bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of peripheral blood E2F3 mRNA as a potential diagnostic biomarker in human papillary thyroid cancer
Authors: Zhao Yue , Zhao Ziqin , Wu Fengyun , Wang Duoduo , Liu Wei , Gu Yelong , Huang Yuan , Liu Chunrong 
Published: August 2020

Abstract
Background: The transcription factor E2F3 plays a vital role in regulating cell cycle progression and proliferation. In addition, many reports have shown that E2F3 exerts an oncogenic role in various cancers and is a promising therapeutic target for the treatment of some human cancers. However, the value of E2F3 in the molecular diagnosis and prognosis evaluation of papillary thyroid cancer (PTC) has rarely been reported. The aim of this study was to evaluate the clinical signiﬁcance of E2F3 in the early diagnosis and monitoring of PTC.Materials and methods: Peripheral blood samples from 20 patients with PTC, 20 patients with benign thyroid lesions and 20 normal controls were collected. Peripheral blood E2F3 mRNA and thyroid sample E2F3 mRNA expression were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The expression of E2F3 protein in normal thyroid tissue and thyroid tissue from benign thyroid lesions and PTC were detected by immunohistochemistry. The optimal cut-off value for differentiating PTC was obtained by using receiver operating characteristic (ROC) curve analysis.Results: E2F3 mRNA expression levels in peripheral blood and thyroid samples were significantly higher in PTC patients than in patients with benign thyroid lesions and normal subjects (P<0.05). Moreover, benign hyperplasia had higher E2F3 expression than normal tissue (P<0.01).There was no significant association between the level of E2F3 mRNA and aggressive clinicopathologic features of PTC, including TNM staging, extrathyroidal invasion, multifocality, and lymph node metastasis (P>0.05).With a cut-off value of 2.3, blood E2F3 mRNA showed 90% sensitivity, 60.9% specificity, a 70.5% positive predictive value, an 85.47% negative predictive value and 74.4% accuracy for discriminating PTC from benign hyperplasia disease of the thyroid and normal tissue. In addition, immunohistochemical results showed that E2F3 protein expression was also higher in the PTC group than in the other groups.Conclusions: The highest expression of E2F3 was found in peripheral blood and thyroid tissue of PTC patients. Moreover, blood E2F3 mRNA can be considered a promising diagnostic marker for discriminating PTC from benign thyroid diseases.
Long Non-Coding RNA CBR3-AS1 Promotes Stem-Like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p
Authors: Xie Liangbao , Cui Guangfei , Li Tao 
Published: August 2020

Abstract
Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.
Hyperglycemia-Induced MIR-467 Drives Tumor Inflammation And Growth In Breast Cancer
Authors: Gajeton Jasmine , Krukovets Irene , Muppala Santoshi , Verbovetskiy Dmitriy , Zhang Jessica , Stenina-Adognravi Olga 
Published: August 2020

Abstract
Background: Tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation. Methods: We used mouse models of hyperglycemia and cancer and specimens from hyperglycemic breast cancer (BC) patients to demonstrate that miR-467 mediates the effects of high blood glucose on cancer inflammation and growth.Results: Hyperglycemic patients have a higher risk of developing breast cancer (BC). We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (P<.001). Tumors from hyperglycemic mice had a 2-fold increase in macrophage accumulation compared to normoglycemic controls (P<.001), and TAM infiltration was prevented by the miR-467 antagonist (P<.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs normoglycemic patients (2.17-fold, P=.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold inc., P=.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (P<.001) and increased 56-fold in adjacent normal tissue (P=.008). Conclusions: Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.
A Young Female Presented With Massive Pulmonary Embolism Wıth Inferior Vena Cava Thrombus as a Complication of Nephrotic Syndrome: A Case Report
Authors: Jeele Mohamed Osman , Mohamud Mohamed Farah Yusuf , Addow Rukia Omar Barre 
Published: August 2020

Abstract
Nephrotic syndrome (NS); the first described in 1827 as the presence of proteinuria of ≥ 3.5 g/24 hours, albuminemia < 3.0 g, peripheral edema, hyperlipidemia, lipiduria, and increased thrombotic risk which has an incidence of three new cases per 100 000 each year in adults. Nephrotic syndrome had complicated by the induction of a hypercoagulable state with both various venous and arterial thromboembolic events. The pathophysiology of hypercoagulability in the nephrotic syndrome is imbalances of prothrombotic and antithrombotic factors, as well as impaired thrombolytic activity occurs. Here we present, a 19 years old female came to the emergency department with a complaint of chest pain and shortness of breath for three days. The patient quickly diagnosed pulmonary embolism and inferior vena cava thrombosis as a complication of nephrotic syndrome, allowing prompt initiation of anticoagulant therapy. After two weeks of admission, the patient's resolved dramatically, and his laboratory results returned to almost normal, and the patient discharged with Oral Prednisolone, Coumadin, Atorvastatin, and Ramipril. We aim to determine which is the likely cause of pulmonary embolism in patients with the nephrotic syndrome.
Coincidence Analysis: A New Method for Causal Inference in Implementation Science
Authors: Whitaker Rebecca Garr , Sperber Nina , Baumgartner Michael , Thiem Alrik , Cragun Deborah , Damschroder Laura , Miech Edward J. , Slade Alecia , Birken Sarah A. 
Published: August 2020

