High-energy molecular-frame photoelectron angular distributions: a molecular bond-length ruler.

We present a study on molecular-frame photoelectron angular distributions (MFPADs) of small molecules using circularly polarized synchrotron light. We find that the main forward-scattering peaks of the MFPADs are slightly tilted with respect to the molecular axis. This tilt angle is directly connected to the molecular bond length by a simple, universal formula. We apply the derived formula to several examples of MFPADs of C 1s and O 1s photoelectrons of CO, which have been measured experimentally or obtained by means of ab initio modeling. In addition, we discuss the influence of the back-scattering contribution that is superimposed over the analyzed forward-scattering peak in the case of homo-nuclear diatomic molecules such as N2.

[Tumor-induced osteomalacia caused by an orbital tumor: a case report].

A 52-year-old patient was initially diagnosed as hypophosphatemic osteomalacia in the Department of Endocrinology due to knee, foot and lumbosacral pain. The symptoms were not significantly relieved after phosphorus and vitamin D supplementation. Later, the imaging examination showed an orbital tumor in the right eye. The tumor was surgically removed, and the symptoms of systemic bone pain were relieved.

LncRNA DSCAM-AS1 promotes non-small cell lung cancer progression via regulating miR-577/HMGB1 axis.

Non-small cell lung cancer (NSCLC) is a major source of cancer mortality. Long non-coding RNA DSCAM-AS1 has been certified to be involved in the pathogenesis of NSCLC. This study aimed to further investigate the potential mechanism of DSCAM-AS1 in NSCLC progression. The expressions of DSCAM-AS1, miR-577, and high mobility group box 1 (HMGB1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry assay was conducted to monitor cell apoptosis. Cell migration and invasion were measured by transwell assay. Wnt/ß-catenin pathway-related factors were detected by western blot assay. The relationship between DSCAM-AS1, miR-577, and HMGB1 was validated by bioinformatics analysis and dual-luciferase reporter assay. The xenograft mouse model was established to analyze tumor growth in vivo. DSCAM-AS1 and HMGB1 were upregulated, while miR-577 was downregulated in NSCLC tissues and cells. DSCAM-AS1 promoted cell proliferation, migration and invasion, and restrained cell apoptosis in NSCLC cells. Overexpression of HMGB1 reversed the effects of DSCAM-AS1 depletion on the progression of NSCLC. DSCAM-AS1 modulated HMGB1 expression by sponging miR-577. DSCAM-AS1 regulated the Wnt/ß-catenin pathway by regulating miR-577 and HMGB1. DSCAM-AS1 knockdown blocked the tumor growth in vivo. In conclusion, DSCAM-AS1 facilitated NSCLC progression by regulating the HMGB1-mediated Wnt/ß-catenin pathway, providing a promising therapeutic target for NSCLC.

A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization.

Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N-(n-nonyl)deoxynojirimycin (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

[The research of proteome profiling change of 1-bromopropane poisoning cases].

Objective: This study was mainly focused on styudy on he proteome profile change between exposure to 1-Bromopropane (1-BP) and 1-BP poisoning. Methods: The samples of serums from exposure to 1-BP and 1-BP poisoning were collected and analyzed through Label free proteome technology platform. The differently expressed proteins between the two groups were quantified and identified, followed by function analysis by bioinformatics. Results: 127 proteins over 2 fold-change were selected, in which 39 proteins were up-regulated and 88 proteins were down-regulated. These different-ly expressed proteins were mainly involved in the process of enzyme active regulation, inflammatory reaction, protein modification, stress response, coagulation, transport. Conclusion: The differently expressed proteins provided the potential protein biomarkers for the early diagnosis of 1-BP poisoning and was beneficial for clinical diagnosis of 1-BP and understanding of the mechanism of 1-BP poisoning.

Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17).

