Obesity is considered an important factor contributing to the development of atherosclerosis. Inflammation plays a key role in endothelial dysfunction (ED), an initial stage of the atherosclerotic process. Several microRNAs (miRNAs) may play an important role in the inflammatory process, but there is a lack of information about their participation in the early stages of atherosclerosis development in patients with obesity. We aimed to assess the relations between plasma concentration of selected miRNAs, ED evaluated by reactive hyperemia index (RHI), inflammatory markers and other factors involved in the pathogenesis of atherosclerosis in adolescents and young adults with obesity. Participants (30 males, 30 females; aged 15 25 years) were divided into two groups: those with overweight/obesity (OW/O) (20 males, 20 females) and controls (C) (10 males, 10 females). The plasma concentrations of inflammatory markers, cytokines, adipocytokines, markers of lipid profile and glucose metabolism and selected miRNAs (miR 92, 126, -146a, -155) were analyzed. No significant differences in any of the miRNAs were found between the groups. MiR-146a correlated positively with RHI. Dividing the group by sex showed more significant associations between miRNA and analyzed parameters (IL-6, fasting glycemia) in men. Several observed correlations indicate a potential role of miRNAs in inflammation, the atherosclerotic process and glycemic control, primarily in male subjects with obesity. The relatively low number of observed associations between assessed parameters related to obesity and the pathogenesis of its complications could be attributed to the early stage of the atherosclerotic process in young subjects with obesity, where only subtle abnormalities are expectedly found. Key words Endothelial dysfunction, Atherosclerosis, Obesity, MicroRNA, Reactive hyperemia index.
- MeSH
- ateroskleróza * krev genetika MeSH
- biologické markery krev MeSH
- cirkulující mikroRNA * krev genetika MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- obezita * krev komplikace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Hand osteoarthritis (OA) is a frequent musculoskeletal disorder with an increasing prevalence during ageing. This study aimed to evaluate circulating microRNAs (miRNAs) in the plasma of patients with hand OA compared with age- and sex-matched healthy control subjects. METHODS: In total, 238 participants (96 with erosive and 73 with non-erosive hand OA patients and 69 healthy control subjects) were included in this study. All patients underwent clinical examinations, including self-reported measures (AUSCAN and Algofunctional index). Radiographs of both hands were scored with the Kallman scale. The profile of miRNAs in plasma was screened using TaqManTM Low-Density Array, and candidate miRNAs were validated on two quantitative real-time PCR (qRT-PCR) systems (QuantStudio and SmartChip). RESULTS: Of all the 754 miRNAs, 40 miRNAs were different between hand OA patients and healthy control subjects in the screening cohort. Following the two-phase validation process, three miRNAs (miR-23a-3p, miR-146a-5p, and miR-652-3p) were increased in patients with hand OA compared with healthy control subjects and were associated with the AUSCAN sum score and AUSCAN pain. Furthermore, an inverse correlation of miR-222-3p with the Kallman radiographic score was found. The expression of miRNAs did not differ between erosive and non-erosive hand OA. CONCLUSION: The profile of circulating miRNAs could unveil candidate biomarkers associated with hand OA symptoms. Longitudinal studies are required to determine the role of miRNAs in hand OA.
- MeSH
- biologické markery MeSH
- bolest MeSH
- cirkulující mikroRNA * MeSH
- lidé MeSH
- mikro RNA * MeSH
- osteoartróza * diagnostické zobrazování genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lipoprotein apheresis (LA) is a therapeutic option for patients with severe hypercholesterolemia who have persistently elevated LDL-C levels despite attempts at drug therapy. MicroRNAs (miRNAs), important posttranscriptional gene regulators, are involved in the pathogenesis of atherosclerosis. Our study aimed to monitor the dynamics of twenty preselected circulating miRNAs in patients under long-term apheresis treatment. Plasma samples from 12 FH patients (men = 50%, age = 55.3 ± 12.2 years; mean LA overall treatment time = 13.1 ± 7.8 years) were collected before each apheresis therapy every sixth month over the course of four years of treatment. Eight complete follow-up (FU) samples were measured in each patient. Dynamic changes in the relative quantity of 6 miRNAs (miR-92a, miR-21, miR-126, miR-122, miR-26a, and miR-185; all p < 0.04) during FU were identified. Overall apheresis treatment time influenced circulating miR-146a levels (p < 0.04). In LDLR mutation homozygotes (N = 5), compared to heterozygotes (N = 7), we found higher plasma levels of miR-181, miR-126, miR-155, and miR-92a (all p < 0.03). Treatment with PCSK9 inhibitors (N = 6) affected the plasma levels of 7 miRNAs (miR-126, miR-122, miR-26a, miR-155, miR-125a, miR-92a, and miR-27a; all p < 0.04). Long-term monitoring has shown that LA in patients with severe familial hypercholesterolemia influences plasma circulating miRNAs involved in endothelial dysfunction, cholesterol homeostasis, inflammation, and plaque development. The longer the treatment using LA, the better the miRNA milieu depicting the potential cardiovascular risk.
