Alternating 3rd- to 2nd-Order Charge Reaction Kinetics on Bismuth Vanadate Photoanodes with Ultrathin Bismuth Metal-Organic-Frameworks.

The most challenging obstacle for photocatalysts to efficiently harvest solar energy is the sluggish surface redox reaction (e. g., oxygen evolution reaction, OER) kinetics, which is believed to originate from interface catalysis rather than the semiconductor photophysics. In this work, we developed a light-modulated transient photocurrent (LMTPC) method for investigating surface charge accumulation and reaction on the W-doped bismuth vanadate (W : BiVO4) photoanodes during photoelectrochemical water oxidation. Under illuminating conditions, the steady photocurrent corresponds to the charge transfer rate/kinetics, while the integration of photocurrent (I~t) spikes during the dark period is regarded as the charge density under illumination. Quantitative analysis of the surface hole densities and photocurrents at 0.6 V vs. reversible hydrogen electrode results in an interesting rate-law kinetics switch: a 3rd-order charge reaction behavior appeared on W : BiVO4, but a 2nd-order charge reaction occurred on W : BiVO4 surface modified with ultrathin Bi metal-organic-framework (Bi-MOF). Consequently, the photocurrent for water oxidation on W : BiVO4/Bi-MOF displayed a 50 % increment. The reaction kinetics alternation with new interface reconstruction is proposed for new mechanism understanding and/or high-performance photocatalytic applications.

Galectin-3 promotes fibrosis in ovarian endometriosis.

Objective: This study aimed to investigate the potential role of galectin-3 (Gal-3) in the pathogenesis of fibrotic alterations in ovarian endometriosis (OVE). Methods: In this study, we collected the ectopic endometrial tissues and eutopic endometrial tissues from 31 OVE patients treated by laparoscopy, and the eutopic endometrial tissues from 23 non-OVE patients with leiomyoma or other benign diseases were used as control. Hematoxylin and eosin (H&E) and Masson's trichrome staining were utilized for histopathological assessment. The primary normal endometrial stromal cells (NESC), ectopic endometrial stromal cells (ECSC), and eutopic endometrial stromal cells (EUSC) were isolated. Gal-3 overexpression plasmids (Gal-OE) and short hairpin RNA targeting Gal-3 (Gal-3-shRNA) were transfected into the immortalized human endometriotic cell line 12Z, respectively. RT-qPCR, Western blot analysis, and immunohistochemistry were used to detect the mRNA and protein expression levels of Gal-3, type I collagen (COL-1), connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA), respectively. Results: H&E and Masson staining showed that ovarian ectopic endometrium exhibited glandular hyperplasia, high columnar glandular epithelium, apical plasma secretion, more subnuclear vacuoles, and obvious fibrosis, compared with normal endometrium. The mRNA and protein levels of Gal-3 , CTGF, α-SMA, and COL-1 were all upregulated in the ectopic endometrial tissues of OVE patients compared to the eutopic endometrial tissues from OVE patients and non-OVE patients. Moreover, ECSC expressed higher levels of Gal-3, CTGF, α-SMA, and COL-1 than EUSC and NESC. Follow-up investigations demonstrated that the Gal-3 overexpression substantially increased fibrosis-related markers including CTGF, α-SMA, and COL-1 within the 12Z cell line. Conversely, Gal-3 knockdown showed the opposite effects. Conclusion: Gal-3 promotes fibrosis in OVE, positioning it as a prospective therapeutic target for mitigating fibrosis in endometriosis.

Fracturing Behaviors and Mechanism of Serial Coal Pillar Specimens with Different Strength.

