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International Immunopharmacology May 2024Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished... (Review)
Review
Endometriosis (EM) is a gynecological inflammatory disease often accompanied by stress, chronic pelvic pain (CPP), anxiety, and depression, leading to a diminished quality of life. This review aims to discuss the relationship between systemic and local inflammatory responses in the central nervous system (CNS), focusing on glial dysfunctions (astrocytes and microglia) as in critical brain regions involved in emotion, cognition, pain processing, anxiety, and depression. The review presents that EM is connected to increased levels of pro-inflammatory cytokines in the circulation. Additionally, chronic stress and CPP as stressors may contribute to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, depleting the production of inflammatory mediators in the circulatory system and the brain. The systemic cytokines cause blood-brain barrier (BBB) breakdown, activate microglia in the brain, and lead to neuroinflammation. Furthermore, CPP may induce neuronal morphological alterations in critical regions through central sensitization and the activation of glial cells. The activation of glial cells, particularly the polarization of microglia, leads to the activation of the NLRP3 inflammasome and the overproduction of inflammatory cytokines. These inflammatory cytokines interact with the signaling pathways involved in neural plasticity. Additionally, persistent inflammatory conditions in the brain lead to neuronal death, which is correlated with a reduced volume of key brain regions such as the hippocampus. This review highlights the involvement of glial cells in the pathogenesis of the mental comorbidities of EM (i.e., pain, anxiety, and depression) and to discuss potential therapeutic approaches for targeting the inflammation and activation of microglia in key brain regions.
Topics: Humans; Female; Endometriosis; Depression; Anxiety; Animals; Neuroglia; Inflammation; Stress, Psychological; Cytokines; Brain
PubMed: 38565045
DOI: 10.1016/j.intimp.2024.111942 -
Current Nutrition Reports Mar 2024Endometriosis (EM) is a chronic gynecological disease that affects about 10% of women worldwide. It is characterized by the implantation of endometrial cells at ectopic... (Review)
Review
PURPOSE OF REVIEW
Endometriosis (EM) is a chronic gynecological disease that affects about 10% of women worldwide. It is characterized by the implantation of endometrial cells at ectopic sites. The most common symptom of EM is painful menstruation, which can often lead to chronic pelvic pain that significantly worsens the quality of life. Because some disease-related processes, such as inflammation, hormonal activity, menstrual cycle, or prostaglandin metabolism, can be modified by diet, nutrition may have a significant impact on development and treatment of EM. The purpose of this article was to overview the current knowledge regarding the dietary management of endometriosis.
RECENT FINDINGS
The attention of researchers has so far concentrated mainly on the role of nutrition in the risk of developing EM, while less attention has been paid to examining the use of diet in the treatment of the disease. Current studies focus primarily on various dietary components that have antiproliferative, anti-inflammatory, antioxidant, analgesic, and estrogen-lowering properties. Exploring different ways of coping with endometriosis can make a significant contribution to improving the quality of life of women at risk or diagnosed with EM.
Topics: Female; Humans; Endometriosis; Quality of Life; Pelvic Pain; Estrogens; Diet
PubMed: 38324218
DOI: 10.1007/s13668-024-00518-y -
IScience Nov 2023Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to...
Hunner-type interstitial cystitis (HIC) is a rare, enigmatic inflammatory disease of the urinary bladder with no curative treatments. In this study, we aimed to characterize the unique cellular and immunological factors specifically involved in HIC by comparing with cystitis induced by bacillus Calmette-Guérin, which presents similar clinicopathological features to HIC. Here, we show that T helper 1/17 +polarized immune responses accompanied by prominent overexpression of interferon (IFN)-γ, enhanced cGAS-STING cytosolic DNA sensing pathway, and increased plasma cell infiltration are the characteristic inflammatory features in HIC bladder. Further, we developed a mouse anti-IFN-γ DNA aptamer and observed that the intravesical instillation of the aptamer significantly ameliorated bladder inflammation, pelvic pain and voiding dysfunction in a recently developed murine HIC model with little migration into the blood. Our study provides the plausible basis for the clinical translation of the anti-IFN-γ DNA aptamer in the treatment of human HIC.