BACKGROUND: Pemetrexed has shown a favourable response rate of about 30% with minimal toxicity when used as a single agent for treatment of advanced urothelial carcinoma. This phase II study evaluated the efficacy and safety of pemetrexed plus cisplatin in advanced urothelial carcinoma. METHODS: This multicentre, single-arm, open-label, phase II clinical trial enrolled patients who had advanced urothelial carcinoma, ECOG PS 0-2, and measurable disease. Pemetrexed 500 mg m(-2) with cisplatin 70 mg m(-2) on day 1 were administered every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: A total of 42 patients were enrolled (median age, 66 years; ECOG 0-1, 100%; visceral metastasis, 54.8%; recurrent disease, 57.1%). Twenty-seven partial responses for an ORR of 64.3% (95% CI, 49.2%-77.0%) were documented. Seven patients had stable disease. Median PFS and OS were 6.9 (95% CI, 6.2-7.6) and 14.4 (95% CI, 10.4-18.4) months, respectively. Grade 3 or 4 neutropenia was observed in 28.6% of patients. No patients experienced febrile neutropenia. CONCLUSION: The combination of pemetrexed and cisplatin is active, and well tolerated in patients with advanced urothelial cancer as a first-line treatment.

Analysis of renal functions and proteinuria in young obese adults.

OBJECTIVE: To investigate the prevalence of obesity in young adults and to analyze the influencing factors on renal functions and proteinuria in this population. METHODS: This study comprised civil servants between 20 and 39 years old, who received physical examinations at the First Affiliated Hospital of Fujian Medical University. The subjects were categorized into four groups based on age (20-24, 25-29, 30-34 and 35-39 years) and the number of risk factors they had (hypertension, dyslipidemia, hyperglycemia and hyperuricemia). The relationships between obesity and the prevalence of proteinuria, between obesity and risk factors and between estimated glomerular filtration rate (eGFR) and proteinuria were analyzed. RESULTS: Among the 2293 young civil servants, in men the prevalence of obesity was 33.3 % and proteinuria was 2.5 %. However in women the prevalence of obesity and proteinuria was 7.5 % and 1.7 %, respectively. The levels of blood pressure, serum uric acid (UA), cholesterol (TC), triglyceride (TG), fasting glucose (FBG) and low-density lipoprotein cholesterol (LDL-C) were lower and the level of serum high-density lipoprotein cholesterol (HDL-C) was higher in nonobese groups compared with obese groups. There were no significant differences in eGFR between the two groups. The eGFR in male subjects was associated with age, UA, body mass index (BMI), FBG, TC, TG, LDL and HDL, and in female subjects associated with UA, age, BMI, diastolic blood pressure, FBG and LDL. BMI in both males and females increased with the higher number of risk factors. Multiple regression analysis revealed that hypertension, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with obesity. eGFR decreased with a higher number of risk factors. Obesity, blood pressure, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with proteinuria. CONCLUSION: Obesity can pose an independent risk factor for proteinuria in young adults. Hypertension, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with obesity. eGFR decreased with a higher number of risk factors.

[The emulation of clinical trials with real-world data: development and application of target trial].

Clinical trial is the gold standard for evaluating the efficacy and safety of interventions; however, it is limited by high costs and long time. Real-world data (RWD) can provide a robust data basis for comparative research, but the quality is uneven. This review introduces the target trial emulation, in which researchers, using RWD and following the design of clinical trials, define exposure and outcome in advance, set eligibility criteria, determine the time zero, estimate sample size, and plan statistical analysis, to enhance the quality of evidence for observational studies. This review preliminarily discusses the standard of evidence quality evaluation in target trial emulation. Then, the target trial emulation is shown through case interpretation.

Constitutively activating mutation in WASP causes X-linked severe congenital neutropenia.

