Search Results (1,410)

Arachidonic acid (ARA) is an indispensable fatty acid for aquatic organisms, playing critical roles in reproductive physiology. This study aimed to evaluate the effects of graded dietary ARA levels on the reproductive performance, tissue fatty acid profiles, plasma sex hormone and prostaglandin concentrations, ovarian molecular responses, and offspring larval quality in female blotched snakehead (Channa maculata). Three experimental diets with ARA levels of 0% (control, C), 1.5% (ARA1.5), and 3.0% (ARA3.0) were formulated and administered to female blotched snakehead for 12 weeks. The results demonstrated that dietary ARA supplementation significantly improved fertilization rate, hatching rate, and larval growth performance, while reducing the larval malformation rate. ARA supplementation enhanced the deposition of ARA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) in both ovaries and muscle tissues. Plasma levels of sex hormones and prostaglandins (PGE2, PGF2α) were significantly elevated with increasing dietary ARA concentrations. Furthermore, qRT-PCR and Western blot results indicated that ARA supplementation upregulated the expression of genes and proteins in the TGF-β/Smad signaling pathway and steroidogenesis-related genes. Metabolomic analysis identified differential metabolites enriched in arachidonic acid metabolism, the VEGF signaling pathway, and glycolysis/gluconeogenesis in ovaries and larvae, with ARA-derived eicosanoids significantly upregulated. Dietary ARA supplementation was associated with improved reproductive performance, accompanied by reproducible molecular alterations in the ovarian TGF-β/Smad signaling pathway, indicating that this cascade represents a plausible underlying regulatory mechanism for this improvement. Full article

The objective of this study is to investigate whether ovarian microvascular endothelial cells (OMECs) from women with polyendocrine metabolic ovarian syndrome (PMOMECs) exhibit altered angiogenic responses compared with cells from healthy oocyte donors (HOMECs). This is a laboratory-based cross-sectional study using HOMECs and PMOMECs obtained from discarded follicular aspirates. Expression of mRNA and protein for VEGF receptors (FLT1, KDR) and PGE2 receptors (PTGER1–4) were assessed using qPCR and immunofluorescence. OMECs were treated in vitro with VEGFA, PGE2, or receptor-selective agonists. Migration was quantified via porous membrane inserts and live cell tracking. Proliferation was measured via BrdU incorporation. FLT1 and KDR mRNA and protein levels were similar between HOMECs and PMOMECs. PTGER2 mRNA was higher and PTGER3 mRNA was lower in PMOMECs. VEGFA and PGE2 significantly stimulated migration and proliferation in HOMECs. In contrast, PMOMECs failed to exhibit increased migration in response to PGE2 or selective PTGER agonists, while VEGFA-induced migration remained comparable to migration of HOMECs. Live cell tracking revealed that PMOMEC migration resulted in decreased overall net distance traveled and reduced directional persistence (less linear movement) compared with HOMECs. These findings demonstrate that ovarian microvascular endothelial cells from women with PMOS display impaired angiogenic responses to PGE2, which may contribute to altered follicle growth and anovulation in PMOS. Full article

M₂-like macrophages contribute to the establishment of immunosuppressive microenvironments through coordinated activation of inflammatory and metabolic programs. Cyclooxygenase-2 (COX2) catalyzes prostaglandin E₂ (PGE₂) production, whereas arginase-1 (ARG1) hydrolyzes L-arginine (ARG) to ornithine (ORN) and urea. However, the ion channel-dependent mechanisms governing these immunometabolic pathways remain poorly defined. Here, we examined the role of the Ca²⁺-activated K⁺ channel K_Ca3.1 in regulating COX2 and ARG1 in THP-1-derived M₂-like macrophages. COX2 and ARG1 were markedly upregulated during M₂-like differentiation, whereas pharmacological activation of K_Ca3.1 with SKA-121 significantly reduced their mRNA and protein expression. K_Ca3.1 activation also decreased PGE₂ production, increased extracellular ARG, and reduced ORN accumulation. Exposure to elevated extracellular K⁺ concentration ([K⁺]_e) further enhanced COX2 and ARG1 expression, increased PGE₂ production, and shifted ARG metabolism toward ORN formation; each of these responses was attenuated by K_Ca3.1 activation. Pharmacological inhibition of ERK or CREB signaling suppressed both COX2 and ARG1 expression, whereas inhibition of JNK, AP-1, NOX2, or NRF2 had limited effects. CREB2 knockdown similarly reduced COX2 and ARG1 under both basal and elevated [K⁺]_e conditions. These findings demonstrate that K_Ca3.1 activation negatively regulates COX2- and ARG1-associated immunometabolic programs in THP-1-derived M₂-like macrophages and suggest a potential role for K_Ca3.1 in modulating macrophage-associated inflammatory and metabolic responses. Full article

