Hua Chen

Piperine inhibits LPS induced expression of inflammatory mediators in RAW 264.7 cells

The aim of the present study was to investigate the effects of piperine on the inflammatory responses to lipopolysaccharide (LPS) in RAW264.7 cells and the signal transduction pathways involved. RAW264.7 cells were pretreated with piperine at 10, 50 or 100 μg/ml and subsequently stimulated with LPS (1 μg/ml) for 24 h. We found that piperine inhibited the production of prostaglandin E2 (PGE2) and nitric oxide (NO) induced by LPS. Piperine significantly decreased LPS-stimulated gene expression and production of tumor necrosis factor-alpha (TNF), inducible NO synthase (iNOS) and COX-2 in RAW264.7 cells. Piperine inhibited the LPS-mediated activation of nuclear factor-kappa B (NF-kappaB) by suppressing the degradation of inhibitor-κB proteins (IκB) and the translocations of p65 subunit of NF-kB from the cytosol to the nucleus. Our results demonstrate the anti-inflammatory activity of piperine in RAW264.7 cells; suggesting that piperine may be a potential agent in the treatment of inflammation.

Silibinin promotes osteoblast differentiation of human bone marrow stromal cells via bone morphogenetic protein signaling

Silibinin is the major active constituent of the natural compound silymarin; several studies suggest that silibinin possesses antihepatotoxic properties and anticancer effects against carcinoma cells. However, no study has yet investigated the effect of silibinin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). The aim of this study was to evaluate the effect of silibinin on osteogenic differentiation of hBMSCs. In this study, the hBMSCs were cultured in an osteogenic medium with 0, 1, 10 or 20 μmol/l silibinin respectively. hBMSCs viability was analyzed by cell number quantification assay and cells osteogenic differentiation was evaluated by alkaline phosphatas (ALP) activity assay, Von Kossa staining and real time-polymerase chain reaction (RT-PCR). We found that silibinin promoted ALP activity in hBMSCs without affecting their proliferation. The mineralization of hBMSCs was enhanced by treatment with silibinin. Silibinin also increased the mRNA expressions of Collagen type I (COL-I), ALP, Osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and Runt-related transcription factor 2 (RUNX2). The BMP antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated silibinin-promoted ALP activity. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by silibinin treatment. These results indicate that silibinin enhances osteoblast differentiation probably by inducing the expressions of BMPs and activating BMP and RUNX2 pathways. Thus, silibinin may play an important therapeutic role in osteoporosis patients by improving osteogenic differentiation of BMSCs.

Myricetin enhances osteogenic differentiation through the activation of canonical Wnt/β-catenin signaling in human bone marrow stromal cells.

Myricetina flavonoid compound, has been reported to possess antioxidative, antiproliferative and anti-inflammatory effects. However, no study has yet investigated the effect of myricetin on osteogenic differentiation of human bone marrow stem cells (hBMSCs). This study was designed to investigate the effects of myricetin on osteogenic differentiation of hBMSCs in vitro. Cell viability was analyzed by MTT and osteogenic differentiation was evaluated by alkaline phosphatase (ALP) activity assay, Alizarin red S dye, real time-polymerase chain reaction (RT-PCR) and Western blot analysis. We found that the ALP activity and the mineralization of hBMSCs were enhanced by treatment with myricetin. Myricetin increased the mRNA expressions of Osteocalcin (OCN), Collagen type I (COL-I), ALP and Runt-related transcription factor 2 (RUNX2). Additionally, we found that myricetin activated the Wnt/β-catenin pathway and increased the expression of several downstream genes including T-cell factor-1(TCF-1) and lymphoid enhancer factor-1 (LEF-1). Depletion of β-catenin almost completely blocked the positive role of myricetin on osteogenic differentiation. Taken together, our findings suggest that myricetin enhanced osteogenic differentiation of hBMSCs by activating the Wnt/β-catenin signaling. The study may aid in the development of a therapeutic approach utilizing myricetin for the enhancement of bone health and prevention of osteoporosis.

The protective effects of silibinin in the treatment of streptozotocin-induced diabetic osteoporosis in rats

Diabetic osteoporosis (DO) is a complication of diabetes mellitus. Our previous study showed that silibinin can attenuate high glucose mediated human bone marrow stem cells dysfunction through antioxidant effect. However, no study has yet investigated the effect of silibinin in diabetic rats. Therefore, we assessed the effects of silibinin on bone characteristics in streptozotocin-induced diabetic rats. The aim of our study was to determine whether providing silibinin in the different supplementation could prevent bone loss in diabetic rats or not. Rats were randomly divided into four groups: (1) control group (CG) (n=10); (2) diabetic group (DG) (n=10); (3) diabetic group with 50mgkg-1day-1 of silibinin orally (DG-50) (n=10); and (4) diabetic group with 100mgkg-1day-1 of silibinin orally (DG-100) (n=10). 12 weeks after streptozotocin (STZ) injection, the femora from all rats were assessed and oxidative stress was evaluated. Bone mineral density was significantly decreased in diabetic rats; these effects were prevented by treatment with silibinin (100mgkg-1day-1 orally). Similarly, in the DG and DG-50 groups, changes in microarchitecture of femoral metaphysis assessed by microcomputed tomography demonstrated simultaneous existence of diabetic osteoporosis; these impairments were prevented by silibinin (100mgkg-1day-1 orally). In conclusion, silibinin supplementation may have potential use as a possible therapy for maintaining skeletal health and these results can enhance the understanding of diabetic osteoporosis induced by diabetes.

