Objective

The purpose of this study was to determine the role of Ureaplasma urealyticum-derived lipidassociated membrane proteins (LAMPs) in the host innate immune system, specifically their effect on Toll-like receptors (TLRs).

Methods

LAMPs were derived from U. urealyticum strains, and human amniotic epithelial cells (HAECs) were isolated from healthy full-term placentas. Cytokine concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and TLR2 mRNA by real-time PCR. Expression of TLR2 was confirmed by Western blotting and immunohistochemistry.

Results

LAMPs induced HAECs to produce inflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α. Cytokine production was reduced after blocking TLR2 using TLR2 inhibitor (anti-hTLR2-IgA).

Conclusions

LAMPs isolated from U. urealyticum induced TLR2-dependent up-regulation of inflammatory genes and cytokines in HAECs.

Objective

Scandix pecten-veneris L. is a less studied wild edible herb and is considered an extinct plant species in many parts of the world. This study was designed to evaluate its phytochemical composition and biological potential of S. pecten-veneris L.

Methods

Phytochemicals including alkaloids, flavonoids, polyphenols, and tannins were determined in extracts of S. pecten-veneris. Antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), while reducing power was tested by ferric reducing/antioxidant power (FRAP) assay. Antimicrobial activity against seven bacterial and four fungal strains was evaluated using agar well diffusion assay. Enzymes inhibition study was performed for urease, phosphodiesterase-I, and catalase-II.

Results

S. pecten-veneris showed moderate antiradical activity and reducing potential of hydroxyl radicals to about 20% of the initial value. The antioxidant activity of various extracts of S. pecten-veneris showed a linear correlation with total phenolic contents in the order of water>n-butanol>chloroform>ethyl acetate>methanol extracts. S. pecten-veneris leaves showed the highest inhibitory activity against Staphylococcus aureus while the highest antifungal activity was observed against Candida albicans. The plant extract was most potent against urease enzymes but showed moderate activity against phosphodiestrase-I and carbonic anhydrase-II.

Conclusions

Our data demonstrate that in addition to its culinary uses, S. pecten-veneris has good medicinal potential and hence could be used for treating some specific health ailments.

Background

Leber congenital amaurosis (LCA) is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology. This study is to identify gene variants responsible for LCA in a Chinese family using direct Sanger sequencing, with the help of phenotype-genotype correlations.

Methods

A Chinese family with six members including two individuals affected with LCA was studied. All patients underwent a complete ophthalmic examination. Based on phenotype-genotype correlation, direct Sanger sequencing was performed to identify the candidate gene on all family members and normal controls. Targeted next-generation sequencing was used to exclude other known LCA genes.

Results

By Sanger sequencing, we identified two novel missense variants in the retinol dehydrogenase 12 (RDH12) gene: a c.164C>A transversion predicting a p.T55K substitution, and a c.535C>G transversion predicting a p.H179D substitution. The two affected subjects carried both RDH12 variants, while their parents and offspring carried only one of heterozygous variants, showing complete cosegregation of the variants. The compound heterozygous variants were not present in 600 normal controls. Besides, the RDH12 variants were confirmed by targeted next-generation sequencing.

Conclusions

The RDH12 compound heterozygous variants might be the cause of the LCA family. Our study adds to the molecular spectrum of RDH12-related retinopathy and offers an effective example of the power of phenotype-genotype correlations in molecular diagnosis of LCA.

Objective

The aim of this study was to formulate polymer-based artesunate nanoparticles for malaria treatment.

Methods

Artesunate was loaded with poly(D,L-lactic-co-glycolic acid) (PLGA) by solvent evaporation from an oil-in-water single emulsion. Nanoparticles were characterized by X-ray diffraction and differential scanning calorimetry analyses. In vivo antimalarial studies at 4 mg/kg were performed on Swiss male albino mice infected with Plasmodium berghei. Hematological and hepatic toxicity assays were performed. In vitro cytotoxicity of free and encapsulated artesunate (Art-PLGA) to cell line RAW 264.7 was determined at concentrations of 7.8–1000 μg/ml.

