Black phosphorus, an advanced versatile nanoparticles of antitumor, antibacterial and bone regeneration for OS therapy.

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

Finite element analysis of the effect of tibial osteotomy on the stress of polyethylene liner in total knee arthroplasty.

AIM: To explore the effects of tibial osteotomy varus angle combined with posterior tibial slope (PTS) on the stress of polyethylene liner in total knee arthroplasty (TKA) by building finite element model (FEM). METHODS: Established the FEM of standard TKA with tibial osteotomy varus angle 0° to 9° were established and divided into 10 groups. Next, each group was created 10 FEMs with 0° to 9° PTS separately. Calculated the stress on polyethylene liner in each group in Abaqus. Finally, the relevancy between tibial osteotomy angle and polyethylene liner stress was statistically analyzed using multiple regression analysis. RESULTS: As the varus angle increased, the area of maximum stress gradually shifted medially on the polyethylene liner. As the PTS increases, the percentage of surface contact forces on the medial and lateral compartmental of the polyethylene liner gradually converge to the same. When the varus angle is between 0° and 3°, the maximum stress of the medial compartmental surfaces of polyethylene liner rises smoothly with the increase of the PTS. When the varus angle is between 4° and 9°, as the increase of the PTS, the maximum stress of polyethylene liner rises first and then falls, forming a trough at PTS 5° and then rises again. Compared to the PTS, the varus angle has a large effect on the maximum stress of the polyethylene liner (p < .001). CONCLUSION: When the varus angle is 0° to 3°, PTS 0° is recommended, which will result in a more equalized stress distribution of the polyethylene liner in TKA.

Collagen-Based Hydrogels for Cartilage Regeneration.

Cartilage regeneration remains difficult due to a lack of blood vessels. Degradation of the extracellular matrix (ECM) causes cartilage defects, and the ECM provides the natural environment and nutrition for cartilage regeneration. Until now, collagen hydrogels are considered to be excellent material for cartilage regeneration due to the similar structure to ECM and good biocompatibility. However, collagen hydrogels also have several drawbacks, such as low mechanical strength, limited ability to induce stem cell differentiation, and rapid degradation. Thus, there is a demanding need to optimize collagen hydrogels for cartilage regeneration. In this review, we will first briefly introduce the structure of articular cartilage and cartilage defect classification and collagen, then provide an overview of the progress made in research on collagen hydrogels with chondrocytes or stem cells, comprehensively expound the research progress and clinical applications of collagen-based hydrogels that integrate inorganic or organic materials, and finally present challenges for further clinical translation.

PRP coating on different modified surfaces promoting the osteointegration of polyetheretherketone implant.

Introduction: Polyetheretherketone (PEEK) material implants have been applied more and more clinically recently. In order to increase the osteogenic activity of PEEK material, the microstructure change of the material surface and the construction of functional microcoatings have become a hot research topic. This study investigated the ability of PEEK surfaces modified by different methods to carry Platelet-rich plasma (PRP) and the osteogenic ability of different PEEK microstructures after carrying PRP in vivo/in vitro. Methods: In this study, PEEK surfaces were modified by sulfuric acid, gaseous sulfur trioxide and sandpaper. Next, PRP from SD rats was prepared and incubated on PEEK material with different surface microstructures. Lactate dehydrogenase test, scanning electron microscope and Elisa assay was used to evaluate adhesion efficiency of PRP. Then in vitro tests such as CCK-8, ALP staining, ARS staining and RT-qPCR et al were used to further evaluate osteogenesis ability of the PRP coating on PEEK surface. Finally, The tibia defects of SD rats were established, and the new bone was evaluated by Micro-CT, HE staining, and immunofluorescence staining. Results: The sandpaper-polished PEEK with the strongest PRP carrying capacity showed the best osteogenesis. Our study found that the modified PEEK surface with PRP coating has excellent osteogenic ability and provided the basis for the interface selection of PRP for the further application of PEEK materials. Discussion: Among the three PEEK modified surfaces, due to the most PRP carrying and the strongest osteogenic ability in vitro/vivo, the frosted surface was considered to be the most suitable surface for the preparation of PRP coating.

