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Mucosal Immunology Jun 2024Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious...
Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated a role for Tregs in immunity and disease in various tissue compartments in the context of "mild" vaginal Zika virus (ZIKV) infection. We found that Tregs are critical to generate robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg sufficient mice, in which there is not CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.
PubMed: 38908483
DOI: 10.1016/j.mucimm.2024.06.007 -
Microbiome Jun 2024Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a...
BACKGROUND
Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a live biotherapeutic containing the Lactobacillus crispatus strain CTV-05, reduced BV recurrence and vaginal inflammation; however, 3 months after product cessation, CTV-05 colonization was only sustained in 48% of participants.
RESULTS
This nested sub-study in 32 participants receiving LACTIN-V finds that 72% (23/32) demonstrate clinically relevant colonization (CTV-05 absolute abundance > 10 CFU/mL) during at least one visit while 28% (9/32) of women demonstrate colonization resistance, even during product administration. Immediately prior to LACTIN-V administration, the colonization-resistant group exhibited elevated vaginal microbiota diversity. During LACTIN-V administration, colonization resistance was associated with elevated vaginal markers of epithelial disruption and reduced chemokines, possibly due to elevated absolute abundance of BV-associated species and reduced L. crispatus. Colonization permissive women were stratified into sustained and transient colonization groups (31% and 41% of participants, respectively) based on CTV-05 colonization after cessation of product administration. These groups also exhibited distinct genital immune profiles during LACTIN-V administration.
CONCLUSIONS
The genital immune impact of LACTIN-V may be contingent on the CTV-05 colonization phenotype, which is in turn partially dependent on the success of BV clearance prior to LACTIN-V administration.
Topics: Humans; Female; Vaginosis, Bacterial; Vagina; Lactobacillus crispatus; Adult; Probiotics; Administration, Intravaginal; Microbiota; Young Adult; Phenotype
PubMed: 38907268
DOI: 10.1186/s40168-024-01828-7 -
Techniques in Coloproctology Jun 2024Four patients with rectal cancer required reconstruction of a defect of the posterior vaginal wall. All patients received neoadjuvant (chemo)radiotherapy, followed by an...
Four patients with rectal cancer required reconstruction of a defect of the posterior vaginal wall. All patients received neoadjuvant (chemo)radiotherapy, followed by an en bloc (abdomino)perineal resection of the rectum and posterior vaginal wall. The extent of the vaginal defect necessitated closure using a tissue flap with skin island. The gluteal turnover flap was used for this purpose as an alternative to conventional more invasive myocutaneous flaps (gracilis, gluteus, or rectus abdominis). The gluteal turnover flap was created through a curved incision at a maximum width of 2.5 cm from the edge of the perineal wound, thereby creating a half-moon shape skin island. The subcutaneous fat was dissected toward the gluteal muscle, and the gluteal fascia was incised. Thereafter, the flap was rotated into the defect and the skin island was sutured into the vaginal wall defect. The contralateral subcutaneous fat was mobilized for perineal closure in the midline, after which no donor site was visible.The duration of surgery varied from 77 to 392 min, and the hospital stay ranged between 3 and 16 days. A perineal wound dehiscence occurred in two patients, requiring an additional VY gluteal plasty in one patient. Complete vaginal and perineal wound healing was achieved in all patients. The gluteal turnover flap is a promising least invasive technique to reconstruct posterior vaginal wall defects after abdominoperineal resection for rectal cancer.
Topics: Humans; Female; Vagina; Buttocks; Rectal Neoplasms; Middle Aged; Plastic Surgery Procedures; Surgical Flaps; Aged; Perineum; Operative Time; Treatment Outcome
PubMed: 38907171
DOI: 10.1007/s10151-024-02941-3 -
Frontiers in Microbiology 2024The concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and...
INTRODUCTION
The concept of a sterile uterus was challenged by recent studies that have described the microbiome of the virgin and pregnant uterus for species including humans and cattle. We designed two studies that tested whether the microbiome is introduced into the uterus when the virgin heifer is first inseminated and whether the origin of the microbiome is the vagina/cervix.
