BIRC5 facilitates cisplatin-chemoresistance in a m6 A-dependent manner in ovarian cancer.

Cisplatin-based chemotherapy is the standard treatment for metastatic ovarian cancer (OC). However, chemoresistance continues to pose significant clinical challenges. Recent research has highlighted the baculoviral inhibitor of the apoptosis protein repeat-containing 5 (BIRC5) as a member of the inhibitor of the apoptosis protein (IAP) family. Notably, BIRC5, which has robust anti-apoptotic capabilities, is overexpressed in numerous cancers. Its dysfunction has been linked to challenges in cancer treatment. Yet, the role of BIRC5 in the chemoresistance of OC remains elusive. In our present study, we observed an upregulation of BIRC5 in cisplatin-resistant cell lines. This upregulation was associated with enhanced chemoresistance, which was diminished when the expression of BIRC5 was silenced. Intriguingly, BIRC5 exhibited a high number of N6-methyladenosine (m6 A) binding sites. The modification of m6 A was found to enhance the expression of BIRC5 by recognizing and binding to the 3'-UTR of mRNA. Additionally, the insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was shown to stabilize BIRC5 mRNA, synergizing with METTL3 and intensifying chemoresistance. Supporting these in vitro findings, our in vivo experiments revealed that tumors were significantly smaller in size and volume when BIRC5 was silenced. This reduction was notably counteracted by co-silencing BIRC5 and overexpressing IGF2BP1. Our results underscored the pivotal role of BIRC5 in chemoresistance. The regulation of its expression and the stability of its mRNA were influenced by m6 A modifications involving both METTL3 and IGF2BP1. These insights presented BIRC5 as a promising potential therapeutic target for addressing cisplatin resistance in OC.

Genome editing mRNA nanotherapies inhibit cervical cancer progression and regulate the immunosuppressive microenvironment for adoptive T-cell therapy.

CRISPR/Cas9-based genome editing is promising for therapy of cervical cancer by precisely targeting human papillomavirus (HPV). To develop CRISPR/Cas9-based genome editing nanotherapies, a pH-responsive hybrid nonviral nanovector was constructed for co-delivering Cas9 mRNA and guide RNAs (gRNAs) targeting E6 or E7 oncogenes. The pH-responsive nanovector was fabricated using an acetalated cyclic oligosaccharide (ACD), in combination with low molecular weight polyethyleneimine. Thus obtained hybrid ACD nanoparticles (defined as ACD NP) showed efficient loading for both Cas9 mRNA and E6 or E7 gRNA, giving rise to two pH-responsive genome editing nanotherapies E6/ACD NP and E7/ACD NP, respectively. Cellularly, ACD NP exhibited high transfection but low cytotoxicity in HeLa cervical carcinoma cells. Also, efficient genome editing of target genes was achieved in HeLa cells, with minimal off-target effects. In mice bearing HeLa xenografts, treatment with E6/ACD NP or E7/ACD NP afforded effective editing of target oncogenes and considerable antitumor activities. More importantly, treatment with E6/ACD NP or E7/ACD NP notably promoted CD8+ T cell survival by reversing the immunosuppressive microenvironment, thereby leading to synergistic antitumor effects by combination therapy using the gene editing nanotherapies and adoptive T-cell transfer. Consequently, our pH-responsive genome editing nanotherapies deserve further development for the treatment of HPV-associated cervical cancer, and they can also serve as promising nanotherapies to improve efficacies of other immune therapies against different advanced cancers by regulating the immunosuppressive tumor microenvironment.

A Prognostic Signature for Colon Adenocarcinoma Patients Based on m6A-Related lncRNAs.

