Search Results (1,006)

Rootstocks are widely used in viticulture as an agronomic measure to cope with biotic and abiotic stresses. In winegrapes, the aroma is one of the major factors defining the quality of grape berries and wines. In the present work, the grape aroma and wine aroma of Cabernet Sauvignon (CS) grafted on three rootstocks were investigated to inform the selection of rootstocks to utilize. 1103P, 5A, and SO₄ altered the composition of aromatic volatiles in CS grapes and wines. Among them, 5A and SO₄ had less effect on green leaf volatiles in the berries and wines, while 1103P increased green leaf volatile concentrations, up-regulating VvADH2 expression in both vintages. VvLOXA, VvLOXC, VvHPL1, VvADH1, VvADH2, and VvAAT were co-regulated by vintage and rootstock. Orthogonal partial least squares regression analysis (OPLS-DA) showed that the differential compounds in CS/1103P and CS berries were dominated by green leaf volatiles. Furthermore, the concentrations of 1-hexanol in the CS/1103P wines were significantly higher than in the other treatments in the two vintages. 1103P altered the expression of genes in the LOX-HPL pathway and increased the concentration of grape green leaf volatiles such as 1-hexanol and 1-hexanal, while vine vigor also affected green leaf volatile concentrations, the combination of which altered the aromatic composition of the wine and gave it more green flavors. Full article

Independent studies reported metabolic alterations in connective tissues of hernia patients, especially involving collagen fibers, compared to healthy controls. In the present work, we evaluated plasma concentrations of metalloproteinases (MMPs) and lysyl oxidase (LOX), enzymes involved in collagen metabolism, and peptides produced during collagen biosynthesis (PINP, PIIINP, and PIVNP) as potential biomarkers for the estimation of hernia risk. Zymography and ELISA assays were performed with plasma samples of 51 patients with primary or recurrent inguinal hernia and 42 healthy controls. A reduction in PINP (p = 0.007) and a concomitant increase in PIIINP (p < 0.001) were observed in patients. In controls, PINP levels were inversely related to age, whereas in patients PIIINP levels increased with age. Body mass index (BMI) showed a strong positive correlation with PIIINP plasma levels in controls but not in patients (p < 0.001). Moreover, patients with larger lesions had the lowest PINP/PIIINP ratio (p = 0.003). PIVNP collagen did not differ between controls and hernia patients. Plasma MMP-9 was reduced in patients (p = 0.015), while MMP-2 and LOX were unchanged. However, MMP-2 concentrations appeared lower in patients with familial history of hernia compared to those without. In regression analysis, the PINP/PIIINP ratio was inversely related to hernia risk, and a cut-off value of 0.948 was found by ROC analysis which classified hernia patients with a sensitivity of 82.9% and a specificity of 77.1%. In conclusion, our findings identified the PINP/PIIINP ratio as the most relevant molecular predictor of inguinal hernia risk. Full article

The distinctive nature of ferroptosis is that it is induced chemically and signifies a regulated cell death dependent on iron-dependent lipid peroxidation. The mechanism of ferroptosis involves oxidative damage to the membrane lipids. It differs from apoptosis and necroptosis, triggering metabolic changes in the iron-lipid homeostasis and antioxidant defense, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4). Herein, the molecular mechanisms of ferroptosis and its role in the tumorigenesis process and infection-related diseases are presented. It also discusses metabolic reprogramming as a factor that modifies the levels of cell-sensitizing polyunsaturated fatty acids (PUFAs), iron dysregulation, and oxidative stress in aggressive cancers and inflammatory diseases such as sepsis, tuberculosis, and COVID-19. Particular attention is given to chemical modulators of ferroptosis, including synthetic inducers and inhibitors, as well as bioactive natural compounds. Our focus is on the significance of analytical tools, such as lipidomics and metabolomics, in understanding the phenomenon of ferroptosis. Finally, we explore novel therapeutic approaches targeting ferroptosis in cancer and infectious diseases, while navigating both the opportunities and challenges in drug development. The review then draws on chemical biology and disease pathology to propose promising areas of study for ferroptosis-related therapies. Full article

