ABSTRACT
@#Receptor activity-modifying proteins(RAMPs) are type I transmembrane proteins,which are activity-modifying proteins of a variety of G-protein-coupled receptors(GPCRs).RAMPs are related to physiological and pathological phenomena such as neurological diseases,cardiovascular diseases,renal function,skeletal development and obesity,and of great significance for disease prevention,which are potential targets for the treatment of various diseases and also closely related to the prognosis of diseases.At present,there are few studies on proteins that may regulate the expression of RAMPs.This paper focuses on the sterol regulatory element-binding factor-2(SREBF-2) that may regulate the transcription and expression of RAMP3, and reviews the research progress of RAMPs in biology,pathology and pharmacology,providing a reference for the further research on RAMPs and the prevention and detection of related diseases.
ABSTRACT
Aim To explore the possibility of resveratrol ( RES) combined with irinotecan ( IRI) in the treatment of colorectal cancer ( CRC ) and the underlying molecular mechanism of RES ameliorating IRI chemoresistance of CRC cells. Methods CRC cells used in this study were HT-29 and RKO cells. The effects of RES, IRI and their combination on the proliferation of CRC cells were analyzed by MTT assay and colony formation assay. The effects of RES,IRI and their combination on the migration of CRC cells were assessed by Wound-healing assay. On this basis,the role of RES in regulating IRI chemoresistance of CRC cells and the underlying molecular mechanisms were further explored. Results The proliferation and migration ability of CRC cells in the RES and IRI combined treatment group were significantly lower than those in the IRI treated group, which showed that RES could enhance the inhibiting effect of IRI on the proliferation and migration of CRC cells, indicating that RES was able to a-meliorate the chemoresistance of CRC cells to IRI. And remarkably lower marker proteins expression levels of EGFR/AKT/mTOR signaling pathway in the RES and IRI combined treatment group was observed. Moreover, both EGFR activator (NSC 228155) and AKT activator (SC79) could reverse the ameliorating effect of RES on IRI chemoresistance of CRC cells, whereas AKT inhibitor (MK2206 ) could partially reverse the effect of NSC 228155. Conclusions RES can inhibit the proliferation and migration of CRC cells by down-regulating EGFR/AKT/mTOR signaling pathway, so as to ameliorate the chemoresistance of CRC cells to IRI, suggesting that RES combined with IRI can be a promising novel treatment for CRC.
ABSTRACT
Objective: To evaluate the risk factors of inferior alveolar nerve injury (IANI) after surgical removal of the mandibular third molars (M3) and present a new risk scoring system to predict the probability of IANI. Methods: Patients who underwent extraction of M3 in the Stomatology Hospital, Zhejiang University School of Medicine from April 2017 to December 2019 were involved. The investigators enrolled a sample composed of 949 mandibular third molars. Prediction model was used for univariate and multivariate analysis of gender, age, M3, inferior alveolar canal (IAC), and the contact between M3 and IAC, to assess the risk factors of IANI. Combined with the risk factors determined by the outcomes of prediction model, the risk scoring system was constructed. The diagnostic performance of each cut-off score was examined to conduct a risk stratification of IANI risk scores. The predictive ability and reliability of the model were evaluated. Results: In prediction model, twenty nine cases (4.4%, 29/664) experienced postoperative IANI. Number of root (P<0.01), depth of impaction (P<0.05), contact between M3 and IAC (P<0.01) and their contact position (P<0.05) were statistically significant as contributing risk factors of IANI. Specifically, the incidence of temporary IANI was higher in those who aged under 25 years (P<0.001), while female suffer more permanent injury (P<0.05). Based on the IANI risk scoring system, patients were stratified into low-risk, middle-risk and high-risk groups at cutoff scores of 3 and 4. The area under the receiver operator characteristic curve of the risk scoring system were 0.81 [95%CI (0.70-0.90), P=0.002] and 0.80 [95%CI (0.68-0.92), P=0.007] towards good discrimination. Conclusions: Age, gender, number of root, depth of impaction, and contact between M3 and IAC were risk factors of IANI. IANI risk scoring system might help in preoperative assessment, recognition of high-risk cases and decision-making to reduce IANI.