N6-methyladenosine (m6A) modification is a common epigenetic modification. It is reported that lncRNA can be regulated by m6A modification. Previous studies have shown that lncRNAs associated with m6A regulation (m6A-lncRNAs) serve as ideal prognostic biomarkers. However, whether lncRNAs are involved in m6A modification in colon adenocarcinoma (COAD) needs further exploration. The objective of this study was to construct an m6A-lncRNAs-based signature for patients with COAD. We obtained the RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was employed to recognize lncRNAs associated with m6A regulation (m6A-lncRNAs). 24 prognostic m6A-lncRNAs was identified by univariate Cox regression analysis. Gene set enrichment analysis (GSAE) was used to investigate the potential cellular pathways and biological processes. We have also explored the relationship between immune infiltrate levels and m6A-lncRNAs. Then, a predictive signature based on the expression of 13 m6A-lncRNAs was constructed by the Lasso regression algorithm, including UBA6-AS1, AC139149.1, U91328.1, AC138207.5, AC025171.4, AC008760.1, ITGB1-DT, AP001619.1, AL391422.4, AC104532.2, ZEB1-AS1, AC156455.1, and AC104819.3. ROC curves and K M survival curves have shown that the risk score has a well-predictive ability. We also set up a quantitative nomogram on the basis of risk score and prognosis-related clinical characteristics. In summary, we have identified some m6A-lncRNAs that correlated with prognosis and tumor immune microenvironment in COAD. In addition, a potential alternative signature based on the expression of m6A-lncRNAs was provided for the management of COAD patients.

Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis.

The present work focused on exploring the role and underlying molecular mechanism of action of the non-coding RNA (miRNA/circRNA) in colorectal cancer (CRC). Here, we found that miR-653 was dramatically upregulated in CRC tissues and cells. CRC Patients with high miR-653 level possessed poor prognosis. miR-653 elevated proliferation, migration, and invasion, meanwhile suppressed apoptosis of CRC cells. Furthermore, circSETD3 directly sponged miR-653 and negatively regulate miR-653 to affect proliferation, migration, invasion, and apoptosis of CRC cells. Moreover, miR-653 served as carcinoma-promoting gene via targeting KLF6, and circSETD3 knockdown significantly reversed the inhibitory effect of KLF6 overexpression on CRC cells. In addition, hypoxia obviously increased expression of miR-653. Knockdown of miR-653 decreased the effects of hypoxia on CRC cell proliferation, migration and invasion. Taken together, these findings indicated that circSETD3/miR-653/KLF6 axis may be an effective therapeutic target for CRC patients.

Influence of Topographic Factors on the Characteristics of Gully Systems in Mountainous Areas of Ningnan Dry-Hot Valley, SW China.

A gully system is an important indicator that reflects the development of regional topography and landforms, and topography is one of the most important factors affecting the development of gullies. However, at present, research on the impact of topography on the development of gully systems in the mountainous area of Ningnan dry-hot valley still needs to be strengthened. In order to study the characteristics of gullies and the influence of topography on the development of gully systems, based on both the visual interpretation of remote sensing images and field investigations, five topographic factors (elevation, slope gradient, aspect, relief, and dissection) were employed and three gully erosion indexes (gully length, density, and frequency) were calculated. The geographical information system was used in this study to carry out the spatial analysis, Ward's hierarchical clustering and correlation analysis. Results showed that the development of gully systems is greatly affected by the degree of relief and dissection, and there is a significant positive correlation (p < 0.01; p < 0.05), while elevation, slope gradient and aspect have little influence on it. Analysis of the gully systems showed that the gully erosion is the most intense in the area with an elevation of 2800−3200 m and slope gradients ≥ 38°. Furthermore, the degree of erosion on shady slopes was greater than that on sunny slopes. These results will help us to understand the spatial distribution and formation of gully systems in mountainous areas.

Molecular characterization of matrix metalloproteinase gene family across primates.