Results

The particle size of the formulated drug was (329.3±21.7) nm and the entrapment efficiency was (38.4±10.1)%. Art-PLGA nanoparticles showed higher parasite suppression (62.6%) compared to free artesunate (58.2%, P<0.05). Platelet counts were significantly higher in controls (305 000.00±148 492.40) than in mice treated with free artesunate (139 500.00±20 506.10) or Art-PLGA (163 500.00±3535.53) (P<0.05). There was no sign of hepatic toxicity following use of the tested drugs. The half maximal inhibitory concentration (IC₅₀) of Art-PLGA (468.0 μg/ml) was significantly higher (P<0.05) than that of free artesunate (7.3 μg/ml) in the in vitro cytotoxicity assay.

Conclusions

A simple treatment of PLGA-entrapped artesunate nanoparticles with dual advantages of low toxicity and better antiplasmodial efficacy has been developed.

Objective

The aim of this study was to explore the association of dopamine receptor D2 (DRD2) polymorphism and alleviation of obesity in children and adolescents after 8-year follow-up.

Methods

This retrospective cohort study included obese children and adolescents with a follow-up period of 8 years. Baseline clinical characteristics and DRD2 polymorphisms (including rs1076562, rs2075654, and rs4586205) were extracted from medical records. A follow-up visit was performed in May 2017 to collect related data including height, weight, diet compliance, and exercise compliance.

Results

One hundred and nine obese children and adolescents were included in the current study. Among three DRD2 single nucleotide polymorphisms, only rs2075654 had a statistically significant association with alleviation of obesity, as the alleviation rate for minor allele carriers (68.6% for TC+TT) was higher compared to the major allele homozygote (43.3% for CC). After adjusting for all related factors, the hazard ratio of rs2075654 minor allele carriers for the alleviation of obesity was 3.34 (95% confidence interval (CI): 1.30?8.58).

Conclusions

The rs2075654 polymorphism of DRD2 is related to long-term obesity alleviation in obese Chinese children and adolescents.

Objective

To investigate the antibacterial mechanism of high-mobility group nucleosomal-binding domain 2 (HMGN2) on Escherichia coli K12, focusing on the antibacterial and antibiofilm formation effects. Its chemotactic activity on human neutrophils was also investigated.

Methods

Human tissue-derived HMGN2 (tHMGN2) was extracted from fresh uterus fiber cystadenoma and purified by HP1100 reversed-phase high-performance liquid chromatography (RP-HPLC). Recombinant human HMGN2 (rHMGN2) was generated in E. coli DE3 carrying PET-32ac(+)- HMGN2. Antibacterial activity of HMGN2 was determined using an agarose diffusion assay and minimum inhibitory concentration (MIC) of HMGN2 was determined by the microdilution broth method. Bacterial membrane permeability assay and DNA binding assay were performed. The antibiofilm effect of HMGN2 was investigated using a crystal violet assay and electron microscopy scanning. The activating effect and chemotactic activity of HMGN2 on neutrophils were determined using a nitroblue tetrazolium (NBT) reduction assay and Transwell chamber cell migration assay, respectively.

Results

HMGN2 showed a relatively high potency against Gram-negative bacteria E. coli and the MIC of HMGN2 was 16.25 μg/ml. Elevated bacterial membrane permeability was observed in HMGN2-treated E. coli K12. HMGN2 could also bind the bacterial plasmid and genomic DNA in a dose-dependent manner. The antibiofilm effect of HMGN2 on E. coli K12 was confirmed by crystal violet staining and scanning electron microscopy. However, the activating effects and chemotactic effects of HMGN2 on human neutrophils were not observed.