High-speed three-dimensional shape measurement based on tripartite complementary Gray-coded light.

In phase-shifting profilometry based on the Gray code, the jump error is inevitably generated and is further amplified in dynamic scenes. To tackle this problem, we propose the robust tripartite complementary Gray code method (TCG). Without projecting additional patterns, TCG uses different combinations of Gray code to calculate three complementary orders able to avoid jump error in the unwrapping process. TCG is efficient and robust, as it fully utilizes the redundant information of the Gray code. Experimental results demonstrate that TCG can realize high-efficiency and high-speed three-dimensional shape measurement at a rate of 500 fps.

Efficacy and safety of glibenclamide therapy after intracerebral haemorrhage (GATE-ICH): A multicentre, prospective, randomised, controlled, open-label, blinded-endpoint, phase 2 clinical trial.

Background: Glibenclamide is a promising agent for treating brain oedema, but whether it improves clinical outcomes in patients with intracerebral haemorrhage (ICH) remains unclear. In this study, we aimed to explore the efficacy and safety of glibenclamide treatment in patients with acute ICH. Methods: The Glibenclamide Advantage in Treating Oedema after Intracerebral Haemorrhage (GATE-ICH) study was a randomised controlled phase 2 clinical trial conducted in 26 hospitals in the northwest of China, recruiting patients with acute ganglia ICH no more than 72 h after onset from Dec 12, 2018 to Sept 23, 2020. During the first 7 days after enrolment, patients randomly assigned to the glibenclamide group were given glibenclamide orally (1.25 mg, 3/day) and standard care, while patients randomly assigned to the control group were given standard care alone. The computer-generated randomisation sequence was prepared by a statistician not involved in the rest of the study. Randomisation was computer-generated with a block size of four. The allocation results were unblinded to participants and investigators. The primary outcome was the percentage of patients with poor outcome (defined as modified Rankin Scale [mRS] score of ≥3) at day 90. The trial was registered at ClinicalTrials.gov (NCT03741530). Findings: 220 participants were randomised and 200 participants (mean [standard deviation] age, 56 [11] years; sex, 128 [64.0%] male and 72 [36.0%] female) were included in the final analysis, with 101 participants randomly assigned to the control group and 99 to the glibenclamide group. The incidence of poor outcome at day 90 was 20/99 (20.2%) in glibenclamide group and 30/101 (29.7%) in control group (absolute difference, 9.5%; 95% confidence interval [CI], -3.2%-21.8%; P = 0.121) with adjusted odds ratios of 0.54 (95% CI, 0.24-1.20; P = 0.129). No significant difference was found in the overall rates of adverse events or serious adverse events between groups. However, the incidence of asymptomatic hypoglycaemia was significantly higher in glibenclamide group than control group (15/99 [15.2%] vs 0/101 [0.0%]; absolute difference, 15.2%; 95% CI, 7.5%-24.1%; P < 0.001). Interpretation: Our study provides no evidence that glibenclamide (1.25 mg, 3/day) significantly reduces the proportion of poor outcome at day 90 after ICH. In addition, glibenclamide could result in higher incidence of hypoglycaemia. Larger trials of glibenclamide with optimised medication regimen are warranted. Funding: Shaanxi Province Key Research and Development Project (2017DCXL-SF-02-02) and Shaanxi Province Special Support Program for Leading Talents in Scientific and Technological Innovation (tzjhjw).

POLR2A blocks osteoclastic bone resorption and protects against osteoporosis by interacting with CREB1.

