Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain ...uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant
Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the
rhizome, which we termed
. The anti-inflammatory and antinociceptive effects of
were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine.
•Selection and modeling of AMPs derived from Lippia transcriptome.•Peptides were active against both gram-positive and gram-negative bacterial strains.•Hemolysis was mitigated through rational design ...of the peptides.•Successful selection of AMPs was modeled from Lippia transcriptome.•Former peptides were active against Gram-positive and Gram-negative bacteria.•Rational design reduced hemolytic activity in blood cells.
Antimicrobial resistance is considered a health issue worldwide. This public health problem underscores the importance of searching for new antimicrobial molecules with different mechanisms of action. Leaf transcriptomes were used to search and develop synthetic antimicrobial peptides derived from mRNA sequences. The in silico search for new AMPs from the L. rotundifolia and L. alba transcriptomes allowed the identification of 120 putative peptide mRNA sequences. Eight of them fitted into optimal parameters and were translated and chemically synthesized antimicrobial peptides. Their biological activity was tested in both Gram-positive and Gram-negative bacteria against which they exhibited antibacterial activity. However, they showed an important hemolytic effect. Afterwards, two active peptides showing bactericidal activity isolated from each plant transcriptome tested were modified and modeled in 11 new variants to increase their antimicrobial activity and stability and to reduce or eliminate their hemolytic effect from their original peptides. The La-AMP1 (MSLLERKLLMHFLRV) the original peptide from L. alba showed a 52% hemolytic effect while the derived peptide La-AMP1a (GLMKLLRELLHMFSRVG) had its hemolytic effect reduced to 0.5% at 128 μg.mL-1. Similarly, we observed that the original peptide from L. rotundifolia, Lr-AMP1 (MRIGLRFVLM), displayed a 71.5% hemolytic effect, while its derived peptide Lr-AMP1f (GSVLRAIMRMFAKLMG) showed 0% hemolysis at 128 μg.mL-1, tested with fresh human erythrocytes. Our results indicate a promising method for the search for novel antimicrobial agents with reduced or zero hemolytic effect, as well as prediction and optimization of their activity from plant mRNA libraries.
Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels CORT and ...behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter CORT, FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated CORT, but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence CORT as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The discovery of antibiotics was a revolutionary feat that provided countless health benefits. The identification of penicillin by Alexander Fleming initiated the era of antibiotics, represented by ...constant discoveries that enabled effective treatments for the different classes of diseases caused by bacteria. However, the indiscriminate use of these drugs allowed the emergence of resistance mechanisms of these microorganisms against the available drugs. In addition, the constant discoveries in the 20th century generated a shortage of new molecules, worrying health agencies and professionals about the appearance of multidrug-resistant strains against available drugs. In this context, the advances of recent years in molecular biology and microbiology have allowed new perspectives in drug design and development, using the findings related to the mechanisms of bacterial resistance to generate new drugs that are not affected by such mechanisms and supply new molecules to be used to treat resistant bacterial infections. Besides, a promising strategy against bacterial resistance is the combination of drugs through adjuvants, providing new expectations in designing new antibiotics and new antimicrobial therapies. Thus, this manuscript will address the main mechanisms of bacterial resistance under the understanding of medicinal chemistry, showing the main active compounds against efflux mechanisms, and also the application of the use of drug delivery systems, and finally, the main potential natural products as adjuvants or with promising activity against resistant strains.
Faced with the global health threat of increasing resistance to antibiotics, researchers are exploring interventions that target bacterial virulence factors. Quorum sensing is a particularly ...attractive target because several bacterial virulence factors are controlled by this mechanism. Furthermore, attacking the quorum-sensing signaling network is less likely to select for resistant strains than using conventional antibiotics. Strategies that focus on the inhibition of quorum-sensing signal production are especially attractive because the enzymes involved are expressed in bacterial cells but are not present in their mammalian counterparts. We review here various approaches that are being taken to interfere with quorum-sensing signal production via the inhibition of autoinducer-2 synthesis, PQS synthesis, peptide autoinducer synthesis, and N-acyl-homoserine lactone synthesis. We expect these approaches will lead to the discovery of new quorum-sensing inhibitors that can help to stem the tide of antibiotic resistance.
The pandemic caused by the Coronavirus 19 (Coronavirus disease 2019, COVID-19) killed countless people in 2020 and it arrived in Brazil in mid-February from the same year. It spread quickly, through ...its facilitated form of transmission by droplets of saliva, coughing, sneezing and contaminated surfaces. Several studies have indicated that male people over 60 years of age with comorbidities such as diabetes mellitus, chronic kidney disease, cardiovascular disease and/ or chronic lung diseases had higher rates of progression to Severe Acute Respiratory Syndrome and greater vulnerability to death. In this sense, this study aimed to describe the clinical and epidemiological profile from suspected and confirmed cases of COVID-19 in a hospital in the city of Anápolis, in the State of Goiás, Brazil, from March to December 2020. A total of 1,170 patients were included in this study, with 54.8% of the patients admitted with symptoms of COVID-19 were women (46.9%) aged between 30 and 59 years old. In addition, it was noted that 11.5% of these patients had some type of comorbidities. Furthermore, the data revealed that 82.2% of the laboratory-confirmed patients who died had comorbidities, most of them men (57%), and from the total of 68.5% had two or more comorbidities, with cardiovascular origin being the most frequent reaching 77.5% from the sample. Thus, it was concluded that the clinical-epidemiological profile of suspected and confirmed patients for COVID-19 in this research was characterized by the majority of female patients between 30 and 49 years of age, although most confirmed cases and deaths occurred in men older than 60 years of age. Most confirmed patients had two or more comorbidities, most of them of cardiovascular origin, followed by metabolic syndromes, lung diseases and others.
