DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N-demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl-donor S-adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5-azacytidine, which was able to inhibit sarcosine-induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role.

• Klíčová slova
• DNA methylation, Dnmts, SAMe, epigenetics, prostate cancer, sarcosine,
• MeSH
• buněčné linie MeSH
• CpG ostrůvky * MeSH
• epigeneze genetická účinky léků   MeSH
• lidé MeSH
• nádory prostaty metabolismus   patologie   MeSH
• prostata metabolismus   patologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• sarkosin farmakologie   MeSH
• upregulace účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• sarkosin MeSH

It is primarily important to define the standard features and factors that affect dental pulp stem cells (DPSCs) for their broader use in tissue engineering. This study aimed to verify whether DPSCs isolated from various teeth extracted from the same donor exhibit intra-individual variability and what the consequences are for their differentiation potential. The heterogeneity determination was based on studying the proliferative capacity, viability, expression of phenotypic markers, and relative length of telomere chromosomes. The study included 14 teeth (6 molars and 8 premolars) from six different individuals ages 12 to 16. We did not observe any significant intra-individual variability in DPSC size, proliferation rate, viability, or relative telomere length change within lineages isolated from different teeth but the same donor. The minor non-significant variances in phenotype were probably mainly because DPSC cell lines comprised heterogeneous groups of undifferentiated cells independent of the donor. The other variances were seen in DPSC lineages isolated from the same donor, but the teeth were in different stages of root development. We also did not observe any changes in the ability of cells to differentiate into mature cell lines-chondrocytes, osteocytes, and adipocytes. This study is the first to analyze the heterogeneity of DPSC dependent on a donor.

• Klíčová slova
• dental stem cells, intra-individual variability, mesenchymal stem cells, regenerative medicine, same donor isolation, stem cell characterization,
• MeSH
• buněčná diferenciace fyziologie   MeSH
• buněčné linie MeSH
• buněčný rodokmen fyziologie   MeSH
• chondrocyty fyziologie   MeSH
• dárci tkání MeSH
• individuální biologická variabilita MeSH
• kmenové buňky fyziologie   MeSH
• lidé MeSH
• mladiství MeSH
• osteocyty fyziologie   MeSH
• proliferace buněk fyziologie   MeSH
• tukové buňky fyziologie   MeSH
• zubní dřeň fyziologie   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Glycation plays a crucial role in the development of chronic vascular complications in diabetes. The total individual glycation is a result of interaction between proglycation and deglycation mechanisms and can be expressed by hemoglobin glycation index (HGI). There is increasing evidence that patients with higher glycation (and higher HGI) suffer from more frequent diabetic complications. In practice, it would therefore be advantageous to identify and treat such patients to stricter glycemic goals.

• Klíčová slova
• hemoglobin glycation index, glucose management indicator, glycated hemoglobin, continuous glucose monitoring, diabetes mellitus,
• MeSH
• diabetes mellitus metabolismus   MeSH
• diabetické angiopatie metabolismus   MeSH
• glykovaný hemoglobin * metabolismus   analýza   MeSH
• lidé MeSH
• produkty pokročilé glykace metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glykovaný hemoglobin * MeSH
• produkty pokročilé glykace MeSH

• Klíčová slova
• JAUNDICE *,
• MeSH
• lidé MeSH
• žloutenka * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

One of the major global health care crises in the 21st century is antibiotic resistance. Almost all clinically used antibiotics have resistance emerging to them. Antibiotic Resistance can be regarded as the 'Faceless Pandemic' that has enthralled the entire world. It has become peremptory to develop treatment options as an alternative to antibiotic therapy for combating antibiotic-resistant pathogens. A clearer understanding of antibiotic resistance is required to prevent the rapid spread of antibiotic-resistant genes and the re-emergence of infections. The present review provides an insight into the different classifications and modes of action of antibiotics to understand how the hosts develop resistance to them. In addition, the association of genetics in the development of antibiotic resistance and environmental factors has also been discussed, emphasizing developing action plans to counter this "quiescent pandemic". It is also pertinent to create models that can predict the early resistance so that treatment strategies may build up in advance with the evolving resistance.

