BioDiscovery最新文献

The motility of breast cancer cells is stimulated by HMGB1/RAGE interaction but the truncated form lacking the C terminus has no effect HMGB1/RAGE相互作用刺激癌症细胞的运动，但缺乏C末端的截短形式没有影响

BioDiscovery Pub Date : 2022-09-12 DOI: 10.3897/biodiscovery.24.e93641

Jordana Todorova, Shazie Myashkova, M. Petrova, A. Gospodinov, E. Pasheva

{"title":"The motility of breast cancer cells is stimulated by HMGB1/RAGE interaction but the truncated form lacking the C terminus has no effect","authors":"Jordana Todorova, Shazie Myashkova, M. Petrova, A. Gospodinov, E. Pasheva","doi":"10.3897/biodiscovery.24.e93641","DOIUrl":"https://doi.org/10.3897/biodiscovery.24.e93641","url":null,"abstract":"HMGB1/RAGE is identified as a ligand-receptor pair that plays an important role in tumorogenesis. HMGB1 and RAGE levels are higher in most human tumors and their overexpression is associated with tumor progression. The causes of breast cancer are still poorly understood. One reason might be the existence of subtypes within various cellular mechanisms as hormone-dependent and hormone -independent malignant processes. We investigated the effect of HMGB1 protein and its truncated form lacking the C terminus on the RAGE expression and cell motility of breast cancer cell lines; MCF7-noninvasive, MDA-MB-231-invasive and normal breast epithelial one MCF10. The results demonstrate that the effects of HMGB1 and HMGB1∆C through RAGE association are observed exclusively for the hormone independent MDA-MB-231 cell line. The mobility of MDA-MB-231 cells was stimulated only by the full length HMGB1. Our results suggest that HMGB1/RAGE signaling should be considered as an essential process for the development of hormone independent breast cancers with great invasive potential. The truncated form plays the role of a blocking molecule that ”locks” the receptor and inactivates it. This makes the tailless molecule a promising therapeutic agent that competes for the biologically active HMGB1 ligand and prevents the downstream signaling through RAGE.","PeriodicalId":89746,"journal":{"name":"BioDiscovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44164536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Aplastic Anemia induced by Nivolumab before a Treatment of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia 异基因造血干细胞移植治疗急性粒细胞白血病前尼武单抗诱导再生障碍性贫血

BioDiscovery Pub Date : 2019-08-26 DOI: 10.3897/biodiscovery.22.e37211

W. Cheng, B. Jackson

引用次数: 1

Environmental pollutants-dependent molecular pathways and carcinogenesis 环境污染物依赖性分子途径与致癌作用

BioDiscovery Pub Date : 2019-02-21 DOI: 10.3897/BIODISCOVERY.22.E29242

Myriam El Helou, P. Cohen, M. Diab‐Assaf, S. Ghayad

{"title":"Environmental pollutants-dependent molecular pathways and carcinogenesis","authors":"Myriam El Helou, P. Cohen, M. Diab‐Assaf, S. Ghayad","doi":"10.3897/BIODISCOVERY.22.E29242","DOIUrl":"https://doi.org/10.3897/BIODISCOVERY.22.E29242","url":null,"abstract":"Exposure to environmental pollutants can modulate many biological and molecular processes such as gene expression, gene repair mechanisms, hormone production and function and inflammation, resulting in adverse effects on human health including the occurrence and development of different types of cancer. Carcinogenesis is a complex and long process, taking place in multiple stages and is affected by multiple factors. Some environmental molecules are genotoxic, able to damage the DNA or to induce mutations and changes in gene expression acting as initiators of carcinogenesis. Other molecules called xenoestrogens can promote carcinogenesis by their mitogenic effects by possessing estrogenic-like activities and consequently acting as endocrine disruptors causing multiple alterations in cellular signal transduction pathways. In this review, we focus on recent research on environmental chemicals-driven molecular functions in human cancers. For this purpose, we will be discussing the case of two receptors in mediating environmental pollutants effects: the established nuclear receptor, the Aryl hydrocarbon receptor (AhR) and the emerging membrane receptor, G-protein coupled estrogen receptor 1 (GPER1).","PeriodicalId":89746,"journal":{"name":"BioDiscovery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49329089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Virtual patient simulations for cardiology education and research: A CircAdapt perspective 用于心脏病学教育和研究的虚拟患者模拟：CircAdapt视角

