scholarly journals The Protective Effects of 18β-Glycyrrhetinic Acid onHelicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Donghui Cao ◽  
Jing Jiang ◽  
Lili You ◽  
Zhifang Jia ◽  
Tetsuya Tsukamoto ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Ph Value ◽  
Glycyrrhetinic Acid ◽  
Therapeutic Drug ◽  
Mongolian Gerbils ◽  
Protective Effects ◽  
Expression Levels ◽  
Significant Difference ◽  
Cox 2 ◽  
H Pylori

18β-Glycyrrhetinic acid (GRA), a major component ofGlycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA onHelicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbilsin vivo. The gerbils were randomly divided into groups: uninfected;H. pylori-infected;H. pylori+ antibiotics (clarithromycin, amoxicillin, and esomeprazole); andH. pylori+ GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in theH. pylori+ GRA group, the intraluminal gastric pH value was lower (2.14±0.08versus3.17±0.23,P<0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P<0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P<0.05) compared with theH. pylori-infected group. There was no significant difference in results between theH. pylori+ GRA group and theH. pylori+ antibiotics group. This study indicated that GRA significantly attenuatedH. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug.

scholarly journals 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

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.

scholarly journals 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

2020 ◽  
Author(s):  
Elizabeth Ruiz-Sánchez ◽  
Janet Jiménez-Genchi ◽  
Yessica M. Alcántara-Flores ◽  
Carlos J. Castañeda-González ◽  
Carlos L. Aviña-Cervantes ◽  
...  
Keyword(s):  
Working Memory ◽  
Mrna Expression ◽  
Genetic Variants ◽  
Mononuclear Cells ◽  
Memory Performance ◽  
Mexican Population ◽  
High Resolution Melt ◽  
Expression Levels ◽  
Neuropsychiatric Diseases ◽  
Significant Difference

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.

scholarly journals Upregulated PD-1 Expression Is Associated with the Development of Systemic Lupus Erythematosus, but Not the PD-1.1 Allele of the PDCD1 Gene

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Qingqing Jiao ◽  
Cuiping Liu ◽  
Ziliang Yang ◽  
Qiang Ding ◽  
Miaomiao Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Disease Activity Index ◽  
Peripheral Tolerance ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Significant Difference

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complicated genetic inheritance. Programmed death 1 (PD-1), a negative T cell regulator to maintain peripheral tolerance, induces negative signals to T cells during interaction with its ligands and is therefore a candidate gene in the development of SLE. In order to examine whether expression levels of PD-1 contribute to the pathogenesis of SLE, 30 patients with SLE and 30 controls were recruited and their PD-1 expression levels in peripheral blood mononuclear cells (PBMCs) were measured via flow cytometry and quantitative real-time-reverse transcription polymerase chain reaction (RT-PCR). Also, whether PD-1 expression levels are associated with the variant of the SNP rs36084323 and the SLE Disease Activity Index (SLEDAI) was studied in this work. The PD-1 expression levels of SLE patients were significantly increased compared with those of the healthy controls. The upregulated PD-1 expression levels in SLE patients were greatly associated with SLEDAI scores. No significant difference was found between PD-1 expression levels and SNP rs36084323. The results suggest that increased expression of PD-1 may correlate with the pathogenesis of SLE, upregulated PD-1 expression may be a biomarker for SLE diagnosis, and PD-1 inhibitor may be useful to SLE treatment.

scholarly journals The protective effects of 18β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway

2018 ◽  
Vol 16 ◽  
pp. 205873921876299 ◽  
Author(s):  
Donghui Cao ◽  
Jing Jiang ◽  
Dan Zhao ◽  
Menghui Wu ◽  
Houjun Zhang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Glycyrrhetinic Acid ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Acid Pathway ◽  
Ep2 Receptor ◽  
Arachidonic Acid Pathway

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for gastrointestinal diseases. Glycyrrhiza glabra, a traditional Chinese medicine, has been shown to safely suppress gastric cancer; however, the anti-inflammatory mechanisms in gastric tumorigenesis have been poorly investigated. Therefore, this study is committed to demonstrate the in vivo anti-inflammatory effect of 18β-glycyrrhetinic acid (GRA), the main active component of G. glabra. The lymphocytes and macrophages were heavily infiltrated in the transgenic mice that highly expressed cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1; however, a significant reduction was observed after treatment with GRA. In addition, GRA downregulated the protein levels of COX-2, GαS, EP2, and β-catenin, which were involved in the arachidonic acid pathway. In conclusion, our study showed the potential protective effects of GRA against inflammatory environment that might be involved in gastric tumorigenesis in vivo through the PGE2-EP2 receptor-mediated arachidonic acid pathway.