This hypothesis originated from the first author’s personal experience in adult neurology, in which selected refractory cranial or postherpetic neuralgias occasionally appeared to improve rapidly after off-label misoprostol. The original records are unavailable; these physician recollections are not efficacy data and serve only as the hypothesis generator. Independent published precedents are limited to small uncontrolled reports in multiple-sclerosis-associated trigeminal neuralgia. A further recollection was that perceived benefit often waned after several weeks at conventional daily exposure, whereas lower or intermittent exposure sometimes appeared to remain useful for longer; this observation is likewise unverifiable and does not define a therapeutic dose. Misoprostol is rapidly converted to misoprostol acid (plasma half-life of 20–40 min). We ask whether a brief, reversible exposure could produce pharmacodynamic persistence, defined here as a reproducible pain-relevant effect that outlasts measurable drug exposure, through EP-receptor trafficking, compartmentalized GPCR signaling, or downstream cellular changes. The model also predicts that the concentration–response relationship may be non-monotonic: increasing or repeated exposure could attenuate or reverse a favorable effect by recruiting opposing EP pathways or adaptive receptor/cellular responses. No direct evidence shows that misoprostol produces such persistence in neural tissue, and PGE2/EP signaling can also be pronociceptive. Receptor-resolved concentration–response and pulse-washout experiments must therefore separately demonstrate receptor signaling, persistent cellular change, altered neuronal excitability, and ultimately blinded analgesic benefit. Neuropathic corneal pain is considered only a secondary mechanistic model. No evidence-based dose can currently be recommended. Full article

Rapid and reliable quality control of honey is crucial for ensuring food safety and preventing food fraud. In this study, novel sensitive and selective molecularly imprinted polymer (MIP) sensors were developed for the direct and sequential determination of L-proline (L-Pro) and 5-hydroxymethyl-2-furfural (HMF). The sensors were fabricated via the electropolymerization of pyrrole (Py) on a pencil graphite electrode (PGE) surface, using L-Pro and HMF as template molecules. The linear working range for L-Pro and HMF using differential pulse voltammetry (DPV) is 10–1600 µM, with limits of detection determined as 5.39 µM and 4.81 µM, respectively. The MIP-PPy/PGEs demonstrated high selectivity against a 25-fold excess of structural analogues (response <25%). The sensors were highly reproducible (RSD 3.20–3.22%, n = 5) and repeatable (RSD 1.97–2.27%, n = 5), maintaining 81.5% stability over 15 days. The developed sensors successfully quantified native L-Pro and HMF levels in six real honey samples, monitoring thermal-stress-induced changes at 70 and 90 °C. Under increasing thermal stress, a consistent inverse relationship was observed, with L-Pro decreasing as HMF increased. The electrochemical results correlated strongly with standard UV and HPLC methods (RSD < 3%), offering a rapid, cost-effective, practical alternative for routine honey quality and authenticity control. Full article

