Vaginal Epithelium Research Articles

Bacterial burden and molecular characterization of Coxiella burnetii in shedding pregnant and postpartum ewes from Saint Kitts

This study aimed to evaluate the bacterial burden and perform molecular characterization of Coxiella burnetii during shedding in pregnant (vaginal, mucus and feces) and postpartum (vaginal mucus, feces and milk) ewes from Saint Kitts. Positive IS1111 DNA (n=250) for C. burnetii samples from pregnant (n=87) and postpartum (n=74) Barbados Blackbelly ewes in a previous investigation were used for this study. Vaginal mucus (n=118), feces (n=100), and milk (n=32) positive IS1111 C. burnetii-DNA were analysed by real time qPCR (icd gene). For molecular characterization of C. burnetii, selected (n=10) IS1111 qPCR positive samples were sequenced for fragments of the IS1111 element and the 16 S rRNA gene. nBLAST, phylogenetic and haplotype analyses were performed. Vaginal mucus, feces and milk had estimated equal amounts of bacterial DNA (icd copies), and super spreaders were detected within the fecal samples. C. burnetii haplotypes had moderate to high diversity, were ubiquitous worldwide and similar to previously described in ruminants and ticks and humans.

Ethanolic extract of Persea americana Mill. (Lauraceae) seeds induced antiestrogenic effects in young female Wistar rats.

The ethanol extract of Persea americana seeds was found to inhibit the development of estrogen-dependent conditions in female Wistar rats, suggesting the ability of its secondary metabolites to interact with estrogen receptors (ERs), either as partial agonists or as antagonists. To test this hypothesis, the abovementioned extract was assessed for its ability to mimic and/or antagonize estradiol effects. Two experiments were conducted in ovariectomized (OVX) rats: (1) animals were treated with estradiol valerate (E2V; 1 mg/kg) or P.americana at doses of 25 and 50 mg/kg; (2) animals were treated with E2V alone (0.75 mg/kg) or in combination with P.americana at the abovementioned doses. Treatments were given orally for 3days and animals were sacrificed for biochemical and histological analyses of the uterus and vagina. When administered alone, P.americana did not change the histomorphology of both organs (uterus and vagina). In combination with E2V, P.americana decreased uterine weight [30 % decrease (p<0.001) at 25 mg/kg and 24 % (p<0.01) at 50 mg/kg] and epithelium height (37 % decrease). This was associated with decreased estradiol levels (at least 86 % decrease, p<0.001) in the uterus. Similarly, vagina epithelium height decreased by at least 34 % (p<0.05) when E2V was co-administered with P.americana. The seed extract of P.americana contains ER antagonist secondary metabolites accounting for its ability to inhibit the development of estrogen-dependent conditions in female rats.

Molecular stratification of the human fetal vaginal epithelium by spatial transcriptome analysis.

The human vaginal epithelium is a crucial component of numerous reproductive processes and serves as a vital protective barrier against pathogenic invasion. Despite its significance, a comprehensive exploration of its molecular profiles, including molecular expression and distribution across its multiple layers, has not been performed. In this study, we perform a spatial transcriptomic analysis within the vaginal wall of human fetuses to fill this knowledge gap. We successfully categorize the vaginal epithelium into four distinct zones based on transcriptomic profiles and anatomical features. This approach reveals unique transcriptomic signatures within these regions, allowing us to identify differentially expressed genes and uncover novel markers for distinct regions of the vaginal epithelium. Additionally, our findings highlight the varied expressions of keratin ( KRT) genes across different zones of the vaginal epithelium, with a gradual shift in expression patterns observed from the basal layer to the surface/superficial layer. This suggests a potential differentiation trajectory of the human vaginal epithelium, shedding light on the dynamic nature of this tissue. Furthermore, abundant biological processes are found to be enriched in the basal zone by KEGG pathway analysis, indicating an active state of the basal zone cells. Subsequently, the expressions of latent stem cell markers in the basal zone are identified. In summary, our research provides a crucial understanding of human vaginal epithelial cells and the complex mechanisms of the vaginal mucosa, with potential applications in vaginal reconstruction and drug delivery, making this atlas a valuable tool for future research in women's health and reproductive medicine.