• Klíčová slova
• Antibiotic resistance, antibiotic stewardship, de novo mutations, environmental factors, modes of action, quiescent pandemic,
• MeSH
• antibakteriální látky * farmakologie   terapeutické užití   MeSH
• antibiotická rezistence MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky * MeSH

Hepcidin deficiency leads to iron overload by increased dietary iron uptake and iron release from storage cells. The most frequent mutation in Hfe leads to reduced hepcidin expression and thereby causes iron overload. Recent findings suggested that HFE activates hepcidin expression predominantly via the BMP type I receptor ALK3. Here, we investigated whether HFE exclusively utilizes ALK3 or other signaling mechanisms also. We generated mice with double deficiency of Hfe and hepatocyte-specific Alk3 and compared the iron overload phenotypes of these double knockout mice to single hepatocyte-specific Alk3 deficient or Hfe knockout mice. Double Hfe-/-/hepatic Alk3fl/fl;Alb-Cre knockouts develop a similar iron overload phenotype compared to single hepatocyte-specific Alk3 deficient mice hallmarked by serum iron levels, tissue iron content and hepcidin levels of similar grades. HFE protein levels were increased in Alk3fl/fl;Alb-Cre mice compared to Alk3fl/fl mice, which was caused by iron overload - and not by Alk3 deficiency. The data provide evidence by genetic means that 1. HFE exclusively uses the BMP type I receptor ALK3 to induce hepcidin expression and 2. HFE protein expression is induced by iron overload, which further emphasizes the iron sensing function of HFE.

• Klíčová slova
• BMP signaling, BMP type I receptor, HFE, Hepcidin, Iron overload,
• MeSH
• hepcidiny * genetika   MeSH
• histokompatibilita - antigeny třídy I genetika   MeSH
• játra metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• přetížení železem * genetika   MeSH
• protein hemochromatózy genetika   MeSH
• receptory morfogenetických kostních proteinů typu I MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Bmpr1a protein, mouse MeSH Prohlížeč
• hepcidiny * MeSH
• Hfe protein, mouse MeSH Prohlížeč
• histokompatibilita - antigeny třídy I MeSH
• protein hemochromatózy MeSH
• receptory morfogenetických kostních proteinů typu I MeSH

The first observation of electroweak production of same-sign W boson pairs in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 35.9 fb^{-1} collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. Events are selected by requiring exactly two leptons (electrons or muons) of the same charge, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. The observed significance of the signal is 5.5 standard deviations, where a significance of 5.7 standard deviations is expected based on the standard model. The ratio of measured event yields to that expected from the standard model at leading order is 0.90±0.22. A cross section measurement in a fiducial region is reported. Bounds are given on the structure of quartic vector boson interactions in the framework of dimension-8 effective field theory operators and on the production of doubly charged Higgs bosons.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION AND HYPOTHESIS: TVT-O production has been modified to laser cutting from mechanical cutting. We compared the behavior of laser and mechanically cut tension-free vaginal tape-obturator (TVT-O) using ultrasound at various time points after surgery. METHODS: This is a retrospective analysis of clinical and ultrasound data from two previously reported randomized controlled trials with TVT-O. Behavior of mechanically cut TVT-O implanted in January 2007 to November 2009 and laser-cut TVT-O implanted in May 2010 to May 2012 was assessed by ultrasound at day 1, the 2nd week, the 3rd month, and the 1st and 2nd years post-operatively. Bladder neck and tape margins positions were described by coordinates in the orthogonal system calculated from polar coordinates. Tape mobility was measured as a change in the upper and lower tape margin position from rest to maximal Valsalva. Comparison of 2-year subjective and objective surgery outcomes was also performed. RESULTS: In total, 68 mechanically cut and 50 laser-cut TVT-Os were implanted. Follow-up data were available from 49 and 45 women respectively. No differences in any baseline characteristics or bladder neck mobility were observed. Significantly lower tape mobility was observed on day 1 and week 2 after mechanically cut TVT-O, although subsequent mobility was comparable to laser-cut TVT-O. The subjective and objective surgery outcomes were comparable. CONCLUSIONS: Although without clinical significance, early postoperative behavior of the mechanically cut and laser-cut TVT-O tapes differs. The less stiff, mechanically-cut TVT-O loosens within 2 weeks of implantation, whereas the stiffer, laser-cut TVT-O keeps its tension.

• Klíčová slova
• TVT-O, Tape elongation properties, Tape mobility, Tape stiffness, Ultrasound,
• MeSH
• chirurgická páska * MeSH
• gynekologické chirurgické výkony přístrojové vybavení   metody   MeSH
• lidé MeSH
• močový měchýř MeSH
• pooperační období MeSH
• retrospektivní studie MeSH
• stresová inkontinence moči chirurgie   MeSH
• suburetrální pásky * MeSH
• ultrasonografie * MeSH
• urologické chirurgické výkony metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The effect of blockade of GABAergic synapses by picrotoxin on the b- and d-wave of frog ERG was investigated under scotopic (0.002 lx), mesopic (2 lx) and photopic (200 lx) background illumination (Ib). Diffuse white stimuli with two levels of contrast (0.5 and 2.5) were used with each Ib. The aim was to compare the effects of picrotoxin at different background levels, but same stimulus contrast. We found that picrotoxin markedly increased the amplitude and rate of rise of the leading edge of the b- and d-wave with each Ib. This effect was most pronounced at mesopic Ib, smaller at photopic Ib and least pronounced at scotopic Ib. It was relatively stronger on the d-wave than on the b-wave amplitude under scotopic and mesopic conditions. Under photopic conditions, the difference between the picrotoxin effect on the b- and d-wave was much smaller. The possible neuronal mechanisms of the above described picrotoxin effects are discussed.

• MeSH
• elektroretinografie účinky léků   MeSH
• GABA antagonisté MeSH
• GABA fyziologie   MeSH
• pikrotoxin farmakologie   MeSH
• Rana ridibunda MeSH
• retina účinky léků   fyziologie   MeSH
• světlo MeSH
• synapse účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• GABA antagonisté MeSH
• GABA MeSH
• pikrotoxin MeSH

There are only few studies that examine the effect of prenatal methamphetamine (MA) exposure on the sensitivity to the same drug and the drug-seeking behavior in adulthood. The aim of the present study was to examine the effect of prenatal MA exposure on exploratory behavior and nociception with respect to challenge dose of the same drug. Mothers of the tested offspring received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male offspring (prenatally MA- or saline-exposed) were divided to groups with challenge dose of MA (1 mg/kg) or saline. A modified Open field test (Laboras) was used to examine behavior in unknown environment. Plantar test was used to measure nociception on forelimbs, hind limbs, and the tail. Conditioned place preference (CPP) test was used to examine drug-seeking behavior. Our results in Laboras demonstrated that prenatal MA exposure sensitized the animals to the challenge dose of MA. Specifically prenatally MA-exposed animals that received the challenge MA in adulthood displayed higher locomotion and rearing activity relative to all the other groups. The Plantar test data suggest analgesic effect of MA (1 mg/kg), which however, did not differ based on the prenatal drug exposure. The results of CPP test showed that MA (5 mg/kg) conditioning resulted in increased drug-seeking behavior, but this effect was not affected by prenatal drug exposure. Thus, our data demonstrate that the effects of prenatal MA exposure and the challenge dose of the same drug in adulthood depend on behavioral model used.

• MeSH
• chování při shánění drogy * účinky léků   MeSH
• chování zvířat * účinky léků   MeSH
• krysa rodu Rattus MeSH
• měření bolesti MeSH
• methamfetamin farmakologie   MeSH
• potkani Wistar MeSH
• stimulanty centrálního nervového systému farmakologie   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• methamfetamin MeSH
• stimulanty centrálního nervového systému MeSH