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Microbiological Research Jun 2024Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to...
Candida albicans is the most leading cause of life-threatening fungal invasive infections, especially for vulvovaginal candidiasis (VVC). Resistance and tolerance to common fungicide has risen great demands on alternative strategies for treating C. albicans infections. In the present study, ferroptosis has been proven to occur in C. albicans by directly exposed to FeSO via induing hallmarks of ferroptosis, including Fe overload burden, ROS eruption and lipid peroxidation. Transcriptomic profile gave the great hints of the possible mechanism for fungal ferroptosis that FeSO disturb pathways associated to ribosome, tyrosine metabolism, triglyceride metabolism and thiamine metabolism, thus mobilizing death-related gene synthesis. Inspired by the results, a FeSO-loaded hydrogel was prepared as an antifungal agent to treat C. albicans infection. This hydrogel exhibited excellent dressing properties and maintained superior antifungal activity by characterization tests. Besides, mice treated by this composite hydrogel displayed excellent therapeutic efficacy. These results highlighted the potential therapeutic use of FeSO as an innovative strategy in treating C. albicans infections by targeting ferroptosis.
Topics: Humans; Female; Animals; Mice; Candidiasis, Vulvovaginal; Candida albicans; Ferroptosis; Antifungal Agents; Hydrogels; Microbial Sensitivity Tests; Ferrous Compounds
PubMed: 38554652
DOI: 10.1016/j.micres.2024.127704 -
Mycoses Apr 2024Recurrent vulvovaginal candidiasis (RVVC) is an important and underestimated fungal infection.
Patients with recurrent vulvovaginal candidiasis exhibit a decrease in both the fungicidal activity of neutrophils and the proliferation of peripheral blood mononuclear cells.
BACKGROUND
Recurrent vulvovaginal candidiasis (RVVC) is an important and underestimated fungal infection.
OBJECTIVE
We aimed to determine the fungicidal and proliferative capacities of neutrophils and peripheral blood mononuclear cells (PBMCs), respectively and the clinical and microbiological characteristics of a cohort of Colombian patients diagnosed with RVVC.
METHODS
A cross-sectional study was conducted. A total of 66 women were included (40 diagnosed with RVVC and 26 healthy women [HW]). Demographic and clinical data were recorded. Vaginal fluid samples were obtained for isolation, identification and antifungal susceptibility testing of Candida species using selective culture media and the Vitek 2.0® system. Blood samples were also obtained to evaluate cell subpopulations; furthermore, neutrophils and PBMCs were isolated to determine their fungicidal and proliferative capacities, respectively.
RESULTS
The median age was 29 (IQR: 34-23) for RVVC and 24 (IQR: 30-23) for HW. Only two species of the genus Candida were identified: Candida albicans (92.5%) and Candida lusitaniae (7.5%). Resistance to fluconazole, voriconazole, flucytosine and amphotericin B was observed on six C. albicans isolates and one C. lusitaniae isolate. Only the family history of vulvovaginal candidiasis was associated with RVVC occurrence. The RVVC group exhibited a significantly higher number of neutrophils but with lower fungicidal activity in comparison to HW; likewise, PBMCs from RVVC patients presented a lower proliferation index when stimulated with C. albicans.
CONCLUSION
Contrary to what has been reported worldwide, in Colombian patients with RVVC, C. albicans was the main isolated species without increased antifungal resistance. The diminished fungicidal and proliferative capacities of neutrophils and PBMCs, respectively, could suggest a possible alteration in the innate and adaptive immune responses.
Topics: Humans; Female; Adult; Candidiasis, Vulvovaginal; Antifungal Agents; Neutrophils; Cross-Sectional Studies; Leukocytes, Mononuclear; Fluconazole; Candida albicans; Candida; Candidiasis, Chronic Mucocutaneous; Cell Proliferation
PubMed: 38551114
DOI: 10.1111/myc.13720 -
Pharmaceutics Feb 2024Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by treatment's efficacy. This study...
