Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene expression, and aberrant DNA methylation patterns are considered a hallmark of cancer. The human diet is a source of micronutrients, bioactive molecules, and mycotoxins that have the ability to alter DNA methylation patterns and are thus a contributing factor for both the prevention and onset of cancer. Micronutrients such as betaine, choline, folate, and methionine serve as cofactors or methyl donors for one-carbon metabolism and other DNA methylation reactions. Dietary bioactive compounds such as curcumin, epigallocatechin-3-gallate, genistein, quercetin, resveratrol, and sulforaphane reactivate essential tumor suppressor genes by reversing aberrant DNA methylation patterns, and therefore, they have shown potential against various cancers. In contrast, fungi-contaminated agricultural foods are a source of potent mycotoxins that induce carcinogenesis. In this review, we summarize the existing literature on dietary micronutrients, bioactive compounds, and food-borne mycotoxins that affect DNA methylation patterns and identify their potential in the onset and treatment of cancer.
β-lactams are the most prescribed class of antibiotics
due
to their potent, broad-spectrum antimicrobial activities. However,
alarming rates of antimicrobial resistance now threaten the clinical
relevance of these drugs, especially for the carbapenem-resistant Enterobacterales expressing metallo-β-lactamases
(MBLs). Antimicrobial agents that specifically target these enzymes
to restore the efficacy of last resort β-lactam drugs, that
is, carbapenems, are therefore desperately needed. Herein, we present
a cyclic zinc chelator covalently attached to a β-lactam scaffold
(cephalosporin), that is, BP1. Observations from in vitro assays (with
seven MBL expressing bacteria from different geographies) have indicated
that BP1 restored the efficacy of meropenem to ≤ 0.5 mg/L,
with sterilizing activity occurring from 8 h postinoculation. Furthermore,
BP1 was nontoxic against human hepatocarcinoma cells (IC50 > 1000 mg/L) and exhibited a potency of (K
iapp) 24.8 and 97.4 μM against Verona integron-encoded
MBL (VIM-2) and New Delhi metallo β-lactamase (NDM-1), respectively.
There was no inhibition observed from BP1 with the human zinc-containing
enzyme glyoxylase II up to 500 μM. Preliminary molecular docking
of BP1 with NDM-1 and VIM-2 sheds light on BP1’s mode of action.
In Klebsiella pneumoniae NDM infected
mice, BP1 coadministered with meropenem was efficacious in reducing
the bacterial load by >3 log10 units’ postinfection.
The findings herein propose a favorable therapeutic combination strategy
that restores the activity of the carbapenem antibiotic class and
complements the few MBL inhibitors under development, with the ultimate
goal of curbing antimicrobial resistance.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.
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