Bone-resorbing osteoclasts significantly contribute to osteoporosis, and understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss. Here, we report that POLR2A is upregulated during osteoclastogenesis. Functional analyses showed that the inhibition of POLR2A decreased osteoclastogenesis, whereas the overexpression of POLR2A had completely opposite effects in vitro. Notably, the osteoclast-specific deletion of POLR2A blocks bone resorption in vivo. Furthermore, POLR2A loss-of-function suppresses estrogen deficiency-induced bone resorption. Mechanistically, POLR2A regulates the assembly of CREB1 on the regulatory elements of its target genes. Collectively, using genetic, pharmacological, and disease mouse models, we have identified a previously undescribed protein that interacts with CREB1 to regulate osteoclastic bone resorption.

Study on the effect of extra capsular arthroscopy plus analgesic tincture in the treatment of external humeral epicondylitis.

External humeral epicondylitis (EHE) is an inflammation and pain of the lateral tendons of the elbow with poor clinical efficacy. In this study, we aim to observe the effect of extra capsular arthroscopy (ECA) plus Traditional Chinese medicine (TCM) analgesic tincture in the treatment of EHE. A retrospective analysis was performed on the follow-up data of 58 patients with intractable EHE treated by ECA plus TCM analgesic tincture over 2 years from January 2017 to October 2018. All patients were followed up during the operation, with a mean follow-up duration of 17.6 months. There were no complications such as infection, nerve injury, wound nonunion and joint stiffness. The postoperative and pronation angles were statistically different from preoperative. The visual analogue scale (VAS) score during rest and movement of the elbow joint after operation was significantly different from that before operation. Postoperative Mayo elbow joint function score was significantly different from preoperative. Postoperative elbow joint function and brachial and shoulder dysfunction scores were statistically significant compared with those before surgery. Postoperative elbow joint function and brachial and shoulder dysfunction scores were statistically significant compared with those before surgery. The satisfaction rate of patients was 100%, with 52 cases of completely satisfied, 6 cases of basically satisfied and no dissatisfied cases. The curative effect of external capsular arthroscopy plus analgesic tincture in the treatment of external humeral epicondylitis was promising, which was worthy of clinical promotion.

[Long-term outcomes of Chiari osteotomy for Legg-Calvé-Perthes disease in children].

OBJECTIVE: To explore long-term outcomes of Chiari osteotomy for Legg-Calvé-Perthes disease in children with type Catterall III or IV, and to analyze clinical effect of osteotomy angle on clinical and radiographic results. METHODS: From March 2005 to July 2013, 26 children with Legg-Calvé-Perthes disease with type Catterall III or IV were treated by Chiari osteotomy, including 17 males and 9 females, aged from 4 to 13 years old with an average of (8.9±2.6) years old. Children were divided into low osteotomy angle group and high osteotomy angle group. according to osteotomy angle. There were 10 children in low osteotomy angle group with an osteotomy angle of 10 degrees, including 8 boys and 2 girls, aged from 4 to 13 years old with an average of (9.2±3.3) years old; while there were 16 children in high osteotomy angle group with an osteotomy angle of 15 degress, including 9 boys and 7 girls, aged from 6 to 12 years old with an average of (8.8±2.1) years old. HHS score before operation and at the latest follow-up were recorded to observe clinical results. CE angle of hip joint, acetabular index, Sharp angle, Shenton's line continuity, femoral head coverage, acetabular depth ratio were recorded to compare radiographic results. Stulberg classification was analyzed to compare reshaping ability of femoral head. RESULTS: Twenty-six children were followed up for 4.5 to 12.0 years with an average of (7.9±1.8) years. All incisions were healed at stage I for 10 to 14 days, with an average of(12.3±1.1) days. No inflammation, skin necrosis and injury of vessel and nerve occurred. All osteotomies achieved bone union for 8 to 13 weeks, with an average of(9.8±1.4) weeks. HHS score increased from 75.8±6.5 before operation to 93.5±2.5 at the latest follow-up in low osteotomy angle group(P<0.05), and form 77.6±6.2 to 97.8±1.6 in high osteotomy angle group (P<0.05). HHS score of high osteotomy angle group at the latest follow-up was higher than that of low osteotomy angle group (P<0.05). The acetabular index decreased from (10.1±2.5)° before operation to (4.5±1.3)° at the latest follow-up in low osteotomy angle group (P<0.05), and from (10.7±3.3)° before operation to (2.0±1.1)° in high osteotomy angle group (P<0.05). The acetabular index of high osteotomy angle group at the latest followup was better than low osteotomy angle group(P<0.05). There was no significant difference in CE angle, Sharp angle, Shenton's continuity, femoral head coverage, acetabular depth ratio between two groups. According to Stulberg classification, the femoral head reshaping ability in high osteotomy angle group was better than that of low osteotomy angle group(P<0.05). CONCLUSIONS: Chiari osteotomy with 15° for Legg-Calvé-Perthes disease in children with type Catterall III or IV could effectively decrease index of acetabulum, and helpful for femoral head reshaping ability, then in further improve clinical effects.

