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1.
Arch Biochem Biophys ; 753: 109884, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218361

RESUMO

The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 µM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells.


Assuntos
Anfotericina B , Antifúngicos , Animais , Camundongos , Antifúngicos/farmacologia , Anfotericina B/farmacologia , Peptídeos/farmacologia , Candida tropicalis , Biofilmes , Testes de Sensibilidade Microbiana , Mamíferos
2.
Int J Mol Sci ; 24(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37958572

RESUMO

Brazil has several important biomes holding impressive fauna and flora biodiversity. Cerrado being one of the richest ones and a significant area in the search for new plant-based products, such as foods, cosmetics, and medicines. The therapeutic potential of Cerrado plants has been described by several studies associating ethnopharmacological knowledge with phytochemical compounds and therapeutic effects. Based on this wide range of options, the Brazilian population has been using these medicinal plants (MP) for centuries for the treatment of various health conditions. Among these, we highlight metabolic diseases, namely obesity and its metabolic alterations from metabolic syndrome to later stages such as type 2 diabetes (T2D). Several studies have shown that adipose tissue (AT) dysfunction leads to proinflammatory cytokine secretion and impaired free fatty acid (FFA) oxidation and oxidative status, creating the basis for insulin resistance and glucose dysmetabolism. In this scenario, the great Brazilian biodiversity and a wide variety of phytochemical compounds make it an important candidate for the identification of pharmacological strategies for the treatment of these conditions. This review aimed to analyze and summarize the current literature on plants from the Brazilian Cerrado that have therapeutic activity against obesity and its metabolic conditions, reducing inflammation and oxidative stress.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Plantas Medicinais , Brasil , Ecossistema , Obesidade/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico
3.
Molecules ; 28(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36677949

RESUMO

Imidazo[1,2-a]pyridines (IPs) have been studied regarding drug development. The objective of this work was to evaluate the antileukemic capacity of IP derivatives by screening their ability as a pro-oxidant. IP derivatives were synthesized and oral bioavailability and toxicity were analyzed in silico. Redox screening was performed on human Kasumi, KG-1, K562, and Jurkat leukemia cells. The IP derivative and the most responsive leukemic cell were selected for cytotoxicity, cell proliferation, cell senescence, and oxidative stress assays. The predictive toxicity analysis showed a possible effect on the reproductive system, but without mutagenic, carcinogenic, or irritability effects. MRK-107 against K562 cells was the compound that showed the best redox profile. MRK-107 did not induce cell death in K562 and monocyte cells. However, this compound was able to decrease cell proliferation and increase cell senescence after 48 and 72 h. Furthermore, MRK-107 induced oxidative stress in K562 cells after 72 h, increasing lipid peroxidation and decreasing reduced glutathione (GSH) contents. This study demonstrated that MRK-107-induced senescence with the involvement of oxidative stress is a possible mechanism of action, addressing this compound as a potential antitumor drug against chronic myeloid leukemia.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucemia Mieloide , Humanos , Apoptose , Estresse Oxidativo , Antineoplásicos/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proliferação de Células , Senescência Celular , Piridinas/farmacologia , Células K562
4.
J Anim Physiol Anim Nutr (Berl) ; 105(2): 364-375, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33226712

RESUMO

Metabolic syndrome (MetS) and obesity are growing in many parts of the world, becoming public health problems. It is proposed that foods with functional properties can assist in the treatment of these diseases. Crude buriti pulp oil (BPO) is a food traditionally consumed by residents in the Pantanal, Cerrado and Brazilian Amazon. It is rich in oleic acid, tocopherols and carotenoids, emerging as a potential functional food. Thus, this study aimed to evaluate the effect of the supplementation of BPO on metabolic disorders caused by a high-fat diet. Four groups of C57BL6 mice were used, a lean group with AIN-93M diet and control oil supplementation, an obese group with a high-fat diet and control oil supplementation, and two obese groups with a high-fat diet and BPO supplementation in the amounts of 50 and 100 mg/kg. BPO worsened the metabolic state caused by the high-fat diet, worsening risk factors associated with MetS, as the abdominal circumference and retroperitoneal fat, serum levels of total cholesterol, uric acid, alanine transaminase, glucose and triglycerides, and renal fat, in addition to changes in glycaemic control and oxidative stress markers. C57BL/6 mice fed with a high-fat diet and supplemented with BPO presented a worsening in metabolic risk factors associated with MetS.


