Search Results (50)

Gardnerella vaginalis (GV), an opportunistic pathogen excessively proliferated in vaginal dysbiosis, causes systemic inflammation including vaginitis, neuroinflammation, and osteitis. To understand its systemic inflammation-triggering factor, we purified extracellular vesicles isolated from GV (gEVs) and examined their effect on the occurrence of vaginitis, osteitis, and neuroinflammation in mice with and without ovariectomy (Ov). The gEVs consisted of lipopolysaccharide, proteins, and nucleic acid and induced TNF-α and RANKL expression in macrophage cells. When the gEVs were vaginally exposed in mice without Ov, they significantly induced RANK, RANKL, and TNF-α expression and NF-κB⁺ cell numbers in the vagina, femur, hypothalamus, and hippocampus, as observed in GV infection. The gEVs decreased time spent in the open field (OT) in the elevated plus maze test by 47.3%, as well as the distance traveled in the central area (DC) by 28.6%. In the open field test, they also decreased the time spent in the central area (TC) by 39.3%. Additionally, gEVs decreased spontaneous alteration (SA) in the Y-maze test by 33.8% and the recognition index (RI) in the novel object recognition test by 26.5%, while increasing the immobility time (IT) in the tail suspension test by 36.7%. In mice with OV (Ov), the gEVs also induced RANK, RANKL, and TNF-α expression and increased NF-κB⁺ cell numbers in the vagina, femur, hypothalamus, and hippocampus compared to vehicle-treated mice. When gEVs were exposed to mice with Ov, gEVs also reduced the DC, TC, OT, SA, and RI to 62.1%, 62.7%, 28.2%, 90.7%, and 85.4% of mice with Ov, respectively, and increased IT to 122.9% of mice with Ov. Vaginally exposed fluorescein-isothiocyanate-tagged gEVs were detected in the blood, femur, and hippocampus. These findings indicate that GV-derived gEVs may induce systemic inflammation through the activation of RANK/RANKL-involved NF-κB signaling, leading to systemic disorders including vaginitis, osteoporosis, depression, and cognitive impairment. Therefore, gEVs may be an important risk factor for vaginitis, osteoporosis, depression, and cognitive impairment in women. Full article

Infections from the protozoa Entamoeba histolytica (E. histolytica), Giardia lamblia (G. lamblia), and Trichomonas vaginalis (T. vaginalis) pose a public health issue, with albendazole and mebendazole serving as the second-line medications for treating these parasitic infections. However, the low aqueous solubility of these compounds has led to the exploration of new strategies to enhance their solubility, with the formation of salts being a commonly employed strategy. The sulfonates A1, A2, and A3 of albendazole, along with M1, M2, and M3 of mebendazole, were synthesized. The antiparasitic activity in vitro was assessed against the trophozoites of E. histolytica, G. lamblia, and T. vaginalis. The salts A2, A3, M2, and M3 demonstrated a greater antiparasitic effect (IC₅₀ 37.95–125.53 µM) compared to the positive controls albendazole and mebendazole. The salts A1, A3, M2, and M3 do not exhibit cytotoxic effects at concentrations of 500 µM on the Vero cell line. Taken together, these findings indicate that the formation of these new solid saline phases enhances the antiparasitic effects in vitro, which is crucial in the current search for improved, safe, and effective antiparasitic agents. Full article

Cranberry oil is known for nutritional benefits, and this work is aimed at studying its soothing properties and potential as an intimate care ingredient. The antioxidant, anti-inflammatory, and anti-irritation properties of cranberry oil were evaluated on epithelial cells and tissues, including the vaginal epithelium. The impact of the oil on vaginal microbiota was assessed in vitro. Cranberry oil reduced oxidative stress in keratinocytes (ROS −43%) and lowered inflammation by lessening the release of cytokines IL-8 (−33%) and TNF-α (−32%). Irritation induced by sodium dodecyl sulfate (SDS) in skin explants was lowered by 24%. Cranberry oil and fruit extract acted synergistically on inflammation, decreasing TNF-α release by 75% (vs. −34% and −16%, respectively). Cranberry oil reduced inflammation on EpiVaginal™ tissue, decreasing IL-6 by 36%. The minimum inhibitory concentration (MIC) of cranberry oil on the pathogenic vaginal microorganisms C. albicans and G. vaginalis was 0.5% and 0.1%, respectively. The oil promoted the growth of commensal L. jensenii (×79 at 0.1%) and favored a high proportion of lactic acid bacteria when co-cultured with C. albicans. Cranberry oil has antioxidant, anti-inflammatory, and soothing properties on skin. Anti-inflammatory activity was confirmed on vaginal epithelium, and initial in vitro evidence indicates that the oil can balance vaginal flora to prevent dysbiosis. Full article

