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1.
Nat Prod Res ; : 1-7, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963903

RESUMO

Mangaba is a fruit native to Brazil, rich in bioactive compounds. To evaluate physicochemical composition, bioactive compounds, antioxidant and antifungal activity of mangaba fruit pulp. Moisture, ash, protein, lipid, energy values and phenolic compounds were determined. Antioxidant activity was determined by capture of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. Evaluation of antifungal activity was performed by Minimum Inhibitory Concentration, according to protocols M07-A9 and M27-S3, and minimum fungicidal concentration. Freeze-dried mangaba pulp presented high levels of carbohydrates, low levels of lipids, and high energy density. Phenolic analysis demonstrated that chlorogenic acid was found in the highest concentration, followed by p-coumaric acid and ferulic acid. Mangaba extract showed antioxidant activity like BHT. Mangaba extract inhibited the growth of Candida albicans (ATCC 90028), Cryptococcus gattii (AFLP4), Candida guilliermondii (ATCC 6260) and Candida albicans (MYA 2876). Freeze-dried mangaba inhibited fungal activity associated with antioxidant effect due to presence of phenolic compounds.

2.
ScientificWorldJournal ; 2024: 8991384, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957454

RESUMO

The medicinal plant Bredemeyera floribunda Willd. is used to treat cardiovascular disease, chronic fatigue, low libido, as well as increased diuresis. However, studies considering the toxicity of this plant are scarce. Develop an aqueous extract of B. floribunda considering traditional use and determine the average lethality (LD50), signs, and symptoms of toxicity. The B. floribunda extract was obtained by immersing the root bark in ultrapure water for 18 hours at 4°C, under constant stirring. The test extract was administered in a single dose of 2.000 mg/kg by gavage to rats. Signs and symptoms of toxicity were determined according to the Hippocratic screening test and compared with the control group. In addition, a necropsy was performed for macroscopic evaluation of the organs in the abdominal cavity. A powder was obtained from aqueous extracts that showed the same organoleptic characteristics and emulsification capacity as those presented by the fresh root when prepared according to popular tradition. The LD50 was greater than the test dose with three animals surviving. On the other hand, necropsy of dead rats showed necrosis and reduction in lung mass, in addition to the presence of foam and excessive distension of the stomach and intestines. The main symptoms of toxicity were anesthesia, ataxia, sedation, loss of muscle strength, and excessive drowsiness in the first 24 hours. There was no difference between the control and extract groups with regard to body mass, food, and water intake, as well as in macroscopy of the heart, liver, lungs, intestines, spleen, pancreas, and kidneys. The aqueous extract of the B. floribunda was considered nontoxic or of very low toxicity. However, it is capable of altering the activity of the central nervous system and causing disorders in the respiratory and digestive systems.


Assuntos
Casca de Planta , Extratos Vegetais , Raízes de Plantas , Animais , Extratos Vegetais/toxicidade , Extratos Vegetais/química , Ratos , Casca de Planta/química , Masculino , Raízes de Plantas/química , Dose Letal Mediana , Feminino , Testes de Toxicidade Aguda , Ratos Wistar , Modelos Animais
3.
Nutrients ; 16(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38999771

RESUMO

The study aimed to evaluate the antithrombotic action of Acrocomia aculeata pulp oil (AAPO) in natura, in an in vitro experimental model. AAPO was obtained by solvent extraction, and its chemical characterization was performed by gas chromatography coupled to a mass spectrometer (GC-MS). In vitro toxicity was evaluated with the Trypan Blue exclusion test and in vivo by the Galleria mellonella model. ADP/epinephrine-induced platelet aggregation after treatment with AAPO (50, 100, 200, 400, and 800 µg/mL) was evaluated by turbidimetry, and coagulation was determined by prothrombin activity time (PT) and activated partial thromboplastin time (aPTT). Platelet activation was measured by expression of P-selectin on the platelet surface by flow cytometry and intraplatelet content of reactive oxygen species (ROS) by fluorimetry. The results showed that AAPO has as major components such as oleic acid, palmitic acid, lauric acid, caprylic acid, and squalene. AAPO showed no toxicity in vitro or in vivo. Platelet aggregation decreased against agonists using treatment with different concentrations of AAPO. Oil did not interfere in PT and aPTT. Moreover, it expressively decreased ROS-induced platelet activation and P-selectin expression. Therefore, AAPO showed antiplatelet action since it decreased platelet activation verified by the decrease in P-selectin expression as well as in ROS production.


