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DENV infection outcomes depend on the host's variable expression of immune receptors and mediators, leading to either resolution or exacerbation. While the NS3 protein is known to induce robust immune responses, the specific impact of its protease region epitopes remains unclear. This study investigated the effect of recombinant NS3 protease region proteins from all four DENV serotypes on splenocyte activation in BALB/c mice (n = 5/group). Mice were immunized with each protein, and their splenocytes were subsequently stimulated with homologous antigens. We measured the expression of costimulatory molecules (CD28, CD80, CD86, CD152) by flow cytometry, along with IL-2 production, CD25 expression, and examined the antigen-specific activation of CD4 + and CD8 + T cells. Additionally, the expression of IL-1, IL-10, and TGF-ß1 in splenocytes from immunized animals was assessed. Apoptosis was evaluated using Annexin V/PI staining and DNA fragmentation analysis. Stimulation of splenocytes from immunized mice triggered apoptosis (phosphatidylserine exposure and caspase 3/7 activation) and increased costimulatory molecule expression, particularly CD152. Low IL-2 production and low CD25 expression, as well as sustained expression of the IL-10 gene. These results suggest that these molecules might be involved in mechanisms by which the NS3 protein contributes to viral persistence and disease pathogenesis.
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Apoptose , Antígeno CTLA-4 , Vírus da Dengue , Camundongos Endogâmicos BALB C , Baço , Proteínas não Estruturais Virais , Animais , Camundongos , Baço/imunologia , Baço/virologia , Vírus da Dengue/imunologia , Vírus da Dengue/genética , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Proteínas não Estruturais Virais/imunologia , Proteínas não Estruturais Virais/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/genética , Imunização , Dengue/imunologia , Dengue/virologia , Citocinas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologiaRESUMO
The 1-acyl thiourea family [R1C(O)NHC(S)NR2R3] exhibits the flexibility to incorporate a wide variety of substituents into their structure. The structural attributes of these compounds are intricately tied to the type and extent of substitution. In the case of 3-mono-substituted thioureas (R2=H), the conformational behavior is predominantly shaped by the presence of an intramolecular N-H â â â O=C hydrogen bond. This study delves into the structural consequences stemming from the inclusion of substituents possessing hydrogen-donor capabilities within four novel 1-acyl-3-mono-substituted thiourea derivatives. A comprehensive suite of analytical techniques, encompassing FTIR, Raman spectroscopy, multinuclear (1H and 13C) NMR spectroscopy, single-crystal X-ray diffraction, and supported by computational methods, notably NBO (Natural Bond Orbital) population analysis, Hirshfeld analysis, and QTAIM (Quantum Theory of Atoms in Molecules), was harnessed to scrutinize and characterize these compounds. In the crystalline state, these compounds exhibit an intricate interplay of intermolecular interactions, prominently featuring an expansive network of hydrogen bonds between the hydroxy (-OH) groups and the carbonyl and thiocarbonyl bonds within the 1-acyl thiourea fragment. Notably, the topological analysis underscores significant distinctions in the properties of the acyl thiourea fragment and the intramolecular >C=O â â â H-N bond when transitioning from the isolated molecule to the crystalline environment.
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Many of the fundamental molecules of life share extraordinary pigment-like optical properties in the long-wavelength UV-C spectral region. These include strong photon absorption and rapid (sub-pico-second) dissipation of the induced electronic excitation energy into heat through peaked conical intersections. These properties have been attributed to a "natural selection" of molecules resistant to the dangerous UV-C light incident on Earth's surface during the Archean. In contrast, the "thermodynamic dissipation theory for the origin of life" argues that, far from being detrimental, UV-C light was, in fact, the thermodynamic potential driving the dissipative structuring of life at its origin. The optical properties were thus the thermodynamic "design goals" of microscopic dissipative structuring of organic UV-C pigments, today known as the "fundamental molecules of life", from common precursors under this light. This "UV-C Pigment World" evolved towards greater solar photon dissipation through more complex dissipative structuring pathways, eventually producing visible pigments to dissipate less energetic, but higher intensity, visible photons up to wavelengths of the "red edge". The propagation and dispersal of organic pigments, catalyzed by animals, and their coupling with abiotic dissipative processes, such as the water cycle, culminated in the apex photon dissipative structure, today's biosphere.
