Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi

Transcriptional regulation by transcriptional regulatory factors (TRFs) of their target TRF genes is central to the control of gene expression. To study a static multi-tiered inter-TRF regulatory network in the human hepatoma cells, we have applied a Matrix RNAi approach in which siRNA knockdown and quantitative RT-PCR are used in combination on the same set of TRFs to determine their interdependencies. This approach focusing on several liver-enriched TRF families, each of which consists of structurally homologous members, revealed many significant regulatory relationships. These include the cross-talks between hepatocyte nuclear factors (HNFs) and the other TRF groups such as CCAAT/enhancer-binding proteins (CEBPs), retinoic acid receptors (RARs), retinoid receptors (RXRs) and RAR-related orphan receptors (RORs), which play key regulatory functions in human hepatocytes and liver. In addition, various multi-component regulatory motifs, which make up the complex inter-TRF regulatory network, were identified. A large part of the regulatory edges identified by the Matrix RNAi approach could be confirmed by chromatin immunoprecipitation. The resultant significant edges enabled us to depict the inter-TRF TRN forming an apparent regulatory hierarchy of (FOXA1, RXRA) → TCF1 → (HNF4A, ONECUT1) → (RORC, CEBPA) as the main streamline

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

スイートピー ノ ハナ ノ コウキ セイブン ノ ヒンシュカンサ

スイートピーの自生種,夏咲き系`Prima Donna\u27,春咲き系`Royal Rose\u27および冬咲き系`茅ケ崎11号\u27を供試して花の香気成分を調査した。花のヘッドスペースから自生種で86成分,`Prima Donna\u27で108成分,`Royal Rose\u27では90成分および`茅ケ崎11号\u27では116成分が,ヘキサン抽出物からは自生種で39成分,`Prima Donna\u27で49成分,`Royal Rose\u27では58成分および`茅ケ崎11号\u27では32成分が同定または推定された。これらの花の香気成分組成には品種間差が認められた。The volatile components of the floral fragrances in sweet pea cultivars ; native in Sicily, \u27Prima Donna\u27 (a summer flowering line), \u27Royal Rose\u27 (a spring flowering line) and \u27Chigasaki No. 11.\u27 (a winter flowering line) were determined using head space and solvent elution combined with gaschromatography-mass spectrometry. Total of 86 in the native species, 108 in \u27Prima Donna\u27, 90 components in \u27Royal Rose\u27, 116 in \u27Chigasaki No. 11.\u27 were identified from headspace of the flowers, and there were clear differences in the volatile composition of the flowers among the cultivars