This study evaluates bone mineral density (BMD) and trabecular bone score (TBS) in relationship with new markers of chronic kidney disease (CKD), fibroblast growth factor 23 (FGF23), and klotho. The patients in this cross-sectional study were divided as follows: group A -patients in stages G1-3; group B -patients in stages G4 - 5 according to KDIGO. Plasma levels of soluble klotho and FGF23 were determined by ELISA. Bone mineral density (BMD) and trabecular bone score (TBS) were measured. 74 patients with CKD (mean age 68.8 years) were included in the study. Higher levels of FGF23 were observed in group B (N=15) compared to group A (N=59; p=0.001) were observed. FGF23 was higher in group A compared to group B. Significant difference in TBS within the first 3 stages of CKD was observed (mean TBS in G1=1.375 vs. G2=1.340 vs. G3a=1.24; p<0.05) and negative correlation of FGF23 and TBS (R=-0.33; p=0.05) and positive correlation between klotho and TBS (R=0.419; p=0.04) was observed. This study confirmed that FGF23 and klotho are associated with TBS, but TBS reflects a decrease in kidney function only in the first 3 stages of CKD. Thus, FGF23 and klotho together with TBS are promising markers of early trabecular bone impairment in CKD., Zuzana Kužmová, Martin Kužma, Andrea Gažová, Magdaléna Kovářová, Peter Jackuliak, Zdenko Killinger, Ján Kyselovič, Juraj Payer., and Obsahuje bibliografii
Transforming growth factor beta 1 (TGF-β1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-β1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-β1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-β1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells., Miriam Kaňuchová, Lukáš Urban, Nikola Melegová, Matúš Čoma, Barbora Dvořánková, Karel Smetana Jr., Peter Gál., and Obsahuje bibliografii
Increased plasma total cysteine (tCys) has been associated with obesity and metabolic syndrome in human and some animal studies but the underlying mechanisms remain unclear. In this study, we aimed at evaluating the effects of high cysteine diet administered to SHR-CRP transgenic rats, a model of metabolic syndrome and inflammation. SHR-CRP rats were fed either standard (3.2 g cystine/kg diet) or high cysteine diet (HCD, enriched with additional 4 g L-cysteine/kg diet). After 4 weeks, urine, plasma and tissue samples were collected and parameters of metabolic syndrome, sulfur metabolites and hepatic gene expression were evaluated. Rats on HCD exhibited similar body weights and weights of fat depots, reduced levels of serum insulin, and reduced oxidative stress in the liver. The HCD did not change concentrations of tCys in tissues and body fluids while taurine in tissues and body fluids, and urinary sulfate were significantly increased. In contrast, betaine levels were significantly reduced possibly compensating for taurine elevation. In summary, increased Cys intake did not induce obesity while it ameliorated insulin resistance in the SHR-CRP rats, possibly due to beneficial effects of accumulating taurine., Jakub Krijt, Jitka Sokolová, Jan Šilhavý, Petr Mlejnek, Jan Kubovčiak, František Liška, Hana Malínská, Martina Hüttl, Irena Marková, Michaela Křížková, Martha H. Stipanuk, Tomáš Křížek, Tamas Ditroi, Peter Nagy, Viktor Kožich, Michal Pravenec., and Obsahuje bibliografii
Diabetic foot ulcer (DFU) is a serious complication of diabetes and hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. The evidence supporting the use of HBOT in DFU treatment is controversial. The aim of this work was to introduce a DFU model in ZDF rat by creating a wound on the back of an animal and to investigate the effect of HBOT on the defect by macroscopic evaluation, quantitative histological evaluation of collagen (types I and III), evaluation of angiogenesis and determination of interleukin 6 (IL6) levels in the plasma. The study included 10 rats in the control group (CONT) and 10 in the HBOT group, who underwent HBOT in standard clinical regimen. Histological evaluation was performed on the 18th day after induction of defect. The results show that HBOT did not affect the macroscopic size of the defect nor IL6 plasma levels. A volume fraction of type I collagen was slightly increased by HBOT without reaching statistical significance (1.35±0.49 and 1.94±0.67 %, CONT and HBOT, respectively). In contrast, the collagen type III volume fraction was ~120 % higher in HBOT wounds (1.41±0.81 %) than in CONT ones (0.63±0.37 %; p=0.046). In addition, the ratio of the volume fraction of both collagens in the wound ((I+III)w) to the volume fraction of both collagens in the adjacent healthy skin ((I+III)h) was ~65 % higher in rats subjected to HBOT (8.9±3.07 vs. 5.38±1.86 %, HBOT and CONT, respectively; p=0.028). Vessels density (number per 1 mm2 ) was found to be higher in CONT vs. HBOT (206.5±41.8 and 124±28.2, respectively, p<0.001). Our study suggests that HBOT promotes collagen III formation and decreases the number of newly formed vessels at the early phases of healing., Jiří Růžička, Martina Grajciarová, Lucie Vištejnová, Pavel Klein, Filip Tichánek, Zbyněk Tonar, Jiří Dejmek, Jiří Beneš, Lukáš Bolek, Robert Bajgar, Jitka Kuncová., and Obsahuje bibliografii
