The aim of this work is to study the expression and regulatory effects of CIP2A protein in breast cancer and the correlation between CIP2A protein expression and the prognosis of breast cancer. The CIP2A protein level was detected by immunohistochemistry staining. The relationship between CIP2A protein and clinicopathological parameters of breast cancer was determined. It was observed that 448 (35.00 %) of the 1,280 cases positively expressed CIP2A protein. Univariate analysis indicated that CIP2A expression was related to histological grade, lymph node metastasis, distant metastasis, and triple-negative breast cancer (P = 0.001, 0.001, 0.001, and 0.001, respectively). Spearman correlation analysis showed that CIP2A expression has line correlation with histological grade, lymph node metastasis, distant metastasis, triple-negative breast cancer, and TNM stage (P = 0.03, 0.001, 0.008, 0.001, and 0.001, respectively). After multivariate analysis, tumor size, histological grade, lymph node metastasis, triple-negative breast cancer, distant metastasis, and TNM stage were related to CIP2A expression (P = 0.035, 0.001, 0.028, 0.001, 0.001, and 0.001, respectively). CIP2A expression also significantly related to chemotherapeutic sensitivity of breast cancer in the neoadjuvant chemotherapy. In the Cox regression test, histological grade, lymph node metastasis, triple-negative breast cancer, and TNM stage were detected as the independent prognostic factors (P = 0.001, 0.006, 0.01, 0.011, and 0.001, respectively). CIP2A expression may be a potential biomarker for chemotherapeutic sensitivity and prognosis of breast cancer.

Sepsis is the most common underlying disease of disseminated intravascular coagulation. Acute kidney injury is a common and serious complications of sepsis. In the present study, a lipopolysaccharide (LPS)-induced human proximal tubule cell line (HK-2 cells) was selected as an in vitro model of septic acute kidney injury. The aim of the present study was to investigate whether aquaporin 1 (AQP-1) has a cytoprotective role in LPS-induced HK-2 cells. HK-2 cells were treated with 0–16 µg/ml LPS for 0–24 h to establish the in vitro model of sepsis. The results demonstrated that AQP-1 levels were the lowest of the eight AQP genes expressed in LPS-induced HK-2 cells. Prior to LPS treatment, HK-2 cells were transfected with pcDNA-AQP-1 or small interfering-AQP-1 and cell counting kint-8 and flow cytometry assays were performed to assess cell viability and apoptosis rate, respectively. Changes in the expression of proinflammatory cytokines and chemokines, as well as important factors in the p38, extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) pathways, were assessed using reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA, respectively. LPS treatment reduced viability, increased apoptosis and upregulated the expression of proinflammatory cytokines and chemokines in HK-2 cells. AQP-1 overexpression significantly reversed the effects of LPS and downregulated the expression of tumor necrosis factor-α, interleukin (IL)-8, IL-1β and monocyte chemoattractant protein-1. The p38, ERK1/2 and JNK pathways were activated by LPS; however, the p38 and ERK1/2 pathways were blocked in AQP-1-overexpressing cells. AQP-1 overexpression was demonstrated to confer a survival advantage to LPS-injured HK-2 cells by controlling cell viability, apoptosis and inflammation, possibly via modulation of the p38 and ERK1/2 pathways. The results of the present study suggest that AQP-1 may be an effective treatment for acute kidney injury caused by sepsis.

BackgroundInflammation is an important pathogenic component of endotoxemia-induced acute kidney injury (AKI), finally resulting in renal failure. Diacerein is an interleukin-1β (IL-1β) inhibitor used for osteoarthritis treatment by exerting anti-inflammatory effects. This study aims to investigate the effects of diacerein on endotoxemia-induced AKI.MethodsMale C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/kg) for 24 h prior to diacerein treatment (15 mg/kg/day) for another 48 h. Mice were examined by histological, molecular and biochemical approaches.ResultsLPS administration showed a time-dependent increase of IL-1β expression and secretion in kidney tissues. Diacerein treatment normalized urine volume and osmolarity, reduced blood urea nitrogen (BUN), fractional excretion of sodium (FENa), serum creatinine and osmolarity, and protected renal function in an endotoxemic AKI mice model. In the histopathologic study, diacerein also improved renal tubular damage such as necrosis of the tubular segment. Moreover, diacerein inhibited LPS-induced increase of inflammatory cytokines, such as IL-1β, tumor necrosis factor-α, monocyte chemoattractant protein-1 and nitric oxide synthase 2. In addition, LPS administration markedly decreased aquaporin 1 (AQP1), AQP2, AQP3, Na,K-ATPase α1, apical type 3 Na/H exchanger and Na-K-2Cl cotransporter expression in the kidney, which was reversed by diacerein treatment. We also found that diacerein or IL-1β inhibition prevented the secretion of inflammatory cytokines and the decrease of AQP and sodium transporter expression induced by LPS in HK-2 cells.ConclusionOur study demonstrates for the first time that diacerein improves renal function efficiently in endotoxemic AKI mice by suppressing inflammation and altering tubular water and sodium handing. These results suggest that diacerein may be a novel therapeutic agent for the treatment of endotoxemic AKI.

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This study investigated the effect of simvastatin on the expression of OX40 and OX40 ligand (OX40L) in vitro and in vivo. OX40 and OX40L mRNA and protein levels were measured in human peripheral blood mononuclear cells, using reverse transcription-polymerase chain reaction and Western blot, respectively, in response to simvastatin alone or given in combination with interferon-g, mevalonate or GW9662, a peroxisome proliferatoractivated receptor-g (PPAR-g) antagonist. Simvastatin induced down-regulation of OX40 and OX40L mRNA and protein in a concentration-dependent manner, and antagonized the interferon-g-induced increase in OX40 and OX40L mRNA and protein levels. Mevalonate, but not GW9662, reversed the simvastatin-induced down-regulation of OX40 and OX40L expression, indicating that these effects were mediated through the mevalonate pathway. Serum levels of soluble OX40L and matrix metalloproteinase 9 levels were significantly reduced in patients with atherosclerotic cerebral infarction who were treated for 6 months with routine therapy plus simvastatin (n = 46) compared with patients receiving routine therapy alone (n = 30). These findings improve our understanding of the anti-inflammatory and immunomodulatory properties of simvastatin treatment for atherosclerotic disorders.