Association between paternal age and singleton birthweight in frozen embryo transfer cycles.

BACKGROUND: Many studies have considered maternal age as a determinant factor for success in assisted reproductive technologies (ART), but the potential role of paternal age on neonatal outcomes has been overlooked. This study aimed to explore the association between paternal age and birthweight in frozen embryo transfer (FET) cycles. METHODS: This retrospective study involved singleton live births born to women undergoing frozen embryo transfer from January 2013 to December 2017 at a tertiary care center in Shanghai, China. The paternal age was classified into four categories: ≤ 30, 31-35, 36-40, and ≥ 41 years. The group consisting of respondents with paternal age of 31-35 was set as the reference group. Singleton birthweight was the primary outcome measure. Z-scores were calculated according to gestational age and newborn gender on birthweight based on the national birthweight reference. Multivariable linear regression analysis was performed to reveal the relationship between paternal age and newborns' birthweight after considering several potential confounders. RESULTS: Exactly 9765 women who fulfilled the inclusion criteria were enrolled. No significant difference was found on mean birthweight (P = 0.082) and gestation-adjusted Z-scores (P = 0.569) among paternal age categories. The reference group and the group with aged 36-40 years had the highest mean birthweight and Z-scores, respectively (3350.2 ± 467.8 g, 0.36 ± 1.00). A decline in mean birthweight with paternal age was observed, and the group over 40 years had the lowest value of 3309.4 ± 474.3 g, but the difference was not statistically significant. In multivariate analyses, the adjusted odds of very low birthweight (LBW), LBW, and high birthweight in the reference group did not significantly differ with the three other groups. After correcting several potential confounders, no significant correlation was observed between paternal age and neonatal birthweight (P = 0.289). CONCLUSION: Paternal age was not associated with mean birthweight and gestational age- and gender-adjusted birthweight (Z-scores) of singletons among women who became pregnant in FET cycles.

Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosis.

Endometriosis (EM) in reproductive females has an incidence of 6-10% and greatly affects female fertility, quality of life, and long-term health. The gut microbiota can affect the physiological and pathological processes of humans through various pathways, such as those involving the nervous and endocrine systems and immunity, and it plays important roles in endocrine and inflammatory diseases. Whether the gut microbiota plays a role in EM has gradually attracted researchers' attention. In the present study, fecal and blood samples were collected from 12 patients with stage 3/4 EM and 12 healthy controls. We performed 16S rRNA high-throughput sequencing to compare the gut microbiota between the EM and control groups. Serum levels of hormones and inflammatory cytokines were measured. We found that compared with the control group, the EM group had a lower α diversity of gut microbiota and a higher Firmicutes/Bacteroidetes ratio. The abundances of various taxa (such as Actinobacteria, Tenericutes, Blautia, Bifidobacterium, Dorea, and Streptococcus) were significantly different between the two groups. The taxon with the highest abundance in the EM group was Prevotella_7, and that in the control group was Coprococcus_2. The serum levels of E2 and IL-8 were significantly higher in the EM group than in the control group (E2: EM group 74.7 ± 22.5 pg/L vs CON group 47.9 ± 12.5 pg/L; IL-8: EM group 6.39 ± 1.59 pg/mL vs CON group 4.14 ± 0.73 pg/mL). Additionally, the gut microbiota of the EM group was enriched for the microbial function categories environmental information processing, endocrine system, and immune system. Correlations were detected between each of Blautia and Dorea abundance and estradiol level and between Subdoligranulum abundance and IL-8 level. This study elucidated the associations between the gut microbiota and both serum hormones and inflammatory factors in EM. However, the findings need to be verified in future studies.

Pioglitazone Metformin Complex Improves Polycystic Ovary Syndrome Comorbid Psychological Distress via Inhibiting NLRP3 Inflammasome Activation: A Prospective Clinical Study.

