scholarly journals Expression of cardiac copper chaperone encoding genes and their correlation with cardiac function parameters in goats

Author(s):  
Ahmed S. Mandour ◽  
Ahmed E. Mahmoud ◽  
Asmaa O. Ali ◽  
Katsuhiro Matsuura ◽  
Haney Samir ◽  
...  

Abstract The expression of copper chaperone (Cu-Ch) encoding genes enables an in-depth understanding of copper-associated disorders, but no previous studies have been undertaken to highlight Cu-Ch disturbances in heart tissue in ruminants after copper deficiency (CuD). The current study aimed to investigate the Cu-Ch mRNA expression in goat’s heart after experimental CuD and highlight their relationship with the cardiac measurements. Eleven male goats were enrolled and divided into the control group (n = 4) and CuD group (treatment, n = 7), which received copper-reducing dietary regimes (molybdenum and sulfur). Heart function was evaluated by electrocardiography and echocardiography, and at the end of the experiment, all animals were sacrificed, and the cardiac tissues were collected for quantitative mRNA expression by real-time PCR. In the treatment group, cardiac measurements revealed increased preload and the existence of cardiac dilatation and significant cardiac tissue damage by histopathology. Also, the relative mRNA expression of Cu-Ch encoding genes; ATP7A, CTr1, LOX, COX17, as well as ceruloplasmin (CP), troponin I3 (TNNI3), glutathione peroxidase (GPX1), and matrix metalloprotease inhibitor (MMPI1) genes were significantly down-regulated in CuD group. Besides, there was a variable significant correlation between investigated genes and cardiac measurements; meanwhile, a significant inverse correlation was observed between histopathological score and ATP7B, CTr1, LOX, and COX17. In conclusion, this study revealed that CuD induces cardiac dilatation and alters the mRNA expression of Cu-Ch genes, in addition to TNNI3, GPX1, and MMPI1 that are considered key factors in clinically undetectable CuD-induced cardiac damage in goats which necessitate further studies for feasibility as biomarkers.

2020 ◽  
Vol 77 (2) ◽  
pp. 165-173
Author(s):  
Zarko Micovic ◽  
Sanja Kostic ◽  
Slavica Mutavdzin ◽  
Aleksa Andrejevic ◽  
Aleksandra Stamenkovic ◽  
...  

Background/Aim. Chronically induced hypermethioninemia leads to hyperhomocysteinemia which causes oxidative stress, atherogenesis, neurodegeneration and cancer. However, little is known about the acute and subchronic effects of DL-methionine (Met). The aim of study was to assess the effects of acutely and subchronically applied Met on oxidative stress parameters in rat plasma [enzymes: catalase (CAT), glutathione peroxidise (GPx), superoxide dismutase (SOD) and index of lipid peroxidation, malondialdehyde (MDA)], and acetylcholinesterase (AChE) activity in rat cardiac tissue. Methods. The enzymes activities, as well as MDA concentration were evaluated following acute (n = 8) and subchronic (n = 10) application of Met [i.p. 0.8 mmoL/kg body weight (b.w.) in a single dose in the acute overload or daily during three weeks in the subchronic overload]. The same was done in the control groups following application of physiological solution [i.p. 1 mL 0.9% NaCl (n = 8) in the acute overload and 0.1?0.2 mL 0.9% NaCl, daily during three weeks (n =10) in the subchronic overload]. Tested parameters were evaluated 60 minutes after application in acute experiments and after three weeks of treatment in subchronic experiments. Results. There were no difference in homocysteine values between the groups treated with Met for three weeks and the control group. Met administration significantly increased the activity of CAT and GPx after 1 h compared to the control group (p = 0.008 for both enzymes), whereas the activity of SOD and MDA concentrations were unchanged. Subchronically applied Met did not affect activity of antioxidant enzymes and MDA level. AChE activity did not show any change in rat cardiac tissue after 1 h, but it was significantly decreased after the subchronic treatment (p = 0.041). Conclusion. Results of present research indicate that Met differently affects estimated parameters during acute and subchronic application. In the acute treatment Met mobilizes the most part of antioxidant enzymes while during the subchronic treatment these changes seems to be lost. On the contrary, the acute Met overload was not sufficient to influence on the AChE activity, while longer duration of Met loading diminished function of the enzyme. These findings point out that methionine can interfere with antioxidant defense system and cholinergic control of the heart function.


