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.
The Id family of helix-loop-helix transcription factors is upregulated in a variety of human malignancies and has been implicated in promoting tumorigenesis through effects on cell growth, differentiation, and tumor angiogenesis. While expression of Id proteins has been associated with tumorigenesis, the precise mechanistic relationship between Id expression and carcinogenesis has not been clearly delineated. We have previously shown that Id1 delays cellular senescence in primary mammalian cells through inhibition of the cell cycle regulatory protein and familial melanoma gene, p16/INK4a.
Silent information regulator 2 (SIR2) is a highly conserved protein, the mammalian orthologue of which, SIRT1, exhibits histone deacetylase activity. SIRT1 is involved not in only longevity due to caloric restriction but in a variety of diseases such as diabetes, cardiovascular dysfunction and neurodegeneration. However, accumulating evidence shows that SIRT1 is overexpressed in various types of malignant cells, and its inhibitors suppress the growth of tumor cells. The relationship between SIRT1 and metastasis remains to be clarified.
Homo sapiens longevity assurance homologue 2 of yeast LAG1 (LASS2), also known as tumor metastasis suppressor gene 1 (TMSG1), is a newly found tumor metastasis suppressor gene in 1999. Preliminary studies showed that it not only suppressed tumor growth but also closely related to tumor metastasis, however, its molecular mechanisms is still unclear.
Aging poses one of the largest risk factors for the development of cardiovascular disease. The increased propensity toward vascular pathology with advancing age maybe explained, in part, by a reduction in the ability of circulating endothelial progenitor cells to contribute to vascular repair and regeneration. Although there is evidence to suggest that colony forming unit-Hill cells and circulating angiogenic cells are subject to age-associated changes that impair their function, the impact of aging on human outgrowth endothelial cell (OEC) function has been less studied.
Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood.
Adaptation is a central organizing principle throughout biology, whether we are studying species, populations, or individuals. Adaptation in biological systems occurs in response to molar and molecular environments. Thus, we would predict that genetic systems and nervous systems would be dynamic (cybernetic) in contrast to previous conceptualizations with genes and brains fixed in form and function. Questions of nature versus nurture are meaningless, and we must turn to epigenetics--the way in which biology and experience work together to enhance adaptation throughout thick and thin.
Our understanding of human disorders that affect higher cognitive functions has greatly advanced in recent decades, and over 20 genes associated with non-syndromic mental retardation have been identified during the past 15 years. However, proteins encoded by "cognition genes" have such diverse neurodevelopmental functions that delineating specific pathogenetic pathways still poses a tremendous challenge.
Transcriptional mechanisms mediated by the binding of transcription factors (TFs) to cis-acting regulatory elements (CREs) in DNA play crucial roles in directing gene expression. While TFs have been extensively studied, less effort has gone towards the identification and functional characterization of CREs and associated epigenetic modulation. However, owing to methodological and analytical advances, more comprehensive studies of regulatory elements and mechanisms are now possible.
Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-?B activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia.