Predictors of airway hyperreactivity in house dust mite allergic patients

Introduction: Airway hyperresponsiveness (AHR) is a cardinal feature of asthma. Asthma is a heterogenous disorder which consists of different phenotypes and endotypes. Mechanisms leading to AHR may differ in different asthma subtypes. Allergy to perennial allergens, including house dust mites (HDM) is a major risk factor for asthma development. The aim of this study was to determine predictors of AHR in a well-characterized population of HDM-allergic patients.Material and methods: In a retrospective analysis 843 patients with HDM-allergic rhinitis with/without asthma were evaluated. The following parameters were included in the analysis: serum concentration of total (t)- and Dermatophagoides pteronyssinus (Dp)-specific IgE, fractional exhaled nitric oxide concentration (FeNO), lung function tests, bronchial challenge with histamine, age sex, and body mass index (BMI). Linear regression analysis was used to determine predictors of AHR.Results: In a simple linear regression analysis baseline lung function results expressed as either forced expiratory volume in 1 s (FEV1) or maximal expiratory flow at 50% of the forced vital capacity (MEF50), FeNO, tIgE, DpIgE, age and BMI affected AHR. A multiple regression analysis demonstrated that in the whole group of HDM-allergic patients the most important, independent predictors of AHR were MEF50, FeNO and DpIgE.Conclusion: Even in a well-characterized asthma phenotype several processes participate in development of AHR. Major, independent predictors of AHR: lung function parameters, FeNO and DpIgE indicate possible targets for therapeutic intervention in a population of HDM-allergic patients

GC-MS analysis of steroids and triterpenoids occurring in leaves and tubers of Tamus edulis Lowe

Tamus edulis Lowe is an endemic perennial plant belonging to Dioscoreaceae family. The plant has long climbing stems, ovate leaves, flowers in spikes, fleshy red berries and long tuberous roots. Young shoots and tuberous roots of T. edulis were used traditionally for nourishment and as a herbal medicine. Leaves and roots analyzed in the present study were collected in the northwest of Madeira island. The GC–MS analysis allowed to detect several steroids in free forms in diethyl ether extracts; and diosgenin with its isomer, yamogenin, in hydrolyzates from methanolic extracts.The obtained results reveal that Tamus edulis has some features common with other Dioscorea species, e.g., the presence of steroidal saponins with diosgenin and yamogenin as aglycones, or the phytosterol composition with predominating sitosterol. However, some other traits, like the relatively high content of free steroids (more than 1 mg/g d.w.) and their profile rich in cholesterol derivatives, can distinguish Tamus edulis from other Dioscorea species studied previously for their steroid and triterpenoid profile.info:eu-repo/semantics/publishedVersio

Imipramine influences body distribution of supplemental zinc which may enhance antidepressant action

Zinc (Zn) was found to enhance the antidepressant efficacy of imipramine (IMI) in human depression and animal tests/models of depression. However, the underlying mechanism for this effect remains unknown. We measured the effect of intragastric (p.o.) combined administration of IMI (60 mg/kg) and Zn (40 mg Zn/kg) in the forced swim test (FST) in mice. The effect of Zn + IMI on serum, brain, and intestinal Zn concentrations; Zn transporter (ZnT, ZIP) protein levels in the intestine and ZnT in the brain; including BDNF (brain-derived neurotrophic factor) and CREB (cAMP response element-binding protein) protein levels in the brain were evaluated. Finally, the effect of IMI on Zn permeability was measured in vitro in colon epithelial Caco-2 cells. The co-administration of IMI and Zn induced antidepressant-like activity in the FST in mice compared to controls and Zn or IMI given alone. This effect correlated with increased BDNF and the ratio of pCREB/CREB protein levels in the prefrontal cortex (PFC) compared to the control group. Zn + IMI co-treatment increased Zn concentrations in the serum and brain compared to the control group. However, in serum, co-administration of IMI and Zn decreased Zn concentration compared to Zn alone treatment. Also, there was a reduction in the Zn-induced enhancement of ZnT1 protein level in the small intestine. Zn + IMI also induced an increase in the ZnT4 protein level in the PFC compared to the control group and normalized the Zn-induced decrease in the ZnT1 protein level in the hippocampus (Hp). The in vitro studies revealed enhanced Zn permeability (observed as the increased transfer of Zn through the intestinal cell membrane) after IMI treatment. Our data indicate that IMI enhances Zn transfer through the intestinal tract and influences the redistribution of Zn between the blood and brain. These mechanisms might explain the enhanced antidepressant efficacy of combined IMI/Zn treatment observed in the FST in mice

Enhancement of Phytosterol and Triterpenoid Production in Plant Hairy Root Cultures—Simultaneous Stimulation or Competition?

