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Article ; Online: Angiotensin-converting enzyme gene (ACE) polymorphisms are associated with dysregulation of biochemical parameters in hypertensive patients

da Agostini, Lívia / Cunha, Warlley R. / Silva, Nayara N. T. / Melo, André S. / Moreira, Luciana B. / Almeida, Tamires C. / Belo, Vanessa A. / Coura-Vital, Wendel / de M. Teixeira, Luiz Fernando / Lima, Angélica A. / da Silva, Glenda Nicioli

Mol Biol Rep. 2023 Feb., v. 50, no. 2 p.1487-1497

2023

Abstract: INTRODUCTION: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding ...

Abstract	INTRODUCTION: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. OBJECTIVE: To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. METHOD: The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn’s post-test for multiple comparisons. RESULTS: The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. CONCLUSION: AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.
Keywords	case-control studies ; education ; genes ; glucose ; hypertension ; lifestyle ; obesity ; pathophysiology ; people ; peptidyl-dipeptidase A ; quantitative polymerase chain reaction ; questionnaires ; regression analysis ; risk ; socioeconomic status ; sodium ; urea ; uric acid ; Brazil
Language	English
Dates of publication	2023-02
Size	p. 1487-1497.
Publishing place	Springer Netherlands
Document type	Article ; Online
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-022-08128-z
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Inhibition of urinary bladder cancer cell proliferation by silibinin.

Barros, Tatiane M B / Lima, Ana P B / Almeida, Tamires C / da Silva, Glenda N

Environmental and molecular mutagenesis

2020 Volume 61, Issue 4, Page(s) 445–455

Abstract: Silibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and ... ...

Abstract	Silibinin, a natural compound extracted from milk thistle, has demonstrated antitumor properties in urinary bladder cancer cells; however, the role of TP53 gene in these effects is unclear. In order to better understand the molecular and antiproliferative mechanisms of this compound, urinary bladder cancer cells with different TP53 gene status, RT4 (low-grade tumor, wild TP53 gene), 5637 (high-grade tumor, Grade 2, mutated TP53 gene), and T24 (high-grade tumor, Grade 3, mutated TP53 gene) were treated with several concentrations of silibinin (1, 5, 10, 50, 100, and 150 μM). Cytotoxicity, prooxidant effect, morphological changes, cell migration, cell cycle progression, global methylation profile, and relative expression of HOXB3, c-MYC, PLK1, SMAD4, SRC, HAT, HDAC, and RASSF1A genes were evaluated. The silibinin presented cytotoxic and prooxidant effects in the three cell lines. In mutated TP53 cells, significant interference in cell migration and cell cycle arrest at the G2/M phase was observed. Additionally, silibinin induced global DNA hypomethylation in the highest grade tumor cells. For wild-type TP53 cells, a sub-G1 apoptotic population was present. Furthermore, there was modulation of gene expression responsible for cell growth (SMAD and c-MYC), migration (SRC), cell cycle kinetics (PLK1), angiogenesis (HOXB3), and of genes associated with epigenetic events such as DNA acetylation (HAT) and deacetylation (HDAC). In conclusion, the silibinin inhibited the urinary bladder tumor cell proliferation independently of TP53 status; however, cell cycle effects, gene expression changes, and alteration of cell migration are dependent on TP53 status. © 2020 Wiley Periodicals, Inc.
MeSH term(s)	Antineoplastic Agents, Phytogenic/pharmacology ; Apoptosis/drug effects ; Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Silybin/pharmacology ; Tumor Suppressor Protein p53/genetics ; Urinary Bladder Neoplasms/drug therapy ; Urinary Bladder Neoplasms/genetics ; Urinary Bladder Neoplasms/pathology
Chemical Substances	Antineoplastic Agents, Phytogenic ; Tumor Suppressor Protein p53 ; Silybin (4RKY41TBTF)
Language	English
Publishing date	2020-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639145-x
ISSN	1098-2280 ; 0893-6692
ISSN (online)	1098-2280
ISSN	0893-6692
DOI	10.1002/em.22363
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Article ; Online: Angiotensin-converting enzyme gene (ACE) polymorphisms are associated with dysregulation of biochemical parameters in hypertensive patients.

