Kinetics of non-structural protein 1, IgM and IgG antibodies in dengue type 1 primary infection

<p>Abstract</p> <p>Background</p> <p>Early and accurate diagnosis of dengue infection is essential for control of disease outbreaks. Recently, the dengue virus non-structural antigen 1 (NS1), a conserved and secreted glycoprotein, has been used as a marker for early diagnosis of dengue with convenience and cost-effectiveness. Serological tests of dengue IgM and IgG antibodies are still the most widely used for diagnosis of dengue. In order to assess combined diagnostic value of these tests, we study the kinetic profiles of circulating NS1, dengue IgM and IgG antibodies over the course of the disease by using an in-house dengue type 1 (DENV1) specific NS1 capture ELISA and the commercial Panbio Dengue IgM and IgG capture ELISAs.</p> <p>Results</p> <p>A panel of 313 acute-and early convalescent-phase serum specimens from 140 DENV1 primary infected patients during an outbreak of dengue in Guangzhou, China, in 2006 were studied. Dengue NS1 presented high levels in acute-phase serum samples. It was detectable as early as day 1 of illness, and up to 14 day after onset. The sensitivity of NS1 detection was ranged from 81.8% to 91.1% with samples taken during the first 7 days. Anti-dengue IgM antibody was detectable on the third day of onset with the positive rate of 42.9%, and rapidly increasing to 100% by day 8 of illness. Anti-dengue IgG antibody was detectable on the fifth day of onset with low level at the first week of onset, and slowly increasing to 100% by day 15 of illness. Combining the results of NS1 and IgM antibody detection allowed positive diagnosis in 96.9% -100% for samples taken after day 3 of onset.</p> <p>Conclusions</p> <p>Dengue NS1 detection might shorten the window period by first few days of illness. A combination of dengue NS1 antigen and IgM antibody testing facilitates enhanced diagnosis rates. The procedures should be suitable for developing countries where dengue is endemic.</p

The protective effect of serum carotenoids on cardiovascular disease: a cross-sectional study from the general US adult population

BackgroundCardiovascular disease (CVD) has become a key global health issue. Serum carotenoids are associated with CVD, while their effects on different diseases remain unclear. Herein, the relationship between the concentration of serum carotenoid and the CVD risk was investigated using nationwide adult samples obtained from the USA.Materials and methodsData of National Health and Nutrition Examination Survey (NHANES) in 2001–2006 were employed. The association of serum carotenoids (total, lycopene, β-carotene, α-carotene, lutein/zeaxanthin, and β-cryptoxanthin) with CVD was explored by using multivariate logistic, linear and weighted quantile sum (WQS) regression analyses. Eventually, data from 12,424 volunteers were analyzed for this study.ResultsMultivariate model data showed that lutein/zeaxanthin, α-carotene, lycopene, and β-cryptoxanthin were negatively associated with the prevalence of CVD (p &lt; 0.05). In comparison with the first quartile, the fourth quartile was associated with α-carotene ([OR] = 0.61 [0.47–0.79]), β-cryptoxanthin (OR = 0.67 [0.50–0.89]), lutein (OR = 0.69 [0.54–0.86]), and lycopene (OR = 0.53 [0.41–0.67]). WQS analysis revealed that the combination of serum carotenoids had negative correlation with the prevalence of total CVD (OR = 0.88, 95% CI: 0.85–0.92, p &lt; 0.001). Additionally, dose–response analysis demonstrated a negative linear association of hypertension with all the carotenoids involved (p &gt; 0.05 for non-linearity).ConclusionThe concentration of serum carotenoids had negative correlation with the prevalence of CVD, with a more significant negative effect against heart attack and stroke

TO901317 regulating apolipoprotein M expression mediates via the farnesoid X receptor pathway in Caco-2 cells

