Current research on triple-negative breast cancer (TNBC) has resulted in delineation into the quadruple-negative breast cancer (QNBC) subgroup. Epigenetic modifications such as DNA methylation, histone posttranslational modifications and associated changes in chromatin architecture have been implicated in breast cancer pathogenesis. Herein, the authors highlight genes with observed epigenetic modifications that are associated with more aggressive TNBC/QNBC pathogenesis and possible interventions. Advanced literature searches were done on PubMed/MEDLINE, Scopus and Google Scholar. The results suggest that nine epigenetically altered genes/differentially expressed proteins in addition to the downregulated androgen receptor are associated with TNBC aggressiveness and could be implicated in the TNBC to QNBC transition. Thus, restoring the normal expression of these genes via epigenetic reprogramming could be therapeutically beneficial to TNBC and QNBC patients.

Trypanosoma congolense is a pathogenic African animal trypanosome species causing devastating conditions leading to death of an infected host. The drawbacks of the existing trypanocidal drugs have led to the search for new drug candidates. In this study, β-ionone at 15 and 30 mg/kg body weight (BW) was orally administered to T. congolense infected rats for 14 days followed by an assessment of anemia, organ damages, and the expression of T. congolense trans-sialidase gene variants. A significant decrease in parasitemia (p < .05) was observed in the animals treated with 15 mg/kg BW β-ionone besides increased animal survival rate. A trypanosome-induced decrease in packed cell volume (PCV) and histopathological changes across tissues was significantly (p < .05) ameliorated following treatment with both doses of βionone. This is in addition to reversing the parasite-induced upsurge in free serum sialic acid (FSA) and expression of T. congolense trans-sialidase gene variants (TconTS1, TconTS3, and TconTS4). Correlation analysis revealed a positive correlation (p > .05) between FSA with the TconTS gene expressions. In addition, the compound inhibited partially purified T. congolense sialidase and phospholipase A 2 via mixed inhibition pattern with inhibition binding constants of 25.325 and 4.550 µM, respectively, while molecular docking predicted binding energies of −5.6 kcal/mol for both enzymes. In conclusion, treatment with β-ionone suppressed T. congolense proliferation and protected the animals against some of the parasite-induced pathologies whilst the effect on anemia development might be due to inhibition of sialidase and PLA 2 activities as well as the expression levels of TconTS3 and TconTS4.

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Background Recent COVID-19 outbreak has prompted the search of novel therapeutic agents to treat the disease. The initial step of the infection involves the binding of the virus through the viral spike protein with the host angiotensin converting enzyme 2 (ACE2). In this study, the interaction of some ACE or ACE2 inhibitors and their analogues as well as selected compounds with the viral spike protein as a strategy to hinder viral-ACE2 interaction were investigated. SARS-CoV-2 spike protein as well as the ligands were retrieved from protein databank and ChEBI database respectively. The molecules were prepared before initiating the virtual screening using PyRx software. Discovery studio was used to further visualize the binding interactions between the compounds and the protein. Results The ACE inhibitors and their analogues fosinopril (1-), fosinopril and moexipril have the best binding affinity to the protein with binding energies < − 7.0 kcal/mol while non-flavonoid stilben-4-ol binds with free binding energy of − 7.1 kcal/mol. Others compounds which belong to either the flavonoids, terpenes and alkaloid classes also have binding energies  < − 7.0 kcal/mol. Such high binding energies were enhanced via hydrogen bond (h-bond) interactions in addition to other interactions observed between the compounds and the amino acid residues of the protein. Conclusions The ACE inhibitors and their analogues as well as the selected compounds could serve as inhibitors of the spike protein as well as lead in drug discovery processes to target the SARS-CoV-2 virus.

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