OBJECTIVE: This study aimed at investigating the therapeutic effect and mechanism of pioglitazone metformin complex preparation (PM) in polycystic ovary syndrome (PCOS) comorbid psychological distress. METHODS: Seventy-five patients with PCOS comorbid psychological distress were randomly allocated into the PM, metformin, and placebo groups. The primary efficacy measure was the change from baseline to week 12 on the Symptom Checklist 90-R (SCL-90-R) scores. NLRP3 inflammasome, IL-1ß, IL-6, TNF-α, and biochemical parameters were determined at baseline and at week 12. The participants were required to meet the criteria for PCOS (Rotterdam, NIH) and psychological distress (any factor scores of SCL - 90 - R > 2). RESULTS: The participants had significantly high scores on the SCL-90-R scales of anxiety and depression. PM significantly decreased anxiety and depression symptom severity (from 2.31 ± 0.75 to 1.65 ± 0.38, p < 0.001, and from 2.08 ± 0.74 to 1.61 ± 0.46, p = 0.010, at week 12, respectively). PM significantly decreased the expression of NRPL3 and caspase-1. Patients in the PM group experienced a significant reduction in IL-1ß (from 98.42 ± 14.38 to 71.76 ± 13.66, p = 0.02), IL-6 (from 87.51 ± 8.74 to 71.98 ± 15.87, p = 0.02), and TNF-α (from 395.33 ± 88.55 to 281.98 ± 85.69, p = 0.04). PM was superior to metformin in reducing total testosterone (2.24 ± 0.74 versus 3.06 ± 0.83, p = 0.024, at week 12). CONCLUSIONS: This study is the first to reveal that PM alleviates psychological distress via inhibiting NLRP3 inflammasome and improves several markers, including total testosterone.

Effect of baseline prolactin levels on the pregnancy outcomes after fresh embryo transfer.

BACKGROUND AND AIMS: There is clinical disagreement on whether to treat hyperprolactinemia with medication before embryo transfer. The aim of this study is to identify the impact of basal prolactin (PRL) levels on pregnancy outcomes in fresh embryo transfer cycles. METHODS: This retrospective study involved 2,648 women who underwent basal PRL level testing and fresh embryo transfer between January 2015 and December 2020 at our Hospital's Department of Assisted Reproduction. Basal PRL levels can be classified into three categories: <30 (n = 2339), 30­60 (n = 255), and ≥60 (n = 54) µg/l. Pregnancy outcome was defined as the primary outcome measure, and the live birth rate was defined as the second outcome measure. Subsequently, univariate and multivariable logistic regression analysis was used to reveal the association between basal PRL levels and pregnancy outcomes after considering several potential confounding factors. RESULTS: Elevated basal PRL levels were found not a risk factor for pregnancy outcomes in patients receiving good-quality embryo transfer (p > .05). For pregnancy or not, female age (OR: 1.03; 95% CI: 1.01-1.05), embryos transferred (OR: 0.52; 95% CI: 0.41-0.65), and normal fertilization rate (OR: 0.68; 95% CI: 0.48-0.97) were found to be an independent risk factor. For ongoing pregnancy or not, female age (OR: 1.07; 95% CI: 1.03-1.11), embryos transferred (OR: 0.57; 95% CI: 0.37-0.88), and menstrual cycle (OR: 1.76; 95% CI: 1.22-2.54) were also independent risk factors. CONCLUSION: There is no adverse impact on pregnancy outcomes during embryo transfer cycles with good-quality embryos when PRL levels are elevated.

Therapeutic effects of Huayu Jiedu formula on endometriosis via downregulating GATA 6 expression.