[Phase I total hip replacement for severe hip osteoarthritis with proximal femoral fractures].

OBJECTIVE: To investigate the effect and prognosis of stage I total hip replacement in the treatment of severe hip osteoarthritis with proximal femoral fracture. METHODS: From July 2014 to October 2017, 8 patients with severe end-stage hip disease and proximal femoral fracture were treated with stage I total hip replacement including 6 males and 2 females, aged 59 to 72 years old with an average age of 65 years old, involving 4 femoral head necrosis with proximal femoral fracture in the right side, 3 femoral head necrosis with proximal femoral fracture in the left side, and 1 left acetabular dysplasia with proximal femoral fracture in the left side. The average time from injury to operation was 7 days. Eight patients were treated with biologically elongated hip prosthesis. RESULTS: Eight patients with stage I total hip arthroplasty were followed up for 12 to 48 months with an average of 31 months. During the follow-up period, there was no loosening or subsidence of the prosthesis. Harris score increased from 33 points (22 to 42 points) preoperatively to 87 points(82 to 90 points) at the last follow-up. Among them, 3 cases were excellent and 5 cases were good. Abandoned abduction and walked 3 months after operation. X-ray films during 3-6 months after operation showed that fracture healing was good, hip pain and function were improved significantly, and the quality of life was greatly improved. CONCLUSIONS: Phase I total hip arthroplasty for severe hip osteoarthritis patients with proximal femoral fracture has the advantages of shortening the treatment time, alleviating patients'pain, reducing hospitalization costs and good prognosis.

MicroRNA-495 enhances chondrocyte apoptosis, senescence and promotes the progression of osteoarthritis by targeting AKT1.

Osteoarthritis (OA) is a common multifactorial degenerative articular disease among the aging population. The current investigation aimed to elucidate the function of microRNA-495 (miR-495) in the development of OA. We found that miR-495 was upregulated in the cartilage of OA patients. Transfection of a miR-495 mimic into rat primary chondrocytes, human chondrocytes (HC) and SW1353 chondrosarcoma cells inhibited AKT1 expression, proliferation and scratch wound closure and induced apoptosis. Transfection of a miR-495 inhibitor produced an opposite effect. Furthermore, the production of cartilage degeneration-related substances was modified by miR-495. Luciferase reporter gene assay revealed that AKT1 is directly repressed by miR-495. Moreover, the levels of AKT1, p-S6 and p-mTOR diminished in chondrocytes overexpressing miR-495. AKT1 overexpression amplified p-S6 and p-mTOR levels as well as abolished miR-495 mimic-induced apoptosis and inhibition of proliferation. In the surgically induced rat OA model, apoptosis of chondrocytes and cartilage degeneration were remedied by the administration of a miR-495 antagomir. Moreover, there was an increased expression of AKT1. These findings indicate that miR-495 induces OA by targeting AKT1 and regulating the AKT/mTOR pathway. Therefore, miR-495 may be a prospective target for OA treatment.

