Abstract 172: The Role of Activin A in Maternal Diabetes-Induced Cardiac Malformations

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Zhiyong Zhao

Diabetes mellitus in pregnancy causes heart defects, especially atrioventricular septal defects (AVSDs), in infants. Manifestation of AVSDs results from dysmorphogenesis of the endocardial cushions in the embryo, which is regulated by members of the transforming growth factor (TGF) β family. Among the TGFβs, we have previously observed that the inhibin βA gene, which encodes a protein to form homodimers as activin A, is markedly downregulated by maternal diabetes. To further determine the involvement of inhibin βA and its signaling in diabetic embryopathy, the levels of inhibin βA protein and activation of its downstream transcription factors, Smad2 and Smad3, were examined using immunohistochemical, proximity ligation, and immunoblot assays, and shown to be decreased in the embryonic hearts of diabetic mice induced via intravenous injection of streptozotocin. To investigate the role of activin A in hyperglycemia-induced cardiac malformations, mouse embryos at embryonic day 9.5 (E9.5) cultured in high glucose (22 mM) were treated with activin A (50 ng/ml) for 24 hours. The treatment rescued the development of the endocardial cushions and cell proliferation (BrdU-incorporation assay) in the myocardium, similar to those in normal glucose control (8.3 mM). The role of activin A in endocardial cell migration, an important process for cellularization of the cardiac jelly, was investigated by treating E10.5 endocardial cushion explants cultured in high glucose with activin A (50 ng/ml) in a collagen matrix-based assay system. The treatment significantly increased the number of migrating cells, compared with that in high glucose-treated group, to the level in the control group. These effects were associated with restoration of the activation of Smad2/3. The results demonstrate that the activin-Smad2/3 signaling system plays an important role in cardiac malformation in diabetic embryopathy.

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Youdi Wang ◽  
Xue Wu ◽  
Mengya Geng ◽  
Jiamin Ding ◽  
Kangjia Lv ◽  
...  

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with chronic inflammation. We have examined the role of the inflammatory chemokine CCL24 in DN. We observed that serum levels of CCL24 were significantly elevated in patients with DN. Not only that, the expression of CCL24 was significantly increased in the kidneys of DN mice. The kidney of DN mice showed increased renal fibrosis and inflammation. We characterized an in vitro podocyte cell model with high glucose. Western blot analysis showed that expression of CCL24 was significantly increased under high-glucose conditions. Stimulation with high glucose (35 mmol/L) resulted in an increase in CCL24 expression in the first 48 hours but changed little after 72 hours. Moreover, with glucose stimulation, the level of podocyte fibrosis gradually increased, the expression of the proinflammatory cytokine IL-1β was upregulated, and the expression of the glucose transporter GLUT4, involved in the insulin signal regulation pathway, also increased. It is suggested that CCL24 is involved in the pathogenesis of DN. In order to study the specific role of CCL24 in this process, we used the CRISPR-Cas9 technique to knock out CCL24 expression in podocytes. Compared with the control group, the podocyte inflammatory response induced by high glucose after CCL24 knockout was significantly increased. These results suggest that CCL24 plays a role in the development of early DN by exerting an anti-inflammatory effect, at least, in podocytes.


2022 ◽  
Vol 12 (3) ◽  
pp. 647-652
Author(s):  
Yang Zhang ◽  
Peng Sun ◽  
Shuying Han ◽  
Duojiao Fan

Mitochondrial autophagy and inflammatory response involves in diabetes. This study mainly explores the role of Silent Information Regulator (SIRT1) in pancreatic β-cells under high glucose conditions and related mechanism. Pancreatic β cells was cultured in a high-glucose environment with SRT1720 and EX527 respectively to define activation group and inhibition group followed by analysis of SIRT1, P-FOXO1, FOXO1, LC3, ATG5, PINK, Parkin, Mfn1, Mfn2, Fis1, IL-6, TNF-α, NLRP3 protein and mRNA expression by qRT-PCR, Western blot and fluorescent probe technology. Compared with control group, SIRT1 protein and mRNA expression in the high glucose group was significantly reduced. Activation group had highest protein and mRNA expression of SIRT1 P-FOXO1, FOXO1, Mfn1, Mfn2, Fis1, PINK, Parkin and mitochondrial membrane potential followed by blank group and inhibition group.SIRT1 secretion by pancreatic β-cells under high glucose environment is reduced. After activating SIRT1, mitochondrial autophagy decreased significantly and inflammatory response is significantly alleviated, indicating that SIRT1 might be used as a therapeutic target.


2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.


2012 ◽  
Vol 15 (2) ◽  
pp. 84 ◽  
Author(s):  
Canturk Cakalagaoglu ◽  
Cengiz Koksal ◽  
Ayse Baysal ◽  
Gokhan Alici ◽  
Birol Ozkan ◽  
...  