Assuntos
Fibrinolíticos , Selectina-P , Óleos de Plantas , Agregação Plaquetária , Espécies Reativas de Oxigênio , Animais , Agregação Plaquetária/efeitos dos fármacos , Selectina-P/metabolismo , Humanos , Óleos de Plantas/farmacologia , Óleos de Plantas/química , Espécies Reativas de Oxigênio/metabolismo , Fibrinolíticos/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos
4.
Front Chem ; 12: 1382954, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873409

RESUMO

N-capping (N-cap) and C-capping (C-cap) in biologically active peptides, including specific amino acids or unconventional group motifs, have been shown to modulate activity against pharmacological targets by interfering with the peptide's secondary structure, thus generating unusual scaffolds. The insertion of capping motifs in linear peptides has been shown to prevent peptide degradation by reducing its susceptibility to proteolytic cleavage, and the replacement of some functional groups by unusual groups in N- or C-capping regions in linear peptides has led to optimized peptide variants with improved secondary structure and enhanced activity. Furthermore, some essential amino acid residues that, when placed in antimicrobial peptide (AMP) capping regions, are capable of complexing metals such as Cu2+, Ni2+, and Zn2+, give rise to the family known as metallo-AMPs, which are capable of boosting antimicrobial efficacy, as well as other activities. Therefore, this review presents and discusses the different strategies for creating N- and C-cap motifs in AMPs, aiming at fine-tuning this class of antimicrobials.

5.
World J Microbiol Biotechnol ; 40(7): 201, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38736020

RESUMO

Cariogenic biofilms have a matrix rich in exopolysaccharides (EPS), mutans and dextrans, that contribute to caries development. Although several physical and chemical treatments can be employed to remove oral biofilms, those are only partly efficient and use of biofilm-degrading enzymes represents an exciting opportunity to improve the performance of oral hygiene products. In the present study, a member of a glycosyl hydrolase family 66 from Flavobacterium johnsoniae (FjGH66) was heterologously expressed and biochemically characterized. The recombinant FjGH66 showed a hydrolytic activity against an early EPS-containing S. mutans biofilm, and, when associated with a α-(1,3)-glucosyl hydrolase (mutanase) from GH87 family, displayed outstanding performance, removing more than 80% of the plate-adhered biofilm. The mixture containing FjGH66 and Prevotella melaninogenica GH87 α-1,3-mutanase was added to a commercial mouthwash liquid to synergistically remove the biofilm. Dental floss and polyethylene disks coated with biofilm-degrading enzymes also degraded plate-adhered biofilm with a high efficiency. The results presented in this study might be valuable for future development of novel oral hygiene products.


Assuntos
Biofilmes , Dextranase , Flavobacterium , Glicosídeo Hidrolases , Streptococcus mutans , Biofilmes/crescimento & desenvolvimento , Dextranase/metabolismo , Dextranase/genética , Flavobacterium/enzimologia , Flavobacterium/genética , Streptococcus mutans/enzimologia , Streptococcus mutans/genética , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Hidrólise , Biotecnologia/métodos
6.
Enferm. foco (Brasília) ; 15: 1-8, maio. 2024. ilus
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1553745

RESUMO

Objetivo: Conhecer as percepções de enfermeiros da Atenção Primária à Saúde sobre a valorização no trabalho. Métodos: Estudo qualitativo, descritivo e exploratório, realizado com 132 enfermeiros que atuavam na atenção primária à saúde, em 23 municípios do estado de Minas Gerais. Os dados foram coletados por meio de formulário on-line, analisados conforme pressupostos da análise de conteúdo, com amparo do software Iramuteq. Resultados: A maioria dos participantes eram do sexo feminino (114 - 86,37%), com idade entre 22 e 60 anos, com carga horária de trabalho semanal de 40 horas e recebiam entre 2- 4 salários mínimos. A partir das análises, os dados foram organizados em três categorias temáticas ­ Valorização: reconhecimento do trabalho do enfermeiro; Valorização: satisfação com o salário e Valorização: interdependência com as condições de trabalho. Conclusão: Os enfermeiros percebem que a valorização está atrelada ao reconhecimento profissional, à satisfação com o salário e às condições adequadas de trabalho, tais como: carga horária menor e recursos materiais. Consideraram que o reconhecimento externado por outros atores envolvidos na relação de cuidado, como gestores, usuários e profissionais de saúde, é essencial para a valorização do trabalho. (AU)