Deregulation of matrix metalloproteinases (MMPs) contributes considerably to cancers, psychiatric disorders, macular degeneration and bone diseases. The use of humans in the development of MMPs as prognostic biomarkers and therapeutic targets is complicated by many factors, while primate models can be useful alternatives for this purpose. Here, we performed genome-enabled identification of putative MMPs across primate species, and comprehensively investigated the genes. Phylogenetic topology of the MMP family showed each type formulates a distinct clade, and was further clustered to classes, largely agreeing with classification based on biochemical properties and domain organization. Across primates, the excess of candidate sites of positive selection was detected for MMP-19, in addition to 1-3 sites in MMP-8, MMP-10 and MMP-26. MMP-26 showed Ka/Ks value above 1 between human and chimpanzee copies. We observed two copies of MMP-19 in the old-world monkey genomes, suggesting gene duplication at the early stage of or prior to the emergence of the lineage. Furin-activatable MMPs demonstrate the most variable properties regarding Domain organization and gene structure. During human aging, MMP-11 showed gradually decreased expression in testis, so as MMP-2, MMP-14, MMP15 and MMP-28 in ovary, while MMP-7 and MMP-21 showed elevated expression, implying their distinct roles in different reproductive organs. Co-expression clusters were formed among human MMPs both within and across classes, and expression correlation was observed in MMP genes across primates. Our results illuminate the utilization of MMPs for the discovery of prognostic biomarkers and therapeutic targets for aging-related diseases and carry new messages on MMP classification.

LRG1 mediated by ATF3 promotes growth and angiogenesis of gastric cancer by regulating the SRC/STAT3/VEGFA pathway.

BACKGROUND: Increasing evidence indicates that leucine-rich-alpha-2-glycoprotein 1 (LRG1) is associated with multiple malignancies, but whether it participates in gastric cancer (GC) angiogenesis remains unclear. METHODS: The expression levels of LRG1 were assessed in GC samples. Endothelial tube formation analysis, HUVEC migration assay, chorioallantoic membrane assay (CAM), and xenograft tumor model were used to investigate the effect of LRG1 on angiogenesis in gastric cancer. The involvement of activating transcription factor 3 (ATF3) was analyzed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. Western blot and enzyme-linked immunosorbent assay were performed to measure the SRC/STAT3/VEGFA pathway. RESULTS: LRG1 was overexpressed in GC tissues and associated with cancer angiogenesis. In addition, LRG1 markedly promoted GC cell proliferation in vitro and in vivo. Moreover, overexpression of LRG1 could stimulate GC angiogenesis in vitro and in vivo. Then, we identified ATF3 promotes the transcription of LRG1 and is a positive regulator of angiogenesis. Additionally, LRG1 could activate VEGFA expression via the SRC/STAT3/ VEGFA pathway in GC cells, thus contributing to the angiogenesis of GC. CONCLUSIONS: The present study suggests LRG1 plays a crucial role in the regulation of angiogenesis in GC and could be a potential therapeutic target for GC.

A Multimodal Affinity Fusion Network for Predicting the Survival of Breast Cancer Patients.

Accurate survival prediction of breast cancer holds significant meaning for improving patient care. Approaches using multiple heterogeneous modalities such as gene expression, copy number alteration, and clinical data have showed significant advantages over those with only one modality for patient survival prediction. However, existing survival prediction methods tend to ignore the structured information between patients and multimodal data. We propose a multimodal data fusion model based on a novel multimodal affinity fusion network (MAFN) for survival prediction of breast cancer by integrating gene expression, copy number alteration, and clinical data. First, a stack-based shallow self-attention network is utilized to guide the amplification of tiny lesion regions on the original data, which locates and enhances the survival-related features. Then, an affinity fusion module is proposed to map the structured information between patients and multimodal data. The module endows the network with a stronger fusion feature representation and discrimination capability. Finally, the fusion feature embedding and a specific feature embedding from a triple modal network are fused to make the classification of long-term survival or short-term survival for each patient. As expected, the evaluation results on comprehensive performance indicate that MAFN achieves better predictive performance than existing methods. Additionally, our method can be extended to the survival prediction of other cancer diseases, providing a new strategy for other diseases prognosis.

