miR-101-loaded exosomes secreted by bone marrow mesenchymal stem cells requires the FBXW7/HIF1α/FOXP3 axis, facilitating osteogenic differentiation.

Exosomes derived from mesenchymal stem cells (MSCs) have emerged as significant mediators of intercellular communication, with studies highlighting their role in the transmission of biological signals between cells. Dominant microRNA (miRNA)-mediated translational repression of messenger RNAs has been extensively investigated in regard to its influence in orchestrating osteogenic differentiation. In the current study, we sought to ascertain the contributory role of miRNA-101 (miR-101) encapsulated in the process of bone marrow mesenchymal stem cell (BMSC)-derived exosomes in osteogenic differentiation. Exosomes were initially extracted from BMSCs at Days 0, 3, 12, and 21 of osteogenic differentiation by ultracentrifugation. Artificial modulation of miR-101 and FBXW7 (silencing and overexpression) were performed in the BMSCs to identify its effects on osteogenic factors, alkaline phosphatase activity, and osteogenic differentiation. Mechanistic exploration was performed to evaluate the binding affinity between miR-101 and FBXW7, the FBXW7-mediated HIF1α ubiquitination, and the HIF1α enrichment in the FOXP3 promoter region. Exosomes from MSCs in the late stage of osteogenic differentiation exhibited enhanced osteogenic differentiation. Upregulated miR-101 in MSC-derived exosomes was detected during osteogenic differentiation, while diminished levels of FBXW7 expression was noted. Importantly, miR-101 was found to specifically bind to the 3'-untranslated region of FBXW7. Meanwhile, data was obtained indicating that FBXW7 could ubiquitinate and degrade HIF1α to repress its upregulation during osteogenic differentiation. HIF1α bound to the promoter region of FOXP3 to facilitate osteogenic differentiation. Ultimately, the findings of the current study demonstrate that BMSC-derived exosomal miR-101 augments osteogenic differentiation in MSCs by inhibiting FBXW7 to regulate the HIF1α/FOXP3 axis.

Long non-coding RNA-H19 stimulates osteogenic differentiation of bone marrow mesenchymal stem cells via the microRNA-149/SDF-1 axis.

Bone defects resulting from non-union fractures or tumour resections are common clinical problems. Long non-coding RNAs (lncRNAs) are reported to play vital roles in stem cell differentiation. The aim of this study was to elucidate the role of lncRNA-H19 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Following the establishment of an osteogenic differentiation model in rats, the expression of H19, microRNA-149 (miR-149) and stromal cell-derived factor-1 (SDF-1) was measured by RT-qPCR. Thereafter, BMMSCs were isolated from rats and treated with a series of mimic, inhibitor or siRNA. SDF-1 expression, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content were detected. The mineralized and calcified nodules were assessed by alizarin red S and Von Kossa staining. BMMSC surface markers were detected by flow cytometry. Western blot analysis was used to measure the expression of ALP, OCN, runt-related transcription factor 2 (RUNX2) and osterix (OSX) proteins. Lastly, dual-luciferase reporter gene assay and RNA immunoprecipitation were applied to verify the relationship of H19, miR-149 and SDF-1. Overexpressed H19 and SDF-1 and poorly expressed miR-149 were found in rats with osteogenic differentiation. H19 increased SDF-1 expression by binding to miR-149. H19 enhanced ALP activity, OCN content, calcium deposit and ALP, OCN, RUNX2 and OSX protein expression of BMMSCS by up-regulating SDF-1 via binding to miR-149. Taken together, up-regulated H19 could promote the osteogenic differentiation of BMMSCs by increasing SDF-1 via miR-149.

Hypermethylation of microRNA-149 activates SDF-1/CXCR4 to promote osteogenic differentiation of mesenchymal stem cells.

