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Nature Communications May 2024The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic...
The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal infection nor pelvic inflammatory disease and thus it was selected for further characterization. We show that human Fallopian tubes express the IL-17C receptor on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.
Topics: Adult; Female; Humans; Cytokines; Epithelium; Fallopian Tubes; Gonorrhea; Inflammation; Interleukin-17; Neisseria gonorrhoeae; Pelvic Inflammatory Disease; Receptors, Interleukin-17
PubMed: 38704381
DOI: 10.1038/s41467-024-48141-3 -
Genes Mar 2024The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this...
The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The , , , and genes, located on chromosomes 12, 10, and 21, were associated with MC at ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The , , and genes were also significantly associated with MC at ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium.
Topics: Animals; Female; Cattle; Genome-Wide Association Study; Cattle Diseases; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; Endometritis; Uterine Diseases
PubMed: 38674374
DOI: 10.3390/genes15040439 -
Journal of Personalized Medicine Mar 2024Ovarian cancer (OC) remains a significant health challenge globally, with high mortality rates despite advancements in treatment. Emerging research suggests a potential... (Review)
Review
Ovarian cancer (OC) remains a significant health challenge globally, with high mortality rates despite advancements in treatment. Emerging research suggests a potential link between OC development and genital dysbiosis, implicating alterations in the microbiome composition as a contributing factor. To investigate this correlation, a meta-analysis was conducted following PRISMA and MOOSE guidelines, involving eight studies encompassing 3504 patients. Studies investigating the role of upper and inferior genital tract dysbiosis were included, with particular reference to HPV infection and/or history of pelvic inflammatory disease. The analysis revealed no significant difference in genital dysbiosis prevalence between OC patients and healthy controls. Although previous literature suggests associations between dysbiosis and gynecologic cancers, such as cervical and endometrial cancers, the findings regarding OC are inconclusive. Methodological variations and environmental factors may contribute to these discrepancies, underscoring the need for standardized methodologies and larger-scale studies. Despite the limitations, understanding the microbiome's role in OC development holds promise for informing preventive and therapeutic strategies. A holistic approach to patient care, incorporating microbiome monitoring and personalized interventions, may offer insights into mitigating OC risk and improving treatment outcomes. Further research with robust methodologies is warranted to elucidate the complex interplay between dysbiosis and OC, potentially paving the way for novel preventive and therapeutic approaches.
PubMed: 38672978
DOI: 10.3390/jpm14040351 -
International Journal of Surgery Case... May 2024Castleman Disease (CD) is a rare benign disorder characterized by abnormal lymphoid tissue growth. It can be classified as unicentric CD (UCD) affecting a single lymph...
INTRODUCTION
Castleman Disease (CD) is a rare benign disorder characterized by abnormal lymphoid tissue growth. It can be classified as unicentric CD (UCD) affecting a single lymph node region or multicentric CD (MCD) involving multiple regions. While UCD typically occurs in the mediastinum, MCD is associated with inflammatory symptoms and abnormal lab findings. We present a case of a young Syrian male with pelvic UCD, exhibiting unusual symptoms. Surgical excision led to complete recovery.
CASE PRESENTATION
A 27-year-old male presented with a well-defined pelvic mass discovered during routine ultrasonography. Symptoms included fever, fatigue, weight loss, and lower extremity numbness. Laboratory analysis revealed lymphocytopenia. Imaging identified a retroperitoneal pelvic mass, raising concerns of lymphoma. Surgical resection confirmed Castleman disease, specifically the hyaline vascular variant, dispelling malignancy concerns. Post-surgery, the patient demonstrated complete recovery, with normalized lymphocyte count and resolution of symptoms, affirming the effectiveness of the treatment.
DISCUSSION
Castleman Disease (CD) is characterized by abnormal lymphoid tissue growth. It presents as Unicentric (UCD) or Multicentric (MCD) forms. UCD cases are usually asymptomatic or show compressive symptoms due to mass effect, while MCD is associated with systemic symptoms. The estimated UCD incidence is 16 cases per million person-years, with median age at diagnosis around 30-34 years. Histologically, UCD is categorized into hyaline vascular (HV) and plasma cell (PC) variants. In this case, systemic symptoms and lymphocytopenia deviated from typical UCD presentation, leading to initial lymphoma suspicions. Surgical intervention facilitated recovery without adjuvant therapies.
CONCLUSION
This study emphasizes the spectrum of Castleman Disease (CD) manifestations, distinguishing Unicentric (UCD) and Multicentric (MCD) forms crucial for accurate management. It highlights atypical pelvic UCD presentation and successful surgical treatment's importance.