<p>Abstract</p> <p>Background</p> <p>Apolipoprotein M (apoM) may have potential antiatherosclerotic properties. It has been reported that apoM expression could be regulated by many intracellar and extracellar factors. In the present study we further investigated regulation of apoM expression in Caco-2 cells stimulated by a liver X receptor (LXR) agonist, TO901317.</p> <p>Materials and methods</p> <p>Caco-2 cells were cultured in the presence of either TO901317, farnesoid X receptor (FXR) antagonist guggulsterone or TO901317 together with guggulsterone at different concentrations for 24 hrs. The mRNA levels of ATP-binding cassette transporter A1 (ABCA1), apoA1, apoM, liver receptor homologue-1 (LRH-1) and short heterodimer partner 1 (SHP1) were determined by real-time RT-PCR.</p> <p>Results</p> <p>When Caco-2 cell cultured with TO901317 alone, the mRNA levels of ABCA1, apoA1, apoM, LRH-1 and SHP1 were significantly increased with dose-dependent manners (<it>p </it>< 0.05), whereas when the cells cultured with guggulsterone alone, the mRNA levels of apoM, SHP1 and LRH-1 (<it>p </it>< 0.05) were strongly inhibited. Moreover, guggulsterone could abolish the TO901317 enhanced mRNA levels of apoA1 apoM, SHP1 and LRH-1.</p> <p>Conclusion</p> <p>The present study demonstrated that LXR agonist TO901317 induced apoM expression in Caco-2 cells might be mediated via the LXR/FXR pathway.</p

Identifying octogenarians with non-small cell lung cancer who could benefit from surgery: A population-based predictive model

BackgroundAs the population ages, there will be an increasing number of octogenarian patients with non-small cell lung cancer (NSCLC). In carefully selected elderly patients, surgery can improve long-term survival. To identify candidates who would benefit from surgery, we performed this study and built a predictive model.Materials and methodsData from NSCLC patients over 80 years old were obtained from the Surveillance, Epidemiology and End Results database. A 1:1 propensity score matching was performed to balance the clinicopathological features between the surgery and non-surgery groups. Kaplan-Meier analyses and log-rank tests were used to assess the significance of surgery to outcome, and Cox proportional-hazards regression and competing risk model were conducted to determine the independent prognostic factors for these patients. A nomogram was built using multivariable logistic analyses to predict candidates for surgery based on preoperative factors.ResultsThe final study population of 31,462 patients were divided into surgery and non-surgery groups. The median cancer-specific survival time respectively was 53 vs. 13 months. The patients’ age, sex, race, Tumor, Node, Metastasis score, stage, chemotherapy use, tumor histology and nuclear grade were independent prognostic factors. Apart from race and chemotherapy, other variates were included in the predictive model to distinguish the optimal surgical octogenarian candidates with NSCLC. Internal and external validation confirmed the efficacy of this model.ConclusionSurgery improved the survival time of octogenarian NSCLC patients. A novel nomogram was built to help clinicians make the decision to perform surgery on elderly patients with NSCLC

Combining high-throughput micro-CT-RGB phenotyping and genome-wide association study to dissect the genetic architecture of tiller growth in rice

Manual phenotyping of rice tillers is time consuming and labor intensive and lags behind the rapid development of rice functional genomics. Thus, automated, non-destructive phenotyping of rice tiller traits at a high spatial resolution and high-throughput for large-scale assessment of rice accessions is urgently needed. In this study, we developed a high-throughput micro-CT-RGB (HCR) imaging system to non-destructively extract 730 traits from 234 rice accessions at 9 time points. We could explain 30% of the grain yield variance from 2 tiller traits assessed in the early growth stages. A total of 402 significantly associated loci were identified by GWAS, and dynamic and static genetic components were found across the nine time points. A major locus associated with tiller angle was detected at nine time points, which contained a major gene TAC1. Significant variants associated with tiller angle were enriched in the 3'-UTR of TAC1. Three haplotypes for the gene were found and rice accessions containing haplotype H3 displayed much smaller tiller angles. Further, we found two loci contained associations with both vigor-related HCR traits and yield. The superior alleles would be beneficial for breeding of high yield and dense planting

Rac1 Is Required for Pathogenicity and Chm1-Dependent Conidiogenesis in Rice Fungal Pathogen Magnaporthe grisea