<p><b>Aim:</b> The goal was to determine the effectiveness of the posterior pericardiotomy technique in preventing the development of early and late pericardial effusions (PEs) and to determine the role of anxiety level for the detection of late pericardial tamponade (PT).</p><p><b>Materials and Methods:</b> We divided 100 patients randomly into 2 groups, the posterior pericardiotomy group (n = 50) and the control group (n = 50). All patients undergoing coronary artery bypass grafting surgery (CABG), valvular heart surgery, or combined valvular and CABG surgeries were included. The posterior pericardiotomy technique was performed in the first group of 50 patients. Evaluations completed preoperatively, postoperatively on day 1, before discharge, and on postoperative days 5 and 30 included electrocardiographic study, chest radiography, echocardiographic study, and evaluation of the patient's anxiety level. Postoperative causes of morbidity and durations of intensive care unit and hospital stays were recorded.</p><p><b>Results:</b> The 2 groups were not significantly different with respect to demographic and operative data (<i>P</i> > .05). Echocardiography evaluations revealed no significant differences between the groups preoperatively; however, before discharge the control group had a significantly higher number of patients with moderate, large, and very large PEs compared with the pericardiotomy group (<i>P</i> < .01). There were 6 cases of late PT in the control group, whereas there were none in the pericardiotomy group (<i>P</i> < .05). Before discharge and on postoperative day 15, the patients in the pericardiotomy group showed significant improvement in anxiety levels (<i>P</i> = .03 and .004, respectively). No differences in postoperative complications were observed between the 2 groups.</p><p><b>Conclusion:</b> Pericardiotomy is a simple, safe, and effective method for reducing the incidence of PE and late PT after cardiac surgery. It also has the potential to provide a better quality of life.</p>


2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.


2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.


2019 ◽  
pp. 58-62
Author(s):  
Vlad Stegariu ◽  
Simona Andreea Popușoi ◽  
Beatrice Abălașei ◽  
Nicolae Lucian Voinea ◽  
Ioan Stelescu ◽  
...  

Chess playing has a significant role in participants’ resources allocation, both at a psychological level, but mostly concerning the cognitive resources. The aim of the present study was to examine the effect of chess playing on the intellectual development of primary-class students. 67 children were tested using the Raven Standard Progressive Matrices and were distributed in three different groups according to their experience with chess, namely: the control group (formed by students with no experience with chess playing), the beginners group (students with less than one year in chess playing training) and the advanced group (children with more than two years experience with chess). Results indicated that chess playing had a significant effect on the SPM performance, indicating that those in the advanced group performed significantly better than those in the control or in the beginners group. Conclusions of this study tap into the benefits of playing chess with a focus on the children’s’ cognitive development.


2018 ◽  
Vol 24 (27) ◽  
pp. 3276-3281 ◽  
Author(s):  
Dorota Raczyńska ◽  
Katarzyna A. Lisowska ◽  
Krzysztof Pietruczuk ◽  
Joanna Borucka ◽  
Mateusz Ślizień ◽  
...  

Objective: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy. Patients and methods: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group). All patients underwent a comprehensive eye examination one day before and 3 weeks after the surgery, including measurements of: best-corrected visual acuity (BVCA) and intraocular pressure (IOP), slit-lamp examination and spectral domain optical coherence tomography (SOCT). Concentrations of cytokines: IL-6, IL-8, IL-12p70, TNF, IL-10, IL-1β were measured in the vitreous body of patients with BD™ Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit. Results: PDR patients who received pretreatment with aflibercept injection showed significantly lower concentrations of IL-12p70, TNF, IL-10 and IL-1β in the vitreous body compared to the control group. Meanwhile, patients without prior aflibercept injection had a significantly higher concentration of IL-8. There was also a significant positive correlation between IOP before PPV and IL-8 concentration in both PDR patients’ groups. Conclusion: Findings of our study suggest an important role of IL-8 in the development of severe PDR. Aflibercept administration on the day before elective vitrectomy facilitated the surgery.


Author(s):  
Muhammad Irfan ◽  
Safdar Abbas ◽  
Beenish Jehan Azhar ◽  
Shakeel Ahmad ◽  
Hafsa Muhammad ◽  
...  

Background: Phytonutrients in peach fruits have health promoting antioxidants against various chronic diseases. However, there is no extensive data to show the nutritional values of Local peach cultivars after post-harvest treatments. Objective: Mainly this study was objective to determine the effect of calcium carbide on nutritional value and quality of fruits of Pakistani peach cultivars. Methods: The peach fruits were collected from three different peach orchids of KPK and the fruits were divided into 4 groups while 5th group was collected from local fruit shop. Each experimental group was treated with different concentration of calcium carbide whereas control group was not treated. The peel and pulp samples were oven dried and ground to fine powder separately. The elemental compositions were determined using Particle Induced X-ray emission and Pelletron Tandem Accelerator. Result: Sixteen elements were identified in peach fruits and the elements were Al, P, S, Cl, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, and Se. In peel, concentration of some elements increased or decreased after treatment with CaC2 while in pulp the conc. of nearly all detected elements was increased in treated samples. We found significantly high amount of heavy metals traces including As, Se, Co, Si, and P in peach fruits treated with CaC2. Interestingly, the presence of trichomes in peach skin prevents the transfer of these heavy metals deep into the pulp which was also verified by the elemental profiling of nectarines. Conclusion: Conclusively, the artificial ripening with CaC2 changed the nutritional value of peach fruits that has higher health risks if consume with the peel. According to our best knowledge, this is the first report that highlights the effects of CaC2 which deteriorate the nutritional value of peach fruits in Pakistan.


2019 ◽  
Vol 16 (1) ◽  
pp. 91-95 ◽  
Author(s):  
Hamid Farhang ◽  
Laleh Sharifi ◽  
Mohammad Mehdi Soltan Dallal ◽  
Mona Moshiri ◽  
Zahra Norouzbabaie ◽  
...  

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &amp;#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &amp;#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &amp;#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p&gt;


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