16 research outputs found
Approaches and Aspects of Advanced Learning in Mechanical Engineering and Economics Studentsâ Classrooms
It is important to identify the situation our students encounter in the process of learning the English language, especially through ESP courses. We came to an idea to actively engage our students in the process of learning/acquisition and assessment, in order to encourage their learning efficiency. The crucial is studentsâ readiness to explore new technologies that can enhance their studying. Establishing proper environment for EMI is of great importance for our students, as well as for our country, in the light of world academic flows
Systemically available bone morphogenetic protein two and seven affect bone metabolism
Bone Morphogenetic Protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis
Background: Bone Morphogenetic Protein (BMP)-7 is protective in different animal models of acute and chronic kidney disease. Its role in human kidneys, and in particular hypertensive nephrosclerosis, has thus far not been described. Methods: BMP-7 mRNA was quantified using real-time PCR and localised by immunostaining in tissue samples from normal and nephrosclerotic human kidneys. The impact of angiotensin (AT)-II and the AT-II receptor antagonist telmisartan on BMP-7 mRNA levels and phosphorylated Smad 1/5/8 (pSmad 1/5/8) expression was quantified in proximal tubular cells (HK-2). Functional characteristics of BMP-7 were evaluated by testing its influence on TGF-b induced epithelial-to-mesenchymal transition (EMT), expression of TGF-b receptor type I (TGF-bRI) and phosphorylated Smad 2 (pSmad 2) as well as on TNF-a induced apoptosis of proximal tubular cells. Results: BMP-7 was predominantly found in the epithelia of the distal tubule and the collecting duct and was less abundant in proximal tubular cells. In sclerotic kidneys, BMP-7 was significantly decreased as demonstrated by real-time PCR and immunostaining. AT-II stimulation in HK-2 cells led to a significant decrease of BMP-7 and pSmad 1/5/8, which was partially ameliorated upon co-incubation with telmisartan. Only high concentrations of BMP-7 (100 ng/ml) were able to reverse TNF-a-induced apoptosis and TGF-b-induced EMT in human proximal tubule cells possibly due to a decreased expression of TGF-bRI. In addition, BMP-7 was able to reverse TGF-b-induced phosphorylation of Smad 2. Conclusions: The findings suggest a protective role for BMP-7 by counteracting the TGF-b and TNF-a-induced negative effects. The reduced expression of BMP-7 in patients with hypertensive nephrosclerosis may imply loss of protection and regenerative potential necessary to counter the disease
Circulating Bone Morphogenetic Protein 1â3 Isoform Increases Renal Fibrosis
Bone morphogenetic proteins (BMPs) participate in organ regeneration through autocrine and paracrine actions, but the existence and effects of these proteins in the systemic circulation is unknown. Using liquid chromatographyâmass spectrometry, we identified BMP6, GDF15, and the BMP1â3 isoform of the Bmp1 gene in plasma samples from healthy volunteers and patients with CKD. We isolated the endogenous BMP1â3 protein and demonstrated that it circulates as an active enzyme, evidenced by its ability to cleave dentin matrix protein-1 in vitro. In rats with CKD, administration of recombinant BMP1â3 increased renal fibrosis and reduced survival. In contrast, administration of a BMP1â3-neutralizing antibody reduced renal fibrosis, preserved renal function, and increased survival. In addition, treating with the neutralizing antibody was associated with low plasma levels of TGFÎČ1 and connective tissue growth factor. In HEK293 cells and remnant kidneys, BMP1â3 increased the transcription of collagen type I, TGFÎČ1, ÎČ-catenin, and BMP7 via a BMP- and Wnt-independent mechanism that involved signaling through an integrin ÎČ1 subunit. The profibrotic effect of BMP1â3 may, in part, be a result of the accompanied decrease in decorin (DCN) expression. Taken together, inhibition of circulating BMP1â3 reduces renal fibrosis, suggesting that this pathway may be a therapeutic target for CKD
Physiological characteristics of rats from high-serotonin (5HT) and low-5HT sublines.
<p>A. Indicators of 5HT homeostasis shown as âfold differenceâ between high- and low-5HT animals with 95% confidence intervals. Reference values were (mean±SD): a) for platelet serotonin level (PSL) 0.80±0.08 ÎŒg 5HT/mg platelet protein; b) for platelet serotonin uptake (PSU) 0.69±0.07 nmol 5HT/mg platelet protein/min. Rats were 2 months (PSU measurements) and 12 months (gut <i>Mao-A</i>, <i>Tph1</i> and <i>5HTT</i> expression) of age. PSL and gut 5HT turnover data are given for animals of 2 and 12 months of age. B. No difference in 5HT production and storage in the gut was observed between high- and low-5HT rat sublines. 5HT visualized by using immunohistochemistry was documented at 40Ă magnification and is depicted by black arrows. C-E. Physical characteristics of high-5HT and low-5HT animals (mean±SD). High-5HT animals are represented by black squares, low-5HT animals by open circles. Câbody weight; Dâfemur length; Eâhanging time in the string test (mean values from three 60-sec trials separated by 10-min intervals). Relative differences (%) are shown for subline*age interaction contrasts. P-values were adjusted for multiple comparisons (n = 6â15 rats/group). H-L indicates a difference between high-5HT and low-5HT animals. 12â2 indicates a difference between 12 months and 2 months old animals. Mao-Aâmonoamine oxidase A; Tph1 âtryptophan hydroxylase 1; 5HTTâserotonin transporter</p
Bone biomarkers and hormones in high-5HT and low-5HT rats.
<p>Depicted are relative differences (%): for the overall difference between the high-5HT (H) and low-5HT (L) sublines, P<0.05 is considered significant; for contrasts between sublines at a given age and between different ages within the same subline, P<0.025 is considered significant (n = 5â10 rats/group). H-L indicates a difference between high-5HT and low-5HT animals. 12â2 indicates a difference between 12 months and 2 months old animals.</p
Systemic role of the peripheral 5HT.
<p>Gut synthesized 5HT enters the platelets via the 5HTT. The quantity of 5HT in platelets depends on the 5HTT activity, while the rate of 5HT synthesis in the gut is equal between both rat sublines (â sign). Changes in the serum Ca<sup>2+</sup> level, influenced by PTH from parathyroid glands and by 1,25(OH)<sub>2</sub>D<sub>3</sub> from the kidney, impact the platelet 5HTT activity, with a bidirectional effect on PSL (green-red arrow). Elevated 5HT bidirectionally influences the plasma insulin level (green-red arrow) and induces the hyperthrophy of pancreatic ÎČ-cells (dashed arrow), leading to type 2 diabetes with an increased plasma glucose, insulin resistance, glucose intolerance, visceral fat volume and decreased muscle strength. In return, plasma insulin level positively correlates with the PSL (+ sign). Increased insulin and 5HT have an additive effect on bone formation (green arrow). Elevated 5HT increases both bone formation and resorption (larger green arrow), thus increasing the bone turnover and resulting in the net bone loss (large red arrow). 5HTâserotonin, 5HTTâserotonin transporter, PSLâplasma serotonin level, PTHâparathyroid hormone.</p
Primer sequences used in RT-PCR analysis.
<p>Primer sequences used in RT-PCR analysis.</p