ABSTRACT
Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gα q activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.
ABSTRACT
Paeoniae Radix Rubra has the effects of clearing heat, cooling blood, dissipating blood stasis and pain relieving (in terms of Chinese medicine). Paeoniae Radix Rubra and its active ingredients have significant pharmacological effects in anti-tumor，protecting liver, nerve and heart. By reviewing the relevant literatures published in recent years, we found that the studies on Paeoniae Radix Rubra are mainly focused in the mechanism of action, drug development and clinical application. In this review, we summarize the research results of the pharmacological effects of Paeoniae Radix Rubra and its active ingredients in order to provide the reference for the future research and clinical application of Paeoniae Radix Rubra.
ABSTRACT
Objective To investigate the influence of cartilage degeneration grades of patellar on the clinical outcomes after total knee arthroplasty (TKA) without patellar resurfacing.Methods 151 patients performed TKA without patellar resurfacing from February 2007 to January 2010 were retrospective studied.There were 65 males and 86 females,with the mean age of 65±5.0 years (range,56-82 years).The mean duration of follow-up was 3.5 years (range,2-5 years).Intraoperatively,the cartilage degeneration was classified according to Outerbridge classification.At the final follow-up,the patients' satisfaction was evaluated,and the incidence of anterior knee pain was assessed using visual analogue scale (VAS).If VAS was more than 3 points,patient was defined suffered anterior knee pain.Compare KSS and patella score of patients with different grades of cartilage degeneration.Results The articular cartilage of the patella was graded according to Outerbridge:grade Ⅰ in 18 patients,grade Ⅱ in 36 patients,grade Ⅲ in 62 patients,and grade Ⅳ in 35 patients.At the final follow-up,the patients' satisfaction rate and the anterior knee pain rate was 96.7％ 046/151) and 4.0％ (6/151),respectively.In the patients with different grades of cartilage degeneration,the patient satisfaction rate (H=5.54,P=0.14),anterior knee pain rate (H=0.56,P=0.91),KSS (knee score:F=1.95,P=0.12； function score:F=2.11,P=0.10) and patella score (F=1.35,P=0.26) were not found to be significantly difference.Conclusion The differentiae grades of cartilage degeneration may not affect the clinical outcomes of TKA.TKA without patella resurfacing appears to be a reasonable option for degenerative osteoarthritis.