Analysis of the relationship between comorbid obstructive sleep apnea and clinical outcomes in patients with asthma in Japan.

BACKGROUND: Asthma and obstructive sleep apnea (OSA) are prevalent chronic respiratory disorders, which often coexist and interact with each other. Obesity is an important risk factor shared by them. The rate of obesity is lower in Japan versus Western countries. Hence, the co-existence of asthma and OSA has not been investigated in Japan. METHODS: Ninety-seven outpatients with asthma were recruited. Patients wore a portable monitor for sleep study. Background data, pulmonary function, blood tests, and patient-reported outcomes including gastroesophageal reflux disease, sleepiness, sleep quality, asthma control, cough and respiratory symptoms, and health status, were assessed. RESULTS: Of the patients, 19 (19.6 %), 40 (41.2 %), 24 (24.7 %), and 14 (14.4 %) were classified into non-, mild, moderate, and severe OSA groups. Non-OSA patients were younger than those in other groups (p < 0.05). The BMI of patients with moderate and severe OSA, was higher than that of non-OSA patients (p < 0.05). Pulmonary function, FeNO, serum IgE, and the number of peripheral eosinophils were not significantly different between groups. Nonetheless, compared with the other groups, treatment step was the highest, and the Asthma Control Test, Leicester Cough Questionnaire, COPD Assessment Test, and Asthma Health Questionnaire-33 yielded worst scores in the severe OSA group, and predicted the severe OSA after adjustment by BMI. CONCLUSIONS: Moderate and severe OSA are highly prevalent among patients with asthma in Japan. Pulmonary function did not differ between groups. However, patients with asthma and severe OSA were linked to more asthma treatment, worse asthma control, more symptoms and cough, and worse health status.

Lewis-Pairing-Induced Electrochemiluminescence Enhancement from Electron Donor-Acceptor Diads Decorated with Tris(pentafluorophenyl)borane as an Electrochemical Protector.

This study reports an effective peripheral decoration of organic donor-acceptor diads with B(C6 F5 )3 for stabilizing electrogenerated radical ions. By employing a common p-type organic semiconductor benzothienobenzothiophene (BTBT) as the donor, tetracoordinate boron complexes showed improved solution electrochemiluminescence (ECL) intensity, reaching a 156-fold increase compared to that of the parent diad. The unprecedented Lewis-pairing-induced ECL enhancement is attributed to the multiple roles of B(C6 F5 )3 : 1) redistributing frontier orbitals, 2) facilitating electrochemical excitation, and 3) restricting molecular motions. Furthermore, B(C6 F5 )3 converted the molecular arrangement of BTBT from conventional 2D herringbones into 1D π-stacks. This robust, highly ordered columnar nanostructure allowed red-shifting of the crystalline film ECL with electrochemical doping through the electronic coupling pathways of BTBT. Our approach will facilitate the development of elaborate metal-free ECL systems.

Solid-State Structures and Photoluminescence of Lamellar Architectures of Cu(I) and Ag(I) Paddlewheel Clusters with Hydrogen-Bonded Polar Guests.