LncRNA RUSC1-AS1 promotes osteosarcoma progression through regulating the miR-340-5p and PI3K/AKT pathway.

Dysregulation of long noncoding RNA (lncRNA) is frequently involved in the progression and development of osteosarcoma. LncRNA RUSC1-AS1 is reported to be upregulated and acts as an oncogene in hepatocellular carcinoma, cervical cancer and breast cancer. However, its role in osteosarcoma has not been studied yet. In the present study, we investigated the role of RUSC1-AS1 in osteosarcoma both in vitro and in vivo. The results showed that the expression of RUSC1-AS1 was significantly upregulated in osteosarcoma cell line U2OS and HOS compared to that in human osteoblast cell line hFOB1.19. Similar results were found in human samples. Silencing RUSC1-AS1 by siRNA significantly inhibited U2OS and HOS cell proliferation and invasion, measured by CCK-8 and transwell assay. Besides, knockdown of RUSC1-AS1 increased cell apoptosis in osteosarcoma cell lines. In addition, RUSC1-AS1 promoted the epithelial-mesenchymal transition (EMT) process of osteosarcoma cells. In vivo experiments confirmed that RUSC1-AS1 knockdown had an inhibitory effect on osteosarcoma tumor growth. Mechanically, we showed that RUSC1-AS1 directly binds to and inhibits miR-340-5p and activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrated that RUSC1-AS1 promoted osteosarcoma development both in vitro and in vivo through sponging to miR-340-5p and activating the PI3K/AKT signaling pathway. Therefore, RUSC1-AS1 becomes a potential therapeutic target for osteosarcoma.

Spatial differentiation of gully clusters based on the regional scale: an example from northeastern China.

Gully erosion represents a serious environmental threat around the world, but their spatial distribution law are unclear at the regional scale. To quantitatively characterize the spatial distribution model of gullies and determine the regularity of regional differentiation, this paper used spatial analyst and statistics method to study the spatial distribution of gullies in 34 sample areas of northeastern China based on interpretations of high-resolution remote sensing images. The results showed that the kernel density could quantitatively describe the continuous spatial clustering of gullies. Gullies in northeastern China had the characteristics of a spatially unbalanced distribution at the scale of the sample area. The average kernel density of the 34 sample areas (Moran's I was 0.43, P¡0.01P < 0.01) also indicated clustering distribution at the regional scale. The horizontal clustering characteristics of gullies exhibited an azonal distribution of being low values in the middle plain and high values on the three mountainous areas. The average kernel density in the southeastern part of the study area was highest (maximum value of 2.38). In the vertical direction, gullies were relatively undeveloped in low- and high-altitude areas, while middle-altitude areas were beneficial to the development of gullies. The effect of height differences on gully development was more significant than altitude. As the height difference increased, gullies tended to be more clustered, which can be expressed by a power function. The results of this study will not only help to understand the regional differentiation characteristics of gullies but will also provide a scientific reference for the study of spatial distribution of gullies in future.

Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer.

Cervical cancer is one of the most common female malignancy that occurs worldwide and is reported to cause over 300,000 deaths in 2018. Autophagy controls the survival and death of cancerous cells by regulating the degradation process of cytoplasm and cellular organelle. In the present study, the differentially expressed autophagy-related genes (ARGs) between healthy and cancerous cervical tissues (squamous cell neoplasms) were obtained using data from GTEx and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology (GO) as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Next, we conducted univariate Cox regression assay and obtained 12 ARGs that were associated with the prognosis of cervical cancer patients. We carried out a multivariate Cox regression analysis and developed six ARG-related prognostic signature for the survival prediction of patients with squamous cell cervical cancer (Risk score = - 0.63*ATG3-0.42*BCL2 + 0.85*CD46-0.38*IFNG+ 0.23*NAMPT+ 0.82*TM9SF1). Following the calculation of risk score using the signature, the patients were divided into high and low-risk groups according to the median value. Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis (P < 0.001). The value for area under the curves corresponding to the receiver operating characteristic (ROC) was 0.740. As observed, the expression of IFNG was negatively associated with lymph node metastasis (P = 0.026), while a high-risk score was significantly associated with increased age (P = 0.008). To further validate the prognostic signature, we carried out a permutation test and confirmed the performance of the risk score. In conclusion, our study developed six ARG-related prognostic signature for patients with squamous cell cervical cancer, which might help in improving the prognostic predictions of such patients.