The fracturing behaviors of serial coal pillars is significant for understanding their failure mechanism. To reveal this, the bearing stress, acoustic emission, electrical resistivity, local strain, force chain distribution, and cracks evolution of serial coal pillars under uniaxial compression were evaluated by experiment and numerical simulation. The results show that four bearing stages are observed during the fracturing process (i.e., nonlinear growth, linear growth, yielding growth, and weakening stages). The acoustic emission features, electrical resistivity responses, strain develops, force chain distributions, cracks evolutions, and local displacement are highly consistent to illustrate the fracturing behaviors. System fracturing of serial coal pillar specimens is appeared along with the collapse of lower uniaxial compressive strength coal pillar specimen. The limit bearing capacity of serial coal pillar specimens is almost equal to the strength of lower uniaxial compressive strength coal pillar specimen. The unbalanced deformation characteristics of serial coal pillar specimens are presented due to the strength differences. The evolution of the key deformation element is the rooted reason for the overall fracturing mechanism of serial coal pillar specimens. For serial coal pillar specimens with different strengths, the critical condition of system fracturing is that the sum of secant modulus of upper and bottom coal pillars is zero, which is expected to predict the system fracturing of serial pillars in the underground coal mining.

Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study.

Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8+ T cells (P = 0.033), CD20+ B cells (P = 0.023), CD56 NK cells (P = 0.041), PD-1+ cells (P = 0.042), and PD-L1+CD68+ macrophages (P = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20+ cells (P = 0.046) and in the M1/M2 ratio (P = 0.038) as well as fewer tumors showing increase in the infiltration of CD56bright cells (P = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8+ cells was positively associated with longer progression-free survival (PFS) (P = 0.011) and overall survival (OS) (P = 0.048). Post-NACT CD20+ and CD163+ macrophages (M2) infiltrates were associated with prolonged (P = 0.005) and shortened PFS (P = 0.021), respectively. Increase in the density of CD4+ T cells was predictive for longer PFS (P = 0.022) and OS (P = 0.023). In the multivariate analysis, high density of CD8+ cells pre-NACT (P = 0.042) were independently associated with improved OS.

miR-24-3p regulation of retinol binding protein 4 in trophoblast biofunction and preeclampsia.

Preeclampsia (PE) is a pregnancy-related disease and is the leading cause of overall maternal mortality and morbidity. Our previous studies have shown that the serum and placental levels of retinol-binding protein 4 (RBP4) in PE are reduced. Our previous bioinformatics analysis predicted that RBP4 is a target of the microRNA miRNA-24-3p. In this study, our database analysis also indicated that RBP4 is a miR-24-3p target. Compared with that of the normal placenta, the expression level of RBP4 in human PE placenta was significantly reduced, and miR-24-3p was highly expressed. In HTR-8/SVneo cells, transfection of exogenous miR-24-3p reduced RBP4 expression. A dual-luciferase reporter assay validated RBP4 as a direct target of miR-24-3p, indicating that it directly binds to the 3'-untranslated region of RBP4. This binding was reversed by a mutation in the microRNA-binding site. Transwell invasion experiments and CCK8 assay showed that inhibitory effect of miR-24-3p reduced RBP4 mediated HTR-8/SVneo cell invasion and proliferation. These data provide a new overarching perspective on the physiological role played by miR-24-3p in regulating RBP4 during trophoblast dysfunction and PE development.

Human monocytes differentiate into tumor-associated macrophages upon SKOV3 cells coculture and/or lysophosphatidic acid stimulation.

