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Background: HMGA2 encodes a small non histone chromatin-associated protein that has no intrinsic transcriptional activity, but can modulate transcription by altering the chromatin architecture. HMGA2 was found overexpressed in a variety of epithelial and mesenchymal tumors and promoted invasion and metastasis in most malignant epithelial tumors. A recent study showed that P53 inhibited CRC progression by targeting HMGA2. However, the mechanism by which HMGA2 affect angiogenesis in CRC has not been clarified. Methods: The expression of HMGA2 was analyzed by IHC, WB and bio infomatic analysis. Cbioportal and mexpress online tools were applied to explore the CNV and methylation of HMGA2 in CRC patients. Single cell data from GEO was used to examine the specific cell type that contribute to the high HMGA2 expression in CRC. Lentivirus was used to knock down HMGA2 in CRC cells and HUVECs was used to study angiogenesis. Results: In the current study, we first detected the expression pattern of HMGA2 in CRC patients and evaluated its clinical values and CNV amplification could possibly contribute to the up regulation of HMGA2 in CRC patients. By analyzing CRC single cell data we found that HMGA2 was specifically up regulated in the colorectal epithelial cells. Furthermore, knocking down of HMGA2 suppresses angiogenesis via dual regulation of VEGF-A and SEMA3A in CRC through inactivating VEGRR2 pathway in HUVECs. Conclusions: HMGA2 might be a promising prognostic marker and target for treating advanced CRC patients.

Dysregulation of long noncoding RNA (lncRNA) is known to be involved in numerous human diseases, including lung cancer. However, the precise biological functions of most lncRNA remain to be elucidated. Here, we identified a novel up-regulated lncRNA, LINC01436 (RefSeq: NR_110419.1), in non-small cell lung cancer (NSCLC). High expression of LINC01436 was significantly associated with poor overall survival. Notably, LINC01436 expression was transcriptionally repressed by E2F6 under normoxia, and the inhibitory effect was relieved in a hypoxic microenvironment. Gain- and loss-of-function studies revealed that LINC01436 acted as a proto-oncogene by promoting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays in nude mice confirmed that LINC01436 promoted tumor growth and metastasis in vivo. Mechanistically, LINC01436 exerted biological functions by acting as a microRNA (miR)-30a-3p sponge to regulate the expression of its target gene EPAS1. Our findings characterize LINC01436 as a new hypoxia-sensitive lncRNA with oncogenic function in NSCLC, suggesting that LINC01436 may be a potential biomarker for prognosis and a potential target for treatment.

Biscuit is one of the common snack foods. With various needs and with the rise of the quality of life, the consumer demand for biscuits in the market is on the rise. At the same time, novel and unique packaging can stimulate consumers’ desire to buy [1]. This paper explores how the psychology of vision and taste synesthesia can arouse the interest of consumers through plane packaging and establish the first impression of products for consumers [2]. By using kansei engineering, the image correlation of perceptual commodities (take cookie packing as an example) is systematically tested and obtained in terms of functions, materials and colors of products, and the graphic design suggests of cookie packing are put forward based on the comprehensive correlation. In this study, the relationship between visual and taste intention and the effect of packaging color on taste reasoning judgment can serve as a reference for biscuit manufacturers to make design plans and adjust the compatibility of appearance and taste according to different consumer groups.

This study used EMG coherence to investigate the correlation between muscle fatigue and beta-band energy after the dynamic biceps brachii contraction. HD-sEMG signals were acquired in experiment. 9 healthy subjects participated in the muscle contraction task (from non-fatigue to fatigue), Each participant was asked to perform two trails of experiments and exert their max-muscular strength in each trial. The result shows a significant correlation [p = 0.0058 < 0.01] between fatigue and energy in beta-band.