Curcumin (CUR) is a natural compound that can be combined with miconazole (MCZ) to improve vulvovaginal candidiasis (VVC) caused by treatment's efficacy. This study aimed to develop ureasil-polyether (U-PEO) vaginal ovules loaded with CUR and MCZ for the treatment of VVC. Physicochemical characterization was performed by thermogravimetry (TGA), differential thermal analysis (DTA), Fourier transform infrared spectroscopy (FTIR), and in vitro release. Antifungal assays were used to determine minimum inhibitory concentrations (MICs) and synergism between CUR and MCZ, and the activity of U-PEO ovules were performed by microdilution and agar diffusion. TGA results showed high thermal stability of the hybrid ovules. In DTA, the amorphous character of U-PEO and a possible interaction between CUR and MCZ were observed. FTIR showed no chemical incompatibility between the drugs. In vitro release resulted in 80% of CUR and 95% of MCZ released within 144 h. The MICs of CUR and MCZ were 256 and 2.5 µg/mL, respectively. After combining the drugs, the MIC of MCZ decreased four-fold to 0.625 µg/mL, while that of CUR decreased eight-fold to 32 µg/mL. Synergism was confirmed by the fractional inhibitory concentration index (FICI) equal to 0.375. U-PEO alone showed no antifungal activity. U-PEO/MCZ and U-PEO/CUR/MCZ ovules showed the greatest zones of inhibition (≥18 mm). The results highlight the potential of the ovules to be administered at a lower frequency and at reduced doses compared to available formulations.
PubMed: 38543206
DOI: 10.3390/pharmaceutics16030312 -
Current Issues in Molecular Biology Mar 2024In the present work, we evaluated the antifungal activities of two novel ebselen analogs, -allyl-benzisoselenazol-3(2H)-one (-allyl-bs) and...
In the present work, we evaluated the antifungal activities of two novel ebselen analogs, -allyl-benzisoselenazol-3(2H)-one (-allyl-bs) and -3-methylbutylbenzisoselenazol-3(2H)-one (-3mb-bs). Colorimetric and turbidity assays were performed to determine the minimum inhibitory concentration (MIC) of these compounds in S1 (fluconazole-sensitive) and S2 (fluconazole-resistant) strains of . -3mb-bs was more active than the -allyl-bs compound. It is noteworthy that the concentration of -3mb-bs observed to inhibit fungal growth by 50% (18.2 µM) was similar to the concentration observed to inhibit the activity of the yeast plasma membrane H-ATPase (Pma1p) by 50% (19.6 µM). We next implemented a mouse model of vulvovaginal candidiasis (VVC) using the S1 strain and examined the mouse and yeast proteins present in the vaginal lavage fluid using proteomics. The yeast proteins detected were predominately glycolytic enzymes or virulence factors associated with while the mouse proteins present in the lavage fluid included eosinophil peroxidase, desmocollin-1, and gasdermin-A. We then utilized the -3mb-bs compound (12.5 mg/kg) in the mouse VVC model and observed that it significantly reduced the vaginal fungal burden, histopathological changes in vagina tissue, and expression of myeloperoxidase (MPO). All in all, the present work has identified a potentially promising drug candidate for VVC treatment.
PubMed: 38534773
DOI: 10.3390/cimb46030157 -
Journal of Lower Genital Tract Disease Apr 2024The study's aim is to assess if vulvar psoriasis and candidiasis may be distinguished by clinical presentation and histopathologic appearance.
OBJECTIVES
The study's aim is to assess if vulvar psoriasis and candidiasis may be distinguished by clinical presentation and histopathologic appearance.
METHODS
The pathology database identified biopsies with corneal or subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate. Exclusions were age younger than 18 years and unavailable or uninterpretable slides. Clinical data included demographics, comorbid conditions, symptoms, examination, microbiology, treatment, and response. Histopathologic review documented site, thickness, and characteristics of stratum corneum and epidermis, distribution of neutrophils, and infiltrate. Cases were stratified by microbiologic presence or absence of Candida albicans.
RESULTS
Biopsies from 62 women with median age of 60 years were associated with C. albicans on vulvovaginal culture in 28 (45%), whereas 26 (42%) were negative, and 8 (13%) lacked microbiologic assessment. Swab-positive women were more likely to have diabetes, receive prereferral estrogen, and report vulvar pain. Specialist clinical impression was candidiasis in 33 (53%), psoriasis in 11 (18%), comorbid candidiasis and psoriasis in 7 (11%), dermatitis in 10 (16%), and unknown in 2 (3%). Visible fungal organisms occurred in 16 (26%) cases and were associated with diabetes and satellite lesions. Other than presence of organisms, there were no histopathologic differences stratified by microbiologic result.
CONCLUSIONS
The histopathologic triad of corneal/subcorneal neutrophils, acanthosis, and dermal lymphocytic infiltrate is common to vulvar psoriasis and candidiasis, and clinical features do not reliably distinguish between them. Microbiologic assessment and single-agent treatment are useful strategies to clarify the diagnosis.