METHODS
The uterine microbiome was measured immediately before and after an artificial insemination (AI; Study 1; = 7 AI and = 6 control) and 14 d after insemination (Study 2; = 12 AI and = 12 control) in AI and non-AI (control) Holstein heifers. A third study (Study 3; = 5 Holstein heifers) that included additional negative controls was subsequently conducted to support the presence of a unique microbiome within the uterus despite the low microbial biomass and regardless of insemination. Traditional bacteriological culture was performed in addition to 16S rRNA gene sequencing on the same samples to determine whether there were viable organisms in addition to those detected based on DNA sequencing (16S rRNA gene sequence).
RESULTS AND DISCUSSION
Inseminating a heifer did not lead to a large change in the microbiome when assessed by traditional methods of bacterial culture or metataxonomic (16S rRNA gene) sequencing (results of Studies 1 and 2). Very few bacteria were cultured from the body or horn of the uterus regardless of whether an AI was or was not (negative control) performed. The cultured bacterial genera (e.g., , and ) were typical of those found in the soil, environment, skin, mucous membranes, and urogenital tract of animals. Metataxonomic sequencing of 16S rRNA gene generated a large number of amplicon sequence variants (ASV), but these larger datasets that were based on DNA sequencing did not consistently demonstrate an effect of AI on the abundance of ASVs across all uterine locations compared with the external surface of the tract (e.g., perimetrium; positive control samples for environment contamination during slaughter and collection). Major genera identified by 16S rRNA gene sequencing overlapped with those identified with bacterial culture and included , and .
PubMed: 38903779
DOI: 10.3389/fmicb.2024.1385505 -
Regenerative Biomaterials 2024Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the...
Promoting cell proliferation and collagen production with ascorbic acid 2-phosphate-releasing poly(l-lactide-co-ε-caprolactone) membranes for treating pelvic organ prolapse.
Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the vagina, causing a feeling of bulging, problems in urination, defaecation and/or sexual function. However, the existing surgical repair methods for relapsed POP remain insufficient, highlighting the urgent need for more effective alternatives. Collagen is an essential component in pelvic floor tissues, providing structural support, and its production is controlled by ascorbic acid. Therefore, we investigated novel ascorbic acid 2-phosphate (A2P)-releasing poly(l-lactide-co-ε-caprolactone) (PLCL) membranes to promote cell proliferation and extracellular matrix protein production to strengthen the natural support of the pelvic fascia for POP applications. We analysed the mechanical properties and the impact of PLCL on cellular responses through cell culture analysis using human vaginal fibroblasts (hVFs) and human adipose-derived stem/stromal cells (hASCs) compared to PLCL. In addition, the A2P release from PLCL membranes was assessed . The PLCL demonstrated slightly lower tensile strength (2.2 ± 0.4 MPa) compared to PLCL (3.7 ± 0.6 MPa) for the first 4 weeks . The A2P was most rapidly released during the first 48 h of incubation. Our findings demonstrated significantly increased proliferation and collagen production of both hVFs and hASCs on A2P-releasing PLCL compared to PLCL. In addition, extracellular collagen Type I fibres were detected in hVFs, suggesting enhanced collagen maturation on PLCL. Moreover, increased extracellular matrix protein expression was detected on PLCL in both hVFs and hASCs compared to plain PLCL. In conclusion, these findings highlight the potential of PLCL as a promising candidate for promoting tissue regeneration in applications aimed for POP tissue engineering applications.
