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During the 20th century, thousands of tons of munitions containing organoarsenic chemical warfare agents (CWAs) were dumped into oceans, seas and inland waters around the world. As a result, organoarsenic CWAs continue to leak from corroding munitions into sediments and their environmental concentrations are expected to peak over the next few decades. There remains, however, a lack of knowledge about their potential toxicity to aquatic vertebrates, such as fish. The aim of this study was to fill in this gap in research, by investigating the acute toxicity of organoarsenic CWAs on fish embryos, using the model species, Danio rerio. To estimate the acute toxicity thresholds of organoarsenic CWAs (Clark I, Adamsite, PDCA), a CWA-related compound (TPA), as well as four organoarsenic CWA degradation products (Clark I[ox], Adamsite[ox], PDCA[ox], TPA[ox]), standardized tests were performed following the OECD no. 236 Fish Embryo Acute Toxicity Test guidelines. Additionally, the detoxification response in D. rerio embryos was investigated by analysing the mRNA expression of five genes encoding antioxidant enzymes (CAT, SOD, GPx, GR and GST). During the 96 h of exposure, organoarsenic CWAs induced lethal effects in D. rerio embryos at very low concentrations (classified as 1st category pollutants according to GHS categorization), and were therefore deemed to be serious environmental hazards. Although TPA and the four CWA degradation products caused no acute toxicity even at their maximum solubility, the transcription of antioxidant-related genes was altered upon exposure to these compounds, indicating the need for further testing for chronic toxicity. Incorporating the results of this study into ecological risk assessments will provide a more accurate prediction of the environmental hazards posed by CWA-related organoarsenicals.
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The present study investigated the antioxidant potential of aqueous methanolic extracts of Hemidesmus indicus (L.) R.Br., followed by a pharmacoinformatics-based screening of novel Keap1 protein inhibitors. Initially, the antioxidant potential of this plant extract was assessed via antioxidant assays (DPPH, ABTS radical scavenging, and FRAP). Furthermore, 69 phytocompounds in total were derived from this plant using the IMPPAT database, and their three-dimensional structures were obtained from the PubChem database. The chosen 69 phytocompounds were docked against the Kelch-Neh2 complex protein (PDB entry ID: 2flu, resolution 1.50 Å) along with the standard drug (CPUY192018). H. indicus (L.) R.Br. extract (100 µg × mL-1) showed 85 ± 2.917%, 78.783 ± 0.24% of DPPH, ABTS radicals scavenging activity, and 161 ± 4 µg × mol (Fe (II)) g-1 ferric ion reducing power. The three top-scored hits, namely Hemidescine (-11.30 Kcal × mol-1), Beta-Amyrin (-10.00 Kcal × mol-1), and Quercetin (-9.80 Kcal × mol-1), were selected based on their binding affinities. MD simulation studies showed that all the protein-ligand complexes (Keap1-HEM, Keap1-BET, and Keap1-QUE) were highly stable during the entire simulation period, compared with the standard CPUY192018-Keap1 complex. Based on these findings, the three top-scored phytocompounds may be used as significant and safe Keap1 inhibitors, and could potentially be used for the treatment of oxidative-stress-induced health complications.
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Antioxidantes , Hemidesmus , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Hemidesmus/química , Hemidesmus/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Extratos Vegetais/químicaRESUMO
Streptococcus mutans, a gram-positive oral pathogen, is the primary causative agent of dental caries. Biofilm formation, a critical characteristic of S. mutans, is regulated by quorum sensing (QS). This study aimed to utilize pharmacoinformatics techniques to screen and identify effective phytochemicals that can target specific proteins involved in the quorum sensing pathway of S. mutans. A computational approach involving homology modeling, model validation, molecular docking, and molecular dynamics (MD) simulation was employed. The 3D structures of the quorum sensing target proteins, namely SecA, SMU1784c, OppC, YidC2, CiaR, SpaR, and LepC, were modeled using SWISS-MODEL and validated using a Ramachandran plot. Metabolites from Azadirachta indica (Neem), Morinda citrifolia (Noni), and Salvadora persica (Miswak) were docked against these proteins using AutoDockTools. MD simulations were conducted to assess stable interactions between the highest-scoring ligands and the target proteins. Additionally, the ADMET properties of the ligands were evaluated using SwissADME and pkCSM tools. The results demonstrated that campesterol, meliantrol, stigmasterol, isofucosterol, and ursolic acid exhibited the strongest binding affinity for CiaR, LepC, OppC, SpaR, and Yidc2, respectively. Furthermore, citrostadienol showed the highest binding affinity for both SMU1784c and SecA. Notably, specific amino acid residues, including ASP86, ARG182, ILE179, GLU143, ASP237, PRO101, and VAL84 from CiaR, LepC, OppC, SecA, SMU1784c, SpaR, and YidC2, respectively, exhibited significant interactions with their respective ligands. While the docking study indicated favorable binding energies, the MD simulations and ADMET studies underscored the substantial binding affinity and stability of the ligands with the target proteins. However, further in vitro studies are necessary to validate the efficacy of these top hits against S. mutans.
