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.

Effect of intermittent pneumatic compression on coagulation function and deep venous hemodynamics of lower limbs after rectal cancer resection / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of intermittent pneumatic compression (IPC) on coagulation function, deep venous hemodynamics and prevention of deep venous thrombosis (DVT) of lower limbs in patients after rectal cancer resection.</p><p><b>METHODS</b>A total of 120 patients undergoing rectal cancer resection were randomly divided into non-IPC group (control group, n=60) and IPC group (n=60). The control group received routine treatment after resection and the IPC group received IPC based on the routine treatments. Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), international normalized ratio (INR) and volume of D-dimer (D-D) were detected before operation and 1-, 3-, 5- and 7-day after operation. Meanwhile, blood flow velocity and caliber of external iliac vein, femoral vein and popliteal vein were examined by color Doppler ultrasound, then the average blood flow velocity and blood flow volume were calculated.</p><p><b>RESULTS</b>Incidence of lower limb DVT was 13.3% (8/60) and 1.7% (1/60) in control group and IPC group respectively with significant difference (P<0.05). The differences in PT, APTT and INR were not significant (P>0.05) at 1-day after operation as compared to the preoperative level, while FIB and D-D both increased (P<0.05), all presented no significant difference among the two groups (P>0.05). PT shortened gradually (P<0.05), APTT and INR did not change significantly (P>0.05), FIB and D-D increased gradually (P<0.05), and no significant differences were found between the two groups at the same time point (all P>0.05). All the above parameters in the control group were significantly lower than those in IPC group (all P<0.05).</p><p><b>CONCLUSIONS</b>IPC can improve hemodynamics indexes of deep veins of lower limb in patients after rectal cancer operation, and prevent the lower limb DVT. IPC is a safe, simple and convenient physical therapy.</p>

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.

Human bone marrow derived multipotent adult progenitor cells differentiating into hepatocyte-like cells after being induced by co-culturing with human hepatocyte line L02 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the possibility of marrow derived multipotent adult progenitor cells (MAPCs) differentiating into hepatocytes by co-culturing with human hepatocyte line L02, and to evaluate the potential use of MAPCs in tissue-engineering either experimentally or clinically.</p><p><b>METHODS</b>(1) Co-culturing without cell-to-cell contact: MAPCs and L02 hepatocytes were spread on coverslips separately (both with a cell density of 1x10(5)/ml), and then they were put in a culture dish (10 cm). The expressions of Alb, AFP, CK18, and CK19 in MAPCs were detected by immunocytochemistry at different time points. A separate culture of L02 hepatocytes served as a positive control and a separate culture of MAPCs served as a negative control. (2) Co-culturing with cell-to-cell contact: MAPCs labeled with CFSE were mixed with L02 hepatocytes (both with a cell density of 1x10(4)/ml), and then the mixed cells were seeded on specific dishes for detection by laser scanning confocal microscope (LSCM). Five days later, the cells were double-stained with SABC-Cy3. The expressions of Alb, AFP, CK18 in MAPCs were observed under LSCM. Similarly, separately cultured L02 hepatocytes served as a positive control and separately cultured MAPCs served as a negative control.</p><p><b>RESULTS</b>(1) Results of co-culturing without cell-to-cell contact: On the first day, the MAPCs expressed a high level of AFP. Then AFP expression tapered daily and there was hardly any expression of AFP on day 7. The expression of Alb was very weak on day 1, but increased significantly by day 3, reached its peak on day 5, and still maintained a high level on day 7. The initial expression of CK18 appeared on day 5 and reached a higher level on day 7. The expression of CK19 was always negative. The positive control cells had a high expression of Alb and CK18, while there was a weak expression of AFP and a negative expression of CK19. The negative control cells had no expressions for the four markers. (2) Results of co-culturing with cell-to-cell contact: On day 5, there were three colors of fluorescence under LSCM: yellow cells were MAPCs differentiating into hepatocytes; green cells were undifferentiated MAPCs; red cells were L02 hepatocytes. The result showed that Alb and CK18 were expressed in many cells and AFP appeared in only a few cells.</p><p><b>CONCLUSION</b>Human MAPCs can be induced to differentiate into mature hepatocyte-like cells by co-culturing with L02 hepatocytes, either with or without cell-to-cell contact, but the former way may be more effective.</p>

Expression and Significance of Apoptosis Related Gene BAG-1 in Digestive Tract Cancer by Tissue Microarray / 中国康复理论与实践

@#ObjectiveTo detect BAG1 expressions in digestive tract cancer by tissue microarray and to evaluate its clinical significance.MethodsTissue microarray of digestive tract cancer and normal tissues were analyzed by DAKO Envision system immunohistochemical staining for apoptosis related gene BAG-1 expression.ResultsThe positive rate of BAG-1 expression among esophagus cancer,gastric cancer and rectal cancer were higher than that of normal tissues respectively(P<0.01).ConclusionThere is an overexpression of BAG-1 in digestive tract cancer,which suggest that apoptosis related gene BAG-1 may be related to these cancer.