Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro

<p>Abstract</p> <p>Background</p> <p>Drug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells.</p> <p>Methods</p> <p>After producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP.</p> <p>Results</p> <p>Compared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was no significant difference in livin expression between parental gastric cancer cells and oxaliplatin-resistant gastric cancer cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on parental cells and oxaliplatin-resistant cells were significantly enhanced compared with L-OHP or CIK alone. And it showed greater synergetic effects against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In addition, survival rate, abdominal circumference and pathomorphology results revealed stronger in vivo anti-tumor effects when the two therapies were combined.</p> <p>Conclusions</p> <p>The mechanism of oxaliplatin-resistant cell secondary multidrug resistance was correlated with the variation of cell cycle distribution, extension of doubling time and upregulation of P-gp expression. The synergistic effect of CIK in combination with L-OHP on killing activity against oxaliplatin-resistant cells was shown in vivo and in vitro.</p

Facile Synthesis and Special Phase Transformation of Hydrophilic Iron Oxides Nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs), γ-Fe2O3, with hydrophilic surfaces are fabricated in ethylene glycol solutions, without surfactant or additive, by solvothermal process from α-Fe2O3 nanoparticle as precursors. With the addition of a trace of hydrazine hydrate, the cubic phase Fe3O4 nanoparticles are obtained instead of γ-Fe2O3. The saturation magnetization value of γ-Fe2O3 nanoparticles is up to 74.3 emu/g. This study provides a low cost, safe, and universal route to serve as excellent biocompatibility magnetic core for future applications in biomedical, agriculture, and horticulture applications

The Dual Roles of MAGE-C2 in p53 Ubiquitination and Cell Proliferation Through E3 Ligases MDM2 and TRIM28

The tumor suppressor p53 is critical for the maintenance of genome stability and protection against tumor malignant transformation, and its homeostasis is usually regulated by ubiquitination. MDM2 is a major E3 ligase of p53 ubiquitination, and its activity is enhanced by TRIM28. TRIM28 also independently ubiquitinates p53 as an E3 ligase activated by MAGE-C2. Moreover, MAGE-C2 is highly expressed in various cancers, but the detailed mechanisms of MAGE-C2 involved in MDM2/TRIM28-mediated p53 ubiquitination remain unknown. Here, we found that MAGE-C2 directly interacts with MDM2 through its conserved MHD domain to inhibit the activity of MDM2 on p53 ubiquitination. Furthermore, TRIM28 acts as an MAGE-C2 binding partner and directly competes with MAGE-C2 for MDM2 interaction, thus releasing the inhibitory role of MAGE-C2 and promoting p53 ubiquitination. MAGE-C2 suppresses cell proliferation in TRIM28-deficient cells, but the overexpression of TRIM28 antagonizes the inhibitory role of MAGE-C2 and accumulates p53 ubiquitination to promote cell proliferation. This study clarified the molecular link of MAGE-C2 in two major E3 systems MDM2 and TRIM28 on p53 ubiquitination. Our results revealed the molecular function of how MAGE-C2 and TRIM28 contribute to p53 ubiquitination and cell proliferation, in which MAGE-C2 acts as a potential inhibitor of MDM2 and TRIM28 is a vital regulator for MAGE-C2 function in p53 protein level and cell proliferation. This work would be helpful to understand the regulation mechanism of tumor suppressor p53

Human Induced Turbidity Changes in Poyang Lake Between 2000 and 2010: Observations from MODIS

A robust retrieval algorithm to estimate concentrations of total suspended sediments (TSS) in Poyang Lake (the largest freshwater lake in China) was developed using Moderate Resolution Imaging Spectroradiometer (MODIS) medium-resolution (250 m) data from 2000 to 2010 and in situ data collected during two cruise surveys. The algorithm was based on atmospherically corrected surface reflectance at 645 nm, with 1240 nm data serving as a reference for aerosols and a nearest-neighbor method was used to avoid land adjacency effect. The algorithm showed an uncertainty of 30–40% for TSS ranging between 3 and 200 mg L−1. Long-term TSS distribution maps derived from MODIS data and the customized TSS algorithm showed significant variations in both space and time, with low TSS (\u3c10 mg L−1) in wet seasons and much higher TSS (\u3e15–20 mg L−1) in dry seasons for the south lake, and generally higher TSS in the north lake. The TSS difference between the north and the south increased significantly after 2002, with mean TSS often reaching \u3e40 mg L−1in the north. While the TSS seasonality was attributed to the seasonal changes of the lake\u27s circulation, the inter-annual variations were primarily driven by sand dredging activities, regulated by management policies. The case study here provides baseline water quality information for future restoration efforts in Poyang Lake, and more generally, an approach to assess water quality changes in similar water bodies, which have resulted from either climate variability or human activities

Human Induced Turbidity Changes in Poyang Lake Between 2000 and 2010: Observations from MODIS

