Search Results (173)

This study describes the development of β-cyclodextrin (β-CD) inclusion complexes of curcumin (CUR) and a synthetic curcuminoid analogue (CN56), which were incorporated into poly(vinyl alcohol)/κ-carrageenan hydrogel films to create a multifunctional system capable of sustained drug release and effective antimicrobial action. Carrageenan was extracted from Gigartina skottsbergii, and hydrogels were prepared using a freeze–thaw crosslinking method. The inclusion complexes were formed at a 1:6 molar ratio, achieving loading efficiencies of 75.62% for CUR and 79.00% for CN56. FTIR confirmed molecular interactions between the complexes and the polymeric matrix, accompanied by reduced crystallinity and increased amorphous character. Thermogravimetric analysis revealed enhanced thermal stability, with degradation onset temperatures above 239 °C, while DSC analysis indicated irreversible amorphization after the first heating cycle. SEM analysis showed improved surface uniformity in complex-loaded films compared with those containing free compounds. Swelling experiments demonstrated significantly greater fluid uptake in complex-loaded hydrogels, particularly for CN56 (1080% after 45 min). Controlled release studies revealed sustained drug release profiles, with 76.49% of CUR and 56.02% of CN56 released over 36 h, following Fickian diffusion mechanisms. In vitro antimicrobial assays confirmed marked activity of CUR and CN56 against Gardnerella vaginalis, a key pathogen associated with bacterial vaginosis. Biocompatibility tests, including hemolysis and MTT reduction assays, indicated low cytotoxicity and satisfactory hemocompatibility. Rheological analysis further demonstrated increased viscosity and potential mucoadhesive behavior. Collectively, these findings highlight the potential of carrageenan-based PVA hydrogels as innovative pharmaceutical platforms for the prevention and treatment of recurrent bacterial vaginosis, offering a promising alternative to conventional therapies. Full article

Background: This study developed a Causal Graphical Model (CGM) to analyze Bacterial Vaginosis (BV), a condition caused by an imbalance in the vaginal microbiota, whose bacterial composition varies among women. While previous studies used variable selection, clustering, and association rules to identify BV-associated bacteria, these approaches lack visual tools to explore causal relationships and determine which are the most relevant. In contrast, the CGM generated in this study allows visualization of associated bacteria and their causal links, thereby identifying those most influential. Methods: Path Analysis (PA), a statistical structural equation modeling method, was used to construct the CGM, with emphasis on observable variables and to assess direct and indirect effects through correlations and covariances. PA was applied to an already-collected third-party dataset related to BV diagnosis, consisting of data from 132 pregnant women between 4 and 24 weeks of gestation. Results: The CGM, built using a theoretical model based on the Spearman correlation matrix, was validated through statistical metrics and by a clinical-biological expert. The resultant model highlights bacteria influencing BV diagnosis, specifically Mycoplasma hominis (Mh), Atopobium vaginae (Av), Gardnerella vaginalis (Gv), Megasphaera Type 1 (MT1), and Bacteria Associated with Bacterial Vaginosis Type 2 (BVAB2). Among them, MT1 and BVAB2 showed the strongest association with BV. Conclusions: The CGM effectively identifies causal associations among bacteria related to BV. Full article

