There are no available clinical tests that can accurately predict peanut allergy (PA) and/or anaphylaxis. This study is aimed at evaluating whether the component-resolved diagnostic (CRD) IgE and IgG4 tests can 1) distinguish PA from asymptomatic peanut sensitization; and 2) differentiate anaphylactic vs. non-anaphylactic PA.
This study included 20 non-atopic controls, 58 asymptomatically peanut-sensitized children, 55 non-anaphylactic and 53 anaphylactic PA cases from the Chicago Food Allergy Study. IgE and IgG4 to 103 allergens were measured using the ImmunoCAP ISAC technology, and were compared among each group of children. The random forest test was applied to estimate each allergen’s ability to predict PA and/or peanut anaphylaxis.
PA cases (with or without anaphylaxis) had significantly higher IgE reactivity to Ara h 1–3 (peanut allergens) and Gly m 5–6 (soy allergens) than asymptomatically-sensitized children (p<0.00001). Similar but more modest relationships were found for IgG4 to Ara h 2 (p<0.01). IgE to Ara h 2 was the major contributor to accurate discrimination between PA and asymptomatic sensitization. With an optimal cutoff point of 0.65 ISU-E, it conferred 99.1% sensitivity, 98.3% specificity, and a 1.2% misclassification rate in the prediction of PA, which represented a higher discriminative accuracy than IgE to whole peanut extract (p=0.008). However, none of the IgE and/or IgG4 tests could significantly differentiate peanut anaphylaxis from non-anaphylactic PA.
IgE to Ara h 2 can efficiently differentiate clinical PA from asymptomatic peanut sensitization, which may represent a major step forward in the diagnosis of PA.
Ara h 2; Component-resolved diagnostics; Diagnostic performance; Peanut allergy; Peanut anaphylaxis
The purpose of this study was to establish an animal model of chronic pulmonary hypertension with a single-dose intraperitoneal injection of monocrotaline (MCT) in young Tibet minipigs, so as to enable both invasive and noninvasive measurements and hence facilitate future studies.
Twenty-four minipigs (8-week-old) were randomized to receive single-dose injection of 12.0 mg/kg MCT (MCT group, n = 12) or placebo (control group, n = 12 each). On day 42, all animals were evaluated for pulmonary hypertension with conventional transthoracic echocardiography, right heart catheterization (RHC), and pathological changes. Findings of these studies were compared between the two groups.
At echocardiography, the MCT group showed significantly higher pulmonary arterial mean pressure (PAMP) compared with the controls (P<0.001). The pulmonary valve curve showed v-shaped signals with reduction of a-waves in minipigs treated with MCT. In addition, the MCT group had longer pulmonary artery pre-ejection phases, and shorter acceleration time and ejection time. RHC revealed higher mean pulmonary arterial pressure (mPAP) in the MCT group than in the control group (P<0.01). A significant and positive correlation between the mPAP values and the PAMP values (R = 0.974, P<0.0001), and a negative correlation between the mPAP and ejection time (R = 0.680, P<0.0001) was noted. Pathology demonstrated evidence of pulmonary vascular remodeling and higer index of right ventricular hypertrophy in MCT-treated minipigs.
A chronic pulmonary hypertension model can be successfully established in young minipigs at six weeks after MCT injection. These minipig models exhibited features of pulmonary arterial hypertension that can be evaluated by both invasive (RHC) and noninvasive (echocardiography) measurements, and may be used as an easy and stable tool for future studies on pulmonary hypertension.
