Prenatal exposure to ambient air multi-pollutants significantly impairs intrauterine fetal development trajectory.

BACKGROUND: Impaired in utero fetal growth trajectory may have long term health consequences of the newborns and increase risk of adulthood metabolic diseases. Prenatal exposure to air pollution has been linked to fetal development restriction; however, the impact of exposure to ambient air pollutants on the entire course of intrauterine fetal development has not been comprehensively investigated. METHODS: During 2015-2018, two cohorts of mother-infant dyads (N = 678 and 227) were recruited in Shanghai China, from which three categories of data were systematically collected: (1) daily exposure to six air pollutants during pregnancy, (2) fetal biometry in the 2nd (gestational week 24, [GW24]) and 3rd trimester (GW36), and (3) neonatal outcomes at birth. We investigated the impact of prenatal exposure to air pollutant mixture on the trajectory of fetal development during the course of gestation, adjusting for a broad set of potential confounds. RESULTS: Prenatal exposure to PM2.5, PM10, SO2 and O3 significantly reduced fetal biometry at GW24, where SO2 had the most potent effect. For every 10 µg/m3 increment increase of daily SO2 exposure during the 1st trimester shortened femur length by 2.20 mm (p = 6.7E-21) translating to 5.3% reduction from the average of the study cohort. Prenatal air pollution exposure also decreased fetal biometry at GW36 with attenuated effect size. Comparing to the lowest exposed quartile, fetus in the highest exposed quartile had 6.3% (p = 3.5E-5) and 2.1% (p = 2.4E-3) lower estimated intrauterine weight in GW24 and GW36, respectively; however, no difference in birth weight was observed, indicating a rapid catch-up growth in the 3rd trimester. CONCLUSIONS: To our knowledge, for the first time, we demonstrated the impact of prenatal exposure to ambient air pollutants on the course of intrauterine fetal development. The altered growth trajectory and rapid catch-up growth in associated with high prenatal exposure may lead to long-term predisposition for adulthood metabolic disorders.

Adipose-derived stem cells transplantation improves endometrial injury repair.

Endometrial injury is an important cause of intrauterine adhesion (IUA), amenorrhea and infertility in women, with limited effective therapies. Recently, stem cells have been used in animal experiments to repair and improve injured endometrium. To date, our understanding of adipose-derived stem cells (ADSCs) in endometrial injury repair and their further therapeutic mechanisms is incomplete. Here, we examined the benefit of ADSCs in restoration of injured endometrium by applying a rat endometrial injury model. The results revealed by immunofluorescence showed that green fluorescent protein (GFP)-labelled ADSCs can differentiate into endometrial epithelial cells in vivo. At 30 days after ADSCs transplantation, injured endometrium was significantly improved, with increased microvessel density, endometrial thickness and glands when compared with the model group. Furthermore, the fertility of rats with injured endometrium in ADSCs group was improved and had a higher conception rate (60% vs 20%, P = 0.014) compared with the control phosphate-buffered saline (PBS) group. However, there was no difference in the control group compared with the sham group. In addition, expression levels of the oestrogen receptor Eα/ß (ERα, ERß) and progesterone receptor (PR) detected by western blot and enzyme-linked immunosorbent assay (ELISA) were higher in the ADSCs group than in the PBS group. Taken together, these results suggested that ADSC transplantation could improve endometrial injury as a novel therapy for IUA.

Excitation of Bloch surface wave on tapered fiber coated with one-dimensional photonic crystal for refractive index sensing.

We have theoretically and experimentally demonstrated a novel approach to excite Bloch surface wave (BSW) on tapered optical fibers, which are coated with one-dimensional photonic crystal (1DPC) consisting of periodic TiO2 and Al2O3 by atomic layer deposition technology. Two resonant dips are found in transmission spectra that are originated from the excitation of BSW for p-polarized light and s-polarized light, respectively. For the first time, we have demonstrated the developed device for refractive index (RI) sensing.

A Fiber-Optic Sensor for Acoustic Emission Detection in a High Voltage Cable System.

