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As a multifunctional filler, carbon materials play an important role in enhancing the comprehensive properties of polypropylene composites. However, it is an important task to balance the relationship between the amount of different carbon materials and the formability and functionality of composite products. In this paper, the properties of carbon fiber, carbon nanotube and graphene, and the effects of these carbon materials on the mechanical, thermal and electrical properties of polypropylene-based multi-scale composites are discussed respectively. It is pointed out that it is a challenging research direction to prepare polypropylene composites filled with high content and hybrid carbon materials by melt deposition 3D printing process in the future. [ABSTRACT FROM AUTHOR]

Background: Patients with severe acute pancreatitis (SAP) have a high mortality, thus early diagnosis and interventions are critical for improving survival. However, conventional tests are limited in acute pancreatitis (AP) stratification. We aimed to assess AP severity by integrating the informative clinical measurements with cell free DNA (cfDNA) methylation markers. Methods: One hundred and seventy-five blood samples were collected from 61 AP patients at multiple time points, plus 24 samples from healthy individuals. Genome-wide cfDNA methylation profiles of all samples were characterized with reduced representative bisulfite sequencing. Clinical blood tests covering 93 biomarkers were performed on AP patients within 24 h. SAP predication models were built based on cfDNA methylation and conventional blood biomarkers separately and in combination. Results: We identified 565 and 59 cfDNA methylation markers informative for acute pancreatitis and its severity. These markers were used to develop prediction models for AP and SAP with area under the receiver operating characteristic of 0.92 and 0.81, respectively. Twelve blood biomarkers were systematically screened for a predictor of SAP with a sensitivity of 87.5% for SAP, and a specificity of 100% in mild acute pancreatitis, significantly higher than existing blood tests. An expanded model integrating 12 conventional blood biomarkers with 59 cfDNA methylation markers further improved the SAP prediction sensitivity to 92.2%. Conclusions: These findings have demonstrated that accurate prediction of SAP by the integration of conventional and novel blood molecular markers, paving the way for early and effective SAP intervention through a non-invasive rapid diagnostic test. [ABSTRACT FROM AUTHOR]

Background: Adipose-derived mesenchymal stem cells (ADMSCs) can promote healing and inhibit inflammation/immune response in local tissues, while the detailed mechanism remains unknown.Results: ADMSCs and peritoneal macrophages were collected from C57BL/6 mice. The culture medium (CM) from ADMSCs (24 hours cultured) was collected. The CM was added to the Mφ culture system with lipopolysaccharide (LPS) or IL-4/IL-13 or blank. And those Mφ cultures without adding CM were used as controls. A series of classification markers and signaling pathways for Mφ polarization were detected by using flow cytometry, RT-PCR, and western blotting. Furthermore, the cell viability of all the groups was detected by CCK8 assay. After CM induction in different groups, M1-Mφ markers and M2a-Mφ were decreased; however, M2b/c-Mφ markers increased. STAT3/SOCS3 and STAT6/IRF4 were suppressed in all 3 CM-treated groups. Moreover, the cell viability of all 3 groups which were induced by CM significantly increased as compared to that of the control groups without adding CM.Conclusion: ADMSCs can induce nonactivated macrophage and M1-Mφ into M2b/c-Mφ. Downregulation of the STAT3 and STAT6 pathway may involve in this process. This data shows that the anti-inflammatory role of ADMSC in local tissues may be partly due to their effect on Mφ to M2b/c-Mφ. [ABSTRACT FROM AUTHOR]

Multiple system atrophy with predominant parkinsonism (MSA-P) is a degenerative disorder that presents with autonomic dysfunction, atypical parkinsonism, and ataxia. Parkinson's disease (PD) is an age-related neurological disorder of the central nervous system. Differentiation between MSA-P and PD is important because treatments, complications, and prognoses differ. The bulbocavernosus reflex (BCR) tests the afferent and efferent signals of the pudendal nerve as well as the sacral cord. In this study, we investigated differences in BCR parameters between MSA-P and PD patients. Thirty-eight MSA-P patients and 32 PD patients were selected to participate in our electrophysiological investigations. The Keypoint EMG/EP system was used to induce the BCR, and latencies and amplitudes were recorded for systematic statistical analyses. Area under the curve of the receiver operating characteristic was used to assess the specificity and sensitivity of the BCR parameters. A BCR was elicited in 76.32% of MSA-P patients and 93.75% of PD patients. The BCR latencies of the MSA-P group were longer than those of the PD group (p < 0.001). In addition, the MSA-P group had a lower BCR amplitude compared to the PD and control groups (p < 0.001). We discovered the difference between MSA-P and PD through BCR latencies and amplitudes. Compared to PD patients, MSA-P patients have longer latencies and lower amplitudes. Therefore, the BCR may be used to discriminate between MSA-P and PD in some cases. [ABSTRACT FROM AUTHOR]

