Therapeutic plasma exchange: A prospective randomized trial to evaluate 2 strategies in patients with liver failure.

OBJECTIVE: To compare two means of performing therapeutic plasma exchange (TPE) in patients with liver failure. METHOD: This open-label monocentric randomized trial, conducted in a single prestigious general healthcare facility, recruited liver failure patients with an indication to receive artificial liver support therapy for TPE. All patients underwent TPE procedures and were administered in a random sequence: heparin-free or systemic heparinization with unfractionated heparin. The primary endpoint was completion of TPE sessions, and the secondary endpoints included the safety and efficacy. RESULTS: In the period of the studying, there were 164 patients being recruited in and underwent total of 398 randomized TPEs: 168 with unfractionated heparin and 230 with heparin-free. In unfractionated heparin group, there were 3 cases (1.79%) being interrupted due to uncontrollable intraoperative pulmonary hemorrhages and gastrointestinal bleeding. In heparin-free group, 228 (99.13%) were completed successfully and 2 of them (0.87%) were switched from heparin-free to unfractionated heparin eventually. No significant differences were found between the two groups for either RRs or IRs (P > 0.05). CONCLUSION: Heparin-free regimen is feasible and safer than systemic heparinization with unfractionated heparin in the process of TPEs in patients with liver failure.

The lncRNA XIST exhibits oncogenic properties via regulation of miR-449a and Bcl-2 in human non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) are associated with the occurrence, development and prognoses of non-small cell lung cancer (NSCLC). In the present study, we investigated the functional mechanisms of the lncRNA XIST in two human NSCLC cell lines, A549 and NCI-H1299. In all the 5 NSCLC cell lines (NL9980, NCI-H1299, NCI-H460, SPC-A-1 and A549) tested, the expression levels of XIST were significantly elevated, as compared with those in normal human bronchial epithelial cell line BEAS-2B. In A549 and NCI-H1299 cells, knockdown of XIST by siRNA significantly inhibited the cell proliferation, migration and invasion, and promoted cell apoptosis. Furthermore, XIST knockdown elevated the expression of E-cadherin, and suppressed the expression of Bcl-2. Moreover, knockdown of XIST significantly suppressed the tumor growth in NSCLC A549 xenograft mouse model. Bioinformatic analysis and luciferase reporter assays revealed that XIST was negatively regulated by miR-449a. We further identified reciprocal repression between XIST and miR-449a, which eventually influenced the expression of Bcl-2: XIST functioned as a miRNA sponge of miR-449a, which was a negative regulator of Bcl-2. These data show that expression of the lncRNA XIST is associated with an increased growth rate and metastatic potential in NSCLC A549 and NCI-H1299 cells partially through miR-449a, and suggest that XIST may be a potential prognostic factor and therapeutic target for patients with NSCLC.

The von Hippel-Lindau protein pVHL inhibits ribosome biogenesis and protein synthesis.

pVHL, the product of von Hippel-Lindau (VHL) tumor suppressor gene, functions as the substrate recognition component of an E3-ubiquitin ligase complex that targets hypoxia inducible factor α (HIF-α) for ubiquitination and degradation. Besides HIF-α, pVHL also interacts with other proteins and has multiple functions. Here, we report that pVHL inhibits ribosome biogenesis and protein synthesis. We find that pVHL associates with the 40S ribosomal protein S3 (RPS3) but does not target it for destruction. Rather, the pVHL-RPS3 association interferes with the interaction between RPS3 and RPS2. Expression of pVHL also leads to nuclear retention of pre-40S ribosomal subunits, diminishing polysomes and 18S rRNA levels. We also demonstrate that pVHL suppresses both cap-dependent and cap-independent protein synthesis. Our findings unravel a novel function of pVHL and provide insight into the regulation of ribosome biogenesis by the tumor suppressor pVHL.

PAX2 protein induces expression of cyclin D1 through activating AP-1 protein and promotes proliferation of colon cancer cells.