Rac1 is a small GTPase involved in actin cytoskeleton organization and polarized cell growth in many organisms. In this study, we investigate the biological function of MgRac1, a Rac1 homolog in Magnaporthe grisea. The Mgrac1 deletion mutants are defective in conidial production. Among the few conidia generated, they are malformed and defective in appressorial formation and consequently lose pathogenicity. Genetic complementation with native MgRac1 fully recovers all these defective phenotypes. Consistently, expression of a dominant negative allele of MgRac1 exhibits the same defect as the deletion mutants, while expression of a constitutively active allele of MgRac1 can induce abnormally large conidia with defects in infection-related growth. Furthermore, we show the interactions between MgRac1 and its effectors, including the PAK kinase Chm1 and NADPH oxidases (Nox1 and Nox2), by the yeast two-hybrid assay. While the Nox proteins are important for pathogenicity, the MgRac1-Chm1 interaction is responsible for conidiogenesis. A constitutively active chm1 mutant, in which the Rac1-binding PBD domain is removed, fully restores conidiation of the Mgrac1 deletion mutants, but these conidia do not develop appressoria normally and are not pathogenic to rice plants. Our data suggest that the MgRac1-Chm1 pathway is responsible for conidiogenesis, but additional pathways, including the Nox pathway, are necessary for appressorial formation and pathogenicity

Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study

The adenosine antagonist 7-methylxanthine (7-mx) works against myopia in animal models. In a clinical trial, 68 myopic children (mean age 11.3 years) received either placebo or 7-mx tablets for 12 months. All participants subsequently received 7-mx for another 12 months, after which treatment was stopped. Axial length was measured with Zeiss IOL-Master and cycloplegic refraction with Nikon Retinomax at −6, 0, 12, 24, and 36 months. Axial growth was reduced among children treated with 7-mx for 24 months compared with those only treated for the last 12 months. Myopia progression and axial eye growth slowed down in periods with 7-mx treatment, but when the treatment was stopped, both myopia progression and axial eye growth continued with invariable speed. The results indicate that 7-mx reduces eye elongation and myopia progression in childhood myopia. The treatment is safe and without side effects and may be continued until 18–20 years of age when myopia progression normally stops

Early over expression of messenger RNA for multiple genes, including insulin, in the Pancreatic Lymph Nodes of NOD mice is associated with Islet Autoimmunity

<p>Abstract</p> <p>Background</p> <p>Autoimmune diabetes (T1D) onset is preceded by a long inflammatory process directed against the insulin-secreting β cells of the pancreas. Deciphering the early autoimmune mechanisms represents a challenge due to the absence of clinical signs at early disease stages. The aim of this study was to identify genes implicated in the early steps of the autoimmune process, prior to inflammation, in T1D. We have previously established that insulin autoantibodies (E-IAA) predict early diabetes onset delineating an early phenotypic check point (window 1) in disease pathogenesis. We used this sub-phenotype and applied differential gene expression analysis in the pancreatic lymph nodes (PLN) of 5 weeks old Non Obese Diabetic (NOD) mice differing solely upon the presence or absence of E-IAA. Analysis of gene expression profiles has the potential to provide a global understanding of the disease and to generate novel hypothesis concerning the initiation of the autoimmune process.</p> <p>Methods</p> <p>Animals have been screened weekly for the presence of E-IAA between 3 and 5 weeks of age. E-IAA positive or negative NOD mice at least twice were selected and RNAs isolated from the PLN were used for microarray analysis. Comparison of transcriptional profiles between positive and negative animals and functional annotations of the resulting differentially expressed genes, using software together with manual literature data mining, have been performed.</p> <p>Results</p> <p>The expression of 165 genes was modulated between E-IAA positive and negative PLN. In particular, genes coding for insulin and for proteins known to be implicated in tissue remodelling and Th1 immunity have been found to be highly differentially expressed. Forty one genes showed over 5 fold differences between the two sets of samples and 30 code for extracellular proteins. This class of proteins represents potential diagnostic markers and drug targets for T1D.</p> <p>Conclusion</p> <p>Our data strongly suggest that the immune related mechanisms taking place at this early age in the PLN, correlate with homeostatic changes influencing tissue integrity of the adjacent pancreatic tissue. Functional analysis of the identified genes suggested that similar mechanisms might be operating during pre-inflammatory processes deployed in tissues i) hosting parasitic microorganisms and ii) experiencing unrestricted invasion by tumour cells.</p