2013-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/682142摘要：流行病學與基礎研究皆指出慢性發炎與現代疾病的密切關係，包括肥胖、風濕性關節炎、心血管疾病、第二型糖尿病、潰瘍性腸炎與各式癌症等。在病理機制上，慢性發炎參與疾病的形成是一漫長且複雜的過程，最重要的特徵即發炎或免疫細胞的浸潤與發炎分子過度表現，引起細胞與組織的生理功能受損。已知環境因素會導致基因改變（genetic change）而起始疾病或癌症的形成，然而近十幾年的研究指出異常（aberrant）epigenetics作用或許才足以解釋現代疾病的多樣性與複雜性，例如人類遺傳性疾病。Epigenetics是指在不影響DNA序列的情況下調控基因表現的作用，常見的方式如DNA methylation與histone acetylation，且在生物體的發育生長過程中相當重要。近期研究顯示，epigenetics作用失常會直接影響發炎分子的表現或藉由活化轉錄因子促使基因表現，皆為影響慢性發炎與現代疾病發展的重要機制。就疾病化學預防的思維觀之，由於epigenetics作用是可逆的，相較於改變基因序列或抑制突變基因表現，藉由調節epigenetics控制基因表現而抑制慢性發炎與疾病形成或許為更適切的化學預防策略。柑橘為台灣最具農產價值的作物，然而相較於果肉的利用性，果皮因附加價值不高而大多用於製作肥料或被視為廢棄物。我們先前研究發現，柑橘果皮中富含polymethoxyflavone（PMFs）與hydroxyl PMFs（OH-PMFs），且具有抗癌、抗發炎、抑制腫瘤生長與腸癌形成的活性。本研究擬以以小鼠皮膚模式探討OH-PMFs抑制發炎、腫瘤形成的功效以及調控epigenetic作用之活性與機制。<br> Abstract: Numerous epidemiological and experimental data has demonstrated a direct link between chronic inflammation and complex diseases such as obesity, rheumatoid arthritis, cardiovascular disease, type 2 diabetes, inflammatory bowel disease and several types of cancer. The major mechanisms by which inflammation is contribute to chronic diseases are infiltration of inflammatory/immune cells and over-production of inflammatory mediators that result in damage of cellular and tissue function. A growing body of literature addressing environmental factors such as infection or diet is known to cause diseases and cancer development through genetic change. However, genetics per se cannot explain the vast diversity of phenotypes such as heritable disease but aberrant epigenetics. Epigenetics is defined as the study of mitotically and meiotically heritable changes in gene function that are not dependent on DNA sequence, such as DNA methylation and histone acetylation that are important for organism development. Recently, studies have shown that aberrant epigenetics are involved in chronic inflammation and diverse diseases through directly regulation of inflammatory genes expression and acts on transcription factors along with epigenetic phenomena. Thus, based on the principles of chemoprevention, targeting on modulation of epigenetics-mediated chronic inflammation and diseases will be more beneficial for preventive strategy. Citrus is one of the most important agriculture in Taiwan. However, compare to the economic value, peels are less utilization and as by-products. It has been found polymethoxyflavone (PMFs) and hydroxyl PMFs (OH-PMFs) are a unique class of flavonoids that almost exclusively exists in citrus genus, especially in the peel.The individual goal and study design are listed below: we will investigate the anti-infalmmatory and anti-skin carcinogeneic effect of OH-PMFs and their epigenetic regulation mechanism by using skin-two stage carcinogenesis model.羥基多甲氧基類黃酮癌症化學預防hydroxyl polymethoxyflavonescancer chemoprevention