da Agostini, Lívia / Cunha, Warlley R / Silva, Nayara N T / Melo, André S / Moreira, Luciana B / Almeida, Tamires C / Belo, Vanessa A / Coura-Vital, Wendel / de M Teixeira, Luiz Fernando / Lima, Angélica A / da Silva, Glenda Nicioli

Molecular biology reports

2022 Volume 50, Issue 2, Page(s) 1487–1497

Abstract: Introduction: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the ... ...

Abstract	Introduction: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. Objective: To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. Method: The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons. Results: The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. Conclusion: AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.
MeSH term(s)	Humans ; Angiotensins ; Case-Control Studies ; Genotype ; Hypertension/genetics ; Hypertension/drug therapy ; Peptidyl-Dipeptidase A/genetics ; Polymorphism, Single Nucleotide/genetics ; Triglycerides
Chemical Substances	Angiotensins ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Triglycerides ; ACE protein, human (EC 3.4.15.1)
Language	English
Publishing date	2022-12-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-022-08128-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: In silico approach of secondary metabolites from Brazilian herbal medicines to search for potential drugs against SARS‐CoV‐2

Amparo, Tatiane R. / Seibert, Janaína B. / Almeida, Tamires C. / Costa, Fernanda S. F. / Silveira, Benila M. / da Silva, Glenda N. / dos Santos, Orlando D. H. / de Souza, Gustavo H. B.

Phytotherapy research. 2021 Aug., v. 35, no. 8

2021

Abstract: The new severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of ... ...

Abstract	The new severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti‐SARS‐CoV‐2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS‐CoV‐2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti‐COVID‐19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID‐19 treatment.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus ; Severe acute respiratory syndrome coronavirus 2 ; computer simulation ; databases ; pandemic ; phytotherapy ; research ; secondary metabolites ; toxicity ; triterpenoids
Language	English
Dates of publication	2021-08
Size	p. 4297-4308.
Publishing place	John Wiley & Sons, Ltd.
Document type	Article
Note	REVIEW
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7097
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: In silico approach of secondary metabolites from Brazilian herbal medicines to search for potential drugs against SARS-CoV-2.

Amparo, Tatiane R / Seibert, Janaína B / Almeida, Tamires C / Costa, Fernanda S F / Silveira, Benila M / da Silva, Glenda N / Dos Santos, Orlando D H / de Souza, Gustavo H B

Phytotherapy research : PTR

2021 Volume 35, Issue 8, Page(s) 4297–4308

Abstract: The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of ... ...

Abstract	The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti-SARS-CoV-2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS-CoV-2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti-COVID-19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID-19 treatment.
MeSH term(s)	Antiviral Agents/pharmacology ; COVID-19/drug therapy ; Humans ; Molecular Docking Simulation ; Phytochemicals/pharmacology ; Plant Preparations/pharmacology ; Plants, Medicinal/chemistry ; SARS-CoV-2/drug effects
Chemical Substances	Antiviral Agents ; Phytochemicals ; Plant Preparations
Language	English
Publishing date	2021-04-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639136-9
ISSN	1099-1573 ; 0951-418X
ISSN (online)	1099-1573
ISSN	0951-418X
DOI	10.1002/ptr.7097
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Article ; Online: Nanostructured Systems Improve the Antimicrobial Potential of the Essential Oil from

Seibert, Janaína B / Viegas, Juliana S R / Almeida, Tamires C / Amparo, Tatiane R / Rodrigues, Ivanildes V / Lanza, Juliane S / Frézard, Frédéric J G / Soares, Rodrigo D O A / Teixeira, Luiz Fernando M / de Souza, Gustavo H B / Vieira, Paula M A / Barichello, José M / Dos Santos, Orlando D H

Journal of natural products

2019 Volume 82, Issue 12, Page(s) 3208–3220

Abstract: The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems ... ...

