Search

Rationale Food Allergy Herbal Formula-2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2. Methods The consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1 mg of berberine or B-FAHF-2 containing an equivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined. Results Berberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the C max of B-FAHF-2 fed mice was 289.30 ± 185.40 ng/mL; whereas berberine alone showed very low bioavailability with C max value of 35.13 ± 47.90 ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%. Conclusions B-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that the anti-asthma traditional Chinese medicine herbal formula ASHMI (anti-asthma simplified herbal medicine intervention) inhibits acetylcholine-induced contractions of tracheal rings from ovalbumin-sensitized and naive mice in a adrenoceptor- independent manner. We sought to determine whether acute in vivo ASHMI administration inhibits airway hyperreactivity (AHR) in a murine model of allergic asthma and acetylcholine-induced tracheal ring constriction ex vivo and to elucidate the cellular mechanisms underlying these effects. Ovalbumin-sensitized mice received a single oral ASHMI dose 2 h before intravenous acetylcholine challenge. AHR was determined by invasive airway measurements. Myography was used to determine the effects of ASHMI on acetylcholine-induced constriction of tracheal rings from asthmatic mice with or without epithelial denudation. The effect of cyclooxygenase inhibition and EP2/EP4 receptor blockade on ASHMI attenuation of acetylcholine contractions was evaluated. Tracheal cAMP and PGE2 levels were measured by ELISA. A single acute oral dose of ASHMI dramatically reduced AHR in response to acetylcholine provocation in ovalbuminsensitized mice (P < 0.001). In ex vivo experiments, ASHMI significantly and dose-dependently reduced tracheal ring constriction to acetylcholine (P < 0.05- 0.001), which was epithelium independent and associated with elevated cAMP levels. This effect was abrogated by cyclooxygenase inhibition or EP2/EP4 receptor blockade. ASHMI also inhibited contraction to high K+ (P < 0.001). ASHMI increased tracheal ring PGE2 release in response to acetylcholine or high K+ (P < 0.05 for both). ASHMI produced direct and acute inhibition of AHR in vivo and blocked acetylcholine-induced tracheal ring constriction via the EP2/EP4 receptor pathway, identifying the mechanism by which ASHMI is an orally active bronchoprotective agent. [ABSTRACT FROM AUTHOR]

The cyclic antibandwidth problem is to embed the vertices of a graph G of n vertices on a cycle C such that the minimum distance (measured in the cycle) of adjacent vertices is maximized. Exact results/conjectures for this problem exist in the literature for some standard graphs, such as paths, cycles, two-dimensional meshes, and tori, but no algorithm has been proposed for the general graphs in the literature reviewed by us so far. In this paper, we propose a memetic algorithm for the cyclic antibandwidth problem (MACAB) that can be applied on arbitrary graphs. An important feature of this algorithm is the use of breadth first search generated level structures of a graph to explore a variety of solutions. A novel greedy heuristic is designed which explores these level structures to label the vertices of the graph. The algorithm achieves the exact cyclic antibandwidth of all the standard graphs with known optimal values. Based on our experiments we conjecture the cyclic antibandwidth of three-dimensional meshes, hypercubes, and double stars. Experiments show that results obtained by MACAB are substantially better than those given by genetic algorithm. [ABSTRACT FROM AUTHOR]

Evaluates the role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone by direct measurement of ET-1 and ET receptor-coupled nitric oxide release and developed isometric tension in thrombin-treated aortic rings. Vascular contraction and reagents; ET receptor desensitization; Synthesis and release of ET-1.

Studies the role of endothelin (ET) receptors in thrombin-induced modulation of vascular tone. Contribution of ET-1 to the increase in nitric oxide production; Significance of ET receptor activation; Thrombin-induced relaxation during pretreatment with endothelin receptor antagonists.

