Network pharmacology and molecular docking-based identification of drug candidates and key targets of Allium sativum for colorectal cancer treatment.

Colorectal cancer (CRC) is a type of cancer with high morbidity and mortality in several developing and developed countries of the world. Its mortality and morbidity are predicted to increase over the next decade, hence, efforts aimed at combating it have remained unabated. In the context of its treatment, the use of chemotherapeutics is often limited by challenges including cost-ineffectiveness, side effects, and drug resistance. Hence, medicinal plants are actively being explored for alternatives. In this study, Allium sativum (A. sativum) was explored for the discovery of key compounds that are worthy of exploration in the context of CRC treatment and the potential mechanism of its anti-CRC effects. The bioactive compounds of A. sativum were retrieved and subjected to drug-likeness and pharmacokinetics properties evaluation, the putative targets of compounds with admirable properties were predicted using PharmMapper while the targets of CRC were retrieved from GeneCards. The interactions between the targets common to both were retrieved from the String database while Cytoscape software was used to visualize and analyze the interactions. Gene set enrichment analysis (GSEA) study revealed the biological processes and pathways A. sativum could potentially restore in CRC. These analyses revealed the key targets via which A. sativum compounds exert their anti-CRC properties, while molecular docking studies of the key compounds against the key targets revealed beta-sitosterol and alpha-bisabolene as the compounds with the highest binding affinity for the key targets. Ultimately, further experimental studies are needed to validate the findings of this study.Communicated by Ramaswamy H. Sarma.

Identification of a 1, 8-naphthyridine-containing compound endowed with the inhibition of p53-MDM2/X interaction signaling: a computational perspective.

Various studies have established that molecules specific for MDMX inhibition or optimized for dual inhibition of p53-MDM2/MDMX interaction signaling are more suitable for activating the Tp53 gene in tumor cells. Nevertheless, there are sparse numbers of approved molecules to treat the health consequences brought by the lost p53 functions in tumor cells. Consequently, this study explored the potential of a small molecule ligand containing 1, 8-naphthyridine scaffold to act as a dual inhibitor of p53-MDM2/X interactions using computational methods. The results obtained from quantum mechanical calculations revealed our studied compound entitled CPO is more stable but less reactive compared to standard dual inhibitor RO2443. Like RO2443, CPO also exhibited good non-linear optical properties. The results of molecular docking studies predicted that CPO has a higher potential to inhibit MDM2/MDMX than RO2443. Furthermore, CPO was stable over 50 ns molecular dynamics (MD) simulation in complex with MDM2 and MDMX respectively. On the whole, CPO also exhibited good drug-likeness and pharmacokinetics properties compared to RO2443 and was found with more anti-cancer activity than RO2443 in bioactivity prediction. CPO is anticipated to elevate effectiveness and alleviate drug resistance in cancer therapy. Ultimately, our results provide an insight into the mechanism that underlay the inhibition of p53-MDM2/X interactions by a molecule containing 1, 8-naphthyridine scaffold in its molecular structure.

Comparative study of the reproductive toxicity and modulation of enzyme activities by crude oil-contaminated soil before and after bioremediation.

Contamination of soil with crude oil is a serious ecological problem with potential adverse public health effects. This study assessed the germ cell toxicity of simulated leachates from crude oil-contaminated soil before and after bioremediation using the murine sperm abnormality assay, sperm count, and testes histopathology. The levels of Total Testosterone (TT), Follicle Stimulating Hormone (FSH), and Luteinizing Hormone (LH); and activities of catalase (CAT), alkaline phosphatase (ALP), superoxide dismutase (SOD), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. The physicochemical, Total Petroleum Hydrocarbon (TPH), and heavy metal analyses of the leachates were also carried out. Male mice were exposed to 50, 25, 10, 5, and 1% (v/v; leachate:distilled water) of the leachate samples for five consecutive days, and were sacrificed after 35 days. The result showed a statistically significant (p < 0.05), concentration-dependent increase in abnormal sperm cells in exposed mice, with aberrations such as folded sperm, amorphous head, wrong tail attachment, distal droplet, no hook, and looped tail. Data further showed a concentration-dependent significant reduction in mean sperm count in the exposed mice. Alterations of seminiferous tubules with different lesions and activities of ALT, AST, ALP, FSH, LH, and TT were also recorded. The high level of selected heavy metals (As, Cr, Cd, Cu, and Pb) and TPH was believed to contribute to the observed reproductive toxicity and modulated enzyme activities in the treated mice. It is therefore concluded that the microbial remediation of the crude oil contaminated soil produced a reduction in the levels of heavy metals and TPH in the soil, reduced reproductive toxicity, and modulation of enzyme activities. However, the induced reproductive toxicity by the bioremediated soil is still significant, hence, further work could be done to employ a consortium of bacteria and extend the period of the bioremediation process to ensure complete removal of the contaminants.

In silico design and validation of a highly degenerate primer pair: a systematic approach.

BACKGROUND: The techniques of amplifying genetic materials have enabled the extensive study of several biological activities outside the biological milieu of living systems. More recently, this approach has been extended to amplify population of genes, from evolutionarily related gene family for detection and evaluation of microbial consortial with several unique potentialities (e.g., enzymatic degradability). Conceivably, primer mixtures containing substitutions of different bases at specific sites (degenerate primers) have enabled the amplification of these genes in PCR reaction. However, the degenerate primer design problem (DPD) is a constraint to designing this kind of primer. To date, different algorithms now exist to solve various versions of DPD problem, many of which, only few addresses and satisfy the criteria to design primers that can extensively cover high through-put sequences while striking the balance between specificity and efficiency. The highly degenerate primer (HYDEN) design software program primarily addresses this variant of DPD problem termed "maximum coverage-degenerate primer design (MC-DPD)" and its heuristics have been substantiated for optimal efficiency from significant successes in PCR. In spite of the premium presented for designing degenerate primers, literature search has indicated relatively little use of its heuristics. This has been thought to result from the complexity of the program since it is run only by command-line, hence limiting its accessibility. To solve this problem, researchers have optionally considered the manual design of degenerate primers or design through software programs that provides accessibility through a graphical user interface (GUI). Realizing this, we have attempted in this study to provide a user-friendly approach for researchers with little or no background in bioinformatics to design degenerate primers using HYDEN RESULTS: Virtual Tests of our designed degenerate primer pair through in silico PCR substantiated the correspondence between efficiency and coverage with the target sequences as pre-defined by the initial HYDEN output, thereby validating the potentials of HYDEN to effectively solve the MC-DPD problem. Additionally, the designed primer-pair mechanistically amplified all sequences used as a positive control with no amplification observed in the negative controls. CONCLUSION: In this study, we provided a turnkey protocol to simplify the design of degenerate primers using the heuristics of the HYDEN software program.