Working Memory Deficits in Schizophrenia Are Associated With the Rs34884856 Variant and Expression Levels of the NR4A2 Gene in a Sample Mexican Population: A Case Control Study

Abstract Background Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. Methods The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. Results Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. In these patients, a decrease of NR4A2 mRNA expression was related to working memory impairment. Conclusions Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients´ genotype in a sample from a Mexican population.

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Working memory deficits in schizophrenia are associated with the rs34884856 variant and expression levels of the NR4A2 gene in a sample Mexican population: a case control study

BMC Psychiatry ◽

10.1186/s12888-021-03081-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Elizabeth Ruiz-Sánchez ◽

Janet Jiménez-Genchi ◽

Yessica M. Alcántara-Flores ◽

Carlos J. Castañeda-González ◽

Carlos L. Aviña-Cervantes ◽

...

Keyword(s):

Working Memory ◽

Genetic Variants ◽

Mononuclear Cells ◽

Memory Performance ◽

Mexican Population ◽

High Resolution Melt ◽

Expression Levels ◽

Neuropsychiatric Diseases ◽

Significant Difference ◽

Peripheral Mononuclear Cells

Abstract Background Cognitive functions represent useful endophenotypes to identify the association between genetic variants and schizophrenia. In this sense, the NR4A2 gene has been implicated in schizophrenia and cognition in different animal models and clinical trials. We hypothesized that the NR4A2 gene is associated with working memory performance in schizophrenia. This study aimed to analyze two variants and the expression levels of the NR4A2 gene with susceptibility to schizophrenia, as well as to evaluate whether possession of NR4A2 variants influence the possible correlation between gene expression and working memory performance in schizophrenia. Methods The current study included 187 schizophrenia patients and 227 controls genotyped for two of the most studied NR4A2 genetic variants in neurological and neuropsychiatric diseases. Genotyping was performed using High Resolution Melt and sequencing techniques. In addition, mRNA expression of NR4A2 was performed in peripheral mononuclear cells of 112 patients and 118 controls. A group of these participants, 54 patients and 87 controls, performed the working memory index of the WAIS III test. Results Both genotypic frequencies of the two variants and expression levels of the NR4A2 gene showed no significant difference when in patients versus controls. However, patients homozygous for the rs34884856 promoter variant showed a positive correlation between expression levels and auditory working memory. Conclusions Our finding suggested that changes in expression levels of the NR4A2 gene could be associated with working memory in schizophrenia depending on patients’ genotype in a sample from a Mexican population.

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The role of CXCR3 and its ligands expression in Brucellar spondylitis

BMC Immunology ◽

10.1186/s12865-020-00390-9 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Xin Hu ◽

Xiaoqian Shang ◽

Liang Wang ◽

Jiahui Fan ◽

Yue Wang ◽

...

Keyword(s):

Protein Expression ◽

Mrna Expression ◽

Mononuclear Cells ◽

Healthy Controls ◽

Inflammatory Infiltration ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Inflammatory Damage ◽

Ifn Γ ◽

Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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Working Memory Performance after Daily Caffeine Intake: Compromised Performance and Reduced Hippocampal Activity.

10.1101/2021.04.19.440520 ◽

2021 ◽

Author(s):

Yu-Shiuan Lin ◽

Janine Weibel ◽

Hans-Peter Landolt ◽

Francesco Santini ◽

Helen Christina Slawik ◽

...

Keyword(s):

