Sickle cell disease (SCD), also known as sickle cell anemia (SCA) is one of the structural hemoglobinopathies that occurs due to a single nucleotide mutation from GAG to GTG, which changes the amino acid of a β-globin chain of hemoglobin (Hb) from glutamate to valine. This singular mutation results to disorderliness in red blood cells (RBCs) with advent of changes in RBC morphology and other pathological conditions. In the 1980s, intermittent red blood cell transfusions, opioids, and penicillin prophylaxis were the only available therapy for SCA and were commonly reserved for acute, life threatening complications. So far, the US Food and Drug Administration (FDA) has granted a total of four drugs approval for the prophylaxis and treatment of the clinical complications of SCD. Due to limitations (adherence, safety, adverse effects) of existing therapies in the prophylaxis and treatment of SCD complications in Nigerian children and their inaccessibility to approved drugs, the present study discusses the therapeutic effects of readily available functional food as one of the therapies or an adjunct therapy to tackle the sickle cell crisis in Nigerian Children.

Myeloid cell leukemia-1 (MCL-1) is a prominent representative of the BCL-2 antiapoptotic protein family and plays a key role in the dysregulation of programmed cell death. Overexpression of MCL-1 has emerged as a survival and drug resistance mechanism in several malignancies. Currently, there’s no FDA-approved MCL-1 inhibitor in clinical use. Herein, we used drug repurposing to address this unmet therapeutic need. We employed a virtual computing technique to screen a customized library of thirty-one antiviral drugs for potential antagonistic activity against MCL-1. We investigated the dynamic interaction of the hits in the MCL-1 binding pocket using molecular dynamics simulation (MDS). The binding affinity of the hits was validated using MMGBSA, and ADMET properties of the hits were evaluated using the ADMET Lab 2.0 platform. Further, MCL-1 dependent cell lines and drug sensitivity were investigated using the DepMap CRISPRGeneEffect and CTD⌃² dataset. Our molecular docking and MMGBSA experiment uncovered bictegravir (− 9.7 kcal/mol) and cabotegravir (− 9.3 kcal/mol) as promising inhibitors of MCL-1. Further, these integrase inhibitors exhibited appealing pharmacokinetic profiles. The 100 ns MDS further exemplifies the drugs’ structural stability in the protein active pocket. Also, our DepMap analysis identified an MCL-1 dependent cell line that exhibits moderate sensitivity to four drugs. Our findings suggest that the hit compounds could be repurposed for MCL-1-dependent cancers. However, further studies involving in vitro and in vivo experimental biological models are required to establish their novel anticancer activity. Graphical Abstract

The non-selectivity of most chemotherapeutics have limited their use during therapy, one of such drug is 5- fluorouracil (5-FU), which is used extensively to treat cancer. Likewise, its side effects has reduced its clinical use. The ameliorative effect of Ethyl Acetate Leaf Extract of Carica papaya was evaluated in blood plasma following 5–fluorouracil-induced toxicity in male Wistar rats. Twenty-four male albino rats of Wistar strain were randomly allocated into four groups: Group A: control (animals injected with 0.1ml of normal saline daily for 21 days), Group B: 5–fluorouracil intoxicated rats (animals intoxicated with 18mg/kg b.wt of 5-fluorouracil intravenously at seven days interval), Group C: Ethyl Acetate Leaf Extract of Carica papaya treated rats (animal subjected to oral treatment of 100mg/kg b.wt of Ethyl Acetate Leaf Extract of Carica papaya daily) and challenged with 5-fluorouracil, and Group D: Ethyl Acetate Leaf Extract of Carica papaya (animals fed with Ethyl Acetate Leaf Extract of Carica papaya only). Hematological parameters such as white blood cell count (WBC), lymphocytes and platelet level, red blood cell count (RBC), hemoglobin (Hb) and packed cell volume (PCV were determined in the plasma. 5–fluorouracil significantly increased (P<0.05) the plasma level of WBC, lymphocyte and platelet while it decreased the plasma level of RBC, Hb and PCV. Treatment with Ethyl Acetate Leaf Extract of Carica papaya significantly decreased (P<0.05) the plasma level of WBC, lymphocyte and platelet, and increased the level of RBC, Hb and PCV. The results of the study showed that the use of 5-Fluorouracil induced oxidative stress and bone marrow toxicity due to its generation of free radicals. Administration of Ethyl Acetate Leaf Extract of Carica papaya significantly reversed the plasma effect of 5-Fluorouracil. Therefore, the protective mechanism of Ethyl Acetate Leaf Extract of Carica papaya might be due to its ameliorating and protecting property. It is therefore recommended that Ethyl Acetate Leaf Extract of Carica papaya intake should be encouraged in cancer chemotherapy.