Paired box (PAX) 2, a transcription factor, plays a critical role in embryogenesis. When aberrantly expressed in adult tissues, it generally exhibits oncogenic properties. However, the underlying mechanisms remain unclear. We reported previously that the expression of PAX2 was up-regulated in human colon cancers. However, the role of PAX2 in colon cancer cells has yet to be determined. The aim of this study is to determine the function of PAX2 in colon cancer cells and to investigate the possible mechanisms underlain. We find that knockdown of PAX2 inhibits proliferation and xenograft growth of colon cancer cells. Inhibition of PAX2 results in a decreased expression of cyclin D1. Expression of cyclin D1 is found increased in human primary colon malignant tumors, and its expression is associated with that of PAX2. These data indicate that PAX2 is a positive regulator of expression of cyclin D1. We find that knockdown of PAX2 inhibits the activity of AP-1, a transcription factor that induces cyclin D1 expression, implying that PAX2 induces cyclin D1 through AP-1. PAX2 has little effect on expression of AP-1 members including c-Jun, c-Fos, and JunB. Our data show that PAX2 prevents JunB from binding c-Jun and enhances phosphorylation of c-Jun, which may elevate the activity of AP-1. Taken together, these results suggest that PAX2 promotes proliferation of colon cancer cells through AP-1.

Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells.

Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors. However, the expression pattern of PKM2 in colorectal cancer (CRC) and the correlation between PKM2 expression and CRC remains unclear. The aim of this study is to investigate PKM2 expression and its possible role in CRC. We found that expression of PKM2 was increased in CRC and the increased PKM2 expression was associated with later stage and lymph metastasis of the tumors. Knockdown of PKM2 suppressed the aerobic glycolysis and decreased lactate production of colon cancer RKO cells. Knockdown of PKM2 repressed proliferation and migration of the cells. Inhibition of PKM2 suppressed xenograft tumor growth of RKO cells in vivo. These results suggest that the expression of PKM2 plays a critical role in development of CRC, and it may provide a growth advantage for colon cancer cells. Thus, PKM2 might be a potential therapeutic target for CRC.

Effect of teach-back health education combined with structured psychological nursing on adverse emotion and patient cooperation during 99mTc-3PRGD2.SPECT/CT.

BACKGROUND: 99mTc-3PRGD2.SPECT/CT is a commonly used examination method in nuclear medicine. However, patients receiving 99mTc-3PRGD2.SPECT/CT have insufficient knowledge of this method and worry about the examination results. AIM: To investigate the effect of teach-back health education combined with structured psychological nursing on adverse emotion and cooperation in patients undergoing 99mTc-3PRGD2.SPECT/CT examination. METHODS: Ninety patients undergoing 99mTc-3PRGD2.SPECT/CT examinations were divided into a study group and a control group using a simple random number table, and 45 cases were allocated to each group. Routine nursing was provided to the control group, and teach-back health education combined with structured psychological nursing was provided to the study group on the basis of the control group. Heart rate, diastolic blood pressure, systolic blood pressure, self-rating depression scale (SDS), and self-rating anxiety scale (SAS) were assessed before and after the intervention, and examination cooperation and intervention satisfaction were assessed in the two groups before, during, and after the examination. RESULTS: Before the examination, heart rate, diastolic blood pressure, and systolic blood pressure in the study group were not significantly different from the values of the control group (P > 0.05). The results of the study group before and after the examination were lower than those in the control group (P < 0.05). Before the intervention, SDS and SAS scores in the study group were not significantly different from those in the control group (P > 0.05). After the intervention, SDS and SAS scores in the study group were lower than those in the control group (P < 0.05). The degree of cooperation was higher in the study group than in the control group (P < 0.05). The satisfaction rate with the intervention was higher in the study group than in the control group (P < 0.05). CONCLUSION: Teach-back health education combined with structured psychological nursing can help maintain the stability of blood pressure and heart rate, relieve negative emotions, and improve the satisfaction and cooperation of patients undergoing 99mTc-3PRGD2.SPECT/CT examinations.

Inositol-1,4,5-trisphosphate and ryanodine-dependent Ca2+ signaling in a chronic dog model of atrial fibrillation.

