Search Results (1,332)

Alterations in sphingolipids (SLs), oxylipins (OLs) and cytokines (CKs) are central to neuroinflammation. However, the effects of low doses Fumonisins B (FBs) on these analytes in the avian brain remain unclear.This study investigated SLs, OLs, CKs, and the activities of phospholipase A2c (PLA2c) and cyclooxygenase 2 (COX2) in the brains of chickens exposed to FB at a nominally safe dose of 14.6 mg FB1 + FB2/kg for 14 and 21 days. Targeted LC-MS/MS analyses revealed that FB exposure increased brain concentrations of sphingosine, N-acetyl-sphingosine, sphingosine 1-phosphate (So1P), ceramides (Cers), and sphingomyelins (SM). The Cer:SM ratio was elevated at 14 days but normalized by 21 days, whereas the So1P:Cer ratio rose at 14 days and continued to increase at 21 days. These changes coincided with elevated PLA2c and COX2 activities. OL profiling indicated a modest rise in pro-inflammatory arachidonic acid-derived COX metabolites at 14 days, while anti-inflammatory OLs derived from COX and lipoxygenase (LOX) pathways, including PGE2, 15-HETE, and 17-HDHA, increased significantly at 21 days. In contrast, the levels of CKs changed only slightly. Brain concentrations of Fumonisin B1 (FB1) indicated increased blood–brain barrier permeability.These findings highlight a key role of Cers in modulating OL production in FB neurotoxicity. Full article

The invasive brown macroalga Rugulopteryx okamurae has rapidly expanded across the Mediterranean–Atlantic region, generating severe ecological impacts. Nevertheless, the considerable amount of biomass available creates opportunities for valorisation within circular bioeconomy frameworks. This study provides an integrated characterization of the chemical profile and bioactivities of freshly collected floating biomass of R. okamurae from southern Portugal. Proximate composition was determined, and lipophilic (hexane) and hydrophilic (water) extracts were analyzed by GC–MS and spectrophotometric methods. Antioxidant activity was assessed using complementary radical-scavenging, reducing power, and metal-chelation assays, and enzyme inhibition was evaluated against targets associated with neurodegenerative, metabolic, and dermatological disorders. The lipophilic fraction was dominated by long-chain alkanes (≈101 mg/g extract) and sterols, particularly fucosterol (≈43 mg/g extract), but exhibited low radical-scavenging capacity (no EC₅₀ reached in DPPH or ABTS assays), and no relevant enzyme inhibition. In contrast, the water extract contained measurable phlorotannins (6.61 mg PGE/g extract) and showed moderate antioxidant (ABTS: EC₅₀ = 5.17 mg/mL; FRAP: EC₅₀ = 0.78 mg/mL) and enzyme inhibition activities (BChE: IC₅₀ = 5.17 mg/mL; tyrosinase: IC₅₀ = 0.78 mg/mL). Compared with previous studies on R. okamurae, this work applies a systematic fractionation of biomass from southern Portugal into polar and non-polar fractions and, for the first time, correlates the resulting detailed chemical profiles with multiple bioactivities. This approach revealed a clear functional differentiation between fractions, with bioactivity being mainly associated with polar metabolites. Overall, these findings highlight the value of structured extraction strategies for biomass valorisation and support the sustainable management of R. okamurae. Full article

To address the issues of suboptimal recovery performance, low timeliness, and poor economic efficiency associated with traditional fault recovery methods following large-scale power outages in active distribution networks (ADNs) caused by extreme weather, this paper proposes a dynamic fault recovery strategy for ADNs based on a two-layer hybrid algorithm under extreme ice and snow conditions. First, a line fault rate model considering the thermal effect of current under extreme ice and snow conditions is constructed, and an information entropy-based typical scenario screening method is introduced to filter the fault scenarios. Second, a photovoltaic (PV) output model and a time-varying load model under the influence of extreme ice and snow conditions are established. Subsequently, a multi-objective dynamic fault recovery model is formulated, incorporating island partitioning and integration constraints based on the concept of single-commodity flow, alongside tightened relaxation constraints. To achieve an accurate and rapid solution for the fault recovery model, a two-layer hybrid algorithm is proposed. This algorithm combines an outer-layer improved binary grey wolf optimizer (IBGWO) and an inner-layer second-order cone relaxation (SOCR) algorithm to solve the discrete and continuous decision variables within the model, respectively. Finally, the effectiveness and superiority of the proposed method are verified using the PG&E 69-bus and IEEE 123-bus systems. Full article

