ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia chebula has an esteemed origin in Indian mythology; its fruits are used to treat many diseases such as digestive, diabetes, colic pain, chronic cough, sore throat, asthma, etc. AIM OF THE STUDY: The water or ethanolic extracts of the fruits were reported to have anti-oxidant, anti-inflammatory, anti-cancer and radio-protector properties. The present study is to isolate and identify the compounds that inhibit COX and 5-LOX, the key enzymes involved in inflammation and carcinogenesis.
BACKGROUND: Persistent activation of hepatic stellate cells (HSC-T6) has been known to cause liver fibrosis. In this study, our objective was to investigate the effects of chebulagic acid and chebulinic acid, two hydrolysable tannins of tropical almond (Terminalia chebula) fruits, on collagen synthesis and signal transduction in transforming growth factor-?1-stimulated HSC-T6 cells.
Nine phenolic compounds, including two phenolic carboxylic acids, 1 and 2, seven hydrolyzable tannins, 3-9, eight triterpenoids, including four oleanane-type triterpene acids, 10-13, and four of their glucosides, 14-17, isolated from a MeOH extract of the gall of Terminalia chebula Retz.
Cellular senescence is a state of irreversible cell cycle arrest in which normal cells at the end of their lifespan fail to enter into DNA synthesis upon serum or growth factor stimulation. We examined whether proteins required for G1/S cell cycle progression were irreversibly down-regulated in senescent human fibroblasts. Both the 44- and 42-kDa forms of the MAP-kinase protein were expressed at similar levels in young and senescent cells.
Studies were conducted to directly test whether the introduction of telomerase protects cancer-prone human mammary epithelial cells from chromosomal instability and spontaneous immortalization. Using a model for Li Fraumeni Syndrome (LFS), infection of human telomerase resulted in maintenance of telomere lengths, extension of in vitro lifespan, and prevention of spontaneous immortalization.
PURPOSE: To investigate the migratory and contractile behavior of isolated human corneal fibroblasts in fibrillar collagen matrices. METHODS: A telomerase-infected, extended-lifespan human corneal fibroblast cell line (HTK) was transfected by using a vector for enhanced green fluorescent protein (GFP)-alpha-actinin. Cells were plated at low density on top of or within 100-microm-thick fibrillar collagen lattices. After 18 hours to 7 days, time-lapse imaging was performed.
Telomere shortening in normal human cells causes replicative senescence, a p53-dependent growth arrest state, which is thought to represent an innate defence against tumour progression. However, although it has been postulated that critical telomere loss generates a 'DNA damage' signal, the signalling pathway(s) that alerts cells to short dysfunctional telomeres remains only partially defined.
The ID (inhibitor of differentiation or DNA binding) helix-loop-helix proteins are important mediators of cellular differentiation and proliferation in a variety of cell types through regulation of gene expression. Overexpression of the ID proteins in normal human keratinocytes results in extension of culture lifespan, indicating that these proteins are important for epidermal differentiation. Our hypothesis is that the ID proteins are targets of the retinoic acid signaling pathway in keratinocytes.
Molecular Therapy: The Journal of the American Society of Gene Therapy
Methylmalonic acidemia (MMA) is an organic acidemia caused by deficient activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). This disorder is associated with lethal metabolic instability and carries a poor prognosis for long-term survival. A murine model of MMA that replicates a severe clinical phenotype was used to examine the efficacy of recombinant adeno-associated virus (rAAV) serotype 8 gene therapy as a treatment for MMA.
AIMS: Resveratrol, a silent information regulator 1 (SIRT1) activator, has been reported to act as an antioxidant contained in red wine and prevent the development of cardiovascular diseases. Histone deacetylase such as SIRT1 is involved in the regulation of lifespan extension. In this study, the effect of resveratrol on matrix metalloproteinases (MMPs) that play an important role in metastasis was examined in human fibrosarcoma cell line, HT1080. MAIN METHODS: The effect of resveratrol on MMPs' activity was evaluated using gelatin zymography.