Lactoferrin-derived chimeric peptide (LFch) strongly boosts TGFß1-mediated inducible Treg differentiation possibly through downregulating TCR/CD28 signalling.

We recently reported that lactoferrin (LF) induces Foxp3+ Treg differentiation through binding to TGFß receptor III (TßRIII), and this activity was further enhanced by TGFß1. Generally, a low T-cell receptor (TCR) signal strength is favourable for Foxp3+ Treg differentiation. In the present study, we explored the effect of lactoferrin chimera (LFch, containing lactoferricin [aa 17-30] and lactoferrampin [aa 265-284]), along with TGFß1 on Foxp3+ Treg differentiation. LFch alone did not induce Foxp3 expression, yet LFch dramatically enhanced TGFß1-induced Foxp3 expression. LFch had little effect on the phosphorylation of Smad3, a canonical transcriptional factor of TGFß1. Instead, LFch attenuated the phosphorylation of S6 (a target of mTOR), IκB and PI3K. These activities of LFch were completely abrogated by pretreatment of LFch with soluble TGFß1 receptor III (sTßRIII). Consistent with this, the activity of LFch on TGFß1-induced Foxp3 expression was also abrogated by treatment with sTßRIII. Finally, the TGFß1/LFch-induced T cell population substantially suppressed the proliferation of responder CD4+ T cells. These results indicate that LFch robustly enhances TGFß1-induced Foxp3+ Treg differentiation by diminishing TCR/CD28 signal intensity.

Prognostic Factors Affecting Clinical Outcomes of Arthroscopic Assisted Reduction and Volar Plating through Preservation of Pronator Quadratus for Intra-Articular Distal Radius Fracture.

Background: This study aimed to evaluate the clinical and radiological outcomes following an arthroscopic-assisted reduction and volar plating (AR-VP) surgery through pronator quadratus (PQ) preservation for treating intra-articular distal radius fractures (IA-DRFs) and to assess prognostic factors that affect functional outcomes. Methods: Between March 2014 and February 2017, 54 patients who had intra-articular DRF and underwent AR-VP through the PQ preservation technique and completed 1-year follow-up were enrolled. Patients were divided into the satisfactory group (excellent and good results) and an unsatisfactory group (fair and poor results) based on the modified Mayo Wrist Scoring System (MMWS) scored at 1-year follow-up to determinate prognostic factors that affected clinical outcomes. Patients' demographics, clinical outcome measures (VAS, DASH, PRWE, etc.), and pre-and post-operative radiographic parameters were analyzed. Results: The outcomes according to MMWS were 10 excellent, 22 good, 14 fair, and 8 poor. A univariate analysis showed a significant difference between the groups (p < .05) for all radiographic parameters, sex, and the presence of an intra-articular comminution. In the multivariate analysis, female gender, presence of an intra-articular comminution, and difference of palmar articular tilt compared to uninjured wrist (> 20.1°) at trauma were considered as significant poor prognostic factors of functional outcome. Conclusions: AR-VP surgery through PQ preservation for intra-articular DRFs has reliable clinical and radiological outcomes. However, female gender, presence of an intra-articular comminution, and difference of palmar articular tilt compared to the uninjured wrist (> 20.1°) at initial injury were considered poor prognostic factors for AR-VP through PQ preservation for intra-articular DRF.