Assuntos
Doenças Metabólicas , Doenças dos Roedores , Animais , Carotenoides , Dieta Hiperlipídica/efeitos adversos , Fígado , Doenças Metabólicas/veterinária , Camundongos , Camundongos Endogâmicos C57BL
5.
Arch Biochem Biophys ; 691: 108487, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32710881

RESUMO

Antimicrobial peptides (AMP) are molecules with a broad spectrum of activities that have been identified in most living organisms. In addition, synthetic AMPs designed from natural polypeptides have been largely investigated. Here, we designed a novel AMP using the amino acid sequence of a plant trypsin inhibitor from Adenanthera pavonina seeds (ApTI) as a template. The 176 amino acid residues ApTI sequence was cleaved in silico using the Collection of Antimicrobial Peptides (CAMPR3), through the sliding-window method. Further improvements in AMP structure were carried out, resulting in adepamycin, an AMP designed from ApTI. Adepamycin showed antimicrobial activity from 0.9 to 3.6 µM against Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus strains. Moreover, this peptide also displayed activity against Candida albicans and Candida tropicalis. No toxic effects were observed on healthy human cells. Studies on the mechanism of action of adepamycin were carried out using an E. coli and C. tropicalis. Adepamycin triggers membrane disturbances, leading to intracellular nucleic acids release in E. coli. For C. tropicalis, an initial interference with the plasma membrane integrity is followed by the formation of intracellular reactive oxygen species (ROS), leading to apoptosis. Structurally, adepamycin was submitted to circular dichroism spectroscopy, molecular modeling and molecular dynamics simulations, revealing an environment-dependent α-helical structure in the presence of 2,2,2- trifluoroethanol (TFE) and in contact with mimetic vesicles/membranes. Therefore, adepamycin represents a novel lytic AMP with dual antibacterial and antifungal properties.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Sequência de Aminoácidos , Antibacterianos/síntese química , Antibacterianos/toxicidade , Antifúngicos/síntese química , Antifúngicos/toxicidade , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/toxicidade , Bactérias/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Fabaceae/química , Hemólise/efeitos dos fármacos , Humanos , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Fosfatidilgliceróis/química
6.
Biofouling ; 36(5): 516-527, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32619153

RESUMO

Candida yeast infections are the fourth leading cause of death worldwide. Peptides with antimicrobial activity are a promising alternative treatment for such infections. Here, the antifungal activity of a new antimicrobial peptide-PEP-IA18-was evaluated against Candida species. PEP-IA18 was designed from the primary sequence of profilin, a protein from Spodoptera frugiperda, and displayed potent activity against Candida albicans and Candida tropicalis, showing a minimum inhibitory concentration (MIC) of 2.5 µM. Furthermore, the mechanism of action of PEP-IA18 involved interaction with the cell membrane (ergosterol complexation). Treatment at MIC and/or 10 × MIC significantly reduced biofilm formation and viability. PEP-IA18 showed low toxicity toward human fibroblasts and only revealed hemolytic activity at high concentrations. Thus, PEP-IA18 exhibited antifungal and anti-biofilm properties with potential applicability in the treatment of infections caused by Candida species.


