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At least 19 recordsLinked to original sources
PubMed2025

KDM3B Regulates Postradiation Fibrotic Responses in Prostate Stroma via N6-methyladenosine Modification of LOX.

PURPOSE: Genome-wide association studies have uncovered single-nucleotide polymorphisms (SNPs) linked to radiation therapy (RT)-induced toxicities in patients with prostate cancer. SNP rs17599026, located in intron 21 of the KDM3B gene, has been associated with late-onset urinary toxicity, with an increased frequency of urination observed 2 years post-RT compared with pretreatment conditions. This study aimed to explore the underlying mechanisms driving this association. METHODS AND MATERIALS: A clustered regularly interspaced short palindromic repeats-dead Cas9 prime editing system was used to mimic KDM3B genetic variants in prostate stromal cell lines. Murine models with wild-type and heterozygous Kdm3b genotypes were used to assess fibrosis following radiation. RNA immunoprecipitation, transcript stability assays, and protein analysis elucidated the role of N6-methyladenosine (m6A) modification in regulating lysyl oxidase (LOX) expression. α-ketoglutarate (α-KG) supplementation was tested for its effects on KDM3B protein stability, LOX expression, and fibrosis mitigation. RESULTS: The rs17599026 SNP reduced KDM3B protein expression via circular RNA and microRNA-mediated mechanisms, leading to decreased m6A modification and increased stability of LOX messenger RNA. Elevated LOX expression promoted collagen cross-linking and fibrosis in prostate stroma. α-KG supplementation restored KDM3B protein levels, reduced LOX expression, and mitigated fibrosis in vitro and in vivo. CONCLUSIONS: KDM3B genetic variations influence radiation-induced fibrosis through posttranscriptional regulation of LOX. Dietary α-KG supplementation may serve as a mechanism-based strategy to alleviate radiation toxicity in patients with prostate cancer, offering a potential therapeutic pathway to improve treatment outcomes.

Male↗
PubMed1992

Exchange of gene activity in transgenic plants catalyzed by the Cre-lox site-specific recombination system.

The Cre-lox site-specific recombination system of bacteriophage P1 was used to excise a firefly luciferase (luc) gene which had previously been incorporated into the tobacco genome. The excision event was due to site-specific DNA recombination between two lox sequences flanking the luc gene and was catalyzed by the Cre recombinase introduced by cross-fertilization. Recombination resulted in the fusion of a promoter with a distally located hygromycin phosphotransferase (hpt) coding sequence and the excision event was monitored as a phenotypic change from expression of luc to expression of hpt. The efficiency of recombination was estimated from the exchange of gene activity and confirmed by molecular analysis. The relevance to potential applications of site-specific deletion-fusion events for chromosome engineering are discussed.

Agrobacterium tumefaciens↗
PubMed2026

A Tripartite AAV System with Engineered Lox Sites Enables Efficient Delivery of the EYS Gene for Retinal Gene Therapy.

Mutations in the Eyes Shut Homolog (EYS) gene are one of the leading causes of autosomal recessive retinitis pigmentosa, a progressive retinal degenerative disease for which no effective treatment currently exists. However, the large size of the EYS coding sequence (∼9.4 kb) exceeds the packaging limit of adeno-associated virus (AAV) vectors, posing a major barrier to gene replacement therapy. To address this challenge, we developed a tripartite AAV vector system that enables delivery and reconstitution of the full-length EYS gene using a Cre-lox-based unidirectional DNA recombination strategy, Uni-directional and Site-specific Transgene Assembly by Recombination (Uni-STAR). The system consists of three AAV constructs carrying discrete EYS segments flanked by engineered, noncompatible lox sites that drive ordered and unidirectional recombination in target cells. We validated this system in vitro by demonstrating successful reconstitution and expression of full-length EYS protein in HEK293T cells. In vivo, subretinal co-injection of the three AAV vectors into mouse eyes led to precise reconstitution and expression of full-length EYS protein in the retina. These findings establish the feasibility of using a tripartite AAV system to deliver the complete EYS gene and provide a foundation for future therapeutic development targeting EYS-associated retinal degenerations.

Dependovirus↗
PubMed2026

Multi-omics and spatial transcriptomics reveal that S100A10 drives CD8+ T-cell exhaustion and immune evasion in hepatocellular carcinoma through cPLA2-5-LOX-mediated arachidonic acid metabolism and ferroptosis.

