scholarly journals Computational Approaches for Cancer-Fighting: From Gene Expression to Functional Foods

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4207
Author(s):  
Francesco Monticolo ◽  
Maria Luisa Chiusano
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Expression Pattern ◽  
Functional Foods ◽  
Computational Study ◽  
Natural Compounds ◽  
Protein Interaction Data ◽  
Cancer Treatments ◽  
Protein Protein Interaction ◽  
Novel Drugs

It is today widely accepted that a healthy diet is very useful to prevent the risk for cancer or its deleterious effects. Nutrigenomics studies are therefore taking place with the aim to test the effects of nutrients at molecular level and contribute to the search for anti-cancer treatments. These efforts are expanding the precious source of information necessary for the selection of natural compounds useful for the design of novel drugs or functional foods. Here we present a computational study to select new candidate compounds that could play a role in cancer prevention and care. Starting from a dataset of genes that are co-expressed in programmed cell death experiments, we investigated on nutrigenomics treatments inducing apoptosis, and searched for compounds that determine the same expression pattern. Subsequently, we selected cancer types where the genes showed an opposite expression pattern and we confirmed that the apoptotic/nutrigenomics expression trend had a significant positive survival in cancer-affected patients. Furthermore, we considered the functional interactors of the genes as defined by public protein-protein interaction data, and inferred on their involvement in cancers and/or in programmed cell death. We identified 7 genes and, from available nutrigenomics experiments, 6 compounds effective on their expression. These 6 compounds were exploited to identify, by ligand-based virtual screening, additional molecules with similar structure. We checked for ADME criteria and selected 23 natural compounds representing suitable candidates for further testing their efficacy in apoptosis induction. Due to their presence in natural resources, novel drugs and/or the design of functional foods are conceivable from the presented results.

scholarly journals Computational Study of Natural Compounds for the Clearance of Amyloid-Βeta: A Potential Therapeutic Management Strategy for Alzheimer’s Disease

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3233 ◽  
Author(s):  
Syed Sayeed Ahmad ◽  
Haroon Khan ◽  
Syed Mohd. Danish Rizvi ◽  
Siddique Akber Ansari ◽  
Riaz Ullah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Computational Study ◽  
Senile Plaques ◽  
Natural Compounds ◽  
Positive Control ◽  
Aβ Peptide ◽  
Protein Protein Interaction ◽  
Lead Compounds ◽  
Glycation End Products

Alzheimer’s disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aβ) peptides in senile plaques. The interaction of Aβ and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aβ into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aβ peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aβ peptide–compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aβ and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aβ and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer’s disease treatment.

Immune checkpoint inhibitor-induced gastrointestinal and hepatic injury: pathologists’ perspective

2018 ◽  
Vol 71 (8) ◽  
pp. 665-671 ◽  
Author(s):  
Dipti M Karamchandani ◽  
Runjan Chetty
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Immune Mediated ◽  
Self Tolerance ◽  
Novel Drugs ◽  
Cell Death Protein

Immune checkpoint inhibitors (CPIs) are a relatively new class of ‘miracle’ dugs that have revolutionised the treatment and prognosis of some advanced-stage malignancies, and have increased the survival rates significantly. This class of drugs includes cytotoxic T lymphocyte antigen-4 inhibitors such as ipilimumab; programmed cell death protein-1 inhibitors such as nivolumab, pembrolizumab and avelumab; and programmed cell death protein ligand-1 inhibitors such as atezolizumab. These drugs stimulate the immune system by blocking the coinhibitory receptors on the T cells and lead to antitumoural response. However, a flip side of these novel drugs is immune-related adverse events (irAEs), secondary to immune-mediated process due to disrupted self-tolerance. The irAEs in the gastrointestinal (GI) tract/liver may result in diarrhoea, colitis or hepatitis. An accurate diagnosis of CPI-induced colitis and/or hepatitis is essential for optimal patient management. As we anticipate greater use of these drugs in the future given the significant clinical response, pathologists need to be aware of the spectrum of histological findings that may be encountered in GI and/or liver biopsies received from these patients, as well as differentiate them from its histopathological mimics. This present review discusses the clinical features, detailed histopathological features, management and the differential diagnosis of the luminal GI and hepatic irAEs that may be encountered secondary to CPI therapy.