Background: Endometriosis (EMs) is a common chronic inflammatory disease which is characterized by multiple clinical symptoms and high recurrence rate due to the absence of effective therapies. Huayu Jiedu Formula (HYJDF), is a traditional Chinese medicine prescription with five major herbs. It has been used as traditional medicine to treat EMs for more than twenty years and exerted a good therapeutic effect. However, the underlying mechanism is unclear. Here we aim to observe the effects of HYJDF on EMs and investigate the therapeutic mechanism. Methods: The extract components of HYJDF were identified and quantified by an UHPLC-QE-MS method. Network pharmacology was used to obtain the core targets of HYJDF for the treatment of EMs and the specific biologic processes involved. A total of 68 EMs cases were randomly divided into control (gestrinone) and observation (HYJDF) groups. The overall effectiveness, pain scores, cyst-size changes, serum CA125 levels, quality-of-life scores, safety, and adverse events were evaluated before and after treatment. For the mechanism research, DNA methylation-chip analysis was performed to determine the differential genes. EMs mice models and human ectopic stromal cells (ESCs) were treated with HYJDF and its pharmaceutical serum, respectively. The ectopic foci was measured via H&E staining while the expressions of the target genes were verified by real-time PCR and Western blot analysis. The inflammatory cytokine levels in the peritoneal fluid of mice were detected by ELISA. The proliferative potential of cells was analyzed by MTS whereas the apoptosis and cell cycle were determined through flow analysis. Results: The total number of components detected in positive and negative ion modes was 839 and 597, respectively. Network pharmacology suggested that HYJDF treated EMs through DNA methylation. We found that HYJDF and gestrinone exerted good therapeutic effect with no obvious difference, but the HYJDF treatment group had fewer side effects. GATA 6, which was hypomethylated and abundant in endometriotic cells, potently induced inflammatory response. This finding indicated the important role of GATA 6 in EMs development. Moreover, HYJDF ameliorated inflammatory response (i.e., reduced the levels of IL-1ß and PGE2 in peritoneal fluid), suppressed ESCs proliferation, and increased cell apoptosis by down-regulating GATA 6 expression. Conclusion: We demonstrated that HYJDF has anti-inflammation activity and increased cell apoptosis through the reduction of GATA 6 expression in ectopic tissues, which showed good therapeutic effect without any obvious side effects. These findings suggest that HYJDF may be a new and efficient traditional Chinese medicine for the treatment of EMs.

Gut Microbiota Disorder Contributes to the Production of IL-17A That Exerts Chemotaxis via Binding to IL-17RA in Endometriosis.

Introduction: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized. Methods: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry. Results: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects. Discussion: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.

Knowledge about, attitudes toward and acceptance and predictors of intention to receive the mpox vaccine among cancer patients in China: A cross-sectional survey.

This study aimed to investigate the knowledge about, attitudes toward, and acceptance and predictors of receiving the mpox vaccine among Chinese cancer patients. Patients were selected using a convenience sampling method. A web-based self-report questionnaire was developed to assess cancer patients' knowledge, attitudes, and acceptance regarding the mpox vaccine. Multivariate logistic regression analysis was used to determine predictors of acceptance of the mpox vaccine. A total of 805 cancer patients were included in this study, with a vaccine hesitancy rate of 27.08%. Approximately 66% of the patients' information about mpox and the vaccine came from the mass media, and there was a significant bias in the hesitant group's knowledge about mpox and the vaccine. Multivariable logistic regression analysis suggested that retirement; chemotherapy; the belief that the mpox vaccine could prevent disease, that vaccination should be compulsory when appropriate and that the mpox vaccine prevents mpox and reduces complications; the willingness to pay for the mpox vaccine; the willingness to recommend that friends and family receive the mpox vaccine; and the belief that the mpox vaccine should be distributed fairly and equitably were factors that promoted vaccination. The belief that mpox worsens tumor prognosis was a driving factor for vaccine hesitancy. This study investigated the knowledge of cancer patients about mpox and the vaccine, evaluated the acceptance and hesitancy rates of the mpox vaccine and examined the predictors of vaccination intention. We suggest that the government scientifically promote the vaccine and develop policies such as free vaccination and personalized vaccination to increase the awareness and acceptance rate of the mpox vaccine.

A Network Pharmacology Study on the Similarities and Differences in the Mechanisms of Zuo Gui Wan/You Gui Wan for the Treatment of Premature Ovarian Failure.

