Vitamin D is a fat-soluble vitamin that plays a role not only in calcium homeostasis, but also in several other functions, including cell growth and immune functions, and is considered a ...neurosteroid. Vitamin D deficiency is highly prevalent worldwide and has been suggested to be associated with an increased risk of emotional disorders. Therefore, the association between vitamin D levels and psychophysiological disorders, such as depression, anxiety, and mood, has been investigated. To list these variables, a bibliographical literature research was conducted in the MEDLINE/PubMed, Web of Science, Scopus, Science Direct and PsycINFO databases, between November and December 2020, with no year limits of publication. The studies involved humans aged between 18 and 59 years without associated diseases. This review presents evidence of the main variables involved in this association, main tools used to verify these variables, and methods used to verify circulating vitamin D levels in populations. Most studies have indicated that the main psychophysiological variables involved with vitamin D levels are depression and anxiety followed by mood, and an association has been observed between increased serum vitamin D levels and reduction in symptoms of depression, anxiety, and mood, and there is a heterogeneity of methods for assessing vitamin D. More studies are clearly needed to improve our understanding of their role in modulating the psychophysiological aspects of vitamin D levels.
Eugenia uniflora is a plant native to Brazil that has a wide geographical distribution and produces a high content of essential oils. The aim of the present study was to investigate the larvicidal ...activity of the hydrolate (Eu-HYD), aqueous extract (Eu-AE), essential oil (Eu-EO), and major compounds obtained from E. uniflora leaves against Aedes aegypti as well as assess the effects on the digestive enzymes of the larvae. Eu-HYD and Eu-AE were obtained from the leaves as byproducts of the EO isolation by hydrodistillation. Selina-1,3,7(11)-trien-8-one (1, 57.55 %) and oxidoselina-1,3,7(11)-trien-8-one (2, 21.18 %) were the major chemical compounds in the EO, as determined by gas chromatography with flame ionization detection and gas chromatography coupled to mass spectrometry. Eu-EO exhibited the most promising larvicidal activity (LC50 = 35.9 ± 1.02 mg/L), followed by Eu-AE (LC50 = 12.205 ± 1.04 mg/L) and Eu-HYD (LC50 = 42.4 ± 1.02 mg/L), whereas compounds 1 and 2 had an LC50 of 77.8 ± 1.06 and 41.2 ± 1.06 mg/L, respectively. Moreover, Eu-EO, Eu-AE, and Eu-HYD inhibited α-amylase activity in the Ae. aegypti larvae. Docking studies on the altered enzymes indicated that the affinity of compound 2 for Ae. aegypti α-amylase is slightly higher than that of compound 1. These results suggest notable larvicidal activity for all products of Eugenia uniflora leaves, making such products bioactive candidates for interrupting the reproduction cycle of Ae. aegypti, which is the main vector of arboviruses.
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•Seline and seline epoxide exhibited notable larvicidal activity against Aedes aegypti.•Aqueous extract, oil and hydrolate showed larvicidal activity against Aedes aegypti.•Oil, aqueous extract and hydrolate inhibited amylase activity of the larval intestine.•Seline epoxide presents significant interactions with α-amylase residues.
The Wnt/β-catenin signaling pathway is associated with the regulation of cancer stem cells, and it can be driven by epigenetic modifications. Here, we aim to identify epigenetic modifications ...involved in the control of the Wnt/β-catenin signaling and investigate the role of this pathway in the accumulation of cancer stem cells (CSC) and chemoresistance of Head and Neck Squamous Cell Carcinoma (HNSCC). Quantitative-PCR, western blot, shRNA assay, viability assay, flow cytometry assay, spheres formation, xenograft model, and chromatin immunoprecipitation were employed to evaluate the Wnt/β-catenin pathway and EZH2 in wild-type and chemoresistant oral carcinoma cell lines, and in the populations of CSC and non-stem cells. We demonstrated that β-catenin and EZH2 were accumulated in cisplatin-resistant and CSC population. The upstream genes of the Wnt/β-catenin signaling (APC and GSK3β) were decreased, and the downstream gene MMP7 was increased in the chemoresistant cell lines. The inhibition of β-catenin and EZH2 combined effectively decreased the CSC population in vitro and reduced the tumor volume and CSC population in vivo. EZH2 inhibition increased APC and GSK3β, and the Wnt/β-catenin inhibition reduced MMP7 levels. In contrast, EZH2 overexpression decreased APC and GSK3β and increased MMP7. EZH2 and β-catenin inhibitors sensitized chemoresistant cells to cisplatin. EZH2 and H3K27me3 bounded the promoter of APC, leading to its repression. These results suggest that EZH2 regulates β-catenin by inhibiting the upstream gene APC contributing to the accumulation of cancer stem cells and chemoresistance. Moreover, the pharmacological inhibition of the Wnt/β-catenin combined with EZH2 can be an effective strategy for treating HNSCC.
