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Aim: Synthetic antimicrobial peptides (SAMPs) present the potential to fight systemic fungal infections. Here, the PHO36 receptor from Candida albicans was analyzed by in silico tools as a possible target for three anticandidal SAMPs: RcAlb-PepIII, PepGAT and PepKAA.Materials & methods: Molecular docking, dynamics and quantum biochemistry were employed to understand the individual contribution of amino acid residues in the interaction region.Results: The results revealed that SAMPs strongly interact with the PHO36 by multiple high-energy interactions. This is the first study to employ quantum biochemistry to describe the interactions between SAMPs and the PHO36 receptor.Conclusion: This work contributes to understanding and identifying new molecular targets with medical importance that could be used to discover new drugs against systemic fungal infections.
Here, computers helped us find new proteins in Candida albicans that may guide the development of new medicines.
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Antifúngicos , Candida albicans , Simulação de Acoplamento Molecular , Candida albicans/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/síntese química , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Simulação de Dinâmica Molecular , Simulação por Computador , Ligação Proteica , HumanosRESUMO
Efflux pump inhibitors are a potential therapeutic strategy for managing antimicrobial resistance and biofilm formation. This article evaluated the effect of carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on the biofilm growth dynamics and the production of virulence factors by Burkholderia pseudomallei. The effects of CCCP on planktonic, growing, and mature biofilm, interaction with antibacterial drugs, and protease and siderophore production were assessed. CCCP MICs ranged between 128 and 256 µM. The CCCP (128 µM) had a synergic effect with all the antibiotics tested against biofilms. Additionally, CCCP reduced (p < .05) the biomass of biofilm growth and mature biofilms at 128 and 512 µM, respectively. CCCP also decreased (p < .05) protease production by growing (128 µM) and induced (p < .05) siderophore release by planktonic cells (128 µM) growing biofilms (12.8 and 128 µM) and mature biofilms (512 µM). CCCP demonstrates potential as a therapeutic adjuvant for disassembling B. pseudomallei biofilms and enhancing drug penetration.
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Antibacterianos , Biofilmes , Burkholderia pseudomallei , Carbonil Cianeto m-Clorofenil Hidrazona , Testes de Sensibilidade Microbiana , Peptídeo Hidrolases , Sideróforos , Biofilmes/efeitos dos fármacos , Sideróforos/farmacologia , Burkholderia pseudomallei/efeitos dos fármacos , Burkholderia pseudomallei/fisiologia , Antibacterianos/farmacologia , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Peptídeo Hidrolases/metabolismo , Fatores de VirulênciaRESUMO
Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. KEY POINTS: ⢠Several T- and B-cell epitopes were identified in all the three proteins. ⢠Four different adjuvants were used in vaccine formulations. ⢠Immunization stimulated significant levels of IgG2/3 in vaccinated animals.
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Anticorpos Antibacterianos , Vacinas Bacterianas , Leptospirose , Lipoproteínas , Animais , Leptospirose/prevenção & controle , Leptospirose/imunologia , Lipoproteínas/imunologia , Lipoproteínas/genética , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Cricetinae , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Adjuvantes Imunológicos/administração & dosagem , Imunoglobulina G/sangue , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Leptospira interrogans/imunologia , Leptospira interrogans/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Vacinação , Imunidade Humoral , Leptospira/imunologia , Leptospira/genética , Imunogenicidade da VacinaRESUMO
BACKGROUND: Theobroma grandiflorum (Malvaceae), known as cupuassu, is a tree indigenous to the Amazon basin, valued for its large fruits and seed pulp, contributing notably to the Amazonian bioeconomy. The seed pulp is utilized in desserts and beverages, and its seed butter is used in cosmetics. Here, we present the sequenced telomere-to-telomere genome of cupuassu, disclosing its genomic structure, evolutionary features, and phylogenetic relationships within the Malvaceae family. FINDINGS: The cupuassu genome spans 423 Mb, encodes 31,381 genes distributed in 10 chromosomes, and exhibits approximately 65% gene synteny with the Theobroma cacao genome, reflecting a conserved evolutionary history, albeit punctuated with unique genomic variations. The main changes are pronounced by bursts of long-terminal repeat retrotransposons at postspecies divergence, retrocopied and singleton genes, and gene families displaying distinctive patterns of expansion and contraction. Furthermore, positively selected genes are evident, particularly among retained and dispersed tandem and proximal duplicated genes associated with general fruit and seed traits and defense mechanisms, supporting the hypothesis of potential episodes of subfunctionalization and neofunctionalization following duplication, as well as impact from distinct domestication process. These genomic variations may underpin the differences observed in fruit and seed morphology, ripening, and disease resistance between cupuassu and the other Malvaceae species. CONCLUSIONS: The cupuassu genome offers a foundational resource for both breeding improvement and conservation biology, yielding insights into the evolution and diversity within the genus Theobroma.
