The bone marrow lipidomics of mice reveal sex-related differences.

Osteoporosis is a common skeletal disorder characterized by an imbalance between bone resorption and formation, exhibiting a higher prevalence in women compared with men. While previous studies have primarily focused on genomics and genetics in osteoporosis susceptibility, there is a lack of systematic exploration of sex-specific differences in lipid levels in mouse bone marrow. Multiple reaction monitoring-based liquid chromatography-trandem mass spectrometry (LC-MS/MS) was used to quantify lipidomic profiles in bone marrow samples from three female mice and three male mice. The LC-MS/MS technique based on the multiple reaction monitoring method identified and quantified 184 lipids from 15 lipid classes. The contents of most lipids in the bone marrow cells of female mice were higher than those in male mice, including four polyunsaturated fatty acids, three phospholipids and four sphingolipids. Among all the lipid molecules, lactosylceramide (d18:0/16:0) showed the highest fold change in female mice, while its precursor lipid, glucosylceramide, was the most up-regulated in male mice. This study, focusing on bone marrow lipidomics, elucidates significant sexual dimorphism in lipid levels within bone marrow cells. It provides novel evidence supporting the higher prevalence of osteoporosis in women and enhances our understanding of the connection between sex-specific lipid levels and the risk of osteoporosis.

The arachidonic acid metabolome reveals elevation of prostaglandin E2 biosynthesis in colorectal cancer.

Arachidonic acid metabolites are a family of bioactive lipids derived from membrane phospholipids. They are involved in cancer progression, but arachidonic acid metabolite profiles and their related biosynthetic pathways remain uncertain in colorectal cancer (CRC). To compare the arachidonic acid metabolite profiles between CRC patients and healthy controls, quantification was performed using a liquid chromatography-mass spectrometry-based analysis of serum and tissue samples. Metabolomics analysis delineated the distinct oxidized lipids in CRC patients and healthy controls. Prostaglandin (PGE2)-derived metabolites were increased, suggesting that the PGE2 biosynthetic pathway was upregulated in CRC. The qRT-PCR and immunohistochemistry analyses showed that the expression level of PGE2 synthases, the key protein of PGE2 biosynthesis, was upregulated in CRC and positively correlated with the CD68+ macrophage density and CRC development. Our study indicates that the PGE2 biosynthetic pathway is associated with macrophage infiltration and progression of CRC tumors.

Cholesterol-Modified DNA Nanostructures Serve as Effective Non-Viral Carriers for Delivering siRNA to the Kidneys to Prevent Acute Kidney Injury.

With the emergence of gene therapy utilizing viral vectors, the potential risks associated with these vectors have prompted increased attention toward non-viral alternatives. DNA nanotechnology enables the assembly of specific oligonucleotide chains into nanostructures possessing defined spatial configurations. Due to their inherent characteristics, DNA nanostructures possess natural advantages as carriers for regulating gene expression in a non-viral manner. Cholesterol modification can convert DNA nanostructures from hydrophilic materials to amphiphilic materials, thereby extending their systemic circulation time. In this study, the high-dimensional design and cholesterol modification are shown to prolong the systemic circulation half-life of DNA nanostructures in mice. Specifically, the tetrahedron structure modified with three cholesterol molecules (TDN-3Chol) exhibit excellent circulation time and demonstrate a preference for renal uptake. The unique characteristics of TDN-3Chol can effectively deliver p53 siRNA to the mouse renal tubular tissue, resulting in successful knockdown of p53 and demonstrating its potential for preventing acute kidney injury. Furthermore, TDN-3Chol is not exhibited significant toxicity in mice, highlighting its promising role as a non-viral vector for targeted gene expression regulation in the kidneys. The designed non-viral vector as a prophylactic medication shows potential in addressing the current clinical challenges associated with nephrotoxic drugs.

Long Intergenic Non-Coding 00162 as Diagnostic Biomarker for Early-Stage Pancreatic Cancer.

