Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis.

BACKGROUND: Gastric cancer (GC) is a digestive system cancer with a high mortality rate globally. Previous experiences and studies have provided clinicians with ample evidence to diagnose and treat patients with reasonable therapeutic options. However, there remains a need for sensitive biomarkers that can provide clues for early diagnosis and prognosis assessment. RESULTS: We found 610 independent prognosis-related 5'-cytosine-phosphate-guanine-3' (CpG) sites (P < 0.05) among 21,121 sites in the training samples. We divided the GC samples into seven clusters based on the selected 610 sites. Cluster 6 had relatively higher methylation levels and high survival rates than the other six clusters. A prognostic risk model was constructed using the significantly altered CpG sites in cluster 6 (P < 0.05). This model could distinguish high-risk GC patients from low-risk groups efficiently with the area under the receiver operating characteristic curve of 0.92. Risk assessment showed that the high-risk patients had poorer prognosis than the low-risk patients. The methylation levels of the selected sites in the established model decreased as the risk scores increased. This model had been validated in testing group and its effectiveness was confirmed. Corresponding genes of the independent prognosis-associated CpGs were identified, they were enriched in several pathways such as pathways in cancer and gastric cancer. Among all of the genes, the transcript level of transforming growth factor ß2 (TGFß2) was changed in different tumor stages, T categories, grades, and patients' survival states, and up-regulated in patients with GC compared with the normal. It was included in the pathways as pathways in cancer, hepatocellular carcinoma or gastric cancer. The methylation site located on the promoter of TGFß2 was cg11976166. CONCLUSIONS: This is the first study to separate GC into different molecular subtypes based on the CpG sites using a large number of samples. We constructed an effective prognosis risk model that can identify high-risk GC patients. The key CpGs sites or their corresponding genes such as TGFß2 identified in this research can provide new clues that will enable gastroenterologists to make diagnosis or personalized prognosis assessments and better understand this disease.

Increased expression of YTHDF1 and HNRNPA2B1 as potent biomarkers for melanoma: a systematic analysis.

BACKGROUND: The incidence and mortality of melanoma is increasing around the world. To deeply explain the mechanism insight into it, we conducted a systematic analysis to examine the levels of regulatory genes of the common RNA epigenetic modification-N6-methyladenosine (m6A) in patients with melanoma compared by the healthy. METHODS: We analyzed the expression of m6A Eraser, Writer, and Reader genes based on publicly available datasets on Oncomine and validated the results with a gene expression omnibus dataset. Hub genes were identified with Cytohubba and the frequency of copy number alterations was analyzed with the cBioPortal tool. RESULTS: The results revealed the up-regulation of YTHDF1 and HNRNPA2B1 in melanoma. Combining the two genes improved the efficacy in diagnosing melanoma by about 10% compared to each gene alone. Hub genes identified with four analysis methods were compared and the overlapping genes were selected. These genes were enriched in several gene ontology terms. Genes related to p53-signaling consisted of CDK2, CDK1, RRM2, CCNB1, and CHEK1. All five genes were positively correlated with either YTHDF1 or HNRNPA2B1, suggesting that both genes may affect m6A modification by the five genes, further up-regulating their expression and facilitate their roles in inhibiting p53 to suppress tumorigenesis. We also observed major mutations in YTHDF1 and HNRNPA2B1 that led to their amplification in melanoma. Significant differences were observed in the clinical characteristics of patients with altered and unaltered m6A regulatory genes such as tumor stage and treatment response. CONCLUSIONS: We, for the first time, identified a combination of m6A regulatory genes to diagnose melanoma. We also analyzed m6A-related genes more comprehensively based on systematic complete data. We found that YTHDF1 and HNRNPA2B1 were altered in melanoma and might influence the development of the disease through signaling pathways such as p53.

Metaproteomics characterizes human gut microbiome function in colorectal cancer.