Two hexanuclear paddlewheel-like clusters appending six carboxylic-acid pendants have been isolated with the inclusion of polar solvent guests: [Cu6(Hmna)6]·7DMF (1·7DMF) and [Ag6(Hmna)6]·8DMSO (2·8DMSO), where H2mna = 2-mercaptonicotininc acid, DMF = N,N'-dimethylformamide, and DMSO = dimethyl sulfoxide. The solvated clusters, together with their fully desolvated forms 1 and 2, have been characterized by FTIR, UV-Vis diffuse reflectance spectroscopy, TG-DTA analysis, and DFT calculations. Crystal structures of two solvated clusters 1·7DMF and 2·8DMSO have been unambiguously determined by single-crystal X-ray diffraction analysis. Six carboxylic groups appended on the clusters trap solvent guests, DMF or DMSO, through H-bonds. As a result, alternately stacked lamellar architectures comprising of a paddlewheel cluster layer and H-bonded solvent layer are formed. Upon UV illumination (λex = 365 nm), the solvated hexasilver(I) cluster 2·8DMSO gives intense greenish-yellow photoluminescence in the solid state (λPL = 545 nm, ΦPL = 0.17 at 298 K), whereas the solvated hexacopper(I) cluster 1·7DMF displays PL in the near-IR region (λPL = 765 nm, ΦPL = 0.38 at 298 K). Upon complete desolvation, a substantial bleach in the PL intensity (ΦPL < 0.01) is observed. The desorption-sorption response was studied by the solid-state PL spectroscopy. Non-covalent interactions in the crystal including intermolecular H-bonds, CH⋯π interactions, and π⋯π stack were found to play decisive roles in the creation of the lamellar architectures, small-molecule trap-and-release behavior, and guest-induced luminescence enhancement.

Dinuclear Triple-Stranded Helicates Composed of Tetradentate Ligands with Aluminum(III) Chromophores: Optical Resolution and Multi-color Circularly Polarized Luminescence Properties.

New chiroptical chromophores, dinuclear triple-stranded helicates, composed of tetradentate ligands with aluminum(III) ions, are described. These are synthesized in two steps using inexpensive pyrrole derivatives, hydrazine, and aluminum chloride. These molecular architectures (ALPHY) show multi-color (cyan, yellow, and orange) photoluminescence in solution and in the solid-state, which depends on the substituents of the ligands. The photoluminescence quantum yields of helicates were up to 54 %. The right-handed (P) and left-handed (M) helicates are so stable that they do not undergo racemization in some solvents and are mirror images according to circular dichroism and circularly polarized luminescence (CPL) with an absolute luminescence dissymmetry factor (glum ) of up to the 10-3 order. Mixing the different helicates produces white-light emission with CPL characters. This study offers a glimpse into the potential applications of chromophores with diverse photophysical properties.

Possible reversibility between epithelioid and sarcomatoid types of mesothelioma is independent of ERC/mesothelin expression.

BACKGROUND: Mesothelioma is histologically divided into three subgroups: epithelioid, sarcomatoid, and biphasic types. The epithelioid or sarcomatoid type is morphologically defined by polygonal or spindle-like forms of cells, respectively. The biphasic type consists of both components. It is not yet understood how histological differentiation of mesothelioma is regulated. ERC/mesothelin is expressed in most cases of the epithelioid type, but not in the sarcomatoid type of mesothelioma. Consequently, its expression is well correlated to the histological subtype. We hypothesized that ERC/mesothelin expression influences the histological differentiation of mesothelioma, and tested this hypothesis. METHODS: We performed studies using the overexpression or knockdown of ERC/mesothelin in mesothelioma cells to examine its effect on cellular morphology, growth kinetics, or migration/invasion activity, in vitro. We then transplanted ERC/mesothelin-overexpressing and control cells into the intraperitoneal space of mice. We examined the effect of ERC/mesothelin overexpression on mouse survival and tumor phenotype. RESULTS: In vitro cell culture manipulations of ERC/mesothelin expression did not affect cellular morphology or proliferation, although its overexpression enhanced cellular adhesion and the migration/invasion activity of mesothelioma cells. The survival rate of mice following intraperitoneal transplantation of ERC/mesothelin-overexpressing mesothelioma cells was significantly lower than that of mice with control cells. The histological evaluation of the tumors, however, did not show any morphological difference between two groups, and our hypothesis was not validated. Unexpectedly, both groups (ERC/mesothelin-overexpressing and control) of mesothelioma cells that were morphologically monophasic and spindle-like in vitro differentiated into a biphasic type consisting of polygonal and spindle-like components in the transplanted tumor, irrespective of ERC/mesothelin expression. CONCLUSIONS: These results suggested that the histological transition of mesothelioma between epithelioid and sarcomatoid types may be reversible and regulated not by ERC/mesothelin, but by other unknown mechanisms.