Caleosin/peroxygenases (CLO/PXGs) play critical functional roles during plant development, oxylipin metabolism, and the response to abiotic/biotic stressors and environmental toxins. In Oryza sativa, peroxygenase-9 (OsPXG9) catabolizes intermediates in oxylipin biosynthesis produced by lipoxygenase-9 (9-LOX) and scavenges HOOH and CuOOH by transferring oxygen to hydroxy fatty acids (HFAs) but not to the free fatty acids. The resulting epoxide derivatives of HFAs are then enzymatically or non-enzymatically hydrolyzed into the corresponding trihydroxy derivatives. Results presented here demonstrate OsPXG9′s specificity for catabolizing products of the 9-LOX (and not for the 13-LOX) pathway of oxylipin biosynthesis. Overexpression of OsPXG9 reduces ROS (reactive oxygen species) abundance and reduces drought- and salt-stress-induced apoptotic cell death. The high expression level of OsPXG9 also stimulates drought- and salt-induced but not basal expression of antioxidant enzymes/pathways in plants, thereby increasing cellular resistance to drought. These results suggest that OsPXG9 decreases ROS abundance and is essential to increase resilience in rice plants exposed to exogenous or endogenous abiotic stress. Full article

Orobanche cumana Wallr. is a root parasitic plant that causes considerable yield losses of up to 50% in sunflower Helianthus annuus plantations. The holoparasite fulfills its entire demand for water, minerals, and organic nutrients from the host’s vascular system. Agronomic practices alone are not effective in controlling this pest. This study investigated the mechanism of a verified plant growth-promoting strain, Streptomyces rochei D74, on the inhibition of the parasitism of O. cumana in a co-culture experiment. We conducted potted and sterile co-culture experiments using sunflower, O. cumana, and S. rochei D74. Our results suggest that the inoculated bacteria invoked the sunflower systemic resistance (SAR and ISR) by increasing the activity of resistance-related enzymes (SOD, POD, PPO, and PAL), the gene expression of systemic resistance marker genes (PR-1 and NPR1), ethylene synthesis genes (HACS. 1 and ACCO1), and JA synthesis genes (pin2 and lox). The expression levels of ISR marker genes (lox, HACS. 1, ACCO1, and pin2) increased by 1.66–7.91-fold in the seedling stage. Simultaneously, S. rochei D74 formed a protective layer on the sunflower root surface, preventing O. cumana from connecting to the vascular system of the sunflower roots. In addition, S. rochei D74 reduced 5DS synthesis of the strigol precursor substance, resulting in a reduction in O. cumana germination. These results demonstrated that the S. rochei D74 strain improved systemic resistance and decreased seed germination to prevent O. cumana parasitism. Full article

Primary dysmenorrhea (PD) is characterized by lower abdominal spasms and painful cramps during menstruation in females with a normal pelvic anatomy. Cymbopogon citratus (DC.) Stapf, commonly known as lemongrass, is consumed in the form of herbal tea around the world. It has been traditionally used for menstrual disorders in several communities. This study aims to evaluate the traditional use of C. citratus for its efficacy in alleviating the symptoms of PD. C. citratus extract (CcE) was chemically characterized using HPLC and GCMS, which indicated the presence of several phenolic compounds and long-chain fatty acids. The anti-inflammatory activity of CcE was assessed by COX-I, COX-II, and 5-LOX enzyme inhibition with IC₅₀ values of 143.7, 91.7, and 61.5 µg/mL, respectively, and showed good total antioxidant capacity and free radical scavenging activity. PD was induced in female Wistar rats by administering estradiol valerate followed by oxytocin to induce PD symptoms. CcE efficacy was assessed at 30, 100, and 300 mg/kg concentrations and compared with ibuprofen. CcE 300 mg/kg reduced abdominal contortions and inflammation in the rat uterus. The inflammatory (COX-II, TNFα and IL-10) and oxidative stress (TAC, TOS, MDA and SOD) markers in uterine tissue homogenate were also improved. An in vivo analgesic assessment through hot-plate, tail-flick, and acetic acid-induced writhing assays showed good analgesic activity by CcE, while ex vivo experiments described tocolytic effects in rat uterine muscles. CcE alleviates PD by its antioxidant, anti-inflammatory, analgesic, and tocolytic effects. Full article

The incidence of Hashimoto’s disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18–55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant (p < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways. Full article

