scholarly journals Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 387
Author(s):  
Venkata Naga Srikanth Garikipati ◽  
Arsen Arakelyan ◽  
Eleanor A. Blakely ◽  
Polly Y. Chang ◽  
May M. Truongcao ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Biological Response ◽  
Rna Isolation ◽  
Degenerative Disease ◽  
Low Doses ◽  
Long Term Effects ◽  
Bioinformatics Analyses ◽  
Particle Radiation ◽  
Tissue Samples ◽  
Linear Pattern

Compared to low doses of gamma irradiation (γ-IR), high-charge-and-energy (HZE) particle IR may have different biological response thresholds in cardiac tissue at lower doses, and these effects may be IR type and dose dependent. Three- to four-month-old female CB6F1/Hsd mice were exposed once to one of four different doses of the following types of radiation: γ-IR 137Cs (40-160 cGy, 0.662 MeV), 14Si-IR (4-32 cGy, 260 MeV/n), or 22Ti-IR (3-26 cGy, 1 GeV/n). At 16 months post-exposure, animals were sacrificed and hearts were harvested and archived as part of the NASA Space Radiation Tissue Sharing Forum. These heart tissue samples were used in our study for RNA isolation and microarray hybridization. Functional annotation of twofold up/down differentially expressed genes (DEGs) and bioinformatics analyses revealed the following: (i) there were no clear lower IR thresholds for HZE- or γ-IR; (ii) there were 12 common DEGs across all 3 IR types; (iii) these 12 overlapping genes predicted various degrees of cardiovascular, pulmonary, and metabolic diseases, cancer, and aging; and (iv) these 12 genes revealed an exclusive non-linear DEG pattern in 14Si- and 22Ti-IR-exposed hearts, whereas two-thirds of γ-IR-exposed hearts revealed a linear pattern of DEGs. Thus, our study may provide experimental evidence of excess relative risk (ERR) quantification of low/very low doses of full-body space-type IR-associated degenerative disease development.

Abstract MP216: Identification Of Novel Phosphoprotein Signaling Pathways In Human Dilated Cardiomyopathy By Integrative Proteomic And Phosphoproteomic Analysis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Cristine J Reitz ◽  
Marjan Tavassoli ◽  
Da Hye Kim ◽  
Sina Hadipour-Lakmehsari ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Tissue ◽  
Regulatory Element ◽  
Critical Role ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Intercalated Disc ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
And Function

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure, yet the majority of the underlying signaling mechanisms remain poorly characterized. Protein phosphorylation is a key regulatory element with profound effects on the activity and function of signaling networks; however, there is a lack of comprehensive phosphoproteomic studies in human DCM patients. We assessed the hypothesis that an integrative phosphoproteomics analysis of human DCM would reveal novel phosphoprotein candidates involved in disease pathophysiology. Combined proteomic and phosphoproteomic analysis of explanted left ventricular tissue samples from DCM patients ( n =4) and non-failing controls ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. From these analyses, we identified αT-catenin as a unique candidate protein with a cluster of 4 significantly hyperphosphorylated sites in DCM hearts ( P <0.0001), with no change in total αT-catenin expression at the protein level. Bioinformatics analyses of human datasets and confocal imaging of human and mouse cardiac tissue show highly cardiac-enriched expression of αT-catenin, localized to the cardiomyocyte intercalated disc. High resolution 3-dimensional reconstruction shows elongated intercalated disc morphology in DCM hearts (10.07±0.76 μm in controls vs. 17.20±1.87 μm in DCM, P <0.05, n =3/group), with significantly increased colocalization of αT-catenin with the intercalated disc membrane protein N-cadherin (Pearson’s coefficient 0.55±0.04 in controls vs. 0.71±0.02 in DCM, P <0.05, n =3/group). To investigate the functional role of cardiac αT-catenin phosphorylation, we overexpressed WT protein vs. non-phosphorylatable forms based on the loci identified in DCM hearts, in adult mouse cardiomyocytes using lentiviral transduction. Confocal imaging revealed significant internalization of the phospho-null form, as compared to the prominent intercalated disc staining of the WT protein (17.78±0.79% of WT vs. 9.25±0.49% of 4A mutant, P <0.0001, n =50 cells/group). Together, these findings suggest a critical role for αT-catenin phosphorylation in maintaining cardiac intercalated disc organization in human DCM.