Ferrocene on Insulator: Silane Coupling to a SiO2 Surface and Influence on Electrical Transport at a Buried Interface with an Organic Semiconductor Layer.

A silane coupling-based procedure for decoration of an insulator surface containing abundant hydroxy groups by constructing redox-active self-assembled monolayers (SAMs) is described. A newly synthesized ferrocene (Fc) derivative containing a triethoxysilyl group designated FcSi was immobilized on SiO2/Si by a simple operation that involved immersing the substrate in a toluene solution of the Fc silane coupling reagent and then rinsing the resulting substrate. X-ray photoelectron spectroscopy (XPS) measurements confirmed that the Fc group was immobilized on SiO2/Si in the Fe(II) state. Cyclic voltammetry measurements showed that the Fc groups were electrically insulated from the Si electrode by the SiO2 layer. The FcSi on SiO2/Si structures were found to serve as a good scaffold for formation of organic semiconductor thin films by vacuum thermal evaporation of C8-BTBT (2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene), which is well-known as an organic field-effect transistor (OFET) material. The X-ray diffraction profile indicated that the conventional standing-up conformation of the C8-BTBT molecules perpendicular to the substrates was maintained in the thin films formed on FcSi@SiO2/Si. Further vacuum thermal evaporation of Au provided an FcSi-based OFET structure with good transfer characteristics. The FcSi-based OFET showed pronounced source-drain current hysteresis between the forward and backward scans. The degree of this hysteresis was varied reversibly via gate bias manipulation, which was presumably accompanied by trapping and detrapping of hole carriers at the Fc-decorated SiO2 surface. These findings provide new insights into application of redox-active SAMs to nonvolatile OFET memories while also creating new interfaces through junctions with functional thin films, in which the underlying redox-active SAMs play supporting roles.

Immobilizing a π-Conjugated Catecholato Framework on Surfaces of SiO2 Insulator Films via a One-Atom Anchor of a Platinum Metal Center to Modulate Organic Transistor Performance.

Chemical modification of insulating material surfaces is an important methodology to improve the performance of organic field-effect transistors (OFETs). However, few redox-active self-assembled monolayers (SAMs) have been constructed on gate insulator film surfaces, in contrast to the numerous SAMs formed on many types of conducting electrodes. In this study, we report a new approach to introduce a π-conjugated organic fragment in close proximity to an insulating material surface via a transition metal center acting as a one-atom anchor. On the basis of the reported coordination chemistry of a catecholato complex of Pt(II) in solution, we demonstrate that ligand exchange can occur on an insulating material surface, affording SAMs on the SiO2 surface derived from a newly synthesized Pt(II) complex containing a benzothienobenzothiophene (BTBT) framework in the catecholato ligand. The resultant SAMs were characterized in detail by water contact angle measurements, X-ray photoelectron spectroscopy, atomic force microscopy, and cyclic voltammetry. The SAMs served as good scaffolds of π-conjugated pillars for forming thin films of a well-known organic semiconductor C8-BTBT (2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene), accompanied by the engagements of the C8-BTBT molecules with the SAMs containing the common BTBT framework at the first layer on SiO2. OFETs containing the SAMs displayed improved performance in terms of hole mobility and onset voltage, presumably because of the unique interfacial structure between the organic semiconducting and inorganic insulating layers. These findings provide important insight into creating new elaborate interfaces through installing coordination chemistry in solution to solid surfaces, as well as OFET design by considering the compatibility between SAMs and organic semiconductors.

Expression status of PD-L1 and B7-H3 in mesothelioma.