Topics: Female; Humans; Middle Aged; Adolescent; Candidiasis; Candida albicans; Psoriasis; Vulvitis; Diabetes Mellitus; Candidiasis, Vulvovaginal
PubMed: 38518215
DOI: 10.1097/LGT.0000000000000801 -
Reproduction & Fertility Apr 2024Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains... (Review)
Review
ABSTRACT
Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome's influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota's production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex steroid levels have significant implications for the interplay between host and microbes throughout the body, ultimately impacting reproductive health. By harnessing interventions that modulate both the vaginal and gut microbiomes, it becomes possible to not only maintain homeostasis but also mitigate pathological conditions. While the field is still working toward making broad clinical recommendations, the current studies demonstrate that manipulating the microbiome holds great potential for addressing diverse gynecologic conditions.
LAY SUMMARY
Manipulating the microbiome has recently entered popular culture, with various diets thought to aid the microbes that live within us. These microbes live in different locations of our body and accordingly help us digest food, modulate our immune system, and influence reproductive health. The role of the microbes living in and influencing the female reproductive tract remains understudied despite known roles in common conditions such as vulvovaginal candidiasis (affecting 75% of females in their lifetime), bacterial vaginosis (25% of females in their lifetime), cervical HPV infection (80% of females in their lifetime), endometriosis (6-10% of females of reproductive age), and polycystic ovary syndrome (10-12% of females of reproductive age). Here, we review four different approaches used to manipulate the female reproductive tract and gastrointestinal system microbiomes: microbiota transplants, probiotics, prebiotics, and dietary interventions, and the use of engineered microbial strains. In doing so, we aim to stimulate discussion on new ways to understand and treat female reproductive health conditions.
Topics: Female; Humans; Animals; Microbiota; Gastrointestinal Microbiome; Probiotics; Prebiotics; Reproduction
PubMed: 38513356
DOI: 10.1530/RAF-23-0060 -
Phytomedicine : International Journal... Jun 2024Vulvovaginal candidiasis (VVC) is a common infection that affects the female reproductive tract. Pulsatilla decoction (PD), a traditional Chinese herbal medicine, is a...
BACKGROUND
Vulvovaginal candidiasis (VVC) is a common infection that affects the female reproductive tract. Pulsatilla decoction (PD), a traditional Chinese herbal medicine, is a classic and effective prescription for VVC. However, its mechanism of action remains unclear.
PURPOSE
This study aimed to evaluate the efficacy and potential mechanism of action of the n-butanol extract of Pulsatilla decoction (BEPD) in VVC treatment.
METHODS
High performance liquid chromatography (HPLC) was used to detect the main active ingredients in BEPD. A VVC-mouse model was constructed using an estrogen-dependent method to evaluate the efficacy of BEPD in VVC treatment. Fungal burden and morphology in the vaginal cavity were comprehensively assessed. Candida albicans-induced inflammation was examined in vivo and in vitro. The effects of BEPD on the Protein kinase Cδ (PKCδ) /NLR family CARD domain-containing protein 4 (NLRC4)/Interleukin-1 receptor antagonist (IL-1Ra) axis were analyzed using by immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and reverse transcription-quantitative polymerase chain reaction (qRT-PCR).
RESULTS
BEPD inhibited fungal growth in the vagina of VVC mice, preserved the integrity of the vaginal mucosa, and suppressed inflammatory responses. Most importantly, BEPD activated the "silent" PKCδ/NLRC4/IL-1Ra axis and negatively regulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby exerting a therapeutic efficacy on VVC.
CONCLUSIONS
BEPD effects on mice with VVC were dose-dependent. BEPD protects against VVC by inhibiting inflammatory response and NLRP3 inflammasome via the activation of the PKCδ/NLRC4/IL-1Ra axis. This study revealed the pharmacological mechanism of BEPD in VVC treatment and provided further evidence for the application of BEPD in VVC treatment.
Topics: Animals; Female; Mice; Candida albicans; Candidiasis, Vulvovaginal; CARD Signaling Adaptor Proteins; Disease Models, Animal; Drugs, Chinese Herbal; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Protein Kinase C-delta; Pulsatilla; Vagina
PubMed: 38484624
DOI: 10.1016/j.phymed.2024.155515 -
International Journal of Molecular... Feb 2024Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural...