Background and Aims Developing a preoperative prediction model for estimating the risk of pancreatic ductal adenocarcinoma (PDAC) patients before pancreaticoduodenectomy is a difficult task. The purpose of current study was to develop a prognostic nomogram based on inflammatory markers for PDAC patients. Methods Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors based on 265 PDAC patients undergone surgery. The nomogram was built to estimate the probability of 1-year, 3-year, and 5-year OS. The predictive accuracy of nomogram was determined by concordance index, calibration curve, and time dependent receiver operating characteristics. Results In multivariable Cox analysis, vascular invasion, Tumor Grade, TNM stage, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and albumin/globulin ratio were significantly associated with OS, which were all assembled into nomogram. The calibration curves for probability of survival showed optimal agreement between nomogram prediction and actual observation. The concordance index for 1-year, 3-year and 5-year OS prediction were 0.860 (95% confidence intervals (CI): 0.837-0.885), 0.837 (95%CI: 0.819-0.856), and 0.809 (95%CI: 0.787-0.829), respectively. The area under time dependent receiver operating characteristics curve of 1-year, 3-year, and 5-year OS prediction were 0.938 (95%CI: 0.886-0.989), 0.844 (95%CI: 0.782-0.906), and 0.884 (95%CI: 0.792-0.976), suggesting high discriminative ability of nomogram. It allowed significant distinction survival outcomes by grouping the patients evenly into three subgroups after sorting by total points. Conclusions Based on clinicopathology characteristics and inflammatory markers, we developed a nomogram providing an individualized risk estimate for PDAC patients. [ABSTRACT FROM AUTHOR]

Background & Aims BCAT1 initiates the catabolism of branched-chain amino acids. Here, we investigated the function of BCAT1 and its transcriptional regulatory mechanism in hepatocellular carcinoma ( HCC). Methods RNASeq was used to evaluate BCAT1 mRNA levels in HCC and normal matched specimens. After the exogenous expression of BCAT1 in BEL-7404 cells and the suppression of endogenous BCAT1 expression with sh RNA in HepG2 cells, the cell proliferation, clone-forming ability and cell-cycle changes were measured with MTT assay, colony-forming assay and flow cytometry respectively. A xenograft model was used to investigate the effect of BCAT1 on cancer growth in vivo. Chromatin immunoprecipitation and luciferase reporter technologies were used to confirm the transcriptional regulation of the BCAT1 gene by MYC. The expression of the BCAT1 and MYC proteins in 122 HCC tissues was determined with an immunohistochemical analysis. Results BCAT1 mRNA was clearly increased in HCC tissues and hepatomas. The ectopic expression of BCAT1 in BEL-7404 cells enhanced their proliferation, clone formation, tumourigenic properties, S-G2/M phase transition and chemoresistance to cisplatin. The suppression of BCAT1 expression in HepG2 cells significantly inhibited their proliferation, clone formation, and S-G2/M phase transition and caused their chemosensitization to cisplatin. MYC affected the transcriptional regulation of BCAT1. Clinical data showed that BCAT1 expression correlated with a significantly poorer prognosis. Conclusion BCAT1 plays a pathogenic role in HCC by causing cell proliferation and chemoresistance. The MYC transcription factor is involved in regulating the transcriptional activity of BCAT1. BCAT1 expression has prognostic significance for the survival of patients with HCC. [ABSTRACT FROM AUTHOR]