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Residual lignocellulosic biomass (RLB) is a valuable resource that can help address environmental issues by serving as an alternative to fossil fuels and as a raw material for producing various value-added molecules. To gain a comprehensive understanding of the use of lignocellulosic waste in South America, a review was conducted over the last 4 years. The review focused on energy generation, biofuel production, obtaining platform molecules (such as ethanol, hydroxymethylfurfural, furfural, and levulinic acid), and other materials of interest. The review found that Brazil, Colombia, and Ecuador had the most RLB sources, with sugarcane, oil palm, and rice crop residues being the most prominent. In South America, RLB is used to produce biogas, syngas, hydrogen, bio-oil, biodiesel, torrefied biomass, pellets, and biomass briquettes. The most studied and produced value-added molecule was ethanol, followed by furfural, hydroxymethylfurfural, and levulinic acid. Other applications of interest that have been developed with RLB include obtaining activated carbon and nanomaterials. Significant progress has been made in South America in utilizing RLB, and some countries have been more proactive in regulating its use. However, there is still much to learn about the potential of RLB in each country. This review provides an updated perspective on the typification and valorization of residual biomass in South America and discusses the level of research and technology being applied in the region. This information can be helpful for future research on RLB in South America.
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Biocombustíveis , Biomassa , Lignina , Lignina/química , América do SulRESUMO
Reactive oxygen species (ROS) are essential signaling molecules that enable cells to respond rapidly to a range of stimuli. The ability of plants to recognize various stressors, incorporate a variety of environmental inputs, and initiate stress-response networks depends on ROS. Plants develop resilience and defensive systems as a result of these processes. Root hairs are central components of root biology since they increase the surface area of the root, anchor it in the soil, increase its ability to absorb water and nutrients, and foster interactions between microorganisms. In this review, we specifically focused on root hair cells and we highlighted the identification of ROS receptors, important new regulatory hubs that connect ROS production, transport, and signaling in the context of two hormonal pathways (auxin and ethylene) and under low temperature environmental input related to nutrients. As ROS play a crucial role in regulating cell elongation rates, root hairs are rapidly gaining traction as a very valuable single plant cell model for investigating ROS homeostasis and signaling. These promising findings might soon facilitate the development of plants and roots that are more resilient to environmental stressors.
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Raízes de Plantas , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/fisiologia , Transdução de SinaisRESUMO
Staphylococcus aureus is the etiologic agent of many nosocomial infections, and its biofilm is frequently isolated from medical devices. Moreover, the dissemination of multidrug-resistant (MDR) strains from this pathogen, such as methicillin-resistant S. aureus (MRSA) strains, is a worldwide public health issue. The inhibition of biofilm formation can be used as a strategy to weaken bacterial resistance. Taking that into account, we analysed the ability of marine sponge-associated bacteria to produce antibiofilm molecules, and we found that marine Priestia sp., isolated from marine sponge Scopalina sp. collected on the Brazilian coast, secretes proteins that impair biofilm development from S. aureus. Partially purified proteins (PPP) secreted after 24 hours of bacterial growth promoted a 92% biofilm mass reduction and 4.0 µg/dL was the minimum concentration to significantly inhibit biofilm formation. This reduction was visually confirmed by light microscopy and Scanning Electron Microscopy (SEM). Furthermore, biochemical assays showed that the antibiofilm activity of PPP was reduced by ethylenediaminetetraacetic acid (EDTA) and 1,10 phenanthroline (PHEN), while it was stimulated by zinc ions, suggesting an active metallopeptidase in PPP. This result agrees with mass spectrometry (MS) identification, which indicated the presence of a metallopeptidase from the M28 family. Additionally, whole-genome sequencing analysis of Priestia sp. shows that gene ywad, a metallopeptidase-encoding gene, was present. Therefore, the results presented herein indicate that PPP secreted by the marine Priestia sp. can be explored as a potential antibiofilm agent and help to treat chronic infections.