- MeSH
- cirkulující mikroRNA * genetika MeSH
- dospělí MeSH
- hyperlipoproteinemie typ II * genetika terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- proproteinkonvertasa subtilisin/kexin typu 9 genetika MeSH
- senioři MeSH
- separace krevních složek * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
MicroRNAs (miRNAs) comprise a large group of small noncoding RNAs within a heterogeneous entity of noncoding RNAs, forming potent functional tools regulating the crucial biological processes within cells and the body. Cell-free miRNAs have become one of the novel promising diagnostic, predictive, and prognostic biomarkers for various diseases extensively investigated in recent years. This is due to their presence within extracellular fractions of various body fluids suggesting their potential as noninvasive "liquid biopsy" in case of their dysregulated expression.Among the body fluids, blood plasma and serum along with urine are the most commonly investigated sources of various types of cell-free miRNAs. Another body fluid, i.e., ascites (effusion, peritoneal/pleural fluid) may be the clinically important fluid particularly associated with carcinogenesis in ovarian carcinomas and hepatocellular carcinomas or in case of liver cirrhosis.Here, we provide a protocol for an expression profiling study based on qPCR analyses aimed at finding novel candidate miRNAs via small-scale or large-scale screening and evaluation experiments using liquid biopsies of blood plasma, ascites, and urine. Using this approach may be worth in cases where no (or limited) information is available on miRNA expression in particular diseases and geographic regions, for validation of previously published miRNAs with promising diagnostic potential, particularly in situations where follow-up study is aimed at validating miRNAs coming from (micro) array or NGS experiments, or where funding for large-scale experiments is not available. We demonstrate that assessment of plasma, ascites, and urine miRNAs expression may represent a feasible method to explore the potential for finding novel diagnostic, predictive, and prognostic biomarkers for various diseases.
BACKGROUND/AIM: Non-invasive circulating tumor biomarkers in liquid biopsy, such as microRNAs (miRNA), provide for better personalization of treatment strategies. The aim of our study was to assess the prognosis of patients with melanoma undergoing tumor resection with curative intent based on analysis of selected circulating miRNAs. PATIENTS AND METHODS: A total of 22 patients with stage I to III melanoma were enrolled into this prospective study. Plasma samples were obtained pre-surgery and early post-surgery from peripheral blood draws. A panel of 23 candidate miRNAs was designed and expression of miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction with exogenous reference control cel-miR-39-3p. RESULTS: Higher preoperative expression levels of miR-99a (p=0.008), miR-320 (p=0.009), miR-1908 (p=0.001), miR-494 (p=0.018) and miR-4487 (p=0.048) were associated with a shorter disease-free interval. Similarly, higher preoperative plasma levels of miR-99a (p=0.017), miR-221 (p=0.026), miR-320 (p=0.016), miR-494 (p=0.009), miR-1260 (p=0.026) and miR-1908 (p=0.024) were associated with worse overall survival. No significant differences between pre- and postoperative plasma miRNA levels were observed. CONCLUSION: Liquid biopsy is a minimally-invasive approach which can lead to a better understanding of cancer behavior and offers the possibility of precise patient prognosis, allowing selection of the most appropriate treatment. Our study showed that preoperative plasma levels of miR-99a, miR-221, miR-320, miR-494, miR-1908 and miR-4487 were associated with disease-free interval and overall survival of patients with early-stage melanoma. This approach may help in decision-making about the appropriateness of modern adjuvant treatment administration in patients with resectable melanoma.