Objectives: Multiple system atrophy (MSA) is characterized by a combination of symptoms including autonomic dysfunction, parkinsonism, cerebellar ataxia, and cortico-spinal disorders. The disease can have either predominant parkinsonism or cerebellar features (MSA-P and MSA-C, respectively). The measurement of the bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potentials (PSEPs) was originally developed to diagnose diabetic cystopathy and other neuropathologic diseases that share similar symptoms with MSA. We investigated the relationship between abnormalities of neurophysiological parameters and MSA, and estimated the potential value of BCR. Methods: Fifty-one MSA patients (28 and 23 MSA-P and 23 MSA-C patients, respectively) and 30 healthy controls who were seen at the Department of Neurology were included in the study. A Keypoint EMG/EP system was used to test BCR and PSEPs, and the latencies and amplitudes were recorded for statistical analyses. Results: The BCR was elicited in 78.4% patients with MSA (22/28 MSA-P, 18/23 MSA-C). Prolonged BCR latencies were found in patients with MSA compared with healthy controls (p < 0.001). BCR amplitudes were significantly lower in the MSA group than the control group (p < 0.001). PSEP P41 amplitudes were not significantly different between the MSA and control groups in males (p = 0.608) or females (p = 0.897). There were no significant differences in PSEP latencies among the MSA-P, MSA-C, and control groups (p = 1.0, p = 0.263, and p = 0.060, respectively). Discussion: MSA patients exhibit prolonged BCR latencies and lower amplitudes, which provides a rough anatomical localization of nervous system lesions in MSA patients. [ABSTRACT FROM AUTHOR]

Background. Functional dyspepsia (FD) is a functional upper gastrointestinal disorder with significant morbidity and medical costs. Previous studies investigated the association of G-protein β3 (GNB3) genetic polymorphisms with FD but with inconsistent results. Therefore, we performed a meta-analysis to derive a precise estimation of the relationship between GNB3 polymorphisms and FD. Methods. We searched different databases including PubMed, EMBASE, CNKI, and the Ovid Library to gather eligible studies on GNB3 polymorphisms and FD. The association was assessed by the odds ratio (OR) with 95% confidence intervals (CI). Results. We identified 12 studies with 1109 cases and 2853 controls for the analysis. We found no associations of GNB3 C825T polymorphism with FD in the overall population (T versus C, OR = 1.06, 95% CI: 0.96–1.18, P=0.26; TT versus CC + CT, OR = 1.16, 95% CI: 0.97–1.39, P=0.11; TT + CT versus CC, OR = 1.01, 95% CI: 0.77–1.31, P=0.96; TT versus CC, OR = 1.15, 95% CI: 0.93–1.44, P=0.20). Subgroup analyses by genotyping method indicated that the magnitude of association was strengthened for additive model (OR = 1.15, 95% CI: 1.07–2.24, P=0.02). Sensitivity analysis did not reveal significant associations under all models. Conclusions. This meta-analysis demonstrates that GNB3 C825T polymorphism may not be a risk factor for FD. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery and enhanced recovery after surgery (ERAS) programs were two major improvements for the management of colorectal diseases. The purpose of this systemic review was to examine whether laparoscopic colorectal surgery still improved short-term postoperative outcomes in comparison with open surgery when both groups of patients received ERAS programs. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared laparoscopic with open surgery in patients undergoing colorectal resection in the context of ERAS programs. The outcome measures were analyzed, and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Five randomized clinical trials encompassing 598 patients were included in the final analysis. Two of them were multicenter trials. The ERAS programs implemented in the five included trials cannot be classified as optimal ERAS programs, but suboptimal ERAS programs. Laparoscopic colorectal surgery significantly reduced total hospital stay (weighted mean difference (WMD) −1.92 days; 95 % confidence interval (CI) −2.61-−1.23 days; P < 0.00001) and number of complications (relative risk (RR) 0.78; 95 % CI 0.66-0.94; P = 0.007) compared with open surgery in the setting of ERAS programs. No significant differences were found between groups for primary hospital stay, number of patients with complications, readmission rates, and mortality. The quality of evidence for all outcomes was low-to-moderate on the GRADE scale, and none had high quality. Conclusions: Laparoscopic colorectal resection significantly reduced total hospital stay and number of complications when compared with open surgery in the setting of suboptimal ERAS programs, but the benefits of laparoscopic colorectal resection remain to be proved within optimal ERAS programs. [ABSTRACT FROM AUTHOR]

