The Protective Effects of Ciji-Hua’ai-Baosheng II Formula on Chemotherapy-Treated H22 Hepatocellular Carcinoma Mouse Model by Promoting Tumor Apoptosis

Ciji-Hua’ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medical formula that has been shown in clinical practice to relieve side effects of chemotherapy and improve quality of life for cancer patients. In order to understand the mechanism of its protective effects on chemotherapy, mice with transplanted H22 hepatocellular carcinoma were employed in this study. Ninety-two mice were injected subcutaneously with H22 HCC cell suspension into the right anterior armpit. After mice were treated with 5-fluorine pyrimidine (5-FU), they were divided into six groups as untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji Capsule group and three groups of 5-FU plus different concentrations of CHB-II-F. Twenty mice were euthanized after 7 days of treatment in untreated and medium concentration of CHB-II-F groups and all other mice were euthanized after 14 days of treatment. Herbal components/metabolites were analyzed by UPLC-MS. Tumors were evaluated by weight and volume, morphology of light and electron microscope, and cell cycle. Apoptosis were examined by apoptotic proteins expression by western blot. Four major components/metabolites were identified from serum of mice treated with CHB-II-F and they are β-Sitosterol, Salvianolic acid, isobavachalcone, and bakuchiol. Treatment of CHB-II-F significantly increased body weights of mice and decreased tumor volume compared to untreated group. Moreover, CHB-II-F treatment increased tumor cells in G0-G1 transition instead of in S phase. Furthermore, CHB-II-F treatment increased the expression of pro-apoptotic proteins and decreased the expression anti-apoptotic protein. Therefore, CHB-II-F could improve mice general condition and reduce tumor cell malignancy. Moreover, CHB-II-F regulates apoptosis of tumor cells, which could contribute its protective effect on chemotherapy

Performance Optimization of Many-core Systems by Exploiting Task Migration and Dark Core Allocation

As an effective scheme often adopted for performance tuning in many-core processors, task migration provides an opportunity for "hot" tasks to be migrated to run on a "cool" core that has a lower temperature. When a task needs to migrate from one processor core to another, the migration can embark on numerous modes defined by the migration paths undertaken and/or the destinations of the migration. Selecting the right migration mode that a task shall follow has always been difficult, and it can be more challenging with the existence of dark cores that can be called back to service (reactivated), which ushers in additional task migration modes. Previous works have demonstrated that dark cores can be placed near the active cores to reduce power density so that the active cores can run at higher voltage/frequency levels for higher performance. However, the existing task migration schemes neither consider the impact of dark cores on each application's performance, nor exploit performance trade-off under different migration modes. Unlike the existing task migration schemes, in this paper, a runtime task migration algorithm that simultaneously takes both migration modes and dark cores into consideration is proposed, and it essentially has two major steps. In the first step, for a specific migration mode that is tied to an application whose tasks need to be migrated, the number of dark cores is determined so that the overall performance is maximized. The second step is to find an appropriate core region and its location for each application to optimize the communication latency and computation performance; during this step, focus is placed on reducing the fragmentation of the free core regions resulting from the task migration. Experimental results have confirmed that our approach achieves over 50% reduction in total response time when compared to recently proposed thermal-aware runtime task migration approachess

EFFECTS OF CIJI HUA’AI BAOSHENG FORMULA ON APOPTOSIS CORRELATION FACTORS OF TUMOR CHEMOTHERAPY MODEL MOUSE WITH H22 HEPATOMA CARCINOMA CELLS

Background: Ciji Hua’ai Baosheng Formula (CHBF) is a traditional Chinese empirical formula that can help the tumor patients who received chemotherapy to antagonize the toxin and side-effects so as to improve and prolong the life. This study is to evaluate the effects of Ciji Hua’ai Baosheng Formula on apoptosis correlation factors of transplanted tumor chemotherapy model mouse with H22 hepatoma carcinoma cells through detecting the protein level of serum Bax, Bcl-2, Caspase-3, epidermal growth factor receptor (EGFR) and the protein expression of CyclinD1 in femur bone marrow. Materials and Methods: H22 hepatoma carcinoma cells were cultivated and diluted to 2×107/ml, and a total of 50 specific pathogen-free Kunming mice were injected subcutaneously into the right anterior armpit with H22 hepatoma carcinoma cells, after 7 days, all mice had formed tumors and were used peritoneal injection of Cytoxan (CTX) (200mg/kg) to establish the mouse chemotherapy model with transplanted tumor, then they were randomly divided into 5 groups such as model, positive control (CTX, 0.033g/kg) and three CHBF (117g/kg, 58.5g/kg and 29.25g/kg) groups with 10 mice in each group. They were administered next day after making model. Survival state was observed. After administering for 10 days, pathological tissue structural change was detected by light microscope, blood was collected through pricking eyeball, protein level of serum Bax, Bcl-2, Caspase-3 and EGFR was detected by enzyme-linked immunosorbent assay (ELISA), the protein expression of CyclinD1 in femur bone marrow was detected by immunohistochemisty. Results: Under the light microscope, the deteriorated degree of tumor tissue and the proliferation degree of tumor cells in three CHBF groups were obviously milder than that of model group. The protein content of the pro-apoptotic gene Bax and effective enzyme Caspase-3 in CHBF (58.5g/kg and 29.25g/kg) groups were obviously higher than that of model groups (