Background: Gynecological infections, including bacterial vaginosis, vulvovaginal candidiasis, and recurrent urinary tract infections, represent a major clinical burden and are often complicated by biofilm formation and antimicrobial resistance. Novel non-antibiotic strategies are urgently needed. We previously demonstrated the antimicrobial activity of silver-bound titanium dioxide (TiAB) against multidrug-resistant bacteria isolated from dermatological infections. Objectives: We evaluated whether TiAB, at concentrations used in marketed medical devices, exerts antibacterial and antifungal effects against clinically relevant vaginal isolates by determining Minimum Inhibitory Concentration/ Minimum Bactericidal and Fungicidal Concentration (MIC, MBC/MFC), and time–kill kinetics. Methods: A total of 73 clinical isolates were collected from vaginal swabs, including Staphylococcus aureus (MSSA, MRSA), Escherichia coli (ESBL+ and non-ESBL), Klebsiella pneumoniae, Enterococcus spp., Streptococcus agalactiae, and Candida albicans. Minimum inhibitory concentrations (MICs) and minimum bactericidal/fungicidal concentrations (MBCs/MFCs) were determined by broth microdilution, and bactericidal activity was confirmed by time-kill assays. Results: TiAB exhibited potent activity against Gram-negative bacteria, with median MIC values of 1–2% (w/v) for E. coli and K. pneumoniae. Gram-positive isolates, including S. agalactiae and Enterococcus spp., showed higher MIC values (2–4%). Candida albicans displayed fungistatic inhibition at 4%. Time-kill assays confirmed rapid bactericidal effects for Gram-negative isolates within 8 h at 2× MIC, while Gram-positive bacteria required prolonged exposure. Conclusions: These findings extend previous evidence of TiAB’s antimicrobial properties to gynecological pathogens, supporting its potential as a topical, non-antibiotic option for managing vaginal infections in an era of rising antimicrobial resistance. Further in vivo validation is warranted. Full article

Bacterial vaginosis (BV) is a highly prevalent vaginal infection characterized by a dysbiotic shift in the vaginal microbiota, with Gardnerella vaginalis acting as a principal pathogen. Despite its association with adverse reproductive outcomes, BV remains underexplored from both mechanistic and therapeutic standpoints. Standard antibiotic regimens frequently fail due to high recurrence rates driven by multidrug-resistant (MDR) G. vaginalis strains and biofilm formation. In response, natural compounds and nutraceuticals, owing to their intrinsic antibacterial, antibiofilm, and immunomodulatory properties, have emerged as promising candidates for alternative BV therapies. In this paper, we first compile and critically evaluate preclinical and clinical evidence on the efficacy of plant extracts, essential oils (EOs), probiotics, vitamins, proteins, fatty acids, and enzymes against G. vaginalis, emphasizing their mechanistic insights in restoring vaginal microbial balance. Next, we focus on the integration of these bioactive agents into engineered nanosystems, such as lipid-based nanoparticles (LNPs), polymeric carriers, and inorganic nanostructures, to overcome limitations related to solubility, stability, and targeted delivery. Nonetheless, comparative studies, combination therapies, and recent patent developments are discussed to highlight how naturally derived molecules can enhance antimicrobial potency and reduce cytotoxicity. In conclusion, these platforms demonstrate superior in vitro and in vivo efficacy, offering a paradigm shift in the management of BV. Key challenges include scalable manufacturing, regulatory approval, and comprehensive safety assessment. Future research should prioritize standardized nanoparticle (NP) synthesis, detailed pharmacokinetic and toxicity profiling, and well-designed clinical trials to validate nature-inspired, nanoengineered therapies against G. vaginalis-induced BV. Full article

Bacterial vaginosis is more than a mild inconvenience for women and has been shown to be an important cause of morbidity and mortality in women through sexually transmitted infections, and in babies due to late miscarriage and preterm birth. The aetiology of bacterial vaginosis remains unclear but there is increasing evidence to support sexual transmission as a cause. Preterm birth is a major cause of neonatal and perinatal mortality and morbidity worldwide and a huge cost on healthcare. The earlier bacterial vaginosis is detected in pregnancy, the greater the risk of an adverse outcome like preterm birth. Bacteriophages influence the vaginal microbiome, resulting in a eubiotic or dysbiotic state that may have implications on the prediction and prevention of preterm birth. We have provided the evidence to link vaginal dysbiosis in the form of bacterial vaginosis with the prediction and prevention of preterm birth. We have also explored the role of bacteriophages in bacterial vaginosis and the possibility of therapeutic interventions. Bacteriophages play an important role in the aetiology of vaginal dysbiosis and novel therapeutic interventions may help in the prediction and prevention of preterm birth through achieving vaginal eubiosis. Full article