Conclusions

As an antimicrobial peptide (AMP), HMGN2 possessed a good capacity for antibacterial and antibiofilm activities on E. coli K12. This capacity might be associated with disruption of the bacterial membrane and combination of DNA, which might affect the growth and viability of E. coli.

Objective

Fruit of Phyllanthus emblica Linn. (PE) is widely consumed as a functional food and used as a folk medicine due to its remarkable nutritional and pharmacological effects. Mitomycin C (MMC) and cisplatin (cDDP) are the most widely used forms of chemotherapeutic drug, but their clinical use is limited by their genotoxicity to normal cells. We aimed to determine whether PE has potential to reduce the genotoxicity, while improving the anticancer effect, of MMC and cDDP.

Methods

Cell proliferation was evaluated using the trypan blue exclusion assay and colony-forming assay. Genomic instability (GIN) was measured using the cytokinesis-block micronucleus assay.

Results

Co-treatment (72 h) with PE at 20–320 μg/ml significantly enhanced the efficacy of MMC (0.05 μg/ml) and cDDP (1 μg/ml) against Colo205 colorectal cancer cells (P<0.05), and at 80–320 μg/ml significantly decreased MMCand cDDP-induced GIN and multinucleation in normal colonic NCM460 cells (P<0.05). PE significantly decreased the mitotic index (P<0.01), blocked mitotic progression (P<0.05), and promoted apoptosis (P<0.01) in MMC- and cDDP-treated NCM460 cells, suggesting that PE-mediated inhibition of mitosis and induction of apoptosis may limit the division and survival of highly damaged cells. Also, PE was found to inhibit the clonal expansion of MMC- and cDDP-treated NCM460 cells (P<0.05) and decrease the heterogeneity of the surviving clones.

Conclusions

PE potentiates the anticancer efficacy of MMC and cDDP, while preventing their genotoxicity and inhibiting clonal expansions of unstable genomes in normal cells. These data suggest that PE has the potential to reduce the risk of secondary cancers induced by chemotherapeutics.

Background

A lot of studies have demonstrated that C242T polymorphism in CYBA genes may play an important role in the pathological process of acute coronary syndrome (ACS). However, the results are not consistent. To further evaluate this debate, we performed a meta-analysis to determine the relationship between C242T polymorphism and ACS.

Methods and results

We screened PubMed/MEDLINE, EBSCIO, and EMBASE research reports until Mar. 2014 and extracted data from 10 studies involving 6102 ACS patients and 8669 controls. Subgroup analysis by ethnicity documented a significant decreased risk of ACS for C242T polymorphism in the Asian population under allelic comparison (odd ratio (OR) 0.73; 95% confidence intervals (CI) 0.64–0.83), dominant model (OR 0.71; 95% CI 0.62–0.82), and homozygote comparison (OR 0.57; 95% CI 0.35–0.92). However, in the overall population and especially with Caucasians, no significant association was uncovered. Further meta-regression analysis revealed that the heterogeneity among studies was largely attributed to ethnicity. No publication bias was detected through a funnel plot and an Egger’s linear regression test.

Conclusions

Taken together, our results suggest that the C242T polymorphism might be a protective factor against developing ACS in the Asian population. Further researches will be needed to identify the confounding factors which modified the protective effect of T allele among Caucasians.

Objective

The purpose of this meta-analysis was to explore the effect of corticosteroids on atrial fibrillation (AF) following catheter ablation.

Methods

We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for published articles describing the effect of corticosteroids in preventing AF recurrence after catheter ablation. Data on study and patient were extracted. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by use of a random-effect model, and P values of <0.05 were considered significant.

Results

Two randomized controlled trials (RCTs) and three cohort studies involving 846 patients were included in this meta-analysis. Within one month of catheter ablation, corticosteroid use was associated with a declined risk of recurrence of AF in RCT (RR 0.57, 95% CI 0.39 to 0.85, P=0.005), but without significant effect in cohort studies (RR 1.01, 95% CI 0.79 to 1.30, P=0.94). After three months of catheter ablation, corticosteroids did not have a significant effect in the prevention of late recurrence of AF in either RCT (RR 0.78, 95% CI 0.38 to 1.59, P=0.49) or cohort studies (RR 0.96, 95% CI 0.70 to 1.31, P=0.78).