Plant in vitro cultures, including hairy roots, can be applied for controlled production of valuable natural products, such as triterpenoids and sterols. These compounds originate from the common precursor squalene. Sterols and triterpenoids distinctly differ in their functions, and the 2,3-oxidosqualene cyclization step is often regarded as a branch point between primary and secondary (more aptly: general and specialized) metabolism. Considering the crucial role of phytosterols as membrane constituents, it has been postulated that unconstrained biosynthesis of triterpenoids can occur when sterol formation is already satisfied, and these compounds are no longer needed for cell growth and division. This hypothesis seems to follow directly the growth-defense trade-off plant dilemma. In this review, we present some examples illustrating the specific interplay between the two divergent pathways for sterol and triterpenoid biosynthesis appearing in root cultures. These studies were significant for revealing the steps of the biosynthetic pathway, understanding the role of particular enzymes, and discovering the possibility of gene regulation. Currently, hairy roots of many plant species can be considered not only as an efficient tool for production of phytochemicals, but also as suitable experimental models for investigations on regulatory mechanisms of plant metabolism

Modulation of Steroid and Triterpenoid Metabolism in Calendula officinalis Plants and Hairy Root Cultures Exposed to Cadmium Stress

The present study investigated the changes in the content of steroids and triterpenoids in C. officinalis hairy root cultures and plants exposed to cadmium stress. The observed effects included the content and composition of analyzed groups of compounds, particularly the proportions among individual sterols (e.g., stigmasterol-to-sitosterol ratio), their ester and glycoside conjugates. The total sterol content increased in roots (by 30%) and hairy root culture (by 44%), whereas it decreased in shoots (by 15%); moreover, these effects were inversely correlated with Cd-induced growth suppression. Metabolic alterations of sterols and their forms seemed to play a greater role in the response to Cd stress in roots than in shoots. The symptoms of the competition between general metabolites (sterols) and specialized metabolites (triterpenoids) were also observed, i.e., the increase of the sterol biosynthesis parallel to the decrease of the triterpenoid content in C. officinalis plant roots and hairy root culture, and the inverse phenomenon in shoots. The similarity of the metabolic modifications observed in the present study on C. officinalis plant roots and hairy roots confirmed the possibility of application of plant in vitro cultures in initial studies for physiological research on plant response to environmental stresses

Distribution of Triterpenoids and Steroids in Developing Rugosa Rose (Rosarugosa Thunb.) Accessory Fruit

Triterpenoids and steroids are considered to be important for the fruit quality and health-promoting properties for the consumers. The aim of the study was the determination of the changes in triterpenoid and steroid biosynthesis and the accumulation in hypanthium and achenes of rugosa rose (Rosa rugosa Thunb.) hip during fruit development and ripening at three different phenological stages (young fruits, fully developed unripe fruits, and matured fruits). Triterpenoids and steroids were also determined in the peel and the pulp of the matured hips. The obtained results indicated that the distribution of the analyzed compounds in different fruit tissues is a selective process. The increased rate of hydroxylation of triterpenoids, the deposition of hydroxylated acids in fruit surface layer, and the continuous biosynthesis of phytosterols in achenes versus its gradual repression in hypanthium accompanied by the accumulation of their biosynthetic intermediates and ketone derivatives seem to be characteristic metabolic features of maturation of rugosa rose accessory fruit. These observations, apart from providing the important data on metabolic modifications occurring in developing fruits, might have a practical application in defining fruit parts, particularly rich in bioactive constituents, to enable the development of novel functional products

