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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 -
Microbial Pathogenesis Jun 2024Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria,...
Endometritis is the inflammation of the endothelial lining of the uterine lumen and is multifactorial in etiology. Escherichia (E.) coli is a Gram-negative bacteria, generally considered as a primary causative agent for bovine endometritis. Bovine endometritis is characterized by the activation of Toll-like receptors (TLRs) by E. coli, which in turn triggers inflammation, oxidative stress, and apoptosis. The objective of this study was to investigate the gene expression of inflammatory, oxidative stress, and apoptotic markers related to endometritis in the uteri of cows. Twenty uterine tissues were collected from the abattoir. Histologically, congestion, edema, hyperemia, and hemorrhagic lesions with massive infiltration of neutrophil and cell necrosis were detected markedly (P < 0.05) in infected uterine samples. Additionally, we identify E. coli using the ybbW gene (177 base pairs; E. coli-specific gene) from infected uterine samples. Moreover, qPCR and western blot results indicated that TLR2, TLR4, proinflammatory mediators, and apoptosis-mediated genes upregulated except Bcl-2, which is antiapoptotic, and there were downregulations of oxidative stress-related genes in the infected uterine tissue. The results of our study suggested that different gene expression regimes related to the immune system reflex were activated in infected uteri. This research gives a novel understanding of active immunological response in bovine endometritis.
Topics: Cattle; Animals; Female; Endometritis; Oxidative Stress; Apoptosis; Cattle Diseases; Escherichia coli; Up-Regulation; Escherichia coli Infections; Uterus; Inflammation; Toll-Like Receptor 4; Inflammation Mediators; Toll-Like Receptor 2; Toll-Like Receptors
PubMed: 38657710
DOI: 10.1016/j.micpath.2024.106660 -
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 -
Sexually Transmitted Diseases Apr 2024Productivity costs of STIs reflect the value of lost time due to STI morbidity and mortality, including time spent travelling to, waiting for, and receiving STI...
BACKGROUND
Productivity costs of STIs reflect the value of lost time due to STI morbidity and mortality, including time spent travelling to, waiting for, and receiving STI treatment. The purpose of this study was to provide updated estimates of the average lifetime productivity cost for chlamydia, gonorrhea, and syphilis, per incident infection.
METHODS
We adapted published decision tree models from recent studies of the lifetime medical costs of chlamydia, gonorrhea, and syphilis in the United States. For each possible outcome of infection, we applied productivity costs that we obtained based on published health economic studies. Productivity costs included the value of patient time spent to receive treatment for STIs and for related sequelae such as pelvic inflammatory disease in women. We used a human capital approach and included losses in market (paid) and non-market (unpaid) productivity. We conducted one-way sensitivity analyses and probabilistic sensitivity analyses.
RESULTS
The average lifetime productivity cost per infection was $28 for chlamydia in men, $205 for chlamydia in women, $37 for gonorrhea in men, $212 for gonorrhea in women, and $411 for syphilis regardless of sex, in 2023 US dollars. The estimated lifetime productivity costs of these STIs acquired in the United States in 2018 was $795 million.
CONCLUSIONS
These estimates of the lifetime productivity costs can help in quantifying the overall economic burden of STIs in the United States beyond just the medical cost burden and can inform cost-effectiveness analyses of STI prevention activities.
PubMed: 38647252
DOI: 10.1097/OLQ.0000000000001973 -
The Journal of Infectious Diseases Apr 2024Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from...
Chlamydia trachomatis (CT) is a sexually transmitted infection that can lead to adverse reproductive health outcomes. CT prevalence estimates are primarily derived from screening using nucleic acid amplification tests (NAATs). However, screening guidelines in the United States only include particular subpopulations, and NAATs only detect current infections. In contrast, seroassays identify past CT infections which are important for understanding the public health impacts of CT, including pelvic inflammatory disease and tubal factor infertility. Older seroassays have been plagued by low sensitivity and specificity and have not been validated using a consistent reference measure, making it challenging to compare studies, define the epidemiology of CT and determine the effectiveness of control programs. Newer seroassays have better performance characteristics. This narrative review summarizes the "state of the science" for CT seroassays that have been applied in epidemiologic studies and provides practical considerations for interpreting the literature and employing seroassays in future research.
PubMed: 38640957
DOI: 10.1093/infdis/jiae199 -
Research in Veterinary Science Jun 2024Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a mucosal commensal of the lower genital tract in horses and is the most isolated bacterium causing...
Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a mucosal commensal of the lower genital tract in horses and is the most isolated bacterium causing endometritis in mares. The aim of this study was to determine the molecular diversity of S. zooepidemicus obtained from endometritis in mares in Buenos Aires province, Argentina. Thirty isolates obtained from the uterus of mares in 2005 and 2017 were studied. The MLST scheme was applied to identify the Argentinian genotypes and the clonal relationships and patterns of evolutionary descent were identified using the eBURST algorithm - goeBURST. Twenty six different Sequence types (STs) were identified, being only 11 of them previously reported in horses and also, from several host species and tissues. The other 15 STs were reported in Argentinian reproductive strains of mares in our study for the first time. The genotypes obtained from uterus in Argentina were not evenly distributed when all the published S. zooepidemicus STs were analysed, thus, it was not possible to establish that the same lineage circulates in our equine population. The fact that the identified genotypes were also reported in other countries, diverse samples and host species suggest that there is not a host, and an anatomical niche adaptation. Finally, the isolation of the same genotype in the vagina/clitoris and the uterus of the same mare highlights the versatility of S. zooepidemicus and its role as an opportunistic pathogen.