Scale-Up Production of Chicken Myoblasts in Microcarrier-Based System

With the rapid development of the cultivated meat industry, large-scale cell culture technology applied to cultivated meat production has received extensive attention. In this study, two microcarriers, Cytodex 1 and 3D TableTrix™, were used for suspension culture of myoblasts in spinner flasks to select a more suitable one for large-scale culture of myoblasts, and then the effects of different culture conditions on the large-scale culture of cells were explored. The microscopic results showed that Cytodex 1 was spheres with a smooth surface and no macroporous structure, and 3D TableTrix™ was irregular spheres with a porous surface and large pores. The results of cell culture in spinner flasks showed that the cells grew on 3D TableTrix™ more efficiently, and after 10 days of culture, the cell yield was 8.97 × 105 cells/mL. The optimal conditions for cell attachment were intermittent stirring at 40 r/min for 10 min with intervals of 50 min. The best cell culture efficiency was obtained by using cell inoculation density of 1 × 105 cells/mL, microcarrier density of 2 mg/mL, agitation speed of 40 r/min, and initial culture serum concentration of 20% as well as replacing the medium with a new one containing 10% serum (V/V) after 24 h of culture, and replacing 50% of the medium with a new one with every other day. By bead to bead transfer of the microcarriers, the cells were transferred to a 2 L spinner flask. Finally, 1.07 × 109 cells were harvested with a survival rate of more than 95%. Microcarriers loaded with cells could be cryopreserved and resuscitated, and no significant differences in proliferation status and morphology were observed compared with thawed cells. The optimized microcarrier based culture process will have promising applications in the industrial scale production of cultivated meat

Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer's Disease.

Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with aging. There are currently no effective treatments for AD. Bazhu decoction (BZD), a traditional Chinese medicine (TCM) formula, has been employed clinically to alleviate AD. However, the underlying molecular mechanisms are still unclear. Here we found that middle- and high-doses of BZD ameliorated the behavioral aspects of 5xFAD transgenic mice in elevated plus maze, Y maze and Morris water maze tests. Moreover, BZD reduced the protein levels of BACE1 and PS1, resulting in a reduction of Aβ plaques. We also identified a beneficial effect of BZD on oxidative stress by attenuating MDA levels and SOD activity in the brains of 5xFAD mice. Together, these results indicate that BZD produces a dose-dependent positive effect on 5xFAD transgenic mouse model by decreasing APP processing and Aβ plaques, and by ameliorating oxidative damage. BZD may play a protective role in the cognitive and anxiety impairments and may be a complementary therapeutic option for AD

Extracellular Signal-regulated Kinase (ERK) Phosphorylates Histone Deacetylase 6 (HDAC6) at Serine 1035 to Stimulate Cell Migration

Histone deacetylase 6 (HDAC6) is well known for its ability to promote cell migration through deacetylation of its cytoplasmic substrates such as α-tubulin. However, how HDAC6 itself is regulated to control cell motility remains elusive. Previous studies have shown that one third of extracellular signal-regulated kinase (ERK) is associated with the microtubule cytoskeleton in cells. Yet, no connection between HDAC6 and ERK has been discovered. Here, for the first time, we reveal that ERK binds to and phosphorylates HDAC6 to promote cell migration via deacetylation of α-tubulin. We have identified two novel ERK-mediated phosphorylation sites: threonine 1031 and serine 1035 in HDAC6. Both sites were phosphorylated by ERK1 in vitro, whereas Ser-1035 was phosphorylated in response to the activation of EGFR-Ras-Raf-MEK-ERK signaling pathway in vivo. HDAC6-null mouse embryonic fibroblasts rescued by the nonphosphorylation mimicking mutant displayed significantly reduced cell migration compared with those rescued by the wild type. Consistently, the nonphosphorylation mimicking mutant exerted lower tubulin deacetylase activity in vivo compared with the wild type. These data indicate that ERK/HDAC6-mediated cell motility is through deacetylation of α-tubulin. Overall, our results suggest that HDAC6-mediated cell migration could be governed by EGFR-Ras-Raf-MEK-ERK signaling

