Lung adenocarcinoma with micropapillary pattern (MPP) has an aggressive malignant behavior. Limited resection should be avoided because of its high recurrence rate. If adenocarcinoma with MPP is diagnosed preoperatively, the selection of proper treatment is possible. To explore a preoperative biomarker for diagnosing MPP, we here conducted RNA sequencing analysis of 25 clinical samples as the training set, including 6 MPP, 16 other adenocarcinoma subtypes and 3 normal lung tissues. Unsupervised hierarchical clustering analysis suggested a presence of subgroup with MPP showing different gene expression phenotype. We extracted differentially expressed genes with high expression levels in MPP samples, and chose VSIG1, CXCL14 and BAMBI as candidate biomarkers for MPP. RT-qPCR analysis confirmed a significantly higher expression of VSIG1 (P=0.03) and CXCL14 (P=0.02) in MPP than others. In validation set of 4 MPP and 4 non-MPP samples, CXCL14 expression was validated to be significantly higher in MPP than in non-MPP (P=0.04). Comparing a total of 10 MPP and 20 non-MPP samples, the AUC of CXCL14 to distinguish MPP from others was 0.89. The threshold value was 0.0116 corresponding to sensitivity 80% and specificity 90%. In immunostaining of CXCL14, the staining score was significantly higher in MPP cases than others, where not only MPP component but also other components showed heterogeneous staining in adenocarcinoma tissues with MPP. Moreover, higher staining score of CXCL14 significantly associated with poorer prognosis, in all patients (P=0.01) or within cases at stage I-III (P=0.01).In summary, we identified CXCL14 as a possible diagnostic biomarker of MPP.

Porphyromonas gingivalis is a keystone pathogen in chronic periodontitis. Its expression of gingipain proteases (Kgp and RgpA/B) is central to the stimulation of chronic inflammation. In this study, we investigated the inflammatory response of oral epithelial cells to P. gingivalis. The cells responded by upregulating the expression of the orphan chemokine CXCL14. The stimulation of CXCL14 expression was largely triggered by the gingipain proteases and was dependent on the host protease-activated receptor PAR-3. Significantly, CXCL14 expression was transcriptionally repressed in response to epidermal growth factor (EGF)-induced activation of the MEK-ERK1/2 pathway. P. gingivalis overcomes the repression of CXCL14 via the gingipain protease-mediated degradation of EGF. Therefore, P. gingivalis not only directly stimulates CXCL14 expression via PAR-3 but also promotes its expression by antagonising EGF signalling. In addition to chemotactic activity, some chemokines also have antimicrobial activities. CXCL14 was demonstrated to have bactericidal activity, against commensal oral streptococci associated with health. Notably though, P. gingivalis was not susceptible to killing by CXCL14, potentially because the gingipain proteases can degrade CXCL14. This suggests that the stimulation of dysregulated CXCL14 expression by P. gingivalis may help promote dysbiosis and the development of chronic periodontitis.

Background: Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders.

Results: This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value < 0.05. The expression profiling and the functional enrichment analysis revealed the role of these genes in cell communication, signal transduction, and immune response. The protein-protein interaction showed the functional association of the source genes (CTNNB1, NNMT, PTCH1, CALD1, CXCL14, CXCL8, and TNFAIP3) with the target proteins, such as AXIN, MAPK, IL6, STAT, APC, GSK3B, and SHH.

Conclusion: The integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.

Keywords: Biomarkers; Colorectal cancer; Functional genomics; Microarrays; PPI network.

Skin provides the first line of physical and immunological defense against the environmental insults. However, the age-related changes in the immune function of the human skin are unclear. Here, we investigated the age-related changes in epidermal Langerhans cells (LCs), which play a sentinel role in the initiation of the immune responses in the skin. We found a significant reduction in the number of epidermal LCs in the sun-protected skin with age. Among the possible explanations for this reduction, we found that the number of CD14⁺ CD207⁺ CCR6⁺ dermal-resident monocytes that can differentiate into epidermal LCs were markedly reduced with age (p = 0.0057). Among the chemokines that can recruit these cells into the skin, the expression of CXCL14 was significantly down-regulated in the epidermal keratinocytes with age. Importantly, we discovered that young skin recruited significantly more monocytic THP-1 cells compared to old skin ex vivo. This recruitment was blocked by CXCL14 neutralizing antibody and was conversely promoted by CXCL14 treatment. Collectively, our findings indicate that decreased CXCL14-mediated recruitment of CD14⁺ monocytes in the human skin results in the reduction of epidermal LCs with age, and CXCL14 may provide a novel therapeutic target for the prevention of age-related LC reduction.