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Antibacterianos , Proteínas de Bactérias , Biofilmes , Staphylococcus aureus , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Antibacterianos/farmacologia , Animais , Testes de Sensibilidade Microbiana , Brasil , Poríferos/microbiologiaRESUMO
Even though molecules are fundamentally quantum entities, the concept of a molecule retains certain classical attributes concerning its constituents. This includes the empirical separability of a molecule into its three-dimensional, rigid structure in Euclidean space, a framework often obtained through experimental methods like X-Ray crystallography. In this work, we delve into the mathematical implications of partitioning a molecule into its constituent parts using the widely recognized Atoms-In-Molecules (AIM) schemes, aiming to establish their validity within the framework of Information Theory concepts. We have uncovered information-theoretical justifications for employing some of the most prevalent AIM schemes in the field of Chemistry, including Hirshfeld (stockholder partitioning), Bader's (topological dissection), and the quantum approach (Hilbert's space definition). In the first approach we have applied the generalized principle of minimum relative entropy derived from the Sharma-Mittal two-parameter functional, avoiding the need for an arbitrary selection of reference promolecular atoms. Within the ambit of topological-information partitioning, we have demonstrated that the Fisher information of Bader's atoms conform to a comprehensive theory based on the Principle of Extreme Physical Information avoiding the need of employing the Schwinger's principle, which has been proven to be problematic. For the quantum approach we have presented information-theoretic justifications for conducting Löwdin symmetric transformations on the density matrix to form atomic Hilbert spaces generating orthonormal atomic orbitals with maximum occupancy for a given wavefunction.
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The ability of an organism to respond to nutritional stress can be a plastic character under the action of natural selection, affecting several characteristics, including life history and energy storage. The genus Drosophila (Diptera; Drosophilidae) presents high variability regarding natural resource exploration. However, most works on this theme have studied the model species D. melanogaster Meigen, 1830 and little is known about Neotropical drosophilids. Here we evaluate the effects of three diets, with different carbohydrate-to-protein ratios, on life history (viability and development time) and metabolic pools (triglycerides, glycogen, and total soluble protein contents) of three Neotropical species of Drosophila: D. maculifrons Duda, 1927; D. ornatifrons Duda, 1927, both of the subgenus Drosophila Sturtevant, 1939, and D. willistoni Sturtevant, 1916 of the subgenus Sophophora Sturtevant, 1939. Our results showed that only D. willistoni was viable on all diets, D. maculifrons was not viable on the sugary diet, while D. ornatifrons was barely viable on this diet. The sugary diet increased the development time of D. willistoni and D. ornatifrons, and D. willistoni glycogen content. Thus, the viability of D. maculifrons and D. ornatifrons seems to depend on a certain amount of protein and/or a low concentration of carbohydrate in the diet. A more evident effect of the diets on triglyceride and protein pools was detected in D. ornatifrons, which could be related to the adult attraction to dung and carrion baited pitfall as food resource tested in nature. Our results demonstrated that the evolutionary history and differential adaptations to natural macronutrient resources are important to define the amplitude of response that a species can present when faced with dietary variation.
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Dieta , Drosophila , Características de História de Vida , Animais , Drosophila/fisiologia , Metabolismo Energético , Feminino , Masculino , Glicogênio/metabolismo , Proteínas Alimentares , Carboidratos da DietaRESUMO
BACKGROUND: Inflammation in adipose tissue, resulting from imbalanced caloric intake and energy expenditure, contributes to the metabolic dysregulation observed in obesity. The production of inflammatory cytokines, such as IL-1ß and IL-18, plays a key role in this process. While IL-1ß promotes insulin resistance and diabetes, IL-18 regulates energy expenditure and food intake. Previous studies have suggested that caspase-1, activated by the Nlrp3 inflammasome in response to lipid excess, mediates IL-1ß production, whereas activated by the Nlrp1b inflammasome in response to energy excess, mediates IL-18 production. However, this has not been formally tested. METHODS: Wild-type and caspase-1-deficient Balb/c mice, carrying the Nlrp1b1 allele, were fed with regular chow or a high-fat diet for twelve weeks. Food intake and mass gain were recorded weekly. At the end of the twelve weeks, glucose tolerance and insulin resistance were evaluated. Mature IL-18 protein levels and the inflammatory process in the adipose tissue were determined. Fasting lipid and cytokine levels were quantified in the sera of the different experimental groups. RESULTS: We found that IL-18 production in adipose tissue is independent of caspase-1 activity, regardless of the metabolic state, while Nlrp3-mediated IL-1ß production remains caspase-1 dependent. Additionally, caspase-1 null Balb/c mice did not develop metabolic abnormalities in response to energy excess from the high-fat diet. CONCLUSION: Our findings suggest that IL-18 production in the adipose tissue is independent of Nlrp3 inflammasome and caspase-1 activation, regardless of caloric food intake. In contrast, Nlrp3-mediated IL-1ß production is caspase-1 dependent. These results provide new insights into the mechanisms underlying cytokine production in the adipose tissue during both homeostatic conditions and metabolic stress, highlighting the distinct roles of caspase-1 and the Nlrp inflammasomes in regulating inflammatory responses.