Ca2+ signaling regulation plays an important role in triggering and/or maintaining atrial fibrillation (AF). Little is known about the relationship of the inositol-1,4,5-triphosphate receptors (InsP3Rs) and ryanodine receptors (RyRs) in left atrium to chronic AF. In this study, we investigated the expression and function of InsP3R1, InsP3R2 and RyR2 in a chronic dog model of AF. AF was induced in 6 dogs by rapid right atrial pacing for 24 weeks, and a sham procedure was performed in 5 dogs (control group). The intact left atrial myocytes were used to examine the expression and function of InsP3Rs, RyRs by BODIPY(O,R) TR-X ryanodine, heparin-fluorescein conjugate, and were stimulated by caffeine, ATP to release Ca2+ through RyRs, InsP3Rs separately. We also assessed the molecular components of left atrial tissue underlying the amount of RyR2, InsP3R1 and InsP3R2 determined by RT-PCR, immunohistochemistry and Western blot analysis. In the chronic AF group, the Ca2+ released through RyRs is not altered, but the Ca2+ released through InsP3Rs increased significantly. RyR2 distributed in cytosol of myocytes, cellular membrane; its expression significantly decreased in AF group compared to controls. InsP3R1 distributed in cytosol, InsP3R2 distributed not only in cytosol, cellular membrane, but also in nuclear envelope and intercalated discs. The InsP3R1 and InsP3R2 expression significantly increased in chronic AF group compared to controls. These results indicated that in a chronic dog model of AF, the expression and function of RyR2 down-regulated; on the contrary, the expression and function of InsP3R1, InsP3R2 up-regulated, and InsP3R2 may be the major InsP3Rs, which regulate intracellular or even intercellular Ca2+ signal transmission.

[Sediment Characteristics of Sewer in Different Functional Areas of Kunming].

The problem of sediment deposition in urban sewer network in different levels, will not only reduce the sewer flow ability, but also release pollutants and generate secondary pollution. The impact of secondary pollution is more serious in the study area, Kunming, because of the combined sewer overflow in rainy season. In order to obtain the characteristics of the sewer sediments in Kunming, the sewer sediments from residential area, service area, cultural district, and business district were investigated and collected. The particle size, density, organic matter (VSS/TSS) and pollutant content of the sediments were analyzed in this study. The results showed that there were different characteristics for the sediments from different areas. The size of the sediments exhibited business district >cultural district >residential area >service area, and the D50 was concentrated in the 20 to 100 µm except the business district. As for VSS/TSS, the order was residential area >cultural district >business district >service area. It was negatively correlated with the dry density with the correlation index of R2=0.9827 and positively correlated with the water content. The contents of sediments showed significant differences in different functional areas. The size of COD presented residential area >cultural district >service area >business district, and the size of TN followed residential area >cultural district >business district >service area. As for TP, it exhibited residential area >service area >cultural district >business district. The COD, TN and TP were proportional to the population density of the area and TP was greatly influenced by sediment particle size. From the branch into the Sub-main sewer, COD and TN were irregular, and TP decreased slightly. TP mainly existed as particulate and was more likely to deposit onto the small particle. As for TN, there was no obvious rule about its distribution in different particle size sections. The pollution load was generally on the high side in Kunming. The content of heavy metals in business district was the highest among all functional areas, and the concentrations of Cu, Zn, Pb, Cd were 284.6, 786.4, 201.2, 2.54 mg·kg-1 respectively. The average contents of Cu, Zn, Pb, Cd in urban area were 2.2, 4.4, 2.5, 8.6 times than the background values. It is suggested to control Cd and Zn with priority.

Review of aerobic glycolysis and its key enzymes - new targets for lung cancer therapy.

Most tumor cells show different metabolic pathways than normal cells. Even under the conditions of sufficient oxygen, they produce energy by a high rate of glycolysis followed by lactic acid fermentation in the cytosol, which is known as aerobic glycolysis or the Warburg effect. Lung cancer is a malignant tumor with one of the highest incidence and mortality rates in the world at present. However, the exact mechanisms underlying lung cancer development remain unclear. The three key enzymes of glycolysis are hexokinase, phosphofructokinase, and pyruvate kinase. Lactate dehydrogenase catalyzes the transfer of pyruvate to lactate. All four enzymes have been reported to be overexpressed in tumors, including lung cancer, and can be regulated by many oncoproteins to promote tumor proliferation, migration, and metastasis with dependence or independence of glycolysis. The discovery of aerobic glycolysis in the 1920s has provided new means and potential therapeutic targets for lung cancer.

TRAF6 upregulates expression of HIF-1α and promotes tumor angiogenesis.