Pathogenesis of colorectal cancer (CRC) is associated with alterations in gut microbiome. Previous studies have focused on the changes of taxonomic abundances by metagenomics. Variations of the function of intestinal bacteria in CRC patients compared to healthy crowds remain largely unknown. Here we collected fecal samples from CRC patients and healthy volunteers and characterized their microbiome using quantitative metaproteomic method. We have identified and quantified 91,902 peptides, 30,062 gut microbial protein groups, and 195 genera of microbes. Among the proteins, 341 were found significantly different in abundance between the CRC patients and the healthy volunteers. Microbial proteins related to iron intake/transport; oxidative stress; and DNA replication, recombination, and repair were significantly alternated in abundance as a result of high local concentration of iron and high oxidative stress in the large intestine of CRC patients. Our study shows that metaproteomics can provide functional information on intestinal microflora that is of great value for pathogenesis research, and can help guide clinical diagnosis in the future.

Increased CD200 levels in peripheral blood mononuclear cells of patients with primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with an unknown etiology. CD200 is associated with many autoimmune diseases, but little is known about its role in pSS. This study aims to correlate the expression of CD200 with pSS and evaluate its significance. METHODS: Plasma CD200, CD200R, and interleukin (IL)-17 levels were measured and analyzed by enzyme-linked immunosorbent assay. Messenger RNA levels of CD200 and CD200R in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). Following pretreatment of CD200-Fc, the protein levels of IL-17A were measured in PBMCs from patients and healthy controls. RESULTS: Results showed that, compared to CD200 in healthy controls, the relative levels in PBMCs from pSS were greater than 2-fold. In addition, CD200 levels in plasma positively correlated with IL-17 levels, as well as between plasma CD200 and pSS activity indexes (including immunoglobulin G and European League Against Rheumatism SS Disease Activity Index). While CD200R levels were significantly decreased in pSS patients, no correlation could be found. Furthermore, the protein level of IL-17 decreased after pretreatment of CD200-Fc in PBMCs from pSS patients. CONCLUSION: Our results suggested that the CD200/CD200R pathway is involved in pSS pathogenesis. It is hypothesized that regulation of IL-17 expression affects Th17 differentiation. This newly discovered pathway could give rise to a novel targeted therapy for pSS.

Nanoporous silica coupled MALDI-TOF MS detection of Bence-Jones proteins in human urine for diagnosis of multiple myeloma.

Bence-Jones protein is a biomarker in urine for multiple myeloma. Traditional methods for urine Bence-Jones protein detection are either less-sensitive or laborious. Herein, we describe a new method for the detection of urine Bence-Jones protein using nanoporous materials and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Macroporous ordered silica foams (MOSF) were used to enrich proteins in urine, and then the materials-proteins composites were analyzed by MALDI-TOF MS. Based on the presence of specific mass spectrometric signals, Bence-Jones protein can be detected for the diagnosis of multiple myeloma. Twenty-one clinical positive and twenty-seven clinical negative urine samples were analyzed by the method. High sensitivity (95.24%, 20/21) and specificity (100%, 27/27) for the diagnosis of multiple myeloma were achieved. Compared to other methods for multiple myeloma diagnosis, e.g. immunofixation electrophoresis and immunonephelometry, our approach is more rapid, economical and convenient, which can be a new choice for the clinical diagnosis of Bence-Jones protein related diseases.

Autoantibody detection is not recommended for chronic pancreatitis: a cross-sectional Study of 557 patients.

BACKGROUND: Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown. METHODS: Hospitalized patients with non-AIP CP from January 2010 to October 2016 were detected for 22 autoantibodies at the time of hospital admission. Autoantibodies with frequency > 0.5% were enrolled to calculate the frequency in historial healthy controls through literature search in PubMed. Differentially expressed autoantibodies were determined between patients and historial healthy controls, and related factors were identified by multivariate logistic regression analysis. RESULTS: In a total of 557 patients, 113 cases were detected with 19 kinds of positive autoantibodies, among them anti-ß2-glycoprotein I (ß2-GPI) antibody was most frequent (9.16%). Compared with historial healthy controls, the frequencies of serum ß2-GPI and anti SS-B antibody in patients were significantly higher, while frequencies of anti-smooth muscle antibody and anticardiolipin antibody were significantly lower (all P < 0.05). Multivariate logistic regression analysis result showed that diabetes mellitus (OR = 2.515) and common bile duct stricture (OR = 2.844) were the risk factors of positive ß2-GPI antibody in patients while diabetes mellitus in first-/second-/third-degree relatives (OR = 0.266) was the protective factor. There were no related factors for other three differentially expressed autoantibodies. CONCLUSIONS: Four autoantibodies were expressed differentially between patients with non-AIP CP and historial healthy controls. Due to limited significance for diagnosis and treatment of chronic pancreatitis, autoantibodies detection is not recommended conventionally unless suspected of AIP.