We have proposed and demonstrated a Michelson interferometer-based fiber sensor for detecting acoustic emission generated from the partial discharge (PD) of the accessories of a high-voltage cable system. The developed sensor head is integrated with a compact and relatively high sensitivity cylindrical elastomer. Such a sensor has a broadband frequency response and a relatively high sensitivity in a harsh environment under a high-voltage electric field. The design and fabrication of the sensor head integrated with the cylindrical elastomer is described, and a series of experiments was conducted to evaluate the sensing performance. The experimental results demonstrate that the sensitivity of our developed sensor for acoustic detection of partial discharges is 1.7 rad / ( m ⋅ Pa ) . A high frequency response up to 150 kHz is achieved. Moreover, the relatively high sensitivity for the detection of PD is verified in both the laboratory environment and gas insulated switchgear. The obtained results show the great potential application of a Michelson interferometer-based fiber sensor integrated with a cylindrical elastomer for in-situ monitoring high-voltage cable accessories for safety work.

YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A.

The malignancy of endometrial carcinoma (EC) largely results from its high invasive feature. The regulation of the mRNA splicing of vascular endothelial growth factor A (VEGF-A) is critical for EC-associated cancer vascularization and invasion. Recently, we have reported that poorly prognostic EC had high levels of YT521, a newly defined RNA splicing protein. However, whether YT521 may similarly regulate the splicing of VEGF-A in EC is unknown. Here, we showed that EC specimens contained significantly higher levels of YT521, compared to the adjacent non-tumor endometrial tissue. Higher levels of YT521 were detected in EC specimens with metastases. High-YT521 EC is associated with poor patient survival. In order to examine whether YT521 may regulate VEGF-A mRNA splicing in EC, we transfected an EC cell line HEC-1A with different doses of YT521 mimics. We found that YT521 dose-dependently increased the ratio of VEGF-165 vs VEGF-121 at both mRNA and protein level, suggesting that YT521 may promote VEGF-A mRNA splicing to favor a VEGF-165 isoform. Moreover, the increases in the ratio of VEGF-165 vs VEGF-121 by YT521 overexpression resulted in increases in EC cell invasion, while decreases in the ratio of VEGF-165 vs VEGF-121 by YT521 depletion resulted in decreases in EC cell invasion in a transwell cell migration assay. Further, overexpression of VEGF-165, but not overexpression of VEGF-121, increased EC cell invasiveness. Finally, a strong correlation was detected between the ratio of VEGF-165 vs VEGF-121 and the levels of YT521 in EC specimens. Together, these data suggest that YT521 may promote EC metastases by regulating mRNA splicing of VEGF-A.

Clinical significance of Sam68 expression in endometrial carcinoma.

Sam68 (Src-associated in mitosis of 68 kDa) is a substrate for tyrosine kinase c-Src during mitosis. The nuclear protein level has been found to be associated with progression and prognosis in various human malignant tumors. The aim of this study is to investigate the clinical value of Sam68 in endometrial carcinoma (EC). Sam68 expression was confirmed by real-time PCR, Western blot, and immunofluorescent assay in primary normal endometrial epithelial cells, endometrial carcinoma cell lines, as well as seven pairs of EC and matched adjacent noncancerous endometrial tissues. Moreover, the protein level of Sam68 was evaluated by immunohistochemistry in a cohort of surgical specimens derived from 131 patients including primary endometrial carcinoma (n = 95), endometrial atypical hyperplasia (precancerous lesions, n = 26), and normal endometria (n = 10). In endometrial cancer cell lines, RNA interfering approach was employed to downregulate Sam68 expression to determine its role in proliferation. Clinicopathological relevance and prognostic associations were examined by statistical analyses. Compared with normal endometrial and endometrial atypical hyperplasia tissues, Sam68 significantly elevated in endometrial cancer samples (P < 0.01), which was negative or low in 37 cases (38.9 %) and high in 58 cases (61.1 %). The high expression of Sam68 was associated with histological grade (P < 0.001), FIGO stage (P = 0.039), and myometrial invasion (P = 0.002). Kaplan-Meier analysis demonstrated that overexpression of Sam68 correlated with shorter overall survival. It is confirmed by univariate and multivariate analysis (P < 0.001 and P = 0.048, respectively). Additionally, we found that Sam68 was highly expressed at both the transcriptional and translational levels in endometrial cancer cell lines (Ishikawa, HEC-1B, AN3CA, KLE, and RL95-2) and siRNA knockdown of Sam68 remarkably inhibited cellular proliferation in in vitro models. Sam68 may be useful prognostic marker for EC, and it plays an important role in promoting the cellular proliferation. Further investigation of Sam68 as a potential therapeutic target for EC patients could be of interest.

