Xin-Yi-Qing-Fei-Tang and its critical components reduce asthma symptoms by suppressing GM-CSF and COX-2 expression in RBL-2H3 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) XYQFT is composed of 10 herbs. According to the NHIRD, XYQFT is one of the top ten most commonly used TCM prescriptions for asthma treatment. AIM OF THE STUDY: The aim of this study was to explore whether XYQFT reduces asthma symptoms in a mouse model of chronic asthma and determine the immunomodulatory mechanism of mast cells. MATERIALS AND METHODS: BALB/c mice were intratracheally (it) stimulated with 40 µL (2.5 µg/µL) of Dermatophagoides pteronyssinus (Der p) once a week for 6 consecutive weeks and orally administered XYQFT at 1 g/kg 30 min before Der p stimulation. Airway hypersensitivity, inflammatory cells in the BALF and total IgE in the blood were assessed in mice. In addition, RBL-2H3 cells (mast cells) were stimulated with DNP-IgE, after which different concentrations of XYQFT were added for 30 min to evaluate the effect of XYQFT on the gene expression and degranulation of DNP-stimulated RBL-2H3 cells. After the compounds in XYQFT were identified using LC‒MS/MS, the PBD method was used to identify the chemical components that inhibited the expression of the GM-CSF and COX-2 genes in mast cells. RESULTS: The airway hypersensitivity assay demonstrated that XYQFT significantly alleviated Der p-induced airway hypersensitivity. Moreover, cell counting and typing of bronchoalveolar lavage fluid revealed a significant reduction in Der p-induced inflammatory cell infiltration with XYQFT treatment. ELISA examination further indicated a significant decrease in Der p-induced total IgE levels in serum following XYQFT administration. In addition, XYQFT inhibited the degranulation and expression of genes (IL-3, IL-4, ALOX-5, IL-13, GM-CSF, COX-2, TNF-α, and MCP-1) in RBL-2H3 cells after DNP stimulation. The compounds timosaponin AIII and genkwanin in XYQFT were found to be key factors in the inhibition of COX-2 and GM-CSF gene expression in mast cells. CONCLUSION: By regulating mast cells, XYQFT inhibited inflammatory cell infiltration, airway hypersensitivity and specific immunity in a mouse model of asthma. In addition, XYQFT synergistically inhibited the expression of the GM-CSF and COX-2 genes in mast cells through timosaponin AIII and genkwanin.

Effects of angel wings on morphological and histological characteristics of White Roman geese.

This study aims to determine the effects of normal and angel wing on morphological and histological characteristics of white Roman geese. Angel wing is a torsion of a wing at the carpometacarpus all the way down to the end, stretching outward away from the body lateral. In this study, 30 geese were raised for observing the whole appearance, including stretched wings and morphologies of defeathered wings at 14 wk old. A group of 30 goslings was raised to observe the feature of conformation development of wing bones from 4 to 8 wk old by X-ray photography. The results show that normal wing on angles of the metacarpals and radioulnar bones has a trend greater than the angel wing group (P = 0.927) at the age of 10 wk. According to 64-slice images of computerized tomography scanner on a group of 10-wk-old geese, the interstice at the carpus joint of the angel wing was larger than that of the normal wing. The slight to moderate dilated space of the carpometacarpal joint was found in the angel wing group. In conclusion, the angel wing is torqued outward away from the body laterals at the carpometacarpus and has a slight to moderate dilated space in the carpometacarpal joint. The normal wing geese exhibited an angel that is 9.24% greater than those of angel wing geese at the age of 14 wk (130 vs. 118.5°).