Vaginal Microbiota and Proinflammatory Status in Patients with Polycystic Ovary Syndrome: An Exploratory Study.

Background/Purpose: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disease most common in patients of childbearing age. This pathology is associated with clinical, metabolic, and reproductive complications. We evaluated the diversity of the vaginal microbiota (VM), the vaginal inflammatory reaction (VIR), the proinflammatory state, and the activation of polymorphonuclear neutrophils (PMN) with the production of neutrophil extracellular traps (NETs). Methods: Thirty-three patients who attended a consultation at the Hospital UTPL-Santa Inés, Loja, Ecuador, from May to August 2023 who were diagnosed with PCOS participated in this study. Blood samples, vaginal discharge, and a survey were obtained. Results: A high number of patients, 23/33 (69.7%), presented altered microbiota in clinical variables associated with PCOS phenotypes A and B, sexual partners (>2), and oligomenorrhoea. A significant statistical association was only observed for sexually transmitted infections at sampling (p = 0.023) and insulin (p = 0.002). All eight cases studied with VIR had PMN/NETotic activity. A high frequency of proinflammatory states was observed in all vaginal microbiota states. Conclusions: These results suggest that the PCOS could trigger a proinflammatory state in the vaginal epithelium independently of the state of the vaginal microbiota. Furthermore, the presence of NETs observed in the cases studied could decrease fertility in these PCOS patients.

Exposure of small ruminants and humans to Coxiella burnetii in the semi-arid region of Northeastern Brazil.

Q fever is a zoonotic disease caused by the obligate intracellular pathogen Coxiella burnetii, for which domestic ruminants are the primary source of infection in humans. Herein, we investigated the presence of C. burnetii in humans, sheep, and goats in the semi-arid region of northeastern Brazil. The presence of anti-C. burnetii antibodies was surveyed using indirect immunofluorescence assay, and detection of C. burnetii DNA was performed by polymerase chain reaction (PCR). Anti-C. burnetii antibodies were detected in 60% of farms, 4.8% of goats, 1.5% of sheep, and 4.5% of human samples. PCR was positive in 18.9% of blood samples, 7.7% of milk samples, and 7.7% of vaginal mucus samples. A DNA sequence of a C. burnetii DNA sample extracted from the goat vaginal mucus showed 99.2-99.4% nucleotide identity with other strains previously reported in Brazil. These results indicate that C. burnetii is present in the surveyed area, where it poses a risk to both public and animal health. These findings indicate an urgent need for educative actions to protect population, as well as better training of veterinarians to detect and report Q fever.

Ameliorating Effects of Arsenic-Induced Toxicity On The Histology Of Vagina And Reproductive Hormones Of Female Sprague Dawley Rats

Objective: To find out the toxic effects of arsenic on the histology of the vagina and reproductive hormones of female Sprague Dawley rats. Methods: 60 female Sprague Dawley rats were divided into control group A and experimental group B with 30 rats in each group. The gross weight of all the rats was checked before and at the end of the experiment. After one week of acclimatization, the control group was administered 10ml of distilled water by oral gavage daily for 14 days and the experimental group was administered 4µg of sodium arsenite dissolved in 10ml of distilled water by oral gavage daily for 14 days. After being euthanized by chloroform inhalation on day 15, blood from each rat was drawn by a single intra-cardiac puncture and stored for biochemical analysis. After that, rats were sacrificed and the whole reproductive tract was removed and vaginal sections were prepared and stained with hematoxylin and eosin (H&amp;E ). The histological parameters were analyzed by using Image J software. Whereas, biochemical parameters e.g. serum LH and FSH levels were analyzed by ELISA. Results: After exposure to a low dose of arsenic administered for a short period, the gross weight of rats, weight of reproductive tract, height of vaginal epithelium and serum FSH and LH values were significantly reduced in experimental animals as compared to control animals with p-value &lt; 0.05. Conclusion: Low dose of arsenic given via contaminated drinking water for a short period is very toxic to the female reproductive tract which is evident by the histological changes in the vagina and deranged hormonal profile of female Sprague Dawley rats. Keywords: Arsenic, FSH, Free radicals, LH, Oxidative stress, Vagina.

