Search

Treatment of p‐toluenesulfonic acid on bipyrenol in PhCl gave a pyrene‐fused furan. The expansion of the molecule induced a narrow HOMO‐LUMO gap, multiple redox processes showing both oxidation and reduction, and a bathochromic shift in the absorption spectrum. A small Stokes shift was caused by the rigidity of the molecule. The structures and electronic states were estimated by theoretical considerations. We found that the heteroatom containing a [5]helicene molecule shows racemization through a planar transition state. [ABSTRACT FROM AUTHOR]

• The 3-perfluoroethylation of Chl- a derivatives red-shifted visible absorption maxima. • The perfluorination intensified and sharpened the redmost Qy absorption bands. • The fluorescence emission red-shifted, enhanced, and elongated by the fluorination. • The substitution effects were independent of the solvents and central metals. • The absorption and emission changes were due to the electron-withdrawing C 2 F 5 group. Methyl 3-perfluoroethyl-pyropheophorbide- a exhibited a redmost visible (Qy) absorption maximum in solution at a longer wavelength than that of the non-fluorinated counterpart, while the former Qy band was sharper and more intense than the latter. In addition, the other visible bands of the fluorinated compound were red-shifted from those of the non-fluorinated. The perfluoroethylated molecule was more fluorescent at a longer wavelength with a longer lifetime, comparing with the ethylated analog. Similar results as in the above free bases were obtained for the corresponding nickel, copper, and zinc complexes. Additionally, the nickel and copper complexes exhibited similar absorption behaviors. This observation was due to the electron-withdrawing perfluoroethyl group bonding directly to the core chlorin π-system. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • C3-Fluoroalkylated chlorophylls- a were prepared via deoxygenative fluorination. • Their absorption and emission bands were red-shifted from those of 3-alkyl-chlorins. • The red-shifts of their maxima were dependent on the fluorination degree. • The fluorescence emission enhanced and elongated with an increase in fluorination. • The C31,C32-fluorination finely tuned their optical properties in dichloromethane. Methyl pyropheophorbides- a possessing a variety of fluoroalkyl groups at the 3-position were prepared via deoxyfluorination or deoxofluorination from naturally occurring chlorophyll- a. The synthetic C3-fluoroalkylated chlorins exhibited monomeric visible absorption spectra in dichloromethane. Their Qx/Qy absorption bands were red-shifted from those of the nonfluorinated counterparts. The red-shift values were dependent on the fluorination degree in the 3-alkyl group. The redmost Qy absorption and main fluorescence emission maxima gradually moved to longer wavelengths by fluorination and trifluoromethylation at the 31-position: λ abs /λ em = 655/659 nm (3-methyl-chlorin) < 676/679 nm (3-perfluoroethyl-chlorin). The substitutions similarly enhanced their fluorescence emission quantum yields and elongated their lifetimes: Φ em /τ em = 18.0%/6.1 ns (3-methyl-chlorin) < 21.5%/7.3 ns (3-perfluoroethyl-chlorin). The fluorination in the peripheral 3-substituent could finely tune the optical properties of the core chlorin chromophores. [ABSTRACT FROM AUTHOR]

Planar-chiral Phanephos, containing the coordinatable P(III), formed P(III)/Tb(III)(hfa)3 hybrid luminophores that successfully emitted characteristic circularly polarised luminescence (CPL) due to 5D4 → 7F5 transitions in solution. On the other hand, BINAP, containing P(III)＝O as axially chiral ligand, exhibited no detectable CPL with Tb(III)(hfa)3. [ABSTRACT FROM AUTHOR]

The sign, wavelength, and intensity of circularly polarised luminescence, generated from two photoexcited pyrene moieties, were successfully controlled by selecting a suitable achiral wired structure to connect two achiral fluorescent pyrenes with an axially chiral binaphthyl backbone. Especially, these circularly polarised luminescence and circular dichroism signs were found to be influenced by the achiral wire structures, i. e. the chiral structures of S1 and S0 states were affected by the achiral wire structure employed. [ABSTRACT FROM AUTHOR]

Abstract: Optically active luminophores capable of emitting circularly polarized light (CPL) are keys in many photonic communication systems. Herein, we report a new cryptochiral CPL‐functioned molecular system composed of a C2‐symmetric 5,5’,6,6’,7,7’,8,8’‐octahydro‐1,1’‐bi‐2‐naphthyl rotamer bearing two flexible linkers attached to two pyrene rings as emitters. Despite exhibiting negligibly weak circular‐dichroism (CD) signals in the ground state, the luminophore displayed a clear CPL signal in the photoexcited state. [ABSTRACT FROM AUTHOR]

Extending the π-conjugation of chiral rotatable oligonaphthyl derivatives results in longer circularly polarised luminescence (CPL) wavelengths and increased unpolarised-photoluminescence (PL) quantum yields. The CPL was observed to shift to a significantly longer wavelength and the PL quantum yield was greatly improved when the number of naphthyl units was extended from two (dimer) to four (tetramer). On the other hand, the wavelength and quantum yield increased less in moving from the tetramer to the octamer in solution and solid films. [ABSTRACT FROM AUTHOR]