A novel signature of two long non-coding RNAs in BRCA mutant ovarian cancer to predict prognosis and efficiency of chemotherapy.

BACKGROUND: In this study we aimed to identify a prognostic signature in BRCA1/2 mutations to predict disease progression and the efficiency of chemotherapy ovarian cancer (OV), the second most common cause of death from gynecologic cancer in women worldwide. METHODS: Univariate Cox proportional-hazards and multivariate Cox regression analyses were used to identifying prognostic factors from data obtained from The Cancer Genome Atlas (TCGA) database. The area under the curve of the receiver operating characteristic curve was assessed, and the sensitivity and specificity of the prediction model were determined. RESULTS: A signature consisting of two long noncoding RNAs(lncRNAs), Z98885.2 and AC011601.1, was selected as the basis for classifying patients into high and low-risk groups (median survival: 7.2 years vs. 2.3 years). The three-year overall survival (OS) rates for the high- and low-risk group were approximately 38 and 100%, respectively. Chemotherapy treatment survival rates indicated that the high-risk group had significantly lower OS rates with adjuvant chemotherapy than the low-risk group. The one-, three-, and five-year OS were 100, 40, and 15% respectively in the high-risk group. The survival rate of the high-risk group declined rapidly after 2 years of OV chemotherapy treatment. Multivariate Cox regression associated with other traditional clinical factors showed that the 2-lncRNA model could be used as an independent OV prognostic factor. Analyses of data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) indicated that these signatures are pivotal to cancer development. CONCLUSION: In conclusion, Z98885.2 and AC011601.1 comprise a novel prognostic signature for OV patients with BRCA1/2 mutations, and can be used to predict prognosis and the efficiency of chemotherapy.

Alteration of tumor associated neutrophils by PIK3CA expression in endometrial carcinoma from TCGA data.

Uterine corpus endometrial carcinoma (UCEC) is one of the most common cancer in female worldwide. PIK3CA has been proven to be a strong prognostic biomarker in UCEC. Nevertheless, current studies have not investigated what effects PIK3CA had on tumor associated neutrophils (TANss). Kaplan-Meier methods were used to compute the survival time of TCGA UCEC patients. GO and KEGG enrichment analysis unveiled relevant pathways PIK3CA affected using DEGs between PIK3CA high expression group and PIK3CA low expression group in TCGA UCEC, as well as GSEA. immune infiltration status was calculated using TIMER. We found that PIK3CA influenced a number of pathways including immune related pathways. The fraction of TANs was certainly altered by PIK3CA expression in UCEC. Our findings suggest that PIK3CA expression may play an important role in tumor immune microenvironment and could alter fraction of TANs in UCEC.

Effect of Bifunctional Montmorillonite on the Thermal and Tribological Properties of Polystyrene/Montmorillonite Nanocomposites.

In this work, the effect of doubly functionalized montmorillonite (MMT) on the structure, morphology, thermal, and tribological characteristics of the resulting polystyrene (PS) nanocomposites was investigated. The modification of the MMT was performed using a cationic surfactant and an anionic surfactant or a silane coupling agent to increase the compatibility with PS matrix. The polystyrene/organo-montmorillonite (PS/OMMT) nanocomposite particles were prepared by soap-free emulsion polymerization. The OMMT was studied using Fourier-transform infrared (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The structural and morphological changes of PS/OMMT nanocomposites were further characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The thermal stability of all the PS/OMMT nanocomposites was higher than that of the pure PS. The anti-wear properties of the polyalphaolefin (PAO) were significantly improved due to the introduction of the PS/OMMT nanocomposite particles. The nanocomposites prepared by a cationic surfactant and a silane coupling agent exhibited the best thermal stability and tribological performance. Our results provide the valuable insights needed to guide the design of lubrication and friction reducing materials.