Hydrogel- and Nanocomposite-Based Drug-Delivery Strategies in the Treatment of Vaginal Infections.

The reproductive health of women is governed by an optimal balance in the host-microbiota interaction. Depletion of the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynaecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With a careful choice of polymers (natural, synthetic, or semisynthetic), hydrogels with specific properties, such as stimuli responsiveness, antimicrobial, and muco-adhesiveness, can be tailored for higher therapeutic efficacy. In this review, the advances in hydrogel strategies for the treatment of vaginal infections are presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Comparative analysis of the vaginal bacteriome and virome in healthy women living in high-altitude and sea-level areas

The vaginal microbiota plays an important role in the health of the female reproductive tract and is closely associated with various pregnancy outcomes and sexually transmitted diseases. Plenty of internal and external factors have strong influence on the changes in a woman's vaginal microbiome. However, the effect of a high-altitude on female vaginal microbiota has not been described. In this study, we characterized the vaginal bacteriome and virome of 13 and 34 healthy women living in high-altitude and sea-level areas, using whole-metagenome shotgun sequencing of their vaginal mucus samples. The results revealed that the vaginal bacteriomes of high-altitude individuals are featured by a significant increase of species diversity, depletion of Lactobacillus crispatus, and more abundant of some anaerobic bacteria, such as Chlamydia trachomatis, Mageeibacillus indolicus, Dialister micraerophilus, and Sneathia amnii). In addition, the vagina samples of sea-level subjects harbor more Lactobacillus strains, whereas the anaerobic bacteroidetes strains mostly appeared in high-altitude subjects. Identified and assembled 191 virus operational taxonomic units (vOTUs), there were significant differences in the abundance of 107 vOTUs between the two groups. Together, the results of this study raised the understanding of bacteriome and virome in the vagina of women at different elevations, and demonstrated that the vaginal microbiome is related to the high-altitude geographic adaptation.

An examination of differences in epigenetic methylation of saliva type samples based on collection method.

In the context of forensic casework, it is imperative to both establish a DNA profile from biological specimens and accurately identify the specific bodily fluid source. To achieve this, DNA methylation markers have been developed for the differentiation of blood, semen, vaginal epithelial secretions, and saliva samples. Saliva, alternatively referred to as oral fluid, is recognized for its heterogeneous cellular composition, characterized by a mixture of epithelial, leukocytic, and bacterial cells. Consequently, our research has revealed variations in methylation percentages that correlate with the method employed for collecting saliva samples. To investigate these concepts, we scrutinized four CpG markers situated within or in proximity to the BCAS4, SLC12A8, SOX2OT, and FAM43A genes. Subsequently, we designed primers based on bioinformatically transformed reference sequences for these markers and rigorously assessed their quality by examining dimer and hairpin formation, melting temperature, and specificity. These loci were identified as saliva markers based on either buccal swabs or spit collection. Yet, there has been minimal or no research conducted to explore the variations in methylation between different collection methods. For this study, buccal, lip, tongue, spit, and nasal swabs were collected from 20 individuals (N=100). Mock forensic samples, which include chewing gum (N=10) and cigarettes (N=10), were also tested. DNA was extracted, bisulfite converted, then amplified using in-house designed assays, and pyrosequenced. The methylation levels were compared to other body fluids (semen, blood, vaginal epithelia, and menstrual blood [N=32]). A total of 608 pyrosequencing results demonstrated that sampling location and collection method can greatly influence the level of methylation, highlighting the importance of examining multiple collection/deposition methods for body fluids when developing epigenetic markers.

Modeling Healthy and Dysbiotic Vaginal Microenvironments in a Human Vagina-on-a-Chip.

