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EN
Cardiovascular diseases remain the primary cause of death in developed countries, including Poland, despite the progress in their treatment and a noticeable decrease in their prevalence. For this reason, the search for biomarkers for early disease risk assessment in primary as well as secondary prevention is the main task. Growth differentiation factor-15 (GDF-15) is becoming a leader among the new protein markers with a high predictive potential for cardiovascular diseases and their complications. An elevated GDF-15 blood level is associated with an increased risk of many cardiovascular diseases, their subclinical presence and their complications, including death. The predictive strength of GDF-15 is independent of and additive to other risk factors. GDF-15 can be used as part of a multimarker strategy to improve risk stratification, although it can also be used alone for death risk assessment. GDF-15 is not heart-specific: in some cardiovascular diseases its expression can be increased in other tissues as well. Elevated GDF-15 blood levels are found in cancer. They are also observed in renal impairment. Due to the strong relationship between GDF-15 and general mortality it is sometimes called “the marker of death.” Its increase often precedes serious clinical events by many months or even years. This provides opportunities for more intensive prevention, both primary and secondary.
PL
Choroby układu sercowo-naczyniowego, mimo postępu w ich leczeniu i zauważalnego spadku częstości ich występowania, są nadal główną przyczyną zgonów w krajach rozwiniętych cywilizacyjnie, w tym także w Polsce. Zatem poszukiwanie biomarkerów do wczesnego określania ryzyka tych chorób zarówno w prewencji pierwotnej, jak i wtórnej jest zadaniem pierwszoplanowym. Spośród nowych markerów białkowych o dużym potencjale predykcyjnym chorób układu sercowo- -naczyniowego i ich powikłań na czoło wysuwa się czynnik różnicowania wzrostu 15 (GDF-15). Jego podwyższone stężenie we krwi wiąże się ze zwiększonym ryzykiem wielu chorób układu sercowo-naczyniowego, ich obecnością w postaci subklinicznej, a także ich powikłaniami, łącznie ze zgonami. Siła predykcyjna GDF-15 jest niezależna od innych czynników ryzyka i addytywna w stosunku do nich. Czynnik ten może być wykorzystywany w strategii wielomarkerowej do poprawienia stratyfikacji ryzyka, chociaż do oceny ryzyka zgonu może być także stosowany samodzielnie. Czynnik różnicowania wzrostu 15 nie jest swoisty dla mięśnia sercowego – w niektórych chorobach układu sercowo-naczyniowego jego zwiększona ekspresja może występować także w innych tkankach. Podwyższone stężenie GDF-15 we krwi stwierdza się w chorobach nowotworowych. Wzrost stężenia tego markera obserwuje się również w stanach upośledzenia czynności nerek. Ze względu na silny związek GDF-15 z umieralnością ogólną określa się go niekiedy mianem „markera śmierci”. Wzrost jego stężenia często poprzedza o wiele miesięcy czy nawet lat wystąpienie dużych zdarzeń klinicznych. Otwiera to pole do intensywniejszej prewencji zarówno pierwotnej, jak i wtórnej.