Background/Objectives: Localized provoked vulvodynia (LPV) is characterized by chronic vulvar pain upon light touch to the vestibule, a specialized ring of tissue immediately surrounding the vaginal opening. LPV affects about 14 million people in the US, yet the etiopathology of the disease is unknown. In LPV, the vestibule expresses elevated levels of the pro-nociceptive pro-inflammatory mediators prostaglandin E₂ (PGE2) and interleukin-6 (IL-6), which corresponds to lower pain thresholds. Previous studies have shown reduced amounts of arachidonic acid (AA)-derived pro-resolving lipid mediators in tissue biopsies from LPV patients that might impede the resolution of inflammation. AA is obtained from dietary linoleic acid, pointing to a defect in the metabolism of dietary polyunsaturated fatty acids in LPV. We aimed to further explore the involvement of AA metabolism in LPV, which appears dysregulated in the vestibule of LPV patients and culminates in chronic inflammation and chronic pain. Methods: Vestibular and vulvar tissue biopsies obtained from LPV and non-LPV patients were used to generate fibroblast strains and assessed for COX/LOX expression using qRT-PCR. Fibroblast strains were treated with inflammatory stimuli, and then COX-1 and COX-2 expression was assessed using Western blot analysis. Pro-inflammatory mediator production was assessed using enzyme-linked immunosorbent assays (ELISAs). ALOX5 and ALOX12 expression was assessed using qRT-PCR. Finally, lipidomic analysis was carried out to screen for 143 lipid metabolites following inflammatory challenge. Results: Tissue and fibroblasts from LPV patients exhibited altered expression of COX/LOX enzymes and production of AA-derived lipid mediators compared to non-LPV patients. Conclusions: Lipid profiles of tissue and vestibular fibroblasts from LPV patients differed from non-LPV patients, and this difference was attributed to differential COX/LOX expression and activity, which metabolizes AA derived from dietary linoleic acid. This dysregulation fosters chronic inflammation and reduced resolution capacity in LPV patients, causing chronic pain. While further work is needed, these findings suggest that dietary modifications could impact the LPV mechanism. Full article

Terpenes represent a structurally diverse class of natural compounds with increasing scientific interest due to their potential anti-inflammatory properties. This study investigates the in silico binding behavior of six plant-derived terpenes—α-pinene, β-pinene, menthol, camphor, limonene, and linalool—against four key enzymes in the arachidonic acid (AA) metabolic pathway: cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and phospholipase A2 (PLA₂). AA serves as a reference for binding energy comparison. Blind rigid-body molecular docking is performed using AutoDock 4.2 and the Lamarckian Genetic Algorithm, with 100 runs per ligand–enzyme pair and the energy-based selection of optimal poses. The analysis includes binding energy (ΔG), inhibition constants (Ki), root-mean-square deviation (RMSD), and residue-level interactions. Several terpenes exhibit favorable binding energies and inhibition constants across the evaluated enzymes. For COX-1 and COX-2, menthol and camphor show low Ki values, indicating stable binding. Menthol and limonene also show the strongest affinities for PLA₂, exceeding AA. The focus is on compounds with potential to modulate arachidonic acid metabolism. In this context, β-pinene engages the catalytic site of PLA₂, linalool forms multiple contacts within key regions of 5-LOX, and menthol, α-pinene, and β-pinene align with functionally important regions in both COX isoforms. These targeted interactions suggest that the highlighted compounds may selectively interfere with enzymatic activity in inflammation-related pathways. By modulating key steps in AA metabolism, these terpenes may influence the biosynthesis of pro-inflammatory mediators, offering a promising avenue for the development of safer, plant-derived anti-inflammatory agents. The findings lay the groundwork for further experimental validation and the structure-based optimization of terpene-derived modulators. Full article