CXCL14 serves as a chemoattractant for activated macrophages, immature dendritic cells and natural killer cells, as well as an antiangiogenic factor by preventing the migration of endothelial cells. CXCL14 also exerts an inhibitory effect on the CXCL12/CXCR4 signaling pathway, which is involved in the maintenance of T-helper (Th)2 bias, and promotes Th1 immune response under the physiological and pathological conditions. Because CXCL14-mediated biological processes seem to be involved in the development of systemic sclerosis (SSc), which is characterized by Th2/Th17-skewed immune polarization and impaired neovascularization, we investigated the clinical correlation of serum CXCL14 levels in patients with this disease. Serum CXCL14 levels were significantly decreased in SSc patients compared with healthy individuals and in diffuse cutaneous SSc patients relative to limited cutaneous SSc patients. SSc patients with digital ulcers had serum CXCL14 levels significantly lower than those without. Furthermore, i.v. cyclophosphamide pulse significantly increased serum CXCL14 levels as compared with the baseline in SSc patients with interstitial lung disease successfully treated with this therapy. These results indicate that decreased CXCL14 expression may contribute to the maintenance of Th2-skewed immune polarization and dysregulated neovascularization, both of which underlie the developmental process of SSc.

BACKGROUND This study aimed to investigate the effects of static cold storage (SCS) and hypothermic machine perfusion (HMP) on the oxidative stress factors (OSF), adhesion molecules (AM), and zinc finger transcription factor (Snail) before and after liver transplantation. MATERIAL AND METHODS Experimental dogs were randomly divided into donor (group A), SCS (group B), and HMP (group C) (n=30) groups. Livers retrieved from group A were transplanted into group B after SCS, and the livers sampled from group B were transplanted into group C after HMP. The dogs in group A were euthanized and discarded, and the livers sampled from group C were used for other experiments. Twenty dogs with successful liver transplants were randomly selected from groups B and C for analysis. RESULTS During the liver sampling process, the levels of OSF, AM, and Snail between the 2 groups showed no significant differences (P>0.05); before the transplantation, the levels of chemokine CXCL14 and Snail between the 2 groups showed no significant differences (P>0.05), and compared with group B, HIF-1α and P-selectin in group C were lower (P<0.01); 60 min after the transplantation, HIF-1α, chemokine CXCL14, P-selectin, and Snail in group C were lower than that in group B (P<0.01). CONCLUSIONS HMP can significantly reduce the levels of OSF and inflammatory factors, which is conducive for liver transplantation.

Microglia, the resident immune cells of the central nervous system, play an important role in the brain. Microglia have a special spatiotemporal distribution during the development of the cerebral cortex. Neural progenitor cells (NPCs) are the main source of neural-specific cells in the early brain. It is unclear whether NPCs affect microglial development and what molecular mechanisms control early microglial localization. H2A.Z.2, a histone variant of H2A, has a key role in gene expression regulation, genomic stability, and chromatin remodeling, but its function in brain development is not fully understood. Here, we found that the specific deletion of H2A.Z.2 in neural progenitor cells led to an abnormal increase in microglia in the ventricular zone/subventricular zone (VZ/SVZ) of the embryonic cortex. Mechanistically, H2A.Z.2 regulated microglial development by incorporating G9a into the promoter region of Cxcl14 and promoted H3k9me2 modification to inhibit the transcription of Cxcl14 in neural progenitor cells. Meanwhile, we found that the deletion of H2A.Z.2 in microglia itself had no significant effect on microglial development in the early cerebral cortex. Our findings demonstrate a key role of H2A.Z.2 in neural progenitor cells in controlling microglial development and broaden our knowledge of 2 different types of cells that may affect each other through crosstalk in the central nervous system.

Background: Tetraspanin CD82 is a tumor metastasis suppressor that is known to down regulate in various metastatic cancers. However, the exact mechanism by which CD82 prevents cancer metastasis is unclear. This study aims to identify genes that are regulated by CD82 in human prostate cell lines.