EN
Introduction: Osteoarthritis (OA) is a widely prevalent joint disease leading to motor disability and pain. Appropriate indicators for identifying patients at risk for this progressive disease, identifying molecular events for detecting early phases of the disease, or biomarkers to screen for treatment responses, however, are lacking. Micro RNAs (miRNAs), which play crucial roles in OA, could be potential biomarkers of OA. Because circulating miRNA levels reflect the disease state, they may be useful for OA screening and as diagnostic tools, reducing the need for invasive procedures and minimizing the cost of current diagnostic methods. Materials and methods: The expression levels of 18 microRNAs (let-7e-5p, miR-21-5p, miR-93-5p, miR-101-3p, miR-103a-3p, miR-130a-3p miR-146a-5p, miR-16-5p, miR-193b-3p miR-199a-3p, miR-210-3p, miR-222-3p, miR-22-3p, miR-27a-3p, miR-27b-3p, miR-335-5p, miR-454-3p, and miR-98-5p) were analyzed by quantitative real-time polymerase chain reaction in the cartilage tissues and serum samples of 28 OA patients and were compared to those of 2 healthy controls. Results: Expression of microRNA-146a-5p was significantly upregulated in the cartilage (p=0.006) and serum (p=0.002) of OA patients. The expression levels of miR-146a-5p in the serum were positively correlated with those in the cartilage (Pearson correlation coefficient R=0.32; p=0.002). Conclusion: miR-146a-5p was significantly overexpressed in patients with OA, both in the articular cartilage tissue and serum, with a positive correlation between the levels in both types of samples. Therefore, the miR-146a-5p serum level could reflect the molecular processes in the cartilage, suggesting its clinical utility as a biomarker for OA management. Implementing noninvasive biomarker using serum miRNAs involves the analysis of the misregulated miRNAs linked to the cartilage pathology.
PL
Wstęp: Choroba zwyrodnieniowa stawów (OA) jest szeroko rozpowszechnioną chorobą stawów prowadzącą do niepełnosprawności ruchowej i bólu. Obecnie brakuje biomarkerów do wczesnej diagnostyki tej postępującej choroby oraz biomarkerów do badania odpowiedzi na leczenie u pacjentów z OA. MikroRNA (miRNA), które odgrywają kluczową rolę w rozwoju OA, mogą być potencjalnymi biomarkerami OA. Ponieważ poziomy krążących miRNA odzwierciedlają stan chorobowy, mogą być użyteczne w badaniach przesiewowych OA i jako narzędzia diagnostyczne, zmniejszając potrzebę inwazyjnych procedur i minimalizując koszty obecnych metod diagnostycznych. Materiały i metody: Poziomy ekspresji 18 miRNA (let-7e-5p, miR-21-5p, miR-93-5p, miR-101-3p, miR-103a-3p, miR-130a-3 p miR-146a 5p, miR-16-5p, miR-193b-3p miR-199a-3p, miR-210-3p, miR-222-3p, miR-22-3p, miR-27a-3p, miR-27b-3p, miR -335-5p, miR-454-3p i miR-98-5p) analizowano za pomocą ilościowej PCR w czasie rzeczywistym w tkankach chrzęstnych i próbkach surowicy od 28 pacjentów OA i porównano je z tymi 2 zdrowymi kontrolami. Wyniki: Ekspresja miRNA-146a-5p była znacząco podwyższona w chrząstce (p = 0,006) i w surowicy krwi (p = 0,002) u pacjentów z OA. Poziom ekspresji miR-146a-5p w surowicy był dodatnio skorelowany z poziomem miR-146a-5p w chrząstce (współczynnik korelacji Pearsona R = 0,32; p = 0,002). Wniosek: U pacjentów z OA, była znaczna nadekspresja miR-146a-5p zarówno w tkance chrząstki stawowej jak i w surowicy krwi, z dodatnią korelacją między poziomami tego miRNA w obu typach próbek. Dlatego poziom w surowicy miR-146a-5p może odzwierciedlać procesy molekularne zachodzące w chrząstce, co sugeruje jego kliniczną użyteczność jako biomarkera do identyfikowania OA. Wykonywanie oznaczania tego biomarkera z surowicy krwi obejmuje analizę miRNA związanych z patologią chrząstki.
EN
Regimen-related mucosal toxicity is extremely common following cytotoxic chemotherapy and radiotherapy. Mucositis is as an important determinant of the inflammatory response and infectious complications in cancer treated patients. Most assessment scales for mucosal damage are focussed on oral mucositis, since it is easy to evaluate. Measuring gastrointestinal musocal damage objectively remains difficult because it cannot be seen directly or readily detected. One of potential non-invasive biomarkers of gastrointestinal mucosal damage is plasma citrulline level. Citrulline is an amino acid produced by small bowel enterocytes. Low concentration of free circulating citrulline signifies severe intestinal mucosal damage in humans with nonmalignant disorders, such as villous atrophy-associated diseases, short bowel syndrome, Crohn's disease, and is used in follow-up after small bowel transplantation. The plasma citrulline level is a reliable and objective biochemical marker of enterocyte mass and function in humans, and therefore can be used to monitor enterocyte toxicity resulting from chemotherapy and radiotherapy during anticancer therapy in patients with severely disturbed gut integrity.
