We examined the upregulation of ET-1/ETBR/eNOS signaling in renoprotective effect of vitamin D in kidney fibrosis model in mice using unilateral ureteral obstruction (UUO). One group was treated with intraperitoneal injection of 0.125 mg/kg of Calcitriol (UUO+VD). Vascular remodeling was quantified based on lumen area and lumen/wall area ratio (LWAR) of intrarenal arteries using Sirius Red staining. ET-1, ETBR, eNOS, CD31 and VEGF mRNA expressions were quantified using qRT-PCR. Focusing on endothelin-1 (ET-1) signaling in endothelial cells (EC), siRNA of ET-1 was performed in human umbilical vein endothelial cells (HUVEC) for reducing ET-1 expression. Then HUVECs were treated with and without 100 nM Calcitriol treatment in hypoxic and normoxic conditions to elucidate ET-1/eNOS signaling. Our in vivo study revealed vascular remodeling and renal ischemia attenuation after Calcitriol treatment. Vascular remodeling was attenuated in the UUO+VD group as shown by increasing lumen areas and LWAR in intrarenal arteries. These findings were associated with significant higher CD31 and VEGF mRNA expression compared to the UUO group. Vitamin D treatment also increased ET-1, ETBR and eNOS mRNA expressions. Our in vitro study demonstrated Calcitriol induced ET-1 and eNOS mRNA expressions upregulation in HUVEC under normoxic and hypoxic condition. Meanwhile, siRNA for ET-1 inhibited the upregulation of eNOS mRNA expression after Calcitriol treatment. Vitamin D ameliorates kidney fibrosis through attenuating vascular remodeling and ischemia with upregulating ET-1/ETBR and eNOS expression., N. Arfian, M. H. H. Kusuma, N. Anggorowati, D. B. Nugroho, A. Jeffilano, Y. Suzuki, K. Ikeda, N. Emoto., and Seznam literatury
Vitamin D had been for a long time investigated for its effects on bone metabolism. Recently has been observed that the incidence of some neurodevelopmental disorders (including autism) increases hand in hand with vitamin D deficiency. Indeed, vitamin D was reported to modulate the biosynthesis of neurotransmitters and neurotrophic factors; moreover, its receptor was found in the central nervous system. Vitamin D deficiency was therefore assessed as a risk factor for autism, however the biological mechanism has not yet been revealed. In our review we focused on potential connections among vitamin D, steroids and autism. Potential mechanisms of vitamin D action are also discussed., L. Máčová, M. Bičíková, D. Ostatníková, M. Hill, L. Stárka., and Obsahuje bibliografii
Starling’s original definition of a hormone from 1905 was “a hormone is a substance produced by glands with internal secretion, which serve to carry signals through the blood to target organs”. Today, this definition is understood to be lacking, but newer definitions also do not encompass the entire meaning of hormones as specific carriers of information. One main problem is that there is no delineation between hormones and other signaling molecules such as cytokines, growth factors or autacoid compounds. It seems that a precise definition is not even possible, since some cytokines and growth factors, such as the cytokines erythropoietin, lipocalin-2 and asprosin or fibroblast growth factor 23, act as hormones under certain conditions., Luboslav Stárka, Michaela Dušková., and Obsahuje bibliografii
Optical mapping is a fluorescence-based physiological method to image spreading of action potential in excitable tissues, such as the heart and central nervous system. Because of the requirements for high speed imaging in low light conditions, highly sensitive high-speed cameras together with an optical system with maximum photon efficiency are required. While the optimization of these two components is relatively straightforward, the choice of the perfect light source is less simple; depending on the other (usually fixed) components, various parameters may acquire different weight in decisionmaking process. Here we describe the rationale for building an optical mapping setup and consider the relative advantages and disadvantages of three different commonly available light sources: mercury vapor lamp (HBO), xenon lamp (XBO), and light emitting diode (LED). Using the same optical system (fluorescence macroscope) and high-speed camera (Ultima L), we have tested each of the sources for its ability to provide bright and even illumination of the field of view and measured its temporal fluctuations in intensity. Then we used each in the actual optical mapping experiment using isolated, perfused adult mouse heart or chick embryonic heart to determine the actual signal to noise ratio at various acquisition rates. While the LED sources have undergone significant improvements in the recent past, the other alternatives may still surpass them in some parameters, so LEDs may not be the automatic number one choice for every application., Veronika Olejnickova, David Sedmera., and Obsahuje bibliografii
The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance., P. Soucek, V. Hlavac, K. Elsnerova, R. Vaclavikova, R. Kozevnikovova, K. Raus., and Obsahuje bibliografii
Josef Thomayer. and Knížka tato nepřijde do obchodu a věnuje ji auktor dle příležitosti darem. Tento výtisk věnován byl profesoru Ferdinandu Strejčkovi. S vlastnoručním podpisem autora.
Metabolic syndrome is a prevalent, complex condition. The search for genetic determinants of the syndrome is currently undergoing a paradigm enhancement by adding systems genetics approaches to association studies. We summarize the current evidence on relations between an emergent new candidate, zinc finger and BTB domain containing 16 (ZBTB16) transcription factor and the major components constituting the metabolic syndrome. Information stemming from studies on experimental models with altered Zbtb16 expression clearly shows its effect on adipogenesis, cardiac hypertrophy and fibrosis, lipid levels and insulin sensitivity. Based on current evidence, we provide a network view of relations between ZBTB16 and hallmarks of metabolic syndrome in order to elucidate the potential functional links involving the ZBTB16 node. Many of the identified genes interconnecting ZBTB16 with all or most metabolic syndrome components are linked to immune function, inflammation or oxidative stress. In summary, ZBTB16 represents a promising pleiotropic candidate node for metabolic syndrome., O. Šeda, L. Šedová, J. Včelák, M. Vaňková, F. Liška, B. Bendlová., and Obsahuje bibliografii
The data derived from rat models and the preliminary results of human studies provide strong indices of involvement of common ZBTB16 variants in a range of cardiovascular and metabolic traits. This cross-sectional study in the Caucasian cohort of 1517 Czech adults aimed to verify the hypothesis that ZBTB16 gene variation directly affects obesity and serum lipid levels. Genotyping of nine polymorphisms of the ZBTB16 gene (rs11214863, rs593731, rs763857, rs2846027, rs681200, rs686989, rs661223, rs675044, rs567057) was performed. A multivariate bidirectional regression with the reduction of dimensionality (O2PLS model) revealed relationships between basal lipid levels and anthropometric parameters and some minor ZBTB16 alleles. In men, the predictors - age and presence of minor ZBTB16 alleles of rs686989, rs661223, rs675044, rs567057 - were associated with significantly higher body mass index, waist to hip ratio, body adiposity index, waist and abdominal circumferences, higher total cholesterol and LDL cholesterol and explained 20 % of variability of these variables. In women, the predictors - age and presence of the rs686989 minor T allele - were also associated with increased anthropometric parameters and total cholesterol and LDL cholesterol but the obtained O2PLS model explained only 7.8 % of the variability of the explained variables. Our study confirmed that the selected gene variants of the transcription factor ZBTB16 influence the obesity-related parameters and lipid levels. This effect was more pronounced in men., B. Bendlová, M. Vaňková, M. Hill, G. Vacínová, P. Lukášová, D. Vejražková, L. Šedová, O. Šeda, J. Včelák., and Obsahuje bibliografii