Nrf2 expands the intracellular pool of the chaperone AHSP in a cellular model of ß-thalassemia.

In ß-thalassemia, free α-globin chains are unstable and tend to aggregate or degrade, releasing toxic heme, porphyrins and iron, which produce reactive oxygen species (ROS). α-Hemoglobin-stabilizing protein (AHSP) is a potential modifier of ß-thalassemia due to its ability to escort free α-globin and inhibit the cellular production of ROS. The influence of AHSP on the redox equilibrium raises the question of whether AHSP expression is regulated by components of ROS signaling pathways and/or canonical redox proteins. Here, we report that AHSP expression in K562 cells could be stimulated by NFE2-related factor 2 (Nrf2) and its agonist tert-butylhydroquinone (tBHQ). This tBHQ-induced increase in AHSP expression was also observed in Ter119+ mouse erythroblasts at each individual stage during terminal erythroid differentiation. We further report that the AHSP level was elevated in α-globin-overexpressing K562 cells and staged erythroblasts from ßIVS-2-654 thalassemic mice. tBHQ treatment partially alleviated, whereas Nrf2 or AHSP knockdown exacerbated, α-globin precipitation and ROS production in fetal liver-derived thalassemic erythroid cells. MafG and Nrf2 occupancy at the MARE-1 site downstream of the AHSP transcription start site was detected in K562 cells. Finally, we show that MafG facilitated the activation of the AHSP gene in K562 cells by Nrf2. Our results demonstrate Nrf2-mediated feedback regulation of AHSP in response to excess α-globin, as occurs in ß-thalassemia.

Acyl-CoA dehydrogenase long chain expression is associated with esophageal squamous cell carcinoma progression and poor prognosis.

BACKGROUND: Acyl-CoA dehydrogenase long chain (ACADL) was revealed to have a correlation with malignant progression of cancer. However, whether ACADL plays a role in clinical therapy remains unclear. The clinicopathological role of ACADL in esophageal squamous cell carcinoma (ESCC) will be discussed in this study. MATERIALS AND METHODS: The expression of ACADL was analyzed via real-time PCR and Western blotting to assess mRNA and protein levels in ESCC cell lines and normal esophageal epithelial cells (NEECs), in six paired ESCC tumors and relative normal tissues. Furthermore, immunohistochemical staining was performed on 135 paraffin-embedded ESCC specimens to assess ACADL expression. The clinicopathological significance of ACADL expression was further investigated via survival analysis and Cox regression analysis. RESULTS: ACADL was found to be markedly upregulated in ESCC cell lines when compared with NEECs. Moreover, various experiments such as quantitative real-time PCR, Western blot, and immunohistochemical analyses all revealed that ACADL expression was increased in all six paired ESCC tumors and matched normal tissues. Furthermore, immunohistochemical analysis revealed an increased level of ACADL protein expression in all 135 paraffin-embedded samples from ESCC patients, which increased with disease progression. CONCLUSION: We demonstrated that ACADL is overexpressed in ESCC, both in cell lines and clinical specimens. ACADL is found to be a vital regulator in ESCC progression and can predict a worse outcome for ESCC patients, suggesting that ACADL might be a valuable molecule to be targeted for clinical therapy of ESCC treatment.

Selecting an appropriate interestingness measure to evaluate the correlation between Chinese medicine syndrome elements and symptoms.

To select the best interestingness measure appropriate for evaluating the correlation between Chinese medicine (CM) syndrome elements and symptoms, 60 objective interestingness measures were selected from different subjects. Firstly, a hypothesis for a good measure was proposed. Based on the hypothesis, an experiment was designed to evaluate the measures. The experiment was based on the clinical record database of past dynasties including 51 186 clinical cases. The selected data set in this study had 44 600 records. Cold and heat were selected as the experimental CM syndrome elements. Three indicators calculated according to the distances between two CM syndrome elements were obtained in the experiment and combined into one indicator. The Z score, ϕ-coefficient, and Kappa were selected from 60 measures after the experiment. The Z score and ϕ-coefficient were selected according to subjective interestingness. Finally, the ϕ-coefficient was selected as the best measure for its low computational complexity. The method introduced in this paper may be used in other similar territories.

The TCM pattern of the six-zang and six-fu organs can be simplified into the pattern of five-zang and one-fu organs.

OBJECTIVE: To simplify the TCM pattern of the zang-fu organs. METHODS: A database of zang-fu syndromes was established. The relationship between the zang-fu syndromes was analyzed by means of frequency analysis, association rule, and phi-coefficient correlation. RESULTS: The six zang-fu organs of the heart, liver, spleen, lung, kidney, and stomach prove to be the main components of the zang-fu pattern. The large intestine, small intestine, gallbladder, bladder, triple energizer, and pericardium have strong association and positive correlation with the above-mentioned six zang-fu organs, and their clinical symptoms can all be included into the symptoms of these six zang-fu organs. CONCLUSION: The traditional TCM pattern of six-zang and six-fu can be simplified into five-zang and one-fu.