BACKGROUND: Serous ovarian carcinoma is the most common type of ovarian carcinoma. Tumor-associated macrophages (TAMs) promote ovarian cancer progression. Most macrophages are generated by monocyte differentiation. Lysophosphatidic acid (LPA) levels are high in blood, tissues and ascites of patients with ovarian cancer. This study investigated whether human monocytes can directly differentiate into TAMs in the serous ovarian carcinoma microenvironment. METHODS: Human monocytes were isolated and purified from umbilical cord blood. A serous ovarian carcinoma-like microenvironment was generated by coculturing monocytes and SKOV3 cells in 0.4-µm-pore-size Transwell chambers. Additionally, the effect of LPA was assessed. The two cultured cell types and supernatants were evaluated. RESULTS: The morphology and function of monocytes cocultured with SKOV3 cells and/or stimulated with LPA were significantly changed compared with those of non-stimulated monocytes. The CD14 + CD163 + and CD206 + phenotype indicated that stimulated cells were TAMs. The induced cells promoted SKOV3 cell proliferation and invasion, further proving that they were TAMs. The level of the cytokine interleukin-6R in the supernatant was significantly elevated in the treatment groups compared to the control monocyte group. Pathway enrichment analysis of ELISA results showed a strong influence of interleukin-6 family signaling, especially the JAK-STAT signaling pathway, further confirming the importance of IL-6R. CONCLUSION: Monocytes can differentiate into TAMs under coculture with SKOV3 cells and/or LPA stimulation. The induced TAMs promote SKOV3 cell proliferation and invasion. The cytokine receptor IL-6sR and the JAK-STAT signaling pathway play an important role in the differentiation of monocytes into TAMs.

Reaction Kinetics of Photoelectrochemical CO2 Reduction on a CuBi2O4-Based Photocathode.

The CO2 reduction reaction (CO2RR) is an essential step in natural photosynthesis and artificial photosynthesis to provide carbohydrate foods and hydrocarbon energy in the carbon-neutral cycle. However, the current solar conversion efficiencies and/or product selectivity of the CO2RR are very sluggish due to its complicated multiple-step charge transfer reactions. Here, we systematically investigate the charge transfer reaction rate during CO2 reduction on CuBi2O4 photocathodes, where the surface is modified with 3-aminopropyltriethoxysilane (APTES). We discover that the surface amine group increases the charge separation rate, significantly enhancing the surface charge transfer reaction rate. However, the surface acidity has less influence on the first-order reaction, indicating that a rate-determining step (RDS) exists in the early stage of the photoelectrochemical cell (PEC) processes. Moreover, the intensity-modulated photocurrent spectroscopy (IMPS) confirms that both surface charge transfer and the recombination rate on APTES-coated CuBi2O4 are larger than bare CuBi2O4 while possessing comparable charge transfer efficiencies. Overall, the surface charge transfer reactions under the PEC condition require designing more effective nanostructured photoelectrodes and powerful characterization methods to intrinsically increase the charge separation and transfer rate while reducing the recombination rate.

Vimentin Protein In Situ Expression Predicts Less Tumor Metastasis and Overall Better Survival of Endometrial Carcinoma.

Background: Vimentin, a cytoplasmic intermediate filament protein, has been recently identified to be a prognostic biomarker in some cancers. However, the function of vimentin in endometrial carcinoma (EC) remains unclear. Our study aimed at evaluating vimentin expression in EC and preliminarily exploring the role of vimentin in EC progression. Methods: In total, 341 EC patients who underwent surgical follow-up were enrolled in the retrospective study. Vimentin expression levels in EC tissues were analyzed using immunohistochemistry. Furthermore, the vimentin (VIM) gene expression levels in 547 samples in The Cancer Genome Atlas (TCGA) were analyzed. To examine the prognostic value of vimentin in EC, Kaplan-Meier survival analysis was performed, and a Cox model was established. Gene set enrichment analysis (GSEA) was also conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to explore the role of vimentin in EC progression. Results: Negative vimentin expression in EC correlated significantly with lymph node metastasis, deep myometrium invasion (MI), lymph vascular space invasion (LVSI), advanced Federation International of Gynecology and Obstetrics Association (FIGO) stages (III and IV), and high tumor grade. Vimentin negativity was more common in type 2 EC than that in type 1 EC, and vimentin-negative patients had poorer overall survival compared with vimentin-positive patients. The results of GSEA suggested that vimentin may interact with classical pathways in EC. Conclusions: Negative vimentin expression correlates with tumor metastasis and worse overall survival in EC, suggesting that it may be an excellent prognostic biomarker for this disease. The mechanism by which vimentin contributes to EC progression needs to be explored in the future.

