Involvement of Activation of Mast Cells via IgE Signaling and Epithelial Cell-Derived Cytokines in the Pathogenesis of Pollen Food Allergy Syndrome in a Murine Model.

Murine models to elucidate the pathogenesis of pollen food allergy syndrome (PFAS), characterized by oral hypersensitivity symptoms induced by specific foods in patients previously sensitized with a pollen, are lacking. The study aimed to examine PFAS pathogenesis in a novel murine model. Birch pollen-immunized mice were orally administered apple extract, and oral symptoms were evaluated based on oral rubbing frequency following the challenge. The birch pollen-immunized mice orally challenged with apple extract exhibited PFAS-like symptoms, including oral rubbing and positive reaction of swelling by the prick test. The apple extract administered with a protease inhibitor reduced the oral rubbing frequency, which was also significantly reduced in the immunized Fcer1a -/- and mast cell-deficient mice compared with the immunized control mice. The oral rubbing frequency, serum IgE levels, and Th2-cytokine production by the cervical lymph node cells were significantly reduced in the immunized Il-33 -/- and thymic stromal lymphopoietin receptor-deficient (Crlf2 -/-) mice as compared with the immunized wild-type mice. IL-33 and thymic stromal lymphopoietin involve the pathogenesis of PFAS. The apple-extract stimulation did not lead to increased Th2-cytokine production in the oral mucosa or number of group 2 innate lymphoid cells or eosinophils. PFAS involves an early-phase response by mast cell degranulation via IgE signaling after the cross-reactivity of Bet v 1-specific IgE and the food allergen, and exacerbation of allergic symptom via proteases in food; PFAS does not involve a late phase with local Th2/eosinophilic inflammation in the oral mucosa. This novel murine model might be used for elucidating the pathogenesis and assessing new therapeutic strategies for PFAS.

Relation between outcomes and expression of estrogen receptor-α phosphorylated at Ser(167) in endometrioid endometrial cancer.

Both ligand-dependent and ligand-independent activation of estrogen receptor (ER)α is modulated by receptor phosphorylation and results in activation of the ERα-dependent pathways that are involved in endometrioid endometrial cancer (EEC) pathogenesis. It is also known that the mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) and MAPK/p90 ribosomal S6 kinase (RSK) signaling pathways coordinately regulate phosphorylated-ERα at Ser(167) (p-Ser(167) -ERα). However, the expression of p-Ser(167) -ERα in EEC and its prognostic role in ECC is largely unexplored. The purpose of the present study was to investigate the expression of p-Ser(167) -ERα in ECC and its relationship with prognosis. Immunohistochemical staining of primary EEC surgical specimens (n = 103) was carried out using antibodies specific for p-Ser(167) -ERα and for p-mTOR/p-S6K1 and p-MAPK/p-RSK. The correlation of p-Ser(167) -ERα expression with clinicopathological features and survival of ECC was studied. Patients that were positive for nuclear p-Ser(167) -ERα had significantly shorter relapse-free survival, and although the result was not significant, levels of nuclear p-Ser(167) -ERα tended to be higher in advanced-stage ECC patients. Nuclear p-Ser(167) -ERα was significantly positively correlated with p-MAPK and p-S6K1, and with significantly shorter relapse-free survival in EEC.

Cyclodextrin polymers as highly effective adsorbents for removal and recovery of polychlorobiphenyl (PCB) contaminants in insulating oil.

A total of 179 countries (parties) ratified the Stockholm Convention on persistent organic pollutants (POPs) and agreed to destroy polychlorobiphenyls (PCBs) and develop a sound management plan by 2028. Currently, still 3 million tons of PCB-contaminated oil and equipment need to be managed under the Stockholm Convention. Thus, the development of a facile and environmentally benign method to treat large amounts of oil stockpiles contaminated with PCBs is a crucial subject. Herein, we report that cyclodextrin (CD) polymers, which are easily prepared by cross-linking the renewable cyclic oligosaccharide γ-cyclodextrin (γ-CD) with dibasic acid dichlorides, are a new selective and powerful adsorbent to remove PCB contaminants in oil. When PCB (100 ppm)-contaminated oil was passed through a column packed with the terephthaloyl-cross-linked γ-CD polymer (TP-γ-CD polymer) at 80-110 °C, the PCB contaminants were completely removed from the oil. Additionally, methyl esterification of the free carboxylic groups of the TP-γ-CD polymer enabled the complete recovery of the PCBs adsorbed on the polymer (with >99.9% recovery efficiency) by simply washing with acetone. The methyl-esterified TP-γ-CD polymer could be recycled at least 10 times for PCB adsorption without any loss in the adsorption capability. These results revealed that the γ-CD polymers can function as highly effective and powerful adsorbents for the removal and recovery of PCBs from PCB-contaminated oil and, thus, significantly contribute to the protection of the global environment.

High M2/M1 Macrophage Ratio Observed in Nasal Polyps Formed in Allergic Fungal Rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) shares similarities with eosinophilic chronic rhinosinusitis (ECRS), both characterized by intractable nasal polyps. The key distinction lies in the presence of fungal infection within the nasal cavity. While ECRS nasal polyps are known for significant infiltration of M2 macrophages and eosinophils, as well as an increase in high endothelial venule (HEV)-like vessels, these features are less commonly reported in AFRS. This study compared clinicopathological findings between AFRS (n=10), ECRS (n=12), and non-ECRS (n=10) patients' nasal polyps using immunohistochemical analysis for CD163 and CD68 to assess the M2/M1 macrophage ratio, and peripheral lymph node addressin (PNAd) and CD34 to evaluate the proportion of HEV-like vessels. AFRS showed a significantly higher number of CD163-positive M2 macrophages and an increased M2/M1 ratio compared with ECRS. However, the percentage of HEV-like vessels and the number of eosinophils infiltrating the nasal polyps were similar in both AFRS and ECRS. The observed increase in M2 macrophages in AFRS nasal polyps is presumed to be induced by fungal infection in the nasal cavity, in comparison with ECRS. These results highlight the distinctive immunological profiles of AFRS and ECRS, emphasizing the role of macrophage polarization in their pathogenesis.

