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      Cold atmospheric plasma therapy for Malassezia folliculitis: Laboratory investigations and a randomized clinical trial

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          Abstract

          Background

          Current treatment options for Malassezia folliculitis (MF) are limited. Recent research has demonstrated the inhibitory effect of cold atmospheric plasma (CAP) on the growth of Malassezia pachydermatis in vitro, suggesting CAP as a potential therapeutic approach for managing MF.

          Objectives

          The objective of our study is to assess the in vitro antifungal susceptibility of Malassezia yeasts to CAP. Additionally, we aim to evaluate the efficacy and tolerability of CAP in treating patients with MF.

          Methods

          We initially studied the antifungal effect of CAP on planktonic and biofilm forms of Malassezia yeasts, using well‐established techniques such as zone of inhibition, transmission electron microscopy, colony count assay and 2,3‐bis(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide salt assay. Subsequently, a randomized (1:1 ratio), active comparator‐controlled, observer‐blind study was conducted comparing daily CAP therapy versus itraconazole 200 mg/day for 2 weeks in 50 patients with MF. Efficacy outcomes were measured by success rate, negative microscopy rate and changes in Dermatology Life Quality Index (DLQI) and Global Aesthetic Improvement Scale (GAIS) scores. Safety was assessed by monitoring adverse events (AEs) and local tolerability.

          Results

          In laboratory investigations, CAP time‐dependently inhibited the growth of Malassezia yeasts in both planktonic and biofilm forms. Forty‐nine patients completed the clinical study. At week 2, success was achieved by 40.0% of subjects in the CAP group versus 58.3% in the itraconazole group ( = 0.199). The negative direct microscopy rates of follicular samples were 56.0% in the CAP group versus 66.7% in the itraconazole group ( p = 0.444). No significant differences were found in the proportion of subjects achieving DLQI scores of 0/1 ( p = 0.456) or in the GAIS responder rates ( p = 0.588) between the two groups. Three patients in the CAP group and one patient in the itraconazole group reported mild AEs.

          Conclusion

          CAP demonstrated significant antifungal activity against Malassezia yeasts in vitro and exhibited comparable efficacy to itraconazole in treating MF patients. Without the associated adverse effects of oral antifungal drugs, CAP can be considered a promising and safe treatment modality for MF.

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          Most cited references23

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          Biogeography and individuality shape function in the human skin metagenome

          Summary The varied topography of human skin offers a unique opportunity to study how the body’s microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here, metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal, and viral communities, which showed not only site-specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalog, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes, and strain tracking and defines the dual influence of biogeography and individuality on microbial composition and function.
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            Fungal Biofilm Resistance

            Fungal biofilm infections have become increasingly recognised as a significant clinical problem. One of the major reasons behind this is the impact that these have upon treatment, as antifungal therapy often fails and surgical intervention is required. This places a large financial burden on health care providers. This paper aims to illustrate the importance of fungal biofilms, particularly Candida albicans, and discusses some of the key fungal biofilm resistance mechanisms that include, extracellular matrix (ECM), efflux pump activity, persisters, cell density, overexpression of drug targets, stress responses, and the general physiology of the cell. The paper demonstrates the multifaceted nature of fungal biofilm resistance, which encompasses some of the newest data and ideas in the field.
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              Malassezia -Associated Skin Diseases, the Use of Diagnostics and Treatment

              Yeasts of the genus, Malassezia, formerly known as Pityrosporum, are lipophilic yeasts, which are a part of the normal skin flora (microbiome). Malassezia colonize the human skin after birth and must therefore, as commensals, be normally tolerated by the human immune system. The Malassezia yeasts also have a pathogenic potential where they can, under appropriate conditions, invade the stratum corneum and interact with the host immune system, both directly but also through chemical mediators. The species distribution on the skin and the pathogenetic potential of the yeast varies between different Malassezia related diseases such as head and neck dermatitis, seborrheic dermatitis, pityriasis versicolor, and Malassezia folliculitis. The diagnostic methods used to confirm the presence of Malassezia yeasts include direct microcopy, culture based methods (often a combination of morphological features of the isolate combined with biochemical test), molecular based methods such as Polymerase Chain Reaction techniques, and Matrix Assisted Laser Desorption/Ionization—Time Of Flight mass spectrometry and the chemical imprint method Raman spectroscopy. Skin diseases caused by Malassezia are usually treated with antifungal therapy and if there are associated inflammatory skin mechanisms this is often supplemented by anti-inflammatory therapy. The aim of this paper is to provide an overview of Malassezia related skin disease, diagnostic methods and treatment options.
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                Author and article information

                Contributors
                yangchunjun9@163.com
                Journal
                Skin Res Technol
                Skin Res Technol
                10.1111/(ISSN)1600-0846
                SRT
                Skin Research and Technology
                John Wiley and Sons Inc. (Hoboken )
                0909-752X
                1600-0846
                09 July 2024
                July 2024
                : 30
                : 7 ( doiID: 10.1111/srt.v30.7 )
                : e13850
                Affiliations
                [ 1 ] Department of Dermatology and Venereology the Second Affiliated Hospital of Anhui Medical University Hefei China
                [ 2 ] The First Clinical College of Anhui Medical University Hefei China
                Author notes
                [*] [* ] Correspondence

                Chunjun Yang, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.

                Email: yangchunjun9@ 123456163.com

                Author information
                https://orcid.org/0000-0002-4337-6337
                https://orcid.org/0000-0003-1887-7735
                Article
                SRT13850
                10.1111/srt.13850
                11232053
                38979986
                974777ac-f793-4b3e-8055-6cb294d7a36b
                © 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 June 2024
                : 21 June 2024
                Page count
                Figures: 5, Tables: 2, Pages: 10, Words: 5156
                Funding
                Funded by: Research Fund of Anhui Medical University
                Award ID: 2019xkj033
                Categories
                Original Article
                Original Article
                Custom metadata
                2.0
                July 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:09.07.2024

                antifungal agents,cold atmospheric plasma,itraconazole,malassezia, malassezia folliculitis

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