Downregulation of microRNA-145 is associated with aggressive progression and poor prognosis in human cervical cancer.

MicroRNAs (miRNAs) play important roles in the processes of tumor initiation and progression. However, miR-145 expression in cervical cancer has been rarely investigated. The aim of this study was to investigate the clinical significance and prognostic value of miR-145 expression in cervical cancer. MiR-145 expression in 114 pairs of human cervical cancer and adjacent normal tissues was detected by real-time quantitative RT-PCR assay. The results showed that miR-145 expression was significantly downregulated in cervical cancer tissues when compared with corresponding adjacent normal tissues (P < 0.001). It was also significantly lower in the cancerous tissues of patients with advanced International Federation of Gynecology and Obstetrics (FIGO) stage cervical cancer than those with early FIGO stage (P = 0.006). In addition, miR-145 was expressed at significantly lower levels in lymph node metastasis-positive patients than in lymph node metastasis-negative patients (P = 0.037). Moreover, poorly differentiated tumors expressed lower miR-145 than well or moderately differentiated tumors (P = 0.012). Patients with vascular invasion or human papillomavirus (HPV) infection also had lower miR-145 expression levels than those without (P = 0.016 and P = 0.025, respectively). Furthermore, Kaplan-Meier analysis showed that cervical cancer patients with low miR-145 expression had shorter overall survival time than those with high miR-145 expression (P < 0.001). When analyzed with a multivariate Cox regression model, miR-145 was identified as an independent prognostic factor for overall survival. Taken together, our results suggest that downregulation of miR-145 in cervical cancer is associated with aggressive progression and poor prognosis and that miR-145 may serve as a prognostic marker.

MicroRNA-222 promotes the proliferation and migration of cervical cancer cells.

PURPOSE: This study aimed to investigate the role of small non-coding RNA-222 (microRNA-222; miR-222) in the development of cervical cancer (CC). METHODS: Normal and CC specimens were obtained from 18 patients. HeLa and SiHa cells were grown in Dulbecco's modified Eagle's medium. RT-PCR, Western blot, migration assay, flow cytometry and immunofluorescence microscopy were used for analyses. RESULTS: When compared with normal cervical tissues, miR-222 was upregulated in human CC, and the extent of up-regulation was associated with the extent and depth of CC invasion. Expression of miR-222 was inversely related to the expression of phosphatase and tensin homolog (PTEN) and p27. The reduced the expression of PTEN and p27 by miR-222 in HeLa cells and SiHa cells was associated with increased proliferation and migration of CC cells. The expression of proteins (E-cadherin and paxillin) related to the proliferation and migration was also elevated. CONCLUSION: MiR-222 plays an important role in the tumorigenesis of CC, possibly by specifically down-regulating p27Kip1 and PTEN. Our findings suggest that miR-222 may serve as a new therapeutic target in CC.