Evaluation of You-Gui-Wan critical compounds inhibiting ALOX-5 and HDC gene expression in RBL-2H3 cells using a fractional factorial design.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) You-Gui-Wan (YGW) has been used to treat asthma for hundreds of years. AIM OF THE STUDY: YGW is composed of 10 types of medicinal materials. However, the immune mechanism of YGW in asthma treatment has not been elucidated. Therefore, this study investigated asthma symptoms attenuated by YGW and the underlying immune regulatory mechanism. MATERIALS AND METHODS: Intratracheal (i.t.) stimulation of BALB/c mice with Dermatophagoides pteronyssinus (Der p) was performed once per week (40 µL, 2.5 µg/µL). For six consecutive weeks, different doses of YGW (0.2 g/kg and 0.5 g/kg) were orally administered 30 min before stimulation with Der p. After the last stimulation, airway hyperreactivity, lung gene expression, and total immunoglobulin E (IgE) in blood were evaluated using a whole-body plethysmograph system, real-time PCR, and ELISA, respectively. In addition, DNP-IgE/DNP-BSA was added to stimulate mast cells (RBL-2H3), and YGW or various compound compositions (Trial) were added to RBL-2H3 cells for 30 min to evaluate the effects of the drug on mast cell degranulation and on gene expression. JMP 5.1 software was used to design and analyze YGW's critical compounds by which it inhibited ALOX-5 and HDC gene expression in RBL-2H3 cells. RESULTS: YGW significantly decreased serum total IgE levels and airway hyperresponsiveness in asthmatic mice. YGW also reduced the gene expression of IL-6, TNF-α, IL-4, IL-13, and COX-2 in the lungs of asthmatic mice and RBL-2H3 cells. YGW and the compound (Trial 21) present in YGW inhibited the gene expression of ALOX-5 and HDC in RBL-2H3 cells. CONCLUSION: The experimental results indicate that YGW exhibits anti-airway hyperresponsiveness and specific immunomodulatory effects. In addition, YGW synergistically inhibits ALOX-5 and HDC gene expression in mast cells through a combination of 21 compounds, including luteolin, quercetin, and ß-carotene.

Pulsatilla decoction suppresses matrix metalloproteinase-7-mediated leukocyte recruitment in dextran sulfate sodium-induced colitis mouse model.

BACKGROUND: Intestinal inflammation is considered to be an important characteristic of ulcerative colitis (UC) and the current medical treatments for UC are usually proposed to suppress abnormal intestinal immune responses. Pulsatilla decoction (PD), a traditional Chinese medicine, is frequently used in UC treatments in Asian countries; however, the mechanism of the action of PD remains unclear. In the present study, the mechanism of the action of PD was elucidated in the dextran sulfate sodium (DSS)-induced colitis mouse model, a model to mimic UC. METHODS: Murine colitis was evaluated by comparing the disease activity index score. The intestinal inflammation was examined by histology analyses. The leukocyte infiltration in the colonic tissues was examined by immunohistochemistry analyses. The cytokines level in colonic tissues was examined by Multi-Plex immunoassay. The epithelial proliferation was evaluated by histological analyses. Immunofluorescence double staining was used to examine the expression of MMP-7 in the immune cells. RESULTS: In the DSS-induced colitis mouse model, administration of PD attenuated the intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells. Immunohistochemical analyses further showed that matrix metalloproteinase-7 (MMP-7) expressed by the infiltrating leukocytes, including neutrophils and macrophages was inhibited by PD treatment. PD increases the cytokine level of IL-6 in colonic tissues. CONCLUSION: PD suppresses intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells, through decreasing MMP-7 expression.

Intestinal Microbiota, Anti-Inflammatory, and Anti-Oxidative Status of Broiler Chickens Fed Diets Containing Mushroom Waste Compost By-Products.

This study investigated the effects of using mushroom waste compost as the residue medium for Pleurotus eryngii planting, which was used as a feed replacement; its consequent influence on broiler chickens' intestinal microbiota, anti-inflammatory responses, and anti-oxidative status was likewise studied. A total of 240 male broilers were used and allocated to four treatment groups: the basal diet-control group (corn-soybean); 5% replacement of a soybean meal via PWMC (Pennisetum purpureum Schum No. 2 waste mushroom compost); 5% replacement of a soybean meal via FPW (Saccharomyces cerevisiae fermented PWMC); 5% replacement of a soybean meal via PP (Pennisetum purpureum Schum No. 2). Each treatment had three replicates and 20 birds per pen. The levels of glutathione peroxidase and superoxide dismutase mRNA as well as protein increased in the liver and serum in chickens, respectively; mRNA levels of inflammation-related genes were also suppressed 2 to 10 times in all treatments as compared to those in the control group. The tight junction and mucin were enhanced 2 to 10 times in all treatment groups as compared to those in the control, especially in the PWMC group. Nevertheless, the appetite-related mRNA levels were increased in the PWMC and FPW groups by at least two times. In ileum and cecum, the Firmicutes/Bacteroidetes ratios in broilers were decreased in the PWMC, FPW, and PP groups. The Lactobacillaceae in the ileum were increased mainly in the PWMC and control groups. Overall, high-fiber feeds (PWMC, FPW, and PP) could enhance the broilers' health by improving their antioxidant capacities and decreasing their inflammatory response as compared to the control. Based on the results, a 5% replacement of the soybean meal via PWMC is recommended in the broiler chickens' diet.

