MDH2 Stimulated by Estrogen-GPR30 Pathway Down-Regulated PTEN Expression Promoting the Proliferation and Invasion of Cells in Endometrial Cancer

PURPOSE: The relationship between endometrial carcinoma and cellular metabolism is unknown. In endometrial cancer, mutation rate of PTEN has been reported very high. Malate dehydrogenase 2 (MDH2) is one of the isoforms of malate dehydrogenase, which is involved in citric acid cycle in mitochondria. Our study aimed to investigate the role MDH2 played in PTEN-regulated endometrial carcinoma. METHODS: To reveal the expression of MDH2 and the co-localization of PTEN and MDH2, immunohistochemistry and immunofluorescent staining were used. Western blot, Real-time PCR, RNA interference and overexpression plasmid DNA transfection were performed to investigate the relationship between PTEN and MDH2 as well as the impact of E2 on the expression of PTEN and MDH2, while CCK8, transwell and flow cytometric analysis were carried out to evaluate the proliferation, migration and invasion and apoptosis of endometrial carcinoma cell lines. RESULTS: Our results demonstrated that as a metabolism related enzyme, MDH2 was overexpressed in endometrial carcinoma tissues and related to the grade of the cancer (P = .038). Western blot, Real-time PCR and immunofluorescent staining revealed MDH2 inhibited the expression of PTEN and was co-localized with PTEN in the cytoplasm of endometrial carcinoma. Proliferation, transwell and apoptosis assay suggested that MDH2 enhanced the proliferation, migration and invasion but inhibited the apoptosis of endometrial cancer cell line through suppressing PTEN. Furthermore, E2 inhibited the expression level of PTEN but enhanced MDH2 via GPR30. CONCLUSIONS: Our study demonstrated that MDH2, stimulated by estrogen, was involved in the development of PTEN-regulated endometrial carcinoma through GPR30-related pathway

Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

PURPOSE: The monocyte-to-lymphocyte ratio (MLR) has been shown to be associated with the prognosis of various solid tumors. This study sought to evaluate the important value of the MLR in ovarian cancer patients. METHODS: A total of 133 ovarian cancer patients and 43 normal controls were retrospectively reviewed. The patients' demographics were analyzed along with clinical and pathologic data. The counts of peripheral neutrophils, lymphocytes, monocytes, and platelets were collected and used to calculate the MLR, neutrophil-to-lymphocyte ratio (NLR). and platelet-to-lymphocyte ratio (PLR). The optimal cutoff value of the MLR was determined by using receiver operating characteristic curve analysis. We compared the MLR, NLR, and PLR between ovarian cancer and normal control patients and among patients with different stages and different grades, as well as between patients with lymph node metastasis and non–lymph node metastasis. We then investigated the value of the MLR in predicting the stage, grade, and lymph node positivity by using logistic regression. The impact of the MLR on overall survival (OS) was calculated by Kaplan-Meier method and compared by log-rank test. RESULTS: Statistically significant differences in the MLR were observed between ovarian cancer patients and normal controls. However, no difference was found for the NLR and PLR. Highly significant differences in the MLR were found among patients with different stages (stage I-II and stage III-IV), grades (G1 and >G1), and lymph node metastasis status. The MLR was a significant and independent risk factor for lymph node metastasis, as determined by logistic regression. The optimal cutoff value of the MLR was 0.23. We also classified the data according to tumor markers (CA125, CA199, HE4, AFP, and CEA) and conventional coagulation parameters (International Normalized Ratio [INR] and fibrinogen). Highly significant differences in CA125, CA199, HE4, INR, fibrinogen levels, and lactate dehydrogenase were found between the low-MLR group (MLR ≤ 0.23) and the high-MLR group (MLR > 0.23). Correspondingly, dramatic differences were observed between the two groups in OS. CONCLUSION: Our results show that the peripheral blood MLR before surgery could be a significant predictor of advanced stages, advanced pathologic grades, and positive lymphatic metastasis in ovarian cancer patients

Rational Construction of LaFeO₃ Perovskite Nanoparticle-Modified TiO₂ Nanotube Arrays for Visible-Light Driven Photocatalytic Activity

LaFeO3 nanoparticle-modified TiO2 nanotube arrays were fabricated through facile hydrothermal growth. The absorption edge of LaFeO3 nanoparticle-modified TiO2 nanotube arrays displaying a red shift to ~540 nm was indicated by the results of diffuse reflectance spectroscopy (DRS) when compared to TiO2 nanotube arrays, which means that the sample of LaFeO3 nanoparticle-modified TiO2 nanotube arrays had enhanced visible light response. Photoluminescence (PL) spectra showed that the LaFeO3 nanoparticle-modified TiO2 nanotube arrays efficiently separated the photoinduced electron⁻hole pairs and effectively prolonged the endurance of photogenerated carriers. The results of methylene blue (MB) degeneration under simulated visible light illumination showed that the photocatalytic activity of LaFeO3 nanoparticle-modified TiO2 nanotube arrays is obviously increased. LaFeO3 nanoparticle-modified TiO2 nanotube arrays with 12 h hydrothermal reaction time showed the highest degradation rate with a 2-fold enhancement compared with that of pristine TiO2 nanotube arrays

Stem cells implanted with nanofibrous mats for injured endometrial regeneration and immune-microenvironment remodeling

Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman’s syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose‐derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-β/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling

Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair

Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair

Janus Nanofibrous Patch with In Situ Grown Superlubricated Skin for Soft Tissue Repair with Inhibited Postoperative Adhesion

The patch with a superlubricated surface shows great potential for the prevention of postoperative adhesion during soft tissue repair. However, the existing patches suffer from the destruction of topography during superlubrication coating and lack of pro-healing capability. Herein, we demonstrate a facile and versatile strategy to develop a Janus nanofibrous patch (J-NFP) with antiadhesion and reactive oxygen species (ROS) scavenging functions. Specifically, sequential electrospinning is performed with initiators and CeO2 nanoparticles (CeNPs) embedded on the different sides, followed by subsurface-initiated atom transfer radical polymerization for grafting zwitterionic polymer brushes, introducing superlubricated skin on the surface of single nanofibers. The poly(sulfobetaine methacrylate) brush-grafted patch retains fibrous topography and shows a coefficient of friction of around 0.12, which is reduced by 77% compared with the pristine fibrous patch. Additionally, a significant reduction in protein, platelet, bacteria, and cell adhesion is observed. More importantly, the CeNPs-embedded patch enables ROS scavenging as well as inhibits pro-inflammatory cytokine secretion and promotes anti-inflammatory cytokine levels. Furthermore, the J-NFP can inhibit tissue adhesion and promote repair of both rat skin wounds and intrauterine injuries. The present strategy for developing the Janus patch exhibits enormous prospects for facilitating soft tissue repair