Search

Background The implementation of antibiotic intravenous-to-oral switch (IVOS) therapy in hospitals can slow down the development of drug resistance, reduce the occurrence of adverse reactions, and bring significant economic benefits. The aim of this study is to investigate the understanding of physicians at the Second Affiliated Hospital of Soochow University in Suzhou, China towards the antibiotic IVOS therapy. Methods 15 physicians working in 9 different departments of the Second Affiliated Hospital of Soochow University participated in this study. A semi-structured face-to-face interview was conducted to collect interview information about the antibiotic IVOS therapy. NVivo12 software was used to organize the entire interview content, and the interview data was analyzed and summarized using the Colaizzi seven step method. Results 60% of participants were not familiar with antibiotic IVOS therapy. Barriers of antibiotic IVOS therapy were included by three key issues: (i) Physicians’ potential cognition: ‘Iv is always better than oral’; (ii) Subjective infusion intention of patients; and (iii) Limitations of drug selection. 60% of participants expressed welcome for pharmacists to help them perform antibiotic IVOS treatment. And electronic recognition technology may be a feasible method for prompting IVOS conversion that recognized by all participants in the interview. Participants also provided some suggestions for pharmacists and IVOS computer reminders. Conclusion Physicians’ in China still have insufficient understanding of antibiotic IVOS therapy. The promotion of antibiotic IVOS therapy in China faces many challenges and obstacles. Strategies such as IVOS therapy computer reminders and clinical pharmacists’ medication guidance were worth studying to help physicians develop antibiotic IVOS treatment. [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery after surgery (ERAS) pathway in spine surgery is increasingly popular which can reduce the length of hospital stay (LOS). However, there are few studies on the safety and effectiveness of ERAS pathway in the treatment of single-level lumbar disc herniation (LDH) by percutaneous endoscopic transforaminal discectomy (PETD). The aim of this study was to investigate whether ERAS can reduce LOS of patients with single segment LDH treated by PETD. Methods: We reviewed the outcomes of all LDH patients (L4/5) who had been treated with PETD at our institution. Quasi-experimental study was adopted between patients treated in an ERAS after PETD with those rehabilitated on a traditional pathway. The two groups were analyzed for LOS, operation time, complications, visual analog scale (VAS), Oswestry Dysfunction Index (ODI), hospitalization expenses (HE), and improved MacNab efficacy assessment criteria (MacNab). Results: A total of 120 single segment LDH patients (ERAS pathway 60 cases, traditional care pathway 60 cases) who were selected from January 2019 to January 2021 met the inclusion criteria. There was a significant difference in mean LOS postoperative VAS scores and ODI on the 3rd day after surgery between the two groups (P < 0.05). The incidence of complications and HE were similar in the two groups (P > 0.05). The mean LOS decreased from 3.47 ± 1.14 days to 5.65 ± 1.39 days after application of ERAS pathway (P < 0.05). Conclusions: The ERAS pathway reduced LOS without resulting in additional complications after PETD. These findings support the application of the perioperative ERAS pathway in the treatment of single-level LDH with PETD. Level of evidence: Level IV, therapeutic [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and treatment is vital for effective tuberculosis (TB) management especially among migrant populations who are a vulnerable group. We aimed to study factors associated with delay before registration at country level among registered migrant TB patients in China (2014-15) who were transferred out (during treatment) through web-based TB information management system (TBIMS).Methods: This was a cross sectional study involving review of TBIMS data. Delays (in days) were classified as follows: patient delay (from symptom onset to first doctor visit), health system delay (from first doctor visit to treatment initiation, divided into health system diagnosis and treatment delay before and after date of diagnosis respectively), diagnosis delay (from symptom onset to diagnosis) and total delay (from symptom onset to treatment initiation). Linear regression was used to build a predictive model (forward stepwise) for the socio-demographic, clinical and health system related factors associated with delay: one model for each type of delay. Delays were log transformed and included in the model.Results: The median (IQR) patient delay, health system delay and total delay was 16 (6, 34), two (0, 6) and 22 (11, 41) days respectively. Factors associated with long patient, diagnosis and total delay were: female gender, age ≥ 65 years, sputum smear positive pulmonary TB and registration at referral hospital. Treatment initiation delay was significantly higher among those registered in referral hospitals, unemployed and previously treated. Among migrant patients having permanent residence out of province, health system diagnosis delay was significantly higher while treatment initiation delay after diagnosis was significantly lower when compared to patients having permanent residence within the prefecture.Conclusion: Among migrant population with TB, patient delay contributed to the total delay. The factors identified including the need for improved coordination between referral hospitals and national programme have to be addressed if China has to end TB. [ABSTRACT FROM AUTHOR]

Background: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014.Methods: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards.Results: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively.Conclusions: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended. [ABSTRACT FROM AUTHOR]

Background: In addition to additive genetic effects, epistatic interactions can play key roles in the control of phenotypic variation of traits of interest. In the current study, 475 male birds from lean and fat chicken lines were utilized as a resource population to detect significant epistatic effects associated with growth and carcass traits. Results: A total of 421 significant epistatic effects were associated with testis weight (TeW), from which 11 sub-networks (Sub-network1 to Sub-network11) were constructed. In Sub-network1, which was the biggest network, there was an interaction between GGA21 and GGAZ. Three genes on GGA21 (SDHB, PARK7 and VAMP3) and nine genes (AGTPBP1, CAMK4, CDC14B, FANCC, FBP1, GNAQ, PTCH1, ROR2 and STARD4) on GGAZ that might be potentially important candidate genes for testis growth and development were detected based on the annotated gene function. In Sub-network2, there was a SNP on GGA19 that interacted with 8 SNPs located on GGA10. The SNP (Gga_rs15834332) on GGA19 was located between C-C motif chemokine ligand 5 (CCL5) and MIR142. There were 32 Refgenes on GGA10, including TCF12 which is predicted to be a target gene of miR-142-5p. We hypothesize that miR-142-5p and TCF12 may interact with one another to regulate testis growth and development. Two genes (CDH12 and WNT8A) in the same cadherin signaling pathway were implicated as potentially important genes in the control of metatarsus circumference (MeC). There were no significant epistatic effects identified for the other carcass and growth traits, e.g. heart weight (HW), liver weight (LW), spleen weight (SW), muscular and glandular stomach weight (MGSW), carcass weight (CW), body weight (BW1, BW3, BW5, BW7), chest width (ChWi), metatarsus length (MeL). Conclusions: The results of the current study are helpful to better understand the genetic basis of carcass and growth traits, especially for testis growth and development in broilers. [ABSTRACT FROM AUTHOR]

Background: The study aims to compare the long-term functional and radiographic outcomes of two devices for the treatment of primary intertrochanteric fractures (IFs, OTA 3.1A2.1-A2.3) in elderly patients with osteoporosis. Methods: Between December 2010 and August 2014, 332 elderly osteoporosis patients with IFs (OTA 3.1A2.1-A2.3) fixed by an InterTAN nail (IT) or a proximal femoral nail anti-rotation (PFNA) device were retrospectively evaluated. Follow-up occurred 1, 3, 6, and 12 months postoperatively and every year thereafter. Mortality was recorded. Patient-related functional and radiographic outcomes were compared. The primary endpoint was the long-term radiographic outcomes. The secondary endpoint was the long-term functional outcomes. Results: A total of 283 patients (283 hips) with osteoporosis (IT, n = 144; PFNA, n = 139) were evaluated with a mean follow-up period of 38.8 months (range, 36-43 months). No between-group significant differences were noted in the patient demographics, operation variables, and postoperative Harris Hip Score. More radiographic complications were noted in terms of screw cut-out, femoral shaft fracture distal or around the tip of the main nail, and varus collapse of the femoral head in the PFNA group compared with that in the IT group (P < 0.05). Conclusion: For osteoporotic IFs (OTA 3.1A2.1-A2.3) in elderly patients, the use of IT aids in decreasing radiographic complications, but the between-group functional outcomes showed no significant difference. [ABSTRACT FROM AUTHOR]

Background: CB-1 and K326 are closely related tobacco cultivars; however, their cold tolerance capacities are different. K326 is much more cold tolerant than CB-1. Results: We studied the transcriptomes and metabolomes of CB-1 and K326 leaf samples treated with cold stress. Totally, we have identified 14,590 differentially expressed genes (DEGs) in CB-1 and 14,605 DEGs in K326; there was also 200 differentially expressed metabolites in CB-1 and 194 in K326. Moreover, there were many overlapping genes (around 50%) that were cold-responsive in both plant cultivars, although there were also many differences in the cold responsive genes between the two cultivars. Importantly, for most of the overlapping cold responsive genes, the extent of the changes in expression were typically much more pronounced in K326 than in CB-1, which may help explain the superior cold tolerance of K326. Similar results were found in the metabolome analysis, particularly with the analysis of primary metabolites, including amino acids, organic acids, and sugars. The large number of specific responsive genes and metabolites highlight the complex regulatory mechanisms associated with cold stress in tobacco. In addition, our work implies that the energy metabolism and hormones may function distinctly between CB-1 and K326. Conclusions: Differences in gene expression and metabolite levels following cold stress treatment seem likely to have contributed to the observed difference in the cold tolerance phenotype of these two tobacco cultivars. [ABSTRACT FROM AUTHOR]

