The tetraploid wheat (Triticum dicoccum (Schrank) Schuebl.) improves nitrogen uptake and assimilation adaptation to nitrogen-deficit stress.

MAIN CONCLUSION: The genetic diversity in tetraploid wheat provides a genetic pool for improving wheat productivity and environmental resilience. The tetraploid wheat had strong N uptake, translocation, and assimilation capacity under N deficit stress, thus alleviating growth inhibition and plant N loss to maintain healthy development and adapt to environments with low N inputs. Tetraploid wheat with a rich genetic variability provides an indispensable genetic pool for improving wheat yield. Mining the physiological mechanisms of tetraploid wheat in response to nitrogen (N) deficit stress is important for low-N-tolerant wheat breeding. In this study, we selected emmer wheat (Kronos, tetraploid), Yangmai 25 (YM25, hexaploid), and Chinese spring (CS, hexaploid) as materials. We investigated the differences in the response of root morphology, leaf and root N accumulation, N uptake, translocation, and assimilation-related enzymes and gene expression in wheat seedlings of different ploidy under N deficit stress through hydroponic experiments. The tetraploid wheat (Kronos) had stronger adaptability to N deficit stress than the hexaploid wheats (YM25, CS). Kronos had better root growth under low N stress, expanding the N uptake area and enhancing N uptake to maintain higher NO3- and soluble protein contents. Kronos exhibited high TaNRT1.1, TaNRT2.1, and TaNRT2.2 expression in roots, which promoted NO3- uptake, and high TaNRT1.5 and TaNRT1.8 expression in roots and leaves enhanced NO3- translocation to the aboveground. NR and GS activity in roots and leaves of Kronos was higher by increasing the expression of TANIA2, TAGS1, and TAGS2, which enhanced the reduction and assimilation of NO3- as well as the re-assimilation of photorespiratory-released NH4+. Overall, Kronos had strong N uptake, translocation, and assimilation capacity under N deficit stress, alleviating growth inhibition and plant N loss and thus maintaining a healthy development. This study reveals the physiological mechanisms of tetraploid wheat that improve nitrogen uptake and assimilation adaptation under low N stress, which will provide indispensable germplasm resources for elite low-N-tolerant wheat improvement and breeding.

Effect of Vaginal Microecological Alterations on Female Pelvic Organ Prolapse.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the correlation between endogenous vaginal microecological alterations and female pelvic organ prolapse (POP). METHODS: Patients who underwent vaginal hysterectomy were retrospectively analyzed as the POP group (n = 30) and the non-POP group (n = 30). The vaginal microbial metabolites and enzyme levels were tested using the dry chemoenzymatic method. The mRNA and protein expression were tested using real-time quantitative PCR and immunohistochemistry. SPSS version 25.0 and GraphPad Prism 8.0 were performed for statistical analysis. RESULTS: Compared with the non-POP group, the vaginal pH, H2O2 positivity and leukocyte esterase positivity were higher in patients with POP (all p < 0.05). Further analysis showed that patients with pelvic organ prolapse quantification (POP-Q) stage IV had higher rates of vaginal pH, H2O2 positivity and leukocyte esterase positivity than those with POP-Q stage III. Additionally, the mRNA expression of decorin (DCN), transforming growth factor beta 1 (TGF-ß1), and matrix metalloproteinase-3 (MMP-3) in uterosacral ligament tissues were higher, whereas collagen I and III were lower. Similarly, the positive expression of MMP-3 in uterosacral ligament tissue was significantly upregulated in the POP group compared with the non-POP group (p = 0.035), whereas collagen I (p = 0.004) and collagen III (p = 0.019) in uterosacral ligament tissue were significantly downregulated in the POP group. Correlation analysis revealed that there was a significant correlation between vaginal microecology and collagen metabolism. In addition, MMP-3 correlated negatively with collagen I and collagen III (p = 0.002, r = -0.533; p = 0.002, r = -0.534 respectively), whereas collagen I correlated positively with collagen III (p = 0.001, r = 0.578). CONCLUSIONS: Vaginal microecological dysbiosis affects the occurrence of female POP, which could be considered a novel therapeutic option.

