Current Biomarkers of Apoptosis Process in Chronically Inflamed Nasal Sinus Epithelium: Representatives of BAX, Bcl-2 and miRNA Group

2021 ◽  
Author(s):  
Monika Morawska-Kochman ◽  
Agnieszka Smieszek ◽  
Klaudia Marcinkowska ◽  
Krzysztof Marycz ◽  
Kamil Nelke ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Tunel Staining ◽  
Mrna Levels ◽  
Upper Respiratory Tract ◽  
Nasal Sinus ◽  
Expression Levels ◽  
Apoptosis Markers ◽  
Cell Proliferative Activity ◽  
Characteristic Features ◽  
Apoptosis Process

Abstract In chronic upper respiratory tract diseases, increased cell proliferative activity is observed, which is coordinated by Bcl-2 proteins as well as by small non-coding RNAs.The aim of this study was to determine the expression of critical apoptosis markers at the mRNA and miRNA level in patients with chronic rhinosinusitis with nasal polyps (CSRwNP).The study group consisted of 10 patients with CSRwNP and 10 healthy controls. TUNEL staining was performed to detect in situ apoptosis in the maxillary sinus mucosa. The levels of selected mRNA transcripts associated with cell survival and apoptosis: BAX, p53, p21, CASP3, CASP9, c-MYC, CCND1, BRIC5 and APAF1 and miRNAs: miR-17-5p, miR-145-5p, miR-146a-5p and miR-203a-3p were determined by RT-qPCR. CSRwNP patients showed increased apoptosis determined by TUNEL assay accompanied by increased expression of BAX, P21, P53, CASP3, CASP9, c-MYC, APAF-1 transcripts and decreased mRNA levels of BCL-2 and BIRC5. There were increased expression levels of miR-203a-3p and decreased expression levels of miR-17-5p and miR-145-5p. These findings appear to be characteristic features of apoptosis in CRSwNP. The proapoptotic effect of miR-203a-3p may be crucial for future treatment strategies for CRSwNP.

scholarly journals Methylobacterium oryzae Influences Isoepoxydon Dehydrogenase Gene Expression and Patulin Production by Penicillium expansum

Water ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1427
Author(s):  
Tiago Barros Afonso ◽  
Lúcia Chaves Simões ◽  
Nelson Lima
Keyword(s):  
Gene Expression ◽  
Distribution Systems ◽  
Water Distribution ◽  
Penicillium Expansum ◽  
Transcriptional Level ◽  
Positive Trend ◽  
Mrna Levels ◽  
Expression Levels ◽  
Production Values ◽  
Methylobacterium Oryzae

Biofilms can be considered the main source of microorganisms in drinking water distribution systems (DWDS). The ecology of a biofilm is dependent on a variety of factors, including the presence of microbial metabolites excreted by its inhabitants. This study reports the effect of the Gram-negative bacteria Methylobacterium oryzae on the idh gene expression levels and patulin production of Penicillium expansum mature biofilms. For this purpose, a RT-qPCR method to quantify idh mRNA levels was applied. In addition, the idh expression levels were compared with the patulin production. The results obtained revealed that the effect of the bacterium on pre-established P. expansum biofilms is dependent on the time of interaction. More mature P. expansum biofilms appear to be more resistant to the inhibitory effect that M. oryzae causes towards idh gene expression and patulin production. A positive trend was observed between the idh expression and patulin production values. The results indicate that M. oryzae affects patulin production by acting at the transcriptional level of the idh gene.

scholarly journals Gene Expression of Nucleic Acid-Sensing Pattern Recognition Receptors in Children Hospitalized for Respiratory Syncytial Virus-Associated Acute Bronchiolitis

