Dysfibrinogenemia and hypofibrinogenemia - Spectrum of pathogenic variants in Slovak patients.

Introduction: Congenital hypofibrinogenemia (CH) and congenital dysfibrinogenemia (CD) are rare coagulation disorders caused by quantitative or qualitative defects in the fibrinogen gene. The aim of this study was to characterize the genetic background and the clinical manifestations of congenital fibrinogen disorders in the patients from Slovakia registered at the National Haemophilia Centre.

Materials And Methods: Results of genetic analysis of the fibrinogen genes FGA, FGB and FGG using polymerase chain reaction followed by direct sequencing were evaluated in 36 patients.

Post-mortem rapid aneuploidy testing for holoprosencephaly.

Background: Abortion and fetal death are common in fetuses with holoprosencephaly, so genetic examinations often have to be made in a post-mortem setting. The efficiency of the conventional karyotyping using cultured fibroblasts in these situations is limited due to frequent culture failure. In the current study, archived cases of holoprosencephaly, where post-mortem genetic evaluation was requested and sufficient frozen material was available, were reevaluated using the quantitative fluorescence polymerase chain reaction (QF-PCR) technique.

Novel Poxin Stable cGAMP-Derivatives Are Remarkable STING Agonists.

2',3'-cGAMP is a cyclic A- and G-containing dinucleotide second messenger, which is formed upon cellular recognition of foreign cytosolic DNA as part of the innate immune response. The molecule binds to the adaptor protein STING, which induces an immune response characterized by the production of type I interferons and cytokines. The development of STING-binding molecules with both agonistic as well as antagonistic properties is currently of tremendous interest to induce or enhance antitumor or antiviral immunity on the one hand, or to treat autoimmune diseases on the other hand.

Association Analysis of GDF5 and Contributing Factors in Developmental Dysplasia of the Hip in Infants.

Background: Developmental dysplasia of the hip (DDH) is a developmental disorder which is reported to be associated with hip instability. When untreated, it can lead to irreversible joint damage. DDH is known to be a multifactorial disease involving genetic, mechanical and environmental factors.

A proper placental sampling for syncytin-1 analysis.

Syncytin-1 (gene ) has been proposed as a marker of pre-eclampsia and malfunctions in placental development. Placenta is heterogeneous tissue, hence the method of biopsy can significantly affect the outcome of analyses. A total of 44 placentae were analyzed by taking 3-30 samples from each.

Correction to: Immunostimulatory RNA leads to functional reprogramming of myeloid-derived suppressor cells in pancreatic cancer.

Following publication of the original article [1], the authors have reported that Fig. 2 and Additional file 1: Figure S1, S2 partially show red scripts.

Immunostimulatory RNA leads to functional reprogramming of myeloid-derived suppressor cells in pancreatic cancer.

Background: The tumor microenvironment (TME) combines features of regulatory cytokines and immune cell populations to evade the recognition by the immune system. Myeloid-derived suppressor cells (MDSC) comprise populations of immature myeloid cells in tumor-bearing hosts with a highly immunosuppressive capacity. We could previously identify RIG-I-like helicases (RLH) as targets for the immunotherapy of pancreatic cancer inducing immunogenic tumor cell death and type I interferons (IFN) as key mediators linking innate with adaptive immunity.

Targeting intrinsic RIG-I signaling turns melanoma cells into type I interferon-releasing cellular antitumor vaccines.

Resistance to cell death and evasion of immunosurveillance are major causes of cancer persistence and progression. Tumor cell-intrinsic activation of the RNA receptor retinoic acid-inducible gene-I (RIG-I) can trigger an immunogenic form of programmed tumor cell death, but its impact on antitumor responses remains largely unexplored. We show that activation of intrinsic RIG-I signaling induces melanoma cell death that enforces cross-presentation of tumor-associated antigens by bystander dendritic cells.

An unusually high frequency of SCAD deficiency caused by two pathogenic variants in the ACADS gene and its relationship to the ethnic structure in Slovakia.

Background: Short-chain acyl-CoA dehydrogenase deficiency (SCADD) represents a rare autosomal recessive inborn metabolic disorder of mitochondrial β-oxidation of monocarboxylic acids. Clinical symptoms can vary from a severe life-threatening condition to an asymptomatic state, reported in the majority of cases. Since the expansion of newborn screenings, more than three hundred probands were admitted for molecular-genetic analysis, most selected because of elevated values of C4-acylcarnitine detected in newborn screenings in Slovakia.

Severe child form of primary hyperoxaluria type 2 - a case report revealing consequence of GRHPR deficiency on metabolism.

Background: Primary hyperoxaluria type 2 is a rare monogenic disorder inherited in an autosomal recessive pattern. It results from the absence of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GRHPR). As a consequence of deficient enzyme activity, excessive amounts of oxalate and L-glycerate are excreted in the urine, and are a source for the formation of calcium oxalate stones that result in recurrent nephrolithiasis and less frequently nephrocalcinosis.

Inhibitors in Severe Hemophilia A: 25-Year Experience in Slovakia.

Unlabelled: We present 25-year experience with inhibitors in previously untreated patients (PUPs) with severe hemophilia A in Slovakia, where safe factor VIII (FVIII) concentrates have been used since 1990. A prospective study focused on inhibitor incidence in PUPs was established in 1997. Out of a total 61 PUPs born between January 1997 and October 2015, 59 were eligible for evaluation; 50 and 9 were treated with > 20 exposure days (ED) of plasma-derived FVIII (pdFVIII) and recombinant FVIII (rFVIII) products, respectively.