Long non-coding RNA Irm enhances myogenic differentiation by interacting with MEF2D.

Recent studies suggest important roles for long non-coding RNAs as essential regulators of myogenic differentiation. Here, we report that lncRNA Irm is upregulated during myogenesis. Functional analyses show that the overexpression of Irm enhances myogenic differentiation, whereas the inhibition of Irm has completely opposite effects in vitro. Notably, the inhibition of Irm blocks damage-induced muscle regeneration in vivo. Mechanistically, Irm regulates the expression of myogenic genes by directly binding to MEF2D, which in turn promotes the assembly of MyoD/MEF2D on the regulatory elements of target genes. Collectively, we have identified a novel lncRNA that interacts with MEF2D to regulate myogenesis.

Long non-coding RNA GClnc1 promotes tumorigenesis in osteosarcoma by inhibiting p53 signaling.

Recent studies suggest important roles for long noncoding RNAs as essential regulators of human cancer. GClnc1 was found to be upregulated in gastric cancer, playing oncogenic roles. However, the biological function and underlying mechanism of GClnc1 in osteosarcoma (OS) remain unclear. Here, we report that GClnc1 is upregulated in OS tissues and its high expression predicts poor prognosis of patients. Functional analyses show that overexpression of GClnc1 promotes OS cells growth; whereas knockdown of GClnc1 has completely opposite effects. Consistently, overexpression of GClnc1 promotes tumorigenicity of OS cells in vivo. Mechanistically, GClnc1 directly binds to p53 and blocks the binding of p53 to acetyltransferase p300, and thereby suppresses acetylation of p53, leading to the reduced expression of p21 and BAX. This study shed light on the oncogene role of lncRNA GClnc1, a new modulator of p53 signaling, in OS.

The effect of PLGA-based hydrogel scaffold for improving the drug maximum-tolerated dose for in situ osteosarcoma treatment.

Although hydrogel-based therapeutic agents have shown great potential for localized cancer treatments, the maximum tolerated dose (MTD) of these methods remains uncertain. To confirm this, doxorubicin (DOX) loaded PLGA-PEG-PLGA hydrogel was employed to investigate the MTD of DOX for localized osteosarcoma treatment. This hydrogel showed good injectable and biodegradable properties in vivo. And the drug remaining time was also obviously prolonged in the tumor site. Different doses of DOX (5.0, 15, 30 mg/kg) with/without hydrogel were adopted to the treatment of tumor-bearing mice. Despite both localized administrations of 5.0 mg/kg DOX showing no obvious systemic toxicity, this dose failed to control the persistent growth of tumors or prolong the survival time in comparison with the control groups. Localized administration of 30 mg/kg DOX showed a high efficacy for suppressing tumor growth, but exhibited obvious body weight losing at the same time. Correspondingly, the DOX-loaded hydrogel with the dose of 15 mg/kg achieved significantly improved anti-tumor efficacy and prolonged mean survival time compared with both the free DOX (15 mg/kg) and other control groups. Furthermore, during the whole therapeutic process, the mice showed no obvious body weight loss, major organs damage or death in this group. The MTD of DOX-loaded agent based on the PLGA-PEG-PLGA hydrogel gave a 2-fold increase compared to the MTD of free DOX (7.5 mg/kg, intravenous injection) for the mouse without significant systemic toxicity.

Saikosaponin A inhibits IL-1ß-induced inflammatory mediators in human osteoarthritis chondrocytes by activating LXRα.