Abstract	The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing
MeSH term(s)	Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Bacteria/drug effects ; Cell Line ; Cell Membrane Permeability/drug effects ; Cymbopogon/chemistry ; Drug Screening Assays, Antitumor ; Fungi/drug effects ; Gas Chromatography-Mass Spectrometry ; Hydrogen-Ion Concentration ; Mice ; Microbial Sensitivity Tests ; Microscopy, Electron, Transmission ; Nanostructures ; Oils, Volatile/chemistry ; Oils, Volatile/pharmacology ; Particle Size ; Plant Leaves/chemistry ; Quantitative Structure-Activity Relationship
Chemical Substances	Anti-Infective Agents ; Oils, Volatile
Language	English
Publishing date	2019-12-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304325-3
ISSN	1520-6025 ; 0163-3864
ISSN (online)	1520-6025
ISSN	0163-3864
DOI	10.1021/acs.jnatprod.8b00870
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Article: Nanostructured Systems Improve the Antimicrobial Potential of the Essential Oil from Cymbopogon densiflorus Leaves

Seibert, Janaína B / Viegas, Juliana S. R / Almeida, Tamires C / Amparo, Tatiane R / Rodrigues, Ivanildes V / Lanza, Juliane S / Frézard, Frédéric J. G / Soares, Rodrigo D. O. A / Teixeira, Luiz Fernando M / de Souza, Gustavo H. B / Vieira, Paula M. A / Barichello, José M / dos Santos, Orlando D. H

Journal of natural products. 2019 Dec. 09, v. 82, no. 12

2019

Abstract: The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing Cymbopogon densiflorus leaf essential oil and to evaluate ... ...

Abstract	The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing Cymbopogon densiflorus leaf essential oil and to evaluate their antimicrobial activity. The essential oil was isolated by hydrodistillation from leaves and analyzed by GC-MS. The main constituents were found to be trans-p-mentha-2,8-dien-1-ol, cis-p-mentha-2,8-dien-1-ol, trans-p-mentha-1(7),8-dien-2-ol, cis-piperitol, and cis-p-mentha-1(7),8-dien-2-ol. In silico prediction analysis suggested that this oil possesses antimicrobial potential and the main mechanism of action might be the peptidoglycan glycosyltransferase inhibition. Nanoemulsions were prepared by the phase inversion method, and liposomes were made by the film hydration method. Qualitative evaluation of the antimicrobial activity was performed by the diffusion disk assay with 24 microorganisms; all of them were found to be sensitive to the essential oil. Subsequently, this property was quantified by the serial microdilution technique, where the nanoformulations demonstrated improved activity in comparison with the free oil. Bactericidal action was tested by the propidium iodide method, which revealed that free essential oil and nanoemulsion increased cytoplasmic membrane permeability, while no difference was observed between negative control and liposome. These results were confirmed by images obtained using transmission electron microscopy. This study has shown an optimization in the antimicrobial activity of C. densiflorus essential oil by a nanoemulsion and a liposomal formulation of the active substances.
Keywords	Cymbopogon ; active ingredients ; antimicrobial properties ; cell membranes ; drug development ; enzyme inhibition ; essential oils ; gas chromatography-mass spectrometry ; hydrodistillation ; leaves ; mechanism of action ; membrane permeability ; microorganisms ; nanoemulsions ; oils ; peptidoglycans ; physicochemical properties ; prediction ; propidium ; transferases ; transmission electron microscopy
Language	English
Dates of publication	2019-1209
Size	p. 3208-3220.
Publishing place	American Chemical Society and American Society of Pharmacognosy
Document type	Article
ZDB-ID	304325-3
ISSN	1520-6025 ; 0163-3864
ISSN (online)	1520-6025
ISSN	0163-3864
DOI	10.1021/acs.jnatprod.8b00870
Database	NAL-Catalogue (AGRICOLA)

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