Although chiral 1,1′-binaphthalene-2,2′-diyl- O , O -bis( N , N -dimethylthiocarbamate) ( 1 ) revealed no circularly polarized luminescence (CPL) signals, Newman–Kwart rearrangement of O -thiocarbamate groups at 1 yielded clear CPL signals from 1,1′-binaphthalene-2,2′-diyl- S , S -bis( N , N -dimethylthiocarbamate) ( 2 ), which acts as a CPL-gen molecule. [ABSTRACT FROM AUTHOR]

Abstract: Chiroptical signs in circularly polarised luminescence (CPL) of Eu(III) luminophores coordinated to C2‐symmetric binaphthyl ring carrying carboxylic acids, (R)‐1 (and (S)‐1)) and (R)‐2 (and (S)‐2)) were inverted by inserting two oxymethylene spacers between the ring and the acids. The subtle difference in reorganization between (R)‐1 and (R)‐2 causes the apparent CPL sign‐swapping characteristics. We assume that (R)‐2 is more likely to undergo this reorganization rather than (R)‐1 because of the highly flexible spacer and vice versa. The subtle difference in the rotational freedom of the ligands with and without the two spacers causes the opposite CPL signs although (R)‐1/Eu and (R)‐2/Eu had the same CD sign in the ground state. This was proven by experimental and theoretical data. [ABSTRACT FROM AUTHOR]

Complexes of Eu(iii)(hfa)3 with a C2-symmetric planar P(iii) ligand exhibited intense circularly polarised luminescence (CPL) due to 5D0→7F1 and 5D0→7F2 transitions, with the signs and shapes of CPL signals depending on the choice of solvent (acetone or chloroform). [ABSTRACT FROM AUTHOR]

[Display omitted] • Phylogenetic trees are essential tools in evolutionary biology. • In this study, Phylogenetic trees were reconstructed through improved graph cut. • A quantum-inspired computer known as the Fujitsu Digital Annealer was used. • The algorithm was named "Normalized-Minimum cut by Digital Annealer (NMcutDA)" • NMcutDA reconstructed better phylogenetic trees than those using other methods. Phylogenetic trees are essential tools in evolutionary biology that present information on evolutionary events among organisms and molecules. From a dataset of n sequences, a phylogenetic tree of (2 n - 5) ! ! possible topologies exists, and determining the optimum topology using brute force is infeasible. Recently, a recursive graph cut on a graph-represented-similarity matrix has proven accurate in reconstructing a phylogenetic tree containing distantly related sequences. However, identifying the optimum graph cut is challenging, and approximate solutions are currently utilized. Here, a phylogenetic tree was reconstructed with an improved graph cut using a quantum-inspired computer, the Fujitsu Digital Annealer (DA), and the algorithm was named the "Normalized-Minimum cut by Digital Annealer (NMcutDA) method". First, a criterion for the graph cut, the normalized cut value, was compared with existing clustering methods. Based on the cut, we verified that the simulated phylogenetic tree could be reconstructed with the highest accuracy when sequences were diverged. Moreover, for some actual data from the structure-based protein classification database, only NMcutDA could cluster sequences into correct superfamilies. Conclusively, NMcutDA reconstructed better phylogenetic trees than those using other methods by optimizing the graph cut. We anticipate that when the diversity of sequences is sufficiently high, NMcutDA can be utilized with high efficiency. [ABSTRACT FROM AUTHOR]

Double‐twisted cyclic binaphthyls, in which two naphthalenes are tethered by ‐O(CH2)nO‐ linkage (n=1–3), have been synthesized. X‐ray analyses and DFT calculations revealed a tightly constrained stereogenic figure‐eight geometry. Tethering of two naphthalenes by short linkage forces a small dihedral angle, and the cyclic binaphthyls with short tether (n=1, 2) exhibit remarkable boosting of the glum value (1.0–1.6×10−2) in circularly polarized luminescence (CPL) and unusual glum/gabs ratios (0.93–1.3). These experimental high |glum| values are in accord with the results of excited state TD‐DFT calculations, which show transannular interactions and that consequent extensive delocalization occurs throughout the figure‐eight π‐core. As a result, the present figure‐eight luminophore promote the elongation of the magnetic transition dipole moment that results in significant increases in glum values. [ABSTRACT FROM AUTHOR]

Chlorophylls (Chls) are one of the most important pigments for the light-harvesting systems in photosynthesis. Methyl pheophorbide- a derivative fused by a π-conjugated E-ring with the C131=C132 double bond was found as a synthetic example of the unique Chl- a derivatives, which showed split Soret absorption bands in the purple and ultraviolet-A regions and a broad absorption band at a near-infrared (NIR) region as its monomeric state, but not its self-aggregated species. The 3-vinyl group of the Chl- a derivative was chemically transformed into ethyl, formyl, hydroxymethyl, and dialkoxymethyl groups. All the resulting chlorins exhibited unique wide bands at a NIR region. The substitution effect on the peaks of their wide NIR bands was similar to that on the sharp redmost Qy maxima at a visible region of the corresponding pheophorbides with the C131–C132 single bond. Protons at the C5-, C10-, and C20-positions as well as of the peripheral C2-, C3-, C7-, and C8-substituents of methyl 3-substituted 131,132-didehydro-131-deoxo-pheophorbides- a were upfield-shifted in 1H nuclear magnetic resonance, compared with those of intact pheophorbides. The shifts were ascribed to the less ring current of the cyclic tetrapyrroles by π-conjugation of the E-ring. The non-fluorescent C3-substituted Chl- a derivatives could be useful as new materials absorbing NIR wavelength light. [Display omitted] • Chlorophyll- a derivatives fused by π-conjugated E-ring with C131=C132 were prepared. • The C131,C132-didehydrogenation led to split Soret and broadened Qy absorption bands. • The unique wide Qy band reached to a near-infrared (NIR) region over 1000 nm. • The Qx/Qy bands at red/NIR regions were dependent on the peripheral C3-substituents. • The didehydrogenation at E-ring reduced the ring current of chlorin core π-system. [ABSTRACT FROM AUTHOR]

