Activity

Multiple myeloma (MM) is a neoplastic dyscrasia of monoclonal immunoglobulin-secreting plasma cells culminating in multi-organ dysfunction. In this study, we sought to investigate whether scutellarin (STN), a flavonoid, could reduce MM progression, mitigate chemoresistance of MM cells to bortezomib (BTB), and cause MM cell apoptosis in a xenograft mouse model of MM. Epigenetic signalling plays a main role in the modulation of various pathways involved in multiple myeloma progression. At the outset, mechanistic analyses of the MM pathways indicated that key epigenetic molecules including HDAC1/3 and miR-34a were up-modulated and down-modulated respectively, in the MM mice. Besides, the downstream signalling analysis of miR-34a depicted that the c-Met/AKT/mTOR pathway was activated in the MM mice. We also investigated the expression of NF-κB, one of the major chemoresistance inducers in cancer treatment, in the MM mice. As anticipated, the tumor-bearing mice expressed more NF-κB along with elevated anti-apoptotic Bcl-xL protein, as well as reduced pro-apoptotic Bim protein. On the other hand, STN+BTB co-treatment effectively combated the MM tumor progression, and STN circumvented the MM tumor resistance to BTB and provoked apoptotic cell death in MM. Based on our study data, we deduce that STN, in combination with BTB, appears to be a reliable tumoricidal strategy. IJCEP Copyright © 2020.INTRODUCTION Circulating tumor DNA (ctDNA) for monitoring the effects of chemotherapy and predicting prognosis in advanced gastric cancer have not been thoroughly investigated. METHODS We performed next-generation sequencing (NGS) of ctDNA from 23 gastric cancer patients. Then the genetic information and clinical information were statistically analyzed. RESULTS In this study, the frequency of TP53 was significantly different between the effective and ineffective groups (P = 0.040), and the number of TP53 mutations was more frequent in the ineffective group. Missense mutation was a significant difference between the treatment effect groups (P = 0.026). The number of gene mutations and the change in copy number levels were related to therapeutic effect. Among the ineffective group, there was a significant difference in the number of gene mutations (P = 0.0006). Takinib concentration We further divided the number of gene mutations into an increase group and a decrease group, and found that there was a significant difference between the effective and ineffective groups (P = 0.038). Finally, it was found that patients with high mutation abundance of gastric cancer had a shorter overall survival than patients with low mutation abundance (P less then 0.05). CONCLUSION ctDNA can be used as an effective tool to monitor the efficacy of chemotherapy and predict prognosis in advanced gastric cancer. IJCEP Copyright © 2020.BACKGROUND Hepatorenal and hepatopulmonary syndrome are common clinical diseases; however, their mechanisms have not been fully elucidated. Our aim was to determine whether liver injury by bile duct ligation (BDL) causes modifications in kidney and lung tissue in mice, and to explore the possible mechanism of these changes. METHODS BDL in mice was used as a research model. Pathologic changes of liver, kidney, and lung tissue were observed by hematoxylin-eosin (H&E) staining. The expression of IGFBPrP1, NF-κB, TNF-α, and IL-6 were investigated in liver, kidney, and lung tissue by immunohistochemical staining and western blot. The correlation between IGFBPrP1 and NF-κB, TNF-α, and IL-6 protein expression in liver, kidney, and lung tissues of each group was analyzed by the Pearson method. RESULTS H&E staining showed, after BDL administration in mice, different degrees of inflammatory change in liver, kidney, and lung tissues of mice in each group. The results of immunohistochemical staining and western blot analysis showed increased expressions of IGFBPrP1, NF-κB, TNF-α, and IL-6 after BDL. Pearson correlation analysis showed that IGFBPrP1 positively correlated with the expressions of NF-κB, TNF-α, and IL-6. CONCLUSION Liver injury caused by bile duct ligation can lead to kidney and lung tissue injury in mice. The mechanism of injury may be related to the high expression of liver injury factor IGFBPrP1, transcription factor NF-κB, proinflammatory cytokine TNF-α, and IL-6 in kidney and lung tissue. Moreover, an increased expression level of IGFBPrP1 may be accompanied by the activation of the NF-κB inflammatory pathway. IJCEP Copyright © 2020.BACKGROUND Neonatal hypoxia-ischemia brain damage (HBID) can cause a series of neurological sequelae, such as movement and cognitive impairment, and there is currently no clinically effective treatment. Changes in epigenetic processes had been shown to be involved in the development of a series of neurodegenerative diseases, and HDAC inhibition by Scriptaid had been shown to reduce severe traumatic brain injury by suppressing inflammatory responses. This study investigated the protective effect of HDAC inhibition by Scriptaid after HBID. METHODS We established the neonatal rat HBID model, and used intraperitoneal injection of HDAC inhibitor scriptaid as a treatment. 7 days after HBID, nuclear magnetic resonance imaging (MRI) was used to detect infarct volume. The otarod test, wire hang test and Morris water maze were used to evaluate the HBID model of neurobehavioral dysfunction. Immunoblotting, immunofluorescence, and quantitative real-time PCR (RT-qPCR) were used to detect gene expression. RESULTS HDAC inhitokines. CONCLUSION After HBID, HDAC inhibitor Scriptaid inhibits inflammatory responses and protects the brain by promoting the polarization of microglia in brain tissue to M2 microglia. IJCEP Copyright © 2020.The present study aimed to investigate the effect of arsenic trioxide (ATO) on the proliferation of retinal pigment epithelium (RPE) and its mechanism. RPE cells were cultivated with 0.5-11 μmol/L ATO for 24, 48, and 72 h and their survival and growth were measured by MTT assay. The expression of p27 and proliferating cell nuclear antigen (PCNA) in RPE cells was detected using cell immunofluorescence and western blotting. Dose-dependency was evident in both the experimental and control groups. The 50% inhibitory concentration was obtained at a concentration of 6 mol/L with cells treated for 3 days. The optimum concentration of ATO was 6 μmol/L based on the result of MTT. After the third day of ATO treatment, the number of cells was significantly lower in the experimental group compared with the control group. The expression of extracellular matrix (ECM) components decreased relative to the control group. The expression of p27 and PCNA declined gradually in cells treated for 72 h at 6 μmol/L ATO compared with the control group.