miR-29c-3p represses the angiogenesis of esophageal squamous cell carcinoma by targeting SERPINH1 to regulate the Wnt signaling pathway

ABSTRACT Purpose: Esophageal squamous cell carcinoma (ESCC) is characterized by early metastasis and late diagnosis. miR-29c-3p is confirmed to repress angiogenesis in multiple tumor types. Yet, the functions of miR-29c-3p in the mechanism of ESCC angiogenesis, which were not sufficiently explored previously, were exactly what we investigated here at the molecular level. Methods: The mRNA level of miR-29c-3p and Serpin peptidase inhibitor clade H member 1 (SERPINH1) in ESCC tissues were assessed via bioinformatics analysis. Thereafter, miR-29c-3p and SERPINH1 (HSP47) mRNA level in ESCC cell lines was evaluated via quantitative real-time polymerase chain reaction. The effects of abnormal miR-29c-3p and SERPINH1 expression on ESCC cell viability, proliferation, migration, invasion, and HUVEC angiogenesis were examined via CCK8, colony formation, transwell, and angiogenesis assays, respectively. The protein levels of SERPINH1, vascular endothelial growth factor-A (VEGFA), Wnt-1, ?-catenin, and p-?-catenin were evaluated via Western blot. Expression of VEGFA secreted by ESCC cells was measured via enzyme-linked immunosorbent assay. Treatment with the Wnt activator BML-284 further revealed the way miR-29c-3p mediated the Wnt signaling pathway and its effects on angiogenesis. Results: Herein, we revealed a decrease of miR-29c-3p expression in ESCC tissues and cells, while the overexpressed miR-29c-3p could remarkably suppress ESCC cell progression, as well as HUVEC angiogenesis. Meanwhile, overexpressed miR-29c-3p notably downregulated VEGFA and repressed the Wnt signaling pathway. Treatment with the Wnt activator BML-284 could reverse the inhibition of HUVEC angiogenesis caused by miR-29c-3p. SERPINH1 was a downstream target of miR-29c-3p. SERPINH1 knockdown suppressed the malignant phenotypes of ESCC cells and impeded the Wnt signaling activation, while such suppression was reversed through miR-29c-3p inhibitor. Conclusions: We confirmed the mechanism that miR-29c-3p targeted SERPINH1, thus regulating angiogenesis in ESCC through the Wnt signaling pathway. It improves the understanding of angiogenesis in ESCC and offers new ideas for the research of ESCC treatment strategies in the future

Multi-omics analyses of glucose metabolic reprogramming in colorectal cancer

BackgroundGlucose metabolic reprogramming (GMR) is a cardinal feature of carcinogenesis and metastasis. However, the underlying mechanisms have not been fully elucidated. The aim of this study was to profile the metabolic signature of primary tumor and circulating tumor cells from metastatic colorectal cancer (mCRC) patients using integrated omics analysis.MethodsPET-CT imaging, serum metabolomics, genomics and proteomics data of 325 high 18F-fluorinated deoxyglucose (FDGhigh) mCRC patients were analyzed. The para-tumor, primary tumor and liver metastatic tissues of mCRC patients were used for proteomics analysis.ResultsThe glucose uptake in tumor tissues as per the PET/CT images was correlated to serum levels of glutamic-pyruvic transaminase (ALT), total bilirubin (TBIL), creatinine (CRE). Proteomics analysis indicated that several differentially expressed proteins were enriched in both GMR and epithelial-mesenchymal transition (EMT)-related pathways. Using a tissue-optimized proteomic workflow, we identified novel proteomic markers (e.g. CCND1, EPCAM, RPS6), a novel PCK1-CDK6-INSR protein axis, and a potential role for FOLR (FR) in GMR/EMT of CRC cells. Finally, CEA/blood glucose (CSR) was defined as a new index, which can be used to jointly diagnose liver metastasis of colorectal cancer.ConclusionsGMR in CRC cells is closely associated with the EMT pathway, and this network is a promising source of potential therapeutic targets

Evaluation of Reactivity of Monoclonal Antibodies Against Omp25 of Brucella spp.

