Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Cell-Penetrating Peptides ; chemistry ; Drug Delivery Systems ; Enzymes ; chemistry ; Humans ; Neoplasms ; drug therapy

Objective To observe the effect of atorvastatin on mixed dyslipidemia in type 2 diabetic patients. Methods 39 patients of type 2 diabetic with mixed dyslipidemia were taken with atorvastatin for 6 months,and the change of total cholesterel(TC),triglyceride(TG),low-debsity-lipoprotein-cholesteral(LDL-C),high-debsity-lipopro- tein-cholesteral(HDL-C)were observed.The incidence of side-effect was recorded.Results TC,TG,LDL-C were obviously reduced and their extent of reduction were 26.17 %,54.97 %,38.92 %.HDL-C was obviously increased and it's extent of increase was 14.81%(P

OBJECTIVETo observe the expressions of Wnt/beta-catenin and the effects of tanshinone IIA (TII A) on Wnt/beta-catenin signaling pathway in high glucose induced renal tubular epithelial cell transdifferentiation.

METHODSHuman kidney proximal tubular epithelial cells (HK-2) were divided into three groups, i. e., the normal glucose group, the high glucose group, and the high glucose plus tanshinone IIA group. The expression of beta-catenin was observed using immunocytochemical staining. The protein expression of beta-catenin, E-cadherin, and alpha-smooth muscle actin (alpha-SMA) were detected by Western blot. The mRNA levels of beta-catenin and E-cadherin were detected by RT-PCR.

RESULTSCompared with the normal glucose group, both the protein and the mRNA expressions of beta-catenin were significantly enhanced (P < 0.01), the expression of E-cadherin significantly decreased (P < 0.01), the expression of beta-catenin increased in the cytoplasm and nucleus in the high glucose group. TIIA at the final concentration of 100 micromol/L significantly reduced the ectopic expression of beta-catenin. At that concentration, the protein and mRNA expressions of beta-catenin in the nucleus significantly decreased, while the protein and mRNA expressions of E-cadherin were up-regulated. Meanwhile, the expression of alpha-SMA obviously decreased.

CONCLUSIONSWnt/beta-catenin signaling pathway participated in the high glucose induced renal tubular epithelial cell transdifferentiation. TIIA inhibited the transdifferentiation process possibly through down-regulating the activities of Wnt/beta-catenin signaling pathway, thus further playing a role in renal protection.

Cadherins ; metabolism ; Cell Line ; Cell Transdifferentiation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Glucose ; adverse effects ; Humans ; Kidney Tubules, Proximal ; cytology ; drug effects ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

Objective To evaluate the quality of the portal images acquired by computed radiography(CR)system and conventional screen-film system,respectively.Methods imaging plates (IP)and X-ray films of a home-devised lead phantom with a leakage of 6.45% were acquired,and modulation transfer function(MTF)curves of the both images were measured using edge method.Portal images of 40 nasopharyngeal cancer patients were acquired by IP and screen-film system respectively.Two doctors with similar experience evaluated the damage degree of petrosa] bone,the receiver operating characteristic(ROC)curve of CR images and general images were drawn according to two doctors evaluation results.Results The identification frequency of CR system and screen-film system were 1.159 and 0.806 Lp/mm respectively.For doctor one,the area under ROC curve of CR images and general images were 0.802 and 0.742 respectively.For doctor two,the area under ROC curve of CR images and general images were 0.751 and 0.600 respectively.The MTF curve and ROC curve of CR are both better than those of screen-film system.Conclusion The image quality of CR portal imaging is much better than that of screen-film system.The utility of CR in linear accelerator for portal imaging is promising in clinic.

