Sex-specific alterations of niacin flush pathway biomarkers in schizophrenia.

Autism spectrum disorder (ASD) arises from interactions between genetic predisposition and prenatal environmental insults. Prostaglandin E2 (PGE2), derived from cyclooxygenase-2 (COX-2), regulates neuronal differentiation and glia-neuron signaling; thus, its inhibition during gestation may impair neurodevelopment. To examine whether prenatal exposure to indomethacin, a non-selective COX inhibitor, induces autism-like alterations in rats with possible sex differences. Sixteen pregnant Wistar rats received indomethacin (1mg/kg, gavage) on Gestational Days 10-14. Adult offspring (P50-P54) underwent behavioral tests (open-field, rearing, rotarod, and three-chamber sociability). Hippocampal and cerebellar tissues were analyzed for PGE2, LC3B (ELISA), MDA (TBARS), neuronal density, and GFAP expression (CA1, CA3 - Nissl, GFAP staining). Indomethacin reduced sociability, exploration, and motor performance, especially in males, and decreased PGE2 and LC3B while increasing MDA (p < 0.001). Histologically, CA1 neuronal counts increased while GFAP immunoreactivity was markedly elevated in hippocampal (CA1 and CA3) and cerebellar regions (p < 0.05), reflecting astroglial activation and neuroinflammatory remodeling. Prenatal inhibition of prostaglandin synthesis may disturb PGE2 signaling, leading to oxidative stress, altered autophagy-related signaling, and glial activation, which together contribute to ASD-relevant behavioral outcomes.

Adiponectin modulates endometrial prostaglandin production during early pregnancy in pigs: An in vitro study.

Comparative evaluation of anti-inflammatory and cytotoxic activities in relation to lichen acid profiles in Xanthoparmelia verruculifera, X. delisei, and X. loxodes.

The dichotomous function of eicosanoid signaling in the pathogenesis and therapeutic management of lung cancer.

Equine asthma (EA) is a chronic inflammatory disease of the lower respiratory tract in horses, which is mainly triggered by dusty hay. EA is becoming increasingly acknowledged as a valuable animal model for studying human asthma. Research on the pathogenesis of EA has primarily focused on the associated cells and cytokines involved. However, the role of inflammation-related lipid mediators (LM) in the development and progression of equine asthma remains elusive. LMs are categorized into pro-inflammatory arachidonic acid (AA)-derived leukotrienes (LTs) and prostaglandins (PGs), as well as inflammation-resolving LMs derived from omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In this study, targeted liquid chromatography-tandem mass spectrometry-based metabololipidomics was employed to analyze LM profiles from serum and stimulated whole blood samples collected from 30 healthy horses and from 30 horses with EA. We found that the levels of free fatty acids, as well as their metabolomes, vary substantially among individual horses in serum. In this regard, we observed no significant differences between healthy horses and those with EA, highlighting the complexity of the pathogenesis of respiratory disease in horses. In detail, we detected 12-hydroxyeicosatetraenoic acid (HETE) as the most abundant LM in serum and stimulated whole blood. Furthermore, we found that the levels of LMs decrease with increasing age of the horses. Conclusively, this study presents the comprehensive assessment of LM profiles in serum and stimulated whole blood from horses, which can serve as scientific basis for transferring findings from equine to human asthma.

Tolfenamic acid (TA) is a non-steroidal anti-inflammatory drug that is commonly used in veterinary medicine. However, information on its pharmacokinetics in calves, particularly following subcutaneous (SC) administration, is limited. The aim of this study was to characterize the disposition of TA in calves following SC, intramuscular (IM) and intravenous (IV) administration. Six calves received TA at a dose of 4mg/kg via each route in a crossover design. TA exhibited route-dependent pharmacokinetics. The terminal elimination half-life increased significantly from IV (6.64h) to IM (12.79h) and SC (15.11h) administration, which is consistent with flip-flop kinetics following extravascular dosing. Following IV administration, the volume of distribution at steady state was moderate (0.67 L/kg), which suggests extensive plasma protein binding. The time to reach the maximum concentration was similar for the IM and SC routes. However, systemic exposure was markedly lower following SC administration, with peak plasma concentration, area under the curve and bioavailability being approximately half of those observed following IM injection. Plasma concentrations exceeded the EC50 values required to inhibit prostaglandin E2 and related inflammatory mediators for up to 24 h after IV administration and up to 48 h after IM or SC administration. These findings demonstrate that SC administration of TA in calves results in prolonged but reduced systemic exposure compared with IM administration. The results support the need for route-specific dosing considerations and provide a basis for further studies on residue depletion and determination of withdrawal period in food-producing calves.

