Biomedical Papers-Olomouc最新文献

Rhegmatogenous retinal detachment (RRD) is a serious ophthalmic condition that, if untreated, can result in significant vision loss. Proliferative vitreoretinopathy (PVR) often complicates RRD and is the leading cause of surgical failure. Proteomic analysis of the vitreous has emerged as a powerful tool for elucidating the molecular mechanisms underlying RRD and PVR. This article reviews proteomic findings related to these conditions. A comprehensive literature search on PubMed was conducted, focusing on studies of vitreous proteomics in RRD and PVR published between 1988 and August 2024. Relevant findings on protein expression, metabolic pathways, and therapeutic targets were synthesized. Proteomic studies reveal significant alterations in photoreceptor-specific proteins, such as rhodopsin and Monocyte Chemoattractant Protein-1 (MCP-1), associated with apoptosis and inflammation during RRD. Metabolic dysregulation is evidenced by changes in glycolytic enzymes and antioxidants, including downregulation of peroxiredoxin-2 and ascorbic acid, suggesting impaired energy production and oxidative stress. Elevated cytokines, complement proteins, and matrix metalloproteinases highlight the role of inflammation and extracellular matrix remodelling in disease progression. Cytokine expression in PVR demonstrates distinct temporal patterns, with early stages marked by T-cell activation and mTOR pathway-related cytokines, and advanced stages characterized by monocyte chemoattractants associated with chronic inflammation. Currently, the potential of pharmacologic interventions in RRD and PVR remains limited. In contrast, proteomics offers critical insights into molecular mechanisms, identifying potential biomarkers and therapeutic pathways. The adoption of single-molecule and top-down proteomics, along with the integration of advanced technologies with artificial intelligence and bioinformatics, holds promise for accelerating progress toward precision medicine. These developments represent a promising avenue for future research and clinical application.

Background: Prostate cancer (PC) is one of the most frequently diagnosed non-skin solid cancers and is a leading cause of cancer-related death and the incidence increasing. Early diagnosis of the disease improves the outcomes. There is an urgent need for new biomarkers with greater discriminative precision for diagnosis, risk-stratification and treatment. The aim of our study was to evaluate the diagnostic and prognostic potential of Fetuin-A and LRG1 in patients with PC.

Methods: Serum levels of Fetuin-A and LRG1 were compared in patients with PC (n=46), a control group 1 including young, healthy subjects (n=26) and control group 2 including patients with negative prostate biopsy (n=46). In PC patients, the levels of both biomarkers were compared in subgroups with different tumour characteristics.

Results: We demonstrated a statistically significant higher concentrations of Fetuin-A in PC patients compared to control group 2 (439 mg/L vs. 372 mg/L), P<0.001. No statistically significant difference was found between PC patients and control group 1, nor for LRG1 levels between the three groups. In PC patients, higher serum levels of LRG1 were found in M1 patients compared to M0 (98 mg/L vs. 42 mg/L), P=0.059.

Conclusion: Fetuin-A levels are significantly higher in patients with prostate cancer than in patients without malignancy but LRG1 levels do not differ between patients with PC and controls.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1 gene. The most important signs are café-au-lait spots, intertriginous freckling, and neurofibromas. The disease has a progressive course, the penetrance is almost complete, and reduces life expectancy by approximately 15%. This review examines the current literature, including NIH (National Institute of Health) diagnostic criteria, genetic testing, genotype-phenotype correlations, and emerging therapies. Genetic testing has improved diagnostic accuracy, particularly for age-dependent clinical features. The genotype-phenotype correlation in NF1 underscores that specific genetic alterations, such as large deletions in the NF1 gene, are frequently linked to more severe clinical outcomes. These deletions often result in early onset of symptoms, a higher frequency of tumor development, and increased tumor burden, all of which contribute to a more complex clinical course. Consequently, individuals with these genetic changes require intensive and continuous monitoring to manage potential complications and prevent further health deterioration. Advances in therapies such as MEK inhibitors offer hope for inoperable plexiform neurofibromas, while surgery remains the primary option for localized tumors, despite the risk of recurrence. Multidisciplinary care and genetic advancements are crucial for improving the prognosis and quality of life of patients with NF1.

Mitochondria, double-membraned organelles within all eukaryotic cells, are essential for the proper functioning of the human organism. The frequently used phrase "powerhouses of the cell" fails to adequately capture their multifaceted roles. In addition to producing energy in the form of adenosine triphosphate through oxidative phosphorylation, mitochondria are also involved in apoptosis (programmed cell death), calcium regulation, and signaling through reactive oxygen species. Recent research suggests that they can communicate with one another and influence cellular processes. Impaired mitochondrial function on the one hand, can have widespread and profound effects on cellular and organismal health, contributing to various diseases and age-related conditions. Regular exercise on the other hand, promotes mitochondrial health by enhancing their volume, density, and functionality. Although research has made significant progress in the last few decades, mainly through the use of modern technologies, there is still a need to intensify research efforts in this field. Exploring new approaches to enhance mitochondrial health could potentially impact longevity. In this review, we focus on mitochondrial research and discoveries, examine the structure and diverse roles of mitochondria in the human body, explore their influence on energy metabolism and cellular signaling and emphasize their importance in maintaining overall health.

