A Systematic Pan-Cancer Analysis of MEIS1 in Human Tumors as Prognostic Biomarker and Immunotherapy Target.

BACKGROUND: We intended to explore the potential immunological functions and prognostic value of Myeloid Ecotropic Viral Integration Site 1 (MEIS1) across 33 cancer types. METHODS: The data were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene expression omnibus (GEO) datasets. Bioinformatics was used to excavate the potential mechanisms of MEIS1 across different cancers. RESULTS: MEIS1 was downregulated in most tumors, and it was linked to the immune infiltration level of cancer patients. MEIS1 expression was different in various immune subtypes including C2 (IFN-gamma dominant), C5 (immunologically quiet), C3 (inflammatory), C4 (lymphocyte depleted), C6 (TGF-b dominant) and C1 (wound healing) in various cancers. MEIS1 expression was correlated with Macrophages_M2, CD8+T cells, Macrophages_M1, Macrophages_M0 and neutrophils in many cancers. MEIS1 expression was negatively related to tumor mutational burden (TMB), microsatellite instability (MSI) and neoantigen (NEO) in several cancers. Low MEIS1 expression predicts poor overall survival (OS) in adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), and kidney renal clear cell carcinoma (KIRC) patients, while high MEIS1 expression predicts poor OS in colon adenocarcinoma (COAD) and low grade glioma (LGG) patients. CONCLUSION: Our findings revealed that MEIS1 is likely to be a potential new target for immuno-oncology.

Understanding the unique mechanism of ferroptosis: a promising therapeutic target.

Ferroptosis is an iron-dependent form of regulated cell death and is characterized by high concentrations of intracellular lipid peroxide and a redox imbalance in the cells. Ferroptosis shows distinct morphological and biological features compared with other prominent mechanisms of programmed cell death. The distinct characteristics of ferroptosis include the dysfunction of the lipid peroxide repair enzyme glutathione peroxidase 4, the presence of ferrous iron overload, and the lipid peroxidation of polyunsaturated fatty acids. Several other metabolic pathways (including iron, lipid, and amino acid metabolism) and ferritinophagy, as well as transcription factors, can modulate ferroptosis. However, to date, the molecular mechanism of ferroptosis has not been elucidated. This review outlines the discovery, characterization, regulatory mechanisms, and crosstalk of ferroptosis. Further, we have noted the controversial elements in the ferroptosis-related mechanisms. Our inferences may provide a partial reference for developing strategies to regulate ferroptosis.

Cross-cultural adaptation and validation of the PedsQL™ stem cell transplant module in China: A methodological and cross-sectional study.

Background: Hematopoietic stem cell transplantation (HSCT), as a mature technology, has significantly improved the survival rate of children. However, there lack efficient scales to assess the quality of life (QoL) of children with HSCT in China, which has important implications in the care of this population. This study aimed to translate the original English Pediatric Quality of Life Inventory™ (PedsQL™) Stem Cell Transplant Module into a Chinese mandarin version, and evaluate its reliability. Methods: Children of ages 2-18 years who had received HSCT at Children's Hospital of Nanjing Medical University and Children's Hospital of Fudan University were recruited. Children or their parents were asked to fill the PedsQL™ 4.0 Generic Core Scales, PedsQL™ Stem Cell Transplant Module, and PedsQL™ Family Information Form. Feasibility was evaluated by completion rate and the percentage of missing items, reliability by the internal consistency and test-retest reliability, and validity by factor analysis and correlation analysis between the scores of total scale and each dimension. Results: A total of 120 children (mean age 6.37, SD = 3.674) and some parents were included. A low percentage of items were missed in returned reports. Cronbach's alpha coefficient reached 0.70 in the majority of dimensions of both child self-report and parent proxy-report. Test-retest reliability was 0.685 in parents' forms and 0.765 in child's forms. Eight factors were extracted, with a cumulative contribution rate of 74.54%. The correlation between PedsQL™ 4.0 and Transplant Module was 0.748 for children self-report and 0.808 for parent proxy-report. Conclusions: This study provides evidence that the Chinese mandarin version of the PedsQL™ Stem Cell Transplant is feasible, reliable and valid in evaluating the QoL of Chinese children after HSCT.