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Tecido Adiposo , Caspase 1 , Caspases Iniciadoras , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Tecido Adiposo/metabolismo , Caspase 1/metabolismo , Caspases/metabolismo , Citocinas/metabolismo , Inflamassomos/metabolismo , Resistência à Insulina , Interleucina-18/metabolismo , Lipídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspases Iniciadoras/metabolismoRESUMO
The release of extracellular vesicles (EVs) has been implicated as an alternative transport mechanism for the passage of macromolecules through the fungal cell wall, a phenomenon widely reported in yeasts but poorly explored in mycelial cells. In the present work, we have purified and characterized the EVs released by mycelia of the emerging, opportunistic, widespread and multidrug-resistant filamentous fungus Scedosporium apiospermum. Transmission electron microscopy images and light scattering measurements revealed the fungal EVs, which were observed individually or grouped with heterogeneous morphology, size and electron density. The mean diameter of the EVs, evaluated by the light scattering technique, was 179.7 nm. Overall, the structural stability of S. apiospermum EVs was preserved during incubation under various storage conditions. The lipid, carbohydrate and protein contents were quantified, and the EVs' protein profile was evidenced by SDS-PAGE, revealing proteins with molecular masses ranging from 20 to 118 kDa. Through immunoblotting, ELISA and immunocytochemistry assays, antigenic molecules were evidenced in EVs using a polyclonal serum (called anti-secreted molecules) from a rabbit inoculated with conditioned cell-free supernatant obtained from S. apiospermum mycelial cells. By Western blotting, several antigenic proteins were identified. The ELISA assay confirmed that the anti-secreted molecules exhibited a positive reaction up to a serum dilution of 1:3200. Despite transporting immunogenic molecules, S. apiospermum EVs slightly induced an in vitro cytotoxicity effect after 48 h of contact with either macrophages or lung epithelial cells. Interestingly, the pretreatment of both mammalian cells with purified EVs significantly increased the association index with S. apiospermum conidia. Furthermore, EVs were highly toxic to Galleria mellonella, leading to larval death in a typically dose- and time-dependent manner. Collectively, the results represent the first report of detecting EVs in the S. apiospermum filamentous form, highlighting a possible implication in fungal pathogenesis.
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The objective of this work was to evaluate the combination of synthetic peptides based on the γ-core motif of defensin PvD1 with amphotericin B (AmB) at different concentrations against Candida albicans. We applied the checkerboard assay using different concentrations of the commercial drug AmB and the synthetic peptides γ31-45PvD1++ and γ33-41PvD1++ against C. albicans, aiming to find combinations with synergistic interactions. Between these two interactions involving γ31-45PvD1++ and AmB, an additive effect was observed. One such interaction occurred at concentrations of 0.009 µM of peptide γ31-45PvD1++ and 13.23 µM of AmB and another condition of 0.019 µM of peptide γ31-45PvD1++ and 6.61 µM of AmB. The other two concentrations of the interaction showed a synergistic effect in the combination of synthetic peptide γ31-45PvD1++ and AmB, where the concentrations were 1.40 µM peptide γ31-45PvD1++ and 0.004 µM AmB and 0.70 µM γ31-45PvD1++ peptide and 0.002 µM AmB. We proceeded with analysis of the mechanism of action involving synergistic effects. This examination unveiled a range of impactful outcomes, including the impairment of mitochondrial functionality, compromise of cell wall integrity, DNA degradation, and a consequential decline in cell viability. We also observed that both synergistic combinations were capable of causing damage to the plasma membrane and cell wall, causing leakage of intracellular components. This discovery demonstrates for the first time that the synergistic combinations found between the synthetic peptide γ31-45PvD1++ and AmB have an antifungal effect against C. albicans, acting on the integrity of the plasma membrane and cell wall.