Assuntos
Antifúngicos/farmacologia , Biofilmes , Candida , Profilinas/farmacologia , Spodoptera/microbiologia , Animais , Candida albicans , Humanos , Testes de Sensibilidade Microbiana , Peptídeos
7.
Arch Microbiol ; 201(2): 223-233, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30483842

RESUMO

We describe the characterization of IETI, the first trypsin inhibitor purified from Inga edulis, a tree widely distributed in Brazil. Two-step chromatography was used to purify IETI, a protein composed of a single peptide chain of 19,685.10 Da. Amino-terminal sequencing revealed that IETI shows homology with the Kunitz family, as substantiated by its physical-chemical features, such as its thermal (up to 70 °C) and wide-range pH stability (from 2 to 10), and the value of its dissociation constant (6.2 nM). IETI contains a single reactive site for trypsin, maintained by a disulfide bridge; in the presence of DTT, its inhibitory activity was reduced in a time- and concentration-dependent manner. IETI presented activity against Candida ssp., including C. buinensis and C. tropicalis. IETI inhibitory activity triggered yeast membrane permeability, affecting cell viability, thus providing support for the use of IETI in further studies for the control of fungal infections.


Assuntos
Antifúngicos/química , Candida/efeitos dos fármacos , Fabaceae/química , Proteínas de Plantas/química , Inibidores da Tripsina/química , Sequência de Aminoácidos , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Brasil , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Sementes/química , Inibidores da Tripsina/isolamento & purificação , Inibidores da Tripsina/farmacologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-28660700

RESUMO

Plant protease inhibitors (PIs) are elements of a common plant defense mechanism induced in response to herbivores. The fall armyworm, Spodoptera frugiperda, a highly polyphagous lepidopteran pest, responds to various PIs in its diet by expressing genes encoding trypsins. This raises the question of whether the PI-induced trypsins are also inhibited by other PIs, which we posed as the hypothesis that Inga laurina trypsin inhibitor (ILTI) inhibits PI-induced trypsins in S. frugiperda. In the process of testing our hypothesis, we compared its properties with those of selected PIs, soybean Kunitz trypsin inhibitor (SKTI), Inga vera trypsin inhibitor (IVTI), Adenanthera pavonina trypsin inhibitor (ApTI), and Entada acaciifolia trypsin inhibitor (EATI). We report that ILTI is more effective in inhibiting the induced S. frugiperda trypsins than SKTI and the other PIs, which supports our hypothesis. ILTI may be more appropriate than SKTI for studies regarding adaptive mechanisms to dietary PIs.


Assuntos
Fabaceae/química , Controle de Insetos , Proteínas de Insetos/antagonistas & inibidores , Spodoptera/enzimologia , Inibidores da Tripsina/química , Animais , Proteínas de Insetos/isolamento & purificação , Larva , Inibidor da Tripsina de Soja de Kunitz , Inibidores da Tripsina/isolamento & purificação
9.
Pestic Biochem Physiol ; 142: 67-76, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29107249

RESUMO

Biotechnological techniques allow the investigation of alternatives to outdated chemical insecticides for crop protection; some investigations have focused on the identification of molecules tailored from nature for this purpose. We, herein, describe the negative effects of water-soluble lectin from Moringa oleifera seeds (WSMoL) on Anagasta kuehniella development. The chitin-binding lectin, WSMoL, impaired the larval weight gain by 50% and affected the activity of the pest's major digestive enzymes. The commitment of the digestive process became evident after controlled digestion studies, where the capacity of protein digestion was compromised by >90%. Upon acute exposure, the lectin was not resistant to digestion; however, chronic ingestion of WSMoL was able to reverse this feature. Thus, we show that resistance to digestion may not be a prerequisite for a lectin's ability to exert negative effects on larval physiology. The mechanism of action of WSMoL involves binding to chitin with possible disruption to the peritrophic membrane, causing disorder between the endo- and ectoperitrophic spaces. Additionally, results suggest that WSMoL may trigger apoptosis in gut cells, leading to the lower enzymatic activity observed in WSMoL-fed larvae. Although assays employing an artificial diet did not demonstrate effects of WSMoL on A. kuehniella mortality, this lectin may hold potential for exerting insecticide effects on other pest insects, as well for use in other experimental approaches, such as WSMoL-expressing plants. Moreover, the use of WSMoL with other biotechnological tools, such as 'pyramid' crops, may represent a strategy for delaying the evolution of pest resistance to transgenic crops, since its multiple site targets could act in synergism with other insecticide compounds.


