Urinary benzophenone concentrations and their association with demographic factors in a South Korean population.

Benzophenone (BP) and its derivatives are widely used in various cosmetics, personal care products, and food packaging ink. The use of BP has raised concerns about the potential health risks associated with its endocrine-disrupting effects. This study evaluated urinary concentrations of BP derivatives in a national sample of the South Koreans population aged 6-89 years. From July to September in each 2010 and 2011, 1576 urine samples were collected. Urinary concentrations of benzophenone-1 (BP-1), benzophenone-2 (BP-2), benzophenone-3 (BP-3), benzophenone-4 (BP-4), benzophenone-8 (BP-8), and 4-hydroxybenzophenone (4-OH-BP) were analyzed using liquid chromatography-mass spectrometry. The detection rate for BP-1 and 4-OH-BP were 56% [limit of detection (LOD) 0.59ng/mL] and 88% (LOD 0.04ng/mL), respectively, whereas those for BP-2, BP-3, BP-4, and BP-8 were all below 25%. The geometric means of urinary BP-1 and 4-OH-BP concentrations were 1.24ng/mL and 0.45ng/mL, respectively. Multiple linear regression analysis indicated that concentrations of BP-1 in and of 4-OH-BP in adults were associated with sex and age. The BP-1 and 4-OH-BP concentration of children and adolescents was associated with sex, age, income, and current area of residence. The correlation was observed between urinary concentrations of BP derivatives, which is an important indication of exposure biomarkers and the metabolic pathways from BP-3. This is the first national study to evaluate the presence of BP derivatives in urine samples from the South Korean population, stratified by demographic factors.

Risk assessment based on urinary bisphenol A levels in the general Korean population.

Bisphenol A (BPA) is a high-volume industrial chemical used in the global production of polycarbonate plastics and epoxy resins, which are used in food and drink containers, such as tableware (plates and mugs). Due to its broad applications, BPA has been detected in human blood, urine and breast milk as well as environmental substances, including water, indoor and outdoor air, and dust. Indeed, exposure to high concentrations of BPA can result in a variety of harmful effects, including reproductive toxicity, through a mechanism of endocrine disruption. Our comparison of reported BPA urinary concentrations among different countries revealed that exposures in Korea may be higher than those in other Asian countries and North America, but lower than or similar to those in European countries. The current study included a total of 2044 eligible subjects of all ages. The subjects were evenly divided between males and females (48.58% and 51.42%, respectively). The geometric mean (GM) of pre-adjusted (adjusted) urinary BPA concentrations was 1.83µg/L (2.01µg/g creatinine) for subjects of all ages, and there was no statistically difference in BPA concentrations between males (1.90µg/L, 1.87µg/g creatinine) and females (1.76µg/L, 2.16µg/g creatinine). Multiple regression analysis revealed only one positive association between creatinine pre-adjusted urinary BPA concentration and age (ß=-0.0868, p<0.001). The 95th percentile levels of 24-hour recall (HR), food frequency questionnaires (FFQ) and estimated daily intake (EDI) through urinary BPA concentrations were 0.14, 0.13, and 0.22µg/kg bw/day, respectively. According to the Ministry of Food and Drug Safety (MFDS), a tolerable daily intake (tDI) of 20µg/kg bw/day was established for BPA from the available toxicological data. Recently, the European Food Safety Authority (EFSA) established a temporary TDI of 4µg/kg bw/day based on current toxicological data. By comparing these TDIs with subjects' exposure, we conclude that there are no health concerns for any age group as a result of current levels of dietary exposure to BPA.

Chiral separation on various modified amino alcohol-derived HPLC chiral stationary phases.

3,5-Dinitrobenzoyl chloride was previously used for the preparation of (R)-phenylglycinol- and (S)-leucinol-derived chiral stationary phases. In this study, 3,5-bis(trifluoromethyl)benzoyl chloride, 2-furoyl chloride, 2-theonyl chloride, 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride, diphenylcarbamoyl chloride, and 1-adamantanecarbonyl chloride were used to prepare six new phenylglycinol-derived chiral stationary phases (CSPs) and five new leucinol-derived CSPs. Using these 11 CSPs, chiral separation of nine π-acidic amino acid derivatives and five π-basic compounds was performed, and the separation results were compared. An adamantyl-derived CSP showed good separation.

Synthesis and Application of C2 and C3 Symmetric (R)-Phenylglycinol-Derived Chiral Stationary Phases.

A C3 symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral stationary phase (CSP) and three C2 symmetric (R)-phenylglycinol CSPs were newly synthesized using o-, m-, and p-phthaloyl dichlorides. These CSPs were used to compare the resolution of 25 chiral samples using a previously reported 3,5-dinitrobenzoyl (R)-phenylglycinol-derived CSP. Even though all CSPs have the same chiral moiety, the C3 symmetric CSP showed the best resolution.

Serum amyloid A3 exacerbates cancer by enhancing the suppressive capacity of myeloid-derived suppressor cells via TLR2-dependent STAT3 activation.

Myeloid-derived suppressor cells (MDSCs), which suppress diverse innate and adaptive immune responses and thereby provide an evasion mechanism for tumors, are emerging as a key population linking inflammation to cancer. Although many inflammatory factors that induce MDSCs in the tumor microenvironment are known, the crucial components and the underlying mechanisms remain elusive. In this study, we proposed a novel mechanism by which serum amyloid A3 (SAA3), a well-known inflammatory factor, connects MDSCs with cancer progression. We found that SAA3 expression in BALB/c mice increased in monocytic MDSCs (Mo MDSCs) with tumor growth. The induction of SAA3 by apo-SAA treatment in Mo MDSCs enhanced their survival and suppressive activity, while it inhibited GM-CSF-induced differentiation. Endogenous SAA3 itself contributed to the increase in the survival and suppressive activity of Mo MDSCs. We demonstrated that SAA3 induced TLR2 signaling, in turn increasing the autocrine secretion of TNF-α, that led to STAT3 activation. In addition, activated STAT3 enhanced the suppressive activity of Mo MDSCs. Furthermore, SAA3 induction in Mo MDSCs contributed to accelerating tumor progression in vivo. Collectively, these data suggest a novel mechanism by which Mo MDSCs mediate inflammation through SAA3-TLR2 signaling and thus exacerbate cancer progression by a STAT3-dependent mechanism.

Tgfbi deficiency leads to a reduction in skeletal size and degradation of the bone matrix.

Transforming growth factor-ß-induced gene product-h3 (TGFBI/BIGH3) is an extracellular matrix protein expressed in a wide variety of tissues. TGFBI binds to type I, II, and IV collagens, as well as to biglycan and decorin and plays important roles in cell-to-cell, cell-to-collagen, and cell-to-matrix interactions. Furthermore, TGFBI is involved in cell growth and migration, tumorigenesis, wound healing, and apoptosis. To investigate whether TGFBI is involved in the maintenance of skeletal tissues, Tgfbi knockout mice were generated by crossing male and female Tgfbi heterozygous mice. Skeletal preparation showed that the skeletal size in Tgfbi knockout mice was smaller than in wild-type and heterozygous mice. However, chondrocytic cell alignment in the growth plates, bone mineral density, and bone forming rates were similar in Tgfbi knockout, wild-type, and heterozygous mice. Alterations in skeletal tissue arrangements in Tgfbi knockout mice were estimated from safranin O staining, trichrome staining, and immunohistochemistry for type II and X collagen, and matrix metalloproteinase 13 (MMP13). Cartilage matrix degradation was observed in the articular cartilage of Tgfbi knockout mice. Although the detection of type II collagen in the articular cartilage was lower in Tgfbi knockout mice than wild-type mice, the detection of MMP13 was markedly higher, indicating that Tgfbi deficiency is associated with the degradation of cartilage matrix. These results suggest that TGFBI plays an important role in maintaining skeletal tissues and the cartilage matrix in mice.

Functional changes in myeloid-derived suppressor cells (MDSCs) during tumor growth: FKBP51 contributes to the regulation of the immunosuppressive function of MDSCs.

Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor injection had stronger suppressive activity than MDSCs obtained at an early time point, as measured by T cell proliferation assays. To find factors in MDSCs that change during tumor growth, we analyzed gene expression profiles from MDSCs at different time points after tumor injection. We found that immune response-related genes were downregulated but protumor function-related genes were upregulated in both monocytic MDSCs (Mo-MDSCs) and polymorphonuclear granulocytic MDSCs (PMN-MDSCs) at the late time point. Among differentially expressed genes, FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein family and plays a role in immunoregulation, was increased in the Mo-MDSCs and PMN-MDSCs isolated from the late time points. Experiments using small interfering RNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing inducible NO synthase, arginase-1, and reactive oxygen species levels and enhancing NF-κB activity. Collectively, our data suggest that FKBP51 is a novel molecule that can be targeted to regulate the immunosuppressive function of MDSCs.

Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

Proposal of a Methodology for Prediction of Indoor PM2.5 Concentration Using Sensor-Based Residential Environments Monitoring Data and Time-Divided Multiple Linear Regression Model.

This study aims to propose an indoor air quality prediction method that can be easily utilized and reflects temporal characteristics using indoor and outdoor input data measured near the indoor target point as input to calculate indoor PM2.5 concentration through a multiple linear regression model. The atmospheric conditions and air pollution detected in one-minute intervals using sensor-based monitoring equipment (Dust Mon, Sentry Co Ltd., Seoul, Korea) inside and outside houses from May 2019 to April 2021 were used to develop the prediction model. By dividing the multiple linear regression model into one-hour increments, we attempted to overcome the limitation of not representing the multiple linear regression model's characteristics over time and limited input variables. The multiple linear regression (MLR) model classified by time unit showed an improvement in explanatory power by up to 9% compared to the existing model, and some hourly models had an explanatory power of 0.30. These results indicated that the model needs to be subdivided by time period to more accurately predict indoor PM2.5 concentrations.

The restoration of myeloid-derived suppressor cells as functional antigen-presenting cells by NKT cell help and all-trans-retinoic acid treatment.

Myeloid-derived suppressor cells (MDSCs), which accumulate during tumor progression, have been shown to function as important suppressor cells. In a previous study, we showed that immunosuppressive MDSCs could function as immunogenic antigen-presenting cells (APCs) with the help of activated natural killer T (NKT) cells. In the current study, however, we found that MDSCs harvested at a late time point after tumor injection (late MDSCs) were poorly immunogenic even when stimulated with activated NKT cells. As tumor growth progressed, the expression of MHC and costimulatory molecules on MDSCs was gradually down-regulated. Late MDSCs also had innate defects in activation and differentiation mediated by cytokine stimuli. Although late MDSCs treated only with all-trans-retinoic acid (ATRA), a stimulating agent for MDSC differentiation, could not become immunogenic, NKT ligand-loaded, ATRA-treated late MDSCs could be converted into immunogenic APCs to induce incremental immune responses. Furthermore, these effects were mediated by NKT cells secreting IFNγ, and ATRA-mediated increases in glutathione (GSH) levels. Thus, combined treatment with differentiating and activating agents is a prerequisite for the conversion of late MDSCs into immunogenic APCs. Collectively, these results suggest that combined treatments are required for the differentiation and activation of late MDSCs in late stage cancer.

Novel microsatellite markers of Meretrix petechialis and cross-species amplification in related Taxa (Bivalvia: Veneroida).

The Asian hard clam, Meretrix petechialis, is an economically important bivalve, but its catch and population sizes are decreasing rapidly, owing to many factors, including large-scale reclamation of its natural habitat on the western coast of the Korean peninsula. Attempts to restore the resources and production of this species require genetic structure and diversity information. In this study, we developed 15 microsatellite markers from a partial genomic library enriched in GT repeats. Nine of these markers were polymorphic, with an average allele number of six, and six were monomorphic in 95 tested individuals. No linkage disequilibrium was found between any pair of loci (p > 0.05), and deviations from the Hardy-Weinberg equilibrium (HWE) test showing excess of heterozygotes was observed in only one of nine loci. In addition, no null alleles or genetic differentiation between two tested populations were detected. A cross-species amplification in 12 species of four families resulted in two M. petechialis-specific loci and three possible universal markers. This information will be useful in the future development of high-quality artificial seedlings and sustainable resource management.