Background: Gardnerella vaginalis is a natural inhabitant of the vagina, but when an imbalance occurs in the vaginal microbiota, this bacterium can cause vaginosis, a condition that must be treated when symptomatic and prior to a gynecological intervention. Cannabidiol (CBD) is an anti-inflammatory compound that also has antibacterial activities against several Gram-positive and certain Gram-negative bacteria. Objectives: Since G. vaginalis is an opportunistic pathogenic Gram-variable bacterium, we investigated its response to CBD. Methods: The antibacterial activity of CBD was studied by broth dilution assay, changes in intracellular ATP levels, and the ability of bacteria to recover on chocolate agar plates. The antibiofilm activity was investigated by MTT metabolic assay, crystal violet staining, and HR-SEM. Flow cytometric analyses were performed to measure changes in membrane potential, membrane perforation, and metabolic activity. Reactive oxygen species (ROS) production was analyzed using the nitro blue tetrazolium (NBT) reagent. Gene expression was determined by semi-quantitative real-time PCR, while protein composition was determined by LC-MS/MS analysis. Results: We observed that G. vaginalis clinical isolates exhibited high susceptibility to CBD with a minimum inhibitory concentration (MIC) of 2.5 µg/mL CBD. CBD induced rapid membrane hyperpolarization and caused cytoplasmic leakage of ATP without increasing propidium iodide uptake. This was accompanied by reduced metabolic activity and loss of survivability. Proteomic analysis revealed decreased expression of some ribosomal-associated proteins. CBD exhibited antioxidant activity by reducing intracellular ROS levels in a dose-dependent manner. The antibacterial effect was neutralized by the free radical scavenger α-tocopherol, suggesting the involvement of radicals in executing the antibacterial effect. Importantly, CBD not only prevented the biofilm formation of G. vaginalis but also reduced the metabolic activity and biofilm biomass of preformed, mature biofilms. Real-time PCR analysis of G. vaginalis treated with CBD for 6 h showed an increase in the expression of biofilm-associated genes, suggesting that the antibiofilm activity of CBD is mainly due to its antibacterial effect. CBD did not alter the ability of G. vaginalis to adhere to HeLa cervical carcinoma cells and CBD-treated bacteria were still phagocytosed by RAW264.7 macrophages. Conclusions: Our study shows that CBD exhibits antibacterial and antibiofilm activities against G. vaginalis clinical isolates and is thus a potential drug for the treatment of vaginosis caused by this bacterium. Full article

Lactobacillus, a genus of lactic acid bacteria, is known to coexist symbiotically in the female vaginal microbiota and has gained attention as a potential probiotic with benefits for female reproductive health. This study aimed to evaluate the probiotic potential of Lactobacillus gasseri BELG74(BELG74), isolated from the vaginal microbiota of Korean women, in promoting vaginal health through growth ability, pH reduction, lactic acid production, and antimicrobial activity. Among 36 Lactobacillus gasseri strains, BELG74 demonstrated the highest growth capacity at 1.84 × 10⁹ CFU/mL and the lowest pH of 3.84. BELG74 produced the most lactic acid at a concentration of 20.12 g/L, which correlated with anti-pathogenic activity against Gardnerella vaginalis, Fannyhessea vaginae, and Candida albicans of more than 90%. It also showed high acid resistance (92.2%) and bile resistance (25.3%), ensuring its survival through the gastrointestinal tract. Furthermore, BELG74 exhibited strong biofilm formation and adhesion capacity of 28.7% to HeLa cells, making it effective in colonizing the vaginal environment and suppressing pathogenic bacteria. The reduction of IL-1β by 63% suggested anti-inflammatory effects. Additionally, BELG74 effectively neutralized trimethylamine and ammonia by over 99.9%, suggesting its ability to reduce unpleasant vaginal odors. These findings indicate that BELG74 could be a promising probiotic for improving vaginal health, with further clinical studies needed to confirm these benefits. Full article