Levonorgestrel-releasing intrauterine system versus medical therapy for menorrhagia: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to compare the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) with conventional medical treatment in reducing heavy menstrual bleeding. MATERIAL AND METHODS: Relevant studies were identified by a search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and clinical trials registries (from inception to April 2014). Randomized controlled trials comparing the LNG-IUS with conventional medical treatment (mefenamic acid, tranexamic acid, norethindrone, medroxyprogesterone acetate injection, or combined oral contraceptive pills) in patients with menorrhagia were included. RESULTS: Eight randomized controlled trials that included 1170 women (LNG-IUS, n=562; conventional medical treatment, n=608) met inclusion criteria. The LNG-IUS was superior to conventional medical treatment in reducing menstrual blood loss (as measured by the alkaline hematin method or estimated by pictorial bleeding assessment chart scores). More women were satisfied with the LNG-IUS than with the use of conventional medical treatment (odds ratio [OR] 5.19, 95% confidence interval [CI] 2.73-9.86). Compared with conventional medical treatment, the LNG-IUS was associated with a lower rate of discontinuation (14.6% vs. 28.9%, OR 0.39, 95% CI 0.20-0.74) and fewer treatment failures (9.2% vs. 31.0%, OR 0.18, 95% CI 0.10-0.34). Furthermore, quality of life assessment favored LNG-IUS over conventional medical treatment, although use of various measurements limited our ability to pool the data for more powerful evidence. Serious adverse events were statistically comparable between treatments. CONCLUSIONS: The LNG-IUS was the more effective first choice for management of menorrhagia compared with conventional medical treatment. Long-term, randomized trials are required to further investigate patient-based outcomes and evaluate the cost-effectiveness of the LNG-IUS and other medical treatments.

Experience with successful treatment of severe recurrent vulvar adhesions: A case report.

Vulvar adhesions are defined as partial or complete adherence of the labia minora and/or labia majora. Vulvar adhesions are rare, especially in postmenopausal women.This article describes a case of postmenopausal recurrent vulvar adhesions successfully treated with surgery. The patient was a 52-year-old woman who had undergone manual separation and surgical adhesion release due to vulvar adhesions, which recurred soon after treatment. The patient then came to our hospital for treatment because of complete dense adhesions to the vulva and laboured urination. The patient received surgical treatment, the anatomical structure of the vulva recovered well, and the symptoms affecting the urinary system disappeared. There was no readhesion during the 3-month follow-up.

Intelligent design of polymersomes for antibacterial and anticancer applications.

Polymersomes (or polymer vesicles) have attracted much attention for biomedical applications in recent years because their lumen can be used for drug delivery and their coronas and membrane can be modified with a variety of functional groups. Thus, polymersomes are very suitable for improved antibacterial and anticancer therapy. This review mainly highlighted recent advances in the synthetic protocols and design principles of intelligent antibacterial and anticancer polymersomes. Antibacterial polymersomes are divided into three categories: polymersomes as antibiotic nanocarriers, intrinsically antibacterial polymersomes, and antibacterial polymersomes with supplementary means including photothermal and photodynamic therapy. Similarly, the anticancer polymersomes are divided into two categories: polymersomes-based delivery systems and anticancer polymersomes with supplementary means. In addition, the bilateral relationship between bacteria and cancer is addressed, since more and more evidences show that bacteria may cause cancer or promote cancer progression. Finally, prospective on next-generation antibacterial and anticancer polymersomes are discussed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology-Inspired Nanomaterials > Lipid-Based Structures.

Prediction of the immunological and prognostic value of five signatures related to fatty acid metabolism in patients with cervical cancer.

A growing attention has been attached to the role of fatty acid metabolism (FAM) in the development of cancer, and cervical cancer (CC) is still the primary cause of cancer-associated death in women worldwide. Therefore, it is imperative to explore the possible prognostic significance of FAM in CC. In this study, CC samples and corresponding normal samples were acquired from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). Single sample gene set enrichment analysis (ssGSEA) was conducted for calculating FAM-related scores (FAMRs) to screen FAM-related genes (FAMRGs). Two subtypes related to FAM were identified by consistent clustering. Among them, subtype C2 had a poor prognosis, and C1 had a high level of immune cell infiltration, while C2 had a high possibility of immune escape and was insensitive to chemotherapy drugs. Based on the differentially expressed genes (DEGs) in the two subtypes, a 5-gene signature (PLCB4, FBLN5, TSPAN8, CST6, and SERPINB7) was generated by the least absolute shrinkage and selection operator (LASSO) and Akaike information criterion (AIC). The model demonstrated a high prognostic accuracy (area under the curve (AUC)>0.7) in multiple cohorts and was one independent prognostic factor for CC patients. Accordingly, FAMRGs can be adopted as a biomarker for the prediction of CC patients' prognosis and help guide the immunotherapy of CC.

SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell via Balancing ERα and PR Signals.

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation. Methods: The therapeutic effects of SCM-198 on EMS and its potential mechanism were analyzed by establishing EMS mouse models and performing an RNA sequencing (RNA-seq) assay. ELISA was performed to detect estrogen and tumor necrosis factor (TNF) -α concentrations in normal endometrial stromal cells (nESCs) and ectopic endometrial stromal cells (eESCs) with or without SCM-198 treatment. Western blotting, RNA silencing, and plasmid overexpression were used to analyze the relationship between inflammation, endocrine factors, and autophagy and the regulatory activity of SCM-198 on the inflammation-endocrine-autophagy axis. Results: Increased estrogen-estrogen receptor (ER) α signaling and decreased progesterone receptor isoform B (PRB) expression synergistically led to a hypo-autophagy state in eESCs, which further inhibited the apoptosis of eESCs. The high expression of TNF-α in eESCs enhanced the antiapoptotic effect mediated by low autophagy through the activation of the aromatase-estrogen-ERα signaling pathway. SCM-198 inhibited the growth of ectopic lesions in EMS mice and promoted the apoptosis of eESCs both in vivo and in vitro. The apoptotic effect of SCM-198 on eESCs was attained by upregulating the autophagy level via the inhibition of the TNF-α-activated aromatase-estrogen-ERα signal and the increase in PRB expression. Conclusion: Inflammation facilitated the progress of EMS by disrupting the estrogen regulatory axis. SCM-198 inhibited EMS progression by regulating the inflammation-endocrine-autophagy axis.

Identification of Potential Hub Genes and miRNA-mRNA Pairs Related to the Progression and Prognosis of Cervical Cancer Through Integrated Bioinformatics Analysis.

In recent years, the incidence and mortality of cervical cancer have increased worldwide. At the same time, increasing data have confirmed that miRNA-mRNA plays a positive or negative regulatory role in many cancers. This study attempted to screen effective miRNA-mRNA in the progression of cervical cancer, and to study the mechanism of miRNA-mRNA in the progression of cervical cancer. The expression profile data of GSE7410, GSE 63514, GSE 86100 and TCGA-CESC were downloaded, and 34 overlapping differentially expressed genes (22 up-regulated and 12 down-regulated) and 166 miRNAs (74 down-regulated and 92 up-regulated) were screened through limma package. Then, miR-197-3p/TYMS pairs were obtained by PPI, functional enrichment, Kaplan-Meier plotter analysis, Cox univariate and multivariate analysis, risk modeling, WGCNA, qPCR and dual-luciferase experiments. The results showed that TYMS was an independent prognostic factor of cervical cancer, and its expression level was negatively correlated with cervical cancer tissue grade (TMN), tumor grade, age, microsatellite stability and tumor mutation load, and positively correlated with methyl expression in DNMT1, DNMT2, DNMT3A and DNMT3B. Functional experiments showed that TYMS knockout could promote the proliferation, migration and invasion of HeLa cells and reduce apoptosis. Overexpression of TYMS showed the opposite trend, miR-197-3p was negatively correlated with the expression of TYMS. MiR-197-3p inhibitor reversed the effect of si-TYMS on the proliferation of HeLa cells. In conclusion, these results reveal that TYMS plays a very important role in the prognosis and progression of cervical cancer, and has the potential to be thought of as cervical cancer biomarkers. At the same time, miR-197-3p/TYMS axis can regulate the deterioration of cervical cancer cells, which lays a foundation for the molecular diagnosis and treatment of cervical cancer.

ADSC Exosomes Mediate lncRNA-MIAT Alleviation of Endometrial Fibrosis by Regulating miR-150-5p.