Background: Recently, the prevalence of chromosomal abnormalities (CA) increased as the increasing proportion of mothers with advanced age. We aimed to explore the prevalence of CA in relation to maternal age and perinatal features. Methods: A retrospective study was performed based on provincial birth defects surveillance data. The relative risk (RR) and 95% confidence interval (CI) were used to calculate maternal age-specific rates of CA. Socio-demographic characteristics of mothers and perinatal features were listed. Results: The total prevalence of CA was 6.38 per 10,000 births, which increased per 10,000 births linearly from 4.02 in 2011 to 9.13 in 2015 (χ²line-trend =52.69, p < 0.001). During this period, the prevalence for CA per 10,000 births among women over 35 years old increased from 15.34 in 2011 to 33.82 in 2015 (χ²line-trend =115121.6, p < 0.001). The RR for overall CA, trisomy 21(T21), trisomy 18(T18) and others in mothers 35 years or older were 6.64 (95% CI 5.55 ~ 7.93), 6.83 (95% CI 5.63 ~ 8.30), 4.06 (95% CI 2.09 ~ 7.90) and 7.54 (95% CI 4.02 ~ 14.11) respectively in comparison to mothers aged 25-29 years old. The stillbirths rate for total CA was 76.45%. T21 and T18 were strongly associated with multiple anomalies, especially congenital heart abnormalities. Conclusions: The prevalence of CA increased as maternal age increased. Cases with CA were associated with other congenital defects and high mortality risk. [ABSTRACT FROM AUTHOR]

Quizalofop-p-ethyl (QPE) is a post-emergence herbicide that effectively controls grass weeds and is often detected in the environment. However, the biochemical and molecular mechanisms of QPE degradation in the environment remains unclear. In this study, a highly effective QPE-degrading bacterial strain J-2 was isolated from acclimated activated sludge and identified as a Pseudomonas sp., containing the QPE breakdown metabolite quizalofop acid (QA) identified by Liquid Chromatography-Ion Trap-Mass Spectrometry (LC-IT-MSn) analysis. A novel QPE hydrolase esterase-encoding gene qpeH was cloned from strain J-2 and functionally expressed in Escherichia coli BL21 (DE3). The specific activity of recombinant QpeH was 198.9 ± 2.7 U mg-1 for QPE with Km and Kcat values of 41.3 ± 3.6 μM and 127.3 ± 4.5 s-1. The optimal pH and temperature for the recombinant QpeH were 8.0 and 30 °C, respectively and the enzyme was activated by Ca2+, Cd2+, Li+, Fe3+ and Co2+ and inhibited by Ni2+, Fe2+, Ag+, DEPC, SDS, Tween 80, Triton X, β-mercaptoethanol, PMSF, and pCMB. In addition, the catalytic efficiency of QpeH toward different AOPP herbicides in descending order was as follows: fenoxaprop-P-ethyl > quizalofop-P-tefuryl > QPE > haloxyfop-P-methyl > cyhalofopbutyl > clodinafop-propargyl. On the basis of the phylogenetic analysis and multiple sequence alignment, the identified enzyme QpeH, was clustered with esterase family V, suggesting a new member of this family because of its low similarity of amino acid sequence with esterases reported previously. . [ABSTRACT FROM AUTHOR]

Background: Ruminants serve as one of the most important reservoirs for pathogenic Escherichia coli. Infection with E. coli, a foodborne enteropathogen, can lead to asymptomatic infections that can cause life-threatening complications in humans. Therefore, from a clinical and human health perspective, it is important to know which virulence genes, phylogenetic groups, serogroups, and antibiotic resistance patterns are present in E. coli strains in yaks with diarrheic infections. Methods: Two-hundred and ninety-two rectal swabs were collected from diarrheic yaks in Qinghai Plateau, China. The antimicrobial sensitivity of each resulting isolate was evaluated according to the disk diffusion method, and different PCR assays were performed for the detection of virulence genes and different phylogroups. Additionally, strains were allocated to different serogroups based on the presence of O antigen via the slide agglutination method. Results: Among the E. coli isolates tested, most of the isolates were multidrug resistant (97%) and harbored at least one virulence gene (100%). We observed ten virulence genes (sfa, eaeA, cnf1, etrA, papC, hlyA, aer, faeG, rfc, and sepA), of which sfa was the most commonly found (96.9%). Significant positive associations between some resistance phenotypes and virulence genes were observed (P < 0.05, OR > 1). The majority of the E. coli isolates belonged to phylogroup A (79.5%), and the others belonged to phylogroups B1 (7.5%), D (4.1%), B2 (5.8%), and F (0.7%). Among all the E. coli strains tested, serogroups O91 and O145 were the most prevalent, accounting for 15.4 and 14.4%, respectively. Conclusions: Our results suggest that yaks with diarrhea serve as a reservoir of pathogenic E. coli carrying various virulence genes and resistance phenotypes. Therefore, clinicians and relevant authorities must ensure the regulatory use of antimicrobial agents and prevent the spread of these organisms through manure to farm workers and foodprocessing plants. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease (CHD) is the most prevalent type of cardiac disease among adults worldwide, including those in Singapore. Most of its risk factors, such as smoking, physical inactivity and high blood pressure, are preventable. mHealth has improved in the last decade, showing promising results in chronic disease prevention and health promotion worldwide. Our aim was to develop and examine the effect of a 4-week Smartphone-Based Coronary Heart Disease Prevention (SBCHDP) programme in improving awareness and knowledge of CHD, perceived stress as well as cardiac-related lifestyle behaviours in the working population of Singapore.Methods: The smartphone app "Care4Heart" was developed as the main component of the programme. App content was reviewed and validated by a panel of experts, including two cardiologists and two experienced cardiology-trained nurses. A pilot randomised controlled trial was conducted. Eighty working people were recruited and randomised to either the intervention group (n = 40) or the control group (n = 40). The intervention group underwent a 4-week SBCHDP programme, whereas the control group were offered health promotion websites only. The participants' CHD knowledge, perceived stress and behavioural risk factors were measured at baseline and on the 4th week using the Heart Disease Fact Questionnaire-2, Perceived Stress Scale, and Behavioural Risk Factor Surveillance System.Results: After the SBCHDP programme, participants in the intervention group had a better awareness of CHD being the second leading cause of death in Singapore (X 2  = 6.486, p = 0.039), a better overall CHD knowledge level (t = 3.171, p = 0.002), and better behaviour concerning blood cholesterol control (X 2  = 4.54, p = 0.033) than participants in the control group.Conclusion: This pilot study partially confirmed the positive effects of the SBCHDP programme in improving awareness and knowledge of CHD among the working population. Due to the small sample size and short follow-up period, this study was underpowered to detect significant differences between groups. A full-scale longitudinal study is required in the future to confirm the effectiveness of the SBCHDP programme. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission.Methods: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method.Results: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China).Conclusion: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China. [ABSTRACT FROM AUTHOR]

Background: The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants.Methods: A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces. All registered re-treated TB patients were investigated using a structured questionnaire covering information on demographics, socio-economic characteristics, and previous anti-TB treatment experiences.Results: Totally, 75.3% of 544 patients visited CTD directly for initial treatment. Patients who were female (OR:1.71, 95% CI: 1.01-2.87), over 40 years of age (OR:2.80, 95% CI: 1.24-6.33), from Jiangsu (OR:3.07, 95% CI: 1.57-6.01) and Sichuan (OR:4.47, 95% CI: 2.29-8.73) and those diagnosed before 2005 (OR:6.87, 95% CI: 4.24-11.13) had a significant higher risk receiving their initial treatment at a non-CTD. Patients were more likely to have standardized diagnosis and treatment regimens in CTD (89.8%) than in non-CTDs (65.9%). Patients treated in non-CTDs versus in CTD had a lower possibility to complete their treatment course during first TB episode (χ 2 = 3.926, P = 0.048), but there was no significant difference in the cure rate between different facilities (CTD 60.8%, Non-CTDs 59.1%). Patients in non-CTDs incurred higher costs (1,360 CNY) than those treated in CTD (920CNY).Conclusion: CTD play a key role in the National Tuberculosis Control Program. Patients should be guided to seek health care in county designated hospital, where they are more likely to receive appropriate examinations, treatment regimens and rigorous supervision, and to bear a lighter economic burden. [ABSTRACT FROM AUTHOR]

