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BioRxiv : the Preprint Server For... May 2024Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen This peptide is a key virulence factor in mouse models of mucosal and hematogenously...
Candidalysin is a cytolytic peptide produced by the opportunistic fungal pathogen This peptide is a key virulence factor in mouse models of mucosal and hematogenously disseminated candidiasis. Despite intense interest in the role of candidalysin in pathogenicity, its host cell targets have remained elusive. To fill this knowledge gap, we performed a genome-wide loss-of-function CRISPR screen in a human oral epithelial cell line to identify specific host factors required for susceptibility to candidalysin-induced cellular damage. Among the top hits were , and , genes that function in glycosaminoglycan (GAG) biosynthesis. Deletion of these genes led to the absence of GAGs such as heparan sulfate on the epithelial cell surface and increased resistance to damage induced by both candidalysin and live Biophysical analyses including surface plasmon resonance and atomic force and electron microscopy indicated that candidalysin physically binds to sulfated GAGs, facilitating its oligomerization or enrichment on the host cell surface. The addition of exogenous sulfated GAGs or the GAG analogue dextran sulfate protected cells against candidalysin-induced damage. Dextran sulfate, but not non-sulfated dextran, also inhibited epithelial cell endocytosis of and fungal-induced epithelial cell cytokine and chemokine production. In a murine model of vulvovaginal candidiasis, topical dextran sulfate administration reduced host tissue damage and decreased intravaginal IL-1β and neutrophil levels. Collectively, these data indicate that GAGs are epithelial cell targets of candidalysin and can be used therapeutically to protect cells from candidalysin-induced damage.
PubMed: 38826446
DOI: 10.1101/2024.05.23.595417 -
Journal of the European Academy of... Jun 2024Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to...
INTRODUCTION
Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early.
OBJECTIVES
The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects.
MATERIALS AND METHODS
The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives.
RESULTS
Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases.
CONCLUSIONS
LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.
PubMed: 38822598
DOI: 10.1111/jdv.20083 -
Journal of the European Academy of... Jun 2024Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to...
INTRODUCTION
Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early.
OBJECTIVES
The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects.
MATERIALS AND METHODS
The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives.
RESULTS
Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases.
CONCLUSIONS
LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.
PubMed: 38822578
DOI: 10.1111/jdv.20082 -
Journal of Microbiology (Seoul, Korea) May 2024Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse...
Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C. albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C. albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C. albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management.
PubMed: 38819759
DOI: 10.1007/s12275-024-00134-z -
Taiwanese Journal of Obstetrics &... May 2024The present study aims to conduct a comprehensive meta-analysis of randomized controlled trials (RCTs) investigating the efficacy of probiotics as an adjunct treatment... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The present study aims to conduct a comprehensive meta-analysis of randomized controlled trials (RCTs) investigating the efficacy of probiotics as an adjunct treatment for preventing and treating gynecological infections.
MATERIALS AND METHODS
The study adopted a systematic review of scientific databases including PubMed, Cochrane, and EMBASE, using defined MeSH terms. The inclusion and exclusion criteria were set to refine the search, with the data extraction and quality assessment being conducted by two independent investigators.
RESULTS
A total of 35 articles, comprising 3751 patients, were included in the meta-analysis. The application of probiotics demonstrated a notable increase in the cure rates of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) as compared to control groups. A significant BV cure rate (OR: 5.972; 95% CI: 2.62-13.59; p-value: 0.01) was noted with probiotic use, which was even more pronounced when used as an adjunctive treatment with antibiotics (OR: 2.504; 95% CI: 1.03-6.06; p-value: 0.04). Additionally, probiotic use significantly reduced the recurrence rates of BV (OR: 0.34; 95% CI: 0.167-0.71; p-value: 0.004). For VVC, a significant increase in the cure rate was observed in the probiotic group (OR: 3.425; 95% CI: 2.404-4.879; p-value: 0.01), along with a lower recurrence rate (OR: 0.325; 95% CI: 0.175-0.606; p-value: 0.01).
CONCLUSION
Our findings underscore the potential role of probiotics as a beneficial adjunctive treatment for gynecological infections, indicating an improved cure rate and decreased recurrence. However, additional well-designed studies are necessary to corroborate these findings.
Topics: Humans; Probiotics; Female; Vaginosis, Bacterial; Candidiasis, Vulvovaginal; Randomized Controlled Trials as Topic; Anti-Bacterial Agents; Treatment Outcome; Combined Modality Therapy; Recurrence
PubMed: 38802199
DOI: 10.1016/j.tjog.2024.03.004 -
Pharmaceuticals (Basel, Switzerland) May 2024The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes...
Transcriptomics Reveals Effect of Decoction Butanol Extract in Alleviating Vulvovaginal Candidiasis by Inhibiting Neutrophil Chemotaxis and Activation via TLR4 Signaling.