HMGB1 enhances the migratory and invasive abilities of A2780/DDP cells by facilitating epithelial to mesenchymal transition via GSK­3ß.

The aim of the present study was to investigate the impact and mechanism of high mobility group box 1 (HMGB1) on the regulation of cell migration and invasion in A2780/DDP cisplatin-resistant ovarian cancer cells. After transfecting small interfering (si)RNA-HMGB1 into A2780/DDP cells, Transwell migration and invasion assays were conducted to assess alterations in the cell migratory and invasive abilities. Additionally, western blotting analyses were performed to examine changes in HMGB1, phosphorylated (p)-GSK-3ß, GSK-3ß, E-cadherin and vimentin expression levels. The results of the present study demonstrated that the migratory and invasive abilities of A2780/DDP cells were significantly higher compared with those of A2780 cells. Additionally, the expression levels of HMGB1, p-GSK-3ß and the mesenchymal phenotype marker, vimentin, in A2780/DDP cells were significantly elevated relative to the levels in A2780 cells. Conversely, the expression level of the epithelial phenotype marker, E-cadherin, was markedly decreased compared with that in A2780 cells. Following transfection of A2780/DDP cells with siRNA-HMGB1, there was a significant reduction in the rate of cell migration and invasion. Simultaneously, the expression levels of HMGB1, p-GSK-3ß and vimentin were downregulated while the level of E-cadherin was upregulated. It was therefore concluded that the high expression of HMGB1 in A2780/DDP cells enhanced the cell migration and invasion abilities by facilitating epithelial to mesenchymal transition via GSK-3ß.

Superior glucose metabolism supports NH4+ assimilation in wheat to improve ammonium tolerance.

The use of slow-release fertilizers and seed-fertilizers cause localized high-ammonium (NH4 +) environments in agricultural fields, adversely affecting wheat growth and development and delaying its yield. Thus, it is important to investigate the physiological responses of wheat and its tolerance to NH4 + stress to improve the adaptation of wheat to high NH4 + environments. In this study, the physiological mechanisms of ammonium tolerance in wheat (Triticum aestivum) were investigated in depth by comparative analysis of two cultivars: NH4 +-tolerant Xumai25 and NH4 +-sensitive Yangmai20. Cultivation under hydroponic conditions with high NH4 + (5 mM NH4 +, AN) and nitrate (5 mM NO3 -, NN), as control, provided insights into the nuanced responses of both cultivars. Compared to Yangmai20, Xumai25 displayed a comparatively lesser sensitivity to NH4 + stress, as evident by a less pronounced reduction in dry plant biomass and a milder adverse impact on root morphology. Despite similarities in NH4 + efflux and the expression levels of TaAMT1.1 and TaAMT1.2 between the two cultivars, Xumai25 exhibited higher NH4 + influx, while maintaining a lower free NH4 + concentration in the roots. Furthermore, Xumai25 showed a more pronounced increase in the levels of free amino acids, including asparagine, glutamine, and aspartate, suggesting a superior NH4 + assimilation capacity under NH4 + stress compared to Yangmai20. Additionally, the enhanced transcriptional regulation of vacuolar glucose transporter and glucose metabolism under NH4 + stress in Xumai25 contributed to an enhanced carbon skeleton supply, particularly of 2-oxoglutarate and pyruvate. Taken together, our results demonstrate that the NH4 + tolerance of Xumai25 is intricately linked to enhanced glucose metabolism and optimized glucose transport, which contributes to the robust NH4 + assimilation capacity.

Analysis of Clinical Characteristics and Prognostic Factors Related to EMs Correlation in Ovarian Cancer Patients.

