ABSTRACT
Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.. Our studies suggested that NCB, NCA and CMC are inhibitors of Organic anion transporter 1 (OAT1). OAT1 is encoded by solute carrier family 22 member 6 gene (SLC22A6) in humans and plays a critical role in the organic anion drug uptake and excretion in the kidney. Lamivudine is the typical substrate of OAT1 and is frequently used in combination with other antiviral drugs in clinical antiviral treatments. The aim of this study is to investigate the interaction and its mechanism between these bi-flavone components in Stellera chamaejasme L. and lamivudine via OAT1 both in vitro and in vivo. In vitro, the uptake studies in Madin-Darby canine kidney (MDCK) cells overexpressing OAT1 suggested that NCB inhibited the uptake of 6-CFL and lamivudine.Similar results were obtained for NCA and CMC. NCB was a noncompetitive and competitive inhibitor interaction with OAT1. IC values of NCB, NCA and CMC for inhibiting OAT1-mediated lamivudine transport were 2.46, 8.35 and 0.61 μmol·L, respectively. In vivo, the pharmacokinetic results of lamivudine in rats showed that the mean area under the plasma concentration-time curve (AUC) and maximal plasma concentration (C) of lamivudine after co-administration is increased 2.94-fold and 1.87-fold, respectively, compared to lamivudine administration alone. The results of interactions between lamivudine and these bi-flavone components in Stellera chamaejasme L. extracts via OAT1 in vivo are consistent with studies in vitro. The inhibition of OAT1-mediated uptake of lamivudine by NCB, NCA and CMC is the possible mechanism for Stellera chamaejasme L. extracts improving the oral bioavailability of lamivudine in rats.
ABSTRACT
Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3'-UTR. Meanwhile, 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP), fluorogenic substrate ,-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP), and oxaliplatin uptake by OCT2 both and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.
ABSTRACT
Treatment of large bone defects caused by trauma, osteomyelitis, and tumors has been a major challenge in clinical. In the past, there have been many ways to repair and reconstruct the large bone defects. However, there is a long period of treatment, high technical requirement and complications such as ununion. After Masquelet reported the induced membrane technology in 2000, the technique was widely used in treatment of trauma, osteomyelitis, and large bone defects caused by tumors. It has been obtained good results. It has the advantages of short course, high healing rate, easy operation and easy to master. The induced membrane has unique structural characteristics and biological characteristics. There are many kinds of osteogenic factors that are included in the membrane, such as vascular endothelial growth factor, and morphogenetic protein-2, transforming growth factor-β1, etc. These osteogenic factors contribute to accelerate bone healing. With the development of induced membrane technology. The technology of Reamer Irrigator Aspirator technology, engineering tissue technology and internal fixation is used in clinic.It can provide bone source, promote bone defect reconstruction, improve long-term limb function and reduce complications.This paper retrospectively summarizes the experimental research and clinical progress of Masquelet technique in the treatment of large bone defects.
ABSTRACT
Objective To compare the anxiety,depressive and personality characteristics between diabetes mellitus patients with or without diabetic retinopathy (DR),and look for psychological treatment and corresponding prevention measures.Methods 435 diabetic patients were enrolled in this study from April to November 2014 in our hospital,including 178 DR cases (group A) and 257 cases without retinopathy (group B).All the patients completed a questionnaire,the Self-Rating Anxiety (SAS),the SelfRating Depression Scale (SDS) and the big five personality scale (NEO-FFI),and were scored by eye doctors.According to the score,SAS can be divided into mild anxiety,moderate anxiety,and severe anxiety.SDS is divided into depression,mild depression,moderate depression and major depression.NEO-FFI was scored from emotional stability,outgoing,openness,easy-going and sense of responsibility.Multiple linear regression analysis was used to analyze the DR risk factors in those scores and education level,high blood pressure,age,alcohol consumption,occupation and other factors.Results There were 110 cases of mild anxiety,57 cases of moderate anxiety,11 cases of severe anxiety;74 cases without depression,53 cases of mild depression,31 cases of moderate depression,20 cases with major depression in group A.There were 181 cases of mild anxiety,53 cases of moderate anxiety,23 cases of severe anxiety;177 cases without depression,44 cases of mild depression,25 cases of moderate depression,11 case with major depression in group B.Group A patients had higher SAS,SDS scores than group B,the difference was statistically significant (P =0.035).Group B patients had higher NEO-FFI score in outgoing,easygoing,responsibility (P=0.022),lower NEO-FFI score in emotional stability (P=0.014) and same NEO-FFI score in openness(P =0.210)compare to Group A patients.Multiple linear regression analysis results showed that education level,high blood pressure,age,weight,drinking,occupation can affect the degree of changes in the retina (P=0.019).Conclusions Compared with those without retinopathy,DR patients were more prone to anxiety and depression.They also had low score in personality characteristics of outgoing,easygoing,responsibility.