Cancer progression and therapeutic resistance are shaped by reciprocal dynamic interactions between malignant cells and the metabolically altered tumor microenvironment (TME). Tumor-associated hypoxia, glucose and amino acid competition, extracellular acidity, lactate accumulation, adenosine, prostaglandin E2 (PGE2) and other metabolic signals can remodel immune cell function and determine whether inflammation is tumoricidal or tumor-supportive. Although B lymphocytes have traditionally been viewed as antibody-producing cells, tumor-infiltrating B (TIL-B) cells comprise functionally heterogeneous populations that can act as antigen-presenting cells, cytokine and chemokine producers, antibody-secreting cells, cytotoxic effectors, regulatory B cells (Bregs) and organizers of tertiary lymphoid structures (TLSs). Their functional state is strongly influenced by the metabolic and spatial context in which they reside. This review focuses on the intersection of B cell biology and tumor immunometabolism, emphasizing how hypoxia, lactate, nutrient limitation, adenosine, PGE2, kynurenine and B cell-derived γ-aminobutyric acid (GABA) may shape B cell states and their interactions with myeloid and lymphoid cells. We discuss how metabolically conditioned Bregs and immunoglobulin (Ig)A-skewed humoral responses can contribute to immune suppression, whereas metabolically competent antigen-presenting, IgG-biased and TLS-associated B cell responses may support effective anti-tumor immunity. Importantly, the effects are tumor type- and context-dependent: B cell/TLS signatures are associated with favorable outcomes in several breast, lung and other solid tumors, whereas B cell-centered immune landscapes can be suppressed or neutral in pancreatic cancer and IgA-dominated responses may be unfavorable in selected malignancies. We further examine how these states may influence sensitivity or resistance to immune checkpoint blockade, chemotherapy, radiotherapy and cellular therapies. Finally, we highlight B cell metabolic pathways as potential therapeutic entry points and identify priorities for spatial metabolomics and prospective interventional studies. Full article

Successful embryo implantation necessitates formation of a complex and tight connection between a well-developed embryo and highly receptive endometrium. Type I interferon IFN-τ is a pregnancy recognition signal in ruminants that promotes the establishment of endometrial receptivity. However, the mechanisms that underpin this process largely remain unknown. Previous CUT&Tag assays revealed that XBP1s preferentially targets genes in the glycolytic pathway. In this study, we found that IFN-τ significantly inhibited glycolysis and lactate production during peri-implantation. In addition, overexpression of XBP1s reversed the inhibition of glycolysis by IFN-τ and promoted expression of glycolysis rate-limiting enzymes (HK1, PFK-1, and PKM1) and lactate production. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that XBP1s directly binds to the promoter of the ninth step gene of glycolysis, ENO1. Moreover, ENO1 and XBP1s exhibited congruent expression patterns, and both factors also reversed IFN-τ-induced endometrial receptivity and inhibition of glycolysis. In contrast, knockdown of ENO1 enhanced the effects of IFN-τ. Interestingly, lactate also inhibited the establishment of endometrial receptivity and PGES expression. In conclusion, our data suggest that XBP1s negatively regulates endometrial function through the transcriptional regulation of ENO1-promoted lactate production. This study provides key insights into the mechanisms by which XBP1s acts in female reproductive development. Full article

Technology-related trace elements (TTEs), including rare earth elements (REEs), platinum-group elements (PGEs), silver, antimony, bismuth, barium, strontium, vanadium and radionuclide-associated elements, are increasingly relevant to environmental exposure assessment. Children and adolescents are important sentinel populations, and scalp hair offers a non-invasive matrix for multielement analysis. However, a reported hair concentration may combine follicular incorporation, sweat and sebum deposition and external particles, and may also be influenced by collection, washing, cosmetic treatment and analytical contamination. Separately, left-censoring and the statistical treatment of non-detects can materially affect population summaries and comparisons. This critical narrative review integrates paediatric, occupational, environmental and multimatrix evidence through a structured evidence matrix and an element-by-element audit of biomonitoring assessment values. Hair can identify spatial contrasts and source-related patterns, but current evidence generally does not support direct inference of absorbed dose or clinical risk. In long-term occupational REE exposure, urine shows stronger exposure-response performance than blood; paired hair–urine data for thorium discriminate exposed groups without establishing quantitative equivalence; antimony findings vary by exposure setting; and barium biomonitoring equivalents are available for urine and plasma, but not hair. No health-based guidance values validated specifically for paediatric scalp hair were identified for any of the target TTEs. A seven-stage weight-of-evidence framework is proposed, positioning hair as a complementary screening and hypothesis-generating matrix within multimatrix assessment. Full article

