Vulnerability of atherosclerotic plaques is associated with type I interferon in a murine model of lupus and atherosclerosis.

This study aimed to investigate the relationship between type I interferon (IFN-I) and plaque stability in pristane-treated apolipoprotein E-knockout (ApoE(-/-)) mice. Antinuclear antibody (ANA) and extractable nuclear antigen antibody (ENA) levels were measured by immunofluorescence and enzyme-linked immunospot assay. Atherosclerotic plaques were detected by Sirius red/fast green staining. Cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling. Gene expression was determined by real-time PCR analyses. We found that pristane-treated ApoE(-/-) mice developed a lupus-like syndrome characterized by an increased production of serum ANA and ENA. Pristane treatment decreased the collagen content and increased the number of apoptotic cells in plaques. Moreover, IFN-induced ISG15, IFIT1-1, and IFIT1-2 gene expression was increased in peripheral blood cells and aortic plaques. An IFN-α-stimulated macrophage supernatant inhibited collagen type I, alpha 1 gene expression in vascular smooth muscle cells. We concluded that the vulnerability of plaques was associated with the activation of IFN-I in pristane-treated ApoE(-/-) mice. Thus, we speculated that the higher prevalence of cardiovascular events in patients with systemic lupus erythematosus could be due to plaque instability.

Hypoxia-inducible factor-1α expression in the different stages of rat thromboangiitis obliterans.

We investigated the expression and effects of hypoxia-inducible factor-1α (HIF-1α) in rat thromboangiitis obliterans (TO). Rats were divided into sham and model groups. The model group was further divided into groups based on observation duration. Lauric acid was injected below an artery clamp to simulate TO in the model group; saline was used in the sham group. Clamps were removed 15 min after injection in both groups, and physiological changes were observed at different times (gross observation and hematoxylin and eosin staining). The animals were killed at various times following the operation and serum and muscle tissues were sampled. For the sham group: the endometrium was relatively intact; medial membrane and epineurium lesions were absent; and blood vessels and surrounding tissues had no inflammatory cell infiltration. For the model group: all subgroups displayed inflammation; large numbers of inflammatory cells were gathered; muscle tissue lost its normal texture and structure; and the internal elastic membrane was integrated. Compared with the preoperative status, HIF-1α expression increased significantly in all subgroups (P < 0.05); there was no change in the sham group. HIF-1α expression in each subgroup was different (F = 14.267, P < 0.05). Femoral artery injection of lauric acid can be used as a rat TO model owing to its simple application and success rate. HIF-1α expression increased in the early stage of TO and gradually decreased with the extension of ischemia time; it may play a leading role in TO development and can be used for diagnosis and cure evaluation.

Changes in the PD-1 and PD-L1 expressions of splenic dendritic cells in multiple-organ dysfunction syndrome mice and their significance.

The aim of this study was to evaluate the expression of surface molecules in splenic dendritic cells (DC) in multiple-organ dysfunction syndrome (MODS) mice and their effects on the immunosuppression of sepsis and MODS. One hundred thirty C57BL/6 mice were divided into 7 groups: 6, 12, 24, 48 h, 5-7 days, 10-12 days, and the normal control group. The sepsis-MODS mouse model was established by zymson injection into the peritoneal cavity. Histopathological changes in the spleen were evaluated by hematoxylin and eosin (HE) staining. After enrichment with BDTM IMag, the expressions of PD-1, PD-L1, MHC-II (I-A(b)), and CD86 in splenic DCs were examined by flow cytometry, and their relationship with sepsis development and MODS was analyzed. The histological structures of the spleen were damaged in the 24-, 48-h, and 10-12-day groups. PD-L1 expression increased 6 h after zymosan injection, decreased to normal levels at 24 and 48 h, and increased at 5-7 days, peaking at 10-12 days. The change in PD-1 expression roughly paralleled that of PD-L1. MHC-II and CD86 increased at 6 and 12 h, and dropped to normal levels at 10-12 days. In the early stage of injury, splenic DCs were mainly activated, whereas in the later stage, the expressions of the negative co-stimulatory molecules, PD-L1 and PD- 1, were upregulated, similar to tolerogenic DCs. Splenic DCs might suppress the stimulation of T lymphocytes in MODS mice through the PD-L1/PD-1 pathway, which would induce immunosuppression and the pathogenesis of MODS.

Effect of radiotherapy on the treatment of patients with extensive stage small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive disease, in which more than 80% of patients present distant metastases at the time of first diagnosis. Chemotherapy is considered as the main treatment of extensive disease of SCLC (ED-SCLC), while the role of radiotherapy in the treatment of ED-SCLC is controversial. A case-control study was undertaken of patients diagnosed as ED-SCLC between 2004 and 2010. Fifty-eight patients with overall survival (OS) over 1 year were chosen, and another 58 patients with OS less than 1 year were selected as the control group, with the age, gender, metastasis or no metastasis of the liver, and the response after the first line of chemotherapy matched. The 1-year, 2-year, 3-year, and median OS of the 75 ED-SCLC patients who received radiation were 81.47, 29.89, 22.77%, and 17 months, respectively, and were 61.18, 23.53, 0%, and 16 months, respectively, for patients who did not receive radiation. The χ(2) test and odds ratio (OR) estimate demonstrated that these differences were statistically significant (χ(2) = 6.38, P = 0.0116; OR = 2.74, 95% confidence interval = 1.24-6.05). These results show that radiotherapy also plays a role in responding patients with extensive stage of SCLC.