BACKGROUND: Secondary infertility remains a major complication of endometrial fibrosis in women. The use of exosomes from adipose-derived mesenchymal stem cells (ADSCs) has shown promising results for the treatment of endometrial fibrosis. However, the mechanisms of action of ADSC-exosome (ADSC-Exo) therapy remain unclear. MATERIALS AND METHODS: An endometrial fibrosis model was established in mice treated with alcohol and endometrial epithelial cells (ESCs) treated with TGF-ß1. ADSCs were isolated from Sprague Dawley (SD) rats, and exosomes were isolated from ADSCs using ExoQuick reagent. Exosomes were identified by transmission electron microscopy (TEM), NanoSight, and Western blot analysis. The expression level of lncRNA-MIAT was detected by qPCR analysis. Western blot analysis was carried out to determine the protein levels of fibrosis markers (TGFßR1, α-SMA, and CK19). A dual-luciferase reporter gene assay was used to verify the relationship between target genes. The endometrial tissues of the endometrial fibrosis model were stained with HE and Masson's trichrome. RESULTS: ADSCs and ADSC-Exos were successfully isolated, and the expression level of lncRNA-MIAT was significantly down-regulated in endometrial tissue and the TGF-ß1-induced ESC injury model, whereas ADSC-Exos increased the expression of lncRNA-MIAT in the TGF-ß1-induced ESC model. Functionally, ADSC-Exo treatment repressed endometrial fibrosis in vivo and in vitro by decreasing the expression of hepatic fibrosis markers (α-SMA and TGFßR1) and increasing the expression of CK19. Moreover, miR-150-5p expression was repressed by lncRNA-MIAT in the TGF-ß1-induced ESC injury model. The miR-150-5p mimic promoted TGF-ß1-induced ESC fibrosis. CONCLUSION: ADSC-Exos mediate lncRNA-MIAT alleviation of endometrial fibrosis by regulating miR-150-5p, which suggests that lncRNA-MIAT from ADSC-Exos may be a viable treatment for endometrial fibrosis.

The high platelet counts as predictor for early foetal demise.

Objectives: Early fetal demise (absence of cardiac activity in a visible fetus) is a very common event, but there are no reliable biomarkers to predict it. The purpose of the study was to assess the association of platelet parameters with early fetal demise.Methods: In this case-control study, we included women with normal deliveries or those ultrasound diagnosed as early fetal demise. For those who were identified with early fetal demise, the platelet parameters were analyzed before the ultrasound diagnosis, which is based on the absence of either an embryo within a gestational sac or cardiac activity in a visible embryo in the 5-10 weeks of gestation. The association between the risk of early fetal demise with the women's mean platelet volume (MPV) and platelet counts was calculated by logistic regression. Duplicate measurements of platelet aggregation were performed with VerifyNow. Results: In total, 99 women identified with early fetal demise and 170 women who had an uncomplicated pregnancy with normal delivery from January 2017 and August 2020 were included in the study. We found that platelet counts in the early fetal demise group were significantly higher than healthy pregnancies. In addition, platelet reactivity is higher in the normal delivery group than those in early fetal demise group (p < .05). High levels of platelet counts resulted in an adjusted odds ratio (OR) of 2.075 (95% confidence interval [95% CI], 1.215-3.544; p = .008) for early fetal demise. Conclusions: Increased platelet counts in the first trimester may be a predictor for the risk of early fetal demise.

Tetracaine combined with propofol for painless oocyte retrieval: from a single center study.

BACKGROUND: In vitro fertilization-embryo transfer is a main assisted reproductive technique that can improve the success rate of conception. At present, the ultrasound-guided oocyte retrieval is often employed in clinics, but this process will cause pain and fear in outpatients. This study explored the safety and satisfaction of patients who received egg retrieval under vaginal topical tetracaine anesthesia combined with intravenous propofol anesthesia. METHODS: Patients who underwent elective egg retrieval in the Reproductive Center of Shanghai Tenth People's Hospital were recruited from January 2017 to August 2018 [tetracaine + propofol group (n=53); propofol group (n=48)]. RESULTS: Results showed that tetracaine combined with propofol anesthesia could effectively reduce the dose of propofol during surgery, ensure the quality of follicles, effectively reduce the postoperative pain and improve the operational satisfaction without affecting the prognosis. CONCLUSIONS: Our findings provide evidence for further clinical applications of this technique.

microRNA-196a promotes osteogenic differentiation and inhibit adipogenic differentiation of adipose stem cells via regulating ß-catenin pathway.

