Iskanje po repozitoriju

A+ | A- | | SLO | ENG

Povzetek: Due to possible diagnostic misjudgment of tumor resectability, patients with pancreatic ductal adenocarcinoma (PDAC) might be exposed to non-radical resection or unnecessary laparotomy. With small extracellular vesicles (sEV) obtained by liquid biopsy, we aimed to evaluate their potential as biomarkers of tumor resectability, radicality of resection and overall survival (OS). Our prospective study included 83 PDAC patients undergoing surgery with curative intent followed-up longitudinally. sEV were isolated from plasma, and their concentration and size were determined. Fifty patients underwent PDAC resection, and thirty-three had no resection. Preoperatively, patients undergoing resection had higher sEV concentrations than those without resection (p = 0.023). Resection was predicted at the cutoff value of 1.88 × 109/mL for preoperative sEV concentration (p = 0.023) and the cutoff value of 194.8 nm for preoperative mean diameter (p = 0.057). Furthermore, patients with R0 resection demonstrated higher preoperative plasma sEV concentrations than patients with R1/R2 resection (p = 0.014). If sEV concentration was above 1.88 × 109/mL or if the mean diameter was below 194.8 nm, patients had significantly longer OS (p = 0.018 and p = 0.030, respectively). Our proof-of-principle study identified preoperative sEV characteristics as putative biomarkers of feasibility and radicality of PDAC resection that also enable discrimination of patients with worse OS. Liquid biopsy with sEV could aid in PDAC patient stratification and treatment optimization in the future.
Ključne besede: extracellular vesicles, pancreatic ductal adenocarcinoma, resection
Objavljeno v DiRROS: 06.08.2026; Ogledov: 162; Prenosov: 107
Celotno besedilo (991,43 KB)
Gradivo ima več datotek! Več...

Povzetek: Background Asbestos exposure is associated with asbestos-related diseases such as pleural plaques, asbestosis, lung cancer, malignant mesothelioma (MM), as well as several other types of cancer. Although the exact mechanism underlying the development of asbestos-related diseases is not yet fully understood, the immune system may play an important role. Immune checkpoints such as programmed cell death receptor 1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) regulate immune responses and are crucial for maintaining immune tolerance, while defects in these mechanisms can lead to the development of cancer. The aim of present study was to investigate the association of polymorphisms in the immune checkpoint genes for PD-1 (PDCD1), PD-L1 (CD274), and CTLA-4 (CTLA4) with the risk of asbestos-related diseases. Subjects and methods We conducted a retrospective case-control study. The cases included individuals with asbestosis or pleural plaques and MM patients. The controls were asbestos-exposed subjects who did not develop asbestos-related diseases. All subjects were genotyped for PDCD1 (rs2227982, rs222798, rs10204525), CD274 (rs2297136, rs4143815, rs4742098) and CTLA4 (rs5742909, rs4553808, rs231775) polymorphisms using competitive allele-specific PCR. Statistical analysis was performed using logistic regression. Results Our study showed that the CTLA4 rs4553808 polymorphism was associated with a decreased risk of asbestosrelated diseases (OR = 0.34, 95% CI = 0.15-0.74, P = 0.007). Homozygous carriers of polymorphic rs4553808 G allele had a lower risk of developing pleural plaques as well as MM compared to the control group (OR = 0.28, 95% CI = 0.11-0.68, P = 0.01, and OR = 0.38, 95% CI = 0.16 -0.93, P = 0.03, respectively). However, carriers of polymorphic CTLA4 rs231775 GG genotype had a higher risk of developing MM compared to the group of subjects with pleural plaques (OR = 1.79, 95% CI = 1.10-2.89, P = 0.02). The other investigated polymorphisms were not associated with any of the asbestos-related diseases. Conclusions CTLA4 polymorphisms may play a role in the susceptibility for asbestos-related diseases. Our results may contribute to a better understanding of the pathogenesis and progression of asbestos-related diseases.
Ključne besede: asbestos, malignant mesothelioma, immune checkpoints, single nucleotide polymorphism
Objavljeno v DiRROS: 22.07.2026; Ogledov: 241; Prenosov: 122
Celotno besedilo (492,94 KB)
Gradivo ima več datotek! Več...