Mesothelioma is a rare, aggressive malignancy with poor outcome, and has limited treatment options. The aim of this study was to perform a comprehensive analysis of programmed death ligand 1 (PD-L1) and B7 homolog 3 (B7-H3) expression in mesothelioma. We investigated the protein expression of PD-L1 and B7-H3 and their potential correlation with histological subtype, which might help to develop new therapies targeting these immune checkpoint molecules. Expression analysis of PD-L1 and B7-H3 was performed by immunohistochemistry using serial tissue sections of specimens obtained from 31 patients with mesothelioma. Tumors were classified into 22 epithelioid, 6 sarcomatoid, and 3 biphasic types. Of the 31 patients, 13 (41.9%) were positive for PD-L1 and 28 (90.3%) were B7-H3 positive. Twelve of the 13 PD-L1 positive patients were positive for B7-H3. PD-L1 and B7-H3 were widely co-expressed in biphasic and sarcomatoid type tumor cells. These findings might provide a rationale for the use of combination therapy for mesothelioma by targeting PD-L1 and B7-H3, as well as the development of anti-B7-H3 or anti-PD-L1 single agents.

Elevated levels of periostin and TGF-ß1 in the bronchoalveolar lavage fluid of patients with idiopathic eosinophilic pneumonia.

BACKGROUND: Periostin is induced in bronchial epithelial cells and fibroblasts by various stimuli including interleukin (IL)13 and transforming growth factor (TGF)-ß1, and is involved in allergic diseases such as asthma and atopic dermatitis, playing an important role in tissue remodeling and fibrosis. The role of periostin in the pathogenesis of eosinophilic lung diseases, however, is unclear. OBJECTIVE: To examine the contribution of periostin to eosinophilic inflammation of the lung in humans, we evaluated periostin, IL-13, and TGF-ß1 levels in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP). METHODS: Periostin, IL-13, and TGF-ß1 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute EP, chronic EP, idiopathic pulmonary fibrosis (IPF), and sarcoidosis. Further, we analyzed the relationship between periostin, IL-13, and TGFß-1, levels and the number of inflammatory cells in the BALF. RESULTS: The absolute number of eosinophils, and the periostin, IL-13, and TGF-ß1 levels in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. Concentrations of periostin significantly correlated with the concentrations of TGF-ß1, but not those of IL-13, in the BALF of patients with EP. Periostin levels also significantly correlated with the absolute number of eosinophils in the BALF of patients with IPF, but not EP. CONCLUSIONS: Our findings suggest that TGF-ß1 might increase the production of periostin in the lungs of patients with EP. Periostin might contribute the pathogenesis of not only EP, but also IPF.

In commemoration of the 2018 Mataro Nagayo Prize: A road to early diagnosis and monitoring of asbestos-related mesothelioma.

Primarily caused by exposure to asbestos, mesothelioma is a typical occupational disease. The latency of mesothelioma is as long as 20-40 years, and the cancer initially progresses mainly along the surfaces of pleura or peritoneum without forming masses. As symptoms do not develop until late stages, it has been challenging to diagnose this disease in its early stages and to carry out complete surgical removal. In responding to Japan's asbestos crisis in the mid-2000s, we have developed and improved ERC/MSLN-based serum and radiological markers and pioneered the use of an N-ERC ELISA kit for screening populations at risk for asbestos exposure. In the present article, we review our research toward early diagnosis of asbestos-related mesothelioma before symptoms develop and share our clinical experience of screening, diagnosing and monitoring of this disease. This paper is dedicated to the author (Dr Okio Hino) to commemorate the honor bestowed upon him as the recipient of the Mataro Nagayo Prize in 2018.

Zwitterionic Mixed Valence: Internalizing Counteranions into a Biferrocenium Framework toward Molecular Expression of Half-Cells in Quantum Cellular Automata.

