The present study was aimed to elucidate the pharmacological effect of Formononetin (FMN) treatment on STZ-induced diabetic cognitive dysfunction. The diabetic model was induced by an ...intraperitoneally injection of 180 mg/kg STZ. The animals were randomly divided into five groups: control group, streptozocin (STZ, 180 mg/kg) group, STZ + metformin (Met, 200 mg/kg) group, STZ + FMN (25 mg/kg) group, STZ + FMN (50 mg/kg) group. The mice were intragastrically administrated with metformin (Met, 200 mg/kg) or FMN (25, 50 mg/kg) once daily for 6 weeks. The blood glucose content and body weight were examined. Morris water maze test and Y maze test were used to evaluate the learning and memory abilities. The cognitive decline was reversed by regulating superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-a (TNF-α), interleukin(IL)-1β, IL-6 in serum and hippocampus. The protein expressions of high mobility group box-1 protein (HMGB1), toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), inhibitor of NF-κB (IκBα), p-IκBα, nuclear factor kappa-B(NF-κB), p-NF-κB, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) and caspase-1 were detected. Furthermore, the SH-SY5Y cells were exposed to high glucose stimulation, FMN (2.5, 5 and 10 μM) treatment, and glycyrrhizin, the selective inhibitor of HMGB1. After an incubation for 22 h, the SH-SY5Y cells were harvested for detection. As a result, FMN treatment effectively attenuated the body weight, learning and memory abilities, as well as the levels of blood glucose, SOD, MDA, TNF-α, IL-1β, IL-6. FMN administration also downregulated the protein expressions of HMGB1, TLR4, MyD88, p-IκB, p-NF-κB, NLRP3, ASC and caspase-1. The inhibition of HMGB1 by glycyrrhizin also confirmed the involvement of HMGB1/TLR4/NF-κB/NLRP3 pathway in high glucose-induced SH-SY5Y cells. In summary, the results suggested that FMN exhibited the protective effect on STZ-induced cognitive impairment possibly via the mediation of HMGB1/TLR4/NF-κB signaling and NLRP3 inflammasome.
Abstract Objective . Epidemiologic and clinical findings are inconsistent concerning the risk for gynecologic cancers associated with statin use. We conducted a detailed meta-analysis of all relevant ...original studies to evaluate the effects of statin on the risk of gynecologic cancers. Methods . We searched PubMed, Embase, and Cochrane library databases up to February 2014 looking for eligible studies. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were used to calculate the risk using random-effects models. Results . A total of 14 (4 randomized controlled trials, 5 cohorts, and 5 case–control) studies, involving 12,904 gynecologic cancer cases, contributed to the analysis. Pooled results indicated a non-significant decrease of total gynecologic cancer risk among statin users (RR = 0.89; 95% CI, 0.78–1.01). Stratified analyses across cancer site revealed a modest protective effect of statin on ovarian cancer (RR = 0.79; 95% CI, 0.64–0.98), while no association was found for endometrial cancer (RR = 0.90; 95% CI, 0.75–1.07). The effect of statin use against cervical cancer and vulvar cancer is not conclusive. Furthermore, long-term statin use (> 5 years use) did not significantly affect the risk of endometrial cancer (RR = 0.69; 95% CI, 0.44–1.10), but had an obvious decrease on the risk of ovarian cancer (RR = 0.48; 95% CI, 0.28–0.80). Conclusions . Our results suggest that statin use was inversely associated with ovarian cancer risk, and the association was stronger for long-term statin use (> 5 years). The evidence for a protective effect of statin use against other gynecologic cancers is suggestive but not conclusive, which deserves further investigation.