Women's health, and particularly diseases of the female reproductive tract (FRT), have not received the attention they deserve, even though an unhealthy reproductive system may lead to life-threatening diseases, infertility, or adverse outcomes during pregnancy. One barrier in the field is that there has been a dearth of preclinical, experimental models that faithfully mimic the physiology and pathophysiology of the FRT. Current in vitro and animal models do not fully recapitulate the hormonal changes, microaerobic conditions, and interactions with the vaginal microbiome. The advent of Organ-on-a-Chip (Organ Chip) microfluidic culture technology that can mimic tissue-tissue interfaces, vascular perfusion, interstitial fluid flows, and the physical microenvironment of a major subunit of human organs can potentially serve as a solution to this problem. Recently, a human Vagina Chip that supports co-culture of human vaginal microbial consortia with primary human vaginal epithelium that is also interfaced with vaginal stroma and experiences dynamic fluid flow has been developed. This chip replicates the physiological responses of the human vagina to healthy and dysbiotic microbiomes. A detailed protocol for creating human Vagina Chips has been described in this article.

Genome-wide association study in Estonia reveals importance of vaginal epithelium associated genes in case of recurrent vaginitis

Recurrent vaginitis is a leading reason for visiting a gynaecologist, with bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) being the most common diagnoses. Reasons and mechanisms behind their recurrent nature are poorly understood. We conducted a genome-wide association study (GWAS) to find possible genetic risk factors for recurrent vaginitis using data from a large population-based biobank, the Estonian Biobank. The study included 6870 cases (at least two episodes of vaginitis) and 5945 controls (no vaginitis episodes). GWAS approach included single marker and gene-based analyses, followed by functional annotation of associated variants and candidate gene mapping.In single marker analysis, one statistically significant (P = 7.8 × 10−9) variant rs1036732378 was identified on chromosome 10. The gene-based association analysis identified one gene, KRT6A, that exceeded the recommended significance threshold (P = 2.6 × 10−6). This is a member of the keratin protein family and is expressed during differentiation in epithelial tissues.Functional mapping and annotation of genetic associations by using adjusted significance level identified 22 potential risk loci that may be associated with recurrent vaginitis phenotype. Comparison of our results with previous studies provided nominal support for LBP (associated with immune response to vaginal bacteria) and PRKCH genes (possible role in keratinocyte differentiation and susceptibility to candidiasis).In conclusion, this study is the first highlighting a potential role of the vaginal epithelium in recurrent vaginitis.

Efficacy of Traditional Kegels Versus Reverse Kegels on Vaginal Atrophy among Post Menopausal Women

Background: Menopause leads to a dramatic drop in ovarian function which lower the oestrogen in the circulatingblood may cause atrophy of vaginal epithelium. Traditionally the atrophy of vaginal epithelium was managed byKegels exercise but not attempted using reverse Kegels exercise.Purpose: This present study attempted the reverse Kegels exercise and compares the effectiveness with traditionalKegels exercise on vaginal atrophy and vaginal pH among postmenopausal women.Materials and Methods: 32 postmenopausal women in the age group between 40 to 60 years with vaginal atrophywere recruited and randomly assigned to one of the two groups: Traditional Kegels group (n=16) and ReverseKegels group (n=16). The vulvovaginal symptom questionnaire (VSQ) and vaginal pH test kit were used asoutcome measures to assess the vulvovaginal symptoms and vaginal pH level before and after the intervention.Results: The t-test analysis was used to analyse the comparison within and between the groups. The p value of theVulvovaginal symptom questionnaire in post-test values between the groups was 0.0256 (p value &lt; 0.05) whichwas statistically significant.Conclusion: Based on the outcome measures the participants in the traditional Kegels exercise found to be betterin reliving the vulvovaginal symptoms. However, the vaginal pH level in both the groups after intervention doesnot show any changes.

Influence of Platelet-Rich Plasma on Recurrent Vesicovaginal Fistula-A Histological and Immunohistochemical Study.