Conclusions

Our meta-analysis suggested that periprocedural administration of corticosteroids of catheter ablation was associated with reduction of early but not late recurrence of AF.

Objective

The relative preventative efficacy of amiodarone and lidocaine for ventricular fibrillation (VF) after release of an aortic cross-clamp (ACC) during open heart surgery has not been determined. This meta-analysis was designed to systematically evaluate the influence of amiodarone, lidocaine, or placebo on the incidence of VF after ACC.

Methods

Prospective randomized controlled trials (RCTs) that compared the VF-preventative effects of amiodarone with lidocaine, or amiodarone or lidocaine with placebo were included. PubMed, EMBASE, and the Cochrane Library were searched for relevant RCTs. Fixed or randomized effect models were applied according to the heterogeneity of the data from the selected studies.

Results

We included eight RCTs in the analysis. Pooled results suggested that the preventative effects of amiodarone and lidocaine were comparable (relative risk (RR)=1.12, 95% confidence interval (CI): 0.70 to 1.80, P=0.63), but both were superior to the placebo (amiodarone, RR=0.71, 95% CI: 0.51 to 1.00, P=0.05; lidocaine, RR=0.63, 95% CI: 0.46 to 0.88, P=0.006). The percentage of patients requiring electric defibrillation counter shocks (DCSs) did not differ significantly among patients administered amiodarone (RR=0.21, 95% CI: 0.04 to 1.19, P=0.08), lidocaine (RR=2.44, 95% CI: 0.13 to 44.02, P=0.55), or the placebo (RR=0.56, 95% CI: 0.25 to 1.25, P=0.16).

Conclusions

Amiodarone and lidocaine are comparably effective in preventing VF after ACC, but the percentage of patients who subsequently require DCSs does not differ among those administered amiodarone, lidocaine, or placebo.

Objective

To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG).

Methods

One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs (^*2,^*3,^*17) were genotyped and possible haplotypes were analyzed.

Results

The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H₀ to H₅) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H₁ showed a significantly lower incidence of HTPR than the reference haplotype (H₀) in the total study population while haplotypes H₁ and H₂ showed significantly lower incidences of HTPR than H₀ in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR.

Conclusions

The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

Objective

Three mainstream techniques—laparoscopic hepatectomy (LH), percutaneous radiofrequency ablation (pRFA), and open hepatectomy (OH)—were compared in this study, in terms of their efficacies in the treatment of small hepatocellular carcinoma (HCC).

Methods

A comparative study was performed within a total of 94 patients diagnosed with small HCC in our hospital from 2005 to 2010, who underwent LH (28), RFA (33), or OH (33). They had either a single tumor lesion of less than 5 cm or up to three nodules with diameters of less than 3 cm each. Outcomes were carefully evaluated throughout a 3-year follow-up interval and statistically interpreted.

Results

The pRFA group had a significantly lower disease-free survival rate compared with the two surgical groups (P=0.001) and significantly shorter overall survival (P=0.005), while the LH group and the OH group had no difference in survival results. For patients younger than 60 years old, surgical approaches offered a better long-term overall survival prognosis (P=0.008). There were no statistically significant differences among the three groups in overall survival for elderly patients (P=0.104).

Conclusions

Among patients with small HCC, LH may provide better curative effects than pRFA without increasing complication rates. pRFA leads to faster recurrence than surgical resections. LH has similar therapeutic effects to OH and causes less trauma. For patients younger than 60 years old, LH may be the best curative treatment. Elderly patients may choose either surgery or pRFA.