Background/Objectives: Guizhi Fuling Capsule (GZFL), a Traditional Chinese Medicine (TCM) formula, is widely used for primary dysmenorrhea and other blood-stasis gynecological disorders. This study aimed to characterize its material basis, elucidate its multi-component, multi-target mechanism against acute primary dysmenorrhea, and establish an integrated pharmacokinetic-pharmacometabolomic-pharmacodynamic (PK-PM-PD) framework for TCM efficacy evaluation. Methods: GZFL constituents and serum metabolites in an oxytocin-/estradiol-induced rat dysmenorrhea model were characterized by UPLC/Q-TOF-MS. Uterine effects of GZFL-containing serum were assessed ex vivo. The active components of GZFL were screened by Chinmedomics, with candidate targets investigated through network pharmacology, transcriptomics, and molecular docking. In total, 23 pharmacodynamic indicators were integrated by principal component analysis into an Efficacy Index (EI). Correlation analysis between pharmacometabolomic and pharmacodynamic data yielded a Metabolite-Efficacy Index (MEI), evaluated across a 21-day time course. Results: Among 197 constituents characterized in GZFL extract, 136 serum-exposed components were detected, with several key metabolites enriched via biotransformation. GZFL-containing serum bidirectionally regulated uterine contractility toward the control level. Integrated analyses revealed 68 candidate therapeutic targets. GZFL suppressed NF-κB/IKKβ signaling, down-regulated COX-2/iNOS, restored the PGF2α/PGE2 balance, and normalized inflammatory cytokines. Eleven efficacy-associated metabolites correlated with pharmacodynamic recovery were revealed and integrated, with MEI achieving the highest predictive performance among five integration strategies (AUC = 0.9) and robustly tracking the full 21-day disease-recovery trajectory. Conclusions: GZFL attenuates dysmenorrhea through coordinated regulation of inflammation, prostaglandin metabolism, and uterine functional homeostasis, rather than through inhibition of a single target. The PK-PM-PD framework, with EI and MEI, offers a reproducible paradigm for evaluating complex TCM therapies. Full article

Symphytum officinale L. is a traditional medicinal plant widely used for wound healing and bone regeneration; however, comparative studies evaluating the biological activities of extracts prepared from different plant organs remain limited. The present study compared the antimicrobial and anti-inflammatory activities of organ-specific S. officinale extracts and investigated their potential molecular mechanisms of bioactivities using molecular docking. Antimicrobial activity was evaluated against six bacterial reference strains by broth serial dilution, whereas anti-inflammatory activity was assessed in a serotonin-induced paw oedema model in rats together with the determination of serum prostaglandin E₂ (PGE₂), tumour necrosis factor-α (TNF-α), and nitrotyrosine levels. Molecular docking was performed against bacterial peptide deformylases, cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX). The 40% ethanolic leaf extract (S-7) and 70% ethanolic flower extract (S-13) exhibited the broadest antimicrobial spectrum, with pronounced activity against S. aureus, E. faecalis, E. coli, and L. monocytogenes. The 70% ethanolic leaf extract (S-8) demonstrated the strongest early anti-exudative activity (47.50%), whereas the 70% ethanolic flower extract (S-13) most effectively reduced PGE₂, TNF-α, and nitrotyrosine levels. Molecular docking suggested that kaempferol-3-O-glucoside may be the principal contributor to antimicrobial activity through interactions with bacterial peptide deformylases, while hyperoside, isoquercitrin, and rosmarinic acid exhibited favourable interactions with COX-2 and 5-LOX, indicating their key role in exerting anti-inflammatory effects. These findings demonstrate pronounced organ-specific pharmacological differences among S. officinale extracts and identify hydroethanolic leaf, flower, and root extracts as promising candidates for further development as multitarget wound-healing phytopharmaceuticals. Full article