Realization of molecular quantum cellular automata (QCA), a promising architecture for molecular computing through current-free processes, requires improved understanding and application of mixed-valence (MV) molecules. In this report, we present an electrostatic approach to creating MV subspecies through internalizing opposite charges in close proximity to MV ionic moieties. This approach is demonstrated by unsymmetrically attaching a charge-responsive boron substituent to a well-known organometallic MV complex, biferrocenium. Guest anions (CN- and F- ) bind to the Lewis acidic boron center, leading to unusual blue-shifts of the intervalence charge-transfer (IVCT) bands. To the best of our knowledge, this is the first reported example of a zwitterionic MV series in which the degree of positive charge delocalization can be varied by changing the bound anions, and serves to clarify the interplay between IVCT parameters. The key underlying factor is the variable zero-level energy difference in the MV states. This work provides new insight into imbuing MV molecules with external charge-responsiveness, a prerequisite of molecular QCA techniques.

Charge-Separated Mixed Valency in an Unsymmetrical Acceptor-Donor-Donor Triad Based on Diarylboryl and Triarylamine Units.

In this study, we report the generation of new mixed-valence (MV) subspecies with charge-separated (CS) characters from an unsymmetrical acceptor-donor-donor (A-D-D) triad. The triad was synthesized by attaching a dimesitylboryl group (A) to a D-D conjugate that consisted of triarylamine (NAr3) units. The MV radical cation, obtained by chemical oxidation of the triad, exhibited a strong intervalence charge transfer (IVCT) absorption derived from the bis(NAr3)•+ moiety in the near-IR region. The charge-separated MV (CSMV) state, obtained by photoexcitation of the triad, caused a blue shift in IVCT energy in the femtosecond transient absorption spectra, reflecting a bias of positive charge distributions to the D end site. This resulted from increased electron density at the A site and restructuring of the central D site from NAr3 to NAr2 sites. Interestingly, any shift in the IVCT energy that was caused by the polarity of the solvent was minimal, reflecting the unique characteristics of the CSMV state. These findings represent the first detailed analysis of the CSMV state, including a comparison with conventional MV states. Therefore, this work provides new insights into counterion-free MV systems and their applications in molecular devices.

Small anion-assisted electrochemical potential splitting in a new series of bistriarylamine derivatives: organic mixed valency across a urea bridge and zwitterionization.

We report the synthesis of a new bistriarylamine series having a urea bridge and investigate its mixed-valence (MV) states by electrochemical and spectroelectrochemical methods. We found that the supporting electrolytes had unusual effects on potential splitting during electrochemical behavior, in which a smaller counteranion thermodynamically stabilized a MV cation more substantially than did a bulky one. The effects contrary to those reported in conventional MV systems were explained by zwitterionization through hydrogen bonding between the urea bridge and the counteranions, increasing the electronic interactions between two triarylamino units. Furthermore, we clarified the intervalence charge transfer characteristics of the zwitterionic MV state.

Biomarkers for differentiation of patients with asthma and chronic obstructive pulmonary disease.

OBJECTIVE: Asthma and chronic obstructive pulmonary disease (COPD) are airflow limitation diseases with similar clinical manifestations but different pathophysiologic mechanisms. To implement the appropriate treatment, it is important to distinguish between asthma and COPD which sometimes might result difficult in clinical practice. We evaluated biomarkers to distinguish between asthma and COPD. METHODS: Blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels were analyzed. Serum periostin, interleukin-25 (IL-25), and immunoglobulin E (IgE) concentrations were compared between patients with asthma (n = 60), including atopic-asthma (n = 30) and non-atopic asthma (n = 30), and patients with COPD (n = 30). RESULTS: Significantly higher peripheral blood eosinophil counts (p < 0.001), FeNO levels (p < 0.001), and total serum IgE (P = 0.003) concentrations, but not serum periostin (p = 0.584) or serum IL-25 (p = 0.085) concentrations, were detected in patients with asthma compared to patients with COPD. Serum periostin and IgE concentrations were increased in patients with atopic-asthma compared with those with non-atopic asthma and COPD (p < 0.05). The FeNO levels were significantly correlated with the peripheral blood eosinophil counts (r = 0.430, p = 0.001) and serum IL-25 concentrations (r = 0.338, p = 0.009) in patients with asthma. The serum periostin concentrations were also correlated with the serum IgE concentrations (r = 0.375, p = 0.003)and FeNO levels (r = 0.291, p = 0.024) in patients with asthma. Asthma patients were effectively differentiated from COPD patients based on the FeNO levels (p < 0.001) and peripheral blood eosinophil counts (p < 0.001). CONCLUSIONS: FeNO levels and peripheral blood eosinophil counts were useful biomarkers for distinguishing between patients with asthma and COPD. Serum periostin and IgE concentrations could be biomarkers for atopic asthma.

