diseaseid	CellDeathType	Disease	pmid	Description
463	netotic_cd	anti-neutrophil antibodies (AAV)	33202203	Similar observations indicate involvement of NETosis in the autoimmune diseases, such as vasculitis associated with anti-neutrophil antibodies (AAV), antiphospholipid syndrome, multiple sclerosis, and psoriasis.
464	netotic_cd	blockage of the pancreatic duct	33202203	In the pancreatic ducts, NETosis can be caused by microcrystals of calcium carbonate, which leads to blockage of the pancreatic duct and pancreatitis [89]. Such crystals cause NETosis in the bile ducts and in the gallbladder, which can lead to the formation of gallstones [90].
465	netotic_cd	cancer	37612413	NETosis plays an important role in the innate immune response because it allows neutrophils to directly combat pathogens. However, excessive or inappropriate NETosis can contribute to the development of inflammatory and autoimmune diseases, such as sepsis, rheumatoid arthritis, lupus, and cancer. Therefore, regulation of NETosis is a topic of ongoing research in the field of immunology.
466	netotic_cd	clear cell renal cell carcinoma	38443363	Clear cell renal cell carcinoma (ccRCC) is one of the most common renal malignancies of the urinary system. Patient outcomes are relatively poor due to the lack of early diagnostic markers and resistance to existing treatment options. Programmed cell death, also known as apoptosis, is a highly regulated and orchestrated form of cell death that occurs ubiquitously throughout various physiological processes. It plays a crucial role in maintaining homeostasis and the balance of cellular activities. The combination of immune checkpoint inhibitors plus targeted therapies is the first-line therapy to advanced RCC. Immune checkpoint inhibitors(ICIs) targeted CTLA-4 and PD-1 have been demonstrated to prompt tumor cell death by immunogenic cell death. Literatures on the rationale of VEGFR inhibitors and mTOR inhibitors to suppress RCC also implicate autophagic, apoptosis and ferroptosis. Accordingly, investigations of cell death modes have important implications for the improvement of existing treatment modalities and the proposal of new therapies for RCC. At present, the novel modes of cell death in renal cancer include ferroptosis, immunogenic cell death, apoptosis, pyroptosis, necroptosis, parthanatos, netotic cell death, cuproptosis, lysosomal-dependent cell death, autophagy-dependent cell death and mpt-driven necrosis, all of which belong to programmed cell death.
467	netotic_cd	diabetic endothelial dysfunction	37918258	Multiple subroutines covered by RCD may be involved in diabetic endothelial dysfunction, including apoptosis, autophagy, necroptosis, pyroptosis, entosis, ferroptosis, ferroautophagy, parthanatos, netotic cell death, lysosome-dependent cell death, alkaliptosis, oxeiptosis, cuproptosis, and PANoptosis.
468	netotic_cd	ischemic stroke	33202203	A recent large-scale clinical study revealed correlation between the level of NETosis and the severity of ischemic stroke and myocardial infarction [84].
469	netotic_cd	ischemic stroke	33202203	A recent large-scale clinical study revealed correlation between the level of NETosis and the severity of ischemic stroke and myocardial infarction [84].
470	netotic_cd	lupus	37612413	NETosis plays an important role in the innate immune response because it allows neutrophils to directly combat pathogens. However, excessive or inappropriate NETosis can contribute to the development of inflammatory and autoimmune diseases, such as sepsis, rheumatoid arthritis, lupus, and cancer. Therefore, regulation of NETosis is a topic of ongoing research in the field of immunology.
471	netotic_cd	multiple sclerosis	33202203	Similar observations indicate involvement of NETosis in the autoimmune diseases, such as vasculitis associated with anti-neutrophil antibodies (AAV), antiphospholipid syndrome, multiple sclerosis, and psoriasis.
472	netotic_cd	myocardial infarction	33202203	A recent large-scale clinical study revealed correlation between the level of NETosis and the severity of ischemic stroke and myocardial infarction [84].
473	netotic_cd	pancreatitis 	33202203	In the pancreatic ducts, NETosis can be caused by microcrystals of calcium carbonate, which leads to blockage of the pancreatic duct and pancreatitis [89]. Such crystals cause NETosis in the bile ducts and in the gallbladder, which can lead to the formation of gallstones [90].
474	netotic_cd	pathogenesis	33202203	NETosis plays an important role in the pathogenesis of thrombosis of various origin [80, 81].
475	netotic_cd	psoriasis	33202203	Similar observations indicate involvement of NETosis in the autoimmune diseases, such as vasculitis associated with anti-neutrophil antibodies  (AAV), antiphospholipid syndrome, multiple sclerosis, and psoriasis.