Background: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti‐IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti‐IgE compounds. Objective: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. Methods: Liquid‐liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE‐producing human myeloma U266 cells, peanut‐allergic murine model and PBMCs from food‐allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. Results: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09μg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut‐specific IgE levels, blocked hypothermia and histamine release in a peanut‐allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL‐5, IL‐13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p <.001 and fold‑change ≥1.5), involving 24 gene ontology terms (p <.001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. Conclusion: Arctigenin markedly inhibited IgE production in U266 cells, peanut‐allergic murine model and PBMCs from allergic patients by down‐regulating cell division, cell cycle‐related genes and up‐regulating anti‐inflammatory factors. [ABSTRACT FROM AUTHOR]

Vertex Bisection Minimization problem (VBMP) consists of partitioning a vertex set V of graph G = (V, E) into two sets B and B' where \B\ = ⌊ ∣V∣/2⌋ such that vertex width (VW) is minimized where vertex width is defined as the number of vertices in B which are adjacent to at least one vertex in B'. It is an NP-complete problem in general. VBMP has applications in fault tolerance and is related to the complexity of sending messages to processors in interconnection networks via vertex disjoint paths. In this paper, we have proposed a new integer linear programming (HP) and quadratically constrained quadratic programming (QCQP) formulation for VBMP. Both of them require number of variables and constraints lesser than existing ILPs and QCQP. We have also implemented ILP and obtained optimal results for various classes of graphs. The result of the experiments with the benchmark graphs shows that the proposed model outperforms the state of the art. Moreover, proposed model obtains optimal result for all the benchmark graphs. [ABSTRACT FROM AUTHOR]

Highlights: [•] S. flavescens inhibited acetylcholine-induced murine airway smooth muscle (ASM) contraction. [•] 3′,7-Dihydroxy-4′-methoxy-isoflavone and trifolirhizin were isolated from the methylene chloride extract of S. flavescens. [•] Trifolirhizin inhibited the acetylcholine-induced ASM contraction through a non-β2-adrenoceptor mediated pathway. [Copyright &y& Elsevier]

Background The effect of ageing on several pathologic features of allergic asthma (pulmonary inflammation, eosinophilia, mucus hypersecretion), and their relationship with airway hyperresponsiveness (AHR) is not well characterized. Objective To evaluate lung inflammation, mucus metaplasia and AHR in relationship with age in murine models of allergic asthma comparing young and older mice. Methods Young (6 weeks) and older (6, 12, 18 months) BALB/c mice were sensitized and challenged with ovalbumin (OVA). AHR and bronchoalveolar fluid (BALF), total inflammatory cell count and differential were measured. To evaluate mucus metaplasia, quantitative PCR for the major airway mucin-associated gene, MUC-5AC, from lung tissue was measured, and lung tissue sections stained with periodic acid-Schiff (PAS) for goblet-cell enumeration. Lung tissue cytokine gene expression was determined by quantitative PCR, and systemic cytokine protein levels by ELISA from spleen-cell cultures. Antigen-specific serum IgE was determined by ELISA. Results AHR developed in both aged and young OVA-sensitized/challenged mice (OVA mice), and was more significantly increased in young OVA mice than in aged OVA mice. However, BALF eosinophil numbers were significantly higher, and lung histology showed greater inflammation in aged OVA mice than in young OVA mice. MUC-5AC expression and numbers of PAS+ staining bronchial epithelial cells were significantly increased in the aged OVA mice. All aged OVA mice had increased IL-5 and IFN-γ mRNA expression in the lung and IL-5 and IFN-γ protein levels from spleen cell cultures compared with young OVA mice. OVA-IgE was elevated to a greater extent in aged OVA mice. Conclusions Although pulmonary inflammation and mucus metaplasia after antigen sensitization/challenge occurred to a greater degree in older mice, the increase in AHR was significantly less compared with younger OVA mice. Antigen treatment produced a unique cytokine profile in older mice (elevated IFN-γ and IL-5) compared with young mice (elevated IL-4 and IL-13). Thus, the airway response to inflammation is lessened in ageing animals, and may represent age-associated events leading to different phenotypes in response to antigen provocation. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease, COVID‐19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID‐19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID‐19 and SARS, including antiviral, anti‐allergy and inflammation, hepatoprotection against drug‐ and infection‐induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti‐influenza, anti‐hepatitis C, anti‐cytomegalovirus, and anti‐alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID‐19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS‐CoV and SARS‐CoV‐2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID‐19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein‐protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic‐berberine nanomedicine, named NIT‐X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN‐γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS‐CoV‐2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL‐1α, IL‐8, IL‐6, and CCL‐2 in SARS‐CoV‐2 infected Calu3 cells were significantly suppressed by NIT‐X. By supporting protective immunity while inhibiting pro‐inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID‐19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID‐19 and SARS. [ABSTRACT FROM AUTHOR]