Background: Little is known about the association of the single nucleotide polymorphism (SNP) of rs364585 near serine palmitoyl-transferase long-chain base subunit 3 gene (SPTLC3) and serum lipid profiles. The present study was detected the association of the SPTLC3 rs364585 SNP and several environmental factors with serum lipid profiles in the Han and Jing populations. Methods: Genotyping of the SPTLC3 rs364585 SNP was performed in 824 unrelated individuals of Han and 783 participants of Jing by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results: There was no significant difference in either genotypic or allelic frequencies between Han and Jing, or between males and females of the both ethnic groups. The levels of serum low-density lipoprotein cholesterol (LDL-C) and the ratio of apolipoprotein (Apo) A1 to ApoB in Han; and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and LDL-C in Jing were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001). Subgroup analysis according to sex showed that the levels of LDL-C in Han males; TC and LDL-C in Jing males; and HDL-C and LDL-C in Jing females were different between the A allele carriers and the A allele non-carriers (P < 0.05-0.001), the A allele carriers had higher LDL-C and TC levels, and lower HDL-C levels than the A allele non-carriers. Serum lipid traits were also associated with several environmental factors in the Han and Jing populations, or in males and females of the both ethnic groups. Conclusions: The present study demonstrates the association between the SPTLC3 rs364585 SNP and serum TC, HDL-C and LDL-C levels in our study populations. These associations might have ethnic- and/or sex-specificity. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Cordyceps sobolifera (C. sobolifera) isolated from cicadae was used as the starting fungus to produce selenium-enriched C. sobolifera extracellular polysaccharide (Se-CEPS). An orthogonal experimental design based on a single-factor experiment was used to optimize the C. sobolifera fermentation conditions, including the potato juice, peptone, and KH2PO4 concentrations. Ultraviolet (UV) and infrared (IR) analyses of CEPS and Se-CEPS were conducted, as well as an in vivo anti-tumor analysis. Results: Under optimal conditions (i.e., 40 potato juice, 0.4 KH2PO4, and 0.5 % peptone), the fermentation yield of Se-CEPS was 5.64 g/L. UV and IR spectra showed that Se-CEPS contained a characteristic absorption peak of a selenite Se = O double bond, demonstrating the successful preparation of Se-CEPS. Activity tests showed that Se-CEPS improved the immune organ index, serum cytokine content, and CD8+ and CD4+ T lymphocyte ratio in colon cancer CT26 tumor-bearing mice, thereby inhibiting tumor growth. When combined with 5-FU, Se-CEPS reduced the toxicity and enhanced the function of 5-FU. Conclusion: The result of these experiments indicated that orthogonal experimental design is a promising method for the optimization of Se-CEPS production, and the Se-CEPS from C. sobolifera can improve the anti-tumor capacity of mice. [ABSTRACT FROM AUTHOR]

Background: NLRP3 inflammasome has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). The activation of NLRP3 inflammasome results in the production of IL-1β and the subsequent inflammation. Anti-dsDNA antibodies (anti-dsDNA Abs) play critical roles in the development and progression of SLE. However, the mechanism of NLRP3 inflammasome activation in SLE is still not known. This study investigated the activation of NLRP3 inflammasome stimulated by anti-dsDNA Abs in monocytes/macrophages from SLE patients.Methods: Monocytes/macrophages from SLE patients or healthy controls were stimulated with anti-dsDNA Ab-positive serum or purified anti-dsDNA Abs. Activation of inflammasome was measured by flow cytometry or Western blot. Anti-dsDNA Abs isolated from active SLE patients were injected into female (NZB × NZW) F1 mice and the activation of NLRP3 inflammasome and the frequencies of Th17 and Treg were examined.Results: The activity of caspase-1 was significantly increased in active SLE patients and was correlated with serum levels of anti-dsDNA Abs and disease activities. The concentrations of IL-1β and IL-17A were also significantly higher in SLE patients compared to healthy controls. Anti-dsDNA Ab-positive serum rather than healthy serum or RF (rheumatoid factor)-positive serum stimulated the activation of caspase-1 in monocytes. Anti-dsDNA Abs bound to TLR4 on macrophages and induced the production of ROS. Mitochondria-targeting antioxidant Mito-TEMPO, IκB kinase inhibitor peptide or TLR4 siRNA inhibited the activation of NLRP3 inflammasome and the secretion of IL-1β induced by anti-dsDNA Abs. Injection of anti-dsDNA Abs into (NZB × NZW) F1 mice resulted in increased caspase-1 activation and production of IL-1β and IL-17A. The Th17/Treg cell ratio also significantly increased following anti-dsDNA Ab injection.Conclusions: Anti-dsDNA Abs activated NLRP3 inflammasome in monocytes/macrophages from SLE patients by binding to TLR4 and inducing the production of mitochondrial ROS. [ABSTRACT FROM AUTHOR]

Background: The filamentous fungus Aspergillus niger is widely exploited as an important expression host for industrial production. The glucoamylase high-producing strain A. niger CICC2462 has been used as a host strain for the establishment of a secretion expression system. It expresses recombinant xylanase, mannase and asparaginase at a high level, but some high secretory background proteins in these recombinant strains still remain, such as alphaamylase and alpha-glucosidase; lead to a low-purity of fermentation products. The aim was to construct an A. niger host strain with a low background of protein secretion. Results: The transcription factor amyR was deleted in A. niger CICC2462, and the results from enzyme activity assays and SDS-PAGE analysis showed that the glucoamylase and amylase activities of the ▵ amyR strains were significantly lower than those of the wild-type strain. High-throughput RNA-sequencing and shotgun LC-MS/MS proteomic technology analysis demonstrated that the expression of amylolytic enzymes was decreased at both the transcriptional and translational levels in the ▵ amyR strain. Interestingly, the ▵ amyR strain growth rate better than the wild-type strain. Conclusions: Our findings clearly indicated that the ▵ amyR strain of A. niger CICC2462 can be used as a host strain with a low background of protein secretion. [ABSTRACT FROM AUTHOR]

Background: China's national tuberculosis control program (NTP) provides free, first-line anti-tuberculosis (TB) drugs to pulmonary TB patients. This treatment regimen follows the World Health Organization's (WHO) guideline. The objective of this paper is to evaluate the current status of anti-TB drug use for newly diagnosed pulmonary TB inpatients treated in prefecture- and county-level designated hospitals. Methods: Three prefecture-level hospitals and nine county-level hospitals were selected for the study. All newly diagnosed pulmonary TB inpatient medical records from 2012 were reviewed and doubly examined by two national senior physicians. The rational use of anti-TB drugs was evaluated based on criteria in line with WHO's guideline. Results: Of the 2,060 total treatment regimens for TB, 53.1% were found to be rational (1093/2060). The percentages in prefecture-level and county-level hospitals were 50.3% (761/1513) and 60.7% (332/547), respectively. The difference between the two levels of hospitals was statistically significant (Chi-square value = 17.44, P < 0.01). The percentages of rational treatment regimens for first-time hospitalizations and for two or more hospitalizations were 59.5% (983/1653) and 27.0% (110/407), respectively, with a statistically significant difference (Chi-square value = 138.00, P < 0.01). The overall use of second-line drugs (SLD) was 54.9% (1131/2060). The percentages for prefecture-level and county-level hospitals were 50.6% (766/1513) and 66.7% (365/547), respectively. A statistically significant difference was found (Chi-square value = 42.06, P < 0.01). The use of SLD for inpatients hospitalized once and inpatients hospitalized twice or more was 58.4% (966/1653) and 40.5% (165/407), respectively, with a statistically significant difference (Chi-square value = 42.26, P < 0.01). Conclusions: Half of inpatients might be treated with irrational regimens, and the use of SLD was more appropriately dispensed in city-level hospitals than in county-level hospitals. Trainings and guidelines for health personnel, supervision led by health authorities and increased investment to designated hospitals may help to improve the rational use of anti-TB drugs. [ABSTRACT FROM AUTHOR]