Use of Complementary and Alternative Medicine (CAM) in Patients With Colorectal Cancer.

This study was conducted to analyze the relationship between cancer-related stress and the types of complementary and alternative medicine (CAM) used by subjects diagnosed with colorectal cancer. The number of study subjects was 142, and for data analysis, descriptive statistics, t-test, χ2 test, logistic regression procedures were performed. Of the subjects, 114 were CAM users, who accounted for 79.6%. When it came to using CAM, 82 (72.6%) said they did "to prevent cancer recurrence." The most popular reason for not using CAM was "to focus on treatment as instructed by the doctor," with 22 (75.8%) respondents selecting the answer. Of those who used CAM, 79 (55.6%) said they took "dietary supplements," followed by 65 (45.8%) who picked "vitamins and minerals." Regarding CAM usage, ginger, aloe, swimming, and walking had the highest satisfaction (4.25 ± 0.71). The cancer-related stress of subjects who use CAM (18.21 ± 15.37) was higher than that of subjects who did not use CAM (10.11 ± 12.08). Logistic regression analysis determined that cancer-related stress were factors significantly associated with CAM use. Patients using CAM had higher cancer-related stress, suggesting that stress on cancer increased CAM interest. Safe and reliable CAM information and standardized recommendations should be provided to cancer survivors. We propose the development of training programs for CAM to improve communication between medical staff and patients and to protect patients.

NKT ligand-loaded, antigen-expressing B cells function as long-lasting antigen presenting cells in vivo.

We had previously shown that activated NKT cells licensed B cells to be immunogenic antigen-presenting cells and helped to elicit a wide spectrum of cancer targeted immune responses. In the current study, we sought to verify the safety of αGalCer-loaded, and adenovirus-transduced B cell-based vaccines, together with mechanism of action. Intravenously injected αGalCer-loaded, antigen-expressing B cells rapidly localized in the spleen and directly primed CD8(+) T cells in an antigen-specific manner. The transferred antigen was sustained for at least 30 days. While some injected B cells produced nonspecific IgG, the antigen-specific IgG response was completely dependent on endogenous B cells. The liver was one of the main tissues where injected B cells were retained; however, we could not find the signs of liver toxicity. Our results demonstrate that αGalCer-loaded, antigen-expressing B cells behave as "antigen-presenting" cells that stimulate endogenous antigen-specific T cells and B cells in vivo without significant toxicity.

Immunosuppressive myeloid-derived suppressor cells can be converted into immunogenic APCs with the help of activated NKT cells: an alternative cell-based antitumor vaccine.

Myeloid-derived suppressor cells (MDSCs), which are known to be accumulated in the blood, spleen, and bone marrow of tumor-bearing mice and cancer patients, were tested as APCs for a cellular vaccine because they have phenotypical similarity with inflammatory monocytes and may be differentiated from the same precursors as monocytes. Although MDSCs have immunosuppressive properties, in vivo transferred MDSCs, which present tumor Ag and NKT cell ligand (alpha-galactosylceramide), significantly prolonged survival time in metastatic tumor-bearing mice in a CD8(+) cell-, NK cell-, and NKT cell-dependent manner vs a CD4(+) T cell- and host dendritic cell-independent manner. Major concerns about using MDSCs as APCs in a vaccine are their suppression of CTLs and their induction of Foxp3(+) regulatory T cells. However, alpha-galactosylceramide-loaded MDSCs did not suppress CD4(+) and CD8(+) T cells and allowed for the generation of Ag-specific CTL immunity without increasing the generation of regulatory T cells. Furthermore, stimulation with activated NKT cells induced changes on MDSCs in phenotypical or maturation markers, including CD11b, CD11c, and CD86. Taken together, these findings suggest that NKT cells facilitate the conversion of immunosuppressive MDSCs into immunogenic APCs, eliciting successful antitumor immunity and providing the basis for alternative cell-based vaccines.

