Hypoxia-inducible factors (HIFs) are transcription factors that activate the transcription of genes necessary to circumvent to hypoxic (low oxygen level) environments. In carcinogenesis, HIFs play a critical role. Indeed, HIF-1α has been validated as a promising target for novel cancer therapeutics, even as clinical investigations have linked increased levels of HIF-1α with aggressive cancer progression as well as poor patient prognosis. More so, inhibiting HIF-1 activity restricted cancer progression. Therefore, HIF-1 is a viable target for cancer therapy. This may be expected considering the fact that cancer cells are known to be hypoxic. In order to survive the hypoxic microenvironment, cancer cells activate several biochemical pathways via the HIF-1α. Additionally, cellular and molecular insights have proved prospects of the HIF-1α pathway for the development of novel anticancer treatment strategies. The biochemical importance of hypoxia-inducible factors (HIFs) cannot be overemphasized as carcinogenesis, cancer progression, and HIFs are intricately linked. Therefore, this review highlights the significance of these linkages and also the prospects of HIFs as an alternative source of cancer therapies.

Colorectal cancer (CRC) is one of the most common and reoccurring diseases, as well as the world’s second largest cause of mortality. Despite existing preventative, diagnostic, and treatment methods, such as chemotherapy, the number of instances rises year after year. As a result, new effective medications targeting specific checkpoints should be developed to combat CRC. Natural compounds, such as curcumin, have shown significant anti-colorectal cancer characteristics among medications that can be used to treat CRC. These chemicals are phenolic compounds that belong to the curcuminoids category. Curcumin exerts its anti-proliferative properties against CRC cell lines in vitro and in vivo via a variety of mechanisms, including the suppression of intrinsic and extrinsic apoptotic signaling pathways, the stoppage of the cell cycle, and the activation of autophagy. Curcumin also has anti-angiogenesis properties. Thus, this review is aimed at emphasizing the biological effect and mode of action of curcumin on CRC. Furthermore, the critical role of these substances in CRC chemoprevention was emphasized.

Reproductive dysfunction is often characterized by malfunction of the reproductive tissues, which may lead to disruption of the synergistic rhythm that should bring about a progression of sexual events and the conception of new life. This may therefore result in the sexual dysfunction and infertility that can be seen in couples having prolonged biological difficulty in reproducing their offspring after having unrestricted sexual intercourse for at least twelve months. Several factors have been implicated in the cause and progression of reproductive dysfunction, including poor nutrition, drug side effects, disease states, and toxicant ingestion. A well-known food additive that has been found to be potent at initiating reproductive anomalies in males is monosodium glutamate (MSG). This regular flavor enhancer is widely used as a taste enhancer in several diets. The different mechanisms by which it may induce reproductive dysfunctions include spermatogenic alteration resulting in a low sperm count, high sperm abnormality, reduced live sperm and decreased sperm pH, oxidative damage (increased lipid peroxidation and reduced antioxidant enzyme activities), histological alteration (blood hemorrhage, distorted germ and Sertoli cells), as well as gonadotropin imbalance (reduced testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations). Therefore, this review discusses various established mechanisms through which MSG may induce reproductive dysfunction and the treatment strategies to ameliorate its toxic effects.

Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm and hypercytokinemia due to activation the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon gamma (INF-γ), while inhibiting IL-33 expression . Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.

Owing to the urgent need for therapeutic intervention against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potential of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C11 scored highest against all targets. C15 scored highest against Spro and C16 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 – ASP 289 – GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies.