Nicotinamide phosphoribosyltransferase as a biomarker for the diagnosis of infectious pleural effusions.

Nicotinamide phosphoribosyltransferase (NAMPT) has been reported to be involved in infectious diseases, but it is unknown whether it plays a role in infectious pleural effusions (IPEs). We observed the levels of NAMPT in pleural effusions of different etiologies and investigated the clinical value of NAMPT in the differential diagnosis of infectious pleural effusions. A total of 111 patients with pleural effusion were enrolled in the study, including 25 parapneumonic effusions (PPEs) (17 uncomplicated PPEs, 3 complicated PPEs, and 5 empyemas), 30 tuberculous pleural effusions (TPEs), 36 malignant pleural effusions (MPEs), and 20 transudative effusions. Pleural fluid NAMPT levels were highest in the patients with empyemas [575.4 (457.7, 649.3) ng/ml], followed by those with complicated PPEs [113.5 (103.5, 155.29) ng/ml], uncomplicated PPEs [24.9 (20.2, 46.7) ng/ml] and TPEs [88 (19.4, 182.6) ng/ml], and lower in patients with MPEs [11.5 (6.5, 18.4) ng/ml] and transudative effusions [4.3 (2.6, 5.1) ng/ml]. Pleural fluid NAMPT levels were significantly higher in PPEs (P < 0.001) or TPEs (P < 0.001) than in MPEs. Moreover, Pleural fluid NAMPT levels were positively correlated with the neutrophil percentage and lactate dehydrogenase (LDH) levels and inversely correlated with glucose levels in both PPEs and TPEs, indicating that NAMPT was implicated in the neutrophil-associated inflammatory response in infectious pleural effusion. Further, multivariate logistic regression analysis showed pleural fluid NAMPT was a significant predictor distinguishing PPEs from MPEs [odds ratio (OR) 1.180, 95% confidence interval (CI) 1.052-1.324, P = 0.005]. Receiver-operating characteristic (ROC) analysis demonstrated that NAMPT was a promising diagnostic factor for the diagnosis of infectious effusions, with the areas under the curve for pleural fluid NAMPT distinguishing PPEs from MPEs, TPEs from MPEs, and IPEs (PPEs and TPEs) from NIPEs were 0.92, 0.85, and 0.88, respectively. In conclusion, pleural fluid NAMPT could be used as a biomarker for the diagnosis of infectious pleural effusions.

Tuning Dielectric Transitions in Two-Dimensional Organic-Inorganic Hybrid Lead Halide Perovskites.

Organic-inorganic hybrid metal halide perovskites possessing unique two-dimensional (2D)-layered structures have been demonstrated with excellent molecular tunability and stability, especially the promising semiconductor properties for solar cell applications. In this work, three 2D lead halide organic-inorganic hybrid perovskites (IAA)2PbX4 (IAA = isoamylammonium cation and X = Cl, Br, and I) were synthesized by employing a solution processing method and demonstrate distinct tuning solid-state phase transitions coupled with dielectric responses, as well as light absorption properties. Among the title perovskites, the phase transition temperature decreases gradually, and their band gap also indicates a narrowing trend. The results are mainly derived from slight changes in the crystal structure by halogen regulation. These findings might provide an effective crystal engineering strategy for exploring high-performance functional perovskite materials.

Optical Control of Polarization Switching in a Single-Component Organic Ferroelectric Crystal.

The optical control of polarization switching is attracting tremendous interest because photoirradiation stands out as a nondestructive, noncontact, and remote-control means beyond an electric or strain field. The current research mainly uses various photoexcited electronic effects to achieve the photocontrol polarization, such as a light-driven flexoelectric effect and a photovoltaic effect. However, since photochromism was discovered in 1867, the structural phase transition caused by photoisomerization has never been associated with ferroelectricity. Here, we successfully synthesized an organic photochromic ferroelectric with polar space group Pna21, 3,4,5-trifluoro-N-(3,5-di-tert-butylsalicylidene)aniline, whose color can change between yellow and orange via laser illumination. Its dielectric permittivity and spontaneous polarization can be switched reversibly with a photoinduced phase transition triggered by structural photoisomerization between the enol form and the trans-keto form. To our knowledge, this is the first photoswitchable ferroelectric crystal to achieve polarization switching through a structural phase transition triggered by photoisomerization. This finding paves the way toward photocontrol of smart materials and biomechanical applications in the future.

A Photoluminescent Lead Bromide Hybrid Perovskite Molecular Ferroelastic Semiconductor with Sequential High-Tc Phase Transitions.

Organic-inorganic hybrid lead halide perovskites have attracted great interest for their use in promising optoelectronic applications. However, reports of photoluminescent perovskite molecular ferroelastic semiconductors with sequential high-Tc phase transitions have been scarce. In this work, a one-dimensional lead bromide hybrid perovskite [N,N-dimethylethanolammonium]PbBr3 has been synthesized, undergoing high-Tc sequential phase transitions at around 351 and 444 K, higher than those of most previously discovered hybrid perovskite phase transition materials. The specific intermolecular hydrogen bond between cationic molecules provides the greatest contribution to its high Tc by increasing the barrier of molecular motion under the temperature stimuli. The prominent ferroelastic domain evolution is visually observed under orthogonally polarized light. In addition, [N,N-dimethylethanolammonium]PbBr3 exhibits semiconducting and orange light emission characteristics. This finding opens up an avenue for designing high-performance ferroelastic materials and provides great motivation for discovering new multifunctional materials for the next generation of smart devices.

Unprecedented 2D Homochiral Hybrid Lead-Iodide Perovskite Thermochromic Ferroelectrics with Ferroelastic Switching.

Chiral perovskites have emerged as a significant class of materials showing promising optoelectronic and spintronic applications. Reports of chiral perovskite ferroelectrics, however, have been scarce. In this work, we have successfully synthesized homochiral lead-iodide perovskite ferroelectrics [(R)-N-(1-phenylethyl)ethane-1,2-diaminium]PbI4 and [(S)-N-(1-phenylethyl)ethane-1,2-diaminium]PbI4 by introducing a methyl group into the organic cation of the parent (N-benzylethane-1,2-diaminium)PbI4 . Vibrational circular dichroism spectra identify the chiral mirroring relationship. They both undergo 222F2-type paraelectric-ferroelectric behavior at around 378 K coupled with clear ferroelastic domain "ON/OFF" switching. Besides, they exhibit an evident thermochromism with color change from orange-yellow to orange-red. To our knowledge, the discovery of integrated ferroelectricity, ferroelasticity, and reversible thermochromism in chiral perovskites is unprecedented.

Record Enhancement of Phase Transition Temperature Realized by H/F Substitution.

A high transition temperature (Tc ) is essential for the practical application of ferroelectrics as electronic devices under extreme thermal conditions in the aerospace, automotive, and energy industries. In recent decades, the isotope effect and strain engineering are found to effectively modulate Tc ; however, these strategies are limited to certain systems. Developing simple, universal, and practical methods to improve Tc has become an imminent challenge for expanding the applications of ferroelectrics. Here, by adopting a molecular design strategy involving H/F substitution on an organic-inorganic hybrid perovskite (1-azabicyclo[2.2.1]heptane)CdCl3 at a Tc of 190 K, the successful synthesis of a multiaxial, ferroelectric hybrid perovskite (4-fluoro-1-azabicyclo[2.2.1]heptane)CdCl3 is reported, which demonstrates a large spontaneous polarization of 11.2 µC cm-2 (greater than that of polyvinylidene difluoride) and a Tc of 419 K (greater than that of BaTiO3 ). This temperature enhancement (229 K) is the largest reported for molecular ferroelectrics, far exceeding the reported enhancements induced by the isotope effect and other techniques. This pioneering technique provides an effective and universal method for improving Tc in ferroelectrics and represents an important step toward the development of high-performance ferroelectric technology.

Six-Fold Vertices in a Single-Component Organic Ferroelectric with Most Equivalent Polarization Directions.

Topological defects such as vortices in ferroelectric materials are attracting tremendous interest because of their splendid possibilities for unique physical phenomena and potential applications in nanoelectronic devices. However, reports of the vortex structure have been scarce in organic ferroelectrics, which are highly desirable for their mechanical flexibility, easy and environment-friendly processing, and low acoustical impedance. Here, we successfully observed the robust triangular domains in a single-component organic ferroelectric, 2-(hydroxymethyl)-2-nitro-1,3-propanediol (1), six of which can form a 6-fold vertex domain structure. To our knowledge, it is the first time that such an intriguing topological vortex gets experimentally confirmed in ferroelectrics. Moreover, the symmetry change of 1 with an Aizu notation of m3mF1 leads to the most 48 crystallographically equivalent polarization directions among all ferroelectrics. With those benefits and excellent piezoelectric properties, compound 1 shows great potential as a reconfigurable electronic element or a mechanical sensor for soft robotics, flexible and wearable devices, and biomachines.

Superior Transverse Piezoelectricity in a Halide Perovskite Molecular Ferroelectric Thin Film.

Piezoelectric materials with inherent mechanical-electric coupling effect are a crucial family of functional materials in high-end information technology. For practical applications, the transverse piezoelectric performance (d31 or d32) is mainly considered, because this parameter is a vitally important index to characterize the performance of piezoelectric thin films. However, the transverse piezoelectricity of the thin films as a key figure of merit is seldom mentioned in molecular ferroelectrics. Herein, we report that a new 1D halide perovskite ferroelectric N,N-dimethylallylammoniumCdCl3 (DMAACdCl3) exhibits an above room-temperature ferroelectric phase transition with a saturated polarization of 1.9 µC cm-2 and a coercive field of 5.0 kV cm-1. The thin film of DMAACdCl3 is successfully fabricated using an easy processing spinning method and maintains well ferroelectric properties verified by piezoresponse force microscopy (PFM). More significantly, the ferroelectric thin film offers superior transverse piezoelectricity with an in-plane piezoelectric response of about 41 pC N-1, which is about twice that of well-known piezoelectric polymer PVDF (21 pC N-1). Transverse piezoelectricity has been scarcely studied in molecular ferroelectrics, and its exploitation would play an important role in the design of next-generation smart piezoelectric devices.

High-Tc Enantiomeric Ferroelectrics Based on Homochiral Dabco-derivatives (Dabco=1,4-Diazabicyclo[2.2.2]octane).

1,4-Diazabicyclo[2.2.2]octane (dabco) and its derivatives have been extensively utilized as building units of excellent molecular ferroelectrics for decades. However, the homochiral dabco-based ferroelectric remains a blank. Herein, by adding a methyl (Me) group accompanied by the introduction of homochirality to the [H2 dabco]2+ in the non-ferroelectric [H2 dabco][TFSA]2 (TFSA=bis(trifluoromethylsulfonyl)ammonium), we successfully designed enantiomeric ferroelectrics [R and S-2-Me-H2 dabco][TFSA]2 . The two enantiomers show two sequential phase transitions with transition temperature (Tc ) as high as 405.8 K and 415.8 K, which is outstanding in both dabco-based ferroelectrics and homochiral ferroelectrics. To our knowledge, [R and S-2-Me-H2 dabco][TFSA]2 are the first examples of dabco-based homochiral ferroelectrics. This finding opens an avenue to construct dabco-based homochiral ferroelectrics and will inspire the exploration of more eminent enantiomeric molecular ferroelectrics.

The Soft Molecular Polycrystalline Ferroelectric Realized by the Fluorination Effect.

For a century ferroelectricity has attracted widespread interest from science and industry. Inorganic ferroelectric ceramics have dominated multibillion dollar industries of electronic ceramics, ranging from nonvolatile memories to piezoelectric sonar or ultrasonic transducers, whose polarization can be reoriented in multiple directions so that they can be used in the ceramic and thin-film forms. However, the realization of macroscopic ferroelectricity in the polycrystalline form is challenging for molecular ferroelectrics. In pursuit of low-cost, biocompatible, and mechanically flexible alternatives, the development of multiaxial molecular ferroelectrics is imminent. Here, from quinuclidinium perrhenate, we applied fluorine substitution to successfully design a multiaxial molecular ferroelectric, 3-fluoroquinuclidinium perrhenate ([3-F-Q]ReO4), whose macroscopic ferroelectricity can be realized in both powder compaction and thin-film forms. The fluorination effect not only increases the intrinsic polarization but also reduces the coercive field strength. More importantly, it is also, as far as we know, the softest of all known molecular ferroelectrics, whose low Vickers hardness of 10.5 HV is comparable with that in poly(vinylidene difluoride) (PVDF) but almost 2 orders of magnitude lower than that in BaTiO3. These attributes make it an ideal candidate for flexible and wearable devices and biomechanical applications.

Antiangiogenesis-Combined Photothermal Therapy in the Second Near-Infrared Window at Laser Powers Below the Skin Tolerance Threshold.

Photothermal agents with strong light absorption in the second near-infrared (NIR-II) region (1000-1350 nm) are strongly desired for successful photothermal therapy (PTT). In this work, titania-coated Au nanobipyramids (NBP@TiO2) with a strong plasmon resonance in the NIR-II window were synthesized. The NBP@TiO2 nanostructures have a high photothermal conversion efficiency of (93.3 ± 5.2)% under 1064-nm laser irradiation. They are also capable for loading an anticancer drug combretastatin A-4 phosphate (CA4P). In vitro PTT studies reveal that 1064-nm laser irradiation can efficiently ablate human lung cancer A549 cells and enhance the anticancer effect of CA4P. Moreover, the CA4P-loaded NBP@TiO2 nanostructures combined with PTT induce a synergistic antiangiogenesis effect. In vivo studies show that such CA4P-loaded NBP@TiO2 nanostructures under mild 1064-nm laser irradiation at an optical power density of 0.4 W cm-2, which is lower than the skin tolerance threshold value, exhibit a superior antitumor effect. This work presents not only the development of the NBP@TiO2 nanostructures as a novel photothermal agent responsive in the NIR-II window but also a unique combined chemo-photothermal therapy strategy for cancer therapy.

Effect of Lang-Chuang-Ding Decoction () on DNA Methylation of CD70 Gene Promoter in Peripheral Blood Mononuclear Cells of Female Patients with Systemic Lupus Erythematosus.

OBJECTIVE: To investigate the effect of Lang-chuang-ding Decoction (, LCD) on the expression of DNA methylation of CD70 gene promoter in peripheral blood mononuclear cells (PBMCs) of females with systemic lupus erythematosus (SLE). METHODS: PBMCs isolated from female patients with SLE or healthy donors were cultured and treated with LCD medicated serum or normal serum for 24 or 48 h. The mRNA expressions of CD70 gene in PBMCs were detected by reverse transcription polymerase chain reaction (PCR); the DNA methylation of the CD70 gene promoter region was detected by methylation-specific PCR. RESULTS: After treated with medicated serum for 48 h, the mRNA expression levels of CD70 in PBMCs of SLE patients were signifificantly higher than those of healthy donors (P<0.05); the DNA methylation levels of CD70 promoter region in PBMCs of SLE patients treated with medicated serum for 48 h were signifificantly higher than those treated with fetal bovine serum (P<0.01). CONCLUSION: LCD could inhibit CD70 gene expression in PBMCs of SLE patients by promoting the DNA methylation of CD70 gene promoter.

Origin of the enhancement in transport properties on polycrystalline SnSe with compositing two-dimensional material MoSe2.

P-type SnSe compositing with 2D MoSe2 materials have been prepared by the solid solution method followed by the spark plasma sintering technique. The total thermal conductivities of SnSe/MoSe2 composites were found to be higher than for pristineSnSe at room temperature; and the disparity between them becomes smaller at higher temperatures, where the low thermal conductivities remained. Both the carrier concentration and the carrier mobility were significantly improved after MoSe2 was introduced into the SnSe matrix along the direction perpendicular to the pressing direction, leading to an extraordinary enhancement in electrical transport performance. The maximum ZT of 0.5 was obtained at 773 K for SnSe + 1.5%MoSe2 along the direction perpendicular to the pressing direction; this value is 1.5 times as large as that of the pristine SnSe.

Conical dispersion and effective zero refractive index in photonic quasicrystals.

It is recognized that for a certain class of periodic photonic crystals, conical dispersion can be related to a zero-refractive index. It is not obvious whether such a notion can be extended to a noncrystalline system. We show that certain photonic quasicrystalline approximants have conical dispersions at the zone center with a triply degenerate state at the Dirac frequency, which is the necessary condition to qualify as a zero-refractive-index medium. The states in the conical dispersions are extended and have a nearly constant phase. Experimental characterizations of finite-sized samples show evidence that the photonic quasicrystals do behave as a near zero-refractive-index material around the Dirac frequency.

Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B.

A novel series of flavokawain B derivatives, chalcone Mannich bases (4-10) were designed, synthesized, characterized, and evaluated for the inhibition activity against acetylcholinesterase (AChE). Biological results revealed that four compounds displayed potent activities against AChE with IC50 values below 20µM. Moreover, the most promising compound 8 was 2-fold more active than rivastigmine, a well-known AChE inhibitor. The logP values of 4-10 were around 2 which indicated that they were sufficiently lipophilic to pass blood brain barriers in vivo. Enzyme kinetic study suggested that the inhibition mechanism of compound 8 was a mixed-type inhibition. Meanwhile, the molecular docking showed that this compound can both bind with the catalytic site and the periphery of AChE.

Nuclear translocation of cysteinyl leukotriene receptor 1 is involved in oxygen-glucose deprivation-induced damage to endothelial cells.

AIM: Cysteinyl leukotriene receptor 1 (CysLT(1) receptor) is located in epithelial cells, and translocates from the plasma membrane to the nucleus in a ligand-dependent manner. Here, we investigated whether CysLT(1) receptors translocated to the nucleus in endothelial cells after ischemic insult in vitro and whether it was involved in ischemic injury to endothelial cells. METHODS: EA.hy926 cell line, derived from human umbilical vein endothelial cells, was subjected to oxygen-glucose deprivation (OGD). The expression and distribution of CysLT(1) receptors were detected by immunofluorescent staining, immunogold labeling and immunoblotting analyses. Cell viability was evaluated using MTT reduction assay. Necrosis and apoptosis were determined by double fluorescent staining with propidium iodide and Hoechst 33342. RESULTS: CysLT(1) receptors were primarily distributed in the cytoplasm and nucleus in EA.hy926 cells, and few was found in the cell membrane. OGD induced the translocation of CysLT(1) receptors from the cytoplasm to the nucleus in a time-depen dent manner, with a peak reached at 6 h. OGD-induced nuclear translocation of CysLT(1) receptors was inhibited by pretreatment with the CysLT(1) receptor antagonist pranlukast (10 µmol/L), or by preincubation with NLS-pep, a peptide corresponding to the nuclear localization sequence of CysLT(1) receptor (10 µg/mL). However, zileuton, an inhibitor of 5-lipoxygenase that was a key enzyme in cysteinyl leukotriene generation, did not inhibit the nuclear translocation of CysLT(1) receptors. Moreover, preincubation with NLS-pep (0.4 µg/mL) significantly ameliorated OGD-induced cell viability reduction and necrosis. CONCLUSION: CysLT(1) receptors in endothelial cells translocate to the nucleus in a ligand-independent manner after ischemic insult in vitro, and it is involved in the ischemic injury.

Transforming growth factor ß1-induced astrocyte migration is mediated in part by activating 5-lipoxygenase and cysteinyl leukotriene receptor 1.

BACKGROUND: Transforming growth factor-ß 1 (TGF-ß 1) is an important regulator of cell migration and plays a role in the scarring response in injured brain. It is also reported that 5-lipoxygenase (5-LOX) and its products, cysteinyl leukotrienes (CysLTs, namely LTC4, LTD4 and LTE4), as well as cysteinyl leukotriene receptor 1 (CysLT1R) are closely associated with astrocyte proliferation and glial scar formation after brain injury. However, how these molecules act on astrocyte migration, an initial step of the scarring response, is unknown. To clarify this, we determined the roles of 5-LOX and CysLT1R in TGF-ß 1-induced astrocyte migration. METHODS: In primary cultures of rat astrocytes, the effects of TGF-ß 1 and CysLT receptor agonists on migration and proliferation were assayed, and the expression of 5-LOX, CysLT receptors and TGF-ß1 was detected. 5-LOX activation was analyzed by measuring its products (CysLTs) and applying its inhibitor. The role of CysLT1R was investigated by applying CysLT receptor antagonists and CysLT1R knockdown by small interfering RNA (siRNA). TGF-ß 1 release was assayed as well. RESULTS: TGF-ß 1-induced astrocyte migration was potentiated by LTD4, but attenuated by the 5-LOX inhibitor zileuton and the CysLT1R antagonist montelukast. The non-selective agonist LTD4 at 0.1 to 10 nM also induced a mild migration; however, the selective agonist N-methyl-LTC4 and the selective antagonist Bay cysLT2 for CysLT2R had no effects. Moreover, CysLT1R siRNA inhibited TGF-ß 1- and LTD4-induced astrocyte migration by down-regulating the expression of this receptor. However, TGF-ß 1 and LTD4 at various concentrations did not affect astrocyte proliferation 24 h after exposure. On the other hand, TGF-ß 1 increased 5-LOX expression and the production of CysLTs, and up-regulated CysLT1R (not CysLT2R), while LTD4 and N-methyl-LTC4 did not affect TGF-ß 1 expression and release. CONCLUSIONS: TGF-ß 1-induced astrocyte migration is, at least in part, mediated by enhanced endogenous CysLTs through activating CysLT1R. These findings indicate that the interaction between the cytokine TGF-ß 1 and the pro-inflammatory mediators CysLTs in the regulation of astrocyte function is relevant to glial scar formation.