MicroRNAs (miRs) involve in osteogenic differentiation and osteogenic potential of mesenchymal stem cells (MSCs). Accordingly, the present study aimed to further uncover role miR-149 plays in osteogenic differentiation of MSCs with the involvement of the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) pathway. Initially, the osteogenic differentiation model was induced. Next, the positive expression of STRO-1 in periosteum, alkaline phosphatase (ALP) activity, osteocalcin (OCN) protein content, and the calcium deposition in MSCs were determined. MSCs were treated with DNA methyltransferase inhibitor 5-aza-CdR, SDF-1 neutralizing antibody, or CXCR4 antagonist AMD3100 to investigate their roles in osteogenic differentiation; with the expression of CD44, CD90, CD14, and CD45 detected. Furthermore, the levels of SDF-1 and CXCR4, and the genes related to stemness (Nanog, Oct-4, and Sox-2) were measured to explore the effects of miR-149. The obtained data revealed the upregulation of STRO-1 in the periosteum. miR-149 could specifically bind to SDF-1. Besides, increased miR-149 methylation, higher ALP activity and OCN content, decreased positive rates of CD44 and CD90, and increased positive rates of CD14 and CD45 were found in osteogenic differentiation of MSCs. Subsequently, 5-Aza-CdR treatment reversed the above-mentioned effects. MSCs were finally treated with SDF-1 neutralizing antibody or AMD3100 to decrease Nanog, Oct-4, and Sox-2 expression. Taken together these results, miR-149 hypermethylation has the potential to activate the SDF-1/CXCR4 pathway and further promote osteogenic differentiation of MSCs.

GNAS knockdown suppresses osteogenic differentiation of mesenchymal stem cells via activation of Hippo signaling pathway.

Bone marrow-derived mesenchymal stem cells (BMSCs) are a suitable option for cell-based tissue engineering therapies due to their ability to renew and differentiate into multiple different tissue types, such as bone. Over the last decade, the effect of GNAS on the regulation of osteoblast differentiation has attracted great attention. Herein, this study aimed to explore the role of GNAS in osteogenic differentiation of MSCs. A total of 85 GNASf/f male mice were selected for animal experiments and 10 GNASf/f male mice for BMSC isolation to conduct cell experiments. The mice and BMSCs were treated with Verteporfin (a Hippo signaling pathway inhibitor) to inhibit the Hippo signaling pathway or recombinant adenovirus-expressing Cre to knockout the GNAS expression. Next, computed tomography scan, Von Kossa staining, and alizarin red staining were performed to detect osteogenic differentiation ability. Moreover, immunohistochemistry and alkaline phosphatase (ALP) staining were used to assess the expression of Oc and Osx in femur tissues and ALP activity. At last, the expression of GNAS, osteogenic markers, and factors related to the Hippo signaling pathway was evaluated. Initially, the results displayed successful knockout of the GNAS gene from mice and BMSCs. Moreover, the data indicated that GNAS knockout inhibits expression of Oc, Osx, ALP, BMP-2, and Runx2, and ALP activity. Additionally, GNAS knockout promotes activation of the Hippo signaling pathway, so as to repress osteogenic differentiation. Collectively, depleted GNAS exerts an inhibitory role in osteogenic differentiation of MSCs by activating Hippo signaling pathway, providing a candidate mediator for osteoporosis.

WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP-14 pathway.

WNT5A, a representative ligand of activating several non-canonical WNT signal pathways, plays significant roles in oncogenesis and tumor inhibition. It has been shown that the non-receptor tyrosine kinase SRC is required for WNT5A-induced invasion of osteosarcoma cells. However, the precise molecular mechanism underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined. The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2 signalings. We found that WNT5A (100 ng/mL) remarkably stimulated migration and invasion of human osteosarcoma MG-63 cells, whereas inhibiting either SRC kinase activity by siRNA-mediated SRC silence or ERK1/2 phosphorylation by PD98059 treatment suppressed these effects, which suggested that the activation of SRC and ERK1/2 is essential for WNT5A-induced MG-63 cells migration and invasion. Furthermore, ERK1/2 phosphorylation induced by WNT5A was dramatically blocked by SRC siRNA. Additionally, our study further demonstrated that MMP-14 was upregulated after exposure to WNT5A in MG-63 cells, and the increased expression was blocked by SRC siRNA or PD98059. Collectively, these results indicate that WNT5A activates SRC/ERK1/2 signal pathway, leading to the upregulation of MMP-14 expression and MG-63 cells migration and invasion.

