Restoring BARX2 in OSCC reverses partial EMT and suppresses metastasis through miR-186-5p/miR-378a-3p-dependent SERPINE2 inhibition.

Tumor cells undergoing partial epithelial-mesenchymal transition (pEMT) are pivotal in local invasion and lymphatic metastasis of oral squamous cell carcinoma (OSCC), yet the mechanisms behind pEMT reversal remain poorly understood. In this study, the loss of BARX2 expression was revealed during the process of oral epithelial carcinogenesis and identified to activate the pEMT program, facilitate metastasis, and be associated with poor prognosis. Restoring BARX2 expression in OSCC cell lines effectively reversed tumor pEMT, evident in E/N-Cadherin switching, reduced cell invasion, proliferation, and stemness, and inhibited murine lung metastasis. BARX2 re-expression negatively correlated with several pEMT markers, notably SERPINE2, which was enriched in the invasive OSCC front, enhancing stemness and promoting metastasis, particularly in cervical lymph nodes. Furthermore, rescuing SERPINE2 impaired the inhibitory effect of BARX2 on the pEMT programs and reconstructed ECM through re-expression of MMP1. Mechanistically, we identified that BARX2 inhibited SERPINE2 through activating miR-186-5p and miR-378a-3p. These miRNAs, upregulated by BARX2, post-transcriptionally degraded SERPINE2 mRNA via targeting specific sequences. Blocking miR-186-5p and miR-378a-3p effectively abolished the negative regulatory effect of BARX2 on SERPINE2. Overall, our findings highlight BARX2 as a partial EMT-reverser in OSCC, providing fresh therapeutic prospects for restoring BARX2 signaling to inhibit invasion and metastasis.

N6-methyladenosine (m6A) Modification in Preeclampsia.

Recently, epitranscriptional modification of N6-methyladenosine (m6A) has received growing attention in the research on the pathogenesis of preeclampsia. Advances in m6A sequencing have revealed the molecular mechanism and importance of m6A modification. In addition, epitranscriptional modification of m6A is closely related to the metabolic processes of placental tissues and cells in preeclampsia. This article reviews the composition, mode of action, and bioinformatics analysis of m6A modification-related proteins, and their biological function in the progression of preeclampsia. The relationship between m6A modification and preeclampsia risk factors, such as diabetes, cardiovascular disease, obesity, and psychological stress, is summarized to provide new ideas for studying PE-targeting molecules.

n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not: NHANES 2007-2016.

Background and aims: Gout, the most prevalent inflammatory arthritis, has undesirable effects on the quality of life. Omega-3 polyunsaturated fatty acids (n-3 PUFA) has a strong link with anti-inflammatory impacts. However, whether the harmful effects of seafood in relation to gout may vary owing to different levels of n-3 PUFA in seafood is still unclear. It was the goal of this study to examine the relationship between n-3 PUFA poor/rich seafood consumption and gout. Methods: Between 2007 and 2016, five NHANES cycles were performed, with 12,505 subjects having complete data for gout and two 24-h dietary intake interviews. The 24-h dietary recalls were utilized to evaluate dietary habits. Gout was defined based on questionnaires. Weighted logistic regression models were conducted to investigate the association between n-3 PUFA poor/rich seafood consumption and gout. Moreover, subgroup analysis was utilized to estimate the stability of results. Covariates including age, gender, race/ethnicity, income, education, body mass index, chronic kidney disease, diabetes mellitus, hypertension, smoking status, and drinking status were stratified in different models. Results: In the fully adjusted model, each unit of increase of n-3 PUFA poor seafood intake was associated with an 8.7% increased risk of gout (OR = 1.087, 95% CI: 1.039, 1.138, P < 0.001), whereas, no correlation was found between n-3 PUFA rich seafood consumption and gout. It also provided a proof-of-concept regarding the potential for n-3 PUFA rich seafood to counteract harmful effects of purines in relation to gout. A dose-response analysis showed that there was a non-linear relationship between n-3 PUFA rich seafood intake and the risk of gout in the female group. Conclusion: Findings suggest that n-3 PUFA poor seafood consumption is associated with higher risk of gout, whereas n-3 PUFA rich seafood is not.

NRF2 controls iron homeostasis and ferroptosis through HERC2 and VAMP8.