Immune evasion in hepatocellular carcinoma (HCC) represents a major biological barrier limiting the efficacy of immunotherapy, yet its molecular basis remains incompletely understood. Increasing evidence indicates that tumor metabolic reprogramming and ferroptosis-related signaling play critical roles in shaping an immunosuppressive tumor microenvironment (TME); however, the specific regulatory factors involved remain unclear. This study aims to systematically elucidate the functional role of S100 calcium-binding protein A10 (S100A10) in immune evasion in HCC, with a particular focus on the molecular mechanisms by which S100A10 regulates CD8+ T-cell exhaustion through arachidonic acid (AA) metabolism and ferroptosis, as well as its potential therapeutic implications. To this end, data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort are integrated to analyze the expression patterns of S100A10, its prognostic value, and its association with the immune microenvironment. S100A10 overexpression and knockout models are established in HCCLM3 and MHCC97L cell lines, and S100A10-mediated metabolic pathway reprogramming is characterized using transcriptomic profiling, untargeted metabolomics, and ferroptosis-related functional assays. In parallel, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics are employed to delineate the cell-type specificity and spatial distribution of S100A10. Furthermore, human CD8+ T-cell co-culture systems and orthotopic mouse HCC models are used to evaluate the impact of S100A10 on immune function and responsiveness to anti-programmed cell death protein 1 (anti-PD-1) therapy. The results demonstrate that S100A10 is significantly upregulated in HCC and is closely associated with poor prognosis and an immunosuppressive state. Mechanistically, S100A10 activates cytosolic phospholipase A2-arachidonate 5-lipoxygenase (cPLA2-5-LOX)-mediated AA oxidative metabolism, leading to the accumulation of lipid peroxidation products and ferroptosis-associated signals, thereby driving CD8+ T-cell exhaustion and promoting immune evasion. Significantly, inhibition of S100A10 reshapes the tumor immune microenvironment (TIME) and enhances the therapeutic efficacy of anti-PD-1 treatment. Collectively, these findings identify S100A10 as a critical regulator of metabolic-immune coupling in HCC and provide a theoretical basis for combinatorial strategies targeting metabolism and immunotherapy.

Arachidonic acid metabolism↗
PubMed1992

Cre-lox recombination in Escherichia coli cells. Mechanistic differences from the in vitro reaction.

The mechanism of the Cre recombinase of bacteriophage P1 in Escherichia coli cells was analyzed by topological methods in order to determine the important features of the in vivo reaction. Lambda infection was used to introduce the cre gene into cells containing plasmid substrates. The products of Cre resolution on substrates with directly repeated sites were predominantly free circles, even though decatenation by DNA gyrase was blocked by the drug norfloxacin. Recombination by Cre was greatly stimulated by negative supercoiling, and inversion occurred inefficiently. These results are strikingly different from those found with purified enzyme in vitro. Our data imply that Cre recombination in vivo is much more tightly controlled than it is in vitro, and that Cre acts predominantly as a resolvase in vivo. We suggest a role for Cre-mediated recombination in P1 plasmid amplification that is consistent with the selectivity of the enzyme in vivo.

Chromosome Inversion↗
PubMed2026

Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.

High metabolic heterogeneity and plasticity of triple-negative breast cancer (TNBC) contribute to therapy resistance, necessitating identification of therapeutic vulnerabilities. Here, we identify non-canonical functions of the extracellular matrix (ECM) remodeler, lysyl oxidase (LOX), in regulating glucose metabolism and mitochondrial homeostasis and show that inhibiting LOX generates targetable vulnerability to ferroptosis. Mechanistically, LOX interacts with PARKIN and its upstream kinase PINK1, which we identified as a substrate of LOX. LOX-mediated PINK1 oxidation suppresses PARKIN phosphorylation, stabilizing hypoxia-inducible factor 1-alpha (HIF-1α) and increasing glycolysis. Concomitantly, LOX inhibits PARKIN-mediated mitophagy and maintains mitochondria-ER contacts through VDAC1 stabilization, while the LOX-HSP90 complex promotes mitochondrial Ca2+ transport and ATP production. Inhibiting LOX suppresses glycolysis, disrupts mitochondrial dynamics, reduces OXPHOS and GPX4/FSP1, and induces compensatory DHODH activity. Our "one-two punch" approach combining LOX inhibition with clinical DHODH inhibitor suppresses tumor growth in vivo in chemo-free setting. Notably, LOX protein correlates with HIF-1α/GLUT1/GPX4 in TNBC patient tumors, supporting its clinical relevance.