BACKGROUND: Premature ovarian failure is a heterogeneous disease that severely affects the quality of life of women in their reproductive years. The ancient classical Chinese medicine compounds Zuo Gui Wan and You Gui Wan have great potential to treat premature ovarian failure, but the similarities and differences in their pharmacological mechanisms for treating POF are not yet clear. METHODS: In this study, the public database was used to screen the active ingredients and potential targets of Zuo Gui Wan and You Gui Wan. The similarities and differences in the potential targets of both pills for the treatment of POF were analysed using the POF-related genes obtained from OMIM and GeneCards. The protein-protein interaction network was established and collated to form a drug-active ingredient-target gene network using STRING. Finally, the drug-target-pathway network was constructed by enrichment analysis to find the differences in target enrichment on the same pathway. RESULTS: Pharmacological analysis of the network showed that Zuo Gui Wan contains 72 active ingredients, while You Gui Wan has 112. A total of 62 common compositions, such as quercetin and kaempferol, were identified. Amongst them were 10 unique compounds, such as hydroxyproline and cholesterol, in Zuo Gui Wan and 50 exclusive compounds, such as Karanjin and betacarotene, in You Gui Wan. In addition, 14 overlapping targets, including MAPK1, CXCL8, TNF, IL6, and EGFR, were determined amongst the first 20 targets in the treatment of POF by both pills, demonstrating that the core mechanism of POF treatment is similar between the two. Pathway enrichment analysis showed 87 identical and significant pathways between Zuo Gui Wan and You Gui Wan, including IL-17, TNF, PI3K-Akt, oestrogen, VEGF, and other pathways. Zuo Gui Wan has 12 special pathways, such as natural killer cell-mediated cytotoxicity and intestinal immune network for IgA production. You Gui Wan has nine unique pathways, such as insulin secretion and glucagon signalling pathway. CONCLUSION: Zuo Gui Wan and You Gui Wan could treat POF by inhibiting oxidative stress and inflammation, regulating hormone levels, improving ovarian function, and promoting follicular development. Zuo Gui Wan is inclined to immune regulation, while You Gui Wan prefers insulin regulation. Therefore, similarities and differences clearly exist in the specific mechanisms of Zuo Gui Wan and You Gui Wan in the treatment of POF.

Double-edged roles of ferroptosis in endometriosis and endometriosis-related infertility.

Endometriosis is strongly associated with infertility. Several mechanisms have been reported in an attempt to elucidate the pathophysiological effects that lead to reduced fertility in women with endometriosis. However, the mechanisms by which endometriosis affects fertility have not been fully elucidated. Ferroptosis is a novel form of nonapoptotic cell death that is characterized by iron-dependent lipid peroxidation membrane damage. In past reports, elevated iron levels in ectopic lesions, peritoneal fluid and follicular fluid have been reported in patients with endometriosis. The high-iron environment is closely associated with ferroptosis, which appears to exhibit a double-edged effect on endometriosis. Ferroptosis can cause damage to ovarian granulosa cells, oocytes, and embryos, leading to endometriosis-related infertility. This article summarizes the main pathways and regulatory mechanisms of ferroptosis and explores the possible mechanisms of the formation of an iron-overloaded environment in endometriotic ectopic lesions, peritoneal fluid and follicular fluid. Finally, we reviewed recent studies on the main and potential mechanisms of ferroptosis in endometriosis and endometriosis-related infertility.

Past and present: a bibliometric study on polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease that has a great impact on women's physical and mental health. It is a burden to social and patients' economy. In recent years, researchers' understanding of PCOS has reached a new level. However, many PCOS reports have different directions, and overlapping phenomena exist. Therefore, clarifying the research status of PCOS is important. This study aims to summarise the research status of PCOS and predict the hot spots of PCOS in the future by Bibliometricx. RESULTS: The keywords of PCOS research focused on PCOS, insulin resistance (IR), obesity and metformin. Keywords plus co-occurrence network showed that PCOS, IR and prevalence were hot spots in the recent 10 years. Moreover, we found that gut microbiota may be a carrier that can be used to study hormone levels, IR-related mechanisms, prevention and treatment in the future. CONCLUSIONS: This study is helpful for researchers to quickly grasp the current situation of PCOS research and enlighten researchers to explore new problems in PCOS.

Tumor-specific expression of microRNA-26a suppresses human hepatocellular carcinoma growth via cyclin-dependent and -independent pathways.