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Evolução Molecular , Genoma de Planta , Filogenia , Cromossomos de Plantas , Genômica/métodos , Malvaceae/genéticaRESUMO
The Chikungunya virus (CHIKV) presents global health challenges, with Brazil experiencing outbreaks since its introduction in 2014. In 2023, following a CHIKV outbreak in Minas Gerais (MG), social media was used to optimize an entomological survey aimed at identifying vectors and viral lineages and assessing insecticide resistance. Following Instagram posts, residents with suspected CHIKV infection were able to schedule mosquito aspirations. In total, 421 mosquitoes (165 Aedes aegypti and 256 Culex quinquefasciatus) were captured from 40 households in Salinas city (MG) and tested for the Dengue, Zika, and Chikungunya viruses through RT-qPCR. Twelve of 57 pools (10 Ae. aegypti and two Cx. quinquefasciatus) tested positive for CHIKV RNA. Viral RNA was also detected in the heads of nine Ae. aegypti, indicating viral dissemination but not in Cx. quinquefasciatus. Genome sequencing yielded the first near-complete genome from the 2023 outbreak, unveiling that the CHIKV strain belonged to the East/Central/South African (ECSA) genotype. Additionally, genetic analyses revealed high frequencies of kdr alleles, including in CHIKV-infected mosquitoes, suggesting resistance to pyrethroid insecticides in this Ae. aegypti population. Social media was important for guiding mosquito-capture efforts in CHIKV transmission hotspots, thus optimizing the opportunity for viral detection. These findings emphasize the urgent need for innovative vector studies and control strategies, as well as interdisciplinary approaches in public health interventions.
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AIMS: Enterococcus faecalis (E. faecalis) is a leading cause of nosocomial infection and presents a wide spectrum of antibiotic resistance, being vancomycin-resistant Enterococcus (VRE) one of the most relevant. Synthetic antimicrobial peptides (SAMPs) are currently a promising option to overcome antimicrobial resistance. Thus, the purpose of this study was to assess the effect of eight SAMPs against vancomycin-resistant E. faecalis, as well as to investigate their mechanism of action and synergy with conventional antibiotics. METHODS AND RESULTS: Here, eight SAMPs, Mo-CBP3-PepI, Mo-CBP3-PepII, Mo-CBP3-PepIII, RcAlb-PepI, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA, were tested for antibacterial activity in vitro against E. faecalis (ATCC® 51299) through broth microdilution. A maximum of 48% of E. faecalis growth inhibition was achieved by treatment with SAMPs alone. However, when these peptides were combined with the antibiotic chloramphenicol, assessed by checkerboard method, the inhibition increased to 55%-76% of inhibition, two to three-folds of increase if compared to the effects of the compounds alone. Microscopic analysis showed that E. faecalis cells treated with a combination of SAMPs and chloramphenicol resulted in bacterial membrane damage. The biofilm inhibition maximum was 22% for SAMPs alone, when combined with chloramphenicol, the maximum increased to 33%. CONCLUSIONS: SAMPs and their combination with chloramphenicol demonstrate antibacterial activity against E. faecalis, possibly by inducing bacterial membrane damage.
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Antibacterianos , Peptídeos Antimicrobianos , Cloranfenicol , Sinergismo Farmacológico , Enterococcus faecalis , Testes de Sensibilidade Microbiana , Enterococos Resistentes à Vancomicina , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/crescimento & desenvolvimento , Antibacterianos/farmacologia , Cloranfenicol/farmacologia , Peptídeos Antimicrobianos/farmacologia , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Vancomicina/farmacologiaRESUMO
BACKGROUND: Fungal keratitis is a severe eye infection that can result in blindness and visual impairment, particularly in developing countries. Fusarium spp. are the primary causative agents of this condition. Diagnosis of Fusarium keratitis (FK) is challenging, and delayed treatment can lead to serious complications. However, there is limited epidemiological data on FK, especially in tropical areas. OBJECTIVES: This study aimed to describe the clinical, laboratorial and epidemiological characteristics of FK in a tropical semi-arid region of Brazil. PATIENTS/METHODS: Adult patients with laboratory-confirmed FK diagnosed between October 2019 and March 2022 were evaluated. Fusarium isolates were characterized at molecular level and evaluated regarding antifungal susceptibility. RESULTS: A total of 226 clinical samples from patients suspected of keratitis were evaluated; fungal growth was detected in 50 samples (22.12%); out of which 42 were suggestive of Fusarium spp. (84%). Molecular analysis of a randomly selected set of 27 isolates identified F. solani species complex (n = 14); F. fujikuroi sensu lato (n = 6) and F. dimerum sensu lato (n = 7); a total of 10 haplotypes were identified among the strains. All but one Fusarium strains were inhibited by amphotericin B, natamycin and fluconazole. Most patients were male (71.42%; 30 out of 42), aged from 27 to 73 years old. Trauma was the most important risk factor for FK (40.47%; 17 out of 42). Patients were treated with antifungals, corticoids and antibiotics; keratoplasty and eye enucleation were also performed. CONCLUSIONS: The study provided insights into the characteristics of FK in tropical regions and emphasized the importance of enhanced surveillance and management strategies.