Vesicovaginal fistula is a cause of deterioration in the quality of life. It is a communication between the bladder and vagina resulting in the uncontrollable leakage of urine through the vagina. Recently, regenerative methods have been used more frequently, and platelet-rich plasma is one of these methods. The functional properties of platelet-rich plasma are based on the synthesis and secretion of multiple growth factors released after platelet activation. The aim of this study was to investigate how platelet-rich plasma influences the condition of the tissue and the healing ability of the urothelium, vaginal epithelium and tissues surrounding the fistulous canal. The study included eight patients who had undergone the Latzko procedure aimed at closing the vesicovaginal fistula. Samples were collected during primary surgery without platelet-rich plasma and after failed surgery, during a second attempt. The specimens were subjected to histological and immunohistochemical evaluation. The histology demonstrated that in platelet-rich plasma patients, greater vascularization and wider subepithelial mucosa layering was observed. Inflammatory infiltration in the subepithelial layer was increased in platelet-rich plasma patients. No localization differences in growth factor proteins were found in either group, but in platelet-rich plasma-patients, the reactions were stronger. It can be concluded that the use of platelet-rich plasma improves the morphological structure of the injected tissues.

In silico and in vitro assessment of an optimized QbD-guided myoinositol and metformin-loaded mucus-penetrating particle-based gel for the amelioration of PCOS.

Polycystic ovarian syndrome (PCOS) is a multi-factorial endocrine disorder affecting women of reproductive age. However, its high prevalence and the unsuccessful translation of conventional modalities have made PCOS a pharmaco-therapeutic challenge. In the present study, we explored bi-formulations (comprising metformin-loaded mucus-penetrating nanoparticles, MTF-MPPs, and myoinositol-loaded mucus-penetrating particles, MI-MPPs) incorporated in a carbomer gel tailored for intravaginal administration. For the development and optimization of the MPPs-gel, a QbD (quality by design) approach was employed, including the initial and final risk assessment, central composite design of experts, and method validation. The optimized MTF-MPPs and MI-MPPs possessed an optimum nanometric particle size (195.0 nm and 178.8 nm, respectively) and a PDI of 0.150 and 0.123, respectively, together with a negligible negative zeta potential (-5.19 mV and -6.19 mV, respectively) through the vaginal mucus. It was observed that the MPPs are small and monodisperse with a neutral surface charge. It was observed that the MPPs-gel formulations released approximately 69.86 ± 4.65% of MTF and 67.14 ± 5.74% of MI within 120 h (5 days), which was observed to be sustained unlike MFT-MI-gel with approximately 94.89 ± 4.17% of MTF and 90.91 ± 15% of MI drugs released within 12 h. The confocal microscopy study of rhodamine-loaded MPPs indicated that they possessed a high fluorescence intensity at a depth of 15 μm, while as the penetration trajectory in the vaginal tissue increased to 35 μm, their intensity was reduced, appearing to be more prominent in the blood vessels. The analyzed data of MPPs-gel suggest that the optimized MPPs-gel formulation has potential to reach the targeted area via the uterovaginal mucosa, which has a wide network of blood vessels. Subsequently, in vivo studies were conducted and the results revealed that the proposed MPPs-gel formulation could regulate the estrous cycle of the reproductive system compared to the conventional formulation. Moreover, the formulation significantly reduced the weight of the ovaries compared to the control and conventional vaginal gel. Biochemical estimation showed improved insulin and sex hormone levels. Thus, the obtained data revealed that the deep penetration and deposition of MTF and MI on the targeted area through intravaginal delivery resulted in better therapeutic effects than the conventional vaginal gel. The obtained results confirmed the amelioration of PCOS upon treatment using the prepared MPPs-gel formulation. According to the relevant evaluation studies, it was concluded that MPPs-gel was retained in the vaginal cavity for systemic effects. Also, the sustained and non-irritating therapeutic effect meets the safety aspects. This work serves as a promising strategy for intravaginal drug delivery.

Characterisation of reproductive tract microbiome and immune biomarkers for bovine genital campylobacteriosis in vaccinated and unvaccinated heifers.