Background: Syphilis remains a global public health threat and can lead to severe complications. In addition to resolution of clinical manifestations, a reduction in nontreponemal antibody titers after treatment is regarded as "proof of cure." However, some patients manifest < 4-fold decline ("serological non-response") or persistently positive nontreponemal titers despite an appropriate decline ("serofast") that may represent treatment failure, reinfection, or a benign immune response. To delineate these treatment phenomena, we conducted a systematic review of the literature regarding serological outcomes and associated factors among HIV-infected and -uninfected subjects.Methods: Six databases (PubMed, Embase, CINAHL, Web of Science, Scopus, and BIOSIS) were searched with no date restrictions. Relevant articles that evaluated serological treatment responses and correlates of serological cure (≥ four-fold decline in nontreponemal titers) were included.Results: We identified 1693 reports in the literature, of which 20 studies met selection criteria. The median proportion of patients who had serological non-response was 12.1% overall (interquartile range, 4.9-25.6), but varied depending on the time points after therapy. The serofast proportion could only be estimated from 2 studies, which ranged from 35.2-44.4%. Serological cure was primarily associated with younger age, higher baseline nontreponemal titers, and earlier syphilis stage. The relationship between serological cure and HIV status was inconsistent; among HIV-infected patients, CD4 count and HIV viral load was not associated with serological cure.Conclusions: Serological non-response and the serofast state are common syphilis treatment outcomes, highlighting the importance of determining the immunological and clinical significance of persistent nontreponemal antibody titers after therapy. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) patients in China still face a number of barriers in seeking diagnosis and treatment. There is evidence that the economic burden on TB patients and their households discourages treatment compliance. Methods: A cross-sectional study was conducted in three cities of China. Patients were selected using probability proportional to size (PPS) cluster sampling of rural townships or urban streets, followed by list sampling from a patient register. Data were collected using a questionnaire survey, key informant interviews and focus group discussions with TB patients to gain an understanding of the economic burden of TB and implications of this burden for treatment compliance. Results: A total of 797 TB patients were surveyed, of which 60 were interviewed in-depth following the survey. More than half had catastrophic health expenditure. TB patients with higher household incomes were less likely to report non-compliance (OR 0.355, 95% CI 0.140-0.830) and patients who felt that the economic burden relating to TB treatment was high more likely to report non-compliance (OR 3.650, 95% CI 1.278-12.346). Those who had high costs for transportation, lodging and food were also more likely to report non-compliance (OR 4.150, 95% CI 1.804-21.999). The findings from the qualitative studies supported those from the survey. Conclusion: The economic burden associated with seeking diagnosis and treatment remains a barrier for TB patients in China. Reducing the cost of treatment and giving patients subsidies for transportation, lodging and food is likely to improve treatment compliance. Improving doctors' salary system to cut off the revenue-oriented incentive, and expanding current insurance's coverage can be helpful to reduce patients' actual burden or anticipated burden. Future research on this issue is needed. [ABSTRACT FROM AUTHOR]

Background: Prolonged isolated thrombocytopenia (PT) is a frequent complication in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it is associated with an adverse prognosis. In this study, we hypothesized that desialylation on platelet surfaces was associated with PT after allo-HSCT. The mechanisms participating in this process may include NEU1 translocation, platelet apoptosis, and phagocytosis by macrophages. Methods: PT was defined as a peripheral platelet count less than 100 × 109/L without sustained anemia or leukopenia for more than 3 months after allo-HSCT. 34 patients were identified consecutively from a cohort of 255 patients who underwent allo-HSCT for hematologic malignancies between May and October 2014 at Peking University Institute of Hematology. Desialylation, enzyme expression, and phagocytosis were detected using flow cytometry, immunofluorescence, RT-PCR, Western blot, and so on. Results: Platelets from the PT patients had significantly fewer sialic acids (P = .001) and increased β-galactose exposure indicative of desialylation on the surface (P = .042), and serum from the PT patients showed a higher sialic acid concentration (8.400 ± 0.2209 μmol/L, P < .001). The sialidase NEU1 was over-expressed from mRNA to protein levels, and its catalytic activity was increased in platelets from the PT patients. Desialylation of GPIbα in the PT patients was correlated with changes in 14-3-3ζ distribution, which, relative to Bad activation, modulated the expression of Bcl-2 family proteins, depolarized the inner membrane of the mitochondria, and initiated the intrinsic mitochondria-dependent pathway of apoptosis. Macrophages derived from the THP-1 cell line preferred to phagocytize desialylated platelets from the PT patients in vitro. We also revealed that oseltamivir (400 μmol/L) could inhibit 50 % of the sialidase activity on platelets and could protect 20 % of platelets from phagocytosis in vitro. Conclusions: Desialylation of platelets was associated with platelet apoptosis and phagocytosis, whereas oseltamivir could reduce platelet destruction in the periphery, indicating a potential novel treatment for PT after allo-HSCT. [ABSTRACT FROM AUTHOR]

Background: Panax Notoginseng flower saponins (PNFS) are the main active component of Panax notoginseng (Burk) F. H. Chen flower bud (PNF) and possess significant anti-inflammatory efficacy. This study aims to explore the mechanisms underlying PNFS' antiflammatory action in RAW264.7 macrophages. Methods: A cell counting kit-8 assay was used to determine the viability of RAW264.7 macrophages. Anti-inflammation effects of PNFS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were measured based on the detection of nitric oxide (NO) overproduction (Griess method, DAF-FM DA fluorescence assay and NOi scavenging assay), and interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha gene overexpression (real-time PCR and ELISA). Inducible nitric oxide synthase (iNOS) gene overexpression was determined by real-time PCR and western blotting. iNOS enzyme activity was also assayed. The mechanisms underlying the suppression of iNOS gene overexpression by PNFS were explored using real-time PCR and western blotting to assess mRNA and protein levels of components of the Toll-like receptor 4 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-kappa B) signaling pathways. Results: PNFS (50, 100, 200 µg/mL) significantly reduced LPS-induced overproduction of NO (P < 0.001, P < 0.001, P < 0.001) and IL-6 (P = 0.103, P < 0.001, P < 0.001), but did not affect TNF-alpha overproduction. PNFS (50, 100, 200 µg/mL) also markedly decreased LPS-activated iNOS (P < 0.001, P < 0.001, P < 0.001) and TLR4 gene overexpression (P = 0.858, P = 0.046, P = 0.005). Furthermore, treatment with PNFS (200 µg/mL) suppressed the phosphorylation of MAPKs including P38 (P = 0.001), c-Jun N-terminal kinase (JNK) (P = 0.036) and extracellular-signal regulated kinase (ERK) 1/2 (P = 0.021). PNFS (200 µg/mL) inhibited the activation of the NF-kappa B signaling pathway by preventing the phosphorylation of inhibitor of NF-kappa B alpha (I-kappa B alpha) (P = 0.004) and P65 (P = 0.023), but PNFS (200 µg/mL) could not activate the LPS-induced PI3K-Akt signaling pathway. Conclusions: PNFS significantly down-regulated iNOS gene overexpression and thereby decreased NO overproduction via the inhibition of TLR4-mediated MAPK/NF-kappa B signaling pathways, but not the PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. We investigated whether KLF12 was associated with impaired decidualization under conditions of repeated implantation failure (RIF). Methods: Uterine tissues were collected from a mouse model of early pregnancy and artificial decidualization for immunohistochemistry, Western blot and real-time PCR analysis. Reporter gene assays, chromatin immunoprecipitation-PCR and avidin-biotin conjugate DNA precipitation assays were performed to analyze the transcriptional regulation of forkhead box O1 (FOXO1) by KLF12. Furthermore, the protein levels of KLF12 and FOXO1 in patients with RIF were analyzed by Western blot and immunohistochemistry. Results: KLF12 led to defective implantation and decidualization in the mouse uterine model of early pregnancy and artificial decidualization by directly binding to the FOXO1 promoter region and inhibiting its expression in human endometrial stromal cells. Elevated KLF12 expression was accompanied by decreased FOXO1 expression in the endometria of patients with RIF. Conclusions: As a novel regulator, KLF12 predominantly controls uterine endometrial differentiation during early pregnancy and leads to implantation failure. [ABSTRACT FROM AUTHOR]

Background: Anti-dsDNA antibodies play an important role in the pathogenesis of lupus nephritis (LN). Endoplasmic reticulum (ER) stress is a physical reaction under stressful condition and can cause inflammation when stimulation is sustained. This study investigated the roles of ER stress in anti-dsDNA antibody-induced inflammation response in human mesangial cells (HMCs). Method: Anti-dsDNA antibodies isolated from LN patients were used to stimulate HMCs. The expression of GRP78, PERK, p-PERK, p-eIF2α, ATF4, p-IRE1α, ATF6 and CHOP in HMCs was measured by western blot. NF-κB activation was detected by examining nuclear translocation of NF-κB p65. The expression and production of IL-1β, TNF-α and MCP-1 were examined by qPCR and ELISA. Results: Flow cytometry and cellular ELISA showed that anti-dsDNA antibodies can bind to HMCs. The binding was not inhibited by blockage of Fc receptor. Anti-dsDNA antibody stimulation significantly enhanced the expression of GRP78, p-PERK, p-eIF2α and ATF4 in HMCs. However, no significant increase in the expression of p-IRE1α and ATF6 was found. In addition, anti-dsDNA antibodies also significantly increased the activation of NF-κB and upregulated the expression of IL-1β, TNF-α and MCP-1, which were suppressed by pretreatment of HMCs with chemical ER stress inhibitor 4-PBA. Transfection of specific ATF4 siRNA also significantly reduced the activation of NF-κB and expression of proinflammatory cytokines. Conclusion: Anti-dsDNA antibodies induce NF-κB activation and inflammation in HMCs via PERK-eIF2α-ATF4 ER stress pathway. [ABSTRACT FROM AUTHOR]