Magnetic-bioluminescent-nanoliposomes for ultrasensitive and portable detection of protein biomarkers in blood.

Protein biomarkers play an important role in the diagnosis and treatment of disease. Herein, we report an ultrasensitive magnetic-bioluminescent-nanoliposome based technique using a portable ATP luminometer for the point-of-care testing (POCT) of protein biomarkers in blood. In this study, we use alpha-fetoprotein (AFP, a protein biomarker associated with hepatocellular carcinoma) as a model protein. The bioluminescent nanoliposomes conjugated to magnetic particles (LBM) enabled target protein capture, isolation and detection. In this assay, we use a portable magnetic bead separation pen to simplify the steps. The output RLUs (relative light units) had a linear correlation with AFP concentration between 0.05 and 1000 ng/mL, with a limit of detection of 0.016 ng/mL. Our LBM assay for AFP based on the portable luminometer exhibited high specificity for AFP, with no cross-reactivity with other proteins tested at 25 ng/mL. Forty clinical samples (twenty AFP positive and twenty AFP negative) were tested by the LBM assay, and the results were in good agreement with those determined by electrochemiluminescence, with relative deviations of less than 10%. The successful application of magnetic-bioluminescent-nanoliposomes with a portable ATP luminometer system to detect protein biomarkers in blood has opened a new avenue for biomarker testing. Thus, our LBM assay holds great potential as a POCT assay for use in clinical diagnostics.

An ultrasensitive polydopamine bi-functionalized SERS immunoassay for exosome-based diagnosis and classification of pancreatic cancer.

Early diagnosis and metastasis monitoring for pancreatic cancer are extremely difficult due to a lack of sensitive liquid biopsy methods and reliable biomarkers. Herein, we developed easy-to-prepare and effective polydopamine-modified immunocapture substrates and an ultrathin polydopamine-encapsulated antibody-reporter-Ag(shell)-Au(core) multilayer (PEARL) Surface-Enhanced Raman Scattering (SERS) nano-tag with a quantitative signal of the Raman reporter at 1072 cm-1, which achieved ultrasensitive and specific detection of pancreatic cancer-derived exosomes with a detection limit of only one exosome in 2 µL of sample solution (approximately 9 × 10-19 mol L-1). Furthermore, by analyzing a 2 µL clinical serum sample, the migration inhibitory factor (MIF) antibody-based SERS immunoassay could not only discriminate pancreatic cancer patients (n = 71) from healthy individuals (n = 32), but also distinguish metastasized tumors from metastasis-free tumors, and Tumor Node Metastasis (TNM) P1-2 stages from the P3 stage (the discriminatory sensitivity was 95.7%). Thus, this novel immunoassay provides a powerful tool for the early diagnosis, classification and metastasis monitoring of pancreatic cancer patients.

Abnormal Expression of Long Noncoding RNAs in Primary Immune Thrombocytopenia: A Microarray Related Study.

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) are important regulators of biological processes and they contribute to the pathological developments of various diseases, including autoimmune diseases. To gain the further understanding, we estimate the expression of lncRNAs in primary immune thrombocytopenia (ITP). METHODS: In this study, microarray studies were performed to characterize expression profiles of various lncRNAs and mRNAs in blood samples collected from ITP patients. Quantitative real-time PCR (qRT-PCR) was performed to confirm the results, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and gene ontology analysis were used to provide functional annotations, co-expression network construction (CNC) analysis was made to reveal the relations between lncRNAs and their targeted genes. RESULTS: A total of 1177 and 632 lncRNAs were significantly up-regulated or down-regulated, respectively, in "newly diagnosed ITP" patients versus healthy individuals. In addition, 1182 genes and 737 genes were up-regulated or down-regulated, respectively, in "chronic recurrent ITP" patients versus healthy individuals. In a KEGG analysis, "TNF signaling pathway-Homo sapiens (human)" was a key result. In a gene ontology analysis, "Granulocyte macrophage colony-stimulating factor production (GO: 0032604, ontology: Biological process, P = 1.69577E-05)" and "coreceptor activity (GO: 0015026, ontology: molecular function, P = 4.67594E-06)" were the two most critical results. Data from qRT-PCR and receiver operating characteristic curves further demonstrated that ENST00000440492, ENST00000528366, NR_038920, and ENST00000552576 can efficiently distinguish different stages of ITP, especially NR_038920 and ENST00000528366. In a CNC analysis, four lncRNAs were emphasized, and NR_038920 and ENST00000528366 were both associated with proteins with important roles in autoimmune diseases. CONCLUSIONS: These results suggest that lncRNAs act through targeted genes to mediate their functions and to mediate their functions and affect the pathogenesis of ITP.