[Effect of montelukast on morphological changes in neurons after ischemic injury].

OBJECTIVE: To determine the effect of montelukast, a cysteinyl leukotriene receptor 1 antagonist, on morphological changes in rat neurons after ischemic injury. METHODS: The in vivo ischemia injury was induced by oxygen-glucose deprivation (OGD) for 2 h and reperfusion (R) for 24 h (OGD/R) in rat neurons primary culture and mixed cortex culture. In the presence or absence of various concentrations of montelukast, neuron number, area of neuron, number of neuritis per neuron, branch number of primary neuritis and primary neurite length were determined for evaluating morphological changes in neurons. RESULTS: OGD/R significantly reduced neuron number, and altered neuron morphology. In cortical neuron cultures, montelukast (0.0001-1 µmol/L) attenuated OGD/R-induced reduction in neuron number, and inhibited OGD/R-induced increase in branch number of primary neuritis. In the mixed cultures, montelukast (0.0001-0.1 µmol/L) increased the primary neurite length, and reduced number of neuritis and branch number of primary neurite after OGD/R. CONCLUSION: Montelukast has a protective effect on ischemic injury in neurons.

[Construction of HEK293 cell lines expressing hCysLT2 receptor and its application in screening of antagonists].

OBJECTIVE: To construct HEK293 cell lines stably expressing hCysLT(2) receptor, and to evaluate its application in screening of synthetic compounds with antagonist activity. METHODS: The recombinant plasmid pcDNA3.1(+)-hCysLT(2) was transfected into HEK293 cells using Lipofectamin 2000. The transfected HEK293 cells were selected in 96 well plates by limiting dilution with 600 µg/ml C418 for 8 weeks. The expression of human CysLT(2) receptor was detected by RT-PCR and immunofluorescence staining. In HEK293 cells stably transfected with hCysLT(2), the agonist LTD(4)-induced elevation of intracellular calcium concentration ([Ca2(+)]i) was measured as the index for screening compounds with antagonist activity. RESULT: After selection in 96 well plates by limiting dilution, 12 monoclones were obtained and 11 of them highly expressed hCysLT(2) receptor. The positive control ATP at 50 µmol/L and LTD(4) at 100 nmol/L elevated [Ca2(+)]i in hCysLT(2)-HEK293 cells. AP-2100984 inhibited LTD(4)-induced [Ca2(+)]i elevation, but selective CysLT(1) receptor antagonists did not exert such an effect. The newly synthesized compounds DXW2, DXW3, DXW4, DXW5, DXW9, DXW25, DXW26, DXW29 and DXW35 at 1 µmol/L significantly inhibited LTD(4)-induced [Ca2(+)]i elevation. The IC(50) values of DXW4 and DXW5 were 0.25 µmol/L and 7.5 µmol/L. CONCLUSION: HEK293 cell lines stably expressing hCysLT(2) receptor have been successfully constructed, and can be used to screen compounds with CysLT(2) receptor antagonist activity.

[Effects of agonist and antagonist of cysteinyl leukotriene receptors on differentiation of rat glioma C6 cells].

OBJECTIVE: To investigate the role of cysteinyl leukotriene (CysLT) receptors in the differentiation of rat glioma C6 cells. METHODS: Rat glioma C6 cells were treated with the agonist LTD(4), the CysLT(1) receptor antagonist montelukast and the differentiation inducer forskolin. Cell morphology and GFAP protein expression were determined after treatments. RESULT: Forskolin (10 µmol/L) induced morphological changes and GFAP protein expression (cell differentiation) in C6 cells, but LTD(4) (0.1-100 nmol/L) did not induce these changes. Montelukast (1 µmol/L) alone did not affect C6 cell differentiation, while it induced the differentiation when combined with the LTD(4) (100 nmol/L). CONCLUSION: The CysLT(2) receptor may modulate the differentiation of rat glioma C6 cells.