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Introduction: As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age- related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of NE-(carboxymethyl)lysine (CML) and N"-(carboxymethyl) arginine (CMA) during the incubation of collagen- derived gelatin with ribose. Materials and methods: EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA. Results: After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (1), Koreanoside E1 (2), and Koreanoside E2 (3)] and 40 known compounds (4-43) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (8), epimedonin E (21), epicornunin B (22), and epicornunin F (24) inhibited the formation of both CML and CMA, with epimedokoreanin B (8) having the most potent inhibitory effect among the isolated compounds. To obtain the structure-activity relationships of 8, the phenolic hydroxy groups of 8 were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of 8. Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay. Discussion: As only 8 showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that 8 could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs. [ABSTRACT FROM AUTHOR]

Surface charging caused by the bombardment of samples with positive ion beams is a significant problem in material processing and surface analysis. The charging potential of an electrically isolated sample is commonly believed to increase with the acceleration voltage of a positive ion beam in the absence of charge compensation. Contrary to the common belief, however, this paper reports that the charging potential of an electrically isolated ionic liquid target decreases with increasing acceleration voltage of a positive cluster ion beam. A typical ionic liquid, 1-ethyl-3-methyl imidazolium bis(trifluoromethanesulfonyl)amide (EMI-TFSA), was used as the target. It was placed on a metal plate that was electrically isolated from the ground, and its charging potential during cluster ion bombardment was measured with a high-impedance electrometer. For comparison, an electrically isolated metal plate was used. This study demonstrates that the charging potential varies significantly depending on cluster ion species and target materials. The charging potential of the metal plate increased monotonically with the irradiation time, whereas that of the ionic liquid target saturated at a lower voltage. The charging potential of the ionic liquid target decreased with increasing acceleration voltage of the ion beam even though the beam current increased. Larger cluster ions (m/z 502) caused less charge buildup than lighter cluster ions (m/z 111). The results obtained are explained by considering secondary ion emission from the ionic liquid target, which reduce the incoming net charge into the target, resulting in reduced surface charging. [ABSTRACT FROM AUTHOR]

Sinus macrophages in draining lymph nodes (DLNs) are involved in anti‐tumor immune reactions. CD169 (Sialoadhesin, Siglec‐1) is expressed on sinus macrophages and is considered a surrogate marker for the immunostimulatory phenotype of macrophages. In this study, the significance of sinus macrophages in immunotherapy was evaluated using mouse models. Treatment with anti‐programmed death‐ligand 1 (PD‐L1) antibody suppressed the subcutaneous tumor growth of MC38 and E0771 cells but was not effective against MB49 and LLC tumors. Decreased cytotoxic T‐lymphocyte (CTL) infiltration in tumor tissues and CD169 expression in sinus macrophages were observed in MB49 and LLC cells compared to corresponding parameters in MC38 and E0771 cells. The anti‐tumor effects of the anti‐PD‐L1 antibody on MC38 and E0771 cells were abolished when sinus macrophages in DLNs were depleted, suggesting that sinus macrophages are involved in the therapeutic effect of the anti‐PD‐L1 antibody. Naringin activated sinus macrophages. Naringin inhibited tumor growth in MB49‐ and LLC‐bearing mice but did not affect that in MC38‐ and E0771‐bearing mice. The infiltration of CTLs in tumor tissues and their activation were increased by naringin, and this effect was impaired when sinus macrophages were depleted. Combination therapy with naringin and anti‐PD‐L1 antibody suppressed MB49 tumor growth. In conclusion, CD169‐positive sinus macrophages in DLNs are critical for anti‐tumor immune responses, and naringin suppresses tumor growth by activating CD169‐positive sinus macrophages and anti‐tumor CTL responses. The activation status of sinus macrophages has been suggested to differ among tumor models, and this should be investigated in future studies. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a complex pulmonary condition characterized by bronchitis, emphysema, and mucus stasis. Due to the variability in symptoms among patients, traditional approaches to treating COPD as a singular disease are limited. This led us to focus on phenotype/endotype classifications. In this study, we explore the potential therapeutic role of thyroid hormone (T3) by using mouse models: emphysema-dominant elastase-induced COPD and airway-dominant C57BL/6-βENaC-Tg to represent different types of the disease. Here, we showed that intratracheal T3 treatment (40, 80 μg/kg, i.t., every other day) resulted in significant improvements regarding emphysema and the enhancement of respiratory function in the elastase-induced COPD model. T3-dependent improvement is likely linked to the up-regulation of Ppargc1a, a master regulator of mitochondrial biogenesis, and Gclm, a factor associated with oxidative stress. Conversely, neither short- nor long-term T3 treatments improved COPD pathology in the C57BL/6-βENaC-Tg mice. Because the up-regulation of extrathyroidal T3-producing enzyme Dio2, which is also considered a marker of T3 requirement, was specifically observed in elastase-induced COPD lungs, these results demonstrate that exogenous T3 supplementation may have therapeutic potential for acute but not chronic COPD exacerbation. Moreover, this study highlights the relevance of considering not only COPD phenotypes but also COPD endotypes (expression levels of Ppargc1a and/or Dio2) in the research and development of better treatment approaches for COPD. [ABSTRACT FROM AUTHOR]