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Cárie Dentária , Percepção de Quorum , Humanos , Biofilmes , Streptococcus mutans , Simulação de Acoplamento Molecular , Ligantes , Cárie Dentária/tratamento farmacológicoRESUMO
Endophytic fungi are a diverse group of microorganisms that colonize the inter- or intracellular spaces of plants and exhibit mutual benefits. Their interactions with the host plant and other microbiomes are multidimensional and play a crucial role in the production of secondary metabolites. We screened bioactive compounds present in the extracts of Aspergillus flavus, an endophytic fungus isolated from the roots of the medicinal grass Cynodon dactylon, for its anticancer potential. An in vitro analysis of the Ethyl acetate extract from A. flavus showed significant cytostatic effects (IC50: 16.25 µg/mL) against breast cancer cells (MCF-7). A morphological analysis of the cells and a flow cytometry of the cells with annexin V/Propidium Iodide suggested that the extract induced apoptosis in the MCF-7 cells. The extract of A. flavus increased reactive oxygen species (ROS) generation and caused a loss of mitochondrial membrane potential in MCF-7 cells. To identify the metabolites that might be responsible for the anticancer effect, the extract was subjected to a gas chromatography-mass spectrometry (GC-MS) analysis. Interestingly, nine phytochemicals that induced cytotoxicity in the breast cancer cell line were found in the extract. The in silico molecular docking and molecular dynamics simulation studies revealed that two compounds, 2,4,7-trinitrofluorenone and 3α, 5 α-cyclo-ergosta-7,9(11), 22t-triene-6beta-ol exhibited significant binding affinities (-9.20, and -9.50 Kcal/mol, respectively) against Bcl-2, along with binding stability and intermolecular interactions of its ligand-Bcl-2 complexes. Overall, the study found that the endophytic A. flavus from C. dactylon contains plant-like bioactive compounds that have a promising effect in breast cancer.
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Antineoplásicos , Neoplasias da Mama , Humanos , Feminino , Aspergillus flavus/metabolismo , Cynodon/metabolismo , Neoplasias da Mama/tratamento farmacológico , Simulação de Acoplamento Molecular , Fungos/química , Antineoplásicos/químicaRESUMO
Plants and their derived molecules have been traditionally used to manage numerous pathological complications, including male erectile dysfunction (ED). Mimosa pudica Linn. commonly referred to as the touch-me-not plant, and its extract are important sources of new lead molecules in drug discovery research. The main goal of this study was to predict highly effective molecules from M. pudica Linn. for reaching and maintaining penile erection before and during sexual intercourse through in silico molecular docking and dynamics simulation tools. A total of 28 bioactive molecules were identified from this target plant through public repositories, and their chemical structures were drawn using Chemsketch software. Graph theoretical network principles were applied to identify the ideal target (phosphodiesterase type 5) and rebuild the network to visualize the responsible signaling genes, proteins, and enzymes. The 28 identified bioactive molecules were docked against the phosphodiesterase type 5 (PDE5) enzyme and compared with the standard PDE5 inhibitor (sildenafil). Pharmacokinetics (ADME), toxicity, and several physicochemical properties of bioactive molecules were assessed to confirm their drug-likeness property. Molecular dynamics (MD) simulation modeling was performed to investigate the stability of PDE5-ligand complexes. Four bioactive molecules (Bufadienolide (-12.30 kcal mol-1), Stigmasterol (-11.40 kcal mol-1), Isovitexin (-11.20 kcal mol-1), and Apigetrin (-11.20 kcal mol-1)) showed the top binding affinities with the PDE5 enzyme, much more powerful than the standard PDE5 inhibitor (-9.80 kcal mol-1). The four top binding bioactive molecules were further validated for a stable binding affinity with the PDE5 enzyme and conformation during the MD simulation period as compared to the apoprotein and standard PDE5 inhibitor complexes. Further, the four top binding bioactive molecules demonstrated significant drug-likeness characteristics with lower toxicity profiles. According to the findings, the four top binding molecules may be used as potent and safe PDE5 inhibitors and could potentially be used in the treatment of ED.