Metabolic profiling of Piper regnellii (Piperaceae) and its dual anti-inflammatory and anti-urolithiatic effects.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, and immune checkpoint inhibitors have become central to systemic treatment for advanced disease. However, durable responses are limited to a subset of patients, indicating the need to clarify tumor-intrinsic mechanisms that shape immune resistance. Nuclear factor erythroid 2-related factor 2 (NRF2), encoded by Nuclear Factor Erythroid 2-Related Factor 2 Like 2 (NFE2L2), is a stress-responsive transcription factor that regulates antioxidant defense, detoxification, metabolism, and redox adaptation. Although transient NRF2 activation protects hepatocytes from oxidative injury, persistent activation in HCC may promote tumor survival, immune escape, and resistance to therapy. Emerging evidence links NRF2 activity to two biologically connected processes: suppression of ferroptosis and remodeling of the tumor immune microenvironment. Through downstream targets involved in glutathione synthesis, cystine transport, iron handling, and lipid peroxide detoxification, NRF2 can reduce ferroptotic vulnerability. In parallel, NRF2-associated inflammatory and immune-regulatory pathways, including the Cyclooxygenase-2 - Prostaglandin E2 (COX2-PGE2) axis, may contribute to immune-cold phenotypes and impaired response to immune checkpoint blockade. This review summarizes current evidence on NRF2/KEAP1 signaling in HCC, with emphasis on its role in immune escape, ferroptosis suppression, and its potential implications as a biomarker and therapeutic target for understanding and potentially improving immune checkpoint inhibitor responsiveness. We also discuss the potential of NRF2-related biomarkers and therapeutic strategies, while emphasizing the challenges of selectively targeting NRF2 in patients with underlying liver dysfunction.

BackgroundAcetylsalicylic acid (aspirin) is a widely used medication with antipyretic, anti-inflammatory, and antiplatelet effects. It also exhibits antitumor properties by enhancing immune responses, downregulating proinflammatory cytokines, and interfering with platelet-tumor cell interactions that promote metastatic dissemination. Identifying effective, safe interventions for brain metastases (BMs) remains a major clinical challenge.ObjectivesThis narrative review synthesizes mechanistic, preclinical, clinical, and safety evidence on aspirin's potential role in preventing or modulating brain metastasis and proposes possible preventive and adjuvant strategies for future investigation.DiscussionThe development of BMs involves tumor-derived factors, extracellular vesicles, and recruited host cells that remodel the brain microenvironment into a premetastatic niche. Platelet activation and the COX-1/TXA2 axis promote platelet-tumor cell aggregates, immune evasion, and endothelial adhesion-key steps in metastatic seeding. Aspirin may inhibit these processes by (1) irreversibly blocking platelet COX-1 (reducing TXA2 and aggregation), (2) lowering prostaglandin E2 (PGE2)-mediated immunosuppression, and (3) preserving blood-brain barrier (BBB) integrity. Preclinical and retrospective clinical studies provide supportive but heterogeneous evidence across cancer types. Combination strategies-aspirin with radiotherapy, antioxidants (e.g., ascorbic acid), or immunotherapy-are biologically plausible and supported by limited data. Major safety concerns remain, particularly bleeding risk and intracranial hemorrhage in patients with intracranial disease.ConclusionAspirin is a low-cost, biologically plausible adjunct for metastasis prevention. However, direct evidence in brain-metastasis settings is limited. Prospective trials with mechanistic biomarkers and careful safety monitoring are required to determine optimal dosing, timing, patient selection, and combination strategies.

The widespread use of electronic cigarettes is due to the variety of appealing flavor additives marketed to consumers. Although perceived as a less harmful alternative to traditional smoking, emerging evidence suggests that inhaled e-cigarettes aerosol poses multiple risks on oral health. Oral fibroblasts which maintain the extracellular matrix and support wound repair, may be vulnerable to chemical injury. While the toxic effects of base e-liquid components such as nicotine have been investigated, limited research has addressed how added flavoring chemicals influence oral fibroblast survival and stress responses. A comprehensive search was conducted across PubMed, ScienceDirect, and Google Scholar to identify peer-reviewed studies evaluating the biological impact of flavored e-cigarette exposure on human oral fibroblasts. Collective findings revealed consistent mechanistic trends: flavoring chemicals, especially aromatic aldehydes such as cinnamaldehyde and vanillin, induced adverse cellular responses, increasing intracellular reactive oxygen species, and triggering oxidative modifications. These oxidative injuries such as protein carbonylation promote pro-inflammatory responses in oral fibroblasts, specifically heightened secretion of cytokine interleukin-8 and lipid mediator prostaglandin E2, which contribute to tissue breakdown. Increased apoptosis, impaired cell survival, and senescence were reported following longer exposure durations. In contrast, menthol and fruit flavors produced moderate responses, while unflavored aerosols showed little toxicity. These results emphasize that flavored e-cigarette products may accelerate oral tissue deterioration, undermining fibroblast health, and limiting the capacity for tissue repair. As flavored aerosol use remains prevalent among the youth, understanding its toxicity is crucial to advancing public health policies and the regulation of vaping products.