EN
The calcium-binding protein S100B is produced primarily by astrocytes and exerts concentration-dependent paracrine and autocrine effects on neurons and glia. The numerous findings of a correlation between S100B and traumatic brain injury (TBI) have resulted in the employment of this protein as a clinical biomarker for such injury. Our present aim was to determine whether cycling with (V) or without (NV) vibration alters serum concentrations of S100B. Twelve healthy, male non-smokers (age: 25.3±1.6 yrs, body mass: 74.2±5.9 kg, body height: 181.0±3.7 cm, VO2peak: 56.9±5.1 ml·min-1·kg-1 (means ± SD)) completed in random order two separate trials to exhaustion on a vibrating bicycle (amplitude 4 mm and frequency 20 Hz) connected to an ergometer. The initial workload of 100 W was elevated by 50 W every 5 min and the mean maximal period of exercise was 25:27±1:30 min. The S100B in venous blood taken at rest, immediately after the test, and 30, 60 and 240 min post-exercise exhibited no significant differences (p>0.05), suggesting that cycling with and without vibration does not influence this parameter.
EN
Objectives: Obesity, insulin resistance and dyslipidemia are the most significant risk factors of non-alcoholic fatty liver disease (NAFLD) but the role of adipokines in the pathogenesis of this disease is not clear. Assessment of retinol binding protein (RBP-4) seems to be promising because data from animal and human studies suggest its role in the patomechanism of insulin resistance. Therefore, the aim of the study was to evaluate the serum levels of RBP-4 in children with NAFLD. Methods: Fasting serum level of RBP-4 was determined in 42 obese children with suspected liver disease and 20 lean controls. The degree of liver steatosis was graded in ultrasound according to Saverymuttu. The intrahepatic lipid content was assessed noninvasively in a semiquantitative fashion using 1HMR spectroscopy (1.5-T scanner with PRESS sequence). Results: Fatty liver was confirmed in 30 children by ultrasonography (16 of them had also increased alanine transaminase (ALT) activity). Serum concentrations of RBP-4 were significantly higher in obese children with NAFLD compared to controls. Significant correlations were found between RBP-4 level and ultrasonographic grade of liver steatosis, intrahepatic lipid content (1HMRS) and triglycerides level, while the serum level of RBP-4 was not significantly higher in children with advanced liver steatosis (grade 2-3, n = 11) compared to patients with mild steatosis (grade 1, n = 19). The ability of RBP-4 to differentiate children with advanced liver steatosis from those with mild steatosis was not significant. Conclusion: RBP-4 can be considered as a convenient serum marker of intrahepatic lipid content in obese children.
EN
INTRODUCTION: The brain-derived neurotrophic factor (BDNF) is a protein belonging to neurotrophins that plays a key role in the proper development and functioning of the mammalian central nervous system. Previous studies have focused on assessment of the BDNF concentration in blood serum as a potential biomarker in neurological disorders. Recently, the BDNF signalling pathway has been recognised as a potential target for anticancer drugs, while its receptor (TrkB) as an oncogene in colorectal cancer cells. Despite the significant role in carcinogenesis, there are few studies on BDNF as a biomarker in colorectal cancer. MATERIAL AND METHODS: The study included 25 patients with clinically and histopathologically confirmed colorectal cancer, who were qualified for treatment. Prior to the first administration of chemotherapy, venous blood samples were collected from the patients and the biochemical parameters routinely determined prior to treatment were evaluated. Additionally, the serum BDNF concentration was determined by the immunoenzymatic method in all the patients. RESULTS: The serum BDNF concentration in patients was 50.24 ± 23.37 ng/ml. The BDNF concentration did not differ significantly between women and men. A negative correlation was found between the BDNF and CRP concentration and the BDNF and LDH concentration. The BDNF levels were significantly higher in patients who underwent primary tumour resection before chemotherapy. There was no correlation between the BDNF concentration and age, gender, BMI, CEA marker and liver enzymes in patients with colorectal cancer. There was no correlation between the BDNF concentration and clinical response to the treatment. CONCLUSIONS: BDNF cannot be considered as a prognostic factor in patients with colorectal cancer.
