INTRODUCTION: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is a rare but serious condition requiring accurate diagnostics. Cerebrospinal fluid (CSF) analysis plays a crucial role, particularly in cases where biopsy is not feasible, and imaging is inconclusive. AREAS COVERED: Chemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including circulating tumor DNA (ctDNA) analysis and microRNAs (miRNAs), are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.This review examines both traditional and emerging methods for CSF analysis in diagnosing CNS involvement in DLBCL. Conventional approaches such as cytomorphology, flow cytometry, and biochemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including ctDNA analysis and miRNAs, are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data. EXPERT OPINION: Advancements in CSF biomarker analysis are improving the diagnosis of CNS lymphoma, aiding early detection and personalized treatment approaches. However, further research and broader clinical validation are necessary for their routine implementation.
- MeSH
- Circulating Tumor DNA cerebrospinal fluid genetics MeSH
- Molecular Diagnostic Techniques methods MeSH
- Lymphoma, Large B-Cell, Diffuse * diagnosis cerebrospinal fluid genetics pathology MeSH
- Interleukin-10 genetics cerebrospinal fluid MeSH
- Humans MeSH
- Meningeal Neoplasms * diagnosis cerebrospinal fluid genetics MeSH
- MicroRNAs genetics cerebrospinal fluid MeSH
- Mutation MeSH
- Myeloid Differentiation Factor 88 genetics MeSH
- Biomarkers, Tumor * cerebrospinal fluid genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Since cell dying in heart failure (HF) may vary based on the aetiology, we examined the main forms of regulated necrosis, such as necroptosis and pyroptosis, in the hearts damaged due to myocardial infarction (MI) or pressure overload. We also investigated the effects of a drug inhibiting RIP3, a proposed convergent point for both these necrosis-like cell death modes. In rat hearts, left ventricular function, remodelling, pro-cell death, and pro-inflammatory events were investigated, and the pharmacodynamic action of RIP3 inhibitor (GSK'872) was assessed. Regardless of the HF aetiology, the heart cells were dying due to necroptosis, albeit the upstream signals may be different. Pyroptosis was observed only in post-MI HF. The dysregulated miRNAs in post-MI hearts were accompanied by higher levels of a predicted target, HMGB1, its receptors (TLRs), as well as the exacerbation of inflammation likely originating from macrophages. The RIP3 inhibitor suppressed necroptosis, unlike pyroptosis, normalised the dysregulated miRNAs and tended to decrease collagen content and affect macrophage infiltration without affecting cardiac function or structure. The drug also mitigated the local heart inflammation and normalised the higher circulating HMGB1 in rats with post-MI HF. Elevated serum levels of HMGB1 were also detected in HF patients and positively correlated with C-reactive protein, highlighting pro-inflammatory axis. In conclusion, in MI-, but not pressure overload-induced HF, both necroptosis and pyroptosis operate and might underlie HF pathogenesis. The RIP3-targeting pharmacological intervention might protect the heart by preventing pro-death and pro-inflammatory mechanisms, however, additional strategies targeting multiple pro-death pathways may exhibit greater cardioprotection.
- MeSH
- Ventricular Function, Left drug effects MeSH
- Protein Kinase Inhibitors * pharmacology MeSH
- Myocytes, Cardiac * drug effects pathology enzymology MeSH
- Rats MeSH
- MicroRNAs metabolism genetics MeSH
- Disease Models, Animal MeSH
- Necroptosis * drug effects MeSH
- Necrosis MeSH
- Rats, Sprague-Dawley MeSH
- Pyroptosis * drug effects MeSH
- Ventricular Remodeling drug effects MeSH
- Receptor-Interacting Protein Serine-Threonine Kinases * antagonists & inhibitors metabolism MeSH
- Heart Failure * pathology enzymology physiopathology drug therapy etiology genetics MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Background and Objectives: Liver cirrhosis is a serious and chronic condition that affects the liver, causing irreversible damage and scarring. The present study is designed to find out a possible correlation of hepatitis B virus (HBV) with cirrhosis by microRNA.Methods: The fold expression of the identified microRNAs by RT qPCR was determined to estimate the concentrations of circulating microRNAs in all samples. This study's main objective was to examine microRNA21-5p expression in liver cirrhosis patients. To extract RNA from samples of whole blood from all specimens in EDTA tubes, the study entailed collecting 60 specimens from the perspective of patients and samples pooled from 60 healthy participants (control group). Data on the patient are gathered for the study.Result: Researchers compared the levels of miRNA-146a in individuals with hepatic cirrhosis and control subjects, and the findings were clear. individuals with hepatic cirrhoses and controls, correspondingly, had mean levels of miRNA-146a of 2.38 3.25 and 1.12 1.01; this alteration was statistically noteworthy (P = 0.002). Both the miRNA-146a cut-off value and the prediction of liver cirrhosis disease should be considered diagnostic or adjuvant diagnostic tests. With sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of 58.3%, 53.3%, 55.6%, 56.1%, and 0.610 (0.508 -0.711), the miRNA-146a cut-off value was > 0.91-fold. The current findings suggest that miRNA-146a is a subpar diagnostic marker.Conclusion: Compared to controls, patients with cirrhosis had significantly higher levels of micro-RNA146A. When compared to those who are healthy, this finding demonstrates that micro-RNA 146A may influence the prognosis of cirrhosis.
- MeSH
- Blood Chemical Analysis methods MeSH
- Gene Expression MeSH
- Hepatitis B diagnosis genetics MeSH
- Liver Cirrhosis * diagnosis genetics MeSH
- Clinical Studies as Topic methods MeSH
- Humans MeSH
- MicroRNAs * genetics MeSH
- Reverse Transcriptase Polymerase Chain Reaction methods MeSH
- Sensitivity and Specificity MeSH
- Check Tag
- Humans MeSH
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
- Atherosclerosis * blood genetics MeSH
- Biomarkers blood MeSH
- Circulating MicroRNA * blood genetics MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Obesity * blood complications genetics MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Airway management is a critical component of out-of-hospital cardiac arrest (OHCA) resuscitation. The primary aim of this study was to describe pre-hospital airway management in adult patients post-OHCA. Secondary aims were to investigate whether tracheal intubation (TI) versus use of supraglottic airway device (SGA) was associated with patients' outcomes, including ventilator-free days within 26 days of randomization, 6 months neurological outcome and mortality. METHODS: Secondary analysis of the Target Temperature Management-2 (TTM2) trial conducted in 13 countries, including adult patients with OHCA and return of spontaneous circulation, with data available on pre-hospital airway management. A multivariate logistic regression model with backward stepwise selection was employed to assess whether TI versus SGA was associated with outcomes. RESULTS: Of the 1900 TTM2 trial patients, 1702 patients (89.5%) were included, with a mean age of 64 years (Standard Deviation, SD = 13.53); 79.1% were males. Pre-hospital airway management was SGA in 484 (28.4%), and TI in 1218 (71.6%) patients. At hospital admission, 87.8% of patients with SGA and 98.5% with TI were mechanically ventilated (p < 0.001). In the multivariate analysis, TI in comparison with SGA was not independently associated with an increase in ventilator-free days within 26 days of randomization, improved neurological outcomes, or decreased mortality. The hazard ratio for mortality with TI vs. SGA was 1.06, 95%Confidence Interval (CI) 0.88-1.28, p = 0.54. CONCLUSIONS: In the multicentre randomized TTM2-trial including patients with OHCA, most patients received prehospital endotracheal intubation to manage their airway. The choice of pre-hospital airway device was not independently associated with patient clinical outcomes. TRIAL REGISTRATION NUMBER: NCT02908308.