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Afrodisíacos , Disfunção Erétil , Mimosa , Afrodisíacos/uso terapêutico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores da Fosfodiesterase 5/químicaRESUMO
Lower doses of capsaicin (8-methyl-N-vanillyl-6-nonenamide) have the potential to serve as an anticancer drug, however, due to its pungency, irritant effect, poor water solubility and high distribution volume often linked to various off-target effects, its therapeutic use is limited. This study aimed to determine the biodistribution and anticancer efficacy of capsaicin loaded solid lipid nanoparticles (SLNs) in human hepatocellular carcinoma in vitro. In this study, SLNs of stearic acid loaded with capsaicin was formulated by the solvent evaporation-emulsification technique and were instantly characterized for their encapsulation efficiency, morphology, loading capacity, stability, particle size, charge and in vitro drug release profile. Synthesized SLNs were predominantly spherical, 80 nm diameter particles that proved to be biocompatible with good stability in aqueous conditions. In vivo biodistribution studies of the formulated SLNs showed that 48 h after injection in the lateral tail vein, up to 15% of the cells in the liver, 1.04% of the cells in the spleen, 3.05% of the cells in the kidneys, 3.76% of the cells in the heart, 1.31% of the cells in the lungs and 0% of the cells in the brain of rats were determined. Molecular docking studies against the identified targets in HepG2 cells showed that the capsaicin is able to bind Abelson tyrosine-protein kinase, c-Src kinase, p38 MAP kinase and VEGF-receptor. Molecular dynamic simulation showed that capsaicin-VEGF receptor complex is highly stable at 50 nano seconds. The IC50 of capsaicin loaded SLNs in HepG2 cells in vitro was 21.36 µg × ml-1. These findings suggest that capsaicin loaded SLNs are stable in circulation for a period up to 3 d, providing a controlled release of loaded capsaicin and enhanced anticancer activity.
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Antineoplásicos/farmacologia , Capsaicina/farmacologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Proteína Tirosina Quinase CSK/metabolismo , Capsaicina/síntese química , Capsaicina/farmacocinética , Carcinoma Hepatocelular/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Lipídeos , Neoplasias Hepáticas/tratamento farmacológico , Modelos Moleculares , Simulação de Dinâmica Molecular , Nanopartículas , Tamanho da Partícula , Proteínas Proto-Oncogênicas c-abl/metabolismo , Ratos , Receptores de Fatores de Crescimento do Endotélio Vascular/química , Solubilidade , Distribuição Tecidual , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 µg ml-1 IC50 value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.
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Flavonoides/farmacologia , Receptores de Folato com Âncoras de GPI/metabolismo , Ácido Fólico/química , Soroalbumina Bovina/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Flavonoides/química , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Estrutura Molecular , Terapia de Alvo Molecular , NanopartículasRESUMO
When prey are scarce, planktivorous fish and other predators feeding on tiny prey should forage within prey-rich patches to attain a net food intake above the ambient mean food concentrations. If they can indeed locate prey-rich patches efficiently, then a patchy distribution of planktonic prey should lead to: (1) an increase in the overall per capita food intake, and (2) greater variability among predators in prey-capture rate due to differences in arrival times. Both phenomena were observed in 34 daily feeding sessions with a cohort of juvenile rudd held in twin experimental systems, each housing the same number of fish free to move in a loop of ten interconnected 200-L tanks. The fish were fed daily with equal numbers of planktonic prey (Artemia nauplii), offered either in a homogeneous or patchy distribution. To simulate low and high temperatures that represent potential global warming scenarios, the feeding protocol was replicated at 16, 21 and 26 °C, on each occasion following a 3-day period of fish acclimation. Up to 40-70 % of fish in the system with the patchy prey distribution assembled rapidly in the high-prey-density tank, the capture rate of first arrivals being up to 60 prey min(-1) at 26 °C, orders of magnitude greater than that of latecomers. The overall capture rates were higher in the system with patchy prey, regardless of the temperature. At the highest temperature (26 °C), the fish located the high-prey-density tank in less than half the time taken at the lowest temperature (16 °C, Q(10) > 2).