This work provides a comprehensive investigation into the synergistic effects of zirconium and oxygen on the microstructural evolution, high-temperature oxidation resistance, and mechanical properties of γ-phase Ti52AlxZr alloys (x = 0, 0.5, 1, and 2 at.%) under systematically controlled oxygen concentrations. Unlike prior studies that have examined these alloying elements in isolation, this study uniquely decouples the contributions of interstitial (oxygen) and substitutional (zirconium) solutes by employing low (LOx) and high (HOx) oxygen levels. Alloys were synthesized via vacuum arc melting and subsequently subjected to homogenization annealing at 1250 °C for 100 h to ensure phase and microstructural stability. Characterization techniques including scanning electron microscopy (SEM), X-ray diffraction (XRD), and electron backscatter diffraction (EBSD) were employed to elucidate phase constitution and grain morphology. Zirconium addition was found to stabilize the γ-TiAl matrix, suppress α₂-phase formation, and promote grain coarsening in LOx specimens. Conversely, elevated oxygen concentrations led to α₂-phase precipitation along grain boundaries. Mechanical testing, comprising Vickers hardness and uniaxial compression at ambient and elevated temperatures (800 °C), revealed that both zirconium and oxygen significantly enhanced strength and hardness, with Ti52Al2Zr delivering optimal mechanical performance. Moreover, zirconium substantially improved oxidation resistance by promoting the formation of a thinner, adherent Al₂O₃ scale while simultaneously inhibiting TiO₂ growth. Collectively, the findings demonstrate the critical role of zirconium in engineering advanced γ-TiAl-based intermetallics with superior high-temperature structural integrity and oxidation resistance. Full article

Consumers are increasingly willing to pay a premium for high-quality extra virgin olive oils (HQ-EVOOs) with specific sensory or nutraceutical properties, and originating from particular botanical or geographical origins. Regarding geographic origin, Italy is one of the main producers, with many local production areas, each characterized by its own distinctive typicity. The aim of this study is the chemical, sensory, and nutraceutical profiling of HQ-EVOO produced over two production years in Montespertoli (province of Florence) by 12 producers involved in the “MontEspertOlio” project, funded by the Tuscan Region. Oils were produced based on a production process previously defined and specifically applied to this territory. The shelf-life of the oil was also evaluated over a 12-month period. Legal quality parameters were analyzed according to EU regulation. Phenolic compounds, tocopherols, fatty acid composition, and volatile compounds were analyzed using HPLC-DAD, HPLC-FLD, HS-SPME-GC-MS, and GC-FID, respectively. Finally, sensory analysis was conducted using the Panel Test method. Results showed that Montespertoli HQ-EVOO is characterized by distinctive sensory and chemical traits that fully match consumer preferences, even across two production years characterized by different growing conditions. The shelf-life performance was excellent over 12 months, also showing a protective effect of greater bottle sizes against oxidation. Full article

Neuroinflammation, triggered by lipoxygenase (LOX), contributes to Alzheimer’s disease (AD) progression. Overexpression of LOX-5 in patients with AD serum highlights its role. This study assessed the efficacy of the LOX-inhibitor-peptide YWCS in an AD rat model induced by Aβ_25–35 injection. Cognitive tests, magnetic resonance imaging (MRI) scans, and molecular analyses were conducted. YWCS treatment significantly improved cognitive function, as evidenced by improved performance in the open field, novel object recognition, elevated plus maze, and Morris water maze tests. MRI scans revealed hippocampal shrinkage in AD rats and no changes were observed from YWCS treatment. Molecular analysis revealed altered expression of LOX-5, LOX-12, Aβ, γ-secretase components, p-Tau¹⁸¹, Akt, p-Akt, and p53 in AD rats. Immunofluorescence staining confirmed increased expression of LOX, Aβ, and p-Tau¹⁸¹ in the hippocampus of AD rats, which was reduced by YWCS treatment. Serum LOX levels were elevated in AD rats and significantly decreased after YWCS treatment, aligning with previous findings in human AD patients and AD cell models. YWCS offered improvements in behavioral and inflammatory marker regulation and also prevented progression of the disease, as shown by MRI results. These results suggest that YWCS, by targeting LOX, has the potential to be a promising therapeutic agent for AD. Full article

