scholarly journals Apoptosis and Cell Cycle Pathway-Focused Genes Expression Analysis in Patients with Different Forms of Thyroid Pathology

2020 ◽  
Vol 8 (B) ◽  
pp. 784-792
Author(s):  
Iryna Bilous ◽  
Larysa Pavlovych ◽  
Inna Krynytska ◽  
Mariya Marushchak ◽  
Aleksandr Kamyshnyi
Keyword(s):  
Cell Cycle ◽  
Mrna Level ◽  
Elevated Serum ◽  
Thyroid Peroxidase ◽  
Mrna Levels ◽  
Pcr Array ◽  
Thyroid Pathology ◽  
Genes Expression ◽  
Cell Cycle Pathway ◽  
Lower Expression

BACKGROUND: Thyroid hormones are key regulators of essential cellular processes including proliferation, differentiation, and finally apoptosis. AIM: The aim of study was to detect changes in the expression of apoptosis and cell cycle pathway-focused genes in patients with different forms of thyroid pathology. PATIENTS AND METHODS: 36 patients with thyroid pathology were enrolled in the study. We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) to identify and verify apoptosis and cell cycle pathway-focused genes expression in patients with postoperative hypothyroidism, hypothyroidism as a result of autoimmune thyroiditis (AIT) and AIT with elevated serum an anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies. RESULTS: It was shown that patients with elevated serum anti-Tg and anti-TPO antibodies and with hypothyroidism resulting from AIT had a significantly lower expression of FAS, TGFB, TP53, TGFA, while the expression of CD40 was increased. The mRNA levels of BCL2 and BAX decreased in the patients with elevated serum anti-Tg and anti-TPO antibodies and increased in the patients with hypothyroidism resulting from AIT and postoperative hypothyroidism. The patients with hypothyroidism resulting from AIT and postoperative hypothyroidism had significantly lower expression of HSPB1. NF1 expression did not change in all groups of patients. CONCLUSION: The results of this study demonstrate that AIT and hypothyroidism affect the mRNA-level expression of apoptosis and cell cycle pathway-focused genes in gene specific manner and that these changes to gene expression can be responsible for the apoptosis signs and symptoms associated with thyroid pathology.

scholarly journals Analysis of the transcriptional activity of genes of neuropeptides and their receptors in the blood of patients with thyroid pathology

2021 ◽  
Vol 14 (2) ◽  
pp. 243-249
Author(s):  
Iryna Ivanivna Kamyshna ◽  
◽  
Larysa Borysivna Pavlovych ◽  
Vitaliy Antonovych Maslyanko ◽  
Aleksandr Mychailovich Kamyshnyi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Autoimmune Thyroiditis ◽  
Peripheral Blood Lymphocytes ◽  
Vital Role ◽  
Thyroid Peroxidase ◽  
Mrna Levels ◽  
Pcr Array ◽  
Thyroid Pathology ◽  
Group 3 ◽  
Group 2

The thyroid hormone plays a vital role in the development and maturation of the nervous system not only during prenatal and perinatal age but also in adults. “Peripheral marker hypothesis” revealed that gene expression changes in some regions of the brain are reflected into the peripheral blood lymphocytes. The objective of the study was to investigate changes in the gene expression profile of neuropeptides and their receptors in patients with different forms of thyroid pathology. One hundred fifty-three patients with thyroid pathology were enrolled in the study. They were divided into three groups: group 1 included 16 patients with postoperative hypothyroidism, group 2 included 65 patients with hypothyroidism resulting from autoimmune thyroiditis (AIT), and group 3 included 72 patients with AIT and elevated levels of anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies in the serum. We used a pathway-specific polymerase chain reaction (PCR) array (RT2 Profiler™ PCR Array Human Neurotrophins & Receptors, QIAGEN, Germany) to identify and verify neuropeptides and receptors pathway-focused gene expression in 12 individuals that were randomly selected from each group using real-time PCR. Our research identified that patients with postoperative hypothyroidism had a considerably increased expression of NPY1R, NTSR1, and NPY4R. The patients with hypothyroidism caused by autoimmune thyroiditis had considerably lower expression of NTSR1, while the expression of NPY1R increased. The mRNA levels of NPY2R and PNOC increased in the patients with elevated levels of autoantibodies anti-Tg and anti-TPO in the serum, and mRNA levels of NPY1R and NTSR1 decreased in this group of patients.

scholarly journals Nerve impulse transmission pathway-focused genes expression analysis in patients with primary hypothyroidism and autoimmune thyroiditis