Phosphoserine promotes osteogenic differentiation of human adipose stromal cells through bone morphogenetic protein signalling

Phosphoserine has potential effectiveness as a simple substrate in preparing bone replacement materials, which could enhance bone forming ability. However, there is a need to investigate the independent effect of phosphoserine on osteogenic differentiation of human adipose stem cells (hADSCs). hADSCs were cultured in an osteogenic medium with phosphoserine. Cell proliferation was analysed by CCK8 and osteogenic differentiation was measured by alkaline phosphatase (ALP) activity, von Kossa staining and real time‐polymerase chain reaction (RT‐PCR). No stimulatory effect of phosphoserine on cell proliferation was noted at Days 1, 4 and 7. Deposition of calcium increased after the addition of phosphoserine. mRNA expression of type I collagen (COL‐I), alkaline phosphatase (ALP), osteocalcin (OCN), Osterix, bone morphogenetic protein‐2 (BMP‐2) and RUNX2 increased markedly with phosphoserine treatment. The BMP‐2 antagonist, noggin, and its receptor kinase inhibitors, dorsomorphin and LDN‐193189, attenuated phosphoserine‐promoted ALP activity. BMP‐responsive and Runx2‐responsive reporters were activated by phosphoserine treatment. Thus phosphoserine can promote osteogenic differentiation of hADSCs, probably by activating BMP and Runx2 pathways, which could be a promising approach for enhancing osteogenic capacity of cell‐based construction in bone tissue engineering.

Comparison of the Tight Rope Technique and Clavicular Hook Plate for the Treatment of Rockwood Type III Acromioclavicular Joint Dislocation

ABSTRACT Aim: Acromioclavicular joint dislocation is one of the most common shoulder problems and may lead to instability or degenerative changes. The aim of this study was to compare the clinical outcomes of the Tight Rope system and clavicular hook plate for Rockwood type III acromioclavicular joint dislocation in adults. Materials and Methods: This was a prospective, randomized study in a hospital setting. From January 2012 to December 2014, 69 patients with type III injury were reviewed. Patients were randomly divided into two groups: Group A was treated using the TightRope system and Group B with the clavicular hook plate. All participants were followed up for 12 months. Clinical outcomes, radiological results and postoperative complications were recorded. Results: The length of incision was significantly shorter in Goup A than that in Group B. The blood loss of surgery was significantly less in the Group A. Significant difference could be found between the two groups regarding the Visual Analogue Scale scores one day after surgery, at the 3 and 12 months follow-up. There were no differences according to the improvement of the Constant–Murley score and the coracoclavicular distance between the groups. Conclusions: The two groups have similar clinical and radiological outcomes. Both treatments could relieve the pain of dislocation, improve the function of Acromioclavicular joint and rectify the coracoclavicular distance measured in plain films. However, the TightRope system exhibited some advantages in terms of length of incision, blood loss of surgery, the pain postoperatively and no need for a second surgery.

Pediatric Femoral Shaft Fractures Treated With Titanium Elastic Nailing

The objective of this study was to prospectively compare intraoperative fluoroscopy time and clinical and radiological results in pediatric femoral shaft fractures treated with titanium elastic nailing (TEN) using a small-incision, blind-hand reduction vs closed reduction. From February 2008 to December 2009, sixty-eight children were enrolled in the study. Patients were divided into 2 groups: group A comprised 34 patients treated with a small-incision, blind-hand reduction technique and group B comprised 34 patients treated with a closed reduction technique. Operative time, intraoperative fluoroscopy time, fracture union time, and complications were recorded in both groups. Clinical and radiological results were assessed using the TEN scoring system. Mean operative time was 30.5±8.5 in group A and 53.0±15.0 minutes in group B, and mean fluoroscopy time was 28.4±18.5 seconds in group A and 65.0±28.5 seconds in group B. Operative time and fluoroscopy time were significantly longer in group B (P<.001). According to the TEN scoring system, the results were excellent in 31 patients and good in 3 patients in group A and excellent in 29 patients and good in 5 patients in group B. There was no significant difference between the 2 groups in terms of clinical and radiological results. There was also no significant difference in terms of fracture healing time, weight-bearing time, and complications. The small-incision, blind-hand reduction technique provided similar clinical results as closed reduction. This technique could be an alternative to closed reduction because it significantly reduced intraoperative radiation exposure and operative time.