PubMed: 38903561
DOI: 10.1093/rb/rbae060 -
NPJ Biofilms and Microbiomes Jun 2024Helicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori... (Review)
Review
Helicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori infection have been proven to be therapeutically insufficient, with low eradication rates and high recurrence rates. Emerging evidence suggests that antibiotic therapy for H. pylori can lead to gastrointestinal and subsequent vaginal dysbiosis, posing challenges for conventional antibiotic approaches. Thus, this article proposes a novel probiotic therapy involving simultaneous oral and intra-vaginal probiotic administration alongside antibiotics for H. pylori treatment, aiming to enhance eradication rates and mitigate dysbiosis. We begin by providing an overview of gastrointestinal and vaginal microbiota and their interconnectedness through the vagina-gut axis. We then review the efficacy of current antibiotic regimens for H. pylori and discuss how antibiotic treatment impacts the vaginal microenvironment. To explore the feasibility of this approach, we evaluate the effectiveness of oral and intra-vaginal probiotics in restoring normal microbiota in the gastrointestinal and vaginal tracts, respectively. Additionally, we analyze the direct mechanisms by which oral and intra-vaginal probiotics act on their respective tracts and discuss potential cross-tract mechanisms. Considering the potential synergistic therapeutic effects of probiotics in both the gastrointestinal and vaginal tracts, dual-channel probiotic therapy holds promise as a more effective approach for H. pylori eradication and dysbiosis mitigation, presenting a novel concept in the collaborative treatment of gastrointestinal and genital disorders.
Topics: Probiotics; Female; Humans; Dysbiosis; Anti-Bacterial Agents; Helicobacter Infections; Vagina; Helicobacter pylori; Administration, Intravaginal; Administration, Oral
PubMed: 38902244
DOI: 10.1038/s41522-024-00521-9 -
Medical Dosimetry : Official Journal of... Jun 2024Rectal toxicity is a significant concern in cervical cancer radiotherapy. Despite advancements in image-guided brachytherapy (IGBT), rectal morbidity remains a...
Rectal toxicity is a significant concern in cervical cancer radiotherapy. Despite advancements in image-guided brachytherapy (IGBT), rectal morbidity remains a challenge. Injectable hydrogel showed promise in creating a space between the vagina and rectum, reducing rectal radiation dose; however, the traditional ultrasound-guided injection revealed some problems, such as the inadequate separation of the upper edge of the cervix, which can be mitigated through adopting CT-guided injection. This case report presents the successful use of computed tomography (CT)-guided hydrogel injection to limit rectal doses and improve treatment outcomes. A forty-year-old female with stage IIIC1r cervical cancer received external-beam radiotherapy and concurrent chemotherapy. Due to the proximity of the tumor to the rectum, a CT-guided hydrogel injection was performed to increase the distance between the cervix and rectum. Post-injection, magnetic resonance imaging (MRI) demonstrated increased distances between the cervix and rectum. Subsequent MRI-based IGBT achieved high clinical target volume doses while limiting rectal doses. During the six-month follow-up, the patient reported only mild adverse effects. CT-guided hydrogel injection offers advantages over ultrasound-guided injection in cervical cancer radiotherapy. The technique allows for better puncture position adjustment, reduced reliance on specialized ultrasound expertise, and shorter puncture distances. This case report highlights the potential of hydrogel injection as a viable method to reduce rectal morbidity and improve treatment outcomes in a broader range of cervical cancer patients. Further studies are warranted to validate these findings and explore its applicability in larger cohorts.
PubMed: 38902140
DOI: 10.1016/j.meddos.2024.04.006 -
International Journal of Surgery Case... Jul 2024Rectovaginal fistula is a complication that may occur due to rectal injury during vaginal reconstructive surgery. To prevent these complications, the recognition of the...
INTRODUCTION AND IMPORTANCE
Rectovaginal fistula is a complication that may occur due to rectal injury during vaginal reconstructive surgery. To prevent these complications, the recognition of the injury is an important factor so that primary repair can be done. The primary repair can reduce the risk of complications such as fistula formation, and also reduce the physical and psychological impact on the patient.
CASE PRESENTATION
A 33-year-old woman, came with a chief complaint of fecal leakage from the vagina and abdominal pain three months before admission with a history of vaginal reconstructive surgery due to vaginal agenesis. Eleven years after the reconstruction, the patient was diagnosed with recurrent obstruction caused by vaginal synechia. During the surgery of synechia release, rectum injury occurred. Even though primary closure repair was done at that time, several months later there was a complication of rectovaginal fistule formation in the form of fecal leakage from the vagina. The corrective surgery is performed in collaboration with a surgical gastroenterologist.