The Wiskott-Aldrich syndrome protein (WASP; encoded by the gene WAS) and its homologs are important regulators of the actin cytoskeleton, mediating communication between Rho-family GTPases and the actin nucleation/crosslinking factor, the Arp2/3 complex. Many WAS mutations impair cytoskeletal control in hematopoietic tissues, resulting in functional and developmental defects that define the X-linked Wiskott-Aldrich syndrome (WAS) and the related X-linked thrombocytopenia (XLT). These diseases seem to result from reduced WASP signaling, often through decreased transcription or translation of the gene. Here we describe a new disease, X-linked severe congenital neutropenia (XLN), caused by a novel L270P mutation in the region of WAS encoding the conserved GTPase binding domain (GBD). In vitro, the mutant protein is constitutively activated through disruption of an autoinhibitory domain in the wild-type protein, indicating that loss of WASP autoinhibition is a key event in XLN. Our findings highlight the importance of precise regulation of WASP in hematopoietic development and function, as impairment versus enhancement of its activity give rise to distinct spectra of cellular defects and clinical phenotypes.

Diffusion MRI correlation with p16 status and prediction for tumor progression in locally advanced head and neck cancer.

Purpose: To investigate p16 effects on diffusion image metrics and associations with tumor progression in patients with locally advanced head and neck cancers. Methods: Diffusion images pretreatment and after 20 Gy (2wk) of RT were analyzed in patients with cT4/N3 p16+ oropharynx cancer (OPSCC) (N=51) and locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) (N=28), enrolled onto a prospective adaptive RT trial. Mean ADC values, subvolumes with ADC <1.2 um2/ms (TVLADC), and peak values of low (µL) and high (µH) components of ADC histograms in primary and total nodal gross tumor volumes were analyzed for prediction of freedom from local, distant, or any progression (FFLP, FFDP or FFLRDP) using multivariate Cox proportional-hazards model with clinical factors. P value with false discovery control <0.05 was considered as significant. Results: With a mean follow up of 36 months, 18 of LAHNSCC patients and 16 of p16+ OPSCC patients had progression. After adjusting for p16, small µL and ADC values, and large TVLADC of primary tumors pre-RT were significantly associated with superior FFLRDP, FFLP and FFDP in the LAHNSCC (p<0.05), but no diffusion metrics were significant in p16+ oropharynx cancers. Post ad hoc analysis of the p16+ OPSCC only showed that large TVLADC of the total nodal burden pre-RT was significantly associated with inferior FFDP (p=0.05). Conclusion: ADC metrics were associated with different progression patterns in the LAHNSCC and p16+ OPSCC, possibly explained by differences in cancer biology and morphology. A deep understanding of ADC metrics is warranted to establish imaging biomarkers for adaptive RT in HNSCC.

A 2-Stage Root Analog Implant with Compact Structure, Uniform Roughness, and High Accuracy.

Immediate implant placement has the advantages of shortening the operation time, reducing the treatment cycle and cost. At present, this technology has been used widely, but the indications of immediate implantation are still limited. Here, a novel type of root analog implant (RAI) was manufactured by selective laser melting technology to address the limitation. Under optimized condition, RAIs were printed with the internal density of 99.73% and the uniform surface roughness of 11 µm (Sa). Besides, the deviation between RAI specimen and design models is controlled within 0.15 mm after optimizing scanning parameters. The substrate printed could promote human bone marrow stromal cell proliferation, spreading, and osteogenic differentiation. The bone-implant contact (BIC, 75% ± 7%) and bone volume/total volume (BV/TV, 74% ± 7%) of RAIs were significantly higher than that of conventional implants (BIC, 66% ± 5%; BV/TV, 62% ± 5%) in in vivo experiments. Further, customized abutments were designed for the RAIs, improving the masticatory ability of the beagle dogs after crown restoration. This study aims to design a personalized 2-stage RAI with compact structure and uniform roughness, in order to achieve better fracture resistance, initial osseointegration efficiency, and dispersed stress in immediate implantation. It provides a certain guiding value for standardizing the manufacture and clinical application of RAI in immediate implantation.

[A comparative study of multiple parallel mediation analysis methods].