The fatigue-induced neuromuscular mechanism remains to be fully elucidated. So far, the macroscopic mechanism using global surface electromyogram (sEMG) has been widely investigated. However, the microscopic mechanism using high-level neural information based on motor unit (MU) spike train from the spinal cord lacks attention, especially for the conditions under dynamic contraction task. The synchronization of the MU spike train is generally assumed to be an excellent indicator to represent the activities of spinal nerves. Accordingly, this study employed synchronization of MU spike train decomposed from high-density sEMG (HD-sEMG) to investigate the fatigue condition in muscular contractions within the Biceps Brachii muscle under both isometric and dynamic contraction tasks, giving a complete picture of the microscopic fatigue mechanism. We compared the synchronization of MU in Delta (1–4 Hz), alpha (8–12 Hz), Beta (15–30 Hz), and Gamma (30–60 Hz) frequency bands during the fatigue condition induced by different contractions. Our results showed that MU synchronization increased significantly ( p 0.05 ) in all frequency bands across the two contraction tasks. The results indicate that the microscopic fatigue mechanism of Biceps Brachii muscle does not vary due to different contraction tasks.

Lipopolysaccharide (LPS) is a known neurotoxin and utilized most extensively as a microglial activator for induction of inflammatory neurodegeneration. Melatonin (MEL) is the main secretory product of pineal gland reported to be responsible for a variety of physiological functions. However, the molecular mechanisms underlying the influence of MEL on microglia activation remain unclear. The aim of this study was to investigate the effect of MEL on cyclooxygenase-2 (COX-2) levels in LPS-induced microglia. The results of RT-PCR and Western blot analysis showed that MEL significantly inhibited LPS-mediated upregulation of COX-2 in microglia. Data from ELISA demonstrated that prostaglandin E2 (PGE2), the downstream effector of COX-2, concentrations were also reduced. In addition, MEL was found to decrease activation of ERK1/2, JNK, p38 MAPK, and NF-κB, the upstream signal pathways of COX-2. Taken together, evidence indicates that MEL may attenuate upregulation of COX-2 by blocking the MAPK/NF-κB signaling pathway in LPS-stimulated microglia.

Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Krüppel erythroid myeloid oncogenic factor, is critical for the tumorigenicity and progression of various cancer types. ZBTB7 has been reported to promote the cell proliferation of colorectal cancers (CRC). However, the function of ZBTB7 to 5-fluorouracil (5‑FU) resistance has not yet been studied. In the current study, ZBTB7 expression and function in 5‑FU resistance in CRC were investigated using with multidisciplinary approaches, including western blot analysis, Transwell assay, CCK8 and a tumor xenograft model. Overexpression of ZBTB7 was increased the level of proteins associated with cell invasion and epithelial-mesenchymal transition. ZBTB7 inhibition attenuated the invasion and enhanced the apoptosis of CRC cells. IC50 values and cell viability were significantly reduced in cells with short hairpin RNA (shRNA)-mediated ZBTB7 depletion compared with the control group. 5‑FU administration decreased viability to a greater extent in the ZBTB7-shRNA group compared with the control, which was dose- and time-dependent. Analysis of gene expression omnibus data demonstrated that ZBTB7 mediated 5‑FU resistance, potentially through nuclear factor (NF)-κB signaling. NF‑κB inhibitor SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings demonstrated that ZBTB7 mediated 5‑FU resistance in CRC cells through NF‑κB signaling. Thus, targeting ZBTB7 and NF‑κB signaling may be an effective strategy to reverse 5‑FU resistance in CRC.

