Biomedical Papers

Independent causal effect of α, β, and γ crystallin on cataract: A Mendelian randomization study

Xin Li, Ling-Li Xu, Jian Cheng, Qi-Di Hu — 2026-07-20 09:09:32

Objective. This study aimed to explore the independent causal relationship between three types of crystallin proteins (α, β, and γ) and risk of cataract, using single nucleotide polymorphisms (SNPs) as instrumental variables for α, β, γ crystallin through Mendelian randomization (MR) analysis. Methods. Genetic instruments associated with α, β, γ crystallin levels and cataract were obtained from the IEU Open GWAS Project (GWAS IDs: prot-a-673, prot-a-674, prot-a-675, and ukb-d-20002_1278). Two-sample MR analyses were conducted using five different MR algorithms containing MR-Egger, inverse variance weighted (IVW), Weighted median, Simple mode, and MR-PRESSO. Results. The MR analysis revealed a significant causal relationship between α crystallin level and the risk of cataract [odds ratio (OR)_IVW= 0.9989, 95% CI 0.9978~0.9999; OR_MR-PRESSO= 0.9988, 95% CI 0.9978~0.9999]. Conversely, no significant causal relationship was found between β or γ crystallin and the risk of cataract. Conclusion. The occurrence of cataract may be potentially linked to abnormal levels of α crystallin, suggesting that monitoring and managing these levels could be crucial in understanding and potentially mitigating the risk of cataract.

The prevalence of increased lipoprotein (a) in the Czech general population and in patients with coronary heart disease

Otto Mayer Jr, Daniel Rajdl, Jan Bruthans, Renata Cifkova, Jan Filipovsky — 2026-07-14 16:09:26

Background. Lipoprotein(a) (Lp(a)) is a cardiovascular risk factor (RF) with potentially high clinical impact. However, in the "real world", it remains largely overlooked, and the epidemiological circumstances of this RF have not yet been systematically studied in the Czech population. The aim of this study was to determine the prevalence of elevated values in cardiovascular patients and in the general population of this country. Methods. A descriptive survey and case-control study were conducted on 2001 subjects [mean age 61.5 years (±SD 12.5); 62.9% males], 1016 cases-patients with manifest coronary heart disease, (CHD), and 985 controls-a random general population sample. Results. The CHD patients had a significantly higher prevalence of increased Lp(a) (≥125 nmol/L) than the control group (25.1 vs 12.9%, P<0.0001). We found a similar relative difference using a lower cut-off, i.e., Lp(a) ≥105 nmol/L (28.9 vs. 14.6%, P<0.0001). In case-control analysis, fully adjusted odds ratio for Lp(a) ≥125 nmol/L was 1.69 (95%CI: 1.13-2.53, P=0.011), while for Lp(a) ≥105 nmol/L, 1.71 (95%CI: 1.16-2.52, P=0.006). Increased Lp(a) was also independent of other conventional RFs, and the only major coincidence we found was elevated LDL cholesterol. Conclusions. This study showed a significantly higher prevalence of Lp(a) in patients with manifest CHD compared to the general population. The systematic screening of this RF and pharmacologic intervention are probably warranted in routine clinical practice.

Structure, function and usage of integrin alpha 6 (CD49f): A comprehensive review

2026-06-15 11:15:07

Integrin alpha-6 (α6ITG, CD49f) has long been considered one of the most reliable markers of stemness, yet emerging evidence challenges this view by revealing its broader role in niche accessibility and survival. As a laminin receptor, α6ITG mediates cellular interactions and participates in signal transduction pathways that help maintain cellular phenotype. Its expression allows for the identification and purification of stem cells from heterogeneous populations. Because α6ITG expression is highly sensitive to environmental cues, it also serves as a sensor of culture conditions and cryopreservation stress, with potential use in biobanking and regenerative medicine. This marker holds significant potential; it may be one of the few markers consistently expressed in all stem cells, potentially qualifying it as a common "stemness" marker. Additionally, the therapeutic implications of α6ITG knockdown using antibodies may greatly influence future cancer treatments. Elevated expression in cancer correlates with growth, invasion, and poor prognosis. The aim of this review is to explore the biological and translational importance of α6ITG in stem cell and cancer biology.