Abstract Background The oil-soluble contrast medium used in hysterosalpingography has been shown to have a fertility-enhancing effect, but the underlying mechanism is unclear, especially regarding ...the role of window of implantation (WOI). This study aimed to assess the endometrial immunological impact of the WOI before and after bathing with the oil-soluble contrast medium in women with recurrent implantation failure (RIF). Methods This descriptive study involved two medical centers between December 18, 2019, and December 30, 2020. We included infertile women who underwent three or more transfer cycles, cumulative transplantation of at least four high-quality cleavage-stage embryos or three high-quality blastocysts without clinical pregnancy, and high-quality frozen embryos that were still available for implantation. Patients received 5 ml of ethiodized poppyseed oil bathing, endometrial biopsy around bathing, and frozen-thawed embryo transfer (FET) within four menstrual cycles after bathing. Patients were excluded if failure to complete anyone. Data on the baseline characteristics and clinical data of the FET cycles were collected, and endometrial biopsy specimens were collected in the luteal phase before and after bathing and subjected to immunohistochemistry. The number of CD56 and CD138 positive cells and H-score of expression of ανβ-3 and HOXA10 in endometrium were collected. Results Thirty-four patients were initially enrolled in the study; ultimately, twelve patients with a median age of 32.5 years (range 27–40 years) completed the research. The median number of embryo transfer cycles was three (range 3–8). A total of 4 of 12 women (33.33%) were diagnosed with chronic endometritis before oil-soluble contrast bathing. After bathing, the median numbers of CD138-positive cells in endometrium decreased from 0.75 (range 0–13.5) to 0.65 (range 0–6), P = 0.035; additionally, the H-score of expression of ανβ-3 in endometrium increased from 148.50 ± 31.63 to 175.58 ± 31.83, P < 0.001. The thickness of the endometrium also significantly increased (8.90 ± 1.45 mm vs.10.11 ± 1.98 mm, P = 0.005). However, no consistent changes were found in the expression of CD56 and HOXA10 in the endometrium. Five patients experienced biochemical pregnancies (41.67%), four had clinical pregnancies (33.33%), and three achieved live births following oil-soluble contrast bathing (25%). Conclusions These results suggest that oil-soluble contrast medium bathing decreased CD138-positive cells and upregulated expression of ανβ-3 during WOI in patients with RIF. This histological impact of endometrium may result in enhanced fertility during FET cycles. Investigating the ability of intrauterine bathing with lower-dosage oil-soluble contrast to improve pregnancy in the RIF population is warranted.
Endometriosis is a multifactorial disease associated with inflammation. Vitamin D has anti-inflammatory, antiproliferative, anti-oxidative, and immunomodulatory effects. Whether vitamin D levels are ...correlated with endometriosis is a subject of ongoing debate. This study aimed to examine the association between endometriosis and serum vitamin D levels. From the National Health and Nutrition Examination Survey, this study examined the cross-sectional data of American women aged 20-54 years from 2001 to 2006. After adjusting for covariates, multivariable logistic regression analysis was used to assess correlations. A total of 3,232 women were included in this study. The multiple linear regression model demonstrated a negative correlation between the serum 25-hydroxyvitamin D3 (cholecalciferol) concentration and the risk of endometriosis after controlling for all confounding variables. The odds ratio was 0.73 with a 95% confidence interval of 0.54-0.97 in the adequate vitamin D level group compared with the insufficient vitamin D level group. Our results showed that endometriosis was inversely correlated with serum 25-hydroxyvitamin D3 levels. Further research is needed to establish a causal relationship and determine the potential benefits of maintaining sufficient vitamin D levels for endometriosis prevention.
Previous studies have suggested that oil-based contrast agents used during hysterosalpingography (HSG) in infertile patients can enhance fertility. However, limited research has investigated the ...effect of oil-based contrast medium specifically in individuals with endometriosis-related infertility.
This study aims to explore the impact of oil-based contrast medium on fertility outcomes in women with endometriosis-related infertility.
Conducted at the First Affiliated Hospital of Guangxi Medical University (January 2020 to June 2022), the study included 512 patients undergoing HSG. Patients were categorized into oil-based and non-oil-based groups, and after propensity score matching, demographic characteristics were compared. Main outcomes included clinical pregnancy rates, live birth rates, early miscarriage rates, and ectopic pregnancy rates.
In our analysis, the Oil-based group showed significantly better outcomes compared to the Non-oil-based group. Specifically, the Oil-based group had higher clinical pregnancy rates (51.39% vs. 27.36%) and increased live birth rates (31.48% vs. 19.93%). This trend held true for expectant treatment, IUI, and IVF/ICSI, except for surgical treatment where no significant difference was observed. After adjusting for various factors using propensity score matching, the Non-oil-based group consistently exhibited lower clinical pregnancy rates compared to the Oil-based group. The Odds Ratio (OR) was 0.38 (95%CI: 0.27-0.55) without adjustment, 0.34 (0.22-0.51) in multivariable analysis, 0.39 (0.27-0.57) using inverse probability of treatment weighting (IPTW), and 0.22 (0.14-0.35) in propensity score matching.