Assuntos
Inseticidas/farmacologia , Lectinas/farmacologia , Moringa oleifera/química , Mariposas/fisiologia , Animais , Quitina/química , Fenômenos Fisiológicos do Sistema Digestório/efeitos dos fármacos , Inseticidas/química , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Lectinas/química , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Sementes/química
10.
Biochim Biophys Acta ; 1848(11 Pt B): 3078-88, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25724815

RESUMO

Resistant bacterial infections are a major health problem in many parts of the world. The major commercial antibiotic classes often fail to combat common bacteria. Although antimicrobial peptides are able to control bacterial infections by interfering with microbial metabolism and physiological processes in several ways, a large number of cases of resistance to antibiotic peptide classes have also been reported. To gain a better understanding of the resistance process various technologies have been applied. Here we discuss multiple strategies by which bacteria could develop enhanced antimicrobial peptide resistance, focusing on sub-cellular regions from the surface to deep inside, evaluating bacterial membranes, cell walls and cytoplasmic metabolism. Moreover, some high-throughput methods for antimicrobial resistance detection and discrimination are also examined. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Bactérias/metabolismo , Infecções Bacterianas/metabolismo , Farmacorresistência Bacteriana , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/patogenicidade , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Membrana Celular/metabolismo , Parede Celular/metabolismo , Ensaios de Triagem em Larga Escala , Interações Hospedeiro-Patógeno , Humanos , Testes de Sensibilidade Microbiana/métodos , Viabilidade Microbiana , Transdução de Sinais
11.
Pestic Biochem Physiol ; 118: 1-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25752423

RESUMO

This paper describes the characterization of a trypsin inhibitor from Poincianella pyramidalis seeds (PpyTI). The partial sequencing of PpyTI revealed homology to Kunitz inhibitors, clustered as a member of Family I03 in MEROPS database. PpyTI has a single polypeptide chain of 19,042 Da and presents stability at high temperatures (up to 70 °C) and a wide range of pH. In vitro assays showed that disulfide bridges have an important stabilization role of reactive site in PpyTI, a characteristic shared among several Kunitz inhibitors. Bioassays carried out with the Mediterranean flour moth (Anagasta kuehniella) revealed a significant decrease in both larval weight and survival of PpyTI-fed larvae, besides a larval stage extension. Through biochemical analysis, we demonstrated that the PpyTI insecticide effects were triggered by digestion process commitment, through the inhibition of trypsin and chymotrypsin activities, the major digestive enzymes in this species. The insecticide effects and biochemical characterization of PpyTI encourage further studies using this inhibitor for insect pest control.


Assuntos
Fabaceae/química , Inseticidas/isolamento & purificação , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Inibidores da Tripsina/isolamento & purificação , Inibidores da Tripsina/farmacologia , Sequência de Aminoácidos , Animais , Digestão , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/enzimologia , Trato Gastrointestinal/fisiologia , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Inseticidas/química , Dados de Sequência Molecular , Mariposas/enzimologia , Extratos Vegetais/química , Alinhamento de Sequência , Inibidores da Tripsina/química
12.
Pestic Biochem Physiol ; 108: 74-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24485318

RESUMO

The Mediterranean flour moth (Anagasta kuehniella) is a pest insect that attacks stored foods. The difficulty in controlling this kind of pest promotes the development of alternatives for pest control, among them the use of proteins with insecticide effect. In this work, we evaluated the role of a trypsin inhibitor purified from Entada acaciifolia seeds (EATI) on the A. kuehniella development. Different concentrations of inhibitor were added to a diet to determine its effects on insect performance. At 0.4%, the EATI decreases the larval weight and survival rates by 54.6% and 15%, respectively; in addition to the extension of the life cycle of insect. The biochemical analysis showed that the inhibitor is refractory to the digestion by midgut proteases, and led to a reduction of 32% in general proteolytic activity. A detailed analysis of the enzymatic activity revealed a decrease of 50% in trypsin activity as the chymotrypsin activity increased by 12%; possibly to compensate the commitment of the digestive process. The trypsins from the EATI-fed group stayed sensitive to the inhibition by EATI, and based on kinetic assays no new trypsin enzymes were produced as adaptation attempt. The insecticides effects observed for the EATI against this pest encourage a more in depth study of its possible long-term use as a biotechnological tool.