Objective: To understand the perceptions of Primary Health Care nurses regarding job appreciation. Methods: A qualitative, descriptive, and exploratory study conducted with 132 nurses working in primary health care across 23 municipalities in the state of Minas Gerais. Data were collected through an online form and analyzed using content analysis assumptions, supported by the Iramuteq software. Results: The majority of participants were female (114 - 86.37%), aged between 22 and 60, with a weekly working hours of 40, and earning between 2-4 minimum wages. Through analysis, data were organized into three thematic categories ­ Appreciation: recognition of the nurse's work; Appreciation: satisfaction with the salary, and Appreciation: interdependence with working conditions. Conclusion: Nurses perceive that appreciation is linked to professional recognition, satisfaction with salary, and appropriate working conditions such as reduced working hours and material resources. They considered external recognition from other stakeholders in the care relationship, such as managers, users, and healthcare professionals, as essential for job appreciation. (AU)


Objetivo: Conocer las percepciones de los enfermeros de la Atención Primaria a la Salud sobre la valorización en el trabajo. Métodos: Estudio cualitativo, descriptivo y exploratorio realizado con 132 enfermeros que trabajaban en la atención primaria a la salud, en 23 municipios del estado de Minas Gerais. Los datos se recopilaron a través de un formulario en línea y se analizaron según los supuestos del análisis de contenido, con el apoyo del software Iramuteq. Resultados: La mayoría de los participantes eran mujeres (114 - 86,37%), con edades entre 22 y 60 años, con una carga horaria de trabajo semanal de 40 horas y recibían entre 2-4 salarios mínimos. A través de análisis, los datos se organizaron en tres categorías temáticas: Valorización: reconocimiento del trabajo del enfermero; Valorización: satisfacción con el salario y Valorización: interdependencia con las condiciones de trabajo. Conclusión: Los enfermeros perciben que la valorización está vinculada al reconocimiento profesional, la satisfacción con el salario y las condiciones de trabajo adecuadas, como una carga horaria reducida y recursos materiales. Consideraron que el reconocimiento externo por parte de otros actores involucrados en la relación de cuidado, como gestores, usuarios y profesionales de la salud, es esencial para la valorización del trabajo. (AU)


Assuntos
Atenção Primária à Saúde , Desejabilidade Social , Trabalho , Enfermagem
7.
J Med Food ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695868

RESUMO

Given the importance of discovering plant species from the Brazilian Cerrado biome with anticancer potential, this study evaluated the antitumor activity of two extracts of Campomanesi adamantium fruits in in vitro and in vivo models of melanoma lung metastasis. Pulp and peel extracts (DEGPU and DEGPE, respectively) were extracted from fresh fruit using dichloromethane as a solvent. As cytotoxicity parameter, concentration values that inhibited 50% cell growth (GI50), total growth inhibition (TGI), and selectivity index (SI) were established. The melanoma lung metastasis model was obtained by injecting 5 × 105/50 µL B16-F10 cells via the tail vein of mice, which received treatment on the 15th day. Metastatic lungs were collected for fluorescence analysis with the IR-780 marker and also macro- and microscopic assessment. In vitro analyses showed that DEGPU was active in K562 (GI50 32.99; TGI 47.93) and U-251 (GI50 32.10; TGI 249.92), whereas DEGPE showed better cytotoxicity results for all tumor cell lines, but was more efficient in K562 (GI50 27.42; TGI 40.20) and U-251 (GI50 4.89; TGI 12.77). Both showed a cytocidal effect on B16F10 at the highest concentration tested, with approximately 25% (DEGPU) and 88% (DEGPE) of cell death. In vivo analyzes showed that both extracts showed significant activity in metastatic lung. Fluorescence images showed differences in intensity between groups owing to greater tumor involvement. Macro- and microscopic images showed that treatments with extracts limited tumor growth and prevented proliferation. The extracts tested have promising activity, thus requiring further research on their active compounds.