MicroRNA-26a (miR-26a) is a tumor suppressor that is reduced in hepatocellular carcinoma (HCC). Increasing evidence indicates that the liver is a hormone-responsive organ like the breast. The purpose of this study was to investigate whether miR-26a, regulated by a human α-fetoprotein (hAFP) and human telomerase reverse transcriptase (hTERT) dual promoter, could be specifically expressed in liver tumor cells to suppress their growth and to clarify whether estrogen receptor-α (ERα) is regulated by miR-26a and involved in the HCC process. Our data show that miR-26a expression driven by a hAFP-TERT dual promoter was tumor-specific and decreased the viability of tumor cells by regulating ERα, progesterone receptor (PR) and P53 except for cyclin D2 or cyclin E2 in vitro and in vivo. Our data also show that estradiol (E2) promotes the growth of liver cancer cells similar to breast cancer cells partly via the E2-ERα pathway and that miR-26a significantly down regulates ERα and prevents the stimulation of hepatoma cell growth by E2. These data suggest that ERα, which is regulated by miR-26a, is important for liver tumor cell growth. Moreover, hAFP-TERT dual promoter-mediated miR-26a expression could specifically exert potential antitumor activity and provide a novel targeting approach for cancer therapy.

[Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model].

OBJECTIVE: To compare angiopoiesis ability of eutopic and ectopic endometrial tissue isolated from women with endometriosis and endometrium isolated from women without endometriosis (control), and to explore the inhibitory effects of medicated serum of Neiyi Recipe, a compound traditional Chinese herbal medicine. METHODS: Chick chorioallantoic membrane (CAM) model of endometriosis was established by transplanting endometrium onto CAM. The CAMs were then hatched with blank serum or medicated serum of danazol or Neiyi Recipe, which were prepared in rats by orally administering. The sizes of the transplanted tissue and new vessels around the transplanted tissue were measured. Expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method. RESULTS: There was no difference in the sizes of transplanted tissue among CAM models of ectopic and eutopic endometrial tissue isolated from women with endometriosis or control (P>0.05), and more new vessels were found around the ectopic and eutopic endometrial tissue than the endometrial tissue of control (P<0.05). Compared with the controls, the size of the transplanted tissue and positive area of new vessels were significantly inhibited by Neiyi Recipe-medicated serum (P<0.01, P<0.05), and similar changes happened in the danazol groups, except for the size of transplanted tissue from ectopic endometrial tissue (P>0.05). Expression of VEGF was significantly higher in eutopic and ectopic endometrial tissue than in the control (P<0.01); the level of VEGF obviously reduced in the Neiyi Recipe and danazol groups (P<0.01), but no significant difference was detected between them. CONCLUSION: Endometrium from women with endometriosis stimulates the formation of new vessels by increase the expression of VEGF. Neiyi Recipe-medicated serum significantly decreases the expression of VEGF in eutopic and ectopic endometrial tissues and thus restrains the formation of new vessels, reduces the blood supply and inhibits growth of ectopic endometrial tissue, which are similar to danazol, but has greater efficacy in suppressing the expression of VEGF.

Curcumin treats endometriosis in mice by the HIF signaling pathway.

OBJECTIVE: The aim of this study was to investigate whether curcumin has a therapeutic effect on endometriosis (EM) and to determine the specific mechanism. METHODS: Network pharmacology was used to obtain the core targets of curcumin for the treatment of EM and the specific biologic processes involved. A mouse model of EM was constructed and divided into different groups, as follows: control, negative control, curcumin, and denogestrel. The number, volume, and degree of adhesions of the lesions in each group were measured. The levels of IL-1ß, IL-6, and VEGFA in the peritoneal cavity were measured by enzyme-linked immunosorbent assay (ELISA). Western blot and Q-PCR were used to detect HIF-1α and VEGFA proteins and gene expression levels in the lesion tissues. RESULTS: Network pharmacology suggested that curcumin treated EM through the HIF signaling pathway, of which IL-6, HIF-1α, and VEGFA are key targets. The number of lesions, volume, and degree of adhesions were significantly reduced in the curcumin group compared to the negative control group and the control group (P < 0.05). IL-6, IL-1ß, and VEGFA levels were reduced in the peritoneal fluid (P < 0.05). HIF-1α and VEGFA protein and gene levels were significantly reduced in the lesions (P < 0.05). No modulation of HIF-1α was shown by denogestins. CONCLUSION: Curcumin played a role in the treatment of EM by modulating the HIF signaling pathway, improving the local hypoxia of the lesion, and reducing the inflammatory state of EM.