Remediation of contaminated soil and groundwater using chemical reduction and solidification/stabilization method: a case study.

This study presents a systematic on-site remediation case involving both heavy metal and organic contaminants in soil and groundwater in a historically industrial-used site in Shanghai, China. Lab-scale experiments and field tests were conducted to determine the optimum parameters for the removal of contaminants in soil and groundwater. It has been found that the remediation goal of hexavalent chromium in soil could be achieved with the mass content of added sodium hydrosulfite and ferrous sulfate reaching 3% + 6%. The total chromium in the groundwater was effectively removed, when the mass ratio of sodium metabisulfite was not less than 3 g/L, and the added quick lime made pH value not less than 9. The concentrations of arsenic and 1,2-dichloropropane in the groundwater decreased evidently after extraction and mixing of groundwater. The pH and calcium chloride dosage added should be larger than 9.5 and 5 g/L, respectively, to remove phosphate in groundwater. The removal efficiency of those contaminants was examined and evaluated after the on-site remediation. The results demonstrated that it was feasible to use the chemical reduction and solidification/stabilization methods for the on-site ex situ remediation of this site, which could be referenced for the realistic remediation of similar sites.

Comprehensive overview of numerical modeling of coupled landfill processes.

Landfilling is the primary method used for municipal solid waste (MSW) disposal. To design, optimize, and manage landfills with a life span of several decades, a deeper understanding of long-term MSW behaviors is necessary and worthwhile. These behaviors should be modeled using approaches that account for coupled processes so as to capture the evolutionary mechanisms that are mainly dominated by biochemical, mechanical, hydraulic, and thermal processes, as well as the complex interactions among them. Many mathematical models have been developed over the past three decades to address this issue. However, most of them only emphasize some of these processes, with only few models accounting for all the processes. In this review, we present a comprehensive overview of the mathematical and numerical formulations of this coupled problem. Each process occurring in landfills is interpreted in detail using different sub-models and the corresponding parameter values. Then, the existing coupled models for MSW are reviewed, and the challenges and perspectives related to the modeling of the long-term behaviors of MSW are highlighted. We conclude that more reliable constitutive formulations based not only on well-designed laboratory tests but also on field tests are necessary to improve the modeling of MSW behaviors in future.

A dual-permeability hydro-biodegradation model for leachate recirculation and settlement in bioreactor landfills.

A dual-permeability hydro-biodegradation model is developed to describe the leachate flow in municipal solid waste (MSW) and predict the long-term settlement induced by biodegradation in bioreactor landfills. The model is verified against Hydrus-1D and a recirculation experiment conducted in a full-scale landfill. Preferential flow and mass transfer between fissure and matrix can be reasonably modeled by the proposed model. A higher recirculation flow rate can speed up the stabilization process of landfill. However, too much recirculation leachate is not economical and environmental friendly. A stabilization speed index and a leachate utilization index are adopted to evaluate the stabilization speed of bioreactor landfill and utilization rate of leachate, respectively, and the optimal recirculation flow rate is estimated. A flow rate of q = 5 × 10-5-5 × 10-4 m/h (equivalent to recirculation intensity of Q = 15-150 L/tonwaste/year) is recommended for recirculation, which has been verified by the field data in numerous bioreactor landfills.

Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways.