Working Memory ◽

Memory Performance ◽

Error Rates ◽

Caffeine Intake ◽

Cognitive State ◽

Placebo Condition ◽

Memory Functions ◽

Acute Withdrawal ◽

Caffeine Withdrawal ◽

Significant Difference

Neuroprotective effects of caffeine have been frequently reported in the context of disease and cognitive dysfunction as well as in epidemiological studies in humans. However, evidence on caffeine effects on neural and memory functions during daily intake in a healthy cognitive state remains scarce. This randomized double-blind placebo-controlled crossover study investigated working memory functions by N-back tasks and functional magnetic resonance imaging (fMRI) after daily caffeine intake compared to a placebo baseline and to acute caffeine withdrawal in 20 young healthy volunteers. Each volunteer was given 3 times 150 mg caffeine for 10 days in the daily caffeine condition, 3 times 150 mg mannitol for 10 days in the placebo condition, and 9-day caffeine plus 1-day mannitol in the acute withdrawal condition. During the 10th day, participants performed 4 N-back sessions (two loads each: 0- and 3-back) under controlled laboratory conditions. During the 4th session of N-Back (i.e. at 5.5 h, 36.5 h and > 10 days after the last caffeine intake in the caffeine, withdrawal, and placebo condition, respectively) we assessed blood-oxygen-level-dependent (BOLD) activity. During the entire 10th day, in 0-back tasks, we observed longer reaction times (RTs) in the withdrawal compared to the placebo (Cohens d = 0.7) and caffeine condition (Cohens d = 0.6), but no significant effects of conditions on error rates. In contrast, in 3-back tasks (controlled for 0-back), the RTs in the caffeine condition were longer compared to placebo (Cohens d = 0.6) and withdrawal (Cohens d = 0.5). Error rates were higher during both caffeine and withdrawal conditions compared to placebo (Cohens d of both contrasts = 0.4). Whole-brain analyses on fMRI data did not reveal significant condition-dependent differences in activities between task loads. Across task loads, however, we observed a reduced hippocampal activation (Cohens d = -1.3) during the caffeine condition compared to placebo, while no significant difference in brain activities between withdrawal and placebo conditions. Taken together, the worse working memory function and the hippocampal hypoactivation implicate a potential detrimental effect of daily caffeine intake on neurocognitive functions of healthy adults. Moreover, they echo the hippocampal volumetric reduction reported previously in the same volunteers. Lastly, acute withdrawal from daily caffeine intake impairs both low-order cognitive processes and working memory performance. Taking earlier studies on acute caffeine effects into account, our findings indicate that daily caffeine intake elicits a dynamic change in cerebral activities during the course of repeated consumption, with unknown consequences in the long run.

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Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer

Tumor Biology ◽

10.1177/1010428320924524 ◽

2020 ◽

Vol 42 (6) ◽

pp. 101042832092452

Author(s):

Lina Olsson ◽

Gudrun Lindmark ◽

Marie-Louise Hammarström ◽

Sten Hammarström ◽

Basel Sitohy

Keyword(s):

Colon Cancer ◽

Lymph Nodes ◽

Mrna Expression ◽

Cancer Patients ◽

Migration Inhibitory Factor ◽

Inhibitory Factor ◽

Expression Levels ◽

Significant Difference ◽

Mrna Expression Levels ◽

Inhibitory Factor 1

Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Results: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p < .0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p < .0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan–Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p = .04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p = .03) at 12 years of follow-up. Conclusion: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.

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Anticitrullinated Protein Antibodies Induce Inflammatory Gene Expression Profile in Peripheral Blood Cells from CCP–positive Patients with RA

The Journal of Rheumatology ◽

10.3899/jrheum.170822 ◽

2018 ◽

Vol 45 (3) ◽

pp. 310-319 ◽

Cited By ~ 1

Author(s):

Smadar Gertel ◽

Gidi Karmon ◽

Eszter Szarka ◽

Ora Shovman ◽

Esther Houri-Levi ◽

...

Keyword(s):

Mrna Expression ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Joint Damage ◽

Cytokine Expression ◽

Diagnostic Significance ◽

Expression Levels ◽

Citrullinated Peptide ◽

Anticitrullinated Protein Antibodies ◽

Mrna Expression Levels

Objective.Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA.Methods.To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)–positive patients with RA and healthy controls were cocultured in vitro with ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested whether the stimulatory effects induced by ACPA could be inhibited by the addition of a new multiepitope citrullinated peptide (Cit-ME).Results.We found that ACPA bind specifically to PBMC from CCP-positive patients with RA through the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4- to 13-fold increase) in PBMC derived from CCP-positive patients with RA. Moreover, ACPA upregulated IL-1β and IL-6 mRNA expression levels by 10- and 6-fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA, inhibited the ACPA-induced upregulation of IL-1β and IL-6 by 30%.Conclusion.ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA to decrease their pathogenic effects might provide a novel direction in developing therapeutic strategies for RA.

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Decreased PERP Expression on Peripheral Blood Mononuclear Cells from Patient with Rheumatoid Arthritis Negatively Correlates with Disease Activity

Clinical and Developmental Immunology ◽

10.1155/2013/256462 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Yanchun Du ◽

Lin Deng ◽

Yan Li ◽

Lu Gan ◽

Yantang Wang ◽

...