Prostaglandin E₂ (PGE₂) plays a critical role in regulating uterine endometrial function and supporting embryonic development during early pregnancy in ruminants. However, its precise roles in shaping the uterine microenvironment remain unclear. Herein, 1 mg PGE₂ was infused daily into the uterus of dairy heifers from days 12 to 14 of the estrus cycle. ULF was subsequently collected for integrated proteomic, metabolomic, and targeted lipidomic analyses. In addition, bovine endometrial epithelial cells were used to evaluate the effects of PGE₂ on epithelial adhesion and responsiveness to interferon tau (IFNT). PGE₂ infusion resulted in 909 differentially abundant proteins (DAPs), which are primarily associated with early embryonic development, immune regulation, and cell adhesion. Untargeted metabolomics analysis identified 587 altered metabolites, which were enriched in sphingolipid, arachidonic acid, phenylalanine, and tryptophan metabolism. Proteomic–metabolomic analyses showed that these alterations were primarily associated with early embryonic development, immune regulation, and cell adhesion. Targeted lipidomic analysis showed a global reduction in lipid accumulation, with glycerophospholipid metabolism and choline metabolism most significantly affected. In vitro, PGE₂ reduced epithelial microvilli density, increased osteopontin (OPN) expression, and decreased the expression of junctional proteins (zona occludens-1 (ZO-1), E-cadherin (CDH1), and fibronectin 1 (FN1)). Moreover, PGE₂ enhanced the responsiveness of bEECs to IFNT by interferon alpha/beta receptor 1 (IFNAR1) and IFNAR2, and prostaglandin E receptor 4 (PTGER4) was identified as the primary receptor mediating this response. Collectively, these findings suggest that PGE₂ may modulate lipid metabolism and adhesion-related processes in the endometrium and influence endometrial responsiveness to IFNT, providing insights into molecular mechanisms associated with pregnancy establishment in dairy cows. Full article

Background: Oral Lichen Planus (OLP) is a chronic inflammatory, autoimmune disorder affecting the skin and mucosa classified within the broad group of Oral Potentially Malignant Disorders (OPMDs). Topical treatment is usually effective in resolving the oral inflammation associated with the process, and the possible relationship to a systemic immunological reaction has not been widely discussed. The aim of this study was to explore the relationship between local and systemic inflammatory signatures in OLP by identifying potential markers in salivary and serum samples, as well as the topical treatment used to relieve inflammation. Methods: The study design was a cross-sectional case–control hospital-based study. A total of 50 blood samples, comprising 31 patients with OLP (study group) and 19 individuals without OLP status (control group), were tested for HLA-B27 in this study. Salivary and serum levels of Prostaglandin E2 (PGE2), matrix metalloprotease 8 (MMP-8), and human IL-1 beta (IL-1β) were measured within and between the control and OLP groups. Results: Salivary IL-1β levels were significantly higher in the OLP group than in controls (p = 0.001; W = 101.5). Serum MMP-8 concentrations were significantly lower in patients with OLP. Serum PGE2 levels were elevated in the OLP group; however, the difference was only borderline statistically significant after correction. HLA-B27 allele frequency in the study and control groups was compared with that in the Polish population. Using Fisher’s Exact Test for Count Data, p-value = 0.1404, no statistically significant differences were found between the control and study groups. Conclusions: These findings could suggest that inflammatory activity in OLP might be predominantly localized to the oral cavity rather than systemic. Elevated salivary IL-1β and reduced systemic MMP-8 levels could support the concept of local immune dysregulation; moreover, salivary IL-1β may serve as a potential non-invasive biomarker for the diagnosis and monitoring of OLP. Studies involving a larger number of subjects should be conducted to strengthen the provided conclusion. Full article