- MeSH
- Intubation, Intratracheal * methods MeSH
- Cardiopulmonary Resuscitation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Hypothermia, Induced methods MeSH
- Emergency Medical Services * methods MeSH
- Airway Management * methods MeSH
- Out-of-Hospital Cardiac Arrest * therapy mortality MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Background: Recent research has linked the spread of microribonucleic acid (miRNA) to numerous disorders, either as a stimulant or an inhibitor. One of these is miRNA-22, which research has connected to oxidative stress and thyroid issues. However, the underlying mechanisms are unknown. This study investigates the expression of miRNA-22 in hypothyroid women and its relationship to the rise in oxidative stress in the patient population.Materials and Methods: 40 women patients with Hypothyroid and 40 in this study, healthy volunteers who served as controls were included. The levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH) were measured by sandwich assay, while free triiodothyronine (FT3) and thyroxine (T4) levels were measured competitive binding immunoenzymatic assay. To assess lipid profiles, an automated analyzer was employed. By enzyme-linked immunosorbent assay (ELISA), Interleukin 6 (IL-6) levels were measured. Malondialdehyde (MDA), superoxide dismutase activity (SOD), catalase activity (CAT), and advanced oxidation protein products (AOPPs), and assessed using a colorimetric technique. The quantitative polymerase chain reaction was used to evaluate the expression of serum miRNA-22.Results: Significantly more SOD and CAT activity was identified in patient groups than in the control group (P<0.05), also the patient group's AOPP and MDA concentrations were discovered to significantly outweigh those of the control group. (P< 0.05). IL-6 levels were significantly higher in the patient group than in (P<0.05) the control group. The level of miRNA-22 was higher in the sick group as compared to the control groups (P<0.05).Conclusions: The pathophysiology of oxidative stress brought on by hypothyroidism involves miRNA-22 expression, there is a reciprocal relationship between the increase in gene expression of the miRNA-22 and the increase in oxidative stress, which results in the disease's development.
- MeSH
- Biomarkers blood MeSH
- Chemistry Techniques, Analytical methods instrumentation MeSH
- Adult MeSH
- Hormones blood MeSH
- Hypothyroidism * blood MeSH
- Humans MeSH
- MicroRNAs * blood MeSH
- Oxidative Stress MeSH
- Spectrum Analysis methods instrumentation MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Clinical Study MeSH
The endothelial-mesenchymal transition (EndMT) of endothelial progenitor cells (EPCs) plays a notable role in pathological vascular remodeling. Emerging evidence indicated that long non-coding RNA-regulator of reprogramming (linc-ROR) can promote epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Nevertheless, the function of linc-ROR in EPC EndMT has not been well elucidated. The present study investigated the effect and possible mechanisms of function of linc-ROR on the EndMT of EPCs. A linc-ROR overexpression lentiviral vector (LV linc-ROR) or a linc-ROR short hairpin RNA lentiviral vector (LV-shlinc-ROR) was used to up or downregulate linc-ROR expression in EPCs isolated from human umbilical cord blood. Functional experiments demonstrated that LV-linc-ROR promoted the proliferation and migration of EPCs, but inhibited EPC angiogenesis in vitro. In the meantime, reverse transcription-quantitative PCR and western blotting results showed that the expression of the endothelial cell markers vascular endothelial-cadherin and CD31 was decreased, while the expression of the mesenchymal cell markers ?-smooth muscle actin and SM22? was increased at both mRNA and protein levels in LV-linc-ROR-treated EPCs, indicating that linc-ROR induced EPC EndMT. Mechanistically, the dual-luciferase reporter assay demonstrated that microRNA (miR/miRNA)-145 was a direct target of linc-ROR, and miR-145 binds to the 3'-untranslated region of Smad3. Moreover, LV-shlinc-ROR increased the expression of miR-145, but decreased the expression of Smad3. In conclusion, linc-ROR promotes EPC EndMT, which may be associated with the miR-145/Smad3 signaling pathway. Keywords: Endothelial progenitor cells, Endothelial to mesenchymal transition, Linc-ROR, MiR-145, Atherosclerosis.
- MeSH
- Endothelial-Mesenchymal Transition MeSH
- Endothelial Progenitor Cells * metabolism MeSH
- Epithelial-Mesenchymal Transition * MeSH
- Cells, Cultured MeSH
- Humans MeSH
- MicroRNAs * metabolism genetics MeSH
- Cell Movement physiology MeSH
- Cell Proliferation MeSH
- Smad3 Protein * metabolism genetics MeSH
- RNA, Long Noncoding * genetics metabolism MeSH
- Signal Transduction * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Deficit alfa-1-antitrypsinu (AATD) je jedním z nejčastějších genetických onemocnění. Většina osob nese dvě kopie divoké alely M genu SERPINA1, který kóduje alfa-1-antitrypsin (AAT), a má normální AAT v krvi. Devadesát pět procent případů těžkého deficitu AAT je důsledkem homozygotní záměny Glu342Lys (alela Z), která je přítomna u 1 z 25 osob evropského původu. Mírný nedostatek AAT je obvykle důsledkem mutace Glu264Val (alela S). AAT je syntetizován v játrech a vylučován do krve, kde je jeho hlavní úlohou chránit plicní tkáň před působením neutrofilní elastázy. Bodové mutace mohou vést k precipitaci AAT v játrech, což vede k jaterní fibróze a cirhóze vlivem proteotoxického stresu („gain of function“). Naopak nedostatek cirkulujícího AAT predisponuje homozygoty s těžkým deficitem k časnému vzniku plicního emfyzému („loss of function“). Článek podává přehled současných poznatků o patofyziologii deficitu AAT, možnostech jeho diagnostiky a diskutuje možnosti léčby plicního onemocnění i nové možnosti léčby jaterního onemocnění.