Ferroptosis↗
PubMed2026

Genome-wide analysis of lipoxygenase genes in Coffea arabica and its diploid progenitors.

Lipoxygenase proteins (LOXs) play a crucial role in plant growth, development, and defense notably through their involvement in jasmonic acid (JA) biosynthesis. Here, we aimed to identify and characterize genes encoding LOXs in three coffee species, Coffea arabica, Coffea canephora, and Coffea eugenioides, and to evaluate whether LOX genes are differentially expressed following hexanoic acid application in Coffea arabica. We found 18 LOX genes in Coffea arabica and 9 genes each in Coffea eugenioides and Coffea canephora. Chromosomal localization analyses revealed strong correspondence between the LOX genes of tetraploid Coffea arabica and those of its putative diploid progenitors, Coffea eugenioides and Coffea canephora. Transcriptomic and enzymatic analyses showed that hexanoic acid application modulates the expression of specific LOX genes and alters LOX activity in leaves and roots of Coffea arabica cvs. Catuaí Vermelho and Obatã. Notably, three LOX genes displayed strong correlations between transcript abundance and enzymatic activity. Together, these results indicate that a subset of LOX genes in Coffea arabica represents promising candidates for detailed functional analyses, as they likely contribute substantially to LOX activity and elicitor-induced defense responses in Coffea species.

Coffea↗
PubMed1979

Lung lysyl oxidase activity: relation to lung growth.

The activity of lysyl oxidase (LOX), the extracellular enzyme responsible for initiating crosslinking of collagen and elastin, was measured during 3 types of postnatal lung growth. Lung parenchymal and pleural LOX activity was high in the first 3 wk of of life, decreasing by 50 % to stable amounts by 4 to 10 wk. In contrast, airway and aortic LOX activity remained high during the first 10 wk of life, decreasing by 50 to 75 % thereafter. After pneumonectomy, lung LOX activity doubled within 24 h, decreasing to control values thereafter. Hypoxia (12 to 13 % O2) resulted in a prompt and sustained increase in lung but not pleural, airway, or aortic LOX activity. Thus, LOX activity can be controlled precisely within specific tissues and appears to be related to early phases of connective-tissue synthesis. Further studies of the synthesis and degradation of LOX should provide important information about the control of connective-tissue formation within the lungs.

Amino Acid Oxidoreductases↗
PubMed2026

Downregulated lysyl oxidase in plasma extracellular vesicles: a biomarker linked to brain metastasis risk in lung adenocarcinoma.

BACKGROUND: Brain metastasis (BrM) is a leading cause of mortality in patients with lung adenocarcinoma (LUAD). Extracellular vesicles (EVs), which carry bioactive molecules, play a critical role in tumor microenvironment remodeling and exhibit metastatic organotropism, holding promise as liquid biopsy biomarkers. This study aims to identify plasma EV-derived proteins associated with LUAD-BrM. METHODS: A multi-omics framework was applied. Plasma EVs from 59 stage IV LUAD patients (30 BrM vs 29 non-BrM) were profiled using data-independent acquisition mass spectrometry proteomics. Candidate proteins were screened via bioinformatics and machine learning (LASSO/RF/SVM). Initial validation included tissue proteomics (n = 13), single-cell transcriptomics (TISCH2), and Western blot analysis of a subset of the discovery samples. Functional experiments were conducted in vitro. The lead candidate was ultimately validated in an independent plasma cohort (n = 158) through ELISA. RESULTS: Proteomic analysis implicated collagen-containing extracellular matrix (ECM) pathways. Lysyl oxidase (LOX), a key ECM cross-linking enzyme, was identified as a lead candidate. LOX and its family member LOXL1 were consistently downregulated in BrM tissues and plasma EVs. Single-cell analysis revealed decreased LOX expression specifically in BrM-associated fibroblasts, which showed suppressed ECM-related pathways. In vitro experiments supported a PI3K/AKT-LOX-ECM regulatory axis. Plasma EV-derived LOX demonstrated strong diagnostic performance in the independent cohort, with an AUC of 0.786 (95% CI 0.713iated fi. CONCLUSIONS: Our study establishes plasma EV-derived LOX as a promising non-invasive biomarker for LUAD-BrM through a comprehensive multi-omics validation strategy. We propose a model wherein downregulation of LOX, potentially driven by PI3K/AKT signaling in tumor-associated fibroblasts, contributes to ECM degradation and may promote brain-tropic metastasis. This finding offers new insights for risk stratification and timely intervention in LUAD patients.

