作者机构：
[Hu, Jia-Qing] Second Peoples Hosp Hunan, Dept Emergency, Changsha 410007, Hunan, Peoples R China.;[Deng, Fang] Second Peoples Hosp Hunan, Dept Pharmacol, Changsha 410007, Hunan, Peoples R China.;[Hu, Xiao-Ping] Guangzhou Med Univ, Affiliated Canc Hosp, Dept Pharmacol, Guangzhou 510095, Guangdong, Peoples R China.;[Zhang, Wei] Second Peoples Hosp Hunan, Dept Radiol, Changsha, Hunan, Peoples R China.;[Zeng, Xiao-Chen] Second Peoples Hosp Hunan, Dept Surg, Changsha, Hunan, Peoples R China.
通讯机构：
[Tian, Xue-Fei] H;Hunan Univ Chinese Med, Clin Med Coll, Peoples Hosp Hunan 2, Dept Oncol, Changsha 410007, Hunan, Peoples R China.
关键词：
sirtuin;post-translational modification;apoptosis;liver cancer
摘要：
Liver cancer is the leading cause of cancer-related mortality worldwide and its incidence is increasing. Considerable effort has been made in recent decades to improve the diagnosis and treatment of liver cancer. Advanced liver cancer often exhibits a poor response to chemotherapy and poor prognosis due to acquired chemoresistance and tumor recurrence. Understanding the precise molecular mechanisms that are responsible for chemotherapeutic drug-induced cell death could potentially identify novel therapeutic targets and improve liver cancer treatment. In the present study, it was demonstrated that in response to doxorubicin, the most frequently used chemical compound for liver cancer treatment, histone deacetylase sirtuin 6 (SIRT6) is specifically downregulated. This enables forkhead box O3 (FOXO3) upregulation, translocation into the nucleus and increased expression of its target genes p27 and Bim, which further induce apoptosis. Overexpression of SIRT6, but not enzyme-inactivated mutants, prevents FOXO3 translocation into the nucleus and doxorubicin-induced cell death. SIRT6 interacts with FOXO3 and this interaction increases FOXO3 ubiquitination and decreases its stability. Finally, it was identified that the effect of SIRT6 in preventing doxorubicin-induced cell death requires FOXO3. Overexpression of SIRT6 could not prevent doxorubicin-induced cell death in FOXO3-knockdown cells. Therefore, it was concluded that SIRT6 plays a central role in determining doxorubicin-induced cell death via modulation of FOXO3 activity. Therapeutic targeting of SIRT6 and/or FOXO3 may offer novel strategies for treatment of liver cancer.
摘要：
Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein 70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium. A thermal tolerance HepG2 (HepG2TT) cell model was established to simulate HSP70 accumulation in the microenvironment. A certain concentration of curcumin was co-cultured with HepG2 and HepG2TT cells to observe the changes of HSP70 and TLR4. Our results revealed that heat stress significantly increased the expression of extracellular HSP70 (eHSP70) and TLR4 (P<0.01), but significantly reduced the expression of intracellular HSP70 (P<0.01). Curcumin inhibited proliferation, invasion, and metastasis of HepG2 cells, caused cells to remain in the DNA S phase, promoted apoptosis, and significantly reduced intracellular HSP70, eHSP70 and TLR4 levels of HepG2TT cells. Following the removal of curcumin, eHSP70 increased again. In summary, our results demonstrated that the antitumor effect of curcumin was related to the inhibition HSP70-TLR4 signaling.