Transcatheter arterial embolization (TAE) is widely used as an effective palliative treatment for hepatocellular carcinoma (HCC), and can prolong survival time. However, the high incidence of tumor recurrence and metastasis after TAE is still a major problem. Recent studies demonstrated that circulating tumor cells (CTCs) contribute to tumor metastasis. In this study, we tried to clarify whether the residual HCC after TAE can increase metastasis by increasing the number of CTCs. An orthotopic liver tumor model in the Buffalo rat was established using green fluorescent protein (GFP)-transfected HCC cell line, McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent TAE treatment from the gastroduodenal artery. Iodized oil or saline was injected intra-arterially. Blood samples were taken on day 0, 1, 3, 7, 14, and 21 for detection of CTCs after TAE treatment. We analyzed the number of CTCs and assessed the metastatic potential of surviving tumor cells in rats between TAE and control groups. Our results demonstrated that the metastatic colonies in the lung were significantly increased by TAE treatment. The number of CTCs was also significantly increased by TAE treatment from day 7 to day 21. The expression of hypoxia-inducible factor (HIF)-1α and epithelial–mesenchymal transition (EMT) marker proteins (N-cadherin and vimentin) was upregulated, but E-cadherin was downregulated after TAE treatment. In conclusion, the metastatic potential of residual HCC can be induced by TAE treatment in a rat liver tumor model, which involves the acquisition of EMT features and an increased number of CTCs.
transcatheter arterial embolization; hepatocellular carcinoma; circulating tumor cells; epithelial–mesenchymal transition
To determine the prevalence of asthenopia and identify any associated risk factors in the college students in Xi'an, China.
From April to September 2012, 1 500 students from five universities in Xi'an were selected according to a multi-stage stratified cluster sampling method. Data on demographic features, lifestyle or dietary habits, health status, living environment conditions, sleep and mental status, and asthenopia symptoms were collected through a self-administered validated questionnaire. Univariate logistic regression and multivariate logistic regression analysis modified by the factor analysis were performed to evaluate risk factors for asthenopia.
Fifty-seven percent of the college students complained of asthenopia. Statistically significant risk factors for asthenopia in the univariate analysis included 13 variables. Multivariate analysis revealed a significant relationship between the use of computer and asthenopia (OR 1.21, 95%CI: 1.09 to 1.35). Good sleep and mental status (OR 0.86, 95%CI: 0.76 to 0.97), good living environment conditions (OR 0.67, 95%CI: 0.60 to 0.76), and high intake of green leafy vegetables (OR 0.89, 95%CI: 0.80 to 0.98) were found to be strong predictors of decreasing the occurrence of asthenopia complaints.
Asthenopia symptom appears to be common among college students; and it is strongly associated with computer use, psychosocial state, environment conditions and dietary habits, suggesting that additional studies are warranted to verify these risk factors and establish prevention guidelines, especially for college students.
asthenopia; risk factor; epidemiological feature; college student
Mutations in the gene encoding CREB-binding protein (CBP) cause deficits in long-term plasticity, learning, and memory. Here, long-term synaptic facilitation (LTF) at Aplysia sensorimotor synapses in cell culture was used as a model system to investigate methods for overcoming deficits in LTF produced by a CBP knockdown. Injecting CBP-siRNA into individual sensory neurons reduced CBP levels and impaired LTF produced by a Standard Protocol of five, 5-min pulses of serotonin (5-HT) delivered at 20 min interstimulus intervals. A computational model, which simulated molecular processes underlying LTF induction, identified a Rescue Protocol of five pulses of 5-HT at non-uniform interstimulus intervals that overcame the consequences of reduced CBP and restored LTF. These results suggest that complementary empirical and computational studies can identify methods for ameliorating impairments of learning due to molecular lesions.
Under the circumstance of global population aging, the issue on how to facilitate the quality of life (QOL) for older people brings us grand challenge. On the way to solve this problem, it is inextricable to measure QOL for older people accurately at onset. This study is aimed at evaluating the reliability and validity of the Chinese version of the World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD).
We received 1005 valid WHOQOL-OLD questionnaires from 1050 respondents who were 60 and older by quota sampling method. To calculate the test-retest correlation coefficient we re-interviewed 101 participants from the community. Psychometric properties were evaluated from the aspect of feasibility, internal consistency reliability, test-retest reliability, content validity, construct validity and discriminant validity.