Humans↗
PubMed1992

Lipoxygenase activity in the brain regions of young chicks: isolation and some properties.

1. The lipoxygenase (LOX) oxygenation pathway of arachidonic acid was investigated in the cerebellum and cerebral hemispheres of young chicks. 2. Lipoxygenase products consisted mainly of 15-hydroxyeicosatetraenoic acid (15-HETE), accompanied by the 15-hydroperoxy analog (15-HPETE) and the 5-HETE product. 3. The yield of 15-HETE was 3 times greater in the cerebellar system than in the cerebrum. 4. PLA2 activity of the cerebellum was twice that of the cerebrum. 5. Affinity chromatography revealed 2 brain fractions with LOX activity which were assayed with either linoleic or arachidonic acid as substrate. 6. The fraction eluted with 0.2 M sodium acetate pH 5.0, produced a higher yield and enrichment of LOX activity than the eluate obtained with 0.1 M Tris-HCl buffer (pH 8.0). 7. A considerably higher yield and enrichment of the enzyme was achieved when the starting material was the cerebellum, compared to the cerebrum. 8. The optimal pH for both purified fractions from cerebrum and cerebellum was 6.5, with either linoleic or arachidonic acid as substrate. 9. The cerebral LOX yielded Michaelis-Menten kinetics when linoleic acid was the substrate, while the corresponding plots for the cerebellar enzyme were sigmoidal. 10. Arachidonic acid as substrate produced sigmoidal plots, except at pH 5.0, where Michaelis-Menten kinetics were observed. 11. These results and the elevated activities of PLA2 and 15-LOX could be significant in relation to the special vulnerability of the cerebellum in chick nutritional encephalomalacia.

Animals↗
PubMed1992

Spreading of HeLa cells on a collagen substratum requires a second messenger formed by the lipoxygenase metabolism of arachidonic acid released by collagen receptor clustering.

HeLa cells attach to a variety of substrata but spread only on collagen or gelatin. Spreading is dependent on collagen-receptor upregulation, clustering, and binding to the cytoskeleton. This study examines whether second messengers are involved in initiating the spreading process on gelatin. The levels of cytosolic free calcium ([Ca++]i), cAMP, and cytoplasmic pH (pHi) do not change during cell attachment and spreading. However, a basal level of [Ca++]i and an alkaline pH(i) are required for spreading. There is an activation of protein kinase C (PKC) and a release of arachidonic acid (AA) on attachment and before cell spreading. Inhibition of PKC does not block cell spreading, indicating that PKC activation is not essential for spreading. Inhibition of phospholipase A2 blocks cell spreading, whereas addition of exogeneous AA overcomes this inhibitory effect. Among AA metabolic pathways, inhibitors of lipoxygenase (LOX) block cell spreading, suggesting that a LOX product(s) formed from AA initiates spreading. Clustering receptors for collagen with polyclonal antibodies, or with anti-collagen-receptor antigen-binding fragments (Fab) in combination with a secondary antibody, induce AA release. Also, AA is released when cells attach to either immobilized gelatin or immobilized Arg-Gly-Asp (RGD) peptide. Thus, AA is released whenever receptor clustering is observed. Receptor occupancy is not sufficient to release AA; when cells are treated with gelatin or RGD peptide in solution or anti-collagen-receptor Fab fragments without secondary antibody, conditions where receptor clustering is not observed, AA is not released. Thus, a LOX metabolite(s) of AA formed by collagen-receptor clustering is a second messenger(s) that initiates HeLa cell spreading. LOX inhibitors also block the spreading of bovine aortic endothelial cells, chicken embryo fibroblasts, and CV-1 fibroblasts on gelatin or fibronectin, indicating that other cells might use the same second messenger system in initiating cell-substratum adhesion.

Amino Acid Sequence↗
PubMed1992

Antitumor activity and cross-resistance of carmethizole hydrochloride in preclinical models in mice.