Brucellosis is a serious zoonosis occurring mainly in developing countries, and its diagnosis is largely dependent on serologic detection and bacterial culture. In this study, we developed the murine monoclonal antibodies (mAbs) against a conserved and major outer membrane protein 25 (Omp25) of Brucella species (B. spp.) for use in clinical diagnosis. The mAbs to Omp25 were produced by hybridoma technique, which were utilized for developing various immunoassays for detection of Brucellae, including Western blot (WB), enzyme-linked immunosorbent assay (ELISA), immunochemical staining (ICS), immunofluorescence staining (IFS), and flow cytometry assay (FCM). A number of five mAbs (2B10, 4A12, 4F10, 6C12, and 8F3) specific to Omp25 were selected, including 2 IgG1, 2 IgG2a, and 1 IgG2b. Among them, mAbs 6C12, 8F3, and 4A12 reacted highly with B. melitensis (M5-90), B. abortus (S19, 104M, and 2308), and B. suis strain (S2). No cross-reactivity with Yersinia enterocolitica O:9, Salmonella spp., and Escherichia coli was found. By mapping Omp25 epitopes, mAb 6C12 was found as reacting with a semi-conformational epitope, and mAbs 4A12 and 8F3 as recognizing a different linear epitope, respectively. The paired mAbs were tested for detecting Brucella species, suggesting that 8F3 was suitable for solid phase capture and 6C12 or 4A12 was suitable for conjugation with HRP for detection of Brucella Omp25 in ELISA. The FCM was established by mAb 6C12 for detecting intracellular Brucellae-infected peripheral blood mononuclear cells (PBMCs) from brucellosis patients. In conclusion, mAbs against Omp25 are precious reagents for detection of Brucellae in clinical samples with various immunoassays. mAb 6C12-based FCM could be potentially used for the monitoring of therapeutic efficacy for brucellosis in clinical practice

A five-collagen-based risk model in lung adenocarcinoma: prognostic significance and immune landscape

As part of the tumor microenvironment (TME), collagen plays a significant role in cancer fibrosis formation. However, the collagen family expression profile and clinical features in lung adenocarcinoma (LUAD) are poorly understood. The objective of the present work was to investigate the expression pattern of genes from the collagen family in LUAD and to develop a predictive signature based on collagen family. The Cancer Genome Atlas (TCGA) samples were used as the training set, and five additional cohort samples obtained from the Gene Expression Omnibus (GEO) database were used as the validation set. A predictive model based on five collagen genes, including COL1A1, COL4A3, COL5A1, COL11A1, and COL22A1, was created by analyzing samples from the TCGA cohort using LASSO Cox analysis and univariate/multivariable Cox regression. Using Collagen-Risk scores, LUAD patients were then divided into high- and low-risk groups. KM survival analysis showed that collagen signature presented a robust prognostic power. GO and KEGG analyses confirmed that collagen signature was associated with extracellular matrix organization, ECM-receptor interaction, PI3K-Akts and AGE-RAGE signaling activation. High-risk patients exhibited a considerable activation of the p53 pathway and cell cycle, according to GSEA analysis. The Collage-Risk model showed unique features in immune cell infiltration and tumor-associated macrophage (TAM) polarization of the TME. Additionally, we deeply revealed the association of collagen signature with immune checkpoints (ICPs), tumor mutation burden (TMB), and tumor purity. We first constructed a reliable prognostic model based on TME principal component—collagen, which would enable clinicians to treat patients with LUAD more individually

Mineral Prospectivity Mapping of Porphyry Copper Deposits Based on Remote Sensing Imagery and Geochemical Data in the Duolong Ore District, Tibet