Assuntos
Fabaceae/química , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Extratos Vegetais/farmacologia , Inibidores da Tripsina/farmacologia , Animais , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Estágios do Ciclo de Vida/efeitos dos fármacos , Mariposas/enzimologia , Sementes/química , Tripsina/metabolismo
13.
Brain Sci ; 14(1)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38248286

RESUMO

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy.

14.
Biochim Biophys Acta Gen Subj ; 1868(5): 130583, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38360076

RESUMO

Antimicrobial peptides (AMP) represent an alternative in the treatment of fungal infections associated with countless deaths. Here, we report a new AMP, named KWI-19, which was designed based on a peptide encrypted in the sequence of an Inga laurina Kunitz-type inhibitor (ILTI). KWI-19 inhibited the growth of Candida species and acted as a fungicidal agent from 2.5 to 20 µmol L-1, also showing synergistic activity with amphotericin B. Kinetic assays showed that KWI-19 killed Candida tropicalis cells within 60 min. We also report the membrane-associated mechanisms of action of KWI-19 and its interaction with ergosterol. KWI-19 was also characterized as a potent antibiofilm peptide, with activity against C. tropicalis. Finally, non-toxicity was reported against Galleria mellonella larvae, thus strengthening the interest in all the bioactivities mentioned above. This study extends our knowledge on how AMPs can be engineered from peptides encrypted in larger proteins and their potential as candicidal agents.


Assuntos
Antifúngicos , Candida , Animais , Antifúngicos/farmacologia , Anfotericina B/farmacologia , Peptídeos/farmacologia , Candida tropicalis , Inibidores de Proteases , Peptídeo Hidrolases
15.
Cien Saude Colet ; 28(5): 1525-1538, 2023 May.
Artigo em Português, Inglês | MEDLINE | ID: mdl-37194884

RESUMO

The aim of the present study was to analyze the management organization of food and nutrition actions in the municipalities of Mato Grosso do Sul. This is a descriptive-exploratory study carried out in Mato Grosso do Sul, in which each municipal food and nutrition manager answered questions about performance, governance and financing profile. Data analysis applied frequency, chi-square test and decision tree tools. All cities were included (n=79). Most of the participants were female (92.4%), white (62%), nurses (45.6%) or nutritionists (36.7%). Financial management proved to be so incipient in the state since specific food and nutrition funding was neglected. The absence of a technical area in the municipality's organizational chart was consistent with the lack of knowledge of actions, goals and resource allocation. Their presence coincided with having formally appointed technical managers, municipal food and nutrition policy, goals and elaboration of specialized materials. The present study also proposed a decision tree pointing that having a nutritionist in the team led to a positive result. The failures found in this study partly clarify the causes of the unsettling situation in the state. Our findings can support the creation of intervention strategies.


Mato Grosso do Sul é líder nacional em mortes atribuíveis ao excesso de peso. O objetivo foi analisar a organização da gestão das ações da área de alimentação e nutrição dos municípios de MS. Estudo descritivo-exploratório realizado em MS, no qual cada gestor municipal de alimentação e nutrição respondeu sobre seu perfil, atuação, governança e financiamento. A análise de dados valeu-se de frequência, teste qui-quadrado e árvore de decisão. Todos participaram (n=79), a maioria era do sexo feminino (92,4%), raça/cor branca (62%), enfermeiros (45,6%) ou nutricionistas (36,7%). A gestão financeira mostrou-se tão incipiente no estado, que financiamentos específicos da área foram desprezados. A ausência de área técnica no organograma do município foi congruente com o desconhecimento de ações, metas e alocação de recursos; sua presença coincidiu com haver responsáveis técnicos formalmente indicados, política de alimentação e nutrição municipal, metas e elaboração de materiais. A árvore de decisão mostra que ter nutricionista na equipe traz efeitos positivos, como mais participação em processos decisórios. Falhas encontradas esclarecem, em parte, causas da grave situação do estado, e podem apoiar a criação de estratégias de intervenção.


