scholarly journals Cytokine and Gene Expression Profiling in Patients with HFE-Associated Hereditary Hemochromatosis according to Genetic Profile

2020 ◽  
pp. 1-12
Author(s):  
Heidi Kristine Grønlien ◽  
Trine Eker Christoffersen ◽  
Camilla Furlund Nystrand ◽  
Lamya Garabet ◽  
Terje Syvertsen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hereditary Hemochromatosis ◽  
Genetic Profile ◽  
C282y Homozygote ◽  
Markers Of Inflammation ◽  
Disease Characteristics ◽  
Hemochromatosis Gene ◽  
Serum Biochemical ◽  
Disease Signatures ◽  
First Time

Background: Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is characterized by downregulation of hepcidin synthesis, leading to increased intestinal iron absorption. Objectives: The objectives were to characterize and elucidate a possible association between gene expression profile, hepcidin levels, disease severity, and markers of inflammation in HFE-associated HH patients. Methods: Thirty-nine HFE-associated HH patients were recruited and assigned to 2 groups according to genetic profile: C282Y homozygotes in 1 group and patients with H63D, as homozygote or in combination with C282Y, in the other group. Eleven healthy first-time blood donors were recruited as controls. Gene expression was characterized from peripheral blood cells, and inflammatory cytokines and hepcidin-25 isoform were quantified in serum. Biochemical disease characteristics were recorded. Results: Elevated levels of interleukin 8 were observed in a significant higher proportion of patients than controls. In addition, compared to controls, gene expression of ζ-globin was significantly increased among C282Y homozygote patients, while gene expression of matrix metalloproteinase 8, and other neutrophil-secreted proteins, was significantly upregulated in patients with H63D. Conclusion: Different disease signatures may characterize HH patients according to their HFE genetic profile. Studies on larger populations, including analyses at protein level, are necessary to confirm these findings.

scholarly journals N-Formyl Methionine Peptide-Mediated Neutrophil Activation in Systemic Sclerosis

2022 ◽  
Vol 12 ◽  
Author(s):  
Runa Kuley ◽  
Ryan D. Stultz ◽  
Bhargavi Duvvuri ◽  
Ting Wang ◽  
Marvin J. Fritzler ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
De Novo ◽  
Neutrophil Activation ◽  
Formyl Peptide Receptor ◽  
Healthy Controls ◽  
Markers Of Inflammation ◽  
Disease Characteristics ◽  
Formyl Peptide ◽  
First Time

Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are reported in systemic sclerosis (SSc) but its involvement in SSc pathogenesis is not clear. In the present study we assessed markers of neutrophil activation and NET formation in SSc patients in relation to markers of inflammation and disease phenotype. Factors promoting neutrophil activation in SSc remain largely unknown. Among the neutrophil activating factors, mitochondrial-derived N-formyl methionine (fMet) has been reported in several autoinflammatory conditions. The aim of the current study is to assess whether SSc patients have elevated levels of fMet and the role of fMet in neutrophil-mediated inflammation on SSc pathogenesis. Markers of neutrophil activation (calprotectin, NETs) and levels of fMet were analyzed in plasma from two SSc cohorts (n=80 and n=20, respectively) using ELISA. Neutrophil activation assays were performed in presence or absence of formyl peptide receptor 1 (FPR1) inhibitor cyclosporin H. Elevated levels of calprotectin and NETs were observed in SSc patients as compared to healthy controls (p<0.0001) associating with SSc clinical disease characteristics. Further, SSc patients had elevated levels of circulating fMet as compared to healthy controls (p<0.0001). Consistent with a role for fMet-mediated neutrophil activation, fMet levels correlated with levels of calprotectin and NETs (r=0.34, p=0.002; r=0.29, p<0.01 respectively). Additionally, plasma samples from SSc patients with high levels of fMet induced de novo neutrophil activation through FPR1-dependent mechanisms. Our data for the first time implicates an important role for the mitochondrial component fMet in promoting neutrophil-mediated inflammation in SSc.

Hemochromatosis gene mutations in the general population of Slovakia

Open Medicine ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. 148-151 ◽  
Author(s):  
Dana Gabriková ◽  
Iveta Boroňová ◽  
Ivan Bernasovský ◽  
Regina Behulová ◽  
Soňa Mačeková ◽  
...  
Keyword(s):  
General Population ◽  
Hereditary Hemochromatosis ◽  
Epidemiologic Study ◽  
Gene Mutations ◽  
Allelic Frequencies ◽  
Slovak Population ◽  
Hemochromatosis Gene ◽  
Taqman Technology ◽  
First Time ◽  
Compound Heterozygotes