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Anfotericina B , Candida albicans , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Peptídeos/farmacologia , Membrana Celular , Parede Celular , Testes de Sensibilidade MicrobianaRESUMO
Natural pigments have received special attention from the market and industry as they could overcome the harm to health and the environmental issues caused by synthetic pigments. These pigments are commonly extracted from a wide range of organisms, and when added to products they can alter/add new physical-chemical or biological properties to them. Fungi from extreme environments showed to be a promising source in the search for biomolecules with antimicrobial and antiparasitic potential. This study aimed to isolate fungi from Antarctic soils and screen them for pigment production with antimicrobial and antiparasitic potential, together with other previously isolated strains A total of 52 fungi were isolated from soils in front of the Collins Glacier (Southeast border). Also, 106 filamentous fungi previously isolated from the Collins Glacier (West border) were screened for extracellular pigment production. Five strains were able to produce extracellular pigments and were identified by ITS sequencing as Talaromyces cnidii, Pseudogymnoascus shaanxiensis and Pseudogymnoascus sp. All Pseudogymnoascus spp. (SC04.P3, SC3.P3, SC122.P3 and ACF093) extracts were able to inhibit S. aureus ATCC6538 and two (SC12.P3, SC32.P3) presented activity against Leishmania (L.) infantum, Leishmania amazonensis and Trypanossoma cruzii. Extracts compounds characterization by UPLC-ESI-QToF analysis confirmed the presence of molecules with biological activity such as: Asterric acid, Violaceol, Mollicellin, Psegynamide A, Diorcinol, Thailandolide A. In conclusion, this work showed the potential of Antartic fungal strains from Collins Glacier for bioactive molecules production with activity against Gram positive bacteria and parasitic protozoas.
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Antiparasitários , Pigmentos Biológicos , Regiões Antárticas , Pigmentos Biológicos/farmacologia , Pigmentos Biológicos/biossíntese , Antiparasitários/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Fungos/efeitos dos fármacos , Fungos/metabolismo , Fungos/classificação , Microbiologia do Solo , Bactérias/efeitos dos fármacos , Bactérias/classificação , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Testes de Sensibilidade Microbiana , Animais , Staphylococcus aureus/efeitos dos fármacosRESUMO
Contrary to the common but potentially misleading belief that when a protonated molecule is excited, it is its most stable protomer that will mandatorily dissociate, we demonstrate herein that, when rationalizing or predicting the chemistry of such ions, we should always search for the most labile protomer. This "most labile protomer" rule, based on the mobile proton model, states therefore that when a protonated molecule is heated, during ionization or by collisions for instance, the loosely bonded proton (H+ ) can acquire enough energy to detach itself from the most basic site of the molecule and then freely "walk through" the molecular framework to eventually find, if available, another protonation site, forming other less stable but more labile protomers, that is, protomers that may display lower dissociation thresholds. To demonstrate the validity of the "most labile protomer" rule as well as the misleading nature of the "most stable protomer" rule, we have selected several illustrative molecules and have collected their ESI(+)-MS/MS. To compare energies of precursors and products, we have also performed PM7 calculations and elaborated potential energy surface diagrams for their possible protomers and dissociation thresholds. We have also applied the "most labile protomer" rule to reinterpret-exclusively via classical charge-induced dissociation cleavages-several dissociation processes proposed for protonated molecules. In an accompanying letter, we have also applied a similar "most labile electromer" rule to ionized molecules.
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The advances in nanocomposites incorporating bioactive substances have the potential to transform the food packaging sector. Different nanofillers have been incorporated into polymeric matrixes to develop nanocomposite materials with improved mechanical, thermal, optical and barrier properties. Nanoclays, nanosilica, carbon nanotubes, nanocellulose, and chitosan/chitin nanoparticles have been successfully included into polymeric films, resulting in packaging materials with advanced characteristics. Nanostructured antimicrobial films have promising applications as active packaging in the food industry. Nanocomposite films containing antimicrobial substances such as essential oils, bacteriocins, antimicrobial enzymes, or metallic nanoparticles have been developed. These active nanocomposites are useful packaging materials to enhance food safety. Nanocomposites are promising materials for use in food packaging applications as practical and safe substitutes to the traditional packaging plastics.