OBJECTIVE: Pancreatic cancer (PC) is the fourth leading cause of cancer death due to insufficient diagnostic methods in early stage of PC. Growing evidence has shown that long intergenic non-coding RNAs (LINCRNAs) is a biomarker of the early-stage of PC. However, the expression level and diagnostic value of LINC00162 remains unclear. METHODS: LINC00162 expression was detected in peripheral blood samples from 155 subjects (52 healthy controls, 52 benign pancreatic disease (BPD) persons and 51 PC patients) by quantitative reverse transcription real-time polymerase chain reaction. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic value of LINC00162, carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199). RESULTS: Our data indicated that the LINC00162 expression was upregulated in PC patients compared with healthy controls and BPD (all P<0.001). Furthermore, PC patients with advanced pathological grades, positive lymph node metastasis and positive distant metastasis showed higher LINC00162 levels (all P<0.001). In addition, the area under the ROC curve (AUC) found that the LINC00162 had higher diagnostic ability than CEA and CA199 in distinguishing the early-stage PC patients (AUC: LINC00162 versus(vs) CEA vs CA199=0.932 vs 0.669 vs 0.725). CONCLUSION: In summary, the LINC00162 may be a noninvasive and efficient marker for identifying patients with the early-stage PC. Further validation studies with a large number of patients and long-term follow-up patients are needed to confirm the potential diagnostic value and clinical utility of LINC00162 in patients with PC.

Long non-coding RNA LINC01793 as a potential diagnostic biomarker of hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: There is growing evidence that long non-coding RNAs (lncRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) and may serve as diagnostic markers. This study investigates the diagnostic efficiency of the long intergenic non-protein-coding RNA 1793 (LINC01793) in hepatitis B virus (HBV)-related HCC. METHODS: Bioinformatics methods were used to screen the aberrantly expressed lncRNAs in HCC tissues based on The Cancer Genome Atlas (TCGA). Quantitative reverse transcription polymerase chain reaction was performed to assess the expression of the candidate lncRNAs in tissues, cells and whole blood samples of patients with HBV-related HCC, liver cirrhosis (LC), chronic hepatitis (CHB), and healthy controls. Then, the correlations between LINC01793 and clinical characteristics were analyzed. Finally, the diagnostic value of LINC01793 was explored based on the receiver operating characteristic curve. RESULTS: LINC01793 was remarkably upregulated in the HCC tissues and cells. It was highly expressed in the whole blood of the HBV-related HCC patients, unlike in that of the healthy controls and of the CHB and LC patients. Subsequent analysis revealed that high LINC01793 was related to the Barcelona Clinic Liver Cancer (P = 0.007), tumor invasion (P = 0.042), the number of tumors (P = 0.031) and serum level of alanine aminotransferase(p = 0.022). The areas under the curve of LINC01793, for distinguishing HCC from healthy controls, CHB and LC patients, were 0.824, 0.767 and 0.756, respectively. In addition, the combination of LINC01793 with alpha fetoprotein (AFP) had a stronger diagnostic value than LINC01793 or AFP alone in AFP-negative HCC patients. CONCLUSION: High expression of LINC01793 is correlated with adverse clinical characteristics and can serve as a non-invasive biomarker of HCC.

Diagnostic value of serum sphingolipids in patients with colorectal cancer.

Background: Abnormal lipid metabolism affects the regulation of tumor progression, though use of serum lipids and sphingolipids for disease progression identification is uncertain. Methods: Serum samples from 51 healthy volunteers and 76 patients were collected and analyzed by liquid chromatography tandem mass spectrometry. Results: Levels of serum total cholesterol and high-density lipoprotein were significantly lower in colorectal cancer patients. Multivariate analysis demonstrated distinct sphingolipid profiles between healthy individuals and patients. Of 106 sphingolipids, 15 metabolites that showed statistical significance were selected, and receiver operating characteristic analysis of these metabolites yielded an area under the curve of 0.868 to 0.9 by machine learning algorithms for distinguishing colorectal cancer from a healthy status. Conclusions: Healthy individuals, polyps patients and colorectal cancer patients have different serum sphingolipid signatures. Serum sphingolipids might be used as biomarkers for early detection or prediction of colorectal cancer.

Predictive Values of the Selected Inflammatory Indexes in Colon Cancer.