A novel mutation in the PEX12 gene causing a peroxisomal biogenesis disorder.

The peroxisomal biogenesis disorders are autosomal recessive diseases morphologically characterised by lacking peroxisomes, biochemically by generalised deficiency of peroxisomal constituent and clinically manifested by serious health problems. Genes involved in the peroxisomal biogenesis are defined as the PEX genes encoding proteins called the peroxins. These peroxins are required for function in assembly of the peroxisomal membrane or in import of the enzymes into the peroxisomes.

Effect of the Schiff base complex diaqua-(N-salicylidene-l-glutamato)copper(II) monohydrate on human tumor cells.

The aim of our study was to estimate cytostatic/cytotoxic activity of the copper(II) Schiff base complex of the composition [Cu(N-salicylidene-l-glutamato)(H2O)2]·H2O, further Cu(SG-L)H2O, against human colon carcinoma cell line HT-29, as well as to determine type of cell death and to find out the molecular mechanism of apoptosis induced by this complex. Two highest concentrations (50, 100 µmol/l) of the complex showed a strong cytotoxic activity against human colon carcinoma cells HT-29 after 72 h of influence. Other concentrations had a cytostatic activity.

The effect of simvastatin on lipid droplets accumulation in human embryonic kidney cells and pancreatic cancer cells.

Background: Statins (HMG-CoA reductase inhibitors) represent a major class of compounds for the treatment of hypercholesterolemia due to their ability to inhibit de novo cholesterol synthesis. In addition to their hypolipidemic effects, chemoprotective properties have been attributed to statins as well. These effects involve multiple mechanisms, which, however, are not known in detail.

The tissue engineering of articular cartilage: cells, scaffolds and stimulating factors.

Damage or loss of articular cartilage as a consequence of congenital anomaly, degenerative joint disease or injury leads to progressive debilitation, which has a negative impact on the quality of life of affected individuals in all age groups. Classical surgical techniques for hyaline cartilage reparation are frequently insufficient and in many cases it is not possible to obtain the expected results. For this reason, researchers and surgeons are forced to find a method to induce complete cartilage repair.

The application of the RT-PCR method for the staging of the prostate cancer progression.

Molecular biology seems to bring more convincing markers for the detection of prostate cancer as well as the development of metastases than immunohistochemistry. The main goal of present work was to detect the expression of prostate specific antigen (PSA) and prostate-specific membrane antigen (PSM) genes in the micrometastases by the RT-PCR to assess the progression of prostate cancer. We analyzed 50 patients: 28 patients with clinically localized or locally advanced prostate cancer who underwent radical prostatectomy, 7 patients with clinically proven metastases, 8 patients with benign prostatic hyperplasia, and 7 healthy young men.

Endometrial cancer--prospective potential to make diagnostic process more specific.

Objective: The incidence of carcinoma of endometrium in younger patients has increased tendency. Experimental data support that mutation of tumor suppressor gene TP53 plays an important role in endometrial carcinogenesis

Material And Methods: Exons 2-11 of the gene TP53 into tissues of endometrial carcinoma and precancerous lesions were analyzed by DNA sequencing and restriction analysis.

Results: A polymorphism CCC/CGC at codon 72 was identified in exon 4 of TP53 gene of all precancerous lesions and carcinomas of endometrium.

Octuplet pregnancy following intracytoplasmic sperm injection and cryo embryo transfer.

Background: It is well known that the frequency of multiple gestation increases after in vitro fertilization in which more than one embryo is transferred. The aim is to report an octuplet pregnancy following intracytoplasmic sperm injection and cryo embryo transfer.

Case Report: A 31-year-old woman and her 35-year-old husband, both Caucasian, complained of primary infertility.

Comparison of in vitro chondrogenic potential of human mesenchymal stem cells derived from bone marrow and adipose tissue.

In the present work, the human bone marrow and adipose tissue-derived mesenchymal stem cells (MSCs) were isolated and expanded under in vitro condition. After their phenotypic analysis, the chondrogenic differentiation was induced by using of the three-dimensional culture system without supplementation of growth factors, and their chondrogenic potential was compared. Obtained results proved that both types of MSCs undergo the process of chondrogenic differentiation.

Morphology of in vitro expanded human muscle-derived stem cells.

Background: Skeletal muscle contains populations of multipotent adult stem cells also referred to as muscle-derived stem cells.

Aim: The main goal of this study was to isolate and culture human adult stem cells from skeletal muscle and characterize them.

Methods: Muscle-derived stem cells were isolated from biopsy specimens of femoral muscle.

Effect of pyridoxylidene aminoguanidine on human diploid cells B-HEF-2: in vitro cytotoxicity test and cytogenetic analysis.

Background: Pyridoxylidene aminoguanidine is an appropriate inhibitor of protein glycation, respectively formation of advanced glycation products, which are connected with mechanism of pathogenesis in chronic diabetic complications. Moreover, it was found that in comparison with aminoguanidine, pyridoxylidene aminoguanidine does not influence the level of vitamin B6 in liver and kidneys in vivo. The aim of this study was to test cytotoxic effect of pyridoxylidene aminoguanidine in vitro, in regard to its potential use as inhibitor of advance protein glycation in diabetic patients.