Antidepressant-like effects of geniposide in chronic unpredictable mild stress-induced mice by regulating the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 networks.

Evidence exists suggesting the anti-depressive activities of geniposide (GP), a major compound in Gardenia jasminoides Ellis. Accordingly, the present study attempts to explore the anti-depressive mechanism of GP in chronic unpredictable mild stress (CUMS)-induced depression-like behaviors of mice. CUMS-induced mice were given GP daily and subjected to behavioral tests to observe the effect of GP on the depression-like behaviors. It was noted that GP administration reduced depression-like behaviors in CUMS mice. Transcriptome sequencing was conducted in three control and three CUMS mice. Differentially expressed circRNAs, lncRNAs and mRNAs were then screened by bioinformatics analyses. Intersection analysis of the transcriptome sequencing results with the bioinformatics analysis results was followed to identify the candidate targets. We found that Gata2 alleviated depression-like behaviors via the metabolism- and synapse-related pathways. Gata2 was a target of miR-25-3p, which had binding sites to circ_0008405 and Oip5os1. circ_0008405 and Oip5os1 competitively bound to miR-25-3p to release the expression of Gata2. GP administration ameliorated depression-like behaviors in CUMS mice through regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks. Taken together, GP may exert a potential antidepressant-like effect on CUMS mice, which is ascribed to regulation of the circ_0008405/miR-25-3p/Gata2 and Oip5os1/miR-25-3p/Gata2 crosstalk networks.

Multimodality imaging of carotid web: A case report and literature review.

OBJECTIVES: The carotid web is a compelling potential mechanism of cryptogenic stroke. It is easy for it to escape diagnosis or be misdiagnosed, since it rarely causes hemodynamic stenosis. Currently, there is a lack of consensus on the prevalence, etiology, imaging evaluation, and treatment strategy of carotid artery. We aimed to present the multimodal imaging of carotid web and comprehensively review the characteristics of carotid web. METHODS: A 38 year-old man with carotid web, who presented with acute left hemispheric syndrome, was not identified by computed tomography angiography and high-resolution magnetic resonance imaging in the initial report, but were identified in retrospect and then confirmed by digital subtraction angiography and histopathology. A literature review of carotid web was performed to identify prevalence, nature history, imaging tools, and optimal management of carotid web. RESULTS: 80 reports including 681 patients with carotid web were identified. The prevalence of symptomatic carotid web was 1.2% in patients with transient ischemic attack/stroke, 6.4% in patients with cryptogenic ischemic stroke, 1.1% in patients with large vessel occlusion stroke, and 4.4% in patients who operated on for carotid stenosis. A total of 23.0% patients had bilateral carotid web. In most patients, carotid web was located on the posterior wall (87.3%) of the carotid artery (98.7%). The mean length was 3.3 mm and mean stenosis rate was 20.9%. A total of 31.6% percent patients had thrombus trapped in carotid web and 75.9% patients had large vessel occlusion. Computed tomography angiography and digital subtraction angiography were favorable tools to detect carotid web. There were rare periprocedural complications and no recurrent strokes in carotid revascularization patients. CONCLUSIONS: carotid web is an under-recognized cause of ischemic stroke. It is easy to be missed or misdiagnosed. Carotid revascularization can effectively prevent recurrent stroke for patients with symptomatic carotid web. Clinicians should strength their learning and understanding of carotid web.

Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China.