Background: Herpes simplex virus (HSV), Epstein–Barr virus (EBV), and cytomegalovirus (CMV) establish lifelong latency in sensory neurons, lymphoid tissue, and myeloid–endothelial cells, respectively. A substantial proportion of adults worldwide are infected with all three viruses and may experience concurrent herpesvirus latency, yet they have largely been studied independently. This review examined whether latent and intermittently reactivating herpesviruses share overlapping inflammatory signatures and whether their combined presence contributes to chronic inflammatory burden. Methods: A narrative integrative review was conducted using MEDLINE, Embase, and Google Scholar (inception–October 2025). Evidence from thirty-one cohort studies and mechanistic investigations spanning virology, immunology, neurology, and clinical medicine was synthesized. Results: Herpesvirus reactivation rates ranged from 23% in general Intensive Care Unit (ICU) populations to 85% in severe COVID-19. Concurrent reactivation of multiple viruses occurred in 34–63% of critically ill patients and was associated with worse clinical outcomes. Notably, simultaneous CMV and EBV reactivation independently predicted mortality (adjusted hazard ratio, 3.17; 95% CI, 1.41–7.13). Across infections, overlapping inflammatory biomarkers, including IL-6, TNF-α, CRP, and PGE₂, were consistently elevated, reflecting convergent activation of IFN and NF-κB signaling pathways. Mechanistic studies suggest cross-compartment immune priming, where CMV-driven T-cell exhaustion facilitates EBV reactivation, and viral cytokine signaling enhances HSV-associated neuroinflammation. Conclusions: HSV, EBV, and CMV triple latency may represent an underrecognized contributor to chronic inflammation in immunocompetent hosts. Understanding this multi-virus inflammatory network may inform mechanistic research, biomarker-guided risk stratification, and therapeutic strategies targeting convergent inflammatory pathways. Prospective interventional studies incorporating concurrent multi-virus monitoring are needed to clarify causal relationships. Full article

Osteosarcoma is a highly aggressive canine bone tumor characterized by early metastasis and resistance to chemotherapy. Vasculogenic mimicry (VM), the ability of tumor cells to form microvascular channels independent of endothelial cells, can contribute to tumor progression and poor prognosis. In this in vitro study, we evaluated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on the canine osteosarcoma cell line D17. Celecoxib treatment significantly inhibited cell proliferation in a dose- and time-dependent manner, induced S-phase cell cycle arrest, and promoted apoptosis. Furthermore, celecoxib effectively disrupted VM formation on Matrigel. Transcriptome analysis revealed that celecoxib downregulated genes associated with angiogenesis and the COX pathway, notably PTGS2. Consistent with this, celecoxib treatment reduced the secretion of prostaglandin E2 (PGE2) in a dose-dependent manner. Crucially, the addition of exogenous PGE2 restored VM formation in celecoxib-treated cells, confirming that celecoxib-mediated VM suppression is dependent on the reduction of PGE2 levels. These findings establish the COX-2/PGE2 signaling axis as a key regulator of VM in D17 canine osteosarcoma cells and that celecoxib warrants further preclinical evaluation as a strategy to target both tumor growth and alternative vascularization. Full article

Platinum group elements (PGE) are six rare highly siderophile metals which have similar chemical characteristics and occur together in mineral deposits: platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru), iridium (Ir) and osmium (Os). In nature, they tend to exist in a metallic state or bond with sulfur and arsenic and occur as trace accessory minerals predominantly in mafic and ultramafic rocks. High industrial demand together with their scarcity in crustal rocks has been reflected in their inclusion in 2025 US Government’s List of Critical Minerals, European Union’s List of Critical Raw Materials and Mongolian List of 11 Critical Minerals. Although Mongolia is not currently a producer, it hosts four types of potentially economic PGE deposits: (1) Podiform chromitites associated with ophiolites; (2) Ni-Cu-PGE sulfide mineralization of rift-related mafic–ultramafic intrusions; (3) Alaskan–Uralian type arc related zoned mafic–ultramafic intrusions; and (4) Placers. Particularly promising are Permian Ni-Cu-PGE sulfide bearing mafic–ultramafic intrusions of the Khangai large igneous province which bear resemblance to mineralized Permian intrusions in Russia (e.g., Norilsk-Talnakh) and N.W. China (e.g., Kalatongke; Tarim basin). In addition, sub-economic ophiolite-hosted PGE mineralization can be extracted as a by-product during chromite mining. There is also the potential for PGE recovery as a by-product in existing gold placer operations in areas hosting ophiolitic massifs and Alaskan–Uralian type intrusions. Mongolia is a promising frontier for PGE exploration and mining. Full article