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Ingestão de Alimentos/fisiologia , Peixes/fisiologia , Temperatura Alta , Distribuição Animal , Animais , Artemia/fisiologia , Temperatura Baixa , Aquecimento Global , Plâncton/fisiologia , Comportamento PredatórioRESUMO
In this study, we investigated the combined effects of hypoxia and NPs on the water flea Daphnia magna, a keystone species in freshwater environments. To measure and understand the oxidative stress responses, we used acute toxicity tests, fluorescence microscopy, enzymatic assays, Western blot analyses, and Ingenuity Pathway Analysis. Our findings demonstrate that hypoxia and NPs exhibit a negative synergy that increases oxidative stress, as indicated by heightened levels of reactive oxygen species and antioxidant enzyme activity. These effects lead to more severe reproductive and growth impairments in D. magna compared to a single-stressor exposure. In this work, molecular investigations revealed complex pathway activations involving HIF-1α, NF-κB, and mitogen-activated protein kinase, illustrating the intricate molecular dynamics that can occur in combined stress conditions. The results underscore the amplified physiological impacts of combined environmental stressors and highlight the need for integrated strategies in the management of aquatic ecosystems.
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Daphnia magna , Estresse Oxidativo , Poluentes Químicos da Água , Animais , Daphnia magna/efeitos dos fármacos , Daphnia magna/fisiologia , Hipóxia , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidadeRESUMO
In this study, we investigated the acute toxicity, in vivo effects, oxidative stress, and gene expression changes caused by hypoxia on the brackish water flea Diaphanosoma celebensis. The no-observed-effect concentration (NOEC) of 48 h of hypoxia exposure was found to be 2 mg/L O2. Chronic exposure to NOEC caused a significant decline in lifespan but had no effect on total fecundity. The induction of reactive oxygen species increased in a time-dependent manner over 48 h, whereas the content of antioxidant enzymes (superoxide dismutase and catalase) decreased. The transcription and translation levels were modulated by hypoxia exposure. In particular, a significant increase in hemoglobin level was followed by up-regulation of hypoxia-inducible factor 1α gene expression and activation of the mitogen-activated protein kinase pathway. In conclusion, our findings provide a better understanding of the molecular mechanism of the adverse effects of hypoxia in brackish water zooplankton.
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Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Cladocera/efeitos dos fármacos , Cladocera/fisiologia , Hipóxia , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Oxigênio/metabolismo , Águas SalinasRESUMO
Heavy metals (HMs) and metalloid occur naturally and are found throughout the Earth's crust but they are discharged into aquatic environments at high concentrations by human activities, increasing heavy metal pollution. HMs can bioaccumulate in higher organisms through the food web and consequently affect humans. In an aquatic environment, various HMs mixtures can be present. Furthermore, HMs adsorb on other environmental pollutants, such as microplastics and persistent organic pollutants, causing a synergistic or antagonistic effect on aquatic organisms. Therefore, to understand the biological and physiological effects of HMs on aquatic organisms, it is important to evaluate the effects of exposure to combinations of complex HM mixtures and/or pollutants and other environmental factors. Aquatic invertebrates occupy an important niche in the aquatic food chain as the main energy link between higher and lower organisms. The distribution of heavy metals and the resulting toxic effects in aquatic invertebrates have been extensively studied, but few reports have dealt with the relationship between HMs, pollutants, and environmental factors in biological systems with regard to biological availability and toxicity. This review describes the overall properties of individual HM and their effects on aquatic invertebrates and comprehensively reviews physiological and biochemical endpoints in aquatic invertebrates depending on interactions among HMs, other pollutants, and environmental factors.