2009 ◽  
Vol 16 (6) ◽  
pp. 816-823 ◽  
Author(s):  
Carolina Scagnolari ◽  
Fabio Midulla ◽  
Alessandra Pierangeli ◽  
Corrado Moretti ◽  
Enea Bonci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pattern Recognition ◽  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Pattern Recognition Receptors ◽  
Mrna Levels ◽  
Acute Bronchiolitis ◽  
Expression Levels ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Given the critical role of pattern recognition receptors (PRRs) in acid nucleic recognition in the initiation of innate immunity and the orchestration of adaptive immunity, the aim of this study was to determine whether any heterogeneity of PRR expression in the airway tracts of infants with respiratory syncytial virus (RSV) infection might explain the broad clinical spectrum of RSV-associated bronchiolitis in infants. For this purpose, the levels of melanoma differentiation-associated protein-5 (MDA-5), retinoic acid inducible gene-1 (RIG-1), and Toll-like receptor 3 (TLR-3), TLR-7, TLR-8, and TLR-9 mRNAs were evaluated, using TaqMan quantitative reverse transcription-PCR, in cells from nasopharyngeal washes collected from 157 infants suffering from acute bronchiolitis whether or not they were associated with respiratory viruses. High interindividual variability was observed in both virus-positive and -negative infants; however, the relative gene expression levels of MDA-5, RIG-1, TLR-7, and TLR-8 were significantly higher in the virus-infected group, whereas the expression levels of TLR-3 and TLR-9 were not significantly different. The differences in the gene expression of MDA-5, RIG-1, TLR-7, and TLR-8 were more evident in infants with RSV infection than in those with bocavirus or rhinovirus infection. In RSV-infected infants, PRR-mRNA levels also were analyzed in relation to interferon protein levels, viral load, clinical severity, days of hospitalization, age, and body weight. A significant positive correlation was observed only between RSV viral load and RIG-1 mRNA levels. These findings provide the first direct evidence that, in infants with respiratory virus-associated bronchiolitis, especially RSV, there are substantial changes in PRR gene expression; this likely is an important determinant of the clinical outcome of bronchiolitis.

HEREDITARY ANGIOEDEMA – A PROBLEM AT THE INTERSECTION OF IMMUNOLOGY AND ALLERGOLOGY: ANALYSIS OF LITERATURE DATA AND DESCRIPTION OF A SERIES OF 34 CASES

2021 ◽  
Vol 100 (2) ◽  
pp. 49-57
Author(s):  
M.N. Guseva ◽  
◽  
E.I. Zinina ◽  
E.N. Suspitsyn ◽  
M.M. Kostik ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Hereditary Angioedema ◽  
Positive Family History ◽  
Clinical Manifestations ◽  
Upper Respiratory Tract ◽  
Upper Airways ◽  
Peripheral Edema ◽  
Dominant Disease ◽  
Characteristic Features ◽  
Head Neck

Hereditary angioedema (HAE) is a rare autosomal dominant disease characterized by isolated recurrent angioedema (AE) of various localizations: skin, the submucosa in the gastrointestinale tract, the respiratory tract. The characteristic features of edema in HAE are the absence of itching, skin flushing, accompanying urticaria, as well as the absence of pronounced effect of systemic corticosteroid therapy, systemic antihistamines therapy and adrenaline. The aim of our study was to present a descriptive characteristics of the group of patients with HAE and to access efficacy and safety of treatment. Materials and methods: the retrospective multicenter continuous nonrandomized uncontrolled study included data on 34 patients: 19 men (56%) and 15 women (44%) with HAE. The diagnosis of HAE was based on clinical and laboratorial data, according to the clinical guidelines of the Russian Association of allergologists and clinical immunologists on HAE (2014). Results The age range of patients at the time of inclusion in the study was 5–82 years, median – 38,8 (20,6; 46,9) years. Median age of first HAE episode was 12,5 (5,8; 16,3) years, ranged from 2 to 40, 22/28 (79%) of the patients manifested before 18 years. HAE was diagnosed at the median age of 30 years (17,5; 44,8) years, in 14,0 (9,0; 25,0) years after onset of the clinical manifestations. Most of the observations described have a positive family history of HAE (91%), in total 9 families were described. In 67% of families the disease manifested itself in two generations and in 33% of families – in three generations. At the onset of HAE peripheral edema was in 29/31 (94%) of the patients, and 22/31 (71%) had edema confined to the distal extremities. 7/31 (29%) patients had peripheral edema combined with edema of other locations. Abdominal attacks were in 6/31 (19%), head, neck and upper airways edema were in 7/31 (23%). The frequency of swelling of head, neck, upper respiratory tract increased statistically significantly from 23% (7/31) to 35% (7/20, p=0,003). 24 patients have recieved Icatibant treatment. No deaths were recorded against the background of this treatment. Conclusions HAE is diagnosed with significant time delays. Icatibant treatment is safe and effective.

scholarly journals A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum

2019 ◽  
Vol 20 (13) ◽  
pp. 3257 ◽  
Author(s):  
Sophie Gravel ◽  
Benoit Panzini ◽  
Francois Belanger ◽  
Jacques Turgeon ◽  
Veronique Michaud
Keyword(s):  
Type 2 Diabetes ◽  
Mrna Expression ◽  
Drug Metabolizing Enzymes ◽  
Mrna Levels ◽  
Metabolizing Enzymes ◽  
Expression Levels ◽  
The Impact ◽  
Duodenal Biopsies ◽  
Mrna Expression Levels