scholarly journals Programmed cell death in the Drosophila CNS is ecdysone-regulated and coupled with a specific ecdysone receptor isoform

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1251-1259 ◽  
Author(s):  
S. Robinow ◽  
W.S. Talbot ◽  
D.S. Hogness ◽  
J.W. Truman
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Expression Pattern ◽  
Pupal Stage ◽  
Adult Emergence ◽  
Heterogeneous Group ◽  
Ecdysone Receptor ◽  
Unique Pattern ◽  
Central Neurons ◽  
Isoform Expression

At adult emergence, the ventral CNS of Drosophila shows a group of approximately 300 neurons, which are unique in that they express 10-fold higher levels of the A isoform of the ecdysone receptor (EcR-A) than do other central neurons. This expression pattern is established early in metamorphosis and persists throughout the remainder of the pupal stage. Although these cells represent a heterogeneous group of neurons, they all share the same fate of undergoing rapid degeneration after the adult emerges from the pupal case. One prerequisite for this death is the decline of ecdysteroids at the end of metamorphosis. Treatment of flies with 20-hydroxyecdysone blocks the death of the cells, but only if given at least 3 hours before the normal time of degeneration. The correlation of a unique pattern of receptor isoform expression with a particular steroid-regulated fate suggests that variations in the pattern of receptor isoform expression may serve as important switches during development.

scholarly journals Effect of Salinomycin on Expression Pattern of Genes Associated with Apoptosis in Endometrial Cancer Cell Line

2020 ◽  
Vol 21 (12) ◽  
pp. 1269-1277
Author(s):  
Kamil Kiełbasiński ◽  
Wojciech Peszek ◽  
Beniamin O. Grabarek ◽  
Dariusz Boroń ◽  
Magdalena Wierzbik-Strońska ◽  
...  
Keyword(s):  
Cell Death ◽  
Endometrial Cancer ◽  
Programmed Cell Death ◽  
Cancer Cells ◽  
Expression Pattern ◽  
Cancer Cell ◽  
Statistical Significance ◽  
Endometrial Cancer Cell ◽  
Significance Level ◽  
Apoptotic Genes

Background:: Salinomycin is part of a group of ionophore antibiotics characterized by an activity towards tumor cells. To this day, the mechanism through which salinomycin induces their apoptosis is not fully known yet. The goal of this study was to assess the expression pattern of genes and the proteins coded by them connected with the process of programmed cell death in an endometrial cancer cell Ishikawa culture exposed to salinomycin and compared to the control. Materials and Methods: Analysis of the effect of salinomycin on Ishikawa endometrial cancer cells (ECACC 99040201) included a cytotoxicity MTT test (with a concentration range of 0.1-100 μM), assessment of the induction of apoptosis and necrosis by salinomycin at a concentration of 1 μM as well the assessment of the expression of the genes chosen in the microarray experiment (microarray HG-U 133A_2) and the proteins coded by them connected with apoptosis (RTqPCR, ELISA assay). The statistical significance level for all analyses carried out as part of this study was p<0.05. Results: It was observed that salinomycin causes the death of about 50% of cells treated by it (50.74±0.80% of all cells) at a concentration of 1μM. The decrease in the number of living cells was determined directly after treatment of the cells with the drug (time 0). The average percent of late apoptotic cells was 1.65±0.24% and 0.57±0.01% for necrotic cells throughout the entire observation period. Discussion: Microarray analysis indicated the following number of mRNA differentiating the culture depending on the time of incubation with the drug: H_12 vs C = 114 mRNA, H_8 vs C = 84 mRNA, H_48 vs. C = 27 mRNA, whereas 5 mRNAs were expressed differently at all times. During the whole incubation period of the cells with the drug, the following dependence of the expression profile of the analyzed transcripts was observed: Bax>p53>FASL>BIRC5>BCL2L. Conclusion: The analysis carried out indicated that salinomycin, at a concentration of 1 μM, stopped the proliferation of 50% of endometrial cancer cells, mainly by inducing the apoptotic process of the cells. The molecular exponent of the induction of programmed cell death was an observed increase in the transcriptional activity of pro-apoptotic genes: Bax;p53;FASL and a decrease in the expression of anti-apoptotic genes: BCL2L2; BIRC5.

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