Mapping trends and hotspot regarding gut microbiota and host immune response: A bibliometric analysis of global research (2011-2021).

Background: Gut microbiota is a complex ecosystem that is vital for the development and function of the immune system, is closely associated with host immunity, and affects human health and disease. Therefore, the current progress and trends in this field must be explored. Purpose: No bibliometric analysis has been conducted on gut microbiota and host immune response. This study aimed to analyze the current progress and developing trends in this field through bibliometric and visual analysis. Methods: Global publications on gut microbiota and host immune response from January 2011 to December 2021 were extracted from the Web of Science (WOS) collection database. GraphPad Prism, VOSviewer software, and CiteSpace were employed to perform a bibliometric and visual study. Results: The number of publications has rapidly increased in the last decade but has declined in the most recent year. The Cooperation network shows that the United States, Harvard Medical School, and Frontiers in Immunology were the most active country, institute, and journal in this field, respectively. Co-occurrence analysis divided all keywords into four clusters: people, animals, cells, and diseases. The latest keyword within all clusters was "COVID," and the most frequently occurring keyword was "SCFA." Conclusion: Gut microbiota and host immune response remain a research hotspot, and their relation to cancer, CNS disorders, and autoimmune disease has been explored. However, additional studies on gut microbiota must be performed, particularly its association with bacterial strain screening and personalized therapy.

Huayu Jiedu Fang Protects Ovarian Function in Mouse with Endometriosis Iron Overload by Inhibiting Ferroptosis.

Endometriosis (EM) is a common chronic inflammatory disease in women. Sampson's retrograde menstruation theory is the most widely accepted theory of EM pathogenesis. The periodic bleeding of ectopic lesions is an important pathological feature of this disease, and the occurrence and progression of EM are closely associated with the iron overload caused by ectopic lesions. However, animal models that simulate menstrual-blood reflux and hemorrhage from EM lesions are lacking. In this study, we performed intraperitoneal injection of endometrial fragments and periodic intraperitoneal blood injection to simulate the real cause and disease state of EM and successfully constructed a mouse model of EM iron overload. Our research found that the number, size, and degree of adhesion of EM lesions in the iron-overload model mouse were significantly higher than those in the model mouse. Moreover, the iron concentration in the abdominal fluid and ovary significantly increased, and the level of malondialdehyde (MDA) in the ovary increased. Conversely, GPX4, GSH, and other anti-ferroptosis-related proteins were downregulated, proving the occurrence of ferroptosis. Huayu Jiedu Fang (HYJDF) is an empirical prescription for EM treatment. This study combined animal experiments, UHPLC-QE-MS analysis, and network pharmacology to analyze whether HYJDF can inhibit ferroptosis to slow down the progression of EM and protect ovarian function. Based on the constructed iron-overload model, HYJDF can reduce the volume of EM lesions and the degree of adhesion, downregulate the total iron concentration in the peritoneal fluid and ovary, upregulate GPX4 expression and GSSG in the ovary, downregulate the level of MDA in the ovary, and promote the development of follicles. We further confirmed that HYJDF can inhibit the progression of EM disease and improve the ovarian function of the model mouse by inhibiting ferroptosis. Finally, through UHPLC-QE-MS and network pharmacology analysis, the natural compounds in HYJDF were identified and verified and the regulatory effect of HYJDF on the EM ferroptosis pathway through the IL-6/hepcidin pathway was preliminarily elucidated.

Mechanism of Thunberg Fritillaria in treating endometriosis based on network pharmacology and the effect of Peiminine on the MEK/ERK pathway.

