Search

Neuregulin receptor degradation protein-1 (Nrdp1) is a newly discovered E3 ligase that plays a role in the apoptosis process of multiple diseases. Previous studies has shown that Nrdp1 exerted a proapoptotic effect in cardiac diseases. The purpose of this study is to investigate the potential involvement of Nrdp1 in the pathological processes of inflammatory bowel disease (IBD). To create a mouse model of experimental colitis, trinitrobenzenesulfonic acid (TNBS) was administered and the severity of colitis was assessed based on changes in weight and histological scores. Using Western blot and immunohistochemistry, significant increase in Nrdp1 expression was observed in intestinal epithelial cells (IECs). This was accompanied with the up-regulation of cleaved PARP and active caspase-3 in IECs, indicating a potential function in IECs. To study this further, we built an in vitro model of tumor necrosis factor-apha (TNF-a)-induced apoptosis using human IEC line HT-29 cells. When Nrdp1 was knocked down, a decrease in apoptosis was observed, suggesting that Nrdp1 may play a proapoptotic role in IEC apoptosis. The mechanism behind this phenomenon is associated with the suppression of downstream targets of Nrdp1, such as protein kinase B (AKT). Furthermore, immunohistochemistry analysis in patients with Crohn's disease (CD) and normal controls supported the same results as observed in experimental colitis. We conclude that Nrdp1 may be a promising new therapeutic target for ameliorating IBD in humans. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to explore the influences of micro ribonucleic acid (miR)-150 on the proliferation and apoptosis of mantle-cell lymphoma (MCL) cells and to investigate the potential underlying mechanism. PATIENTS AND METHODS: Differentially expressed miRNAs in MCL tissues were excavated via microarray analysis of miRNA expression profiles. Subsequently, the expression of miRNAs were verified by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qP-CR). The influence of miRNA expression on the survival of patients was detected based on clinical data. Besides, the potential targets of miRNAs were determined using Luciferase reporter gene assay combined with qRT-PCR and Western blotting. Primary tumor cells were extracted, and the influences of miR-150 expression on cell proliferation were detected via Cell Counting Kit (CCK)-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Finally, Western blotting and flow cytometry were performed to explore the impact of miR-150 on the apoptosis of primary tumor cells. RESULTS: Microarray analysis of miRNA expression profiles and RT-qPCR verified that the expression levels of hsa-miR-486, hsa-miR-4746, and hsa-miR-3158 rose considerably in MCL tissues, while those of hsa-miR-29b-3p, hsa-miR-150, and hsa-miR-142-5p remarkably declined. According to the results of survival analysis, the survival time was notably prolonged in patients with higher expression levels of miR-150 and miR-486, especially in those with higher expression level of miR-150. Luciferase reporter gene assay and RT-qPCR and Western blotting results demonstrated that miR-150 negatively regulated the expression level of MET. Subsequent CCK-8 assay and EdU staining results revealed that up-regulation of miR-150 significantly suppressed the proliferation of primary MCL cells. Finally, Western blotting and flow cytometry found that increased expression of MET remarkably facilitated the apoptosis of primary MCL cells. CONCLUSIONS: MiR-150 inhibits the proliferation and promotes the apoptosis of MCL cells by negatively regulating MET expression. [ABSTRACT FROM AUTHOR]

In today's global economy, manufacturing companies must be able to change both the product variety and production quantity without incurring major disturbances in the production process. A manufacturing system capable of performing these changes efficiently needs a control system flexible enough to go from one state to another without significant delays in production. To compensate for the deficiencies of both hierarchical and heterarchical control systems, a control architecture based on the holonic concept is proposed. After presenting the general holonic control architecture, the paper focuses on the integration of the holonic-based control concept in the design of an automated material-handling control system. When performing transport activities in a manufacturing system, due to its architecture, the holonic system can operate both as a hierarchical system, following a predefined schedule during normal operation conditions, and as a heterarchical system in the presence of disturbances. [ABSTRACT FROM AUTHOR]

The coordinated control strategy of a hybrid energy storage system (HESS) operated in an islanded AC Micro-Grid (MG) is researched, based on which an improved active power allocation strategy is proposed. The ultracapacitor (UC) in the HESS is under droop control to regulated the system frequency and voltage directly. The lead-acid battery in the HESS is controlled based on the droop characteristic of the system frequency, and is responsible for maintaining the SOC of the UC under control and compensating the non-instantaneous power fluctuations in the AC MG. Simulation results have certificated that the presented control strategy is effective. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cellular stress response 1 (CSR1) is a tumor suppressor gene that was frequently down-regulated in prostate cancer. CSR1 has critical roles in the regulation of cell apoptosis via inactivation of CPSF3 or preventing the interaction of XIAP with caspases. However, whether CSR1 plays a role in human hepatocellular carcinoma (HCC) is completely unknown. PATIENTS AND METHODS: The expression of CSR1 in HCC clinic samples and cell lines was detected by Real-time PCR and Western blot. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system was used to knockout CSR1 gene in HepG2 cells. The proliferation of HCC cells was measured by MTT assay. The migration and invasion abilities of HepG2 cells were determined by in vitro scratch wounding and matrigel invasion assays. Co-immunoprecipitation assay was used to determine the interaction between CSR1 and hematopoietic PBX interacting protein (HPIP). RESULTS: The mRNA and protein levels of CSR1 were down-regulated in human HCC cell lines and clinic HCC tissues. Over-expression of CSR1 inhibited cell proliferation, migration and invasion in human HCC cell lines. Knockout of CSR1 gene by CRISPR-Cas9 in HepG2 cells achieved the opposite effects. At the molecular level, we found that CSR1 associated with HPIP and inhibited the activation PI3K/AKT pathway. CONCLUSIONS: For the first time we demonstrated that CSR1 inhibited HCC cell proliferation, migration and invasion through inactivation of HPIP and its downstream PI3K/AKT signaling pathway and suggested CSR1 as a potential therapy target for HCC treatment. [ABSTRACT FROM AUTHOR]