The Potential Utilization of High-Fiber Agricultural By-Products as Monogastric Animal Feed and Feed Additives: A Review.

With the increase in world food demand, the output of agricultural by-products has also increased. Agricultural by-products not only contain more than 50% dietary fiber but are also rich in functional metabolites such as polyphenol (including flavonoids), that can promote animal health. The utilization of dietary fibers is closely related to their types and characteristics. Contrary to the traditional cognition that dietary fiber reduces animal growth, it can promote animal growth and maintain intestinal health, and even improve meat quality when added in moderate amounts. In addition, pre-fermenting fiber with probiotics or enzymes in a controlled environment can increase dietary fiber availability. Although the use of fiber has a positive effect on animal health, it is still necessary to pay attention to mycotoxin contamination. In summary, this report collates the fiber characteristics of agricultural by-products and their effects on animal health and evaluates the utilization value of agricultural by-products.

Assessment of Intestinal Immunity and Permeability of Broilers on Partial Replacement Diets of Two-Stage Fermented Soybean Meal by Bacillus velezensis and Lactobacillus brevis ATCC 367.

The effect of soybean peptides from fermented soybean meal on the intestinal immunity and tight junction of broilers was assessed. Roughly, two-stage fermented soybean meal prepared with Bv and Lb (FSBMB+L), which has nearly three times higher soluble peptides than soybean meal (SBM), and reduced galacto-oligosaccharide (GOS) content and allergen protein. The one-stage fermented by Bv (FSBMB) has the highest soluble peptides, while commercial lactic acid bacteria (FSBML) has the highest Lactic acid bacteria count; these were used to compare the differences in the process. Ross308 broilers (n = 320) were divided into four groups: SBM diet and a diet replaced with 6% FSBMB+L, FSBMB, or FSBML. The growth performance was recorded during the experiment, and six birds (35-day-old) per group were euthanized. Analysis of their jejunum and ileum showed that the fermented soybean meal significantly improved the villus height in the jejunum (p < 0.05) and reduced the crypt hyperplasia. The FSBMB group had the highest reducing crypt depth; however, the FSBMB+L group had the highest villus height/crypt depth in the ileum (p < 0.05). In the jejunum, the relative mRNA of CLDN-1 and Occludin increased 2-fold in the treatments, and ZO-1 mRNA increased 1.5 times in FSBML and FSBMB+L (p < 0.05). Furthermore, the level of NF-κB and IL-6 mRNAs in FSBML increased, respectively, by 4 and 2.5 times. While FSBMB, along with FSBMB+L, had a 1.5-fold increase in the mRNA of IL-10, that of NF-κB increased 2-fold. FSBMB+L and FSBMB singly led to a 2- and 3-fold increase in IL-6 mRNA, respectively (p < 0.05). FSBMB and FSBMB+L can also upregulate MUC2 in the jejunum (p < 0.05). In short, using the soybean peptides from two-stage fermented soybean meal can ameliorate the negative factors of SBM and effectively regulate immune expression and intestinal repair, which will help broilers maintain intestinal integrity.

Effect of You-Gui-Wan on House Dust Mite-Induced Mouse Allergic Asthma via Regulating Amino Acid Metabolic Disorder and Gut Dysbiosis.

Chinese herbal remedies have long been used for enhancing immunity and treating asthma. However, the evidence-based efficacy remains to be supported. This study aimed to explore the potential bio-signatures in allergic asthma and the effect of You-Gui-Wan (YGW), a traditional Chinese herbal prescription, on dust mite-induced mouse allergic asthma. Extract of Dermatophagoides pteronyssinus (Der p), a dust mite, was intratracheally administered to induce allergic asthma in mice. Serum metabolomic and 16S rRNA-based microbiome profiling were used to analyze untargeted metabolites with levels significantly changed and gut microbiota composition, respectively. Results indicated that 10 metabolites (acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine), mainly associated with branched-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism were markedly elevated after Der p treatment. YGW administration reversed the levels for 7 of the 10 identified metabolites, chiefly affecting BCAA metabolism. On 16S DNA sequencing, disordered Der p-induced gut microbiota was significantly alleviated by YGW. Multiple correlation analysis showed a good correlation between gut microbiota composition and levels of selected metabolites. Our study showed YGW administration effectively alleviated BCAA metabolic disorder and improved gut dysbiosis. This study provides support for YGW administration with benefits for allergic asthma.