Background: Post-translational modification by ubiquitin is a fundamental regulatory mechanism that is implicated in many cellular processes including the cell cycle, apoptosis, cell adhesion, angiogenesis, and tumor growth. The low stoichiometry of ubiquitylation presents an analytical challenge for the detection of endogenously modified proteins in the absence of enrichment strategies. The recent availability of antibodies recognizing peptides with Lys residues containing a di-Gly ubiquitin remnant (K-ε-GG) has greatly improved the ability to enrich and identify ubiquitylation sites from complex protein lysates via mass spectrometry. To date, there have not been any published studies that quantitatively assess the changes in endogenous ubiquitin-modification protein stoichiometry status at the proteome level from different tissues. Results: In this study, we applied an integrated quantitative mass spectrometry based approach using isobaric tags for relative and absolute quantitation (iTRAQ) to interrogate the ubiquitin-modified proteome and the cognate global proteome levels from luminal and basal breast cancer patient-derived xenograft tissues. Among the proteins with quantitative global and ubiquitylation data, 91 % had unchanged levels of total protein relative abundance, and less than 5 % of these proteins had up- or down-regulated ubiquitylation levels. Of particular note, greater than half of the proteins with observed changes in their total protein level also had up- or down-regulated changes in their ubiquitylation level. Conclusions: This is the first report of the application of iTRAQ-based quantification to the integrated analysis of the ubiquitylated and global proteomes at the tissue level. Our results underscore the importance of conducting integrated analyses of the global and ubiquitylated proteomes toward elucidating the specific functional significance of ubiquitylation. [ABSTRACT FROM AUTHOR]

Background: Hco-gal-m and -f were two isoforms of galectin cloned from male and female Haemonchus contortus, respectively, and it was demonstrated that recombinant Hco-gal-m and -f could act as immune suppressors. However, little is known about the receptors or binding partners of these galectins in the host. The research of the molecular mechanisms that govern the interactions between these galectins and host molecules will fill a gap in our understanding how parasite galectins interact with host cells. Methods: A yeast two-hybrid system was used to identify the binding partners of Hco-gal-m and -f in this research. The interaction between rHco-gal-m and candidate binding protein was validated by co-immunoprecipitation. The localization of transmembrane protein 63A (TMEM63A) in peripheral blood mononuclear cells (PBMCs) was detected by immunofluorescence. The distribution of TMEM63A in T cells, B cells and monocytes in PBMCs was detected by flow cytometry. The immunomodulatory effects of Hco-gal-m and TMEM63A on cell proliferation, migration, apoptosis, nitric oxide production and cytokine secretion were observed by co-incubation of rHco-gal-m and TMEM63A-siRNA with goat PBMCs and monocytes. Results: We found that TMEM63A, a functionally unknown protein, from goat PBMCs could bind to Hco-gal-m and -f. Immunofluorescence showed that TMEM63A was localized to the cell membrane. Flow cytometric analysis revealed that TMEM63A was expressed in the majority of goat PBMCs. After using RNA interference to knockdown expression of TMEM63A, the PBMC proliferation and migration were significantly increased, while the influence of rHco-gal-m on monocyte phagocytosis, PBMC nitric oxide production and migration were potently blocked. In addition, the production of IL-10, IFN-γ and TGF-β induced by rHco-gal-m were also altered. Conclusions: Our results show that TMEM63A is a binding partner of Hco-gal-m/f, and involved in the immune responses of host PBMCs induced by Hco-gal-m for the first time. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to identify a prospective association between CA125 and tumorigenic ovarian cancer cells, using the new method of orthotopic transplantation (1). Method: After making the surgical ovarian cancer specimen into cell suspension, we separated the tumorigenic cells from the nontumorigenic cancer cells based on cell surface marker (cancer antigen CA125 and lineage markers) expression. We developed a SCID mice model in which the CA125+/lineage- and CA125-/lineage- cells were injected into ovarian parenchyma by use of a microinjector. As a measure of effectiveness of tumor-forming, tumor weight, abdominal distension, ascites volume and activity, subcutaneous fat were determined or observed. Immunohistochemistry was done to determine tumor cell markers. Results: We found that the cells of CA125+/lineage- were able to form new tumors; whereas, an equal quantity of CA125-/lineage- cells failed to form any tumors. The new generated tumor contained additional CA125-/lineage- tumorigenic cells as well as the phenotypically diverse population of nontumorigenic cells. Quantities were judged to be significantly different P < 0.0001. Conclusion: CA125+/lineage- cells, which may be ovarian cancer stem cells, were the source for tumor recurrence. The strategies designed to target this cell population may lead to more effective therapies. [ABSTRACT FROM AUTHOR]

Background: The prognosis for pancreatic cancer (PC) is very poor. The SnoN gene may have a role in cell proliferation and apoptosis in human cancer. However, the influence of SnoN on cell proliferation and apoptosis in human PC cells remains unknown. Methods: SnoN expression was assessed in SW1990 PC cell lines using real-time polymerase chain reaction (PCR). A luciferase reporter assay was used to confirm the target associations. The effect of SnoN on cell proliferation in vitro was confirmed using Cell Counting Kit-8. Apoptosis was confirmed using flow cytometry. Gene and protein expression were examined using real time PCR and Western blotting, respectively. Results: SnoN siRNA significantly inhibited the growth of SW1990 cells by decreasing cell proliferation (P < 0.05) and increasing cell apoptosis (P < 0.05), compared with the blank group and the negative control group. The highest inhibition of cell proliferation appeared at 3 days post-transfection. Cell apoptosis more obvious at 48 h after transfection. Conclusions: In summary, our results reveal that the RNAi-mediated downregulation of SnoN effectively inhibited the proliferation of PC cells. SnoN-siRNA also enhanced SW1990 PC cell apoptosis. These findings indicate that SnoN gene plays an important role in pancreatic cancer development, and might serve as a potential therapeutic target for pancreatic cancer. However, further in vivo studies are needed to clarify the influence of SnoN gene silencing by siRNA on pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Background: It has been shown that heat shock-related 70-kDa protein 2 (HSPA2), a member of the HSP70 family of heat shock proteins, is important for cancer cell growth and metastasis. However, the status of HSPA2 expression and its prognostic significance in pancreatic cancer remain unknown. Methods: Quantitative reverse transcriptase ploymerase chain reaction (qRT-PCR) was applied to examine HSPA2 messenger RNA (mRNA) expression in 104 pairs of pancreatic cancer tissues and adjacent noncancerous tissues. Statistical analyses were applied to evaluate the diagnostic value and associations of HSPA2 expression with clinicopathological characteristics. Results: HSPA2 mRNA was significantly overexpressed in pancreatic cancer tissues (3.9 ± 0.8) than in adjacent normal tissues (1.1 ± 0.4) (P < 0.001). Clinicopathological analysis showed that HSPA2 expression was significantly correlated with tumor size (P = 0.024), histological differentiation (P = 0.012), TNM stage (P = 0.006), lymph node metastasis (P = 0.043) and serum CA19-9 level (P = 0.046). Moreover, patients with higher HSPA2 expression levels had shorter overall survival time than those with lower HSPA2 expression levels (P = 0.019). Furthermore, Cox regression analyses showed that HSPA2 expression was an independent predictor of overall survival (P = 0.011). Conclusions: Our results suggest that overexpression of HSPA2 in pancreatic cancer is associated with aggressive progression and poor prognosis and that HSPA2 may be served as a prognostic marker. [ABSTRACT FROM AUTHOR]

Background: The transformation of endometrium into decidua is essential for normal implantation of the blastocyst. However, the post-transcriptional regulation and the miRNAs involved in decidualization remain poorly understood. Here, we examined microRNA-181a (miR-181a) expression in decidualized human endometrial stromal cell (hESC). In addition, we investigated the functional effect of miR-181a on hESC decidualization in vitro. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect the profile of miR-181a in decidualized hESC. qRT-PCR, enzyme-linked fluorescent assay, and immunofluorescence assay were performed to investigate decidualization marker genes' expression after enhancing or inhibition of miR-181a expression in hESC. Luciferase reporter assay, western blotting, qRT-PCR, and immunofluorescence assay were carried out to identify the relationship between miR-181a and Krüppel-like factor 12 (KLF12). Results: miR-181a expression levels increased dramatically in hESC treated with 8-Br-cAMP and MPA. Increased miR-181a expression promoted hESC decidualization-related gene expression and morphological transformation; conversely, inhibition of miR-181a expression compromised hESC decidualization in vitro. Further analysis confirmed that miR-181a interacted with the 3' untranslated region of the transcription factor KLF12 and down-regulated KLF12 at the transcriptional and translational levels. KLF12 overexpression abolished miR-181a-induced decidualization. Conclusions: Our findings suggest that miR-181a plays a functionally important role in human endometrial stromal cell decidualization in vitro by inhibiting KLF12. [ABSTRACT FROM AUTHOR]