Identification of galectin-3 as a possible antibody target for secondary progressive multiple sclerosis.

BACKGROUND: Recent studies have revealed that the disruption of the blood-brain barrier (BBB) might contribute to the induction of neurodegeneration in the progressive stage of multiple sclerosis (MS). OBJECTIVE: We investigated a potential target for the serum auto-antibodies responsible for the BBB impairment in patients with secondary progressive MS (SPMS). METHODS: We identified undetermined target antigens in human brain microvascular endothelial cells (BMECs) that reacted with auto-antibodies in sera from SPMS patients using a proteomic approach. In addition, we examined how the identified auto-antibodies compromise the BBB integrity. RESULTS: We found that 10 of 11 SPMS sera had auto-antibodies against galectin-3, although the patients with other neurological diseases did not have these antibodies. Downregulation of galectin-3 led to elevated intercellular adhesion molecule-1 (ICAM-1) and phospho-nuclear factor-kappa (NFκ) B p65 expression in the BMECs. Exposure to SPMS patients' sera also increased the protein levels of ICAM-1 and phospho-NFκB p65 in BMECs, but these effects induced by anti-galectin-3 immunoreactivity were canceled by the downregulation of galectin-3. CONCLUSION: Galectin-3 is a possible immunological target molecule of the pathogenic auto-antibodies and contributes to the persistent BBB breakdown in patients with SPMS. These antibodies may also serve as a novel biomarker for SPMS.

Possible Role of IL-25 in Eosinophilic Lung Inflammation in Patients with Chronic Eosinophilic Pneumonia.

PURPOSE: Interleukin (IL)-25 and IL-33 induce IL-5 production by various types of cells, such as type 2 helper T (Th2) cells and type 2 innate lymphoid cells. The number of Th2 cells and concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) are increased in patients with eosinophilic pneumonia (EP). To examine the contribution of IL-25 and IL-33 to eosinophilic inflammation of the lung in humans, we evaluated IL-5, IL-25 and IL-33 levels in the BALF of patients with EP. METHODS: IL-5, IL-25, and IL-33 concentrations in the BALF were measured by enzyme-linked immunosorbent assay in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), idiopathic pulmonary fibrosis (IPF), and sarcoidosis. RESULTS: The absolute number of eosinophils, and IL-5 levels, but not IL-33 levels, in the BALF were significantly higher in patients with EP than in patients with IPF and sarcoidosis. IL-25 levels in the BALF were significantly higher in patients with CEP, but not in patients with AEP, than in patients with IPF and sarcoidosis. The absolute number of eosinophils was significantly correlated with the IL-5 concentration in the BALF of patients with EP. IL-5 concentrations were significantly correlated with IL-25 concentrations in the BALF of patients with CEP, but not in patients with AEP. IL-5 levels were not correlated with IL-33 levels in the BALF of patients with EP. CONCLUSIONS: Our findings suggest that IL-25 plays an important role via IL-5 in eosinophilic lung inflammation in patients with CEP.

Conformational Change in Molecular Assembly of Nickel(II) Tetra(n-propyl)porphycene Triggered by Potential Manipulation.