BACKGROUND: The gut microbiota (GM) has been proven to play a role in the regulation of host lipid metabolism, which provides a new theory about the pathogenesis of dyslipidemia. However, the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation. AIM: To investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population. METHODS: This study ultimately recruited 142 participants (73 females and 69 males) at Honghui Hospital, Xi'an Jiaotong University. The anthropometric and blood metabolic parameters of all participants were measured. According to their serum lipid levels, female and male participants were classified into a high triglyceride (H_TG) group, a high total cholesterol (H_CHO) group, a low high-density lipoprotein cholesterol (L_HDL-C) group, and a control (CON) group with normal serum lipid levels. Fresh fecal samples were collected for 16S rRNA gene sequencing. UPARSE software, QIIME software, the RDP classifier and the FAPROTAX database were used for sequencing analyses. RESULTS: The GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM. Different GM features were identified between females and males, and the associations between GM and serum lipid profiles were different in females and males. The GM features in different dyslipidemia subgroups changed in both female patients and male patients. Proteobacteria, Lactobacillaceae, Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females, while Coriobacteriia were enriched in L_HDL-C females. In the comparison among the three dyslipidemia subgroups in females, Lactobacillus_salivarius were enriched in H_CHO females, and Prevotellaceae were enriched in L_HDL-C females. Compared with CON or H_TG males, Prevotellaceae, unidentified_Ruminococcaceae, Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males (P value < 0.05), and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups. Additionally, Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels, and Roseburia were positively correlated with serum TG level. Furthermore, Proteobacteria (0.724, 95%CI: 0.567-0.849), Lactobacillaceae (0.703, 95%CI: 0.544-0.832), Lactobacillus (0.705, 95%CI: 0.547-0.834) and Lactobacillus_salivarius (0.706, 95%CI: 0.548-0.835) could distinguish H_CHO females from CON females, while Coriobacteriia (0.710, 95%CI: 0.547-0.841), Coriobacteriales (0.710, 95%CI: 0.547-0.841), Prevotellaceae (0.697, 95%CI: 0.534-0.830), Roseburia (0.697, 95%CI: 0.534-0.830) and Roseburia_inulinivorans (0.684, 95%CI: 0.520-0.820) could discriminate H_TG males from CON males. Based on the predictions of GM metabolic capabilities with the FAPROTAX database, a total of 51 functional assignments were obtained in females, while 38 were obtained in males. This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females, but decreased in L_HDL-C males compared with CON males. CONCLUSION: This study indicates associations of GM with serum lipid profiles, supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia, and sex differences should be considered.

Lipid metabolism analysis for peripheral blood in patients with alcohol-induced and steroid-induced osteonecrosis of the femoral head. / é ’ç²¾æ€§å’Œæ¿€ç´ æ€§è‚¡éª¨å¤´åæ­»çš„å¤–å‘¨è¡€è„‚è´¨ç»„å­¦åˆ†æž.

OBJECTIVES: Osteonecrosis of the femoral head (ONFH), also known as vascular necrosis of the femoral head, is combined with lipid metabolism disorders in most patients. This study aims to explore the lipid metabolism profiles in different subtypes of ONFH. METHODS: The subjects were divided into an alcohol-induced osteonecrosis of the femoral head (AONFH) group, a steroid-induced osteonecrosis of the femoral head (SONFH) group, and a normal control (NC) group (n=16, 29, and 32, respectively). Ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) was used to detect the lipidomics analysis in the peripheral blood samples of subjects and identify the underlying biomarkers. The samples were preprocessed, the partial least squares discriminant analysis (PLS-DA) was adopted, and the variable importance for the projection (VIP) values were calculated to measure the expression pattern of each lipid metabolite and observe the influence and explanatory power of the expression pattern of each lipid metabolite on the classification and discrimination between the different groups. The lipid metabolites with fold change (FC)>2, P<0.05 and VIP>1 in the different groups were screened as differential lipids. Among them, the differential lipids co-existing in the AONFH group and the SONFH group were regarded as common differential lipids for ONFH, and the differential lipids that exist separately were regarded as specific differential lipids in the AONFH group or the SONFH group. Binary logistic regression was used to evaluate the diagnostic value of differential lipid metabolites on the basis of the receiver operator characteristic (ROC) curve analysis. Based on the disease stage information, the correlation between the differential lipids and the disease stage was analyzed in the AONFH group and the SONFH group. RESULTS: In this study, 1 358 lipid metabolites were detected in each plasma sample. Compared with the NC group, there were significant difference in the expression patterns of lipid metabolism profiles in the AONFH group and the SONFH group. A total of 62 and 64 differential lipid metabolites were screened in the AONFH and SONFH patients (FC>2, P<0.05, VIP>1) respectively, and these differential lipids were mainly up-regulated in the disease samples. Nine differential lipid metabolites were further identified, which were shared by the AONFH group and the SONFH group; the area under the curve (AUC) in 6 kinds of lipid components was greater than 0.7, including 1-myristoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, hypoxanthin, serotonin, PE (19:0/22:5), PE (19:0/22:5), and cholest-5-en-3-yl beta-D-glucopyranosiduronic acid. Fifty-three specific differential lipid metabolites were identified in the AONFH group, and 55 specific differential lipid metabolites were identified in the SONFH group. The AUC in 6 kinds of lipid components was greater than 0.9, including 1D-myo-Inositol 1,2-cyclic phosphate, L-pyroglutamic acid, DL-carnitine, 8-amino-7-oxononanoic acid, Clobetasol, and presqualene diphosphate. In the AONFH group, there were 9 differential lipid metabolites related to the disease stages, including LPG 18:1, serotonin, PC (22:4e/23:0), PC (19:2/18:5), hypoxanthin, PE (18:1/20:3), LPE 18:1, 1-stearoyl-2-arachidonoyl-sn-glycerol, and PE (16:0/18:1); with AONFH disease progresses from I/II stages to III/IV stages, the relative content of these 9 differential lipid metabolites was increased. In the SONFH group, 8 differential lipid metabolites were found to be related to the stage of the disease, including TM6076000, 4-(1,1-dimethylpropyl)phenol, D-617, asarone, phenylac-gln-OH, creatine, leu-pro, and 8-amino-7-oxononanoic acid; and with the SONFH progressed from stage I/II to stage III/IV, the content of these 8 differential lipid metabolites were gradually increased. CONCLUSIONS: This study analyzes the characteristics of the plasma lipid metabolism profile in the AONFH and SONFH patients, and which identifies the differential lipid metabolites related to disease diagnosis and evaluation. These results provide evidence for exploring lipid metabolism alterations and the mining of novel lipid biomarkers for the ONFH.