Abstract P160: Non-invasive Method to Assess Human Circadian Rhythms

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Daian Chen ◽  
S Justin Thomas ◽  
David A Calhoun ◽  
David M Pollock ◽  
Jennifer S Pollock
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Salivary Cortisol ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Light Exposure ◽  
Rna Isolation ◽  
Buccal Cells ◽  
Non Invasive ◽  
Salivary Melatonin

Circadian rhythms are controlled by an endogenous time-keeping system oscillating approximately on a 24-h cycle under constant conditions. These rhythms depend on a network of interacting genes and proteins, including transcriptional activators such as CLOCK, NPAS2, and ARNTL (BMAL1), which induce transcription of the clock genes Period ( Per1 , Per2 , and Per3 ) and Cryptochrome ( Cry1 and Cry2 ). Human salivary cortisol and melatonin follow a clear circadian rhythm as well. Disruption of the circadian rhythm and sleep-wake cycles are considered risk factors for a variety of health problems, especially hypertension and other cardiovascular and metabolic diseases. Here we put together practical methods for assessing circadian rhythms in adult subjects conducted by each individual. This method is non-invasive, inexpensive and provides a predictive profile of an individual’s circadian rhythm related to clock-controlled gene expression in buccal cells, salivary cortisol, salivary melatonin, and subject’s activity or sleep. Subjects are instructed on how to obtain buccal cells using swabs (Whatman OmniSwab) from the inside of their cheeks and collect saliva using salivettes (Sarstedt) every 4 hours starting at 6am, for 2 consecutive days. Subjects also wear actigraphy watches (Phillips Respironics) during the 2 days, to record their activity, light exposure and estimates of sleep times. To monitor adherence to correct time point collections, each subject is given an electronic vial called eCAP (Information Mediary Corp) that records the exact time the container is opened to place samples once collected. We demonstrate feasibility to extract up to 150ng/μl of RNA (Ambion RNAqueous-Micro Total RNA Isolation Kit) from buccal cells swabs. Salivary melatonin and cortisol are measured by radioimmunoassay (Buhlmann Lab) with melatonin peak levels ranging from 14 to 23 pg/ml and cortisol peak levels ranging from 10 to 24 ng/ml. We suggest that buccal cell expression of clock-controlled genes, salivary melatonin, salivary cortisol, and actigraphy data are valuable in providing reliable assessment of human circadian rhythm profiles under a variety of conditions.

DRAXIN as a Novel Diagnostic Marker to Predict the Poor Prognosis of Glioma Patients

2021 ◽  
Author(s):  
Zhendong Liu ◽  
Runze Liu ◽  
Xingbo Cheng ◽  
Binfeng Liu ◽  
Yongjie Zhu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Clinical Information ◽  
Drug Analysis ◽  
Bioinformatics Analyses ◽  
Carcinogenic Effect ◽  
Tissue Samples ◽  
Reverse Transcription Quantitative Pcr ◽  
Biological Target ◽  
The Relationship

Abstract An increasing number of evidences have shown that the carcinogenic effect of DRAXIN plays an important role in the malignant process of tumors, but the mechanism of its involvement in glioma has not yet been revealed. The main aim of this study is to explore the relationship between DRAXIN and the prognosis and pathogenesis of glioma through a large qualities of data analysis. Firstly, thousands of tissue samples with clinical information were collected based on various public databases. Then, a series of bioinformatics analyses were performed to mine data from information of glioma samples extracted from several reputable databases to reveal the key role of DRAXIN in glioma development and progression, with the confirmation of basic experiments. Our results showed high expression of the oncogene DRAXIN in tumor tissue and cells could be used as an independent risk factor for poor prognosis in glioma patients and was strongly associated with clinical risk features. The reverse transcription-quantitative PCR technique was then utilized to validate the DRAXIN expression results we obtained. In addition, co-expression analysis identified respectively top 10 genes that were closely associated with DRAXIN positively or negatively. Finally, four drugs that may have inhibitory effects on DRAXIN were gained by Cmap drug analysis. To sum up, this is the first report of DRAXIN being highly expressed in gliomas and leading to poor prognosis of glioma patients. DRAXIN may not only benefit to explore the pathogenesis of gliomas, but also serve as a novel biological target for the treatment of glioma.