Background: P. vietnamensis var. fuscidiscus, called "Yesanqi" in Chinese, is a new variety of P. vietnamensis, which was first found in Jinping County, the southern part of Yunnan Province, China. Compared with other Panax plants, this species contains higher content of ocotillol-type saponin, majonoside R2. Despite the pharmacological importance of ocotillol-type saponins, little is known about their biosynthesis in plants. Hence, P. vietnamensis var. fuscidiscus is a suitable medicinal herbal plant species to study biosynthesis of ocotillol-type saponins. In addition, the available genomic information of this important herbal plant is lacking. Results: To investigate the P. vietnamensis var. fuscidiscus transcriptome, Illumina HiSeq™ 2000 sequencing platform was employed. We produced 114,703,210 clean reads, assembled into 126,758 unigenes, with an average length of 1,304 bp and N50 of 2,108 bp. Among these 126,758 unigenes, 85,214 unigenes (67.23%) were annotated based on the information available from the public databases. The transcripts encoding the known enzymes involved in triterpenoid saponins biosynthesis were identified in our Illumina dataset. A full-length cDNA of three Squalene epoxidase (SE) genes were obtained using reverse transcription PCR (RT-PCR) and the expression patterns of ten unigenes were analyzed by reverse transcription quantitative real-time PCR (RT-qPCR). Furthermore, 15 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely to involve in triterpenoid saponins biosynthesis pathway were discovered from transcriptome sequencing of P. vietnamensis var. fuscidiscus. We further analyzed the data and found 21,320 simple sequence repeats (SSRs), 30 primer pairs for SSRs were randomly selected for validation of the amplification and polymorphism in 13 P. vietnamensis var. fuscidiscus accessions. Meanwhile, five major triterpene saponins in roots of P. vietnamensis var. fuscidicus were determined using high performance liquid chromatography (HPLC) and evaporative light scattering detector (ELSD). Conclusions: The genomic resources generated from P. vietnamensis var. fuscidiscus provide new insights into the identification of putative genes involved in triterpenoid saponins biosynthesis pathway. This will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level. The SSR markers identified and developed in this study show genetic diversity for this important crop and will contribute to marker-assisted breeding for P. vietnamensis var. fuscidiscus. [ABSTRACT FROM AUTHOR]

Background The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer. Methods and materials From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed. Results With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95%CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95%CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95%CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873). Conclusions An elevated baseline NLR is a valuable and easily available prognostic factor for OS in addition to tumor response after neoadjuvant therapy. Baseline NLR could be a useful candidate factor for stratifying patients and making treatment decisions in locally advanced rectal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Adipose tissue-derived stromal cells (ADSCs) are abundant and easy to obtain, but the diversity of differentiation potential from different locations may vary with the developmental origin of their mesenchymal compartment. We therefore aim to compare the myogenic differentiation and reparative activity of ADSCs derived from the pericardial tissue to ADSCs of subcutaneous origin. Methods: Pericardial and inguinal adipose tissues from Wistar rats were surgically obtained, and the stromal fraction was isolated after enzymatic digestion. The phenotypic epitopes of the resultant two types of ADSCs were analyzed with flow cytometry, and the expression of transcriptional factors was analyzed with immunostaining. Furthermore, their potential toward adipogenic, osteogenic, and myogenic differentiation also was compared. Finally, the reparative activity and the resultant functional benefits were examined by allograft transplantation into an infarcted model in rats. Results: ADSCs from two adipose sources showed identical morphology and growth curve at the initial stage, but inguinal ADSCs (ingADSCs) sustained significantly vigorous growth after 25 days of cultivation. Although both ADSCs shared similar immunophenotypes, the pericardial ADSCs (periADSC) intrinsically exhibited partial expression of transcription factors for cardiogenesis (such as GATA-4, Isl-1, Nkx 2.5, and MEF-2c) and more-efficient myogenic differentiation, but less competent for adipogenic and osteogenic differentiation. After in vivo transplantation, periADSCs exhibited significantly vigorous reparative activity evidenced by thickening of ventricular wall and pronounced vasculogenesis and myogenesis, although the majority of prelabeled cells disappeared 28 days after transplantation. The structural repair also translated into functional benefits of hearts after infarction. Conclusions: Although two sources of ADSCs are phenotypically identical, pericADSCs constituted intrinsic properties toward myogenesis and vasculogenesis, and thus provided more potent reparative effects after transplantation; therefore, they represent an attractive candidate cell donor for cardiac therapy. [ABSTRACT FROM AUTHOR]

A new technique has successfully established the non-obese diabetic/severely combined immunodeficiency (NOD/SCID) mouse model of ovarian cancer. Under 4% chloral hydrate (0.1 mL/g dose) anesthesia, female mice were inoculated with tumor-cell suspension. The expression rate of OVCAR3 to CA125 was assessed using flow cytometry. The inoculated site was hand palpated and the signs and symptoms related to tumor growth were observed with the naked eye. The allophycocyanin (APC) indirectly labeled mouse-antihuman CA125 and fluorescein isothiocyanate (FITC)-labeled anti-mouse MHC Class I molecule (H-2Kd/H-2Dd) were observed using a confocal laser scanning microscope. The animal model of ovarian cancer constructed using this method can more directly reflect the characteristics of cancer cells. It provides reliable experimental results and presents a technical platform for the research of ovarian cancer stem cells. [ABSTRACT FROM AUTHOR]

Background The chicken (Gallus gallus) is an important model organism that bridges the evolutionary gap between mammals and other vertebrates. Copy number variations (CNVs) are a form of genomic structural variation widely distributed in the genome. CNV analysis has recently gained greater attention and momentum, as the identification of CNVs can contribute to a better understanding of traits important to both humans and other animals. To detect chicken CNVs, we genotyped 475 animals derived from two broiler chicken lines divergently selected for abdominal fat content using chicken 60 K SNP array, which is a high-throughput method widely used in chicken genomics studies. Results Using PennCNV algorithm, we detected 438 and 291 CNVs in the lean and fat lines, respectively, corresponding to 271 and 188 CNV regions (CNVRs), which were obtained by merging overlapping CNVs. Out of these CNVRs, 99% were confirmed also by the CNVPartition program. These CNVRs covered 40.26 and 30.60 Mb of the chicken genome in the lean and fat lines, respectively. Moreover, CNVRs included 176 loss, 68 gain and 27 both (i.e. loss and gain within the same region) events in the lean line, and 143 loss, 25 gain and 20 both events in the fat line. Ten CNVRs were chosen for the validation experiment using qPCR method, and all of them were confirmed in at least one qPCR assay. We found a total of 886 genes located within these CNVRs, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed they could play various roles in a number of biological processes. Integrating the results of CNVRs, known quantitative trait loci (QTL) and selective sweeps for abdominal fat content suggested that some genes (including SLC9A3, GNAL, SPOCK3, ANXA10, HELIOS, MYLK, CCDC14, SPAG9, SOX5, VSNL1, SMC6, GEN1, MSGN1 and ZPAX) may be important for abdominal fat deposition in the chicken. Conclusions Our study provided a genome-wide CNVR map of the chicken genome, thereby contributing to our understanding of genomic structural variations and their potential roles in abdominal fat content in the chicken. [ABSTRACT FROM AUTHOR]

A weighted biological sequence is a string in which a set of characters may appear at each position with respective probabilities of occurrence. We attempt to locate all the tandem repeats in a weighted sequence. A repeated substring is called a tandem repeat if each occurrence of the substring is directly adjacent to each other. By introducing the idea of equivalence classes in weighted sequences, we identify the tandem repeats of every possible length using an iterative partitioning technique. We also present the algorithm for recording the tandem repeats, and prove that the problem can be solved in O(n2) time. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP) and osteoarthritis (OA) are two common musculoskeletal disorders that affect the quality of life in aged people. An inverse relationship between OP and OA was proposed four decades ago. However, the difference in microstructure of the trabecular bone of these two disorders by high-resolution MRI (HR-MRI) has not been compared. The primary objective of the study is to explain the actual relationship between OA and OP based on differences between bone microstructure of these two diseases. The secondary objectives are to find out the significance of Euler number and its relationship with other structural parameters, and important role of HR-MRI to reveal the microstructure of trabecular bone directly. Methods: Totally, 30 women with OP and 30 women with OA (n = 60) were included in this study. Primary OA of hip, knee, as well as spinal arthrosis were diagnosed according to plain X-ray film findings. Osteoporosis was defined based on the latest criteria of World Health Organization (WHO). Structural and textural parameters derived from HR-MRI images of proximal tibia were calculated and compared with special software. Results: There were significant differences in apparent bone volume fraction, trabecular thickness, mean roundness, Euler number, entropy and inverse different moment between OP and OA patients. In OP group, apparent trabecular separation (Tb.Sp), inertia, absolute value and contrast were positively correlated with Euler number, whereas apparent trabecular number (Tb.N), mean trabecular area, inverse difference and inverse different moment were negatively correlated. Apparent trabecular bone volume fraction (BV/TV), mean trabecular area, mean trabecular perimeter and mean skeleton length negatively correlated with Euler number in OA group. Inverse different moment was the texture parameter, which influenced bone mineral density (BMD) of femoral neck, meanwhile contrast influenced BMD of both great trochanter and Ward's triangle in OP group. While in OA group, Euler number was the exclusive parameter, which affected BMD of femoral neck and Ward's triangle. Conclusions: We found significant differences in microstructure parameters derived from HR-MRI images between postmenopausal women with OP and OA. It convincingly supports the hypothesis that there might be an inverse relationship between OP and OA. [ABSTRACT FROM AUTHOR]