Cancer is a complex, multifactorial disease that modern medicine ultimately aims to overcome. Downstream of tyrosine kinase 2 (DOK2) is a well-known tumor suppressor gene, and a member of the downstream protein DOK family of tyrosine kinases. Through a search of original literature indexed in PubMed and other databases, the present review aims to extricate the mechanisms by which DOK2 acts on cancer, thereby identifying more reliable and effective therapeutic targets to promote enhanced methods of cancer prevention and treatment. The review focuses on the role of DOK2 in multiple tumor types in the lungs, intestines, liver, and breast. Additionally, we discuss the potential mechanisms of action of DOK2 and the downstream consequences via the Ras/MPAK/ERK or PI3K/AKT/mTOR signaling pathways., Pei Sun, Rumeng Li, Yingying Meng, Shijun Xi, Qinqi Wang, Xiulan Yang, Xiaochun Peng, Jun Cai., and Obsahuje bibliografii
Application of knowledge about ischemic tolerance to clinic requires the solid understanding of mechanism of creation of this phenomenon. This review summarizes research that has been carried out in many laboratories over a long period of time, but the main focus will be on own experimental research. The main emphasis is devoted to the possibility of preparing full tolerance in the donor's body and its transfer to the patient in the form of activated blood plasma. Such plasma could be administered as soon as the patient is transported to the hospital and would take effect immediately after administration to the patient's bloodstream. One chapter is also devoted to anticonditioning, i.e. the possibility of preventing the activation of tolerance. Anticonditioning could be used to treat oncologic patients. We expect that this method could increase effectiveness of cancer treatment. Cross-tolerance with a wide range of diverse stressors gives us the courage to assume that activated plasma can significantly help with a wide range of pathological events., Jozef Burda, Rastislav Burda., and Obsahuje bibliografii
According to several studies, women with Crohn's disease (CD) had reduced fertility, which is mostly due to voluntary decisions and reduced ovarian reserve. In our study, we aimed to compare reproductive health parameters (RHP), previous pregnancy complications and outcomes, and ovarian reserve (OR) assessed by the anti-Mullerian hormone (AMH) in CD patients with healthy controls. In CD patients, we also compared OR according to disease phenotypes. Consecutive pre-menopausal women with CD from two IBD centers were included. The control group consisted of age and BMI-matched healthy controls. We used a questionnaire that included RHP, CD phenotype, and CD activity. Serum AMH was assessed by the Elecsys AMH plus essay. We enrolled 50 patients and 56 controls with a median age of 31 years. All CD patients were in clinical remission. We observed no difference in RHP or AMH (median 2.6 vs. 2.1 ug/l, p = 0.98), or the proportion of low OR (AMH<1,77, 38 vs. 41.1 %, p=0.84). The slope of age-related decrease did not differ between the groups. The subgroup of CD patients after surgery and those older than 30 years with CD for >5years had a steeper decrease in AMH (slope -0.12 vs. -0.29, p = 0.04 and - 0.31 vs. -0.2, p = 0.029). In a multivariate analysis, age was the single independent predictor of low OR (OR=1.25). In women with Crohn’s disease, once the disease activity is under control, the reproductive health and ovarian reserve do not substantially differ from healthy controls., Tomáš Koller, Jana Kollerová, Tibor Hlavatý, Barbora Kadlečková, Juraj Payer., and Obsahuje bibliografii