Several large-scale porphyry copper deposits (PCDs) with high economic value have been excavated in the Duolong ore district, Tibet, China. However, the high altitudes and harsh conditions in this area make traditional exploration difficult. Hydrothermal alteration minerals related to PCDs with diagnostic spectral absorption features in the visible–near-infrared–shortwave-infrared ranges can be effectively identified by remote sensing imagery. Mainly based on hyperspectral imagery supplemented by multispectral imagery and geochemical element data, the Duolong ore district was selected to conduct data-driven PCD prospectivity modelling. A total of 11 known deposits and 17 evidential layers of multisource geoscience information related to Cu mineralization constitute the input datasets of the predictive models. A deep learning convolutional neural network (CNN) model was applied to mineral prospectivity mapping, and its applicability was tested by comparison to conventional machine learning models, such as support vector machine and random forest. CNN achieves the greatest classification performance with an accuracy of 0.956. This is the first trial in Duolong to conduct mineral prospectivity mapping combined with remote imagery and geochemistry based on deep learning methods. Four metallogenic prospective sites were delineated and verified through field reconnaissance, indicating that the application of deep learning-based methods in PCD prospecting proposed in this paper is feasible by utilizing geoscience big data such as remote sensing datasets and geochemical elements

Cognitive Biases of Consumers’ Risk Perception of Foodborne Diseases in China: Examining Anchoring Effect

Consumer cognitive biases arise from judgment and decision-making due to their limitations in information processing. As one of the important cognitive biases, the anchoring effect plays a significant role in interfering with consumers’ risk perception. With a stratified random approach, we collected survey data from 375 consumers in Wuxi, Jiangsu Province, China. Based on these data, this study attempted to analyze the anchoring effect in consumers’ risk perception of foodborne diseases (FBDs) and the differences in their perception before and after intervention in a contrast experiment using the anchoring index and the Wilcoxon signed-rank test. The results confirm the existence of the proposed anchoring effect. Moreover, the experimenter-provided anchor value, a history of FBD, and familiarity with FBD were found to be important factors influencing this anchoring effect. Therefore, improving consumers’ risk perception of FBD is critical to the long-term prevention of FBD risks by the government and consumers. The government should strengthen active monitoring, publicity, and education about FBD

Social Co-Governance for Food Safety Risks

We review relevant literature to propose the connotation and operation logic of food safety co-governance, systematically constitute by roles, functions, as well as the boundaries of public government, enterprise, and social forces. The major thesis is that social co-governance is a kind of societal-wide innovation (i.e., social innovation) that integrates diverse resources and efforts from multiple stakeholders for better and sustainable development of an economy’s food institution and system. We then put forward a prospect of the future research on food safety risk co-governance. Theoretical, practical, and policy implications are discussed

Business Models for Social Innovation of Municipal Solid Waste Recycling Companies: Comparison of Two Business Cases in Thailand and Taiwan

The significant increase of municipal solid wastes (e.g., food disposals, biomedical wastes, recyclable materials, etc.) is a very important environmental issue around the world. Waste recycling, reduction, and reuse are not only methods to solve environmental problems, but also directions for social innovation for business to create potential social value. This study investigates the business models of two waste recycling companies in Thailand and Taiwan. First, the basic micro and macro environmental factors were analyzed, including the period of firm’s business operations, location of the firm, space for separating and storing recyclable waste and various types of recyclable waste purchasing affecting the firms’ performance in these two economies. Second, different recyclable waste materials, volumes and price strategies between the case companies were compared. Third, this study also investigates the impacts of factors regarding resource characteristics, a firm’s capabilities and an entrepreneur’s abilities to improve a firm’s performance all compose a critical business model. The results showed that there were an increasing number of owners of waste recycling businesses developing and adapting to new business models. Detailed comparisons are reported and discussed in the article to shed light on managerial and policy implications

Breaking the land degradation-poverty nexus in drylands

This work was supported by the National Natural Science Foundation of China (41991230), the Joint CAS (Chinese Academy of Sciences) & MPG (Max-Planck-Gesellschaft) Research Project (HZXM20225001MI), and the International Partnership Program of the Chinese Academy of Sciences (121311KYSB20170004)