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The present study aimed to investigate changes in cellular immune function and regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC) prior to and following transcatheter arterial chemoembolization (TACE) and their clinical significance. The proportion of CD4+ and CD8+ T cells and Tregs in the peripheral blood between healthy volunteers and patients with HCC were detected by flow cytometry prior to (1 day) and one month following TACE. The level of interleukin (IL)‑35 in the peripheral blood was examined by ELISA. In the peripheral blood of patients with HCC, the proportion of CD4+ T cells in the total T lymphocytes was significantly lower compared with that of healthy volunteers (26.71 ± 5.57, vs. 34.74 ± 2.86%; P<0.05) and the ratio of CD4+/CD8+ T lymphocytes in patients with HCC was lower compared with that of healthy adults prior to TACE (1.03 ± 0.14, vs. 1.68 ± 0.16, P<0.05). The ratio markedly increased following TACE treatment (30.52 ± 4.19, vs. 1.29 ± 0.14). The percentage of CD4+CD25+ Treg cells in the total CD4+ T cells isolated from the patients with HCC was markedly higher compared with that of healthy adults prior to TACE (11.12 ± 3.58%, vs. 4.98 ± 1.45%, P<0.05) and it was significantly decreased following TACE (7.58±2.65%; P<0.05). No statistically significant difference in the expression of IL‑35 was detected prior to or following TACE in patients with HCC and healthy adults (369.66 ± 95.53, 352.28 ± 107.50 and 316.24 ± 89.21 pg/ml, respectively). The level of AFP, an oncofetal protein of ~72 kDa, which is produced by normal gastrointestinal cells, yolk sac cells and fetal hepatocytes immediately following birth, was increased in patients with HCC (1674 ± 1649 ng/ml) and was significantly decreased following TACE (827 ± 981 ng/ml). Treg cells changed in positive correlation with the change of AFP, with a correlation coefficient of 0.401. TACE markedly improved the immune function of patients with HCC.

Many lncRNA and mRNA sense-antisense transcripts have been systematically identified in malignant cells. However, the molecular mechanisms of most lncRNA-mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer-associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is significantly down-regulated in gastric cancer and could promote tumor growth in vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11 via the ASK1-p38MAPK/JNK signaling pathway. These findings suggest that decreased expression of SLC7A11-AS1 contributes to the progression of gastric cancer and may be a novel diagnostic biomarker and effective therapeutic target in gastric cancer patients.

No abstract

Muscle cells could serve as antigen-presenting cells, and participate in the activation of immune response. Immunological characteristics of muscle cells, and their capacities to equip themselves with immunorelevant molecules, remain to be elucidated. In this study, we investigated the immunological properties of myoblasts and differentiated myotubes in vitro and in vivo, under the IFN-γ induced inflammatory condition. We found that the fused C C myotubes are more sensitive to inflammatory stimulation, and significantly upregulated the expression levels of MHC-I/II and TLR3/7 molecules, than that of proliferated myoblasts. As well, some co-stimulatory/-inhibitory molecules, including CD40, CD86, ICAM-I, ICOS-L, and PD-L1, were prominently upregulated in IFN-γ induced myotubes. Notably, we detected the protein levels of ASC, NLRP3, and Caspase-1 increased in stimulated myotubes, and IL-1β in cell culture supernatant, implying the activation of NLRP3 inflammasomes in IFN-γ treated myotubes. The pro-inflammatory cytokines and chemokines mRNA levels in IFN-γ induced C C myotubes and myoblasts, involving IL-1, IL-6, and MCP-1, increased markedly. T cell activation test further verified IFN-γ induced C C myotubes prompt to the proliferation of the splenic CD4 and CD8 T cells. In Cardiotoxin-damaged tibialis anterior (TA) muscle, some regenerated myofibers expressed both MHC class I and class II molecules under IFN-γ enhanced inflammatory condition. Thus, our work demonstrates that muscle cells are active participants of local immune reactions. Anat Rec, 301:1551-1563, 2018. © 2018 Wiley Periodicals, Inc.