PubMed: 38026177
DOI: 10.1016/j.isci.2023.108262 -
The Journal of Molecular Diagnostics :... Nov 2023Bacterial commensals of the human genitourinary tract, Mycoplasma hominis and Ureaplasma species (parvum and urealyticum) can be sexually transmitted, and may cause...
Bacterial commensals of the human genitourinary tract, Mycoplasma hominis and Ureaplasma species (parvum and urealyticum) can be sexually transmitted, and may cause nongonococcal urethritis, pelvic inflammatory disease, and infertility. Mycoplasma hominis and Ureaplasma species may also cause severe invasive infections in immunocompromised patients. Current culture-based methods for Mycoplasma/Ureaplasma identification are costly and laborious, with a turnaround time between 1 and 2 weeks. We developed a high-throughput, real-time multiplex PCR assay for the rapid detection of M. hominis and Ureaplasma species in urine, genital swab, body fluid, and tissue. In total, 282 specimens were tested by PCR and compared with historic culture results; a molecular reference method was used to moderate discrepancies. Overall result agreement was 99% for M. hominis (97% positive percentage agreement and 100% negative percentage agreement) and 96% for Ureaplasma species (96% positive percentage agreement and 97% negative percentage agreement). Specimen stability was validated for up to 7 days at room temperature. This multiplex molecular assay was designed for implementation in a high-complexity clinical microbiology laboratory. With this method, >90 samples can be tested in one run, with a turnaround time of 4 to 5 hours from specimen extraction to reporting of results. This PCR test is also more labor effective and cheaper than the conventional culture-based test, thus improving laboratory efficiency and alleviating labor shortages.
Topics: Mycoplasma hominis; Humans; Ureaplasma; Multiplex Polymerase Chain Reaction; Real-Time Polymerase Chain Reaction; Ureaplasma Infections; Mycoplasma Infections; Sensitivity and Specificity; High-Throughput Screening Assays; DNA, Bacterial; Reproducibility of Results
PubMed: 37683891
DOI: 10.1016/j.jmoldx.2023.07.004 -
Heliyon Mar 2024Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and... (Review)
Review
Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and obstetric outcomes, including preterm delivery, sexually transmitted infections and pelvic inflammatory disease. Although effective control of VVC is achievable with the use of traditional treatment strategies (i.e., antifungals), the possibility of drug intolerance, treatment failure and recurrence, as well as the appearance of antifungal-resistant species remain critical challenges. Therefore, alternative therapeutic strategies against VVC are urgently required. In recent years, an improved understanding of the dysbiotic vaginal microbiota (VMB) during VVC has prompted the consideration of administering -biotics to restore the balance of the VMB within the context of VVC prevention and treatment. Here, we aim to summarize the current evidence of the anti- effects of probiotics, postbiotics and synbiotics and their potential use as an alternative/complementary therapy against VVC. Additionally, this review discusses advantages and challenges associated with the application of -biotics in VVC to provide guidance for their later use. We also review new developments in VVC therapy, i.e., vaginal microbiota transplantation (VMT) as an emerging live biotherapeutic therapy against VVC and discuss existing shortcomings associated with this nascent field, expecting to stimulate further investigations for introduction of new therapies against VVC.
PubMed: 38463778
DOI: 10.1016/j.heliyon.2024.e27239 -
EBioMedicine Aug 2023Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel...
BACKGROUND
Radiotherapy is effective in the treatment of cancer but also causes damage to non-cancerous tissue. Pelvic radiotherapy may produce chronic and debilitating bowel symptoms, yet the underlying pathophysiology is still undefined. Most notably, although pelvic radiotherapy causes an acute intestinal inflammation there is no consensus on whether the late-phase pathophysiology contains an inflammatory component or not. To address this knowledge gap, we examined the potential presence of a chronic inflammation in mucosal biopsies from irradiated pelvic cancer survivors.