Murine Pancreatic Adenocarcinoma Reduces Ikaros Expression and Disrupts T Cell Homeostasis

Background Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros is essential for lymphocyte development including T cells. Alterations in Ikaros expression occur in blood malignancies in humans and mice. In this study, we investigated the role of Ikaros in regulating T cell immune balance in pancreatic cancer mouse models. Methodology and Principal Findings Using our Panc02 tumor-bearing (TB) mouse model, western blot analysis revealed a reduction in Ikaros proteins while qRT-PCR showed no differences in Ikaros mRNA levels in TB splenocytes compared to control. Treatment of naïve splenocytes with the proteasomal inhibitor, MG132, stabilized Ikaros expression and prevented Ikaros downregulation by Panc02 cells, in vitro. Western blot analyses showed a reduction in protein phosphatase 1 (PP1) and protein kinase CK2 expression in TB splenocytes while CK2 activity was increased. Immunofluorescence microscopy revealed altered punctate staining of Ikaros in TB splenocytes. Flow cytometry revealed a significant decrease in effector CD4+ and CD8+ T cell percentages but increased CD4+CD25+ regulatory T cells in TB splenocytes. Similar alterations in T cell percentages, as well as reduced Ikaros and CK2 but not PP1 expression, were observed in a transgenic, triple mutant (TrM) pancreatic cancer model. Ikaros expression was also reduced in enriched TB CD3+ T cells. MG132 treatment of naïve CD3+ T cells stabilized Ikaros expression in the presence of Panc02 cells. Western blots showed reduced PP1 and CK2 expression in TB CD3+ T cells. Conclusions/Significance The results of this study suggest that the pancreatic tumor microenvironment may cause proteasomal degradation of Ikaros, possibly via dysregulation of PP1 and CK2 expression and activity, respectively. This loss of Ikaros expression may contribute to an imbalance in T cell percentages. Ikaros may potentially be a therapeutic target to restore T cell homeostasis in pancreatic cancer hosts, which may be critical for effective anti-tumor immunity

ONE-POT SYNTHESIS OF HIGHLY LUMINESCENT CdTe QUANTUM DOTS USING SODIUM TELLURITE AS TELLURIUM SOURCE IN AQUEOUS SOLUTION

A novel technology has been developed for the synthesis of thioglycolic acid (TGA)-capped CdTe quantum dots (QDs) in aqueous medium. The reaction was carried out in air atmosphere with one-pot by using Na2TeO3 to replace Te or Al2Te3. The mechanism for the formation of CdTe QDs is elucidated. The influences of various experimental variables, including refluxing time, pH value, Cd/Te and Cd/TGA molar ratios, on the luminescent properties of the obtained CdTe QDs have been systematically investigated. Furthermore, the obtained QDs were characterized by fourier transform infrared spectra (FTIR), X-ray powder diffraction (XRD) and transmission electron microscopy (TEM), respectively. The results demonstrate that, under the optimized experimental conditions, the obtained CdTe QDs exhibited a narrow photoluminescence band (fwhm33-45 nm) with reproducible room-temperature quantum yields as high as 28 %, the emission color is tunable from green to orange with increasing diameter of QDs

Object Tracking via 2DPCA and l2-Regularization

We present a fast and robust object tracking algorithm by using 2DPCA and l2-regularization in a Bayesian inference framework. Firstly, we model the challenging appearance of the tracked object using 2DPCA bases, which exploit the strength of subspace representation. Secondly, we adopt the l2-regularization to solve the proposed presentation model and remove the trivial templates from the sparse tracking method which can provide a more fast tracking performance. Finally, we present a novel likelihood function that considers the reconstruction error, which is concluded from the orthogonal left-projection matrix and the orthogonal right-projection matrix. Experimental results on several challenging image sequences demonstrate that the proposed method can achieve more favorable performance against state-of-the-art tracking algorithms