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result(s) for
"Menezes, Regina"
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Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage
2023
Parkinson’s Disease (PD) is a common neurodegenerative disorder affecting millions of people worldwide for which there are only symptomatic therapies. Small molecules able to target key pathological processes in PD have emerged as interesting options for modifying disease progression. We have previously shown that a (poly)phenol-enriched fraction (PEF) of
Corema album
L. leaf extract modulates central events in PD pathogenesis, namely α-synuclein (αSyn) toxicity, aggregation and clearance. PEF was now subjected to a bio-guided fractionation with the aim of identifying the critical bioactive compound. We identified genipin, an iridoid, which relieves αSyn toxicity and aggregation. Furthermore, genipin promotes metabolic alterations and modulates lipid storage and endocytosis. Importantly, genipin was able to prevent the motor deficits caused by the overexpression of αSyn in a
Drosophila melanogaster
model of PD. These findings widens the possibility for the exploitation of genipin for PD therapeutics.
In this work, the authors identify Genipin as a small iridoid able to prevent alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage.
Journal Article
Polyphenols and Their Metabolites in Renal Diseases: An Overview
by
Ferreira-Pêgo, Cíntia
,
Costa, João G.
,
Guerreiro, Íris
in
Acids
,
acute kidney injury
,
Antioxidants
2022
Kidney diseases constitute a worldwide public health problem, contributing to morbidity and mortality. The present study aimed to provide an overview of the published data regarding the potential beneficial effects of polyphenols on major kidney diseases, namely acute kidney injury, chronic kidney disease, diabetic nephropathy, renal cancer, and drug-induced nephrotoxicity. This study consists of a bibliographical review including in vitro and in vivo studies dealing with the effects of individual compounds. An analysis of the polyphenol metabolome in human urine was also conducted to estimate those compounds that are most likely to be responsible for the kidney protective effects of polyphenols. The biological effects of polyphenols can be highly attributed to the modulation of specific signaling cascades including those involved in oxidative stress responses, anti-inflammation processes, and apoptosis. There is increasing evidence that polyphenols afford great potential in renal disease protection. However, this evidence (especially when in vitro studies are involved) should be considered with caution before its clinical translation, particularly due to the unfavorable pharmacokinetics and extensive metabolization that polyphenols undergo in the human body. Future research should consider polyphenols and their metabolites that indeed reach kidney tissues.
Journal Article
Small Molecule Fisetin Modulates Alpha–Synuclein Aggregation
by
Marques, Daniela
,
Fleming Outeiro, Tiago
,
Nunes dos Santos, Cláudia
in
alpha-Synuclein - metabolism
,
Analytical Chemistry
,
Apoptosis
2021
Phenolic compounds are thought to be important to prevent neurodegenerative diseases (ND). Parkinson’s Disease (PD) is a neurodegenerative disorder known for its typical motor features, the deposition of α-synuclein (αsyn)-positive inclusions in the brain, and for concomitant cellular pathologies that include oxidative stress and neuroinflammation. Neuroprotective activity of fisetin, a dietary flavonoid, was evaluated against main hallmarks of PD in relevant cellular models. At physiologically relevant concentrations, fisetin protected SH-SY5Y cells against oxidative stress overtaken by tert-butyl hydroperoxide (t-BHP) and against methyl-4-phenylpyridinuim (MPP+)-induced toxicity in dopaminergic neurons, the differentiated Lund human Mesencephalic (LUHMES) cells. In this cellular model, fisetin promotes the increase of the levels of dopamine transporter. Remarkably, fisetin reduced the percentage of cells containing αsyn inclusions as well as their size and subcellular localization in a yeast model of αsyn aggregation. Overall, our data show that fisetin exerts modulatory activities toward common cellular pathologies present in PD; remarkably, it modulates αsyn aggregation, supporting the idea that diets rich in this compound may prove beneficial.
