{"id":2769,"date":"2019-02-28T17:34:41","date_gmt":"2019-02-28T16:34:41","guid":{"rendered":"https:\/\/clinomic.ai\/?p=2769"},"modified":"2020-11-16T15:33:45","modified_gmt":"2020-11-16T15:33:45","slug":"heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning","status":"publish","type":"post","link":"https:\/\/www.clinomic.ai\/ro\/2019\/02\/28\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\/","title":{"rendered":"Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\">Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger\/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-<em>In silico<\/em>&nbsp;approach that combines conventional cell culture experiments with machine learning algorithms, we aimed to reduce a significant part of the expensive and time-consuming cell culture experiments and data generation by using computational intelligence (refinement and replacement). <\/p>\n\n\n\n<div class=\"wp-block-image\"><figure class=\"aligncenter\"><img decoding=\"async\" src=\"https:\/\/clinomic.ai\/wp-content\/uploads\/2019\/02\/Screen-Shot-2019-02-28-at-17.35.51-1024x785.png\" alt=\"\" class=\"wp-image-2772\"\/><\/figure><\/div>\n\n\n\n<p class=\"wp-block-paragraph\">Cardiomyocytes exposed to HS showed an activation of the intrinsic apoptosis signal pathway&nbsp;<em>via<\/em>&nbsp;cytochrome C and the activation of caspase 3 (both&nbsp;<em>p<\/em>\u2009&lt;\u20090.001). Notably, the exposure of HS resulted in the induction of necroptosis by tumor necrosis factor \u03b1 and receptor interaction protein 3 (<em>p<\/em>\u2009&lt;\u20090.05;&nbsp;<em>p<\/em>\u2009&lt;\u20090.01) and, hence, an increased level of necrotic cardiomyocytes. In conclusion, using this novel Medical-<em>In silico<\/em>&nbsp;approach, our data suggest (i) that HS induces necroptosis in cardiomyocytes by phosphorylation (activation) of receptor-interacting protein 3, (ii) that HS is a therapeutic target in trauma- or sepsis-associated cardiomyopathy, and (iii) indicate that this proof-of-concept is a first step toward simulating the extent of activated components in the pro-apoptotic pathway induced by HS with only a small data set gained from the&nbsp;<em>in vitro<\/em>&nbsp;experiments by using machine learning algorithms.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29616016\">Link to full text<\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger\/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase [&#8230;]<\/p>\n<p><a class=\"btn btn-secondary understrap-read-more-link\" href=\"https:\/\/www.clinomic.ai\/ro\/2019\/02\/28\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\/\">Read More&#8230;<\/a><\/p>\n","protected":false},"author":4,"featured_media":3103,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"iawp_total_views":21,"footnotes":""},"categories":[10],"tags":[],"class_list":["post-2769","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning - Clinomic<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.clinomic.ai\/2019\/02\/28\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\/\" \/>\n<meta property=\"og:locale\" content=\"ro_RO\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning - Clinomic\" \/>\n<meta property=\"og:description\" content=\"Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger\/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase [...]Read More...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.clinomic.ai\/2019\/02\/28\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\/\" \/>\n<meta property=\"og:site_name\" content=\"Clinomic\" \/>\n<meta property=\"article:published_time\" content=\"2019-02-28T16:34:41+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2020-11-16T15:33:45+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.clinomic.ai\/wp-content\/uploads\/2019\/02\/science-1029385_1920-1024x683-1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1024\" \/>\n\t<meta property=\"og:image:height\" content=\"683\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Arne Peine\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Scris de\" \/>\n\t<meta name=\"twitter:data1\" content=\"Arne Peine\" \/>\n\t<meta name=\"twitter:label2\" content=\"Timp estimat pentru citire\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minut\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/www.clinomic.ai\\\/2019\\\/02\\\/28\\\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.clinomic.ai\\\/2019\\\/02\\\/28\\\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\\\/\"},\"author\":{\"name\":\"Arne Peine\",\"@id\":\"https:\\\/\\\/www.clinomic.ai\\\/#\\\/schema\\\/person\\\/96e364f58fe927a66f5cfbfe4064b257\"},\"headline\":\"Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning\",\"datePublished\":\"2019-02-28T16:34:41+00:00\",\"dateModified\":\"2020-11-16T15:33:45+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/www.clinomic.ai\\\/2019\\\/02\\\/28\\\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\\\/\"},\"wordCount\":279,\"commentCount\":0,\"image\":{\"@id\":\"https:\\\/\\\/www.clinomic.ai\\\/2019\\\/02\\\/28\\\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.clinomic.ai\\\/wp-content\\\/uploads\\\/2019\\\/02\\\/science-1029385_1920-1024x683-1.jpg\",\"articleSection\":[\"Publications with partner universities\"],\"inLanguage\":\"ro-RO\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.clinomic.ai\\\/2019\\\/02\\\/28\\\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\\\/\",\"url\":\"https:\\\/\\\/www.clinomic.ai\\\/2019\\\/02\\\/28\\\/heparan-sulfate-induces-necroptosis-in-murine-cardiomyocytes-a-medical-in-silico-approach-combining-in-vitro-experiments-and-machine-learning\\\/\",\"name\":\"Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning - 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