Knockdown of RBM15 inhibits tumor progression and the JAK-STAT signaling pathway in cervical cancer.

BACKGROUND: RNA binding motif protein 15 (RBM15), a writer of N6-methyladenosine (m6A) methylation, contributes significantly to the development of various tumors. However, the function of RBM15 in cervical cancer (CC) has not been determined. METHODS: Based on the GSE9750, GSE63514, and m6A datasets, m6A-related differentially expressed genes (DEGs) were screened out. The hub genes were identified by generating a Protein-Protein Interaction (PPI) network. RT-qPCR was conducted to assess the mRNA expression of hub genes. CCK8, scratch wound healing, and transwell assays were utilized to examine the influence of RBM15 on HeLa and SiHa cells. Tumor xenograft models were used to assess the effects of RBM15 on tumorigenesis. A mechanistic analysis of RBM15 in CC tumors was conducted using the GeneCards and Coxpresdb databases, followed by a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the pathway-related genes were subsequently validated using Western blotting. RESULTS: Five DEGs were screened, including WTAP, RBM15, CBLL1, and YTHDC2. Among them, WTAP, RBM15, CBLL1, and YTHDC2 were hub genes and can be used as biomarkers for CC. RBM15 expression was considerably increased, while WTAP, CBLL1, and YTHDC2 were significantly downregulated. Knockdown of RBM15 significantly suppressed the proliferation, invasion, and migration of CC cells and tumorigenesis. Moreover, knockdown of RBM15 significantly reduced the expression levels of proteins related to the JAK-STAT pathway. CONCLUSIONS: Knockdown of RBM15 inhibited the progression of CC cells, which probably by inhibiting the JAK-STAT pathway pathway.

Calbindin-Expressing CA1 Pyramidal Neurons Encode Spatial Information More Efficiently.

Hippocampal pyramidal neurons (PNs) are traditionally conceptualized as homogeneous population. For the past few years, cumulating evidence has revealed the structural and functional heterogeneity of hippocampal pyramidal neurons. But the in vivo neuronal firing pattern of molecularly identified pyramidal neuron subclasses is still absent. In this study, we investigated the firing patterns of hippocampal PNs based on different expression profile of Calbindin (CB) during a spatial shuttle task in free moving male mice. We found that CB+ place cells can represent spatial information more efficiently than CB- place cells, albeit lower firing rates during running epochs. Furthermore, a subset of CB+ PNs shifted their theta firing phase during rapid-eye movement (REM) sleep states compared with running states. Although CB- PNs are more actively engaged in ripple oscillations, CB+ PNs showed stronger ripple modulation during slow-wave sleep (SWS). Our results pointed out the heterogeneity in neuronal representation between hippocampal CB+ and CB- PNs. Particularly, CB+ PNs encode spatial information more efficiently, which might be contributed by stronger afferents from the lateral entorhinal cortex to CB+ PNs.

Application of serum markers in diagnosis and staging of ovarian endometriosis.

AIMS: Laparoscopic surgery is widely used for diagnosing ovarian endometriosis but it has medical risks. This study explored the application of blood indicators in diagnosis and staging of ovarian endometriosis, aiming to develop a noninvasive diagnostic method. METHODS: A total of 190 ovarian endometriosis patients were included in observation group, among these participants, 77 patients among them were stages I-II, and the rest 113 patients were stages III-IV, and a total of 103 healthy women as control group. Serum biochemical indexes, tumor markers, and cytokines levels in two groups were used for the diagnosis and staging of the disease. Area under the receiver operating characteristic (ROC) curve (AUC) predicted the value of individual and joint tests for indicators. RESULTS: Biochemical indexes, namely, alkaline phosphatase (ALP), total protein (TP), and glucose (Glu) could distinguish patients from normal women; and that ALP and Glu could indicate disease staging. In tumor markers, alpha fetoprotein (AFP), carcinoembryonic antigen (CA) 125, CA199 and human epididymis protein 4 (HE4) helped to diagnose endometriosis; CA125, HE4, and cytokeratin 19 fragment (CYFRA21-1) could differentiate stages. In cytokines, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6, soluble fms-like tyrosine kinase receptor 1 (sflt-1), monocyte chemoattractant protein (MCP)-1 therefore, have values to diagnose endometriosis; VEGF, TNF-α, IL-6, and sflt-1 helped to differentiate disease staging. CONCLUSION: Serological indicators in ovarian endometriosis patients were different from healthy women, which were of certain differential values in diagnosis and disease staging. The current study provided a novel strategy for endometriosis diagnosis.