PURPOSE: Ample evidence has revealed that the lymphocyte-to-monocyte ratio (LMR), albumin-to-globulin ratio (AGR), and mean platelet volume (MPV) are cancer-related inflammatory markers. The present study aimed to combine these indicators to better assess the progression of colon cancer. METHODS: This retrospective study enrolled 251 patients with colon cancer, 171 patients with benign colon diseases, and 187 healthy control subjects. The receiver operating characteristic curve and area under the curve (AUC) were used to determine the diagnostic values of the selected inflammatory index. RESULTS: The levels of LMR, AGR, and MPV were decreased in the colon cancer group compared with the healthy control and benign colon disease groups. The LMR, AGR, and MPV were all correlated with tumor size. Moreover, LMR and AGR was associated with lymph node metastasis and clinical stage, AGR was related to distant metastasis. Both the LMR (P = .030) and AGR (P = .005) were negatively correlated with the concentration of carcinoembryonic antigen (CEA). The AUC value of MPV combined with CEA had a good diagnostic ability for distinguishing colon cancer cases (AUC = .950) and patients with benign colon diseases (AUC = .886) from controls. Meanwhile, the combination of LMR or AGR with CEA could enhance larger AUC (.746 for LMR + CEA, .737 for AGR + CEA) than CEA, LMR, or AGR alone in detecting colon cancer from benign colon diseases. CONCLUSIONS: CEA combined with the LMR, AGR, or MPV may be used as better blood-based biomarkers in the progression of colon cancer patients.

5-Amino-4-Imidazolecarboxamide Ribonucleotide Transformylase/IMP Cyclohydrolase Polymorphisms Affect the Susceptibility to Multiple Myeloma.

OBJECTIVE: The upregulation of 5-amino-4-imidazolecarboxamide ribonucleotide transformylase/IMP cyclohydrolase (ATIC) may affect tumorigenesis and multiple myeloma (MM) development. MATERIALS AND METHODS: A total of 97 patients with MM and 102 healthy control patients were included in the study. The SNaPshot technique was used to detect the ATIC gene polymorphisms. Linkage disequilibrium (LD) and haplotype analyses were conducted using SHEsis software. RESULTS: The genotype distribution or allele frequency of rs3772078 and rs16853834 was significantly different between the patients with MM and the healthy control patients (all P < .05). The rs16853834 A allele, rs3772078 CT genotype, and C allele were associated with a decreased risk of MM (all P < .05). Five single-nucleotide polymorphism combinations showed strong LD. Three haplotypes were associated with MM risk (all P < .05). We found that ATIC rs7604984 was significantly associated with serum lactate dehydrogenase levels (P = .050). CONCLUSION: We determined that the rs3772078 and rs16853834 polymorphisms are associated with a decreased risk of MM.

Diagnostic value of long noncoding RNA LINC01485 in patients with colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) were considered as transcription noise without biological functions. However, accumulated evidence shows that lncRNAs are expressed heterogeneously in tumor tissues. This study aims to identify the specific expression of lncRNAs in colorectal cancer patients and to perform verification analysis. METHODS: The differentially expressed lncRNAs and mRNAs in colorectal cancer and normal tissues were screened by bioinformatics methods. Subsequently, the qRT-PCR method was used to verify the expression of differential lncRNAs in tumor tissues and blood samples. Concurrently ROC curves were used to analyze the diagnostic efficacy of lncRNAs. Moreover, the correlation between lncRNAs and clinicopathological features was also analyzed. Finally, functional annotation analysis was performed for lncRNAs. RESULTS: Eleven lncRNAs differentially expressed in colorectal cancer tissues and normal tissues were screened. In the validation tissue sample set, FOXD3-AS1 was down-regulated in colorectal cancer tissues (P < 0.001), while LINC01485 was up-regulated in colorectal cancer tissues compared with the adjacent tissues (P < 0.05). In a further verification of the whole blood sample set, LINC01485 showed high sensitivity and specificity (sensitivity = 98.33%, specificity = 84.00%) in differentiating colorectal cancer patients from healthy controls (P < 0.001). Simultaneously, there was no difference in the expression of LINC01485 in other gastrointestinal tumors (hepatocellular carcinoma, esophageal cancer, gastric cancer, and pancreatic cancer) and healthy controls. LINC01485 is significantly related to the clinical staging, lymph node metastasis, and distant metastasis of colorectal cancer. CONCLUSIONS: The expression, diagnostic efficiency, and functional analysis of the lncRNA file of colorectal cancer reveals the important role of LINC01485 in colorectal cancer and provides an important clinical reference value for the early diagnosis and targeted therapy of colorectal cancer.

