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Pharmacological Reviews Sep 2023In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a... (Review)
Review
In 1959, Ivar Sperber contrasted bile formation with that of urine and proposed that water flow into the canalicular conduit is in response to an osmotic, not a hydrostatic, gradient. Early attempts to support the hypothesis using a bile acid, sodium taurocholate, and the hormone secretin to stimulate bile flow led to conflicting data and a moratorium on attempts to further develop the initial proposal. However, current data amplify the initial proposal and indicate both paracellular and transcellular water flow into hepatic ductules and the canalicular conduit in response to an osmotic gradient. Also, the need to further modify the initial proposal became apparent with the recognition that bile acid aggregates (micelles), which form in the canalicular conduit, generate lecithin-cholesterol vesicles that contain water unrelated to an osmotic gradient. As part of this development is the recent introduction of the fluorescent localization after photobleaching technique for direct determination of hepatic duct flow and clarification of the role of biomarkers such as mannitol and polyethylene glycol 900. With the new paradigm, these biomarkers may prove useful for quantifying paracellular and transcellular water flow, respectively. SIGNIFICANCE STATEMENT: It is essential to identify and characterize all the sites for water flow during hepatic bile formation to obtain more precision in evaluating the causes and possible therapeutic approaches to cholestatic syndromes. Updating the Sperber proposal provides a new paradigm that addresses the advances in knowledge that have occurred.
Topics: Humans; Bile; Liver; Bile Acids and Salts; Cholestasis; Water
PubMed: 37532432
DOI: 10.1124/pharmrev.122.000799 -
Natural Product Research 2023β-D-Fructopyranose (1), D-Xylopyranose (2), D-Mannitol (3), and flavonoids including quercetin-3-α-L-arabinofuranoside (4) and quercetin-3-O-glucopyranoside (5) were...
β-D-Fructopyranose (1), D-Xylopyranose (2), D-Mannitol (3), and flavonoids including quercetin-3-α-L-arabinofuranoside (4) and quercetin-3-O-glucopyranoside (5) were isolated from the leaves of for the first time. Isolated compounds were identified using 1 D- (H-NMR, C-NMR) and 2 D- NMR (HMBC, HSQC, COSY) spectroscopic techniques and comparison of the literature data. In our study, a relatively high amount of Quercetin-3-O-glucopyranoside was isolated (4%). As a result, our research showed that leaves of could be a good source of monosaccharides, sugar alcohols and bioactive flavonoid glycosides.
Topics: Quercetin; Rhododendron; Molecular Structure; Flavonoids; Glycosides; Plant Leaves; Magnetic Resonance Spectroscopy
PubMed: 35319328
DOI: 10.1080/14786419.2022.2055015 -
Foods (Basel, Switzerland) Dec 2023This review highlights 's promising possibilities as a proficient mannitol producer and its potential implications for sugar reduction, with a focus on its use in... (Review)
Review
This review highlights 's promising possibilities as a proficient mannitol producer and its potential implications for sugar reduction, with a focus on its use in sourdough-based baked good products. Mannitol, a naturally occurring sugar alcohol, has gained popularity in food items due to its low calorie content and unique beneficial qualities. This study summarizes recent research findings and investigates the metabolic pathways and culture conditions that favor increased mannitol production by . Furthermore, it investigates the several applications of mannitol in baked goods, such as its function in increasing texture, flavor and shelf life while lowering the sugar content. Sourdough-based products provide an attractive niche for mannitol integration, as customer demand for healthier and reduced-sugar options increases.
PubMed: 38201124
DOI: 10.3390/foods13010096 -
Genes Jul 2023Salt and osmotic stress seriously restrict the growth, development, and productivity of horticultural crops in the greenhouse. The papain-like cysteine proteases (PLCPs)...
Salt and osmotic stress seriously restrict the growth, development, and productivity of horticultural crops in the greenhouse. The papain-like cysteine proteases (PLCPs) participate in multi-stress responses in plants. We previously demonstrated that salt and osmotic stress affect cysteine protease 15 of pepper ( L.) (); however, the role of in salt and osmotic stress responses is unknown. Here, the function of in regulating pepper salt and osmotic stress resistance was explored. Pepper plants were subjected to abiotic (sodium chloride, mannitol, salicylic acid, ethrel, methyl jasmonate, etc.) and biotic stress ( inoculation). The was silenced through the virus-induced gene silencing (VIGS) and transiently overexpressed in pepper plants. The full-length fragment is 1568 bp, with an open reading frame of 1032 bp, encoding a 343 amino acid protein. CaCP15 is a senescence-associated gene 12 (SAG12) subfamily member containing two highly conserved domains, Inhibitor 129 and Peptidase_C1. expression was the highest in the stems of pepper plants. The expression was induced by salicylic acid, ethrel, methyl jasmonate, and was infected by inoculation. Furthermore, was upregulated under salt and osmotic stress, and silencing in pepper enhanced salt and mannitol stress resistance. Conversely, transient overexpression of increased the sensitivity to salt and osmotic stress by reducing the antioxidant enzyme activities and negatively regulating the stress-related genes. This study indicates that negatively regulates salt and osmotic stress resistance in pepper via the ROS-scavenging.