Enhancing the intracellular labile iron pool (LIP) represents a powerful, yet untapped strategy for driving ferroptotic death of cancer cells. Here, we show that NRF2 maintains iron homeostasis by controlling HERC2 (E3 ubiquitin ligase for NCOA4 and FBXL5) and VAMP8 (mediates autophagosome-lysosome fusion). NFE2L2/NRF2 knockout cells have low HERC2 expression, leading to a simultaneous increase in ferritin and NCOA4 and recruitment of apoferritin into the autophagosome. NFE2L2/NRF2 knockout cells also have low VAMP8 expression, which leads to ferritinophagy blockage. Therefore, deletion of NFE2L2/NRF2 results in apoferritin accumulation in the autophagosome, an elevated LIP, and enhanced sensitivity to ferroptosis. Concordantly, NRF2 levels correlate with HERC2 and VAMP8 in human ovarian cancer tissues, as well as ferroptosis resistance in a panel of ovarian cancer cell lines. Last, the feasibility of inhibiting NRF2 to increase the LIP and kill cancer cells via ferroptosis was demonstrated in preclinical models, signifying the impact of NRF2 inhibition in cancer treatment.

Relationship between diet-related inflammation and bone health under different levels of body mass index.

BACKGROUND: Osteoporosis is a major public health problem. Dietary inflammatory preference and body mass index (BMI) are emerging factors that tends to affect bone health. There is limited evidence regarding the joint influence of BMI and dietary status on the bone health. This study aimed to investigate the relationship between dietary inflammatory index (DII) and bone health among adults under different levels of BMI utilizing the National Health and Nutrition Examination Survey (NHANES). METHODS: Data were collected from 2005-2010, 2013-2014 to 2017-2018 in NHANES. In total, 10,521 participants who aged ≥ 20 years and had complete data for dietary intake interview, bone mineral density (BMD) and bone mineral content (BMC) were included. DII was performed to evaluate the dietary inflammatory potential based on dietary intake interview. We evaluated bone health by femoral neck BMD and BMC measured by dual energy X-ray absorptiometry. Weighted multivariable linear regression and BMI-stratified subgroup analysis were performed. RESULTS: The average DII score for 10,521 participants was 1.24 ± 0.04, mean femoral neck BMD was 0.82 ± 0.00 g/cm2 and mean BMC was 4.37 ± 0.01 g. In the fully adjusted model, there was a negative correlation between DII with BMD (ß = - 0.016, P < 0.001) and BMC (ß = - 0.011, P < 0.001) in the most anti-inflammatory diet. Using BMI-stratified subgroup analysis, this correlation became more evident in both the overweight (BMD: ß = - 0.024, P < 0.001; BMC: ß = - 0.058, P = 0.042) and obese groups (BMD: ß = - 0.015, P = 0.049; BMC: ß = - 0.009, P = 0.042), while this correlation was opposite in DII tertile 2 (middle DII score) in the underweight group (BMD: ß = 0.047, P = 0.038; BMC: ß = 0.274, P = 0.010). CONCLUSION: Relationship between higher consumption of pro-inflammatory and increased risk of lower BMD and BMC was only existed in overweight and obese participants.

The Long-Term Clinical Outcomes of Selectively Extracranial Radiofrequency Thermocoagulation for Trigeminal Neuralgia Guided by Three-Dimensionally Printed Personalized Template.

ABSTRACT: The purpose of this study was to assess the long-term pain relief and the complications of selectively extracranial radio-frequency thermocoagulation (RFT) for trigeminal neuralgia (TN) guided by a three-dimensionally (3D) printed personalized template. The authors conducted a retrospective study of 117 TN patients, who were treated with selectively extracranial RFT under 3D printed personalized template guidance between September 2014 and January 2019. The mean follow-up duration was 42.8 months (range: 28-83 months). Favorable pain relief of patients was 100% at discharge, 86.3% at 1 year, 80.3% at 2 years, 78.6% at 3 years, and 75.4% at 5 years. No complication associated with a puncture or intracranial complication was observed during or after RFT. Postoperative complications included facial numbness in 91 patients (77.8%), masticatory muscle weakness in 15 patients (12.8%), ear paresthesia in 3 patients (2.6%), limited mouth opening in 2 patients (1.7%), and taste hypesthesia in 2 patients (1.7%). Most of these symptoms were improved during the visits and their life was not severely affected. Selectively extracranial RFT guided by a 3D printed personalized template is a clinically practical, effective, and safe approach for TN patients.

The Regrowth of Mandibular Coronoid Process After Coronoidectomy: A Retrospective Analysis of 57 Cases.