Off-label reduced-dose apixaban does not reduce hemorrhagic risk in Taiwanese patients with nonvalvular atrial fibrillation: A retrospective, observational study.

ABSTRACT: East Asians are reportedly at high risk of anticoagulant-related bleeding; therefore, some physicians prefer to prescribe low-dose direct oral anticoagulants (DOACs). Little is known about the therapeutic effectiveness and safety of off-label reduced-dose apixaban in East Asians with nonvalvular atrial fibrillation (AF). We aimed to investigate the effectiveness and safety of off-label reduced-dose apixaban in Taiwanese patients with nonvalvular AF.This retrospective cohort study enrolled 1073 patients with nonvalvular AF who took apixaban between July 2014 and October 2018 from 4 medical centers in southern Taiwan. The primary outcomes included thromboembolic events (stroke/transient ischemic attack or systemic embolism), major bleeding, and all-cause mortality.Among all patients, 826 (77%) patients were classified as the "per-label adequate-dose" treatment group (i.e., consistent with the Food and Drug Administration label recommendations) while 247 (23%) patients were the "off-label reduced-dose" treatment group. The mean follow-up period was 17.5 ±â€Š13 months. The "off-label reduced-dose" group did not have a lower major bleeding rate than the "per-label adequate-dose" group (4.8% vs 3.8%, adjusted hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.69-2.09), but had a nonsignificantly higher incidence of thromboembolic events (4.23% vs 3.05%, adjusted HR: 1.29, 95% CI: 0.71-2.34).An off-label reduced-dose apixaban treatment strategy may not provide incremental benefits or safety for Taiwanese patients with nonvalvular AF.

The Herbal Cocktail GSYJ Attenuated Airway Inflammatory Cell Infiltration in a Chronic Asthmatic Mouse Model.

This study explored the potential therapeutic efficacy of GSYJ in attenuating asthma symptom severity and aimed to determine the immunomodulatory mechanism of GSYJ. A mouse model of chronic asthma induced by repeated Dermatophagoides pteronyssinus (Der p) challenge was established. In addition, 30 minutes before Der p challenge, the mice were orally administered GSYJ (1 g/kg). The mice were sacrificed to evaluate inflammatory cell infiltration, collagen deposition in the lung, total IgE in serum, and expression profiles of various cytokines in bronchoalveolar lavage fluid (BALF) and various genes in lung tissue. Furthermore, 30 minutes after the addition of GSYJ to RAW264.7 cell cultures, 100 ng/ml LPS was added to evaluate the effect of the drug on the LPS-induced expression of genes, proteins, and transcription factors. GSYJ may regulate transcription factors (cJUN/IRF3/NF-κB) to decrease the expression of IL-1ß, IL-6, RANTES, and iNOS in macrophages and affect the IL-12, IFN-γ, IL-5, and IL-6 levels in the BALF of mice to relieve asthma symptoms, such as inflammatory cell infiltration, hyperresponsiveness, and increased serum total IgE levels. Therefore, GSYJ has the potential to be developed into a drug treatment for chronic asthma.

Production performances and antioxidant activities of laying hens fed Aspergillus oryzae and phytase co-fermented wheat bran.