476	netotic_cd	rheumatoid arthritis	37612413	NETosis plays an important role in the innate immune response because it allows neutrophils to directly combat pathogens. However, excessive or inappropriate NETosis can contribute to the development of inflammatory and autoimmune diseases, such as sepsis, rheumatoid arthritis, lupus, and cancer. Therefore, regulation of NETosis is a topic of ongoing research in the field of immunology.
477	netotic_cd	rheumatoid arthritis (RA)	33202203	In rheumatoid arthritis (RA), the development of pathology correlated with accumulation of the NETosis markers, such as DNA-MPO complexes and antibodies against citrullinated histones [103, 104]. 
478	netotic_cd	Sepsis	27820735	NETs are “traps” because their physical sequestering function prevents microorganism dissemination. Recently, in vivo imaging has provided insight into the containment function of NETs, which may prove to be its essential value in septic host defense. This containment comes at the expense of significant tissue damage, the balance of which must be weighed when considering NETosis as a therapeutic target in the septic patient.
479	netotic_cd	sepsis	37612413	NETosis plays an important role in the innate immune response because it allows neutrophils to directly combat pathogens. However, excessive or inappropriate NETosis can contribute to the development of inflammatory and autoimmune diseases, such as sepsis, rheumatoid arthritis, lupus, and cancer. Therefore, regulation of NETosis is a topic of ongoing research in the field of immunology.
480	netotic_cd	systemic lupus erythematosus	34039100	In this context, the development of autoimmune diseases like systemic lupus erythematosus has been linked to the prolonged or persistent extracellular exposure of histone complexes resulting from impaired NET degradation.
id	Symbol	Type	hgncid	name	locus_type	status	entrez_id	ensembl_gene_id	uniprot_ids
939	ELANE	netotic_cd	HGNC:3309	elastase, neutrophil expressed	gene with protein product	Approved	1991	ENSG00000197561	P08246
940	MMP1	netotic_cd	HGNC:7155	matrix metallopeptidase 1	gene with protein product	Approved	4312	ENSG00000196611	P03956
941	MPO	netotic_cd	HGNC:7218	myeloperoxidase	gene with protein product	Approved	4353	ENSG00000005381	P05164
942	CAMP	netotic_cd	HGNC:1472	cathelicidin antimicrobial peptide	gene with protein product	Approved	820	ENSG00000164047	P49913
943	PADI4	netotic_cd	HGNC:18368	peptidyl arginine deiminase 4	gene with protein product	Approved	23569	ENSG00000159339	Q9UM07
944	EIPA	netotic_cd	unknown	unknown	unknown	unknown	unknown	unknown	unknown
945	NCX1	netotic_cd	HGNC:11068	solute carrier family 8 member A1	gene with protein product	Approved	6546	ENSG00000183023	P32418
946	MIA	netotic_cd	HGNC:7076	MIA SH3 domain containing	gene with protein product	Approved	8190	ENSG00000261857	Q16674
lncid	cdtype	lncRNA	lnctarget	pmid	description
11442	netotic_cd	CT69	PADI4	24297251	starBase v2.0
11443	netotic_cd	MIR100HG	PADI4	24297251	starBase v2.0
mirnaid	cdtype	mirna	mitarget	pmid	description
6439	netotic_cd	hsa-let-7a-5p	MMP1	24297251	starBase v2.0
6440	netotic_cd	hsa-let-7b-5p	MMP1	24297251	starBase v2.0
6441	netotic_cd	hsa-let-7c-5p	MMP1	24297251	starBase v2.0
6442	netotic_cd	hsa-let-7d-5p	MMP1	24297251	starBase v2.0
6443	netotic_cd	hsa-let-7e-5p	MMP1	24297251	starBase v2.0
6444	netotic_cd	hsa-let-7f-5p	MMP1	24297251	starBase v2.0
6445	netotic_cd	hsa-miR-98-5p	MMP1	24297251	starBase v2.0
6446	netotic_cd	hsa-miR-221-3p	MMP1	24297251	starBase v2.0
6447	netotic_cd	hsa-let-7g-5p	MMP1	24297251	starBase v2.0
6448	netotic_cd	hsa-let-7i-5p	MMP1	24297251	starBase v2.0
6449	netotic_cd	hsa-miR-361-5p	MMP1	24297251	starBase v2.0
celldeathtype	datasource	pathwayname	pathwayid	intersection_num	pathwaygene_num	celldeathgenenum	genesymbols	p_value
1819	netotic_cd	KEGG	Drug metabolism - other enzymes - Homo sapiens (human)	hsa00983	1	80	8	MPO	0.0315610125554039