Methods: We used whole human genome microarray to obtain gene expression profiles in a normal prostate epithelial cell line that expressed CD82 (PrEC-31) and a metastatic prostate cell line that does not express CD82 (PC3). Then, siRNA silencing was used to knock down CD82 expression in PrEC-31 while CD82 was re-expressed in PC3 to acquire differentially-expressed genes in the respective cell line.

Results: Differentially-expressed genes with a P < 0.05 were identified in 3 data sets: PrEC-31 (+CD82) vs PrEC-31(-CD82), PC3-57 (+CD82) vs. PC3-5 V (-CD82), and PC3-29 (+CD82) vs. PC3-5 V (-CD82). Top 25 gene lists did not show overlap within the data sets, except (CALB1) the calcium binding protein calbindin 1 which was significantly up-regulated (2.8 log fold change) in PrEC-31 and PC3-29 cells that expressed CD82. Other most significantly up-regulated genes included serine peptidase inhibitor kazal type 1 (SPINK1) and polypeptide N-acetyl galactosaminyl transferase 14 (GALNT14) and most down-regulated genes included C-X-C motif chemokine ligand 14 (CXCL14), urotensin 2 (UTS2D), and fibroblast growth factor 13 (FGF13). Pathways related with cell proliferation and angiogenesis, migration and invasion, cell death, cell cycle, signal transduction, and metabolism were highly enriched in cells that lack CD82 expression. Expression of two mutually inclusive genes in top 100 gene lists of all data sets, runt-related transcription factor (RUNX3) and trefoil factor 3 (TFF3), could be validated with qRT-PCR.

Conclusion: Identification of genes and pathways regulated by CD82 in this study may provide additional insights into the role that CD82 plays in prostate tumor progression and metastasis, as well as identify potential targets for therapeutic intervention.

Keywords: CD82; Gene expression; KAI1; Metastasis tumor suppressor; Microarray; Prostate cancer.

The occurrence of portal vein tumor thrombus (PVTT) is strongly correlated to the staging and poor prognosis of hepatocellular carcinoma (HCC) patients. However, the mechanisms of PVTT formation remain unclear. This study aimed to investigate differentially expressed genes (DEGs) between primary tumor (PT) and PVTT tissues and comprehensively explored the underlying mechanisms of PVTT formation. The DEGs between PT and paired PVTT tissues were analyzed using transcriptional data from the Gene Expression Omnibus (GEO) database. The expression, clinical relevance, prognostic significance, genetic alternations, DNA methylation, correlations with immune infiltration, co-expression correlations, and functional enrichment analysis of the DEGs were explored using multiple databases. As result, 12 DEGs were commonly down-expressed in PVTT compared with PT tissues among three datasets. The expression of DCN, CCL21, IGJ, CXCL14, FCN3, LAMA2, and NPY1R was progressively decreased from normal liver, PT, to PVTT tissues, whose up-expression associated with favorable survivals of HCC patients. The genetic alternations and DNA methylation of the DEGs frequently occurred, and several methylated CpG sites of the DEGs significantly correlated with outcomes of HCC patients. The immune infiltration in the tumor microenvironment of HCC was correlated with the expression level of the DEGs. Besides, the DEGs and their co-expressive genes participated in the biological processes of extracellular matrix (ECM) organization and focal adhesion. In summary, this study indicated the dysregulation of ECM and focal adhesion might contribute to the formation of PVTT. And the above seven genes might serve as potential biomarkers of PVTT occurrence and prognosis of HCC patients.

Keywords: bioinformatics; hepatocellular carcinoma; immune infiltration; portal vein tumor thrombus; prognosis.

The utility of the urinary proteome in infectious diseases remains unclear. Here, we analyzed the proteome and metabolome of urine and serum samples from patients with COVID-19 and healthy controls. Our data show that urinary proteins effectively classify COVID-19 by severity. We detect 197 cytokines and their receptors in urine, but only 124 in serum using TMT-based proteomics. The decrease in urinary ESCRT complex proteins correlates with active SARS-CoV-2 replication. The downregulation of urinary CXCL14 in severe COVID-19 cases positively correlates with blood lymphocyte counts. Integrative multiomics analysis suggests that innate immune activation and inflammation triggered renal injuries in patients with COVID-19. COVID-19-associated modulation of the urinary proteome offers unique insights into the pathogenesis of this disease. This study demonstrates the added value of including the urinary proteome in a suite of multiomics analytes in evaluating the immune pathobiology and clinical course of COVID-19 and, potentially, other infectious diseases.