Clinical Significance of Decreased Interleukin-35 Expression in Patients with Psoriasis.

In psoriasis, a chronic, recurrent, inflammatory skin disease, CD4+T cells and their related cytokines play an important role in its pathogenesis. The role of interleukin (IL)-35, an immunosuppressive cytokine involved in many autoimmune diseases, is unclear in the pathogenesis of psoriasis. This study evaluated IL-35 expression and clinical significance in psoriasis. Protein and mRNA levels of specified markers were measured by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. Results showed that plasma IL-35 concentrations were lower in patients with psoriasis than in healthy individuals (Z = -6.525, P < .0001). Ebi3 and p35 showed lower mRNA levels in peripheral blood mononuclear cells from patients with psoriasis than in healthy individuals (Z = -5.078, P < .0001, Z = -2.609, P = .009, respectively). The areas under the receiver-operating characteristic (ROC) curves of IL-35, Ebi3, and p35 for patients with psoriasis versus the control were 0.86, 0.78, and 0.64, respectively. Pearson correlation analysis showed that plasma IL-35 expression negatively correlated with interferon-gamma, tumor necrosis factor-alpha, levels of IL-23, -17, and -22, or the Psoriasis Activity and Severity Index and positively correlated with levels of transforming growth factor beta and IL-10 levels in patients with psoriasis. Summarily, IL-35 might mediate psoriasis pathogenesis by influencing the expression of Th1/Th17/Treg -related cytokines and might be a putative target in monitoring or treating psoriasis.

DNase I enzyme-aided fluorescence signal amplification based on graphene oxide-DNA aptamer interactions for colorectal cancer exosome detection.

Exosomes have proved to be an effective cancer biomarker with significant potential, and several cell-specific molecules have been found in colorectal cancer (CRC) exosomes. Nevertheless, it is challenging to use exosomes in clinical lab diagnostics due to their nanoscale and the lack of a convenient and effective detection platform. Here, we developed a DNase I enzyme-aided fluorescence amplification method for CRC exosome detection, based on graphene oxide (GO)-DNA aptamer (CD63 and EpCAM aptamers) interactions. The fluorescence of fluorophore-labeled aptamers quenched by GO, recovered after incubation with samples containing CRC exosomes. The DNase I enzyme digested the single-stranded DNA aptamers on the exosome surface and the exosomes were able to interact with more fluorescent aptamer probes, resulting in an increase of signal amplification. The limit of detection for CRC exosomes is 2.1 × 104 particles/µl. Consequently, a rapid and effective method with high sensitivity was established. The method was verified in 19 clinical blood serum samples to distinguish healthy and CRC patients, showing significant diagnostic power. Moreover, it can be expanded to other kinds of cancer exosomes, in addition to CRC.