OBJECTIVE: To explore the mechanism of Thunberg Fritillaria in treating endometriosis (EMs) based on network pharmacology and the effect of Peiminine on the MEK/ERK pathway. METHODS: We applied Chinese medicine system pharmacology analysis platform (TCMSP) database and literature search to screen the main chemical components of Fritillaria thunbergii Miq and created a Vanny map from the databases of TCMSP, GENECARDS, Online Mendelian Inheritance in Man (OMIM), and some others. The STRING database was used to construct the protein interaction network of Fritillaria thunbergii Miq and EMs. The overlapping targets and enriched pathways were discovered using the cells of the innate immune annotation database (DAVID) and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To test the mechanism of Peiminine, the active ingredients of Fritillaria thunbergii, in the therapy of EMs, we designed cell assays and animal research. EMs mouse models were treated with several therapies, including fibrosis inhibitor in Peiminine by utilizing Hematoxylin-eosin staining (HE staining), MASSON staining, Immunohistochemistry, Immunofluorescence, quantitative real-time PCR (qRT-PCR) experiment, and Western blotting test. We evaluated the anti-endometriotic effects of Peiminine using 12Z human endometriotic cells. Cell Counting Kit 8 was used to assess the vitality of 12z cells (CCK8). We evaluated the migration ability of 12z cells by cell scratch test. RESULTS: The effective active ingredients of Fritillaria thunbergii Miq in the treatment of EMs are Pelargonidin, Beta-sitosterol syringaresinol, Peimisine Pelargonidin-3, 5-diglucoside Ziebeimine Zhebeiresinol Verticine Solatubin OSI-2040 Chaksine Peiminine Peiminoside Peiminoside_qt, and 6-Methoxyl-2-acetyl-3-methyl-1, 4-naphthoquinone-8-O-beta-D-glucopyranoside. The critical targets for Fritillaria thunbergii Miq treating EMs are NOS2/PTGS1/AR/PPARG/PTGS2/NCOA2/RXRA/PGR/NR3C1/NCOA1/SLC6A4/OPRM1/BCL2 and ESR1. The results of GO function and KEGG enrichment analysis showed that the role pathway was estrogen-related signaling and thyroid hormone-related signaling. The expression of E-cadherin was decreased in EMs while MEK1/2, P-ERK, N-cadherin and vimentin were all increased in MASSON, immunofluorescence, Real-time PCR and Western blotting. In epithelial 12Z cells, high concentrations of Peiminine can block cell activity and migration, which is directly related to blocking cell fibrosis. CONCLUSION: Overall, this study partially verified the network pharmacological prediction that Peiminine regulates the MAPK pathway in inhibiting 12Z cell proliferation and migration, and finally protects against EMs.

Characteristics and possible mechanisms of metabolic disorder in overweight women with polycystic ovary syndrome.

Background: Polycystic ovary syndrome (PCOS) is a kind of endocrine and metabolic disorder, disturbing the females of reproductive age. Here, we aimed to investigate the metabolic characteristics of overweight women with PCOS and analyze the possible mechanisms. Methods: We conducted a cross-sectional study on 947 patients with PCOS, who were classified according to body mass index (BMI) as overweight (BMI ≥ 24 kg/m2) or non-overweight (BMI ≤ 23.9 kg/m2). The clinical symptoms, endocrine features, metabolic status, and inflammatory levels of the patients were comprehensively assessed and compared between the patients of the two groups. Additionally, a predictive study on the correlation between inflammation and metabolism was performed using STRING and Cytoscape software, and the possible mechanisms of metabolic disorders involved in the overweight PCOS were preliminarily explored. Results: Overweight PCOS was associated with increased average age, waist-to-hip ratio, and the incidence of acanthosis nigricans. These patients were susceptible to familial hypertension and diabetes, and exhibited evident characteristics of low levels of luteinizing hormone (LH) and the ratio of LH to follicle-stimulating hormone, and were more inclined to insulin resistance (IR). Furthermore, overweight PCOS presented with a chronic low-grade inflammation state with increased levels of inflammatory cytokines complement components C5/C5α, CXCL12/SDF-1, MIF, and Serpin E1/PAI-1 evidently compared with those in non-overweight PCOS. Pearson analysis showed that these inflammatory cytokines were directly or indirectly correlated with IR. The STRING and Cytoscape network analysis predicted that inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1 and MIF might be crucial for inducing IR in overweight PCOS women through various biological functions and signal transductions including the JAK-STAT cascade, ATP biosynthesis, and HIF-1 signaling. Conclusions: Overweight patients with PCOS are prone to low gonadal levels, IR, and chronic low-grade inflammation. Inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1and MIF might lead to IR through multiple biological functions and signal transductions in overweight PCOS.