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Poluentes Ambientais , Metaloides , Metais Pesados , Poluentes Químicos da Água , Animais , Humanos , Metaloides/toxicidade , Plásticos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Metais Pesados/análise , Invertebrados , Organismos AquáticosRESUMO
Hematological malignancies are a heterogeneous group of neoplasms in the blood characterized by dysregulated hematopoiesis and classified as leukemia, lymphoma, and myeloma. The occurrence and progression of hematological malignancies depend on transformed hematopoietic stem cells, which refract to chemotherapy and often cause relapse. In recent years, monoclonal antibody therapies are preferred for hematopoietic cancers, owing to their inherent mechanisms of action and improved outcomes. However, efficient drug delivery methods and the establishment of novel biomarkers are currently being investigated and warranted to improve the outcome of patients with hematological malignancies. For instance, non-viral-mediated, natural carriers have been suggested for latent intracellular drug delivery. In this purview, repurposing small vesicles (e.g., exosomes) is considered a latent approach for myeloma therapy. Exosomes (nano-vesicles) have many advantages in that they are secreted by various animals and plants and become sought after for therapeutic and diagnostic purposes. The size of the cellular membrane of exosomes (30-150 nm) facilitates ligand binding and targeted delivery of the loaded molecules. Furthermore, exosomes can be modified to express specific target moiety on their cell membrane and can also be featured with desired biological activity, thereby potentially employed for various convoluted diseases, including hematological malignancies. To advance the current knowledge, this review is focused on the source, composition, function and surface engineering of exosomes pertaining to hematological malignancies.
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Exossomos , Neoplasias Hematológicas , Linfoma , Mieloma Múltiplo , Animais , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/metabolismo , Neoplasias Hematológicas/terapia , Biomarcadores/metabolismoRESUMO
Global deoxygenation in aquatic systems is an increasing environmental problem, and substantial oxygen loss has been reported. Aquatic animals have been continuously exposed to hypoxic environments, so-called "dead zones," in which severe die-offs among organisms are driven by low-oxygen events. Multiple studies of hypoxia exposure have focused on in vivo endpoints, metabolism, oxidative stress, and immune responses in aquatic invertebrates such as molluscs, crustaceans, echinoderms, and cnidarians. They have shown that acute and chronic exposure to hypoxia induces significant decreases in locomotion, respiration, feeding, growth, and reproduction rates. Also, several studies have examined the molecular responses of aquatic invertebrates, such as anaerobic metabolism, reactive oxygen species induction, increased antioxidant enzymes, immune response mechanisms, regulation of hypoxia-inducible factor 1-alpha (HIF-1α) genes, and differently expressed hemoglobin/hemocyanin. The genetic basis of those molecular responses involves HIF-1α pathway genes, which are highly expressed in hypoxic conditions. However, the identification of HIF-1α-related genes and understanding of their applications in some aquatic invertebrates remain inadequate. Also, some species of crustaceans, rotifers, sponges, and ctenophores that lack HIF-1α are thought to have alternative defense mechanisms to cope with hypoxia, but those factors are still unclear. This review covers the formation of hypoxia in aquatic environments and the various adverse effects of hypoxia on aquatic invertebrates. The limitations of current hypoxia research and genetic information about the HIF-1α pathway are also discussed. Finally, this paper explains the underlying processes of the hypoxia response and presents an integrated program for research about the molecular mechanisms of hypoxic stresses in aquatic invertebrates.
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Male sexual dysfunction is considered one of the major consequences of diabetes mellitus. The medicinal plant, Mimosa pudica Linn. is believed to have numerous therapeutic effects, including anti-diabetic, anti-obesity, aphrodisiac, and a sexual behaviour-enhancing properties. In the present study, the significant effect of ethanolic extract of M. pudica L. to scavenge excessive free radicals and alleviate the deleterious effects of alloxan-induced diabetes on the male sexual system of rats was demonstrated. The rats treated with the M. pudica L. extract recovered their body weight, the weight of their reproductive organs, the characteristics of the sperm and the histocellular arrangement of the testes. In addition, significant levels of hormones (testosterone, follicle-stimulating hormone and luteinising hormone) increased in both serum and testicular homogenates of male diabetic rats treated with M. pudica L. extract. Further, antioxidant enzymes, SOD, CAT, GSH, and GPx levels are increased, and oxidative stress markers MDA and ROS are reduced in both serum and testicular homogenates of M. pudica L. extract treated male rats. Furthermore, an in silico molecular docking study was performed to predict high potential compounds of M. pudica L. extract against the PDE5 receptor. Two bioactive compounds, namely 3-Dibenzofuranamine (-11.1 kcal × mol-1), Stigmasta-7,16-dien-3-ol (-10.4 kcal × mol-1) showed the highest binding affinities with PDE5 enzyme, much higher than the reference drug sildenafil (-9.9 kcal × mol-1). According to these findings, bioactive compounds rich in ethanolic extract of M. pudica L. have significant aphrodisiac performance in diabetic rats.Communicated by Ramaswamy H. Sarma.