Type 2 Diabetes Mellitus (T2DM) is a widespread metabolic disorder that can affect brain health, primarily through the damaging effects of prolonged hyperglycemia. This condition increases oxidative stress (OS), neuroinflammation, and neuroapoptosis, ultimately impairing cognitive function. Acrylamide (ACY), a neurotoxicant formed during high-temperature food processing and present in cigarette smoke, may further aggravate these neurological disturbances. The present experiment examined the exacerbating effects of T2DM and ACY exposure on cognitive function, neurodegeneration, OS, neuroinflammation, and neuroapoptosis in diabetic rats. T2DM was induced via intraperitoneal injections of nicotinamide and streptozotocin, followed by daily oral doses of ACY for a month. Behavioral assessments (EPM, NOR, and Y-maze) evaluated cognitive performance. Brain tissues were analyzed for biochemical markers of neurodegeneration (GSK-3β, AChE, BACE1), OS (MDA, GSH, Catalase), neuroinflammation (NF-κB, TNF-α, PGE2, COX-2), and neuroapoptosis (Bcl-2, Bax, Caspase-3). Immunohistochemistry of Bcl-2, Bcl-6, CD138, and NF assessed structural brain changes. Results indicated that T2DM and ACY exposure significantly increased the incidence of neurological disturbances. Notably, through increased COX-2, PGE2, MDA, Bax, Bcl-6, Caspase-3, and cognitive decline deficits. This study highlights the harmful neurotoxic amplification of T2DM and ACY exposure, emphasizing the importance of public health measures to reduce ACY exposure through dietary and lifestyle changes, particularly among T2DM populations. Further research into neuroprotective strategies and underlying mechanisms is necessary. Full article

Background/Objectives: Macrophages polarized into M1 and M2 phenotypes differentially regulate immune and drug responses. Despite their distinct functional roles, differences in UDP-glucuronosyltransferase (UGT) expression and enzymatic activity between M1 and M2 macrophages remain poorly understood. This study aimed to characterize differential UGT expression in M1 and M2 macrophages and to elucidate how UGT-mediated prostaglandin E₂ (PGE₂) glucuronidation modulates macrophage inflammatory responses. Methods: THP-1 cells were chemically differentiated into macrophages (M0) and subsequently polarized into M1 and M2 phenotypes. UGT expression profiles were assessed using RT-PCR, quantitative RT-PCR (qRT-PCR), and Western blot. UGT activity was compared by quantifying glucuronide metabolites derived from UGT-specific substrates using LC-MS/MS, along with measurement of free PGE₂ and PGE₂-glucuronide by ELISA. Pro-inflammatory cytokine expression and secretion in M1 macrophages were quantified using qRT-PCR and ELISA. Results: Expression of UGT1A1, UGT1A4, UGT1A5, UGT1A9, and UGT2B7 were markedly higher in M1 compared with M2 macrophages at both the mRNA and protein levels. Enhanced UGT activity in M1 macrophages was reflected by increased formation of estradiol-3-glucuronide and naloxone-3-glucuronide (both p < 0.01) and was attenuated in a concentration-dependent manner by diclofenac. Furthermore, PGE₂ glucuronidation was more pronounced in M1 macrophages, and inhibition of UGTs with atazanavir reduced PGE₂-glucuronide formation and pro-inflammatory cytokine production, including IL-1β, IL-6, and TNF-α. Conclusion: UGT-mediated PGE₂ glucuronidation in M1 macrophages contributes to the regulation of pro-inflammatory cytokine production. Collectively, these findings support a role for UGTs as modulators of inflammatory signaling, with differential expression and activity between M1 and M2 macrophages. Full article