Plasma lipidomics analysis reveals altered lipids signature in patients with osteonecrosis of the femoral head.

INTRODUCTION: Although studies have established a link between lipid metabolism disorder and osteonecrosis of the femoral head (ONFH), the characteristics of the circulating lipidome signature of ONFH have not yet been investigated and need to be explored. OBJECTIVES: We aimed to explore the plasma lipidome signatures in patients with ONFH, and to identify specific lipid biomarkers of ONFH. METHODS: In this study, a comprehensive detection and analysis of plasma lipidomics was conducted in clinical human cohort, including 32 healthy normal control (NC) subjects and 91 ONFH patients in different subgroups [alcohol-induced ONFH (AONFH), steroid-induced ONFH (SONFH), and traumatic-induced ONFH (TONFH)] or at different disease stages (stage I, II, III and IV of ONFH) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Overall, the plasma lipidome profile differs between ONFH and NC samples. Lipidome signature including 22 common differentially expressed lipids (DELs) in all three subgroups (variable importance in projection > 1, P < 0.05, fold change > 1.5 or < 0.67, compared to the NC group) was identified. Besides, the subtype-specific lipidome profiles for each ONFH subgroup were also analyzed. Generally, the AONFH subgroup has the largest number of DELs, and the plasma levels of triacylglycerol lipid compounds increased obviously in the AONFH samples. In the subgroup of SONFH, the relative abundance of lipid 4-Aminobenzoic acid increased significantly with changes in the expression of several of its interactive genes. We have identified that 9 stage-positive and 2 stage-negative lipids may function as novel biomarkers predicting the progression of ONFH. CONCLUSION: Our study presents an overview of the phenotype-related plasma lipidome signature of patients with ONFH. The results will provide insight into the mechanisms underlying the metabolism of lipids in the pathogenesis and progression of ONFH and help identify novel lipids biomarkers or disease diagnosis and treatment targets.

Regulation of Neurogenesis and Neuronal Differentiation by Natural Compounds.