PURPOSE: Coronoidectomy is carried out frequently as a part of the cranial-maxillofacial surgery procedure. There are few articles on the fate of coronoid process after coronoidectomy, except that several case reports mentioned that coronoid process had regenerated. This study aimed to radiographically access the anatomic outcomes of coronoid process and investigate which factors were associated with the outcomes after coronoidectomy. MATERIALS AND METHODS: A retrospective cohort study included patients undergoing coronoidectomy over a 7-year period. The primary outcome variable was the new coronoid process occurrence (yes/no). Secondary outcome variable was the type of the new coronoid process by evaluating its size, shape and position. Radiograph at 1-year postoperative visit was used to determine the outcomes. The predictor variables included age, sex, surgical purpose, surgical side, surgical approach and the maximal interincisal opening. Appropriate statistics were analyzed by SPSS version 22. χ2 test and binary logistic regression were used to assess the association between predictor factors and anatomic outcomes (P <.05). RESULTS: The study sample included 57 patients. In total, 96 coronoidectomies were performed. Seventy-four coronoid processes (77.1%) showed complete (n = 44, 45.8%), nonunion (n = 19, 19.8%) or partial (n = 11, 11.5%) regrowth, whereas no evidence of regeneration in 22 sites was observed radiographically at 1-year postoperative visit. Binary logistic regression showed that a young age (odds ratio 0.704; 95% confidence interval 0.562-0.882; P = .002) was significantly associated with regeneration of coronoid process. CONCLUSIONS: Coronoid process can mostly regenerate after coronoidectomy. A young age may contribute to regrowth of coronoid process.

Maternal and neonatal outcomes of repeated antepartum bleeding in 493 placenta previa cases: a retrospective study.

OBJECTIVE: To explore the effect of antepartum bleeding caused by PP on pregnancy outcomes. STUDY DESIGN: We retrospectively analyzed 493 pregnant women complicated with PP. Patients were divided into antepartum repeated bleeding and non-bleeding groups. Maternal characteristics and pregnancy outcomes were compared. RESULTS: The risk of antepartum hemorrhage was 2.038 times higher when gravidity was 5 (95% CI 1.104-3.760, p = .023). Pregnant women with a history of more than three intrauterine procedures had a 1.968 times higher risk of antepartum hemorrhage (95% CI 1.135-3,412, p = .016) compared to pregnant women without any intrauterine procedures. The risk of antepartum bleeding was found to be decreasing with the pregnancy advancing; When the placenta edge was noted to be over cervical os, the risk of antepartum bleeding was 4.385-fold than the low-lying plcaenta cases (95%CI2.454-8.372, p = .000). In the respect of maternal outcomes, the repeated bleeding group, the risk of emergency surgery was 7.213 times higher than elective surgery (95% CI 4.402-11.817, p = .000). As for the neonatal outcomes, the risk of asphyxia was 2.970 times and the risk of neonatal intensive care unit (NICU) admission was 2.542-fold higher in repeated bleeding group compared to non-bleeding group, respectively. CONCLUSIONS: Obstetricians should be aware of the increased risk of antepartum bleeding especially for ≤34 weeks and placenta edge over cervical os PP patients, they have a higher risk of antepartum bleeding. These women have higher possibility of emergency C-section and need preterm newborn resuscitation.

A Benzenesulfonamide-Based Mitochondrial Uncoupler Induces Endoplasmic Reticulum Stress and Immunogenic Cell Death in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies and requires new therapeutic strategies to improve clinical outcomes. EOC metastasizes in the abdominal cavity through dissemination in the peritoneal fluid and ascites, efficiently adapt to the nutrient-deprived microenvironment, and resist current chemotherapeutic agents. Accumulating evidence suggests that mitochondrial oxidative phosphorylation is critical for the adaptation of EOC cells to this otherwise hostile microenvironment. Although chemical mitochondrial uncouplers can impair mitochondrial functions and thereby target multiple, essential pathways for cancer cell proliferation, traditional mitochondria uncouplers often cause toxicity that precludes their clinical application. In this study, we demonstrated that a mitochondrial uncoupler, specifically 2,5-dichloro-N-(4-nitronaphthalen-1-yl)benzenesulfonamide, hereinafter named Y3, was an antineoplastic agent in ovarian cancer models. Y3 treatment activated AMP-activated protein kinase and resulted in the activation of endoplasmic reticulum stress sensors as well as growth inhibition and apoptosis in ovarian cancer cells in vitro Y3 was well tolerated in vivo and effectively suppressed tumor progression in three mouse models of EOC, and Y3 also induced immunogenic cell death of cancer cells that involved the release of damage-associated molecular patterns and the activation of antitumor adaptive immune responses. These findings suggest that mitochondrial uncouplers hold promise in developing new anticancer therapies that delay tumor progression and protect patients with ovarian cancer against relapse.

