4 results on '"William Y. Yang"'
Search Results
2. Organelle Crosstalk Regulators Are Regulated in Diseases, Tumors, and Regulatory T Cells: Novel Classification of Organelle Crosstalk Regulators
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Ming Liu, Na Wu, Keman Xu, Fatma Saaoud, Eleni Vasilopoulos, Ying Shao, Ruijing Zhang, Jirong Wang, Haitao Shen, William Y. Yang, Yifan Lu, Yu Sun, Charles Drummer, Lu Liu, Li Li, Wenhui Hu, Jun Yu, Domenico Praticò, Jianxin Sun, Xiaohua Jiang, Hong Wang, and Xiaofeng Yang
- Subjects
0301 basic medicine ,Autophagosome ,organelle crosstalk ,viral infections ,Cell ,Inflammation ,Cardiovascular Medicine ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Lysosome ,Mitophagy ,medicine ,Diseases of the circulatory (Cardiovascular) system ,IL-2 receptor ,Original Research ,Endoplasmic reticulum ,endothelial cell activation ,Cell biology ,Treg ,030104 developmental biology ,medicine.anatomical_structure ,inflammation ,RC666-701 ,030220 oncology & carcinogenesis ,cancers and tumors ,medicine.symptom ,Cardiology and Cardiovascular Medicine - Abstract
To examine whether the expressions of 260 organelle crosstalk regulators (OCRGs) in 16 functional groups are modulated in 23 diseases and 28 tumors, we performed extensive -omics data mining analyses and made a set of significant findings: (1) the ratios of upregulated vs. downregulated OCRGs are 1:2.8 in acute inflammations, 1:1 in metabolic diseases, 1:1.2 in autoimmune diseases, and 1:3.8 in organ failures; (2) sepsis and trauma-upregulated OCRG groups such as vesicle, mitochondrial (MT) fission, and mitophagy but not others, are termed as the cell crisis-handling OCRGs. Similarly, sepsis and trauma plus organ failures upregulated seven OCRG groups including vesicle, MT fission, mitophagy, sarcoplasmic reticulum–MT, MT fusion, autophagosome–lysosome fusion, and autophagosome/endosome–lysosome fusion, classified as the cell failure-handling OCRGs; (3) suppression of autophagosome–lysosome fusion in endothelial and epithelial cells is required for viral replications, which classify this decreased group as the viral replication-suppressed OCRGs; (4) pro-atherogenic damage-associated molecular patterns (DAMPs) such as oxidized low-density lipoprotein (oxLDL), lipopolysaccharide (LPS), oxidized-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (oxPAPC), and interferons (IFNs) totally upregulated 33 OCRGs in endothelial cells (ECs) including vesicle, MT fission, mitophagy, MT fusion, endoplasmic reticulum (ER)–MT contact, ER– plasma membrane (PM) junction, autophagosome/endosome–lysosome fusion, sarcoplasmic reticulum–MT, autophagosome–endosome/lysosome fusion, and ER–Golgi complex (GC) interaction as the 10 EC-activation/inflammation-promoting OCRG groups; (5) the expression of OCRGs is upregulated more than downregulated in regulatory T cells (Tregs) from the lymph nodes, spleen, peripheral blood, intestine, and brown adipose tissue in comparison with that of CD4+CD25− T effector controls; (6) toll-like receptors (TLRs), reactive oxygen species (ROS) regulator nuclear factor erythroid 2-related factor 2 (Nrf2), and inflammasome-activated regulator caspase-1 regulated the expressions of OCRGs in diseases, virus-infected cells, and pro-atherogenic DAMP-treated ECs; (7) OCRG expressions are significantly modulated in all the 28 cancer datasets, and the upregulated OCRGs are correlated with tumor immune infiltrates in some tumors; (8) tumor promoter factor IKK2 and tumor suppressor Tp53 significantly modulate the expressions of OCRGs. Our findings provide novel insights on the roles of upregulated OCRGs in the pathogenesis of inflammatory diseases and cancers, and novel pathways for the future therapeutic interventions for inflammations, sepsis, trauma, organ failures, autoimmune diseases, metabolic cardiovascular diseases (CVDs), and cancers.