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Treatment against visceral leishmaniasis (VL) presents problems, mainly related to drug toxicity, high cost and/or by emergence of resistant strains. In the present study, two vanillin synthetic derivatives, 3 s [4-(2-hydroxy-3-(4-octyl-1H-1,2,3-triazol-1-yl)propoxy)-3-methoxybenzaldehyde] and 3 t [4-(3-(4-decyl-1H-1,2,3-triazol-1-yl)-2-hydroxypropoxy)-3-methoxybenzaldehyde], were evaluated as therapeutic candidates in a murine model against Leishmania infantum infection. Molecules were used pure (3 s and 3 t) or incorporated into Poloxamer 407-based micelles (3 s/M and 3 t/M) in the infected animals, which also received amphotericin B (AmpB) or Ambisome® as control. Results showed that 3 s/M and 3 t/M compositions induced a Th1-type immune response in treated animals, with higher levels of IFN-γ, IL-2, TNF-α, IL-12, nitrite, and IgG2a antibodies. Animals presented also low toxicity and significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as compared as control groups mice, with the evaluations performed one and 30 days after the application of the therapeutics. In conclusion, preliminary data suggest that 3 s/M and 3 t/M could be considered for future studies as therapeutic agents against VL.
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Benzaldeídos , Leishmaniose Visceral , Leishmaniose , Camundongos , Animais , Micelas , Interleucina-12 , Camundongos Endogâmicos BALB CRESUMO
SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.
El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.
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Animais , Camundongos , Cicatrização/efeitos dos fármacos , Queimaduras/tratamento farmacológico , Naftoquinonas/administração & dosagem , Pele , Técnicas In Vitro , Naftoquinonas/farmacologia , Fosfatidilinositol 3-Quinases , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas Proto-Oncogênicas c-akt , Fibroblastos , Camundongos Endogâmicos C57BLRESUMO
While Alzheimer's disease (AD) diagnosis, management, and care have become priorities for healthcare providers and researcher's worldwide due to rapid population aging, epidemiologic surveillance efforts are currently limited by costly, invasive diagnostic procedures, particularly in low to middle income countries (LMIC). In recent years, wastewater-based epidemiology (WBE) has emerged as a promising tool for public health assessment through detection and quantification of specific biomarkers in wastewater, but applications for non-infectious diseases such as AD remain limited. This early review seeks to summarize AD-related biomarkers and urine and other peripheral biofluids and discuss their potential integration to WBE platforms to guide the first prospective efforts in the field. Promising results have been reported in clinical settings, indicating the potential of amyloid ß, tau, neural thread protein, long non-coding RNAs, oxidative stress markers and other dysregulated metabolites for AD diagnosis, but questions regarding their concentration and stability in wastewater and the correlation between clinical levels and sewage circulation must be addressed in future studies before comprehensive WBE systems can be developed.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides , Vigilância Epidemiológica Baseada em Águas Residuárias , Águas Residuárias , Estudos Prospectivos , BiomarcadoresRESUMO
Breast cancer remains a pressing public health issue primarily affecting women. Recent research has spotlighted bioactive peptides derived from laminin-111, implicated in breast tumor development. Remarkably, the sequences IKVAV, YIGSR, and KAFDITYVRLKF from the α1, ß1, and γ1 chains, respectively, have garnered significant attention. This study aims to assess the potential of these radiolabeled peptides as targeting agents for breast cancer. The three peptides were synthesized using the Fmoc strategy, purified via reversed-phase high-performance liquid chromatography (RP-HPLC), and characterized through mass spectrometry. Iodine-131 (131I) radiolabeling was performed using the chloramine T method, exhibiting high radiochemical yield and stability for [131I]I-YIKVAV and [131I]I-YIGSR. Conversely, [131I]I-KAFDITYVRLKF demonstrated low radiochemical yield and stability and was excluded from the biological studies. The lipophilicity of the compounds ranged from - 2.12 to - 1.10. Serum protein binding assay for [131I]I-YIKVAV and [131I]I-YIGSR reached â 48% and â 25%, respectively. Affinity for breast cancer cells was evaluated using MDA-MB-231 and MCF-7 tumor cell lines, indicating the affinity of the radiopeptides with these tumor cells. Ex vivo biodistribution profiles of the radiopeptides were assessed in the MDA-MB-231 breast tumor animal model, revealing tumor tissue accumulation, supported by a high tumor-to-contralateral muscle ratio and autoradiography. These results signify the effective penetration of YIKVAV and YIGSR into tumor tissue. Therefore, the synthesized α1 and ß1 peptide fragments exhibit favorable characteristics as potential breast cancer-targeting agents, promising future exploration as radiopharmaceuticals for breast cancer.
