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Cell Biochemistry and Biophysics Jun 2024Toll-like receptors 3 (TLR3) are innate immune receptors expressed on a wide range of cell types, including glial cells. Inflammatory responses altered by hyperglycemia...
Toll-like receptors 3 (TLR3) are innate immune receptors expressed on a wide range of cell types, including glial cells. Inflammatory responses altered by hyperglycemia highlight the need to explore the molecular underpinnings of these changes in cellular models. Therefore, here we estimated TLR3-mediated response of astrocytes cultured at normal (NG, 5 mM) and high (HG, 22.5 mM) glucose concentrations for 48 h before stimulation with polyinosinic:polycytidylic acid Poly(I:C) (PIC) for 6 h. Seahorse Extracellular Flux Analyzer (Seahorse XFp) was used to estimate the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Although adaptation to HG affected ECAR and OCR, the stimulation of cells with PIC had no effect on ECAR. PIC reduced maximal OCR, but this effect disappeared upon adaptation to HG. PIC-stimulated release of cytokines IL-1β, IL-10 was reduced, and that of IL-6 and iNOS was increased in the HG model. Adaptation to HG reduced PIC-stimulated synthesis of COX-derived oxylipins measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Adaptation to HG did not alter PIC-stimulated p38 activity, ERK mitogen-activated protein kinase, STAT3 and ROS production. Metformin exhibited anti-inflammatory activity, reducing PIC-stimulated synthesis of cytokines and oxylipins. Cell adaptation to high glucose concentration altered the sensitivity of astrocytes to TLR3 receptor activation, and the hypoglycemic drug metformin may exert anti-inflammatory effects under these conditions.
PubMed: 38918312
DOI: 10.1007/s12013-024-01380-z -
BioRxiv : the Preprint Server For... Jun 2024Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. Here, we leveraged a diversity outbred mouse population to map the...
UNLABELLED
Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. Here, we leveraged a diversity outbred mouse population to map the genetic drivers of fresh/stored RBC metabolism and extravascular hemolysis upon storage and transfusion in 350 mice. We identify the ferrireductase Steap3 as a critical regulator of a ferroptosis-like process of lipid peroxidation. Steap3 polymorphisms were associated with RBC iron content, in vitro hemolysis, and in vivo extravascular hemolysis both in mice and 13,091 blood donors from the Recipient Epidemiology and Donor evaluation Study. Using metabolite Quantitative Trait Loci analyses, we identified a network of gene products (FADS1/2, EPHX2 and LPCAT3) - enriched in donors of African descent - associated with oxylipin metabolism in stored human RBCs and related to Steap3 or its transcriptional regulator, the tumor protein TP53. Genetic variants were associated with lower in vivo hemolysis in thousands of single-unit transfusion recipients.
HIGHLIGHTS
Steap3 regulates lipid peroxidation and extravascular hemolysis in 350 diversity outbred miceSteap3 SNPs are linked to RBC iron, hemolysis, vesiculation in 13,091 blood donorsmQTL analyses of oxylipins identified ferroptosis-related gene products FADS1/2, EPHX2, LPCAT3Ferroptosis markers are linked to hemoglobin increments in transfusion recipients.
PubMed: 38915523
DOI: 10.1101/2024.06.11.598512 -
Bioorganic & Medicinal Chemistry Letters Sep 2024We have synthesized 10 analogs of oxylipins, which are nitrogen signaling factors (NSFs) that mediate cell-to-cell communication in the fission yeast Schizosaccharomyces...
We have synthesized 10 analogs of oxylipins, which are nitrogen signaling factors (NSFs) that mediate cell-to-cell communication in the fission yeast Schizosaccharomyces pombe, and evaluated their structure-activity relationships with the aim of developing molecular probes for NSFs. We found that the OH or OAc group at C10 could be replaced with a compact amide (17) or carbamate (19). Introducing an alkyne as a detection tag at C10 led to decreased, though still sufficient, activity. Introducing an alkyne at the C18 position showed a similar trend, suggesting tolerance is relatively low even for compact functional groups such as alkynes. Although introduction of a diazirine moiety as a photoreactive group at the C5 position decreased the activity, we found that introducing diazirine at the C13 position was acceptable, and compound 38 exhibited potent NSF activity. These findings will be helpful in the development of molecular probes for NSFs.