OBJECTIVE: Wheat bran (WB) was co-fermented with Aspergillus oryzae and phytase (Phy) to determine whether co-fermentation improve WB phosphorus and fiber utilization in Isa-brown layers. METHODS: A total of 112 Isa brown layer were randomly divided into 7 treatments with 8 replicates per a treatment and 2 hens per a replicate. The treatments included basal diet (control), basal diet supplemented with 250 unit/kg Phy (control+Phy), diet with 10% WB (10% WB), diet with 5% WB and 250 unit/kg Phy (5% WB+Phy) diet with 10% WB and 250 unit/kg Phy (10% WB+Phy), diet with 5% fermented WB supplemented with molasses and phy (PCFWH) and 125 unit/kg Phy (5% PCFWH), and diet with 10% PCFWH (10% PCFWH). The intestinal microbial population, intestinal morphology, serum antioxidant enzyme activities, and excreta phosphorus content were assessed. RESULTS: In PCFWH, spore counts, protease activity, xylanase activity, and ferulic acid were 8.50 log/g dry matter (DM), 190 unit/g DM, 120 unit/g DM, and 127 µg/g, respectively. Xylobiose and xylotriose were released in PCFWH, while they were not detectable in WB. Antioxidant capacity was also enhanced in PCFWH compared to WB. The 10% WB+Phy and 10% PCFWH groups produced higher egg mass, but hens fed 5% WB+Phy had the lowest amount of feed intake. Eggs from 10% PCFWH had better eggshell weight, eggshell strength, and eggshell thickness. Birds fed with 10% PCFWH also had higher serum superoxide dismutase and catalase activities. Compare to control, 10% PCFWH significantly reduced excreta phosphorus content. CONCLUSION: Diet inclusion of 10% PCFWH improved egg quality, antioxidant status, and excreta phosphorus content of laying hens.

Effects of Saccharomyces cerevisiae and phytase co-fermentation of wheat bran on growth, antioxidation, immunity and intestinal morphology in broilers.

OBJECTIVE: The aim of this study was to investigate the effects of different amounts of wheat bran (WB) inclusion and postbiotics form by Saccharomyces cerevisiae and phytase cofermented wheat bran (FWB) on the growth performance and health status of broilers. METHODS: Study randomly allocated a total of 300 male broilers to a control and 4 treatment groups (5% WB, 5% FWB, 10% WB, and 10% FWB inclusion, respectively) with each pen having 20 broilers and 3 pens per treatment. RESULTS: The WB does not contain enzymes, but there are 152.8, 549.2, 289.5, and 147.1 U/g dry matter xylanase, protease, cellulase and ß-glucanase in FWB, respectively. Furthermore, FWB can decrease nitric oxide release of lipopolysaccharide stimulated chicken peripheral blood mononuclear cells by about two times. Results show that 10% FWB inclusion had significantly the highest weight gain (WG) at 1 to 21 d; 5% FWB had the lowest feed conversion rate at 22 to 35 d; 10% WB and 10% FWB inclusion have the highest villus height and Lactobacillus spp. number in caecum; and both 5% and 10% FWB can increase ash content in femurs. Compared to control group, all treatments increase mucin 2, and tight junction (TJ), such as occludin, claudin-1, zonula occludens-1, and mRNA expression in ileum by at least 5 folds. In chicken peripheral blood mononuclear cells, nicotinamide adenine dinucleotide phosphate-oxidase-1 mRNA expression decreases from 2 to 5 times, and glutamate-cysteine ligase catalytic subunit mRNA expression also increases in all treatment groups compared to control group. The mRNA expression of pro-inflammatory cytokines, including interleukin-6 (IL-6), nuclear factor-κB, and IL-1ß, decreases in 5% and 10% FWB groups compared to control group. CONCLUSION: To summarize, both WB and FWB inclusion in broilers diets increase TJ mRNA expression and anti-oxidation and anti-inflammation, but up to 10% FWB groups have better WG in different stages of broiler development.

Laying Diet Supplementation with Ricinus communis L. leaves and Evaluation of Productive Performance and Potential Modulation of Antioxidative Status.

This study evaluated the antioxidant capacity of Ricinus communis L. (RC) leaves and powder when used as a feed additive for laying hens. Results showed that the total phenolic content of the aqueous leaf extract of Ricinus communis L. (RCE) was 48.39 mg gallic acid equivalent (GAE) per gram dry weight (DW). The flavonoid content was 9.76 mg quercetin dihydrate equivalent (QE)/g DW. Ferrous chelating activity was approximately 56.2% with an RCE concentration of 1 mg/mL; the highest chelating activity was 91.2% with 4 mg/mL extract. The reducing power of 1 mg/mL RC was 1.17 times better than 1 mg/mL butylated hydroxytoluene (BHT). The Trolox equivalent antioxidant capacity (TEAC) value of 12.5 mg/mL RCE was equivalent to 3.09 mg/mL Trolox. RCE (10 mg/mL) had a lipid oxidative inhibition capacity of 35.3%. A total of 80 ISA brown laying hens at twenty-nine weeks of age were randomly allocated into the control or 1 of 3 treatment groups; the latter received 0.5%, 1% or 2% of RC, respectively, for 12 weeks. Results showed that the RC supplementation improved the feed conversion rate and 0.5% RC generated the best results. Additionally, the egg yolk score was significantly increased in all RC-supplemented groups. Moreover, there was no significant difference in serum characteristics between the treatment groups. Serum antioxidant enzyme activity showed that superoxide dismutase (SOD) activity increased in the RC-supplemented groups relative to the control but was not significantly different. mRNA expression levels of the antioxidant regulatory genes GCLC, GST, HO-1, SOD1, and SOD2 were significantly increased with 2% RC supplementation. In summary, RC is a suitable feed additive for laying hens and the addition of 0.5% RC leaf powder resulted in the greatest benefits.