Abstract
BackgroundImplementation of multifaceted interventions typically involves many diverse elements working together in interrelated ways, including intervention components, implementation strategies, and features of local context. Given this real-world complexity, implementation researchers may be interested in a new mathematical, cross-case method called Coincidence Analysis (CNA) that has been designed explicitly to support causal inference, answer research questions about combinations of conditions that are minimally necessary or sufficient for an outcome, and identify the possible presence of multiple causal paths to an outcome. CNA can be applied as a standalone method or in conjunction with other approaches, and can reveal new empirical findings related to implementation that might otherwise have gone undetected.MethodsWe applied CNA to a publicly available dataset from Sweden with county-level data on human papillomavirus (HPV) vaccination campaigns and vaccination uptake in 2012 and 2014 and then compared CNA results to the published regression findings.ResultsThe original regression analysis found vaccination uptake was positively associated only with the availability of vaccines in schools. CNA produced different findings and uncovered an additional solution path: high vaccination rates were achieved by either (1) offering the vaccine in all schools or (2) a combination of offering the vaccine in some schools and media coverage.ConclusionsCNA offers a new comparative approach for researchers seeking to understand how implementation conditions work together and link to outcomes.
Shikonin Enhances the Antitumor Effect of Cabazitaxel in Prostate Cancer Stem Cells and Reverses Cabazitaxel Resistance by Inhibiting the Expression of ABCG2 and ALDH3A1
Authors: Wang Lili , Stadlbauer Birgit , Lyu Chen , Buchner Alexander , Pohla Heike 
Published: August 2020

Abstract
Background: Cancer stem cells (CSCs) are a small population among cancer cells, defined as capable of self-renewal, and driving tumor growth, metastasis, and therapeutic relapse. The development of therapeutic strategies to target CSCs is of great importance to prevent tumor metastasis and relapse. Increasing evidence shows that shikonin has inhibiting effects on CSCs. This study was to determine the effect of shikonin on prostate CSCs, and on drug resistant cells.Methods: Sphere formation assay was used to enrich prostate CSCs. The effect of shikonin on viability, proliferation, migration, and invasion was studied. Typical CSCs markers were analyzed by flow cytometry and RT-qPCR. The cytotoxic mechanism of shikonin was analyzed by staining for annexin V, reactive oxygen species (ROS) and mitochondrial membrane potential. To study the effect of shikonin on drug resistant cells a cabazitaxel resistant cell line was established.Results: Shikonin inhibited the viability, proliferation, migration, and invasion of prostate CSCs. Shikonin enhanced the antitumor effect of cabazitaxel, which is a second-line chemotherapeutic drug in advanced prostate cancer. Shikonin induced apoptosis through generating ROS and disrupting the mitochondrial membrane potential. Furthermore, shikonin suppressed the expression of ALDH3A1 and ABCG2 in prostate CSCs, which are two markers related to drug-resistance. When inhibiting the expression of ABCG2 and ALDH3A1, the cabazitaxel resistant cells acquired more sensibility to cabazitaxel. Conclusions: Shikonin enhances the cytotoxic activity of cabazitaxel in prostate CSCs and reverses the cabazitaxel-resistant state.
ERRα/VDR Axis Promotes Calcitriol Degradation and Estrogen Signaling Activation and Correlates with Poor Prognosis in Basal-like Breast Cancer Patients.
Authors: Danza Katia , Porcelli Letizia , Summa Simona De , Fonte Roberta Di , Pilato Brunella , Lacalamita Rosanna , Serratì Simona , Azzariti Amalia , Tommasi Stefania 
Published: August 2020