METHODS
We biopsied 24 cancer survivors two to 20 years after pelvic radiotherapy, and four non-irradiated controls. Using tandem mass tag (TMT) mass spectrometry and mRNA sequencing (mRNA-seq), we charted proteomic and transcriptomic profiles of the mucosal tissue previously exposed to a high or a low/no dose of radiation. Changes in the immune cell populations were determined with flow cytometry. The integrity of the protective mucus layers were determined by permeability analysis and 16S rRNA bacterial detection.
FINDINGS
942 proteins were differentially expressed in mucosa previously exposed to a high radiation dose compared to a low radiation dose. The data suggested a chronic low-grade inflammation with neutrophil activity, which was confirmed by mRNA-seq and flow cytometry and further supported by findings of a weakened mucus barrier with bacterial infiltration.
INTERPRETATION
Our results challenge the idea that pelvic radiotherapy causes an acute intestinal inflammation that either heals or turns fibrotic without progression to chronic inflammation. This provides a rationale for exploring novel strategies to mitigate chronic bowel symptoms in pelvic cancer survivors.
FUNDING
This study was supported by the King Gustav V Jubilee Clinic Cancer Foundation (CB), The Adlerbertska Research Foundation (CB), The Swedish Cancer Society (GS), The Swedish State under the ALF agreement (GS and CB), Mary von Sydow's foundation (MA and VP).
PubMed: 37480626
DOI: 10.1016/j.ebiom.2023.104691 -
Sexual Medicine Reviews Dec 2023Chronic pelvic pain syndrome (CPPS) is a common urologic condition that can cause significant disability in affected individuals. Physiologic explanations of chronic... (Review)
Review
INTRODUCTION
Chronic pelvic pain syndrome (CPPS) is a common urologic condition that can cause significant disability in affected individuals. Physiologic explanations of chronic pain are often incomplete; appropriate management of CPPS includes recognition of biological, psychological, and social elements, known as the biopsychosocial model.
OBJECTIVE
The aim of this narrative review is to investigate treatments for men with CPPS, with a special focus on those utilizing the biopsychosocial model of care.
METHODS
A comprehensive literature search was conducted on the electronic databases PubMed, Embase, and Cochrane Library, using relevant Medical Subject Heading terms and keywords related to CPPS treatments. The search was limited to studies published in English from inception to January 2023. Additionally, reference lists of selected studies were manually reviewed to find studies not identified by the initial search. Studies were included if they investigated pharmacologic or nonpharmacologic treatments for men with CPPS.
RESULTS
A total of 30 studies met the inclusion criteria. Antibiotics, α-blockers, nonsteroidal anti-inflammatory drugs, gabapentinoids, antidepressants, and phosphodiesterase type 5 inhibitors were among the pharmacologic agents included in trials attempting to reduce symptoms of male CPPS. Studies that focused on treating CPPS without medication included interventions such as shockwave therapy, acupuncture, physical therapy, botulinum toxin, cryotherapy, electrotherapy, exercise, and cognitive behavioral therapy.
CONCLUSION
α-Blockers and nonsteroidal anti-inflammatory drugs have shown promising results in treating CPPS in men, while the effectiveness of antibiotics remains controversial. Antidepressants and phosphodiesterase type 5 inhibitors may also be useful in decreasing symptoms in patients with CPPS. Treatments such as pelvic floor muscle therapy, acupuncture, shockwave therapy, and cognitive behavioral therapy must be considered effective complements to medical management in men with CPPS. While these interventions demonstrate benefits as monotherapies, the individualization and combination of treatment modalities are likely to result in reduced pain and improved quality of life.