PL
WSTĘP: Neurotropowy czynnik pochodzenia mózgowego (Brain-Derived Neutortophic Factor – BDNF) jest białkiem należącym do rodziny neurotrofin, które odgrywa kluczową rolę w prawidłowym rozwoju i funkcjonowaniu ośrodkowego układu nerwowego ssaków. Dotychczasowe badania dotyczyły głównie oceny stężenia BDNF w surowicy krwi, jako potencjalnego biomarkera w schorzeniach neurologicznych. Ostatnio ścieżka sygnałowa BDNF uznana została za potencjalne miejsce uchwytu leków przeciwnowotworowych, a jego receptor (TrkB) za onkogen w komórkach raka jelita grubego. Pomimo znaczącej roli w nowotworzeniu, niewiele jest prac dotyczących BDNF jako biomarkera w raku jelita grubego. MATERIAŁ I METODY: Badaniem objęto grupę 25 osób z potwierdzonym klinicznie i histopatologicznie rakiem jelita grubego, którzy zostali zakwalifikowani do leczenia. Przed pierwszorazowym podaniem chemioterapii od pacjentów pobrano próbki krwi żylnej i dokonano oceny parametrów biochemicznych oznaczanych rutynowo przed leczeniem. Dodatkowo metodą immunoenzymatyczną oznaczono stężenia BDNF w surowicy krwi wszystkich badanych pacjentów. WYNIKI: Stężenie BDNF w surowicy pacjentów wyniosło 50,24 ± 23,37 ng/ml i nie różniło się istotnie pomiędzy kobietami i mężczyznami. Stwierdzono ujemną korelację między stężeniem BDNF i CRP oraz BDNF i LDH. Stężenie BDNF było znamiennie wyższe u chorych, którzy przed chemioterapią byli poddani resekcji guza pierwotnego. Nie wykazano zależności pomiędzy stężeniem BDNF a wiekiem, płcią, wskaźnikiem BMI, markerem CEA oraz enzymami wskaźnikowymi wątroby u pacjentów z RJG. Nie zaobserwowano zależności pomiędzy stężeniem BDNF a odpowiedzią kliniczną na zastosowane leczenie. wnioski: BDNF nie może być uznany za czynnik prognostyczny u chorych z rakiem jelita grubego.
Kosmos
|
2018
|
vol. 67
|
issue 2
347-359
PL
Przewaga procesów prooksydacyjnych w organizmie skutkuje wystąpieniem stresu oksydacyjnego objawiającego się m.in. utlenianiem białek. Bezpośrednia analiza ilości reaktywnych form tlenu i azotu jest zadaniem bardzo trudnym, dlatego w ocenie nasilenia stresu oksydacyjnego częściej wykorzystuje się markery uszkodzeń, powstające w wyniku reakcji wolnych rodników z białkami. Są one o wiele trwalsze, a przez to łatwiejsze do analizy. Wśród najważniejszych biomarkerów oksydacyjnych uszkodzeń białek wyróżnia się pochodne karbonylowe, 3-nitrotyrozynę, S-nitrotriazole, kynureninę, 3-chlorotyrozynę, bromotyrozynę, sulfotlenek metioniny, dityrozynę, oksohistydynę oraz tzw. zaawansowane produkty oksydacji białek (AOPP). W ocenie oksydacyjnych uszkodzeń białek u zwierząt laboratoryjnych najlepiej sprawdzają się pochodne karbonylowe, 3-nitrotyrozyna i AOPP. Ich zawartość w ustroju wyraźnie wzrasta w odpowiedzi na stres oksydacyjny wywołany takimi czynnikami, jak: niewłaściwa dieta, niedobór mikroelementów, zatrucie substancjami toksycznymi, infekcje czy starzenie.