Neuronal damage or degeneration is the main feature of neurological diseases. Regulation of neurogenesis and neuronal differentiation is important in developing therapies to promote neuronal regeneration or synaptic network reconstruction. Neurogenesis is a multistage process in which neurons are generated and integrated into existing neuronal circuits. Neuronal differentiation is extremely complex because it can occur in different cell types and can be caused by a variety of inducers. Recently, natural compounds that induce neurogenesis and neuronal differentiation have attracted extensive attention. In this paper, the potential neural induction effects of medicinal plant-derived natural compounds on neural stem/progenitor cells (NS/PCs), the cultured neuronal cells, and mesenchymal stem cells (MSCs) are reviewed. The natural compounds that are efficacious in inducing neurogenesis and neuronal differentiation include phenolic acids, polyphenols, flavonoids, glucosides, alkaloids, terpenoids, quinones, coumarins, and others. They exert neural induction effects by regulating signal factors and cellspecific genes involved in the process of neurogenesis and neuronal differentiation, including specific proteins (ß-tubulin III, MAP-2, tau, nestin, neurofilaments, GFAP, GAP-43, NSE), related genes and proteins (STAT3, Hes1, Mash1, NeuroD1, notch, cyclin D1, SIRT1, Reggie-1), transcription factors (CREB, Nkx-2.5, Ngn1), neurotrophins (BDNF, NGF, NT-3), and signaling pathways (JAK/STAT, Wnt/ß-catenin, MAPK, PI3K/Akt, GSK-3ß/ß-catenin, Ca2+/CaMKII/ATF1, Nrf2/HO-1, BMP).The natural compounds with neural induction effects are of great value for neuronal regenerative medicine and provide promising prevention and treatment strategies for neurological diseases.

Spectrophotometric evaluation of color errors generated in the visual color duplication procedure for current ceramic veneers.

BACKGROUND/PURPOSE: Color errors associated with the visual color duplication approach for ceramic laminate veneers are still challenging in esthetic dentistry. The aim of this study is to evaluate color errors generated during traditional visual shade matching approach. MATERIALS AND METHODS: Eighteen stooth-shaped veneer discs (shade A2 and 0.7 mm in thickness) were fabricated using six veneer materials. The veneer specimens placed on five extracted teeth with nominal shade A2 formed veneer-tooth combinations. Color coordinates of the A2 shade tab, the extracted teeth, and the veneer-tooth combinations were measured using a spectrophotometer. Then, the veneers were reduced to 0.5 mm, and 0.3 mm in thickness consecutively. Color measurements were performed repeatedly. Color differences of the extracted teeth to veneer-tooth combinations (ΔEt-v), veneer-tooth combinations to shade tab (ΔEv-s), and translucency parameter (TP) values were calculated and analyzed using Two-way ANOVA. RESULTS: ΔEt-v ranged from 2.0937 to 5.0603 (mean of 3.1833±1.5485). Mean of ΔEv-s was 4.0103±1.8508. ΔEt-v and ΔEv-s values were significantly influenced by veneer material and thickness (P<0.05). TP values decreased gradually with the lessening of veneers thickness. CONCLUSION: Acceptable color duplication of ceramic veneers cannot be achieved by routine visual shade replica protocols, when the thickness of veneers is less than 0.7 mm. Specified color matching standards for the ceramic veneers are needed.

Serum anti-Müllerian hormone levels are associated with low bone mineral density in premenopausal women.

OBJECTIVE: To investigate the associations between anti-Müllerian hormone (AMH) and bone mineral density (BMD) induced by ovarian insufficiency in premenopausal women. METHODS: Subjects were consecutively enrolled from January 2015 to December 2018. Dual energy X-ray absorptiometry (DXA) examination was set as the gold standard, with T-scores less than -2.5/1 as thresholds for the definition of osteoporosis (OP)/osteopenia. RESULTS: A total of 87 subjects were included in the low BMD group, and 39 subjects were included in the control group. Serum AMH levels were decreased significantly in the low BMD group (p < 0.05) with a negative correlation between AMH and age. Strong positive correlations between AMH and BMD/T-score existed in all subjects and subjects with low BMD, and remained even after age adjustment. An exploratory multivariate regression model indicated that age and AMH remained predictive and might be independent risk factors with adjusted odds ratios (ORs) of 0.9 (p = 0.009) and 36 (p < 0.001), respectively. The receiver operating characteristic (ROC) curve analysis estimated that the sensitivity and specificity were 78.2 and 76.9%, respectively, for identifying low BMD subjects from controls when the cut-off value for AMH was set to 0.800 ng/mL. CONCLUSIONS: Serum AMH levels are associated with low BMD in premenopausal women with suspected ovarian insufficiency.