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- 2021
3. Twenty Novel Disease Group-Specific and 12 New Shared Macrophage Pathways in Eight Groups of 34 Diseases Including 24 Inflammatory Organ Diseases and 10 Types of Tumors
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Bin Lai, Jiwei Wang, Alexander Fagenson, Yu Sun, Jason Saredy, Yifan Lu, Gayani Nanayakkara, William Y. Yang, Daohai Yu, Ying Shao, Charles Drummer, Candice Johnson, Fatma Saaoud, Ruijing Zhang, Qian Yang, Keman Xu, Kevin Mastascusa, Ramon Cueto, Hangfei Fu, Susu Wu, Lizhe Sun, Peiqian Zhu, Xuebin Qin, Jun Yu, Daping Fan, Ying H. Shen, Jianxin Sun, Thomas Rogers, Eric T. Choi, Hong Wang, and Xiaofeng Yang
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Immunology ,Inflammation ,Biology ,Exosome ,Proinflammatory cytokine ,trained immunity ,03 medical and health sciences ,0302 clinical medicine ,Immunity ,Neoplasms ,medicine ,Data Mining ,Humans ,Immunology and Allergy ,Macrophage ,Original Research ,Innate immune system ,Microarray analysis techniques ,Immune checkpoint ,macrophages ,immune checkpoint receptors ,030104 developmental biology ,disease-specific and shared pathways ,medicine.symptom ,lcsh:RC581-607 ,immunometabolism pathways ,Signal Transduction ,030215 immunology - Abstract
The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ markers than lean adipose tissue Mφ (ATMφ) physiologically. (3) Pro-adipogenic TFs C/EBPα and PPARγ and proinflammatory adipokine leptin upregulate the expression of M1 Mφ markers. (4) Among 10 immune checkpoint receptors (ICRs), LLSI-Mφ and bone marrow (BM) Mφ express higher levels of CD274 (PDL-1) than ATMφ, presumably to counteract the M1 dominant status via its reverse signaling behavior. (5) Among 24 intercellular communication exosome mediators, LLSI- and BM- Mφ prefer to use RAB27A and STX3 than RAB31 and YKT6, suggesting new inflammatory exosome mediators for propagating inflammation. (6) Mφ in peritoneal tissue and LLSI-Mφ upregulate higher levels of immunometabolism enzymes than does ATMφ. (7) Mφ from peritoneum and LLSI-Mφ upregulate more trained immunity enzyme genes than does ATMφ. Our results suggest that multiple new mechanisms including the cell surface, intracellular immunometabolism, trained immunity, and TFs may be responsible for disease group-specific and shared pathways. Our findings have provided novel insights on the pathophysiological regulation of tissue Mφ, the disease group-specific and shared pathways of Mφ, and novel therapeutic targets for cancers and inflammations.
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- 2019
4. DNA Checkpoint and Repair Factors Are Nuclear Sensors for Intracellular Organelle Stresses—Inflammations and Cancers Can Have High Genomic Risks
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Huihong Zeng, Gayani K. Nanayakkara, Ying Shao, Hangfei Fu, Yu Sun, Ramon Cueto, William Y. Yang, Qian Yang, Haitao Sheng, Na Wu, Luqiao Wang, Wuping Yang, Hongping Chen, Lijian Shao, Jianxin Sun, Xuebin Qin, Joon Y. Park, Konstantinos Drosatos, Eric T. Choi, Qingxian Zhu, Hong Wang, and Xiaofeng Yang
- Subjects
0301 basic medicine ,Genome instability ,Programmed cell death ,danger associated molecular patterns (DAMPs) ,Physiology ,DNA damage ,Inflammation ,Gene mutation ,Biology ,lcsh:Physiology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Intracellular organelle ,Physiology (medical) ,cancers ,medicine ,Original Research ,DNA damage checkpoint and repair factors ,lcsh:QP1-981 ,G2-M DNA damage checkpoint ,genomic instability ,3. Good health ,Cell biology ,030104 developmental biology ,chemistry ,inflammation ,030220 oncology & carcinogenesis ,medicine.symptom ,DNA - Abstract
Under inflammatory conditions, inflammatory cells release reactive oxygen species (ROS) and reactive nitrogen species (RNS) which cause DNA damage. If not appropriately repaired, DNA damage leads to gene mutations and genomic instability. DNA damage checkpoint factors (DDCF) and DNA damage repair factors (DDRF) play a vital role in maintaining genomic integrity. However, how DDCFs and DDRFs are modulated under physiological and pathological conditions are not fully known. We took an experimental database analysis to determine the expression of 26 DNA DDCFs and 42 DNA DDRFs in 21 human and 20 mouse tissues in physiological/pathological conditions. We made the following significant findings: (1) Few DDCFs and DDRFs are ubiquitously expressed in tissues while many are differentially regulated.; (2) the expression of DDCFs and DDRFs are modulated not only in cancers but also in sterile inflammatory disorders and metabolic diseases; (3) tissue methylation status, pro-inflammatory cytokines, hypoxia regulating factors and tissue angiogenic potential can determine the expression of DDCFs and DDRFs; (4) intracellular organelles can transmit the stress signals to the nucleus, which may modulate the cell death by regulating the DDCF and DDRF expression. Our results shows that sterile inflammatory disorders and cancers increase genomic instability, therefore can be classified as pathologies with a high genomic risk. We also propose a new concept that as parts of cellular sensor cross-talking network, DNA checkpoint and repair factors serve as nuclear sensors for intracellular organelle stresses. Further, this work would lead to identification of novel therapeutic targets and new biomarkers for diagnosis and prognosis of metabolic diseases, inflammation, tissue damage and cancers.
- Published
- 2018
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