Measurement of Atmospheric Dimethyl Sulfide with a Distributed Feedback Interband Cascade Laser.

This paper presents a mid-infrared dimethyl sulfide (CH3SCH3, DMS) sensor based on tunable laser absorption spectroscopy with a distributed feedback interband cascade laser to measure DMS in the atmosphere. Different from previous work, in which only DMS was tested and under pure nitrogen conditions, we measured DMS mixed by common air to establish the actual atmospheric measurement environment. Moreover, we used tunable laser absorption spectroscopy with spectral fitting to enable multi-species (i.e., DMS, CH4, and H2O) measurement simultaneously. Meanwhile, we used empirical mode decomposition and greatly reduced the interference of optical fringes and noise. The sensor performances were evaluated with atmospheric mixture in laboratory conditions. The sensor's measurement uncertainties of DMS, CH4, and H2O were as low as 80 ppb, 20 ppb, and 0.01% with an integration time 1 s, respectively. The sensor possessed a very low detection limit of 9.6 ppb with an integration time of 164 s for DMS, corresponding to an absorbance of 7.4 × 10-6, which showed a good anti-interference ability and stable performance after optical interference removal. We demonstrated that the sensor can be used for DMS measurement, as well as multi-species atmospheric measurements of DMS, H2O, and CH4 simultaneously.

Membership Function-Weighted Non-Linear Fitting Method for Optical-Sensing Modeling and Reconstruction.

Imprecise measurements present universally due to variability in the measurement error. We devised a very simple membership function to evaluate fuzzily the quality of optical sensing with a small dataset, where a normal distribution cannot be assumed. The proposed membership function was further used as a weighting function for non-linear curve fitting under expected mathematical model constraints, namely the membership function-weighted Levenberg⁻Marquardt (MFW-LM) algorithm. The robustness and effectiveness of the MFW-LM algorithm were demonstrated by an optical-sensing simulation and two practical applications. (1) In laser-absorption spectroscopy, molecular spectral line modeling was greatly improved by the method. The measurement uncertainty of temperature and pressure were reduced dramatically, by 53.3% and 43.5%, respectively, compared with the original method. (2) In imaging, a laser beam-profile reconstruction from heavy distorted observations was improved by the method. As the dynamic range of the infrared camera increased from 256 to 415, the detailed resolution of the laser-beam profiles increased by an amazing 360%, achieving high dynamic-range imaging to capture optical signal details. Therefore, the MFW-LM algorithm provides a robust and effective tool for fitting a proper physical model and precision parameters from low-quality data.

Pelargonidin induces antitumor effects in human osteosarcoma cells via autophagy induction, loss of mitochondrial membrane potential, G2/M cell cycle arrest and downregulation of PI3K/AKT signalling pathway.

PURPOSE: Osteosarcoma is the most common type of primary malignancy of bone in children and adults. The treatment options for osteosarcoma are limited and are associated with a number of drawbacks. Therefore there is an urgent need to look for more efficient options for the treatment of this disease. Flavonoids have been considered as important anticancer agents due to their efficacy and lower cytotoxicity. In the present study we evaluated the anticancer effects of pelargonidin in U2OS osteosarcoma cell line. METHODS: Cell viability was assessed by MTT assay. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and cell cycle analysis was done by flow cytometry. Expression of proteins was examined by western blotting. RESULTS: Pelargonidin exhibited significant anticancer effects on osteosarcoma U2OS cell line with an IC50 of 15 µM. The anticancer effects of pelargonidin were due to induction of autophagy as evidenced from the expression of LC3-I, LC-3II and Beclin-1. Moreover, pelargonidin triggered ROSinduced reduction in MMP and triggered G2/M cell cycle arrest. In addition, pelargonidin inhibited the expression of p-PI3K and p-AKT in a concentration-dependent manner. CONCLUSIONS: Taken together, these results indicated that pelargonidin may prove a potential lead drug for the treatment of osteosarcoma.

Long Noncoding RNA GAS5 Suppresses Cell Growth and Epithelial-Mesenchymal Transition in Osteosarcoma by Regulating the miR-221/ARHI Pathway.

Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The lncRNA growth arrest-specific 5 (GAS5) is reported to be a tumor suppressor in multiple cancers. However, the roles of GAS5 and its related miRNAs in osteosarcoma are poorly understood. This study explored the potential functions and mechanisms of GAS5 in the tumorigenesis of osteosarcoma. Here, the expression of GAS5, miR-221 and aplasia Ras homologue member I (ARHI) was determined in osteosarcoma tissues and cells by Real-time PCR (RT-qPCR). The underlying mechanism of GAS5 in osteosarcoma growth was analyzed via MTT, Transwell, RT-qPCR, Western blot, dual-luciferase reporter assay, RNA immunoprecipitation, and xenograft models after GAS5 overexpression. GAS5 and ARHI levels were significantly reduced, while miR-221 increased, both in osteosarcoma tissues and cells. Overexpression of GAS5 suppressed the proliferation, migration, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. GAS5 could directly bind to miR-221 to decrease miR-221 expression and enhance ARHI expression. The effect of GAS5 overexpression on the proliferation, migration and EMT was reversed by miR-221 mimics or ARHI siRNA in osteosarcoma cells. Additionally, GAS5 suppressed tumor volume, Ki-67 and PCNA staining, and EMT process in the development of osteosarcoma in vivo. Taken together, lncRNA GAS5 functions as a competing endogenous RNA for miR-221 to suppress cell growth and EMT in osteosarcoma by regulating the miR-221/ARHI pathway. J. Cell. Biochem. 118: 4772-4781, 2017. © 2017 Wiley Periodicals, Inc.

Zebularine enhances apoptosis of human osteosarcoma cells by suppressing methylation of ARHI.

ARHI is an imprinted tumor suppressor gene and its methylation suppresses ARHI transcription levels to cause the development and progression of malignant tumors. Zebularine exerts a demethylation function for tumor suppressor genes. Our study aims to investigate the effect and mechanism of action of zebularine on the epigenetic modification of the ARHI gene, and whether this effect may modulate the viability and apoptosis of human osteosarcoma cells. We found that zebularine inhibited the viability and promoted apoptosis in osteosarcoma cells. Zebularine potentiated the expression of ARHI at both the protein and mRNA level. This was related to the downregulation of methylation of ARHI caused by zebularine. Zebularine suppressed the interaction of DNA methyltransferase 1 (DNMT1) with histone methyltransferase G9a, but had no effect on G9a alone. Knockdown of DNMT1 or G9a can induce a reduction of ARHI methylation. Therefore, we inferred that zebularine was likely to directly repress DNMT1 alone, but G9a was necessary to regulate the function of DNMT1 on ARHI methylation. Moreover, knockdown of ARHI rescued cell viability and apoptosis under the zebularine-treated condition. We showed that zebularine inhibited viability and promoted apoptosis by disturbing the interaction between DNMT1 and G9a, thereby resulting in lower ARHI methylation and elevated ARHI expression in osteosarcoma cells.

Perineural dexamethasone does not enhance the analgesic efficacy of ultrasound-guided subcostal transversus abdominis plane block during laparoscopic cholecystectomy.

BACKGROUND: Ultrasound-guided transversus abdominis plane (TAP) block is an adjunct therapy to provide effective postoperative analgesia in abdominal surgical procedures. Dexamethasone is a supplement agent that can improve the efficacy of local anesthesia. However, information about its additive effect is limited. This study aimed to compare the analgesic efficiency using ultrasound-guided TAP block with and without perineural dexamethasone for patients who underwent laparoscopic cholecystectomy. METHODS: Sixty patients who underwent laparoscopic cholecystectomy were randomly divided into three groups: group I, controls; group II, TAP; and group III, TAP+perineural dexamethasone supplement. The requirement of additional analgesia and the first-time request of rescue-analgesia were recorded after operation and the numerical rating scale was evaluated at specific intervals. RESULTS: Compared to group I, the first-time requirement of rescue-analgesia in groups II and III was significantly delayed (403.0+/-230.9, 436.0+/-225.3 vs 152.3+/-124.7, P<0.01). Compared with those in group I, patients in groups II and III were associated with lower numerical rating scale pain scores (P<0.01) and less postoperative analgesic consumption (P<0.01). There was no significant difference in the variables mentioned above between groups II and III (P>0.05). CONCLUSION: Perineural dexamethasone has no additive/synergistic effect with subcostal TAP block on analgesic efficacy for the patients undergoing laparoscopic cholecystectomy.