CLINICAL DISCUSSION
Iatrogenic rectal injury may occur during gynecological surgery. A fistula that occurs after the reconstruction of vaginal agenesis is a high-type rectovaginal fistula, making the repairs more complex. Collaboration surgery between surgical gastroenterologist and gynecologist may be an option in such cases.
CONCLUSION
Rectovaginal fistula is a rare but serious complication of vaginal reconstructive surgery. Early recognition, immediate management, and postoperative follow-up are essential in cases of rectal injury during vaginal reconstructive surgery.
PubMed: 38901383
DOI: 10.1016/j.ijscr.2024.109856 -
Journal of Cellular and Molecular... Jun 2024Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential...
Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSCs) can alleviate the symptoms of pelvic floor dysfunction (PFD) in rats. However, the potential therapeutical effects of exosomes derived from BMSCs treated with tumour necrosis factor (TNF)-α on the symptoms of PFD in rats are unknown. Exosomes extracted from BMSCs treated with or without TNF-α were applied to treat PFD rats. Our findings revealed a significant elevation in interleukin (IL)-6 and TNF-α, and matrix metalloproteinase-2 (MMP2) levels in the vaginal wall tissues of patients with pelvic organ prolapse (POP) compared with the control group. Daily administration of exosomes derived from BMSCs, treated either with or without TNF-α (referred to as Exo and TNF-Exo), resulted in increased void volume and bladder void pressure, along with reduced peak bladder pressure and leak point pressure in PFD rats. Notably, TNF-Exo treatment demonstrated superior efficacy in restoring void volume, bladder void pressure and the mentioned parameters compared with Exo treatment. Importantly, TNF-Exo exhibited greater potency than Exo in restoring the levels of multiple proteins (Elastin, Collagen I, Collagen III, IL-6, TNF-α and MMP2) in the anterior vaginal walls of PFD rats. The application of exosomes derived from TNF-α-treated BMSCs holds promise as a novel therapeutic approach for treating PFD.
Topics: Animals; Exosomes; Mesenchymal Stem Cells; Female; Tumor Necrosis Factor-alpha; Rats; Humans; Pelvic Organ Prolapse; Matrix Metalloproteinase 2; Rats, Sprague-Dawley; Interleukin-6; Pelvic Floor; Disease Models, Animal; Bone Marrow Cells; Vagina; Mesenchymal Stem Cell Transplantation; Pelvic Floor Disorders; Middle Aged
PubMed: 38898783
DOI: 10.1111/jcmm.18451 -
Current Microbiology Jun 2024Delftia has been separated from freshwater, sludge, and soil and has emerged as a novel opportunistic pathogen in the female vagina. However, the genomic...
Delftia has been separated from freshwater, sludge, and soil and has emerged as a novel opportunistic pathogen in the female vagina. However, the genomic characteristics, pathogenicity, and biotechnological properties still need to be comprehensively investigated. In this study, a Delftia strain was isolated from the vaginal discharge of a 43-year-old female with histologically confirmed cervical intraepithelial neoplasm (CIN III), followed by whole-genome sequencing. Phylogenetic analysis and average nucleotide identity (ANI) analysis demonstrated that it belongs to Delftia lacustris, named D. lacustris strain LzhVag01. LzhVag01 was sensitive to β-lactams, macrolides, and tetracyclines but exhibited resistance to lincoamines, nitroimidazoles, aminoglycosides, and fluoroquinolones. Its genome is a single, circular chromosome of 6,740,460 bp with an average GC content of 66.59%. Whole-genome analysis identified 16 antibiotic resistance-related genes, which match the antimicrobial susceptibility profile of this strain, and 11 potential virulence genes. These pathogenic factors may contribute to its colonization in the vaginal environment and its adaptation and accelerate the progression of cervical cancer. This study sequenced and characterized the whole-genome of Delftia lacustris isolated from vaginal discharge, which provides investigators and clinicians with valuable insights into this uncommon species.
Topics: Delftia; Genome, Bacterial; Vaginal Discharge; Humans; Female; Adult; Phylogeny; Anti-Bacterial Agents; Drug Resistance, Bacterial; Virulence Factors; Species Specificity
PubMed: 38898312
DOI: 10.1007/s00284-024-03758-x