Gastric cancer ranks as the fifth-leading contributor to global cancer incidence and the fourth-highest in terms of cancer-related mortality. Helicobacter pylori (H. pylori) infection leads to inflammation and ulceration, atrophic and chronic gastritis, and eventually, increases the risk of developing gastric adenocarcinoma. In this paper, we delve into the combined impact of a high-salt diet (HSD) and concurrent H. pylori infection, which act as predisposing factors for gastric malignancy. A multitude of mechanisms come into play, fostering the development of gastric adenocarcinoma due to the synergy between an HSD and H. pylori colonization. These encompass the disruption of mucosal barriers, cellular integrity, modulation of H. pylori gene expression, oxidative stress induction, and provocation of inflammatory responses. On the whole, gastric cancer patients were reported to have a higher median sodium intake with respect to healthy controls. H. pylori infection constitutes an additional risk factor, with a particular impact on the population with the highest daily sodium intake. Consequently, drawing from epidemiological discoveries, substantial evidence suggests that diminishing salt intake and employing antibacterial therapeutics could potentially lower the susceptibility to gastric cancer among individuals.

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects.

Cataracts, an eye lens clouding disease, are debilitating and while operable, remain without a cure. αA66-80 crystallin peptide abundant in cataracted eye lenses contributes to aggregation of αA-crystallin protein leading to cataracts. Inspired by the versatility of macrocycles and programmable guest selectivity through discrete functionalizations, we report on three water-soluble ionic resorcinarene receptors (A, B, and C) that disrupt the aggregation of αA66-80 crystallin peptide. A and B each possess four anionic sulfonate groups, while C includes four cationic ammonium groups with four flexible extended benzyl groups. Through multiple non-covalent attractions, these receptors successfully disrupt and reverse the aggregation of αA66-80 crystallin peptide, which was studied through spectroscopic, spectrometric, calorimetric, and imaging techniques. The αA66-80·receptor complexes were also explored using molecular dynamics simulation, and binding energies were calculated. Even though each of the three receptors can bind with the peptide, receptor C was characterized by the highest binding energy and affinity for three different domains of the peptide. In effect, the most efficient inhibitor was a cationic receptor Cvia extended aromatic interactions. These results highlight the potential of versatile and tunable functionalized resorcinarenes as potential therapeutics to reverse the aggregation of α-crystallin dominant in eye cataracts.

Copper (Cu) and zinc (Zn) metal ions play important roles in the proper functioning and localization of neurological proteins, such as transactive response DNA-binding protein 43 (TDP-43), which is linked to amyotrophic lateral sclerosis (ALS). Previous experimental and computational studies have identified putative Zn-binding regions within the RNA recognition motif 1 (RRM1) of TDP-43. However, Cu-binding interactions have been less explored despite their redox activity in regulating thiol (C173/175) conversion to disulfide within the RRM1 domain, influencing protein structure and function. Herein, the structural characterization and fragmentation pattern analysis of a TDP-43 decapeptide (166-HMIDGRWCDC-175), within RRM1, coordinated to Cu(II) and Zn(II) ions using electrospray ionization tandem mass spectrometry (ESI-MS/MS) was conducted under non-denaturing conditions. Higher-energy collision dissociation (HCD) fragmentation analysis identified that Cu(II) prefers His/Met residues, while Zn(II) was weakly coordinated to various binding sites in the peptide, specifically His, Met, Glu, Cys, Trp and Asp residues. Computational modeling using a metal ion binding server (MIB2) confirmed the binding sites and coordination sphere of metal-peptide complexes. No significant coordination to C173 and C175 was observed with Cu or Zn, as identified by using a double Cys mutant peptide. A complete thiol-to-disulfide conversion was observed in the presence of Cu(II)/(I) only, which was confirmed by the comparison of a preformed intramolecular disulfide peptide. Overall, unique differential coordination environments were observed for each metal ion with the peptide. The study provides new insights into metal ion interactions with TDP-43 RRM1 peptide, leading to a greater understanding of metal homeostasis in TDP-43 protein biochemistry and neurodegeneration.