Lower Plasma Levels of IL-35 in Patients with Primary Biliary Cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease. Its histological characteristics, such as progressive intrahepatic bile duct destruction, cholestasis, and liver cirrhosis, are caused by the body's autoimmune disorders. Interleukin (IL)-35 has two subunits (p35 and Ebi3) and is a member of the IL-12 family of heterodimeric cytokines. IL-35 has immunosuppressive functions and plays an important role in many autoimmune diseases. In this study, we compared plasma levels of IL-35 and relative mRNA expression levels of p35 and Ebi3 in peripheral blood mononuclear cells (PBMCs) from 70 PBC patients and 70 healthy individuals. The results showed that the relative expression levels of Ebi3 mRNA were lower in PBMCs from PBC patients than in PBMCs from healthy individuals, whereas the levels of p35 mRNA were similar in both groups. Plasma IL-35 concentrations were lower in patients with PBC than in healthy individuals. Plasma levels were higher in PBC patients at an advanced stage compared to patients at an early stage. Variable plasma levels with different stages were also found in transforming growth factor beta (TGF-ß), which is mainly produced by regulatory T cells (Tregs). IL-35 and TGF-ß levels were positively correlated with each other, and IL-35 was capable of promoting the inhibitory functions of Tregs in PBC patients at both the early and late stages of disease. Lower plasma IL-35 levels were accompanied by higher levels of typical clinical parameters, such as alkaline phosphatase, or of proinflammatory cytokines, such as interferon-gamma (IFN-γ), in PBC patients (P < 0.05 for each). We propose that IL-35 may be involved in the pathogenesis of PBC and could be a potential biomarker for diagnosing this disease.

UVB induces apoptosis via downregulation of CALML3-dependent JNK1/2 and ERK1/2 pathways in cataract.

The aim of the current study was to understand the mechanisms of apoptosis occurring in cultured human lens epithelial cells (HLECs) following ultraviolet B (UVB) irradiation. The investigations intended to confirm the presence of apoptosis and to reveal the roles of oxidative stress, calcium (Ca2+), c­Jun NH2­terminal kinase (JNK)1/2, and extracellular signal­regulated kinase (ERK)1/2 signaling pathway in these progresses. Cell apoptosis, ROS generation and intracellular Ca2+ concentration was measured by flow cytometry. The expression of CALML3, caspase-3, Bax, Bcl-2, p-JNK1/2, JNK1/2, p-ERK1/2 and ERK1/2 was measured by RT-qPCR and western blot analysis. Annexin V­fluorescein isothiocyanate/propidium iodide staining demonstrated that UVB irradiation increased the apoptotic rate, reactive oxygen species (ROS) production and intracellular Ca2+ concentration of HLECs in dose­ and time­dependent manners. Overexpression of calmodulin like 3 (CALML3) reversed the effects of UVB irradiation on apoptosis, ROS production and Ca2+ concentration of HLECs, and decreased expressions of caspase­3 and Bax, with increased expressions of Bcl­2. Notably, silencing of CALML3 had similar effects to UVB irradiation and inhibited the activation JNK1/2 and ERK1/2 pathways. Nimodipine, a Ca2+­channel antagonist, significantly attenuated the damages induced by CALML3 downregulation. In conclusion, UVB irradiation induced increase in apoptosis, ROS production and Ca2+ concentration of HLECs, in part, by downregulating the expression of CALML3 and involved oxidative stress, Ca2+, JNK1/2 and ERK1/2 signaling pathways, suggesting that investigating CALML3 may useful for developing cataract treatment.

Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis.

BACKGROUND/AIMS: MicroRNAs (miRNAs) have been described to have important roles in primary immune thrombocytopenia (ITP). To gain additional understanding, we have now further evaluated the involvement of miRNAs in ITP. METHODS: Microarray experiments were performed to examine the expression profiles of miRNAs and mRNAs in samples from subjects with newly diagnosed ITP (G1), chronic ITP (G2), and normal controls. The systematic Pipeline of Outlier MicroRNA Analysis framework was applied to identify key miRNAs expressed in the G1 and G2 samples. Quantitative PCR and receiver operator characteristic curves were used to confirm the performance of key miRNAs. RESULTS: Compared with normal controls, 14 miRNAs (12 over-expressed and 2 under-expressed) and 7 over-expressed miRNAs were identified as key in G1 and G2 samples, respectively. miR-106b-5p, miR-200c-3p, and miR-92a-3p exhibited significantly different expression profiles among the groups. In particular, miR-106b-5p and miR-200c-3p were expressed at higher levels in patients with ITP compared to the normal controls. Furthermore, these two miRNAs expressions were even higher in patients with chronic ITP. CONCLUSION: MiR-106b-5p and miR-200c-3p may represent valuable biomarkers of ITP, although further studies are needed to confirm and assess the value of these potential biomarkers at various stages of ITP.

Nano-biotinylated liposome-based immunoassay for the ultrasensitive detection of protein biomarker in urine.

