The role of Th17 cells in endocrine organs: Involvement of the gut, adipose tissue, liver and bone

T Helper 17 (Th17) cells are adaptive immune cells that play myriad roles in the body. Immune–endocrine interactions are vital in endocrine organs during pathological states. Th17 cells are known to take part in multiple autoimmune diseases over the years. Current evidence has moved from minimal to substantial that Th17 cells are closely related to endocrine organs. Diverse tissue Th17 cells have been discovered within endocrine organs, including gut, adipose tissue, liver and bone, and these cells are modulated by various secretions from endocrine organs. Th17 cells in these endocrine organs are key players in the process of an array of metabolic disorders and inflammatory conditions, including obesity, insulin resistance, nonalcoholic fatty liver disease (NAFLD), primary sclerosing cholangitis (PSC), osteoporosis and inflammatory bowel disease (IBD). We reviewed the pathogenetic or protective functions played by Th17 cells in various endocrine tissues and identified potential regulators for plasticity of it. Furthermore, we discussed the roles of Th17 cells in crosstalk of gut-organs axis

Context-Aware Block Net for Small Object Detection.

State-of-the-art object detectors usually progressively downsample the input image until it is represented by small feature maps, which loses the spatial information and compromises the representation of small objects. In this article, we propose a context-aware block net (CAB Net) to improve small object detection by building high-resolution and strong semantic feature maps. To internally enhance the representation capacity of feature maps with high spatial resolution, we delicately design the context-aware block (CAB). CAB exploits pyramidal dilated convolutions to incorporate multilevel contextual information without losing the original resolution of feature maps. Then, we assemble CAB to the end of the truncated backbone network (e.g., VGG16) with a relatively small downsampling factor (e.g., 8) and cast off all following layers. CAB Net can capture both basic visual patterns as well as semantical information of small objects, thus improving the performance of small object detection. Experiments conducted on the benchmark Tsinghua-Tencent 100K and the Airport dataset show that CAB Net outperforms other top-performing detectors by a large margin while keeping real-time speed, which demonstrates the effectiveness of CAB Net for small object detection

Allogeneic Mesenchymal Stem Cell Therapy for Bisphosphonate-Related Jaw Osteonecrosis in Swine

Bisphosphonates (BPs), which are used to treat a variety of clinical disorders, have the side effect of jawbone necrosis. Currently, there is no reliable treatment for BP-related osteonecrosis of the jaw (BRONJ) due to a lack of understanding of its pathogenesis. To investigate the pathogenesis of BRONJ and observe the treatment effect of bone marrow mesenchymal stem cell (BMMSC) transplantation, we established a preclinical animal model of BRONJ in miniature pigs (minipigs). After treatment with zoledronic acid, the clinical and radiographic manifestations of BRONJ could be observed in minipigs after first premolar extraction. The biological and immunological properties of BMMSCs were impaired in the BP-treated minipigs. Moreover, the ratio of Foxp3-positive regulatory T-cells (Tregs) in peripheral blood decreased, and interleukin (IL)-17 increased in the serum of BP-treated minipigs. After allogeneic BMMSC transplantation via intravenous infusion, mucosal healing and bone reconstruction were observed; IL-17 levels were reduced; and Tregs were elevated. In summary, we established a clinically relevant BRONJ model in minipigs and tested a promising allogeneic BMMSC-based therapy, which may have potential clinical applications for treating BRONJ. © Copyright 2013, Mary Ann Liebert, Inc. 2013

PDCD6 is an independent predictor of progression free survival in epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Programmed cell death 6 (PDCD6) beside its known proapoptotic functions may be a player in survival pathways in cancer. The purpose of this study is to further explore the roles of PDCD6 in epithelial ovarian cancer.</p> <p>Methods</p> <p>Lentiviral vector with shRNA for PDCD6 was used to investigate the effects of PDCD6 knockdown on cell growth, cell cycle, apoptosis and motility in ovarian cancer cells. Two hundred twelve epithelial ovarian cancer tissues were analyzed for mRNA expression of <it>PDCD6 </it>using RT-PCR. Associations of its expression with clinical pathological factors, progression free and overall survival were evaluated.</p> <p>Results</p> <p>PDCD6 is highly expressed in metastatic ovarian cancer cells and positively regulates cell migration and invasion. Significantly, the level of <it>PDCD6 </it>expression in epithelial ovarian cancer correlates with clinical progression. Patients with medium or high levels of <it>PDCD6 </it>mRNA were at higher risk for disease progression, compared to those with low levels (HR, 1.29; <it>P </it>= 0.024 for medium levels; and HR, 1.57; <it>P </it>= 0.045 for high levels) after adjusting for age, disease stage, tumor grade, histologic type and residual tumor size. Kaplan-Meier survival analysis demonstrated similar results. However, no association was found between <it>PDCD6 </it>expression and overall survival.</p> <p>Conclusions</p> <p>PDCD6 seems to play an important role in ovarian cancer progression and it may be an independent predictor of progression free survival in epithelial ovarian cancer. Further studies are needed to more completely elucidate the molecular mechanisms of PDCD6 involve in ovarian cancer progression.</p