A series of cyclic oligomers with Dn symmetry (n = 2–5) based on chiral (R)/(S)-binaphthyl exhibiting intensive chiroptical properties were synthesized by using a Ni(0)-catalyzed coupling reaction. The intensity and the handedness of circularly polarized luminescence (CPL) were dependent on the ring size of the cyclic oligomers, in which the 1,1′-binaphthyl moieties form s-cis (n = 2, 3) or s-trans (n = 4, 5) conformers in the excited state. The relationship between the structure and chiroptical properties is discussed with the aid of X-ray analysis and DFT calculations. [ABSTRACT FROM AUTHOR]

A stereogenic π‐system based on dimer (2) and trimer (3) of [2.2]paracyclophane (PC) and biphenyl was prepared and its structural, photophysical, and chiroptical properties were investigated. X‐ray analysis revealed that the quaterphenyl moieties in 2 adopt a double helical structure anchoring [2.2]PC from both sides. Furthermore, 3 forms a isosceles triangle structure with a large chiral cavity. A homodesmotic reaction using DFT calculations revealed that 2 has a larger strain energy than 3 owing to its highly twisted phenylene linkers. Electronic and circular dichroic (CD) spectra were recorded in CH2Cl2 solution. The spectra of both 2 and 3 are similar, and their longest absorption band accompanying a remarkable Cotton effect is attributed to the transition from HOMO to LUMO, which is delocalized to the quaterphenyl moiety. These compounds exhibit fairly high fluorescence quantum yields (ϕ=0.70–0.83) and moderate dissymmetry factor (|gCPL|=1.6×10−3) in circularly polarized luminescence (CPL). [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are Masashi Hasegawa, Yoshitane Imai and co‐workers at Kitasato University and Kindai University. The image depicts the reported figure‐eight molecule as an M. C. Escher‐inspired 'impossible object'. Read the full text of the article at 10.1002/chem.202005320. [ABSTRACT FROM AUTHOR]

Front Cover: Small Figure-Eight Luminophores: Double-Twisted Tethered Cyclic Binaphthyls Boost Circularly Polarized Luminescence (Chem. Eur. J. 19/2021) Keywords: binaphthyl; chiral; circularly polarized luminescence; DFT calculations; figure-eight molecule EN binaphthyl chiral circularly polarized luminescence DFT calculations figure-eight molecule 5830 5830 1 04/05/21 20210401 NES 210401 B Impossible object in the molecular world b : a stereogenic figure-eight molecule, which exhibits remarkable CPL properties, is depicted in the cover image. GLO:OLD/01apr21:chem202100231-toc-0001.jpg PHOTO (COLOR): . gl GLO:OLD/01apr21:chem202100231-toc-0001.jpg PHOTO (COLOR): . gl B Impossible object in the molecular world b : a stereogenic figure-eight molecule, which exhibits remarkable CPL properties, is depicted in the cover image. [Extracted from the article]

A curved stereogenic [6]paraphenylene ([6]PP), anchoring a chiral binaphthyl scaffold at 7,7'‐positions, was prepared and investigated for its properties as a solid‐state circularly polarized luminescence (CPL) dye. X‐ray analysis revealed a helically twisted structure of PP units induced by axial chirality of binaphthyl framework. The curved [6]PP exhibits fluorescence in powder and polymethyl methacrylate (PMMA) film as well as solution. A significant increase in quantum yield was observed for a non‐fluid PMMA film owing the suppression of the molecular motion. The gCPL values of the dye in solution and as PMMA film were almost the same (4.3–4.4×10−3) and lager than that in powder. TD‐DFT calculations in the excited state suggest that the exciton can be delocalized into a twisted PP unit to produce a larger magnetic transition dipole moment. [ABSTRACT FROM AUTHOR]

• Novel axially chiral oligonaphthyl ligands were successfully synthesized. • Binaphthyl-Eu(III) organometallic luminophores having circularly polarized luminescence (CPL) properties were successfully prepared. • The CPL signs of these Eu(III) luminophores were successfully inverted by inserting bulky units into the binaphthyl backbone. • This work offers a novel approach for controlling the CPL signs of organometallic circularly polarized luminophores. The circularly polarized luminescence (CPL) signs of Eu(III) luminophores coordinated to axially chiral binaphthyl derivatives carrying acetic acid residues [(R,R,R)- 4 were inverted compared to those bearing compounds (R)- 1–3 by inserting bulky naphthalene units into the binaphthyl backbone. The suitable steric difference between the phenyl group and the highly bulky naphthalene group on the binaphthyl backbone causes a chiral coordination change for all ligands on Eu(III). This substituent domino effect on the 1,1,1,5,5,5-hexafluoro-pentane-1,4-dione (hfa) ligands on Eu(III) caused by the bulky naphthyl group on the binaphthyl ligand causes the apparent change of the CPL sign in the photo-excited state, although (R)- 1 – 3 /Eu and (R,R,R)- 4 /Eu exhibited the same circular dichroism sign in the ground state. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons consisting of three fused anthracene units were designed as new π‐conjugated compounds having helical structures. These expanded helicenes were synthesized by Pt‐catalyzed cycloisomerization of the corresponding ethynyl‐substituted precursors. The nonplanar and helical structure was confirmed by X‐ray analysis and DFT calculations, and the barrier to helical inversion was estimated to be 34 kJ mol−1. The enantiomers of the diphenyl derivative were successfully resolved by chiral HPLC. Enantiopure samples showed good chiroptical performance in the CD (|Δϵ| 1380 L mol−1 cm−1) and CPL (|glum| 0.013) spectra, and these values were considerably large for simple organic molecules. The unique chiroptical properties are discussed on the basis of the molecular structure and the electronic state with the aid of time‐dependent DFT calculations. [ABSTRACT FROM AUTHOR]