1820	netotic_cd	KEGG	PPAR signaling pathway - Homo sapiens (human)	hsa03320	1	75	8	MMP1	0.0296143043196309
1821	netotic_cd	KEGG	Neutrophil extracellular trap formation - Homo sapiens (human)	hsa04613	4	191	8	CAMP,MPO,PADI4,ELANE	5.47614303236799e-07
1822	netotic_cd	KEGG	IL-17 signaling pathway - Homo sapiens (human)	hsa04657	1	94	8	MMP1	0.0369936281797497
1823	netotic_cd	KEGG	Salivary secretion - Homo sapiens (human)	hsa04970	1	93	8	CAMP	0.0366064704846615
1824	netotic_cd	KEGG	Staphylococcus aureus infection - Homo sapiens (human)	hsa05150	1	96	8	CAMP	0.0377675351757395
1825	netotic_cd	KEGG	Transcriptional misregulation in cancer - Homo sapiens (human)	hsa05202	2	193	8	MPO,ELANE	0.00249669492780358
1826	netotic_cd	KEGG	Bladder cancer - Homo sapiens (human)	hsa05219	1	41	8	MMP1	0.0162856409847978
1827	netotic_cd	KEGG	Acute myeloid leukemia - Homo sapiens (human)	hsa05221	1	67	8	MPO	0.0264924488038676
1828	netotic_cd	KEGG	Rheumatoid arthritis - Homo sapiens (human)	hsa05323	1	93	8	MMP1	0.0366064704846615
substance_id	chemicals	cdtype	type	pmid	description
1187	NET 	netotic_cd	inducer	30948788	Netotic cell death is driven by NET release, which is regulated by NADPH oxidase-mediated ROS production and histone citrullination. 
1188	GSDMD	netotic_cd	inducer	30948788	GSDMD is also involved in the induction of NETosis to digest the pathogen
1189	NADPH oxidases	netotic_cd	inducer	29362479	NETotic cell death has been suggested to result from a signaling pathway that involves Raf-1 proto-oncogene, serine/threonine kinase (RAF1), mitogen-activated protein kinase kinases (MAP2Ks), and ERK2, culminating with NADPH oxidase activation and consequent ROS generation
1190	ROS	netotic_cd	inducer	29362479	intracellular ROS would drive NETotic cell death (1) by triggering the release of elastase, neutrophil expressed (ELANE), and myeloperoxidase (MPO) from neutrophil granules to the cytosol, followed by their translocation to the nucleus, and (2) by promoting the MPO-dependent proteolytic activity of ELANE
1191	 the necroptotic apparatus	netotic_cd	inducer	29362479	Finally, NETotic cell death has been proposed to depend (at least in part) on components of the necroptotic apparatus
1192	PAD4	netotic_cd	inducer	37918258	peptidyl arginine deiminase 4 (PAD4), an enzyme converting arginine to citrulline in histones, is responsible for NETosis initiation. 
1193	IL-8	netotic_cd	inducer	38443363	pathogens, IL-8, and other inducers stimulate the neutrophils, leading to a rapid increase in intracellular ROS levels
1194	Ripk3	netotic_cd	inhibitor	29362479	Ripk3−/− genotype appeared to inhibit NET extrusion and neutrophil lysis 
1195	PMA	netotic_cd	inducer	36265832	In this study, using a global metabolomics approach during the phorbol 12-myristate 13-acetate (PMA) induced NETosis in human neutrophils, various metabolic pathways were found to be altered which includes intermediates related to, carbohydrate metabolism, and redox related metabolites, nucleic acid metabolism, and amino acids metabolism. Enrichment analysis of the metabolite sets highlighted the importance of the pentose phosphate pathway (PPP) and glutathione metabolism PMA-induced NETotic neutrophils.
1196	SP600125	netotic_cd	inhibitor	28611461	JNK inhibitors SP600125 and TCSJNK6o, and a TLR4 inhibitor TAK242 suppress reactive oxygen species production and NETosis in LPS-, but not PMA-treated neutrophils.
1197	TCSJNK6o	netotic_cd	inhibitor	28611461	JNK inhibitors SP600125 and TCSJNK6o, and a TLR4 inhibitor TAK242 suppress reactive oxygen species production and NETosis in LPS-, but not PMA-treated neutrophils.
1198	TAK242	netotic_cd	inhibitor	28611461	JNK inhibitors SP600125 and TCSJNK6o, and a TLR4 inhibitor TAK242 suppress reactive oxygen species production and NETosis in LPS-, but not PMA-treated neutrophils.