2019 ◽  
Vol 6 (1) ◽  
pp. 5 ◽  
Author(s):  
Adriana Rodriguez ◽  
Viravuth Yin

Stimulating cardiomyocyte regeneration after an acute injury remains the central goal in cardiovascular regenerative biology. While adult mammals respond to cardiac damage with deposition of rigid scar tissue, adult zebrafish and salamander unleash a regenerative program that culminates in new cardiomyocyte formation, resolution of scar tissue, and recovery of heart function. Recent studies have shown that immune cells are key to regulating pro-inflammatory and pro-regenerative signals that shift the injury microenvironment toward regeneration. Defining the genetic regulators that control the dynamic interplay between immune cells and injured cardiac tissue is crucial to decoding the endogenous mechanism of heart regeneration. In this review, we discuss our current understanding of the extent that macrophage and regulatory T cells influence cardiomyocyte proliferation and how microRNAs (miRNAs) regulate their activity in the injured heart.


2017 ◽  
Vol 3 (1) ◽  
pp. 76
Author(s):  
Siti Asiyah ◽  
Dwi Estuning Rahayu ◽  
Wiranti Dwi Novita Isnaeni

The needed of Iron Tablet in pregnancy was increase than mother who not pregnant.  That  cause of  high metabolism at the pregnancy for formed of  fetal organ and energy. One of effort for prevent anemia in mother pregnant with giving the Iron tablet and vitamin c. The reason of  this research in 4 June – 11 July 2014 is for compare the effect of  iron tablet suplementation with and without vitamin C toward Hemoglobin level in mother pregnant With Gestational Age Of 16-32 Weeks In Desa Keniten Kecamatan Mojo Kabupaten Kediri. This research method using comparative analytical.  Research design type of Quasy Eksperiment that have treatment group and control group. Treatment group will giving by Iron tablet and 100 mg vitamin C, and control group just giving by iron tablet during 21 days. Population in this research are all of mother pregnant with Gestational Age Of 16-32 Weeks with Sampling technique is  cluster random sampling is 29 mother pregnant. Comparison analysis of  iron tablet suplementation effect with and without vitamin C toward Hemoglobin level in mother pregnant With Gestational Age Of 16-32 Weeks, data analysis using Mann Whitney U-test and the calculated U value (44,5) less than U-table (51). So there was difference of iron tablet suplementation effect with and without vitamin C toward Hemoglobin level in mother pregnant With Gestational Age Of 16-32 Weeks Therefore, the addition of vitamin C on iron intake is needed to increase the uptake of iron tablets. When the amount of iron uptake increases, the reserves of iron in the body will also increase, so as to prevent anemia in pregnant women; Keywords : Iron Tablet (Fe), Vitamin C, Hemoglobin level, Mother Pregnant


2019 ◽  
Vol 70 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Venera Cristina Dinescu ◽  
Ileana Puiu ◽  
Sorin Nicolae Dinescu ◽  
Diana Rodica Tudorascu ◽  
Elena Catalina Bica ◽  
...  

The aim of this study was to identify correlations between electrocardiographic and echocardiographic changes in patients with silicosis prior to the occurrence of chronic pulmonary heart disease. We conducted a prospective, descriptive, analytical study, in which we included a group of 67 patients consecutively admitted to the Health Promotion and Occupational Medicine Clinic between December 2016 and January 2018, aged 47 to 78 years.There was a biochemical and electrocardiographic evaluation for each patient as well as a right ventricle echocardiographic evaluation (diameters, volumes, function). A control group, including 25 patients with benign minor diseases that required a cardiologist consultation, was also used. From the electrocardiographic point of view, slight changes were observed regarding the waves of electrical activity of the right ventricle. Taking into account the degree of ventilatory dysfunction (depending on FEV1), changes in right heart echocardiographic parameters were identified. Thus, in what the most important right ventricular parameters, including the tricuspid annular plane systolic excursion (TAPSE) or the RV index of myocardial performance (RVMPI) were concerned, values at the upper limit of normality were recorded in most patients with moderate and severe ventilatory dysfunction. Values of echocardiographic parameters of the right heart at the upper limit of normality, correlated with the degree of ventilatory dysfunction, are early markers for cardiovascular damage in patients with pulmonary silicosis prior to the occurrence of chronic pulmonary heart disease also known ascor pulmonale.


2020 ◽  
Vol 20 (7) ◽  
pp. 790-799 ◽  
Author(s):  
Farnaz D. Moghaddam ◽  
Pejman Mortazavi ◽  
Somayeh Hamedi ◽  
Mohammad Nabiuni ◽  
Nasim H. Roodbari