Objective: To investigate the clinical characteristics and prognostic factors in patients with endometriosis-associated ovarian cancer. Methods: In this study, we retrospectively analyzed the medical records of 135 ovarian cancer patients admitted to our hospital from January 2016 to January 2018. Based on the presence of concomitant endometriosis (EMs), the patients were divided into two groups: the Endometriosis-Associated Ovarian Cancer (EAOC) group (n=64) and the non-EAOC (NEAOC) group (n=71). We compared the clinical characteristics of the two groups. Additionally, in the EAOC group, we followed up with patients for 5 years, categorized them into the survival group (n=40) and the deceased group (n=24) based on their prognosis, and conducted univariate and multivariate logistic regression analyses to identify influencing factors. Results: In comparison to the NEAOC group, patients in the EAOC group exhibited higher rates of menopause occurrence, pathological stages I-II, vaginal bleeding, and history of cesarean section, with statistical significance (P < .05). They also had a lower incidence of dysmenorrhea, lymph node metastasis, and abdominal distension, as well as an earlier age of onset, all of which were statistically significant (P < .05). There were no statistically significant differences (P > .05) between the two groups in terms of parity, gravidity, tumor diameter, abdominal pain incidence, and body mass index. Based on prognosis, the patients were categorized into a survival group (n=40) and a deceased group (n=24). Comparison between the two groups showed statistically significant differences (P < .05) in terms of postoperative residue, epithelial-mesenchymal transition, and lymph node metastasis. In contrast, there were no statistically significant differences (P > .05) in terms of tumor laterality, histological type, tumor stage, differentiation degree, and vaginal bleeding. The variables with P < .05 were assigned as independent variables, with the prognosis of death as the dependent variable. Multivariate logistic regression analysis revealed that epithelial-mesenchymal transition and lymph node metastasis were independent risk factors for mortality in EAOC patients (P < .05). Conclusion: Clinical characteristics of EAOC patients show significant differences, with epithelial-mesenchymal transition and lymph node metastasis being identified as independent adverse prognostic factors associated with poor outcomes in EAOC patients. However, this study has limitations such as a relatively small sample size, and further research is therefore necessary.

Improved chloroplast Pi allocation helps sustain electron transfer to enhance photosynthetic low-phosphorus tolerance of wheat.

Phosphorus (P) deficit limits high wheat (Triticum aestivum L.) yields. Breeding low-P-tolerant cultivars is vital for sustainable agriculture and food security, but the low-P adaptation mechanisms are largely not understood. Two wheat cultivars, ND2419 (low-P-tolerant) and ZM366 (low-P-sensitive) were used in this study. They were grown under hydroponic conditions with low-P (0.015 mM) or normal-P (1 mM). Low-P suppressed biomass accumulation and net photosynthetic rate (A) in both cultivars, whereas ND2419 was relatively less suppressed. Intercellular CO2 concentration did not decrease with the decline of stomatal conductance. Additionally, maximum electron transfer rate (Jmax) decreased sooner than maximum carboxylation rate (Vcmax). Results indicate that impeded electron transfer is directly responsible for decreased A. Under low-P, ND2419 exhibited greater PSII functionality (potential activity (Fv/Fo), maximum quantum efficiency (Fv/Fm), photochemical quenching (qL) and non-photochemical quenching (NPQ) required for electron transfer than ZM366, resulting more ATP for Rubisco activation. Furthermore, ND2419 maintained higher chloroplast Pi concentrations by enhancing chloroplast Pi allocation, compared with ZM366. Overall, the low-P-tolerant cultivar sustained electron transfer under low-P by enhancing chloroplast Pi allocation, allowing more ATP synthesis for Rubisco activation, ultimately presenting stronger photosynthesis capacities. The improved chloroplasts Pi allocation may provide new insights into improve low-P tolerance.

Long non-coding RNA MYU promotes ovarian cancer cell proliferation by sponging miR-6827-5p and upregulating HMGA1.