Background/Objectives: This study examined whether dexamethasone (Dex) and decanoic acid (DA) exert complementary effects on inflammatory signaling, catabolic gene expression, and peroxisome proliferator-activated receptor gamma (PPARγ) activation in human chondrocytes. Methods: Two donor-specific primary human chondrocyte models, each derived from a single knee donor, were used, in which cells were treated with Dex (≤0.1 µM), DA (≤500 µM), or combinations thereof. Acute Interleukin-1β(IL-1β)-induced PGE₂ release was evaluated in normal donor cells, whereas prolonged transcriptional responses and PPARγ DNA-binding activity were evaluated in OA donor cells. IL-1β-induced prostaglandin E₂ (PGE₂) release was measured by competitive ELISA after 24 h. Glyceraldehyde-3-phosphate dehydrogenase-normalized transcription of Collagen type II alpha 1, Collagen type I alpha 1, Aggrecan, SRY-Box Transcription Factor 9, Runt-Related Transcription Factor 2, and Matrix Metalloproteinase 13 (MMP13) was assessed by qRT-PCR at 7, 10–14, and 20–28 days. In addition, PPARγ DNA-binding activity was measured after 1 week. Interactions were evaluated by Loewe additivity and highest single agent (HSA) analyses. Results: Dex and DA each reduced PGE₂ release, whereas co-treatment increased potency and maximal inhibition, with a Loewe combination index of 0.4 at 1 nM Dex plus 19 µM DA. In the temporal analysis, Dex plus DA showed a positive MMP13 ΔCt difference versus Dex at 10–14 days (2.42 ± 2.14; p = 0.065) and a more consistent difference at 20–28 days (1.11 ± 0.25; p = 0.016). This agreed with fixed-dose HSA findings at 14 and 28 days (ΔHSA ≈ −75 for 0.1 µM Dex plus 100 µM DA versus Dex). Co-treatment was also associated with increased PPARγ activation beyond the HSA reference (ΔHSA ≈ 0.09 for 0.1 µM Dex plus 100–250 µM DA versus Dex). Conclusions: Dex plus DA co-treatment produced complementary effects on acute PGE₂ inhibition, as well as late-onset MMP13 suppression and PPARγ activity in the donor-specific chondrocyte models studied. These hypothesis-generating findings provide an in vitro rationale for future evaluation of this combination as a corticosteroid-sparing strategy. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and ginger contains phenolic constituents with anti-inflammatory potential. This study evaluated the antiarthritic efficacy of ginger ethanolic extract (GE) and explored its potential mechanisms through integrated pharmacological and computational approaches. Methods: GE was prepared by 70% ethanol reflux extraction and administered to adjuvant-induced arthritis (AIA) rats, with methotrexate as a positive control. Body weight; paw swelling; arthritis index; spleen index; and serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured. Chemical profiling was performed by ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Results: GE attenuated paw edema, arthritis index elevation, splenic enlargement, and elevated serum inflammatory mediators in AIA rats. UPLC-Q-TOF-MS/MS annotated 38 constituents, mainly gingerols, shogaols, gingerdiones, gingerdiols, and related phenolic derivatives. Network analysis identified 217 overlapping ginger- and RA-associated targets, with TNF, IL6, and matrix metalloproteinase 9 (MMP9) prioritized among inflammatory and matrix-remodeling nodes. Docking and MD simulations supported stable predicted interactions for 8-gingerol-TNF and 6-gingerol-MMP9. Conclusions: GE showed antiarthritic activity in AIA rats. The integrated chemical, in vivo, and computational data suggest that ginger phenolics may modulate inflammatory mediators and candidate RA-related pathways; however, these mechanisms remain exploratory and require histological, tissue-level, and molecular validation. Full article