Epidemiological analysis of the Kaohsiung city strategy for dengue fever quarantine and epidemic prevention.

BACKGROUND: Dengue is endemic in over 100 countries and is an important public health problem worldwide. Dengue fever is not endemic in Taiwan; the importation of dengue viruses from neighboring countries via close commercial links and air travel is considered to be the cause of local outbreaks. Therefore, efforts toward disease control have focused on preventing the importation of dengue into Taiwan. In this study, we investigated the relationships between the numbers of imported and indigenous dengue cases to test the validity of this strategy. METHODS: Data on cases of dengue fever that occurred between 2013 and 2018 were obtained from the surveillance systems of the Taiwan Center for Disease Control and Kaohsiung City Health Department. Standard epidemiological data, including the monthly numbers of indigenous and imported cases of dengue, were calculated. Potential associations between the numbers of indigenous and imported cases were investigated using correlation analyses. RESULTS: We identified a possible relationship between the period of disease concealment and the number of imported dengue cases, which resulted in epidemics of indigenous dengue fever within local communities. Further analysis of confirmed cases during previous epidemics in Kaohsiung City found that the risk of indigenous dengue fever may be related to the likelihood that patients with imported dengue fever will stay within local communities. CONCLUSION: Given the correlations found between imported and indigenous cases of dengue fever, as well as the relationship between the disease concealment period and the risk of indigenous dengue fever, prevention of disease importation and efficient identification of dengue cases within high-risk communities remain the major priorities for disease control.

DFSG, a novel herbal cocktail with anti-asthma activity, suppressed MUC5AC in A549 cells and alleviated allergic airway hypersensitivity and inflammatory cell infiltration in a chronic asthma mouse model.

AIM OF THE STUDY: To develop a novel anti-asthma drug. DFSG is a novel herbal cocktail composed of 4 types of herbal medicines. This study explored whether DFSG has the potential to attenuate asthma symptom severity and aimed to determine the immunomodulatory mechanism of DFSG using a chronic asthmatic mouse model induced by repeated challenges with Dermatogoides pteronyssinus (Der p). MATERIALS AND METHODS: BALB/c mice were intratracheally inoculated with Der p (50 µl, 1 mg/ml) once a week for 5 weeks. In addition, 30 min before Der p challenge, the mice were orally administered 1x DFSG (1 g/kg) or 1/2x DFSG (0.5 g/kg). Three days after the final challenge, the mice were sacrificed to evaluate inflammatory cell infiltration, lung histological features, blood total IgE, and cytokine levels in pulmonary alveolar lavage fluid. Furthermore, 30 min after the addition of DFSG, caffeic acid, p-coumaric acid or chlorogenic acid to A549 cells, 10 ng/ml IL-1ß was added to evaluate the effect of the drug on mucin 5AC (MUC5AC) gene expression after stimulation of A549 cells by IL-1ß. RESULTS: DFSG significantly reduced Der p-induced airway hyperresponsiveness, bronchial inflammatory cell infiltration, and total IgE and IgG1 serum levels. Furthermore, DFSG significantly inhibited TH2 cytokines and increased the expression of TH1 cytokines. In addition, immunohistochemical staining demonstrated that DFSG inhibited MUC5AC expression in the bronchial epithelial cells. DFSG and a mixture of caffeic acid, p-coumaric acid, and chlorogenic acid inhibited MUC5AC gene expression in A549 cells after stimulation with IL-1ß. CONCLUSION: These results suggest that by regulating TH1 and TH2 cytokines and MUC5AC expression, DFSG exhibits anti-airway inflammatory cell infiltration and anti-hyperresponsiveness activity and inhibits specific immunity in a chronic asthmatic mouse model. Therefore, DFSG has potential for development into a drug for chronic asthma treatment.