Circular RNA hsa_circ_0004543 Aggravates Cervical Cancer Development by Sponging MicroRNA hsa-miR-217 to Upregulate Hypoxia-Inducible Factor.

Cervical cancer (CC) is the 4th principal source of cancer death in females with 604,000 new patients and 342,000 deaths in 2020 worldwide. It has been extensively shown that circRNAs are involved in regulating CC development. Nevertheless, the function and mechanisms of hsa_circ_0004543 in regulating CC need to be clearly elucidated. Herein, hsa_circ_0004543 expressions were compared between 40 paired paracancerous and cancerous specimens from CC patients and between 6 CC cell lines and a normal human cervical epithelial cell line based on qRT-PCR. Potential complementary binding sites between hsa-miR-217 and hsa_circ_0004543 were predicted using the interactome, while binding sites for the hypoxia-inducible factor-1a (HIF-1a) were predicted by TargetScan. The function and mechanism of hsa_circ_0004543 in the development of CC were estimated by silencing hsa_circ_0004543 with/without hsa-miR-217 or HIF-1a overexpression. The association between gene expressions was evaluated with Pearson's correlation analysis. Molecular mechanisms were explored by ribonucleic acid (RNA) pulldown, dual-luciferase activity, and rescue experimental assays. Our results revealed that the hsa_circ_0004543 expression was considerably increased in CC tissues and cells. Its silencing repressed proliferation and metastasis, while it increased apoptosis of CC cells. The investigation of the mechanism showed that hsa-miR-217 silencing or HIF-1a overexpression rescued hsa_circ_0004543, and silencing inhibited malignant phenotypes of CC cells. hsa_circ_0004543 upregulated the HIF-1α expression by sponging hsa-miR-217 in CC development. Therefore, the hsa_circ_0004543 functioned as a competing endogenous RNA (ceRNA) of hsa-miR-217 to increase CC oncogenesis and metastasis by the upregulation of the HIF-1α expression. Consequently, targeting the hsa_circ_0004543/hsa-miR-217/HIF-1α axis might be a potential treatment approach for CC.

Hypoxic stress disrupts HGF/Met signaling in human trophoblasts: implications for the pathogenesis of preeclampsia.

BACKGROUND: Preeclampsia (PE), a placenta-associated pregnancy complication, is the leading cause of maternal and perinatal morbidity and mortality. Met/Erk signaling is inhibited in the placentas of patients with early-onset preeclampsia (E-PE), but the underlying mechanisms remain elusive. In this study, the expression modes of Met and endocytic vesicles in normal and preeclamptic placentas were compared. Biotinylation internalization/recycling assays were used to measure the endocytosis of Met under hypoxia and normoxia in HTR8/SVneo cells. In addition, the expression level of Cbl, a specific E3 ligase of Met, was measured under hypoxia and normoxia, and the endocytosis of Met was studied by using confocal microscopy. RESULTS: We found considerable intracellular accumulation of Met, which was colocalized with caveolin-1 (CAV-1), in trophoblasts from E-PE placentas. Prolonged hypoxic stimulation led to the remarkable augmentation of CAV-1-mediated Met endocytosis in HTR8/SVneo cells. In addition, the expression of Cbl was substantially repressed by sustained hypoxia, disrupting ubiquitin degradation and the subsequent intracellular accumulation of Met in HTR8/SVneo cells. The abnormal degradation of Met hampered the ability of hepatocyte growth factor (HGF) to promote trophoblast cell invasion. In E-PE placentas, aberrant upregulation of CAV-1 and downregulation of Cbl were observed in parallel to the intracellular accumulation of Met. CONCLUSIONS: These findings reveal that prolonged hypoxic stress induces the augmentation of endocytosis and repression of ubiquitin-mediated Met degradation, which leads to the impaired regulation of trophoblast invasion by HGF/Met signaling. These data provide novel evidence for elucidating the pathogenesis of preeclampsia, especially of the early-onset subtype.

Ambient climate determines the directional trend of community stability under warming and grazing.