The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes. Full article

Background/Objectives: Bacterial vaginosis (BV), an infection caused primarily by Gardnerella vaginalis, is the most prevalent vaginal infection. Although BV is often characterized by an asymptomatic course, it can lead to considerable health complications. Currently, BV therapy choices are limited, and available treatments are complicated by concerns about antibiotic resistance. Ceragenins, which together comprise an innovative class of low molecular-weight, cholic acid-based antibacterial agents, have emerged as potential alternatives to conventional treatments. Methods: This study investigates (i) the antibacterial activity of ceragenins against G. vaginalis in in vitro experimental settings at varied pH, and (ii) the effectiveness and anti-inflammatory properties of CSA-13 in a G. vaginalis-induced bacterial vaginosis animal model. Results and Conclusions: We demonstrate that ceragenins, particularly CSA-13, maintain their antibacterial efficacy throughout pH range of 4.5–7, with the highest activity observed at neutral pH (7.0). Additionally, in an animal model, beneficial effects of ceragenins are attributed to anti-inflammatory properties of these compounds, making these compounds promising agents as potential new treatment options against G. vaginalis-associated vaginal infections. Full article

Gardnerella vaginalis is a Gram-variable bacillus capable of causing bacterial vaginosis, a condition prevalent in reproductive-age women, this bacterium is present in almost 100% of cases and is also considered a gateway to various sexually transmitted infections. This organism exhibits high pathogenicity linked to virulence and resistance genes acquired throughout evolution, showcasing elevated resistance to a broad spectrum of drug classes. This study conducted comparative genomic analyses to identify these genes and correlate their presence with positive Darwinian selection. Additionally, new drug targets were selected through docking and molecular modeling, guided by the heightened antimicrobial resistance exhibited by this microbial species. The available genomes of G. vaginalis were analyzed, and the orthologous genes were delineated and positively selected, whereby 29 groups were found. Of these genes, one of great importance was predicted, Mef(A), which is related to resistance to the macrolide group of antibiotics, which are one of the main choices for the treatment of sexually transmitted infections. Additionally, two potential protein candidates were selected as drug targets. These proteins were linked with a natural compound each and are considered good potential drug targets. The analyses in this study contribute to analyzing the evolution of the species and how resistance genes are related to their permanence as a potential pathogen. Full article

Metronidazole (MTZ) is the most common drug used against Trichomonas vaginalis (T. vaginalis) infections; however, treatment failures and high rates of recurrence of trichomoniasis have been reported, suggesting the presence of resistance in T. vaginalis to MTZ. Therefore, research into new therapeutic options against T. vaginalis infections has become increasingly urgent. This study investigated the trichomonacidal activity of a series of five imidazole carbamate compounds (AGR-1, AGR-2, AGR-3, AGR-4, and AGR-5) through in vitro susceptibility assays to determine the IC₅₀ value of each compound. All five compounds demonstrated potent trichomonacidal activity, with IC₅₀ values in the nanomolar range and AGR-2 being the most potent (IC₅₀ 400 nM). To gain insight into molecular events related to AGR-induced cell death in T. vaginalis, we analyzed the expression profiles of some metabolic genes in the trophozoites exposed to AGR compounds and MTZ. It was found that both AGR and MTZ compounds reduced the expression of the glycolytic genes (CK, PFK, TPI, and ENOL) and genes involved in metabolism (G6PD, TKT, TALDO, NADHOX, ACT, and TUB), suggesting that disturbing these key metabolic genes alters the survival of the T. vaginalis parasite and that they probably share a similar mechanism of action. Additionally, the compounds showed low cytotoxicity in the Caco-2 and HT29 cell lines, and the results of the ADMET analysis indicated that these compounds have pharmacokinetic properties similar to those of MTZ. The findings offer significant insights that can serve as a basis for future in vivo studies of the compounds as a potential new treatment against T. vaginalis. Full article

