Human adipose stem cells were cultured in smooth muscle inductive media and seeded into synthetic bladder composites to tissue engineer bladder smooth muscle. 85:15 poly-lactic-glycolic acid bladder dome composites were cast using an electropulled microfiber luminal surface combined with an outer porous sponge. Cell seeded bladders expressed smooth muscle actin, myosin heavy chain, calponinin, and caldesmon via RT-PCR and immunoflourescence. Nude rats (n=45) underwent removal of half their bladder and repair using: (i) augmentation with the adipose stem cell seeded composites, (ii) augmentation with a matched acellular composite, or (iii) suture closure. Animals were followed for 12 weeks post-implantation and bladders were explanted serially. Results showed that bladder capacity and compliance were maintained in the cell seeded group throughout the 12 weeks, but deteriorated in the acellular scaffold group sequentially with time. Control animals repaired with sutures regained their baseline bladder capacities by week 12, demonstrating a long term limitation of this model. Histological analysis of explanted materials demonstrated viable adipose stem cells and increasing smooth muscle mass in the cell seeded scaffolds with time. Tissue bath stimulation demonstrated smooth muscle contraction of the seeded implants but not the acellular implants after 12 weeks in vivo. Our study demonstrates the feasibility and short term physical properties of bladder tissue engineered from adipose stem cells.

Five-year survival rate of esophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is <20%. Our study aimed to investigate whether cancer-associated fibroblasts (CAFs), one major component of tumor microenvironment, were involved in tumor radioresistance in ESCC. By use of human chemokine/cytokine array, human chemokine CXCL1 was found to be highly expressed in CAFs compared with that in matched normal fibroblasts. Inhibition of CXCL1 expression in CAFs significantly reversed CAF-conferred radioresistance in vitro and in vivo. CAF-secreted CXCL1 inhibited the expression of reactive oxygen species (ROS)-scavenging enzyme superoxide dismutase 1, leading to increased ROS accumulation following radiation, by which DNA damage repair was enhanced and the radioresistance was mediated. CAF-secreted CXCL1 mediated the radioresistance also by activation of Mek/Erk pathway. The cross talk of CAFs and ESCC cells induced CXCL1 expression in an autocrine/paracrine signaling loop, which further enhanced tumor radioresistance. Together, our study highlighted CAF-secreted CXCL1 as an attractive target to reverse tumor radioresistance and can be used as an independent prognostic factor of ESCC patients treated with chemoradiotherapy.

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Trimethyltin chloride (TMT) has been known as a classic neurotoxicant which can cause serious neuronal degeneration diseases. Nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways play pivotal role in the central nerves system. In the present study, the intracellular pathways involved in TMT-induced apoptosis on human neuroblastoma cells SY5Y (SH-SY5Y) were investigated. We observed high level of nuclear NF-κB p65 submit, activated JNK, ERK, and p38 by TMT exposure. In contrast, low level of Bcl-2 and XIAP (two known NF-κB-regulated endogenous anti-apoptotic molecules) was present. To further investigate the role of these pathways and the relationship between them, specific inhibitors were used and the alteration of each pathway was evaluated. Pretreatment with MG132, an inhibitor of proteasome activity, and BAY11-7082, an inhibitor of IκBα phosphorylation, both inhibited NF-κB p65 translocation and significantly promoted apoptosis. NF-κB inhibition also induced down-expression of Bcl-2 and XIAP, exaggerated JNK phosphorylation, and ERK inhibition. SP600125 and U0126, by blocking the phosphorylation of c-Jun and MEK1/2, inhibited JNK and ERK phosphorylation, respectively, and attenuated apoptosis significantly. JNK and ERK inhibition also induced IκBα degradation and NF-κB p65 translocation, leading to expression of Bcl-2 and XIAP. The detrimental role of MG132 and BAY11-7082 appears related to the exaggerated JNK phosphorylation. The SP600125 and U0126 neuroprotection appears related to NF-κB-regulated transcriptional control of Bcl-2 and XIAP. These results suggest that the cross-talk and a balance between NF-κB and MAPKs may be involved in TMT-induced apoptosis on SH-SY5Y cells.

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This study presents a recurrent wavelet-based neuro-fuzzy network with dynamic symbiotic evolution (RWNFN-DSE) for dynamic system processing. The proposed RWNFN-DSE model combines the traditional Takagi-Sugeno-Kang (TSK) fuzzy model and the wavelet neural networks (WNN). This study adopts the non-orthogonal and compactly supported functions as wavelet neural network bases. Temporal relations embedded in the network are caused by adding some feedback connections representing the memory units into the second layer. A novel evolution learning called dynamic symbiotic evolution (DSE) is used to tune the parameter of the RWNFN-DSE model. The better chromosomes will be initially generated while the better mutation points will be determined for performing dynamic-mutation. Simulation results have shown that the proposed RWNFN-DSE model obtain better performance than other existing models.

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