Nonsense suppressors partially revert the decrease of the mRNA level of a nonsense mutant allele in yeast

1990 ◽  
Vol 17 (1) ◽  
pp. 77-79 ◽  
Author(s):  
D. Gozalbo ◽  
S. Hohmann
Keyword(s):  
Mutant Allele ◽  
Mrna Level ◽  
Nonsense Mutant ◽  
Nonsense Suppressors

Sequence of the human glycogen-associated regulatory subunit of type 1 protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with NIDDM

Diabetes ◽  
1994 ◽  
Vol 43 (10) ◽  
pp. 1234-1241 ◽  
Author(s):  
Y. H. Chen ◽  
L. Hansen ◽  
M. X. Chen ◽  
C. Bjorbaek ◽  
H. Vestergaard ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Mrna Level ◽  
Regulatory Subunit ◽  
Coding Region

INTERRELATION OF ALLELIC VARIANTS OF HEMOSTASIS SYSTEM GENES ON THE DEVELOPMENT AND COURSE OF LUPUS NEPHRITIS

2019 ◽  
Vol 23 (2) ◽  
pp. 77-81
Author(s):  
E. N. Borisov ◽  
L. V. Ivanitsky ◽  
L. M. Samokhodskaya ◽  
T. N. Krasnova ◽  
E. P. Pavlikova ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Mutant Allele ◽  
Impaired Renal Function ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Renal Survival ◽  
Mutant Genotype ◽  
Hemostatic System ◽  
Allelic Variations ◽  
Pai 1

THE AIM: to evaluate the effect of allelic variations in the hemostatic system genes on the development and course of lupus nephritis. PATIENTS AND METHODS. The study analyzed 100 patients with SLE Caucasians. 80 women and 20 men aged 16 to 73 years (mean age 37, ± 14 years). The duration of observation was for 73 patients over 5 years, for 18 – from 1 year to 5 years and for 9 – less than 1 year A rise in the level of creatinine in the blood above or equal to 2 mg / dl was considered a significant sign of impaired renal function. RESULTS. Among the patients included in the study, kidney damage was detected in 61 people (61%). In 33 of them (54.1%), a variant of renal pathology was observed according to the type of rapidly progressive lupus nephritis (BPVN). In patients with BH, mutations in the MTHFR (C677T) gene were statistically significantly more frequent (p = 0.033). The OR for the mutant genotype is 6.146 with 95% CI from 1.692 to 22.326. In patients with PWHD, mutations in the MTHFR (C677T) gene were statistically significantly more frequent (p = 0.031). The OR for the mutant genotype is 1.625 with 95% CI from 1.034 to 4.771. The five-year renal survival in carriers of the mutant allele of the MTHFR gene (C677T) is statistically significantly lower (72.8%) than in patients without this mutation (81.9%) (p = 0.027). Ten-year renal survival in carriers of the mutant allele of the MTHFR gene (C677T) is statistically significantly less (55.6%) than in patients without this mutation (70.5%) (p = 0.016). In patients with BH, mutations in the PAI-1 gene (4G / 5G 675) were statistically significantly more frequent (p = 0.046). OR for mutant genotype – 1.766 with 95% CI from 1.061 to 4.758. CONCLUSION. The mutant alleles of the MTHFR (C677T) and PAI-1 (4G / 5G 675) genes are likely to be associated with the development of BH. Polymorphism of the MTHFR gene (C677T) is associated with an unfavorable course of HH.

Estrogen responsive finger protein as a new potential biomarker for breast cancer

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Carcinoma ◽  
Cancer Patients ◽  
Mrna Level ◽  
Significant Prognostic Factor ◽  
Breast Carcinomas ◽  
Finger Protein ◽  
Potential Biomarker ◽  
Human Breast Carcinomas

Purpose: Estrogen-responsive finger protein (Efp) is amember ofRINGfinger-B box-Coiled Coilfamily and is also a downstream target of estrogen receptor a. Previously, Efp was shown tomediate estrogen-induced cell growth, which suggests possible involvement in the developmentof human breast carcinomas. In this study, we examined expression of Efp in breast carcinomatissues and correlated these findings with various clinicopathologic variables.Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistryand laser capture microdissection/real-time PCR of Efp. Immunohistochemistryfor Efp was also done in 151breast carcinoma specimens fixed with formalin and embedded inparaffinwax.Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantlyassociated with the mRNA level (n = 30). Efp immunoreactivity was positively associated withlymph node status or estrogen receptor a status and negatively correlated with histologic gradeor 14-3-3j immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlatedwith poor prognosis of breast cancer patients, and multivariate analyses of disease-freesurvival and overall survival for151breast cancer patients showed that Efp immunoreactivity wasthe independentmarker.Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor inbreast cancer patients. These findings may account for an oncogenic role of Efp in the tumorprogression of breast carcinoma.

Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Differentially Expressed ◽  
Thyroid Tumors ◽  
Papillary Thyroid

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.

The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 307-317
Author(s):  
Yuan Yang ◽  
Jin Huang ◽  
Jianzhong Li ◽  
Huansheng Yang ◽  
Yulong Yin
Keyword(s):  
Cell Viability ◽  
P38 Mapk ◽  
Butyric Acid ◽  
Cell Apoptosis ◽  
Mapk Pathway ◽  
Mrna Level ◽  
Dependent Manner ◽  
M Phase ◽  
High Concentrations ◽  
Underlying Mechanisms

Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.

Pharmacological Inhibition of Transient Receptor Potential Melastatin 2 (TRPM2) Channels Attenuates Diabetes-induced Cognitive Deficits in Rats: A Mechanistic Study

2020 ◽  
Vol 17 (3) ◽  
pp. 249-258 ◽  
Author(s):  
Pavan Thapak ◽  
Mahendra Bishnoi ◽  
Shyam S. Sharma
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Ache Activity ◽  
Transient Receptor Potential ◽  
Mrna Level ◽  
Receptor Potential ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channels ◽  
Transient Receptor ◽  
Gsk 3Β

Background: Diabetes is a chronic metabolic disorder affecting the central nervous system. A growing body of evidence has depicted that high glucose level leads to the activation of the transient receptor potential melastatin 2 (TRPM2) channels. However, there are no studies targeting TRPM2 channels in diabetes-induced cognitive decline using a pharmacological approach. Objective: The present study intended to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB), a TRPM2 inhibitor, in diabetes-induced cognitive impairment. Methods: Streptozotocin (STZ, 50 mg/kg, i.p.) was used to induce diabetes in rats. Animals were randomly divided into the treatment group, model group and age-matched control and pre se group. 2-APB treatment was given for three weeks to the animals. After 10 days of behavioural treatment, parameters were performed. Animals were sacrificed at 10th week of diabetic induction and the hippocampus and cortex were isolated. After that, protein and mRNA expression study was performed in the hippocampus. Acetylcholinesterase (AchE) activity was done in the cortex. Results: : Our study showed the 10th week diabetic animals developed cognitive impairment, which was evident from the behavioural parameters. Diabetic animals depicted an increase in the TRPM2 mRNA and protein expression in the hippocampus as well as increased AchE activity in the cortex. However, memory associated proteins were down-regulated, namely Ca2+/calmodulin-dependent protein kinase II (CaMKII-Thr286), glycogen synthase kinase 3 beta (GSK-3β-Ser9), cAMP response element-binding protein (CREB-Ser133), and postsynaptic density protein 95 (PSD-95). Gene expression of parvalbumin, calsequestrin and brain-derived neurotrophic factor (BDNF) were down-regulated while mRNA level of calcineurin A/ protein phosphatase 3 catalytic subunit alpha (PPP3CA) was upregulated in the hippocampus of diabetic animals. A three-week treatment with 2-APB significantly ameliorated the alteration in behavioural cognitive parameters in diabetic rats. Moreover, 2-APB also down-regulated the expression of TRPM2 mRNA and protein in the hippocampus as well as AchE activity in the cortex of diabetic animals as compared to diabetic animals. Moreover, the 2-APB treatment also upregulated the CaMKII (Thr-286), GSK-3β (Ser9), CREB (Ser133), and PSD-95 expression and mRNA levels of parvalbumin, calsequestrin, and BDNF while mRNA level of calcineurin A was down-regulated in the hippocampus of diabetic animals. Conclusion: : This study confirms the ameliorative effect of TRPM2 channel inhibitor in the diabetes- induced cognitive deficits. Inhibition of TRPM2 channels reduced the calcium associated downstream signaling and showed a neuroprotective effect of TRPM2 channels in diabetesinduced cognitive impairment.

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.

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