The effects of a fungal elicitor from Trichothecium roseum on signal pathways of salicylic acid (SA), jasmonic acid (JA), and Ca²⁺ in potato tubers were investigated. The results showed that fungal elicitor treatment effectively inhibited the lesion diameter of Fusarium sulphureum in vivo, which was 17.5% lower than that of the control. In addition, fungal elicitor treatment triggered an increase in O₂⁻ production and H₂O₂ content. The fungal elicitor enhanced the activities and gene expression levels of isochorismate synthase (ICS), phenylalanine ammonia lyase (PAL), allene oxide cyclase (AOC), allene oxide synthase (AOS), lipoxygenase (LOX), and Ca²⁺-ATPase. Furthermore, the fungal elicitor promoted an increase in calmodulin (CaM) content. Protective enzymes (dismutase (SOD), catalase (CAT), polyphenol oxidase (PPO), chitinase (CHI), and β-1,3-glucanase (Glu)) and disease-resistance-related genes (PR1, PR2, and PDF1.2) were induced to be upregulated by elicitor treatment. These results indicated that the fungal elicitor induced disease resistance by accelerating the accumulation of reactive oxygen species (ROS), activating SA, JA, and Ca²⁺ signaling, and upregulating resistance genes. The results of this study revealed the molecular mechanism of fungal elicitor-induced resistance in the potato, which provides a theoretical basis for the mining of new, safe, and efficient elicitor-sourced antifungal agents and is of great importance for the effective control of potato dry rot disease. Full article

Oxidized low-density lipoprotein (oxLDL) exhibits differential expression in microsatellite-stable (MSS) and microsatellite instability-high (MSI) colorectal cancer (CRC), highlighting its potential therapeutic role in immune checkpoint inhibitor (ICI) resistance in MSS CRC. Elevated oxLDL levels in MSS CRC contribute to tumor progression and diminish ICI efficacy by modulating metabolic reprogramming and immunosuppressive mechanisms within the tumor microenvironment (TME) by activating receptors such as LOX-1 and CD36. oxLDL triggers signaling pathways, including NF-κB, PI3K/Akt, and MAPK, leading to the expansion of immunosuppressive cells like regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and M2 macrophages, while concurrently suppressing effector T cell functions. Additionally, oxLDL enhances oxidative stress and promotes fatty acid oxidation (FAO) and glycolytic metabolism, resulting in nutrient competition within the TME and establishing an immunosuppressive milieu, ultimately culminating in ICI resistance. This review systematically examines the disparities in oxLDL expression between MSS and MSI CRC and elucidates the molecular mechanisms through which oxLDL mediates ICI resistance. Furthermore, it explores potential therapeutic strategies targeting oxLDL, offering novel avenues to overcome immunotherapy resistance in MSS CRC. Full article

Saccharina japonica (S. japonica) is a large-scale intertidal aquatic plant that exhibits characteristics such as rhizoid, holdfast, and blade differentiation. It demonstrates remarkable environmental adaptability. However, compared with higher plants, details about its phytohormone content, distribution, synthesis, and accumulation remain poorly understood. In this study, the phytohormone contents distribution and expression patterns of synthetic genes in different parts of S. japonica, including the rhizoid, petiole, basis, middle, and tip, were analyzed in detail by combining targeted metabolomics and transcriptomics analyses. A total of 20 phytohormones were detected in S. japonica, including auxin, abscisic acid (ABA), cytokinin (CTK), ethylene (ETH), gibberellin (GA), jasmonate acid (JA), and salicylic acid (SA), with significant site-differentiated accumulation. ABA and JA were significantly enriched in the tips (28.01 ng·g⁻¹ FW and 170.67 ng·g⁻¹ FW, respectively), whereas SA accumulated specifically only in the rhizoid. We also identified 12 phytohormones, such as gibberellin A1, methyl jasmonate, and trans-zeatin for the first time in S. japonica. Transcriptomic profiling revealed the tissue-specific expression of phytohormone biosynthesis genes, such as CYP735A (CTK synthesis), in the rhizoids and LOX/NCED (JA/ABA synthesis) in the tips. Key pathways, such as carotenoid biosynthesis and cysteine methionine metabolism, were found to be differentially enriched across tissues, aligning with hormone accumulation patterns. Additionally, an enrichment analysis of differentially expressed genes between various parts indicated that different parts of S. japonica performed distinct functions even though it does not have organ differentiation. This study is the first to uncover the distribution characteristics of phytohormones and their synthetic differences in different parts of S. japonica and elucidates how S. japonica achieves functional specialization through non-specific phytohormone regulation despite lacking organ differentiation, which provides an important theoretical basis for research on the developmental biology of macroalgae and their mechanisms of response to adversity. Full article