Objective: To introduce and compare four analysis methods of multiple parallel mediation model, including pure regression method, method based on inverse probability weighting, extended natural effect model method and weight-based imputation strategies. Methods: For the multiple parallel mediation model, the simulation experiments of three scenarios were carried out to compare the performance of different methods in estimating direct and indirect effects in different situations. Dataset from UK Biobank was then analyzed by using the four methods. Results: The estimation biases of the regression method and the inverse probability weighting method were relatively small, followed by the extended natural effect model method, and the estimation results of the weight-based imputation strategies were quite different from the other three methods. Conclusions: Different multiple parallel mediation analysis methods have different application situations and their own advantages and disadvantages. The regression method is more suitable for continuous mediator, and the inverse probability weighting method is more suitable for binary mediator. The extended natural effect model method has better performances when the residuals of two parallel mediators are positively correlated and the correlation degree is small. The weight-based imputation strategies might not be appropriate for parallel mediation analysis. Therefore, appropriate methods should be selected according to the specific situation in practice.

[Numb activates the mTORC1 signaling pathway in proximal tubular epithelial cells by upregulating V1G1 expression].

OBJECTIVE: To investigate the role of Numb in regulating mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway. METHODS: Male BALB/C mouse models of acute kidney injury (AKI) were subjected to intravenous injections of Numb-siRNA or NC-siRNA with or without intraperitoneal cisplatin injections. After the treatments, the expressions and distribution of Numb and megalin in the renal tissues of the mice were detected with immunohistochemistry, and the renal expressions of Numb, S6, p-S6, S6K1, p-S6K1, 4EBP1 and p-4EBP1 were examined with Western blotting. The proximal renal tubular epithelial cells were isolated from the mice transfected with Numb-siRNA for in vitro culture. In NRK-52E cells, the effects of amino acid stimulation, Numb knockdown, and V1G1 overexpression, alone or in combination, on expressions of Numb, S6 and p-S6 were detected with Western blotting; the expressions of AMPK and p-AMPK were also detected in transfected NRK-52E cells, mouse kidneys and cultured mouse renal tubular epithelial cells. RESULTS: In BALB/C mice, injection of Numb-siRNA caused significant reductions of Numb and p-S6 expressions without affecting megalin expression in the renal proximal tubules (P < 0.05). Cisplatin treatment obviously upregulated p-S6K1 and p-4EBP1 expressions in the kidneys of the mice (P < 0.05), and this effect was significantly inhibited by treatment with Numb-siRNA (P < 0.05). In NRK-52E cells, amino acid stimulation significantly upregulated the expression of p-S6 (P < 0.05), which was strongly suppressed by transfection with Numb-siRNA (P < 0.05). Numb knockdown inhibited AMPK activation in NRK-52E cells, mouse kidneys and primary proximal tubular epithelial cells (P < 0.05). Numb knockdown significantly downregulated V1G1 expression in NRK-52E cells (P < 0.05), and V1G1 overexpression obviously reversed the inhibitory effect of Numb-siRNA on S6 phosphorylation (P < 0.05). CONCLUSION: Numb promotes the activation of mTORC1 signaling in proximal tubular epithelial cells by upregulating V1G1 expression.

Saturation Transfer Difference NMR Spectroscopy for the Elucidation of Supramolecular Albumin-Polymer Interactions.

Albumin has consistently demonstrated its potential for enhancing the delivery of drugs and polymer-drug conjugates, binding via supramolecular forces within its multiple binding sites. Herein, we introduce saturation transfer difference (STD-NMR) as a method to identify the interactions between a polymer library and bovine serum albumin (BSA). With STD-NMR, the binding ability of polymers can be quickly screened by focusing on their individual structural features, making this technique more suitable for high throughput screening in comparison to traditional fluorescence studies.

Clinical diagnosis of fissure caries with conventional and laser-induced fluorescence techniques.

We studied the in vivo validity of dentinal fissure caries diagnosis by visual examination, bitewing radiography, and use of a laser-induced fluorescence device (DIAGNOdent). A total of 144 and second molars with macroscopically intact occlusal surfaces in 41 Chinese young adults were examined visually, by bitewing radiography, and by DIAGNOdent. Visual examination after pit and fissure opening was used as the reference standard. The sensitivity and specificity of detecting caries that had extended into the dentin were, respectively, 0.89 and 0.44 by visual detection of opacity or discoloration after air drying, 0.13 and 1.00 by bitewing radiography to detect radiolucency extending into the dentin, and 0.70 and 0.84 by DIAGNOdent testing with a cut-off score of 40. Caries detection by a combination of visual examination and DIAGNOdent had a sensitivity of 0.67 and specificity of 0.94. Receiver operating characteristic analysis showed that this combined approach was superior to the other methods.