Predictors of Airway Hyperreactivity in House Dust Mite Allergic Patients

Introduction: Airway hyperresponsiveness (AHR) is a cardinal feature of asthma. Asthma is a heterogenous disorder which consists of different phenotypes and endotypes. Mechanisms leading to AHR may differ in different asthma subtypes. Allergy to perennial allergens, including house dust mites (HDM) is a major risk factor for asthma development. The aim of this study was to determine predictors of AHR in a well-characterized population of HDM-allergic patients. Material and methods: In a retrospective analysis 843 patients with HDM-allergic rhinitis with/without asthma were evaluated. The following parameters were included in the analysis: serum concentration of total (t)- and Dermatophagoides pteronyssinus (Dp)-specific IgE, fractional exhaled nitric oxide concentration (FeNO), lung function tests, bronchial challenge with histamine, age sex, and body mass index (BMI). Linear regression analysis was used to determine predictors of AHR. Results: In a simple linear regression analysis baseline lung function results expressed as either forced expiratory volume in 1 s (FEV1) or maximal expiratory flow at 50% of the forced vital capacity (MEF50), FeNO, tIgE, DpIgE, age and BMI affected AHR. A multiple regression analysis demonstrated that in the whole group of HDM-allergic patients the most important, independent predictors of AHR were MEF50, FeNO and DpIgE. Conclusions: Even in a well-characterized asthma phenotype several processes participate in development of AHR. Major, independent predictors of AHR: lung function parameters, FeNO and DpIgE indicate possible targets for therapeutic intervention in a population of HDM-allergic patients

The Influence of Exogenous Jasmonic Acid on the Biosynthesis of Steroids and Triterpenoids in Calendula officinalis Plants and Hairy Root Culture

The interplay between steroids and triterpenoids, compounds sharing the same biosynthetic pathway but exerting distinctive functions, is an important part of the defense strategy of plants, and includes metabolic modifications triggered by stress hormones such as jasmonic acid. Two experimental models, Calendula officinalis hairy root cultures and greenhouse cultivated plants (pot plants), were applied for the investigation of the effects of exogenously applied jasmonic acid on the biosynthesis and accumulation of steroids and triterpenoids, characterized by targeted GC-MS (gas chromatography-mass spectroscopy) metabolomic profiling. Jasmonic acid elicitation strongly increased triterpenoid saponin production in hairy root cultures (up to 86-fold) and their release to the medium (up to 533-fold), whereas the effect observed in pot plants was less remarkable (two-fold enhancement of saponin biosynthesis after a single foliar application). In both models, the increase of triterpenoid biosynthesis was coupled with hampering the biomass formation and modifying the sterol content, involving stigmasterol-to-sitosterol ratio, and the proportions between ester and glycoside conjugates. The study revealed that various organs in the same plant can react differently to jasmonic acid elicitation; hairy root cultures are a useful in vitro model to track metabolic changes, and enhanced glycosylation (of both triterpenoids and sterols) seems to be important strategy in plant defense response

Genome-Based Insights into the Production of Carotenoids by Antarctic Bacteria, Planococcus sp. ANT_H30 and Rhodococcus sp. ANT_H53B

Antarctic regions are characterized by low temperatures and strong UV radiation. This harsh environment is inhabited by psychrophilic and psychrotolerant organisms, which have developed several adaptive features. In this study, we analyzed two Antarctic bacterial strains, Planococcus sp. ANT_H30 and Rhodococcus sp. ANT_H53B. The physiological analysis of these strains revealed their potential to produce various biotechnologically valuable secondary metabolites, including surfactants, siderophores, and orange pigments. The genomic characterization of ANT_H30 and ANT_H53B allowed the identification of genes responsible for the production of carotenoids and the in silico reconstruction of the pigment biosynthesis pathways. The complex manual annotation of the bacterial genomes revealed the metabolic potential to degrade a wide variety of compounds, including xenobiotics and waste materials. Carotenoids produced by these bacteria were analyzed chromatographically, and we proved their activity as scavengers of free radicals. The quantity of crude carotenoid extracts produced at two temperatures using various media was also determined. This was a step toward the optimization of carotenoid production by Antarctic bacteria on a larger scale