Literature Mining for the Discovery of Hidden Connections between Drugs, Genes and Diseases

The scientific literature represents a rich source for retrieval of knowledge on associations between biomedical concepts such as genes, diseases and cellular processes. A commonly used method to establish relationships between biomedical concepts from literature is co-occurrence. Apart from its use in knowledge retrieval, the co-occurrence method is also well-suited to discover new, hidden relationships between biomedical concepts following a simple ABC-principle, in which A and C have no direct relationship, but are connected via shared B-intermediates. In this paper we describe CoPub Discovery, a tool that mines the literature for new relationships between biomedical concepts. Statistical analysis using ROC curves showed that CoPub Discovery performed well over a wide range of settings and keyword thesauri. We subsequently used CoPub Discovery to search for new relationships between genes, drugs, pathways and diseases. Several of the newly found relationships were validated using independent literature sources. In addition, new predicted relationships between compounds and cell proliferation were validated and confirmed experimentally in an in vitro cell proliferation assay. The results show that CoPub Discovery is able to identify novel associations between genes, drugs, pathways and diseases that have a high probability of being biologically valid. This makes CoPub Discovery a useful tool to unravel the mechanisms behind disease, to find novel drug targets, or to find novel applications for existing drugs

Tracking the turnover of SARS-CoV-2 VOCs gamma to delta in a Brazilian state (Minas Gerais) with a high-vaccination status

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting

FGF-2 is overexpressed in myoepithelial cells of carcinoma ex-pleomorphic adenoma in situ structures

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Increasing emphasis has been placed on the role of myoepithelial cells, the contractile components of secretory glands, in the in situ to invasive carcinoma transition. These cells are placed at the interface between luminal epithelial cells and the stromal compartment, which favors their crosstalk with all other cell types comprising the tumor micro-environment. To obtain some clues about this cross-talk and also to better understand our previous immunoprofile study of myoepithelial cells in salivary gland carcinoma ex-pleomorphic adenoma (CXPA), we investigated FGF-2 expression in CXPA in situ structures as well as in cells cultured under conditions attempting to simulate the cellular interactions of this tumor stage. We have observed by immunohistochemistry that myoepithelial cells of CXPA in situ structures over-express FGF-2. In addition, our results supported by qPCR and Western blotting, demonstrated that the expression of FGF-2 in the benign myoepithelial cells was in fact increased by stimulation with the conditioned medium from malignant cells. Low molecular weight FGF-2, known to be primarily released from the cells to exert its biological activity through receptors, was the predominant FGF-2 form detected in the benign myoepithelial cells. Specific FGF-2 receptors were found in the malignant epithelial but not in the benign myoepithelial cells of CXPA, indicating a paracrine role for benign myoepithelial cell-derived FGF-2. Abnormal paracrine myoepithelial/epithelial cell interactions and also myoepithelial/stromal cell interactions could favor tumor growth, invasion and metastasis.O TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE FEVEREIRO DE 2015.241155160Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [04/07960-0, 08/58721-7, 08/58722-3

Osteogenic potential of human dental pulp stem cells cultured onto poly-ε-caprolactone/poly (rotaxane) scaffolds

Bioengineering aims to develop innovative scaffolds to improve cellular activities for tissue regeneration. To evaluate the biological behavior of human dental pulp stem cells (hDPSCs) seeded onto an experimental polymeric-based scaffold comprising poly-ε-caprolactone/poly (rotaxane). Adhesion, viability, and proliferation as well as alkaline phosphatase (ALP) activity, mineralized nodule formation (alizarin red assay), and expression of genes related to osteogenic differentiation, including ALP, type 1 collagen alpha 1 (COL1A1), Runt-related transcription factor (Runx-2), and osteocalcin (BGLAP/OCN), were evaluated in hDPSCs seeded onto polymeric scaffolds. hDPSCs expressed typical levels of mesenchymal stem cell surface markers. Cell growth increased upon cultivation on polymeric blend scaffold and the cells gained osteoblast-like appearance. Fourteen days after seeding hDPSCs on the scaffolds, irrespective to the culture medium used (clonogenic or mineralization medium), the cells presented ALP activity higher than that of control cells grown in clonogenic medium. The cells cultivated in mineralization medium on the scaffold showed significantly higher expression of all genes than the control cells, except for BGLAP gene expression. At 21 days, the group cultivated on the scaffold and mineralization medium showed maximum level of mineralization. Poly-ε-caprolactone/poly (rotaxane) blend is noncytotoxic to hDPSCs and improved genomic and functional osteogenic differentiation. Thus, poly-ε-caprolactone/poly (rotaxane) blend may serve as a promising bioactive biomaterial for bone tissue bioengineering351217401749To Renato Contessotto (Technologic Characterization Laboratory – Polytechnique Engineering School – USP – SP). To the Basic Research Laboratory of the Department of Dentistry of the School of Dentistry of the University of São Paulo (FOUSP). To Assistant Professor Carla Sipert (qPCR – assistance), to Full Professor Fabio Daumas Nunes (Stem cells Laboratory – LABTRON – FOUSP). To Prof. Chang Tien Kiang (IPEN) for technical support in polymer blend scienc