Saikosaponin a (SSa), one of the main active components of Bupleurum falcatum, has been reported to have anti-inflammatory effect. In the present study, we investigated the anti-inflammatory effect of SSa on IL-1ß-stimulated human osteoarthritis chondrocytes. The cells were pretreated with SSa 12 h before IL-1ß treatment. The production of PGE2 and NO were detected by ELISA and Griess method. The levels of MMP1, MMP3, and MMP13 were measured by ELISA and qRT-PCR. The expression of NF-κB and LXRα were tested by western blot analysis. The results showed that SSa inhibited IL-1ß-induced PGE2 and NO production in a concentration-dependent manner. SSa also suppressed IL-1ß-induced MMP1, MMP3, and MMP13 production. Furthermore, SSa significantly attenuated IL-1ß-induced phosphorylation levels of NF-κB p65 and IκBα. SSa also up-regulated the expression of LXRα. The inhibition of SSa on PGE2, NO, MMP1, MMP3, and MMP13 production were reversed by LXRα siRNA or GGPP, the inhibitor of LXRα. In conclusion, our results demonstrated that SSa inhibited inflammatory responses in human chondrocytes in vitro. SSa might be a potential therapeutic drug for osteoarthritis.

Biomechanical comparison of xenogeneic bone material treated with different methods.

Bone xenografting is considered one of the most effective ways to address the shortage of bone autografts and allografts. Various methods have been employed to minimize the immune rejection issues associated with bone xenografts. However, the side effects of such methods on bone biomechanical properties remain unclear. As such, the objective of this study was to compare the influence of different treatments on the biomechanical properties of porcine bones. Fresh pig ribs were cut into 1.5 × 0.5 × 0.4 cm specimens, which were randomly divided into four groups and subjected to different modification regimes: group A by degreasing and partial deproteinization, group B by cryopreservation, group C by cryopreservation and enzyme digestion, and group D was a control group using fresh bone. Biomechanical tests and α-Gal antigen detection were performed for all groups. In the axial compression test, the values for maximum load were as follows: group D > group C > group B > group A. The maximum load in group A was significantly less than in the other groups (P < .05). There were no differences between groups D, C, and B in terms of the maximum stress and elastic modulus (P > .05). The maximum stress and elastic modulus values recorded for group A were significantly less than for the other groups (P < .05). There were no significant differences in the maximum load or elastic modulus among groups B, C, and D, in the three-point bending test (P > .05). However, the maximum load and elastic modulus values recorded for group A were significantly lower than the other groups (P < .05). In groups A and C, no α-Gal antigen-positive expression was detected. In group B, there was low level α-Gal antigen-positive expression, while a high level of α-Gal antigen-positive expression was observed in fresh bone samples. The results indicated that xenogeneic bone subjected to degreasing and partial deproteinization had the worst biomechanical properties. Cryopreservation and cryopreservation with enzyme digestion had little effect on the bone biomechanical properties, although enzyme digestion resulted in the complete elimination of the α-Gal antigen. Cryopreservation with enzyme digestion treatment presented the best results in terms of removing the immune-response triggering α-Gal antigen, while preserving the good biomechanical properties of bone xenografts.

BMP-2 immobilized PLGA/hydroxyapatite fibrous scaffold via polydopamine stimulates osteoblast growth.

Combining biomaterials scaffolds with bone morphogenetic protein-2 (BMP-2) is currently used to promote the regeneration of bone tissue. However, the traditional strategies used to add BMP-2 into the polymer scaffolds directly suffer from limitations that can result in lower growth factor loading and damage the bioactivity of growth factors. In this study, we report the fabrication of poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) composite fibrous scaffolds via melt-spinning method to mimic native extracellular matrix (ECM). In order to effectively immobilize BMP-2 on PLGA/HA composite fibrous scaffolds, the surface of the scaffold was modified with polydopamine (PDA) (PDA-PLGA/HA). PDA was chosen as an adhesive polymeric bridge-layer between PLGA/HA fibrous scaffolds and BMP-2. Analysis of the scaffold using scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscope revealed that the PDA coating was attached to the scaffold surface. Moreover, analysis of the scaffold using water contact angle demonstrated an increased hydrophilicity via PDA modification. Furthermore, the PDA coating effectively immobilized BMP-2 on the PDA-PLGA/HA fibrous scaffold and a sustained release profile of BMP-2 was achieved in the BMP-2-immobilized PLGA/HA fibrous scaffold. In vitro experiments showed that BMP-2-immobilized PLGA/HA fibrous scaffold significantly promoted the attachment and proliferation of MC3T3-E1 cells. More importantly, the ALP activity, mRNA expression of osteosis-related genes and calcium deposition in MC3T3-E1 cells cultured on BMP-2-immobilized PLGA/HA fibrous scaffold were significantly increased. These results collectively demonstrate that the BMP-2-immobilized PLGA/HA fibrous scaffold is a promising candidate for bone regeneration.