TNF receptor (TNFR)-associated factor TRAF6 is a key activator of NF-κB, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upregulates expression of hypoxia-inducible factor (HIF)-1α. TRAF6 affects HIF-1α protein levels but has little effect on mRNA level. TRAF6 increases HIF-1α protein independent of oxygen. We found that TRAF6 binds HIF-1α and mediates its K63-linked polyubiquitination. The E3 ligase activity of TRAF6 was required to increase HIF-1α protein levels. Finally, we showed that TRAF6 promoted tumor angiogenesis and growth. Our results reveal how TRAF6 functions to upregulate HIF-1α expression and promote tumor angiogenesis.

The orphan nuclear receptor EAR2 is overexpressed in colorectal cancer and it regulates survivability of colon cancer cells.

EAR2 is a member of the chick ovalbumin upstream promoter-transcription factors (COUP-TFs). COUP-TFs belong to orphan nuclear receptors and regulate many biological processes. Little is known regarding EAR2 in cancer, though much progress has been made in understanding the function of other COUP-TF members. The aim of this study is to investigate the expression and possible function of EAR2 in colorectal cancer. We determined expression of EAR2 in human primary colorectal malignant tumors and their paired adjacent normal colorectal tissues. We found that expression of EAR2 was upregulated in colorectal tumors. Knockdown of EAR2 induced apoptosis of colon cancer cells, suggesting that EAR2 may function to regulate survivability of colon cancer cells. In vivo tumor study demonstrated that knockdown of EAR2 inhibited the xenograft growth of colon cancer cells. We found that knockdown of EAR2 inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP), suggesting that EAR2 regulates cell survivability, at least partly, through XIAP. In this manuscript, we demonstrated that expression of EAR2 was elevated in colorectal cancer and knockdown of EAR2 reduced survivability and tumor growth of colon cancer cells. Our results suggest that EAR2 plays an important role in development of colorectal cancer. The findings also suggest that EAR2 may serve as a potential therapeutic target of colorectal cancer.

Event-related potential correlates of suspicious thoughts in individuals with schizotypal personality features.

Suspiciousness is a common feature of schizophrenia. However, suspicious thoughts are also commonly experienced by the general population. This study aimed to examine the underlying neural mechanism of suspicious thoughts in individuals with and without schizotypal personality disorder (SPD)-proneness, using an event-related potential (ERP) paradigm. Electroencephalography (EEG) was recorded when the "feeling of being seen through" was evoked in the participants. The findings showed a prominent positive deflection of the difference wave within the time window 250-400 ms after stimuli presentation in both SPD-prone and non-SPD-prone groups. Furthermore, the P3 amplitude was significantly reduced in the SPD-prone group compared to the non-SPD-prone group. The current density analysis also indicated hypoactivity in both frontal and temporal regions in the SPD-prone group, suggesting that the frontotemporal cortical network may play a role in the onset of suspicious thoughts. The P3 of difference wave was inversely correlated with the cognitive-perception factor and the suspiciousness/paranoid ideation trait, which provided preliminary electrophysiological evidence for the association of suspiciousness with SPD features.

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin ß 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

Luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin.

Luteolin, a common dietary flavonoid, has been found to have antitumor properties and therefore poses special interest for the development of preventive and/or therapeutic agent for cancers. E-cadherin, a marker of epithelial cells, mediates cell-cell adhesion. Decreased expression of E-cadherin results in a loss of cell-cell adhesion and an increased cell invasion. Many studies have shown the antiproliferative activities of luteolin on cancer cells. However, the effects of luteolin on invasion of cancer cells remain unclear. In this article, we show that luteolin inhibits invasion of prostate cancer PC3 cells through E-cadherin. We found that Luteolin induced expression of E-cadherin through mdm2. Overexpression of mdm2 or knockdown of E-cadherin could restore invasion of PC3 cells after luteolin treatment. Luteolin inhibits mdm2 through AKT and overexpression of active AKT attenuated luteolin-induced expression of E-cadherin, suggesting that luteolin regulates E-cadherin through AKT/mdm2 pathway. The in vivo experiments showed that luteolin inhibited spontaneous lung metastasis of PC3 cells implanted onto the nude mice. These findings provide a new sight into the mechanisms that luteolin is against cancer cells, and suggest that molecular targeting of E-cadherin by luteolin may be a useful strategy for treatment of invasive prostate cancers.