Journal Article
The influence of vegetarian and omnivorous diet quality on metabolic profiles and cardiovascular risk
2025
Cardiovascular diseases are the leading global cause of mortality and a major contributor to disability. As inadequate nutrition accounts for approximately 50% of cardiovascular deaths, understanding the impact of different dietary patterns is crucial. This study aimed to compare cardiovascular risk factors and 10-year cardiovascular risk in adults following a vegetarian (VG) or omnivorous (OM) diet. Cardiovascular risk was calculated using SCORE2, body composition was assessed through dual-energy X-ray absorptiometry, biochemical parameters were determined from capillary blood, and diet quality was evaluated using the 14-item Mediterranean Diet (MD) adherence questionnaire for OM, and the healthful plant-based diet index for VG. A cross-sectional design was performed with 110 participants (55 OM and 55 VG). No significant differences between groups were found in the 10-year cardiovascular risk. However, for biochemical parameters, OM showed higher levels of total cholesterol (
p
< 0.001), LDL cholesterol (
p
= 0.001), and non-HDL cholesterol (
p
= 0.004). Conversely, for body composition, VG men showed lower Appendicular Lean Mass Index (ALMI) values (
p
= 0.005). Upon analyzing diet quality, high adherence to the MD in the OM group (OR 0.861;
p
= 0.013) and high diet quality in the VG group (OR 0.590;
p
= 0.001) were protective factors against high cardiovascular risk. When reanalyzing data only for individuals with high-quality diets, OM individuals showed lower values of fat mass (
p
= 0.003) and Visceral Adipose Tissue (
p
= 0.023). Meanwhile, VG individuals showed significantly lower total cholesterol levels (
p
= 0.013). A high-quality VG diet demonstrated better results concerning lipid profile, while an OM diet with high adherence to the MD showed greater potential regarding body composition. Additionally, the key factor for optimal cardiovascular health does not seem to be related to a specific dietary pattern but rather to the quality of the diet adopted.
Journal Article
Supercritical CO2 Extraction as a Tool to Isolate Anti-Inflammatory Sesquiterpene Lactones from Cichorium intybus L. Roots
by
dos Santos, Cláudia Nunes
,
Matias, Ana A.
,
Anastácio, José D.
in
Analytical Chemistry
,
anti-inflammatory potential
,
Carbon dioxide
2021
Cichorium intybus L. or chicory plants are a natural source of health-promoting compounds in the form of supplements such as inulin, as well as other bioactive compounds such as sesquiterpene lactones (SLs). After inulin extraction, chicory roots are considered waste, with most SLs not being harnessed. We developed and optimized a new strategy for SL extraction that can contribute to the conversion of chicory root waste into valuable products to be used in human health-promoting applications. In our work, rich fractions of SLs were recovered from chicory roots using supercritical CO2. A response surface methodology was used to optimize the process parameters (pressure, temperature, flow rate, and co-solvent percentage) for the extraction performance. The best operating conditions were achieved at 350 bar, 40 °C, and 10% EtOH as a co-solvent in a 15 g/min flow rate for 120 min. The extraction with supercritical CO2 revealed to be more selective for the SLs than the conventional solid–liquid extraction with ethyl acetate. In our work, 1.68% mass and a 0.09% sesquiterpenes yield extraction were obtained, including the recovery of two sesquiterpene lactones (8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin), which, to the best of our knowledge, are not commercially available. A mixture of the abovementioned compounds were tested at different concentrations for their toxic profile and anti-inflammatory potential towards a human calcineurin/NFAT orthologue pathway in a yeast model, the calcineurin/Crz1 pathway. The SFE extract obtained, rich in SLs, yielded results of inhibition of 61.74 ± 6.87% with 50 µg/mL, and the purified fraction containing 8-deoxylactucin and 11β,13-dihydro-8-deoxylactucin inhibited the activation of the reporter gene up to 53.38 ± 3.9% at 10 µg/mL. The potential activity of the purified fraction was also validated by the ability to inhibit Crz1 nuclear translocation and accumulation. These results reveal a possible exploitable green technology to recover potential anti-inflammatory compounds from chicory roots waste after inulin extraction.
Journal Article
Rice Compounds with Impact on Diabetes Control
by
Menezes, Regina
,
Lourenço, Vanda M.