Aspirin reduces sFlt-1-mediated apoptosis of trophoblast cells in preeclampsia.

Preeclampsia (PE) is a hypertensive disorder that occurs during pregnancy. Low-dose aspirin is used to reduce the occurrence of early-onset PE; however, the mechanisms are not clear. The aim of this study was to reveal the underlying mechanism of aspirin in reducing sFlt-1-mediated apoptosis of trophoblast cells in PE. Serum sFlt-1 and sEng profiles and placental oxidative stress levels were significantly decreased in PE patients treated with aspirin compared with untreated patients without it, whereas serum PLGF and placental SOD profiles were increased in PE patients with aspirin. Aspirin attenuated the role of sFlt-1 in oxidative stress and endothelial dysfunction and reduced apoptosis of trophoblasts by inactivating the NF-κB signalling pathway in HTR-8/SVneo trophoblast cells. Blood pressure, urine protein, swelling of the villous vessels and mitochondrial parameters were noted to be much better after aspirin administrated to sFlt-1 treated pregnant mice. In conclusion, aspirin reverses the endothelial dysfunction and oxidative stress caused by sFlt-1 and thus reduces apoptosis of preeclamptic trophoblasts by inactivating NF-κB signalling pathway.

Identification of miPEP133 as a novel tumor-suppressor microprotein encoded by miR-34a pri-miRNA.

BACKGROUND: Very few proteins encoded by the presumed non-coding RNA transcripts have been identified. Their cellular functions remain largely unknown. This study identifies the tumor-suppressor function of a novel microprotein encoded by the precursor of miR-34a. It consists of 133 amino acid residues, thereby named as miPEP133 (pri-microRNA encoded peptide 133). METHODS: We overexpressed miPEP133 in nasopharyngeal carcinoma (NPC), ovarian cancer and cervical cancer cell lines to determine its effects on cell growth, apoptosis, migration, or invasion. Its impact on tumor growth was evaluated in a xenograft NPC model. Its prognostic value was analyzed using NPC clinical samples. We also conducted western blot, immunoprecipitation, mass spectrometry, confocal microscopy and flow cytometry to determine the underlying mechanisms of miPEP133 function and regulation. RESULTS: miPEP133 was expressed in normal human colon, stomach, ovary, uterus and pharynx. It was downregulated in cancer cell lines and tumors. miPEP133 overexpression induced apoptosis in cancer cells and inhibited their migration and invasion. miPEP133 inhibited tumor growth in vivo. Low miPEP133 expression was an unfavorable prognostic marker associated with advanced metastatic NPC. Wild-type p53 but not mutant p53 induced miPEP133 expression. miPEP133 enhanced p53 transcriptional activation and miR-34a expression. miPEP133 localized in the mitochondria to interact with mitochondrial heat shock protein 70kD (HSPA9) and prevent HSPA9 from interacting with its binding partners, leading to the decrease of mitochondrial membrane potential and mitochondrial mass. CONCLUSION: miPEP133 is a tumor suppressor localized in the mitochondria. It is a potential prognostic marker and therapeutic target for multiple types of cancers.

Insights into carbohydrate metabolism from an insulin-like peptide in Macrobrachium rosenbergii.

This study identified an insulin-like peptide (ILP) in Macrobrachium rosenbergii termed Mr-ILP and further investigated its function through glucose injection and RNAi. With the analysis of five other glucose metabolism related genes, this study shed light on the molecular mechanism of carbohydrate metabolism in crustaceans. Mr-ILP shared the typical skeleton with six conserved cysteine and mainly expressed in neuroendocrine system. In M. rosenbergii, the elevated hemolymph glucose concentration after glucose injection returned to basal levels in short time, implying an efficient regulatory system in carbohydrate metabolism. Hyperglycemic related genes answered the elevated hemolymph glucose concentration quickly with significant decreased expression level, while Mr-ILP showed delayed response. Instead, glycolysis increased after glucose injection, which indicated glycolysis might play an important role in lowering the abnormally high glucose level. In vivo silencing of Mr-ILP, by injecting the prawns with double-stranded RNA (dsRNA) for 21 days reduced its expression by approximately 75%. Accordingly, glycogen synthase decreased and the trehalose and glycogen level in the hepatopancreas were significantly reduced, indicating the function of Mr-ILP in oligosaccharide and polysaccharide accumulation. When Mr-ILP was silenced, the expression of hyperglycemic related genes were enhanced, but the hemolymph glucose level was not elevated significantly, which might attribute to the increased glycolysis to keep a balanced glucose level in hemolymph.