Preterm prelabor rupture of membranes (PPROM) is a leading cause of preterm birth and significant neonatal morbidity. The vaginal microbiome is implicated in its pathogenesis, but its detailed characteristics and functional consequences remain to be fully elucidated. This study aimed to provide a comprehensive, multi-faceted analysis of the vaginal microbiome and its functional potential in pregnant women with PPROM compared to healthy term controls. We collected vaginal fluid samples from eight PPROM and seven healthy control (HC) pregnant women. The vaginal microbiome was analyzed using 16S rRNA gene sequencing. We assessed community composition and state types (CSTs), alpha and beta diversity, co-occurrence networks, and predicted functional pathways using PICRUSt2. A molecular bacterial vaginosis (molBV) score was also calculated to determine the clinical relevance of the dysbiosis. The PPROM microbiome was characterized by a significant depletion of Lactobacillus crispatus–dominated communities (CST I) and a shift towards L. iners–dominated (CST III) or polymicrobial (CST IV) communities, which was consistent with a BV-positive molBV score. Alpha diversity was significantly higher in the PPROM group, and beta diversity analysis confirmed a distinct microbial structure between the two groups. Co-occurrence network analysis revealed a collapse of the protective, Lactobacillus-centered network in the PPROM group, which was replaced by a densely interconnected network of anaerobic bacteria with Gardnerella vaginalis as a key hub. Functionally, the PPROM microbiome was enriched for amino acid biosynthesis pathways, in contrast to the HC group, which was enriched for nucleotide and peptidoglycan biosynthesis. PPROM appears to be linked with a complex vaginal dysbiosis that encompasses significant alterations in microbial composition, diversity, interactions, and functional potential. These findings highlight the vaginal microbiome as a critical factor in the pathogenesis of PPROM and suggest its potential for risk stratification and as a therapeutic target to improve pregnancy outcomes. Full article

Background/Objectives: Preterm birth (PTB) is a leading cause of neonatal mortality, particularly in women with a short cervix. Vaginal dysbiosis has been associated with increased PTB risk. Progesterone (PR) and Arabin pessary (PE) are commonly used for PTB prevention, but their impact on vaginal microbiome composition is unclear. This study aimed to compare the effects of these interventions on the vaginal microbiome in women at risk of PTB. Methods: In a secondary analysis of a randomized trial at Hospital das Clínicas, Universidade de São Paulo, 203 women with singleton pregnancies and cervical length ≤ 25 mm at the second trimester were assigned to daily vaginal PR (200 mg) or PE. Vaginal swabs from 44 participants (n = 22 per group) were collected at baseline and 4 weeks post-treatment and analyzed via 16S rRNA gene sequencing. Results: From 88 samples analyzed, 80 showed a low-diversity, Lactobacillus-dominated microbiota, 42 classified into Lactobacillus iners-dominated community state type (CST-III), and 38 presented other Lactobacillus species dominance (termed CST-I/II/V). The remaining eight samples presented non-Lactobacillus dominance (CST-IV). Comparing the two groups, no significant changes in CST were observed between sampling timepoints (PE group, p = 0.368; PR group, p = 0.223). Similarly, Shannon alpha diversity did not change (PE group, p = 0.62; PR group, p = 0.30), and Bray–Curtis dissimilarity also did not change after treatment (p = 0.96, before; p = 0.87, after treatment). Conclusions: Arabin pessary and vaginal progesterone maintain vaginal microbiome stability in women at high PTB risk, supporting the microbiological safety of both interventions. Full article

Automatic detection of clue cells is crucial for rapid diagnosis of bacterial vaginosis (BV), but existing algorithms suffer from low sensitivity. This is because clue cells are highly similar to normal epithelial cells in terms of macroscopic size and shape. The key difference between clue cells and normal epithelial cells lies in the surface texture and edge morphology. To address this specific problem, we propose an clue cell detection algorithm named CA-YOLO. The contributions of our approach lie in two synergistic and custom-designed feature extraction modules: the context-aware module (CAM) extracts and captures bacterial distribution patterns on the surface of clue cells; and the shuffle global attention mechanism (SGAM) enhances cell edge features and suppresses irrelevant information. In addition, we integrate focal loss into the classification loss to alleviate the severe class imbalance problem inherent in clinical samples. Experimental results show that the proposed CA-YOLO achieves a sensitivity of 0.778, which is 9.2% higher than the baseline model, making the automated BV detection more reliable and feasible. Full article