Assuntos
Estado Nutricional , Organizações , Humanos , Brasil , Cidades , Tomada de Decisões
16.
Toxins (Basel) ; 15(1)2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36668862

RESUMO

In recent years, antimicrobial peptides isolated from amphibian toxins have gained attention as new multifunctional drugs interacting with different molecular targets. We aimed to rationally design a new peptide from temporin-PTa. Hp-MAP3 (NH2-LLKKVLALLKKVL-COOH), net charge (+4), hydrophobicity (0.69), the content of hydrophobic residues (69%), and hydrophobic moment (0.73). For the construction of the analog peptide, the physicochemical characteristics were reorganized into hydrophilic and hydrophobic residues with the addition of lysines and leucines. The minimum inhibitory concentration was 2.7 to 43 µM against the growth of Gram-negative and positive bacteria, and the potential for biofilm eradication was 173.2 µM. Within 20 min, the peptide Hp-MAP3 (10.8 µM) prompted 100% of the damage to E. coli cells. At 43.3 µM, eliminated 100% of S. aureus within 5 min. The effects against yeast species of the Candida genus ranged from 5.4 to 86.6 µM. Hp-MAP3 presents cytotoxic activity against tumor HeLa at a concentration of 21.6 µM with an IC50 of 10.4 µM. Furthermore, the peptide showed hemolytic activity against murine erythrocytes. Structural studies carried out by circular dichroism showed that Hp-MAP3, while in the presence of 50% trifluoroethanol or SDS, an α-helix secondary structure. Finally, Amphipathic Hp-MAP3 building an important model for the design of new multifunctional molecules.


Assuntos
Proteínas de Anfíbios , Peptídeos Catiônicos Antimicrobianos , Animais , Humanos , Camundongos , Sequência de Aminoácidos , Proteínas de Anfíbios/química , Proteínas de Anfíbios/farmacologia , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Dicroísmo Circular , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Ranidae , Staphylococcus aureus/efeitos dos fármacos
17.
J Insect Sci ; 12: 62, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22938183

RESUMO

The objective of this work was to study the insecticidal effect of labramin, a protein that shows lectin-like properties. Labramin was isolated from seeds of the Beach Apricot tree, Labramia bojeri A. DC ex Dubard (Ericales: Sapotaceae), and assessed against the development of the Mediterranean flour moth Ephestia kuehniella Zeller (Lepidoptera: Pyralidae), an important pest of stored products such as corn, wheat, rice, and flour. Results showed that labramin caused 90% larval mortality when incorporated in an artificial diet at a level of 1% (w/w). The presence of 0.25% labramin in the diet affected the larval and pupal developmental periods and the percentage of emerging adults. Treatments resulted in elevated levels of trypsin activity in midgut and fecal materials, indicating that labramin may have affected enzyme-regulatory mechanisms by perturbing peritrophic membranes in the midgut of is. kuehniella larvae. The results of dietary experiments with E. kuehniella larvae showed a reduced efficiency for the conversion of ingested and digested food, and an increase in approximate digestibility and metabolic cost. These findings suggest that labramin may hold promise as a control agent to engineer crop plants for insect resistance.


Assuntos
Inseticidas/isolamento & purificação , Mariposas/efeitos dos fármacos , Extratos Vegetais/química , Lectinas de Plantas/isolamento & purificação , Sapotaceae/química , Animais , Ingestão de Alimentos/efeitos dos fármacos , Eletroforese em Gel de Poliacrilamida , Feminino , Inseticidas/toxicidade , Larva/efeitos dos fármacos , Mariposas/enzimologia , Mariposas/crescimento & desenvolvimento , Extratos Vegetais/toxicidade , Lectinas de Plantas/toxicidade , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/toxicidade , Sementes/química , Tripsina/metabolismo
18.
Int J Mol Sci ; 13(11): 15241-51, 2012 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-23203122