Abstract
Background Vitamin D is used to reduce cancer risk and improve the outcome of cancer patients, but the VDR pathway needs to be functionally intact to ensure the biological effects of circulating calcitriol. Besides ERα, another nuclear receptor, ERRα, has recently been shown to interfere with the VDR pathway, but its role in the cytotoxicity and transactivation activity of calcitriol is completely unknown in breast cancer (BC).Methods We investigated the function of ERRα on BC cell proliferation and calcitriol cytotoxicity and transactivation activity by silencing ERRα expression. We then performed a colony formation assay and cell cycle analysis to assess cell proliferation, and western blot and RT-PCR to investigate underlying mechanisms of cytotoxicity and VDR genomic action. Immunofluorescence was used to investigate VDR and ERRα cellular distribution. Bioinformatics analyses were performed to uncover the interaction network of VDR and ERRα. The translational significance of both bioinformatics and in vitro results were studied in the TCGA-BRCA (BReast CAncer) cohort.ResultsERRα functionally supported the proliferation of BC cell lines and acted as a calcitriol-induced co-activator of the VDR complex. As such, ERRα deregulated the calcitriol/VDR genomic action by enhancing CYP24A1 and both ESR1 and aromatase (CYP19A1) expression in calcitriol-treated cells. In contrast, ERRα functionally supported calcitriol cytotoxicity by enhancing calcitriol- induced G0/G1 phase cell cycle arrest and by affecting the expression of cyclin D1 and p21/Waf1. The interactome analysis suggested PPARGC1A and PELP-1 were key players in genomic actions of the calcitriol/VDR/ERRα axis. Evaluation of patients’ outcome in the TCGA dataset definitely showed the translational significance of VDR/ERRα biological effects, highlighting that VDR-CYP24A1-ESRRA overexpression correlates with poor prognosis in basal-like breast cancer setting. ConclusionsCollectively, our findings identified a novel VDR/ERRα axis in breast cancer through which ERRα promotes the corruption of VDR genomic action and drives worsening of prognosis in BC patients.
Identification and biochemical characterisation of Acanthamoeba castellanii cysteine protease 3
Authors: Wang Zhixin , Wu Duo , Tachibana Hiroshi , Feng Meng , Cheng Xunjia 
Published: August 2020

Abstract
Background: Acanthamoeba spp. are free-living amoeba that are ubiquitously distributed in the environment. This study examines pathogenic Acanthamoeba cysteine proteases (AcCPs) belonging to the cathepsin L-family and explores the mechanism of AcCP3 interaction with host cells.Methods: Six AcCP genes were amplified by PCR. Quantitative real-time polymerase chain reaction was used to analyse the relative mRNA expression of AcCPs during the encystation process, and between pre- and post-reactivated trophozoites. To further verify the role of AcCP3 in these processes, AcCP3 recombinant proteins were expressed in Escherichia coli, and the hydrolytic activity of AcCP3 was determined. The influence of the AcCP3 on the hydrolytic activity of trophozoites and the toxicity of trophozoites to human corneal epithelial cells (HCECs) was examined by inhibiting AcCP3 expression using siRNA. Further, the levels of p-Raf and p-Erk were examined in HCECs following coculture with AcCP3 gene knockdown trophozoites by western blotting.Results: During encystment, five out of six AcCPs exhibited decreased expression, and only AcCP6 was substantially up-regulated at the mRNA level, indicating that most AcCPs were not directly correlated to encystation. Further, six AcCPs exhibited increased expression level following trophozoite reactivation with HEp2 cells, particularly AcCP3, indicating that these AcCPs might be virulent factors. After refolding the AcCP3 recombinant protein, the 27 kDa mature protein from the 34 kDa pro-protein hydrolysed host haemoglobin, collagen and albumin, and showed high activity in an acidic environment. After AcCP3 knockdown, the hydrolysis activity of trophozoite crude protein against gelatin was decreased, suggesting that these trophozoite had decreased toxicity. Compared with untreated trophozoites or negative control siRNA-treated trophozoites, AcCP3-knockdown trophozoites were less able to penetrate and damage monolayers of HCECs. Western blot analysis showed that after inhibiting the expression of trophozoite AcCP3, the activation levels of the Ras/Raf/Erk/p53 signalling pathways in HCECs were decreased.Conclusions: AcCP6 was correlated to encystation. Further, AcCP3 is a virulent factor in trophozoites, and participated in the activation of the Ras/Raf/Erk/p53 signalling pathways of host cells.
MiR-103 Assumes Signifying Capacity in Prostate Cancer Diagnosis
Authors: Li Sheng , Ruan Xiaolan , Liu Tongzu 
Published: August 2020