PubMed: 38669805
DOI: 10.1016/j.ijscr.2024.109688 -
Nutricion Hospitalaria Apr 2024pelvic inflammatory disease (PID) is a common gynecological condition. The dietary inflammatory index (DII) scoring algorithm is a novel tool for evaluating the...
BACKGROUND
pelvic inflammatory disease (PID) is a common gynecological condition. The dietary inflammatory index (DII) scoring algorithm is a novel tool for evaluating the inflammatory potential of a diet. However, the association between DII and PID remains unexplored. This study aimed to evaluate and quantify the relationship between DII and the risk for PID.
MATERIAL AND METHODS
the present study included two cycles of the National Health and Nutrition Examination Survey (NHANES) conducted between 2015 and 2018. A total of 2769 participants with complete information were enrolled. Weighted univariate and multivariate logistic regression analyses were performed to examine the association between DII and the risk for PID. Subsequently, the association was graphically represented using a restricted cubic spline (RCS).
RESULTS
univariate and multivariate regression analyses revealed a strong correlation between DII and PID occurrence. After adjusting for all covariates, the odds ratio for the effect of DII on PID remained significant (OR = 1.220, 95 % CI: 1.024-1.452). The correlation analysis revealed a linear relationship between DII and the risk for PID.
CONCLUSIONS
This study unravels a significant positive correlation between DII and the risk for PID. This finding highlights the potential of anti-inflammatory diet therapy as a novel therapeutic intervention for PID. However, due to the limitations of the study design, further research is needed to explore this relationship in detail.
PubMed: 38666343
DOI: 10.20960/nh.04975 -
Frontline Gastroenterology May 2024Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the most established restorative operative approach for patients with ulcerative colitis. It has...
BACKGROUND
Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the most established restorative operative approach for patients with ulcerative colitis. It has associated morbidity and the potential for major repercussions on quality of life. As such, patient selection is crucial to its success. The main aim of this paper is to present an institutional preoperative checklist to support clinical risk assessment and patient selection in those considering IPAA.
METHODS
A literature review was performed to identify the risk factors associated with surgical complications, decreased functional outcomes/quality of life, and pouch failure after IPAA. Based on this, a preliminary checklist was devised and modified through an iterative process. This was then evaluated by a consensus group comprising the pouch multidisciplinary team (MDT) core members.
RESULTS
The final preoperative checklist includes assessment for risk factors such as gender, advanced age, obesity, comorbidities, sphincteric impairment, Crohn's disease and pelvic radiation therapy. In addition, essential steps in the decision-making process, such as pouch nurse counselling and discussion regarding surgical alternatives, are also included. The last step of the checklist is discussion at a dedicated pouch-MDT.
DISCUSSION
A preoperative checklist may support clinicians with the selection of patients that are suitable for pouch surgery. It also serves as a useful tool to inform the discussion of cases at the MDT meeting.
PubMed: 38665796
DOI: 10.1136/flgastro-2023-102503 -
Scientific Reports Apr 2024It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to...
It is important to study the bacteria that cause endometritis to identify effective therapeutic drugs for dairy cows. In this study, 20% oxytetracycline was used to treat Holstein cows (n = 6) with severe endometritis. Additional 10 Holstein cows (5 for healthy cows, 5 for cows with mild endometritis) were also selected. At the same time, changes in bacterial communities were monitored by high-throughput sequencing. The results show that Escherichia coli, Staphylococcus aureus and other common pathogenic bacteria could be detected by traditional methods in cows both with and without endometritis. However, 16S sequencing results show that changes in the abundance of these bacteria were not significant. Endometritis is often caused by mixed infections in the uterus. Oxytetracycline did not completely remove existing bacteria. However, oxytetracycline could effectively inhibit endometritis and had a significant inhibitory effect on the genera Bacteroides, Trueperella, Peptoniphilus, Parvimonas, Porphyromonas, and Fusobacterium but had no significant inhibitory effect on the bacterial genera Marinospirillum, Erysipelothrix, and Enteractinococcus. During oxytetracycline treatment, the cell motility, endocrine system, exogenous system, glycan biosynthesis and metabolism, lipid metabolism, metabolism of terpenoids, polyketides, cofactors and vitamins, signal transduction, and transport and catabolism pathways were affected.
Topics: Oxytetracycline; Animals; Female; Cattle; Endometritis; Uterus; Anti-Bacterial Agents; Bacteria; Cattle Diseases; RNA, Ribosomal, 16S; Microbiota
PubMed: 38664449
DOI: 10.1038/s41598-024-59674-4 -
European Journal of Pharmacology Jul 2024Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this...
Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.
Topics: Animals; Dextran Sulfate; NF-kappa B; STAT3 Transcription Factor; Colitis; Gastrointestinal Microbiome; Mice; Signal Transduction; Indoles; Mice, Inbred C57BL; Disease Models, Animal; Colon; Male; Humans
PubMed: 38663540
DOI: 10.1016/j.ejphar.2024.176611 -
PloS One 2024The purpose of this study was to look at the relationship between the Systemic Immune Inflammatory Index (SII) and bone mineral density (BMD) in the pelvis, left upper...
BACKGROUND
The purpose of this study was to look at the relationship between the Systemic Immune Inflammatory Index (SII) and bone mineral density (BMD) in the pelvis, left upper and lower limbs, lumbar spine, thoracic spine, and trunk in a chronic kidney disease (CKD) population in the United States.
METHODS
The National Health and Nutrition Examination Survey (2011-2016) yielded 2302 people with CKD aged >18 years. CKD was defined as eGFR less than 90 ml/min/1.73 m2 or eGFR greater than 90 ml/min/1.73 m2 with urine ACR greater than 30 mg/L.SII was calculated as PC * (NC / LC) from platelet count (PC), neutrophil count (NC), and lymphocyte count (LC). Multiple logistic regression was used to examine the relationship between BMD and SII at different sites in CKD patients, smoothed curve-fitting and generalized weighting models were used to investigate non-linear relationships, and a two-tailed linear regression model was used to find potential inflection points in the model.
RESULTS
We discovered a negative correlation between SII and pelvic BMD among 2302 participants after controlling for gender, age, and race [β = -0.008; 95% confidence value -0.008; 95% confidence interval (CI) -0.014, -0.002]. Lower PEBMD was related to increasing SII (trend p = 0.01125). After additional correction, only pelvic BMD remained adversely linked with SII [value -0.006; 95% CI -0.012, -0.000, p = 0.03368]. Smoothed curve fitting revealed a consistent inverse relationship between SII and pelvic BMD. Further stratified analyses revealed a substantial positive negative connection between SII and pelvic BMD in individuals who did not have hypertension, diabetes, a BMI of more than 30 kg/m2, or stage 2 CKD. The connection between SII and PEBMD in people without diabetes revealed a strong inverted U-shaped curve.
CONCLUSION
In individuals with CKD in the United States, there was a negative connection between the systemic immunoinflammatory index (SII) and pelvic BMD. The SII might be a low-cost and simple test for CKD-related BMD loss.
Topics: Humans; Bone Density; Renal Insufficiency, Chronic; Male; Female; Middle Aged; Cross-Sectional Studies; Nutrition Surveys; Adult; Aged; Inflammation; United States; Glomerular Filtration Rate
PubMed: 38662733
DOI: 10.1371/journal.pone.0302073 -
Women's Health Reports (New Rochelle,... 2024Secondary infertility is characterized by the inability to conceive for a period of 1 year, after having previously conceived at least once.
INTRODUCTION
Secondary infertility is characterized by the inability to conceive for a period of 1 year, after having previously conceived at least once.
OBJECTIVES
To explore the risk factors of secondary infertility and compare sociodemographics and anthropometric variables of each studied group.
METHODS
Study was conducted at University Institute of Public Health, Faculty of Allied Health Sciences, The University of Lahore, collecting data from Gilani Ultrasound Center in 18 months after approval of synopsis. Total 690 females (345 cases and 345 controls) were enrolled. Participants were included in case group if they were 20-45 years of age, having any parity, and confirmed diagnosis of secondary infertility.
RESULTS
The mean age of cases and controls was 33.08 ± 4.17 years and 31.37 ± 4.36 years, respectively. The mean body mass index (BMI) in cases was 27.61 ± 4.27 kg/m, and in controls the mean BMI was 25.52 ± 4.30 kg/m. There was not a significant difference among religion that shows no association ( = 0.73) with secondary infertility as profession has association with it ( = 0.01). History of polycystic ovary syndrome, pelvic inflammatory disease, endometriosis, uterine fibroids, menorrhagia, intermenstrual bleeding, and history of abortion are associated with secondary infertility.
CONCLUSIONS
While several sociodemographic features and medical disorders have been associated to secondary infertility, it is vital to stress that not all of these factors are controllable by medical therapy. Factors like age and certain medical issues may be unaffected by intervention. However, for controllable variables like BMI and certain medical diseases, focused therapies and lifestyle changes may reduce the chance of subsequent infertility.
PubMed: 38655147
DOI: 10.1089/whr.2023.0145