Network Pharmacology, Molecular Docking, and Molecular Dynamics Study to Explore the Effect of Resveratrol on Type 2 Diabetes.

This network pharmacology study represents a significant step in understanding the potential of Resveratrol as an antidiabetic agent and its molecular targets. Targets for Type 2 diabetes were obtained from the MalaCards and DisGeNET databases, while targets for Resveratrol were sourced from the STP and CTD databases. Subsequently, we performed matching to identify common disease-compound targets. The identified genes were analyzed using the ShinGO-0.76.3 database for functional enrichment analysis and KEGG pathway mapping. A protein-protein interaction network was then constructed using Cytoscape software, and hub genes were identified. These hub genes were subjected to molecular docking and dynamic simulations using AutoDock Vina and Gromacs software. According to functional enrichment and KEGG pathway analysis, Resveratrol influences insulin receptors, endoplasmic reticulum functions, and oxidoreductase activity and is involved in the estrogen and HIF-1 pathways. Ten hub genes were identified, including ESR1, PTGS2, SRC, NOS3, MMP9, IGF1R, CYP19A1, MTOR, MMP2, and PIK3CA. The proteins associated with these genes exhibited high interaction with Resveratrol in the molecular docking analysis, and molecular dynamics showed a stable interaction of Resveratrol with ESR1, MMP9, PIK3CA, and PTGS2. In conclusion, our work enhances the understanding of the antidiabetic activity of Resveratrol, which future studies should experimentally corroborate.

Molecular Docking Integrated with Network Pharmacology Explores the Therapeutic Mechanism of Cannabis sativa against Type 2 Diabetes.

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.

Innate and adaptive immunity of periodontal disease. From etiology to alveolar bone loss.

Periodontal disease refers to inflammation of the tissues that support the tooth. It is of multifactorial etiology. Innate and adaptive immune cells participate jointly through the release of their molecules and mechanisms of action in order to maintain homeostasis in periodontal tissues, so the host's immune response plays an essential role in defense against microorganisms. However, bacterial persistence and the dysregulation of the immune system as an exaggerated response can lead to the worsening of periodontal disease, leading to loss of gingival tissue and alveolar bone and thereby loss of teeth. Therefore, a better understanding of the cellular mechanisms involved in the development of periodontal disease is necessary to design new treatments and prophylactic measures in order to decrease the prevalence of this disease that afflicts a large part of the world population.

Tumour necrosis factor-alpha polymorphism -308 G/a and its protein in subjects with gingivitis.

OBJECTIVE: This study examined the association between tumour necrosis factor-alpha (TNF- α) (-308 G/A) polymorphism and gingivitis, and serum and salivary TNF- α levels, in a Mexican population. MATERIAL AND METHODS: This study enrolled 171 subjects, divided into two groups: healthy subjects and gingivitis patients. TNF- α (-308 G/A) gene polymorphism was analyzed by PCR-RFLP assay. Salivary and serum samples were used to measure cytokine levels through the ELISA technique. RESULTS: TNF- α (-308 G/A) polymorphism was shown to have a protective effect in carriers of the A/A genotype and allele A. The G/A genotype is associated with an increase in high-density lipoprotein cholesterol (HDL-C) levels in the gingivitis group. Healthy individuals had higher levels of salivary TNF- α and HDL-C, and increased salivary flow. Triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels were increased in the gingivitis group. No statistical differences were found in serum TNF- α levels. CONCLUSION: Our data demonstrate that the TNF- α -308 A/A genotype exerts a protective effect against gingivitis. Moreover, oral conditions are associated with some biochemical parameters.

Effect of Administration of Selenium Nanoparticles Synthesized Using Onion Extract on Biochemical and Inflammatory Parameters in Mice Fed with High-Fructose Diet: In Vivo and In Silico Analysis.

Fructose consumption has increased globally and has been linked to obesity, insulin resistance, and diabetes. Selenium nanoparticles (SeNPs) can regulate glucose and lipid concentrations and have immunoregulatory properties. Four study groups (n = 7/group) of eight-week-old male mice (Balb/c) were formed for this investigation. One group received a standard diet (C), another standard diet plus SeNPs (C + SeNPs), a high fructose diet (F), and a group with a high fructose diet plus SeNPs (F + SeNPs). Weight, glucose, triglycerides, and cholesterol were evaluated. In the end, mice were sacrificed, blood samples were obtained to assess cytokine profile, and liver, kidney, and pancreas were removed for histological examination. The study was complemented with an in silico analysis where the CTD, STITCH, ToppGene Suite, ShinyGO 0.76.3 databases, and Cytoscape software were implemented. The results of in vivo analysis showed that SeNPs regulated biochemical parameters and showed anti-inflammatory effects by decreasing the concentrations of TNF-alpha, IL-1beta, and IFN-gamma and increasing IL-10. No damage was observed in the studied organs. In addition, SeNPs regulate oxidative stress, preserve cell organelles, and regulate metabolic pathways to avoid the adverse effects of fructose consumption, according to bioinformatics analysis. In conclusion, SeNPs protect against the undesirable effects of a diet rich in fructose.

A Docking and Network Pharmacology Study on the Molecular Mechanisms of Curcumin in Dental Caries and Streptococcus mutans.

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.

Pharmacological network study on the effect of 6-gingerol on cervical cancer using computerized databases.