Objective

Salmonella enterica remains a major cause of food-borne disease in humans, and Salmonella Typhimurium (ST) contamination of poultry products is a worldwide problem. Since macrophages play an essential role in controlling Salmonella infection, the aim of this study was to evaluate the effect of glycyrrhizic acid (GA) on immune function of chicken HD11 macrophages.

Methods

Chicken HD11 macrophages were treated with GA (0, 12.5, 25, 50, 100, 200, 400, or 800 μg/ml) and lipopolysaccharide (LPS, 500 ng/ml) for 3, 6, 12, 24, or 48 h. Evaluated responses included phagocytosis, bacteria-killing, gene expression of cell surface molecules (cluster of differentiation 40 (CD40), CD80, CD83, and CD197) and antimicrobial effectors (inducible nitric oxide synthase (iNOS), NADPH oxidase-1 (NOX-1), interferon-γ (IFN-γ), LPS-induced tumor necrosis factor (TNF)-α factor (LITAF), interleukin-6 (IL-6), and IL-10), and production of nitric oxide (NO) and hydrogen peroxide (H₂O₂).

Results

GA increased the internalization of both fluorescein isothiocyanate (FITC)-dextran and ST by HD11 cells and markedly decreased the intracellular survival of ST. We found that the messenger RNA (mRNA) expression of cell surface molecules (CD40, CD80, CD83, and CD197) and cytokines (IFN-γ, IL-6, and IL-10) of HD11 cells was up-regulated following GA exposure. The expression of iNOS and NOX-1 was induced by GA and thereby the productions of NO and H₂O₂ in HD11 cells were enhanced. Notably, it was verified that nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways were responsible for GA-induced synthesis of NO and IFN-γ gene expression.

Conclusions

Taken together, these results suggested that GA exhibits a potent immune regulatory effect to activate chicken macrophages and enhances Salmonella-killing capacity.

Objective

The aim of this study was to compare complications and oncologic outcomes of patients undergoing laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (LDP) at a single center.

Methods

Distal pancreatectomies performed for pancreatic ductal adenocarcinoma during a 4-year period were included in this study. A retrospective analysis of a database of this cohort was conducted.

Results

Twenty-two patients underwent LDP for pancreatic ductal adenocarcinoma, in comparison to seventy-six patients with comparable tumor characteristics treated by LDP. No patients with locally advanced lesions were included in this study. Comparing LDP group to LDP group, there were no significant differences in operation time (P=0.06) or blood loss (P=0.24). Complications (pancreatic fistula, P=0.62; intra-abdominal abscess, P=0.44; postpancreatectomy hemorrhage, P=0.34) were similar. There were no significant differences in the number of lymph nodes harvested (11.2±4.6 in LDP group vs. 14.4±5.5 in LDP group, P=0.44) nor the rate of patients with positive lymph nodes (36% in LDP group vs. 41% in LDP group, P=0.71). Incidence of positive margins was similar (9% in LDP group vs. 13% in LDP group, P=0.61). The mean overall survival time was (29.6±3.7) months for the LDP group and (27.6±2.1) months for LDP group. There was no difference in overall survival between the two groups (P=0.34).

Conclusions

LDP is a safe and effective treatment for selected patients with pancreatic ductal adenocarcinoma. A slow-compression of pancreas tissue with the GIA stapler is effective in preventing postoperative pancreatic fistula. The oncologic outcome is comparable with the conventional open approach. Laparoscopic radical antegrade modular pancreatosplenectomy contributed to oncological clearance.

Objective

To evaluate the comparative therapeutic efficacy of radiofrequency ablation (RFA) and hepatic resection (HR) for breast cancer liver metastases (BCLMs).

Methods

Studies that had examined the outcomes for both RFA and HR for BCLM were identified by searching the electronic databases PubMed, EMBASE, and the Cochrane Library. Pooled analyzes of the overall survival (OS), disease-free survival (DFS), and short-term outcomes of BCLM were performed.

