O­GlcNAcylation mediates endometrial cancer progression by regulating the Hippo­YAP pathway.

The incidence of endometrial cancer (EC) is rapidly increasing worldwide. The majority of endometrial cancers are diagnosed at an early stage and are associated with a good prognosis; however, patients with advanced­stage EC have a poor prognosis and present with invasive metastasis. The mechanisms responsible for the invasion and metastasis of endometrial cancer remain unknown. Here, the present study aimed to examine the effects of O­GlcNAcylation on the malignancy of EC and its association with Yes­associated protein (YAP). It was found that the expression of O­GlcNAc transferase (OGT) and O­GlcNAcylation were increased in EC tissues; the decrease in O­GlcNAcylation levels was found to lead to the decreased proliferation, migration and invasion of EC cells. Mass spectrometric analysis revealed that OGT knockdown reduced the O­GlcNAcylation of YAP. Furthermore, it was found that the reduction in the O­GlcNAcylation of YAP promoted its phosphorylation, which in turn inhibited the access of YAP to the nucleus and downstream target gene activation, demonstrating that the level of O­GlcNAcylation affects the development of EC. On the whole, the findings of the present study indicate that YAP is a key molecule linking the O­GlcNAcylation and Hippo pathways, which together regulate the progression of EC.

LMNB1 deletion in ovarian cancer inhibits the proliferation and metastasis of tumor cells through PI3K/Akt pathway.

Ovarian cancer (OC) is a common malignant tumor in gynecology. LMNB1 is an important component of the nuclear skeleton. The expression of LMNB1 in ovarian cancer is significantly higher than that in normal tissues, but its role in tumor still needs comprehensive investigation. In this study, we overexpressed and knocked down LMNB1 in ovarian cancer cells and explore the effect of LMNB1 on the cell proliferation, migration and the underlying mechanism. We analyzed the expression levels of LMNB1 in ovarian cancer and their clinical relevance by using bioinformatics methods, qRT-PCR, Western blot and immunohistochemistry. To state the effect and mechanism of LMNB1 on OC in vitro and in vivo, we performed mouse xenograft studies, CCK8, cloning formation, Edu incorporation, wound healing, transwell and flow cytometry assay in stable LMNB1 knockdown OC cells, following by RNA-seq. Overexpression of LMNB1 indicates the progression of OC. LMNB1 knockdown inhibited the proliferation and migration of OC cells by suppressing the FGF1-mediated PI3K-Akt signaling pathway. Our study shows LMNB1 as a novel prognostic factor and therapeutic target in OC.

Procedures and technical considerations of robotic-assisted human uterus transplantation.

BACKGROUND: Uterus transplantation is the only treatment for absolute uterine factor infertility. Complex vascular anatomy, long operation time, and intraoperative injuries are the main factors that limit progress in uterus transplantation. Moreover, robot-assisted uterus transplantation is not popular at present due to technical difficulties, with only a few countries reporting success. METHODS: In this paper, we present the key technical points of robot-assisted uterine transplantation by analyzing and summarizing our surgical experience and other successful cases of robot-assisted uterine transplantation. This study provides an evidence-based reference for clinicians planning robot-assisted uterine transplantation procedures. CONCLUSION: Minimally invasive technologies can shorten the operation time, reduce injuries, and contribute to analyzing the anatomy of complex blood vessels. Therefore, robot-assisted uterine transplantation is an important direction for the future of uterine transplantation, and the findings and procedures reported herein contribute to the standardization and promotion of robot-assisted uterine transplantation operations.

Reduced O-GlcNAcylation of SNAP-23 promotes cisplatin resistance by inducing exosome secretion in ovarian cancer.

Exosomes have been associated with chemoresistance in various cancers, but such a role in ovarian cancer is not yet clear. Here, using in vitro cell-based and in vivo mouse model experiments, we show that downregulation of O-GlcNAcylation, a key post-translational protein modification, promotes exosome secretion. This increases exosome-mediated efflux of cisplatin from cancer cells resulting in chemoresistance. Mechanistically, our data indicate that downregulation of O-GlcNAclation transferase (OGT) reduces O-GlcNAclation of SNAP-23. Notably, O-GlcNAcylation of SNAP-23 is vital for regulating exosome release in ovarian cancer cells. Reduced O-GlcNAclation of SNAP-23 subsequently promotes the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of SNAP-23, VAMP8, and Stx4 proteins. This enhances exosome release causing chemoresistance by increasing the efflux of intracellular cisplatin.