Background: Long non-coding RNAs (lncRNAs) have been confirmed to play vital roles in tumorigenesis. LncRNA MYU has recently been reported as an oncogene in several kinds of tumors. However, MYU's expression status and potential involvement in ovarian cancer (OC) remain unclear. In this study, we explored the underlying role of MYU in OC. Methods and results: The expression of MYU was upregulated in OC tissues, and MYU's overexpression was significantly correlated with the FIGO stage and lymphatic metastasis. Knockdown of MYU inhibited cell proliferation in SKOV3 and A2780 cells. Mechanistically, MYU directly interacted with miR-6827-5p in OC cells; HMGA1 is a downstream target gene of miR-6827-5p. Furthermore, MYU knockdown increased the expression of miR-6827-5p and decreased the expression of HMGA1. Restoration of HMGA1 expression reversed the influence on cell proliferation caused by MYU knockdown. Conclusion: MYU functions as a ceRNA that positively regulates HMGA1 expression by sponging miR-6827-5p in OC cells, which may provide a potential target and biomarker for the diagnosis or prognosis of OC.

Melatonin alleviates chromium toxicity by altering chromium subcellular distribution and enhancing antioxidant metabolism in wheat seedlings.

The endogenous stimulating molecule melatonin (N-acetyl-5-methoxytryptamine, MT) has an important function in mitigating the impact of multiple abiotic stressors. However, the ameliorating effect of MT on chromium (Cr) stress and its mechanisms remains unclear. Therefore, the present study aimed to clarify the mitigating effect of exogenous MT (0 µM and 100 µM) on wheat seedlings under Cr (0 µM and 50 µM) stress stemming from the growth and physiological characteristics, phytochelatin (PC) biosynthesis, Cr subcellular distribution, and antioxidant system of the plants in these treatments. The results showed that endogenous MT application significantly promoted plant growth and improved root morphology of wheat seedlings under Cr stress due to decreased Cr and reactive oxygen species (ROS) accumulation in both roots and leaves. Accumulation and transport of Cr from roots to leaves were reduced by MT, because enhanced vacuolar sequestration via upregulated PC accumulation, took place, derived from the fact that MT upregulated the expression of key genes for PC synthesis (TaPCS and Taγ-ECS). Furthermore, MT pre-treatment alleviated Cr-induced oxidative damage by diminishing lipid peroxidation and cell apoptosis, profiting from the enhanced scavenging ability of ROS as a result of the MT-induced increase in the activities of superoxide dismutase, catalase, ascorbate peroxidase, and glutathione reductase, and the related encoding gene expression levels of TaSOD2, TaCAT, TaAPX, and TaGR. In conclusion, endogenous MT application improved the growth traits, antioxidant system, and decreased Cr accumulation especially at the leaf level in wheat seedlings under Cr stress mainly through enhancing antioxidant enzyme activities and altering Cr subcellular distribution via strengthening PC biosynthesis. The mechanisms of MT-induced plant tolerance to Cr stress could help develop new strategies for secure crop production in Cr-polluted soils.

Enhanced Stomatal Conductance Supports Photosynthesis in Wheat to Improved NH4+ Tolerance.

The impact of ammonium (NH4+) stress on plant growth varies across species and cultivars, necessitating an in-depth exploration of the underlying response mechanisms. This study delves into elucidating the photosynthetic responses and differences in tolerance to NH4+ stress by investigating the effects on two wheat (Triticum aestivum L.) cultivars, Xumai25 (NH4+-less sensitive) and Yangmai20 (NH4+-sensitive). The cultivars were grown under hydroponic conditions with either sole ammonium nitrogen (NH4+, AN) or nitrate nitrogen (NO3-, NN) as the nitrogen source. NH4+ stress exerted a profound inhibitory effect on seedling growth and photosynthesis in wheat. However, these effects were less pronounced in Xumai25 than in Yangmai20. Dynamic photosynthetic analysis revealed that the suppression in photosynthesis was primarily attributed to stomatal limitation associated with a decrease in leaf water status and osmotic potential. Compared to Yangmai20, Xumai25 exhibited a significantly higher leaf K+ concentration and TaAKT1 upregulation, leading to a stronger stomatal opening and, consequently, a better photosynthetic performance under NH4+ stress. In conclusion, our study suggested stomatal limitation as the primary factor restricting photosynthesis under NH4+ stress. Furthermore, we demonstrated that improved regulation of osmotic substances contributed to higher stomatal conductance and enhanced photosynthetic performance in Xumai25.

