Abnormal function of endothelial cells (ECs) is an important reason for vascular endothelial remodeling and atherosclerotic plaque formation in patients with atherosclerosis (AS). Here, we report for the first time that the vascular ECs with apoptosis resistance phenotype (ARECs) exist in peripheral blood of AS patients. Our research data showed that the switch of regulation modes between HIF-1α and Bax operated by lncRNA-ASLNC18810 is the direct cause for the formation of ARECs. When ASLNC18810 is low or missing, HIF-1α indirectly negatively regulates the Bax in post-transcription through HIF-1α/miR-559/Bax pathway which makes ECs acquire apoptosis resistance and form ARECs. The functional experiments results showed that ASLNC18810 could effectively eliminate the anti-apoptotic properties of ARECs by blocking the HIF-1α/miR559/Bax pathway and maintaining HIF-1α/Bax pathway. In a word, our study shows that ASLNC18810 has full potential to become a biological target for the prevention and treatment of atherosclerotic plaques by regulating ARECs. ASLNC18810 was significantly upregulated in ECs compared to ARECs. With high level of ASLNC18810 in ECs, ASLNC18810 binds to miR-559 as a miRNA sponge and suppresses the inhibition effect of miR-559 on Bax protein, this direct positive transcriptional regulation between HIF-1α and Bax endows the apoptotic property in ECs induced by Ox-LDL. However, with low expression of ASLNC18810 in ARECs, the post-transcriptional regulation of Bax by miR-559 dominates and the indirect negative regulation between HIF-1α and Bax endows the anti-apoptotic property of ARECs. To sum up, low ASLNC18810 expression-mediated switching of HIF-1α/Bax pathway to HIF-1α/miR-559/Bax pathway is the internal reason for ECs to obtain apoptosis resistance and the formation of ARECs under the ox-LDL induction.

Proper activation of Toll-like receptor (TLR)-mediated signaling and production of proinflammatory cytokines are critical for the initiation of innate immunity, while the specific mechanism maintaining inflammatory homeostasis remains mostly unknown. Here, we show that Ets2 is upregulated following LPS and VSV stimulation. Ets2 knockdown or knockout leads to increased IL-6, TNF-α, and IFN-β production in macrophages. Consistently, Ets2-deficient mice show exacerbated inflammatory cytokine production and are more susceptible to CLP-induced sepsis. Mechanistically, Ets2 inhibits the LPS- and VSV-induced activation of ERK1/2, JNK, p38, and p65. Ets2 also binds to the promoter of IL-6 to inhibit transcription. Collectively, the results of the present study show the negative regulatory role of Ets2 in LPS- and VSV-induced inflammation through the suppression of MAPK/NF-κB signaling, direct binding to the IL-6 promoter and inhibition of transcription.

OBJECTIVE:To explore the effects of resveratrol on astrocyte and TNF-α in hippocampus of Alzheimer's disease (AD) model rats. METHODS:Sixty rats were randomly divided into six groups: sham control group, model group, resveratrol 20, 40, 80 mg/kg group, and estradiol valerate group (0.8 mg/kg). The model of AD was established by ovariectomy combined injection of D-galactose (100 mg/kg). Twelve weeks later, the heart perfusion in vivo was done and then the hippocampus was fixed. Additionally, the changes of hippocampal astrocytes and TNF-α expression were detected by immunohistochemistry. RESULTS:The levels of glial fibrillary acidic protein (GFAP) and TNF-α in the model group were significantly higher than those of the sham control group (P < 0.01). No marked difference in the production of GFAP was observed between the resveratrol 20 mg/kg group and the model group (P > 0.05). However, the resveratrol 40, 80 mg/kg and estradiol valerate treated groups showed a decrease in the expression of GFAP compared with the model group (P < 0.01). Moreover, with the increasing of resveratrol concentration, the expression of GFAP decreased gradually. The levels of TNF-α decreased markedly in Res 20, 40, 80 mg/kg and estradiol valerate group compared with the model group (P < 0.01). CONCLUSION:These results suggest that the activation of astrocytes and the secretion of TNF-α can be inhibited by Res in AD rats.

Prostate cancer remains the second leading cause of cancer death in men due to inefficiency of androgen deprivation therapy or androgen blockade. Endothelins (ETs) and the two endothelin receptor family members A and B (ETA and ETB) are known to play important roles in the progression of many malignancies, including prostate cancer. However, phase III clinical studies did not reach a unanimous conclusion regarding ETA receptor antagonists in prostate cancer treatment. Here, we provide a meta-analysis of clinical studies using ETA receptor antagonists to treat prostate cancer, especially the hormone refractory prostate cancer (HRPC). Data were extracted from nine studies that used Zibotentan or Atrasentan, two selective ETA receptor antagonists, to treat prostate cancer and meet the selection criteria. The results indicated that the overall survival (OS) and the progression-free survival (PFS) of patients treated with Zibotentan did not show significant difference with the patients treated with placebo (pooled hazard ratio (HR) for OS, 0.86, 95% CI 0.70-1.06; pooled HR for PFS, 0.98, 95% CI 0.91-1.06). No statistically significant difference was detected either as to the OS and PFS of patients between the Atrasentan treated group and the group treated with placebo (pooled HR for OS, 0.99, 95% CI 0.90-1.08; pooled HR for PFS, 0.94, 95% CI 0.86-1.02). Notably, the level of prostate-specific antigen (PSA) and the incidence of bone pain were significantly lower in the Atrasentan treated patients compared to the controls (pooled HR for time of PSA progression, 0.87, 95% CI 0.78-0.97; and pooled relative risk (RR) for bone pain, 0.68, 95% CI 0.48-0.97). In addition, increasing of PSA and bone alkaline phosphatase (BALP) were significantly delayed with Atrasentan treatment (P<0.05). Together, these data suggest that Atrasentan has an effect on cancer-related bone pain and skeletal-events in patients with prostate cancer.