Topics: Structure-Activity Relationship; Schizosaccharomyces; Nitrogen; Oxylipins; Molecular Structure; Signal Transduction
PubMed: 38909706
DOI: 10.1016/j.bmcl.2024.129857 -
BMC Plant Biology Jun 2024Drought stress poses a significant threat to agricultural productivity, especially in areas susceptible to water scarcity. Sunflower (Helianthus annuus L.) is a widely...
Mitigation of drought-induced stress in sunflower (Helianthus annuus L.) via foliar application of Jasmonic acid through the augmentation of growth, physiological, and biochemical attributes.
Drought stress poses a significant threat to agricultural productivity, especially in areas susceptible to water scarcity. Sunflower (Helianthus annuus L.) is a widely cultivated oilseed crop with considerable potential globally. Jasmonic acid, a plant growth regulator, plays a crucial role in alleviating the adverse impacts of drought stress on the morphological, biochemical, and physiological characteristics of crops. Experimental detail includes sunflower varieties (Armani Gold, KQS-HSF-1, Parsun, and ESFH-3391), four drought stress levels (0, 25%, 50%, and 75% drought stress), and three levels (0, 40ppm, 80ppm) of jasmonic acid. The 0% drought stress and 0ppm jasmonic acid were considered as control treatments. The experimental design was a completely randomized design with three replicates. Drought stress significantly reduced the growth in all varieties. However, the exogenous application of jasmonic acid at concentrations of 40ppm and 80ppm enhanced growth parameters, shoot and root length (1.93%, 19%), shoot and root fresh weight (18.5%, 25%), chlorophyll content (36%), photosynthetic rate (22%), transpiration rate (40%), WUE (20%), MDA (6.5%), Phenolics (19%), hydrogen peroxide (7%) proline (28%) and glycine betaine (15-30%) under water-stressed conditions, which was closely linked to the increase in stomatal activity stimulated by jasmonic acid. Furthermore, JA 80 ppm was found to be the most appropriate dose to reduce the effect of water stress in all sunflower varieties. It was concluded that the foliar application of JA has the potential to enhance drought tolerance by improving the morphological, biochemical, and physiological of sunflower.
Topics: Oxylipins; Cyclopentanes; Helianthus; Droughts; Plant Growth Regulators; Stress, Physiological; Plant Leaves; Photosynthesis; Chlorophyll
PubMed: 38907232
DOI: 10.1186/s12870-024-05273-4 -
Molecules (Basel, Switzerland) May 2024This study was aimed at investigating the phytochemical profile and bioactivity of subsp. (Brassicaceae), a species from central-southern Sicily (Italy), where it is...
This study was aimed at investigating the phytochemical profile and bioactivity of subsp. (Brassicaceae), a species from central-southern Sicily (Italy), where it is consumed as a salad. For this purpose, LC-ESI/HRMS analysis of the ethanolic extract was performed, highlighting the occurrence, along with flavonoids, hydroxycinnamic acid derivatives, and oxylipins, of sulfated secondary metabolites, including glucosinolates and various sulfooxy derivatives (e.g., C13 nor-isoprenoids, hydroxyphenyl, and hydroxybenzoic acid derivatives), most of which were never reported before in the Brassicaeae family or in the genus. Following ethnomedicinal information regarding this species used for the treatment of various pathologies such as diabetes and hypercholesterolemia, ethanolic extract was evaluated for its antioxidant potential using different in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), Ferric Reducing Ability Power, and -carotene bleaching tests. The inhibitory activity of carbohydrate-hydrolyzing enzymes (α-amylase and α-glucosidase) and pancreatic lipase was also assessed. In the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid assay, an IC value comparable to the positive control ascorbic acid (2.87 vs. 1.70 μg/mL, respectively) was obtained. The wild-wall rocket salad extract showed a significant α-amylase inhibitory effect. Obtained results indicate that Sicilian wild-wall rocket contains phytochemicals that can prevent hyperglycemia, hyperlipidemia, and obesity.