Organic fluorescent molecules are gaining importance because of their potential applications in many devices. Optically active N,N′ -bis((1 R)-1-naphthylethyl)perylene-3,4,9,10-tetracarboxylic diimide [(R,R)- 1-BNP ] and N,N′- bis((1 R)-2-naphthylethyl)perylene-3,4,9,10-tetracarboxylic diimide [(R,R)- 2-BNP ] and their antipode, [(S,S)- 1-BNP and (S,S)- 2-BNP ], emit aggregation-induced enhanced (AIEnh) circularly polarized luminescence (CPL) on both a solid organic polymer film (poly(methyl methacrylate)) and solid inorganic KBr pellet. An opposite chirality is essential for generating CPL of inverted sign. However, a pair of enantiomeric organic molecules may not always be easy to prepare. Interestingly, the chiral perylene fluorophores synthesized in this study can emit both positive and negative AIEnh-CPL in the solid state, depending on their position on the naphthylene groups. In addition, no CPL was observed in these compounds from their dilute solutions. Image 1 • Optically active N,N′- bis((1 R)-1-naphthylethyl)perylene-3,4,9,10-tetracarboxylic diimide [(R,R)- 1-BNP ] and N,N′- bis((1 R)-2-naphthylethyl)perylene-3,4,9,10-tetracarboxylic diimide [(R,R)- 2-BNP ] and their antipode, [(S,S)- 1-BNP and (S,S)- 2-BNP ] were successfully prepared. • These chiral perylene diimides could emit aggregation-induced enhanced (AIEnh) circularly polarized luminescence (CPL) on both a solid organic polymer film (poly(methyl methacrylate)) and solid inorganic KBr pellet. • Chiral bis-naphthylethylperylene diimides can emit both positive and negative AIEnh-CPL in the solid state, depending on their position on the naphthylene groups. [ABSTRACT FROM AUTHOR]

The absorbance and fluorescence spectra of 3,3′-diethylthiatricarbocyanine iodide (DTCI), a near-infrared dye, were measured in methanol and water at different concentrations. DTCI exhibited distinctive monomer and excimer (dimer) fluorescence emission bands on photo excitation in the two solvents. The monomer emission band at around 600–700 nm is unprecedented, and the dimeric nature of the typical emission band at around 750–850 nm has not been recognized in solution. In the ground state, DTCI is proposed to form π-stacked and unstacked aggregates in methanol and water, respectively, at higher concentrations. The proposed unstacked aggregates in water may be of high molar mass leading to a short relaxation time in NMR analysis, which did not show clear signals. [ABSTRACT FROM AUTHOR]

Background and objective: A multi-institutional phase II trial combining uracil-tegafur (UFT) and cisplatin (CDDP) was conducted in patients with previously untreated advanced non-small cell lung cancer (NSCLC) to evaluate the safety and efficacy of this combined treatment regimen. Methods: The entry criteria for this study were previously untreated NSCLC, measurable disease, age <80 years, performance status <2, and adequate haematological, hepatic and renal function. Patients were treated with 400 mg/m2 oral UFT from day 1 to day 14 and 80 mg/m2 cisplatin on day 15. The treatment course was repeated every 3 weeks. Results: Of the 68 patients enrolled, 64 (27 with stage IIIB and 37 with stage IV disease) were eligible for treatment. Twenty of the 64 patients responded to the chemotherapy (response rate 31.3%; 95% CI 21.2–43.4%). The median survival time was 8.6 months, and the 1-year survival was 41.5%. Haematological toxicity ≥WHO grade 3 was seen in 3 (4.7%) patients. For non-haematological toxicities, anorexia with WHO grade 3 was seen in 8 (12.5%) patients, nausea and vomiting with WHO grade 3 in 4 (6.3%), diarrhoea with WHO grade 4 in 1 (1.6%), and liver dysfunction with WHO grade 4 in 1 (1.6%) patient. Conclusions: The combination of oral UFT plus cisplatin was found to be a safe and active treatment against advanced NSCLC. The observed low toxicity of this combined regimen may warrant its application to the treatment of elderly patients. [ABSTRACT FROM AUTHOR]