Bovine genital campylobacteriosis (BGC) is a globally important venereal disease of cattle caused by Campylobacter fetus subspecies venerealis. Diagnosis of BGC is highly challenging due to the lack of accurate diagnostic tests. To characterise the biomarkers for C. fetus venerealis infection, a total of twelve cycling heifers were selected and categorised as vaccinated (n = 6) with Vibrovax® (Zoetis™) and unvaccinated (n = 6). All heifers were oestrous synchronised with a double dose of prostaglandin (PGF2α) 11 days apart and when in oestrous intravaginally challenged with 2.7 x 109 CFU live C. fetus venerealis. DNA extracted from vaginal mucus samples was screened using a C. fetus qPCR and 16S rRNA was characterised using Illumina sequencing (V5-V8 region). Relative abundances of serum proteins were calculated using sequential window acquisition of all theoretical fragment ion spectra coupled to tandem mass spectrometry (SWATH-MS) for all heifers at three timepoints: pre-challenge, post-challenge and post-recovery. In 16S rRNA sequencing of vaginal mucus, Campylobacter spp. appeared two days following challenge in unvaccinated compared to 14 days in vaccinated animals, consistent with the qPCR results. Increased relative abundances of Firmicutes and Campylobacterota were identified after C. fetus venerealis challenge and were associated with C. fetus venerealis in vaccinated and unvaccinated heifers. Greater relative abundance of Streptococcus spp. was observed during oestrous rather than dioestrous. In both vaccinated and unvaccinated heifers, Acinetobacter spp. increased after challenge with higher abundance of Corynebacterium spp. in the vaccinated group. A total of 130 unique proteins were identified in SWATH analysis of the serum samples, and the number of differentially abundant proteins found was higher in the vaccinated group after recovery from infection compared to pre-and post-challenge (adjusted P < 0.05 and Log2FC > 0.2). Coglutinin, clusterin, HP homologs, vitamin D binding protein and fetuin B were identified as potential biomarkers for C. fetus venerealis infection and need further study to validate their efficiency as immune biomarkers for BGC.

Vaginal reconstruction by collagen scaffolds loaded with vaginal epithelial and smooth muscle cells in pigs.

In women, a healthy and functional vagina is important for the maintenance of a good quality of life. Various factors, including congenital anomalies, cancer, trauma, infections, inflammation, or iatrogenic injuries, can lead to damage or loss of the vaginal structure, necessitating repair or replacement. Often, such reconstruction procedures involve the use of nonvaginal tissue substitutes, like segments of the large intestine or skin, which are less than ideal both anatomically and functionally. Therefore, there is an urgent need to develop new methods of vaginal reconstruction. In this study, we established a new method for isolation and expansion of vaginal epithelial and smooth muscle cells. Subsequently, collagen scaffolds designed for vaginal reconstruction were loaded with vaginal epithelial and smooth muscle cells in vitro and tested in vivo using the vaginal excision pig model. The results showed that the collagen scaffold loaded with vaginal epithelial and smooth muscle cells significantly promotes the reconstruction of the vagina compared with small intestinal submucosa (SIS) membrane or bare collagen scaffold. Notably, the reconstructed vaginal tissues exhibit remarkable similarity to their normal counterparts, encompassing not only the vaginal epithelium and smooth muscle but also the intricate networks of blood vessels and nerves. These compelling results underscore the feasibility of a tissue engineering approach in vaginal reconstruction, offering promising prospects for improving the quality of life in affected individuals.

The differences of electrical resistance values of vaginal mucus (ERVM) in yearling and mature saanen goats

It has been reported that during the oestrous cycle, an increase in the volume of cervical mucus occurs due to the influence of high oestrogen concentration on vaginal vasodilation, leading to a decrease in the electrical resistance of vaginal mucus (ERVM) as the goat approaches estrus. The present study aims to understand the differences between yearling (n:14) and mature (n:22) Saanen goats when continuous measurements of ERVM were taken by using the digital Draminski® device (Draminski Electronics, Poland). Oestrus was synchronized using intravaginal sponges and the ERVM measurement was taken every 6 hours right after the sponge removal until insemination. The results indicate that ERVM measurements for mature Saanen goats were significantly lower at 0, 6, 12, 30, 36, and 42 hours compared to those of yearling Saanen goats. Additionally, within the yearling Saanen group, there was a significant difference between the measurement taken at the 18th hour and the measurements taken at other time points. Furthermore, as goats approached estrus, the differences in ERVM measurements between mature and yearling Saanen goats disappeared. Based on these results, the ERVM values in yearling Saanen goats can be reliably used for predicting time of estrus, while a more cautious approach should be taken for mature Saanen goats.