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Antifúngicos , Infecções Oculares Fúngicas , Fusariose , Fusarium , Ceratite , Testes de Sensibilidade Microbiana , Humanos , Brasil/epidemiologia , Fusarium/genética , Fusarium/efeitos dos fármacos , Fusarium/isolamento & purificação , Fusarium/classificação , Masculino , Feminino , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Adulto , Ceratite/microbiologia , Ceratite/epidemiologia , Ceratite/tratamento farmacológico , Pessoa de Meia-Idade , Fusariose/microbiologia , Fusariose/epidemiologia , Fusariose/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Idoso , Adulto Jovem , Adolescente , Clima Tropical , Idoso de 80 Anos ou mais , Anfotericina B/farmacologia , Anfotericina B/uso terapêuticoRESUMO
Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy.
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Neoplasias da Mama , Aprendizado de Máquina , Humanos , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Contagem de Células Sanguíneas/métodos , Medição de Risco/métodos , Detecção Precoce de Câncer/métodos , Brasil/epidemiologiaRESUMO
OBJECTIVE: To create a protocol for performing minimally invasive autopsies (MIA) in detecting deaths from arboviruses and report preliminary data from its application in Ceará state, Brazil. METHODS: Training was provided to medical pathologists on MIA. RESULTS: A protocol was established for performing MIA, defining criteria for sample collection, storage methods, and diagnoses to be carried out according to the type of biological sample; 43 MIAs were performed in three months. Of these, 21 (48.8%) arrived at the Death Verification Service (SVO) with arboviruses as a diagnostic hypothesis, and seven (16.3%) were confirmed (six chikungunya cases and one dengue case); cases of COVID-19 (n = 9), tuberculosis (n = 5), meningitis (n = 4), cryptococcosis (n = 1), Creutzfeldt-Jakob disease (n = 1), breast cancer (n = 1), and human rabies (n = 1) were also confirmed. CONCLUSION: The protocol implemented enabled identification of a larger number of suspected arbovirus-related deaths, as well as confirmation of other diseases of interest for surveillance. MAIN RESULTS: A protocol was developed to perform minimally invasive autopsies (MIAs) in Death Verification Services (SVO), capable of expanding the system's capacity to identify a greater number of deaths suspected to be due to arboviruses. IMPLICATIONS FOR SERVICES: The experience suggests that in-service trained health professionals are able to perform MIA, and that use of this technique in SVOs has been shown to be capable of increasing the system's sensitivity in detecting deaths of interest to public health. PERSPECTIVES: Trained professionals will be able to collect biological material in hospitals, through MIA, in cases of interest for health surveillance and when family members do not allow a complete conventional autopsy to be performed.
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Infecções por Arbovirus , Autopsia , Humanos , Brasil/epidemiologia , Autopsia/métodos , Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/diagnóstico , Infecções por Arbovirus/patologia , Feminino , Sensibilidade e Especificidade , Masculino , Pessoa de Meia-Idade , Adulto , Adolescente , Adulto Jovem , Arbovírus/isolamento & purificação , Idoso , Vigilância da População/métodos , Monitoramento Epidemiológico , Causas de Morte , Criança , Pré-EscolarRESUMO
Chitosan is a cationic polysaccharide derived from chitin deacetylation. This polysaccharide and its oligosaccharides have many biological activities and can be used in several fields due to their favorable characteristics, such as biodegradability, biocompatibility, and nontoxicity. This review aims to explore the antifungal potential of chitosan and chitooligosaccharides along with the conditions used for the activity and mechanisms of action they use to kill fungal cells. The sources, chemical properties, and applications of chitosan and chitooligosaccharides are discussed in this review. It also addresses the threat fungi pose to human health and crop production and how these saccharides have proven to be effective against these microorganisms. The cellular processes triggered by chitosan and chitooligosaccharides in fungal cells, and prospects for their use as potential antifungal agents are also examined.
