scholarly journals Alteration mRNA Expression Profile of Autophagy Related mTOR Pathway in Schizophrenic Patients with Olanzapine Treatment.

2021 ◽  
Author(s):  
Fengwei Cui ◽  
Shuguang Gu ◽  
Yue Gu ◽  
Jiajun Yin ◽  
Chunxia Fang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Mtor Pathway ◽  
Average Dose ◽  
Healthy Controls ◽  
Expression Levels ◽  
Pairwise Correlation ◽  
Acute Schizophrenia ◽  
Olanzapine Treatment ◽  
Significant Difference ◽  
Mrna Expression Levels

Abstract Background: mTOR signaling pathway involves in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions of antipsychotic drugs, which might mediate by mTOR-dependent autophagy impairment. This study aimed to examine the mRNA expression levels of Mammalian rapamycin target protein (mTOR) pathway genes in schizophrenia patients with olanzapine treatment, which is considered to be an mTOR inhibitor and autophagy inducer. Methods: Thirty-two acute schizophrenia patients had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d), along with 32 healthy volunteers. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of schizophrenia patients, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RPTOR, and DEPTOR, were detected by real-time quantitative PCR with the fasting venous blood of all the samples. Results: The MTOR and RICTOR mRNA expression levels of acute schizophrenia patients significantly decreased than them of healthy controls, and furtherly significantly decreased after four weeks of olanzapine treatment. While DEPTOR mRNA expression levels of acute schizophrenia patients had no significant difference with them of healthy controls, but significantly increased after treatment. And the mRNA expression levels of RPTOR had no significant difference in the three groups. The pairwise correlation of MTOR, DEPTOR, RPTOR, and RICTOR mRNA expression levels in acute schizophrenia patients and healthy controls showed significant correlationships. After olanzapine treatment, the correlationships of mRNA expression levels disappeared between DEPTOR and MTOR, and also between DEPTOR and RICTOR. Conclusions: The results inferred the abnormalities of mTOR pathway, especially DEPTOR, might play important roles in autophagy mechanism of the pathophysiology in schizophrenia and olanzapine treatment.

scholarly journals Alteration in the mRNA expression profile of the autophagy-related mTOR pathway in schizophrenia patients treated with olanzapine

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fengwei Cui ◽  
Shuguang Gu ◽  
Yue Gu ◽  
Jiajun Yin ◽  
Chunxia Fang ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Venous Blood ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Average Dose ◽  
Healthy Controls ◽  
Expression Levels ◽  
Acute Schizophrenia ◽  
Olanzapine Treatment ◽  
Mrna Expression Levels

Abstract Background The mammalian target of rapamycin protein (mTOR) signaling pathway is involved in the pathogenesis of schizophrenia and the mechanism of extrapyramidal adverse reactions to antipsychotic drugs, which might be mediated by an mTOR-dependent autophagy impairment. This study aimed to examine the expression of mTOR pathway genes in patients with schizophrenia treated with olanzapine, which is considered an mTOR inhibitor and autophagy inducer. Methods Thirty-two patients with acute schizophrenia who had been treated with olanzapine for four weeks (average dose 14.24 ± 4.35 mg/d) and 32 healthy volunteers were recruited. Before and after olanzapine treatment, the Positive and Negative Syndrome Scale (PANSS) was used to evaluate the symptoms of patients with schizophrenia, and the mRNA expression levels of mTOR pathway-related genes, including MTOR, RICTOR, RAPTOR, and DEPTOR, were detected in fasting venous blood samples from all subjects using real-time quantitative PCR. Results The MTOR and RICTOR mRNA expression levels in patients with acute schizophrenia were significantly decreased compared with those of healthy controls and further significantly decreased after four weeks of olanzapine treatment. The DEPTOR mRNA expression levels in patients with acute schizophrenia were not significantly different from those of healthy controls but were significantly increased after treatment. The expression levels of the RAPTOR mRNA were not significantly different among the three groups. The pairwise correlations of MTOR, DEPTOR, RAPTOR, and RICTOR mRNA expression levels in patients with acute schizophrenia and healthy controls were significant. After olanzapine treatment, the correlations between the expression levels of the DEPTOR and MTOR mRNAs and between the DEPTOR and RICTOR mRNAs disappeared. Conclusions Abnormalities in the mTOR pathway, especially DEPTOR and mTORC2, might play important roles in the autophagy mechanism underlying the pathophysiology of schizophrenia and effects of olanzapine treatment.

scholarly journals Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xiaoke Yang ◽  
Mingyue Zhang ◽  
Shengqian Xu ◽  
Haifeng Pan ◽  
Ruixue Leng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mrna Expression ◽  
Chinese Population ◽  
Quantitative Polymerase Chain Reaction ◽  
Healthy Controls ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Expression Levels ◽  
Significant Difference ◽  
Mrna Expression Levels