Background: The adverse effects of maternal diabetes on oocyte maturation and embryo development have been reported. Methods: In this study, we used time-lapse live cell imaging confocal microscopy to investigate the dynamic changes of ER and the effects of diabetes on the ER's structural dynamics during oocyte maturation, fertilization and early embryo development. Results: We report that the ER first became remodeled into a dense ring around the developing MI spindle, and then surrounded the spindle during migration to the cortex. ER reorganization during mouse early embryo development was characterized by striking localization around the pronuclei in the equatorial section, in addition to larger areas of fluorescence deeper within the cytoplasm. In contrast, in diabetic mice, the ER displayed a significantly higher percentage of homogeneous distribution patterns throughout the entire ooplasm during oocyte maturation and early embryo development. In addition, a higher frequency of large ER aggregations was detected in GV oocytes and two cell embryos from diabetic mice. Conclusions: These results suggest that the diabetic condition adversely affects the ER distribution pattern during mouse oocyte maturation and early embryo development. [ABSTRACT FROM AUTHOR]

Background The purpose of this meta-analysis is to compare the efficacy of pancreatoduodenectomy (PD) with extended lymphadenectomy (PD/ELND) versus standard PD in the treatment of pancreatic cancer, with the hope of providing evidence for clinical practice. Methods The retrieval of relevant literature published before September 2012 was carried out on PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) by computer. Information was extracted according to Cochrane systematic review methods, and analyzed using software Stata 11.0. Results Five prospective randomized controlled trials (RCTs) were included in this meta-analysis of 555 cases (278 in the PD/ELND group and 277 in the standard PD group). The PD/ELND group showed a significantly lower 3-year survival rate (relative risk (RR) = 1.46, 95% confidence interval (CI) 1.03 to approximately 2.06, P = 0.034), prolonged operative time (weighted mean difference WMD = -1.03, 95% CI -1.96 to approximately -0.10, P = 0.029) and higher incidence of postoperative complications (RR = 0.56, 95% CI 0.42 to approximately 0.77, P = 0.000) by comparing with standard PD group. Besides, no significant difference was observed in the 1-year survival rate (RR = 0.87, 95% CI 0.60 to approximately 1.25, P = 0.69), 5-year survival rate (RR = 1.04, 95% CI 0.68 to approximately 1.58, P = 0.854), postoperative mortality (RR = 1.14, 95% CI 0.43 to approximately 3.00, P = 0.789), length of stay (WMD = -0.32, 95% CI -2.57 to approximately 1.94 , P = 0.784) and the amount of blood transfusions (WMD = -0.14, 95% CI -0.36 to approximately 0.08, P = 0.213). Conclusions PD/ELND does not have an advantage over standard PD in the survival rate for patients with pancreatic cancer, but does increase operative time and incidences of postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Peritoneal metastasis in gastric cancer represents a ubiquitous human health problem but effective therapies with limited side effects are still lacking. Although previous research suggested that u-PA was involved in some tumor metastasis such as lung-specific metastasis, the role of u-PA for peritoneal metastasis in gastric cancer is still unclear. The aim of this study was to explore whether selective pharmacological blockade of u-PA is able to affect the peritoneal metastasis of gastric cancer both in vivo and in vitro. Methods: In the present study, we evaluated the effects and explored the anti-tumor mechanisms of amiloride, a selective u-PA inhibitor, on a panel of gastric cancer cell lines and in a murine model of human gastric cancer MKN45. Results: The study showed that amiloride significantly inhibited the tumor growth and prolonged the survival of the tumor-bearing mice. In vitro, compared with controls, amiloride could not only significantly down-regulate the mRNA expression and protein level of u-PA from MKN45 cells with dose dependence but also inhibit the adhesion of HMrSV5 cells, migration and invasion of MKN45 cells. Conclusions: The findings in our current report provide evidence that selective u-PA inhibitor amiloride has potent effects against peritoneal metastasis in gastric cancer, suggesting its possible therapeutic value for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Porcine cytomegalovirus (PCMV) induces silent infection in adult pigs but more frequently causes fatal, generalized infection in newborn piglets. This study aimed to develop a new loop-mediated isothermal amplification (LAMP) method for the sensitive, rapid, and inexpensive detection of PCMV under field conditions. Methods: Tissue obtained from nine-week-old PCMV-free Landrace pigs or pig samples from postmortem examinations were analyzed. The samples were found to have clinical signs and lesions consistent with inclusion body rhinitis. Six specific primers were designed by targeting the PCMV DNA polymerase (DPOL) DNA. The LAMP reaction was optimized in a water bath. The sensitivity and specificity of LAMP and polymerase chain reaction (PCR) were compared. Results: PCMV DNA was amplified at 65°C, and the result could be detected as early as 30 min into the reaction. Positive reactions could be visualized by the naked eye as a color change brought on by the addition of SYBR Green. The sensitivity and specificity of LAMP were found to be similar to those of the PCR. Conclusions: LAMP is a high-throughput technique for the detection of PCMV and has a high specificity, sensitivity and simplicity; these factors make it suitable for detection of PCMV under field conditions. [ABSTRACT FROM AUTHOR]

Background: Genomic regions controlling abdominal fatness (AF) were studied in the Northeast Agricultural University broiler line divergently selected for AF. In this study, the chicken 60KSNP chip and extended haplotype homozygosity (EHH) test were used to detect genome-wide signatures of AF. Results: A total of 5357 and 5593 core regions were detected in the lean and fat lines, and 51 and 57 reached a significant level (P<0.01), respectively. A number of genes in the significant core regions, including RB1, BBS7, MAOA, MAOB, EHBP1, LRP2BP, LRP1B, MYO7A, MYO9A and PRPSAP1, were detected. These genes may be important for AF deposition in chickens. Conclusions: We provide a genome-wide map of selection signatures in the chicken genome, and make a contribution to the better understanding the mechanisms of selection for AF content in chickens. The selection for low AF in commercial breeding using this information will accelerate the breeding progress. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine the methylation status of Transforming growth factor-beta-inducible gene-h3 (TGFBI) and its correlation with paclitaxel chemoresistance in ovarian cancer. The methylation status of TGFBI was examined in ovarian cancer and control groups by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). The TGFBI expression and cell viability were compared by Quantitative Real-Time PCR, Western Blotting and MTT assay before and after demethylating agent 5-aza-2'-deoxycytidine (5-aza-dc) treatment in 6 cell lines (SKOV3, SKOV3/TR, SKOV3/DDP, A2780, 2780/TR, OVCAR8). In our results, TGFBI methylation was detected in 29/40 (72.5%) of ovarian cancer and 1/10 (10%) of benign ovarian tumors. No methylation was detected in normal ovarian tissues (P < 0.001). No statistical correlation between RUNX3 methylation and clinicopathological characteristics was observed. A significant correlation between TGFBI methylation and loss of TGFBI mRNA expression was found (P < 0.001). The methylation level of TGFBI was significantly higher in paclitaxel resistant cell lines (SKOV3/TR and 2780/TR) than that in the sensitive pairs (P < 0.001). After 5-aza-dc treatment, the relative expression of TGFBI mRNA and protein increased significantly in SKOV3/TR and A2780/TR cells. However, no statistical differences of relative TGFBI mRNA expression and protein were found in other cells (all P > 0.05), which showed that re-expression of TGFBI could reverse paclitaxel chemoresistance. Our results show that TGFBI is frequently methylated and associated with paclitaxel-resistance in ovarian cancer. TGFBI might be a potential therapeutic target for the enhancement of responses to chemotherapy in ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background: We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL)-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK), a member of mitogen-activated protein kinase (MAPK) family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS)-induced phosphorylated JNK (pJNK) expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods: Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results: The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions: The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Two major ways of macrophage (MΦ) activation can occur in radiation-induced pulmonary injury (RPI): classical and alternative MΦ activation, which play important roles in the pathogenesis of RPI. MΦ can produce chemokine MΦ inflammatory protein-1α (MIP-1α), while MIP-1α can recruit MΦ. The difference in the chemotactic ability of MIP-1α toward distinct activated MΦ is unclear. We speculated that there has been important interaction of MIP-1α with different activated MΦ, which might contribute to the pathogenesis of RPI.Methods: Classically and alternatively activated MΦ were produced by stimulating murine MΦ cell line RAW 264.7 cells with three different stimuli (LPS, IL-4 and IL-13); Then we used recombinant MIP-1α to attract two types of activated MΦ. In addition, we measured the ability of two types of activated MΦ to produce MIP-1α at the protein or mRNA level.Results: Chemotactic ability of recombinant MIP-1α toward IL-13-treated MΦ was the strongest, was moderate for IL-4-treated MΦ, and was weakest for LPS-stimulated MΦ (p<0.01). The ability of LPS-stimulated MΦ to secrete MIP-1α was significantly stronger than that of IL-4-treated or IL-13-treated MΦ (p<0.01). The ability of LPS-stimulated MΦ to express MIP-1α mRNA also was stronger than that of IL-4- or IL-13-stimulated MΦ (p<0.01).Conclusions: The chemotactic ability of MIP-1α toward alternatively activated MΦ (M2) was significantly greater than that for classically activated MΦ (M1). Meanwhile, both at the mRNA and protein level, the capacity of M1 to produce MIP-1α is better than that of M2. Thus, chemokine MIP-1α may play an important role in modulating the transition from radiation pneumonitis to pulmonary fibrosis in vivo, through the different chemotactic affinity for M1 and M2. [ABSTRACT FROM AUTHOR]