Preterm birth is a major cause of perinatal mortality and morbidity in newborns, and its risk is increased by bacterial vaginosis (BV) during pregnancy. This multicenter prospective cohort study aimed to evaluate whether Flora select™ (FS), a newly developed real-time polymerase chain reaction test, is clinically useful for assessing the effectiveness of BV treatment during pregnancy. The vaginal microbiome characterized by relative dominance rates of Lactobacillus ≤ low (<50%), together with a positive test for Gardnerella, Prevotella, or Atopobium species, was defined as BV-FS A criterion. The vaginal microbiome characterized by Lactobacillus medium (50%≤, <80%), together with positive tests for Gardnerella plus either Prevotella species or Atopobium species, was defined as BV-FS B criterion. This study enrolled 25 pregnant women with classical BV (Nugent score ≥ 7) at initial examinations, and they met the BV-FS A (n = 23) and BV-FS B (n = 2) criteria. No woman with classical BV had a missed diagnosis of molecular BV. Treatments with metronidazole vaginal tablets resulted in the improvement of 88.0% (22/25) of classical BV, 65.2% (15/23) of BV-FS A, and 50.0% (1/2) of BV-FS B cases, whereas positive rates of Ureaplasma species in women with classical BV increased by 42.9%. Although most classical BV cases were cured following metronidazole treatments, a considerable proportion still harbored molecular BV detected by FS. Although the Nugent scoring system revealed that 80.0% (20/25) of women with classical BV (Nugent score ≥ 7) were sufficiently cured as BV-negative (Nugent scores 0–3), 5 (25%) of the 20 cured cases still met the BV-FS A/B criteria. FS particularly detected Ureaplasma species in 9 (45%) of the 20 cured cases. It could identify pregnant women who require additional treatments for residual molecular BV and Ureaplasma species. Therefore, the FS test may be clinically useful for assessing the vaginal microbiome and evaluating the effectiveness of BV treatments. Full article

Background and Clinical Significance: Anaerococcus tetradius (A. tetradius) and Gardnerella vaginalis (G. vaginalis) are rare etiological factors for postpartum endometritis and are typically associated with bacterial vaginosis. However, in some cases, G. vaginalis and A. tetradius can cause serious postpartum endometritis with complications such as sepsis. Case Presentation: 26-year-old pregnant woman expecting monochorionic diamniotic twins presented to the hospital at 35 weeks and 3 days of gestation and two male infants were delivered via the Cesarean section. On the fifth day after delivery, the patient began to complain of intense abdominal pain, a fever of 37.9 °C, and overall weakness. Blood tests revealed neutrophilic leukocytosis, increased C-reactive protein (CRP) of 225.4 mg/L. Upon examination, abdominal distension, tenderness on palpation, and positive symptoms of peritoneal irritation were present and the site of the abdominal incision was inflamed with flowing foul-smelling greenish pus. Ultrasound examination revealed free fluid collection in the peritoneal cavity, under the liver, and around the uterus. Later, the condition of the patient worsened with progressing hypotension and respiratory distress. As a result, suppurative peritonitis and sepsis was suspected and the patient underwent urgent total hysterectomy without oophorectomy. Acute endometritis, focal myometritis, and chronic cervicitis were concluded from histopathological examination of the removed uterus. Microbiological tests showed the most abundant growth of A. tetradius in the wound cultures and great abundance of G. vaginalis in the abdominal cavity cultures. After trying three different treatment schemes and difficulties with determining the antibiotic sensitivity tests for pathogens, the antibacterial therapy was escalated to Meropenem, which was found to be effective, and the patient was discharged home. Conclusions: This case report highlights the severity of complications of postpartum endometritis that can be caused by rare pathogens (such as G. vaginalis and A. tetradius), and strategies for how to manage it. The clinical presentation of a patient should be monitored closely for several days after Cesarean section and if endometritis is suspected, microbiological cultures are necessary to determine the cause of infection and implement an appropriate treatment. Full article