Synergistic effects of galectin-1 and reactive astrocytes on functional recovery after contusive spinal cord injury.

INTRODUCTION: Galectin-1 (Gal-1), a carbohydrate-binding protein, is differentially expressed by various normal and pathological tissues and appears to be functionally polyvalent. Recent evidence indicates that Gal-1 is involved in the proliferation of adult neural progenitor cells in neurogenic regions during adulthood. However, localization and functional roles of Gal-1 in the adult spinal cord have not been clarified. METHOD: Here, we investigated the spatio-temporal profile of endogenous Gal-1 expression by in situ hybridization before and after experimental adult spinal cord injury and examined the correlation of Gal-1 with the fate of dividing cells in vivo, using double-labeling methods. Gal-1 mRNA was detectable at a relatively low level in uninjured spinal cord, but was markedly increased in the gray matter and/or white matter and in the ependyma rostral and caudal to the lesion site after injury. RESULTS: Co-localization results revealed that Gal-1 was expressed predominantly by GFAP-positive reactive astrocytes. In addition, intrathecal infusion of recombinant Gal-1 enhanced cell division and reactive astrocytosis in the adult spinal cord. To explore further whether Gal-1 and reactive astrocytes provide a synergistic effect on neurological recovery following SCI, we investigated the differences in behavioral analysis between wild-type (WT) and reactive astrocyte-deficient transgenic mice after injury and found neuroprotective effects of Gal-1 appeared to be specifically mediated through reactive astrocytes. CONCLUSION: These results indicate that Gal-1 exhibits great potential as a novel neuroprotective agent for the treatment of SCI.

MicroRNA-15b shuttled by bone marrow mesenchymal stem cell-derived extracellular vesicles binds to WWP1 and promotes osteogenic differentiation.

BACKGROUND: Osteogenic differentiation is an essential process for bone regeneration involving bone marrow mesenchymal stem cells (BMSCs). BMSC-secreted extracellular vesicles (EVs) enriched with microRNAs (miRs) have vital roles to play in mediating osteogenic differentiation. Therefore, this study aimed to explore the effect of BMSC-derived EVs loaded with miR-15b on osteogenic differentiation. METHODS: Human BMSCs (hBMSCs) were cultured and treated with plasmids overexpressing or knocking down KLF2, WWP1, and miR-15b to define the role of derived EVs in osteogenic differentiation in vitro. The expression of osteogenic differentiation-related marker was measured by Western blot analysis. The interaction among miR-15b, WWP1, and ubiquitination of KLF2 was investigated by dual-luciferase reporter, immunoprecipitation, and GST pull-down assays. Moreover, EVs from hBMSCs transfected with miR-15b inhibitor (EV-miR-15b inhibitor) were injected into ovariectomized rats to verify the effect of miR-15b on bone loss in vivo. RESULTS: WWP1 was downregulated, and KLF2 was upregulated during osteogenic differentiation. After co-culture with EVs, miR-15b expression was elevated and WWP1 expression was reduced in hBMSCs. Upregulation of miR-15b or KLF2 or downregulation of WWP1 or NF-κB increased ALP activity and cell mineralization, as well as osteogenic differentiation-related marker expression in hBMSCs. Mechanistically, miR-15b targeted and inhibited WWP1, thus attenuating KLF2 degradation and inhibiting NF-κB activity. Co-culture of EVs increased the bone volume and trabecular number, but decreased bone loss in ovariectomized rats, which could be reversed after treatment with EV-miR-15b inhibitor. CONCLUSION: Collectively, BMSC-derived EVs loaded with miR-15b promoted osteogenic differentiation by impairing WWP1-mediated KLF2 ubiquitination and inactivating the NF-κB signaling pathway.

X-ray exposure induces apoptosis of some proliferative epidermal cells following traumatic spinal cord injury in adult rats.