Qi-Wei-Du-Qi-Wan and its major constituents exert an anti-asthmatic effect by inhibiting mast cell degranulation.

ETHNOPHARMACOLOGICAL RELEVANCE: In Asia, Qi-Wei-Du-Qi-Wan (QWDQW) is a traditional Chinese medicine that has been used to treat chest tightness, cough, shortness of breath, night sweats, frequent urination and asthma. QWDQW is recorded in Yi Zong Yi Ren Pian (Medical Physician's Compilation), which was written by Yang Cheng Liu during the Qing Dynasty. AIM OF THE STUDY: The traditional Chinese medicine QWDQW is composed of 7 ingredients and has been used in the treatment of asthma in Asia for hundreds of years. However, the mechanism through which QWDQW affects the immune system in the treatment of asthma is not known. Therefore, this study aimed to investigate whether QWDQW alleviates asthmatic symptoms in mice with chronic asthma induced by repeated stimulation with Dermatophagoides pteronyssinus (Der p) and to explore the underlying immune modulatory mechanism. MATERIALS AND METHODS: BALB/c mice were stimulated intratracheally (i.t.) with Der p (40 µl, 2.5 µg/µl) once weekly for 6 weeks. Thirty minutes prior to Der p stimulation, the mice were treated with QWDQW (0.5 g/kg and 0.17 g/kg) orally. Three days after the last stimulation, the mice were sacrificed, and infiltration of inflammatory cells, lung histological characteristics, gene expression of lung and serum total IgE were assessed. In other experiments, RBL-2H3 cells were stimulated with DNP-IgE/DNP-BSA and then treated with QWDQW, quercetin, ß-carotene, luteolin or a mixture of the three chemicals (Mix13) for 30 min, and the effects of the drugs on RBL-2H3 cell degranulation after DNP stimulation were determined. RESULTS: QWDQW significantly reduced Der p-induced airway hyperreactivity (AHR) and decreased total serum IgE and Der p-specific IgE levels. Histopathological examination showed that QWDQW reduced inflammatory cell infiltration and sputum secretion from goblet cells in the lungs. Gene expression analysis indicated that QWDQW reduced overproduction of IL-12、IFN-γ、IL-13、IL-4、RNATES、Eotaxin and MCP-1in lung. Additionally, QWDQW and Mix13 suppressed DNP induced RBL-2H3 degranulation, and the effect was maximal when quercetin, ß-carotene and luteolin were administered together. CONCLUSION: These results indicate that QWDQW plays a role in suppressing excessive airway reaction and in specific immune modulation in a mouse model of chronic asthma and that QWDQW suppresses mast cell degranulation at defined doses of quercetin, ß-carotene and luteolin.

Jin Gui Shen Qi Wan, a traditional Chinese medicine, alleviated allergic airway hypersensitivity and inflammatory cell infiltration in a chronic asthma mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: In Asia, Jin Gui Shen Qi Wan (JGSQW) has been used for hundreds of years to treat asthma. AIM OF THE STUDY: The traditional Chinese medicine JGSQW is composed of Rehmannia glutinosa, Dioscorea opposita, Cornus officinalis, Poria cocos, Paeonia suffruticosa, Alisma orientalis, Aconitum carmichaelii and Cinnamomum cassia. However, the immunological mechanism underlying the effect of JGSQW treatment on asthma remains unclear. This study examined whether JGSQW has the potential to reduce asthma symptoms in mice with chronic asthma induced by recurrent Dermatophagoides pteronyssinus (Der p) stimulation, as well as its immunoregulatory mechanisms. MATERIALS AND METHODS: The airways of BALB/c mice were stimulated with Der p (i.t.) once per week (50 µL, 1 mg/mL) for 6 consecutive weeks, and the mice were fed JGSQW (1 g/kg) 30 min prior to the Der p stimulation. Three days after the last stimulation, the mice were sacrificed to evaluate the airway remodelling, infiltration of inflammatory cells, lung histological features, and total IgE in the blood. Additionally, after A549 cells were treated with JGSQW, loganin, or paeoniflorin for 30 min, 10 ng/mL IL-1ß was added to stimulate the A549 cells to evaluate the effect of the medicine on the ICAM-1 gene expression after IL-1ß stimulation. RESULTS: JGSQW significantly reduced the Der p-induced infiltration of inflammatory cells into airways and decreased the total IgE and Der p-specific IgG1 in serum. Collagen assays and histopathological examinations showed that JGSQW reduced lung airway remodelling. Additionally, an electrophoretic mobility shift assay and immunohistochemical staining verified that JGSQW inhibited the NF-kB expression in airway epithelial cell nuclei. JGSQW, loganin, and paeoniflorin inhibited the ICAM-1 gene expression caused by the IL-1ß stimulation of A549 cells, and loganin and paeoniflorin had the maximum inhibitory effect when mixed according to the combination of doses in JGSQW. CONCLUSION: These results indicated that in the chronic asthma mouse model, JGSQW inhibits the infiltration of inflammatory cells into the airways and airway remodelling and exhibits specific immunoregulatory effects. JGSQW with certain doses of loganin and paeoniflorin inhibited ICAM-1 gene expression in epithelial cells.