Changes in ecological processes over time in ambient treatments are often larger than the responses to manipulative treatments in climate change experiments. However, the impacts of human-driven environmental changes on the stability of natural grasslands have been typically assessed by comparing differences between manipulative plots and reference plots. Little is known about whether or how ambient climate regulates the effects of manipulative treatments and their underlying mechanisms. We collected two datasets, one a 36-year long-term observational dataset from 1983 to 2018, and the other a 10-year manipulative asymmetric warming and grazing experiment using infrared heaters with moderate grazing from 2006 to 2015 in an alpine meadow on the Tibetan Plateau. The 36-year observational dataset shows that there was a nonlinear response of community stability to ambient temperature with a positive relationship between them due to an increase in ambient temperature in the first 25 years and then a decrease in ambient temperature thereafter. Warming and grazing decreased community stability with experiment duration through an increase in legume cover and a decrease in species asynchrony, which was due to the decreasing background temperature through time during the 10-year experiment period. Moreover, the temperature sensitivity of community stability was higher under the ambient treatment than under the manipulative treatments. Therefore, our results suggested that ambient climate may control the directional trend of community stability while manipulative treatments may determine the temperature sensitivity of the response of community stability to climate relative to the ambient treatment. Our study emphasizes the importance of the context dependency of the response of community stability to human-driven environmental changes.

High-Temperature Oxidation Behavior of Fe-10Cr Steel under Different Atmospheres.

Using a thermogravimetric analyzer (TGA), Fe-10Cr steel was oxidized in dry air and in a mixed atmosphere of air and water vapor at a relative humidity of 50% and a temperature of 800-1200 °C for 1 h. The oxidation weight gain curves under the two atmospheres were drawn, the oxidation activation energy was calculated, and the phase and cross-sectional morphology of the iron oxide scales were analyzed and observed by X-ray diffractometry (XRD) and optical microscopy (OM). The results showed that when the oxidation temperature was 800 °C, the spheroidization of Fe-10Cr steel occurred, and the oxidation kinetics conformed to the linear law. At 900-1200 °C, the oxidation kinetics followed a linear law in the preliminary stage and a parabolic law in the middle and late stages. In an air atmosphere, when the oxidation temperature reached 1200 °C, Cr2O3 in the inner oxide layer was partially ruptured. In an atmosphere with a water vapor content of 50%, Cr2O3 at the interface reacted with H2O to generate volatile CrO2(OH)2, resulting in a large consumption of Cr at the interface. At the same time, a large number of voids and microcracks appeared in the iron oxide layer, which accelerated the entry of water molecules into the substrate, as well as the oxidation of Fe-10Cr steel, and caused the iron oxide scales to fall off. Due to the volatilization of Cr2O3 and the conversion from internal oxidation to external oxidation, the internal oxidation zone (IOZ) of Fe-10Cr steel under water vapor atmosphere decreased or even disappeared.

Placental trophoblast syncytialization potentiates macropinocytosis via mTOR signaling to adapt to reduced amino acid supply.

During pregnancy, the appropriate allocation of nutrients between the mother and the fetus is dominated by maternal-fetal interactions, which is primarily governed by the placenta. The syncytiotrophoblast (STB) lining at the outer surface of the placental villi is directly bathed in maternal blood and controls feto-maternal exchange. The STB is the largest multinucleated cell type in the human body, and is formed through syncytialization of the mononucleated cytotrophoblast. However, the physiological advantage of forming such an extensively multinucleated cellular structure remains poorly understood. Here, we discover that the STB uniquely adapts to nutrient stress by inducing the macropinocytosis machinery through repression of mammalian target of rapamycin (mTOR) signaling. In primary human trophoblasts and in trophoblast cell lines, differentiation toward a syncytium triggers macropinocytosis, which is greatly enhanced during amino acid shortage, induced by inhibiting mTOR signaling. Moreover, inhibiting mTOR in pregnant mice markedly stimulates macropinocytosis in the syncytium. Blocking macropinocytosis worsens the phenotypes of fetal growth restriction caused by mTOR-inhibition. Consistently, placentas derived from fetal growth restriction patients display: 1) Repressed mTOR signaling, 2) increased syncytialization, and 3) enhanced macropinocytosis. Together, our findings suggest that the unique ability of STB to undergo macropinocytosis serves as an essential adaptation to the cellular nutrient status, and support fetal survival and growth under nutrient deprivation.