Correction to: Nanog interaction with the androgen receptor signaling axis induce ovarian cancer stem cell regulation: studies based on the CRISPR/Cas9 system.

AbstractThe original article [1] contains errors in Figs. 6 and 8. The corrected figures can be shown ahead.

Anion amphiphilic random copolymers and their performance as stabilizers for O/W nanoemulsions.

A series of anionic amphiphilic random copolymers with sodium p-styrene sulfonate and dodecyl methacrylate side chains were synthesized via free radical polymerization and their properties in the formation and stabilization of nano-emulsions were investigated. Using poly(sodium p-styrene sulfonate)-ran-poly(dodecyl methacrylate) and Brij 30 as a stabilizer to prepare nanoemulsions, we obtained small droplet size and unimodal distribution nanoemulsions by a low-energy phase inversion composition (PIC) method. The p(SSS)-ran-p(LMA)-Brij 30 co-stabilized nanoemulsions show extraordinary long-term stability and heat resistance, there were almost no variations of droplet size after storing for 35 days and no phase inversion occurred when heating the temperature up to 90 °C. The influence of salinity on the properties of the nanoemulsions was also discussed.

The mechanical properties, microstructures and mechanism of carbon nanotube-reinforced oil well cement-based nanocomposites.

High performance cement-based nanocomposites were successfully fabricated through the use of oil well cement filled with multiwalled carbon nanotubes (MWCNTs) as reinforcements. The dispersibilities of four dispersing agents for the MWCNTs were investigated and compared. The dispersed morphologies and structural characteristics of the MWCNTs were analyzed via TEM, FTIR and Raman spectroscopy studies. The effects of MWCNT addition on the rheological behavior and fluidity of oil well cement slurry were discussed. The mechanical properties of the cement-based nanocomposites with different MWCNT content values and different curing ages were explored and analyzed. Furthermore, the microstructures of the MWCNT reinforced cementitious nanocomposites were characterized via XRD, SEM, EDS, total porosity and pore size distribution studies. The results demonstrated that the 28 day compressive strength and 28 day flexural strength of the 0.05 wt% MWCNT cementitious nanocomposite increased by 37.50% and 45.79%, respectively, compared with a pure cement matrix. The elastic moduli of a 0.05 wt% MWCNT cementitious sample declined by 19.07% and 35.39% under uniaxial and triaxial stress, respectively. XRD and pore structure analysis indicated that the MWCNTs could accelerate the hydration process, increase the amount of hydration products and optimize the pore size distribution within the matrix. Additionally, crack bridging, pulling out, network filling and a calcium-silicate-hydrate (C-S-H) phase were exhibited by SEM images. Meanwhile, the reinforcing and toughening mechanism of MWCNTs was also discussed; these had a beneficial influence on the mechanical properties.

An Efficient Feature Selection Strategy Based on Multiple Support Vector Machine Technology with Gene Expression Data.

The application of gene expression data to the diagnosis and classification of cancer has become a hot issue in the field of cancer classification. Gene expression data usually contains a large number of tumor-free data and has the characteristics of high dimensions. In order to select determinant genes related to breast cancer from the initial gene expression data, we propose a new feature selection method, namely, support vector machine based on recursive feature elimination and parameter optimization (SVM-RFE-PO). The grid search (GS) algorithm, the particle swarm optimization (PSO) algorithm, and the genetic algorithm (GA) are applied to search the optimal parameters in the feature selection process. Herein, the new feature selection method contains three kinds of algorithms: support vector machine based on recursive feature elimination and grid search (SVM-RFE-GS), support vector machine based on recursive feature elimination and particle swarm optimization (SVM-RFE-PSO), and support vector machine based on recursive feature elimination and genetic algorithm (SVM-RFE-GA). Then the selected optimal feature subsets are used to train the SVM classifier for cancer classification. We also use random forest feature selection (RFFS), random forest feature selection and grid search (RFFS-GS), and minimal redundancy maximal relevance (mRMR) algorithm as feature selection methods to compare the effects of the SVM-RFE-PO algorithm. The results showed that the feature subset obtained by feature selection using SVM-RFE-PSO algorithm results has a better prediction performance of Area Under Curve (AUC) in the testing data set. This algorithm not only is time-saving, but also is capable of extracting more representative and useful genes.