Background: Hospital readmission is gathering increasing attention as a measure of health care quality and a potential cost-saving target. The purpose of this prospective study was to determine risk factors for readmission within 30 days of discharge after gastrectomy for patients with gastric cancer. Methods: We conducted a prospective study of patients undergoing radical gastrectomy for gastric cancer from October 2013 to November 2014 in our institution. The incidence, cause and risk factors for 30-day readmission were determined. Results: A total of 376 patients were included in our analysis without loss in follow-up. The 30-day readmission rate after radical gastrectomy for gastric cancer was 7.2% (27of 376). The most common cause for readmission included gastrointestinal complications and postoperative infections. On the basis of multivariate logistic regression analysis, preoperative nutritional risk screening 2002 score ≥ 3 was an independent risk factor for 30-day readmission. Factors not associated with a higher readmission rate included a history of a major postoperative complication during the index hospitalization, prolonged primary length of hospital stay after surgery, a history of previous abdominal surgery, advanced age, body mass index, pre-existing cardiopulmonary comorbidities, American Society of Anesthesiology grade, type of resection, extent of node dissection and discharge disposition. Conclusions: Readmission within 30 days of discharge after radical gastrectomy for gastric cancer is common. Patients with nutritional risk preoperatively are at high risk for 30-day readmission. Preoperative optimization of nutritional status of patients at nutritional risk may effectively decrease readmission rates. [ABSTRACT FROM AUTHOR]

miRNAs are small, non-coding RNAs that regulate the expression of multiple target genes at the post-transcriptional level. Single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and have been implicated in the pathogenesis of multiple forms of arthritis, including rheumatoid arthritis (RA) and osteoarthritis. The present study explored the association between ankylosing spondylitis (AS) and two single nucleotide polymorphisms (SNPs), miR-146a rs2910164G>C and miR-499 rs3746444T>C, in a Han Chinese population. A case–control study consisting of 102 subjects with AS and 105 healthy controls was designed. The two miRNA SNPs were identified by direct sequencing. Subsequently, their gene and genotype frequencies were compared with healthy controls. A significant difference was observed in the miR-146a rs2910164G>C SNP. The frequency of the G allele was markedly higher in the AS patients than in the healthy controls (P = 0.005, Pc = 0.01, OR = 1.787), and the frequency of the GG genotype was higher in AS patients than in controls (P = 0.014, Pc = 0.042, OR = 2.516). However, no significant association was found between the miR-499 rs3746444T>C variant and susceptibility to AS. This is the first study to address the association between the miR-146a rs2910164G>C and miR-499 rs3746444T>C polymorphisms and AS, and it suggests a potential pathogenic factor for AS. Further studies are needed to validate our findings in a larger series, as well as in other ethnic backgrounds. [ABSTRACT FROM AUTHOR]

RT-qPCR is the accepted technique for the quantification of microRNA (miR) expression: however, stem-loop RT-PCR, the most frequently used method for quantification of miRs, is time- and reagent-consuming as well as inconvenient for scanning. We established a new method called ‘universal stem-loop primer’ (USLP) with 8 random nucleotides instead of a specific sequence at the 3′ end of the traditional stem-loop primer (TSLP), for screening miR profile and to semi-quantify expression of miRs. Peripheral blood samples were cultured with phytohaemagglutinin (PHA), and then 87 candidate miRs were scanned in cultured T cells. By USLP, our study revealed that the expression of miR-150-5p (miR-150) decreased nearly 10-fold, and miR-155-5p (miR-155) increased more than 7-fold after treated with PHA. The results of the dissociation curve and gel electrophoresis showed that the PCR production of the USLP and TSLP were specificity. The USLP method has high precision because of its low ICV (ICV<2.5%). The sensitivity of the USLP is up to 103 copies/µl miR. As compared with the TSLP, USLP saved 75% the cost of primers and 60% of the test time. The USLP method is a simple, rapid, precise, sensitive, and cost-effective approach that is suitable for screening miR profiles. [ABSTRACT FROM AUTHOR]

