Inhibition of pancreatic stellate cell activity by adipose-derived stem cells.

BACKGROUND: Pancreatic stellate cells (PSCs) play a critical role in the development of pancreatic fibrosis. In this study we used a novel method to isolate and culture rat PSCs and then investigated the inhibitory effects of adipose-derived stem cells (ADSCs) on activation and proliferation of PSCs. METHODS: Pancreatic tissue was obtained from Sprague-Dawley rats for PSCs isolation. Transwell cell cultures were adopted for co-culture of ADSCs and PSCs. PSCs proliferation and apoptosis were determined using CCK-8 and flow cytometry, respectively. alpha-SMA expressions were analyzed using Western blotting. The levels of cytokines [nerve growth factor (NGF), interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1)] in conditioned medium were detected by ELISA. Gene expression (MMP-2, MMP-9 and TIMP-1) was analyzed using qRT-PCR. RESULTS: This method produced 17.6+/-6.5X10(3) cells per gram of the body weight with a purity of 90%-95% and a viability of 92%-97%. Co-culture of PSCs with ADSCs significantly inhibited PSCs proliferation and induced PSCs apoptosis. Moreover, alpha-SMA expression was significantly reduced in PSCs+ADSCs compared with that in PSC-only cultures, while expression of fibrinolytic proteins (e.g., MMP-2 and MMP-9) was up-regulated and anti-fibrinolytic protein (TIMP-1) was down-regulated. In addition, NGF expression was up-regulated, but IL-10 and TGF-beta1 expressions were down-regulated in the co-culture conditioned medium compared with those in the PSC-only culture medium. CONCLUSIONS: This study provided an easy and reliable technique to isolate PSCs. The data demonstrated the inhibitory effects of ADSCs on the activation and proliferation of PSCs in vitro.

A Porphyrin-Based 3D Metal-Organic Framework Featuring [Cu8Cl6]10+ Cluster Secondary Building Units: Synthesis, Structure Elucidation, Anion Exchange, and Peroxidase-Like Activity.

Herein, we report a rare example of cationic three-dimensional (3D) metal-organic framework (MOF) of [Cu5Cl3(TMPP)]Cl5 ⋅ xSol (denoted as Cu-TMPP; H2TMPP=meso-tetrakis (6-methylpyridin-3-yl) porphyrin; xSol=encapsulated solvates) supported by [Cu8Cl6]10+ cluster secondary building units (SBUs) wherein the eight faces of the Cl--based octahedron are capped by eight Cu2+. Surface-area analysis indicated that Cu-TMPP features a mesoporous structure and its solvate-like Cl- counterions can be exchanged by BF4 -, PF6 -, and NO3 -. The polyvinylpyrrolidone (PVP) coated Cu-TMPP (denoted as Cu-TMPP-PVP) demonstrated good ROS generating ability, producing ⋅OH in the absence of light (peroxidase-like activity) and 1O2 on light irradiation (650 nm; 25 mW cm-2). This work highlights the potential of Cu-TMPP as a functional carrier of anionic guests such as drugs, for the combination therapy of cancer and other diseases.

Association of serum annexin A1 with treatment response and prognosis in patients with esophageal squamous cell carcinoma.

OBJECTIVE: Annexin A1 (ANXA1), a calcium-dependent phospholipid binding protein, is known to be regulated by microRNA-196a (miR-196a) in esophageal adenocarcinoma, and its high expression in tumor tissue is correlated with the poor prognosis of esophageal squamous cell carcinoma (ESCC). However, the role of ANXA1 in the serum of patients with ESCC remains unclear. MATERIALS AND METHODS: In this study, we used enzyme-linked immunosorbent assay to evaluate the levels of ANXA1 and real-time polymerase chain reaction to detect the expression of miR-196a in the serum of ESCC patients (healthy donors as controls) and evaluated the relationship between ANXA1 and clinical outcomes. RESULTS: The results showed that the level of serum ANXA1 in ESCC patients was significantly lower than that in controls (P = 0.001) but increased after chemoradiotherapy (P = 0.001). There was no correlation between the baseline level of serum ANXA1 and the short-term efficacy of treatment (P = 0.26) as well as the 1-year progression-free survival (PFS) (P = 0.094). However, there existed a significant correlation between the increases of serum ANXA1 expression and the 1-year PFS (P = 0.04). A higher increase (>2-fold of baseline) in the serum ANXA1 levels was correlated with a poorer PFS (hazard ratio = 3.096, 95% confidence interval 1.239-7.861). There was an inverse correlation between the expressions of miR-196a and ANXA1 in serum (Pearson's correlation of -0.54, P = 0.021). CONCLUSION: Our data revealed that the expression of serum ANXA1 in ESCC patients increases after chemoradiotherapy and the increased fold change in serum ANXA1 confers independent negative prognostic impact in ESCC. The higher the increase in serum ANXA1 levels, the poorer the outcome.