Alpha-1-antitrypsin (AAT) deficiency (AATD) is one of the most common genetic disorders. Most people carry two copies of the wild-type M allele of the SERPINA1 gene, which encodes AAT, and have normal blood concentrations of AAT. Ninety-five percent of cases of severe AAT deficiency result from the homozygous Glu342Lys substitution (Z allele), which is present in 1 in 25 persons of European descent. Mild AAT deficiency is usually due to the Glu264Val mutation (S allele). AAT is synthesized in the liver and secreted into the blood. Its primary role is to protect lung tissue from neutrophil elastase attack. Point mutations can lead to the retention of AAT in the liver, leading to liver fibrosis and cirrhosis due to proteotoxic stress ("gain of function"), whereas the lack of circulating AAT predisposes homozygotes with severe deficiency to early onset of pulmonary emphysema ("loss of function"). This article reviews current knowledge of the pathophysiology of AAT deficiency, and its diagnostic options and discusses treatment options for pulmonary and novel treatment strategies in liver disease.
Background: Recent evidence has shown that circulating microribonucleic acid (miRNA) has been related to many diseases either as an inhibitor or a stimulant factor, among them miRNA-122 which has proven through studies its relationship with insulin resistance, an adversative lipid profile, obesity, type 2 diabetes, and metabolic syndrome in several studies; however, the mechanisms involved are unknown. This study investigates the role of miRNA-122 expression in overweight patients suffering from metabolic disorders such as diabetes and hypertension and its relationship to the development of oxidative stress in patient groups.Materials and Methods: 30 patients with type 2 diabetes mellitus (T2DM), 30 people with hypertension (HTN), 30 patients with T2DM+HTN, and 30 healthy persons who served as controls were enrolled in this study. An ARCHITECT c4000 clinical chemistry analyzer was used to assess lipid profiles. The sandwich immunodetection approach was used to assess whole blood hemoglobinA1c. By colorimetric methodology, catalase activity (CAT), superoxide dismutase activity (SOD), malondialdehyde (MDA) levels, and advanced oxidation protein products (AOPPs) levels were measured. The expression of serum miRNA-122 was determined using the quantitative polymerase chain reaction.Results: The activity of SOD and CAT in patient groups was found to be substantially lower than in the control group (p < 0.05), whereas MDA and AOPP concentrations were found to be significantly higher in patient groups compared to the control group (p < 0.05). When patient groups were compared to control groups, the miRNA-122 level was higher in the patients (p< 0.05).Conclusions: miRNA-122 expression is involved in the pathogenesis of T2DM and HTN-induced oxidative stress, there is a reciprocal relationship between the increase in gene expression of the miRNA-122 and the increase in oxidative stress accompanied by a decrease in the effectiveness of antioxidant enzymes, which leads to the development of the disease.
- MeSH
- Blood Chemical Analysis methods instrumentation statistics & numerical data MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Malondialdehyde blood MeSH
- Metabolic Diseases * blood pathology MeSH
- MicroRNAs * blood MeSH
- Oxidative Stress MeSH
- Advanced Oxidation Protein Products blood MeSH
- Superoxide Dismutase blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Publication type
- Clinical Study MeSH
- MeSH
- Anesthesia MeSH
- Aorta, Thoracic surgery MeSH
- Aortic Dissection nursing pathology MeSH
- Echocardiography, Transesophageal MeSH
- Endovascular Procedures methods MeSH
- Intraoperative Neurophysiological Monitoring methods instrumentation MeSH
- Cardiovascular Surgical Procedures * methods MeSH
- Humans MeSH
- Extracorporeal Circulation MeSH
- Monitoring, Physiologic methods MeSH
- Perfusion classification MeSH
- Perioperative Care * classification adverse effects MeSH
- Hypothermia, Induced methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