Purpose: Fast-track surgery aims to attenuate the surgical stress response, reduce complications, and shorten hospital stay. The goal of the present meta-analysis is to assess the safety and effectiveness of fast-track surgery in patients undergoing gastrectomy for gastric cancer compared with conventional perioperative care. Methods: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and reference lists of the identified studies were searched to identify randomized clinical trials that compared fast-track surgery with conventional perioperative care in patients undergoing gastrectomy for gastric cancer. Results: Five studies with a total of 400 patients were included in the meta-analysis. Meta-analysis shows that postoperative hospital stay (weighted mean difference (WMD) −1.87 days, 95 % confidence interval (CI), −2.46 to −1.28 days, P < 0.00001), time to first passage of flatus (WMD −0.71 days, 95 % CI, −1.03 to −0.39 days, P < 0.0001), and hospital costs (WMD −505.87 dollars, 95 % CI, −649.91 to −361.84 dollars, P < 0.00001) were significantly reduced for fast-track surgery. No significant differences were found for readmission rates (relative risk (RR), 1.97 95 % CI, 0.37 to 10.64, P = 0.43) and total postoperative complications (RR, 0.99 95 % CI, 0.56 to 1.76, P = 0.97). Conclusions: Fast-track surgery is safe and effective in gastrectomy for gastric cancer. Further randomized trials are needed to strengthen the conclusions. [ABSTRACT FROM AUTHOR]

Background: The safety and effectiveness of early oral feeding after colorectal surgery has not been determined. We performed a meta-analysis to evaluate surgical outcomes following early oral feeding compared with traditional oral feeding in patients undergoing elective colorectal surgery. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched to identify randomized clinical trials comparing the outcomes following early oral feeding versus traditional oral feeding in patients undergoing elective colorectal surgery. The trials must have reported at least one of the following end points: anastomotic dehiscence, pneumonia, wound infection, nasogastric tube reinsertion, vomiting, mortality, length of hospital stay, hospital costs, and quality of life. Results: Seven trials, which included a total of 587 patients, met our inclusion criteria. Compared with traditional oral feeding, early oral feeding reduced the length of hospital stay (weighted mean difference -1.58 days; 95% CI -2.77 to -0.39; p = 0.009) and the total postoperative complications (relative risk 0.70; 95% CI 0.50-0.98; p = 0.04). There were no significant differences in the risk of anastomotic dehiscence, pneumonia, wound infection, rate of nasogastric tube reinsertion, vomiting, or mortality. Conclusions: Early oral feeding is safe and effective in patients undergoing elective colorectal surgery. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Recently, two hepatic lineage markers epithelial cell adhesion molecule (EpCAM) and α-fetoprotein (AFP) were used to classify hepatocellular carcinoma (HCC) into four subtypes with prognostic implication. In the present study, we further evaluated the clinicopathologic and angiogenic characteristics among these HCC subtypes. EpCAM expression was investigated by immunohistochemistry in 115 HCC primary tumors. Based on EpCAM immunostaining and serum AFP levels, 115 HCC cases were classified into four subtypes: EpCAM+AFP+ (26.1%), EpCAM-AFP+ (20.0%), EpCAM+AFP- (20.8%), and EpCAM-AFP- (33.1%). EpCAM+AFP+ and EpCAM-AFP+ HCC were associated with late TNM stages and high frequencies of venous invasion, whereas EpCAM+AFP- and EpCAM-AFP- subtypes were associated with early TNM stages and low frequencies of venous invasion. Furthermore, EpCAM+AFP+ HCC had a significantly higher microvessel density (MVD) and higher level of VEGF (Vascular epithelial growth factor) expression than the other three subtypes. In conclusion, our study indicated that subtype classification of HCC based on EpCAM and AFP status had clinicopathologic and biologic implications in aggressive phenotype and angiogenesis. We also suggest that the EpCAM+AFP+ HCC patients might be potential therapeutic candidates for anti-angiogenesis therapy. [ABSTRACT FROM AUTHOR]