LncRNA HOTAIR regulates cell invasion and migration in endometriosis through miR-519b-3p/PRRG4 pathway.

Endometriosis is a common benign disease in gynecology and has malignant biological behaviors, such as hyperplasia, invasion, metastasis, and recurrence. However, the pathogenesis of endometriosis remains unclear. The present study aimed to investigate whether LncRNA HOTAIR regulates cell invasion and migration in endometriosis by regulating the miR-519b-3p/PRRG4 pathway. The qRT-PCR results showed that the average relative expression of LncRNA HOTAIR was much higher in ectopic endometrial tissues than in eutopic endometrial tissues. Scratch and transwell assays showed that the cell migration and invasion ability of LncRNA HOTAIR overexpression group was significantly higher than those in the control group. Conversely, the LncRNA HOTAIR knockdown group showed the opposite results. Bioinformatics analysis suggested that the downstream target genes of LncRNA HOTAIR were miR-519b-3p and Prrg4. Knockdown of LncRNA HOTAIR can reduce the up-regulation of Prrg4 by miR-519b-3p and then inhibit the invasion and migration ability of endometrial stromal cells. In Conclusion, LncRNA HOTAIR can regulate the ability of invasion and migration of endometrial stromal cells, and its mechanism is proved by regulating the miR-519b-3p/PRRG4 pathway.

Seed soaking with melatonin promotes seed germination under chromium stress via enhancing reserve mobilization and antioxidant metabolism in wheat.

Chromium (Cr) pollution has serious harm to crop growth, while little is known on the role of melatonin (MT) on seed germination and physiology in Cr-stressed wheat. The effects of seed soaking with MT on growth, reserve mobilization, osmotic regulation and antioxidant capacity of wheat seeds during germination under hexavalent chromium (100 µM) stress were investigated. The results indicated that Cr toxicity decreased the seed germination rate by 16% and suppressed the growth of germinated seeds compared to unstressed seeds. MT in the concentration-dependent manner increased germination rate and promoted subsequent growth when seeds were exposed to Cr stress, but the effect could be counteracted at high concentration. Seed soaking with MT (100 µM) markedly decreased Cr accumulation in seeds, radicals and coleoptiles by 15%, 6% and 15%, respectively, and enhanced α-amylase activity and soluble sugar and free amino acids content in seeds to improve reserve mobilization under Cr stress, compared with Cr treatment. Furthermore, decreasing the level of osmotic regulators (soluble sugar and soluble protein) in radicles under MT combined with Cr treatment confirmed the reduction of osmotic stress caused by Cr stress. Importantly, MT pretreatment reduced H2O2 content by 19% and O2·- release rate by 45% in radicles under Cr toxicity compared with Cr-stressed wheat, in terms of promoting scavenging ability and decreasing production ability, which was to upregulate the activities and encoding genes expression levels of superoxide dismutase (SOD), catalase (CAT), ascorbic acid peroxidase (APX) and peroxidase (POD) and to downregulate plasma membrane-bound NADPH oxidase (NOX) encoding genes (TaRbohD, TaRbohF) expression, respectively. In all, these results provided evidence that seed soaking with MT could be a potentially method to protect wheat seeds from Cr toxicity, which effectively ameliorated germination under Cr stress by enhancing reserve mobilization and antioxidant metabolism in wheat.

Emodin Reverses the Epithelial-Mesenchymal Transition of Human Endometrial Stromal Cells by Inhibiting ILK/GSK-3ß Pathway.