8.
J Bacteriol ; 206(5): e0007124, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38629875

RESUMO

Bovine mastitis is a frequent infection in lactating cattle, causing great economic losses. Staphylococcus aureus represents the main etiological agent, which causes recurrent and persistent intramammary infections because conventional antibiotics are ineffective against it. Mastoparan-like peptides are multifunctional molecules with broad antimicrobial potential, constituting an attractive alternative. Nevertheless, their toxicity to host cells has hindered their therapeutic application. Previously, our group engineered three mastoparan-L analogs, namely mastoparan-MO, mastoparan-R1, and [I5, R8] MP, to improve cell selectivity and potential. Here, we were interested in comparing the antibacterial efficacy of mastoparan-L and its analogs against bovine mastitis isolates of S. aureus strains, making a correlation with the physicochemical properties and structural arrangement changes promoted by the sequence modifications. As a result, the analog's hemolytic and/or antimicrobial activity was balanced. All the peptides displayed α-helical folding in hydrophobic and membrane-mimetic environments, as determined by circular dichroism. The peptide [I5, R8] MP stood out for its enhanced selectivity and antibacterial features related to mastoparan-L and the other derivatives. Biophysical approaches revealed that [I5, R8] MP rapidly depolarizes the bacterial membrane of S. aureus, causing cell death by subsequent membrane disruption. Our results demonstrated that the [I5, R8] MP peptide could be a starting point for the development of peptide-based drugs for the treatment of bovine mastitis, with the advantage of no residue in milk, which would help reduce the use of classical antibiotics.IMPORTANCEStaphylococcus aureus is a leading cause of mastitis, the world's most important dairy cattle disease. The multidrug resistance and zoonotic potential of S. aureus, besides the likelihood of antibiotic residues in milk, are of critical concern to public and animal health. Antimicrobial peptides offer a novel antimicrobial strategy. Here, we demonstrate that [I5, R8] MP is a potent and selective peptide, which acts on S. aureus by targeting the bacterial membrane. Therefore, understanding the physicochemical determinants and the modes of action of this class of antimicrobials opens novel prospects for peptide development with enhanced activities in the bovine mastitis context.


Assuntos
Antibacterianos , Peptídeos e Proteínas de Sinalização Intercelular , Mastite Bovina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Bovinos , Mastite Bovina/microbiologia , Mastite Bovina/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Feminino , Antibacterianos/farmacologia , Antibacterianos/química , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/tratamento farmacológico , Peptídeos/farmacologia , Peptídeos/química , Venenos de Vespas/farmacologia , Venenos de Vespas/química
9.
Hematol Transfus Cell Ther ; 46 Suppl 1: S1-S4, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508946

RESUMO

Patient Blood Management (PBM) is a multidimensional approach that seeks to optimize the use of blood and its components in patients. This matter emerged as a response to the need to reduce unnecessary exposure to blood transfusions and their potential risks. In the past, blood transfusion was often overused resulting in complications and high costs. The advent of Patient Blood Management has caused a paradigm shift, highlighting anemia prevention, bleeding control and maximizing the production of blood cells by the organism itself. Patient Blood Management guidelines include the early identification of anemia, strategies to minimize blood loss during surgery, intraoperative blood conservation techniques, preoperative hemoglobin optimization and evidence-based approaches to the rational use of blood transfusions. Aiming to improve clinical outcomes, decrease transfusion-related complications and reduce associated costs, this multidisciplinary approach counts on doctors, nurses, pharmacists and other healthcare professionals. Based on research and clinical evidence, Patient Blood Management continues to evolve thereby promoting safer, more effective patient-centered practices. Its implementation has proven beneficial in various medical contexts thereby contributing to improvements in the quality of care provided to patients. Our goal with this Consensus is to present readers with a broad and diverse view of Patient Blood Management so that they have the building blocks to implement this new technique.