,
Brites, Carla
in
Bioactive compounds
,
Biological activity
,
Cereals
2021
Rice is one of the most cultivated and consumed cereals worldwide. It is composed of starch, which is an important source of diet energy, hypoallergenic proteins, and other bioactive compounds with known nutritional functionalities. Noteworthy is that the rice bran (outer layer of rice grains), a side-stream product of the rice milling process, has a higher content of bioactive compounds than white rice (polished rice grains). Bran functional ingredients such as γ-oryzanol, phytic acid, ferulic acid, γ-aminobutyric acid, tocopherols, and tocotrienols (vitamin E) have been linked to several health benefits. In this study, we reviewed the effects of rice glycemic index, macronutrients, and bioactive compounds on the pathological mechanisms associated with diabetes, identifying the rice compounds potentially exerting protective activities towards disease control. The effects of starch, proteins, and bran bioactive compounds for diabetic control were reviewed and provide important insights about the nutritional quality of rice-based foods.
Journal Article
Rubella antibodies in vertically and horizontally HIV-infected young adults vaccinated early in life and response to a booster dose in those with seronegative results
by
Araujo, Beatriz Collaço
,
de Menezes Succi, Regina Célia
,
Carmo, Fabiana B
in
adolescence
,
adulthood
,
Allergy and Immunology
2022
•Over 2/3 vertically HIV individuals lack rubella antibodies 16y after vaccination.•There is a 7% higher chance of rubella seronegativity for each y of the last dose.•80.6% rubella seronegative vertically HIV individuals respond to an extra MMR dose.
Very limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life.
Prospective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards.
Time since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm3; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels.
As vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose.
Journal Article
RNA-seq, de novo transcriptome assembly and flavonoid gene analysis in 13 wild and cultivated berry fruit species with high content of phenolics
by
Ramírez-González, Ricardo
,
Naesby, Michael
,
Martin, Cathie
in
13 berry fruit species
,
Analysis
,
Animal Genetics and Genomics
2019
Background
Flavonoids are produced in all flowering plants in a wide range of tissues including in berry fruits. These compounds are of considerable interest for their biological activities, health benefits and potential pharmacological applications. However, transcriptomic and genomic resources for wild and cultivated berry fruit species are often limited, despite their value in underpinning the in-depth study of metabolic pathways, fruit ripening as well as in the identification of genotypes rich in bioactive compounds.
Results
To access the genetic diversity of wild and cultivated berry fruit species that accumulate high levels of phenolic compounds in their fleshy berry(-like) fruits, we selected 13 species from Europe, South America and Asia representing eight genera, seven families and seven orders within three clades of the kingdom
Plantae
. RNA from either ripe fruits (ten species) or three ripening stages (two species) as well as leaf RNA (one species) were used to construct, assemble and analyse de novo transcriptomes. The transcriptome sequences are deposited in the BacHBerryGEN database (
http://jicbio.nbi.ac.uk/berries
) and were used, as a proof of concept,
via
its BLAST portal (
http://jicbio.nbi.ac.uk/berries/blast.html
) to identify candidate genes involved in the biosynthesis of phenylpropanoid compounds. Genes encoding regulatory proteins of the anthocyanin biosynthetic pathway (MYB and basic helix-loop-helix (bHLH) transcription factors and WD40 repeat proteins) were isolated using the transcriptomic resources of wild blackberry (
Rubus genevieri
) and cultivated red raspberry (
Rubus idaeus
cv. Prestige) and were shown to activate anthocyanin synthesis in
Nicotiana benthamiana
. Expression patterns of candidate flavonoid gene transcripts were also studied across three fruit developmental stages
via
the BacHBerryEXP gene expression browser (
http://www.bachberryexp.com
) in
R. genevieri
and
R. idaeus
cv. Prestige.
Conclusions
We report a transcriptome resource that includes data for a wide range of berry(-like) fruit species that has been developed for gene identification and functional analysis to assist in berry fruit improvement. These resources will enable investigations of metabolic processes in berries beyond the phenylpropanoid biosynthetic pathway analysed in this study. The RNA-seq data will be useful for studies of berry fruit development and to select wild plant species useful for plant breeding purposes.