PURPOSE: To explore the exact mechanism through which emodin down-regulates the migration and invasion abilities of endometrial stromal cells. Moreover, to explore the theoretical basis of emodin in the treatment of endometriosis. PATIENTS AND METHODS: Endometriosis endometrial stromal cells (EESs) were cultured from 15 women with endometriosis and control endometrial stromal cells (CESs) were cultured from 12 women without endometriosis. The levels of proteins were evaluated by Western blot. The migration and invasion abilities of cells were detected by transwell assays. RESULTS: The abilities of migration and invasion of EESs were much stronger than those of CESs. After treated with emodin, the migration and invasion abilities of EESs and CESs were significantly down-regulated, and the levels of integrin-linked kinase (ILK) and p-GSK-3ß were statistically down-regulated in EESs. Besides that, the expression of keratin was up-regulated while the expression of vimentin, ß-catenin and slug were all down-regulated by emodin in a dose- and time-dependent manner. Silencing of ILK gene in EESs also achieved the above effects, which were strengthened by emodin. Conversely, exogenous expression of ILK in CESs increased the expression of p-GSK-3ß, which were abrogated by emodin. Furthermore, SB216763 increased migration and invasion abilities of CESs by facilitating the epithelial-mesenchymal transition (EMT) through up-regulating levels of p-GSK-3ß, ß-catenin and slug, which were also abrogated by emodin. CONCLUSION: Emodin inhibits the migration and invasion abilities of human endometrial stromal cells by reversing the EMT via ILK/GSK-3ß pathway. So, emodin may be considered as a promising targeted therapy for endometriosis.

Indirubin suppresses ovarian cancer cell viabilities through the STAT3 signaling pathway.

BACKGROUND: Indirubin is the active component of Danggui Longhui Wan, a traditional Chinese medicine formulation. Due to its anti-inflammation and anti-tumor effects, indirubin has been widely used for the treatment of inflammation, cancer, and other chronic disease. Herein, we aimed to investigate the role and mechanism of indirubin in human ovarian cancer cell proliferation. MATERIALS AND METHODS: The cell viability was determined by Cell Counting Kit-8 and colony formation assays by treatment with different dosages of indirubin over 72 hours. Apoptosis was examined by flow cytometry with fluorescein isothiocyanate Annexin V Apoptosis Detection Kit. Western blot assay was finally applied to analyze the expression of cancer-related STAT3 pathway and its downstream proteins. RESULTS: Indirubin was found to significantly inhibit cell viability and induce apoptosis in 2 human ovarian cancer cell lines. Mechanistic studies revealed that indirubin treatment led to reduced levels of phosphorylated-STAT3, thus repressing the downstream pro-survival proteins and elevating pro-apoptosis ones. CONCLUSION: Our study provided the evidence for anti-survival activity of indirubin by inhibiting cell viability and inducing apoptosis in human ovarian cancer cells, which involved impaired STAT3 signaling pathway. Our findings further support indirubin as a potential drug candidate against human ovarian cancer.

ILK enhances migration and invasion abilities of human endometrial stromal cells by facilitating the epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) plays a significant part in the pathogenesis of endometriosis by facilitating the migration and invasion abilities of cells. Integrin-linked kinase (ILK) increases the cell migration and invasion abilities by inducing the EMT. Eutopic and control endometrial stromal cells (EuSCs and CSCs) were isolated and cultured. Cell migration and invasion abilities were detected by transwell assays. Levels of proteins were detected by Western blot. EuSCs showed higher levels of ILK, N-cadherin, vimentin and stronger migration and invasion abilities. After transfection of siRNA-ILK, E-cadherin and keratin levels were increased while N-cadherin and vimentin levels were decreased in EuSCs. Besides that, the migration and invasion abilities of EuSCs were significantly decreased after transfection of siRNA-ILK. On the contrary, levels of ILK, N-cadherin and vimentin were increased while levels of E-cadherin and keratin were decreased simultaneously after transfecting CSCs with pEGFP-C1-ILK. Simultaneously, the migration and invasion abilities of CSCs were increased after transfection of pEGFP-C1-ILK. Our study verified that high expression of ILK enhanced the migration and invasion abilities of ESCs by facilitating the EMT. Given that ILK played crucial roles in the pathogenesis of endometriosis, it may be considered as a promising targeted therapy for endometriosis.