Cyclooxygenase-2 (COX-2) is a key player in inflammation; it is often over-activated in HNSCC, which consequently increases the levels of prostaglandin E2 (PGE2) (an inflammatory mediator) leading to tumor proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), immune evasion, metastasis, and therapy resistance. In this review, we describe the available molecular regulation and biological function of COX-2 in HNSCC with respect to its interactions with various signaling mediators (EGFR, NF-κB, PI3K/Akt, etc.) involved in chronic inflammation. We also summarize preclinical and clinical studies examining selective COX-2 inhibitors, combinations of COX-2 inhibitors with anti-EGFR agents/chemoradiation, and potential approaches for immune modulation/ferroptosis sensitization. Although high levels of COX-2 expression have been associated with a poor prognosis and unfavorable clinicopathological characteristics; the current evidence base cannot agree on this due to the data being very heterogeneous and based largely on small or early phase studies. Pathway redundancy, biomarker differences, and potential for cardiovascular toxicity are challenges for the clinical application of targeted therapy against COX-2. In this review, we review COX-2 as a leading therapeutic target for HNSCC with an emphasis on the transition from molecular pathology to clinical application. We prioritize the discussion on (i) established clinical evidence and prognostic value, (ii) robust preclinical data supporting therapeutic combinations, and (iii) emerging strategies such as ferroptosis-sensitization and immune-modulatory approaches.

Fabrication of Spanlastics as a potential transdermal delivery of lornoxicam for efficient management of osteoarthritis and side effect mitigation: Formula optimization, in vitro characterization, ex vivo, and in vivo assessments.

To investigate the mechanism of electroacupuncture (EA) at sensitized "Sanyinjiao" (SP6) in improving primary dysmenorrhea (PDM), with a focus on the role of Piezo1 protein in EA effects. Sixty female rats were randomly divided into a blank group (n=10) and a model establishment group (n=50). Mechanical pain thresholds at the left SP6 acupoint were measured using a von Frey electronic algometer. According to the change rate of mechanical pain threshold, the model establishment group was further divided into model high-sensitization group, model low-sensitization group, EA high-sensitization group, and EA low-sensitization group (n=10 each). The PDM rat model was established by combined injection of estradiol benzoate and oxytocin. The two EA groups received EA at SP6 (50 Hz, dense wave, 20 min/d) for 5 consecutive days.Writhing responses were recorded to evaluate abdominal pain severity;uterine blood flow was observed by laser speckle imaging;uterine histopathology was examined by HE staining;mast cell degranulation rate at the SP6 region was detected by toluidine blue staining;ultrastructural changes of uterine tissue were observed by transmission electron microscopy;levels of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) in serum and uterine homogenate, and serum tumor necrosis factor-α (TNF-α) were measured by ELISA;protein expressions of Piezo1, calcitonin gene-related peptide (CGRP), and Tryptase in the SP6 region, as well as Piezo1 in the uterus, were detected by Western blot;immunofluorescence was used to detect CGRP and Tryptase expressions at SP6;RT-qPCR was performed to measure mRNA expressions of Piezo1 and cyclooxygenase-2 (COX-2) in the uterus. Compared with the blank group, the model high-sensitization and model low-sensitization groups showed increased writhing times, writhing scores and writhing latencies (P<0.01), decreased uterine blood perfusion (P<0.01), elevated uterine pathological scores (P<0.01), and increased mast cell degranulation rate (P<0.01). Serum and uterine PGF2α contents, serum TNF-α content and PGF2α/PGE2 ratio were significantly increased (P<0.01), while serum and uterine PGE2 contents were significantly decreased (P<0.01). Protein expressions of Piezo1, CGRP, Tryptase, and positive expressions of CGRP and Tryptase at the acupoint, mRNA and protein expressions of Piezo1, and COX-2 mRNA in the uterus were up-regulated (P<0.01), accompanied by ultrastructural damage in uterine tissue. Compared with the corresponding model groups, the writhing latencies were increased further, and the other indicators mentioned above were significantly reversed in the two EA groups (P<0.01, P<0.05). Moreover, the EA high-sensitization group exhibited more obvious improvements than the EA low-sensitization group (P<0.01). EA at SP6 with different sensitization states effectively alleviates pain in PDM rats, with a better effect in the high-sensitization state. The mechanism is dependent on acupoint sensitization, which may involve regulating Piezo1 expression at the acupoint, inhibiting mast cell degranulation and neurogenic inflammation, and down-regulating the Piezo1/COX-2/PGs pathway in the uterus to reduce inflammatory factor release, thereby producing analgesic effects.