The microbial landscape of the genital tract of healthy cows with different gestation periods

The doctrine of the normal microflora of the human and animal body is currently in the focus of attention of clinical microbiologists and a wide range of clinical specialists. It is known that the microflora of the vagina depends on many factors of the internal and external environment, therefore, it is now considered to be an ecosystem with a unique set of mechanisms that ensure its resistance to foreign microorganisms and support reproductive health. The aim of the study was to study changes in vaginal microbiocenosis in cows during different periods of pregnancy. The object of the study was clinically healthy cows (n=10) of a redmottled breed (holshitinized), and the subject of the study was cervical–vaginal mucus. On the 150-160, 210-220 and 260-265 days of pregnancy, mucus samples were taken from cows using sterile probe tampons for bacteriological studies. It was found that representatives of the normoflora, as well as conditionally pathogenic and pathogenic microflora were present in the vaginal secretions of animals of all periods of pregnancy. However, the total bacterial contamination of the genital tract in cows in the first half and second half of the third trimester of pregnancy was characterized by its decrease by 29.2 and 33.3%, respectively, relative to the data obtained in the second trimester. It should also be noted that by the second half of the third trimester of pregnancy, there is an increase in obligate normoflora due to lacto- and bifidobacteria by 27.1% and 4 times, respectively, with the predominance of the genus Lactobacillus in quantitative terms. Against this background, the amount of transient microflora decreased by 34.2-57.1% (P0.05).

Sustained delivery of statistically optimized transfersomal gel of miconazole nitrate for vaginal candidiasis

Miconazole nitrate (MN), an antifungal drug with poor solubility, is used in the treatment of vaginal candidiasis. Conventional vaginal formulations have lower residence time and poor drug penetration resulting in the recurrence of the infection. Hence, transfersomes were formulated that would alleviate fungal infection by improving drug solubility and allowing effective permeation through the vaginal mucus and epithelium. MN-loaded transfersomes (MN-TF) were prepared by the thin film method. The optimization of the MN-TF was done by using 32 full factorial design. The Lipoid S100® and Tween 80® were selected as the phospholipid and edge activator, respectively. The responses, such as particle size, PDI, and entrapment efficiency were studied and found to be 180.70±2.11 nm, 0.293±0.012, and −13.2±1.3 mV, respectively. The optimized MN-TF was incorporated into the thermosensitive gel. The morphological study through TEM confirmed the nano size of the formulation. The FTIR study showed compatibility between the drug and excipients. The microbiological screening was performed against Candida albicans which showed a higher zone of inhibition for MN-TF than the marketed gel. The ex vivo transvaginal permeation study was done for MN-TF gel and compared with the marketed gel Daktarin®. The permeability of the MN-TF was increased by 5.8-folds as compared to the marketed gel. The HET-CAM assay for the MN-TF gel demonstrated no irritation and hence was nontoxic and safe for vaginal administration. Therefore, the MN-TF gel had sustained drug release.

Preliminary study of HPV integration status on the occurrence and development of vaginal intraepithelial neoplasia.

The aim of this study was to investigate how the integration status of HPV in the vaginal epithelium affects the development of vaginal intraepithelial neoplasia (VaIN). Twenty-four vaginal tissues were collected before applying high-throughput viral integration detection (HIVID), medical records of them were documented, including age, thin-prep cytologic test (TCT) and HPV test results, colposcopic biopsy pathology, and other clinical data, such as history of total hysterectomy for cervical lesions, whether they were infected with HPV16/18 with a follow-up span of 2 years. We summarized the distribution of HPV integration on the host chromosome and HPV type, as well as the hotspot integration gene and its role in the development of VaIN. In this study, 24 cases suffered from VaIN were involved. HPV integration was detected in 11 cases; furthermore, we discovered HPV 16 and 73, chromosome 1 and 2 possessed most HPV integration sites while EMBP1, CLO5A1, EHF, ELF5 as dominate hot spots. Taken clinical outcome into account, we found a significant difference between HPV integration occurrence and VaIN (p = 0.011). (1) This study found a statistical difference between HPV integration and the occurrence of VaIN; (2) HPV integration may provide a new clinical predictor for VaIN and facilitate risk assessment and stratified management of high-risk patients.