EN
The prevalence of prooxidative processes in the body is associated with development of oxidative stress, one of the symptoms of which is oxidation of proteins. Direct analysis of the amount of reactive forms of oxygen and nitrogen is a very difficult task. Therefore, in assessing the severity of oxidative stress, markers generated by free radical reactions with proteins are often used. They are much more durable and thus easier to analyze. The most important biomarkers of oxidative damage of proteins are protein carbonyl compounds, 3-nitrothyrosine, S-nitrotriazoles, kynurenine, 3-chlorothyrozine, bromothyroxine, methionine sulfoxide, dithyrosine, oxohistidine and and so called advanced oxidation protein products (AOPP). Protein carbonyls, 3-nitrotyrosine and AOPP are the best indicators for evaluating of oxidative damage of proteins in laboratory animals. Their content in the body is clearly increasing in response to oxidative stress caused by such factors as improper diet, micronutrient deficiencies, toxic poisoning, infections or aging.
|
2015
|
vol. 2
7-19
EN
What is the microbe that we are dealing with? Whether it is cholera or anthrax, we want to know the disease-causing microorganism as quickly as possible since prompt identification of the causative organism would help control disease spread - and potentially save lives through provision of appropriate care and medication. Yet, despite the advent of rapid microbial identification tools – particularly those based on mass spectrometry – most undergraduate curricula continue to focus on culture- and nucleic acid-based identification techniques since they are widely used for detecting and identifying microbes in clinical and environmental samples. Mass spectrometry-based methods, however, have increasingly complemented traditional approaches in clinical and research laboratories - but are rarely featured in undergraduate curricula. Motivated by the desire to address the curriculum gap, the author of this study developed an inquiry-based laboratory exercise for introducing students to the operating principles and methodology of mass spectrometry-based microbial identification. By requiring students to identify microbes in environmental water samples – a real-life problem with unknown answers – the exercise piqued the students’ interest in learning, while helping to stir their curiosity through an interesting field activity in which they could put on a scientist’s hat in solving a mystery. This synopsis article summarizes a piece of published educational research and expands on the discussion of concepts underlying matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based microbial identification. Herein, the article discusses the relative advantages and disadvantages of the pattern recognition and proteome database search approaches for analyzing mass spectra data. Additionally, the effect of general and tailored sample preparation protocols on identification accuracy is also elaborated. Finally, the pedagogical utility of field- and inquiry-based educational tools is also discussed in greater detail from a post-publication perspective. A full-length synopsis of the work and a structured abstract can be found in the accompanying PDF file, the original article being entitled: “Teaching Microbial Identification with Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) and Bioinformatics Tools”.
EN
Peptides in human body fluids closely mirror processes of protein synthesis, processing and degradation. Since peptide levels and composition in the circulation fluctuate in close correlation with specific condition (either physiological or pathological) of an individual, comprehensive peptide analysis may unravel novel disease biomarkers or pave the way to new diagnostic approaches. Discovery of novel peptide biomarkers could facilitate drug development, as peptides can be used to monitor response to drugs, and thus help determine an optimal therapeutic dosage and assess toxic effects. In this review, we will provide a short overview of typical mass spectrometry-based peptidomics workflow, and give the examples from current literature of how peptidomics studies could potentially improve detection and treatment of cancer and neurodegenerative diseases, the latter including Alzheimer’s and Creutzfeldt-Jakob disease.
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