MUC16 affects the biological functions of ovarian cancer cells and induces an antitumor immune response by activating dendritic cells.

BACKGROUND: Ovarian cancer is the 5th most common lethal gynecological malignancy with a 5-year survival rate of about 47% and a localized stage diagnosis of 15%, leading to about 125,000 global deaths each year. Therefore, it is urgent to explore novel and effective strategies for radical cure. METHODS: Short hairpin RNA targeting the Mucin16 (MUC16) gene was used to establish MUC16 knockdown in ovarian cancer cells. RT-PCR was performed to quantify the expression of MUC16 mRNA, and western blotting was performed to detect the expression of MUC16 and epithelial-mesenchymal transition-related proteins. Cell counting kit 8 (CCK8) wound healing and transwell assays were performed to assess cell proliferation and cell invasion. Flow cytometry was used to detect CD80-, CD83-, and CD86-expressing dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) activated by MUC16-pulsed DCs. RESULTS: In this study, we identified MUC16 as a novel target antigen for immunotherapy against ovarian cancer, which was significantly up regulated in ovarian cancer cells and high-grade ovarian serous adenocarcinoma tissues. MUC16 knockdown in Ovcar3 cells using short hairpin RNA targeting the MUC16 gene suppressed the proliferation of migration, invasion, epithelial-mesenchymal transition (EMT), and PI3K/Akt signaling pathway in Ovcar3 cells markedly. MUC16 significantly up-regulated CD80, CD83, and CD86 (mature makers) expression in DCs and T-cell transformation into CD8+ T-cells detected by Flow cytometry. CONCLUSIONS: For malignant ovarian cancer, MUC16 overexpression promoted cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. MUC16 pulsing mediated DC maturation and activated CTL response in vitro. Our study offers promising DC-based immunotherapy of considerable clinical value for patients with ovarian cancer.

Association of high-risk human papillomavirus infection duration and cervical lesions with vaginal microbiota composition.

BACKGROUND: Cervical cancer is reportedly caused by the synergistic effects of persistent high-risk human papillomavirus (HPV) infection. Cervical microbiota represent a unique and dynamically changing microecological system that is directly exposed to the vagina. The relationship between HPV and the composition of the cervical microbiome has long been a primary focus of research. METHODS: To determine the specific differential florae throughout the process of cervical cancer development, in the present study, 16S rRNA sequencing was combined with KEGG pathway enrichment analysis to analyse five groups of cervical scraping samples with increasing durations of HPV infection and cervical intraepithelial neoplasia pathological classification. RESULTS: The findings revealed that decreasing levels of probiotics, including Shuttleworthia, Prevotella, Lactobacillus, and Sneathia, and increasing levels of pathogenic bacteria, including Dispar, Streptococcus, and Faecalibacterium prausnitzii, could be the direct result of early HPV infection. Other pathogenic bacteria, such as Bifidobacteriaceae, might represent key factors in cancer progression. Additionally, KEGG pathway enrichment analysis indicated that HPV infection directly inhibits multiple pathways, including those of sporulation, porphyrin and chlorophyll metabolism, arginine and proline metabolism, isoquinoline alkaloid biosynthesis, and ansamycin biosynthesis, which may lead to the development of early symptoms of cervical cancer. Biomarkers were predicted based on operational taxonomic unit (OTU) abundance data, and OTU851726 and OTU715913 were undoubtedly the best potential indicators of cervical cancer. CONCLUSIONS: The findings of the present study could assist with the development of a guideline for screening new clinical drugs for cervical cancer.