Long non­coding RNA XIST promotes cell proliferation of pancreatic cancer through miR­137 and Notch1 pathway.

OBJECTIVE: Long non-coding ribonucleic acids X-inactive specific transcript (lncRNA XIST) is one lncRNAs which involved in multiple human cancers. However, the functions and potential molecular regulatory mechanisms of XIST/microRNA-137 (miR­137) in pancreatic cancer (PC) still need to explore. PATIENTS AND METHODS: PC tissues and cell lines were analyzed for XIST, miR-137 and Notch1 expressions through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Nude mouse xenograft tumor assay was used to detect XIST effects on pancreatic tumorigenesis in vivo. Cell Counting Kit (CCK-8) assay was performed to detect PC cell proliferation. Dual-Luciferase reporter assay, qRT-PCR, RNA immunoprecipitation (RIP) and Western blot assays were applied to validate the target relationship of XIST, miR­137 and Notch1. RESULTS: Results demonstrated that XIST expression was increased in PC tissues and cells. XIST knockdown inhibited PC cell proliferation in vitro and also repressed the tumor growth in vivo. XIST directly interacted with miR-137 and negatively regulated its expression. Notch1 was identified as a target gene of miR-137 and XIST acted as a competitive endogenous RNA (ceRNA) to positively regulate Notch1 expression by suppressing miR-137. In addition, we detected miR-137 was negatively correlated with XIST and Notch1 respectively, and a positive correlation between Notch1 and XIST expression in PC tissues. Furthermore, Notch1 overexpression could offset the suppressing effect of XIST knockdown or miR-137 overexpression on cell proliferation. Therefore, XIST may play an important role in promoting cell proliferation through miR­137 and Notch1 pathway in PC. CONCLUSIONS: To sum up, these results proposed that XIST functioned as an endogenous sponge in promoting PC cell proliferation through competing for miR-137 to regulate Notch1 expression, and may provide more therapeutic targets for the patients with PC.

Knockdown of long non-coding RNA LINC00518 inhibits cervical cancer proliferation and metastasis by modulating JAK/STAT3 signaling.

OBJECTIVE: Long intergenic non-protein coding RNA 518 (LINC00518) was reported to be implicated and aberrantly expressed in multiple cancers. However, the pathogenic implications of LINC00518 in cervical cancer (CC) are still unclear. In this study, we focused on LINC00518 and investigated its expression pattern, clinical significance, and biological function in CC. PATIENTS AND METHODS: The expression levels of LINC00518 in CC tissues and cell lines were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and its clinical significance was assessed by statistical analysis. Cell apoptosis was determined by flow cytometry. The cell proliferation was evaluated by MTT assay and colony forming assay, and the migration and invasion were evaluated by wound healing assays and transwell assay. Western blot was used to detect the expression of relative proteins, including EMT markers and the JAK/STAT3 signaling markers. RESULTS: We found that LINC00518 was upregulated in CC tissues and associated with International Federation of Gynaecology and Obstetrics (FIGO) stage, lymph node metastasis, depth of cervical invasion and poor survival of CC patients. Univariate and multivariate Cox regression analysis showed that LINC00518 played a significant role of independent prognostic markers in overall survival rates. Furthermore, knocking down LINC00518 expression significantly suppressed CC cell proliferation, migration and invasion, and induced apoptosis in vitro. Mechanistically, the downregulation of LINC00518 suppressed JAK/STAT3 activation and subsequently decreased N-Cadherin and Vimentin. CONCLUSIONS: The present work first suggests that LINC00518 acts as an oncogene in CC via regulation of the JAK/STAT3 signaling pathway. In the future, LINC00518 may serve as a predictive biomarker and potential therapeutic target for CC patients.

