BAG3 and HIF-1α Coexpression Detected by Immunohistochemistry Correlated with Prognosis in Hepatocellular Carcinoma after Liver Transplantation

Objective. The objective is to determine the effects of BAG3 and HIF-1α expression on the prognosis of HCC patients after liver transplantation. Methods. Samples from 31 patients with HCC receiving liver transplantation were collected for this study. The immunohistochemistry was used to detect the expression of BAG3 and HIF-1α of HCC samples. Results. According to the immunohistochemistry results, BAG3 and HIF-1α staining were significantly associated with tumor TNM stage (P=0.004, P=0.012). A significant association between high BAG3/HIF-1α levels and a shorter overall survival was detected, so as the combined BAG3 and HIF-1α analysis. Conclusion. The results suggested that the expression level of BAG3 and HIF-1α is efficient prognostic parameters in patients with HCC after liver transplantation

Pro-thrombotic changes associated with exposure to ambient ultrafine particles in patients with chronic obstructive pulmonary disease: roles of lipid peroxidation and systemic inflammation.

BACKGROUND: Exposure to particulate matter air pollution is associated with an increased risk of cardiovascular mortality in patients with chronic obstructive pulmonary disease (COPD), but the underlying mechanisms are not yet understood. Enhanced platelet and pro-thrombotic activity in COPD patients may explain their increased cardiovascular risk. We aim to explore whether short-term exposure to ambient particulate matter is associated with pro-thrombotic changes in adults with and without COPD, and investigate the underlying biological mechanisms in a longitudinal panel study. Serum concentration of thromboxane (Tx)B2 was measured to reflect platelet and pro-thrombotic activity. Lipoxygenase-mediated lipid peroxidation products (hydroxyeicosatetraenoic acids [HETEs]) and inflammatory biomarkers (interleukins [ILs], monocyte chemoattractant protein-1 [MCP-1], tumour necrosis factor alpha [TNF-α], and macrophage inflammatory proteins [MIPs]) were measured as potential mediating determinants of particle-associated pro-thrombotic changes. RESULTS: 53 COPD and 82 non-COPD individuals were followed-up on a maximum of four visits conducted from August 2016 to September 2017 in Beijing, China. Compared to non-COPD individuals, the association between exposure to ambient ultrafine particles (UFPs) during the 3-8 days preceding clinical visits and the TxB2 serum concentration was significantly stronger in COPD patients. For example, a 103/cm3 increase in the 6-day average UFP level was associated with a 25.4% increase in the TxB2 level in the COPD group but only an 11.2% increase in the non-COPD group. The association in the COPD group remained robust after adjustment for the levels of fine particulate matter and gaseous pollutants. Compared to the non-COPD group, the COPD group also showed greater increases in the serum concentrations of 12-HETE (16.6% vs. 6.5%) and 15-HETE (9.3% vs. 4.5%) per 103/cm3 increase in the 6-day UFP average. The two lipid peroxidation products mediated 35% and 33% of the UFP-associated increase in the TxB2 level of COPD patients. UFP exposure was also associated with the increased levels of IL-8, MCP-1, MIP-1α, MIP-1β, TNF-α, and IL-1β in COPD patients, but these inflammatory biomarkers did not mediate the TxB2 increase. CONCLUSIONS: Short-term exposure to ambient UFPs was associated with a greater pro-thrombotic change among patients with COPD, at least partially driven by lipoxygenase-mediated pathways following exposure. Trial registration ChiCTR1900023692 . Date of registration June 7, 2019, i.e. retrospectively registered

Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma

Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2-associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2’s potential role as a therapeutic target in HCC

Preparation of the thienopyridine derivatives loaded liposomes and study on the effect of compound-lipid interaction on release behavior

The article describes characterization of two liposome formulations containing thienopyridine derivatives, namely TP-58 and TP-67. By preparing the liposomes, the concentration of the two compounds in ultrapure water was increased up to three orders of magnitude. After i.v. administration of the liposomes in rats, the initial compound plasma concentrations were enhanced more than fifty times relative to that after i.g. administration of the compound suspensions. It was found out that the release rate of TP-67 from the liposome both in vitro and in vivo was not significantly different from that of TP-58. TP-58 was more lipophilic than TP-67 according to partition coefficiency, and TP-67 had greater polarity than TP-58 based on polar surface area (PSA). With DSC, it was found out that the interaction magnitude between TP-67 and the lipid bilayer was not significantly different from that between TP-58 and the lipid bilayer, which accounted for the similarity of the two compounds in release rate both in vitro and in vivo. It indicated liposome can be used as a potential carrier for broading the application of TP-58 and TP-67. Interaction between the thienopyridine derivatives and the lipid bilayer is probably the decisive factor for compound release from the liposomes