Oil-based contrast medium used in HSG for women with endometriosis-related infertility is associated with higher clinical pregnancy rates and live birth rates compared to Non-oil-based contrast medium.
Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to ...preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered.
This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes.
We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English.
Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I
: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I
: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I
: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I
: 0.00%, fixed effect).
Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation.
INPLASY202390008.
Aim
The chronic endometritis (CE) prevalence in people experiencing infertility is 2.8–56.8%, pregnancy rates in patients with infertility increase after hysterosalpingography with oil‐based ...contrast, but the effect and mechanism are not clear. Here, we analyzed the effects of intrauterine ethiodized poppyseed oil (EPO) bathing on a rat model of CE and the possible underlying mechanism.
Methods
CE rats were induced by lipopolysaccharide (LPS) exposure, and rats were subjected to intrauterine bathing with EPO or phosphate‐buffered saline (PBS) after model verification. Serum and uterus levels of IFN‐γ, IL‐4, TNF‐α, and IL‐1β were detected by ELISA kit, and the number of CD138+ and CD68+ cells and uterine IFN‐γ, IL‐4, TNF‐α, IL‐1β, and NF‐κB P65 expression were detected by immunohistochemistry after bathing.
Results
LPS exposure induced the typical CE phenotype with CD138+ phagocyte infiltration of the endometrial stroma. Compared with PBS bathing, bathing with EPO in CE rats showed decreases in the CD138+ and CD68+ cells populations and significant decreases in serum and uterine IFN‐γ levels, moreover, uterine IL‐4 levels were slightly higher, and the IFN‐γ/IL‐4(Th1/Th2‐type cytokine ratio) in the uterus was significantly lower. Local IFN‐γ, TNF‐α, and NF‐κB P65 expression in the endometrium was significantly downregulated, while IL‐4 expression was upregulated.
Conclusion
Intrauterine oil‐based contrast bathing significantly alleviated local inflammation in the rat CE model by downregulating NF‐κB P65 expression, reducing IFN–γ (Th1), increasing IL‐4 levels (Th2) in the endometrium, and regulating the Th1/Th2‐type cytokine trends toward Th2.
Melioidosis is a severe infectious disease caused by gram-negative, facultative intracellular pathogen Burkholderia pseudomallei (B. pseudomallei). Although cases are increasing reported from other ...parts of the world, it is an illness of tropical and subtropical climates primarily found in southeast Asia and northern Australia. Because of a 40% mortality rate, this life-threatening disease poses a public health risk in endemic area. Early detection of B. pseudomallei infection is vital for prognosis of a melioidosis patient. In this study, a novel isothermal recombinase polymerase amplification combined with lateral flow dipstick (LF-RPA) assay was established for rapid detection of B. pseudomallei. A set of primer-probe targeting orf2 gene within the putative type III secretion system (T3SS) cluster genes was generated and parameters for the LF-RPA assay were optimized. Result can be easy visualized in 30 minutes with the limit of detection (LOD) as low as 20 femtogram (fg) (ca. 25.6 copies) of B. pseudomallei genomic DNA without a specific equipment. The assay is highly specific as no cross amplification was observed with Burkholderia mallei, members of the Burkholderia cepacia-complex and 35 non-B. pseudomallei bacteria species. Moreover, isolates from patients in Hainan (N = 19), Guangdong (N = 1), Guangxi (N = 3) province of China as well as in Australia (N = 3) and Thailand (N = 1) were retrospectively confirmed by the newly developed method. LODs for B. pseudomallei-spiked soil and blood samples were 2.1×103 CFU/g and 4.2×103 CFU/ml respectively. The sensitivity of the LF-RPA assay was comparable to TaqMan Real-Time PCR (TaqMan PCR). In addition, the LF-RPA assay exhibited a better tolerance to inhibitors in blood than TaqMan PCR. Our results showed that the LF-RPA assay is an alternative to existing PCR-based methods for detection of B. pseudomallei with a potentiality of early accurate diagnosis of melioidosis at point of care or in-field use.
Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety ...worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence.
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