N6-methyladenosine (m 6 A) messenger RNA methylation play important role in cell proliferation and tumorigenicity of endometrial cancer, but the key mechanism is not fully clear. Here, we found that RNA demethylase ALKBH5 expression was significantly upregulated in endometrial cancer, ALKBH5 was then identified to positively regulate proliferation and invasion of endometrial cancer. Mechanistically, the m 6 A eraser ALKBH5 demethylated target transcripts IGF1R and enhanced IGF1R mRNA stability, consequently promoting IGF1R translation and activating IGF1R signaling pathway. Thus, we demonstrated that ALKBH5 promoted proliferation and invasion of endometrial cancer via erasing IGF1R m 6 A-modifications, which suggests a potential therapeutic target for endometrial cancer.
Polycystic ovary syndrome (PCOS) is a common endocrine disease regulated by metabolic disorders, the effective intervention of which depends on diverse phenotypes (e.g., insulin resistance). Serum metabolic fingerprint (SMF) holds promise in characterizing the pathogenesis stress related to diseases; yet, PCOS diagnosis and phenotyping are time‐consuming and challenging due to the lack of an integrated metabolic tool. Here, a nanoparticle‐enhanced laser desorption/ionization mass spectrometry platform is introduced for one‐time serum metabolic fingerprinting and to identify the metabolic heterogeneity associated with obesity in PCOS patients. A decision tree based on the acquired SMFs is constructed, and real‐world simulations on independent internal and external cohorts are performed. The decision tree yields the area under the receiver operating characteristic curves (AUC) of 0.967 for PCOS diagnosis and AUC of 0.898 for phenotyping, respectively. The technical robustness of the “one‐stop shop” decision tree across laboratories is validated for clinical utility. The decision tree aims to improve PCOS management in comparison to clinical assessment, leading to a potential reduction in multiple blood tests and physician workload.
Background: Colposcopy is indispensable for the diagnosis of cervical lesions.However, its diagnosis accuracy for high-grade squamous intraepithelial lesion (HSIL) is at about 50%, and the accuracy is largely dependent on the skill and experience of colposcopists. The advancement in computational power made it possible for the application of artificial intelligence (AI) to clinical problems. Here, we explored the feasibility and accuracy of the application of AI on precancerous and cancerous cervical colposcopic image recognition and classification.
Methods:The images were collected from 6002 colposcopy examinations of normal control, low-grade squamous intraepithelial lesion (LSIL), and HSIL. For each patient, the original, Schiller test, and acetic-acid images were all collected.We built a new neural network classification model based on the hybrid algorithm. EfficientNet-b0 was used as the backbone network for the image feature extraction, and GRU(Gate Recurrent Unit)was applied for feature fusion of the three modes examinations (original, acetic acid, and Schiller test).
Results:The connected network classifier achieved an accuracy of 90.61% in distinguishing HSIL from normal and LSIL. Furthermore, the model was applied to "Trichotomy", which reached an accuracy of 91.18% in distinguishing the HSIL, LSIL and normal control at the same time.
Conclusion:Our results revealed that as shown by the high accuracy of AI in the classification of colposcopic images, AI exhibited great potential to be an effective tool for the accurate diagnosis of cervical disease and for early therapeutic intervention in cervical precancer.
This study investigated the expression of IL-10 and Ki-67 in human cervical cancer and cervical intraepithelial neoplasia (CIN) and the correlation with human papillomavirus infection. A total of 110 patients with cervical lesions undergoing surgical treatment in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine from 2016 to 2017 were selected. Those patients included 36 cases of cervical cancer and 74 cases of CIN. At the same time, 30 cases of chronic cervicitis were selected as the control group. RT-qPCR was used to detect the expression of IL-10 and Ki-67 in cervical tissue. PCR was used to detect HPV infection in cervical tissue. The expression levels of IL-10 and Ki-67 in the cervical cancer and CIN groups were higher than those in the control group. Moreover, the expression levels of IL-10 and Ki-67 in the cervical cancer and CIN II–III groups were higher than those in the CIN I group (P<0.05). In addition, the expression levels of IL-10 and Ki-67 in the cervical cancer group were significantly higher than those in the CIN II–III group. Furthermore, the expression levels of IL-10 and Ki-67 were positively correlated with HPV infection (r=0.783 or 0.712, P<0.05). Finally, the expression levels of IL-10 and Ki-67, and HPV infection in the cervical lesions studied were significantly different. Therefore, combined detection of IL-10, Ki-67 and HPV infection can improve the diagnosis of CIN and early cervical cancer.
Cervical cancer is a unique and common malignancy that occurs in women. Britannin has been proven to inhibit the progression of human liver and breast cancers. However, its efficacy in cervical cancer is still unclear. Human cervical squamous cell carcinoma SiHa cells were used to analyze
the effect of britannin administration on cervical tumors by xenotransplantation of human tumor cells. The Cell Counting Kit-8 was used to determine the half maximal inhibitory concentration (IC50) of britannin on SiHa, and the cell invasion ability was measured using Transwell
invasion assay. Cell migration was measured using the scratch-healing assay, while the clonogenic assay was performed to determine cell proliferation. Dichloro-dihydro-fluorescein diacetate was used to label reactive oxygen species (ROS) in cells or tissues. Intracellular autophages were stained
with monodansylcadaverine. Western blotting assisted by nanomagnetic beads was performed to study the expression of p62, light chain 3 beta (LC3B), Beclin 1, and autophagy-related protein 5 (ATG5) in cells or tissues, as well as the phosphorylation of AMP-activated protein kinase (AMPK) and
unc-51-like autophagy activating kinase 1 (ULK1). Hematoxylin and eosin staining was performed to analyze the pathological changes in the tumor cells. The expression of Ki-67, B-cell lymphoma 2 (Bcl-2), and Bax in the tumor cells was analyzed by immunohistochemistry. The IC50 obtained
for britannin against SiHa was 10.01 μM. Britannin inhibited the proliferation, invasion, and migration of SiHa cells, and promoted the generation and autophagy of ROS in tumor cells and tissues. Furthermore, p-AMPK/AMPK and p-ULK1/ULK1, LC3B, Beclin 1, and ATG5 were upregulated,
whereas p62 was downregulated in cells and tissues. Tumor development was inhibited; tissue inflammation was reduced; Ki-67 and Bcl-2 expression was downregulated; and Bax expression was upregulated. The expression of cleaved caspase-3, cleaved poly-ADP-ribose polymerases, and voltage-dependent
anion-selective channel 1 was upregulated. These effects can be partially reversed by the AMPK inhibitor dorsomorphin dihydrochloride (BML-275). In vivo and in vitro studies showed that britannin upregulated the of ROS content of human cervical squamous cell carcinoma cells,
leading to significant autophagy, thereby inhibiting the occurrence and development of cervical squamous cell carcinoma. The mechanism may be related to the ROS/AMPK/ULK1 signaling pathway.
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