To characterize effects of type 2 diabetes (T2D) on mRNA expression levels for 10 Cytochromes P450 (CYP450s), two carboxylesterases, and three drug transporters (ABCB1, ABCG2, SLCO2B1) in human duodenal biopsies. To compare drug metabolizing enzyme activities of four CYP450 isoenzymes in duodenal biopsies from patients with or without T2D. mRNA levels were quantified (RT-qPCR) in human duodenal biopsies obtained from patients with (n = 20) or without (n = 16) T2D undergoing a scheduled gastro-intestinal endoscopy. CYP450 activities were determined following incubation of biopsy homogenates with probe substrates for CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2J2 (ebastine), and CYP3A4/5 (midazolam). Covariables related to inflammation, T2D, demographic, and genetics were investigated. T2D had no major effects on mRNA levels of all enzymes and transporters assessed. Formation rates of metabolites (pmoles mg protein−1 min−1) determined by LC-MS/MS for CYP2C9 (0.48 ± 0.26 vs. 0.41 ± 0.12), CYP2J2 (2.16 ± 1.70 vs. 1.69 ± 0.93), and CYP3A (5.25 ± 3.72 vs. 5.02 ± 4.76) were not different between biopsies obtained from individuals with or without T2D (p > 0.05). No CYP2B6 specific activity was measured. TNF-α levels were higher in T2D patients but did not correlate with any changes in mRNA expression levels for drug metabolizing enzymes or transporters in the duodenum. T2D did not modulate expression or activity of tested drug metabolizing enzymes and transporters in the human duodenum. Previously reported changes in drug oral clearances in patients with T2D could be due to a tissue-specific disease modulation occurring in the liver and/or in other parts of the intestines.

scholarly journals Synaptotagmin 13 Is Highly Expressed in Estrogen Receptor-Positive Breast Cancer

2021 ◽  
Vol 28 (5) ◽  
pp. 4080-4092
Author(s):  
Takahiro Ichikawa ◽  
Masahiro Shibata ◽  
Takahiro Inaishi ◽  
Ikumi Soeda ◽  
Mitsuro Kanda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mrna Expression ◽  
Cell Lines ◽  
Mrna Levels ◽  
Pcr Array ◽  
Array Analysis ◽  
Expression Levels ◽  
Er Positive ◽  
Mrna Expression Levels

Background: Accumulating evidence indicates tumor-promoting roles of synaptotagmin 13 (SYT13) in several cancers; however, no studies have investigated its expression in breast cancer (BC). This study aimed to clarify the significance of SYT13 in BC. Methods: SYT13 mRNA expression levels were evaluated in BC cell lines. Polymerase chain reaction (PCR) array analysis was conducted to determine the correlation between expression levels of SYT13 and other tumor-associated genes. Then, the association of SYT13 expression levels in the clinical BC specimens with patients’ clinicopathological factors was evaluated. These findings were subsequently validated using The Cancer Genome Atlas (TCGA) database. Results: Among 13 BC cell lines, estrogen receptor (ER)-positive cells showed higher SYT13 mRNA levels than ER-negative cells. PCR array analysis revealed positive correlations between SYT13 and several oncogenes predominantly expressed in ER-positive BC, such as estrogen receptor 1, AKT serine/threonine kinase 1, and cyclin-dependent kinases 4. In 165 patients, ER-positive specimens exhibited higher SYT13 mRNA expression levels than ER-negative specimens. The TCGA database analysis confirmed that patients with ER-positive BC expressed higher SYT13 levels than ER-negative patients. Conclusion: This study suggests that SYT13 is highly expressed in ER-positive BC cells and clinical specimens, and there is a positive association of SYT13 with the ER signaling pathways.

scholarly journals Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma

2021 ◽  
Author(s):  
Ridwan Dwi Saputro ◽  
Hanggoro Tri Rinonce ◽  
Yayuk Iramawasita ◽  
Muhammad Rasyid Ridho ◽  
Maria Fransiska Pudjohartono ◽  
...  
Keyword(s):  
Target Genes ◽  
Therapy Response ◽  
Mrna Levels ◽  
Independent Predictive Factor ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Nodular Melanoma ◽  
Expression Levels ◽  
Melanoma Tissue

Abstract Objective Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue and clinicopathologic characteristics and survival in Indonesian patients with primary nodular melanoma. Results Thirty-two tissue samples were analyzed. Upregulated PD-L1 was associated with shorter overall survival (hazard ratio: 2.930; 95% confidence interval: 1.011–8.489, p = 0.048) compared with patients with normoregulated PD-L1. A significant positive correlation was found between the expression levels of PD-L1 and NKG2A (rs: 0.768, p < 0.001). However, no clinicopathologic associations with PD-L1 and NKG2A mRNA levels were statistically proven. Comparison with other studies suggested that the choice of adjuvant therapy and the presence of TILs affect the prognostic role of PD-L1 expression. NKG2A was not proven to be an independent predictive factor but may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The combination of the mRNA levels of these two target genes may provide a novel prognostic and therapeutic direction for immunotherapy.

