No abstract

BackgroundDespite accumulating evidence that long noncoding RNAs (lncRNAs) are associated with cancer development in multiple types of cancer, the biological roles of many lncRNAs in human hepatocellular carcinoma (HCC) metastasis have not been well characterized.MethodsA lncRNA+ mRNA human gene expression microarray analysis was used to identify differentially expressed lncRNAs in metastatic HCC tissues compared to non-metastatic tissue.ResultsWe observed remarkable overexpression of HOXD-AS1 in metastatic cancer tissues. In vitro and in vivo gain- or loss-of-function studies re-affirmed that HOXD-AS1 is able to facilitate cancer metastasis and inhibit apoptosis. Moreover, we identified that HOXD-AS1 upregulated the Rho GTPase activating protein 11A (ARHGAP11A) by competitively binding to microRNA-19a (miR19a), resulting in induced metastasis. Interestingly, the regulator of G-protein signaling 3 (RGS3), a potential inhibitor of the MEK-ERK1/2 signaling axis, was also found to be downregulated by ectopic HOXD-AS1 overexpression, leading to a remarkably reduced apoptotic effect.ConclusionsThe present investigation strongly indicates that HOXD-AS1 is an oncogenic lncRNA that promotes HCC metastasis and that its pro-metastatic phenotype can partially be attributed to the HOXD-AS1/miR19a/ARHGAP11A signaling axis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12943-017-0676-x) contains supplementary material, which is available to authorized users.

Collectively, our results demonstrated for the first time that CB2R plays a protective role in EAE through promoting autophagy and inhibiting NLRP3 inflammasome activation.

BackgroundSpinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology.ResultsRNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group). Compared with the sham-control group, the number of differentially expressed genes was 1797 in the acute phase (1223 upregulated and 574 downregulated), 6590 in the subacute phase (3460 upregulated and 3130 downregulated), and 3499 in the chronic phase (1866 upregulated and 1633 downregulated), with an adjusted P-value <0.05 by DESeq. Gene ontology (GO) enrichment analysis showed that differentially expressed genes were most enriched in immune response, MHC protein complex, antigen processing and presentation, translation-related genes, structural constituent of ribosome, ion gated channel activity, small GTPase mediated signal transduction and cytokine and/or chemokine activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most enriched pathways included ribosome, antigen processing and presentation, retrograde endocannabinoid signaling, axon guidance, dopaminergic synapses, glutamatergic synapses, GABAergic synapses, TNF, HIF-1, Toll-like receptor, NF-kappa B, NOD-like receptor, cAMP, calcium, oxytocin, Rap1, B cell receptor and chemokine signaling pathway.ConclusionsThis study has not only characterized changes in global gene expression through various stages of SCI progression in rats, but has also systematically identified the critical genes and signaling pathways in SCI pathology. These results will expand our understanding of the complex molecular mechanisms involved in SCI and provide a foundation for future studies of spinal cord tissue damage and repair.The sequence data from this study have been deposited into Sequence Read Archive (http://www.ncbi.nlm.nih.gov/sra; accession number PRJNA318311).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3532-x) contains supplementary material, which is available to authorized users.

Local activated macrophages derived from infiltrating monocytes play an important role in the damage and repair process of spinal cord injury (SCI). The present study investigates the dynamic change of classically activated proinflammatory (M1) and alternatively activated anti-inflammatory (M2) cells in a rat model with contusive SCI by flow cytometry (FCM) and immunohistochemistry. The macrophage subsets were immunophenotyped by using antibodies against cluster of differentiation (CD)-68, C-C chemokine receptor type 7 (CCR7), CD163, and arginase 1 (Arg1). The CD68(+) CD163(-) and CD68(+) CCR7(+) cells were determined to be M1 subsets, whereas the CD68(+) CD163(+) and CD68(+) Arg1(+) cell subpopulations represented M2 cells. The subsets of macrophages in the injured spinal cord at 1, 3, 5, 7, 14, and 28 days postinjury (dpi) were examined. In the sham-opened spinal cord, few M1 or M2 cells were found. After SCI, the phenotypes of both M1 and M2 cells were rapidly induced. However, M1 cells were detected and maintained at a high level for up to 28 dpi (the longest time evaluated in this study). In contrast, M2 cells were transiently detected at high levels before 7 dpi and returned to preinjury levels at 14 dpi. These results indicate that M1 cell response is rapidly induced and sustained, whereas M2 induction is transient after SCI in rat. Increasing the fraction of M2 cells and prolonging their residence time in the injured local microenvironment is a promising strategy for the repair of SCI.