Aims: To present a case of primary ventriculitis in a 53-year-old patient caused by Streptococcus intermedius, emphasizing the rarity of the condition and the challenges in achieving clinical improvement despite targeted therapy.

Methods: The patient underwent clinical evaluation, including CT and MRI imaging, as well as CSF analysis. Empirical antibiotic therapy was initiated with cefotaxime and metronidazole, followed by targeted therapy based on CSF culture results. External ventricular drainage was performed surgically.

Results: No predisposing factors were identified in the patient. Initial imaging showed no acute changes, but follow-up imaging revealed significant ventricular inflammation. CSF analysis confirmed the presence of Streptococcus intermedius. Despite early and targeted antibiotic therapy, and surgical intervention, the patient's clinical condition did not improve.

Conclusion: This case highlights the rarity of primary ventriculitis caused by Streptococcus intermedius and the challenges in managing it. The lack of clinical improvement despite prompt and targeted treatment underscores the need for further research to develop more effective therapeutic strategies for such infections.

Background: Recent regenerative studies imply conflicting results on knee osteoarthritic (OA) chondrocytes and mesenchymal stem cells (MSC)-mediated cartilage constructs in terms of compressive properties and tensile strength. This could be attributed to different gene expression patterns between MSC and OA chondrocytes during chondrogenic differentiation. Therefore, we analyzed differentially expressed genes (DEGs) between OA and MSC-derived chondrocytes using bioinformatics tools.

Methods: We downloaded and analyzed the GSE19664 dataset from the Gene Expression Omnibus to identify DEGs. DAVID was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, while a protein-protein interaction network of DEGs was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) and identified hub genes by CytoHubba.

Results: A total of 43 DEGs identified (15 downregulated and 28 upregulated) were found to be deregulated between OA and MSC-derived chondrocytes. KEGG analysis revealed the enrichment of complement and coagulation cascades and other pathways among the studied chondrocytes. The pathway enrichment identified top KEGG, gene ontology biological process, molecular function, and cellular component. The hub networks identified the top 5 hub genes involved in chondrogenesis, including CLU, PLAT, CP, TIMP3, and SERPINA1.

Conclusions: Our results identified significant genes involved in chondrogenesis. These findings provide new avenues for exploring the genetic mechanism underlying cartilage synthesis and novel targets for preclinical intervention and clinical treatment.

Backround and aims: Early evaluation of cardiac remodeling may be useful in predicting heart failure in patients with arterial hypertension. The identification of biomarkers as useful clinical tools in this regard is ongoing. The aim of this study was to evaluate the association of selected cardiac biomarkers levels with parameters of cardiac structure and function in patients with arterial hypertension.

Patients and methods: Included in the study were patients with arterial hypertension with normal left ventricular ejection fraction (LV EF) and absence of signs of heart failure. The levels of selected biomarkers: NT-proBNP, sST2, Galectin-3, GDF-15, Cystatin C, TIMP-1 and ceruloplasmin were measured and assessed together with other biochemical and echocardiographic parameters.

Results: A total of 92 patients (61% men) mean age 61.5 years were included. Mean LV EF was 64.7% and mean LV mass index was 91.7 g/m2. NT-proBNP level correlated significantly with the parameters of LV diastolic function: velocity of E wave (r=0.377, P<0.002), and with E/A ratio, (r=0.455, P<0.0001), with E lat (r=-0.354, P=0.006), E/E' ratio, r=0.393, P<0.002, with ePAP (r=0.390, P=0.014), and with age (r=0.384, P<0.0001). Statistically significant correlations for GDF-15 were as follows: with age (r=0.426, P<0.0001) and left atrial diameter (LA) (r=0.401, P<0.0001), for Cystatin C there are statistically significant correlation with age (r=0.288, P=0.006) and LA (r=0.329, P=0.004). Only sST2 level correlated significantly with parameters of cardiac structure: with LV mass (r=0.290, P<0.01) and LV mass index (r=0.307, P=0.012) and with posterior wall thickness PW (r=0.380, P<0.001). No other observed variables including Galectin-3 and TIMP-1, correlated significantly with age or echocardiographic variables. In a comparison of patients with and without left ventricular hypertrophy, statistically significant differences were found only in LA (P<0.0001) and sST2 (P=0.004). In a multivariate logistic regression, sST2 and TIMP were independent predictors of left ventricular hypertrophy.

Conclusion: NT-proBNP level as a biomarker of cardiac remodeling correlated with parameters of LV diastolic function in patients with arterial hypertension. Soluble ST2 correlated with parameters of cardiac structure. Biomarkers sST2 and TIMP-1 were associated with left ventricular hypertrophy.

Background: Nearly 50% of ST elevation myocardial infarction (STEMI) patients have multivessel coronary artery disease. The optimal selection of non-culprit lesions for complete revascularization is a matter of current debate. Little is known about the predictive value of myocardial perfusion study (MPS) in this scenario.