Metal-coordinated porphyrin and related compounds are important for developing molecular architectures that mimic enzymes. Porphycene, a structural isomer of porphyrin, has shown unique properties in semiartificial myoglobin. To explore its potential as a molecular building block, we studied the molecular assembly of nickel(II) tetra(n-propyl)porphycene (NiTPrPc), a metalloporphycene with introduced tetra n-propyl moieties, on the Au(111) electrode surface using in situ scanning tunneling microscopy. Because of the low molecular symmetry of NiTPrPc, the molecular assembly undergoes unique phase transitions due to conformational change of the n-propyl moieties. The phase transitions can be precisely controlled by the electrode potential, demonstrating that the latter can play an important role in the porphycene molecular assembly on Au surface. This new discovery indicates possible uses of this porphycene framework in molecular engineering.

Covalently Attached Porphycene-Ferrocene Dyads: Synthesis, Redox-Switched Emission, and Observation of the Charge-Separated State.

Two new porphycenes functionalized with ferrocenyl pendants have been synthesized and characterized spectroscopically and structurally. The porphycene-based emission in porphycene-ferrocene dyads was switched on and off by the reversible control of the ferrocenyl pendant redox states. Transient absorption spectroscopy with a femtosecond laser-pulsed technique has successfully detected the picosecond charge-separated excited state of the dyad upon Q-band excitation of the porphycene ring.

An Electropolymerized Crystalline Film Incorporating Axially-Bound Metalloporphycenes: Remarkable Reversibility, Reproducibility, and Coloration Efficiency of Ruthenium(II/III)-Based Electrochromism.

Oxidative electropolymeization of an axially bound, bithiophene-pyridine complex of ruthenium(III)-porphycene [Ru(TPrPc) (btp)2]PF6 (1) gives a submicrometer-thick, polymeric film on an ITO electrode with a crystalline morphology. The polymeric film, the first example of axially linked multimetalloporphycene coordination arrays, exhibits highly stable and reproducible electrochromic response with high electrochromic efficiency upon electrochemical control over the metal-centered electron transfer process (Ru(II)/Ru(III)).

Increased Galectin-9 Concentration and Number of CD4+Foxp3high+Cells in Bronchoalveolar Lavage Fluid of Patients with Cryptogenic Organizing Pneumonia.

PURPOSE: Galectin-9 (Gal-9) is a ß-galactoside-binding protein that exhibits various biological reactions, such as chemoattraction, cell aggregation, and apoptosis. Recent studies demonstrated that Gal-9 has a role as an immunomodulator in excessive immunological reactions by expanded regulatory T cells (Tregs). We examined the role of Gal-9 in the pathogenesis of one of the major idiopathic interstitial pneumonias, cryptogenic organizing pneumonia (COP) as compared with idiopathic pulmonary fibrosis (IPF). METHODS: Gal-9, transforming growth factor-ß1, and interleukin (IL)-10 levels in the bronchoalveolar lavage fluid (BALF) of patients with COP and IPF were estimated by enzyme-linked immunosorbent assay. Forkhead box protein 3 (Foxp3) expressing Tregs were evaluated by flow cytometry. The effect of Gal-9 on interactions between human lung fibroblast cells and hyarulonan was assessed in vitro. RESULTS: Gal-9 and IL-10 levels in the BALF were significantly higher in patients with COP than in patients with IPF. The number of CD4+Foxp3high+cells was significantly higher in the BALF of patients with COP than in those with IPF. Gal-9 levels significantly correlated with the absolute number of CD4+CD25+Foxp3+cells or CD4+Foxp3high+cells, but not with the absolute number of CD4+CD25+Foxp3-cells, in the BALF of patients with COP. Gal-9 suppressed the CD44-dependent interaction of human lung fibroblast cells with hyarulonan in a dose-dependent manner. CONCLUSIONS: Our findings suggest that increased Gal-9 levels in the lung have a protective role against lung inflammation and fibrosis in patients with COP through the induction of Tregs in the lung and CD44-dependent inhibitory effects on lung fibroblast cells.