Identifying patients likely to develop breast cancer recurrence remains a challenge. Thus, the discovery of biomarkers capable of diagnosing recurrence is of the utmost importance. MiRNAs are small, non-coding RNA molecules which are known to regulate genetic expression and have previously demonstrated relevance as biomarkers in malignancy. To perform a systematic review evaluating the role of miRNAs in predicting breast cancer recurrence. A formal systematic search of PubMed, Scopus, Web of Science, and Cochrane databases was performed. This search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist. A total of 19 studies involving 2287 patients were included. These studies identified 44 miRNAs which predicted breast cancer recurrence. Results from nine studies assessed miRNAs in tumour tissues (47.4%), eight studies included circulating miRNAs (42.1%), and two studies assessed both tumour and circulating miRNAs (10.5%). Increased expression of 25 miRNAs were identified in patients who developed recurrence, and decreased expression of 14 miRNAs. Interestingly, five miRNAs (miR-17-5p, miR-93-5p, miR-130a-3p, miR-155, and miR-375) had discordant expression levels, with previous studies indicating both increased and reduced expression levels of these biomarkers predicting recurrence. MiRNA expression patterns have the ability to predict breast cancer recurrence. These findings may be used in future translational research studies to identify patients with breast cancer recurrence to improve oncological and survival outcomes for our prospective patients.
- MeSH
- cirkulující mikroRNA * MeSH
- lidé MeSH
- malá nekódující RNA * MeSH
- mikro RNA * genetika metabolismus MeSH
- nádorové biomarkery genetika MeSH
- nádory prsu * diagnóza genetika metabolismus MeSH
- prospektivní studie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
Cancer belongs to multifactorial diseases characterized by uncontrolled growth and proliferation of abnormal cells. Breast cancer, non-small cell lung cancer, and colorectal cancer are the most frequently diagnosed malignancies with a high mortality rate. These carcinomas typically contain multiple genetically distinct subpopulations of tumor cells leading to tumor heterogeneity, which promotes the aggressiveness of the disease. Early diagnosis is necessary to increase patient progression-free survival. Particularly, miRNAs present in exosomes derived from tumors represent potential biomarkers suitable for early cancer diagnosis. Identification of miRNAs by liquid biopsy enables a personalized approach with the subsequent better clinical management of patients. This review article highlights the potential of circulating exosomal miRNAs in early breast, non-small cell lung, and colorectal cancer diagnosis.
- MeSH
- cirkulující mikroRNA * genetika MeSH
- kolorektální nádory * diagnóza genetika MeSH
- lidé MeSH
- mikro RNA * MeSH
- nádorové biomarkery genetika MeSH
- nádory plic * diagnóza genetika MeSH
- nemalobuněčný karcinom plic * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Potenciální komplikací angiochirurgických výkonů na břišní aortě je ischémie nitrobřišních orgánů. Akutní ischémie střeva (akutní mezenterická ischémie – AMI) je jednou z nejzávažnějších. Udávaná incidence AMI po otevřené resekci aneuryzmatu abdominální aorty (AAA) je 3 % pro elektivní a až 60 % pro výkony urgentní, s mortalitou až 90 %. Časná detekce AMI je naprosto esenciální pro zahájení léčby v době, kdy je stav ještě reverzibilní. Klinická diagnostika AMI je velice obtížná, specifický laboratorní marker neexistuje. Diagnostické zobrazovací metody jsou limitovány senzitivitou a specifitou. Angiografie a koloskopie jsou vyšetření invazivní, omezeně dostupná a ne vždy proveditelná. Ischémií modifikovaný albumin (IMA) a mikroRNA jsou nové technologie potenciálně vhodné k časné diagnostice AMI. Změny koncentrací těchto markerů v reakci na ischemické inzulty byly již popsány pro jiné orgány. Domníváme se, že kinetická analýza koncentrací IMA a cirkulujících mikroRNA umožňuje monitoring tkáňové ischémie po aortálních rekonstrukcích a potenciálně i časnou diagnostiku AMI.; A potential complication of abdominal aortic vascular surgery is an ischemia of intra-abdominal organs. Acute mesenteric ischemia (AMI) is one of the most serious conditions. Reported incidence for open abdominal aortic aneurysm (AAA) repair is 3 % for elective and up to 60 % for emergent procedures, with mortality up to 90 %. Early detection of AMI is essential for timely treatment, when AMI is still reversible. Clinical diagnosis of AMI is extremely difficult; there is no specific laboratory marker. Diagnostic imaging methods provide limited sensitivity and specificity. Angiography and colonoscopy are invasive, with limited availability and not always feasible. Ischemia modified albumin (IMA) and circulating microRNAs are new technologies potentially useful for early AMI detection. Blood level changes of these markers as a reaction to ischemic insults have already been described for other organs. We hypothesize that kinetic analysis of IMA and microRNA blood levels allows monitoring of tissue ischemia and potentially early AMI detection.