Background and Purpose: Melittin, as the main ingredient of honeybee venom, that has shown anticancer properties. The present study aimed at investigating the cytotoxic impacts of melittin on 4T1 breast cancer cells. Methods: Hemolytic activity of different concentrations (0.125, 0.25, 0.5, 1, 2, 4, 8μg/ml) of melittin was assayed and then cytotoxicity of selected concentrations of melittin (2, 4, 8, 16, 32, and 64μg/ml), 2 and 4μg/ml of cisplatin and 0.513, 0.295 and 0.123μg/ml of doxorubicin was evaluated on 4T1 cells using MTT assay. We used Morphological evaluation and flow cytometric analysis was used. Real time PCR was also used to determine mRNA expression of Mfn1 and Drp1 genes. Results: All compounds showed anti-proliferative effects on the tumor cell line with different potencies. Melittin had higher cytotoxicity against 4T1 breast cancer cells (IC50= 32μg/ml-72h) and higher hemolytic activity (HD50= 1μg/ml), as compared to cisplatin and doxorubicin. Mellitin at 16 and 32μg/ml showed apoptotic effects on 4T1 cells according to the flow cytometric analysis. The Real time PCR analysis of Drp1 and Mfn1 expression in cells treated with 16μg/ml of melittin revealed an up-regulation in Drp1 and Mfn1 genes mRNA expression in comparison with control group. Treatment with 32μg/ml of melittin was also associated with a rise in mRNA expression of Drp1 and Mfn1 as compared to the control group. Conclusion: The results of this study showed that melittin has anticancer effects on 4T1 cell lines in a dose and time dependent manner and can be a good candidate for further research on breast cancer treatment.


2020 ◽  
Vol 45 (4) ◽  
pp. 351-357
Author(s):  
Bilge Özerman Edis ◽  
Muhammet Bektaş ◽  
Rüstem Nurten

AbstractObjectivesCardiac damage in patient with diphtheritic myocarditis is reported as the leading cause of mortality. Diphtheria toxin (DTx) is a well-known bacterial toxin inducing various cytotoxic effects. Mainly, catalytic fragment inhibits protein synthesis, induces cytotoxicity, and depolymerizes actin filaments. In this study, we aimed to demonstrate the extent of myofibrillar damage under DTx treatment to porcine cardiac tissue samples.MethodsTissue samples were incubated with DTx for 1–3 h in culture conditions. To analyze whole toxin (both fragments) distribution, conjugation of DTx with FITC was performed. Measurements were carried out with fluorescence spectrophotometer before and after dialysis. Immunofluorescence microscopy was used to show localization of DTx-FITC (15 nM) on cardiac tissue incubated for 2 h. Ultrastructural characterization of cardiac tissue samples treated with DTx (15 or 150 nM) was performed with transmission electron microscopy.ResultsDTx exerts myofibrillar disorganization. Myofilament degeneration, mitochondrial damage, vacuolization, and abundant lipid droplets were determined with 150 nM of DTx treatment.ConclusionsThis finding is an addition to depolymerization of actin filaments as a result of the DTx-actin interactions in in vitro conditions, indicating that myofilament damage can occur with DTx directly besides protein synthesis inhibition. Ultrastructural results support the importance of filamentous actin degeneration at diphtheritic myocarditis.


2021 ◽  
Vol 10 (10) ◽  
pp. 2215
Author(s):  
Karina Limburg ◽  
Katharina Radziej ◽  
Heribert Sattel ◽  
Peter Henningsen ◽  
Marianne Dieterich ◽  
...  

We tested the efficacy of an integrative psychotherapeutic group treatment (IPGT) in reducing vertigo/dizziness-related impairment along with depression, anxiety, and somatization by conducting a randomized controlled superiority trial comparing IPGT to self-help groups moderated by a clinical psychologist (SHG). Adult patients with functional vertigo and dizziness symptoms were randomly allocated to either the IPGT or SHG as active control group. Outcomes were assessed at baseline (t0), after treatment lasting 16 weeks (t1), and 12 months after treatment (t2). A total of 81 patients were assigned to IPGT and 78 patients were assigned to SHG. Vertigo-related impairment was reduced in both conditions (IPGT: t0–t1: d = 1.10, t0–t2: d = 1.06; SHG: t0–t1: d = 0.86, t0–t2: d = 1.29), showing the efficiency of both IPGT and SHG. Clinically relevant improvements were also obtained for depression in both groups. Linear mixed model analyses revealed no differences between groups for all outcomes (effect of group for the primary outcome: b = −1.15, SE = 2.13, t = −0.54, p = 0.59). Attrition rates were higher in SHG (52.6%) than in IPGT (28.4%). Both conditions improved primary and secondary outcomes while IPGT was better accepted by patients than SHG. Trial registration: ClinicalTrials.gov, Identifier: NCT02320851.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 738
Author(s):  
Sasikarn Looprasertkul ◽  
Amornpun Sereemaspun ◽  
Nakarin Kitkumthorn ◽  
Kanidta Sooklert ◽  
Tewarit Sarachana ◽  
...  