β-Adrenoceptor agonists reportedly decrease spontaneous apoptosis of peripheral blood eosinophils; however, its signaling pathway is unknown. Survival signals can be elicited by the activation of phosphatidylinositol 3-kinase (PI3K) and Akt, both of which are known to be potent regulators of apoptosis, and Akt in turn inactivates Forkhead transcription factors, including FKHR (Forkhead in rhabdomyosarcoma). We have investigated the effect of β-agonists on apoptosis of local eosinophils isolated from the airways and the involvement of PI3K, Akt, and FKHR in its survival signal. Eosinophils obtained from immunized mice by bronchoalveolar lavage after allergen provocation underwent apoptosis in a time-dependent manner. Incubation of eosinophils with isoproterenol or formoterol dose-dependently inhibited both spontaneous eosinophil apoptosis and apoptosis induced by Fas receptor activation. Incubation with cAMP or forskolin also inhibited eosinophil apoptosis. The PI3K inhibitors wortmannin and LY-294002 and an Akt inhibitor, 1-L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, but not a mitogen-activated protein kinase kinase inhibitor PD-98059, blocked isoproterenol-mediated eosinophil survival. Wortmannin also inhibited cAMP-mediated eosinophil survival. Isoproterenol rapidly induced phosphorylation of Akt and FKHR in eosinophils in a PI3K-dependent manner. These findings indicate that the PI3K-Akt-FKHR pathway conveys a critical survival signal induced by β-agonists in airway eosinophils. [ABSTRACT FROM AUTHOR]

Background: Although Clara cell secretory protein (CC-10) has been ascribed an anti-inflammatory role in lung diseases, its precise role remains unclear. Objective: To further our understanding of the role of CC-10 in inflammatory lung diseases, CC-10 protein levels were measured. Methods: Sera or bronchiole cleavage (BAL) fluids were collected from patients with different inflammatory lung diseases including bronchial asthma, chronic obstructive lung disease (COPD), sarcoidosis, idiopathic interstitial pneumonia (IIP), chronic eosinophilic pneumonia (CEP), pneumonia and lung cancer. Serum CC-10 concentrations were measured by enzyme-linked immunosorbent assay using urinary protein-1 antibody. Then, the relationships between CC-10 concentrations and lung diseases were investigated. Immunohistochemistry was performed using lung biopsy samples. Results: Increased serum CC-10 levels were recognized in IIP patients, while CC-10 levels were decreased in bronchial asthma patients and CEP patients. Immunohistochemistry revealed an aberrant expression in areas of fibrosis in IIP patients. Serum CC-10 concentrations were not associated with severity among IIP, COPD, and sarcoidosis. In contrast, serum CC-10 concentrations were correlated with FEV1/FVC in bronchial asthma patients. Conclusions: Although the number of patients was quite limited, these data provide new insights into the role of CC-10 in lung diseases, and the possibility that the CC-10 concentration in serum could be a new marker indicating the severity of bronchial asthma. [ABSTRACT FROM AUTHOR]

Monocyte chemoattractant protein-1 (MCP-1) is a proinflammatory chemokine and may play an important role in the development of pulmonary fibrosis. We examined a new therapeutic strategy that comprises the transfection of the mutant MCP-1 gene into skeletal muscles as a biofactory for anti-MCP-1 therapy against bleomycin-induced pulmonary fibrosis in mice. Overexpression of the mutant MCP-1 gene at 10-14 days after intratracheai instillation of bleomycin resulted in decreased DNA damage, apoptosis, and pulmonary fibrosis at 14 days. However, overexpression of the mutant MCP-1 at 0-4 days after bleomycin instillation did not result in decreased pathological grade, DNA damage, or apoptosis at 7 and 14 days. Because, in this model, inflammatory cell infiltration begins at 3 days and is followed by interstitial fibrosis, it is likely that MCP-1 has an important role to play in the development of fibrogenesis but not in the development of early lung inflammation. This method does not require the use of viral vector or neutralizing antibody, and, as such, it is possible to avoid problems regarding the pathogenicity of the viral vector or immunocomplex. This new strategy may be a beneficial method of treating pulmonary fibrosis from the viewpoint of clinical application. [ABSTRACT FROM AUTHOR]

Alveolar epithelial cells are known to be present at the primary site of lung damage in pulmonary fibrosis. Apoptosis has been implicated as being involved in epithelial cell damage and pulmonary fibrosis. Because the cyclin-dependent kinase inhibitor p21 induces G1 arrest and DNA repair and because it also prevents apoptosis in some cells, we hypothesized that p21 gene transfer may attenuate bleomycin-induced pulmonary fibrosis in mice, the pathogenesis of which likely involves epithelial cell apoptosis. Human p21 proem was expressed in mouse alveolar epithelial cells at 1–7 days in vitro and was detected predominantly in lung epithelial cells at 1–7 days in vivo after adenoviral transfer of the human p21 gene. Inflammt0ry cell infiltration and fibrosis had already begun at 7 days in this model. Adenoviral transfer of the human p21 gene at 7 days after intratracheal instillation of bleomycin led to a decrease in the number 0fapoptotic cells, lung inflammation, and fibrosis at 14 days. Therefore, the forced expression of p21 exerted both anti-apoptotic and anti-fibrotic effects, which would facilitate the ultimate goal of treatment for pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