BioDiscovery Pub Date : 2018-08-15 DOI: 10.3897/biodiscovery.21.e28591

D. Trifonov, Peter R. Huntjens, E. Willemen, T. Delhaas, J. Lumens

{"title":"Virtual patient simulations for cardiology education and research: A CircAdapt perspective","authors":"D. Trifonov, Peter R. Huntjens, E. Willemen, T. Delhaas, J. Lumens","doi":"10.3897/biodiscovery.21.e28591","DOIUrl":"https://doi.org/10.3897/biodiscovery.21.e28591","url":null,"abstract":"Nowadays cardiac simulations are becoming increasingly sophisticated. This trend, part of the maturing field of computational medicine, has provided medical students and cardiologists alike with a new tool for education and research – their very own virtual “patient”. The CircAdapt biophysical model of the human heart and circulation (www.circadapt.org) allows the creation of a virtual “patient” for the study of the cardiovascular system and circulatory haemodynamics under diverse physiological and pathophysiological conditions in real time. The interactive CircAdapt model with its modular design based on established physical and physiologial principles allows dynamic monitoring of blood flow velocities, pressures and volumes in the heart and blood vessels, and across valves and shunts. As an educational tool, the CircAdapt model enables medical students and residents in cardiology, neonatology and intensive care medicine to analyze complex situations while improving their comprehension of cardiovascular physics and (patho)physiology. Moreover, the CircAdapt model has been successfully utilized as a research tool for cardiac resynchronization therapy as well as for various cardiovascular pathologies (e.g. pulmonary arterial hypertension, LBBB). All in all the CircAdapt perspective is as follows: bridge education and research - from classroom to bedside – to foster the future of clinical practice.","PeriodicalId":89746,"journal":{"name":"BioDiscovery","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44681871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Modelling c-Abl Signalling in Activated Neutrophils: the Anti-inflammatory Effect of Seliciclib. 活化中性粒细胞中c-Abl信号的模拟:Seliciclib的抗炎作用。

BioDiscovery Pub Date : 2013-03-01 DOI: 10.7750/BioDiscovery.2013.7.4

Robert C Jackson, Tomas Radivoyevitch

{"title":"Modelling c-Abl Signalling in Activated Neutrophils: the Anti-inflammatory Effect of Seliciclib.","authors":"Robert C Jackson, Tomas Radivoyevitch","doi":"10.7750/BioDiscovery.2013.7.4","DOIUrl":"https://doi.org/10.7750/BioDiscovery.2013.7.4","url":null,"abstract":"When mammalian tissues are infected by bacteria or fungi, inflammatory cytokines are released that cause circulating neutrophils to invade the infected tissue. The cytosolic tyrosine kinase, c-Abl, in these tissue neutrophils is activated by TNFα. c-Abl then phosphorylates STAT transcription factors, which results in production of the antiapoptotic protein Mcl-1. The normally short-lived tissue neutrophils are then unable to enter apoptosis. c-Abl also causes release of reactive oxygen species (ROS) from the mitochondria of the activated neutrophils. These ROS, and ROS generated by NADPH oxidase, are bactericidal agents of the innate immune system. In some inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), the invading neutrophils become permanently activated, and the resulting ROS overproduction causes severe tissue damage. The cyclin-dependent kinase inhibitor, seliciclib, blocks transcription through inhibition of cdk9. This results in a relatively rapid decline of antiapoptotic Mcl-1 transcripts in activated neutrophils, an increase in neutrophil apoptosis, and less ROS leakage and oxidative damage. We present here a model of neutrophil kinetics that simulates the principal pathways of c-Abl signalling and use it to explore possible treatment options for inflammatory lung disease.","PeriodicalId":89746,"journal":{"name":"BioDiscovery","volume":"7 4","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994723/pdf/nihms-559904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32290264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Identification of a novel deletion mutant strain in Saccharomyces cerevisiae that results in a microsatellite instability phenotype. 一种导致微卫星不稳定表型的酿酒酵母缺失突变株的鉴定。

BioDiscovery Pub Date : 2012-07-23 DOI: 10.7750/BioDiscovery.2012.1.4

Hanlee P Ji, Shannon Morales, Katrina Welch, Cam Yuen, Kyle Farnam, James M Ford

{"title":"Identification of a novel deletion mutant strain in Saccharomyces cerevisiae that results in a microsatellite instability phenotype.","authors":"Hanlee P Ji, Shannon Morales, Katrina Welch, Cam Yuen, Kyle Farnam, James M Ford","doi":"10.7750/BioDiscovery.2012.1.4","DOIUrl":"https://doi.org/10.7750/BioDiscovery.2012.1.4","url":null,"abstract":"The DNA mismatch repair (MMR) pathway corrects specific types of DNA replication errors that affect microsatellites and thus is critical for maintaining genomic integrity. The genes of the MMR pathway are highly conserved across different organisms. Likewise, defective MMR function universally results in microsatellite instability (MSI) which is a hallmark of certain types of cancer associated with the Mendelian disorder hereditary nonpolyposis colorectal cancer. (Lynch syndrome). To identify previously unrecognized deleted genes or loci that can lead to MSI, we developed a functional genomics screen utilizing a plasmid containing a microsatellite sequence that is a host spot for MSI mutations and the comprehensive homozygous diploid deletion mutant resource for Saccharomyces cerevisiae. This pool represents a collection of non-essential homozygous yeast diploid (2N) mutants in which there are deletions for over four thousand yeast open reading frames (ORFs). From our screen, we identified a deletion mutant strain of the PAU24 gene that leads to MSI. In a series of validation experiments, we determined that this PAU24 mutant strain had an increased MSI-specific mutation rate in comparison to the original background wildtype strain, other deletion mutants and comparable to a MMR mutant involving the MLH1 gene. Likewise, in yeast strains with a deletion of PAU24, we identified specific de novo indel mutations that occurred within the targeted microsatellite used for this screen.","PeriodicalId":89746,"journal":{"name":"BioDiscovery","volume":" 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649769/pdf/nihms-444200.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31424815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4