Cutting edge: Programmed death-1/programmed death ligand 1 interaction regulates the induction and maintenance of invariant NKT cell anergy.

Invariant NKT (iNKT) cells are a distinct subset of T lymphocytes that recognize glycolipid Ags. Upon TCR stimulation, iNKT cells promptly secrete a wide range of cytokines and therefore have been investigated as a target for immunotherapy. However, after primary activation, iNKT cells become hyporesponsive toward their ligand (anergy). The further mechanism behind iNKT cell anergy is poorly understood. We found that a low level of programmed death-1 (PD-1) was constitutively expressed on iNKT cells and that PD-1 expression was increased after stimulation and lasted at least 2 mo. Moreover, not only did blocking of the PD-1/PD ligand 1 (PD-L1) pathway prevent the induction of anergy in iNKT cells, but anergic iNKT cells also recovered responsiveness and these "rescued" cells efficiently mediated antitumor immunity. Our findings suggest that the PD-1/PD-L1 interaction is essential for the induction and maintenance of iNKT cell anergy.

FOXO activity adaptation safeguards the hematopoietic stem cell compartment in hyperglycemia.

Hematopoietic stem cell (HSC) activity is tightly controlled to ensure the integrity of the hematopoietic system during the organism's lifetime. How the HSC compartment maintains its long-term fitness in conditions of chronic stresses associated with systemic metabolic disorders is poorly understood. In this study, we show that obesity functionally affects the long-term function of the most immature engrafting HSC subpopulation. We link this altered regenerative activity to the oxidative stress and the aberrant constitutive activation of the AKT signaling pathway that characterized the obese environment. In contrast, we found minor disruptions of the HSC function in obese mice at steady state, suggesting that active mechanisms could protect the HSC compartment from its disturbed environment. Consistent with this idea, we found that FOXO proteins in HSCs isolated from obese mice become insensitive to their normal upstream regulators such as AKT, even during intense oxidative stress. We established that hyperglycemia, a key condition associated with obesity, is directly responsible for the alteration of the AKT-FOXO axis in HSCs and their abnormal oxidative stress response. As a consequence, we observed that HSCs isolated from a hyperglycemic environment display enhanced resistance to oxidative stress and DNA damage. Altogether, these results indicate that chronic metabolic stresses associated with obesity and/or hyperglycemia affect the wiring of the HSCs and modify their oxidative stress response. These data suggest that the uncoupling of FOXO from its environmental regulators could be a key adaptive strategy that promotes the survival of the HSC compartment in obesity.

Multidisciplinary team training reduces the error rate of DXA image.

Establishing the hospital's own standard operating procedures (SOPs) and team training including physicians and technologists reduces the error rate of dual-energy X-ray absorptiometry (DXA) measurement. In addition, when monitoring DXA images, it is necessary to check whether region of interest (ROI) and bone mapping are properly set as well as patient positioning. INTRODUCTION: Physicians often experience poor quality DXA images, which affects osteoporosis treatment. The purpose of this study is to analyze the change in the error rate of DXA images after a multidisciplinary team training including physicians and technologists. METHODS: Experienced physicians and DXA technologists formed a training team to establish SOPs for DXA measurement. The training team instructed the other related hospital personnel for a month. We set the criteria of measurement errors (9 items for the lumbar spine image and 8 items for the proximal femur image). With these criteria, a total of 637 images (320 images before training and 317 images after training) were analyzed to check the frequency and distribution of errors before and after training. RESULTS: The most common error when measuring the lumbar spine image before training was inadequate bone mapping (51.9%), and when measuring the proximal femur image was the incorrect area of the ROI of the femoral neck (37.2%). The most improved error after training was inadequate bone mapping (33.3% improvement) in the lumbar spine image and inadequate internal rotation (13.6% improvement) in the proximal femur image. Errors were significantly reduced by 23.2% in the lumbar spine, 9.0% in the proximal femur, and 9.2% in both the regions. CONCLUSIONS: Establishing SOPs and multidisciplinary team training effectively reduced the error rate of DXA images.

