RESUMO
The cancer cell metabolism, notably characterized by the Warburg effect, has been the focus of intense investigation regarding the mechanisms of the uptake of glucose analogs, opening up perspectives for diagnosis and treatment of cancer disease. In this review, we delve into the ever-evolving landscape of cancer research, centering on fluorescent probes based on glucose analogs. These analogs, resulting from modifications in the carbohydrate structure with functional groups, have stood out as versatile molecules in applications ranging from disease comprehension to therapeutic innovation, especially when combined with fluorescent compounds. Fluorescence-based assays have provided valuable contributions to the revelation of complex biological mechanisms in life sciences. This review presents selected studies from about the past six years up to 2024 related to the use of glucose-based fluorescent probes for the investigation of their uptake profile as well as for therapeutic purposes. We believe that these investigations offer insights into the intricate interaction between glucose analogs and cancer cell metabolism, guiding future research and clinical applications in this field.
RESUMO
Lectins are proteins widely distributed among plants, animals and microorganisms that have the ability to recognize and interact with specific carbohydrates. They have varied biological activities, such as the inhibition of the progression of infections caused by fungi, bacteria, viruses and protozoa, which is related to the interaction of these proteins with the carbohydrates present in the cell walls of these microorganisms. Leishmaniasis are a group of endemic infectious diseases caused by protozoa of the genus Leishmania. In vitro and in vivo tests with promastigotes and amastigotes of Leishmania demonstrated that lectins have the ability to interact with glycoconjugates present on the cell surface of the parasite, it prevents their development through various mechanisms of action, such as the production of ROS and alteration of membrane integrity, and can also interact with defense cells present in the human body, thus showing that these molecules can be considered alternative pharmacological targets for the treatment of leishmaniasis. The objective of the present work is to carry out a bibliographic review on lectins with leishmanicidal activity, emphasizing the advances and perspectives of research in this theme. Through the analysis of the selected studies, we were able to conclude that lectins have great potential for inhibiting the development of leishmaniasis. However, there are still few studies on this subject.
Assuntos
Lectinas , Leishmania , Leishmaniose , Leishmania/efeitos dos fármacos , Humanos , Lectinas/farmacologia , Lectinas/química , Lectinas/metabolismo , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Animais , Antiprotozoários/farmacologia , Antiprotozoários/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
Antibiotic resistance is a pressing public health threat. Despite rising resistance, antibiotic development, especially for Gram-negative bacteria, has stagnated. As the traditional antibiotic research and development pipeline struggles to address this growing concern, alternative solutions become imperative. Synthetic molecular nanomachines (MNMs) are molecular structures that rotate unidirectionally in a controlled manner in response to a stimulus, such as light, resulting in a mechanical action that can propel molecules to drill into cell membranes, causing rapid cell death. Due to their broad destructive capabilities, clinical translation of MNMs remains challenging. Hence, here, we explore the ability of nonlethal visible-light-activated MNMs to potentiate conventional antibiotics against Gram-negative bacteria. Nonlethal MNMs enhanced the antibacterial activity of various classes of conventional antibiotics against Gram-negative bacteria, including those typically effective only against Gram-positive strains, reducing the antibiotic concentration required for bactericidal action. Our study also revealed that MNMs bind to the negatively charged phospholipids of the bacterial inner membrane, leading to permeabilization of the cell envelope and impairment of efflux pump activity following light activation of MNMs. The combined effects of MNMs on membrane permeability and efflux pumps resulted in increased antibiotic accumulation inside the cell, reversing antibiotic resistance and attenuating its development. These results identify nonlethal MNMs as pleiotropic antibiotic enhancers or adjuvants. The combination of MNMs with traditional antibiotics is a promising strategy against multidrug-resistant Gram-negative infections. This approach can reduce the amount of antibiotics needed and slow down antibiotic resistance development, thereby preserving the effectiveness of our current antibiotics.
Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla , Antibacterianos/metabolismo , Bactérias Gram-Negativas , Transporte Biológico , PermeabilidadeRESUMO
Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
Assuntos
Angiotensinas , Genoma , BetacoronavirusRESUMO
Many ant species displaying synanthropic behavior that have successfully dispersed in urban areas can cause problems in hospitals by acting as bacterial vectors. In this study, we encountered bacteria on ants collected at the Universidade Federal de Uberlândia hospital, in the campus and at households nearby. The ants were identified as Tapinoma melanocephalum (Fabricius) and Camponotus vittatus (Forel) (Hymenoptera: Formicidae) and the bacterial strains found here belong to the group of the coagulase-positive staphylococcus, coagulase-negative staphylococcus and gram negative bacilli, including antimicrobial drug-resistant strains. An investigation of the bacteria found in the ants and in the environment revealed that some ants carried non-isolated bacteria from the same environment and with high levels of resistance, evidencing the transmission potential of these insects.
Muitas espécies de formigas de comportamento sinantrópico que tiveram sucesso na dispersão em áreas urbanas podem causar problemas em hospitais ao atuarem como vetoras, transportando bactérias. Neste estudo, foram encontradas bactérias em formigas coletadas no Hospital de Clínicas da Universidade Federal de Uberlândia, no campus e em residências próximas. As formigas coletadas foram identificadas como Tapinoma melanocephalum (Fabricius) e Camponotus vittatus (Forel) (Hymenoptera: Formicidae) e as cepas bacterianas encontradas pertenciam ao grupo dos estafilococos coagulase positivos, estafilococos coagulase negativos e bacilos gram negativos, tendo sido encontradas cepas resistentes a antimicrobianos. O estudo de bactérias encontradas nas formigas e no ambiente mostrou que algumas formigas carreavam bactérias não isoladas do mesmo ambiente e com níveis de resistência mais elevados, evidenciando o potencial transmissor desses insetos.
Assuntos
Animais , Formigas/microbiologia , Bactérias/isolamento & purificação , Vetores de Doenças , Infecção Hospitalar/microbiologia , Saúde da População UrbanaRESUMO
Estudos transversais recentes mostraram alta prevalência de doenças crônicas e incapacidades físicas entre idosos. Considerando o rápido processo de envelhecimento do Brasil e as conseqüências que esse aumento de idosos com doenças crônicas e incapacidades associadas acarretará para o sistema de saúde, fazia-se necessário estudo que pudesse superar as limitaçöes dos dados transversais, permitindo determinar quais os fatores determinantes de uma vida longa e livre de doenças incapacitantes, o chamado envelhecimento bem sucedido. É apresentada a metodologia do primeiro estudo epidemiológico longitudinal com idosos residentes na comunidade, no Brasil. O perfil do cohorte inicial é comparado com dados de estudos anteriores a com o perfil dos näo respondentes para avaliar a validade de análises longitudinais futuras. O projeto EPIDOSO (Epidemiologia do Idoso) seguiu por dois anos 1.667 idosos (65+), residentes em Säo Paulo. Consistiu de duas ondas, cada qual com três inquéritos: domiciliar, clínico e laboratorial. O perfil da populaçäo näo diferiu de estudos anteriores, mostrando maioria de mulheres, viúvas, vivendo em domicílios multigeracionais, com uma alta prevalência de doenças crônicas, distúrbios psiquiátricos e incapacidades físicas. A despeito de todas as dificuldades inerentes a um estudo longitudinal, o grupo de näo-respondentes ao segundo inquérito domiciliar näo diferiu significativamente dos respondentes, assegurando análises longitudinais livres desse tipo de viés. Em relaçäo aos inquéritos clínico e laboratorial, os näo-respondentes mostraram-se mais velhos e mais incapacitados que os respondentes, limitando o uso dos dados clínicos e laboratoriais a análises pertinentes a uma cohorte mais jovem e saudável. Sexo, educaçäo, apoio familiar e nível socioeconômico näo influenciaram de forma significativa a taxa de näo-resposta, ao contrário do que se costuma verificar