Journal Article
Molecular characterization of TaSTOP1 homoeologues and their response to aluminium and proton (H+) toxicity in bread wheat (Triticum aestivumL.)
by
Garcia-Oliveira, Ana Luísa
,
Guedes-Pinto, Henrique
,
de Andrade Menezes, Regina
in
acid soils
,
Agriculture
,
aluminum
2013
Background
Aluminium (Al) toxicity is considered to be one of the major constraints affecting crop productivity on acid soils. Being a trait governed by multiple genes, the identification and characterization of novel transcription factors (TFs) regulating the expression of entire response networks is a very promising approach. Therefore, the aim of the present study was to clone, localize, and characterize the
TaSTOP1
gene, which belongs to the zinc finger family (Cys2His2 type) transcription factor, at molecular level in bread wheat.
Results
TaSTOP1
loci were cloned and localized on the long arm of homoeologous group 3 chromosomes [3AL (
TaSTOP1-A
), 3BL (
TaSTOP1-B
) and 3DL (
TaSTOP1-D
)] in bread wheat. TaSTOP1 showed four potential zinc finger domains and the homoeologue TaSTOP1-A exhibited transactivation activity in yeast. Expression profiling of
TaSTOP1
transcripts identified the predominance of homoeologue
TaSTOP1-A
followed by
TaSTOP1-D
over
TaSTOP1-B
in root and only predominance of
TaSTOP1-A
in shoot tissues of two diverse bread wheat genotypes. Al and proton (H
+
) stress appeared to slightly modulate the transcript of
TaSTOP1
homoeologues expression in both genotypes of bread wheat.
Conclusions
Physical localization of
TaSTOP1
results indicated the presence of a single copy of
TaSTOP1
on homoeologous group 3 chromosomes in bread wheat. The three homoeologues of
TaSTOP1
have similar genomic structures, but showed biased transcript expression and different response to Al and proton (H
+
) toxicity. These results indicate that
TaSTOP1
homoeologues may differentially contribute under Al or proton (H
+
) toxicity in bread wheat. Moreover, it seems that
TaSTOP1-A
transactivation potential is constitutive and may not depend on the presence/absence of Al at least in yeast. Finally, the localization of
TaSTOP1
on long arm of homoeologous group 3 chromosomes and the previously reported major loci associated with Al resistance at chromosome 3BL, through QTL and genome wide association mapping studies suggests that
TaSTOP1
could be a potential candidate gene for genomic assisted breeding for Al tolerance in bread wheat.
Journal Article
Evaluation of the Hematological Patterns from Up to 985 Days of Long COVID: A Cross-Sectional Study
by
Falcão, Luiz Fábio Magno
,
Palácios, Vera Regina da Cunha Menezes
,
Galúcio, Vanessa Costa Alves
in
Amazonia
,
Biological markers
,
Blood
2023
Long COVID affects many individuals following acute coronavirus disease 2019 (COVID-19), and hematological changes can persist after the acute COVID-19 phase. This study aimed to evaluate these hematological laboratory markers, linking them to clinical findings and long-term outcomes in patients with long COVID. This cross-sectional study selected participants from a ‘long COVID’ clinical care program in the Amazon region. Clinical data and baseline demographics were obtained, and blood samples were collected to quantify erythrogram-, leukogram-, and plateletgram-related markers. Long COVID was reported for up to 985 days. Patients hospitalized in the acute phase had higher mean red/white blood cell, platelet, and plateletcrit levels and red blood cell distribution width. Furthermore, hematimetric parameters were higher in shorter periods of long COVID than in longer periods. Patients with more than six concomitant long COVID symptoms had a higher white blood cell count, a shorter prothrombin time (PT), and increased PT activity. Our results indicate there may be a compensatory mechanism for erythrogram-related markers within 985 days of long COVID. Increased levels of leukogram-related markers and coagulation activity were observed in the worst long COVID groups, indicating an exacerbated response after the acute disturbance, which is uncertain and requires further investigation.
Journal Article