Results

Patients with BCLM gained many more survival benefits from HR than from RFA with regard to the 3-year OS rate (combined odds ratio (OR) 0.41, 95% confidence interval (CI) 0.29–0.59, P<0.001), 5-year OS rate (combined OR 0.38, 95% CI 0.32–0.46, P<0.001), 3-year DFS (combined OR 0.36, 95% CI 0.27–0.49, P<0.001), and 5-year DFS (combined OR 0.51, 95% CI 0.40–0.66, P<0.001). RFA had fewer postoperative complications (combined OR 0.30, 95% CI 0.20–0.44, P<0.001) and shorter hospital stays (combined OR -9.01, 95% CI -13.49–4.54, P<0.001) than HR.

Conclusions

HR takes precedence over RFA in the treatment of patients with BCLM, considering the better survival rate. RFA gives rise to fewer complications and can be carried out with a shorter hospital stay, compared to HR. RFA should be reserved for patients who are not optimum candidates for resection.

Background and objective

Rivaroxaban is a new oral anticoagulant for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), which has less drug–food interaction than warfarin. We conducted this prospective randomized study to evaluate the metabolic benefits as well as the safety and efficacy with rivaroxaban versus warfarin in patients with NVAF following radiofrequency catheter ablation (RFCA).

Methods

From April to July 2014, 60 patients with NVAF undergoing RFCA were prospectively enrolled in our study. Following RFCA, all patients were randomly assigned to receive rivaroxaban (Group R, n=30) or warfarin (Group W, n=30). Metabolic indices including serum total protein, albumin, globulin, and high-density lipoprotein (HDL) as well as bleeding, stroke, and systemic thromboembolism events were evaluated and compared during follow-up after 15, 30, 60, and 90 d of RFCA procedure.

Results

Serum total protein, albumin, globulin, and HDL levels were all significantly elevated at each follow-up stage in Group R when compared to the baseline (P<0.05 respectively). In Group W, the metabolic indices decreased at first and then had an increasing trend. There were no deaths or thromboembolic complications in each group. The prevalence of total bleeding complications was similar between Group R and Group W (11/30, 36.7% vs. 10/30, 33.3%, P=0.79).

Conclusions

Patients with NVAF receiving rivaroxaban after RFCA procedures appear to benefit from a metabolic perspective compared with warfarin, providing practical clinical reference for the choice of the anticoagulant. Rivaroxaban seems to be as safe and effective in preventing thromboembolic events as warfarin for these patients.

Objective

This study explored the effects of different light curing modes and ethanol-wet bonding on dentin bonding strength and durability.

Methods

A total of 54 molars were randomly divided into three groups: Single Bond 2, Gluma Comfort Bond, and N-Bond. Based on the three light-curing modes and presence or absence of ethanol pretreatment, the samples were assigned to six subgroups: high-light mode, ethanol pretreatment+high-light mode, soft-start mode, ethanol pretreatment+soft-start mode, standard mode, and ethanol pretreatment+standard mode. All samples were bonded with resin based on the experimental groups. After 24 h and 6 months of water storage, a universal testing machine was used to measure microtensile bond strength. Scanning electron microscopy (SEM) was applied to observe mixed layer morphology.

Results

The 24-h and 6-month microtensile bond strengths of the ethanol pretreatment groups were significantly higher than those of the non-ethanol pretreatment groups at the same light modes (P<0.05). With or without ethanol pretreatment, the microtensile bond strengths of the high-light modes were significantly lower than those of the soft-start modes and standard modes (P<0.05). The microtensile bond strengths of samples from the 6-month water storage group significantly decreased compared with those of samples from the 24-h water storage group (P<0.05). The soft-start groups and standard groups formed better mixed layers than the high-light mode groups, whereas the ethanol pretreatment groups formed more uniform mixed layers than those without ethanol pretreatment.

Conclusions

Ethanol-wet bonding technique, soft-start, and standard modes could improve dentin bonding properties.