Precision N-Glycoproteomic Profiling of Murine Peritoneal Macrophages After Different Stimulations.

Macrophages are important immune cells that participate in both innate and adaptive immune responses, such as phagocytosis, recognition of molecular patterns, and activation of the immune response. In this study, murine peritoneal macrophages were isolated and then activated by LPS, HSV and VSV. Integrative proteomic and precision N-glycoproteomic profiling were conducted to assess the underlying macrophage activation. We identified a total of 587 glycoproteins, including 1239 glycopeptides, 526 monosaccharide components, and 8326 intact glycopeptides in glycoproteomics, as well as a total of 4496 proteins identified in proteomic analysis. These glycoproteins are widely involved in important biological processes, such as antigen presentation, cytokine production and glycosylation progression. Under the stimulation of the different pathogens, glycoproteins showed a dramatic change. We found that receptors in the Toll-like receptor pathway, such as Tlr2 and CD14, were increased under LPS and HSV stimulation. Glycosylation of those proteins was proven to influence their subcellular locations.

D-Dimer Combined With CRP Can Improve the Differential Value of Bacterial Meningitis and Tuberculous Meningitis.

OBJECTIVE: To explore the diagnostic value of the coagulation marker D-dimer and its combination with the traditional marker C-reactive protein (CRP) in distinguishing bacterial meningitis (BM) from tuberculous meningitis (TM). METHODS: We performed a retrospective study on specimens from 173 patients with meningitis who were hospitalized at the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from 2012 through 2020. The patient records were divided into the BM group and the TM group, and hematological parameters D-dimer and CRP were evaluated for the 2 groups. RESULTS: The levels of D-dimer and CRP in the BM group were significantly higher than those levels in the TM group (P ˂.001 for each), and the sensitivity and specificity of the combined detection of the 2 markers was 86.3% to 100%; the area under the receiver operating characteristic (ROC) curve reached 0.983 (95% confidence interval [CI], 0.966-0.999). CONCLUSION: D-dimer testing has high specificity in distinguishing between BM and TM; CRP testing also has high sensitivity. The combined diagnosis of the 2 biomarkers helps to distinguish TM from BM.

Metabolomics analysis provides new insights into the medicinal value of flavonoids in tobacco leaves.

Tobacco is a traditional Chinese medicine containing a variety of biologically active substances. In addition to being used to make cigarettes, tobacco is also a vastly underdeveloped medicinal resource. In order to identify and clarify the biological activities and medicinal value of tobacco leaves, the metabolomes of tobacco leaves were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based on multiple reaction monitoring (MRM). In total, 1169 metabolites were identified and quantified. The results showed that the metabolic profiles of the tobacco cultivars K326 and Yun87 are similar to each other but different from that of Hongda. Moreover, the curing process affects the metabolic profiles of tobacco leaves. Flavonoids are the largest class of metabolites in tobacco leaves. Flavonoids have multiple biological functions; for example, they can promote or inhibit inflammation. We found that quercetin provides anti-inflammatory activity by inhibiting the il-1ß mRNA expression, while glycitin and neohesperidin can promote il-1ß and il-6 production. Our results provide in-depth insights into the medical uses and biological mechanisms of tobacco leaves.

Diagnostic Values of the Prealbumin-to-Fibrinogen, Albumin-to-Fibrinogen, and Monocyte-to-Lymphocyte Ratios in Gastric Cancer.