Topics: Humans; Male; Chronic Pain; Chronic Disease; Quality of Life; Phosphodiesterase 5 Inhibitors; Prostatitis; Pelvic Pain; Adrenergic alpha-Antagonists; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antidepressive Agents
PubMed: 37717957
DOI: 10.1093/sxmrev/qead038 -
BMC Infectious Diseases Jul 2023Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of...
BACKGROUND
Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS).
METHODS
We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with LGUTS as determined by selected International Classification of Diseases codes between January 2010 and December 2019. Testing of STIs and relevant drug claims were captured, and distribution of testing patterns and drug claims were described.
RESULTS
In total, 23,537,812 episodes with LGUTS (87.4% from women; 12.6% from men) were analyzed from 12,341,154 patients. CT/NG testing occurred in only 17.6% of all episodes. For episodes where patients received treatment within 2 weeks of the visit date, 89.3% received treatment within the first 3 days (likely indicating presumptive treatment), and 77.7% received it on the first day. For women with pelvic inflammatory disease and men with orchitis/epididymitis and acute prostatitis, ≤ 15% received CT/NG testing, and around one-half received antibiotic treatment within 3 days.
CONCLUSIONS
Our study revealed low CT/NG testing rates, even in patients diagnosed with complications commonly associated with these STIs, along with high levels of potentially inappropriate presumptive treatment. This highlights the need for timely and accurate STI diagnosis in patients with LGUTS to inform appropriate treatment recommendations.
Topics: Adult; Adolescent; Male; Humans; Female; United States; Young Adult; Middle Aged; Gonorrhea; Outpatients; Chlamydia Infections; Sexually Transmitted Diseases; Chlamydia trachomatis; Neisseria gonorrhoeae; Prevalence
PubMed: 37442964
DOI: 10.1186/s12879-023-08434-2 -
Reproductive Sciences (Thousand Oaks,... Jan 2024Autoimmune primary ovarian insufficiency (POI) is a devastating disease with limited clinical guidance. The objective of this systematic review was to identify... (Review)
Review
Autoimmune primary ovarian insufficiency (POI) is a devastating disease with limited clinical guidance. The objective of this systematic review was to identify treatments for autoimmune POI and analyze their efficacy. A comprehensive search of CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science was performed from inception to April 2022. English language publications that evaluated women with autoimmune POI after a documented intervention were included. Animal models of autoimmune POI were also included. Risk of bias was assessed with the SYRCLE's risk of bias tool for animal studies or the NIH Quality Assessment Tool for Case Series as appropriate. Twenty-eight studies were included in this review, with 11 RCTs, 15 case reports, and 2 case series. Seventeen studies were in humans, and 11 were in animal models. No completed RCTs, cohort studies, or case-control studies were identified in humans. In observational human studies, corticosteroids were effective in select patients. In many case reports, adequate treatment of comorbid autoimmune conditions resulted in return of menses, hormonal normalization, or spontaneous pregnancy. In terms of assisted reproductive technologies, there was case report evidence for both in vitro fertilization (IVF) and in vitro maturation (IVM) in women wishing to conceive with their own oocytes. Ovulation induction, IVF, and IVM resulted in a total of 15 pregnancies and 14 live births. In animal models, there was additional evidence for stem cell therapies and treatments used in traditional Chinese medicine, although this research may not be generalizable to humans. Furthermore, litter size was not evaluated in any of the animal studies. Additional research is needed to establish the efficacy of current treatments for autoimmune POI with a controlled experimental design and larger sample size. Additionally, there is a critical need to develop novel therapies for this condition, as understanding of its pathophysiology and available tools to modulate the immune response have progressed.
Topics: Animals; Female; Humans; Pregnancy; Fertilization in Vitro; Infertility, Female; Live Birth; Oophoritis; Polyendocrinopathies, Autoimmune; Pregnancy Rate; Reproductive Techniques, Assisted
PubMed: 37500976
DOI: 10.1007/s43032-023-01299-5