2020 ◽  
Vol 54 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Iryna I. Bilous ◽  
Mykhaylo M. Korda ◽  
Inna Y. Krynytska ◽  
Aleksandr M. Kamyshnyi
Keyword(s):  
Autoimmune Thyroiditis ◽  
Blood Cells ◽  
White Blood Cells ◽  
Elevated Serum ◽  
Nerve Impulse ◽  
Neurological Complications ◽  
Pcr Array ◽  
Thyroid Pathology ◽  
Genes Expression ◽  
Peripheral White Blood Cells

AbstractObjective. Thyroid hormones have important actions in the adult brain. They regulate genes expression in myelination, differentiation of neuronal and glial cells, and neuronal viability and function.Methods. We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) to identify and verify nerve impulse transmission pathway-focused genes expression in peripheral white blood cells of patients with postoperative hypothyroidism, hypothyroidism as a result of autoimmune thyroiditis (AIT) and AIT with elevated serum an anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies.Results. It was shown that patients with postoperative hypothyroidism and hypothyroidism resulting from AIT had significantly lower expression of BDNF and CBLN1. In patients with AIT with elevated serum anti-Tg and anti-TPO antibodies, the expression of GDNF was significantly down-regulated and the expression of PNOC was up-regulated. The expression levels of MEF2C and NTSR1 were decreased in the group of patients with postoperative hypothyroidism and AIT, correspondingly.Conclusions. The results of this study demonstrate that AIT and hypothyroidism can affect the expression of mRNA nerve impulse transmission genes in gene specific manner and that these changes in gene expressions can be playing a role in the development of neurological complications associated with thyroid pathology. Detection of the transcriptional activity of nerve impulse transmission genes in peripheral white blood cells can be used as an important minimally invasive prognostic marker of the risk for developing neurological complications comorbid with thyroid pathology.

scholarly journals GRO-alpha in normal and pathological thyroid tissues and its regulation in thyroid-derived cells

2001 ◽  
Vol 170 (3) ◽  
pp. 513-520 ◽  
Author(s):  
G Aust ◽  
M Steinert ◽  
C Boltze ◽  
S Kiessling ◽  
C Simchen
Keyword(s):  
T Cells ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Thyroid Peroxidase ◽  
Mrna Levels ◽  
Carcinoma Cell Lines ◽  
Leukocytic Infiltration ◽  
Cellular Source ◽  
Mrna And Protein Expression

Thyroid glands affected by Graves' disease (GD) show striking leukocytic infiltration, mainly by T-cells. The mechanisms by which the various leukocytes are maintained in the thyroid are unknown. Growth-regulated oncogene-alpha (GRO-alpha) in interaction with its receptor CXCR2 is a chemoattractant for both T-cells and neutrophils and may be one of the chemokines involved in the cell maintenance. GRO-alpha and CD18 mRNA as a marker of leukocytic infiltration were quantified in thyroid tissue using competitive RT-PCR. We found very high GRO-alpha mRNA levels in all thyroid tissues. In GD patients (n=16), the GRO-alpha mRNA did not correlate with the CD18 mRNA level or thyroid peroxidase and TSH-receptor antibodies in patients' sera. In thyroid autonomy (n=10), the GRO-alpha mRNA levels were significantly lower in autonomous single adenomas compared with the corresponding normal tissue. In order to define the cellular source of GRO-alpha mRNA and protein, we examined various thyroid-derived cells. Thyrocytes, thyroid-derived leukocytes and fibroblasts showed basal GRO-alpha mRNA and protein expression, which was remarkably upregulated by different stimuli in vitro. The expression of GRO-alpha by thyroid carcinoma cell lines confirms that thyrocytes may actually produce GRO-alpha. As shown by flow cytometry and immunohistology, CD68+ monocytes/macrophages are the only cell population strongly expressing CXCR2 in the thyroid.

Sodium butyrate induces cellular senescence in neuroblastoma and prostate cancer cells

2011 ◽  
Vol 7 (1) ◽  
Author(s):  
Viola Lorenz ◽  
Wiebke Hessenkemper ◽  
Julia Rödiger ◽  
Sergiy Kyrylenko ◽  
Florian Kraft ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Tumor Cells ◽  
Cellular Senescence ◽  
Sodium Butyrate ◽  
Mrna Level ◽  
Hdac Inhibitors ◽  
Mrna Levels ◽  
Cellular Division