Templated-Construction of Hollow MoS2 Architectures with Improved Photoresponses

: Despite the outstanding optoelectronic properties of MoS2 and its analogues, synthesis of such materials with desired features including fewer layers, arbitrary hollow structures, and particularly specifically customized morphologies, via inorganic reactions has always been challenging. Herein, using predesigned lanthanide-doped upconversion luminescent materials (e.g., NaYF4:Ln) as templates, arbitrary MoS2 hollow structures with precisely defined morphologies, widely variable dimensions, and very small shell thickness (≈2.5&nbsp;nm) are readily constructed. Most importantly, integration of the near-infrared-responsive template significantly improves the photoresponse of up to 600 fold in device made of NaYF4:Yb/Er@MoS2 compared with that of MoS2 nanosheets under 980&nbsp;nm laser illumination. Multichannel optoelectronic device is further fabricated by simply changing luminescent ions in the template, e.g., NaYF4:Er@MoS2, operating at 1532&nbsp;nm light excitation with a 276-fold photoresponse enhancement. The simple chemistry, easy operation, high reliability, variable morphologies, and wide universality represent the most important advantages of this novel strategy that has not been accessed before

Oncogenic state and cell identity combinatorially dictate the susceptibility of cells within glioma development hierarchy to IGF1R targeting

Glioblastoma is the most malignant cancer in the brain and currently incurable. It is urgent to identify effective targets for this lethal disease. Inhibition of such targets should suppress the growth of cancer cells and, ideally also precancerous cells for early prevention, but minimally affect their normal counterparts. Using genetic mouse models with neural stem cells (NSCs) or oligodendrocyte precursor cells (OPCs) as the cells‐of‐origin/mutation, it is shown that the susceptibility of cells within the development hierarchy of glioma to the knockout of insulin‐like growth factor I receptor (IGF1R) is determined not only by their oncogenic states, but also by their cell identities/states. Knockout of IGF1R selectively disrupts the growth of mutant and transformed, but not normal OPCs, or NSCs. The desirable outcome of IGF1R knockout on cell growth requires the mutant cells to commit to the OPC identity regardless of its development hierarchical status. At the molecular level, oncogenic mutations reprogram the cellular network of OPCs and force them to depend more on IGF1R for their growth. A new‐generation brain‐penetrable, orally available IGF1R inhibitor harnessing tumor OPCs in the brain is also developed. The findings reveal the cellular window of IGF1R targeting and establish IGF1R as an effective target for the prevention and treatment of glioblastoma

Human IL-17 and TNF-α Additively or Synergistically Regulate the Expression of Proinflammatory Genes, Coagulation-Related Genes, and Tight Junction Genes in Porcine Aortic Endothelial Cells

Immune rejection is the major limitation for porcine xenograft survival in primate recipients. Proinflammatory cytokines play important roles in immune rejection and have been found to mediate the pathological effects in various clinical and experimental transplantation trials. IL-17 and TNF-α play critical pathological roles in immune disorders, such as psoriasis and rheumatoid arthritis. However, the pathological roles of human IL-17 (hIL-17) and human TNF-α (hTNF-α) in xenotransplantation remain unclear. Here we found that hIL-17 and hTNF-α additively or synergistically regulate the expression of 697 genes in porcine aortic endothelial cells (PAECs). Overall, 415 genes were found to be synergistically regulated, while 282 genes were found to be additively regulated. Among these, 315 genes were upregulated and 382 genes were downregulated in PAECs. Furthermore, we found that hIL-17 and hTNF-α additively or synergistically induced the expression of various proinflammatory cytokines and chemokines (e.g., IL1α, IL6, and CXCL8) and decreased the expression of certain anti-inflammatory genes (e.g., IL10). Moreover, hIL-17 plus hTNF-α increased the expression of IL1R1 and IL6ST, receptors for IL1 and IL6, respectively, and decreased anti-inflammatory gene receptor expression (IL10R). hIL-17 and hTNF-α synergistically or additively induced CXCL8 and CCL2 expression and consequently promoted primary human neutrophil and human leukemia monocytic cell migration, respectively. In addition, hIL-17 and hTNF-α induced pro-coagulation gene (SERPINB2 and F3) expression and decreased anti-coagulation gene (TFPI, THBS1, and THBD) expression. Additionally, hIL-17 and hTNF-α synergistically decreased occludin expression and consequently promoted human antibody-mediated complement-dependent cytotoxicity. Interestingly, hTNF-α increased swine leukocyte antigen (SLA) class I expression; however, hIL-17 decreased TNF-α-mediated SLA-I upregulation. We concluded that hIL-17 and hTNF-α likely promote the inflammatory response, coagulation cascade, and xenoantibody-mediated cell injury. Thus, blockade of hIL-17 and hTNF-α together might be beneficial for xenograft survival in recipients