Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant”. After 70 years, we are witnessing the fulfilment of Fleming’s prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections.

Thymosin β4 (Tβ4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tβ4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron²⁺ and iron³⁺ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tβ4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tβ4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.

(1) Background: Ozone (O3) proved to oxidize organic and inorganic compounds, and its efficacy against bacteria, viruses and fungi plasma membranes was of interest. Ozone vehicle can be a gaseous form, ozonated water or ozonized oil. The aim of this in-vitro study was to evaluate the efficacy of ozonated olive oil against Streptococcus mutans. (2) Methods: Two different commercial mouthwashes were tested: Ialozon Blu (IB) (Gemavip, Cagliari, Italy), with ozonated olive oil, and Ialozon Rose (IR) (Gemavip, Cagliari, Italy), with ozonated olive oil, hyaluronic acid and vitamin E. All formulates were analyzed in a dilution range from 2- to 256-folds in saline solution, as to reproduce the salivary dilution. Streptococcus mutans CIP103220 strain was used for the antimicrobial susceptibility test, and the Kirby–Bauer inhibition method was performed to evaluate the Minimum Inhibitory (MIC), Minimum Bactericidal (MBC), and Minimum Biofilm Inhibitory Concentration (MBIC). (3) Results: Both formulates showed the same antimicrobial activity. MIC, MBC, and MBIC were observed for dilution factors of 1/32, 1/8 and 1/8, respectively. The mean value of inhibition zone diameter was 16.5 mm for IB, and 18 mm for IR. (4) Conclusions: The results suggested that ozonized olive oil formulates were able to inactivate Streptococcus mutans avoiding the salivary dilution effect in the oral cavity.

Background: Fusobacterium nucleatum is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in tumor progression and resistance to chemotherapy. The mechanism by which it transforms from a commensal to a pathogen remains unknown. For this reason, we investigated the role of oxidative status as an initiatory factor in changing the bacterium’s pathogenicity profile. Methods: A clinical strain of F. nucleatum subsp. animalis biofilm was exposed to different oxidative stress levels through varying subinhibitory amounts of H₂O₂. Subsequently, we investigated the bacterium’s behavior in vitro by infecting the HT-29 cell line. We evaluated bacterial colonization, volatile sulfur compounds production, and the infected cell’s oxidative status by analyzing HMOX1, pri-miRNA 155, and 146a gene expression. Results: The bacterial colonization rate, dimethyl sulfide production, and pri-miRNA 155 levels all increased when stressed bacteria were used, suggesting a predominant pathogenic function of these strains. Conclusions: The response of F. nucleatum to different oxidative conditions could potentially explain the increase in its pathogenic traits and the existence of environmental factors that may trigger the bacterium’s pathogenicity and virulence.

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC₅₀ value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management.