Topics: Animals; Horses; Horse Diseases; Female; Argentina; Endometritis; Streptococcal Infections; Genotype; Genetic Variation; Multilocus Sequence Typing; Uterus; Streptococcus; Streptococcus equi
PubMed: 38640833
DOI: 10.1016/j.rvsc.2024.105242 -
Brazilian Journal of Microbiology :... Jun 2024In this study, the main agents associated with endometritis in cows in the state of Santa Catarina, Brazil, were identified and the resistance profile and virulence...
In this study, the main agents associated with endometritis in cows in the state of Santa Catarina, Brazil, were identified and the resistance profile and virulence mechanisms of the bacterial isolates were evaluated. Isolates of Escherichia coli and Trueperella pyogenes were tested for their biofilm forming ability and the antimicrobial action of bromhexine hydrochloride in combination with other antimicrobials. A total of 37 uterine lavage samples were collected from cows with endometritis. Of the 55 bacteria isolated, 25.4% were identified as T. pyogenes and 16.3% as E. coli. The bacterial isolates showed greater resistance to sulfamethoxazole + trimethoprim (58.2%) and tetracycline (56.3%). Among the species, E. coli showed the highest resistance rates, with 100% of isolates showing resistance to amoxicillin, streptomycin, and gentamicin. The results of the minimum inhibitory concentration for the T. pyogenes isolates showed that 91.6% of the isolates were resistant to enrofloxacin and tetracycline, and 75% were resistant to ceftiofur and sulfamethoxazole + trimethoprim. All E. coli and T. pyogenes isolates showed biofilm forming ability. The plo, fimA, and nanH genes were identified in 100% of T. pyogenes isolates. In parallel, 100% of E. coli isolates had the fimH gene, and 11.1% had the csgD gene. Bromhexine hydrochloride showed antimicrobial activity against 100% of E. coli isolates and 66.6% of T. pyogenes isolates. Furthermore, when associated with antimicrobials, bromhexine hydrochloride has a synergistic and additive effect, proving to be an option in the treatment of endometritis in cows and an alternative for reducing the use of antimicrobials.
Topics: Cattle; Animals; Endometritis; Female; Escherichia coli; Anti-Bacterial Agents; Microbial Sensitivity Tests; Cattle Diseases; Actinomycetaceae; Escherichia coli Infections; Actinomycetales Infections; Biofilms; Brazil; Drug Resistance, Bacterial
PubMed: 38639845
DOI: 10.1007/s42770-024-01320-2 -
Revista Espanola de Medicina Nuclear E... 2024
Topics: Humans; Fluorodeoxyglucose F18; Female; Fever of Unknown Origin; Radiopharmaceuticals; Salpingitis; Positron-Emission Tomography; Adult
PubMed: 38636826
DOI: 10.1016/j.remnie.2024.500010 -
Urology Journal May 2024To compare 90-day perioperative complications and pathological outcomes between laparoscopic radical cystectomy (LRC) and extraperitoneal radical cystectomy (EORC)... (Comparative Study)
Comparative Study
PURPOSE
To compare 90-day perioperative complications and pathological outcomes between laparoscopic radical cystectomy (LRC) and extraperitoneal radical cystectomy (EORC) approaches.
MATERIALS AND METHODS
All operations were performed in a single high-volume tertiary referee center by the same surgical team.Males ≥ 18 years with pre-cystectomy clinical T1-T3 disease and having undergone an ileal conduit were included. Exclusion criteria included patients with inflammatory bowel disease, previous pelvic and/or abdominal irradiation, neo-adjuvant chemotherapy, and/or clinical T4 disease. Perioperative outcomes such as operative time, estimated blood loss, transfusion rate, hospital stay, and 90-day complications were evaluated. The recovery duration of regular bowel activity, mean stool passage,and ileus rates were recorded.
RESULTS
A total of 221 patients met the inclusion criteria(81 LRC and 130 EORC). Demographics and preoperative parameters were comparable. Intraoperative estimated blood lossfavored LRC by a median of 450 mL (200-900) P=.021) vs. a median of 700 mL (300-2900) for EORC. The transfusion rate did not differ between the two groups; %14.8 (N=12) for the LRC and %20.8 (N=27) for EORC (P=.37). The median hospital stay was 9 (4-49) days for EORC and 8 (4-29) days for LRC (P=.011). The need for analgesics to control pain through an epidural catheter was higher for EORC (P=.042). There was no difference in overall complication rates (P=.47).
CONCLUSION
Although LRC appears to have a slight advantage over EORC, both techniques yield satisfactory results in regard to ileus rates and 90-day perioperative complications.
Topics: Humans; Laparoscopy; Male; Cystectomy; Middle Aged; Prostatectomy; Aged; Urinary Bladder Neoplasms; Treatment Outcome; Postoperative Complications; Retrospective Studies; Length of Stay; Blood Loss, Surgical; Operative Time
PubMed: 38629198
DOI: 10.22037/uj.v21i03.7937