The effects of harmaline on the viability and apoptosis of human liver carcinoma were investigated in vitro. HepG2 cells were treated with harmaline (0-10 µM), and the proliferation and apoptosis of HepG2 cells were investigated using an MTT assay and flow cytometry, respectively. The protein expression of cellular tumor antigen p53 (p53), cyclin-dependent kinase inhibitor 1 (p21), tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand (FasL) and caspase-8 was subsequently measured using western blotting. In addition, an ELISA was used to analyze caspase-8/3 activity. Harmaline significantly increased p53, p21, Fas and FasL protein expression in HepG2 cells. Additionally, treatment with harmaline significantly increased the expression of caspase-8 and caspase-8/3 activity. The results from the present study suggest that harmaline suppresses the viability, but induces the apoptosis, of human liver carcinoma cells through upregulation of the p53/p21 and Fas/FasL signaling pathways.

The use of electrical resistivity tomography and borehole to characterize leachate distribution in Laogang landfill, China.

Leachate is a polluting liquid which may cause harmful effects on human health or the environment without a tightly control manner. The leachate management is an important part of the design and operation of bioreactor landfills. To detect the leachate distribution in Laogang Landfill, China, the measurement of electrical resistivity tomography (ERT) was carried out in three areas with different ages. ERT method proved to be an effective non-invasive geophysical method in bioreactor landfills, and the physical properties of waste samples obtained by boreholes were tested in a laboratory. The correlation between the resistivity and the moisture content was described by Archie's law. The result shows that the moisture content of fresh waste is inhomogeneous, while that of aged waste increases with depth. A pseudo 3D model of the moisture content was proposed to improve the understanding of leachate distribution and exhibit the accuracy of the ERT method.

[Change of cytokine expressions on bone marrow mesenchymal stem cells in patients with bone marrow failure syndromes and its significance].

This study was aimed to investigate the expressions of multiple cytokines on bone marrow mesenchymal stem cells (MSC) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), and its significance. The semi-quantitative reverse transcriptase-PCR (RT-PCR) was used to detect the expressions of IL-1ß, SCF, G-CSF at mRNA level in bone marrow MSC of patients with AA and MDS. The real time quantitative polymerase chain reaction (RQ-PCR) technique was used to detect the mRNA expression of TPO in bone marrow MSC of AA and MDS patients. The results indicated that the expression of SCF in AA group was much lower than that in the normal control group (p < 0.05), and the expression of TPO in AA group was higher than that in the normal control group (p < 0.05), while the expression of IL-1ß of AA had no significant difference when compared with the normal control group (p > 0.05). Compared with normal control group, the expressions of SCF of MDS patients was lower (p < 0.05), but the expressions of IL-1ß and TPO did not show significant difference (p > 0.05). The expressions of IL-1ß, SCF and TPO were no significant difference between AA and MDS groups (p > 0.05). Neither the AA patients, MDS patients nor the normal control group had the expression of G-CSF. It is concluded that the expression of SCF and TPO in bone marrow MSC of AA patients are obviously abnormal, the expression of SCF is also abnormal in bone marrow MSC of MDS patients.

[Effect of bortezomib and arabinoside on proliferation and apoptosis of K562 cell.].

OBJECTIVE: To investigate the effect of bortezomib (Bor) alone and in combination with arabinoside (Ara-C) on proliferation and apoptosis of leukemia cell line K562. METHODS: K562 cells were treated with 20 nmol/L Bor and 0.2 microg/ml Ara-C alone and in combination for 48 h. MTT was used to study the inhibitory effects on cell growth and the apoptosis rate was analysed by flow cytometry. After K562 cells treated with 20 nmol/L Bor or 0.2 microg/ml Ara-C for 6 h, the activity of NF-kappaB was analyzed by SP immunohistochemistry and cell cycle by flow cytometry. RESULTS: The inhibition and apoptosis rates of K562 cells in combination groups were higher than those in the two single treatment groups (P < 0.01), especially in the combined treatment group in which K562 cells were treated first with Ara-C for 6 h then with Bor combined,the inhibition and apoptosis rates were the highest [(81.5 +/- 4.0)% and (29.2 +/- 3.1)%, respectively] (P < 0.01). In the other two combined groups in which the cells were treated with Bor for 6 h then with Ara-C combined, or treated with the two drugs simultaneously, the inhibition and apoptosis rates were (54.1 +/- 4.2)% and (18.7 +/- 3.5)%, and (66.2 +/- 2.8)% and (21.1 +/- 2.2)%, respectively. Treatment of K562 cells with 20 nmol/L Bor for 6 h, the activity of NF-kappaB was decreased significantly, and the cells were apparently arrested in G(2)/M phase, and treatment with 0.2 microg/ml Ara-C in the same manner, the activity of NF-kappaB was increased significantly, and the cells were apparently arrested in G(1) phase. CONCLUSIONS: Bor can effectively inhibit K562 cell proliferation, and induced its apoptosis. This effect was enhanced significantly when in combination with Ara-C. Pretreatment of K562 cells with Ara-C lead to the increased activity of NF-kappaB and the fraction of G(1) phase cells.