RESUMO

Insect pests have caused economic losses valued at billions of dollars in agricultural production. Anagasta kuehniella (Zeller), the Mediterranean flour moth, is of major economic importance as a flour and grain feeder and is often a severe pest in flourmills. This study provides a suitable route for the direct preparation of thiosulfonates 2 and 3 from thiols, under mild conditions, with good yields; these thiosulfonates were tested for their regulatory effect on insect growth. The chronic ingestion of thiosulfonates resulted in a significant reduction in larval survival and weight. In addition, the tryptic activity of larvae was sensitive to these thiosulfonates. Results suggest that thiosulfonates 2 and 3 have a potential antimetabolic effect when ingested by A. kuehniella. The use of AgNO(3)/BF(3)·OEt(2) and Al(H(2)PO(4))(3)/HNO(3) provides a suitable route for the direct preparation of thiosulfonates from thiols under mild conditions with good yields. These thiosulfonates were toxic for A. kuehniella larvae, suggesting their potential as biotechnological tools.


Assuntos
Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Ácidos Tiossulfônicos/farmacologia , Animais , Controle de Insetos , Inseticidas/administração & dosagem , Inseticidas/síntese química , Larva , Ácidos Tiossulfônicos/administração & dosagem , Ácidos Tiossulfônicos/síntese química
19.
Pharmaceuticals (Basel) ; 15(6)2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35745643

RESUMO

Nature presents a wide range of biomolecules with pharmacological potential, including venomous animal proteins. Among the protein components from snake venoms, phospholipases (PLA2) are of great importance for the development of new anticancer compounds. Thus, we aimed to evaluate the PLA2 anticancer properties from Bothrops moojeni venom. The crude venom was purified through three chromatographic steps, monitored by enzymatic activity and SDS-PAGE (12%). The purified PLA2 denominated BmPLA2 had its molecular mass and N-terminal sequence identified by mass spectrometry and Edman degradation, respectively. BmPLA2 was assayed against human epithelial colorectal adenocarcinoma cells (Caco-2), human rhabdomyosarcoma cells (RD) and mucoepidermoid carcinoma of the lung (NCI-H292), using human fibroblast cells (MRC-5) and microglia cells (BV-2) as a cytotoxicity control. BmPLA2 presented 13,836 Da and a 24 amino acid-residue homologue with snake PLA2, which showed a 90% similarity with other Bothrops moojeni PLA2. BmPLA2 displayed an IC50 of 0.6 µM against Caco-2, and demonstrated a selectivity index of 1.85 (compared to MRC-5) and 6.33 (compared to BV-2), supporting its selectivity for cancer cells. In conclusion, we describe a new acidic phospholipase, which showed antitumor activity and is a potential candidate in the development of new biotechnological tools.

20.
Biochim Biophys Acta Gen Subj ; 1866(12): 130244, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36162730

RESUMO

Antimicrobial peptides (AMPs) are promising tools for developing new antibiotics. We described the design of IKR18, an AMP designed with the aid of computational tools. IKR18 showed antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). CD studies revealed that IKR18 assumes an alpha-helical structure in the membrane-mimetic environment. The action mechanism IKR18 involves damage to the bacteria membrane, as demonstrated by Sytox green uptake. Furthermore, IKR18 displayed synergic and additive effects in combination with antibiotics ciprofloxacin and vancomycin. The peptide showed anti-biofilm activity in concentration and efficiency compared with commercial antibiotics, involving the direct death of bacteria, as confirmed by scanning electron microscopy. The anti-infective activity of IKR18 was demonstrated in the Galleria mellonella model infected with S. aureus, MRSA, and Acinetobacter baumannii. The novel bioinspired peptide, IKR18, proved to be effective in the control of bacterial infection, opening opportunities for the development of further assays, including preclinical models.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Mariposas , Animais , Peptídeos Antimicrobianos , Staphylococcus aureus , Testes de Sensibilidade Microbiana , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias
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