- MeSH
- aneurysma břišní aorty chirurgie MeSH
- aorta abdominalis chirurgie MeSH
- biologické markery MeSH
- cirkulující mikroRNA analýza MeSH
- lidský sérový albumin analýza MeSH
- mezenteriální ischemie diagnóza MeSH
- pooperační komplikace diagnóza MeSH
- výkony cévní chirurgie škodlivé účinky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- angiologie
- chirurgie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
BACKGROUND: Through regulation of signaling pathways, microRNAs (miRNAs) can be involved in sepsis and associated organ dysfunction. The aims of this study were to track the 7-day time course of blood miRNAs in patients with sepsis treated with vancomycin, gentamicin, or a non-nephrotoxic antibiotic and miRNA associations with neutrophil gelatinase-associated lipokalin (NGAL), creatinine, procalcitonin, interleukin-6, and acute kidney injury (AKI) stage. METHODS: Of 46 adult patients, 7 were on vancomycin, 20 on gentamicin, and 19 on another antibiotic. Blood samples were collected on days 1, 4, and 7 of treatment, and miRNAs were identified using quantitative reverse transcription PCR. RESULTS: The results showed no relationship between miRNA levels and biochemical variables on day 1. By day 7 of gentamicin treatment miR-15a-5p provided good discrimination between AKI and non-AKI (area under curve, 0.828). In patients taking vancomycin, miR-155-5p and miR-192-5p positively correlated with creatinine and NGAL values, and miR-192-5p and miR-423-5p positively correlated with procalcitonin and interleukin-6 in patients treated with a non-nephrotoxic antibiotic. In patients together we found positive correlation between miR-155-5p and miR-423-5p and all biochemical markers. CONCLUSION: The results suggest that these four miRNAs may serve as diagnostic or therapeutic tool in sepsis, renal injury and nephrotoxic treatment. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT04991376 . Registered on 27 July 2021.
- MeSH
- akutní poškození ledvin * komplikace MeSH
- antibakteriální látky terapeutické užití MeSH
- cirkulující mikroRNA * MeSH
- dospělí MeSH
- gentamiciny MeSH
- interleukin-6 metabolismus MeSH
- kreatinin MeSH
- lidé MeSH
- lipokalin-2 MeSH
- mikro RNA * genetika MeSH
- prokalcitonin MeSH
- sepse * komplikace MeSH
- vankomycin terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Identification of screening tests for the detection of head and neck cancer (HNC) at an early stage is an important strategy to improving prognosis. Our objective was to identify plasma circulating miRNAs for the diagnosis of HNC (oral and laryngeal subsites), within a multicenter International Head and Neck Cancer Epidemiology consortium. METHODS: A high-throughput screening phase with 754 miRNAs was performed in plasma samples of 88 cases and 88 controls, followed by a validation phase of the differentially expressed miRNAs, identified in the screening, in samples of 396 cases and 396 controls. Comparison of the fold changes (FC) was carried out using the Wilcoxon rank-sum test and the Dunn multiple comparison test. RESULTS: We identified miR-151-3p (FC = 1.73, P = 0.007) as differentially expressed miRNAs in the screening and validation phase. The miR-151-3p was the only overexpressed miRNA in validation sample of patients with HNC with early stage at diagnosis (FC = 1.81, P = 0.008) and it was confirmed upregulated both in smoker early-stage cases (FC = 3.52, P = 0.024) and in nonsmoker early-stage cases (FC = 1.60, P = 0.025) compared with controls. CONCLUSIONS: We identified miR-151-3p as an early marker of HNC. This miRNA was the only upregulated in patients at early stages of the disease, independently of the smoking status. IMPACT: The prognosis for HNC is still poor. The discovery of a new diagnostic biomarker could lead to an earlier tumor discovery and therefore to an improvement in patient prognosis.
- MeSH
- cirkulující mikroRNA * MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- nádorové biomarkery genetika MeSH
- nádory hlavy a krku * diagnóza genetika MeSH
- průřezové studie MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