Missing item responses took up 0.0%-2.7% in the scale. The WHOQOL-OLD showed satisfactory reliability with Cronbach’s Alpha coefficients ranging from 0.711 (Social participation) to 0.842 (Sensory ability) for each domain. The intra-class correlation coefficients (ICC) presenting test-retest reliability were all over 0.7. In Confirmatory Factor Analysis (CFA), Root Mean Square Error of Approximation (RMSEA) was 0.084 (a little more than 0.08) and comparative fit index (CFI) 0.95 (>0.90) which meant acceptable construct validity. There were higher correlation coefficients between items and their hypothesized domains than other domains (P < 0.001), indicating good content validity. The results of t-test showed good discriminant validity of the WHOQOL-OLD between the healthy group and the unhealthy group (P < 0.0083).
The Chinese version of WHOQOL-OLD showed good feasibility, reliability and validity in this study. However, before it can be used national-widely, further research should be conducted in other areas of China.
Elderly; Quality of life; Reliability; Validity; WHOQOL-OLD
The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has previously been reported to be overexpressed in estrogen receptor α (ERα)-positive breast tumors and to promote breast cell proliferation; however, its mechanism is unknown. In this study, we demonstrated that silencing of BCA2 by small interfering RNAs (siRNAs) in two ERα-positive breast cancer cell lines, MCF-7 and T47D, decreases cell proliferation and increases the protein levels of the cyclin-dependent kinase inhibitor p21Waf/Cip1. The protein stability of p21 was negatively regulated by BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and proteasomal degradation. Knockdown of p21 partially rescues the cell growth arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes ERα-positive breast cancer cell proliferation at least partially through downregulating the expression of p21.
Ages at natural menarche and menopause are influenced by several genetic factors. This study aimed to investigate the possible relationship between the apolipoprotein E (ApoE) genotype and the age at menarche and natural menopause in Chinese females. In the current study, 398 (elderly group, aged 47–80 years) and 825 (young group, aged 15–25 years) Chinese females were enrolled under informed content. Ages at natural menarche and menopause were obtained by questionnaires. ApoE genotypes were identified by restriction fragment length polymorphism analysis. In the elderly group, the number of pregnancies and live births and breastfeeding were associated with the age at menopause (P = 0.008, P = 0.002, and P = 0.023, respectively). One-way ANOVA analysis revealed that the ApoE genotype was significantly associated with age at natural menopause (ANM; P = 0.010). Compared with ApoE ε3/3 carriers, ApoE ε3/4 females showed a 1.8-year delay in ANM (P = 0.002). Single ApoE allele-positive/allele-negative analysis also showed that the age at menopause of ApoE ε4 carriers was delayed compared with those who were not carriers (P = 0.023). In the young group, no statistical difference was found in the age of menarche between the carriers of ApoE ε3/3 and ε3/4. Single ApoE allele-positive/allele-negative analysis showed that the age at menarche in ApoE ε4 carriers was slightly earlier than in those who were not carriers (P = 0.048). Meanwhile, univariate association analysis revealed that the ApoE genotypes were not significantly associated with the age at menarche using age as a covariate in the pooled group (young + elderly) (P = 0.143). We demonstrated that the ApoE genotype is significantly linked to the age at natural menopause.
ApoE genotype; Age at menopause; Age at menarche
To evaluate associations between adiposity trajectories over time and insulin sensitivity and glucose deterioration in a Chinese twin cohort.
RESEARCH DESIGN AND METHODS
This study focused on 341 males and 292 females aged 20–50 years at baseline who had physical clinical examinations and oral glucose tolerance test at two time points with an average of 6 years apart. BMI, waist circumference, percent body fat (PBF), and percent trunk fat (PTF) trajectories were classified into five track groups based on age- and sex-specific tertiles at each visit. We calculated the odds of the insulin sensitivity index(0,120) [ISI(0,120)] or glycemic deterioration at follow-up among five defined trajectories (tertilebaseline → tertilefollow-up) using generalized estimate equation models. Additionally, we applied structural equation models to examine genetic and environmental influences on adiposity, adiposity change over time (ACO), ISI(0,120), and the interrelationships among them.
Participants with stable adiposity (BMI, waist circumference, PBF, and PTF) in the highest tertile or shifting to the highest tertile tended to have the lowest ISI(0,120) at follow-up or experience glycemic deterioration. Genetic factors exerted the major influence on adiposity, but environmental factors unique to each twin contributed more strongly to ISI and ACO. Correlations between adiposity/ACO and insulin sensitivity were mainly due to environmental influences.