Targeted use of Prostaglandin E1 Therapy in "Duct-dependent" Congenital Diaphragmatic Hernia.

Due to delayed symptoms and dependence of behavioral assessment, early diagnosis of autism spectrum disorder remains challenging. Identification of multivariate biomarker for the etiological mechanisms of ASD may enhance diagnostic accuracy. Multivariable logistic regression combines many predictors into a single risk score (linear predictor), resulting in an optimised ROC curve that enhances diagnostic accuracy over individual markers. The method comprises modelling a binary result, determining the likelihood, and visualising ROC based on the projected probabilities, which often improves individual marker AUCs. In the present study a diagnostic performance for a biomarker panel reflecting glutamatergic dysfunction, oxidative stress, and neuroinflammation was evaluated. Plasma levels of glutaminase, 8-isoprostane, and prostaglandin E₂ (PGE₂) obtained from 44 children with ASD and 40 age-matched controls were evaluated using receiver operating characteristic (ROC) analysis, both individually and in combined ROC models. Glutaminase showed significant negative correlations with both 8-isoprostane and PGE₂, whereas a positive correlation was observed between 8-isoprostane and PGE₂. All the three-biomarker showed good diagnostic performance for ASD on its own with statistically significant (p = 0.001) values of AUC of 0.830 for glutaminase, AUC of 0.815 for 8-Isoprostane and AUC of 0.818 for PGE₂. However combined ROC modeling substantially improved diagnostic accuracy by achieving high apparent discriminative performance with AUC value of 0.977 with 92.3% sensitivity and 100.0% specificity. In conclusion, the diagnostic usefulness of independent glutaminase, 8-isoprostane, and prostaglandin E₂ (PGE₂) biomarkers may be enhanced by combining ROC. Combined markers show strong apparent discriminating power in a case-control method, but estimates are biassed towards optimism and are not diagnostic. Comprehensive assay validation, calibration, and clinically representative cohorts (including females and relevant differentials) are required for replication.

Investigation of the Pharmacodynamic Material Basis and Mechanism of Gexia Zhuyu Decoction in the Treatment of Primary Dysmenorrhea with Qi Stagnation and Blood Stasis Based on Chinmedomics.

Brain metastases (BrM) remain a major cause of mortality in breast cancer (BC), yet the spatial organization and molecular circuitry of the metastatic immune microenvironment are poorly defined. To address this gap, we integrated high-plex imaging mass cytometry (IMC) performed on human primary breast tumors (n=20 regions of interests (ROIs)) and human brain-metastasis tissues (n=40 ROIs) with publicly available datasets, including single-cell RNA sequencing (scRNA-seq) from BC (n=10) and BrM (n=12) and spatial transcriptomic (ST) data from BC (n=7) and BrM (n=1), enabling single-cell resolution of tissue architecture, functional states, and intercellular signaling. IMC resolved nine major cell classes and diverse epithelial, myeloid, and T-cell subtypes, and revealed a striking shift in macrophage polarization: CD163-CD11b- macrophages were markedly depleted in brain metastases, whereas CD163+ subsets persisted. Spatial analysis demonstrated the loss of the immune-permissive CN1 neighborhood in brain metastases, which is enriched in memory T cells, B cells, and dendritic cells, and the expansion of the immunosuppressive CN9 niche in brain metastases, containing CD163+ macrophages, invasion-like epithelial cells, and exhausted T cells. ScRNA-seq integration corroborated these findings by refining the annotation of major immune and stromal lineages and confirming CD163 expression patterns across macrophage subsets. ST deconvolution further reproduced these CN1-like and CN9-like domains in situ, validating their anatomical organization across BC and BrM. Ligand-receptor inference highlighted specific inhibitory pathways-including programmed cell death protein 1/programmed death-ligand 1, growth arrest-specific 6-Tyro3, Axl, and Mer receptor tyrosine kinase family, nectin cell adhesion molecule 2 (NECTIN2)-T-cell immunoreceptor with Ig and ITIM domains, and prostaglandin E2 (PGE2)-prostaglandin E2 receptor 4-that are associated with immune evasion and metastatic growth. Functional validation in an in vivo brain metastasis model further supported the therapeutic relevance of targeting these immunoregulatory pathways. Together, these findings show a shift from permissive to suppressive immune niches, accompanied by pronounced macrophage reprogramming, as central features of BC adaptation to the brain. This spatially resolved framework provides mechanistic insight into the poor responsiveness of brain metastases to current immunotherapies and identifies defined inhibitory ligand-receptor axes as actionable targets for combination immunotherapy.

Cortical prostaglandin D2 contributes to behavioral sensitization and anxiety in peripheral inflammation.

Cancer-associated fibroblast subtypes differentially modulate natural killer cells in cancer.