Xuzhou Medical College

About: Xuzhou Medical College is a education organization based out in Xuzhou, China. It is known for research contribution in the topics: Cancer & Cell growth. The organization has 12721 authors who have published 7802 publications receiving 102970 citations.

Extracellular signal-regulated kinase and c-Jun N-terminal protein kinase in ischemic tolerance.

Abstract: The alterations and involvement of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK) activation were examined in the hippocampal CA1 region in a rat model of global brain ischemic tolerance. Western blotting study showed that ERK activation (diphosphorylation) level was decreased (3.75-, 0.56-, and 0.23-fold vs sham control) and JNK activation level was increased (3.82-, 4.63-, and 5.30-fold vs sham control) 3 days after more severe ischemic insults (6 min, 8 min, and 10 min of ischemia, respectively). These alterations were significantly prevented by pretreatment with preconditioning ischemia, which also provided neuronal protection against ischemic injury. Inhibition of ERK activation after preconditioning ischemia by PD98059, a specific ERK kinase inhibitor, significantly prevented the inhibitory effects of preconditioning ischemia on both JNK activation and ischemic injury. The results suggest that ERK activation after preconditioning ischemia may result in the prevention of JNK activation and thus be involved in the protective responses in ischemic tolerance in hippocampal CA1 region.

Robust graph regularized unsupervised feature selection

Abstract: Recent research indicates the critical importance of preserving local geometric structure of data in unsupervised feature selection (UFS), and the well studied graph Laplacian is usually deployed to capture this property. By using a squared l2-norm, we observe that conventional graph Laplacian is sensitive to noisy data, leading to unsatisfying data processing performance. To address this issue, we propose a unified UFS framework via feature self-representation and robust graph regularization, with the aim at reducing the sensitivity to outliers from the following two aspects: i) an l2, 1-norm is used to characterize the feature representation residual matrix; and ii) an l1-norm based graph Laplacian regularization term is adopted to preserve the local geometric structure of data. By this way, the proposed framework is able to reduce the effect of noisy data on feature selection. Furthermore, the proposed l1-norm based graph Laplacian is readily extendible, which can be easily integrated into other UFS methods and machine learning tasks with local geometrical structure of data being preserved. As demonstrated on ten challenging benchmark data sets, our algorithm significantly and consistently outperforms state-of-the-art UFS methods in the literature, suggesting the effectiveness of the proposed UFS framework.

Injectable polypeptide hydrogel-based co-delivery of vaccine and immune checkpoint inhibitors improves tumor immunotherapy.

Abstract: Immunotherapy, an attractive option for cancer treatment, necessitates the direct stimulation of immune cells in vivo and the simultaneous effective inhibition of immunosuppressive tumor microenvironments. Methods: In the present study, we developed an injectable PEG-b-poly(L-alanine) hydrogel for co-delivery of a tumor vaccine and dual immune checkpoint inhibitors to increase tumor immunotherapy efficacy. Tumor cell lysates, granulocyte-macrophage colony stimulating factor (GM-CSF), and immune checkpoint inhibitors (anti-CTLA-4/PD-1 antibody) were readily encapsulated in the porous hydrogel during the spontaneous self-assembly of polypeptide in aqueous solution. Results: Sustained release of tumor antigens and GM-CSF persistently recruited and activated dendritic cells (DCs) and induced a strong T-cell response in vivo, which was further enhanced by the immune checkpoint therapy. The hydrogel vaccine also upregulated the production of IgG and the secretion of cytokines including IFN-γ, IL-4, and TNF-α. Importantly, the hydrogel-based combination therapy had superior immunotherapy effects against melanoma and 4T-1 tumor in comparison with the vaccine alone or in addition with a single immune checkpoint blockade. In studying the underlying mechanism, we found that the hydrogel-based combinatorial immunotherapy not only significantly increased the activated effector CD8+ T cells within the spleens and tumors of vaccinated mice, but also reduced the ratio of Tregs. Conclusion: Our findings indicate that the polypeptide hydrogel can be used as an effective sustained delivery platform for vaccines and immune checkpoint inhibitors, providing an advanced combinatorial immunotherapy approach for cancer treatment.

MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5

Abstract: MicroRNA-106a-5p (MiR-106a-5p), a small non-coding RNA, has been reported to be downregulated in astrocytoma, osteosarcoma and colorectal cancer. However, the expression levels and biological function in renal cell carcinoma (RCC) have not been studied yet. In this study, we found that the miR-106a-5p was significantly downregulated in RCC tissues and cell lines, and that overexpression of miR-106a-5p led to decreased cell metastasis ability in a xenograft model. Inhibition of miR-106a-5p in RCC cell lines altered the cell migration, invasion and wound healing abilities. Mechanistic studies demonstrated that miR-106a-5p directly bound to the 3'-UTR of the PAK5 mRNA and mediated a decrease in the protein expression of PAK5. We further proved that PAK5 protein levels were negatively correlated with the miR-106a-5p expression in both patient samples and xenograft model. In epigenetics, methylation specific PCR experiments indicated that the upstream gene promoter of miR-106a-5p was hypermethylated in RCC, which might be responsible for its downregulation. Our findings suggested that miR-106a-5p might be a potential gene therapy target for the treatment of RCC metastasis.

The transcription factor PU.1 promotes alternative macrophage polarization and asthmatic airway inflammation

Abstract: The transcription factor PU.1 is involved in regulation of macrophage differentiation and maturation. However, the role of PU.1 in alternatively activated macrophage (AAM) and asthmatic inflammation has yet been investigated. Here we report that PU.1 serves as a critical regulator of AAM polarization and promotes the pathological progress of asthmatic airway inflammation. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, conditional PU.1-deficient (PU/ER(T)(+/-)) mice displayed attenuated allergic airway inflammation, including decreased alveolar eosinophil infiltration and reduced production of IgE, which were associated with decreased mucous glands and goblet cell hyperplasia. The reduced asthmatic inflammation in PU/ER(T)(+/-) mice was restored by adoptive transfer of IL-4-induced wild-type (WT) macrophages. Moreover, after treating PU/ER(T)(+/-) mice with tamoxifen to rescue PU.1 function, the allergic asthmatic inflammation was significantly restored. In vitro studies demonstrate that treatment of PU.1-deficient macrophages with IL-4 attenuated the expression of chitinase 3-like 3 (Ym-1) and resistin-like molecule alpha 1 (Fizz-1), two specific markers of AAM polarization. In addition, PU.1 expression in macrophages was inducible in response to IL-4 challenge, which was associated with phosphorylation of signal transducer and activator of transcription 6 (STAT6). Furthermore, DRA challenge in sensitized mice almost abrogated gene expression of Ym-1 and Fizz-1 in lung tissues of PU/ER(T)(+/-) mice compared with WT mice. These data, all together, indicate that PU.1 plays a critical role in AAM polarization and asthmatic inflammation.