Sexually transmitted infections (STIs) are a significant global health concern, affecting millions of people worldwide, particularly sexually active adolescents and young adults. These infections, caused by various pathogens, including bacteria, viruses, parasites, and fungi, can have profound implications for women’s reproductive health and fertility. This review explores the role of vaginal and uterine infections in women’s infertility, focusing on the most common pathogens and their impact on reproductive outcomes. Bacterial infections, such as those caused by intracellular bacteria (Mycoplasma, Ureaplasma, and Chlamydia), Neisseria gonorrhoeae, and bacterial vaginosis, are among the most prevalent causes of infertility in women. Studies have shown that these infections can lead to pelvic inflammatory disease, tubal occlusion, and endometrial damage, all of which can impair fertility. Mycobacterium tuberculosis, in particular, is a significant cause of genital tuberculosis and infertility in high-incidence countries. Viral infections, such as Human papillomavirus (HPV) and Herpes simplex virus (HSV), can also affect women’s fertility. While the exact role of HPV in female infertility remains unclear, studies suggest that it may increase the risk of endometrial implantation issues and miscarriage. HSV may be associated with unexplained infertility. Parasitic infections, such as trichomoniasis and schistosomiasis, can directly impact the female reproductive system, leading to infertility, ectopic pregnancy, and other complications. Fungal infections, such as candidiasis, are common but rarely have serious outcomes related to fertility. The vaginal microbiome plays a crucial role in maintaining reproductive health, and alterations in the microbial balance can increase susceptibility to STIs and infertility. Probiotics have been proposed as a potential therapeutic strategy to restore the vaginal ecosystem and improve fertility outcomes, although further research is needed to establish their efficacy. In conclusion, vaginal and uterine infections contribute significantly to women’s infertility, with various pathogens affecting the reproductive system through different mechanisms. Early diagnosis, appropriate treatment, and preventive measures are essential to mitigate the impact of these infections on women’s reproductive health and fertility. Full article

Background/Objectives: Endocrine disruptors (EDs) are xenobiotic chemicals that disrupt hormone signaling and homeostasis within the human body. Accumulative evidence proposes that EDs could affect systemic hormone balance and local microbial communities, including the female genital tract (FGT) microbiome. The FGT microbiome, and especially the vaginal microbiota, contributes significantly to reproductive health maintenance, defense against infection, and favorable pregnancy outcomes. Disruption of the delicate microbial environment is associated with conditions like bacterial vaginosis, infertility, and preterm birth. Methods: The present narrative review summarizes the existing literature on EDs’ potential for changing the FGT microbiome. We discuss EDs like bisphenol A (BPA), phthalates, and parabens and their potential for disrupting the FGT microbiome through ED-induced hormone perturbations, immune modulation, and epithelial barrier breach, which could lead to microbial dysbiosis. Results: Preliminary evidence suggests that ED exposure–microbial composition changes relationships; however, robust human evidence for EDs’ changes on the FGT microbiome remains scarce. Conclusions: Our review addresses major research gaps and suggests future directions for investigation, such as the necessity for longitudinal and mechanistic studies that combine microbiome, exposome, and endocrine parameters. The relationship between EDs and the FGT microbiome could be critical for enhancing women’s reproductive health and for steering regulatory policies on exposure to environmental chemicals. Full article