Nanog interaction with the androgen receptor signaling axis induce ovarian cancer stem cell regulation: studies based on the CRISPR/Cas9 system.

BACKGROUND: Ovarian cancer stem cells (OCSCs) contribute to the poor prognosis of ovarian cancer. Involvement of the androgen receptor (AR) in the malignant behaviors of other tumors has been reported. However, whether AR associates with Nanog (a stem cell marker) and participates in OCSC functions remain unclear. In this study, we investigated the interaction of Nanog with AR and examined whether this interaction induced stem-like properties in ovarian cancer cells. METHODS: AR and Nanog expression in ovarian tumors was evaluated. Using the CRISPR/Cas9 system, we constructed a Nanog green fluorescent protein (GFP) marker cell model to investigate the expression and co-localization of Nanog and AR. Then, we examined the effect of androgen on the Nanog promoter in ovarian cancer cell lines (A2780 and SKOV3). After androgen or anti-androgen treatment, cell proliferation, migration, sphere formation, colony formation and tumorigenesis were assessed in vitro and in vivo. RESULTS: Both AR and Nanog expression were obviously high in ovarian tumors. Our results showed that Nanog expression was correlated with AR expression. The androgen 5α-dihydrotestosterone (DHT) activated Nanog promoter transcription. Meanwhile, Nanog GFP-positive cells treated with DHT exhibited higher levels of proliferation, migration, sphere formation and colony formation. We also observed that the tumorigenesis of Nanog GFP-positive cells was significantly higher than that of the GFP-negative cells. Xenografts of Nanog GFP-positive cells showed significant differences when treated with androgen or anti-androgen drugs in vivo. CONCLUSIONS: The interaction of Nanog with the AR signaling axis might induce or contribute to OCSC regulation. In addition, androgen might promote stemness characteristics in ovarian cancer cells by activating the Nanog promoter. This finding merits further study because it may provide a new understanding of OCSC regulation from a hormone perspective and lead to the reevaluation of stem cell therapy for ovarian cancer.

[Efficacy and safety of lactulose on the treatment of puerperal constipation].

OBJECTIVE: To observe the therapeutic effects and security of oral lactulose solution on treatment of puerperal constipation. METHODS: A total of 200 patients with puerperal constipation who received regular antenatal cares from early pregnancy in our department and delivered in our hospital from January 2013 to October 2013, were randomly divided into two groups. The patients in control group (n = 100) received defecation habits training, diet management and drinking adequate water etc. The patients in therapy group (n = 100) received 20 ml oral lactulose solution, twice a day and constantly treatment for 4 weeks. The frequency of defecation per week were recorded (including before treatment, period during the treatment, and the first week after finish the whole treatment). The adverse reactions and recurrence of constipation after treatment were analyzed. RESULTS: The frequency of defecation per week in the therapy group was higher than that in the control group at the first week after treatment (t = 2.178, P = 0.869), and significantly increase in the fourth week (t = 8.390, P = 0.000). The efficiency of the lactulose groups was 92%, and the control group was 21% (χ² = 112.530, P = 0.000). The total recurrence of constipation in lactulose group was lower than that in the control group by follow up 120 days (4% vs 18%, χ² = 10.010, P = 0.001). CONCLUSION: Oral lactulose solution is effective and safe for puerperal consipation.