Objectives. The aim of our study was to investigate the association of single-nucleotide polymorphism (SNP) and mRNA expression profile of single immunoglobulin IL-1-related receptor (SIGIRR) in rheumatoid arthritis (RA) in a Chinese population. Methods. SIGIRR rs7396562 polymorphism was genotyped using TaqMan allelic discrimination assay in 517 RA patients and 601 healthy controls. Simultaneously, the SIGIRR mRNA expression levels of 79 RA patients and 76 healthy controls were examined by real-time quantitative polymerase chain reaction (RT-qPCR). Results. The frequency of SIGIRR rs7396562 T allele was significantly higher in RA patients compared with healthy controls (T versus G: OR = 1.277 , 95 % CI = 1.079 − 1.511 , P = 0.004 ). The TT genotype of SIGIRR rs7396562 was more frequent in RA patients than in healthy controls ( OR = 1.547 , 95 % CI = 1.107 − 2.163 , P = 0.011 ). Moreover, we also found a significant difference in the recessive model (TT versus TG+GG: OR = 1.439 , 95 % CI = 1.122 − 1.847 , P = 0.004 ). However, no significant evidence was observed for the association of the SIGIRR rs7396562 with RA in dominant model (TT+TG versus GG: OR = 1.275 , 95 % CI = 0.947 − 1.717 , P = 0.109 ). Further analysis showed no association between SIGIRR rs7396562 polymorphism and laboratory parameters of RA patients (all P > 0.05 ). The mRNA expression of SIGIRR was decreased in PBMCs of patients with RA when compared to healthy controls ( Z = − 2.459 , P = 0.014 ). No significant differences in SIGIRR mRNA expression levels were observed in patients with RA with different genotypes ( P = 0.280 ). Conclusions. Our findings demonstrated that the dysregulation of SIGIRR might be associated with the pathogenesis of RA, and SIGIRR rs7396562 polymorphism might contribute to RA susceptibility in the Chinese population.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

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.

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

Tumor Biology ◽  
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.

scholarly journals The decreased expression of IKBKE in systemic lupus erythematosus

2020 ◽  
Vol 39 (9) ◽  
pp. 2611-2617
Author(s):  
Tingting Zhu ◽  
Jiaqi Hong ◽  
Zongwen Shuai ◽  
Shengqian Xu ◽  
Danfeng Qian ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mrna Expression ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Regulatory Function ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Lower Expression ◽  
Mrna Expression Levels

Abstract Objective The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE. Methods We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms. Results The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients. Conclusion In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals. Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
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.

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

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.

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

2016 ◽  
Vol 35 (1) ◽  
pp. 63-68 ◽  
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.

scholarly journals Blood CDKN2A Gene Expression in Aging and Neurodegenerative Diseases

2021 ◽  
pp. 1-8
Author(s):  
Hiroaki Mori ◽  
Yu Funahashi ◽  
Yuta Yoshino ◽  
Hiroshi Kumon ◽  
Yuki Ozaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Diseases ◽  
Mrna Expression ◽  
Kinase Inhibitor ◽  
Methylation Status ◽  
Healthy Controls ◽  
Expression Levels ◽  
Cdkn2a Gene ◽  
Potential Biomarker ◽  
Mrna Expression Levels

Background: Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important gene in cellular senescence and aging. Objective: This study assessed the utility of blood CDKN2A mRNA expression levels and methylation status as a potential biomarker for aging and the pathogenesis of Alzheimer’s disease (AD). Methods: The correlation between CDKN2A mRNA expression levels and age was examined in 45 healthy subjects, after which mRNA expression levels were compared among 46 AD patients, 20 mild cognitive impairment due to AD patients, 21 Parkinson’s disease patients, 21 dementia with Lewy bodies patients, and 55 older healthy controls. The methylation rates of the second exon of the CDKN2A gene, known to influence its expression levels, was also examined. Results: A significant correlation between CDKN2A mRNA expression levels and age was found (Spearman’s rank correlation coefficient: r = 0.407, p = 0.005). CDKN2A mRNA expression levels in blood were significantly decreased in AD patients, although those of healthy controls were significantly increased with age. Further, only in AD patients were CDKN2A mRNA expression levels significantly and positively correlated with methylation rates. Conclusion: Although further research with a larger sample size is needed to elucidate the relationships between CDKN2A gene expression in blood and the development of other neurodegenerative diseases, CDKN2A mRNA expression in blood may be a biomarker for differentiating AD from normal aging and other neurodegenerative diseases.

scholarly journals The effect of genistein on lipid levels and LDLR, LXRα and ABCG1 expression in postmenopausal women with hyperlipidemia

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Tao Zhang ◽  
Xiao-Xing Chi
Keyword(s):  
Mrna Expression ◽  
Postmenopausal Women ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Expression Levels ◽  
Significant Difference ◽  
Mrna Expression Levels

Abstract Background This study investigates the effect of genistein (Gen) on the lipid profiles and expression of low-density lipoprotein receptor (LDLR), liver X receptor α (LXRα) and ATP-binding cassette transporter G1 (ABCG1) in the plasma macrophages of postmenopausal women with hyperlipidemia in China. Methods This study considered 187 cases, where 160 postmenopausal women had hyperlipidemia. The subjects were divided into placebo group (PG) and experimental group (EG). EG received 60 mg/day of Gen, PG received placebo for 6 months. Body weight, height, waist circumference, body mass index and glucose levels were determined according to standard operating procedures. The triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), apolipoprotein-A1 (Apo-A1) and apolipoprotein-B (Apo-B) levels were detected in the plasma macrophages using ELISA. The protein and mRNA expression levels of LDLR, LXRα and ABCG1 were detected by western blot and real-time PCR techniques, respectively. Results Compared to the baseline, Gen effectively lowered TG, TC and LDL-C levels, whereas HDL-C levels as well as the protein and mRNA expression levels of LDLR, LXRα and ABCG1 (p < 0.05) were increased. There was a significant difference in the expression of LDLR protein between the two groups (p < 0.05). The mRNA expression levels of LDLR, LXRα and ABCG1 were significantly increased in the EG compared to the PG. Conclusion Gen effectively modulated the plasma lipid indices. The cholesterol-lowering effects of Gen may be attributed to its regulation on some of the key genes involved in cholesterol homeostasis.

Sign in / Sign up

Export Citation Format

Share Document