Background: The systematic expression characteristics and functions of collagen genes in gastric cancer (GC) have not been reported. Through public data integration, combined with bioinformatics analysis, we identified a panel of collagen genes overexpressed in GC. The functions of these genes were analyzed and validated in a GC-related cohort. microRNAs that may potentially target such genes were investigated in vitro. Methods: Four GC-related datasets retrieved from the Gene Expression Omnibus (GEO) were used to extract differentially expressed genes (DEGs) in GC. Functional annotation was performed to identify the potential roles of the identified DEGs. The association of candidate genes involved in the prognosis of GC patients (n=876) was determined using data provided by the Kaplan-Meier-plotter database, The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) repository, and a GC-related dataset (GSE15459). The expression characteristics of candidate genes and their associations with clinical parameters were validated in our in-house cohort (n=58). MicroRNAs able to target the identified candidate genes were predicted and confirmed using qRT-PCR, Western blotting, and dual-luciferase reporter assays in vitro. Results: After the integration of four GEO datasets, 76 DEGs were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that these DEGs were significantly enriched in ECM-related functions and pathways. A group of collagen genes was significantly upregulated in the GC tissues and constituted a proteinprotein interaction network as important nodes. Some of these collagen genes were closely associated with poor prognosis in GC patients. Overexpression of COL1A1 and COL4A1 was confirmed in our in-house cohort, and this was related to prognosis and certain clinicopathological parameters. We found that microRNA-29c-3p could directly target COL1A1 and COL4A1 in BGC-823 cells. Conclusions: Collagen genes identified in this study were associated with patient prognosis in GC and may represent diagnostic markers or potential therapeutic targets. Aberrant expression of such candidate genes may be induced by microRNA-29c-3p.

The objective of this study is to investigate the role of Calmodulin-dependent protein kinase IV (CaMKIV) in Cardiotoxin (CTX)-induced mice muscle inflammation. CTX injection i.m. was performed to induce B6 mice acute tibialis anterior (TA) muscle injury. The mice were then injected i.p. with the recombinant CaMKIV protein or its antagonist KN-93. Immunoblotting was used to assess Calmodulin (CaM) and CaMKIV levels. Immunofluorescence was used to detect intramuscular infiltration or major histocompatibility complex (MHC)-I expression in damaged muscle. The extent of infiltration was evaluated by fluorescent intensity analysis. Cytokines/chemokines levels were determined by qPCR. CaMKIV gene knockdown in C2C12 cells was performed in order to evaluate the effects of CaMKIV on immuno-behavior of muscle cells. CTX administration induced a strong up-regulation of CaM and p-CaMKIV levels in infiltrated mononuclear cells and regenerated myofibers. In vivo adding of the recombinant CaMKIV protein enhanced intramuscular infiltration of monocytes/macrophages in damaged muscle and increased the number of proinflammatory Ly-6CF4/80 macrophage cells. CaMKIV protein treatment induced a striking up-regulation of mRNA levels of IL-1, IL-6, MCP-1, and MCP-3 in CD45 cells sorted from damaged muscle; increased the infiltration of CD8 T cells; and induced the up-regulation of MHC-I in partial regenerated myofibers, which was rarely observed in muscle damage alone. Additionally, CaMKIV protein treatment diminished the regulatory T cells (Tregs) number and led to the damaged TA muscle repair delay. In vitro CaMKIV gene knockdown reversed IFN-γ-induced up-regulation of MHC-I/II and TLR3 in the differentiated C2C12 myotubes. CaMKIV can act as an immunostimulation molecule and enhances the acute muscle inflammatory responses.

ADTR by jejunal interposition presents similar rates of tumor recurrence, metastasis and long-term survival compared with classical reconstruction with RY esophagojejunostomy; however, it offers considerably improved near-term quality of life, especially in terms of early recovery and decreased reflux esophagitis. Thus, ADTR is recommended as a worthwhile digestive tract reconstruction method for Siewert types II and III AEG.