Marek’s disease (MD), caused by the oncogenic Marek’s disease virus (MDV), is a highly contagious avian infection that induces lymphoproliferative tumors. The RNA-binding protein ELAVL1 is known to regulate tumor cell proliferation and apoptosis, but its role in MDV-induced oncogenesis remains unclear. This study investigated whether ELAVL1 modulates proliferation and apoptosis in the MDV-transformed MSB1 cell line and whether its effects involve the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway. MSB1 cells were transiently transfected with ELAVL1-overexpressing plasmids (pEGFP-C-ELAVL1) or ELAVL1-specific siRNA, with expression confirmed by real-time PCR (qRT-PCR). Cell proliferation was assessed using the CCK-8 assay, while cell cycle distribution and apoptosis rates were analyzed by flow cytometry. COX-2 and PGE2 expression levels were determined by qRT-PCR, Western blotting, and ELISA. Overexpression of ELAVL1 significantly promoted the proliferation of MSB1 cells, decreased transition into the G1 phase, increased the proportions of S and G2 phase cells, and suppressed apoptosis. Correspondingly, both mRNA and protein levels of COX-2 and PGE2 were significantly elevated. Conversely, ELAVL1 knockdown significantly inhibited proliferation, induced G1 phase arrest, decreased S phase cells, and significantly decreased COX-2 and PGE2 expression. These findings indicate that ELAVL1 promotes proliferation and inhibits apoptosis in MDV-transformed MSB1 cells, potentially via the COX-2/PGE2 signaling pathway. Full article

This study evaluated the anti-inflammation and anti-photoaging effects of Camellia sinensis seed flavonoids (CSF) against UVB and UVA irradiation and elucidated the underlying mechanisms. Using UVB-irradiated human keratinocytes and UVA-irradiated human dermal fibroblasts, we found that CSF significantly reduced intracellular ROS and suppressed the secretion of inflammatory factors (PGE-2, TNF-α, IL-6, IL-8) by inhibiting the p38/JNK and NF-κB pathways, along with iNOS and COX-2 expression. In keratinocytes, CSF also downregulated Caspase-3 and upregulated barrier proteins filaggrin and Claudin-1. In fibroblasts, CSF counteracted UVA damage by upregulating collagen IV and XVII at the dermo-epidermal junction and enhancing the production of collagen I, III, and hyaluronic acid in the dermis, mediated via AP-1 inhibition and TGF-β/Smad pathway modulation. These results demonstrate that CSF coordinated anti-inflammatory, barrier-repair, and anti-photoaging actions, highlighting its potential as a promising skincare ingredient. Full article

Thin, stratiform ore bodies pose persistent challenges for conventional underground mining due to limited thickness, high ore-grade dilution, and restricted operating space. This study introduces a morphology-based scoring framework for assessing the suitability of ore deposits for the Narrow Reef Mining Equipment method—an ultra-low-profile mechanized technique designed for stoping width up to 1.7 m and inclination up to 22°. A dataset comprising 178 ore deposits/mines was evaluated using integrated geological, morphological, and economic criteria. The results demonstrate that NRE suitability is primarily controlled by ore morphology, which is governed by the genetic model. The highest compatibility is associated with stratiform mineralization formed in layered mafic–ultramafic intrusions (e.g., Bushveld Complex, Great Dyke) and sediment-hosted stratiform copper and gold deposits developed along laterally extensive depositional or redox-controlled interfaces (e.g., Kupferschiefer, Witwatersrand). Although genetic origin defines deposit-scale suitability, secondary geological disturbances—post-genetic tectonism and hydrothermal overprinting—restrict NRE applicability to individual ore bodies within otherwise favourable deposits. By formalizing ore body dip and thickness into standardized efficiency and suitability classes, the proposed scoring system provides a reproducible early-stage geological screening methodology for evaluating NRE applicability during initial mine project development. Economic evaluation based on data from the Unki Mine provides operational validation of the proposed scoring framework and demonstrates that NRE increases monthly output at reduced stoping widths while maintaining ore grades and improving operational safety compared to conventional methods. Full article