[Expression of vascular cell adhesion molecule-1 in patients with multiple myeloma and its significance].

In order to investigate the expression of vascular cell adhesion molecule-1 (VCAM-1) in patients with multiple myeloma and its significance, the expression of VCAM-1 in 23 patients were detected by reverse transcription-PCR (RT-PCR) and then compared with that in normal control. The results showed that the expression of VCAM-1 in patients with newly diagnosed and relapsed/refractory multiple myeloma was much higher than that in normal control and in patients reached plateau stage (p < 0.05). There was no statistically significant difference between newly diagnosed and relapsed/refractory patients (p > 0.05). It is concluded that the expression of VCAM-1 in patients with multiple myeloma is abnormal, which may be an important factor for the pathogenesis of multiple myeloma.

[Effects of human bone marrow mesenchymal stem cells on proliferation and apoptosis of K562 cells].

This study was aimed to compare K562 cell proliferation, cell cycle and apoptosis before and after adhesive culture with MSCs of the same and different counts, so as to investigate the effect of human bone marrow mesenchymal stem cells (MSCs) on the growth of K562 cells. Culture system of bone marrow MSCs and co-culture system of K562 cells and BMSCs in vitro were established. And K562 cell proliferation curves were drawn by co-cultured of K562 cells with different counts of BMSCs. Cell cycle and apoptosis were determined by flow cytometry. The results showed that compared with the control, the proliferation of K562 cells cultured with the same amounts of MSCs was inhibited. After co-culture with the different amounts of MSCs, MSCs exhibited a dose-dependent anti-proliferation effect on K562 cells. The percentages of K562 cells in G(1) phase and G(2) phase were higher than those of the control. It is concluded that the normal bone marrow mesenchymal stem cells can inhibit the proliferation, the progress of cell cycle and the rate of apoptosis of K562 cells. As the number of mesenchymal stem cells increased, their anti-proliferation effect on the K562 cells were enhanced in a certain range.

[Effects of proteasome inhibitor bortezomib on NF-kappaB activity and ICAM-1 mRNA expression of K562 cells].

This study was aimed to investigate the effects of proteasome inhibitor bortezomib (Velcade, PS-341) on the activation of NF-kappaB and the expression of intercellular adhesion molecule-1 (ICAM-1) in K562 cells. The K562 cells were incubated in the culture of RPMI 1640 with 10% calf serum in 12-well plates and exposed to 0, 10, 20, 30, 50 and 100 nmol/L of bortezomib for 6 hours. The activation of NF-kappaB was analyzed by SP immunohistochemistry, meanwhile RT-PCR was performed to detect expression of ICAM-1. The results showed that the activation of NF-kappaB and the expression of ICAM-1 in K562 cells decreased significantly after bortezomib treatment. The inhibitory effect on ICAM-1 was probably related with the activity suppression of NF-kappaB. It is concluded that proteasome inhibitor bortezomib downregulates the expression of K562 cell ICAM-1 by inhibiting the activity of NF-kappaB, which provides a new way for the target therapy in acute leukemia.