The present study aimed to explore whether the stretch of ischemic myocardium could modulate the electrophysiological characteristics via mechanoelectric feedback (MEF), as well as the effect of phalloidin on the electrophysiological changes. Thirty-two Wistar rats were randomly divided into 4 groups: control group (n=9), phalloidin group (n=7), myocardial infarction (MI) group (n=9), MI + phalloidin group (n=7). The acute myocardial infarction (AMI) was conducted by ligation of the left anterior descending (LAD) coronary artery for 30 min in isolated rat heart. The volume alternation of a water-filled latex balloon in the left ventricle produced the stretch of myocardium. After perfused on Langendorff, the isolated hearts were stretched for 5 s by an inflation of 0.1, 0.2 and 0.3 mL separately and the effect of stretch was observed for 30 s, including the left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), ±dp/dt(max), monophasic action potential duration at 90% repolarization (MAPD90), and occurrence of premature ventricular beats (PVB) and ventricular tachycardia (VT). The stretch caused an increase of MAPD(90) in both control and MI rats (P<0.05, P<0.01). Moreover, MAPD(90) in MI group increased more significantly than that in the control group at the same degree of stretch (P<0.05, P<0.01). Phalloidin (1 μmol/L) had no effect on MAPD(90) in basal state. After stretch, MAPD(90) in phalloidin group slightly increased but was not significantly different from that in the control group. However, phalloidin reduced MAPD(90) in infarcted myocardium, especially when ΔV=0.3 mL (P<0.05). The incidence rates of PVB and VT in MI group were higher than that in the control group (both P<0.01). And there was no significant difference in the incidence rates of PVB and VT between phalloidin group and control group. Phalloidin inhibited the occurrence of PVB and VT in infarcted hearts (both P<0.01). LVSP and +dp/dt(max) in MI group obviously decreased (P<0.01 vs control). With application of phalloidin, LVSP slightly, but not significantly increased in infarcted hearts, while -dp/dt(max) significantly increased (P<0.05). It is suggested that MI facilitates the generation and maintenance of malignant arrhythmias, while phalloidin obviously inhibits the occurrence of arrhythmias.
Action Potentials ; Animals ; Arrhythmias, Cardiac ; prevention & control ; Coronary Vessels ; Heart ; drug effects ; physiopathology ; Heart Ventricles ; Myocardial Infarction ; physiopathology ; Phalloidine ; pharmacology ; Rats ; Rats, Wistar

OBJECTIVETo identify factors associated with YMDD mutation in patients with chronic hepatitis B before and after lamivudine treatment in Zunyi region.

METHODS53 patients with chronic hepatitis B were enrolled in this study, HBV DNA,HBV markers, ALT, AST, TBil, albumin in the serum were examined at 0, 3, 6, 12, 18 and 24 months after lamivudine treatment. HBV genotype and YMDD mutation were determined by sequencing before lamivudine treatment. YMDD mutation was checked again if serum HBV DNA rebound to more than 1 x 10(4) copies/ml after the initial decrease.

RESULTSHBV genotype in Zunyi region is constitute of B, C and B+C genotype. YMDD mutation occurred in 18 cases after lamivudine treatment, the rate of YMDD mutation was 15.1%, and 34.0% after 1 year and 2 years treatment. There are four types of mutation: rtL180M/M204V, rtL180M/M204I, rtM204I, rtL180M. rtM204V mutation in C gene was always accompanied by rtL180M mutation (100%). The rate of rtL180M/M204V mutation in genotype C group was significantly higher than that in genotype B group (77.8% to 25.0%), the same was true for the rtL180M/ M204I mutation (22.2% to 12.5%). There was no point mutation in genotype C group. The point mutation of rtM204I and rtL180M appeared only in genotype B group. Gender, nation, family history of hepatitis B and HBeAg were not associated with YMDD mutation (P more than 0.05), while the mutation rate was associated with the disease course and severity of disease. YMDD mutation did not occur in patients with low HBV DNA level (less than 10(5) copies/ml).

CONCLUSIONYMDD mutation after lamivudine therapy is associated with HBV genotype and P gene mutation type, and prolonged treatment increases the the mutation rate. In order to reduce the incidence of YMDD mutation, patients with shorter disease course, lower HBV DNA level, more serious liver damage should be treated with lamivudine.

Adult ; Alanine Transaminase ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; blood ; China ; epidemiology ; DNA Mutational Analysis ; DNA Primers ; DNA, Viral ; blood ; genetics ; Drug Resistance, Viral ; Female ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Mutation ; Polymerase Chain Reaction

OBJECTIVETo explore the molecular mechanism of dutasteride inhibiting fertility by studying its effects on the expressions of the epididymal epithelial junction proteins Claudin1 and β-catenin in rats.

METHODSSixteen 3-month-old SD male rats were equally divided into an experimental and a negative control group to be treated intragastrically with dutasteride at 40 mg/kg per day and the same dose of solvent, respectively, for 14 consecutive days. Then, the sperm motility and morphology of the rats were detected by computer-assisted sperm analysis, the serum levels of testosterone (T) and dihydrotestosterone (DHT) measured by ELISA, changes in the tight junction of epididymal cells observed under the transmission electron microscope, the protein and gene expressions of Claudin1 and β-catenin determined by RT-PCR and immunohistochemistry, and the conception rate of the mated female rats calculated.