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Because nanoplastics (NPs) can transport pollutants, the absorption of surrounding pollutants into NPs and their effects are important environmental issues. This study shows a combined effect of high concentrations of NPs and copper (Cu) in the marine rotifer Brachionus plicatilis. Co-exposure decreased the growth rate, reproduction, and lifespan. The highest level of NP ingestion was detected in the co-treated group, but the Cu concentration was higher in the Cu single-exposure group. ERK activation played a key role in the downstream cell signaling pathway activated by the interaction of NPs and Cu. The increased sensitivity of B. plicatilis to Cu could be due to the impairment of MXR function caused by a high concentration of NPs, which supports our in vivo experiment results. Our results show that exposure to NPs could induce the dysfunction of several critical molecular responses, weakening resistance to Cu and thereby increasing its physiological toxicity in B. plicatilis.
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Poluentes Ambientais , Rotíferos , Poluentes Químicos da Água , Animais , Cobre/toxicidade , Microplásticos , Poluentes Químicos da Água/toxicidadeRESUMO
Numerous studies have revealed that artificial light at night alters the natural patterns of light in space and time and may have various ecological impacts at different ecological levels. However, only a few studies have assessed its effect on interactions between organisms in aquatic environments, including predator-prey interactions in lakes. To fill this gap, we performed a preliminary enclosure experiment in which we compared the foraging effect of juvenile perch (Perca fluviatilis) on a natural lake zooplankton community in the absence and presence of light of high-pressure sodium (HPS) lamps mimicking artificial light emitted by a boat. The results revealed that even short-lasting exposure to HPS lamps may result in increasing fish predation, which in turn decreased the mean body size in zooplankton populations (e.g. Bosmina thersites) and affected the relative proportion between different taxa in zooplankton communities.
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Microplastic pollution is currently one of the most intensely studied ecological issues. Numerous studies have estimated the distribution and concentration of microplastics in various environments and determine how they affect their inhabitants. Much less effort has been place on assessing the possible effects of microplastics on interactions between organisms, including interspecific competition. Our aim was to test the hypothesis that the presence of microplastics affects the proportion of individuals of coexisting species and the elimination rate of the inferior competitor. The hypothesis was tested in competitive experiments done in the absence and presence of spherical non-biodegradable polystyrene and polyethylene and biodegradable polyhydroxybutyrate in environmentally relevant densities. In each of the experiments, we used three different pairs of closely related planktonic species of the genus Daphnia composed of the superior and inferior competitor: D. pulex and D. magna, D. magna and D. galeata, D. pulex and D. galeata. The results support our hypothesis and demonstrate each microplastic type had a different effect on the density of the competing species. The presence of polystyrene and polyethylene lowered the density of the superior competitor in each of the three pairs, at least partially due to a reduction in the number of gravid females, but not their fecundity. The presence of the polyhydroxybutyrate, in turn, increased the population density of D. magna in the variants with each of the two remaining species. Moreover, the presence of microplastics affected the elimination rate of the inferior competitor, i.e. polystyrene expedited the exclusion of D. magna by D. pulex, and polyhydroxybutyrate hampered the exclusion of D. magna by D. pulex. Our results suggest that long-term exposure to environmentally relevant densities of both non-biodegradable and biodegradable microplastics may affect the relative abundance of co-occurring species in zooplankton communities, and thus the functioning of aquatic ecosystems.