We investigated whether X-ray radiation induced apoptosis of the proliferative ependymal cells (ECs) in adult rats with spinal cord injury (SCI) and the effect of X-ray radiation on the proliferative activities of ECs. A rat model with SCI was developed and used to determine the proliferation and apoptosis of ECs in the spinal cords after X-ray exposure. TUNEL assay and BrdU incorporation were used to detect apoptosis and proliferation respectively. We found that there were few TUNEL-positive cells in proliferative ependymal zone (EZ) after SCI except at the epicenter, and approximately half of the irradiated ECs became TUNEL-positive. However, these radiated ECs did not lose their proliferative activity until 1 week later and started to decrease rapidly after 1 week. The observation suggested that only part of ECs were sensitive to radiation and the nonsensitive cells continued their mitosis process. These findings indicated that X-ray exposure of the rats with SCI in early stage induced apoptosis of the proliferative ECs and partially inhibited their proliferative activities.

Does Kinematic Alignment Improve Short-Term Functional Outcomes after Total Knee Arthroplasty Compared with Mechanical Alignment? A Systematic Review and Meta-analysis.

This meta-analysis was conducted to study whether kinematically aligned total knee arthroplasty (TKA) improves short-term functional outcomes compared with mechanical alignment without changing the hip-knee-ankle angle. Prospective cohort studies were searched from electronic literature databases, including PubMed, Web of Science, Embase (Ovid interface), and Cochrane Library (Ovid interface). Total 1,159 records were identified. Six trials involving 561 patients were eligible for data extraction and meta-analysis. The included studies recorded outcomes in the follow-up range from 6 to 34 months. Primary outcomes were to assess the functional outcomes in follow-up, and KA group achieved better performance on WOMAC score (mean difference [MD] = -18.82, 95% CI: -16.06 to -5.58), knee function score (MD = 7.23, 95% CI: 0.52-13.94), Oxford knee score (MD = 4.76, 95% CI: 0.40-9.12), and knee range of flexion (MD = 4.48, 95% CI: 2.09-6.86), whereas other parameters including Knee Society score, knee range of extension, VAS pain score, and the occurrence of the complications were without significant difference (p > 0.05). Second outcomes evaluated the perioperative clinic indexes. Our meta-analysis showed that KA group had a shorter time of operation (MD = -15.44, 95% CI: -27.47 to -3.71) and a longer walk distance before discharge (MD = 53.24, 95% CI: 21.32-85.15) when compared with the MA group, whereas the change in hemoglobin, incision length, knee range of flexion before discharge, and length of stays were without significant difference (p > 0.05). Third outcomes were used to analyze the alignment data. Our study showed that KA had larger angles of femoral component and mechanical axis of the femur (MD = -1.95,95% CI: -2.77 to -1.13), tibial component and mechanical axis of tibia (MD = 2.06, 95% CI: 1.43-2.70), anatomic knee angle (MD = -0.72, 95% CI: -1.33 to -0.11), and operative limb alignment (MD = -1.97, 95% CI: -2.50 to -1.45,) compared with the MA group, but the hip-knee-ankle angles between the two groups were similar. KA provided better functional outcomes and better flexion following short-term follow-up of TKA. However, longer-term follow-up and larger sample studies are needed to put into research in the future.

Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway.

Prostate cancer has become the most commonly diagnosed and the second leading cause of cancer-related deaths in males. The long noncoding RNA second chromosome locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in a subset of prostate cancer. However, the significance and mechanism of SChLAP1 in prostate cancer are not well known. In this study, we explored the role of SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1 expression was significantly increased in prostate cancer cells and tissues. Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and invasion in vitro and in vivo. In addition, a potential bonding site between miR-198 and SChLAP1 was predicted, and a low expression of miR-198 was found in prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased the expression of miR-198, and SChLAP1 overexpression markedly decreased it, indicating that SChLAP1 acted as a negative regulator in the expression of miR-198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and subsequently modulated the MAPK1 signaling pathway in prostate cancer. In conclusion, our study has identified a novel pathway through which SChLAP1 exerts its oncogenic role in prostate cancer at the level of miRNAs and provided a molecular basis for potential applications of SChLAP1 in the prognosis and treatment of prostate cancer.

