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1.
Dent J (Basel) ; 12(6)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38920854

RESUMO

BACKGROUND: Dental caries is a dynamic, multifactorial disease that destroys teeth and can affect anyone's quality of life because it can cause tooth loss and make chewing difficult. Dental caries involves various factors, such as Streptococcus mutans and host factors. Currently, adjuvant therapies, such as curcumin, have emerged, but how they work has not been adequately described. Therefore, this work aims to identify the molecular mechanism of curcumin in caries and Streptococcus mutans. METHODS: We obtained differentially expressed genes from a GEO dataset, and curcumin targets were obtained from other databases. The common targets were analyzed according to gene ontology enrichment, key genes were obtained, and binding to curcumin was verified by molecular docking. RESULTS: Our analysis showed that curcumin presents 134 therapeutic targets in caries. According to the gene ontology analysis, these targets are mainly involved in apoptosis and inflammation. There are seven key proteins involved in the action of curcumin on caries: MAPK1, BCL2, KRAS, CXCL8, TGFB1, MMP9, and IL1B, all of which spontaneously bind curcumin. In addition, curcumin affects metabolic pathways related to lipid, purine, and pyrimidine metabolism in Streptococcus mutans. CONCLUSIONS: Curcumin affects both host carious processes and Streptococcus mutans.

2.
Curr Issues Mol Biol ; 45(9): 7228-7241, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37754241

RESUMO

The incidence of type 2 diabetes (T2D) is rising, and finding new treatments is important. C. sativa is a plant suggested as a potential treatment for T2D, but how it works needs to be clarified. This study explored the pharmacological mechanism of C. sativa in treating T2D. We identified the active compounds in C. sativa and their targets. From there, we examined the genes associated with T2D and found overlapping genes. We conducted an enrichment analysis and created a protein-protein and target-compound interactions network. We confirmed the binding activities of the hub proteins and compounds with molecular docking. We identified thirteen active compounds from C. sativa, which have 150 therapeutic targets in T2D. The enrichment analysis showed that these proteins are involved in the hormone, lipid, and stress responses. They bind transcription factors and metals and participate in the insulin, PI3K/Akt, HIF-1, and FoxO signaling pathways. We found four hub proteins (EGFR, ESR1, HSP90AA1, and SRC) that bind to the thirteen bioactive compounds. This was verified using molecular docking. Our findings suggest that C. sativa's antidiabetic action is carried out through the insulin signaling pathway, with the participation of HIF-1 and FoxO.

3.
Biomed Res Int ; 2022: 6828837, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35445138

RESUMO

Colorectal cancer (CRC) is the most diagnosed cancer with the highest mortality rate each year globally. Although there are treatments for CRC, the development of resistance to therapies decreases the success of treatments. In vitro studies using the Caco-2 cell line have revealed the anticancer properties of silver nanoparticles (AgNPs) as a possible treatment for this disease. This study considered four researches that evaluated the proteomic profiles of cells of the Caco-2 line exposed to AgNPs. We performed a bioinformatics analysis to predict protein-protein interaction, hub genes, Gene Ontology (molecular function, biological process, and cellular components), KEGG pathways, analysis of expression, and immune cell infiltration. For these analyses, the STRING, DAVID, UALCAN, GEPIA2, and TISIDB databases were used. The results in Gene Ontology show that AgNPs cause a deregulation of genes related to cell-cell adhesion, the cytoplasm, the centriole, and carbon metabolism. Hub genes were identified, including GADPH, ENO1, EEF2, and ATP5A1, which showed differential expression in patients with adenocarcinoma of the colon and rectum. Additionally, the expression of the hub genes and immune cells was correlated. It was found that ATP5A1 and ENO1 were positively correlated with the infiltration of CD4+ T lymphocytes in colon adenocarcinoma and a negative correlation between GADPH and PDIA3 with the infiltration of NK cells and CD4+ T lymphocytes in rectal adenocarcinoma, respectively. In conclusion, the administration of AgNPs causes an alteration of biological processes, cellular components, metabolic pathways, deregulation of hub genes, and the activity of immune cells leading to a potential anticancer effect.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Neoplasias Colorretais , Nanopartículas Metálicas , Adenocarcinoma/genética , Células CACO-2 , Neoplasias do Colo/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Proteômica , Prata/farmacologia
4.
Nutr Hosp ; 39(2): 313-319, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35156380