Background: Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI)) exposure can cause DNA damage in electroplating workers. Methods: 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%). Urinary 8-OHdG levels were measured by ELISA. Results: Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L) than that in control subjects (1.54 μg/L, P < 0.001). The medians (range) of Olive tail moment, tail length and tail DNA% in exposed workers were 1.13 (0.14-6.77), 11.17 (3.46-52.19) and 3.69 (0.65-16.20), and were significantly higher than those in control subjects (0.14 (0.01-0.39), 3.26 (3.00-4.00) and 0.69 (0.04-2.74), P < 0.001). Urinary 8-OHdG concentration was 13.65 (3.08-66.30) μg/g creatinine in exposed workers and 8.31 (2.94-30.83) μg/g creatinine in control subjects (P < 0.001). The differences of urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA% between these two groups remained significant (P < 0.001) even after stratification by potential confounding factors such as age, gender, and smoking status. Chromium exposure was found to be positively associated with chromium levels in erythrocytes, urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA %. Positive dose-response associations were also found between chromium levels in erythrocytes and Olive tail moment, tail length and tail DNA%. Conclusion: The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage. [ABSTRACT FROM AUTHOR]

Background: MTA1(metastasis associated-1) is a tumor metastasis associated candidate gene and overexpression in many human tumors, including breast cancer. In this study, we investigated depressive effect on MTA1 by MTA1-specific short hairpin RNA(shRNA) expression plasmids in human breast cancer cell lines MDA-MB-231 and MCF-7, and effect on protein levels of ER alpha, MMP-9, cyclinD1, and tumor cell invasion, proliferation. Methods: ShRNA expression vectors targeting MTA1 was constructed and transfected into human breast cancer cell lines MDA-MB-231 and MCF-7. The transfection efficiency was evaluated by fluorescence microscopy, mRNA levels of MTA1 were detected by reverse transcription-polymerase chain reaction (RT-PCR), protein levels of ER alpha, MMP-9 and cyclinD1 were detected by Western blotting, respectively. Tumor cells invasive ability were evaluated by Boyden chamber assay, the cells proliferation were evaluated using cell growth curve and MTT analysis, the cell cycle analysis was performed using flow cytometry. Results: Down-regulation of MTA1 by RNAi approach led to re-expression of ER alpha in ER-negative breast cancer cell lines MDA-MB-231, and reduced protein levels of MMP-9 and CyclinD1, as well as decreased tumor cell invasion and proliferation, more cells were blocked in G0/G1 stage(P < 0.05). However, after inhibiting mRNA levels of MTA1, protein expression of ER alpha, MMP-9, cyclinD1 and the changes of cancer cells invasiveness, proliferation, cells cycle were no statistical difference in ER-positive human breast cancer cell lines MCF-7 (P > 0.05). Conclusions: ShRNA targeted against MTA1 could specifically mediate the MTA1 gene silencing and consequentially recover the protein expression of ER alpha, resulting in increase sensitivity of antiestrogens, as well as suppress the protein levels of MMP-9 and cyclinD1 in ER-negative human breast cancer cell lines MDA-MB-231. Silencing effect of MTA1 could efficiently inhibit the invasion and proliferation in MDA-MB-231 cells. The shRNA interference targeted against MTA1 may have potential therapeutic utility in human breast cancer. [ABSTRACT FROM AUTHOR]

Background: Drug resistance remains a great challenge in the treatment of gastric cancer. The goal of this study was to explore the anti-tumor effects and mechanism of cytokine-induced killer (CIK) cell combined with oxaliplatin (L-OHP) in human oxaliplatin-resistant gastric cancer cells. Methods: After producing oxaliplatin-resistant gastric cancer cells, cell morphology, growth and doubling time were observed, followed by detection of cell cycle distribution and apoptosis, drug sensitivity (e.g., L-OHP) and expression of P-gp and livin. MTT assay, in vivo pharmacodynamics and pathomorphology experiments were used to detect killing activities of CIK combined with L-OHP. Results: Compared with parental gastric cancer cells, oxaliplatin-resistant gastric cancer cells in S phase were reduced and cell apoptosis rate was increased (P < 0.05), the inhibition rate of 10 chemotherapeutics on oxaliplatin-resistant gastric cancer cells was significantly lower and the expression of P-gp was significantly higher (P < 0.05). However, there was no significant difference in livin expression between parental gastric cancer cells and oxaliplatin-resistant gastric cancer cells (P > 0.05). The in vitro killing activity of CIK combined with L-OHP on parental cells and oxaliplatin-resistant cells were significantly enhanced compared with L-OHP or CIK alone. And it showed greater synergetic effects against oxaliplatin-resistant cells compared with parental cells (P < 0.05). In addition, survival rate, abdominal circumference and pathomorphology results revealed stronger in vivo anti-tumor effects when the two therapies were combined. Conclusions: The mechanism of oxaliplatin-resistant cell secondary multidrug resistance was correlated with the variation of cell cycle distribution, extension of doubling time and upregulation of P-gp expression. The synergistic effect of CIK in combination with L-OHP on killing activity against oxaliplatin-resistant cells was shown in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Recent investigation of Cullin 4 (CUL4) has ushered this class of multiprotein ubiquitin E3 ligases to center stage as critical regulators of diverse processes including cell cycle regulation, developmental patterning, DNA replication, DNA damage and repair, and epigenetic control of gene expression. CUL4 associates with DNA Damage Binding protein 1 (DDB1) to assemble an ubiquitin E3 ligase that targets protein substrates for ubiquitin-dependent proteolysis. CUL4 ligase activity is also regulated by the covalent attachment of the ubiquitin-like protein NEDD8 to CUL4, or neddylation, and the COP9 signalosome complex (CSN) that removes this important modification. Recently, multiple WD40-repeat proteins (WDR) were found to interact with DDB1 and serve as the substrate-recognition subunits of the CUL4-DDB1 ubiquitin ligase. As more than 150-300 WDR proteins exist in the human genome, these findings impact a wide array of biological processes through CUL4 ligase-mediated proteolysis. Here, we review the recent progress in understanding the mechanism of CUL4 ubiquitin E3 ligase and discuss the architecture of CUL4-assembled E3 ubiquitin ligase complexes by comparison to CUL1-based E3s (SCF). Then, we will review several examples to highlight the critical roles of CUL4 ubiquitin ligase in genome stability, cell cycle regulation, and histone lysine methylation. Together, these studies provide insights into the mechanism of this novel ubiquitin ligase in the regulation of important biological processes. [ABSTRACT FROM AUTHOR]

Background: Coexistence of splenic marginal zone lymphoma with hepatocellular carcinoma is rare. Although some reports have suggested the possible pathogenic role of HBV, HCV, chronic and persistent antigenic stimulation in lymphoma, their role in causing lymphomas is still unclear. Case presentation: We describe a hepatocellular carcinoma with concomitant splenic marginal zone lymphoma in a 64-year-old Chinese man with cirrhosis. Serum hepatitis B virus surface antigen was positive and antihepatitis C virus antibody was negative. The resected liver mass measuring 4 × 3 × 3 cm was grey and soft with a small area of bleeding, necrosis and intact capsule. Cut surface of the spleen was red-purple and had a diffuse reticulonodular appearance indicative of prominent white pulp. On histologic sections, the liver mass was well and moderately differentiated hepatocellular carcinoma, and the splenic tumor was a specific low-grade small B-cell lymphoma. Immunohistochemical staining and gene rearrangement studies supported that the splenic tumor represents a clonal B-cell lymphoma. Therefore, the diagnosis of SMZL was made from the splenic specimen. Conclusion: To our knowledge, this is the second case report describing coexistence of hepatocellular carcinoma and splenic marginal zone lymphoma in the course of chronic HBV infection. However, we cannot assert at present that hepatitis B virus is directly involved in splenic lymphomagenesis until more information is collected from more cases in the future. [ABSTRACT FROM AUTHOR]