Environmental sustainability is an increasing challenge in the pharmaceutical field, leading to the search for eco-friendly active ingredients. Among natural ingredients, propolis arises as an excellent alternative, being a complex substance with pharmacological properties. This work aims to explore the potential of propolis as a new pharmaceutical ingredient for the replacement of conventional vulvovaginal antifungals. Propolis extracts were obtained by Ultrasound-Assisted Extraction using different solvents (water, water/ethanol (50:50, /), and ethanol). Afterwards, the extracts were characterized regarding total phenolic content (TPC), antioxidant/antiradical activities, radical scavenging capacity, antifungal activity against strains of Candida species, and viability effect on two female genital cell lines. The aqueous extract achieved the best TPC result as well as the highest antioxidant/antiradical activities and ability to capture reactive oxygen species. A total of 38 phenolic compounds were identified and quantified by HPLC, among which ferulic acid, phloridzin and myricetin predominated. Regarding the anti- spp. activity, the aqueous and the hydroalcoholic extracts achieved the best outcomes (with MIC values ranging between 128 and 512 μg/mL). The cell viability assays confirmed that the aqueous extract presented mild selectivity, while the hydroalcoholic and alcoholic extracts showed higher toxicities. These results attest that propolis has a deep potential for vulvovaginal candidiasis management, supporting its economic valorization.
Topics: Female; Humans; Propolis; Antioxidants; Candidiasis, Vulvovaginal; Ethanol; Phenols; Antifungal Agents; Candida; Water; Plant Extracts
PubMed: 38473725
DOI: 10.3390/ijms25052478 -
International Microbiology : the... Mar 2024Candida infections are growing all over the world as a result of their resistance to anti-fungal drugs. This raises concerns about public health, particularly in cases...
Candida infections are growing all over the world as a result of their resistance to anti-fungal drugs. This raises concerns about public health, particularly in cases of vulvovaginal candidiasis (VVC). Therefore, the need for effective treatment options for Candida infections has become crucial. The main goal of the study is to evaluate the efficacy of novel palladium metal complexes against fluconazole-resistant Candida spp., particularly C. albicans and C. auris. The process begins with identifying the minimum inhibitory concentration (MIC), followed by growth curve assays, colony morphology analysis, characterization, and gene expression analysis. The investigation revealed that sub-MIC of Pd(II) complex B (250 μg/mL) inhibited Candida spp. more effectively than amphotericin B (500 μg/mL). Further, Pd(II) complex B drastically reduced the growth of Candida spp. biofilms by 70-80% for nascent biofilms and 70-75% for mature biofilms. Additionally, the yeast-to-hyphal switch and SEM studies revealed that Pd(II) complex B effectively hinders the growth of drug-resistant Candida cells. The gene expression investigation also evidenced that Pd(II) complex B downregulated virulence genes in C. albicans (ERG, EFG, UME6, and HGC) and C. auris (ERG, CDR, and HGC). The findings showed that Pd(II) complex B effectively inhibited the growth of Candida biofilm formation and was reported as a potential anti-biofilm agent against Candida spp. that are resistant to drugs.
PubMed: 38467906
DOI: 10.1007/s10123-024-00497-8 -
Heliyon Mar 2024Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and... (Review)
Review
Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and obstetric outcomes, including preterm delivery, sexually transmitted infections and pelvic inflammatory disease. Although effective control of VVC is achievable with the use of traditional treatment strategies (i.e., antifungals), the possibility of drug intolerance, treatment failure and recurrence, as well as the appearance of antifungal-resistant species remain critical challenges. Therefore, alternative therapeutic strategies against VVC are urgently required. In recent years, an improved understanding of the dysbiotic vaginal microbiota (VMB) during VVC has prompted the consideration of administering -biotics to restore the balance of the VMB within the context of VVC prevention and treatment. Here, we aim to summarize the current evidence of the anti- effects of probiotics, postbiotics and synbiotics and their potential use as an alternative/complementary therapy against VVC. Additionally, this review discusses advantages and challenges associated with the application of -biotics in VVC to provide guidance for their later use. We also review new developments in VVC therapy, i.e., vaginal microbiota transplantation (VMT) as an emerging live biotherapeutic therapy against VVC and discuss existing shortcomings associated with this nascent field, expecting to stimulate further investigations for introduction of new therapies against VVC.
PubMed: 38463778
DOI: 10.1016/j.heliyon.2024.e27239