TAZ overexpression is associated with epithelial-mesenchymal transition in cisplatin-resistant gastric cancer cells.

Gastric cancer is one of the common malignant diseases. The poor treatment outcome is mainly due to chemotherapeutic resistance. Therefore, it is important to determine the molecular mechanism of drug resistance in gastric cancer. To explore the mechanisms of cisplatin resistance in gastric cancer cells, several approaches were performed including MTT assay, real-time RT-PCR, western blot analysis, migration and invasion assays, wound healing assay, and transfection. We found that cisplatin-resistant (CR) gastric cancer cells acquired epithelial-mesenchymal transition (EMT) phenotype. The CR cells with EMT features obtained higher migratory and invasive activities. Moreover, we observed that TAZ was highly expressed in CR cells. Consistently, depletion of TAZ caused partial reversal of EMT to MET in CR cells. Our results suggest that TAZ plays a pivotal role in CR-induced EMT. Targeting TAZ could be a potential therapeutic strategy for gastric cancer.

[Repairing diabetic rats with bone defect by VEGF165 gene modified adipose-derived stem cells].

OBJECTIVE: To explore repairing results of VEGF165 gene modified adipose-derived stem cells for diabetic rats with bone defect. METHODS: Seventy-eight male Wistar rats weighted 180 to 220 g were selected, 72 rats were established diabetic animal models by streptozotocin inducement method, blood glucose level was more than 16.7 mmol/L. Experimental animals were randomly divided into 5 groups, 6 rats in normal group and each 18 rats in other groups. VEGF165 gene modified adipose-derived stem cells were implanted into normal group with bone defect; single diabetic rats with bone defect were named as diabetic group;vascular endothelial growth factor implanted into single diabetic rats with bone defect named as growth factor group; adipose-derived stem cells implanted into diabetic rats with bone defect names as stem cell group; VEGF165 gene modified adipose-derived stem cells implanted diabetic rats with bone defect named as experimental group. After combination of VEGF165-ADSCs (5×106) cells combined with gel sponge, implanted into diabetic rats with bone defect. On the forth week, general form of defect repairing tissue were observed by optical microscopy;local density of micro-vessel were detected by immunohistochemistry method; content of Ca, P and ALP of repairing callus were detected by IRIS Intrepid XSP inductively coupled plasma emission spectrometer. Efficacy of the VEGF165-ADSCs repairing function was evaluated by SPSS statistic software. RESULTS: Fluorescent staining results showed that expression of VEGF165 located on cytoplasm of ADSCs, expression percentage was more than 87%; general histology results showed that callus formation and quality was near to normal group, repairing results in diabetes group, growth factor group and stem cell group were poor. On the Forth week after implantation, content of Ca, P and ALP of repairing callus in experimental group were higher than those in growth group and stem cell group, and without significant differences compared with normal group; blood vessel density in experimental group was lower than normal group, but higher than other groups. CONCLUSIONS: VEGF165 gene modified adipose-derived stem cells for repairing diabetic rats with bone defect has advantages of osteogenesis and angiogenesis, and should be one of the effective method for repairing diabetic rats with bone defect.