Medium and long-term effects of low doses of Chlorpyrifos during the postnatal, preweaning developmental stage on sociability, dominance, gut microbiota and plasma metabolites

2020 ◽  
Vol 184 ◽  
pp. 109341 ◽  
Author(s):  
Cristian Perez-Fernandez ◽  
Miguel Morales-Navas ◽  
Luis Manuel Aguilera-Sáez ◽  
Ana Cristina Abreu ◽  
Laia Guardia-Escote ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Developmental Stage ◽  
Plasma Metabolites ◽  
Low Doses ◽  
Long Term Effects

Climatic and oceanic influences on the abundance of gelatinous zooplankton in the North Sea

2009 ◽  
Vol 90 (6) ◽  
pp. 1153-1159 ◽  
Author(s):  
C.P. Lynam ◽  
M.J. Attrill ◽  
M.D. Skogen
Keyword(s):  
North Sea ◽  
Biological Response ◽  
Winter Precipitation ◽  
Gelatinous Zooplankton ◽  
Aurelia Aurita ◽  
Future Research ◽  
Long Term Effects ◽  
The North ◽  
The North Sea ◽  
Northern North Sea

Oceanographically based mechanisms are shown to explain the spatial variation in the climatic relationship between the abundance of medusae (Aurelia aurita and Cyanea spp. of the class Scyphozoa), in the North Sea between 1971 and 1986 during June–August, and the winter (December–March) North Atlantic Oscillation Index (NAOI). A scyphomedusa population to the west of Denmark shows a strong inverse relationship between medusa abundance and fluctuations in the NAOI; the NAOI correlates strongly (P < 0.001) with both annual sea surface temperature (SST) at 6.5°E 56.5°N (1950–2008) and with winter precipitation on the Danish coast at Nordby (1900–2008) suggesting a direct link between the influence of climate and medusae abundance. In contrast, scyphomedusa abundance and distribution in the northern North Sea appears to be influenced by oceanic and mixed water inflow, which may overwhelm or mask any direct climatic influence on jellyfish abundance. Similarly, advection can also explain much of the interannual variability (1959–2000) in the abundance of other gelatinous zooplankton taxa (Cnidaria, Ctenophora and Siphonophora) in the northern North Sea as identified by the capture of gelatinous tissue and nematocysts (stinging cells) in Continuous Plankton Recorder samples. Jellyfish (Scyphozoa) in the southern North Sea may benefit from low temperature anomalies and the long-term effects of global warming might suppress Aurelia aurita and Cyanea spp. populations there. However, the biological response to temperature is complex and future research is required in this area.

scholarly journals Long-Term Exposure of Psoralen and Isopsoralen Induced Hepatotoxicity and Serum Metabolites Profiles Changes in Female Rats

Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 263 ◽  
Author(s):  
Yingli Yu ◽  
Pengli Wang ◽  
Ruili Yu ◽  
Jiaxi Lu ◽  
Miaomiao Jiang ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Female Rats ◽  
Proton Nuclear Magnetic Resonance ◽  
Long Term Effects ◽  
Serum Samples ◽  
Drug Induced ◽  
Clinical Safety ◽  
Tissue Samples ◽  
Unsaturated Lipids

Pre-clinical safety evaluation of traditional medicines is imperative because of the universality of drug-induced adverse reactions. Psoralen and isopsoralen are the major active molecules and quality-control components of a traditional herbal medicine which is popularly used in Asia, Fructus Psoraleae. The purpose of this study is to assess the long-term effects of psoralen and isopsoralen with low levels on the biochemical parameters and metabolic profiles of rats. Three doses (14, 28, and 56 mg/kg) of psoralen and one dose (28 mg/kg) of isopsoralen were administered to rats over 12 weeks. Blood and selected tissue samples were collected and analyzed for hematology, serum biochemistry, and histopathology. Metabolic changes in serum samples were detected via proton nuclear magnetic resonance (1H-NMR) spectroscopy. We found that psoralen significantly changed the visceral coefficients, blood biochemical parameters, and histopathology, and isopsoralen extra influenced the hematological index. Moreover, psoralen induced remarkable elevations of forvaline, isoleucine, isobutyrate, alanine, acetone, pyruvate, glutamine, citrate, unsaturated lipids, choline, creatine, phenylalanine, and 4-hydroxybenzoate, and significant reductions of ethanol and dimethyl sulfone. Isopsoralen only induced a few remarkable changes of metabolites. These results suggest that chronic exposure to low-level of psoralen causes a disturbance in alanine metabolism, glutamate metabolism, urea cycle, glucose-alanine cycle, ammonia recycling, glycine, and serine metabolism pathways. Psoralen and isopsoralen showed different toxicity characteristics to the rats.