Keywords: COVID-19; CXCL14; ESCRT super-complex; metabolomics; proteomics; renal injury; serum; urine.

Pulmonary fibrosis (PF) is a heterogeneous pathological process in lung tissues with a considerable mortality rate. Currently, combination therapy represents an effective approach to treat PF. Dexamethasone (Dxs) and berberine (BBR) are widely applied to inhibit the progression of PF. Dxs plus penehyclidine hydrochloride or alfacalcidol have been reported more effective in therapy compared with any single drug treatment. However, whether Dxs plus BBR induces an increased antifibrotic effect remains unknown. The current study aimed to evaluate the therapeutic effect of BBR plus Dxs in bleomycin (BLM)-induced PF. A PF model in rats was established and rats were divided into control, BLM, BBR, Dxs and BBR plus Dxs groups (n=9/group). On days 3, 7 and 14, blood samples were collected from the eyes of the rats (n=6/group). CXC chemokine ligand 14 (CXCL14), collagen I, collagen III, matrix metalloproteinase (MMP)2 and MMP9 serum levels were measured by ELISA. On day 14, all rats were sacrificed. Hematoxylin and eosin analysis, Masson staining and hydroxyproline (Hyp) assessment were performed to observe histopathological changes and collagen deposition. mRNA and protein levels of CXCL14, CXC chemokine receptor 4 (CXCR4), collagen I/III, α-smooth muscle actin (α-SMA), MMP2/9 and phosphorylated-Smad 2/3 in lung tissue were further evaluated. Similar effects in preventing lung damage were observed histopathologically for Dxs and BBR compared with the BLM group. These treatments further reduced levels of Hyp, CXCL14, CXCR4, collagen I/III, MMP2/9, α-SMA and p-Smad 2/3. The combination of Dxs and BBR exhibited increased effectiveness compared with the single treatments. Results further suggested that antifibrotic mechanisms were involved in inhibiting CXCL14 and MMP2/MMP9 expression, and preventing the activation of Smad2/3 and hedgehog signaling pathways. The combined use of Dxs and BBR may represent a potential therapeutic approach for PF.

Chemokines are important in the development and progression of tumors. We investigated the expression of CXCL14 and CXCL16 in colon cancer. Expression of mRNA was assessed in primary tumors and lymph nodes and CXCL16 mRNA levels were correlated to patient's survival. Protein expression was investigated by two-color immunofluorescence and immunomorphometry. CXCL14 and CXCL16 mRNA levels and protein expression were significantly higher in colon cancer primary tumors compared to apparently normal colon tissue. Positive cells were tumor cells, as revealed by anti-CEA and anti-EpCAM staining. CXCL16, but not CXCL14, mRNA levels were significantly higher in hematoxylin and eosin positive (H&E(+)) compared to H&E(-) colon cancer lymph nodes or control nodes (P < 0.0001). CXCL16 mRNA was expressed in 5/5 colon cancer cell lines while CXCL14 was expressed significantly in only one. Kaplan-Meier analysis revealed that colon cancer patients with lymph nodes expressing high or very high levels (7.2 and 11.4 copies/18S rRNA unit, respectively) of CXCL16 mRNA had a decreased mean survival time of 30 and 46 months at the 12-year follow-up (P = 0.04, P = 0.005, respectively). In conclusion, high expression of CXCL16 mRNA in regional lymph nodes of colon cancer patients is a sign of a poor prognosis.

Skeletal muscle in adults retains a robust ability to regenerate after injury, which progressively declines with age. Many of the regulators of skeletal myogenesis are unknown or incompletely understood. Intriguingly, muscle cells secrete a wide variety of factors, such as cytokines, which can influence muscle development and regeneration in an autocrine or paracrine manner. Here we describe chemokine (C-X-C motif) ligand 14 (Cxcl14) as a novel negative regulator of skeletal myogenesis. We found that Cxcl14 expression in myoblasts prevented cell cycle withdrawal, thereby inhibiting subsequent differentiation. Knockdown of Cxcl14 in vitro enhanced myogenic differentiation through promoting cell cycle withdrawal in an ERK1/2-dependent manner. Recapitulating these in vitro observations, the process of muscle regeneration following injury in young adult mice was accelerated by Cxcl14 depletion, accompanied by reduced cell proliferation. Furthermore, impaired capacity for muscle regeneration in aging mice was fully restored by Cxcl14 depletion. Our results indicate that Cxcl14 may be a promising target for development of therapeutics to treat muscle disease, especially aging-related muscle wasting.

Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. Enhancer of homolog 2 (EZH2), is a histone methyltransferase that methylates lysine residue 27, and thereby, suppresses gene expression. EZH2 plays integral role in the uterus and other reproductive organs. We have previously shown that conditional deletion of uterine EZH2 results in increased proliferation of luminal and glandular epithelial cells, and RNAseq analyses reveal several uterine transcriptomic changes in Ezh2 conditional (c) knockout (KO) mice that can affect estrogen signaling pathways. To pinpoint the origin of such gene expression changes, we used the recently developed spatial transcriptomics (ST) method with the hypotheses that Ezh2cKO mice would predominantly demonstrate changes in epithelial cells and/or ablation of this gene would disrupt normal epithelial/stromal gene expression patterns. Uteri were collected from ovariectomized adult WT and Ezh2cKO mice and analyzed by ST. Asb4, Cxcl14, Dio2, and Igfbp5 were increased, Sult1d1, Mt3, and Lcn2 were reduced in Ezh2cKO uterine epithelium vs. WT epithelium. For Ezh2cKO uterine stroma, differentially expressed key hub genes included Cald1, Fbln1, Myh11, Acta2, and Tagln. Conditional loss of uterine Ezh2 also appears to shift the balance of gene expression profiles in epithelial vs. stromal tissue toward uterine epithelial cell and gland development and proliferation, consistent with uterine gland hyperplasia in these mice. Current findings provide further insight into how EZH2 may selectively affect uterine epithelial and stromal compartments. Additionally, these transcriptome data might provide the mechanistic understanding and valuable biomarkers for human endometrial disorders with epigenetic underpinnings.

Keywords: Endometrial Cancer; Endometrium; Epigenetics; Estrogen; Female Reproduction; Histone Proteins; RNA-seq; Uterus.

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1^GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.

Keywords: RNA-sequencing; age-related macular degeneration (AMD); aging; choroidal neovascularization (CNV); immunosenescence; microglia; myeloid cells.

The RNA-binding protein Apobec1 complementation factor (A1CF) regulates posttranscriptional ApoB mRNA editing, but the range of RNA targets and the long-term effect of altered A1CF expression on liver function are unknown. Here we studied hepatocyte-specific A1cf-transgenic (A1cf+/Tg), A1cf+/Tg Apobec1-/-, and A1cf-/- mice fed chow or high-fat/high-fructose diets using RNA-Seq, RNA CLIP-Seq, and tissue microarrays from human hepatocellular cancer (HCC). A1cf+/Tg mice exhibited increased hepatic proliferation and steatosis, with increased lipogenic gene expression (Mogat1, Mogat2, Cidea, Cd36) associated with shifts in polysomal RNA distribution. Aged A1cf+/Tg mice developed spontaneous fibrosis, dysplasia, and HCC, and this development was accelerated on a high-fat/high-fructose diet and was independent of Apobec1. RNA-Seq revealed increased expression of mRNAs involved in oxidative stress (Gstm3, Gpx3, Cbr3), inflammatory response (Il19, Cxcl14, Tnfα, Ly6c), extracellular matrix organization (Mmp2, Col1a1, Col4a1), and proliferation (Kif20a, Mcm2, Mcm4, Mcm6), and a subset of mRNAs (including Sox4, Sox9, Cdh1) were identified in RNA CLIP-Seq. Increased A1CF expression in human HCC correlated with advanced fibrosis and with reduced survival in a subset with nonalcoholic fatty liver disease. In conclusion, we show that hepatic A1CF overexpression selectively alters polysomal distribution and mRNA expression, promoting lipogenic, proliferative, and inflammatory pathways leading to HCC.

Keywords: Hepatology; Liver cancer; Metabolism; RNA processing.

OBJECTIVE

To identify differentially expressed genes in Modic changes by gene microarray method.

METHODS

From August 2014 to December 2014, gene expression profiling analysis of 5 lumbar endplates with Modic changes and 5 control specimens without Modic changes were performed in Department of Orthopaedics, Zheng Linhai Second People's Hospital and Department of Orthopaedics, Shanghai Jiaotong University School of Medicine. The functional analysis (Gene Ontology and KEGG) of deregulated genes was carried out.The qRT-PCR analysis was performed to validate differential expression genes.