Prinsepia utilis Royle seeds are traditionally used in Northwestern Yunnan to relieve skin inflammation and irritation. However, its active constituents and potential molecular mechanisms remain unclear. To investigate the bioactive constituents and anti-inflammatory and skin-soothing effects of P. utilis seed-derived extracts, we characterized their chemical profiles and investigated the potential molecular mechanisms through phytochemical, computational, and complementary biological approaches, as well as in vitro and in vivo tests in this study. The results of this study show that the 75% ethanol eluate (QC04) of P. utilis seeds exhibited the strongest inhibitory effect on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with an IC₅₀ value of 239.21 ± 6.70 μg/mL. Subsequently, untargeted metabolomics identified 1039 metabolites, and 20 representative compounds were selected for downstream analysis. Furthermore, network pharmacology analysis identified AKT1, MAPK1, MAPK8, and MAPK14 as core targets, which are mainly involved in the TNF and MAPK signaling pathways. Molecular docking confirmed favorable binding interactions between representative metabolites and these core proteins; meanwhile, a 100 ns molecular dynamics simulation verified the conformational stability of the euscaphic acid–AKT1 complex. Moreover, in the UVB-induced 3D epidermal model (EpiKutis^®), QC04 treatment reduced IL-6 and PGE₂ secretion and downregulated TNF-α and NF-κB p65 expression. In vivo zebrafish assays further demonstrated that QC04 inhibited copper sulfate-induced neutrophil recruitment and histamine-induced vasodilation. Overall, these findings link the metabolites identified in the activity-enriched QC04 fraction with predicted molecular targets and anti-inflammatory and skin-soothing effects, providing experimental evidence for the biological potential of P. utilis seed-derived preparations and supporting further investigation of QC04 as a potential skin-soothing active fraction. Full article

Nasal polyposis is a multifactorial disorder arising from complex interactions among cellular, molecular, and inflammatory mechanisms. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and other ion channels are essential for epithelial ion transport, mucosal hydration, and barrier integrity in the nasal airway. Prostaglandin E₂ (PGE₂) acts not only as an inflammatory mediator but also as a regulator of ion exchange through CFTR-dependent and CFTR-independent pathways. Ionocytes, specialized epithelial cells that regulate ion balance and fluid secretion in the respiratory tract, are closely associated with CFTR function. Both eosinophilic and non-eosinophilic inflammation may alter ionocyte abundance and function, thereby reducing normal CFTR activity. Chronic rhinosinusitis with nasal polyps (CRSwNP) is also characterized by diminished PGE₂ production. The I³PGE₂ hypothesis proposes that CRSwNP results from the combined effects of ion channel dysfunction, persistent inflammation, altered ionocyte number and function, and impaired PGE₂ synthesis. Together, these abnormalities disrupt nasal physiology and promote polyp formation. We hypothesize that corticosteroids and biologic therapies may improve CRSwNP by reducing inflammation, restoring ion channel activity, improving ionocyte function, and recovering PGE₂ production. These effects enhance hydration and mucociliary clearance, limit mucus accumulation, restore epithelial homeostasis and mucosal host defense, and ultimately contribute to the reduction or resolution of nasal polyps. Full article

PFCP-2-1 (polysaccharide-2-1 of Finger Citron-pickled products), a water-soluble polysaccharide enriched in galacturonic acid, was isolated from Laoxianghuang by hot water extraction and purified using DEAE-52 and agarose CL-6B chromatography. Structural analysis showed that PFCP-2-1 had a smooth surface, flakes of varying sizes and shapes, irregular ellipsoidal structures, and cylindrical-like forms, which likely represent aggregated assemblies formed by the association and curling of polysaccharide chains. It was determined to have an average molecular weight of 749.38 kDa and to consist of rhamnose, galactose, glucose, and galacturonic acid (molar ratio 0.147:0.238:0.059:0.556). FT-IR spectroscopy revealed both α- and β-pyranose configurations, while methylation and NMR analyses identified 16 types of glycosidic linkages, of which 9 were the main types, consistent with a pectic-type structure. In an ethanol-induced acute gastric ulcer mouse model, PFCP-2-1 exhibited significant mucosal protection by elevating prostaglandin E2 (PGE2), transforming growth factor-α (TGF-α), and mucin 5AC (MUC5AC) levels and upregulating Occludin and zonula occludens-1 (ZO-1) expression. It also modulated the gut microbiota by increasing the abundance of Bacteroides and Prevotella_UCG-001, and enhanced short-chain fatty acid (acetate and butyrate) levels. These findings suggest that PFCP-2-1 may exhibit a protective effect against ethanol-induced gastric damage under the conditions of this experiment, suggesting its potential for further development as a functional food ingredient. Full article