KEY WORDS: COVID-19; epidemiology; comorbidity.
. Display omitted
► Pg-AMP1 was expressed and purified in heterologous peptide. ► The expressed peptide Pg-AMP1 showed activity against human pathogenic bacteria. ► Theoretical structure was proposed ...in order to provide mechanistic insights.
Antimicrobial peptides (AMPs) are compounds that act in a wide range of physiological defensive mechanisms developed to counteract bacteria, fungi, parasites and viruses. These molecules have become increasingly important as a consequence of remarkable microorganism resistance to common antibiotics. This report shows Escherichia coli expressing the recombinant antimicrobial peptide Pg-AMP1 previously isolated from Psidium guajava seeds. The deduced Pg-AMP1 open reading frame consists in a 168bp long plus methionine also containing a His6 tag, encoding a predicted 62 amino acid residue peptide with related molecular mass calculated to be 6.98kDa as a monomer and 13.96kDa at the dimer form. The recombinant Pg-AMP1 peptide showed inhibitory activity against multiple Gram-negative (E. coli, Klebsiella pneumonia and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Staphylococcus epidermides) bacteria. Moreover, theoretical structure analyses were performed in order to understand the functional differences between natural and recombinant Pg-AMP1 forms. Data here reported suggest that Pg-AMP1 is a promising peptide to be used as a biotechnological tool for control of human infectious diseases.
Enterobacter cloacae is a Gram-negative bacterium associated with high morbidity and mortality in intensive care patients due to its resistance to multiple antibiotics. Currently, therapy against ...multi-resistant bacteria consists of using colistin, in spite of its toxic effects at higher concentrations. In this context, colistin-resistant E. cloacae strains were challenged with lower levels of colistin combined with other antibiotics to reduce colistin-associated side effects. Colistin-resistant E. cloacae (ATCC 49141) strains were generated by serial propagation in subinhibitory colistin concentrations. After this, three colistin-resistant and three nonresistant replicates were isolated. The identity of all the strains was confirmed by MALDI-TOF MS, VITEK 2 and MicroScan analysis. Furthermore, cross-resistance to other antibiotics was checked by disk diffusion and automated systems. The synergistic effects of the combined use of colistin and chloramphenicol were observed via the broth microdilution checkerboard method. First, data here reported showed that all strains presented intrinsic resistance to penicillin, cephalosporin (except fourth generation), monobactam, and some associations of penicillin and β-lactamase inhibitors. Moreover, a chloramphenicol and colistin combination was capable of inhibiting the induced colistin-resistant strains as well as two colistin-resistant clinical strains. Furthermore, no cytotoxic effect was observed by using such concentrations. In summary, the data reported here showed for the first time the possible therapeutic use of colistin-chloramphenicol for infections caused by colistin-resistant E. cloacae.
Clavanins is a class of peptides (23aa) histidine-rich, free of post-translational modifications. Clavanins have been studied largely for their ability to disrupt bacterial membranes. In the present ...study, the interaction of clavanin A with membranes was assessed by dynamic light scattering, zeta potential and permeabilization assays. We observed through those assays that clavanin A lysis bacterial cells at concentrations corresponding to its MIC. Further, the structure and function of clavanin A was investigated. To better understand how clavanin interacted with bacteria, its NMR structure was elucidated. The solution state NMR structure of clavanin A in the presence of TFE-d3 indicated an α-helical conformation. Secondary structures, based on circular dichroism measurements in anionic sodium dodecyl sulfate (SDS) and TFE (2,2,2-trifluorethanol), in silico lipid-peptide docking and molecular simulations with lipids DPPC and DOPC revealed that clavanin A can adopt a variety of folds, possibly influencing its different functions. Microcalorimetry assays revealed that clavanin A was capable of discriminating between different lipids. Finally, clavanin A was found to eradicate bacterial biofilms representing a previously unrecognized function.
Abstract Aims: To introduce a platform called “InteractiveLab” (ILab) for collecting and analyzing ball passing networks during soccer games. Methods: The software was organized to collect data ...through a mobile interface and touch screen and simultaneously access that data from a remote database, allowing the automated acquisition, storage, and processing of data during games through an application from the web. The analysis is based on the concept of social networks, characterized by the interaction of players through passing exchanges. Results: This descriptive study presents the construction architecture and functioning of the developed software. It also presents the results of intra- and inter-rater reliability and a comparison with the manual collection method. Data were extracted and viewed according to the attacking unit classifications, with the following four outcomes: (a) interception, (b) lost ball, (c) incompletion, and (d) completion. This classification allows for the configuration of the data for a more precise analysis. Some limitations were highlighted, as well as future projections for the improvement of applications and analysis of the interactions network in the context of soccer. Conclusion: It is concluded that the InteractiveLab platform is a viable and beneficial tool that offers new possibilities for analysing performance in soccer. Moreover, given the lack of solutions that work similarly, this product also has market potential.
PDF