RESUMO

Introduction: Background: many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL32 gene. Objectives: this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. Methods: this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL32 gene network and infer transcription factors that bind to this polymorphic site. Results: subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL32 is involved in metabolic pathways related to viral infections. Conclusion: the TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse.


Introducción: Introducción: la interleucina 32 es una citocina proinflamatoria. El rs45499297 es un polimorfismo de nucleótido simple del gen de IL32, situado en la región promotora y caracterizado por un cambio de T/C. Objetivo: evaluar el polimorfismo rs45499297 y su asociación con la obesidad, y realizar un análisis in silico. Métodos: el estudio fue transversal e incluyó 333 sujetos clasificados por índice de masa corporal y porcentaje de grasa. Se midieron la glucosa y el perfil lipídico, así como los niveles séricos de IL-32 mediante ELISA y el genotipo del polimorfismo rs45499297 mediante PCR-RFLP. Para el análisis in silico se utilizaron varias bases de datos para hacer la red de genes de IL32 e inferir factores de transcripción unidos al sitio polimórfico. Resultados: los sujetos con bajo peso y bajo porcentaje de grasa tienen niveles más bajos de IL-32. El genotipo TC y el alelo C se encontraron con menos frecuencia en los sujetos con sobrepeso/obesidad que en los normopeso, resultado que permaneció solo en el género masculino. Se encontró que el factor nuclear de los hepatocitos y la proteína de especificidad 1 se unen a este sitio polimórfico. Se infiere que IL32 está involucrado en vías metabólicas relacionadas con las infecciones virales. Conclusión: el genotipo TC está asociado al sobrepeso/la obesidad. La disminución de los niveles de IL-32 observada en los sujetos con bajo peso y bajo porcentaje de grasa podría ser por un perfil inflamatorio alterado. El análisis in silico mostró que varios factores de transcripción se unen al sitio polimórfico y que el enriquecimiento de las vías metabólicas es diverso.


Assuntos
Interleucinas , Obesidade , Estudos Transversais , Predisposição Genética para Doença , Genótipo , Humanos , Interleucinas/sangue , Interleucinas/genética , Masculino , México/epidemiologia , Polimorfismo de Nucleotídeo Único
5.
Mini Rev Med Chem ; 21(14): 1798-1812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33535949

RESUMO

Diabetes mellitus is a disease that presents great challenges for healthcare systems worldwide, and the identification of alternative therapies for the treatment of this disease is of vital importance. Metallic nanoparticles (gold, silver, and selenium) and metallic oxide (ZnO) have been studied in different areas such as medicine, biotechnology, the environment, and the food industry with promising results. In medicine, current research has revealed these nanoparticles' anti-diabetic properties thanks to the implementation of animal models. This review will address the existing antecedents and the effects of gold, silver, selenium, and zinc oxide nanoparticles in diabetes administered alone, functionalized with other molecules, or combined with drugs that have shown promising therapeutic effects. The anti-diabetic effects of these nanoparticles are related to the regulation of glucose, insulin, and lipid profiles. In addition, oxidative stress markers, liver and kidney markers, the reduction of inflammation, apoptosis of the pancreas, and the restoration of normal liver and kidney histology are also reported in the literature after using these nanoparticles. However, the therapeutic effects that these nanoparticles provide are limited due to the lack of specific protocols dictated by international organizations to evaluate the risks of using these nanoparticles.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ouro/química , Hipoglicemiantes/uso terapêutico , Nanopartículas Metálicas/química , Selênio/química , Prata/química , Zinco/química , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Hipoglicemiantes/química , Nanopartículas Metálicas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
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