With the development of proteomics and the continuous discovery of biomarkers of trace proteins, it is important to accurately quantify low abundance protein, especially in urine for clinical diagnostics. In this paper, we reported a novel nano-biotinylated liposome-based immuno-loop-mediated isothermal amplification (LI-LAMP) for the ultrasensitive detection of REG1A (a biomarker for pancreatic ductal adenocarcinoma (PDAC) in urine) with high specificity. The detection range was 1µg/mL to 1fg/mL, with a detection limit of 1fg/mL, and no cross-reactivity was observed to occur in this assay. Compared with the amount of REG1A added, REG1A recovery using this method was 130% and 89%. Detection of REG1A concentrations using the LI-LAMP assay from real samples were in good agreement with those determined using ELISA, and relative deviations were not more than 10%. LI-LAMP shows good potential as a clinical diagnostic assay.

Identification and validation of PSAT1 as a potential prognostic factor for predicting clinical outcomes in patients with colorectal carcinoma.

The aim of the present study was to explore the existence of known or candidate drug-target genes that are upregulated in colorectal cancer (CRC) and may serve as novel prognostic factors or therapeutic targets for this type of malignancy. An in silico analysis was conducted using the Oncomine tool to compare the expression levels of a list of drug-target genes between cancerous and normal tissues in 6 independent CRC cohorts retrieved from the Oncomine database. Phosphoserine aminotransferase 1 (PSAT1) was identified as the top-ranked upregulated gene in CRC tumors, and was highly expressed in patients with chemoresistant disease. Subsequently, the expression of PSAT1 was further experimentally validated using immunohistochemistry in an independent cohort of CRC specimens. The immunohistochemistry results demonstrated that PSAT1 was overexpressed in the CRC tissues compared with the normal colorectal tissues, which was consistent with the previous in silico analysis. Furthermore, PSAT1 overexpression was associated with response to irinotecan, 5-fluorouracil and leucovorin chemotherapy, and with shorter survival time, and retained significance as an independent prognostic factor for CRC when subjected to the multivariate analysis with a Cox's proportional hazards model. Therefore, the present results implicate PSAT1 as a potential prognostic biomarker and a promising therapeutic target for CRC. Targeted PSAT1 inhibition in the treatment of CRC warrants further investigation.

Extent of agreement between the body fluid model of Sysmex XN-20 and the manual microscopy method.

BACKGROUND: Although the correlations concerning cellular component analysis between the Sysmex XN-20 body fluid (BF) model and manual microscopy have been investigated by several studies, the extent of agreement between these two methods has not been investigated. METHODS: A total of 90 BF samples were prospectively collected and analyzed using the Sysmex XN-20 BF model and microscopy. The extent of agreement between these two methods was evaluated using the Bland-Altman approach. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of high-fluorescence (HF) BF cells for malignant diseases. RESULTS: The agreements of white blood cell (WBC), red blood cell (RBC), and percentages of neutrophils, lymphocytes, and monocytes between the Sysmex XN-20 BF model and manual microscopy were imperfect. The areas under the ROC curves for absolute and relative HF cells were 0.67 (95% confidence interval [CI]: 0.56-0.78) and 0.60 (95% CI: 0.48-0.72), respectively. CONCLUSION: Due to the Sysmex XN-20 BF model's imperfect agreement with manual microscopy and its weak diagnostic accuracy for malignant diseases, the current evidence does not support replacing manual microscopy with this model in clinical practice.

Oridonin Suppresses Proliferation of Human Ovarian Cancer Cells via Blockage of mTOR Signaling.

Oridonin, an ent-kaurane diterpenoid compound isolated from the traditional Chinese herb Rabdosia rubescens, has shown various pharmacological and physiological effects such as anti-tumor, anti-bacterial, and anti-inflammatory properties. However, the effect of oridonin on human ovarian cancer cell lines has not been determined. In this study, we demonstrated that oridonin inhibited ovarian cancer cell proliferation, migration and invasion in a dose-dependent manner. Furthermore, we showed oridonin inhibited tumor growth of ovarian cancer cells (SKOV3) in vivo. We then assessed mechanisms and found that oridonin specifically abrogated the phosphorylation/activation of mTOR signaling. In summary, our results indicate that oridonin is a potential inhibitor of ovarian cancer by blocking the mTOR signaling pathway.