Methods: We enrolled 49 STEMI patients (61.5 ± 10.3 years) with at least one major non-culprit lesion (50-90%) other than left main coronary artery lesions. Overall 63 non-infarct- related artery (IRA) stenoses (65.2 ± 11.9%) were recommended for further evaluation using Fractional Flow Reserve (FFR) measurement as is standard in our institution. Prior to FFR, all patients were scheduled for non-invasive MPS using single-photon emission computed tomography (SPECT). Both FFR and MPS were performed 4-8 weeks after STEMI with MPS preceding FFR within no more than 48 hours. An FFR value of ≤0.80 was considered significant and guided the final revascularization strategy. The results of MPS were correlated to FFR as well as to the clinical and angiographic characteristics of both culprit and non-infarct-related lesions.

Results: Based on FFR, 30 out of 63 stenoses (47.6%) in 27 patients were considered hemodynamically significant (FFR 0.69 ± 0.08, range 0.51-0.79) compared to residual 33 stenoses considered negative (FFR 0.87 ± 0.04, range 0.81-0.96). The MPS revealed abnormal myocardium (23.6% average, range 5-56%) in 21 patients (42.8%). Among those patients, only 9 showed the evidence of ischemic myocardium (average 10.8%, range 4-18%) with low sensitivity of MPS in predicting positive FFR. Besides that, higher proportion of patients (71.4% vs. 42.9%, P=0.047) with overall lower FFR values (0.73 vs. 0.80, P=0.014, resp.) in non-IRAs as well as higher proportion of patients with more severely compromised flow in IRAs (P=0.048) during STEMI had MPS-detected abnormal myocardium.

Conclusion: In STEMI patients with multivessel coronary artery disease, we observed rather weak correlation between MPS using SPECT and invasive hemodynamic measurement using FFR in ischemia detection.

Aim: The main objective of this study was to determine whether urinary trauma increases the risk of acute kidney injury (AKI) in patients with severe trauma. As a secondary objective, we assessed the reliability of neutrophil gelatinase-associated lipocalin (NGAL) in the early prediction of AKI in this patient population.

Methods: Retrospective analysis of two prospective observational studies involving 179 adult patients with severe trauma (Injury Severity Score >16). NGAL levels were measured by taking a blood sample 24 h after admission. AKI was diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) classification.

Results: The overall incidence of AKI was 29%. Kidney or vascular injury was an independent risk factor for AKI (risk ratio [RR] = 3.1, 95% confidence interval [CI] 1.93-4.90). Trauma to urinary passages was also associated with an increased risk of AKI (RR = 4.2, 95% CI 2.70-6.46). Among patients without urinary tract injury, serum NGAL levels were significantly higher in trauma patients who developed AKI during the first 5 days in the intensive care unit (ICU) compared to patients without this organ dysfunction (214.6 µg/L [IQR 167.3] vs. 90.6 µg/L [IQR 58.4]; P<0.001). In patients with urinary tract trauma, there was no difference in the NGAL levels between the two groups (184.6 µg/L [IQR 139.9] vs. 118.3 µg/L [IQR 118.1]; P=0.216). NGAL was not a reliable predictor of AKI in patients with urinary trauma (AUC 0.660).

Conclusion: Urinary tract injury is associated with a significant increase in AKI in patients with severe trauma during the first 5 days of hospitalization in the intensive care unit. In these patients, NGAL is not a reliable predictor of the development of AKI.

Background and aim: In a previous follow-up of glaucoma patients taking carteolol or latanoprost, we found a greater progression of visual field changes with the prostaglandin than the betablocker. In the present study we compared the impact of carteolol and latanoprost on peripapillary vessel density in newly diagnosed primary open-angle glaucoma (POAG) patients.

Methods: The study consisted of two groups of POAG patients. There were 46 patient eyes treated with carteolol (Carteol LP 2%) in the first group and 52 eyes treated with latanoprost (Xalatan 0.005%) in the second. Intraocular pressure (IOP), vessel density (VD) and visual field were assessed in all patients. VD was measured peripapillary by optical coherence tomography angiography (OCTA) with the Avanti RTVue XR in eight segments: Inferior Temporal - IT (1); Temporal Inferior -TI (2); Temporal Superior - TS (3); Superior Temporal - ST (4); Superior Nasal - SN (5); Nasal Superior - NS (6); Nasal Inferior - NI (7) and Inferior Nasal - IN (8). The measurements were compared before and after three months of treatment. The visual field was examined with a fast threshold glaucoma program using a Medmont M 700 instrument from Medmont International Pty Ltd. and only when a diagnosis of POAG was done. The overall defect (OD) was assessed.

Results: Before treatment, there was no difference between groups in either OD or VD. After treatment, there was a decrease in IOP in both groups. In the carteolol-treated group, the mean decrease was 5.8 mmHg and in the latanoprost-treated eyes, the mean decrease was 7 mmHg. The difference was not statistically significant (P=0.133). After treatment with carteolol, there was a statistically significant increase in VD in segments 4, 5 and 6. After latanoprost treatment, VD was statistically significantly improved only in segment 5. A greater increase in VD values was found in eyes treated with carteolol than in eyes treated with latanoprost.

Conclusion: Carteolol had a better effect on vessel density than latanoprost.