scholarly journals The impact of COVID-19 on rare metabolic patients and healthcare providers: results from two MetabERN surveys

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
C. Lampe ◽  
◽  
C. Dionisi-Vici ◽  
C. M. Bellettato ◽  
L. Paneghetti ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Healthcare Providers ◽  
Relevant Information ◽  
European Population ◽  
Reference Network ◽  
Long Term Effects ◽  
European Reference Network ◽  
Hereditary Metabolic Diseases ◽  
Hospital To Home ◽  
The Impact

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic has caused disruption in all aspects of daily life, including the management and treatment of rare inherited metabolic disorders (IMDs). To perform a preliminary assessment of the incidence of COVID-19 in IMD patients and the impact of the coronavirus emergency on the rare metabolic community between March and April 2020, the European Reference Network for Hereditary Metabolic Diseases (MetabERN) has performed two surveys: one directed to patients’ organizations (PO) and one directed to healthcare providers (HCPs). The COVID-19 incidence in the population of rare metabolic patients was lower than that of the general European population (72.9 × 100,000 vs. 117 × 100,000). However, patients experienced extensive disruption of care, with the majority of appointments and treatments cancelled, reduced, or postponed. Almost all HCPs (90%) were able to substitute face-to-face visits with telemedicine, about half of patients facing treatment changes switched from hospital to home therapy, and a quarter reported difficulties in getting their medicines. During the first weeks of emergency, when patients and families lacked relevant information, most HCPs contacted their patients to provide them with support and information. Since IMD patients require constant follow-up and treatment adjustments to control their disease and avoid degradation of their condition, the results of our surveys are relevant for national health systems in order to ensure appropriate care for IMD patients. They highlight strong links in an interconnected community of HCPs and PO, who are able to work quickly and effectively together to support and protect fragile persons during crisis. However, additional studies are needed to better appreciate the actual impact of COVID-19 on IMD patients’ health and the mid- and long-term effects of the pandemic on their wellbeing.

scholarly journals Maternal protein restriction impairs the transcriptional metabolic flexibility of skeletal muscle in adult rat offspring

2014 ◽  
Vol 112 (3) ◽  
pp. 328-337 ◽  
Author(s):  
Raquel da Silva Aragão ◽  
Omar Guzmán-Quevedo ◽  
Georgina Pérez-García ◽  
Raul Manhães-de-Castro ◽  
Francisco Bolaños-Jiménez
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Diseases ◽  
Plasma Concentrations ◽  
Acid Oxidation ◽  
Metabolic Flexibility ◽  
Long Term Effects ◽  
Transcriptional Responses ◽  
Predisposing Factor ◽  
Adult Rats ◽  
Metabolic Inflexibility

Skeletal muscle exhibits a remarkable flexibility in the usage of fuel in response to the nutrient intake and energy demands of the organism. In fact, increased physical activity and fasting trigger a transcriptional programme in skeletal muscle cells leading to a switch from carbohydrate to lipid oxidation. Impaired metabolic flexibility has been reported to be associated with obesity and type 2 diabetes, but it is not known whether the disability to adapt to metabolic demands is a cause or a consequence of these pathological conditions. Inasmuch as a poor nutritional environment during early life is a predisposing factor for the development of metabolic diseases in adulthood, in the present study, we aimed to determine the long-term effects of maternal malnutrition on the metabolic flexibility of offspring skeletal muscle. To this end, the transcriptional responses of the soleus and extensor digitorum longus muscles to fasting were evaluated in adult rats born to dams fed a control (17 % protein) or a low-protein (8 % protein, protein restricted (PR)) diet throughout pregnancy and lactation. With the exception of reduced body weight and reduced plasma concentrations of TAG, PR rats exhibited a metabolic profile that was the same as that of the control rats. In the fed state, PR rats exhibited an enhanced expression of key regulatory genes of fatty acid oxidation including CPT1a, PGC-1α, UCP3 and PPARα and an impaired expression of genes that increase the capacity for fat oxidation in response to fasting. These results suggest that impaired metabolic inflexibility precedes and may contribute to the development of metabolic disorders associated with early malnutrition.