When adiposity stays or becomes high, insulin sensitivity falls and risk of glycemic deterioration rises. Additionally, we found that genetic factors exerted the major influence on adiposity, while environmental factors played the principal role for ACO and insulin sensitivity.
The aim of the present study was to determine the efficacy of microsurgery treatment for parasagittal meningioma in the central gyrus region. A microsurgical technique was used to treat 26 patients with large parasagittal meningioma in the central gyrus region. The Rolandic and draining veins and the peritumoral normal brain tissue were retained, and the associated sagittal sinus was appropriately protected. A Simpson grade I, II or III resection was performed in 8 (30.8%), 12 (46.2%) and 6 (23.1%) patients, respectively, with no post-operative mortalities. Following treatment, 9 patients exhibited hemiparalysis. No tumor recurrence was found in 21 patients during the follow-up examination. The treatment protocol described in the current study included sufficient pre-operative imaging evaluations, a skilled microsurgical technique, improved protection of the Rolandic vein and treatment of the sagittal sinus, and was found to significantly increase the total tumor removal rate and decrease post-operative recurrence.
parasagittal meningioma; central gyrus region; microsurgery; Rolandic vein
The objective of this study was to evaluate the outcome of image-guided delivery of intraarterially infused chemotherapeutic drugs for patients with locally advanced breast cancer.
Twenty-eight patients with pathologically proven, locally advanced breast cancer received intraarterial chemoinfusion therapy (chemoinfusion) with docetaxel 75 mg/m2 and epirubicin 50 mg/m2. Digital subtraction angiography was performed to determine tumor arterial blood supply and to guide chemotherapy infusion. Patients were evaluated for complete remission (CR) and partial remission (PR).
Twenty-eight patients received a total of 64 intraarterial chemoinfusions, 20 patients (71.4%) received two infusions, and eight patients (28.6%) received three infusions. One patient (3.6%) had CR and 23 (82.1%) had PR. The total effectiveness rate (CR and PR) was 85.7% (24/28). All stage 3 patients underwent Phase II surgical resection after chemoinfusion, and the surgical resection participation rate was 100% (26/26). The mean time from the first chemoinfusion to surgery was 2 ± 1.2 months. Two patients with stage 4 cancer died of distant metastasis and cachexia, and the remaining 26 patients were still alive.
Intraarterial chemoinfusion is a safe and effective therapy, achieving down-staging in a relatively short period for locally advanced breast cancer.
advanced breast cancer; intraarterial infusion; chemotherapy; therapeutic effect
Knock-in mice with the common human BDNF Val66Met polymorphism have impaired trafficking of BDNF mRNA to dendrites. Given evidence that local synapse formation is dependent on dendritic translation of BDNF mRNA, it was hypothesized that loss-of-function Met allele mice would show synaptic deficits both at baseline and in response to ketamine, an NMDA antagonist that stimulates synaptogenesis in prefrontal cortex (PFC).
Whole-cell recordings from layer V medial PFC pyramidal cells in brain slices were combined with 2-photon laser scanning for analysis of WT, Val/Met, and Met/Met mice both at baseline and in response to a low dose of ketamine.
Val/Met and Met/Met mice were found to have constitutive atrophy of distal apical dendrites and decrements in apically-targeted excitatory postsynaptic currents (EPSCs) in layer V pyramidal cells of PFC. In addition, spine density and diameter were decreased, indicative of impaired synaptic formation/maturation (synaptogenesis). In Met/Met mice the synaptogenic effect of ketamine was markedly impaired, consistent with the idea that synaptogenesis is dependent on dendritic translation/release of BDNF. In parallel behavioral studies we found that the antidepressant response to ketamine in the forced swim test was blocked in Met/Met mice.
The results demonstrate that expression of the BDNF Met allele in mice results in basal synaptic deficits and blocks synaptogenic and antidepressant actions of ketamine in PFC, suggesting that the therapeutic response to this drug may be attenuated or blocked in depressed patients who carry the loss of function Met allele.
antidepressant; dendritic spines; EPSC; hypocretin; major depression; NMDA; serotonin
Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5′UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3′UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.