scholarly journals Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3170
Author(s):  
Ana Paula Girol ◽  
Caroline de Freitas Zanon ◽  
Ícaro Putinhon Caruso ◽  
Sara de Souza Costa ◽  
Helena Ribeiro Souza ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Mononuclear Cells ◽  
Formyl Peptide Receptor ◽  
Annexin A1 ◽  
Protective Effects ◽  
Mimetic Peptide ◽  
Formyl Peptide ◽  
Leukocyte Influx ◽  
Cox 2 ◽  
Anti Inflammatory

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.

scholarly journals Long-Term Infection of Mongolian Gerbils with Helicobacter pylori: Microbiological, Histopathological, and Serological Analyses

2005 ◽  
Vol 12 (2) ◽  
pp. 347-353 ◽  
Author(s):  
Shigehito Nakagawa ◽  
Takako Osaki ◽  
Yasunori Fujioka ◽  
Hiroyuki Yamaguchi ◽  
Shigeru Kamiya
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Real Time ◽  
Mononuclear Cells ◽  
Bacterial Colonization ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mongolian Gerbils ◽  
Rt Pcr ◽  
H Pylori

ABSTRACT The effects of long-term infection with Helicobacter pylori on the gastric mucosa of Mongolian gerbils were examined. Colonization by H. pylori was evaluated by both microaerobic cultivation and real-time reverse transcriptase PCR (RT-PCR). Persistent infection with H. pylori in gastric mucosa was detected by real-time RT-PCR during 6 months after infection, but no H. pylori was isolated 4 months after infection by cultivation. Infiltration with neutrophils and mononuclear cells was observed from 2 months after infection. Both intestinal metaplasia and gastric atrophy were also detected from 2 months after infection. The results by enzyme-linked immunosorbent assay indicated that antibody titers against whole H. pylori antigens, H. pylori heat shock protein 60 (HSP60), and Escherichia coli GroEL were significantly higher in the infected gerbils than in noninfected gerbils. After long-term infection with H. pylori for 18 months, marked atrophy of gastric mucosa and multiple cysts in the submucosa were observed in the glandular stomach of the infected gerbils. In addition, squamous cell papilloma with hyperkeratosis was observed in cardia of all the infected gerbils. These results indicate that evaluation of bacterial colonization during long-term infection can be done by real-time RT-PCR and that mucosal damage might be induced by host immune response against whole H. pylori antigen.

scholarly journals Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Tingting Zhu ◽  
Yuandi Huang ◽  
Danfeng Qian ◽  
Yuming Sheng ◽  
Chaowen Zhang ◽  
...  
Keyword(s):  
Drug Target ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Susceptibility Genes ◽  
Regulatory Function ◽  
Therapeutic Drug ◽  
Eqtl Analysis ◽  
Expression Levels ◽  
A Genome ◽  
Lower Expression

A genome-wide association study (GWAS) has discovered that a polymorphism in the ZFP90 gene is associated with systemic lupus erythematosus (SLE). In this study, we explored the candidate function of a ZFP90 variant (rs1170426) in the context of SLE and detected the relationship between SLE susceptible genes and SLE drug target genes. First, we investigated the regulatory role of rs1170426 on ZFP90 expression by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells (PBMCs), T, B, and monocytes cells and annotated the regulatory function of rs1170426 using bioinformatic databases. Second, we compared the case-control difference in ZFP90 expression levels. Third, we analyzed the association of genotype and ZFP90 expression levels with SLE clinical characters. Last, we showed the interaction of SLE susceptibility genes with SLE drug target genes. Subjects with the risk allele “C” of rs1170426 had lower expression levels of ZFP90 in PBMCs (P = 0.006) and CD8+ T cells (P = 0.003) from controls. SLE cases also had lower expression levels compared with controls (P = 2.78E-9). After correction for multiple testing, the ZFP90 expression levels were related to serositis (FDR p = 0.004), arthritis (FDR p = 0.020), hematological involvement (FDR p = 0.021), and increased C-reactive protein (CRP) (FDR p = 0.005) in cases. Furthermore, the SLE susceptible genes and the recognized SLE drug target genes were more likely to act upon each other compared with non-SLE genetic genes (OR = 2.701, P = 1.80E-5). These findings suggest that ZFP90 might play a role in the pathogenesis of SLE, and SLE genetics would contribute to therapeutic drug discovery.