摘要：
Aims: Neutrophil extracellular traps (NETs) comprise a unique form of non-apoptotic cell death exhibited by neutrophils, which occurs in a stepwise process termed NETosis. It has been postulated that NETosis plays an important role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate serum levels of NET remnants in patients with rheumatoid arthritis (RA), as well as potential associations between NET remnants and indicators of RA. Methods: Serum levels of myeloperoxidase (MPO)-DNA complexes (NET remnants) were examined in 74 RA patients and 50 healthy controls using a modified enzyme-linked immunosorbent assay. Associations between the levels of these complexes and indicators of RA were then statistically evaluated. Results: RA patients exhibited significantly higher levels of MPO-DNA complexes than the healthy controls, and these levels were associated with increased neutrophil counts and positivity for rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA). Among the 63 ACPA-positive RA patients examined, those with ACPA titers > 1600 U/mL showed significantly increased MPO-DNA levels. Receiver operating characteristic analysis determined that the area under the curve for all 74 RA patients was 0.798, with a sensitivity of 91.9% and a specificity of 56.0%, while that for the ACPA-negative patients was 0.891, with a sensitivity and specificity of 81.8% and 84.0%, respectively. Conclusions: The results of this study suggest that the disease status of RA is associated with increased NETosis. In particular, evaluation of serum MPO-DNA levels may comprise a useful complementary tool for discriminating RA patients from healthy individuals.
通讯机构：
[Ren, Biqiong] H;Hunan Prov Second Peoples Hosp, Clin Lab, 427 Furong Rd Changsha, Changsha 410007, Hunan, Peoples R China.
关键词：
Heat shock protein 70;Sperm-associated antigen 9;Auto-antibody;Hepatocellular carcinoma;Lung cancer
摘要：
There are different views of how the immune system participates in the reaction to cancer. Here, we evaluated expression of DAMP proteins HSP70 and cancer-testis antigen SPAG9 in patients with hepatocellular carcinoma (HCC) and lung cancer to explore tumor immunity. Our analysis showed that levels of HSP70 and SPAG9 antibody were significantly higher in the serum of lung cancer and HCC patients than in the serum of healthy subjects (P < 0.001), but there were no differences in levels of HSP70 antibody in patients and controls. Levels of serum SPAG9 antibody in newly diagnosed lung cancer patients were significantly higher than in treated lung cancer patients (P < 0.05), but there were no differences in levels of HSP70 or HSP70 antibody. Levels of serum HSP70 and SPAG9 antibody, but not HSP70 antibody, were also higher in hepatitis/cirrhosis patients than in healthy subjects (P = 0.005, P < 0.001). Levels of serum SPAG9 antibody were significantly higher in HCC patients than in hepatitis/cirrhosis patients, but there were no differences in HSP70 or HSP70 antibody levels. Finally, levels of serum HSP70 and SPAG9 antibody were significantly higher in HCC patients than in lung cancer patients (P < 0.05, P < 0.001). These results indicate that cancer-testis antigen SPAG9 induces a strong humoral immune response in cancer patients but HSP70 does not. These results show that SPAG9 has potential as a tumor-specific biomarker.
摘要：
We investigated the effects of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the proliferation and invasion of human cervical cancer cell lines, as well as the molecular pathways underlying these effects. MTT cell proliferation assays revealed a time- and concentration-dependent cytotoxic effect of PA-MSHA on HeLa cells but not H8 cells. Flow cytometry with propidium iodide and annexin-V-fluorescein isothiocyanate labeling (FITC) indicated that various concentrations of PA-MSHA could induce apoptosis and G2-M cell cycle arrest in HeLa cells. PA-MSHA also impaired the migration and invasion abilities of HeLa cells in Wound healing and Transwell invasion assays. Western blot results demonstrated that PA-MSHA reduced the expression of p-AKT, p-GSK3beta, BCL-2, Vimentin and beta-catenin, but increased the levels of PTEN, BAD, BAX and E-cadherin in HeLa cells. Importantly, PTEN siRNA induced the activity of p-AKT, while PA-MSHA partly inhibited this induction, indicating that PA-MSHA may reduce the cell proliferation and invasion potential by activating PTEN and thus inhibiting the AKT pathway in vitro. These data suggest the potential application of PA-MSHA to the treatment of human cervical cancer.