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Microplásticos , Poluentes Químicos da Água , Animais , Daphnia , Ecologia , Ecossistema , Plásticos/toxicidade , Polietilenos/farmacologia , Poliestirenos/farmacologia , Poluentes Químicos da Água/análiseRESUMO
Pseudomonas aeruginosa is an opportunistic pathogen that can cause acute and severe infections. Increasing resistance to antibiotics has given rise to the urgent need for an alternative antimicrobial agent. A promising strategy is the inhibition of iron sequestration in the bacteria. The current work aimed to screen for inhibitors of pyoverdine-mediated iron sequestration in P. aeruginosa. As a drug target, we choose l-ornithine-N5-monooxygenase (PvdA), an enzyme involved in the biosynthesis of pyoverdine that catalyzes the FAD-dependent hydroxylation of the side chain amine of ornithine. As drug repurposing is a fast and cost-efficient way of discovering new applications for known drugs, the approach may help to solve emerging clinical problems. In this study, we use data about molecules from drug banks for screening. A total of 15 drugs that are similar in structure to l-ornithine, the substrate of PvdA, and 30 drugs that are sub-structures of l-ornithine were virtually docked against PvdA. N-2-succinyl ornithine and cilazapril were found to be the top binders with a binding energy of -12.8 and -9.1 kcal mol-1, respectively. As the drug-likeness and ADME properties of the drugs were also found to be promising, molecular dynamics studies were performed to further confirm the stability of the complexes. The results of this in silico study indicate that N-2-succinyl ornithine could potentially be explored as a drug for the treatment of P. aeruginosa infections.
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Oxigenases de Função Mista , Infecções por Pseudomonas , Reposicionamento de Medicamentos , Humanos , Ferro/metabolismo , Oxigenases de Função Mista/metabolismo , Ornitina/metabolismo , Pseudomonas aeruginosa/metabolismoRESUMO
Several hundred thousand tonnes of munitions containing chemical warfare agents (CWAs) are lying on the seafloor worldwide. CWAs have started leaking from corroded munitions, and their presence in the environment and in organisms inhabiting dump sites has been detected. The presence of CWAs in the water negatively affects fish, macrobenthos and free-living bacteria. It can be expected that the presence of CWAs would also affect the gut-associated bacteria in fish, which are vital for their condition. The main aim of this study was to test if the microbiota of cod collected in the Baltic Bornholm Deep (highly polluted with CWAs) is dysregulated. To investigate this, we conducted metagenomic studies based on 16S rRNA gene sequencing. We found that the microbiota of cod inhabiting the dump site was significantly less taxonomically diverse compared to those from a non-polluted reference site. Moreover, taxa associated with fish diseases (e.g., Vibrionaceae, Aeromonadaceae) were more prevalent, and probiotic taxa (e.g., Actinobacteriota, Rhodobacteraceae) were less frequent in the guts of individuals from the dump site, than those from the reference site. The differences in vulnerability of various bacterial taxa inhabiting cod gastrointestinal tracts to CWAs were hypothesised to be responsible for the observed microbiota dysregulation.
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The current study focuses on developing a tumour-targeted functionalised nanocarrier that wraps hollow mesoporous silica nanoparticles. The guanidine carbonate and curcumin are immobilised on the surface of 3-aminopropyl-triethoxy silane (APTES)-decorated hollow mesoporous silica nanoparticles (HMSNP), as confirmed through XPS and NMR analysis. XPS analysis demonstrates that the shape of the hysteresis loops is modified and that pore volume and pore diameter are consequently decreased compared to control. Guanidine (85%) and guanidine-curcumin complex (90%) were successfully encapsulated in HMSNAP and showed a 90% effective and sustained release at pH 7.4 for up to 72 h. Acridine orange/ethidium bromide dual staining determined that GuC-HMNSAP induced more late apoptosis and necrosis at 48 and 72 h compared with Gu-HMNSAP-treated cells. Molecular investigation of guanidine-mediated apoptosis was analysed using western blotting. It was found that cleaved caspases, c-PARP, and GSK-3ß (Ser9) had increased activity in MCF-7 cells. GuC-HMSNAP increased the activity of phosphorylation of oncogenic proteins such as Akt (Ser473), c-Raf (Ser249), PDK1 (Ser241), PTEN (Ser380), and GSK-3ß (Ser9), thus inducing cell death in MCF-7 cells. Altogether, our findings confirm that GuC-HMNSAP induces cell death by precisely associating with tumour-suppressing proteins, which may lead to new therapeutic approaches for breast cancer therapy.