Diagnostic and prognostic value of HABP2 as a novel biomarker for endometrial cancer.

BACKGROUND: Endometrial cancer is the fifth most common malignant disorder in women, with its incidence increasing. A biomarker with diagnostic and prognostic value remains to be found. The HABP2 protein, or Factor VII-activating protease, encodes a hyaluronic acid-binding protein. METHODS: Patient data including clinical characteristics and RNAseq information of HABP2 was obtained from The Cancer Genome Atlas (TCGA), and analyzed by R statistic packages. A total of 370 women with endometrial cancer were enrolled in the study. To study the diagnostic value of HABP2 in patients with endometrial cancer, receiver operating characteristic (ROC) curves were plotted by the pROC package. To study the prognostic value of HABP2 in patients with endometrial cancer, the survival package in R was used and the Cox model was established. RESULTS: HABP2 expression was lower in endometrial cancer compared with normal endometrial tissues. HABP2 showed moderate diagnostic value for endometrial cancer, with HBP2 expression associated with vital status, histologic grade, and residual tumor. HABP2 was an independent prognostic factor, with low HABP2 expression indicating a better overall survival. CONCLUSIONS: HABP2 has diagnostic and prognostic value and maybe a novel biomarker for endometrial cancer.

A Polyethylene Glycol-Based Method for Enrichment of Extracellular Vesicles from Culture Supernatant of Human Ovarian Cancer Cell Line A2780 and Body Fluids of High-Grade Serous Carcinoma Patients.

OBJECTIVE: This study tried to evaluate whether 8% polyethylene glycol (PEG) 6000 precipitation combined with differential ultracentrifugation (PPDU) was an efficient and practical method for the enrichment and purification of extracellular vesicles (EVs) derived from the culture supernatant of human ovarian cancer cell line A2780 and from body fluids of patients with high-grade serous carcinoma (HGSC). METHODS: PPDU was used to enrich and purify the EVs derived from body fluids of patients with HSGC and cell culture supernatant of subclones of human ovarian cancer cell line A2780 with high/low invasive capacity (named as A-H/A-L, respectively). Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) were used to identificate the EVs size and distribution. Western blots (WB) were used to detect the expression of CD9, CD63, Alix and Calnexin. The high-purity EVs derived from the cell culture supernatant of A-H/A-L were detected by the protein profile. Expression of integrins (ITGs) αV, ß1 and ß3 in the EVs derived from body fluids of HGSC patients was also evaluated. RESULTS: The diameter of EVs was about 30-260 nm observed under the TEM. Under the NTA identification, the peak size of EVs was ranged from 70 to 159nm. EVs derived from different specimens did not significantly differ in mean size and peak size. Presence of CD9, CD63 and Alix and absence of Calnexin were confirmed in the EVs. The protein concentrations of EVs' sample extracted from A-H/A-L cell culture supernatant were 0.36µg/µL and 0.20µg/µL, respectively. The total amount of protein obtained from 300ul EVs was 108.02ug and 61.44ug, respectively. Totally, 2397 peptides and 952 proteins were identified by isobaric tags for relative and absolute quantitation (ITRAQ). The expression of ITGαV, ß1, and ß3 in the EVs from plasma and ascites of HGSC patients was significantly higher than the control group (plasma: all P<0.0001; ascites: P=0.036, 0.001 and 0.004, respectively). The expression level of ITGαV and ß1 in EVs of HGSC's ascites was significantly higher than that in plasma (P= 0.004, 0.001, respectively). The expression of ITGß3 was also slightly elevated in EVs-derived HGSC patients' ascites (P=0.492). CONCLUSION: PPDU was an efficient and practical method to enrich EVs from body fluids and cell culture supernatant. The characteristic expression of ITGαV, ß1 and ß3 in ascites and plasma EVs of patients with HGSC provided useful information on the development of EVs in HGSC.