Silencing of Synuclein-γ inhibits human cervical cancer through the AKT signaling pathway.

BACKGROUND: Synuclein-γ has been demonstrated to be highly expressed in various human cancers including cervical cancer, and has been shown to play a critical role in tumor aggressiveness. We aimed to investigate the role of Synuclein-γ in human cervical cancer in vitro and in vivo. METHOD: Reverse transcription-quantitative polymerase chain reaction assay and Western blot assay were used to detect the mRNA and protein expression, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay were performed to measure the viabilities of cancer cells. Flow cytometry assay was used to detect the cell cycle and apoptosis. Moreover, an animal experiment was performed to evaluate the biological behavior of Synuclein-γ in vivo. RESULTS: In the current study, we found that Synuclein-γ was obviously over-expressed in cervical cancer tissues compared to the adjacent non-cancer tissues. Cervical cancer cells transfected with Synuclein-γ siRNA demonstrated significant inhibition of cancer proliferation (P < 0.01), cell cycle arrest at G0/G1 phase, and cell apoptosis (P < 0.05). Moreover, down-regulation of Synuclein-γ significantly inhibited cervical cancer growth in vivo. In addition, protein levels of AKT, c-Myc and Cyclin D1 were much lower in the Synuclein-γ siRNA-treated groups than that in the control group. CONCLUSIONS: Synuclein-γ inhibition reduced cervical cancer tumor growth through the AKT pathway. This effect represented a therapeutic opportunity and provided a novel target for cervical cancer treatment.

Enhanced chemotherapeutic efficacy of the low-dose doxorubicin in breast cancer via nanoparticle delivery system crosslinked hyaluronic acid.

Despite the development of treatment options in breast cancer, many patients die of recurrence and metastasis. Owing to enhanced permeability and retention in solid tumor tissue, nanoparticle (NP) delivery systems have been emerged as novel strategy in cancer chemotherapy. As extracellular matrix, glycosaminoglycan hyaluronan (HA) could bind its surface receptor adhesion molecule CD44 which is strongly expressed on breast cancer. We have previously reported a doxorubicin (DOX)-loaded HA-Lys-LA X-NPs (X-NP-DOX) NP delivery system for breast cancer treatment. In this study, we further investigated the antitumor effect of X-NP-DOX NP delivery system using low-dose DOX in both in vitro and in vivo systems. We demonstrated that low-dose X-NP-DOX possessed the ability for inhibiting MCF-7 breast cancer cell growth, invasion, and migration, and inducing apoptosis in vitro. In in vivo experiments, injection of low-dose X-NP-DOX into tumor-bearing mouse resulted in significant reduction of tumor size. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining further revealed that low-dose X-NP-DOX induced higher percentage of apoptotic cells compared with free DOX or saline. Furthermore, our study demonstrated that low-dose X-NP-DOX inhibited Notch1 and Ras/MAPK pathways, decreased cancer stem cell population, and reduced tumorigenesis compared to free DOX in both in vitro and in vivo settings. Owing to its enhanced efficacy and higher targetability compared to free DOX, low-dose DOX delivered by NP system may be a promising novel strategy for breast cancer treatment.

[Comparative study on trace elements in natural colored cotton and white cotton].

A method was studied for simultaneous determination of multi-elements in natural colored cotton by microwave digestion and ICP-AES. The contents of Ca, Mg, Fe, Cu, Ba, Zn, Al, Sr, Mn and Si in colored and white cotton were determined by this method. The recovery ratio obtained by standard addition method ranged between 93% and 111%, and the relative standard deviation was below 4% (n = 5). The results showed that the contents of Ca, Cu, Zn, Al, Fe, Sr and Si in green and brown cotton are higher than those in white cotton. The data from the study gives some references for further researches on the colored cotton.