1 Theophylline, a nonselective phosphodiesterase inhibitor, has long been regarded as a major bronchodilator in the treatment of human asthma. Using front-surface fluorometry with fura-2 and α-toxin permeabilization, the effects of theophylline on intracellular Ca[sup2+] concentration ([Ca[sup2+]]), tension development and Ca[subp2+] sensitivity of the contractile apparatus were investigated in porcine tracheal smooth muscle strips. 2 Application of theophylline induced a relaxation without a significant decrease in [Ca[sub2+]], when strips were precontracted by 40mM K[sup+] depolarization, while theophylline significantly decreased both (Ca[sup2+]], and tension induced by carbachol. 3 The effects of theophylline on the increases in [Ca[sup2+], and tension induced by carbachol were significantly inhibited by iberiotoxin, an inhibitor of large-conductance Ca[sup2+] -activated K[sup+] channels. 4 In the absence of extracellular [Ca[sub2+], theophylline significantly attenuated carbachol-induced transient increases in tension development, while it did not affect Carbachol-induced transient increase in [Ca[sup2+]. 5 The [Ca[sup2+]],—force relationship, which was determined by cumulative applications of extracellular Ca[sup2+] (0—5mM) during 40mM K[sup+] depolarization, was significantly shifted to the right by theophylline. 6 In α-toxin permeabilized strips, theophylline significantly increased the EC[sub50] value of [Ca[sup2+]], for contraction and enhanced the effect of cAMP, but not of cGMP. 7 These results indicate that theophylline induces relaxation of the porcine tracheal smooth muscle through an activation of BK channels, and a resultant decrease in [Ca[sup2+], and an attenuation of Ca[sup2+] sensitivity, presumably through the action of cAMP. [ABSTRACT FROM AUTHOR]

Air pollution causes increased cardiopulmonary morbidity and mortality. Airway inflammation plays a major role in the pathophysiology of many lung diseases. Proinflammatory cytokines, such as interleukin-8 (IL-8), are responsible in part for the initiation and maintenance of airway inflammation. Asbestos exposure and particulate air pollution have been reported to stimulate the expression of IL-8 and to induce NF-κB activation. However, it is unknown whether polycyclic aromatic hydrocarbons (PAH), mainly existed in most airborne particulates, can separately induce IL-8 expression. In the present study, we investigated the effect of benzo(a)pyrene (B[a]P) and 1-nitropyrene (1-NP), two representative PAH, on IL-8 expression using ELISA and Northern blot analysis. Gel shift assay was performed to study the NF-κB activation. We have assessed the effect of adenovirus-mediated overexpression of the NF-κB inhibitor, IκBα on PAH-induced IL-8 expression in A549 cell line. Both B[a]P and 1-NP stimulated IL-8 gene expression in A549 cells. This effect was associated with induction of NF-κB activation. Overexpression of IκBα inhibited 1-NP-induced transcription of IL-8. This suggests that PAH-induced IL-8 gene regulation may be mediated by NF-κB. These data indicate that PAH alone, either B[a]P or 1-NP, is sufficient to stimulate NF-κB activation and IL-8 transcription. [Copyright &y& Elsevier]

Abstract: A 49-year-old man with diabetes mellitus and alcoholic liver cirrhosis presented with dyspnoea and fever. A chest computed tomography scan revealed three areas of loculated pleural effusion. Initially, the patient was thought to have an intrapleural empyema and was treated with intravenous antibiotics and closed drainage. However, as he did not improve, he was then treated with open drainage. During open drainage, the patient was diagnosed to have an extrapleural empyema and improved following open drainage treatment. [ABSTRACT FROM AUTHOR]

Objective: The Fas–Fas ligand (FasL) pathway is one of the important apoptosis-signalling molecule systems. We previously determined that this pathway may be involved in the pathogenesis of fibrosing lung diseases. In the present study, we evaluated the clinical significance of the levels of soluble forms of Fas (sFas) and FasL (sFasL) in serum from patients with fibrosing lung diseases. Methodology: We measured sFas, sFasL, KL-6 (a measure of alveolar type II cell damage), surfactant protein D (SP-D), and surfactant protein A (SP-A) levels in serum from 35 patients with idiopathic pulmonary fibrosis (IPF), 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and 13 normal healthy controls using enzyme-linked immunosorbent assays (ELISA). Results: The serum levels of sFasL were significantly increased in patients with active IPF and CVD-IP, compared with those with inactive disease and controls. There was no significant difference in sFasL levels between patients with inactive disease and controls. Serum sFasL levels were significantly correlated with lactate dehydrogenase and KL-6 levels in IPF. The decrease in sFasL levels following corticosteroid therapy was not correlated with the clinical course of IPF. There was no significant difference in serum sFas levels between IPF or CVD-IP patients and controls. Conclusions: Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP. [ABSTRACT FROM AUTHOR]

The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a [sup 32]P-postlabelling method from 42 subjects. XPD ex23 genotypes were identified by the PCR-RFLP method. Subjects with the XPD ex23 heterozygous genotype (AC) showed significantly lower DNA adduct levels (0.63 ± 0.19 per 10[sup 8] nucleotides, n = 6) than those (0.92 ± 0.38, n = 36) with major homozygous genotypes (AA). This result suggests that the genotype of the repair enzyme may be one of the important determinants for DNA adduct levels. [ABSTRACT FROM AUTHOR]

Investigates whether anti-interleukin-12 (anti-IL-12) antibody treatment suppresses the development of bleomycin-induced lung injury and fibrosis in mice. Suppression of tumor necrosis factor-alpha and Fas-Fas ligand messenger RNA expression in lung tissue; Suggestion that the administration of anti-IL-12 could be a novel therapy against lung injury and pulmonary fibrosis.

