptolysin, a
Leptospira
metalloprotease of the pappalysin family identified in a previous exoproteomic study. Comparative molecular analysis of leptolysin with two other pappalysins from prokaryotes, ulilysin and mirolysin, reveals similarities regarding calcium, zinc, and arginine -binding sites conservation within the catalytic domain, but also discloses peculiarities. Variations observed in the primary and tertiary structures may reflect differences in primary specificities. Purified recombinant leptolysin of
L. interrogans
was obtained as a ~50 kDa protein. The protease exhibited maximal activity at pH 8.0 and 37°C, and hydrolytic activity was observed in the presence of different salts with maximum efficiency in NaCl. Substrate specificity was assessed using a small number of FRET peptides, and showed a marked preference for arginine residues at the P1 position.
L. interrogans
leptolysin proteolytic activity on proteinaceous substrates such as proteoglycans and plasma fibronectin was also evaluated. All proteins tested were efficiently degraded over time, confirming the protease´s broad-spectrum activity
in vitro
. In addition, leptolysin induced morphological alterations on HK-2 cells, which may be partially attributed to extracellular matrix (ECM) degradation. Hemorrhagic foci were observed in the dorsal skin of mice intradermally injected with leptolysin, as a plausible consequence of ECM disarray and vascular endothelium glycocalyx damage. Assuming that leptospiral proteases play an important role in all stages of the infectious process, characterizing their functional properties, substrates and mechanisms of action is of great importance for therapeutic purposes.
Besides their clinical application, chronic misuse of opioids has often been associated to drug addiction due to their addictive properties, underlying neuroadaptations of AMPA ...glutamate-receptor-dependent synaptic plasticity. Topiramate (TPM), an AMPAR antagonist, has been used to treat psychostimulants addiction, despite its harmful effects on memory. This study aimed to evaluate the effects of a novel topiramate nanosystem on molecular changes related to morphine reinstatement. Rats were previously exposed to morphine in conditioned place preference (CPP) paradigm and treated with topiramate-chitosan nanoparticles (TPM–CS–NP) or non-encapsulated topiramate in solution (S-TPM) during CPP extinction; following memory performance evaluation, they were re-exposed to morphine reinstatement. While morphine-CPP extinction was comparable among all experimental groups, TPM–CS–NP treatment prevented morphine reinstatement, preserving memory performance, which was impaired by both morphine-conditioning and S-TPM treatment. In the NAc, morphine increased D1R, D2R, D3R, DAT, GluA1 and MOR immunoreactivity. It also increased D1R, DAT, GluA1 and MOR in the dorsal hippocampus. TPM–CS–NP treatment decreased D1R, D3R and GluA1 and increased DAT in the NAc, decreasing GluA1 and increasing D2 and DAT in the dorsal hippocampus. Taken together, we may infer that TPM–CS–NP treatment was able to prevent the morphine reinstatement without memory impairment. Therefore, TPM–CS–NP may be considered an innovative therapeutic tool due to its property to prevent opioid reinstatement because it acts modifying both dopaminergic and glutamatergic neurotransmission, which are commonly related to morphine addiction.
•Topiramate chitosan nanoparticles (TPM–CS–NP) prevent morphine reinstatement.•Nanoencapsulation decreases memory impairment related to topiramate treatment.•Morphine exposure upregulates D1-and D2-R in NAC and GluA1 in NAc and hippocampus.•TPM–CS–NP modulates both dopaminergic and glutamatergic neurotransmission.
Chamomilla recutita (Asteraceae) is used worldwide as a soothing, anti-inflammatory and aromatherapy. In Brazil, it is one of the most cultivated medicinal species. However, the cultivation form may ...alter the production of compounds in the secondary metabolism and compromise the therapeutic purpose of this species.
Evaluation of antiproliferative and genotoxic effects of infusions and essential oil of chamomile, cultivated with homeopathy, on the cell cycle of Allium cepa, as well as the determination of the phenolic compounds present in the infusions of the chamomile inflorescences.
For the Allium cepa test, two concentrations of 10 and 40 g L−1 of inflorescences of chamomile were used for the preparation of the infusions and essential oil diluted to 0.10%, referring to the six treatments obtained in field cultivation, in which were carried out the applications of homeopathy from the emergence to the harvest of the plants. Distilled water and ethanol were used as negative control and glyphosate 2% as a positive control. The determination of phenolic compounds present in the infusions was carried by liquid chromatography in a UHPLC apparatus.
Chamomile infusions at concentrations of 10 and 40 g L−1 of inflorescence reduced mitotic index and emphasized antiproliferative activity on the cell cycle of Allium cepa. However, the treatments related to essential oil diluted to 0.10% showed a response variation dependent on the dynamization used, as well as for apigenin concentration.
Therefore, cultivation with homeopathy does not induce a genotoxic effect in the use of infusions and essential oil of chamomile and it emphasize antiproliferative activity on the cell cycle of Allium cepa, favoring the sustainable cultivation and the safe use of this medicinal species when cultivated with homeopathy.
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