10.
Hematol Transfus Cell Ther ; 46 Suppl 1: S5-S7, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38523042

RESUMO

Managing the patient's blood and hematopoietic system is like managing any of the other organs and organ systems during patient care. Specialists control the heart, kidneys, endocrine system, etc. and the patient's blood requires similar clinical treatment. The hematopoietic system and its circulatory products are fundamental for the healthy functioning of the human body. In simple terms, Patient Blood Management (PBM) is an organized, patient-centered approach in which the entire healthcare team coordinates efforts to improve outcomes by managing and preserving the patient's own blood. By reducing dependence on blood transfusions, PBM seeks to improve clinical outcomes, reduce the risks and costs associated with transfusions, and improve the safety and quality of patient care. Essentially, the concept of PBM is about the holistic management and preservation of the patient's own blood in the medical and surgical context.

11.
Hematol Transfus Cell Ther ; 46 Suppl 1: S8-S11, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38548507

RESUMO

Patient Blood Management (PBM) is a holistic approach to managing blood as a resource of each patient; it is a multimodal strategy that is implemented using a set of techniques that can be applied in individual cases. In fact, the overall result of the implementation of PBM cannot be fully appreciated or explained by simply summing up the effects of the individual strategies and techniques used, since they can only produce the expected ideal result if combined. Implementing a PBM program in healthcare offers several benefits including improved patient safety, better outcomes, cost savings, conservation of resources, evidence-based practice, transfusion alternatives, improved quality of care, compliance with accreditation standards, patient-centered care, and professional education and training.

12.
Nutrients ; 16(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38474865

RESUMO

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.


Assuntos
Vesículas Extracelulares , Proteômica , Humanos , Camundongos , Animais , Obesidade/metabolismo , Processamento de Proteína Pós-Traducional , Proteoma/metabolismo , Vesículas Extracelulares/metabolismo
13.
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
14.
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.

15.
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
16.
FEBS J ; 291(5): 865-883, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37997610

RESUMO

Mastoparans are cationic peptides with multifunctional pharmacological properties. Mastoparan-R1 and mastoparan-R4 were computationally designed based on native mastoparan-L from wasps and have improved therapeutic potential for the control of bacterial infections. Here, we evaluated whether these peptides maintain their activity against Escherichia coli strains under a range of salt concentrations. We found that mastoparan-R1 and mastoparan-R4 preserved their activity under the conditions tested, including having antibacterial activities at physiological salt concentrations. The overall structure of the peptides was investigated using circular dichroism spectroscopy in a range of solvents. No significant changes in secondary structure were observed (random coil in aqueous solutions and α-helix in hydrophobic and anionic environments). The three-dimensional structures of mastoparan-R1 and mastoparan-R4 were elucidated through nuclear magnetic resonance spectroscopy, revealing amphipathic α-helical segments for Leu3-Ile13 (mastoparan-R1) and Leu3-Ile14 (mastoparan-R4). Possible membrane-association mechanisms for mastoparan-R1 and mastoparan-R4 were investigated through surface plasmon resonance and leakage studies with synthetic POPC and POPC/POPG (4:1) lipid bilayers. Mastoparan-L had the highest affinity for both membrane systems, whereas the two analogs had weaker association, but improved selectivity for lysing anionic membranes. This finding was also supported by molecular dynamics simulations, in which mastoparan-R1 and mastoparan-R4 were found to have greater interactions with bacteria-like membranes compared with model mammalian membranes. Despite having a few differences in their functional and structural profiles, the mastoparan-R1 analog stood out with the highest activity, greater bacteriostatic potential, and selectivity for lysing anionic membranes. This study reinforces the potential of mastoparan-R1 as a drug candidate.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Peptídeos , Animais , Peptídeos/farmacologia , Venenos de Vespas/farmacologia , Escherichia coli , Cloreto de Sódio , Computadores , Mamíferos
17.
Hematol., Transfus. Cell Ther. (Impr.) ; 46(supl.1): 1-4, 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557898