scholarly journals Review on Toxic Effects of Di(2-ethylhexyl) Phthalate on Zebrafish Embryos

Toxics ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 193
Author(s):  
Wing Sum Kwan ◽  
Vellaisamy A. L. Roy ◽  
Kwan Ngok Yu
Keyword(s):  
Metabolic Diseases ◽  
Consumer Products ◽  
Dermal Absorption ◽  
Embryonic Stage ◽  
In Vivo Model ◽  
Zebrafish Embryos ◽  
Long Term Effects ◽  
High Fecundity ◽  
Embryo Stage ◽  
Ethylhexyl Phthalate

Di(2-ethylhexyl) phthalate (DEHP) is widely used as a plasticizer in consumer products. People are continuously exposed to DEHP through ingestion, inhalation and dermal absorption. From epidemiological studies, DEHP has been shown to associate with various adverse health effects, such as reproductive abnormalities and metabolic diseases. Health concerns have been raised regarding DEHP exposures; therefore, relevant risk assessment has become necessary through toxicological testing of DEHP. In the past 10 years, an increasing number of DEHP toxicity studies have been using zebrafish embryos as an in vivo model due to their high fecundity, rapid embryonic development as well as optical transparency, which have now been established as an alternative of the more conventional rodent model. The aim of the present paper is to review the effects of acute (from embryo stage to ≤1 week) and chronic (from embryo stage to >1 week) DEHP exposures on zebrafish, which start from the embryonic stage, and to analyze acute and potential long-term effects induced by acute exposure and effects induced by chronic exposure of DEHP upon subjecting to exposures, starting from the embryonic stage to different developmental stages, with a view to facilitate risk assessments on DEHP exposures.

scholarly journals Slug and Vimentin Downregulation at the Metastatic Site Is Associated With Skip-N2 Metastasis of Lung Adenocarcinoma

2022 ◽  
Author(s):  
Yasemin SAYGIDEGER ◽  
Alper AVCI ◽  
Emine BAGIR ◽  
Burcu SAYGIDEĞER DEMİR ◽  
Aycan SEZAN Ms ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
E Cadherin

Abstract Objective: Lung cancer displays heterogeneity both in the tumor itself and in its metastatic regions. One interesting behavior of the tumor is known as Skip N2 metastasis, which N2 lymph nodes contain tumor cells while N1 are clean. In this study, mRNA levels of epithelial mesenchymal transition (EMT) related genes in skip N2 and normal N2 involvements of non-small cell lung cancer tissues were investigated to evaluate the possible molecular background that may contribute to the pathogenesis of Skip N2 metastasis. Materials and Methods: Eighty-three surgically resected and paraffin embedded lymph node samples of lung cancer patients were analyzed in this study, which 40 of them were Skip N2. N2 tissues were sampled from 50% tumor containing areas and total RNA was extracted. mRNA levels for 18S, E-cadherin, Vimentin, ZEB1 and SLUG were analyzed via qPCR and E-cadherin and vimentin protein levels via immunohistochemistry (IHC). Bioinformatic analysis were adopted using online datasets to evaluate significantly co-expressed genes with SLUG in lung cancer tissue samples.Results: Skip-N2 patients who had adenocarcinoma subtype had better survival rates. Comparative analysis of PCR results indicated that Skip N2 tumor tissues had increased E-Cadherin/Vimentin ratio and ZEB1 mRNA expression, and significantly decreased levels of SLUG. E-cadherin IHC staining were higher in Skip N2 and Vimentin were in Non-Skip N2. TP63 had a strong correlation with SLUG expression in the bioinformatics analyses.Conclusion: The results indicate that, at molecular level, Skip N2 pathogenesis has different molecular background and regulation of SLUG expression may orchestrate the process.

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