•β-catenin and EZH2 were accumulated in HNSCC cisplatin-resistant and in cancer stem cells.•EZH2 and β-catenin inhibitors sensitized chemoresistant cells to cisplatin.•The combined inhibition of β-catenin and EZH2 reduced the tumor volume, and the cancer stem cells in vivo.•EZH2 directly binding to the promoter region of APC in chemoresistant cells and in cancer stem cells.
•Tablets containing a lectin-rich fraction of Moringa oleifera seeds were developed.•The composition of the fraction did not change when mixed with the components.•Tablets containing 10% and 15% ...fraction caused mortality of the larvae and eggs.•Tablets containing 15% fraction exert a repellent effect on oviposition.•The formulation developed showed potential for use in the control of this mosquito.
The measures currently used to minimize the spread of arboviruses, comprising dengue, Chikungunya, and Zika virus, involve controlling the size of population of the mosquito Aedes aegypti. However, the search for formulations containing new insecticides is gaining pace due to reports of mosquito populations showing resistance to commonly used compounds. In this study, tablets containing a protein fraction of Moringa oleifera seeds enriched in the WSMoL lectin, known to show larvicidal and ovicidal activities against A. aegypti, were developed. The compatibility between the fraction and the excipients used in obtaining the tablets was evaluated by thermogravimetry (TG), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) absorption spectroscopy. The larvicidal and ovicidal activities of the resulting tablets 5%, 10%, and 15% (w/w) of the fraction were evaluated, as well as their effect on mosquito oviposition. Assays were also performed using a placebo tablet. According to the TG, DSC, and FTIR results, the protein composition of the fraction did not change when mixed with the components of the formulation. Tablets containing 10% and 15% WSMoL-rich fraction caused mortality of 42.5% and 95% of the larvae after 48 h, respectively, with larvae incubated with these tablets showing reduced acetylcholinesterase activity. All tablets inhibited egg hatching after 72 h (36–74%), and tablets containing 15% fraction were found to exert a repellent effect on oviposition. Our results show that the formulation developed in this study interfered with the life cycle of A. aegypti, and thus show potential for use in the control of this mosquito.
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Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and ...neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization. Long-term potentiation (LTP) was decreased in the prefrontal cortex (PFC), but not in the CA1 hippocampus or amygdala. This was associated with a decreased density of sirtuin-1 in cerebrocortical synaptosomes and a decreased density of sirtuin-1 and sestrin-2 in total cerebrocortical extracts, without alterations of sirtuin-3 levels or of synaptic markers (syntaxin, synaptophysin, SNAP25, PSD95). However, activation of sirtuin-1 did not affect or recover PFC-LTP deficit in APP/PS1 female mice; instead, inhibition of sirtuin-1 increased PFC-LTP magnitude. It is concluded that mood and memory dysfunction in 9-month-old female APP/PS1 mice is associated with a parallel decrease in synaptic plasticity and in synaptic sirtuin-1 levels in the prefrontal cortex, although sirtiun1 activation failed to restore abnormal cortical plasticity.
•PgTeL is an antifungal agent against C. albicans and C. krusei.•The lectin caused energy collapse and oxidative stress in yeast cells.•Treatment with PgTeL led to damage of cell wall and rupture of ...yeast cells.•PgTeL showed antibiofilm effect on C. albicans at sub-inhibitory concentrations.•PgTeL effects can be linked to the bioactivities attributed to P. granatum fruit.