microRNAs play important roles in proliferation and differentiation of stem cells, but mechanisms by which microRNAs regulate osteogenic or adipogenic differentiation of adipose stem cells (ASCs) are still poorly understood. In the present study, results showed up-regulation of microRNA-196a was able to promote the osteogenic differentiation of ACSs, but down-regulation of microRNA-196a induced adipogenic differentiation. Further investigation indicated microRNA-196a could regulate Wnt signaling pathway to affect osteogenic or adipogenic differentiation of ASCs, addition of Wnt agonist 1 was able to reverse the down-regulated osteogenic differentiation of ASCs caused by microRNA-196a deficiency and inhibition of Wnt signaling pathway with XAV939 promoted the adipogenic differentiation of ASCs. Taken together, microRNA-196a may regulate Wnt signaling pathway to promote the osteogenic differentiation and inhibit the adipogenic differentiation of ASCs.

Epidermal growth factor promotes proliferation and maintains multipotency of continuous cultured adipose stem cells via activating STAT signal pathway in vitro.

This study aimed to investigate the effects of epidermal growth factor (EGF) on the proliferation and differentiation of adipose stem cells (ASC) during the repeated passaging and probe the underlying signal pathway. Results showed that the Ki67 positive rate remained at a high level, the number of ASCs in G0/G1 phase reduced significantly, but ASCs in G2/M phase and S phase increased markedly in ASCs treated with EGF when compared with ASCs without EGF treatment, indicating that EGF made more ASCs in proliferation phase. The adipogenic capability of ASCs without EGF was compromised when compared with that of ASCs after EGF treatment, although significant difference was not observed. The osteogenic and chondrogenic potencies increased significantly in ASC with EGF treatment indicating EGF could maintain differentiative capacity of ASCs. Gene Set Enrichment Analysis showed EGF upregulated the expression of molecules in the epithelial mesenchymal transition and G2/M checkpoint signal pathways. GeneMANIA database analysis indicated the network interaction between EGF and STAT. EGF receptor (EGFR) inhibitor and STAT3 inhibitor were independently used to validate the role of both pathways in these effects. After inhibition of EGFR or STAT3, the proliferation of ASCs was significantly inhibited, and Western blotting showed EGF was able to markedly increase the expression of EGFR and STAT3. These findings suggest EGF not only promotes the proliferation of ASCs and delays their senescence, but also maintains the differentiation potency of ASCs, which are related to the EGF-induced activation of STAT signal pathway.

Comparison of the cervista HPV HR test and luminex XMAP technology for the diagnosis of cervical intraepithelial neoplasia.

OBJECTIVES: This study was designed to compare the Cervista high risk (HR) human papillomavirus (HPV) test with Luminex XMAP technology for the detection of the relationship between HPV infection and cervical intraepithelial neoplasia. METHODS: In total, 3280 patients in a cervical specialty clinic were divided into two groups for either Cervista (1855 patients) or Luminex (1425 patients). Subsequent colposcopy examinations were performed in 1270 women with cytologic results showing ASCUS or higher level lesions. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated. RESULTS: The positive rates of the Cervista and Luminex groups were 61.48% and 67.43%, respectively, and occurrence in those 30-40 years old was most common. The typing of HPV showed that A9 positive cases were the most prevalent genotype (33.53%), followed by A5/A6 (16.44%) and A7 (11.37%) in the Cervista group, and HPV-16 was the most prevalent genotype (25.81%), followed by HPV-18 (18.6%) and HPV-31 (8.6%) in the Luminex group. Moreover, the overall concordance rate was 96.26% (95% confidence interval, 93.51-99.00%) in the 187 women with cytologic results of ASCUS or higher. There were no significant differences in the positive rates of HPV between the Cervista and Luminex groups, and both had a high sensitivity and NPV. CONCLUSIONS: The results showed a high good concordance between the two methods in diagnostic accuracy. Among the patients in the cervical specialty clinic, both the A9 group of HPV and HPV-16 showed the highest positive rate. Cervista and Luminex shared similar a clinical value in the detection of CIN2 or higher.