Bacterial vaginosis (BV) affects 30% of women annually, but many face barriers to in-person care. Here we present real-world outcomes of remote BV diagnosis and management through self-collected vaginal microbiome (VMB) testing and telemedicine visits, focusing on symptom resolution, recurrence, and overall microbial shifts. Among the 1159 study participants, 75.5% experienced symptom resolution at four weeks when managed with our algorithm-guided treatment protocol. At a median follow-up of 4.4 months after the initial visit, 30.0% of patients experienced recurrent BV, which is lower than the typical recurrence rates seen in historical in-person cohorts. Across the entire cohort, metagenomic data demonstrated a significant increase in Lactobacillus abundance (mean of 32.9% to 48.4%, p < 0.0001) and a corresponding decrease in BV-associated taxa such as Gardnerella, Prevotella, and Fannyhessea. A PERMANOVA of pairwise Bray–Curtis distances showed significant separation between pre-and post-treatment samples (pseudo-F = 37.6, p < 0.0001), driven by an increase in Lactobacillus-dominated samples. Treatment adherence was high (a total of 78% reported perfect or near-perfect adherence), and adverse events were generally mild (in total, 22% reported vaginal irritation, and 13% reported abnormal discharge). These results demonstrate that Evvy’s at-home metagenomic platform, paired with telemedicine and a smart treatment algorithm, delivers robust clinical and microbial outcomes. This work offers a novel approach to managing bacterial vaginosis, a challenging condition characterized by persistently high recurrence rates. Full article

Introduction: Vaginal microbiota has emerged as an important factor influencing human papillomavirus (HPV) persistence and host immunity. While HPV infection is often transient, persistent infections with high-risk HPV genotypes significantly increase the risk of cervical carcinogenesis. Thus, this study aims to investigate the association between microflora/sexually transmitted infections (STIs) and HPV infection, with a focus on the prevalence of coinfection and the potential role of genital tract microecological disorders. Methods: A prospective cohort study was conducted at a tertiary care center in Astana, Kazakhstan, between November 2024 and March 2025. A total of 396 non-pregnant women aged 18–45 years were enrolled during routine gynecological screening. Cervical samples were collected for high-risk HPV genotyping and the detection of 11 other vaginal microorganisms using real-time PCR. Results: HPV-positive women were significantly younger and more likely to be single compared to HPV-negative participants. They also had fewer pregnancies and deliveries and were more likely to use barrier contraception. Among STIs, Mycoplasma hominis demonstrated a significant association with HPV infection (adjusted OR = 2.16, 95% CI: 1.15–4.05, p = 0.017). Overall STI presence (adjusted OR = 2.16, p = 0.017) and STI multiplicity (adjusted OR = 1.36 per additional STI, p = 0.017) were also significantly associated with HPV positivity. Correlation analysis revealed a moderate association between Chlamydia trachomatis and Trichomonas vaginalis (ϕ = 0.39, p < 0.001), suggesting shared ecological or transmission pathways. Conclusion: The findings highlight the relevance of specific vaginal pathogens, particularly Mycoplasma hominis, and co-infection patterns in increasing the risk of HPV infection. These results underscore the importance of comprehensive STI screening and microbial profiling in cervical cancer prevention strategies, especially in populations with limited access to HPV vaccination. Further longitudinal and mechanistic studies are warranted to elucidate causal pathways and progression to cervical neoplasia. Full article

Vaginitis is a major health concern among women, with inadequate treatment potentially leading to reproductive complications. This study aimed to assess vaginitis prevalence, identify predominant pathogens, and evaluate associated risk factors among female patients at Da Nang Dermato-Venereology Hospital. A prospective study of 796 female patients undergoing physical examinations was conducted, with demographic, clinical, and microbiological data collected. Vaginitis was diagnosed in 180 (22.6%) of 796 female patients, predominantly caused by Candida spp. (66.1%) and bacterial pathogens (31.7%), with no Trichomonas vaginalis detected, and was most prevalent in women aged 20–30 years. Poor hygiene practices, including infrequent sanitary pad changes (OR = 5.01, p < 0.001) and routine vaginal douching (OR = 6.77, p < 0.001), were significantly associated with vaginitis. The Amsel criteria showed high specificity (99.1%) for bacterial vaginosis diagnosis. The absence of T. vaginalis suggests a potential shift in the epidemiology of vaginal infections. The Amsel criteria are a practical diagnostic tool in resource-limited settings. Our findings highlight the need for targeted hygiene education to reduce vaginitis prevalence in Vietnam. Full article