Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0241981 (loss of balance)
 452 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria are semi-autonomous organelles of eukaryotic cells. They perform crucial functions such as generating most of the cellular energy through the oxidative phosphorylation (OXPHOS) system and some other metabolic processes. In addition, mitochondria are involved in regulation of cell death and reactive oxygen species (ROS) generation. Also, mitochondria play important roles in carcinogenesis via altering energy metabolism, resistance to apoptosis, increase of production of ROS and mtDNA (mitochondrial genome) changes. Studies have suggested that aerobic glycolysis is high in malignant tumors. Probably, it correlates with high glucose intake of cancerous tissues. This observation is contrary to Warburg's theory that the main way of energy generation in cancer cells is non-oxidative glycolysis. Further studies have suggested that in tumor cells both oxidative phosphorylation and glycolysis were active at various rates. An increase of intracellular oxidative stress induces damage of cellular structure and somatic mutations. Further studies confirmed that permanent activity of oxidative stress and the influence of chronic inflammation damage the healthy neighboring epithelium and may lead to carcinogenesis. For instance, chronic inflammatory bowel disease could be related to high risk of colon adenocarcinoma. The data have shown a role of ROS generation, mtDNA or nDNA alterations and abnormal apoptotic machinery in endometrial cancer progress. Recent studies suggest that mtDNA mutations might play a potential role in endometrial cancer progress and indicate an increase of mitochondrial biogenesis in this cancer. The investigators suggested that MtCOI and MtND6 alteration has an influence on assembly of respiratory complexes in endometrial cancer. In many human cancers, there is a deregulation of the balance between cell growth and death. The tumor cells can avoid apoptosis through a loss of balance between anti- and pro-apoptotic proteins, reduced caspase function and impaired death receptor signaling. Over-expression of the anti-apoptotic BCL-2 gene has also been identified in numerous cancers including colon, thyroid, breast and endometrial cancer. Most studies have found low BCL-2 family gene expression, which could be a sign of blocking apoptosis in breast and endometrial cancer. Moreover, BCL-2 gene expression is correlated with the degree of aggressiveness and differentiation in endometrial cancer. As a result, it could be a valuable predictor of disease progression.
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PMID:Mitochondrial dysfunction in cancer. 2632 44

Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis.
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PMID:IL-33/ST2 Axis in Organ Fibrosis. 3040 26