Androgen Excess Induced Mitochondrial Abnormality in Ovarian Granulosa Cells in a Rat Model of Polycystic Ovary Syndrome.

Background: Androgen excess could profoundly lead to follicular dysplasia or atresia, and finally result in polycystic ovary syndrome (PCOS); however, the exact mechanism remains to be fully elucidated. Methods: PCOS model rats were induced by dehydroepiandrosterone, and their fertility was assessed. The ovarian granulosa cells (GCs) from matured follicles of PCOS model rats were collected and identified by immunofluorescence. The mitochondrial ultrastructure was observed by transmission electron microscope and the mitochondrial function was determined by detecting the adenosine triphosphate (ATP) content and mtDNA copy number. Besides, the expressions of respiratory chain complexes and ATP synthases in relation to mitochondrial function were analyzed. Results: The PCOS model rats were successfully induced, and their reproductive outcomes were obviously adverse. The GCs layer of the ovarian was apparently cut down and the mitochondrial ultrastructure of ovarian GCs was distinctly destroyed. The ATP content and mtDNA copy number of ovarian GCs in PCOS model rats were greatly reduced, and the expressions of NDUFB8 and ATP5j were significantly down-regulated without obvious deletion of mtDNA 4834-bp. Conclusions: Androgen excess could damage mitochondrial ultrastructure and function of GCs in rat ovary by down-regulating expression of NDUFB8 and ATP5j in PCOS.

Therapeutic Prospects of Polysaccharides for Ovarian Cancer.

Ovarian cancer (OC) is ranked as the leading cause of death among cancers of the female reproductive tract. First-line platinum treatment faces the severe challenges associated with the patient relapse and poor prognosis. Thus, it is imperative to develop natural antitumor drugs for OC with high efficacy. Natural polysaccharides have significant biological activities and antitumor effects. Our work has demonstrated that polysaccharides play key roles by inhibiting the cell proliferation and growth, regulating the tumor cell cycle, inducing apoptosis, suppressing the tumor cell migration and invasion, improving the immunomodulatory activities, and enhancing the efficacy of chemotherapy (cisplatin) in OC, which provide powerful evidence for the application of polysaccharides as novel anticancer agents, supplementary remedies, and adjunct therapeutic agents alone or in combination with cisplatin for preventing and treating the OC.

Adverse Effects of Polycystic Ovarian Syndrome on Pregnancy Outcomes in Women With Frozen-Thawed Embryo Transfer: Propensity Score-Matched Study.

Purpose: This work aimed to evaluate the adverse effect of polycystic ovary syndrome (PCOS) on pregnancy outcomes of singletons after vitrification in women with frozen-thawed embryo transfer (FET). Methods: Patients with/without PCOS who underwent FET from January 2013 and December 2018 were included. Propensity score matching (PSM) was used to reduce the influence of bias. Logistic regression was applied to identify the risk factors of adverse pregnancy outcomes of singletons in women with PCOS. Result: After PSM, the PCOS group had shorter gestational age (P<0.001) and lower newborn birth weight than the non-PCOS group (P=0.045). Compared with the non-PCOS group, the PCOS group had an increased risk of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) (P<0.001), placenta and membrane abnormality (P<0.001), stillbirth (P<0.001), neonatal complication (P=0.014), and miscarriage rate (P<0.001). Neonatal complication was associated with parity (adjusted OR=1.202, 95% CI=1.002-1.443, P=0.048) and basal P level (adjusted OR=1.211, 95% CI=1.021-1.436, P=0.028). According to multivariable logistic regression analysis, the miscarriage rate was related to parity (adjusted OR=1.201, 95% CI=1.057-1.166, P=0.005) and basal E2 (adjusted OR=1.002, 95% CI=1.000-1.004, P=0.019) and P levels on the day of embryo transfer (adjusted OR=0.971, 95% CI=0.957-0.985, P<0.001). Conclusions: Compared with non-PCOS women, women with PCOS have a higher risk of GDM and PIH, and neonatal complications and therefore require additional care during pregnancy and parturition.