Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells.

NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 µg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p>0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 µg/ml) treated group (p<0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 µg/ml) treated group (p<0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.

Proximal femoral nail vs. dynamic hip screw in treatment of intertrochanteric fractures: a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to compare the outcomes of proximal femoral nail (PFN) and dynamic hip screw (DHS) in treatment of intertrochanteric fractures. MATERIAL AND METHODS: Relevant randomized or quasi-randomized controlled studies comparing the effects of PFN and DHS were searched for following the requirements of the Cochrane Library Handbook. Six eligible studies involving 669 fractures were included. Their methodological quality was assessed and data were extracted independently for meta-analysis. RESULTS: The results showed that the PFN group had significantly less operative time (WMD: -21.15, 95% CI: -34.91 - -7.39, P=0.003), intraoperative blood loss (WMD: -139.81, 95% CI: -210.39 - -69.22, P=0.0001), and length of incision (WMD: -6.97, 95% CI: -9.19 - -4.74, P<0.00001) than the DHS group. No significant differences were found between the 2 groups regarding postoperative infection rate, lag screw cut-out rate, or reoperation rate. CONCLUSIONS: The current evidence indicates that PFN may be a better choice than DHS in the treatment of intertrochanteric fractures.

Gestational Leucylation Suppresses Embryonic T-Box Transcription Factor 5 Signal and Causes Congenital Heart Disease.

Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the association between maternal amino-acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine-leucylation (K-Leu), which is catalyzed by leucyl-tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K-Leu modification of lysine 339 within T-box transcription factor TBX5, whereas SIRT3 removes K-Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K-Leu levels in high-leucine-diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K-Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K-Leu modification, and decrease the occurrence of CHD in high-leucine-diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.

Strategy for Scanning Peptide-Coding Circular RNAs in Colorectal Cancer Based on Bioinformatics Analysis and Experimental Assays.

Background: Colorectal cancer (CRC) is the third most common cause of cancer deaths worldwide. Numerous studies have reported that circular RNAs (circRNAs) have important functions in CRC. It was first thought that circRNAs were non-coding RNA; however, more recently they were discovered to encode peptides and play a pivotal role in cancer development and progression. It was shown that most circRNAs possess coding potential; however, not all of them can truly encode peptides. Therefore, a practical strategy to scan for coding circRNAs is needed. Method: Sequence analyses included open reading frame (ORF) prediction, coding peptide prediction, and the identification of unique sequences. Then, experimental assays were used to verify the coded peptides, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was introduced to detect sequences of circRNAs with coding potential, and Western blot was used to identify the encoded peptides. Finally, the functions of the circRNAs were primarily explored. Result: An efficient strategy for searching circRNAs with coding potential was created. We verified this schedule using public databases and LC-MS/MS, then two of these circRNAs were selected for further verification. We used commercial antibodies that can also identify the predicted peptides to test the coded peptides. The functions of the circRNAs were explored primarily, and the results showed that they were mainly involved in the promotion of proliferation and invasion ability. Discussion: We have constructed an efficient strategy of scanning circRNAs with coding potential. Our strategy helped to provide a more convenient pathway for identifying circRNA-derived peptides, which can be a potential therapeutic target or a diagnostic biomarker.