Background/Objectives: Perfluorooctane sulfonic acid (PFOS), a persistent industrial chemical, has been associated with impairments in cognition. While several studies have attempted to identify the underlying mechanisms, the precise pathways mediating these cognitive deficits remain incompletely understood. PFOS induces cell death in basal forebrain cholinergic neurons (BFCNs), a population critically involved in maintaining cognitive function, partially through the disruption of thyroid hormone signaling. These neurotoxic effects could be mediated through multiple interconnected pathways, including the generation of oxidative stress, dysregulation of prostaglandin E2 (PGE2) signaling, and disruption of nerve growth factor (NGF) homeostasis, all of which have been independently linked to BFCN degeneration and cognitive dysfunction and reported to be induced after PFOS exposure. Methods: To systematically evaluate PFOS-induced neurodegeneration in BFCNs, we employed the SN56 cholinergic cell line derived from the basal forebrain. Cells were exposed to PFOS across a concentration range (0.1–40 μM) in combination with various pharmacological agents: triiodothyronine (T3; 15 nM), recombinant NGF (20 μM), MF-63 (1 μM), and N-acetylcysteine (1 mM). Results: Our experimental results show that PFOS exposure (both single 1-day and repeated 14-day treatments) triggers oxidative stress through reactive oxygen species accumulation coupled with diminished NRF2 pathway activity. Furthermore, PFOS disrupts both PGE2 signaling and the NGF/TrkA/P75^NTR neurotrophic pathways, ultimately leading to BFCN cell death. These neurotoxic effects appear to be partially mitigated through T3 treatment, among other mechanisms. Conclusions: These findings provide valuable mechanistic insights into PFOS-induced BFCN neurodegeneration and the consequent cognitive decline while simultaneously suggesting potential therapeutic strategies to counteract these detrimental effects. Full article

Objectives: This study is intended to reveal whether the boost in immune function in immunocompromised mice from niacin supplementation is connected to the upkeep of intestinal homeostasis and the modulation of the hydroxycarboxylic acid receptor 2 (HCAR2)/NOD-like receptor protein 3 (NLRP3) and prostaglandin endoperoxide synthase 2 (PTGS2)/prostaglandin E2 (PGE2) signaling pathways. Methods: Balb/c mice were employed in this study as a model for immunosuppression caused by cyclophosphamide (CTX) injection. Results: The study showed that niacin supplementation restored spleen and liver indices, enhanced cytokine secretion, and increased Th1/Th2 cytokine levels. Niacin effectively enhanced the phagocytic index, natural killer cell (NK cell) activity, splenic lymphocyte activity and delayed-type hypersensitivity (DTH) reaction in immunocompromised mice. Histopathological examination showed that niacin intervention alleviated injury in mice ilea. Intestinal barrier tight junction proteins were expressed at much higher levels, while the serum concentrations of diamine oxidase (DAO) and fatty acid-binding protein 2 (FABP2) were markedly lowered. Furthermore, the expression of the intestinal HCAR2/NLRP3 signaling pathway and subsequent inflammatory mediators was significantly elevated after niacin administration compared with the CTX group. Niacin supplementation improved the composition of the gut microbiota, increasing the Firmicutes/Bacteroidetes (F/B) ratio. Spearman correlation analysis showed significant correlations between cytokine-related indices and several gut microbiotas. Within a network pharmacology framework including target screening, network construction and molecular docking, PTGS2 emerged as a candidate target of niacin, suggesting its role in counteracting immunosuppression. Further experimental findings showed that niacin markedly decreased the protein expression of PTGS2 and the levels of its downstream mediators PGE2, E-prostanoid receptor type 2 (EP2) and (E-prostanoid receptor type 4 (EP4) in the ileal tissue of mice treated with CTX. Conclusions: In conclusion, niacin supplementation alleviated CTX-induced immunosuppression by maintaining intestinal homeostasis and regulating the intestinal HCAR2/NLRP3 and PTGS2/PGE2/EP2-EP4 pathways. Full article