AbstractCellular senescence leads to an irreversible block of cellular division capacity both in cell culture and in vivo. The induction of an irreversible cell cycle arrest is very useful for treatment of cancer. Histone deacetylases (HDACs) are considered as therapeutic targets to treat cancer patients. HDAC inhibitors repress cancer growth and are used in various clinical trials. Here, we analyzed whether sodium butyrate (NaBu), an inhibitor of class I and II HDACs, induces cellular senescence in neuroblastoma and prostate cancer (PCa) including an androgen-dependent as well as an androgen-independent human PCa cell line. We found that the HDAC inhibitors NaBu and valproic acid (VPA) induce cellular senescence in tumor cells. Interestingly, also an inhibitor of SIRT1, a class HDAC III, induces cellular senescence. Both neuroblastoma and human prostate cancer cell lines express senescence markers, such as the Senescence Associated-β-galactosidase (SA-β-Gal) and Senescence Associated Heterochromatin Foci (SAHF). Furthermore, NaBu down-regulates the proto-oncogenes c-Myc, Cyclin D1 and E2F1 mRNA levels. The mRNA level of the cell cycle inhibitor p16 remains unchanged whereas that of the tumor suppressor p21 is strongly up-regulated. Interestingly, NaBu treatment robustly increases reactive oxygen species (ROS) levels. These results indicate an epigenetic regulation and an association of HDAC inhibition and ROS production with cellular senescence. The data underline that tumor cells can be driven towards cellular senescence by HDAC inhibitors, which may further arise as a potent possibility for tumor suppression.

scholarly journals Cell-Cycle–Dependent Regulation of Erythropoietin Receptor Gene

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1182-1188 ◽  
Author(s):  
Norio Komatsu ◽  
Keita Kirito ◽  
Yoshifumi Kashii ◽  
Yusuke Furukawa ◽  
Jiro Kikuchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Growth ◽  
Receptor Gene ◽  
Mrna Level ◽  
State Level ◽  
Erythropoietin Receptor ◽  
Cycle Phase ◽  
Mrna Levels ◽  
Mobility Shift

Abstract To understand the regulatory mechanism of erythropoietin (EPO) receptor (EPOR) gene expression, the effect of EPO on the steady-state level of EPOR mRNA was examined using the human EPO-dependent cell line UT-7 as a model system. We found that the treatment of UT-7 cells with EPO resulted in a transient decrease of the EPOR mRNA level. This transient downregulation was also induced by stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF ), another stimulator of UT-7 cell growth. These results raised the possibility that EPOR gene expression is in part related to cell growth. Moreover, it was found that EPO-induced downregulation of EPOR mRNA level was preceded by a transient downregulation of GATA-1 mRNA. To examine the relationship between the expression of EPOR, GATA-1, and GATA-2 mRNA levels and the cell cycle, logarithmically growing UT-7 cells were centrifugically fractionated according to the cell-cycle phase. Both EPOR and GATA-1 mRNA levels, but not the GATA-2 mRNA level, concomitantly decreased at the G0/G1 phase and increased at the S and G2/M phases. An electrophoretic mobility shift assay (EMSA) showed that in EPO-stimulated UT-7 cells, the dynamic changes in EPOR gene expression paralleled the GATA-1 DNA-binding activity to the oligonucleotide probe containing a GATA-binding site located at the promoter region of the EPOR gene. These findings suggest that the regulation of EPOR mRNA level is mainly associated with GATA-1 gene expression in UT-7 cells undergoing proliferation, and that these serial events are under the control of, or related to, the cell cycle.

scholarly journals The Associations of Urinary DEHP Metabolites Levels, Serum Thyroid Hormones and Thyroid Related Genes Among the Adolescent Students from China – A Cross-Sectional Study

2021 ◽  
Author(s):  
Yaming Zhao ◽  
Xinyue Song ◽  
Shuang Ding ◽  
Wen Qi ◽  
Yuezhu Zhang ◽  
...  
Keyword(s):  
Mrna Level ◽  
Cross Sectional Study ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Mrna Levels ◽  
Sodium Iodide Symporter ◽  
Free Triiodothyronine ◽  
Cross Sectional ◽  
Adolescent Students ◽  
Thyroid Transcription Factor 1

Abstract Our study aimed to investigate the associations between DEHP exposure and serum thyroid hormone levels in 347 adolescents and young adults. We measured DEHP metabolites including mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono(2-carboxmethyl)hexyl phthalate (MCMHP) in their urine. Total thyroxine (TT4), total triiodothyronine, free triiodothyronine, free thyroxine (FT4), thyroid-stimulating hormone and the mRNA levels of thyroid peroxidase (TPO), thyroglobulin (TG), sodium iodide symporter (NIS), thyroid transcription factor 1 (TTF-1) and paired box gene 8 (PAX-8) in serum were measured. The results of statistical analysis showed that urinary DEHP metabolites were generally negatively associated with TT4 levels in serum. In the males, the FT4 levels showed positive associations with urinary MEHP, MECPP, MCMHP, and ∑DEHP. The mRNA level of TG was significantly positively correlated with the levels of MECPP, MCMHP and ∑DEHP, while the level of NIS mRNA was significantly positively correlated with the levels of MEOHP. There was a significant positive correlation between TTF-1 mRNA level and urinary MEOHP, MECPP, MCMHP and ∑DEHP.