RESULTS

Of 263 significantly differential expression genes (P<0.05, Fold Change>> 2), 107 were over-expressed and 156 under-expressed genes.Those deregulated genes were mainly involved in chemotaxis and cell motion. The qRT-PCR analysis of 2 up-regulated genes (CXCL14, KCNMA1) and 4 under-regulated genes (MARCKS, ZEB2, PSMF1, and CNN2) mRNA expression levels validated the results from the microarray analysis.

CONCLUSIONS

There are differentially expressed genes between lumbar endplate with Modic changes and without Modic changes.Modic changes may be multiple genes involved and regulated pathological changes.

Although chemokines mainly function to activate leukocytes and to direct their migration, novel evidence indicates non-immune functions for chemokines within the nervous and endocrine systems. These include development of the nervous system, neuromodulation, neuroendocrine regulation and direct neurotransmitter-like actions. In order to clarify a potential role for chemokines and their receptors in the stress response of fish, we studied changes in the expression patterns of CXC ligands and their receptors in the stress axis organs of carp, during a restraint stress procedure. We showed that stress down-regulated the gene expression of CXCL9-11 (CXCb1 and CXCb2) in stress axis organs and up-regulated expression of CXCR4 chemokine receptor in NPO and pituitary. Moreover, upon stress, reduced gene expression of CXCL12a and CXCL14 was observed in the head kidney. Our results imply that in teleost fish, CXC chemokines and their receptors are involved in neuroendocrine regulation. The active regulation of their expression in stress axis organs during periods of restraint indicates a significant role in the stress response.

OBJECTIVE

To explore the predictive value of the prognosis and outcome for optic neuritis (ON) and neuromyelitis optica (NMO) by investigating the levels and variation of CXCL12, PDGF and CXCL14 in CSF of patients with ON and NMO.

METHODS

Retrospective study. Thirty-five patients with ON, 10 patients with NMO and 10 patients with cerebral venous sinus thrombosis (CVST) were scheduled in the research unit from September 2012 to September 2013 in Neuro-Ophthalmology Department of PLA General Hospital. Clinical data and cerebrospinal fluid (CSF) parameters were collected. CXCL12, PDGF and CXCL14 concentrations were measured in CSF using enzyme linked immunosorbent assay (ELISA). The CXCL12, PDGF and CXCL14 levels in CSF were compared by using ANOVA in different diseases with different phases and recurrent cases found by MRI. Multiple comparisons were used by LSD method. The comparison of positive rate for MRI in ON different phases was used by exact probability. Meanwhile, correlation analysis was conducted between CXCL12, PDGF, CXCL14 and white blood cells (WBC), IgG and protein in CSF.

RESULTS

Compared with NMO group (3.69±0.35, 2.04±0.24, 7.05±0.94), the CXCL12, PDGF and CXCL14 levels in CSF were higher in ON (4.39±0.51, 2.51±0.39, 8.65±1.55) and CVST(4.84± 0.49, 2.79±0.47, 10.53±1.11) group (F=14.593, 10.060, 10.003,P<0.001, <0.001, <0.001), especially the CXCL12, PDGF and CXCL14 levels in CSF of CVST group patients were higher than that in ON group. Among them, the CXCL12 and PDGF levels in CSF were higher in acute phase of ON (4.63±0.50, 2.65±0.40) and CVST(4.84±0.49, 2.79±0.47) group than stationary phase of ON (4.13±0.39, 2.34±0.32) group (F=8.823, 4.906, P=0.001, 0.012). In addition, 28 of 35 ON patients were conducted the cerebral or orbital magnetic resonance imaging (MRI). The result showed that the CXCL12 and PDGF levels in CSF of patients with positive finding in MRI (3.96±0.30, 2.23±0.16) were higher than those patients with negative finding in MRI (4.64±0.42, 2.62±0.42) (t=-4.754, -2.977, all P<0.01). Besides that, there was higher correlation between the CXCL12 level and PDGF in CSF (P<0.01).

CONCLUSIONS

Reduced concentration of cytokine that promoted remyelination such as CXCL12 and PDGF in cerebrospinal fluid of the ON and NMO patients may predict a bad myelin regeneration.