Sexually transmitted diseases (STDs) are a global concern because approximately 1 million new cases emerge daily. Most STDs are curable, but if left untreated, they can cause severe long-term health implications, including infertility and even death. Therefore, a test enabling rapid and accurate screening and genotyping of STD pathogens is highly awaited. Herein, we present the development of the DNA-based 6STD Genotyping 9G Membrane test, a lateral flow strip membrane assay, for the detection and genotyping of six STD pathogens, including Trichomonas vaginalis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Mycoplasma genitalium. Here, we developed a multiplex PCR primer set that allows PCR amplification of genomic materials for these six STD pathogens. We also developed the six ssDNA probes that allow highly efficient detection of the six STD pathogens. The 6STD Genotyping 9G Membrane test lets us obtain the final detection and genotyping results in less than 30 m after PCR at 25 °C. The accuracy of the 6STD Genotyping 9G membrane test in STD genotyping was confirmed by its 100% concordance with the sequencing results of 120 clinical samples. Therefore, the 6STD Genotyping 9G Membrane test emerges as a promising diagnostic tool for precise STD genotyping, facilitating informed decision-making in clinical practice. Full article

The parasite Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common non-viral sexually transmitted disease worldwide. This infection often remains asymptomatic and is related to several health complications. The traditional treatment for trichomoniasis is the use of drugs of the 5-nitroimidazole family, such as metronidazole; however, scientific reports indicate an increasing number of drug-resistant strains. Benzimidazole derivatives could offer an alternative in the search for new anti-trichomonas drugs. In this sense, two attractive candidates are the compounds O₂N-BZM7 and O₂N-BZM9 (1H-benzimidazole derivatives), since, through in vitro tests, they have shown a higher trichomonacide activity. In this study, we determined the effect on the expression level of metabolic genes in T. vaginalis. The results show that genes involved in redox balance (NADHOX, G6PD::6PGL) are overexpressed, as well as the gene that participates in the first reaction of glycolysis (CK); on the other hand, structural genes such as ACT and TUB are decreased in expression in trophozoites treated with the compound O₂N-BZM9, which would probably affect its morphology, motility and virulence. These results align with the trichomonacidal activity of the compounds, with benzimidazole O₂N-BZM9 being the most potent, with an IC₅₀ value of 4.8 μM. These results are promising for potential future therapeutic applications. Full article

Introduction: Polycystic ovary syndrome (PCOS) is a multifactorial, heterogeneous endocrine and metabolic disorder in women. Due to its association with the menstrual cycle and fertility disorders, the importance of this problem is emphasized especially in patients of reproductive age. Based on a number of analyses, the effect of PCOS on altering the diversity of the microbiome (e.g., intestinal or vaginal) is suggested. Vaginal dysbiosis can result in BV (bacterial vaginosis). The purpose of this study was to assess the prevalence of BV in patients with PCOS, as well as to determine the most reliable diagnostic factors. Material and Methods: Retrospective analysis of microbiological findings (2018–2022) of PCOS patients (n = 594) of reproductive age. The present analysis focused on the results of patients with PCOS (n = 380) and vaginal discharge with pH ≥ 4.4 and suspected BV. Biological material was a vaginal swab/vaginal secretion. The most commonly used routine methods for assessing BV were the Amsel analysis and the Nugent scoring system. Results: Patients with PCOS and vaginal fluid pH ≥ 4.4 and suspected BV (n = 380) accounted for 64% of all PCOS patients (n = 594). The relationship between pH and detection of “clue cells” showed significant dependency and increased with leukocytes. The pH measurement also showed dependency on high G. vaginalis counts. In addition, the elimination of lactic acid bacteria (LAB) in vaginal secretions was associated with an increase in the number of leukocytes with increasing pH values. A marked increase in G. vaginalis was found in more than half (56.8%) of PCOS women (n = 380) with suspected BV. No dependency was observed between the absence of LAB and the diagnosis of BV on a positive G. vaginalis culture. Of the n = 380 patients with PCOS, 191 (50%) had a Nugent score ≥ 7 positive for BV. No dependency was observed between the number of patients with Candida sp. in vaginal secretions and pH, BV (with clue cells), or elevated leukocyte levels. The LRM was adjusted and the statistical model represented by the following formula was obtained: log(p/(1 − p)) = −1.18 + 1.24 × Group4.6 + 1.08 × Group4.8 + 1.66 × Group5.4. Conclusions: Based on the present analysis, BV appears to be more common in patients with PCOS than in the non-PCOS population. Chronic inflammation in PCOS patients and abnormalities in the vaginal microbiome may predispose to the development of BV. In women with PCOS, BV may be one of the unrecognized causes of infertility or complications of pregnancy. Despite the potential link between PCOS and the development of BV, the extent to which this syndrome contributes to vaginal dysbiosis and reproductive complications requires further study. Full article