scholarly journals The effects of short-term genistein intervention on prostate biomarker expression in patients with localised prostate cancer before radical prostatectomy

2012 ◽  
Vol 108 (12) ◽  
pp. 2138-2147 ◽  
Author(s):  
Bato Lazarevic ◽  
Clara Hammarström ◽  
Jin Yang ◽  
Hakon Ramberg ◽  
Lien M. Diep ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Mrna Level ◽  
Neuron Specific Enolase ◽  
Neuroendocrine Differentiation ◽  
Tissue Microarrays ◽  
Nuclear Antigen ◽  
Gleason Grade ◽  
Mrna Levels ◽  
Double Blind

Nutritionally relevant levels of genistein, the predominant isoflavone in soyabean associated with lower risk of prostate cancer (PCa), may modulate the expression of prostate tissue biomarkers associated with cancer prediction and progression. A phase 2 placebo-controlled, randomised, double-blind clinical trial was conducted in forty-seven Norwegian patients before prostatectomy. Intervention was 30 mg genistein or placebo capsules daily for 3–6 weeks. Luminal cells from malignant and benign glands were isolated with laser capture microdissection and the mRNA levels of androgen-related biomarkers (androgen receptor, NK3 homeobox 1, kallikrein-related peptide 4 (KLK4)) and cell cycle-related genes (p21Waf1/Cip1, p27Kip1, p53) were analysed with real-time semiquantitative PCR. Immunohistochemistry of androgen-, cell cycle-, proliferative- (Ki67 nuclear antigen), apoptotic- (B-cell CLL/lymphoma 2 (BCL-2) and BCL-2-associated X protein) and neuroendocrine differentiation-related biomarkers (neuron-specific enolase and cytoplasmic chromogranin A) was performed using tissue microarrays containing normal, Gleason grade 3 and grade 4 prostate tissues. There were no significant effects by genistein intervention on proliferation-, cell cycle-, apoptosis- or neuroendocrine biomarkers. Genistein intervention, however, significantly reduced the mRNA level of KLK4 in tumour cells (P = 0·033) and there was a non-significant reduction in androgen and cell cycle-related biomarkers, except for p27Kip1, whose expression in the nuclear compartment was increased. Genistein intervention modulated the expression of several biomarkers which may be related to PCa prediction and progression. The present study supports genistein as a chemopreventive agent in PCa. Further investigation is warranted in larger and longer-duration studies.

HIF1A is Overexpressed in Medulloblastoma and its Inhibition Reduces Proliferation and Increases EPAS1 and ATG16L1 Methylation

2018 ◽  
Vol 18 (3) ◽  
pp. 287-294 ◽  
Author(s):  
Gustavo Alencastro Veiga Cruzeiro ◽  
Maristella Bergamo dos Reis ◽  
Vanessa Silva Silveira ◽  
Regia Caroline Peixoto Lira ◽  
Carlos Gilberto Carlotti Jr ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Line ◽  
Cellular Proliferation ◽  
Mrna Level ◽  
Relevant Information ◽  
Protein Stabilization ◽  
Mrna Levels ◽  
Medulloblastoma Cell Line ◽  
Pediatric Medulloblastoma ◽  
Fresh Frozen

Background: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxiarelated genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions. Objective: Our study focused on evaluation the of CA9, CA12, HIF1A, EPAS1, SCL2A1 and VEGF genes in 41 pediatric fresh-frozen medulloblastoma sample. Additionally, we analyzed the effect of hypoxia and normoxia in the pediatric medulloblastoma cell-line UW402. Furthermore, we assessed the effects of HIF1A knockdown in cell-proliferation and methylation levels of genes related to hypoxia, apoptosis and autophagy. Method: qPCR was performed to evaluate mRNA levels, and Western blot to confirm HIF1A silencing in both patient samples and cell line. Pyrosequencing was performed to asses the methylation levels after HIF1A knockdown in the UW402 cell line. Results: A higher HIF1A mRNA level was observed in MB patients when compared to the cerebellum (non-tumor match). In UW402 MB cell-line, chemically induced hypoxic resulted in an increase of mRNA levels of HIF1A, VEGF, SCL2A1 and CA9 genes. Additionally, HIF1A knockdown induced a decrease in the expression of hypoxia related genes and a decrease of 30% in cell proliferation was also observed. Also, a significant increase in the methylation of ATG16L1 promoter and decrease in the methylation of EPAS1 promoter were observed after HIF1A knockdown. Conclusion: HIF1A knockdown in medulloblastoma cells lead to decreased cellular proliferation, suggesting that HIF1A can be a potential therapeutic target to be explored in the medulloblastoma. However, the mechanisms behind HIF1A protein stabilization and function are very complex and more data need to be generated to potentially use HIF1A as a therapeutical target.