Carmethizole hydrochloride [1-methyl-2-methylthio-4,5-bis(hydroxymethyl)imidazole-4', 5'-bis(N-methylcarbamate)hydrochloride, NSC 602,668; hereafter called carmethizole] is a new antitumor drug that has shown relatively broad activity in initial evaluations against several murine tumors and human tumor xenografts in vivo. The present studies were designed to address questions about carmethizole's activity against established disease, its activity on different treatment schedules, and the extent of its cross-resistance with established drugs. Human MX-1 mammary carcinoma, human NCI-H82 small-cell lung carcinoma, and human LOX amelanotic melanoma xenografts in athymic mice were used to determine the drug's activity against established disease; the NCI-H82 lung-tumor xenograft in athymic mice was used to explore its schedule dependence; and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. When injected i.p., carmethizole exhibited antitumor activity against advanced-stage s.c. MX-1 mammary, s.c. NCI-H82 lung, and i.p. LOX melanoma xenografts and was as effective against established disease (MX-1 and LOX) as it was against early-stage disease (no data are available for early-stage NCI-H82). The therapeutic effect of carmethizole was not route-dependent, as was evidenced by the similar delays observed in tumor growth following i.p. and i.v. administration. The use of a split-dose schedule on a single day instead of one bolus injection yielded an increase in the total dose delivered, resulting in an increased delay in tumor growth. Murine leukemias resistant to vincristine (VCR), amsacrine (AMSA), or methotrexate (MTX) were not cross-resistant to carmethizole. However, murine leukemias resistant to doxorubicin (ADR), melphalan (L-PAM), cisplatin (DDPt), 1-beta-D-ara-binofuranosylcytosine (ara-C), and 5-fluorouracil (5-FU) were cross-resistant to carmethizole, suggesting that patients who have previously been treated with any of these agents might be less likely to respond to carmethizole than those who have had no opportunity to develop resistance to any of these compounds. We anticipate that the information derived from these studies may be useful in the design of clinical trials of carmethizole and may stimulate additional basic research on the mechanism of action of this new agent.

Animals↗
PubMed2025

Reproducible autosomal gene expression changes with loss of typical X and Y complement across tumor types.

Although there are known sex differences in cancer incidence, severity, and treatment, the sex chromosomes are typically excluded from genomic analyses because of the unique technical challenges associated with assessing their copy number, sequence variation, and expression. Here we assess sex chromosome complement in three widely-used human genomics datasets from normal (non-cancerous) tissues, primary tumors, and cancer cell lines and study the effects on genome-wide gene expression. Expected sex chromosome complements based on reported patient sex were observed in non-cancerous tissues, but about half of tumors and cancer cell lines showed loss of typical sex chromosome gene expression across tissue types with three categories: loss of chromosome Y (LOY), loss of chromosome X (LOX) and reactivation of the inactive X chromosome (XaXa). Genes consistently differentially expressed in tumors with loss of chromosome X, loss of chromosome Y, or loss of X chromosome inactivation are associated with the hallmarks of cancer and include both sex-linked and autosomal genes from nearly all chromosomes, druggable genes, and genes with molecular functions relevant to cancer signaling, such as kinase activity. Strikingly, tumors that are X0, including tumors from female patients that have lost an X chromosome and tumors from male patients that have lost a Y chromosome, cluster together by gene expression profile. Patients with tumors that have LOX or LOY had poorer survival outcomes compared to those with tumors that had maintained their sex chromosome complement. Further, LOX and LOY eliminates nearly all of the differential gene expression between tumors from different patient sexes, affecting sex chromosomal and autosomal gene expression. Going forward, considering patient sex as well as the entire genome, including assessment of the sex chromosome complement, will provide additional insights into personalized tumor etiology, progression, treatment, and patient outcome.

Journal Article↗
PubMed2025

The 13-lipoxygenase GmLOX6 is involved in JA biosynthesis and serves as a positive regulator of salt stress tolerance in soybean.