Povzetek: Introduction/Aims Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA. Methods The cross-sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30–51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin-like growth factor-1 (IGF-1). Blood glucose, insulin, and beta-hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated. Results In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF-1 negatively correlated with FM. Discussion Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes.
Ključne besede: spinal muscular atrophy, endocrine manifestations, adults
Objavljeno v DiRROS: 15.06.2026; Ogledov: 258; Prenosov: 226
Celotno besedilo (1,26 MB)
Gradivo ima več datotek! Več...

Povzetek: Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Their treatment options are rather limited, and no neuroprotective or disease-modifying treatments are available. Anti-diabetic drugs, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonists, have been suggested as a potential therapeutic option. Aims: Assess GLP1R and GIPR genetic variability in relation to AD- and PD-related phenotypes. Methods: AD, PD patients and healthy control subjects were included in the study. Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease were measured in AD patients, while cognitive impairment was evaluated in PD. All participants were genotyped for three SNPs: GLP1R rs10305420, GLP1R rs6923761 and GIPR rs1800437. Results: GLP1R rs10305420 genotypes were associated with increased odds for AD and PD development. GLP1R rs10305420 and GLP1R rs6923761 genotypes were significantly associated with Aβ42/40 ratio (p = 0.041 and p = 0.050), while GLP1R rs6923761 was also associated with p-tau levels (p = 0.022). Finally, GIPR rs1800437 heterozygotes as well as carriers of at least one GIPR rs1800437 C allele presented with increased odds for the development of dementia in PD (OR = 1.92; 95 % CI = 1.05-3.51; p = 0.034 and OR = 1.95; 95 % CI = 1.08-3.52; p = 0.027, respectively). Conclusion: GLP1R and GIPR genetic variability may affect the occurrence of AD and PD and is also associated with AD CSF biomarkers for Alzheimer's disease and dementia in PD. The data on GLP1R and GIPR genetic variability may support the function of incretin receptors in neurodegeneration.
Ključne besede: Alzheimer's disease, biomarker, glucagon-like peptide 1 receptor, glucose-dependent insulinotropic polypeptide, Parkinson's disease, polymorphism
Objavljeno v DiRROS: 09.06.2026; Ogledov: 274; Prenosov: 253
Celotno besedilo (556,43 KB)
Gradivo ima več datotek! Več...

Povzetek: Introduction: Cholecystokinin (CCK) is involved in several metabolic pathways and CCK agonist are considered as potential novel treatment option in populations with increased metabolic risk, including polycystic ovary syndrome (PCOS). As genetic variability of cholecystokinin A and B receptor genes (CCKAR and CCKBR, respectively) may modify its biological actions, we investigated the impact of CCKAR and CCKBR genetic variability on anthropometric and metabolic parameters in patients with PCOS. Material and methods: Our cross-sectional study included 168 patients with PCOS and 82 healthy female controls genotyped for polymorphisms in CCKAR (rs6448456 and rs1800857) and CCKBR (rs2929180, rs1800843, rs1042047 and rs1042048) genes. Results: The investigated polymorphisms were not associated with anthropometric characteristics of patients with PCOS, however, among healthy controls carriers of at least one polymorphic CCKBR rs1800843 allele had bigger waist circumference (p=0.027) and more visceral fat (p=0.046). Among PCOS patients carriers of at least one polymorphic CCKAR rs6448456 C allele had significantly higher total blood cholesterol and LDL, and significantly lower blood glucose levels after 30, 60 and 90 minutes of the oral glucose tolerance test (all p<0.05). Healthy controls with at least one polymorphic CCKAR rs1800857 C allele were less likely to have high metabolic syndrome burden (p=0.029). Conclusions: Genetic variability in CCKAR affects lipid profile and post-load glucose levels in patients with PCOS and is associated with metabolic sydrome burden in healthy young women. Further investigation of the role of genetic variability in CCKAR and CCKBR could contribute to development of individually tailored treatment strategies with CCK receptor agonists.
Ključne besede: polymorphism, PCOS, cholecystokinin
Objavljeno v DiRROS: 03.06.2026; Ogledov: 306; Prenosov: 173
Celotno besedilo (131,40 KB)
Gradivo ima več datotek! Več...