Gold nanoparticles (AuNPs) are used for diagnostic and therapeutic purposes, especially antiangiogenesis, which are accomplished via inhibition of endothelial cell proliferation, migration, and tube formation. However, no research has been performed on the effects of AuNPs in pericytes, which play vital roles in endothelial cell functions and capillary tube formation during physiological and pathological processes. Therefore, the effects of AuNPs on the morphology and functions of pericytes need to be elucidated. This study treated human placental pericytes in monoculture with 20 nm AuNPs at a concentration of 30 ppm. Ki-67 and platelet-derived growth factor receptor-β (PDGFR-β) mRNA expression was measured using real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration was assessed by Transwell migration assay. The fine structures of pericytes were observed by transmission electron microscopy. In addition, 30 ppm AuNP-treated pericytes and intact human umbilical vein endothelial cells were cocultured on Matrigel to form three-dimensional (3D) capillary tubes. The results demonstrated that AuNPs significantly inhibited proliferation, reduced PDGFR-β mRNA expression, and decreased migration in pericytes. Ultrastructural analysis of pericytes revealed AuNPs in late endosomes, autolysosomes, and mitochondria. Remarkably, many mitochondria were swollen or damaged. Additionally, capillary tube formation was reduced. We found that numerous pericytes on 3D capillary tubes were round and did not extend their processes along the tubes, which resulted in more incomplete tube formation in the treatment group compared with the control group. In summary, AuNPs can affect pericyte proliferation, PDGFR-β mRNA expression, migration, morphology, and capillary tube formation. The findings highlight the possible application of AuNPs in pericyte-targeted therapy for antiangiogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bokyung Ahn ◽  
Yang Seok Chae ◽  
Soo Kyung Lee ◽  
Moa Kim ◽  
Hyeon Soo Kim ◽  
...  

AbstractAdenylate kinase 5 (AK5) belongs to the adenylate kinase family that catalyses reversible phosphate transfer between adenine nucleotides, and it is related to various energetic signalling mechanisms. However, the role of AK5 in colorectal cancer (CRC) has not been reported. In this study, AK5 was significantly hypermethylated in CRC compared to adjacent normal tissues (P < 0.0001) and normal tissues (P = 0.0015). Although the difference in mRNA expression was not statistically significant in all of them, the selected 49 cases of CRC tissues with AK5 hypermethylation with the cut off value of 40% showed a significant inverse correlation with mRNA expression (P = 0.0003). DNA methylation of AK5 promoter significantly decreased and AK5 expression recovered by 5-aza-2′-deoxycytidine, DNA methyltransferase inhibitor in CRC cell lines. In addition, AK5 promoter activity significantly decreased due to DNA methyltransferase, and it increased due to 5-aza. Moreover, AK5 regulated the phosphorylated AMPK and mTOR phosphorylation and inhibited the cell migration and cell invasion in CRC cell lines. Furthermore, low AK5 expression is associated with poor differentiation (P = 0.014). These results demonstrate that the AK5 promoter is frequently hypermethylated and induced methylation-mediated gene down-regulation. AK5 expression regulates AMPK/mTOR signalling and may be closely related to metastasis in colorectal adenocarcinoma.


2008 ◽  
Vol 86 (6) ◽  
pp. 299-309 ◽  
Author(s):  
W. Goettsch ◽  
A. Schubert ◽  
H. Morawietz

A key step in endothelin-1 (ET-1) synthesis is the proteolytic cleavage of big ET-1 by the endothelin-converting enzyme-1 (ECE-1). Four alternatively spliced isoforms, ECE-1a to ECE-1d, have been discovered; however, regulation of the expression of specific ECE-1 isoforms is not well understood. Therefore, we stimulated primary human umbilical vein endothelial cells (HUVECs) with angiotensin II (Ang II). Furthermore, expression of ECE-1 isoforms was determined in internal mammary arteries of patients undergoing coronary artery bypass grafting surgery. Patients had received one of 4 therapies: angiotensin-converting enzyme inhibitors (ACE-I), Ang II type 1 receptor blockers (ARB), HMG-CoA reductase inhibitors (statins), and a control group that had received neither ACE-I, ARB (that is, treatment not interfering in the renin–angiotensin system), nor statins. Under control conditions, ECE-1a is the dominant isoform in HUVECs (4.5 ± 2.8 amol/μg RNA), followed by ECE-1c (2.7 ± 1.0 amol/μg), ECE-1d (0.49 ± 0.17 amol/μg), and ECE-1b (0.17 ± 0.04 amol/μg). Stimulation with Ang II did not change the ECE-1 expression pattern or the ET-1 release. We found that ECE-1 mRNA expression was higher in patients treated with statins than in patients treated with ARB therapy (5.8 ± 0.76 RU versus 3.0 ± 0.4 RU), mainly attributed to ECE-1a. In addition, ECE-1a mRNA expression was higher in patients receiving ACE-I therapy than in patients receiving ARB therapy (1.68 ± 0.27 RU versus 0.83 ± 0.07 RU). We conclude that ECE-1a is the major ECE-1 isoform in primary human endothelial cells. Its expression in internal mammary arteries can be regulated by statin therapy and differs between patients with ACE-I and ARB therapy.


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