[Sensitivity analysis method for unmeasured confounding interference in observational study].

Objective: To introduce the methods for sensitivity analysis, discuss and compare the advantages and disadvantages of different methods. Methods: The difference between confounding function method and bounding factor method in accuracy of identifying unmeasured confounding factors in observational studies through simulation trials and actual clinical data was compared. Results: The results of simulation trials and actual clinical data showed that when there was unmeasured confounding between exposure (X) and outcome (Y), the results of confounding function and the bounding factor analysis were similar in terms of the effect of unmeasured confounding factor to lead to the complete change of the magnitude and direction of the observed effect value. However, the confounding function method needed smaller confounding effect to fully interpret the observed effect value than the bounding factor needed. In addition, the bounding factor method needed to analyze two confounding parameters, while only one parameter was needed in the confounding function method. The confounding function method was simpler and more sensitive than the bounding factor method. Conclusion: For real-world observational data, the sensitivity analysis process is essential in analyzing the causal effects between exposure (X) and outcome (Y). In terms of the calculation process and result interpretation the sensitivity analysis method of confounding function is worth to recommend.

[Estimation on the individual treatment effect among heterogeneous population, using the Causal Forests method].

Objective: This project aimed to explore the effectiveness of estimating individual treatment effect on real data, among the heterogeneous population, with Causal Forests (CF) method, to find out the characteristics of heterogeneous population. Methods: We designed and conducted four computer simulation schemes to verify the effect of estimating on individual treatment, using the CF under four different environments of the treatment effects. Real data was then analyzed for the catheterization on right heart. Results: Results from the simulation process showed that the values on individual treatment effect that were estimated by causal forests were consistent with the population effect as well as in line with the expected distribution under the setting of four different effect values. Results of real data analysis showed that values of individual treatment effect among most patients appeared positive, so the use of RHC could cause an increase of the '180-day mortality rate' in the sampled population. Patients with lower predicted probability of 2-mo survival and albumin were more likely to have a lower risk of death after using the RHC. Conclusion: CF method could be effectively used to estimate the individual treatment effect and helping the individuals to make decision on the receipt of treatment.

Post-allergen challenge inhibition of poly(ADP-ribose) polymerase harbors therapeutic potential for treatment of allergic airway inflammation.

BACKGROUND: Identifying therapeutic drugs that block the release or effects of T-helper type 2 (Th2) cytokines after allergen exposure is an important goal for the treatment of allergic inflammatory diseases including asthma. We recently showed, using a murine model of allergic airway inflammation, that poly(ADP-ribose) polymerase (PARP) plays an important role in the pathogenesis of asthma-related lung inflammation. PARP inhibition, by single injection of a novel inhibitor, thieno[2,3-c]isoquinolin-5-one (TIQ-A), before ovalbumin (OVA) challenge, prevented airway eosinophilia in C57BL/6 mice with concomitant suppression of Th2 cytokine production and mucus secretion. OBJECTIVE: To evaluate the efficacy of the drug when it is given after OVA challenge for its possible therapeutic potential. METHODS: This study was conducted using a murine model of allergic airway inflammation. RESULTS: A single injection of TIQ-A (6 mg/kg) one or 6 h post-allergen challenge conferred similar reduction in OVA challenge-induced eosinophilia. More significantly, post-allergen challenge administration of the drug exerted even better suppression on the production of IL-4, IL-5, IL-13, and IgE and prevented airway hyperresponsiveness to inhaled-methacholine. The significant decrease in IL-13 was accompanied by a complete absence of airways mucus production indicating a potential protection against allergen-induced airway remodelling. CONCLUSION: The coincidence of the inflammation trigger and the time of drug administration appear to be important for the drug's more pronounced protection. The observed time window for efficacy, 1 or 6 h after allergen challenge may be of great clinical interest. These findings may provide a novel therapeutic strategy for the treatment of allergic airway inflammation, including asthma.