Factors associated with a failed closed reduction for supracondylar fractures in children

PURPOSE OF THE STUDY The aim of this retrospective study is to analyze the risk factors causing the failure of closed reduction of children supracondylar fracture. PATIENTS AND METHODS The children with supracondylar humerus fractures who were treated in our hospital from February 2008 to February 2013, were recorded as well as their age, sex, BMI, injured side, mechanism of injury, associated injuries, fracture type, delay from injury to surgery. Mean comparisons or Chi(2) test were used for univariate analysis of the above factors, and then multivariate logistic regression analysis was used to analyse the possible risk factors, in order to elicit the risk factors associated with a failed closed reduction for supracondylar fractures in children. RESULTS Univariate analysis showed that BMI, fracture type, duration from injury to surgery, and mechanism of injury had statistically significant association with the failure of closed reduction for children supracondylar fracture (*P=0.021, 0.044, 0.000 and 0.037 respectively). Multivariate logistic regression analysis demonstrated that fracture type (P=0.027, OR=1.177), time from injury to surgery (P=0.022, OR=2.003), and mechanism of injury (P=0.044, OR=4.182) were independent risk factors of a failed closed reduction for paediatric supracondylar fractures. DISCUSSIONS Gartland type III supracondylar fractures, the peak period of soft tissue swelling and high-energy injury are significant risk factors to warrant open reduction. Treating surgeons should preoperatively carefully evaluate these risk factors and be prepared to treat these injuries accordingly. LEVEL OF EVIDENCE Level IV retrospective study.

Comparison of three surgical fixation methods for dual-bone forearm fractures in older children: A retrospective cohort study

BACKGROUND The aim of this study was to compare the outcomes of dual ESIN (D-ESIN) fixation, hybrid fixation, and open reduction and dual plate (d-plate) fixation in the treatment of dual-bone forearm fractures in children aged 10-16 years. MATERIALS AND METHODS 137 patients with dual-bone forearm fractures (48 patients in the D-ESIN group, 45 patients in the hybrid group, and 44 patients in the d-plate group) were reviewed. Duration of surgery, length of incision, intraoperative blood loss, intraoperative times of fluoroscopy, and duration of postoperative immobilisation were recorded. Radiographic outcomes, functional outcomes, and complication rate were also recorded. RESULTS Surgeries and incisions were significantly shorter, and less intraoperative blood loss occurred, in the hybrid group than the d-plate group (P < 0.001). The hybrid group was also characterised by less intraoperative fluoroscopy times and shorter duration of postoperative immobilisation compared with the D-ESIN group (P < 0.001). The union rate of the ulna at 3 months postoperatively was higher in the hybrid and d-plate groups than in the D-ESIN group (P = 0.003). The union rate of the radius was similar in all three groups (P = 0.403). No significant difference in the union rate of the radius or ulna was observed among groups at 6 months postoperatively (P = 0.052). The mean union time was notably later in the D-ESIN group than in the hybrid and d-plate groups. However, no significant difference in functional outcome or complication rate was observed among the three groups (P = 0.822 and P = 0.912). CONCLUSION Hybrid fixation was superior in terms of the duration of surgery, intraoperative use of fluoroscopy, intraoperative blood loss, duration of postoperative immobilisation, delayed union of the ulna, and bone union time. Therefore, hybrid fixation is a safe and effective treatment for dual-bone forearm fractures in children aged 10-16 years.

The outcomes of pediatric femoral shaft fractures treated surgically by different types of orthopedists

BACKGROUND The objective of this study was to compare the outcomes of pediatric femoral shaft fractures treated with titanium elastic nail (TEN) by pediatric orthopedists and non-pediatric orthopedists. METHODS From May 2006 to June 2014, 88 children with femoral shaft fractures were randomized to operative stabilization either by pediatric orthopedists (Group A, 44 cases) or by non-pediatric orthopedists (Group B, 44 cases). Demographic data and clinical characteristics (age, sex, weight, fracture side and type, cause of injury, associated injuries and interval from injury to surgery) were comparable between the two groups before surgery. Peri-operative data, clinical and functional outcomes between the two groups were recorded. RESULTS The mean follow-up period was 20.9±4.5months for Group A and 20.0±3.6months for Group B (P=0.356). There was no significant difference in the time to union, length of hospitalization, full weight-bearing time and TEN scores between the two groups (P=0.785, P=0.835, P=0.803, P=0.940, respectively). However, the mean operating time and radiation time was longer in Group B than in Group A (P=0.001 and P=0.047, respectively). Also, there was a trend for patients of Group B to have a higher rate of open reduction (P=0.047). When comparing the total complications, no significant difference existed between the groups (P=0.978). CONCLUSIONS This study indicated that both pediatric and non-pediatric orthopedists provided satisfactory clinical and functional results in treating these common injuries.