CpG; DIP test; DNA Methylation; empirical bayes; genome-wide; normal mixture
A continuous and compact CdS quantum dot-sensitive layer was synthesized on TiO2 nanorods by successive ionic layer adsorption and reaction (SILAR) and subsequent thermal annealing. The thickness of the CdS quantum dot layer was tuned by SILAR cycles, which was found to be closely related to light absorption and carrier transformation. The CdS quantum dot-sensitized TiO2 nanorod array photoelectrodes were characterized by scanning electron microscopy, X-ray diffraction, ultraviolet–visible absorption spectroscopy, and photoelectrochemical property measurement. The optimum sample was fabricated by SILAR in 70 cycles and then annealed at 400°C for 1 h in air atmosphere. A TiO2/CdS core-shell structure was formed with a diameter of 35 nm, which presented an improvement in light harvesting. Finally, a saturated photocurrent of 3.6 mA/cm2 was produced under the irradiation of AM1.5G simulated sunlight at 100 mW/cm2. In particular, the saturated current density maintained a fixed value of approximately 3 mA/cm2 without decadence as time passed under the light conditions, indicating the steady photoelectronic property of the photoanode.
Quantum dots; CdS; Nanocable arrays; SILAR
In this paper, the effects of two-dimensional correlation spectroscopy (2DCOS) on chance correlations in the spectral data, generated from the correlations between glucose concentration and some undesirable experimental factors, such as instrument drift, sample temperature variations, and interferent compositions in the sample matrix, are investigated. The aim is to evaluate the validity of the spectral data set, instead of assessing the calibration models, and then to provide a complementary procedure for better verifying or rejecting the data set. It includes tracing back to the source of the chance correlation on the chemical basis, selecting appropriate preprocessing methods before building multivariate calibration models, and therefore may avoid invalid models. The utility of the proposed analysis is demonstrated with a series of aqueous solutions using near-infrared spectra over the overtone band of glucose. Results show that, spectral variations from chance correlations induced by those experimental factors can be determined by the 2DCOS method, which develops avenues for prospectively accurate prediction in clinical application of this technology.
(170.1470) Blood or tissue constituent monitoring; (300.6340) Spectroscopy, infrared; (070.4790) Spectrum analysis
Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.
Schistosoma blood flukes, which cause schistosomiasis affecting 200 million people in the world, are dependent on signals from host CD4+ T cells to facilitate parasite growth and development in the mammalian host and to induce Th2-biased inflammatory granulomas. B cells, however, are reported to down-regulate granulomatous pathology in schistosomiasis, but not to affect the development of blood flukes together with CD4+ T lymphocytes. Thus it is not clear whether B cells mediate parasite development, reproduction and egg granuloma formation of schistosomes without the help of CD4+ T lymphocytes. Using mice that have severe combined immunodeficiency (scid) and mice lacking T cells (nude), we found that the absence of B cells can more seriously hamper the development and paring of adult worms, but granuloma formation of Schistosoma japonicum in scid mice was not down-regulated comparing with that in nude mice. The level of IL-10 in the sera of nude mice was significantly higher than of scid mice at 43 days post infection (p.i.). Thus multiple mechanisms of immune modulation seem to be involved in parasite development and reproduction by helminth-induced regulatory B cells. Our findings have significance for understanding the molecular connections between schistosomes and T- and B-cells, indicating that more research is needed to develop efficient vaccine-based therapies for schistosomiasis.
Currently available medications have significant limitations, most notably low response rate and time lag for treatment response. Recent clinical studies have demonstrated that ketamine, an NMDA receptor antagonist produces a rapid antidepressant response (within hours) and is effective in treatment resistant depressed patients. Molecular and cellular studies in rodent models demonstrate that ketamine rapidly increases synaptogenesis, including increased density and function of spine synapses, in the prefrontal cortex (PFC). Ketamine also produces rapid antidepressant actions in behavioral models of depression, and reverses the deficits in synapse number and behavior resulting from chronic stress exposure. These effects of ketamine are accompanied by stimulation of the mammalian target of rapamycin (mTOR), and increased levels of synaptic proteins. Together these studies indicate that ketamine rapidly reverses the atrophy of spines in the PFC and thereby causes a functional reconnection of neurons that underlies the rapid behavioral responses. These studies identify new targets for rapid acting antidepressants that are safer than ketamine.