Does Probiotic Lactobacillus Have an Adjunctive Effect in the Nonsurgical Treatment of Peri-Implant Diseases? A Systematic Review and Meta-analysis.

OBJECTIVE: To evaluate the additional effect of probiotic Lactobacillus in the nonsurgical management of peri-implant diseases (peri-implant mucositis and peri-implantitis). METHODS: Six databases were searched up to May 2019 without time and language restrictions. Study selection and data extraction were conducted independently by 2 reviewers. The inclusion criteria for this systematic review were defined based on the participants, intervention, comparison, outcomes, and study design (PICOS) format. Randomized controlled trials comparing nonsurgical treatment combined with probiotic Lactobacillus or placebo agent in patients with peri-implant diseases were included. The methodological quality of retrieved studies was assessed according to the Cochrane Collaboration's Risk of Bias tool, and the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Odds ratio and 95% confidence interval (CI) were used to describe dichotomous data, while mean difference and standardized mean difference with 95% CI were used to describe continuous variables. RESULTS: Seven randomized controlled trials with 296 implants were included in this meta-analysis. The mean difference of probing pocket depth (PPD) was -0.05 (95% CI: -0.28 to 0.18; P = .67) immediately after treatment termination and -0.17 (95% CI: -1.01 to 0.67, P = .69) at least 2 months after treatment termination. There was a slight reduction of PPD after treatment termination. Compared with placebo, Lactobacillus provided limited benefits in peri-implant mucositis. There were no significant differences in the secondary outcomes of bleeding on probing or plaque index (P > .05). In a narrative synthesis of peri-implantitis, the effect of Lactobacillus on PPD and bleeding on probing remained controversial. CONCLUSIONS: This systematic review and meta-analysis showed that probiotic Lactobacillus provide limited benefits to the nonsurgical treatment of peri-implant mucositis or peri-implantitis.

Proteomic profiling analysis of postmenopausal osteoporosis and osteopenia identifies potential proteins associated with low bone mineral density.

Postmenopausal osteoporosis (PMOP) is a major global public health concern and older women are more susceptible to experiencing fragility fractures. Our study investigated the associations between circulating proteins with bone mineral density (BMD) in postmenopausal women with or without low BMD (osteoporosis and osteopenia) using a tandem mass tag (TMT) labeling proteomic experiment and parallel reaction monitoring testing. Across all plasma samples, we quantitatively measured 1,092 proteins, and the OP and normal control (NC) samples were differentiated by principal component analysis and a partial least squares-discrimination analysis model based on the protein profiling data. The differentially abundant proteins between the low BMD and NC samples mostly exhibited binding, molecular function regulator, transporter and molecular transducer activity, and were involved in metabolic and cellular processes, stimulus response, biological regulation, immune system processes and so forth. TMT analysis and RRM validation indicated that the expression of protein Lysozyme C (P61626) was negatively related to BMD, while the expression of proteins Glucosidase (A0A024R592) and Protein disulfideisomerase A5 (Q14554) was positively related to BMD values. Collectively, our results suggest that postmenopausal women with low BMD have a different proteomic profile or signature. Protein alterations may play an important role in the pathogenesis of PMOP, and they may act as novel biomarkers and targets of therapeutic agents for this disease.

