Prognostic signature for hepatocellular carcinoma based on 4 pyroptosis-related genes.

BACKGROUND: Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Many recent studies have suggested that pyroptosis is important in tumour progression. However, the role of pyroptosis-related genes (PRGs) in HCC remains unclear. MATERIALS AND METHODS: We identified differentially expressed PRGs in tumours versus normal tissues. Through univariate, LASSO, and multivariate Cox regression analyses, a prognostic PRG signature was established. The signature effectiveness was evaluated by time-dependent receiver operating characteristic (t-ROC) curve and Kaplan-Meier (KM) survival analysis. The signature was validated in the ICGC (LIRI-JP) cohort. In addition, single-sample gene enrichment analysis (ssGSEA) showed the infiltration of major immune cell types and the activity of common immune pathways in different subgroups. RESULTS: Twenty-nine pyroptosis-related DEGs from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were detected, and four genes (CTSV, CXCL8, MKI67 and PRF1) among them were selected to construct a prognostic signature. Then, the patients were divided into high- and low-risk groups. The pyroptosis-related signature was significantly associated with overall survival (OS). In addition, the patients in the high-risk group had lower levels of immune infiltration. CONCLUSION: The prognostic signature for HCC based on 4 pyroptosis-related genes has reliable prognostic and predictive value for HCC patients.

Optimization of Properties for Alumina-Spinel Refractory Castables by CMA (CaO-MgO-Al2O3) Aggregates.

Aiming at optimizing properties of alumina-spinel refractory castables, coarse corundum particles were replaced partially with the particles of a novel porous multi-component CMA (CaO-MgO-Al2O3) aggregate in the same size. Properties including the bulk density, apparent porosity, strength, slag corrosion resistance, thermal shock resistance and thermal fatigue resistance of alumina-spinel refractory castables containing CMA aggregates were evaluated contrastively. The results demonstrated that the incorporation of CMA aggregates can significantly improve thermal shock resistance and thermal fatigue resistance of castables, although companying with slight decrease in the bulk density and strength. Moreover, slag penetration resistance of castables can also be enhanced by CMA aggregates with appropriate particle size. The influence of CMA aggregates on properties of alumina-spinel refractory castables depended strongly on their particle size.

Identification of a novel pyroptosis-related gene signature correlated with the prognosis of diffuse glioma patients.

BACKGROUND: Diffuse glioma is the most common primary tumor of the central nervous system and has a poor prognosis. Recently, a new type of programmed cell death (PCD), pyroptosis, has been found to be widely involved in the process of tumor diseases. However, the expression of pyroptosis-related genes (PRGs) in diffuse gliomas and their relationship with prognosis have rarely been evaluated. METHODS: In this study, we obtained RNA sequencing and clinical data from the Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA) of diffuse glioma patients. Simultaneously, differentially expressed PRGs between TCGA-Glioma tumor samples and the normal brain samples from the Genome Tissue Expression (GTEx) were investigated. Besides, univariate and multivariate Cox regression analysis were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve and principal component analysis (PCA) was undertaken to assess the prognostic capacity of the signature. Gene set enrichment analyses (GSEA) and single sample GSEA (ssGSEA) were used to further understand the molecular mechanisms and the difference of immune microenvironment. External validation of two separate cohorts from the CGGA database was then performed. RESULTS: Caspase 3 (CASP3) and interleukin-18 (IL18) were identified as potential prognostic biomarkers. A novel prognostic model was constructed to predict diffuse glioma patients' overall survival (OS) time. Patients in high-risk subgroup had shorter survival than those with high-risk with P<0.0001. GSEA and ssGSEA showed the activation of immune-related pathways and the extensive infiltration of immune cells [such as cytotoxic T cells, dendritic cells (DC), natural killer T cell (NKT), induced regulatory T cells (iTreg), naturally occurring regulatory T cells (nTreg)] in high-risk subgroup. CONCLUSIONS: A novel two-PRGs prognostic signature based on gene expression was identified, which could predict diffuse glioma patients' OS time. Pyroptosis may be involved in the establishment of immune microenvironment in diffuse glioma.

Long noncoding RNA Alu-mediated p21 transcriptional regulator promotes proliferation, migration, and pipe-formation of human microvascular endothelial cells by sponging miR-126.

Peripheral artery disease (PAD) is a serious hazard to the elderly in the lower extremity atherosclerotic plaque, accompanied by a large number of angiogenesis. Long noncoding RNA Alu-mediated p21 transcriptional regulator (APTR) exerts important functions in promoting cell growth. Therefore, we planned to research the mechanism of APTR in angiogenesis in PAD. CCK-8 assay, flow cytometry analysis, and migration assay were to detect cell viability, apoptosis, and migration respectively. The interaction between APTR and miR-12 was tested through luciferase activity test. In vitro angiogenesis assay was used to test the number of tubular cells. qRT-PCR and Western blot were to test expression of APTR, miR-126, and angiogenesis relative factors. There was spontaneously pipe-formation in HEMC-1 cells under matrigel condition. Knockdown of APTR inhibited cell viability and migration and reduced the number of tubular cells. Further, APTR sponged miR-126 and downregulating miR-126 to promote angiogenesis. Overexpression of APTR promoted cell activity and migration and increased the number of tubular cells via negatively regulating miR-126. APTR could elevate activating phosphatidylinositol 3 kinase/protein kinase B and mitogen extracellular kinase/extracellular signal-regulated kinase signal pathways via negatively regulating miR-126 to promote cell proliferation, migration, and pipe-formation. We researched the mechanism of angiogenesis that APTR elevated proliferation, migration, and pipe-formation via negatively regulating miR-126.

Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction.

The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment.

Electroacupuncture at Qiuxu (GB 40) for treatment of migraine--a clinical multicentral random controlled study.

OBJECTIVE: To observe the therapeutic effects of electroacupuncture (EA) at Qiuxu (GB 40) for treatment of migraine so as to provide clinical evidence for compilation of the Acupoints' Dictionary of the People's Republic of China. METHODS: 275 migraine patients admitted in 3 hospitals were randomly divided into a treatment group treated by EA at Qiuxu (GB 40), and a control group treated by EA at Tianshu (ST 25). The indexes of the migraine symptoms and the 5-HT level were observed in both the groups before and after treatment. RESULTS: There was a significant difference in VAS score between the two groups of the 3 clinical centers (P<0.01). The therapeutic effects of a 4-week treatment were much better in the treatment group than that of the control group. The 3-month follow-up survey showed that the long-term effects were in favor of the treatment group of the first and third clinical centers, though no significant difference was found in the treatment group of the second clinical center as compared with the control group. The results from the 6-month follow-up survey showed better effects in the treatment group of all the 3 clinical centers. CONCLUSION: EA at Qiuxu (GB 40) may show effect for migraine.

[Study on the therapeutic effect of electroacupuncture on migraine and influencing factors].

OBJECTIVE: To compare therapeutic effects of electrical acupuncture (EA) at Qiuxu (GB 40) and Tianshu (ST 25), and to probe the factors of influencing the therapeutic effect. METHODS: Two hundred and seventy-five cases were randomly divided into the test group of 138 cases treated with EA at Qiuxu (GB 40) and the control group of 137 cases treated with EA at Tianshu (ST 25). Their therapeutic effects were observed and the factors influencing the therapeutic effect were analyzed. RESULTS: The transient effective rate was 70.3% in the test group and 58.4% in the control group with a significant difference between the two groups (P<0.05), and there were very significant differences between the two groups in the therapeutic effects at treatment of 4 weeks, and following-up 3 and 6 months later (P<0.001), the transient analgesic effect of EA at Qiuxu (GB 40) being better. EA had better transient effect on migraine for the mental workers, or the patient with high pain score at treatment, or more frequent attack. The long-term analgesic effect of EA at Qiuxu (GB 40) was better than Tianshu (ST 25). CONCLUSION: The analgesic effect of EA at Qiuxu (GB 40) is better than Tianshu (ST 25) and the profession and conditions of the patient are the factors influencing the therapeutic effect.

Structural basis for the function of DCN-1 in protein Neddylation.

Covalent modification by Nedd8 (neddylation) stimulates the ubiquitin-protein isopeptide ligase (E3) activities of Cullins. DCN-1, an evolutionarily conserved protein, promotes neddylation of Cullins in vivo, binds directly to Nedd8, and associates with Cdc53 in the budding yeast Saccharomyces cerevisiae. The 1.9A resolution structure of yeast DCN-1 shows that the region encompassing residues 66-269 has a rectangular parallelepiped-like all alpha-helical structures, consisting of an EF-hand motif N-terminal domain and a closely juxtaposed C-terminal domain with six alpha-helices. The EF-hand motif structure is highly similar to that of the c-Cbl ubiquitin E3 ligase. We also demonstrate that DCN-1 directly binds to Rbx-1, a factor important for protein neddylation. The structural and biochemical results are consistent with the role of DCN-1 as a scaffold protein in a multisubunit neddylation E3 ligase complex.

Dynamic metabolic modeling for a MAB bioprocess.

Production of monoclonal antibodies (MAb) for diagnostic or therapeutic applications has become an important task in the pharmaceutical industry. The efficiency of high-density reactor systems can be potentially increased by model-based design and control strategies. Therefore, a reliable kinetic model for cell metabolism is required. A systematic procedure based on metabolic modeling is used to model nutrient uptake and key product formation in a MAb bioprocess during both the growth and post-growth phases. The approach combines the key advantages of stoichiometric and kinetic models into a complete metabolic network while integrating the regulation and control of cellular activity. This modeling procedure can be easily applied to any cell line during both the cell growth and post-growth phases. Quadratic programming (QP) has been identified as a suitable method to solve the underdetermined constrained problem related to model parameter identification. The approach is illustrated for the case of murine hybridoma cells cultivated in stirred spinners.