Keyword(s):

Disease Activity ◽

Mrna Expression ◽

Mononuclear Cells ◽

Cell Types ◽

Healthy Controls ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Cell Type Specific ◽

Mrna Expression Levels

Background. PERP, p53 apoptosis effector related to PMP-22, is a p53-dependent apoptosis in diverse cell types and has cell type-specific roles in p53-mediated apoptosis. However, its role in PBMCs of RA patients has remained largely unclear.Objectives. The aim of this study was to detect the expression levels of PERP on PBMCs of RA patients and healthy controls and analyze the role of PERP in the pathogenesis of RA.Methods. The mRNA expression levels of PERP and IL-17 were detected by real-time PCR in PBMCs from patients with RA (n=40) and healthy controls (n=40). The correlations of PERP expression levels to IL-17 transcripts and disease activity parameters were analyzed.Results. The PERP and IL-17 expression levels in the PBMCs were significantly decreased and increased in comparison of which in healthy controls. The mRNA expression levels of PERP in PBMCs from patients with RA were negatively correlated with IL-17 and disease activity parameters DAS28, RF, CRP, and ESR rather than Anti-CCP and ANA.Conclusions. These results demonstrated that PERP might be involved in the pathogenesis and a potential therapeutic target of RA by regulating the expression of IL-17.

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Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽

10.1182/blood.v110.11.3847.3847 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3847-3847 ◽

Cited By ~ 1

Author(s):

Yunfeng Cheng ◽

Shanhua Zou ◽

Feng Li

Keyword(s):

Plasma Concentration ◽

Mrna Expression ◽

Mononuclear Cells ◽

Control Group ◽

Gene Expressions ◽

Expression Levels ◽

Tnf Α ◽

Healthy Control ◽

Ifn Γ ◽

Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

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ERCC1 expression as a predictor for chemosensitivity in recurrent colorectal cancer patients receiving cisplatinum (CDDP) plus S-1 chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13065 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13065-13065

Author(s):

K. Uchida ◽

K. Hayashi ◽

H. Kuramochi ◽

K. Kudo ◽

S. Miyakura ◽

...

Keyword(s):

Colorectal Cancer ◽

Mrna Expression ◽

Recurrent Colorectal Cancer ◽

Internal Reference ◽

Expression Levels ◽

Significant Difference ◽

Mrna Gene ◽

Ercc1 Expression ◽

Colorectal Cancer Patients ◽

Mrna Expression Levels

13065 Background: To test the hypotheses of whether the relative mRNA expression of excision cross complement-1 (ERCCI) are associated with response to CDDP+S-1 chemotherapy in recurrent colorectal cancer (CRC). We assessed the relationship between ERCC1 mRNA expression levels and the response. Methods: Thirty four patients with relapsed CRC were treated with cisplatin 30 mg/m2 on Day 1 and Day 8, and S-1 twice daily (BSA = 1.5 m2, 60 mg/day) for 21 days, followed by a 2-week period of no treatment. cDNA was derived from paraffin-embeded tumor specimens to determine ERCC1 mRNA expression relative to the internal reference gene beta-actin using fluorescence-based, real-time reverse transcriptase polymerase chain reaction (Taqman) system. Results: Among 34 CRC patients, 4 patients were evaluated as CR, 13 as PR, and 17 as NC/PD. Relative ERCC1 mRNA gene expression level showed significant difference by the response with median expression levels of 0.70/1.33/1.80 in CR/PR/NC+PD patients respectively (P = 0.04). Conclusions: These data suggest that intratumoral ERCC1 mRNA expression levels are independent predictive markers of response to CDDP+S-1 chemotherapy in colorectal cancer. No significant financial relationships to disclose.

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Survivin and Vegf as Novel Biomarkers in Diagnosis of Endometriosis/ Survivin i vegf kao novi biomarkeri u dijagnostici endometrioze

Journal of Medical Biochemistry ◽

10.1515/jomb-2015-0005 ◽

2016 ◽

Vol 35 (1) ◽

pp. 63-68 ◽

Cited By ~ 8

Author(s):

Milena Acimovic ◽

Snezana Vidakovic ◽

Natasa Milic ◽

Katarina Jeremic ◽

Milos Markovic ◽

...

Keyword(s):

Mrna Expression ◽

Peripheral Blood ◽

Transvaginal Ultrasound ◽

False Negative ◽

Diagnostic Tools ◽

Expression Levels ◽

Diagnostic Score ◽

Significant Difference ◽

Serum Ca125 ◽

Mrna Expression Levels

Summary Background: The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. Methods: This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann - Whitney test. Results: There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). Conclusions: Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis.

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