Presents information on a study which examined whether the anti-interleukin-12 antibody prevents cell-mediated immune responses. Cytotoxic effect of the Fas-Fas ligand pathway; Materials and methods; Results and discussion.

Tests the hypothesis that platelet-activating factor (PAF) mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways. Effect of repeated exposure to cigarette smoke on goblet cell counts in the tracheal epithelium of guinea pigs; Cell profiles and PAF levels in brochoalveolar lavage fluid after smoke exposure.

Study Objectives: The Fas-Fas ligand (FasL) pathway is a representative system of apoptosis-signaling receptor molecules. We previously described that this pathway may play an important role in the pathogenesis of fibrosing lung diseases. In this study, we hypothesized that soluble form of Fas (sFas) and FasL (sFasL) may also be associated with this disorder.Measurements and Results: We measured sFas and sFasL levels in BAL fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia associated with collagen vascular diseases (CVD-IP), and bronchiolitis obliterans organizing pneumonia (BOOP), using enzyme-linked immunosorbent assay. BALF from all patients was obtained before prednisolone therapy. sFasL levels were relatively increased in IPF patients (p = 0.084), and significantly increased in CVD-IP patients (p < 0.05) and BOOP patients (p < 0.05), compared with control subjects. BALF sFasL levels were elevated in the IPF or CVD-IP subgroups with an indication for prednisolone therapy, compared with those without an indication for therapy. The BALF sFasL level in IPF patients was correlated with the number of total cells and lymphocytes. The BALF sFasL level in BOOP patients was relatively or significantly correlated with the number of total cells or lymphocytes, respectively. The BALF sFas level was significantly increased in BOOP patients, but not in IPF or CVD-IP patients.Conclusions: We conclude that BALF sFasL levels may be associated with the accumulation of inflammatory cells and reflect the degree of lymphocyte alveolitis in IPF. The elevation of sFasL may be associated with the deterioration of IPF and CVD-IP. The elevation of the BALF sFas level may abrogate the cytotoxicity of FasL in BOOP patients, which may be associated with better prognosis of BOOP, compared with IPF or CVD-IP. [ABSTRACT FROM AUTHOR]

Background: Hypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis and loosely formed granulomas in lung biopsy specimens. HP improves or disappears altogether after cessation of antigen exposure. The Fas-Fas ligand (FasL) system is one of the representative systems of apoptosis-signaling receptor molecules, and is involved in various inflammatory diseases. We hypothesized that the Fas-FasL system may be associated with this disorder. Methods: We examined the expression of FasL and Fas proteins in lung tissues from patients with HP using immunohistochemistry. We also measured the soluble form of FasL (sFasL) and sFas levels in serum and bronchoalveolar lavage fluid (BALF) from patients with HP using enzyme-linked immunosorbent assay (ELISA). Furthermore, we also measured the cytotoxic activity of BALF sFasL in vitro. Results: FasL was detected in infiltrating mononuclear cells, and Fas was detected in infiltrating mononuclear cells, alveolar macrophages, and epithelioid cells in HP, whereas FasL was not detected and Fas was detected in few alveolar macrophages in controls. The levels of sFasL and sFas in BALF, but not in serum, were significantly increased in HP compared with controls. BALF of HP that included high levels of sFasL had no cytotoxic activity for bronchiolar epithelial cells in vitro. Conclusions: In HP, there is an upregulation of FasL and Fas in lung tissues. Since there is no incidence of apoptosis and no cytotoxic activity for lung epithelial cells in BALF from patients with HP, the increased levels of BALF sFasL and sFas may reflect the activation and sequestration of inflammatory cells rather than apoptosis.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The aim of the present study is to identify the optimal anticancer agents for use in combination with gene therapy using wild-type (wt) p53 gene transfer. We used adenoviral vectors expressing human wt p53 (AdCAp53) and investigated the effects of wt p53 gene transfer in combination with 12 anticancer agents on a human pulmonary squamous cell carcinoma cell line, NCI-H157, and a human pulmonary large cell carcinoma cell line, NCI-H1299. Solutions containing anticancer agents at various concentrations were added followed by the addition of recombinant adenovirus solutions; after a 5-day incubation period, the anticancer activity was then evaluated by a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Each 50% inhibitory concentration was calculated based on the dose-response curves. The agents showing a high degree of effectiveness on NCI-H157 cells were cisplatin (CDDP), 5-fluorouracil (5-FU), bleomycin, and 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of irinotecan (CPT-11); conversely, cyclophosphamide and paclitaxel showed a low degree of effectiveness. Based on these data, an isobologram was performed to investigate the interaction between AdCAp53 and some anticancer agents. A supra-additive effect was thus observed for 5-FU and SN-38 on NCI-H157 cells. An additive effect was also observed for CDDP, paclitaxel, bleomycin, and cyclophosphamide on NCI-H157 cells. CDDP, paclitaxel, 5-FU, and SN-38 had an additive effect on NCI-H1299 cells. No drug showed any subadditive or protective effects. These findings suggest that CPT-11 and 5-FU may thus be useful as possible anticancer agents for use in a combination therapy regimen using wt p53 gene transfer. CDDP and CPT-11 had a significant antitumoral effect on H157 cell xenografts of nude mice in vivo. These results indicate that CPT-11 as well as CDDP would be a candidate for the combination of chemotherapy and gene therapy for non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: We have previously reported that the inhalation of anti–Fas antibody induced pulmonary fibrosis in mice. To induce an effective immune response, antigen–presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. The purpose of this study is to investigate whether B7 family costimulating molecules and interleukin–12 (IL–12), which primarily promote cellular immunity, are associated with anti–Fas antibody–induced pulmonary fibrosis. Methods: We examined the expression of B7–1, B7–2, and IL–12 using the revese transcription–polymerase chain reaction (RT–PCR), RT–in situ PCR, and immunohistochemistry. Results: We observed the upregulation of B7–1, B7–2, and IL–12 p40 mRNA after anti–Fas antibody inhalation. B7–2 and IL–12 p40 mRNA appeared to be expressed in mononuclear cells, while B7–1 mRNA and protein were expressed in bronchiolar epithelial cells as well as macrophages. Conclusion: These findings indicate that the T–cell–mediated immune response in this model involved the upregulation of B7–1, B7–2, and IL–12, and that the aberrant expression of B7–1 in bronchiolar epithelial cells may induce autoreactive T cell proliferation against themselves. [ABSTRACT FROM AUTHOR]