Transplantation of copper-doped calcium polyphosphate scaffolds combined with copper (II) preconditioned bone marrow mesenchymal stem cells for bone defect repair.

Calcium polyphosphate is a bioactive ceramic that possesses similar mineral components to bone and possess good physicochemical properties. However, pure calcium polyphosphate scaffold is brittle, and it is insufficient in promoting vascularization and osteoinductivity. This study was conducted to assess whether copper (Cu) incorporated into calcium polyphosphate could improve the scaffolds' inherent shortcomings. In the experiments, Cu-calcium polyphosphate scaffolds' mechanical strength, biocompatibility, and biodegradability were researched primarily. And then, hypoxia-inducible factor 1-alpha expression along with angiogenesis and osteogenesis potential when the scaffolds treated with the bone marrow mesenchymal stem cells (BMMSCs) were analyzed in vitro. In in vivo studies, the Cu-calcium polyphosphate scaffolds combined with the liquid extract preconditioned BMMSCs were implanted into animal model to repair the bone defects. Meanwhile, we also evaluate the expression of angiogenic and osteogenic factors. For comparison, Cu-calcium polyphosphate, calcium polyphosphate, and blank control groups were designed. According to the results, proper content of Cu incorporated with calcium polyphosphate (0.1% Cu-calcium polyphosphate) did not significantly change the scaffold's degradation velocity, but it obtained higher compress mechanical strength and Cu-doped scaffolds were less brittle. Besides, these scaffolds incorporated with Cu showed better cytocompatibility and cell proliferation activity. Moreover, after Cu was doped, the hypoxia-inducible factor 1-alpha expression was up-regulated with the angiogenic and osteogenic factors levels increased both in in vitro and in vivo study. The bone defect healing capacity was accessed, using Cu-calcium polyphosphate combined with preconditioned BMMSCs further enhanced new bone formation and improved hypoxia-inducible factor 1-alpha, alkaline phosphatase, osteocalcin, and vascular endothelial growth factor expression. In conclusion, doped Cu into calcium polyphosphate was an alternative strategy for improving calcium polyphosphate's mechanical property and promoting the osteogenesis and angiogenesis potential. Using Cu-calcium polyphosphate scaffolds combined with Cu preconditioned BMMSCs to treat bone defect could enhance bone defect healing.

[Progress on diagnosis and treatment of the terrible triad of elbow joint].

The terrible triad of elbow is a kind of complex elbow fracture dislocation, after reduction, it should get a concentric circles joint reduction and elbow stability, if radial and coronoid process fractures is less piece, the conservative treatment can be performed, but regularly follow up is mandatory. If surgical treatment was chosen, radial head fractures and the lateral collateral ligament complex must be repaired. Single lateral approach can be used and also can be combined with anteromedial approach in surgery. Some problems are still controversial in the treatment of coronoid process fracture with Morry type I and type II, such as fixation or not, whether additional external fixation and repair of the medial collateral ligament injury at the same time.

Aplasia Ras homologue member â overexpression inhibits tumor growth and induces apoptosis through inhibition of PI3K/Akt survival pathways in human osteosarcoma MG-63 cells in culture.

Aplasia Ras homologue member Ⅰ (ARHI), an imprinted tumor-suppressor gene, is downregulated in various types of cancer. However, the expression, function and specific mechanisms of ARHI in human osteosarcoma (OS) cells remain unclear. The aim of the present study was to assess the effect of ARHI on OS cell proliferation and apoptosis and its associated mechanism. In the study, ARHI mRNA and protein levels were markedly downregulated in OS cells compared with the human osteoblast precursor cell line hFOB1.19. By generating stable transfectants, ARHI was overexpressed in OS cells that had low levels of ARHI. Overexpression of ARHI inhibited cell viability and proliferation and induced apoptosis. However, caspase­3 activity was not changed by ARHI overexpression. In addition, phosphorylated Akt protein expression decreased in the ARHI overexpression group compared to that in the control vector group. The knockdown of ARHI also resulted in the promotion of cell proliferation and the attenuation of apoptosis in MG­63 cells. Additionally, ARHI silencing increased the level of p­Akt. The present results indicate that ARHI inhibits OS cell proliferation and may have a key role in the development of OS.