摘要：
Interleukin 35 (IL-35) is a newly discovered anti-inflammatory cytokine. Recent studies have indicated that it plays a crucial role in the pathogenesis of autoimmune diseases. In humans, IL-35 is predominantly secreted from regulatory T cells. This study aimed to measure serum IL-35 levels in patients with rheumatoid arthritis (RA) and in control individuals, and analyze its association with disease indicators of RA. One hundred patients with RA were recruited, and 50 volunteers were enrolled as healthy controls. Serum IL-35 levels were measured using an enzyme-linked immunosorbent assay kit. RA patients showed significantly lower serum levels of IL-35 compared with healthy controls (p < 0.001). RA patients suffering from erosive arthritis (n = 31) had lower IL-35 levels than those with non-erosive arthritis (n = 69, p = 0.022). In addition, serum IL-35 level was significantly lower in 22 patients with elevated percentage (> 75%) of neutrophils (p < 0.001). Correlation analysis indicated a significantly negative association between IL-35 and age, rheumatoid factor (RF), or percentage of neutrophils. In contrast, the serum IL-35 levels were not significantly different between patients with anti-cyclic citrullinated peptide (CCP) antibodies (n = 78) and those without anti-CCP antibodies (n = 22). However, among patients without anti-CCP antibodies, the serum IL-35 levels were lower in patients with erosive arthritis (n = 8) than those patients without erosion (n = 14) (p < 0.001), although no significant difference was detected in patients with anti-CCP antibodies. In conclusion, IL-35 plays a protective role in the pathogenesis of RA.
摘要：
Aims: The clinical significance of myeloperoxidase (MPO) has been the focus of investigation because it may contribute to the chronic, non-microbial inflammatory process in various diseases. Here, we determined serum MPO levels in rheumatoid arthritis (RA) and other autoimmune or inflammatory conditions, and investigated the associations between MPO levels and disease activity indicators in RA. Main methods: The distribution of MPO was determined in serum samples from patients with RA, systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS), dermatomyositis (DM), or ankylosing spondylitis (AS) and from healthy controls using commercial ELISA kits. Associations of serum MPO levels with the disease variables of RA patients were evaluated. Key findings: All patient samples analyzed showed higher serum levels of MPO than healthy controls. Furthermore, MPO levels in RA were significantly higher than those in the other diseases with the exception of DM. Higher MPO levels were observed in RA patients with increased C-reactive protein (p = 0.005) or neutrophil percentage (p < 0.001), as well as in those with highly active disease (p < 0.001). Moderate positive correlations between MPO levels and IgM (r = 0.334, p = 0.001),C-reactive protein (r = 0.293, p = 0.003), erythrocyte sedimentation rate (r = 0.240, p = 0.016), or DAS28 (r = 0.350, p < 0.001) were also demonstrated. Significance: The MPO concentration is likely to increase in patients with chronic inflammation. The associations between MPO and the disease variables of RA patients support a role for MPO in the inflammatory process of the disease. (C) 2014 Elsevier Inc. All rights reserved.
摘要：
Objective: To probe into the mechanisms of electroacupuncture (EA) at Shangjuxu (ST 37) for treatment of the ulcerative colitis (UC). Methods: Forty male Wistar rats were randomly divided into 4 groups: a normal group, a model group, a Shangjuxu group and a non-acupoint group, 10 rats in each group. The UC rat model was made with enema of trinitro-benzenesulfonic acid (TNBSA), and the changes of interleukin-1 beta (IL-1 beta) and interleukin-4 (IL-4) contents after EA at Shangjuxu (ST 37) were observed. Results: EA at Shangjuxu (ST 37) could significantly decrease the IL-1 beta content and increase the IL-4 content in the colic tissues of the UC rats with significant differences as compared with the model group and the non-acupoint group (P<0.05 or P<0.01). Conclusion: The mechanisms of EA at Shangjuxu (ST 37) for treatment of the UC rats is possibly related with the decrease of IL-1 beta, a inflammation-promoting cytokine, and the increase of IL-4, a anti-inflammatory cytokine.
