Safety of Prolonged Exposure of Human Skin to Aqueous Ozone in a Test Hand Hygiene Model.

AIMS: This research assessed the safety of aqueous ozone (AO) on human skin after multiple exposures for up to 40 hours. METHODS AND RESULTS: Full thickness recombinant human skin (EpiDerm FT, EFT-400) was exposed to AO for 7 seconds per minute for the first 6 minutes of each hour, repeated hourly over four time periods (4, 10, 20 and 40 hours). An MTT assay assessed viability of skin cells after exposure, compared to incubator control, negative control and vehicle control (distilled water). No significant difference in tissue viability was found between the AO condition and any of the control conditions through 20 hours of exposures. At 40 hours of exposure, tissue viability was lower in the AO group when compared with negative control (p = 0.030) but not the other controls. CONCLUSIONS: The current study supports further consideration of repeated application of AO on human skin, such as for hand hygiene. IMPACT STATEMENT: The present research is the first well-controlled in vitro study assessing the cytotoxicity of repeated exposures of AO on a full-thickness human skin model. This information helps to inform the evaluation of AO as a potential alternative for hand and wound antisepsis.

In vitro inactivation of SARS-CoV-2 by ozonated water via novel hand hygiene device.

AIMS: The COVID-19 pandemic has heightened awareness of the need for novel surface disinfectants and hand-hygiene modalities. Ozone gas is an effective surface disinfectant, but toxicity limits its use in human applications. Ozonated water is a safer means to use ozone for disinfection, especially for human antisepsis. However, there are little data available regarding the effectiveness of ozonated water in eliminating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS AND RESULTS: This study utilizes a novel hand hygiene device that produces a stable ozone concentration of 0.5 +/-0.1 ppm in water and applies it using a proprietary spray that controls droplet size, velocity, and direction. The Device was used to apply ozonated water to a known quantity of SARS-CoV-2 Delta Variant viral particles on a non-porous surface (glass) for seven seconds. Post-exposure growth was compared to the unexposed matched control utilizing the Spearman-Karber method. Compared to control, ozonated water decreased SARS-CoV-2 viral growth by a mean log10 reduction of 4.33, or >99.99% reduction. CONCLUSIONS: These results suggest that the ozonated water, when applied by a spray hand hygiene device, is highly effective at surface disinfection of SARS-CoV-2.

Liquid ozone therapies for the treatment of epithelial wounds: A systematic review and meta-analysis.

Ozonated water and ozonated oils are emerging as potential therapies for wound care, but their efficacy has not been appropriately evaluated. The aim of this systematic review and meta-analysis was to evaluate the therapeutic potential of topical ozone in the treatment of mammalian wounds. A structured search of five scientific databases returned a total of 390 unique studies. Of these, 22 studies were included in this review. Four studies provided enough data to be included in a meta-analysis evaluating the time to complete wound healing. All studies were randomised controlled trials of humans or other mammalian animals that reported clinical signs of wound healing. Each study was critically analysed by a six-point assessment of the risk of bias. Wounds treated with topical ozone had a greater reduction in wound size than similar wounds treated with controls or standard of care in all studies. Those treated with ozonated liquids also had a shorter time to wound healing by approximately one week. In conclusion, topical ozone contributed to enhanced wound healing in all studies. While additional human experiments would be helpful to quantify ozone's specific effects on wound healing compared to standard treatment, topical ozone should be considered as part of an overall wound management strategy.

Risks of ozonated oil and ozonated water on human skin: A systematic review.

Ozonated water and oil are emerging as potential dermatologic therapeutics, particularly for the treatment of various wounds. However, the safety of these liquids has not been extensively studied. The aim of this systematic review was to evaluate the risks of ozonated liquids to human skin tissue based on the available literature. We completed a structured search of five scientific databases and identified 378 articles for consideration. Based on pre-established inclusion/exclusion criteria, nine studies were included in this review. Two studies specifically evaluated the cytotoxicity of ozonated liquids on human cells, five studies evaluated ozonated liquids in randomised controlled trials (RCTs), one was a post-market surveillance study, and one was a crossover study in humans. None of the included studies found any significant human dermatologic risks associated with ozonated water or liquid. Because of the small sample size, however, additional short- and long-term RCTs specifically designed to evaluate the dermatological risks of ozonated liquids are recommended.

Daedal Facets of Splice Modulator Optimization.

The spliceosome has been shown to be a promising target for the development of new anticancer therapeutics. Synthetic and chemical biological efforts directed toward the development of natural product-based splice modulators (SPLMs) have shown that the potency of these compounds derives from their ability to selectively affect the alternate splicing of apoptotic genes in tumor cells. However, questions remain regarding the mechanistic understanding of splice modulation as well as the selectivity with which SPLMs impact certain genes.

A Challenging Pie to Splice: Drugging the Spliceosome.

Since its discovery in 1977, the study of alternative RNA splicing has revealed a plethora of mechanisms that had never before been documented in nature. Understanding these transitions and their outcome at the level of the cell and organism has become one of the great frontiers of modern chemical biology. Until 2007, this field remained in the hands of RNA biologists. However, the recent identification of natural product and synthetic modulators of RNA splicing has opened new access to this field, allowing for the first time a chemical-based interrogation of RNA splicing processes. Simultaneously, we have begun to understand the vital importance of splicing in disease, which offers a new platform for molecular discovery and therapy. As with many natural systems, gaining clear mechanistic detail at the molecular level is key towards understanding the operation of any biological machine. This minireview presents recent lessons learned in this emerging field of RNA splicing chemistry and chemical biology.

A Carbohydrate-Derived Splice Modulator.

Small-molecule splice modulators have recently been recognized for their clinical potential for diverse cancers. This, combined with their use as tools to study the importance of splice-regulated events and their association with disease, continues to fuel the discovery of new splice modulators. One of the key challenges found in the current class of materials arises from their instability, where rapid metabolic degradation can lead to off-target responses. We now describe the preparation of bench-stable splice modulators by adapting carbohydrate motifs as a central scaffold to provide rapid access to potent splice modulators.

Optimized quinoline amino alcohols as disruptors and dispersal agents of Vibrio cholerae biofilms.

The biofilm state is an integral part of the lifecycle of many bacterial pathogens. Identifying inhibitors as molecular probes against bacterial biofilms has numerous potential biomedical applications. Here we report quinoline amino alcohol as a highly potent disruptor of V. cholerae biofilms. Additionally, was able to disperse preformed biofilms, an activity exhibited by few compounds with biofilm inhibiting activity.

Abyssomicin 2 reactivates latent HIV-1 by a PKC- and HDAC-independent mechanism.

Screening of a marine natural products library afforded three new analogues of the tetronic acid containing polyketide abyssomicin family and identified abyssomicin 2 as a selective reactivator of latent HIV virus. Examination of the mode of action of this new latent HIV reactivating agent demonstrated that it functions via a distinct mechanism compared to that of existing reactivating agents and is effective at reactivating latent virus in a subset of primary patient cell lines.

Development of quinoline-based disruptors of biofilm formation against Vibrio cholerae.

Biofilm formation is a major cause of bacterial persistence in nosocomial infections, leading to extended treatment times and increased rates of morbidity and mortality. Despite this, there are currently no biofilm inhibitors approved for clinical use. The synthesis and biological evaluation of a library of amino alcohol quinolines as lead compounds for the disruption of biofilm formation in Vibrio cholerae is now reported. Application of selective metal-halogen exchange chemistry installed both stereocenters in one step, to afford a simpler scaffold than the initial lead molecule, with an EC50 < 10 µM.