microRNAs (miRNAs) have been documented playing a critical role in cancer development and progression. In this study, we investigated the role of miR-548l in non-small cell lung cancer (NSCLC) migration and invasion. microRNAs microarray analysis was used to detect the differentially expressed miRNAs between various metastatic levels of NSCLC cells and further confirmed by real-time PCR analysis. To facilitate the delineation of the role of selected miR-548l in NSCLC pathology, we detected its expression in 22 NSCLC tissues. Proliferation, apoptosis, invasion and metastasis effects of the miRNA were evaluated using MTT, flow cytometry, wound healing and invasion assay following transfection with mimics and inhibitors. Luciferase assay and Western blot analysis were performed to assess miR-548l binding to AKT1 gene. AKT1 expression in the clinical tissues was evaluated using immunohistochemical staining. The results showed a negative relationship between miR-548l expression and lymph node metastasis of NSCLC. Functional assays showed that over-expression of miR-548l suppressed NSCLC cell migration and invasion. Luciferase assays confirmed that miR-548l could directly bind to the 3′ untranslated region of AKT1. Further data showed that the over-expression of AKT1 could rescue the effects of miR-548l in NSCLC cells, and the miR-548l expression was inversely correlated with AKT1 expression in NSCLC tissues. These results indicated that AKT1 was involved in miR-548l-induced suppression of NSCLC cell migration and invasion. These results suggested that miR-548l may play a causal role through AKT1 in NSCLC invasion and metastasis.

Abstract 4929 Background Multiple myeloma myeloma accounts for approximately 1 percent of all cancers and 10 percent of hematologic cancers. It is incurable with conventional chemotherapy. Recent studies suggest that rHuEpo has additional biological effects which significantly prolonged the expected survival of six end-stage multiple myeloma (MM) patients and led to hypothesize that Epo might have an anti-neoplastic or anti-myeloma effect. This latter observation was further supported by studies. Objective Based on the myeloma models which established in BALB/c murine with MPC-11 myeloma cell line, our study is to verify the true effects, to research the suitable dose and administration way of recombinant human erythropietin(rHuEPO) for individuals with MM, as well as the possible antitumor mechanism in BALB/c murine myeloma models. Methods 550 healthful BALB/c mice were injected s.c. with 6×105 MPC-11 cells to establish the multiple myeloma models. When small palpable tumors were observed, the tumor-bearing mice were randomizedly divided into five groups which were respectively administrated the various rHuEPO doses (10,20,30,40 and 50 units per injection) and a placebo group with the saline. In the study, rHuEPO treatment was strated in 5 days after the initial MPC-11 cells injection, daily s.c. injections of rHuEPO for 30 consecutive days, followed by one injection per week for 4 weeks with a same dose as before. Hemoglobin, serum IL-6 and TNF-α were monitored before the start of rHuEPO administration and in 15 days, 30 days and 60 days after the start of rHuEPO administration. Immunofixation electrophoresis(IFE) was performed to detect the existence of the serum monoclonal immunoglobulin before the rHuEPO treatment and in 60 days after the rHuEPO-treatment. In the second part of the study, microvessel density(MVD) and TdT-mediated dUTP nick end labeling (TUNEL) techniques were performed to evaluate the tumor proliferation burden and tumor cell apoptosis respectively. Tumor volume change was monitored twice a week and weight change of tumour-bearing mice was measured once a week for every individual mouse during the whole study. Results The serum monoclonal immunoglobulin appeared in 12 days after the initial MPC-11 cells injection. There wasn't a significant decrease in tumor size of bearing cancer mice after administration of rHuEPO, and there was no significant difference among each dosage group. rHuEPO can obviously increase Hb levels in bearing cancer mice. The mice with a smaller tumor size had a higher Hb level, which resulting in a longer survival. Individual survival showed a significant positive correlation with Hb level (Spearman's rho 0.821, p=0.000), and in contrast, it had a negative correlation with tumor size (Spearman's rho 0.475, p=0.009). The serum levels of IL-6 showed no significant differences between the each rHuEPO treatment group and the placebo group, and the result was the same in the serum levels of TNF-α. Also, there is no difference in MVD between the treatment groups and placebo group. The apoptotic index of the treatment groups with rHuEPO seemed a little higher than that of the placebo group. Conclusion rHuEPO administration to the tumor-bearing mice seemed to prolong their individual survival. Insufficient evidence was found for the anti-MM therapeutic role of rHuEPO in our study. Disclosures No relevant conflicts of interest to declare.