Salinity represents a major abiotic stressor that significantly impairs soybean growth and yield. Although jasmonic acid (JA) has been firmly established as a key regulator of plant defense against salt stress, the precise functions of lipoxygenase (LOX) genes responsible for initiating JA biosynthesis remain poorly defined. Here, a comprehensive genome-wide analysis of the soybean LOX gene family was performed, and a detailed functional characterization of GmLOX6 was carried out. Subcellular localization confirmed that GmLOX6 is targeted to chloroplasts, while enzymatic assays demonstrated that it acts as a 13-LOX enzyme with a strong preference for α-linolenic acid as substrate. To clarify its role under salt stress, we generated both overexpression and CRISPR/Cas9-mediated knockout lines of soybean. Phenotypic and molecular evaluations revealed that GmLOX6 facilitates JA production under salt stress, thereby contributing to enhanced JA accumulation. This elevation in JA levels was associated with improved salt tolerance through multiple physiological adaptations, including the activation of antioxidant enzymes for the detoxification of reactive oxygen species (ROS), enhanced Na+ extrusion to preserve ionic balance, and reinforced membrane stability. Moreover, GmRWP-RK11 was identified as a transcriptional repressor of GmLOX6. Functional disruption of GmRWP-RK11 via CRISPR/Cas9 conferred greater salt tolerance, further supporting its negative regulatory role. Collectively, these findings uncover a novel regulatory axis in which GmLOX6-mediated JA biosynthesis enhances soybean resistance to salinity through modulation of ROS homeostasis and Na+ transport. These insights provide an expanded understanding of the transcriptional and biochemical mechanisms underpinning JA-driven stress adaptation in soybean.

Glycine max↗
PubMed1975

A double-blind comparison of loxitane--loxapine succinate and trifluoperazine hydrochloride in chronic schizophrenic patients.

Therapeutic efficacy and safety of loxapine succinate (LOX) and trifluoperazine hydrochloride were compared by means of a controlled, double-blind study involving 49 chronic schizophrenic inpatients. The data indicated that LOX in dosages ranging from 40 - 65 mg/day, (usually administered on a b.i.d. schedule) had demonstrable anti-psychotic activity in 14 of 25 chronic schizophrenic patients (56%), while TFP treatment in appropriate dosage showed a similar activity in 9 of 23 patients (39%). Both LOX and TFP displayed essentially the same profile and incidence of side effects. Clinical laboratory abnormalities were minor. On the basis of this study, and in comparison with trifluoperazine, it appears that loxapine is an efficacious and essentially safe medication, suitable for the treatment of chronic schizophrenia.

Adult↗
PubMed2025

Sex-dependent upregulation in oxylipins involved in inflammation resolution in the cerebellum of Niemann-Pick disease C1 mice.

Unresolved inflammation in the cerebellum is implicated in motor and cognitive decline in Niemann-Pick disease type C (NPC), a neurodegenerative lysosomal storage disorder caused by pathogenic mutations in the Npc1 gene encoding a cholesterol transporter protein. It is unclear whether unresolved inflammation in NPC stems from impairments in lipid-mediated resolution. For this reason, free lipid mediators (i.e., oxylipins) involved in inflammation resolution, as well as esterified lipid mediators known to regulate the bioavailability of free oxylipins were quantified using Reverse-Phase Ultra- Performance Liquid Chromatography coupled to negative Electrospray Ionization and Triple Quadrupole Tandem Mass Spectrometry (RP-UPLC-ESI(-)-QqQ-MS/MS) in Npc1 knock-in (NPC1ki) and Wildtype (WT) mice. Total cholesterol and fatty acids including polyunsaturated fatty acid (PUFA) precursors to oxylipins, were quantified using Gas Chromatography coupled to Flame Ionization Detection (GC-FID). Compared to WT mice, female NPC1ki mice, but not males, exhibited significantly elevated levels of free pro-resolving fatty acid epoxides (EpETrE and EpDPE) from the cytochrome P450 (CYP) pathway. Esterified mono- and dihydroxy lipid mediators derived from the lipoxygenase (LOX) and soluble epoxide hydrolase (sEH) pathways were mainly increased in NPC1ki females, suggesting enhanced sequestration of pro-inflammatory LOX and sEH metabolites. While PUFAs and cholesterol concentrations were not significantly different between groups, myristic (C14:0) and palmitoleic acid (C16:1n-7) were significantly elevated in female NPC1ki mice compared to WT controls. These findings suggest sex-specific adaptations in inflammation resolution pathways in NPC, with females exhibiting distinct inflammatory responses that may drive sex-related differences in disease pathogenesis. Our findings underscore the need for sex-specific therapeutic approaches to improve NPC treatment outcomes.

Animals↗