Biomarker identification and trans-regulatory network analyses in esophageal adenocarcinoma and Barrett's esophagus.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive disease with high mortality and an overall 5-year survival rate of less than 20%. Barrett's esophagus (BE) is the only known precursor of EAC, and patients with BE have a persistent and excessive risk of EAC over time. Individuals with BE are up to 30-125 times more likely to develop EAC than the general population. Thus, early detection of EAC and BE could significantly improve the 5-year survival rate of EAC. Due to the limitations of endoscopic surveillance and the lack of clinical risk stratification strategies, molecular biomarkers should be considered and thoroughly investigated. AIM: To explore the transcriptome changes in the progression from normal esophagus (NE) to BE and EAC. METHODS: Two datasets from the Gene Expression Omnibus (GEO) in NCBI Database (https://www.ncbi.nlm.nih.gov/geo/) were retrieved and used as a training and a test dataset separately, since NE, BE, and EAC samples were included and the sample sizes were adequate. This study identified differentially expressed genes (DEGs) using the R/Bioconductor project and constructed trans-regulatory networks based on the Transcriptional Regulatory Element Database and Cytoscape software. Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms was identified using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. The diagnostic potential of certain DEGs was assessed in both datasets. RESULTS: In the GSE1420 dataset, the number of up-regulated DEGs was larger than that of down-regulated DEGs when comparing EAC vs NE and BE vs NE. Among these DEGs, five differentially expressed transcription factors (DETFs) displayed the same trend in expression across all the comparison groups. Of these five DETFs, E2F3, FOXA2, and HOXB7 were up-regulated, while PAX9 and TFAP2C were down-regulated. Additionally, the majority of the DEGs in trans-regulatory networks were up-regulated. The intersection of these potential DEGs displayed the same direction of changes in expression when comparing the DEGs in the GSE26886 dataset to the DEGs in trans-regulatory networks above. The receiver operating characteristic curve analysis was performed for both datasets and found that TIMP1 and COL1A1 could discriminate EAC from NE tissue, while REG1A, MMP1, and CA2 could distinguish BE from NE tissue. DAVID annotation indicated that COL1A1 and MMP1 could be potent biomarkers for EAC and BE, respectively, since they participate in the majority of the enriched KEGG and GO terms that are important for inflammation and cancer. CONCLUSION: After the construction and analyses of the trans-regulatory networks in EAC and BE, the results indicate that COL1A1 and MMP1 could be potential biomarkers for EAC and BE, respectively.

Unique Image Characteristics of an Occipital Primary Chondroblastic Osteosarcoma: A Rare Case Report and a Brief Literature Review.

Primary osteosarcomas of the skull and skull base are rare and comprise < 2% of all skull tumors. In head and neck osteosarcomas, the chondroblastic subtype occurs most frequently, which has an exceedingly poor outcome, but its image characteristic remains unknown. Herein, we report a case in the right occipital bone of the skull base and the unique characteristics of image. Pathologic examination of the surgical specimens led to the diagnosis of chondroblastic osteosarcomas. We believe those image characteristics can improve the understanding of skull chondroblastic osteosarcoma and the preoperative diagnosis.

Two cases of hemolymphangioma in the thoracic spinal canal and spinal epidural space on MRI: The first report in the literature.

RATIONALE: Hemolymphangioma is a rare, noninvasive benign tumor of mesenchymal origin resulting from malformation of vascular and lymphatic vessels. The incidence of hemolymphangioma in the spinal canal is low. PATIENT CONCERNS: This report describes 2 patients with a lesion located in the thoracic spinal canal or spinal epidural space, who were misdiagnosed with suspected meningioma or suspected schwannoma, respectively, based on magnetic resonance imaging (MRI). DIAGNOSES: Hemolymphangioma. INTERVENTIONS: The application of a surgery was designed to treat the 2 patients. OUTCOMES: 2 patients stated that symptoms were improved after the operation. LESSONS: This report should raise awareness among clinicians that careful image analysis and consideration of patient history and pathology is required for accurate differential diagnosis of hemolymphangioma in the spinal canal and spinal epidural space.

Knockdown of EWSR1/FLI1 expression alters the transcriptome of Ewing sarcoma cells in vitro.

Ewing sarcoma breakpoint region 1 (EWSR1) fusion with Friend leukemia integration 1 transcription factor (FLI1) induced by a translocation of chromosome 11 with 22 contributes to Ewing sarcoma development. To date, the precise molecular mechanisms about EWSR1/FLI1 involving in Ewing sarcoma development remains to be defined. This study explored the potential critical gene targets of EWSR1/FLI1 knockdown in Ewing sarcoma cells on the gene expression profile based on online dataset, performed Limma algorithm for differentially expressed genes identification, constructed the transcriptional factor (TF)-gene regulatory network based on integrate transcriptional regulatory element database (TRED). The data showed up- and down-regulation of differentially expressed genes over time and peaked at 72 h after EWSR1/FLI1 knockdown in Ewing sarcoma cells. SMAD3 were up-regulated and FLI1, MYB, E2F1, ETS2, WT1 were down-regulated with more than half of their targets were down-regulated after EWSR1/FLI1 knockdown. The Gene Ontology (GO) and pathway annotation of these differentially expressed genes showed a consistent trend in each group of samples. Totally, there were 355 differentially expressed genes occurring in all five comparison groups of different time points, in which 39 genes constructed a dysregulated TF-gene network in Ewing sarcoma cell line A673 after EWSR1/FLI1 knockdown. These data demonstrated that knockdown of EWSR1/FLI1 expression led to transcriptome changes in Ewing sarcoma cells and that Ewing sarcoma development and progression caused by altered EWSR1/FLI1 expression may be associated with more complex transcriptome changes.