Serum Thyroid Peroxidase Antibody Level and Incident Hypertension in Iranian Men: A Suggestion for the Role of Thyroid Autoimmunity

2020 ◽  
Vol 20 (10) ◽  
pp. 1711-1718
Author(s):  
Maryam Tohidi ◽  
Aidin Baghbani-Oskouei ◽  
Atieh Amouzegar ◽  
Ladan Mehran ◽  
Fereidoun Azizi ◽  
...  
Keyword(s):  
Total Population ◽  
Thyroid Autoimmunity ◽  
Elevated Serum ◽  
Thyroid Peroxidase ◽  
Incident Hypertension ◽  
Natural Logarithm ◽  
Hazard Ratios ◽  
Thyroid Peroxidase Antibody ◽  
Unit Increase

Background: Dysfunction of the thyroid gland has profound effects on the cardiovascular system. Objective: We aimed to explore the relation of serum thyroid peroxidase antibody (TPO-Ab), as a marker of thyroid autoimmunity with incident hypertension among a euthyroid population. Methods: A total of 3681 participants (1647 men) entered the study. Multivariate Cox proportional hazard models were conducted to estimate the association between TPO-Ab and incident hypertension. Results: The mean age (standard deviation) of the participants was 37.5 (12.8) years. During a median follow-up of 12.2 years, 511 men and 519 women developed hypertension. The multivariable hazard ratios (HRs) and related 95% confidence intervals (CIs) of 1-unit increase in natural logarithm (ln) of TPO-Ab for incident hypertension were 1.09 (1.00-1.19), 1.03 (0.97-1.10), and 1.05 (1.00-1.11) for men, women, and total population, respectively. Moreover, considering the TPO-Ab status as a categorical variable (i.e. TPO-Ab positive or TPO-Ab negative), the multivariate-adjusted HRs (95% CIs) of TPO-Ab positivity for incident hypertension, were 1.33 (0.95-1.85), 1.12 (0.86-1.45) and 1.19 (0.97- 1.46) for men, women, and total population, respectively. Conclusion: Elevated serum TPO-Ab level can contribute to the development of hypertension among euthyroid men during a long follow-up; suggesting a role for thyroid autoimmunity.

scholarly journals ACE2, TMPRSS2 and L-SIGN expression in placentae from HIV-positive pregnancies exposed to antiretroviral therapy–implications for SARS-CoV-2 placental infection

2021 ◽  
Author(s):  
Smriti Kala ◽  
Ksenia Meteleva ◽  
Lena Serghides
Keyword(s):  
Antiretroviral Therapy ◽  
Pregnant Women ◽  
Viral Entry ◽  
Cell Entry ◽  
Hiv Positive ◽  
Mrna Levels ◽  
Black Race ◽  
Entry Receptor ◽  
Lower Expression ◽  
Human Placentae

Abstract Background SARS-CoV-2 binding receptor ACE2 and the spike protein priming protease TMPRSS2 are co-expressed in human placentae. It is unknown whether their expression is altered in the context of HIV infection and antiretroviral therapy (ART). Methods We compared mRNA levels of SARS-CoV-2 cell-entry mediators ACE2, TMPRSS2 and L-SIGN (an alternative entry receptor) by qPCR in 105 placentae: 45 from pregnant women with HIV (WHIV) exposed to protease inhibitor (PI)-based ART, 17 from WHIV on non-PI-based ART, and 43 from HIV-uninfected women. Results ACE2 levels were lower, while L-SIGN levels were higher in placentae from WHIV on PI-based ART as compared to those on non-PI-based ART and to HIV-uninfected women. TMPRSS2 levels were similar between groups. Black race was significantly associated with lower expression of ACE2 and higher expression of L-SIGN. ACE2 levels were significantly higher in placentae of female fetuses. Discussion We have identified pregnant women of Black race and WHIV who are on PI-based ART to have relatively lower expression of placental ACE2 than those of White race and HIV-uninfected women. This effect may potentially contribute to altered susceptibility to COVID-19 in these women, either favorably; by reduced viral entry, or detrimentally; by loss of ACE2 protection against hyperinflammation.

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