Topics: Plant Extracts; Antioxidants; Phytochemicals; Sicily; Flavonoids
PubMed: 38893326
DOI: 10.3390/molecules29112450 -
Nutrients May 2024Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The... (Review)
Review
Osteoarthritis (OA) is a degenerative joint disease characterized by the destruction of the articular cartilage, resulting in a pro-inflammatory response. The progression of OA is multifactorial and is influenced by the underlying cause of inflammation, which includes but is not limited to trauma, metabolism, biology, comorbidities, and biomechanics. Although articular cartilage is the main tissue affected in osteoarthritis, the chronic inflammatory environment negatively influences the surrounding synovium, ligaments, and subchondral bone, further limiting their functional abilities and enhancing symptoms of OA. Treatment for osteoarthritis remains inconsistent due to the inability to determine the underlying mechanism of disease onset, severity of symptoms, and complicating comorbidities. In recent years, diet and nutritional supplements have gained interest regarding slowing the disease process, prevention, and treatment of OA. This is due to their anti-inflammatory properties, which result in a positive influence on pain, joint mobility, and cartilage formation. More specifically, omega-3 polyunsaturated fatty acids (PUFA) have demonstrated an influential role in the progression of OA, resulting in the reduction of cartilage destruction, inhibition of pro-inflammatory cytokine cascades, and production of oxylipins that promote anti-inflammatory pathways. The present review is focused on the assessment of evidence explaining the inflammatory processes of osteoarthritis and the influence of omega-3 supplementation to modulate the progression of osteoarthritis.
Topics: Humans; Osteoarthritis; Fatty Acids, Omega-3; Dietary Supplements; Cartilage, Articular; Disease Progression; Inflammation; Anti-Inflammatory Agents; Animals
PubMed: 38892583
DOI: 10.3390/nu16111650 -
International Journal of Molecular... Jun 2024The elongation of the mesocotyl plays an important role in the emergence of maize deep-sowing seeds. This study was designed to explore the function of exogenous...
The elongation of the mesocotyl plays an important role in the emergence of maize deep-sowing seeds. This study was designed to explore the function of exogenous salicylic acid (SA) and 6-benzylaminopurine (6-BA) in the growth of the maize mesocotyl and to examine its regulatory network. The results showed that the addition of 0.25 mmol/L exogenous SA promoted the elongation of maize mesocotyls under both 3 cm and 15 cm deep-sowing conditions. Conversely, the addition of 10 mg/L exogenous 6-BA inhibited the elongation of maize mesocotyls. Interestingly, the combined treatment of exogenous SA-6-BA also inhibited the elongation of maize mesocotyls. The longitudinal elongation of mesocotyl cells was the main reason affecting the elongation of maize mesocotyls. Transcriptome analysis showed that exogenous SA and 6-BA may interact in the hormone signaling regulatory network of mesocotyl elongation. The differential expression of genes related to auxin (IAA), jasmonic acid (JA), brassinosteroid (BR), cytokinin (CTK) and SA signaling pathways may be related to the regulation of exogenous SA and 6-BA on the growth of mesocotyls. In addition, five candidate genes that may regulate the length of mesocotyls were screened by Weighted Gene Co-Expression Network Analysis (WGCNA). These genes may be involved in the growth of maize mesocotyls through auxin-activated signaling pathways, transmembrane transport, methylation and redox processes. The results enhance our understanding of the plant hormone regulation of mesocotyl growth, which will help to further explore and identify the key genes affecting mesocotyl growth in plant hormone signaling regulatory networks.
Topics: Zea mays; Salicylic Acid; Purines; Benzyl Compounds; Gene Expression Regulation, Plant; Plant Growth Regulators; Oxylipins; Cytokinins; Seeds; Gene Expression Profiling; Signal Transduction; Indoleacetic Acids; Cyclopentanes
PubMed: 38892338
DOI: 10.3390/ijms25116150 -
International Journal of Molecular... Jun 2024is a medicinal plant that has important pharmacological value, and the bulbils serve as the primary reproductive organ; however, the mechanisms underlying bulbil...