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Antifúngicos , Quitosana , Fungos , Oligossacarídeos , Quitosana/química , Quitosana/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Fungos/efeitos dos fármacos , Humanos , Quitina/química , Quitina/farmacologia , Quitina/análogos & derivados , Testes de Sensibilidade MicrobianaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.
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Antifúngicos , Farmacorresistência Fúngica Múltipla , Testes de Sensibilidade Microbiana , Extratos Vegetais , Folhas de Planta , Antifúngicos/farmacologia , Antifúngicos/isolamento & purificação , Animais , Extratos Vegetais/farmacologia , Folhas de Planta/química , Candida auris/efeitos dos fármacos , Candida auris/isolamento & purificação , Fluconazol/farmacologia , Tenebrio , Sinergismo Farmacológico , Brasil , Candida/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacosRESUMO
The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Doenças Neuroinflamatórias , Disbiose/tratamento farmacológico , Antidepressivos/farmacologia , Inflamação/metabolismo , Anti-Inflamatórios/uso terapêuticoRESUMO
Aim: This study explores chia oil, rich in ω-3 fatty acids and nutraceutical components, as a potential remedy for diseases, especially those linked to inflammation and cancer. Methods/materials: A chia oil-based nanoemulsion, developed through single emulsification, underwent comprehensive analysis using various techniques. In vitro and in vivo assays, including macrophage polarization, nitrite and cytokine production, cellular uptake and biodistribution, were conducted to assess the anti-inflammatory efficacy. Results & conclusion: Results reveal that the chia nanoemulsion significantly inhibits inflammation, outperforming pure oil with twice the efficacy. Enhanced uptake by macrophage-like cells and substantial accumulation in key organs indicate its potential as an economical and effective anti-inflammatory nanodrug, addressing global economic and health impacts of inflammation-related diseases.
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Antibacterianos , Bactérias , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/genética , Humanos , Percepção de Quorum/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Infecções Bacterianas/microbiologia , Infecções Bacterianas/tratamento farmacológicoRESUMO
Antifungal infections are becoming a major concern to human health due to antimicrobial resistance. Echinocandins have been promising agents against resistant fungal infections, primarily caspofungin, which has a more effective mechanism of action than azoles and polyenes. However, fungi such as Cryptococcus neoformans appear to be inheritably resistant to these drugs, which is concerning due to the high clinical importance of C. neoformans. In this review, we review the history of C. neoformans and the treatments used to treat antifungals over the years, focusing on caspofungin, while highlighting the C. neoformans problem and possible explanations for its inherent resistance.
Caspofungin is a drug used to treat several types of fungal infections. Resistance to caspofungin is a huge problem, especially in those that are immunocompromised. It is important to understand the history of caspofungin discovery, its clinical applications and its mechanism of action, as well as if a new drug target could be used overcome resistance. This review may perform guide new studies combining caspofungin with other drugs and indicate new potential targets for caspofungin.
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Antifúngicos , Caspofungina , Criptococose , Cryptococcus neoformans , Farmacorresistência Fúngica , Caspofungina/uso terapêutico , Caspofungina/farmacologia , Cryptococcus neoformans/efeitos dos fármacos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Humanos , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Equinocandinas/uso terapêutico , Equinocandinas/farmacologia , Animais , Testes de Sensibilidade Microbiana , Lipopeptídeos/uso terapêutico , Lipopeptídeos/farmacologiaRESUMO
High infestations of epibiont ciliates on vertebrates or invertebrates are normally related to aquaculture tanks or similar environments, and the importance of this relationship in natural habitats is often disregarded. Here, we describe the first record of high infestation of ciliates on Aegla serrana in South America and conduct a brief morphological and phylogenetic characterization of these ciliates. Our findings confirm that cases of high infestation of ciliates on metazoans can indeed occur in natural environments.
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Anomuros , Cilióforos , Animais , Brasil , Filogenia , Cilióforos/genética , EcossistemaRESUMO
Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma. Fusion occurs when the ALK gene fuses with another gene, resulting in a chimeric protein with constitutive kinase activity and promoting oncogenesis. ALK mutations are less common but can also result in the activation of ALK signaling pathways. Targeted therapies for ALK variations in gastric adenocarcinoma have been developed, including ALK inhibitors that have shown promising results in pre-clinical studies. Future studies are needed to elucidate the ALK role in gastric cancer and to identify predictive biomarkers to improve patient selection for targeted therapy. Overall, ALK alterations are a relevant biomarker for gastric adenocarcinoma treatment and targeted therapies for ALK may improve patients' overall survival.