The Role of Lysophosphatidic Acid Receptors in Ovarian Cancer: A Minireview.

Lysophosphatidic acid (LPA) is a bioactive lipid component of ovarian cancer activating factor, which is present at a high concentration in the ascitic fluid and plasma of patients with ovarian cancer. A group of six lysophosphatidic acid receptors (LPARs), LPAR1 through LPAR6, which belong to the G protein-coupled receptor superfamily (GPCR), mediate cellular activities of LPA and activates a series of downstream molecules and cellular responses, including biological and pathological effects. LPARs are widely expressed in normal ovary, benign tumor, and ovarian cancer tissues and cancer cell lines with a broad range of levels. The LPA/LPAR axis is involved in tumorigenesis and development of ovarian cancer through mediating the cellular responses to LPA and influencing the expression and function of oncogenic molecules. In the present review, the roles of LPARs in ovarian cancer, including the expression, function, and downstream molecules, are summarized, and we discuss the implications for ovarian cancer treatment that targets LPARs.

Transthyretin increases migration and invasion of rat placental trophoblast cells.

Preeclampsia (PE) is a hypertensive disorder of pregnancy. Early diagnosis of PE is currently contingent on regular prenatal physical examinations and may be facilitated by identification of novel diagnostic markers. Transthyretin (TTR), also known as prealbumin, is primarily responsible for maintaining the normal levels of thyroxine and retinol binding protein. The expression of TTR is lower in patients with severe PE as compared with healthy controls. Here, we examined the suitability of TTR as a diagnostic marker in pregnant hypertensive rats. N'-nitro-l-arginine-methylesterhydrochloride (l-NAME) was used to generate a rat model of hypertension during pregnancy. Rat placental trophoblast cells were divided into control and TTR groups for in vitro experiments. Systolic blood pressure, diastolic blood pressure, mean blood pressure and urinary protein of hypertensive pregnant rats were higher than those of healthy pregnant rats, but these effects could be reversed by TTR treatment. There were no significant changes in blood pressure and urinary protein in healthy pregnant rats before or after TTR treatment. TTR levels in the serum and placental tissues of pregnant hypertensive rats were significantly reduced compared with those of healthy pregnant rats. Changes in placental and fetal weights in the hypertensive model could also be rescued by TTR treatment. TTR treatment significantly increased the level of matrix metalloproteinase-2/9 in hypertensive rats. Finally, in vivo and in vitro experiments demonstrated that TTR effectively increased the migration and invasion of rat placental trophoblast cells, as well as matrix metalloproteinase-2/9 levels in these cells. In conclusion, our data from a rat model suggest that TTR may have potential as a novel marker for PE diagnosis.

Effect of Metformin on a Preeclampsia-Like Mouse Model Induced by High-Fat Diet.

BACKGROUND: Metformin has been reported to decrease insulin resistance and is associated with a lower risk of pregnancy-induced hypertension and preeclampsia. It is widely accepted that the placenta plays a crucial role in the development of preeclampsia. Our aim is to explore the effect of metformin on preeclampsia. STUDY DESIGN: We examined control diet-fed (isocaloric diet) pregnant mice (CTRL group), pregnant mice fed a high-fat diet (HF group), and high-fat-diet-fed pregnant mice treated with metformin (HF-M group). The HF mice were fed a high-fat diet six weeks before pregnancy to establish a preeclampsia-like model; then, the group was randomly divided into a HF group and a HF-M group after pregnancy. Blood pressure, urine protein, pregnancy outcomes, protein expression, and histopathological changes in the placentas of all groups were examined and statistically analysed. RESULTS: We observed that metformin significantly improved high blood pressure, proteinuria, and foetal and placental weights in the HF-M group compared with the HF group. Metformin significantly improved placental labyrinth and foetal vascular development in preeclampsia. In addition, metformin effectively increased matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) levels in the placenta. CONCLUSIONS: Our results suggest that metformin can improve preeclamptic symptoms and pregnancy outcomes.