TET1 and TET3 are essential in induction of Th2-type immunity partly through regulation of IL-4/13A expression in zebrafish model.

It has been considered that epigenetic modulation can affect a diverse array of cellular activities, in which ten eleven translocation (TET) methylcytosine dioxygenase family members refer to a group of fundamental components involved in catalyzation of 5-hydroxymethylcytosine and modification of gene expression. Even though the function of TET proteins has been gradually revealed, their roles in immune regulation are still largely unknown. Recent studies provided clues that TET2 could regulate several innate immune-related inflammatory mediators in mammals. This study sought to explore the function of TET family members in potential T-helper (Th) cell differentiation involved in adaptive immunity by utilizing a zebrafish model. As shown by results, soluble antigens could induce expression of zebrafish IL-4/13A (i.e. a pivotal Th2-type cytokine essential in Th2 cell differentiation and functions), and further trigger the expression of Th1- and Th2-related genes. It is noteworthy that this response was accompanied by the up-regulation of two TET family members (TET1 and TET3) both in immune organs (spleen and kidney) and cells (peripheral lymphocytes). Knocking-down of TET1 and TET3 will give rise to the decreased responses of IL-4/13A induction against exogenous soluble antigen stimulation, and further restrain the expression of Th2-related genes, which indicates a restrained Th2 cell differentiation. Nonetheless, TET2 did not exhibit effect on the modification of Th1/Th2 related gene expression. Hence, these data showed that TET1 and TET3 might be two significant epigenetic regulators involved in Th2 differentiation through regulation of IL-4/13A expression. This is the first report to show that TET family members play indispensable roles in Th2-type immunity, indicating an epigenetic modulation manner involved in adaptive immune regulations and responses.

Correlation of apparent diffusion coefficient with Ki-67 in the diagnosis of gliomas.

OBJECTIVE: To study the correlation between apparent diffusion coefficient (ADC) and Ki-67, a marker of tumor activity, in the diagnosis of gliomas. METHODS: Conventional magnetic resonance imaging (MRI), enhanced scanning, and diffusion-weighted imaging were performed in 76 patients with pathologically confirmed gliomas. The ADC values were measured at tumor parenchyma and the corresponding contralateral normal brain. The relatively ADC (rADC) values of the tumor parenchyma were calculated. The correlation of the ADC values with tumor grades was analyzed. The expression of Ki-67 was detected by immunohistochemical staining. The correlation between ADC value and Ki-67 in the diagnosis of gliomas was analyzed. RESULTS: The ADC values and rADC values of high-grade gliomas were significantly lower than those of low-grade gliomas. The ADC values of tumor parenchyma were inversely associated with the degree of malignancy of the gliomas (r=-0.898, r=-0.868; P<0.01). The expression of Ki-67 was significantly higher in high-grade gliomas than that in low-grade gliomas. The Ki-67 labeling index in grade 3 and 4 gliomas were (29.48 ± 19.78)% and (31.21 ± 17.50)%, respectively. Both of them were significantly higher than Ki-67 labeling index in low-grade (grade 1 and 2) gliomas [(2.33 ± 2.20)%] (P<0.01). Nevertheless, the Ki-67 labeling index showed no significant difference between grade 3 and 4 gliomas (P>0.05). The expression of Ki-67 was negatively correlated with the ADC values and rADC values in tumor parenchyma (r=-0.627, r=-0.607; P<0.01). CONCLUSION: The ADC and rADC values of tumor parenchyma can indirectly reflect the proliferation and malignancy of gliomas and therefore can be useful for the grading of glioma.