To determine the predictive value of the expression of p53 and glutathione S-transferase-π (GST-π) with respect to chemotherapy response, immunostaining was performed on transbronchial biopsy specimens from previously untreated patients with non-small cell lung cancer. Of the 54 patients, 34 patients (63%) and 37 patients (69%) were positive for p53 and GST-π, respectively. The response rates in the p53-positive and p53-negative group were 15 and 45%, and those in GST-π-positive and GST-π-negative groups were 16 and 47%, respectively. A multiple logistic regression analysis revealed that positive immunostaining for GST-π was a significant risk factor for clinical chemotherapy resistance. The combination of these two markers was the most important independent factor in predicting a response to chemotherapy in multiple logistic regression analysis. Immunohistochemical expression of p53 and GST-π was independently related to clinical chemoresistance in patients with non-small cell lung cancer. Combined use of these two biomarkers may be a useful predictor of clinical chemoresistance.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Studies have shown the importance of apoptosis in vascular injury in vitro. We postulated that apoptosis of the endothelium contributes to vascular injury in vivo and may be involved in acute lung injury. Methods: To test this hypothesis, we investigated the incidence of endothelial cell apoptosis in acute lung injury induced in mice by the administration of lipopolysaccharide (LPS). Male ICR mice were administered LPS (20 mg/kg body weight) intravenously and sacrificed at specified times thereafter. Results: Histologic findings were consistent with acute lung injury which increased with time from 3 to 48 h after injection. Electrophoretic analysis of DNA that was extracted from lung tissue and 3'–end–labeled with digoxigenin demonstrated a fragmentation of DNA starting at 6 h. In situ terminal deoxynucleotidyl transferase–mediated dUTP biotin nick end–labeling (TUNEL) demonstrated DNA strand breaks in the endothelial cells. TUNEL also revealed DNA strand breaks in bronchial and alveolar epithelial cells as well as inflammatory cells in the interstitium. These TUNEL–positive cells appeared 6 h after injection. Electron–microscopic examination of the endothelium strongly suggested the morphological characteristics of apoptosis. Conclusion: Apoptosis was induced by LPS administration in endothelial cells in vivo. A role for such apoptosis is suggested in acute lung injury. [ABSTRACT FROM AUTHOR]

Background: The bleomycin–induced pneumopathy involves a T cell–mediated immune response. T cell activation requires both antigen/MHC recognition and costimulatory signals. The CD28 receptor on T cells with its ligand B7 represents one of the most important examples of this costimulation. Interleukin 12 (IL–12) has a strong synergistic effect with the B7–1/CD28 interaction on inducing proliferation and cytokine production in T cells. Methods: In this study, we investigated the expression of B7–1, B7–2, and IL–12 in bleomycin–induced pneumopathy in mice using reverse transcription polymerase chain reaction (RT–PCR), RT in situ PCR, and immunohistochemistry. Results: We observed concurrent upregulation of B7–1, B7–2, and IL–12p40 mRNA in the lung tissues at 1 h to 7 days after bleomycin instillation into the trachea. B7–1 mRNA and protein were found in bronchiolar epithelial cells as well as macrophages, B7–2 and IL–12p40 mRNA appeared to be expressed in mononuclear cells. Conclusions: These findings indicate that T cell–mediated immune response in this model involves the upregulation of B7–1, B7–2, and IL–12p40 mRNA, and also demonstrate the aberrant expression of B7–1 in bronchiolar epithelial cells. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are Masashi Hasegawa, Yoshitane Imai, Yasuhiro Mazaki and co‐workers at Kitasato University, Kindai University and Osaka University. The image depicts a stereogenic twisted cycloparaphenylene that exhibits circularly polarized luminescence in a polymethyl methacrylate thin film. Read the full text of the article at 10.1002/chem.202004283. [ABSTRACT FROM AUTHOR]

Keywords: binaphthyl; circular dichroism; circularly polarized luminescence; cycloparaphenylene; PMMA film EN binaphthyl circular dichroism circularly polarized luminescence cycloparaphenylene PMMA film 1160 1160 1 01/20/21 20210118 NES 210118 B A stereogenic twisted cycloparaphenylene b that glows with helical green light in a polymer matrix is depicted in the cover image. Binaphthyl, circular dichroism, circularly polarized luminescence, cycloparaphenylene, PMMA film. [Extracted from the article]