The pomegranate (Punica granatum) sarcotesta contains a chitin-binding lectin (PgTeL) with antibacterial activity against human pathogenic species. In this work, the structural stability of PgTeL was evaluated by fluorimetric analysis and the lectin was evaluated for cytotoxicity to human peripheral blood mononuclear cells (PBMCs) and antifungal activity against Candida albicans and Candida krusei. PgTeL folding was impaired when lectin was incubated at pH≥6.0. On the other hand, the lectin did not undergo unfolding even when heated at 100°C. PgTeL (1, 10, and 100μg/mL) was not cytotoxic to PBMCs. Antifungal activity was detected for C. albicans (MIC: 25μg/mL; MFC: 50μg/mL) and C. krusei (MIC and MFC of 12.5μg/mL). Treatment of yeast cells with PgTeL resulted in decrease of intracellular ATP content even at sub-inhibitory concentrations (½MIC and ¼MIC) and induced lipid peroxidation. In addition, PgTeL damaged the integrity of fungal cell wall of both species, with more pronounced effects in C. krusei. The lectin showed significant antibiofilm activity on C. albicans at sub-inhibitory concentrations (0.195 and 0.39μg/mL). In conclusion, PgTeL is an anti-Candida agent whose action mechanism involves oxidative stress, energetic collapse, damage to the cell wall and rupture of yeast cells.
Lectins are carbohydrate-binding proteins with several bioactivities, including antimicrobial properties.
Portulaca elatior
is a species found at Brazilian Caatinga and data on the biochemical ...composition of this plant are scarce. The present work describes the purification of
P. elatior
leaf lectin (PeLL) as well as the assessment of its antimicrobial activity and toxicity. PeLL, isolated by chromatography on a chitin column, had native liquid charge and subunit composition evaluated by electrophoresis. Hemagglutinating activity (HA) of PeLL was determined in the presence of carbohydrates or divalent cations, as well as after heating and incubation at different pH values. Changes in the lectin conformation were monitored by evaluating intrinsic tryptophan fluorescence and using the extrinsic probe bis-ANS. Antimicrobial activity was evaluated against
Pectobacterium
strains and
Candida
species
.
The minimal inhibitory (MIC), bactericidal (MBC), and fungicidal (MFC) concentrations were determined. Finally, PeLL was evaluated for in vitro hemolytic activity in human erythrocytes and in vivo acute toxicity in mice (5 and 10 mg/kg b.w
.
per os). PeLL (pI 5.4; 20 kDa) had its HA was inhibited by mannose, galactose, Ca
2+
, Mg
2+
, and Mn
2+
. PeLL HA was resistant to heating at 100 °C, although conformational changes were detected. PeLL was more active in the acidic pH range, in which no conformational changes were observed. The lectin presented MIC and MBC of 0.185 and 0.74 μg/mL for all
Pectobacterium
strains, respectively; MIC of 1.48 μg/mL for
C. albicans
,
C
.
tropicalis
, and
C. krusei
; MIC and MFC of 0.74 and 2.96 μg/mL for
C. parapsilosis
. No hemolytic activity or signs of acute toxicity were observed in the mice. In conclusion, a new, low-toxic, and thermostable lectin was isolated from
P. elatior
leaves, being the first plant compound to show antibacterial activity against
Pectobacterium
.
Schistosomiasis is a neglected disease that affects millions of people around the world, being common in the state of Maranhão. A total of 225 rodents of the Holochilus sciureus species from the ...Western Lowland Maranhão were studied, of which 144 animals (64%) exhibited Schistosoma eggs in their feces samples. Macroscopic lesions characterized as well-defined whitish areas on the liver and spleen surfaces were observed. Histopathological examination revealed multifocal granulomas in the esophagus, liver, spleen, pancreas and duodenum, with structures compatible with Schistosoma mansoni eggs, as well as severe hepatic micro-vacuolar degeneration, multifocal and coalescent, with proliferation of random bile ducts and associated epithelial hyperplasia to areas of fibrosis. Adult forms of the parasite were observed in the blood vessels of the portal space. The lungs exhibited moderate and diffuse interstitial pneumonia with intralesional S. mansoni eggs. In the kidneys, hyaline cylinders were observed in the pelvis and diffuse hemorrhage. In conclusion, H. sciureus displays a pathological picture similar to human being. This rodent plays a role as sentinel in Baixada Maranhense.
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