Topics: Osmoregulation; Sodium Chloride; Capsicum; Antioxidants; Salicylic Acid; Mannitol
PubMed: 37510313
DOI: 10.3390/genes14071409 -
Indian Journal of Pediatrics Sep 2023To compare the efficacy and safety of two hyperosmolar agents (hypertonic saline vs. mannitol) used for the reduction of elevated intracranial pressure (ICP) in children. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy and safety of two hyperosmolar agents (hypertonic saline vs. mannitol) used for the reduction of elevated intracranial pressure (ICP) in children.
METHODS
A meta-analysis of randomized controlled trials (RCTs) was conducted and GRADE system (Grading of Recommendations, Assessment, Development and Evaluation) of evidence was applied. Relevant databases were searched till 31 May 2022. Primary outcome was mortality rate.
RESULTS
Of 720 citations retrieved, 4 RCTs were included in the meta-analysis (n = 365, male = 61%). Traumatic and non-traumatic cases of elevated ICP were included. There was no significant difference in the mortality rate between the two groups [relative risk (RR), 1.09; (95% confidence interval (CI), 0.74 to 1.6)]. No significant difference was found for any of the secondary outcomes, except serum osmolality (being significantly higher in mannitol group). Adverse events like shock and dehydration were significantly higher in the mannitol group, and hypernatremia in the hypertonic saline group. The evidence generated for primary outcome was of "low certainty", and for secondary outcomes, it varied from "very-low to moderate certainty".
CONCLUSIONS
There is no significant difference between hypertonic saline and mannitol used for the reduction of elevated ICP in children. The evidence generated for primary outcome (mortality rate) was of "low certainty", and for secondary outcomes, it varied from "very-low to moderate certainty". More data from high-quality RCTs are needed to guide any recommendation.
Topics: Child; Humans; Male; Brain Injuries; Databases, Factual; Intracranial Hypertension; Intracranial Pressure; Mannitol; Saline Solution, Hypertonic; Female
PubMed: 37225962
DOI: 10.1007/s12098-023-04532-w -
Thorax Oct 2023Inhaled mannitol provokes bronchoconstriction mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for...
BACKGROUND
Inhaled mannitol provokes bronchoconstriction mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin.
METHODS
Participants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography-mass spectrometry.
RESULTS
Forty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge.
CONCLUSION
Inhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.
Topics: Humans; Middle Aged; Volatile Organic Compounds; Asthma; Bronchial Provocation Tests; Biomarkers; Mannitol; Breath Tests
PubMed: 37495368
DOI: 10.1136/thorax-2022-219708 -
The Journal of Allergy and Clinical... Apr 2024Thymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a type-2 inflammatory response, and is...
BACKGROUND
Thymic stromal lymphopoietin (TSLP) is released from the airway epithelium in response to various environmental triggers, inducing a type-2 inflammatory response, and is associated with airway inflammation, airway hyperresponsiveness (AHR), and exacerbations. TSLP may also induce AHR via a direct effect on airway smooth muscle and mast cells, independently of type-2 inflammation, although association between airway TSLP and AHR across asthma phenotypes has been described sparsely.
OBJECTIVES
This study sought to investigate the association between AHR and levels of TSLP in serum, sputum, and bronchoalveolar lavage in patients with asthma with and without type-2 inflammation.
METHODS
A novel ultrasensitive assay was used to measure levels of TSLP in patients with asthma (serum, n = 182; sputum, n = 81; bronchoalveolar lavage, n = 85) and healthy controls (serum, n = 47). The distribution and association among airway and systemic TSLP, measures of AHR, type-2 inflammation, and severity of disease were assessed.