Elevated periostin in serum and peritoneal washing fluids as potential biomarkers for endometriosis.

BACKGROUND: To identify the level of periostin in serum and peritoneal washing fluids (PWF) from women with and without endometriosis, as well as to explore the potential of periostin as a biomarker of endometriosis. METHODS: Samples were obtained from 184 women with and without endometriosis. Concentrations of periostin in PWF and blood were measured by enzyme-linked immunosorbent assay. RESULTS: Levels of periostin both in serum and PWF were notably elevated in women with endometriosis in both the proliferative and secretory phase. Combined with dysmenorrhea and infertility, two potential covariates, the serum periostin had a sensitivity of 75.00%, specificity of 65.00%, and area under the curve (AUC) of 0.774, whereas the PWF periostin had a sensitivity of 94.23%, specificity of 90.00%, and AUC of 0.967 for the diagnosis of endometriosis. CONCLUSION: Serum and PWF periostin concentrations may be new potential biomarkers for endometriosis, especially when combined with dysmenorrhea and infertility.

Emodin Inhibits Migration and Invasion of Human Endometrial Stromal Cells by Facilitating the Mesenchymal-Epithelial Transition Through Targeting ILK.

OBJECTIVE: To determine whether emodin facilitates the mesenchymal-epithelial transition (MET) of endometrial stromal cells (ESCs) as well as to explore the mechanism through which emodin favored the MET of ESCs. METHODS: Cell viability was tested by methyl thiazolyl tetrazolium assay. Cell migration and invasion abilities were detected by transwell assays. Levels of integrin-linked kinase (ILK) and epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot. RESULTS: Upregulated ILK and increased abilities of migration and invasion were confirmed in the eutopic and ectopic ESCs (EuSCs and EcSCs), especially in the EcSCs. After treated with emodin, the expression of ILK was statistically downregulated in EcSCs, resulting in the MET and decreased migration and invasion abilities of EcSCs. Additionally, silencing of the ILK gene in EcSCs also achieved the above-mentioned effects, which were strengthened by emodin. Furthermore, exogenous expression of ILK in control ESCs (CSCs) resulted in the EMT and increased abilities of migration and invasion of CSCs, which can be abrogated by emodin. Besides, exogenous expression of ILK also abrogated the effects of emodin on CSCs. CONCLUSION: Emodin inhibits the migration and invasion abilities of human ESCs by facilitating the MET through targeting ILK.

Periostin Facilitates the Epithelial-Mesenchymal Transition of Endometrial Epithelial Cells through ILK-Akt Signaling Pathway.

Although periostin was confirmed to facilitate the pathogenesis of endometriosis by enhancing the migration, invasion, and adhesion of human endometrial stromal cells (ESCs), its effect on the endometrial epithelial cells (EECs) is still unknown. The current study aimed to determine whether periostin enhanced the epithelial-mesenchymal transition (EMT) of EECs. EECs were isolated from 12 women with endometriosis. The migration and invasion abilities of EECs were evaluated by transwell assays. Expressions of proteins were detected by western blot. After treatment with periostin, the migration and invasion abilities of EECs were enhanced. Additionally, E-cadherin and keratin were downregulated while N-cadherin and vimentin were upregulated in EECs. Simultaneously, levels of ILK, p-Akt, slug, and Zeb1 were all upregulated in EECs. After silencing the expression of ILK in EECs, levels of p-Akt, slug, Zeb1, N-cadherin, and vimentin were downregulated while E-cadherin and keratin were upregulated. Although periostin weakened the above effects in EECs after silencing the expression of ILK, it failed to induce the EMT of EECs. Thus, periostin enhanced invasion and migration abilities of EECs and facilitated the EMT of EECs through ILK-Akt signaling pathway. Playing a pivotal role in the pathogenesis of endometriosis, periostin may be a new clinical therapy target for endometriosis.

Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis.

PURPOSE: To investigate whether postoperative GnRH agonist (GnRH-a) treatment can prevent endometriosis recurrence. METHODS: This meta-analysis searched PubMed, Embase and Cochrane Library for relevant studies published online before June 2015. Seven randomized controlled trials including 328 patients with postoperative GnRH-a treatment and 394 patients in control group were included in the meta-analysis. In the meta-analysis, the recurrence rate of GnRH-a group compared with control group was evaluated with odds ratio (OR) and its 95 % confidence interval (CI). Heterogeneity, small study effect and publication bias were, respectively, assessed using Higgins I (2), sensitivity analysis and funnel plot. RESULTS: Postoperative GnRH-a treatment for endometriosis (pooled OR = 0.71; 95 % CI 0.52-0.96) was superior to expectant or placebo treatment in prevention of the recurrence. The recurrence rate decreased significantly in patients who received 6 months GnRH-a treatment (pooled OR = 0.59, 95 % CI 0.38-0.90), whereas no significant difference of recurrence rate existed between patients with 3 months post-surgical GnRH-a therapy and the control group (pooled OR = 0.87, 95 % CI 0.56-1.34). No significant heterogeneity and small study effect were found in the meta-analysis. However, publication bias did existed in the present meta-analysis. CONCLUSIONS: Longer-term (6 months) postoperative administration of GnRH-a can decrease the recurrence risk of endometriosis, whereas 3 months duration of GnRH-a therapy makes no significant difference in preventing the recurrence of endometriosis. Therefore, instead of a 3 month therapy, the duration of the postoperative administration should be longer enough (6 months) to prevent the recurrence of endometriosis.

Risk of endometrial polyps in women with endometriosis: a meta-analysis.

BACKGROUND: Endometrial polyps (EP) and endometriosis are both estrogen-dependent overgrowths of the endometrium. Several studies have shown a higher frequency of EP in endometriosis patients when compared with women without endometriosis. Therefore, we performed a meta-analysis to investigate the risk of EP in women with endometriosis. METHODS: This meta-analysis searched for articles published between 1964 and 2014 in PubMed, Embase, and Cochrane Library, as well as in Chinese databases, including CNKI, VIP and Wanfang, regarding the association between endometriosis and EP. Nine cohort studies and one case-control study including 2896 women were included in this meta-analysis. The EP risk was evaluated using relative risk (RR) with a 95% confidence interval (CI). Heterogeneity, small study effect and publication bias were assessed using Higgins I(2), sensitivity analysis and funnel plots, respectively. RESULTS: The risk of EP increased in women with endometriosis compared with those without endometriosis (the pooled RR, 2.81; 95% CI, 2.48-3.18). No significant heterogeneity, small study effect or publication bias was found. The risk of EP slightly increased in women with endometriosis at stages 2-4 compared with those at stage 1 (Pooled effect size: stage 2 versus stage 1, RR, 1.22, 95% CI, 1.04 - 1.42; stage 3 versus stage 1, RR, 1.23, 95% CI, 1.06-1.42; stage 4 versus stage 1, RR, 1.29, 95% CI, 1.11-1.51; stages 2-4 versus stage 1, RR, 1.24, 95% CI, 1.10-1.40); however, no significantly different risk of EP in women with endometriosis existed between the other stages. CONCLUSION: The results suggest that it is important to identify whether patients with endometriosis also have EP and then remove any coexisting EP via hysteroscopy, especially for infertile patients. This process will be clinically helpful to treat endometriosis-related infertility in patients with endometriosis, especially for those with endometriosis that is more serious than stage 1.