Cervical cancer (CC) is the most frequent cancer in the female population worldwide. Although there are treatments available, they are ineffective and cause adverse effects. 6-gingerol is an active component in ginger with anticancer activity. This research aims to discover the mechanism by which 6-gingerol act as an anticancer agent on CC through a pharmacological network using bioinformatics databases. From MalaCard, Swiss Target Prediction, Comparative Toxicogenomics Database, and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, we obtained the target genes for 6-gingerol and CC and matched them. We got 26 genes and analyzed them in ShinyGO-0.76.3 and DAVID-Bioinformatics Resources. Then, we generated a protein-protein interaction network in Cytoscape and obtained 12 hub genes. Hub genes were analyzed in Gene Expression Profiling Interactive Analysis and TISIDB. In addition, molecular docking studies were performed between target proteins with 6-gingerol using SwissDock database. Finally, molecular dynamics studies for three proteins with the lowest interaction energy were implemented using Gromacs software. According to gene ontology results, 6-gingerol is involved in processes of apoptosis, cell cycle, and protein kinase complexes, affecting mitochondria and pathways related to HPV infection. CTNNB1 gene was negatively correlated with CD8+ infiltration but was not associated with a higher survival rate. Furthermore, the molecular docking study showed that 6-gingerol has a high binding to proteins, and the molecular dynamics showed a stable interaction of 6-gingerol to AKT1, CCNB1, and CTNNB1 proteins. Conclusion, our work helps to understand the anticancer activity of 6-gingerol in CC that should be studied experimentally.Communicated by Ramaswamy H. Sarma.

Molecular mechanism of curcumin on periodontitis: A pharmacological network study.

OBJECTIVE: This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy. METHODS: The potential therapeutic targets of curcumin and differentially expressed genes in periodontitis were identified. Subsequently, we extracted the molecules in common and analyzed them. A metabolic pathway enrichment and gene ontology analysis were performed and the protein-protein interaction network was inferred. These analyses allowed the identification of key proteins. Finally, a molecular docking of the main key proteins was performed with curcumin. RESULTS: Our results showed that 55 genes are differentially expressed in periodontitis and are potential targets of curcumin. In addition, we observed that these genes participate in cell motility and immune response and are related to chemokine receptors (CXCRs) and enzymatic activity, such as arachidonate 5-lipoxygenase (ALOX5). We identified six key proteins, IL1B, CXCL8, CD44, MMP2, EGFR, and ITGAM; molecular docking revealed that these six proteins spontaneously bind to curcumin. CONCLUSION: The results of this study helps us understand the molecular mechanism of curcumin in periodontitis. We propose that curcumin affects proinflammatory cytokines, ALOX5, and cell migration through chemokine receptors and acts on the cell membrane. Additionally, we identified six key proteins that are essential in this mechanism, all of which spontaneously bind to curcumin.

Anticancer Activity of Selenium Nanoparticles In Vitro Studies.

Health systems worldwide consider cancer a disease that causes the highest number of deaths per year. The low efficacy of current cancer therapies has led other areas of science to search for new alternatives, including nanomaterial sciences. Selenium nanoparticles have anticancer activity, as revealed by in vitro tests performed on prostate, breast, cervical, lung, colorectal, and liver cancer cell lines. Studies attribute anticancer activity to the anti-metastatic effect due to the inhibition of migration and invasion processes. The antiproliferative effect is the low expression of molecules such as cyclin D1, cyclin E, and CDK2. In addition to the activation of cell apoptosis by caspase-dependent mechanisms, there is a low expression of anti-apoptotic proteins such as Bcl-2 and a high expression of the apoptotic proteins like Bax and Bad. Other studies attribute anticancer activity to the activation of cell necroptosis, where molecules such as TNF and IRF1 participate. The pharmacological potential of selenium nanoparticles depends primarily on the administered dose, particle size, and chemical composition. Furthermore, several studies have shown that the administration of these nanoparticles is safe due to their low toxicity in non-cancerous cells. In this review, the most relevant antecedents on the anticancer potential of selenium nanoparticles in prostate, breast, cervical, lung, liver, and colorectal cancer cell lines are discussed.

Bioinformatic Analysis of the Effect of Silver Nanoparticles on Colorectal Cancer Cell Line.

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.

Relation of serum IL-32 levels and gene polymorphism rs45499297 with obesity in Mexican patients: a laboratory and in silico analysis.

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.

A Review of the Antimicrobial Activity of Selenium Nanoparticles.

Antimicrobial resistance has become a severe problem for health systems worldwide, and counteractions are challenging because of the lack of interest of pharmaceutical companies in generating new and effective antimicrobial drugs. Selenium nanoparticles have attracted considerable interest in treating bacteria, fungi, parasites, and viruses of clinical importance due to their high therapeutic efficacy and almost zero generation of adverse effects. Some studies have revealed that the antimicrobial activity of these nanoparticles is due to the generation of reactive oxygen species, but more studies are needed to clarify their antimicrobial mechanisms. Other studies show that their antimicrobial activity is increased when the surface of the nanoparticles is functionalized with some biomolecules or when their surface carries a specific drug. This review addresses the existing background on the antimicrobial potential offered by selenium nanoparticles against viruses, bacteria, fungi, and parasites of clinical importance.

A Review of the Effects of Gold, Silver, Selenium, and Zinc Nanoparticles on Diabetes Mellitus in Murine Models.

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.