RESUMO

Abstract Patient Blood Management (PBM) is a multidimensional approach that seeks to optimize the use of blood and its components in patients. This matter emerged as a response to the need to reduce unnecessary exposure to blood transfusions and their potential risks. In the past, blood transfusion was often overused resulting in complications and high costs. The advent of Patient Blood Management has caused a paradigm shift, highlighting anemia prevention, bleeding control and maximizing the production of blood cells by the organism itself. Patient Blood Management guidelines include the early identification of anemia, strategies to minimize blood loss during surgery, intraoperative blood conservation techniques, preoperative hemoglobin optimization and evidence-based approaches to the rational use of blood transfusions. Aiming to improve clinical outcomes, decrease transfusion-related complications and reduce associated costs, this multidisciplinary approach counts on doctors, nurses, pharmacists and other healthcare professionals. Based on research and clinical evidence, Patient Blood Management continues to evolve thereby promoting safer, more effective patient-centered practices. Its implementation has proven beneficial in various medical contexts thereby contributing to improvements in the quality of care provided to patients. Our goal with this Consensus is to present readers with a broad and diverse view of Patient Blood Management so that they have the building blocks to implement this new technique.

18.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557904

RESUMO

Abstract Managing the patient's blood and hematopoietic system is like managing any of the other organs and organ systems during patient care. Specialists control the heart, kidneys, endocrine system, etc. and the patient's blood requires similar clinical treatment. The hematopoietic system and its circulatory products are fundamental for the healthy functioning of the human body. In simple terms, Patient Blood Management (PBM) is an organized, patient-centered approach in which the entire healthcare team coordinates efforts to improve outcomes by managing and preserving the patient's own blood. By reducing dependence on blood transfusions, PBM seeks to improve clinical outcomes, reduce the risks and costs associated with transfusions, and improve the safety and quality of patient care. Essentially, the concept of PBM is about the holistic management and preservation of the patient's own blood in the medical and surgical context.

19.
Pharmaceuticals (Basel) ; 16(12)2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38139761

RESUMO

Nucleic acid-based therapies have the potential to address numerous diseases that pose significant challenges to more traditional methods. RNA-based therapies have emerged as a promising avenue, utilizing nanoformulation treatments to target a range of pathologies. Nanoformulation offers several advantages compared to other treatment modalities, including targeted delivery, low toxicity, and bioactivity suitable for drug loading. At present, various types of nanoformulations are available, such as liposomes, polymeric nanoparticles (NPs), magnetic NPs, nanoshells, and solid lipid nanoparticles (SLNs). RNA-based therapy utilizes intracellular gene nanoparticles with messenger RNA (mRNA) emerging prominently in cancer therapy and immunotechnology against infectious diseases. The approval of mRNA-based technology opens doors for future technological advancements, particularly self-amplifying replicon RNA (repRNA). RepRNA is a novel platform in gene therapy, comprising viral RNA with a unique molecular property that enables the amplification of all encoded genetic information countless times. As a result, repRNA-based therapies have achieved significant levels of gene expression. In this context, the primary objective of this study is to furnish a comprehensive review of repRNA and its applications in nanoformulation treatments, with a specific focus on encapsulated nanoparticles. The overarching goal is to provide an extensive overview of the use of repRNA in conjunction with nanoformulations across a range of treatments and therapies.

20.
Heliyon ; 9(11): e22108, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027799

RESUMO

Antibiotic resistance challenges the treatment of bacterial biofilm-related infections, but the use of nanoparticles as a treatment is a promising strategy to overcome bacterial infections. This study applied nitrogen-doped titanium dioxide (N-TiO2) conjugated with folic acid (FA) on biofilm-forming resistant bacteria. The photocatalytic effect of TiO2 nanoparticles (NPs) was studied under ultraviolet (UV), visible light, and dark conditions at 60, 120, and 180 min against planktonic cells and biofilms of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa. TiO2 NPs were in the anatase phase, spherical shaped with sizes of 10-13 nm, and effectively doped and conjugated with N and FA. The FA-conjugated nanoparticles (N-TiO2-FA and FA-TiO2) were shown to have a bactericidal effect on all bacteria between 60 and 180 min under UV and visible light conditions. Concerning biofilms, N-TiO2-FA was shown to have a highly disruptive effect on all bacterial biofilms under UV irradiation at 180 min. Meanwhile, the nanoparticles did not show DNA damaging potential and they had no cytostatic effect, indicating that these NPs are biocompatible. In sum, nanoparticle conjugation with FA promoted photocatalytic effectiveness, revealing the promise this nanomaterial holds as a biocompatible antimicrobial agent.

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