Beneficial effects of Sambucus nigra L. (black elder) as a traditional medicine have been associated with the phytoconstituents including polyphenols, terpenes and lectins. Various antioxidant rich natural products have also been implicated with improvement of reproductive health and fertility, however, the effect of Sambucus nigra on the ovarian cell functions has not been investigated yet. The objectives of the present study were to screen the polyphenols in the elderflower and elderberry extracts, and to examine the secretion activity of steroid hormones 17β-estradiol and progesterone by human ovarian granulosa cells HGL5 after supplementation of the extracts at a concentration range of 12.5 to 100 µg.ml-1 . Qualitative as well as quantitative screening of polyphenols by high-performance liquid chromatography with diode-array detector (HPLC-DAD) analysis revealed rutin to be the most abundant polyphenol in both elderflower and elderberry extracts. In culture, neither elderflower nor elderberry extract caused any significant impact (p>0.05) in cell viability as studied by AlamarBlue assay in comparison to control. However, a dosedependent stimulation of 17β-estradiol release was detected by ELISA after supplementation of elderflower (at 50 µg.ml-1 ; p<0.01) and elderberry (at 100 µg.ml-1 ; p<0.05) extracts at higher doses used in the study. On the other hand, both elderflower and elderberry extracts stimulated the secretion of progesterone by HGL5 cells at a lower dose (12.5 µg.ml-1 ; p<0.05), as compared to control. Therefore, elderflower and elderberry extracts may have the potential to regulate steroidogenesis in ovarian cells., Simona Baldovska, Shubhadeep Roychoudhury, Marek Bandik, Michal Mihal, Erika Mnahoncakova, Julius Arvay, Ales Pavlik, Petr Slama, Adriana Kolesarova., and Obsahuje bibliografii
Parathyroid hormone (PTH) increases the release of serum calcium through osteoclasts, which leads to bone resorption. Primary, PTH stimulates osteoblasts leading to increase RANKL (receptor activator for nuclear factor kappa-B ligand) expression and thus differentiation of osteoclasts. In kidneys, PTH increases calcium and decrease phosphate reabsorption. In kidneys, PTH stimulates 1alpha-hydroxylase to synthesize active vitamin D. Primary hyperparathyroidism (PHPT) is characterized by skeletal or renal complications. Nowadays, the classical form of PHPT is less seen and asymptomatic or subclinical (oligo symptomatic) forms are more frequent. Previously, it was thought that cortical bone is preferably affected by PHPT and that predispose bones to fracture at sites with a higher amount of cortical bone. However, an increased risk of vertebral fractures has been found by most of the studies showing that also trabecular bone is affected. Bone Mass measurement (BMD) at all skeletal sites is advised, but another specific tool for fracture assessment is needed. Trabecular bone score (TBS), an indirect measure of trabecular bone, maybe a useful method to estimate fracture risk. TBS is associated with vertebral fractures in PHPT regardless of BMD, age, BMI and gender. Furthermore, there is an association between TBS and high resolution peripheral quantitative computed tomography (HR-pQCT) parameters in the trabecular and cortical compartment. However, studies considering the effect of PHPT treatment on TBS are more conflicting. Secondary hyperparathyroidism caused by vitamin D deficiency was associated with impaired bone microarchitecture in all age categories, as measured by TBS and Hr-pQCT with further improvement after treatment with vitamin D. and Martin Kužma, Peter Jackuliak, Zdenko Killinger, Juraj Payer.
Ankylosing spondylarthritis (AS) is associated falsely increased lumbar spine bone mineral density (BMD). New tool for discrimination of subjects at fracture risk is needed. Vertebral fracture (VF) prediction of routine methods for osteoporosis assessment, BMD and trabecular bone score (TBS), in patients with AS. Cross-sectional study of all AS patients regularly followed at the rheumatology outpatient clinics of two centers. All subjects undergone BMD measurement at lumbar spine (LS), total hip (TH) and femoral neck (FN) using Hologic® Horizon device. TBS at L1-4 in all subjects by TBS InSight® software were assessed. Vertebral fracture assessment (VFA) was performed using the lateral spine imaging IVA™ and graded using Genant semi-quantitative approach. 119 AS subjects (90 males/29 females), mean age 47.6 years were included in the study. In 20 patients 34 VFs were detected, from whom 7 patients had multiple fractures. Subjects with VF were older and had lower FN BMD, TBS in comparison to non-VF subjects. No differences in LS BMD, FN BMD or BASDAI between groups were observed. Among patients with VF only 3 had T-score less than -2.5 but 7 has TBS less than 1.23 which means highly degraded microarchitecture. AS patients with VF have lower TBS and FN BMD in comparison to non-VF subjects. In addition, TBS was able to detect 20 % more VFs than BMD. Therefore, TBS seems promising in VF discrimination among patients with AS., Zdenko Killinger, Martin Kužma, Soňa Tomková, Kristína Brázdilová, Peter Jackuliak, Juraj Payer., and Obsahuje bibliografii