Development of Nanoscale Oil Bodies for Targeted Treatment of Lung Cancer.

Lung cancer is the most widespread disease and is frequently associated with a high level of epidermal growth factor receptor (EGFR). This study was thus conducted to provide a proof-of-concept approach for targeted therapy of lung cancer by development of nanoscale oil bodies (NOBs). This was carried out by fusion of anti-EGFR affibody (ZEGFR2) with oleosin (Ole), a structure protein of plant seed oils. The fusion protein (Ole-ZEGFR2) was produced in Escherichia coli. NOBs were spontaneously assembled from plant oil, phospholipids, and Ole-ZEGFR2. Consequently, Ole-ZEGFR2-based NOBs were selectively internalized by EGFR-positive lung cancer cells with an efficiency exceeding 90%. Furthermore, the hydrophobic anticancer drug, camptothecin (CPT), was encapsulated into Ole-ZEGFR2-based NOBs. The administration of the CPT formulation based on NOBs resulted in a strong antitumor activity both in vitro and in vivo.

Analogous corticosteroids, 9A and EK100, derived from solid-state-cultured mycelium of Antrodia camphorata inhibit proinflammatory cytokine expression in macrophages.

Antrodia camphorata mycelium is used in traditional Chinese medicine in Taiwan. The wild-type mycelium is rare and expensive, so a solid-state-cultured mycelium of A. camphorata (SCMAC) has been developed. Previous studies have found SCMAC to have anti-inflammatory effects. However, the immunomodulatory effects of SCMAC and of its active phytosterol compounds EK100 and 9A on asthma remain unknown. In this study, BALB/c mice were repeatedly exposed to Dermatogoides pteronyssinus (Der p) at 1-week intervals and were orally administered crude SCMAC extract before the Der p challenge. The mice were sacrificed 72 h after the last challenge to examine the airway remodeling, inflammation, and expression profiles of cytokines and various genes. Then, 30-µg/mL Der p-stimulated MH-S cells with 9A or EK100 were collected for real-time PCR analysis, and the effects of 9A and EK100 on macrophages were evaluated. The crude extract reduced Der p-induced airway hyperresponsiveness, total serum immunoglobulin E levels, and recruitment of inflammatory cells to the bronchoalveolar lavage fluid through cytokine downregulation and Th1/Th2/Th17 response modulation. Additionally, 9A and EK100 inhibited IL-1ß and IL-6 expression in alveolar macrophages. These results indicate that the pharmacologically active compounds in a crude SCMAC extract exert synergistic effects on multiple targets to relieve asthma symptoms.

Synthetic Consortium of Escherichia coli for n-Butanol Production by Fermentation of the Glucose-Xylose Mixture.

The microbial production of n-butanol using glucose and xylose, the major components of plant biomass, can provide a sustainable and renewable fuel as crude oil replacement. However, Escherichia coli prefers glucose to xylose as programmed by carbohydrate catabolite repression (CCR). In this study, a synthetic consortium consisting of two strains was developed by transforming the CCR-insensitive strain into a glucose-selective strain and a xylose-selective strain. Furthermore, the dual culture was reshaped by distribution of the synthetic pathway of n-butanol into two strains. Consequently, the co-culture system enabled effective co-utilization of both sugars and production of 5.2 g/L n-butanol at 30 h. The result leads to the conversion yield and productivity accounting for 63% of the theoretical yield and 0.17 g L-1 h-1, respectively. Overall, the technology platform as proposed is useful for production of other value-added chemicals, which require complicated pathways for their synthesis by microbial fermentation of a sugar mixture.