Rapamycin; glutamate; depression; synaptogenesis
Recent studies have shown that circulating microRNAs might be useful, novel biomarkers for the diagnosis of acute myocardial infarction. The aims of this study were to evaluate the expression of cardiac-specific miRNAs (miR-1, -133a, -208b, and -499) in patients with acute myocardial infarction and to compare the diagnostic values of these miRNAs with that of cardiac troponin T.
Sixty-seven plasma samples obtained from patients with acute myocardial infarction and 32 plasma specimens collected from healthy volunteers were analyzed in this study. The levels of cardiac-specific miRNAs (miR-1, -133a, -208b, and -499) were measured by quantitative reverse transcription-polymerase chain reaction, and the concentrations of plasma cardiac troponin T were measured using electrochemiluminescence-based methods and an Elecsys 2010 Immunoassay Analyzer.
The levels of plasma miR-1, -133a, -208b, and -499 were significantly higher in acute myocardial infarction patients (all p<0.001) than in healthy volunteers. The expression of the cardiac-specific miRNAs in acute myocardial infarction patients decreased to close to the baseline levels at the time of hospital discharge (all p>0.05). There were no correlations between the levels of the four circulating miRNAs and the clinical characteristics of the study population (all p>0.05). Furthermore, receiver operating characteristic curve analyses showed that the four plasma miRNAs were not superior to cardiac troponin T for the diagnosis of acute myocardial infarction (all p>0.05).
Our results demonstrate that circulating miR-1, -133a, -208b, and -499 may be useful biomarkers in acute myocardial infarction patients but that these miRNAs are not superior to cardiac troponin T for the diagnosis of acute myocardial infarction.
microRNAs; cardiac troponin T; Acute Myocardial Infarction; Circulating Biomarkers
It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy. However, the epidemiological evidence is conflicting. We aim to examine if cord blood VDD is associated with FS and if such association can be modified by genetic variants in a prospective birth cohort.
This study included 649 children who were enrolled at birth and followed from birth onward at the Boston Medical Center. We defined VDD as cord blood 25(OH)D < 11ng/ml, and FS as specific IgE ≥ 0.35kUA/L to any of eight common food allergens in early childhood. We genotyped potentially functional single nucleotide polymorphisms (SNPs) in 11 genes known to be involved in regulating IgE and 25(OH)D concentrations. Logistic regressions were used to test the effects of VDD on FS individually and jointly with SNPs.
Among the 649 children, 44% had VDD and 37% had FS. When examined alone, VDD was not associated with FS. When examined jointly with SNPs, a significant interaction between IL4 gene polymorphism (rs2243250) and VDD (pinteraction=0.003, pFDR=0.10) was found: VDD increased the risk of FS among children carrying CC/CT genotypes (OR=1.79, 95%CI: 1.15–2.77). Similar but weaker interactions were observed for SNPs in MS4A2 (rs512555), FCER1G (rs2070901), and CYP24A1 (rs2762934). When all four SNPs were simultaneously considered, a strong gene-VDD interaction was evident (pinteraction=9×10−6).
Our data demonstrate that VDD may increase the risk of FS among individuals with certain genotypes, providing evidence of gene-vitamin D interaction on FS.
