Crude Extracts of Caenorhabditis elegans Suppress Airway Inflammation in a Murine Model of Allergic Asthma

Epidemiological studies suggest an inverse relationship between helminth infections and allergic disease, and several helminth-derived products have been shown to suppress allergic responses in animals. This study was undertaken to evaluate the effect of a crude extract of Caenorhabditis elegans on allergic airway inflammation in a murine model of asthma. Allergic airway inflammation was induced in BALB/c mice by sensitization with ovalbumin. The effect of the C. elegans crude extract on the development of asthma and on established asthma was evaluated by analyzing airway hyperresponsiveness, serum antibody titers, lung histology and cell counts and cytokine levels in the bronchoalveolar lavage fluid. The role of IFN-γ in the suppression of asthma by the C. elegans crude extract was investigated in IFN-γ knockout and wild-type mice. When mice were sensitized with ovalbumin together with the crude extract of C. elegans, cellular infiltration into the lung was dramatically reduced in comparison with the ovalbumin-treated group. Treatment of mice with the C. elegans crude extract significantly decreased methacholine-induced airway hyperresponsiveness and the total cell counts and levels of IL-4, IL-5 and IL-13 in the bronchoalveolar lavage fluid but increased the levels of IFN-γ and IL-12. Sensitization with the C. elegans crude extract significantly diminished the IgE and IgG1 responses but provoked elevated IgG2a levels. However, the suppressive effect of the C. elegans crude extract was abolished in IFN-γ knockout mice, and the Th2 responses in these mice were as strong as those in wild-type mice sensitized with ovalbumin. The crude extract of C. elegans also suppressed the airway inflammation associated with established asthma. This study provides new insights into immune modulation by the C. elegans crude extract, which suppressed airway inflammation in mice not only during the development of asthma but also after its establishment by skewing allergen-induced Th2 responses to Th1 responses

Effect of Bisphosphonates on Anodized and Heatâ Treated Titanium Surfaces: An Animal Experimental Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141247/1/jper1035.pd

Peptidyl arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study

Introduction: Anti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status.Methods: All 2,317 unrelated Korean subjects including 1,313 patients with RA and 1,004 unaffected controls were genotyped for three nonsynonymous (padi4_89, padi4_90, and padi4_92) and one synonymous (padi4_104) singlenucleotide polymorphisms (SNPs) in PADI4 and for HLA-DRB1 by direct DNA sequence analysis. Odds ratios (OR) were calculated by multivariate logistic regression. Interaction was evaluated by attributable proportions (AP), with 95% confidence intervals (CI).Results: A functional haplotype of the three fully correlated nonsynonymous SNPs in PADI4 was significantly associated with susceptibility to not only anti-CCP-positive (adjusted OR 1.73, 95% CI 1.34 to 2.23) but also -negative RA (adjusted OR 1.75, 95% CI 1.15 to 2.68). A strong association with both non-erosive (adjusted OR 1.62, 95% CI 1.29 to 2.05) and erosive RA (adjusted OR 1.62, 95% CI 1.14 to 2.31) was observed for PADI4 haplotype. Gene-gene interactions between the homozygous RA-risk PADI4 haplotype and SE alleles were significant in both anti-CCP-positive (AP 0.45, 95% CI 0.20 to 0.71) and -negative RA (AP 0.61, 95% CI 0.29 to 0.92). Theses interactions were also observed for both non-erosive (AP 0.48, 95% CI 0.25 to 0.72) and erosive RA (AP 0.46, 95% CI 0.14 to 0.78). In contrast, no interaction was observed between smoking and PADI4 polymorphisms.Conclusions: A haplotype of nonsynonymous SNPs in PADI4 contributes to development of RA regardless of anti-CCP or erosive joint status. The homozygous PADI4 haplotype contri bution is affected by gene-gene interactions with HLADRB1 SE alleles.We are grateful to many research workers for assistance with sample preparation, data collection, and technical study. Dr. Bang's work was supported by a grant from the Korea Healthcare Technology R&D Project (A090706). Dr. Bae's work was supported by a grant from the Korea Healthcare Technology R&D Project (A084794 and A010252). Dr. Kang's work was supported by a grant from the Research Program for New Drug Target Discovery (M10748000231-08N4800-23110)

Diurnal variation in quantitative pupillary reactivity in large hemispheric stroke

Background Pupillary light reflex (PLR) assessment is an important neurological examination reflecting neurological deterioration in severe stroke cases. This study investigated the impact of diurnal variation in the PLR using quantitative pupillometry in stable patients with large hemispheric stroke. Methods We included 35 patients with large hemispheric stroke without neurological worsening, who were admitted to the neurological intensive care unit between April 2017 and November 2021. Quantitative pupillometry was performed every 4 hours. Pupillometer parameters of maximum pupil size, percentage of constriction (%CH), latency (LAT), constriction velocity (CV), dilation velocity (DV), maximum constriction velocity (MCV), and neurological pupil index (NPi) score were recorded. We evaluated changes in the pupillometer parameters over time using linear mixed model analysis. Results The diurnal variations revealed that the following parameters were significantly higher at 04:00 than at 20:00: maximum pupil size (right [Rt]: 3.59 vs. 3.21 mm, P<0.001; left [Lt]: 3.51 vs. 3.18 mm, P<0.001), %CH (Rt: 31.48 vs. 25.72, P<0.001; Lt: 31.42 vs. 24.98, P<0.001), CV (Rt: 1.97 vs. 1.68 mm/sec, P<0.001; Lt: 1.98 vs. 1.65 mm/sec, P<0.001), and DV (Rt: 0.97 vs. 0.84 mm/sec, P<0.001; Lt: 0.94 vs. 0.82 mm/sec, P=0.001). However, no significant diurnal variations were observed in the NPi values. Conclusion Pupillary dynamics based on quantitative pupillometer parameters, including the NPi, demonstrated diurnal variations over 24 hours in large hemispheric stroke patients without neurological worsening. However, all changes in the pupillometer parameters were within normal ranges

Perovskite-polymer composite cross-linker approach for highly-stable and efficient perovskite solar cells.

Manipulation of grain boundaries in polycrystalline perovskite is an essential consideration for both the optoelectronic properties and environmental stability of solar cells as the solution-processing of perovskite films inevitably introduces many defects at grain boundaries. Though small molecule-based additives have proven to be effective defect passivating agents, their high volatility and diffusivity cannot render perovskite films robust enough against harsh environments. Here we suggest design rules for effective molecules by considering their molecular structure. From these, we introduce a strategy to form macromolecular intermediate phases using long chain polymers, which leads to the formation of a polymer-perovskite composite cross-linker. The cross-linker functions to bridge the perovskite grains, minimizing grain-to-grain electrical decoupling and yielding excellent environmental stability against moisture, light, and heat, which has not been attainable with small molecule defect passivating agents. Consequently, all photovoltaic parameters are significantly enhanced in the solar cells and the devices also show excellent stability