scholarly journals Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics

2021 ◽  
Vol 22 (23) ◽  
pp. 12791
Author(s):  
Alexia Grangeon ◽  
Valérie Clermont ◽  
Azemi Barama ◽  
Fleur Gaudette ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Intestine ◽  
Protein Expression ◽  
Mrna Levels ◽  
Targeted Proteomics ◽  
Tissue Samples ◽  
Human Organ ◽  
Expression Levels ◽  
Protein Levels ◽  
Human Small Intestine

The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.e., duodenum (one section, N = 7 tissue samples), jejunum (three subsections (proximal, mid and distal), N = 9 tissue samples) and ileum (three subsections, (proximal, mid and distal), N = 9 tissue samples), using liquid chromatography tandem mass spectrometry (LC-MS/MS) based targeted proteomics. CYP450 absolute protein expression levels were compared to mRNA levels and enzyme activities by using established probe drugs. Proteins corresponding to seven of sixteen potential CYP450 isoforms were detected and quantified in various sections of the small intestine: CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, CYP3A5 and CYP4F2. Wide inter-subject variability was observed, especially for CYP2D6. CYP2C9 (p = 0.004) and CYP2C19 (p = 0.005) expression levels decreased along the small intestine. From the duodenum to the ileum, CYP2J2 (p = 0.001) increased, and a trend was observed for CYP3A5 (p = 0.13). CYP3A4 expression was higher in the jejunum than in the ileum (p = 0.03), while CYP4F2 expression was lower in the duodenum compared to the jejunum and the ileum (p = 0.005). CYP450 protein levels were better correlated with specific isoform activities than with mRNA levels. This study provides new data on absolute CYP450 quantification in human small intestine that could improve physiologically based pharmacokinetic models. These data could better inform drug absorption profiles while considering the regional expression of CYP450 isoforms.

scholarly journals Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Jingli Qian ◽  
Guoping Li ◽  
Xiaosheng Jin ◽  
Chunfang Ma ◽  
Wanru Cai ◽  
...  
Keyword(s):  
Lung Injury ◽  
Western Blot ◽  
Molecular Mechanisms ◽  
Mrna Level ◽  
Intestinal Injury ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Group Model ◽  
Expression Levels

Abstract Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot. Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

scholarly journals Heterogeneous recruitment abilities to RNA polymerases generate nonlinear scaling of gene expression with cell volume

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qirun Wang ◽  
Jie Lin
Keyword(s):  
Gene Expression ◽  
Cell Volume ◽  
Direct Consequence ◽  
Rna Polymerases ◽  
Mrna Levels ◽  
Expression Levels ◽  
Promoter Sequences ◽  
Biophysical Mechanism ◽  
Expression Model ◽  
Cycle Regulation

AbstractWhile most genes’ expression levels are proportional to cell volumes, some genes exhibit nonlinear scaling between their expression levels and cell volume. Therefore, their mRNA and protein concentrations change as the cell volume increases, which often have crucial biological functions such as cell-cycle regulation. However, the biophysical mechanism underlying the nonlinear scaling between gene expression and cell volume is still unclear. In this work, we show that the nonlinear scaling is a direct consequence of the heterogeneous recruitment abilities of promoters to RNA polymerases based on a gene expression model at the whole-cell level. Those genes with weaker (stronger) recruitment abilities than the average ability spontaneously exhibit superlinear (sublinear) scaling with cell volume. Analysis of the promoter sequences and the nonlinear scaling of Saccharomyces cerevisiae’s mRNA levels shows that motifs associated with transcription regulation are indeed enriched in genes exhibiting nonlinear scaling, in concert with our model.

Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis

2018 ◽  
Vol 127 (05) ◽  
pp. 281-288 ◽  
Author(s):  
Mario Štefanić ◽  
Stana Tokić ◽  
Mirjana Suver-Stević ◽  
Ljubica Glavaš-Obrovac
Keyword(s):  
T Cells ◽  
Autoimmune Thyroiditis ◽  
Thyroid Volume ◽  
Thyroid Peroxidase ◽  
Mrna Levels ◽  
Expression Levels ◽  
Chronic Autoimmune Thyroiditis ◽  
End Stage ◽  
Hypothyroid Patients

Abstract Background Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. Methods Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. Results The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. Conclusions Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.

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