Characterization of the Streptococcus pneumoniae BgaC protein as a novel surface beta-galactosidase with specific hydrolysis activity for the Galbeta1-3GlcNAc moiety of oligosaccharides.

Streptococcus pneumoniae is a causative agent of high morbidity and mortality. Although sugar moieties have been recognized as ligands for initial contact with the host, only a few exoglycosidases have been reported to occur in S. pneumoniae. In this study, a putative beta-galactosidase, encoded by the bgaC gene of S. pneumoniae, was characterized for its enzymatic activity and virulence. The recombinant BgaC protein, expressed and purified from Escherichia coli, was found to have a highly regiospecific and sugar-specific hydrolysis activity for the Galbeta1-3-GlcNAc moiety of oligosaccharides. Interestingly, the BgaC hydrolysis activity was localized at the cell surface of S. pneumoniae, indicating that BgaC is expressed as a surface protein although it does not have a typical signal sequence or membrane anchorage motif. The surface localization of BgaC was further supported by immunofluorescence microscopy analysis using an antibody raised against BgaC and by a reassociation assay with fluorescein isothiocyanate-labeled BgaC. Although the bgaC deletion mutation did not significantly attenuate the virulence of S. pneumoniae in vivo, the bgaC mutant strain showed relatively low numbers of viable cells compared to the wild type after 24 h of infection in vivo, whereas the mutant showed higher colonization levels at 6 and 24 h postinfection in vivo. Our data strongly indicate for the first time that S. pneumoniae bgaC encodes a surface beta-galactosidase with high substrate specificity that is significantly associated with the infection activity of pneumococci.

High-throughput quantitative analysis of plant N-glycan using a DNA sequencer.

High-throughput quantitative analytical method for plant N-glycan has been developed. All steps, including peptide N-glycosidase (PNGase) A treatment, glycan preparation, and exoglycosidase digestion, were optimized for high-throughput applications using 96-well format procedures and automatic analysis on a DNA sequencer. The glycans of horseradish peroxidase with plant-specific core alpha(1,3)-fucose can be distinguished by the comparison of the glycan profiles obtained via PNGase A and F treatments. The peaks of the glycans with (91%) and without (1.2%) alpha(1,3)-fucose could be readily quantified and shown to harbor bisecting beta(1,2)-xylose via simultaneous treatment with alpha(1,3)-mannosidase and beta(1,2)-xylosidase. This optimized method was successfully applied to analyze N-glycans of plant-expressed recombinant antibody, which was engineered to contain a minor amount of glycan harboring beta(1,2)-xylose. These results indicate that our DNA sequencer-based method provides quantitative information for plant-specific N-glycan analysis in a high-throughput manner, which has not previously been achieved by glycan profiling based on mass spectrometry.

Effects of tranilast and pentoxifylline in a mouse model of chronic asthma using house dust mite antigen.

Tranilast has been used in allergic diseases because of its inhibitory effect on mast cells; it also has an anti-fibrotic effect in several diseases. Pentoxifylline (PTX), a methylxanthine derivative, is a potent anti-inflammatory drug that is known to manifest its effect through the inhibition of Th1 cytokine, but with an uncertain effect on Th2 cytokine. Seven-week-old female BALB/c mice were studied as a chronic asthma model. The mice were challenged with house dust mite (HDM) antigen for 7 weeks. Each group of mice was given an intraperitoneal injection of tranilast, PTX, or tranilast plus PTX before antigen administration. In this mouse model of chronic asthma, tranilast, and PTX each had an inhibitory effect on airway remodeling as well as on airway hyperresponsiveness (AHR) and airway inflammation. The improved events of these drugs were related with the inhibition of the Th2 cytokine IL-13 and TGF-beta 1. Immunohistochemical analysis showed that decreases in the peribronchial trichrome stained area in each treatment group were associated with improvements in the peribronchial smooth muscle hyperplasia, collagen type I, and collagen type III deposition. These drugs could have potential beneficial effects on chronic asthma, especially with respect to airway remodeling.