Screening and Identification of a Specific Binding Peptide to Ovarian Cancer Cells from a Phage-Displayed Peptide Library.

To select specific binding peptides for imaging and detection of human ovarian cancer. The phage 12-mer peptide library was used to select specific phage clones to ovarian cancer cells. After four rounds of biopanning, the binding specificity of randomly selected phage clones to ovarian cancer cells was determined by enzyme-linked immunosorbent assay (ELISA). DNA sequencing and homology analysis were performed on specifically bound phages. The binding ability of the selected peptides to SKOV3 cells was confirmed by fluorescence microscopy and flow cytometry. After four rounds of optimized biological panning, phage recovery was 34-fold higher than that of the first round, and the specific phage clones bound to SKOV3 cells were significantly enriched. A total of 32 positive phage clones were preliminarily identified by ELISA from 54 randomly selected clones, and the positive rate was 59.3%. S36 was identified as the clone with best affinity to SKOV3 cells via fluorescence microscopy and flow cytometry. A representative clone of OSP2, S36 is expected to be an effective probe for diagnosis and treatment of ovarian cancer.

Classification of Prostate Transitional Zone Cancer and Hyperplasia Using Deep Transfer Learning From Disease-Related Images.

Purpose The diagnosis of prostate transition zone cancer (PTZC) remains a clinical challenge due to their similarity to benign prostatic hyperplasia (BPH) on MRI. The Deep Convolutional Neural Networks (DCNNs) showed high efficacy in diagnosing PTZC on medical imaging but was limited by the small data size. A transfer learning (TL) method was combined with deep learning to overcome this challenge. Materials and methods A retrospective investigation was conducted on 217 patients enrolled from our hospital database (208 patients) and The Cancer Imaging Archive (nine patients). Using T2-weighted images (T2WIs) and apparent diffusion coefficient (ADC) maps, DCNN models were trained and compared between different TL databases (ImageNet vs. disease-related images) and protocols (from scratch, fine-tuning, or transductive transferring). Results PTZC and BPH can be classified through traditional DCNN. The efficacy of TL from natural images was limited but improved by transferring knowledge from the disease-related images. Furthermore, transductive TL from disease-related images had comparable efficacy to the fine-tuning method. Limitations include retrospective design and a relatively small sample size. Conclusion Deep TL from disease-related images is a powerful tool for an automated PTZC diagnostic system. In developing regions where only conventional MR scans are available, the accurate diagnosis of PTZC can be achieved via transductive deep TL from disease-related images.

Neurovascular decoupling in type 2 diabetes mellitus without mild cognitive impairment: Potential biomarker for early cognitive impairment.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for mild cognitive impairment (MCI) and the acceleration of MCI to dementia. The high glucose level induce disturbance of neurovascular (NV) coupling is suggested to be one potential mechanism, however, the neuroimaging evidence is still lacking. To assess the NV decoupling pattern in early diabetic status, 33 T2DM without MCI patients and 33 healthy control subjects were prospectively enrolled. Then, they underwent resting state functional MRI and arterial spin labeling imaging to explore the hub-based networks and to estimate the coupling of voxel-wise cerebral blood flow (CBF)-degree centrality (DC), CBF-mean amplitude of low-frequency fluctuation (mALFF) and CBF- mean regional homogeneity (mReHo). We further evaluated the relationship between NV coupling pattern and cognitive performance (false discovery rate corrected). T2DM without MCI patients displayed significant decrease in the absolute CBF-mALFF, CBF-mReHo coupling of CBFnetwork and in the CBF-DC coupling of DCnetwork. Besides, networks which involved CBF and DC hubs mainly located in the default mode network (DMN). Furthermore, less severe disease and better cognitive performance in T2DM patients were significantly correlated with higher coupling of CBF-DC, CBF-mALFF or CBF-mReHo, especially for the cognitive dimensions of general function and executive function. Thus, coupling of CBF-DC, CBF-mALFF and CBF-mReHo may serve as promising indicators to reflect NV coupling state and to explain the T2DM related early cognitive impairment.