Objective. Postoperative fatigue syndrome (POFS) is a general and main complication after surgery. However, there is no stable and standardized animal model for POFS. The aim of the present study was to establish a rodent model of POFS by small intestinal resection, with POFS evaluated by acknowledged physical and behavioral methods. Material and Methods. Forty-two Sprague-Dawley rats were randomly divided into four groups according to the length of a 'middle' small intestinal resection: 0% (sham group; i.e., laparotomy alone), 10%, 40% and 70% groups, with corresponding lengths of small intestinal resections. Following surgery, the general state of health was evaluated. Tail suspension test, open field test and Morris water maze test were used to evaluate the degree of POFS. Serum albumin, transferrin, prealbumin and fibronectin were measured to assess the nutritional status, and superoxide dismutase (SOD) and malondialdehyde (MDA) were also measured. Results. As compared with the other three groups, the 70% small intestinal resection group showed the worst general state of health, decreased strength of the tail suspension test and decreased score of Morris water maze test ( p < 0.05) after operation. All rats in whom the small intestinal resection was done demonstrated a certain degree of malnutrition and behavior of depression, and the 70% resection group had the lowest levels of transferrin, prealbumin and fibronectin as compared with the other groups ( p < 0.05), as well as decreased SOD and increased MDA in serum ( p < 0.05). Conclusions. Resection of 70% of the small intestine resulted in typical characteristics of POFS. As this procedure is simple, stable and easily reproducible, it may serve as a model for research on POFS. [ABSTRACT FROM AUTHOR]

The magnetization reversal mechanism and temperature dependence of magnetic properties of \Cr(50\ \nm)/\break[\SmCo6(9\ \nm)/\Cu({ x\,\nm})/\Fe(5\ \nm)/\Cu( x\,\nm)]6/\Cr(100\ \nm)/a\-SiO2\,({ x}=0\--0.75) exchange spring multilayer films are reported. The initial curves and angular-dependent coercivities measurement indicate that the magnetization reversal mechanism of multilayer films is determined by domain-wall pinning. With lowering the temperature, the coercivities of multilayer films increase largely. By inserting Cu layer between the hard and soft layers can increase the coercivity of the multilayer films, especially at low temperatures. The hysteresis loops of the film with x=0.75 annealed at 500 ^\circ\C measured from 10 to 400 K show all the single-phase behavior, although the film contains a large amount of soft phase (\approx40 vol%), indicating the strong exchange coupling between the hard and soft phase and the extremely large nucleation field in the soft layers. With the decrease of temperature, the maximum energy product (BH)max and remanence also increase. A large (BH)max of about 37.4 MGOe is obtained at 10 K for the film with x=0.75 annealed at 500 ^\circ\C. The recoiling curves as well as the irreversible change in magnetization -\Delta Mirrev(H)/2Mr=[Mr-Md(H)]/2Mr versus the reverse field H demonstrate the increase of the inhomogeneity and pinning in the hard layer at the low temperature as well as after the addition of Cu, therefore, an improved coercivity. [ABSTRACT FROM AUTHOR]

Objective. Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. Materials and methods. Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, αα-smooth muscle actin (αα-SMA) and transforming growth factor-ββ1 (TGF-ββ1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. Results. Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group ( p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group ( p < 0.01). The expression of αα-SMA and TGF-ββ1 in HDg was less than that in the fibrosis group and LDg ( p < 0.01). Conclusion. Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation. [ABSTRACT FROM AUTHOR]

Delivery to intracellular target sites is still one of the main obstacles in the development of peptide nucleic acids (PNAs) as antisense-antigene therapeutics. Here, we designed a self-assembled oligonucleotide scaffold that included a central complementary region for self-assembly and lateral regions complementing the PNAs. Assembly of cell-penetrating peptide (CPP)-PNAs on the scaffold significantly promoted endocytosis of PNAs by at least 10-fold in cell cultures, particularly for scaffolds in which the central complementary region was assembled by poly(guanine) and poly(cytosine). The antisense activity of CPP-PNAs increased by assembly on the scaffold and was further enhanced after co-assembly with endosomolytic peptide (EP)-PNA. This synergistic effect was also observed following the assembly of antigene CPP-PNAs\EP-PNAs on the scaffold. However, antigene activity was only observed by targeting episomal viral DNA or transfected plasmids, but not the chromosome in the cell cultures. In conclusion, assembly on oligonucleotide scaffolds significantly enhanced the antisense-antigene activity of PNAs by promoting endocytosis and endosomal escape. This oligonucleotide scaffold provided a simple strategy for assembly of multiple functional peptide-PNA conjugates, expanding the applications of PNAs and demonstrating the potential of PNAs as antiviral therapeutics. [ABSTRACT FROM AUTHOR]