Several microaerophilic parasites such as Giardia lamblia, Trichomonas vaginalis, and Plasmodium falciparum are major disease-causing organisms and are responsible for spreading infections worldwide. Despite significant progress made in understanding the metabolism and molecular biology of microaerophilic parasites, chemotherapeutic treatment to control it has seen limited progress. A current proposed strategy for drug discovery against parasitic diseases is the identification of essential key enzymes of metabolic pathways associated with the parasite’s survival. In these organisms, glucose-6-phosphate dehydrogenase::6-phosphogluconolactonase (G6PD:: 6PGL), the first enzyme of the pentose phosphate pathway (PPP), is essential for its metabolism. Since G6PD:: 6PGL provides substrates for nucleotides synthesis and NADPH as a source of reducing equivalents, it could be considered an anti-parasite drug target. This review analyzes the anaerobic energy metabolism of G. lamblia, T. vaginalis, and P. falciparum, with a focus on glucose metabolism through the pentose phosphate pathway and the significance of the fused G6PD:: 6PGL enzyme as a therapeutic target in the search for new drugs. Full article

The potential involvement of a sexually transmitted agent has been suggested to contribute to the high number of prostate cancers in the United States and worldwide. We investigated the relationship of Trichomonas vaginalis seropositivity with prostate cancer risk in a nested case–control study within the Multiethnic Cohort in Hawaii and California using blood samples collected prior to cancer diagnoses. Incident cases of advanced prostate cancer (intermediate- to high-grade based on Gleason score ≥ 7 and/or disease spread outside the prostate) were matched to controls by age, ethnicity, and the date of blood collection. T. vaginalis serostatus was measured using an ELISA detecting IgG antibodies against a recombinant T. vaginalis α-actinin protein. Seropositivity to T. vaginalis was observed in 35 of 470 (7.4%) cases and 26 of 470 (5.5%) controls (unadjusted OR = 1.47, 95% CI 0.82–2.64; adjusted OR = 1.31, 95% CI 0.67–2.53). The association was similarly not significant when cases were confined to extraprostatic tumors having regional or distant spread (n = 121) regardless of grade (unadjusted OR = 1.37, 95% CI 0.63–3.01; adjusted OR = 1.20, 95% CI 0.46–3.11). The association of T. vaginalis with prostate cancer risk did not vary by aspirin use. Our findings do not support a role for T. vaginalis in the etiology of advanced prostate cancer. Full article

Infant microbiota shaping strictly influences newborns’ well-being and long-term health, and babies born by cesarean-section and formula-fed generally show low microbial gut diversity and are more prone to develop various disorders. The supplementation with beneficial microbes of vaginal origin or derivatives (postbiotics, including heat-inactivated cells) represents a valid strategy to drive the correct gut microbiota shaping. Here, we explored for the first time the bifidogenic activity of a heat-killed vaginal strain (Limosilactobacillus vaginalis BC17), in addition to the assessment of its safety. L. vaginalis BC17 whole genome was sequenced by Nanopore technology and highlighted the absence of antibiotic resistance genes and virulence factors, indicating the strain safety profile for human health. MIC values confirmed that L. vaginalis BC17 is susceptible to widely employed antibiotics. Heat-killed BC17 cells significantly enhanced the planktonic growth of Bifidobacterium spp. For the first time, stimulating effects were observed also toward biofilm formation of bifidobacteria and their pre-formed biofilms. Conversely, heat-killed BC17 cells exerted antibacterial and anti-biofilms activities against Gram-positive and Gram-negative pathogens. Lyophilized heat-killed BC17 cells were formulated in a sunflower oil suspension (10¹⁰ heat-killed cell/g) intended for infant oral intake. This possessed optimal technological (i.e., re-dispersibility and stability) and functional properties (i.e., bifidogenic activity) that were maintained even after pre-digestion in acidic conditions. Full article