Role of cyclooxygenase-2 inHelicobacter pylori- induced gastritis in Mongolian gerbils

2000 ◽  
Vol 279 (4) ◽  
pp. G791-G798 ◽  
Author(s):  
Satoru Takahashi ◽  
Takuya Fujita ◽  
Akira Yamamoto
Keyword(s):  
Cytokine Production ◽  
Neutrophil Infiltration ◽  
Normal Mucosa ◽  
Interferon Γ ◽  
Mongolian Gerbils ◽  
Pathological Changes ◽  
Cox 2 ◽  
H Pylori ◽  
Cox 1

Cyclooxygenase (COX)-2 expression is induced in the gastric mucosa of Helicobacter pylori-infected patients, but its role remains unclear. We examined the effects of NS-398 and indomethacin on gastric pathology in H. pylori-infected Mongolian gerbils. COX-1 was detected in both normal and H. pylori-infected mucosa, whereas COX-2 was expressed only in the infected mucosa. PGE2production was elevated by H. pylori infection, and the increased production was reduced by NS-398, which did not affect PGE2production in normal mucosa. Indomethacin inhibited PGE2production in both normal and infected mucosa. Hemorrhagic erosions, neutrophil infiltration, lymphoid follicles, and epithelium damage were induced by H. pylori infection. NS-398 and indomethacin aggravated these pathological changes but did not increase viable H. pylori number. H. pylori-increased production of neutrophil chemokine and interferon-γ was potentiated by NS-398 and indomethacin. Neither NS-398 nor indomethacin caused any pathological changes or cytokine production in normal animals. These results indicate that COX-2 as well as COX-1 might play anti-inflammatory roles in H. pylori-induced gastritis.

Protective effects of icariin on traumatic brain injury

2021 ◽  
Vol 19 ◽  
Author(s):  
Anni Du ◽  
Rui Cai ◽  
Jingshan Shi ◽  
Qin Wu
Keyword(s):  
Traumatic Brain Injury ◽  
Cerebral Cortex ◽  
Brain Injury ◽  
Protein Expression ◽  
Chinese Herb ◽  
Inflammatory Factors ◽  
Therapeutic Drug ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Expression Levels

Background: Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Icariin (ICA) is a flavonoid derived from the genus Epimedium which is a traditional Chinese herb, a potential therapeutic drug for TBI. This study aims to explore the protective effect of ICA on TBI and its mechanism Methods: Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received ICA (15 mg/kg, 30 mg/kg and 60 mg/kg), while the sham group was gavaged with equal volumes of saline. The beam-balance testing and prehensile traction test were used for neurological scoring. Pathological changes were observed by H&E staining. The protein expression levels of inflammatory factors were measured by Western blot analysis Results: It was found that ICA significantly improved the neuroethology function and alleviated the pathological injury in TBI rats. The protein expression levels of inflammatory factors COX-2, IL-1β, and TNF-α and its regulatory proteins p-NF-κB-p65, p-ERK1/2, p-JNK, and p-p38 were increased in the cerebral cortex injured by TBI. The protein expression levels of inflammatory cytokines were markedly decreased in cerebral cortex of TBI rats when administrated with ICA. Conclusion: The present study demonstrates that ICA may be a promising therapeutic strategy for reducing inflammation in TBI.

scholarly journals The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 14 (3) ◽  
Author(s):  
Mojca Stražišar ◽  
Vid Mlakar ◽  
Damjan Glavač
Keyword(s):  
Expression Patterns ◽  
Large Cell ◽  
Rt Pcr ◽  
Expression Levels ◽  
Significant Difference ◽  
Different Types ◽  
Polymerase Chain ◽  
Cox 2 ◽  
The Individual ◽  
Relative Differences

AbstractSeveral studies have reported different expression levels of certain genes in NSCLC, mostly related to the stage and advancement of the tumours. We investigated 65 stage I-III NSCLC tumours: 32 adenocarcinomas (ADC), 26 squamous cell carcinomas (SCC) and 7 large cell carcinomas (LCC). Using the real-time reverse transcription polymerase chain reaction (RT-PCR), we analysed the expression of the COX-2, hTERT, MDM2, LATS2 and S100A2 genes and researched the relationships between the NSCLC types and the differences in expression levels. The differences in the expression levels of the LATS2, S100A2 and hTERT genes in different types of NSCLC are significant. hTERT and COX-2 were over-expressed and LATS2 under-expressed in all NSCLC. We also detected significant relative differences in the expression of LATS2 and MDM2, hTERT and MDM2 in different types of NSCLC. There was a significant difference in the average expression levels in S100A2 for ADC and SCC. Our study shows differences in the expression patterns within the NSCLC group, which may mimic the expression of the individual NSCLC type, and also new relationships in the expression levels for different NSCLC types.

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