OBJECTIVE: This study aimed to assess the diagnostic value of the prealbumin-to-fibrinogen ratio (PFR), monocyte-to-lymphocyte ratio (MLR), and albumin-to-fibrinogen ratio (AFR) as single or combined indicators of gastric cancer. METHODS: The study included 162 healthy controls and 155 patients with gastric adenocarcinoma. The differences in the experimental indicators and pathological characteristics between the groups were compared using the Kruskal-Wallis H test and Mann-Whitney U test. We evaluated the independent risk factors for gastric cancer through logistic regression and assessed the diagnostic values of PFR, AFR, and MLR for gastric cancer using receiver operating characteristic (ROC) curves. RESULTS: PFR, AFR, and MLR were different between the healthy control and gastric cancer groups. PFR and AFR were related to the pathological characteristics of gastric cancer, such as tumor size, TNM stage, and clinical stage (P<0.05). PFR, MLR, and AFR were not related to age, tumor site, or degree of differentiation (P>0.05). Regression analysis suggested that PFR, MLR, and AFR might be independent factors predictive of gastric cancer. When combining PFR, MLR, and AFR, the area under the curve (AUC) was 0.951, and the sensitivity and specificity were 87.10% and 95.06%, respectively. This combination had the highest diagnostic value for gastric cancer patients. CONCLUSION: The combination of PFR, MLR, and AFR is more valuable than each indicator alone in the diagnosis of gastric cancer.

Microarray investigation of glycan remodeling during macrophage polarization reveals α2,6 sialic acid as an anti-inflammatory indicator.

Glycosylation is a widely occurring posttranslational modification. Here, we applied a quick, convenient and high-throughput strategy (lectin array) to investigate the variation in glycans on different macrophage subtypes derived from THP-1 and RAW264.7 cells. For THP-1 cells, there were more significant differences in the glycan on M2 macrophages compared to the other two subtypes. In contrast, M1 macrophages exhibited more significant glycan remodeling than the other subtypes for the RAW264.7 cell line. The response of the lectins which recogonize the N-glycan and α2,6 sialic acid was higher during polarization into anti-inflammatory phase (THP-1 derived M2 subtypes), and lower in pro-inflammatory phase (RAW264.7 M1 subtypes). The regulation of several α2,6 sialyltransferase genes was coincident with the regulation of the α2,6 sialic acid on the two cell lines. The lectin response and glycosyltranferase gene expression confirmed that α2,6 sialic acid showed higher expression in the anti-inflammatory phase. This indicated that α2,6 sialic acid was a potential indicator for the anti-inflammatory response.

Association of Growth Differentiation Factor-15 Polymorphisms and Growth Differentiation Factor-15 Serum Levels with Susceptibility to Multiple Myeloma in a Chinese Population.

BACKGROUND: The aim of our study was to evaluate the relationship between growth differentiation factor-15 (GDF15) rs1058587, rs4808793, and rs1059369 polymorphisms, serum concentrations of GDF15, and International Staging System (ISS) staging or Durie-Salmon staging system (DS) staging in multiple myeloma patients and whether its polymorphism affects the expression of serum GDF15 in Chinese population. METHODS: A total of 120 patients with multiple myeloma and 119 healthy controls were included in the study. The SNaPshot technique was used to detect the GDF15 gene polymorphisms. Serum GDF15 levels were measured using an Enzyme-Linked ImmunoSorbent Assay (ELISA) kit. RESULTS: There was no significant difference in genotype distribution or allele frequency of three loci between multiple myeloma patients and healthy controls. However, the genotype distribution and allele frequencies of rs1059369 in ISS stage I were significantly different from those in ISS stage II (p = 0.008), and the distribution of rs1058587 genotype was different between ISS stage II and ISS stage III (p = 0.014). The overall serum concentration of GDF15 and the same genotype at the same locus (rs1058587: GC, GG; rs4808793: CC, GC; rs1059369: AA, AT, and TT) in patients with multiple myeloma was significantly higher than in the healthy control group (all p < 0.05). CONCLUSIONS: Our results showed the genotype distribution and allele frequencies of rs1059369 and rs1058587 of GDF15 gene have some association with ISS and DS stage. But the polymorphism of GDF15 did not affect the expression of serum GDF15 in patients with multiple myeloma.

Single and Combined Use of Preoperative Inflammatory Biomarkers and CA199 in Diagnosing Pancreatic Cancer.