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Neoplasias da Mama , Animais , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Estudos Prospectivos , Distribuição Tecidual , Peptídeos/farmacologia , LamininaRESUMO
The Amazon biome is home to many scorpion species, with around two hundred identified in the region. Of these, forty-eight species have been reported in Brazil so far and six of them are of medical importance: Tityus apiacas, T. metuendus, T. obscurus, T. raquelae, T. silvestris, and T. strandi. Three non-medically important species have also been studied: Opisthanthuscayaporum, Brotheas amazonicus and Rhopalurus laticauda. The venom of the scorpion T. obscurus is the most studied, followed by O. cayaporum. We aim to update the study of these Amazonian scorpion species. We will explore the harmful and beneficial properties of scorpion venom toxins and how they could be applied in drug development. This systematic review will focus on collecting and analyzing venoms from scorpions in Brazil. Only papers on Amazonian scorpion venom studies published between 2001 and 2021 (scientific articles, theses, and dissertations) were selected, based on the lists of scorpions available in the literature. Species found in the Amazon but not confirmed to be Brazilian were omitted from the review. Theses and dissertations were chosen over their derived articles. We found 42 eligible studies (13 theses, 27 articles and 2 patents) out of 17,950 studies and a basic statistical analysis was performed. The literature showed that T. obscurus was the most studied venom with 28 publications, followed by O. cayaporum with seven articles, B. amazonicus with four articles, T. metuendus with two article and R. laticauda with one article. No publication on the characterization of T. silvestris and T. apiacas venoms were found during the reviewed period, only the clinical aspects were covered. There is still much to be explored despite the increasing number of studies conducted in recent years. Amazonian scorpions have promising potential for pharmaceutical and clinical applications.
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The present study explores the potential of rhizobacteria isolated from Baccharis linearis and Solidago chilensis in metal(loid)-contaminated soil for producing N-acyl-homoserine lactones (AHLs)-type signal molecules and promoting plant growth. A total of 42 strains were isolated, four demonstrating the production of AHL-type signal molecules. Based on 16S rRNA gene sequencing analyses and MALDI-TOF analyses, these four isolates were identified as belonging to the Pseudomonas genus, specifically P. brassicacearum, P. frederickberguensis, P. koreensis, and P. orientalis. The four AHL-producing strains were evaluated for metal(loid)s tolerance, their plant growth promotion traits, AHL quantification, and their impact on in vitro Lactuca sativa plant growth. The study found that four strains exhibited high tolerance to metal(loid)s, particularly As, Cu, and Zn. Additionally, plant growth-promoting traits were detected in AHL-producing bacteria, such as siderophore production, ammonia production, ACC deaminase activity, and P solubilization. Notably, AHL production varied among strains isolated from B. linearis, where C7-HSL and C9-HSL signal molecules were detected, and S. chilensis, where only C7-HSL signal molecules were observed. In the presence of copper, the production of C7-HSL and C9-HSL significantly decreased in B. linearis isolates, while in S. chilensis isolates, C7-HSL production was inhibited. Further, when these strains were inoculated on lettuce seeds and in vitro plants, a significant increase in germination and plant growth was observed. Mainly, the inoculation of P. brassicacearum and P. frederickberguensis led to extensive root hair development, significantly increasing length and root dry weight. Our results demonstrate that rhizospheric strains produce AHL molecules and stimulate plant growth, primarily through root development. However, the presence of copper reduces the production of these molecules, potentially affecting the root development of non-metalloid tolerant plants such as S. chilensis, which would explain its low population in this hostile environment.