RESULTS
TSLP in sputum was associated with AHR independently of levels of eosinophils and fractional exhaled nitric oxide (ρ = 0.49, P = .005). Serum TSLP was higher in both eosinophil-high and eosinophil-low asthma compared to healthy controls: geometric mean: 1600 fg/mL (95% CI: 1468-1744 fg/mL) and 1294 fg/mL (95% CI: 1167-1435 fg/mL) versus 846 fg/mL (95% CI: 661-1082 fg/mL), but did not correlate with the level of AHR. Increasing age, male sex, and eosinophils in blood were associated with higher levels of TSLP in serum, whereas lung function, inhaled corticosteroid dose, and symptom score were not.
CONCLUSIONS
The association between TSLP in sputum and AHR to mannitol irrespective of markers of type-2 inflammation further supports a role of TSLP in AHR that is partially independent of eosinophilic inflammation.
Topics: Humans; Male; Asthma; Cytokines; Eosinophilia; Eosinophils; Inflammation; Sputum; Thymic Stromal Lymphopoietin
PubMed: 38081546
DOI: 10.1016/j.jaci.2023.11.915 -
The Journal of Allergy and Clinical... Jul 2023Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the...
BACKGROUND
Airway hyperresponsiveness is a hallmark of asthma across asthma phenotypes. Airway hyperresponsiveness to mannitol specifically relates to mast cell infiltration of the airways, suggesting inhaled corticosteroids to be effective in reducing the response to mannitol, despite low levels of type 2 inflammation.
OBJECTIVE
We sought to investigate the relationship between airway hyperresponsiveness and infiltrating mast cells, and the response to inhaled corticosteroid treatment.
METHODS
In 50 corticosteroid-free patients with airway hyperresponsiveness to mannitol, mucosal cryobiopsies were obtained before and after 6 weeks of daily treatment with 1600 μg of budesonide. Patients were stratified according to baseline fractional exhaled nitric oxide (Feno) with a cutoff of 25 parts per billion.
RESULTS
Airway hyperresponsiveness was comparable at baseline and improved equally with treatment in both patients with Feno-high and Feno-low asthma: doubling dose, 3.98 (95% CI, 2.49-6.38; P < .001) and 3.85 (95% CI, 2.51-5.91; P < .001), respectively. However, phenotypes and distribution of mast cells differed between the 2 groups. In patients with Feno-high asthma, airway hyperresponsiveness correlated with the density of chymase-high mast cells infiltrating the epithelial layer (ρ, -0.42; P = .04), and in those with Feno-low asthma, it correlated with the density in the airway smooth muscle (ρ, -0.51; P = .02). The improvement in airway hyperresponsiveness after inhaled corticosteroid treatment correlated with a reduction in mast cells, as well as in airway thymic stromal lymphopoietin and IL-33.
CONCLUSIONS
Airway hyperresponsiveness to mannitol is related to mast cell infiltration across asthma phenotypes, correlating with epithelial mast cells in patients with Feno-high asthma and with airway smooth muscle mast cells in patients with Feno-low asthma. Treatment with inhaled corticosteroids was effective in reducing airway hyperresponsiveness in both groups.
Topics: Humans; Mast Cells; Nitric Oxide; Asthma; Adrenal Cortex Hormones; Respiratory Hypersensitivity; Mannitol; Phenotype
PubMed: 36907566
DOI: 10.1016/j.jaci.2023.03.001 -
Chinese Medicine Aug 2023Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to...
BACKGROUND
Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications.
METHODS
Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction.
RESULTS
Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin.
CONCLUSIONS
EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.
PubMed: 37568235
DOI: 10.1186/s13020-023-00801-0 -
Plants (Basel, Switzerland) Jan 2024Plant cells are capable of uptaking exogenous organic substances. This inherited trait allows the development of heterotrophic cell cultures in various plants. The most... (Review)
Review
Plant cells are capable of uptaking exogenous organic substances. This inherited trait allows the development of heterotrophic cell cultures in various plants. The most common of them are and . Plant cells are widely used in academic studies and as factories for valuable substance production. The repertoire of compounds supporting the heterotrophic growth of plant cells is limited. The best growth of cultures is ensured by oligosaccharides and their cleavage products. Primarily, these are sucrose, raffinose, glucose and fructose. Other molecules such as glycerol, carbonic acids, starch, and mannitol have the ability to support growth occasionally, or in combination with another substrate. Culture growth is accompanied by processes of specialization, such as elongation growth. This determines the pattern of the carbon budget. Culture ageing is closely linked to substrate depletion, changes in medium composition, and cell physiological rearrangements. A lack of substrate leads to starvation, which results in a decrease in physiological activity and the mobilization of resources, and finally in the loss of viability. The cause of the instability of cultivated cells may be the non-optimal metabolism under cultural conditions or the insufficiency of internal regulation.
PubMed: 38256830
DOI: 10.3390/plants13020277