cord blood plasma 25(OH)D; food sensitization; gene-vitamin D deficiency interaction; SNP
A new approach of fabricating supramolecular nanoparticles generated by self-assembly polyrotaxanes for antitumor drug delivery has been reported. Cinnamic-acid-modified poly(ethylene glycol) chains were threaded in α-cyclodextrins to form polyrotaxanes. The polyrotaxanes self-assembled supramolecular nanoparticles. The morphology of the nanoparticles was changed from nanovesicle to micelle after the antitumor drug, doxorubicin, was loaded. The release profile of the drug-loaded nanoparticles was investigated, and it was found that the sustaining release time could last for 32 hours. The drug-loaded nanoparticles were co-cultured with mouse 4T1 breast cancer cells with a drug concentration of 10 μg/mL; the cell survival rate was 3.3% after a 72-hour incubation. In an in vivo study of breast cancer in a mouse model, the drug-loaded nanoparticles were injected in the tail veins of mice with a dose of 5 mg/kg body weight. The tumor inhibition rate of drug-loaded nanoparticles was 53%, which was better than that of doxorubicin hydrochloride. The cardiac toxicity of doxorubicin was decreased greatly after the encapsulation into supramolecular polyrotaxane nanoparticles.
polyrotaxane; self-assembly; nanoparticle; doxorubicin; supermolecular
To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity.
This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration, and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire modified for a Chinese population. Multivariate linear regressions were applied to examine the association of sleep duration with HOMA-IR, with and without adjustment for adiposity variables, along with other relevant covariates.
In this sample of relatively lean rural Chinese adults, short sleep duration was associated with HOMA-IR in women but not in men. In women, short (≤7 hrs/night) sleep duration was associated with a higher HOMA-IR (p=0.003) compared with normal sleep duration (>7 to ≤8 hrs/night) after adjustment for all the covariates except adiposity. Further adjustment for BMI or %TF attenuated the sleep-HOMA-IR association, but the association remained significant upon adjustment for BMI (p=0.013); and upon adjustment for %TF (p=0.026). Long sleep duration (>8 hrs/night) was not significantly associated with HOMA-IR.
In this rural Chinese cohort, short sleep duration is independently associated with increased insulin resistance among women only, even after adjusting for adiposity and other potential confounders.
sleep duration; insulin resistance; adiposity; gender; rural; adults
Two methoxyl poly(ethylene glycol)-poly(L-histidine)-poly(L-lactide) (mPEG-PH-PLLA) triblock copolymers with different poly(L-histidine) chain lengths were synthesized. The morphology and biocompatibility of these self-assembled nanoparticles was investigated.
Doxorubicin, an antitumor drug, was trapped in the nanoparticles to explore their drug-release behavior. The drug-loaded nanoparticles were incubated with HepG2 cells to evaluate their antitumor efficacy in vitro. The effects of poly(L-histidine) chain length on the properties, drug-release behavior, and antitumor efficiency of the nanoparticles were investigated.
The nanoparticles were pH-sensitive. The mean diameters of the two types of mPEG-PH- PLLA nanoparticle were less than 200 nm when the pH values were 5.0 and 7.4. The nanoparticles were nontoxic to NIH 3T3 fibroblasts and HepG2 cells. The release of doxorubicin at pH 5.0 was much faster than that at pH 7.4. The release rate of mPEG45-PH15-PLLA82 nanoparticles was much faster than that of mPEG45-PH30-PLLA82 nanoparticles at pH 5.0.
The inhibition effect of mPEG45-PH15-PLLA82 nanoparticles on the growth of HepG2 cells was greater than that of mPEG45-PH30-PLLA82 nanoparticles when the concentration of encapsulated doxorubicin was less than 15 μg/mL.
poly(ethylene glycol); poly(L-histidine); poly(L-lactide); pH sensitivity; doxorubicin; drug release; nanoparticle
Learning and memory are influenced by the temporal pattern of training stimuli. The mechanisms that determine the effectiveness of a particular training protocol are not well understood, however. The hypothesis that the efficacy of a protocol is determined, in part, by interactions among biochemical cascades that underlie learning and memory was examined. Previous studies suggest that the PKA and ERK cascades are necessary to induce long-term synaptic facilitation (LTF) in Aplysia, a neuronal correlate of memory. A computational model of the PKA and ERK cascades was developed, and used the model to identify a novel training protocol that maximized PKA/ERK interactions. In vitro studies confirmed that the protocol enhanced LTF. Moreover, the protocol enhanced levels of phosphorylation of the transcription factor CREB1. Behavioral training confirmed that long-term memory also was enhanced by the protocol. These results illustrate the feasibility of using computational models to design training protocols that improve memory.