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Quinase do Linfoma Anaplásico , Terapia de Alvo Molecular , Mutação , Inibidores de Proteínas Quinases , Neoplasias Gástricas , Humanos , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Terapia de Alvo Molecular/métodos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Rearranjo Gênico , Transdução de Sinais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
BACKGROUND: Transcriptomics has been used to evaluate immune responses during malaria in diverse cohorts worldwide. However, the high heterogeneity of cohorts and poor generalization of transcriptional signatures reported in each study limit their potential clinical applications. METHODS: We compiled 28 public data sets containing 1556 whole-blood or peripheral blood mononuclear cell transcriptome samples. We estimated effect sizes with Hedge's g value and the DerSimonian-Laird random-effects model for meta-analyses of uncomplicated malaria. Random forest models identified gene signatures that discriminate malaria from bacterial infections or malaria severity. Parasitological, hematological, immunological, and metabolomics data were used for validation. RESULTS: We identified 3 gene signatures: the uncomplicated Malaria Meta-Signature, which discriminates Plasmodium falciparum malaria from uninfected controls; the Malaria or Bacteria Signature, which distinguishes malaria from sepsis and enteric fever; and the cerebral Malaria Meta-Signature, which characterizes individuals with cerebral malaria. These signatures correlate with clinical hallmark features of malaria. Blood transcription modules indicate immune regulation by glucocorticoids, whereas cell development and adhesion are associated with cerebral malaria. CONCLUSIONS: Transcriptional meta-signatures reflecting immune cell responses provide potential biomarkers for translational innovation and suggest critical roles for metabolic regulators of inflammation during malaria.
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Biomarcadores , Malária Falciparum , Plasmodium falciparum , Malária Falciparum/diagnóstico , Malária Falciparum/parasitologia , Humanos , Biomarcadores/sangue , Plasmodium falciparum/genética , Transcriptoma , Perfilação da Expressão Gênica , Malária Cerebral/diagnóstico , Malária Cerebral/genética , Malária Cerebral/sangue , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/imunologiaRESUMO
INTRODUCTION: Nanoceria is a well-known nanomaterial with various properties, including antioxidant, proangiogenic, and therapeutic effects. Despite its potential, there are still aspects that require further exploration, particularly its anti-inflammatory and antimicrobial activities. METHOD: The global demand for novel anti-inflammatory and antimicrobial drugs underscores the significance of understanding nanoceria in both contexts. In this study, we evaluated the effect of nanoceria on macrophage polarization to better understand its anti-inflammatory effects. Additionally, we investigated the mechanism of action of nanoceria against Cryptococcus neoformans (ATCC 32045), Candida parapsilosis (ATCC 22019), Candida krusei (ATCC 6258), and Candida albicans. RESULT: The results demonstrated that nanoceria can polarize macrophages toward an anti-inflammatory profile, revealing the cellular mechanisms involved in the anti-inflammatory response. Concerning the antimicrobial effect, it was observed that nanoceria have a more pronounced impact on Candida parapsilosis, leading to the formation of pronounced pores on the surface of this species. CONCLUSION: Finally, biochemical analysis revealed transitory alterations, mainly in liver enzymes. The data support the use of nanoceria as a potential anti-inflammatory and antimicrobial drug and elucidate some of the mechanisms involved, shedding light on the properties of this nanodrug.
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Resistance to antimicrobial drugs has been considered a public health problem. Likewise, the increasing resistance of cancer cells to drugs currently used in therapy has also become a problem. Therefore, the research and development of synthetic peptides bring a new perspective on the emergence of new drugs for treating this resistance since bioinformatics provides a means to optimize these molecules and save time and costs in research. Peptides have several mechanisms of action, such as forming pores on the cell membrane and inhibiting protein synthesis. Some studies report the use of antimicrobial peptides with the potential for action against cancer cells, suggesting a repositioning of antimicrobial peptides to fight back cancer resistance. There is an alteration in the microenvironment, making its net charge negative for the survival and growth of cancer cells. The changes in glycoproteins favor the membrane to have a more negative charge, favoring the interaction between the cells and the peptide, thus making possible the repositioning of these antimicrobial peptides against cancer. Here, we will discuss the mechanism of action, targets and effects of peptides, comparison between microbial and cancer cells, and proteomic changes caused by the interaction of peptides and cells.