AbstractThis is an epidemiologic study of the Slovak population with the aim of determining the frequencies of three hemochromatosis gene (HFE) variants C282Y, H63D and S65C known to be associated with manifestation of hereditary hemochromatosis and to assess deviations of these frequencies from those reported elsewhere. Mutations were detected in 359 ethnic Slovaks by real-time PCR assay based on TaqMan technology. The allelic frequencies were 4.03% for C282Y, 12.67% for H63D and 1.25% for S65C mutation. We observed 0.28% of C282Y/C282Y homozygotes, 3.34% H63D/H63D homozygotes, 0.84% of C282Y/H63D compound heterozygotes and 0.56% of H63D/S65C compound heterozygotes. This is the first time the frequencies of H63D and S65C mutations have been reported in the general population in Slovakia. The observed allelic frequencies are consistent with the previous studies of Slavic and Central European populations.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

scholarly journals Integrating metabolomics and targeted gene expression to uncover potential biomarkers of fungal/oomycetes-associated disease susceptibility in grapevine

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marisa Maia ◽  
António E. N. Ferreira ◽  
Rui Nascimento ◽  
Filipa Monteiro ◽  
Francisco Traquete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plant Defence ◽  
Breeding Programs ◽  
Analysis Group ◽  
Expression Of Genes ◽  
Leucoanthocyanidin Reductase ◽  
Defence Responses ◽  
Targeted Gene Expression ◽  
Plant Defence Responses ◽  
First Time

Abstract Vitis vinifera, one of the most cultivated fruit crops, is susceptible to several diseases particularly caused by fungus and oomycete pathogens. In contrast, other Vitis species (American, Asian) display different degrees of tolerance/resistance to these pathogens, being widely used in breeding programs to introgress resistance traits in elite V. vinifera cultivars. Secondary metabolites are important players in plant defence responses. Therefore, the characterization of the metabolic profiles associated with disease resistance and susceptibility traits in grapevine is a promising approach to identify trait-related biomarkers. In this work, the leaf metabolic composition of eleven Vitis genotypes was analysed using an untargeted metabolomics approach. A total of 190 putative metabolites were found to discriminate resistant/partial resistant from susceptible genotypes. The biological relevance of discriminative compounds was assessed by pathway analysis. Several compounds were selected as promising biomarkers and the expression of genes coding for enzymes associated with their metabolic pathways was analysed. Reference genes for these grapevine genotypes were established for normalisation of candidate gene expression. The leucoanthocyanidin reductase 2 gene (LAR2) presented a significant increase of expression in susceptible genotypes, in accordance with catechin accumulation in this analysis group. Up to our knowledge this is the first time that metabolic constitutive biomarkers are proposed, opening new insights into plant selection on breeding programs.

scholarly journals Liver-Metabolizing Genes and Their Relationship to the Performance of Elite Spanish Male Endurance Athletes; a Prospective Transversal Study

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
David Varillas Delgado ◽  
Juan José Tellería Orriols ◽  
Carlos Martín Saborido
Keyword(s):  
Binary Logistic Regression ◽  
Endurance Performance ◽  
Endurance Athletes ◽  
Genetic Profile ◽  
Glutathione S Transferase ◽  
Binary Logistic Regression Model ◽  
Genotypic Distribution ◽  
Endurance Runner ◽  
Cytochrome P450 Family ◽  
First Time

Abstract Background The genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population. Methods Genotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the “optimal” polygenic profile has been quantified using the genotype score (GS). Results Statistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213–4.760 (p = 0.002)) in the polymorphisms studied. Conclusions Genotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity.

scholarly journals Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

2008 ◽  
Vol 3 ◽  
pp. BMI.S590 ◽  
Author(s):  
Han-Jin Park ◽  
Jung Hwa Oh ◽  
Seokjoo Yoon ◽  
S.V.S. Rana
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
General Purpose ◽  
Time Dependent ◽  
Expression Data ◽  
Benzene Exposure ◽  
Microarray Analyses ◽  
First Time ◽  
Affymetrix Gene Chip

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.

scholarly journals Prognostic significance of esterase gene expression in multiple myeloma

2021 ◽  
Author(s):  
Romika Kumari ◽  
Muntasir Mamun Majumder ◽  
Juha Lievonen ◽  
Raija Silvennoinen ◽  
Pekka Anttila ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Markers ◽  
Prognostic Significance ◽  
Genomic Variation ◽  
High Expression ◽  
Genetic Profile ◽  
Esterase Gene ◽  
Low Expression

Abstract Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

scholarly journals Antimicrobial peptides play a functional role in bumblebee anti-trypanosome defense

2014 ◽  
Author(s):  
Soni Deshwal ◽  
Eamonn Mallon
Keyword(s):  
Gene Expression ◽  
Gut Microbiota ◽  
Antimicrobial Peptides ◽  
Functional Role ◽  
Immune Gene ◽  
Ecological Immunology ◽  
Previous Evidence ◽  
Immune Gene Expression ◽  
Crithidia Bombi ◽  
First Time

Bumblebees, amongst the most important of pollinators, are under enormous population pressures. One of these is disease. The bumblebee and its gut trypanosome Crithidia bombi are one of the fundamental models of ecological immunology. Although there is previous evidence of increased immune gene expression upon Crithidia infection, recent work has focussed on the bumblebee's gut microbiota. Here, by knocking down gene expression using RNAi, we show for the first time that antimicrobial peptides (AMPs) have a functional role in anti-Crithidia defense.

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