Abstract
Background: Prostate cancer is one of the common cancers among males with high incidence and mortality. MiR-103 has been reported to be involved in several human cancers. In our study, we aimed to explore the diagnostic value of miR-103 in PCa.Methods: In this study, qRT-PCR was performed to investigate the expression levels of miR-103 in serum specimens collected from 141 PCa patients and 77 healthy volunteers. MTT and cell invasion assay were performed to detect the effects of miR-103 on the proliferation and invasion of PCa cells. The diagnostic value of miR-103 in PCa was evaluated by ROC curve.Results: The results showed that serum miR-103 levels were higher in PCa patients than that in healthy group (P<0.001). And the expression of miR-103 was significantly associated with PSA (P=0.007), differentiation (P=0.009), and lymph node metastasis (P=0.037). Cell experiments in vitro demonstrated that miR-103 could promote PCa cell line proliferation and invasion. In addition, ROC analysis suggested that miR-103 could discriminate between PCa patients and healthy individuals at the cut-off value of 0.970. The AUC was 0.885, with the sensitivity of 97.2% and specificity of 81.8%.Conclusions: The increased miR-103 levels can promote proliferation and invasion of PCa cells. Serum miR-103 is significantly associated with tumor progression, which may be a novel biomarker for PCa diagnosis.
The Function of LINC00662/miR-340-5p/STAT3 Regulation Loop in Promoting Tumorigenesis and Development of Glioma
Authors: Ji Wei , Li Zhengwei , Song Likun , Cheng Chao , Sun Jun , Liu Yuankun , Huang Weiyi , Huang Jin , Liu Jin , Xu Bin , Jiao Jiantong , Shao Junfei , Liu Hongyi 
Published: August 2020

Abstract
Background: Long noncoding RNAs( lncRNAs) have been reported to be associated with tumorigenesis and development of glioma. LINC00662 has been implicated in pathogenesis of various human cancers. However, role of LINC00662 in glioma remains unknown.Methods: Bioinformatics methods were used to analysis the expression of LINC00662 in glioma. RT-qPCR was performed to examine the expression levels of LINC00662 in glioma tissues and cell lines. The effect of LINC00662 in cell proliferation and invasion was evaluated by Cell Counting Kit-8(CCK-8), clone colony formation and transwell assay. Luciferase reporter assays were performed to investigate the interaction between miR-340-5p and LINC00662, 3’UTR of STAT3. CHIP-qPCR and Luciferase reporter assays were used to demonstrate the interaction between STAT3 and the promoter region of LINC00662. Rescue assays and Tumor xenografts in nude mice were applied to verify the effect of LINC00662 in modulating miR-340-5p/ STAT3 signal pathway.Results: LINC00662 was frequently high expressed and associated with malignant phenotype of glioma. LINC00662 knockdown inhibited proliferation, invasion and glioma-genesis of glioma. Moreover, LINC00662 knockdown repressed development of glioma by inhibiting the expression and activation of STAT3 pathway. Mechanically, LINC00662 acted as a ceRNA sponging miR-340-5p to protect the expression of STAT3. More importantly, LINC00662 was one of direct target genes of STAT3.Conclusions: There was a positive regulation loop between LINC00662 and STAT3. LINC00662 might be an oncogene in glioma. Targeting LINC00662 was a potential strategy in glioma therapy.
Interleukin-33 Promotes Cell Survival via P38 MAPK-mediated Interleukin-6 Gene Expression and Release in Pediatric AML
Authors: Wang Yiqian , Su Haibo , Yan Muxia , Zhang Li , Li Quanxin , Gu Xiaoqiong , Gong Qing 
Published: August 2020

Abstract
BackgroundAcute myeloid leukemia (AML) is a fatal disease characterized by an accumulation of immature myeloid blasts in the bone marrow (BM). Cytokine provide signals for leukemia cell to better survive in the BM microenvironment. Previously, we identified interleukin-33 (IL-33) as a stimulator of cell survival in human AML cell line and primary mouse leukemia cells. However, the mechanism on how IL-33 regulates AML activity is not well known.MethodsFlow cytometry, ELISA and cytometric bead array (CBA) were used to investigate the expression of IL1RL1 and serum cytokine levels in AML patient samples and cell culture supernatant. The correlation of serum IL-33 and IL-6 levels was calculated by Pearson R test. Annexin V staining was used to examine the apoptosis of AML cells. RT-PCR was used to measure IL-6 expression in leukemia cells.ResultsThe cell surface expression of IL-33-specific receptor, IL1RL1, is elevated in BM cells from AML patients at diagnosis, and the serum level of IL-33 in AML patients is higher than that of healthy donor controls. Moreover, IL-33 levels are positively associated with IL-6 levels in pediatric patients with AML. In vitro, IL-33 treatment increased IL-6 mRNA expression and protein level in BM and peripheral blood (PB) cells from AML patients. IL-33 inhibited cell apoptosis by activating p38 MAPK pathway using human AML cell line as well as AML patient samples. Finally, IL-33 activated IL-6 expression in a manner that required p38 MAPK pathway using clinical AML samples.ConclusionsTaken together, we demonstrate that p38 MAPK pathway is important for IL-33-mediated anti-apoptotic process as well as cytokine expression and release in pediatric patients with AML.