is a medicinal plant that has important pharmacological value, and the bulbils serve as the primary reproductive organ; however, the mechanisms underlying bulbil initiation remain unclear. Here, we characterized bulbil development via histological, transcriptomic, and targeted metabolomic analyses to unearth the intricate relationship between hormones, genes, and bulbil development. The results show that the bulbils initiate growth from the leaf axillary meristem (AM). In this stage, jasmonic acid (JA), abscisic acid (ABA), isopentenyl adenosine (IPA), and salicylic acid (SA) were highly enriched, while indole-3-acetic acid (IAA), zeatin, methyl jasmonate (MeJA), and 5-dexoxystrigol (5-DS) were notably decreased. Through OPLS-DA analysis, SA has emerged as the most crucial factor in initiating and positively regulating bulbil formation. Furthermore, a strong association between IPA and SA was observed during bulbil initiation. The transcriptional changes in (), (), (), (), (), (), (), (), (S), (), x (), (), (), (O), (), (), (), (), (), (), (), (), (), (), (), (M), (), and S () were highly correlated with hormone concentrations, indicating that bulbil initiation is coordinately controlled by multiple phytohormones. Notably, eight TFs (transcription factors) that regulate AM initiation have been identified as pivotal regulators of bulbil formation. Among these, (), (), (), and (R) have been observed to exhibit elevated expression levels. Conversely, demonstrated contrasting expression patterns. The intricate expression profiles of these TFs are closely associated with the upregulated expression of (), suggesting a intricate regulatory network underlying the complex process of bulbil initiation. This study offers a profound understanding of the bulbil initiation process and could potentially aid in refining molecular breeding techniques specific to .
Topics: Plant Growth Regulators; Gene Expression Regulation, Plant; Pinellia; Transcriptome; Gene Expression Profiling; Cyclopentanes; Oxylipins; Plant Proteins; Acetates; Plant Leaves; Plant Roots
PubMed: 38892337
DOI: 10.3390/ijms25116149 -
International Journal of Molecular... May 2024In wounded leaves, four 13-lipoxygenases (AtLOX2, AtLOX3, AtLOX4, AtLOX6) act in a hierarchical manner to contribute to the jasmonate burst. This leads to defense...
In wounded leaves, four 13-lipoxygenases (AtLOX2, AtLOX3, AtLOX4, AtLOX6) act in a hierarchical manner to contribute to the jasmonate burst. This leads to defense responses with LOX2 playing an important role in plant resistance against caterpillar herb-ivory. In this study, we sought to characterize the impact of AtLOX2 on wound-induced phytohormonal and transcriptional responses to foliar mechanical damage using wildtype (WT) and mutant plants. Compared with WT, the mutant had higher constitutive levels of the phytohormone salicylic acid (SA) and enhanced expression of SA-responsive genes. This suggests that AtLOX2 may be involved in the biosynthesis of jasmonates that are involved in the antagonism of SA biosynthesis. As expected, the jasmonate burst in response to wounding was dampened in plants. Generally, 1 h after wounding, genes linked to jasmonate biosynthesis, jasmonate signaling attenuation and abscisic acid-responsive genes, which are primarily involved in wound sealing and healing, were differentially regulated between WT and mutants. Twelve h after wounding, WT plants showed stronger expression of genes associated with plant protection against insect herbivory. This study highlights the dynamic nature of jasmonate-responsive gene expression and the contribution of AtLOX2 to this pathway and plant resistance against insects.
Topics: Arabidopsis; Gene Expression Regulation, Plant; Arabidopsis Proteins; Lipoxygenase; Oxylipins; Cyclopentanes; Transcriptome; Salicylic Acid; Plant Growth Regulators; Plant Leaves; Mutation; Gene Expression Profiling; Lipoxygenases
PubMed: 38892085
DOI: 10.3390/ijms25115898 -
International Archives of Allergy and... Jun 2024Eosinophils have numerous roles in type 2 inflammation depending on their activation states in the blood and airway or after encounter with inflammatory mediators.... (Review)
Review
BACKGROUND
Eosinophils have numerous roles in type 2 inflammation depending on their activation states in the blood and airway or after encounter with inflammatory mediators. Airway epithelial cells have a sentinel role in the lung and, by instructing eosinophils, likely have a foundational role in asthma pathogenesis.
SUMMARY
In this review, we discuss various topics related to eosinophil-epithelial cell interactions in asthma, including the influence of eosinophils and eosinophil products, e.g., granule proteins, on epithelial cell function, expression, secretion, and plasticity; the effects of epithelial released factors, including oxylipins, cytokines, and other mediators on eosinophils, e.g., on their activation, expression, and survival; possible mechanisms of eosinophil-epithelial cell adhesion; and the role of intra-epithelial eosinophils in asthma.
KEY MESSAGES
We suggest that eosinophils and their products can have both injurious and beneficial effects on airway epithelial cells in asthma and that there are bidirectional interactions and signaling between eosinophils and airway epithelial cells in asthma.
PubMed: 38885626
DOI: 10.1159/000539309