RESULTSDutasteride significantly suppressed the serum DHT level, sperm motility, and fertility of the rats (P <0.05). Interspaces between epididymal epithelial cell tight junctions were observed, the volume of epididymal fluid obviously increased, and the expressions of Claudin1 and β-catenin gene and protein remarkably downregulated in the experimental rats (P <0.05).

CONCLUSIONDutasteride can significantly inhibit the fertility of male rats by reducing the serum DHT level, suppressing Claudin1 and β-catenin expressions, and damaging epididymal epithelial cell junctions.

Animals ; Azasteroids ; pharmacology ; Claudin-1 ; metabolism ; Dihydrotestosterone ; blood ; Dutasteride ; Epididymis ; drug effects ; metabolism ; Female ; Fertility ; drug effects ; Humans ; Intercellular Junctions ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Testosterone ; blood ; Urological Agents ; pharmacology ; beta Catenin ; metabolism

OBJECTIVEAn intrinsically colored machinable glass-ceramic containing tetrasilicic fluormica as the predominant crystal phase was studied, which was used in molar crown in dental CAD/CAM system.

METHODSOrthogonal design analysis was used to select appropriate base formula, coloration and heat treatment process.

RESULTSFactors influencing the color appearance of mica glass ceramic were nucleation agent and the ratio of Mg(2+) to K(+) in base formula; Cerium oxide (CeO(2)) was used as the main coloration; The preferred heat treatment was 650 degrees C for 1 h and 1,000 degrees C or 1,050 degrees C for 3 h - 4 h.

CONCLUSIONSThis mica glass-ceramic could provide 4 to 5 color appearance for dental use, it showed excellent machinability which was eminently suitable for use in dental CAD/CAM system.

Aluminum Silicates ; chemistry ; Color ; Computer-Aided Design ; Crowns ; Dental Porcelain ; chemistry ; Glass ; chemistry ; Molar

Objective: To analyze the epidemiological characteristics of coronavirus disease 2019 ( COVID-19 ) clusters in Lishui, so as to provide basis for the prevention and control of COVID-19 clusters. Methods: The data of COVID-19 clusters in Lishui from January 23 to March 29, 2020 were collected through China Disease Control and Prevention Information System-Public Health Emergency Information System, and analyzed time, space, scale, source of infection, exposure and transmission route by descriptive epidemiological method. Results: There were 31 cases in 8 clusters ( about 4 cases per cluster ), with no death. The report time was bimodal, peaked first from January 20 to February 10 with 4 clusters imported from domestic and peaked second from March 1 to 29 with 4 clusters imported from overseas. Qingtian County reported 4 clusters, Liandu District, Yunhe County, Qingyuan County and Jingning County each reported 1 cluster. Thirteen cases were restaurant employees, accounting for 41.94%. The cases were mainly occurred in the condition that exposed in the same family ( 6 clusters ), in the same dinner and car ( 1 clusters ), and in the same party ( 1 clusters ). The exposure modes that caused more cases infected were through the same family (9 cases) and through the same dinner and car ( 6 cases ). There were 3 clusters with first-generation cases, 3 clusters with second-generation cases and 2 clusters with third-generation cases. The recurrence rate of the 8 clusters ranged from 1.49% to 7.69%, with a median of 3.47%. Conclusions The COVID-19 clusters in Lishui imported from domestic in the early stage and later from overseas. Most cases were reported from Qingtian County, were engaged in catering business, and exposed by living with families.

OBJECTIVETo explore the role of miR-205 in regulating epithelial-messenchymal transition (EMT) in proximal tubular cell line HK-2 cells and the underlying mechanism.

METHODSHK-2 cells transfected with miR-205 mimics or a scrambled control sequence were examined for miR-205 expressions and mRNA levels of ZEB1, E-cadherin, and α-SMA using real-time qPCR; the protein levels of ZEB1, ZEB2, E-cadherin, and α-SMA were detected with Western blotting. Immunohistochemistry was performed to examine the ectopic expression of β-catenin and E-cadherin expression in the cells.

RESULTSThe expression levels of ZEB1 and ZEB2 decreased significantly (P<0.01) while E-cadherin expression was up-regulated (P<0.01) in cells transfected with miR-205 mimics. Transfection with miR-205 mimics also markedly down-regulated the expression of α-SMA (P<0.01), a marker of mesenchymal cells that play an important role in EMT of HK-2 cells. The ectopic expression of β-catenin was inhibited by miR-205 mimics in HK-2 cells.

CONCLUSIONmiR-205 inhibits EMT in HK-2 cells by down-regulating the expression levels of ZEB1 and ZEB2.