The Pulsatilla decoction is a well-known herbal remedy used in clinical settings for treating vulvovaginal candidiasis (VVC). However, the specific mechanism that makes it effective is still unclear. Recent studies have shown that in cases of VVC, neutrophils recruited to the vagina, influenced by heparan sulfate (HS), do not successfully engulf (). Instead, they release many inflammatory factors that cause damage to the vaginal mucosa. This study aims to understand the molecular mechanism by which the n-butanol extract of Pulsatilla decoction (BEPD) treats VVC through transcriptomics. High-performance liquid chromatography was used to identify the primary active components of BEPD. A VVC mouse model was induced using an estrogen-dependent method and the mice were treated daily with BEPD (20 mg/kg, 40 mg/kg, and 80 mg/kg) for seven days. The vaginal lavage fluid of the mice was analyzed for various experimental indices, including fungal morphology, fungal burden, degree of neutrophil infiltration, and cytokines. Various assessments were then performed on mouse vaginal tissues, including pathological assessment, immunohistochemistry, immunofluorescence, Western blot (WB), quantitative real-time PCR, and transcriptome assays. Our results showed that BEPD reduced vaginal redness and swelling, decreased white discharge, inhibited hyphae formation, reduced neutrophil infiltration and fungal burden, and attenuated vaginal tissue damage compared with the VVC model group. The high-dose BEPD group even restored the damaged vaginal tissue to normal levels. The medium- and high-dose groups of BEPD also significantly reduced the levels of IL-1β, IL-6, TNF-α, and LDH. Additionally, transcriptomic results showed that BEPD regulated several chemokine (CXCL1, CXCL3, and CXCL5) and S100 alarmin (S100A8 and S100A9) genes, suggesting that BEPD may treat VVC by affecting chemokine- and alarmin-mediated neutrophil chemotaxis. Finally, we verified that BEPD protects the vaginal mucosa of VVC mice by inhibiting neutrophil recruitment and chemotaxis in an animal model of VVC via the TLR4/MyD88/NF-κB pathway. This study provides further evidence to elucidate the mechanism of BEPD treatment of VVC.
PubMed: 38794163
DOI: 10.3390/ph17050594 -
Tropical Medicine and Infectious Disease May 2024Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives.... (Review)
Review
Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all spp., remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal-fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.
PubMed: 38787047
DOI: 10.3390/tropicalmed9050114 -
Journal of Fungi (Basel, Switzerland) May 2024The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected...
The United Arab Emirates has very little data on the incidence or prevalence of fungal diseases. Using total and underlying disease risk populations and likely affected proportions, we have modelled the burden of fungal disease for the first time. The most prevalent serious fungal conditions are recurrent vulvovaginitis (~190,000 affected) and fungal asthma (~34,000 affected). Given the UAE's low prevalence of HIV, we estimate an at-risk population of 204 with respect to serious fungal infections with cryptococcal meningitis estimated at 2 cases annually, 15 cases of pneumonia (PCP) annually, and 20 cases of esophageal candidiasis in the HIV population. PCP incidence in non-HIV patients is estimated at 150 cases annually. Likewise, with the same low prevalence of tuberculosis in the country, we estimate a total chronic pulmonary aspergillosis prevalence of 1002 cases. The estimated annual incidence of invasive aspergillosis is 505 patients, based on local data on rates of malignancy, solid organ transplantation, and chronic obstructive pulmonary disease (5.9 per 100,000). Based on the 2022 annual report of the UAE's national surveillance database, candidaemia annual incidence is 1090 (11.8/100,000), of which 49.2% occurs in intensive care. Fungal diseases affect ~228,695 (2.46%) of the population in the UAE.
PubMed: 38786708
DOI: 10.3390/jof10050353 -
Ethiopian Journal of Health Sciences Sep 2023Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vulvovaginal candidiasis is one of the most common vaginal infections worldwide. We conducted this systematic review and meta-analysis to determine the effect of probiotics in the treatment of vulvovaginal candidiasis.
METHODS
A comprehensive search of databases including PubMed, Scopus, Cochrane, Scientific Information Database (SID), IranMedex, and Google Scholar search engine was performed. The search was conducted from inception to 1 October 2022, to identify published English or Persian language randomized control trials (RCTs) of women with vulvovaginal candidiasis who received probiotics as medical treatment. The quality of the included studies was assessed using the Oxford Center for Evidence Based Medicine checklist All statistical analyses were performed using Comprehensive Meta-analysis (CMA) version 2.
RESULTS
Six RCTs were included in this review. The results showed that treatment with probiotic was not different from placebo regarding the rate of positive culture (OR: 1.12; 95% CI: 0.390 to 3.26, P=0.825); treatment with probiotic was more effective compared to placebo regarding the rate of recurrence. (OR: 0.14; P= 0.01; 95 % CI: 0.028-0.7).
CONCLUSION
Probiotics have a beneficial effect in the treatment of women with vulvovaginal candidiasis. Our results provide evidence for an alternative treatment modality for vaginal candidiasis using probiotics.
Topics: Candidiasis, Vulvovaginal; Probiotics; Humans; Female; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38784519
DOI: 10.4314/ejhs.v33i5.18 -
Obstetrics and Gynecology Clinics of... Jun 2024Mindfulness is defined as present-moment, nonjudgmental awareness. By reducing self-criticism, and depression, and increasing self-compassion, attention, and... (Review)
Review
Mindfulness is defined as present-moment, nonjudgmental awareness. By reducing self-criticism, and depression, and increasing self-compassion, attention, and interoceptive awareness, mindfulness has been found across a variety of systematic reviews and meta-analyses to significantly improve sexual desire, sexual pain, and sex-related distress. It helps individuals connect with their bodies, fostering a deeper understanding of sensations and desires while reducing the focus on negative, judgmental, and catastrophic sex-related and pain-related thoughts. By teaching individuals to focus on bare sensations, mindfulness has also been found to significantly reduce vulvovaginal pain intensity with improvements retained a year later.
Topics: Humans; Female; Mindfulness; Vulvodynia; Sexual Dysfunctions, Psychological; Libido; Pain Management; Dyspareunia
PubMed: 38777483
DOI: 10.1016/j.ogc.2024.02.002