BACKGROUND: To determine the diagnostic value of preoperative inflammatory biomarkers and CA199, alone or in combination, in diagnosing pancreatic cancer (PCC). METHODS: This retrospective study was comprised of 75 PCC patients and 83 healthy controls (HC). The participant's medical data was mined from the electronic records of the First Affiliated Hospital of Guangxi Medical University. The data included the preoperative circulating albumin/fibrinogen ratio (AFR), the platelet/lymphocyte ratio (PLR), the lymphocyte/monocyte ratio (LMR), the neutrophil/lymphocyte ratio (NLR), and the derived NLR (dNLR). The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC) were used to evaluate the diagnostic efficacy of these candidate biomarkers for PCC. RESULTS: A single AFR significantly distinguished PCC from the healthy controls (AUROC: 0.903, 95% CI: 0.846 - 0.945) and had a significantly higher sensitivity and larger AUROC than CA199 (AUROC: 0.814, 95% CI: 0.774 - 0.871). The combinations of AFR with CA199 (AUROC: 0.932, 95% CI: 0.881 - 0.966), RDW with CA199 (AUROC: 0.905, 95% CI: 0.849 - 0.946), Alb with CA199 (AUROC: 0.869, 95% CI: 0.806 - 0.917), and Fib with CA199 (AUROC: 0.921, 95% CI: 0.868 - 0.958) also yielded higher sensitivities and larger AUROCs than CA199 alone. CONCLUSIONS: Circulating AFR was an effective biomarker in diagnosing PCC. Combining AFR, RDW, Alb, and Fib with CA199 could improve the diagnostic efficacy for PCC.

SIRT5 Contributes to Colorectal Cancer Growth by Regulating T Cell Activity.

Over the past several years, SIRT5 has attracted considerable attention in metabolic regulation. However, the function of SIRT5 in tumorigenesis by regulating tumor microenvironment is poorly understood. In this work, we found that Sirt5 knockout mice were resistant to AOM and DSS-induced colitis-associated colorectal tumorigenesis and the level of IFN-γ in their tumor microenvironment was higher. Additionally, proteome and network analysis revealed that SIRT5 was important in the T cell receptor signaling pathway. Furthermore, we determined that a deficiency of Sirt5 induced stronger T cell activation and demonstrated that SIRT5 played a pivotal role in regulating the differentiation of CD4+ regulatory T (Treg) cells and T helper 1 (Th1) cells. An imbalance in the lineages of immunosuppressive Treg cells and the inflammatory Th1 subsets of helper T cells leads to the development of colon cancer. Our results revealed a regulatory role of SIRT5 in T cell activation and colorectal tumorigenesis.

Correlation between Pretreatment Hematologic Parameters and Cervical Cancer Patients Undergoing Hysterectomy: a Retrospective Study.

BACKGROUND: The objective of this study is to investigate the correlation of mean platelet volume (MPV), MPV/ platelet count, and monocyte to lymphocyte ratio (MLR) between cervical cancer patients and healthy people and to evaluate the value of those parameters in early diagnosis of cervical cancer. METHODS: The study population included 137 cervical cancer patients undergoing hysterectomy and 113 healthy controls. The clinical features (age, pathology type, tumor staging, and tumor size) were collected from the hospital information system. The hematology parameters (white blood cell, red blood cell, hemoglobin, platelet count, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet distribution width) are obtained in the laboratory information system. RESULTS: We found that the monocyte count and MLR value are higher in the cervical cancer group. The MPV and MPV/platelet are lower in the cervical cancer group. The receiver operating characteristic (ROC) analysis shows that MPV+MLR can generate a moderate specificity with 71.68%, sensitivity with 65.69%, and AUC with 0.718 to distinguish cervical cancer and healthy people. CONCLUSIONS: MPV/platelet and MLR may be helpful for the early diagnosis of cervical cancer. A larger clinical data analysis is necessary to evaluate the diagnostic value of hematologic parameters in cervical cancer.

Lipidomic profiling of virus infection identifies mediators that resolve herpes simplex virus-induced corneal inflammatory lesions.

Lipid mediators (LMs) play a pivotal role in the induction and resolution of inflammation. To identify and elucidate their involvement during virus infection, multiple reaction monitoring (MRM) based liquid chromatography-tandem mass spectrometry lipidomic profiling of 62 lipid species was performed in this study. Results show that RAW264.7 macrophages differentially produce specific LMs signals depending on difference in virus pathogenicity. Integration of large-scale lipidomics with targeted gene expression data revealed mediators, such as RVD3, 18-HEPE, 11(12)-EET etc. correlated with the pathogenic phase of the infection. The herpes simplex virus (HSV)-induced keratitis model demonstrates that 11(12)-EET treatment represents a novel alternative for treating viral infection.