A robust retrieval algorithm to estimate concentrations of total suspended sediments (TSS) in Poyang Lake (the largest freshwater lake in China) was developed using Moderate Resolution Imaging Spectroradiometer (MODIS) medium-resolution (250 m) data from 2000 to 2010 and in situ data collected during two cruise surveys. The algorithm was based on atmospherically corrected surface reflectance at 645 nm, with 1240 nm data serving as a reference for aerosols and a nearest-neighbor method was used to avoid land adjacency effect. The algorithm showed an uncertainty of 30–40% for TSS ranging between 3 and 200 mg L−1. Long-term TSS distribution maps derived from MODIS data and the customized TSS algorithm showed significant variations in both space and time, with low TSS (\u3c10 mg L−1) in wet seasons and much higher TSS (\u3e15–20 mg L−1) in dry seasons for the south lake, and generally higher TSS in the north lake. The TSS difference between the north and the south increased significantly after 2002, with mean TSS often reaching \u3e40 mg L−1in the north. While the TSS seasonality was attributed to the seasonal changes of the lake\u27s circulation, the inter-annual variations were primarily driven by sand dredging activities, regulated by management policies. The case study here provides baseline water quality information for future restoration efforts in Poyang Lake, and more generally, an approach to assess water quality changes in similar water bodies, which have resulted from either climate variability or human activities

MODIS Observations of the Bottom Topography and Its Inter-annual Variability of Poyang Lake

Using MODIS 250-m resolution data, we developed a novel approach to derive the bottom topography of Poyang Lake, the largest freshwater lake of China (\u3e 3000 km2 at maximum inundation) for every year between 2000 and 2009. The approach differs from other traditional methods (sonar, Lidar, optical inversion, and Radar) but takes advantage of the fast-changing nature of the lake\u27s inundation area. On every image, the water/land boundary is effectively a topographic isobath after correction for the water level gradient. Thus, the ~ 10/year carefully selected MODIS images provided incremental topographic isobaths, from which bottom topography was derived every year. Such-derived topographic maps were validated using limited historical data and other consistency checks. Most of the lake bottom showed an elevation of 12 m to 17 m (referenced against the elevation reference of the Woosung Horizontal Zero). Significant inter-annual variability of the bottom topography from 2000 to 2009 was found for some of the lake\u27s bottom, with more areas associated with bottom elevation increases than decreases. The changes and inter-annual variability in the bottom topography were attributed to the combined effect of human activities (e.g., sand dredging and levee construction) and weather events. One example was the increased bottom elevation from 2002 to 2003, which was apparently due to the excessive precipitation in 2002 and the impoundment of the Three-Gorges Dam in 2003. The 10-year record of the bottom topography of this highly dynamic lake provides baseline information to monitor the impact of future engineering and management activities, to estimate the lake\u27s water and sediment budgets, and to aid ship navigation

Assessment of Inundation Changes of Poyang Lake Using MODIS Observations Between 2000 and 2010

China\u27s largest freshwater lake, Poyang Lake, is well known for its ecological and economic importance as well as its rapid changes in lake inundation areas. However, due to technical difficulties, to date long-term records of its dynamic inundation areas are lacking, not to mention how they are affected by climate change and/or human activities. Using Moderate Resolution Imaging Spectroradiometer (MODIS) medium-resolution (250-m) data collected between 2000 and 2010 and an objective water/land delineation method, we documented and studied the short- and long-term characteristics of lake inundation. Significant seasonality and inter-annual variability were found in the monthly and annual mean inundation areas. The inundation area ranged between 714.1 km2 in October 2009 and 3162.9 km2 in August 2010, and the inundation area during any particular year could change by a factor of 2.3–3.2. During the 11-year period, the maximum possible inundation area was 14 times the minimum possible inundation area, indicating extreme variability. Both the annual mean and minimum inundation areas showed statistically significant declining trends from 2000 to 2010 (− 30.2 km2 yr− 1 and−23.9 km2 yr− 1, p \u3c 0.05). The changes of the inundation area were primarily driven by local precipitation during non-summer months, while during summer months of July to September when the outflow into the Yangtze River was impeded the effect of precipitation became less significant. These results provide long-term baseline data to monitor future changes in Poyang Lake\u27s inundation area in a timely fashion, for example quantifying the extreme drought conditions during spring 2011

Genome-Wide Association Study on Seedling Phenotypic Traits of Wheat under Different Nitrogen Conditions

Nitrogen fertilizer input is the main determinant of wheat yield, and heavy nitrogen fertilizer application causes serious environmental pollution. It is important to understand the genetic response mechanism of wheat to nitrogen and select wheat germplasm with high nitrogen efficiency. In this study, 204 wheat species were used to conduct genome-wide association analysis. Nine phenotypic characteristics were obtained at the seedling stage in hydroponic cultures under low-, normal, and high-nitrogen conditions. A total of 765 significant loci were detected, including 438, 261, and 408 single nucleotide polymorphisms (SNPs) associated with high-, normal, and low-nitrogen conditions, respectively. Among these, 14 SNPs were identified under three conditions, for example, AX-10887638 and AX-94875830, which control shoot length and root–shoot ratio on chromosomes 6A and 6D, respectively. Additionally, 39 SNPs were pleiotropic for multiple traits. Further functional analysis of the genes near the 39 SNPs shows that some candidate genes play key roles in encoding proteins/enzymes, such as transporters, hydrolases, peroxidases, glycosyltransferases, oxidoreductases, acyltransferases, disease-resistant proteins, ubiquitin ligases, and sucrose synthetases. Our results can potentially be used to develop low-nitrogen-tolerant species using marker-assisted selection and provide a theoretical basis for breeding efficient nitrogen-using wheat species