Neural stem cell (NSC) transplantation is a major focus of current research for treatment of spinal cord injury (SCI). However, it is very important to promote the survival and differentiation of NSCs into myelinating oligodendrocytes (OLs). In this study, myelin basic protein-activated T (MBP-T) cells were passively immunized to improve the SCI microenvironment. Olig2-overexpressing NSCs were infected with a lentivirus carrying the enhanced green fluorescent protein (GFP) reporter gene to generate Olig2-GFP-NSCs that were transplanted into the injured site to differentiate into OLs. Transferred MBP-T cells infiltrated the injured spinal cord, produced neurotrophic factors, and induced the differentiation of resident microglia and/or infiltrating blood monocytes into an "alternatively activated" anti-inflammatory macrophage phenotype by producing interleukin-13. As a result, the survival of transplanted NSCs increased fivefold in MBP-T cell-transferred rats compared with that of the vehicle-treated control. In addition, the differentiation of MBP-positive OLs increased 12-fold in Olig2-GFP-NSC-transplanted rats compared with that of GFP-NSC-transplanted controls. In the MBP-T cell and Olig2-GFP-NSC combined group, the number of OL-remyelinated axons significantly increased compared with those of all other groups. However, a significant decrease in spinal cord lesion volume and an increase in spared myelin and behavioral recovery were observed in Olig2-NSC-and NSC-transplanted MBP-T cell groups. Collectively, these results suggest that MBP-T cell adoptive immunotherapy combined with NSC transplantation has a synergistic effect on histological and behavioral improvement after traumatic SCI. Although Olig2 overexpression enhances OL differentiation and myelination, the effect on functional recovery may be surpassed by MBP-T cells.

Objective To develop a new method to restore hip rotation center exactly and rapidly in total hip arthroplasty (THA) with the assistance of three dimensional (3D) printing technology and evaluate its clinical and radiological outcomes. Methods From March 2014 to July 2018, a total of 17 patients (five hips of four men and 16 hips of 13 women) with end‐stage osteoarthritis secondary to developmental dysplasia of the hip who underwent THA were analyzed and followed up retrospectively. The average age is 58.00 ± 8.12 years (range from 45 to 71 years). Simulated operations were performed on 3D printed hip models for preoperative planning. The morphology of Harris fossa and acetabular notches were recognized and restored to locate the acetabular center. The size of bone defect was measured by the bone wax method. The agreement on the size of acetabular cup and bone defect between simulated operations and actual operations were analyzed. Harris Hip Score (HHS) was used to evaluate the recovery of hip joint function. The vertical distance and horizontal distance of the rotation center on the pelvis plain radiograph were measured, which were used to assess the efficacy of restoring hip rotation center and acetabular cup migration. Results The mean sizes of bone defect in simulated operations and THA were 4.58 ± 2.47 cm2 and 4.55 ± 2.57 cm2 respectively. There was no significant difference statistically between the sizes of bone defect in simulated operations and the actual sizes of bone defect in THA (t = 0.03, P = 0.97). The sizes of the acetabular cup of simulated operations on 3D print models showed a high rate of coincidence with the actual sizes in the operations (ICC = 0.93). All 17 patients were available for clinical and radiological follow‐up. The average follow‐up time was 18.35 ± 6.86 months (range, 12–36 months. The average HHS of the patients was improved from (38.33 ± 6.07) preoperatively to the last follow‐up (88.61 ± 3.44) postoperatively. The mean vertical and horizontal distances of hip rotation center on the pelvic radiographs were restored to 15.12 ± 1.25 mm and 32.49 ± 2.83 mm respectively. No case presented dislocation or radiological signs of loosening until last follow‐up. Conclusions The application of 3D printing technology facilitates orthopedists to recognize the morphology of Harris fossa and acetabular notches, locate the acetabular center and restore the hip rotation center rapidly and accurately.

PurposeTo restore rotation center exactly in total hip arthroplasty (THA) is technically challenging for patients with end-stage osteoarthritis due to developmental dysplasia of the hip (DDH). The technical difficulty is attributable to the complex acetabular changes. In this study, we investigated the pathomorphology of acetabulum and Harris fossa of Crowe types I to IV and discussed the method of restoring rotation center of the hip.MethodsThis study retrospectively reviewed 56 patients (59 hips) who underwent cementless THA due to end-stage osteoarthritis of DDH. The pathomorphology of acetabulum and Harris fossa was observed during operations. Using the preoperative and postoperative pelvic radiographs, the vertical and the horizontal distances of hip rotation center were measured in order to evaluate the effects of restoring rotation center of the hip.ResultsAdult DDH acetabulum could be classified into four basic pathological types which include the shallow cup shape, the dish shape, the shell shape, and the triangular shape. Adult DDH Harris fossa could be classified into four pathological types, including the crack shape, the closed shape, the triangle shape, and the shallow shape, in accordance with the osteophyte coverage. The vertical and horizontal distances of hip rotation center on the pelvic radiographs before and after operations were as follows: the preoperative vertical distance of hip rotation center was (39.96 ± 5.65) mm, and the postoperative one was (13.83 ± 2.66) mm; the preoperative horizontal distance of hip rotation center was (42.15 ± 6.42) mm, and the postoperative one was (28.12 ± 4.56) mm.ConclusionsThe acetabulum and Harris fossa can display different pathological types on account of different degrees of dislocation and osteophyte hyperplasia in the end-stage osteoarthritis of adult DDH. The hip rotation center can be accurately restored by locating the acetabular center with Harris fossa and acetabular notch as the marks.