Paeoniflorin inhibits activation of the IRAK1-NF-κB signaling pathway in peritoneal macrophages from lupus-prone MRL/lpr mice.

Systemic lupus erythematosus (SLE) is a chronic and multisystemic autoimmune disease. Interleukin-1 receptor-associated kinase 1 (IRAK1) is associated with the susceptibility of SLE in humans and paeoniflorin has recently been reported to exhibit immunosuppressive properties. The aim of this study was to determine the effect of paeoniflorin on lipopolysaccharide (LPS)-triggered macrophage activation and and its role in LPS-induced IRAK1-nuclear factor κB (NF-κB) signaling pathways. Peritoneal macrophages from lupus-prone MRL/lpr mice and ICR mice were isolated, prepared and cultured. Cells were treated with LPS alone or LPS with paeoniflorin, and macrophage proliferation was analyzed using the CCK8 assay. The expression of IRAK1 in cells was analyzed by immunofluorescence staining. The level of gene expression of IRAK1, NF-κB, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by RT-PCR, and TNF-α, IL-6 levels in the cell supernatant were determined by ELISA. The protein expression of IRAK1 and downstream molecules tumor necrosis factor receptor-associated factor 6 (TRAF6), inhibitor of nuclear factor kappa-B kinase (IKK), NF-kappa-B inhibitor alpha (IKBα), and NF-κB was detected by Western-blot analysis. Paeoniflorin was found to decrease the phosphorylation of IRAK1 and its downstream proteins induced by LPS and inhibit the expression of TNF-α and IL-6. Taken together, the data obtained indicate that paeoniflorin inhibits LPS-induced cell activation by inhibiting the IRAK1-NF-κB pathway in MRL/lpr mouse macrophages. Therefore, paeoniflorin may be a potential therapy for SLE.

Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy loss.

BACKGROUND: Aberrant DNA methylation is considered to be a potential cause of recurrent pregnancy loss (RPL), while potential mechanism has not yet been elucidated. METHODS: In order to uncover the contribution of the perturbation of DNA methylation in RPL, we performed genome-wide DNA methylation analysis combined with genome-wide gene expression in decidua tissue. FINDINGS: Totally, 539 differentially methylated regions (DMRs) were identified and significantly correlated with gene expressions. We observed that hypo-methylated DMR near CREB5 recruited transcription factors binding, such as P53 and SP1, and in turn upregulated CREB5. Compromised cell migration and apoptosis were observed in human CREB5 overexpression trophoblast cell lines, indicating dysfunctional trophoblast cells might contribute to RPL after hypo-methylation of CREB5. In addition, overexpression of CREB5 altered cell cycle. INTERPRETATION: Our data highlights a role of CREB5 involved in the pathogenesis of RPL, and CREB5 maybe a potential diagnostic biomarker for RPL.

MiR-616-3p modulates cell proliferation and migration through targeting tissue factor pathway inhibitor 2 in preeclampsia.

OBJECTIVES: Despite improvements in diagnosis and treatment, preeclampsia (PE) continues to pose a significant risk of maternal and foetal morbidity and mortality if not addressed promptly. An increasing number of studies have suggested that tissue factor pathway inhibitor 2 (TFPI2) acts as a suppressor gene, possibly inhibiting multiple serine proteases affecting cell proliferation and migration. It plays an essential role in the occurrence and development of PE, but the pathogenesis remains unclear. MATERIALS AND METHODS: In our research, we performed western blotting, immunohistochemistry and qPCR assays to investigate TFPI2 and miR-616-3p expression in preeclamptic placental tissues. Cell assays were performed in HTR-8/SVneo and JEG3 cell lines. Cell proliferation and migration events were investigated by MTT, EdU and transwell assays. In conjunction with bioinformatics analysis, luciferase reporter assays were performed to elucidate the mechanism by which miR-616-3p binds to TFPI2 mRNA. RESULTS: We established that TFPI2 protein levels were significantly upregulated in PE placental tissues. In addition, we found that miR-616-3p binds specifically to the 3'-UTR region of TFPI2 mRNA. Furthermore, miR-616-3p knockdown or TFPI2 overexpression substantially impaired cell growth and migration, whereas miR-616-3p upregulation or TFPI2 knockdown stimulated cell proliferation and migration. This miR-616-3p/TFPI2 axis was also found to affect the epithelial-mesenchymal transition process in PE. CONCLUSIONS: Our results demonstrated that TFPI2 plays a vital role in the progression of PE and might provide a prospective therapeutic strategy to mitigate the severity of the disorder.

