ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model

by Ravi Jothi, Seong-Tshool Hong, Munkhtur Enkhtsatsral, Shunmugiah Karutha Pandian, Shanmugaraj Gowrishankar

Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing Candida species viz., C. albicans, C. tropicalis and C. glabrata. Furthermore, the study validates 3BP’s therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing >99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 μg/mL against all tested Candida spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all Candida strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of Candida spp., achieving a maximum eradication level of 90%. Toxicity/safety profiling in both in vitro erythrocyte lysis and in vivo Galleria mellonella survival assay authenticated the non-toxic nature of 3BP up to 512 μg/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against Candida species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.

Insights of healthcare professionals regarding waterbirths and water immersion during labour: A mixed studies review

Abstract

Aim

To consolidate healthcare professionals' insights about waterbirths and water immersion during labour.

Design

Mixed studies review.

Data Sources

Seven electronic databases were searched from their inception dates till June 2023: PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, ProQuest Dissertations and Theses Global.

Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and Pluye and Hong's mixed studies review framework guided this review. The quality of included studies was evaluated using the Mixed Methods Appraisal Tool. Findings were synthesized using the convergent qualitative synthesis method, and results were thematically analysed using Braun and Clarke's framework.

Results

Three main themes were identified from the 22 included studies: (1) believing in waterbirths, (2) opposing forces and (3) plotting the course ahead.

Conclusion

Healthcare professionals reported different views about waterbirths and water immersion practices; midwives were most likely to support these practices, followed by nurses and lastly, few physicians supported them. Reasons for opposing waterbirths include insufficient training and support from colleagues as well as concerns about work efficiency, waterbirth safety and litigation issues.

Impact

The available evidence suggests the need to provide waterbirth training for healthcare professionals, equip healthcare facilities with necessary waterbirth-related infrastructure and develop appropriate waterbirth policies/guidelines. Healthcare professionals could also consider providing antenatal waterbirth education to women and obtain women's feedback to improve current policies/guidelines. Future research should explore the views of different types of healthcare professionals from more diverse cultures.

Reporting Method

The PRISMA guidelines.

No Patient or Public Contribution

Systematic review.