The Percentage of PNAd-Expressing Vessels is Correlated with Disease Severity in Eosinophilic Chronic Rhinosinusitis.

BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory condition of the paranasal sinuses characterized by intractable nasal polyps with prominent eosinophil infiltration. These eosinophils are presumably recruited from peripheral blood via vessels expressing peripheral lymph node addressin (PNAd), a set of glycoproteins decorated with 6-sulfo sialyl Lewis x (sLex) glycans that serve as L-selectin ligands. Based on the severity classification algorithm proposed by the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) study group, ECRS is divided into mild, moderate and severe groups; however, as yet there are few reports comparing the clinicopathological differences among these groups. OBJECTIVE: Our goal was to elucidate clinicopathological differences among the three different severities of ECRS with special reference to eosinophils and PNAd-expressing vessels. METHODS: We performed quantitative immunohistochemical analysis of PNAd-expressing vessels using surgical specimens of nasal polyps from patients exhibiting varying severity of ECRS (n = 35) and from individuals with non-ECRS (n = 10). To this end, we immunostained tissue sections with anti-PNAd and anti-CD34 monoclonal antibodies, and then determined the number of vessels immunolabeled with each antibody. RESULTS: The number of eosinophils infiltrating nasal polyps was correlated with ECRS severity. We also found that the PNAd + /CD34 + vessel ratio, namely, the percentage of PNAd-expressing vessels among all vessels, was positively correlated not only with ECRS severity but also with the number of eosinophils infiltrating nasal polyps formed in ECRS. CONCLUSION: These results strongly suggest that PNAd-expressing vessels play at least a partial role in eosinophil recruitment to nasal polyps and consequent severity of ECRS.

Unique organogel formation with a channel-type cyclodextrin assembly.

A channel-type assembly of gamma-cyclodextrin (gamma-CD(channel)) forms organogels in a variety of oils and organic solvents at ambient temperature through the construction of a three-dimensional network of micrometer-sized cubic particles composed of gamma-CD(channel).

6-O-Modified beta-cyclodextrin enabling inclusion complex formation in nonpolar media.

Heptakis(6-O-tert-butyldimethylsilyl)-beta-cyclodextrin (TBDMS-beta-CD) effectively forms inclusion complexes with chlorinated benzenes in nonpolar solvents such as benzene-d(6) and cyclohexane-d(12). The inclusion selectivity toward 1,2- and 1,3-dichlorobenzenes can be switched by changing the solvent from benzene-d(6) to cyclohexane-d(12). Moreover, 1,2,4-trichlorobenzene (90 ppm) is perfectly removed from insulating oil by using TBDMS-beta-CD as an adsorbent.

Complete removal of chlorinated aromatic compounds from oils by channel-type gamma-cyclodextrin assembly.

This paper describes the complete removal of chlorinated aromatic compounds from insulating oil by a channel-type gamma-cyclodextrin (gamma-CD) assembly as a new adsorbent. Using this type of adsorbent (50-60 wt % of oil), 1,2,4- and 1,3,5-trichlorobenzenes, 2- and 4-chlorobiphenyls (2- and 4-MCBs), 4,4'-dichlorobiphenyl (4,4'-DiCB), and 3,4,4'-trichlorobiphenyl (3,4,4'-TrCB), whose initial concentrations were 100 ppm, were completely removed from the insulating oil. Competitive adsorption experiments using a mixture of 2-MCB and 4-MCB or a mixture of 4-MCB, 4,4'-DiCB, and 3,4,4'-TrCB revealed that selective adsorption based on the shape and size of the chlorinated aromatics was achieved by the channel-type gamma-CD assembly, implying that inclusion into the cavity of the channel-type gamma-CD was responsible for the removal of chlorinated aromatics from insulating oil. It was also found that more than 70% of adsorbed chlorinated aromatics was easily recovered from the channel-type gamma-CD by simply washing with n-hexane, and chlorinated aromatics were completely removed from the insulating oil even by the regenerated adsorbent, indicating that the gamma-CD assembly can be easily regenerated and recycled.

Outcomes after pylorus-preserving gastrectomy for early gastric cancer: a prospective multicenter trial.

The aim of the present study was to compare in a prospective, multicenter trial the results early and late after pylorus-preserving gastrectomy (PPG) versus conventional distal gastrectomy (CDG) with Billroth I anastomosis for early gastric cancer. Eighty-one patients with early gastric cancer were randomized and then underwent either PPG or CDG. Duration of operation, intraoperative blood loss, days until removal of the nasogastric tube, days until start of oral intake, and decrease in body weight were studied as parameters for outcomes early after the surgery. Late results were studied in patients followed for longer than 3 years. Change in body weight, status of oral intake, symptoms suggesting early dumping syndrome, and overall satisfaction were addressed in the questionnaire. The presence of gallstones was examined with ultrasonography. There were no differences in early results between PPG and CDG. The incidence of early dumping syndrome was lower in PPG (8%) than in CDG (33%). Other late results including the incidence of gallstones were not different between the 2 groups. These results indicate that PPG is as safe as CDG and has an advantage in terms of early dumping syndrome.