High expression of Sonic hedgehog in allergic airway epithelia contributes to goblet cell metaplasia.

Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs; however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly upregulated in the airway epithelia of children with asthma or mouse models with allergic airway disease. Specifically, airway-specific SMO loss of function significantly suppresses allergen-induced goblet cell phenotypes, whereas an airway-specific SMO gain of function markedly enhances the goblet cell phenotypes in mouse models with allergic airway disease. Notably, intratracheal administration with SHH-neutralizing antibody or cyclopamine robustly attenuates goblet cell phenotypes in mouse models with allergic airway disease. Finally, we identify that Muc5AC gene encoding MUC5AC mucin serves as a direct target of GLI transcriptional factors in response to SHH, whereas the SAM-pointed domain-containing ETS transcription factor and Forkhead box A2, critical transcriptional factors for goblet cell phenotypes, both function as the effectors of GLIs in response to SHH stimulation. Together, the upregulation of SHH expression in allergic bronchial epithelia contributes to goblet cell metaplasia; thus, blockage of SHH signaling is a rational approach in a therapeutic intervention of epithelial remodeling in chronic airway diseases.

The Lnc RNA SPRY4-IT1 Modulates Trophoblast Cell Invasion and Migration by Affecting the Epithelial-Mesenchymal Transition.

Preeclampsia is a common, pregnancy-specific disease and a major contributor to maternal and foetal morbidity and mortality. Some placental abnormalities, including deficient implantation, abnormal trophoblast cell function, and improper placental vascular development, are believed to lead to preeclampsia. The long noncoding RNA SPRY4-IT1 is more highly expressed in preeclamptic human placentas than in normal placentas. We assessed the role of epithelial-mesenchymal transition (EMT)-associated invasion and migration in HTR-8/SVneo trophoblast cells. Overexpression of SPRY4-IT1 suppressed trophoblast cell migration and invasion, whereas reduced expression of SPRY4-IT1 prevented the EMT process. Mechanistically, an RNA immunoprecipitation experiment showed that SPRY4-IT1 bound directly to HuR and mediated the ß-catenin expression associated with EMT in HTR-8/SVneo cells. Moreover, the expression levels of genes in the WNT family, such as WNT3 and WNT5B, were changed after transfection of HTR-8/SVneo with SPRY4-IT1. Together, our results highlight the roles of SPRY4-IT1 in causing trophoblast cell dysfunction by acting through the Wnt/ß-catenin pathway, and consequently in impairing spiral artery remodelling. These results suggest a new potential therapeutic target for intervention against preeclampsia.

Decorin-Mediated Inhibition of Human Trophoblast Cells Proliferation, Migration, and Invasion and Promotion of Apoptosis In Vitro.

Preeclampsia (PE) is a unique complication of pregnancy, the pathogenesis of which has been generally accepted to be associated with the dysfunctions of extravillous trophoblast (EVT) including proliferation, apoptosis, and migration and invasion. Decorin (DCN) has been proved to be a decidua-derived TGF-binding proteoglycan, which negatively regulates proliferation, migration, and invasiveness of human extravillous trophoblast cells. In this study, we identified a higher expression level of decorin in severe PE placentas by both real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). And an inhibitory effect of decorin on proliferation, migration, and invasion and an enhanced effect on apoptosis in trophoblast cells HTR-8/SVneo and JEG-3 were validated in vitro. Also the modulations of decorin on trophoblast cells' metastasis and invasion functions were detected through regulating the matrix metalloproteinases (MMP2 and MMP9). Thus, we suggested that the contribution of decorin to the modulation of trophoblast cells might have implications for the pathogenesis of preeclampsia.