Personalised treatment strategies in heart failure: A literature review and new proposed algorithm for device therapy selection

Lucie Kohoutkova, Martin Augustynek, Henryk Szymeczek — 2026-06-09 00:00:00

This article provides a synthesis of key clinical trials on device-based therapy in heart failure within the context of the current trend toward personalized medicine. Its main contribution is the proposal of a novel decision-making algorithm that integrates risk stratification based on underlying etiology, electrophysiological and functional parameters, as well as prognostic indicators including current non-invasive methods. The review also reflects current developments in clinical practice, including the growing role of physiological pacing, and supports an individualized approach to improving patient prognosis and quality of life.

Effectiveness of motor imagery techniques in the treatment of chronic musculoskeletal pain: A scoping review

2026-06-09 00:00:00

Motor imagery techniques, such as motor imagery, mirror therapy, and graded motor imagery, have the capacity to activate brain regions that overlap with those involved in actual movement execution. In individuals with chronic pain, these areas may undergo structural and functional changes due to persistent nociceptive input. Engaging in motor imagery can stimulate brain activity and potentially contribute to the restoration of more typical neural patterns. This scoping review of randomized controlled trials demonstrates that patients with chronic musculoskeletal pain may benefit from these techniques. Compared to control groups, participants receiving MI-based interventions experienced reductions in pain both immediately after therapeutic sessions and during follow-up assessments conducted up to several months post-intervention.

Advancements in immunotherapy for oropharyngeal cancer: Current landscape and future prospects

Xixi Shen, Shizhi He — 2026-06-09 00:00:00

This review provides an updated overview of emerging immune-based therapies for oropharyngeal malignancies, particularly those associated with HPV infection. It summarizes current evidence on checkpoint blockade, engineered T-cell approaches, monoclonal antibodies, and therapeutic vaccination strategies, while discussing their clinical relevance and translational potential. The article further evaluates the influence of viral biology, tumor microenvironment, and predictive biomarkers on therapeutic response. Key limitations, including resistance and immune escape, are also highlighted, together with future opportunities for individualized and combination-based treatment strategies in head and neck oncology.

Treatment and survival of patients with heart failure: An updated analysis from the Czech National Healthcare Database

Josef Danek, Jiri Jarkovsky, Klara Benesova, Milos Taborsky — 2026-06-09 00:00:00

Heart failure (HF) remains a growing public health concern. This study provides an updated analysis of HF incidence, prevalence, hospitalizations, and mortality trends in the Czech Republic (2015-2023). Using data from the National Healthcare Reimbursement Database (NRHZS), the authors evaluated key epidemiological patterns. Findings show a rising prevalence, stable incidence, and a slight decline in hospitalizations, while in-hospital mortality remains around 10%. Increased use of novel HF therapies, including ARNIs and SGLT2 inhibitors, was observed. These insights highlight the need for improved guideline adherence and multidisciplinary care models.

Induction of supraventricular tachycardias in patients undergoing pulmonary vein isolation for paroxysmal atrial fibrillation is safe and reasonable

2026-06-09 00:00:00

Patients with atrial fibrillation (AF) may experience other supraventricular tachycardias (SVT) that can trigger AF and cause similar symptoms. This study aimed to analyse the safety and efficacy of inducing SVT in patients undergoing catheter ablation (CA) for AF. The authors enrolled 61 patients with paroxysmal AF who underwent CA between January 2022 and March 2023. This electrophysiological study was performed after pulmonary vein isolation (PVI) to induce SVT. Induced arrhythmias were mapped and ablated. All patients were followed at 3, 6 and 12 months after the procedure and seven-day ECG Holter monitoring was carried out after 6 and 12 months from the procedure. SVT inducibility after successful pulmonary vein isolation was 39%. Age differed significantly in patients with arrhythmia inducibility compared to those without (64.5± 7.6 and 58.2±10.5, P=0.04). There were no significant differences in procedure time (P=0.408) or fluoroscopy dose (P=0.458) between patients with inducible arrhythmia and those without. None of the echocardiographic parameters showed any significant differences between groups. The conclusion of the study is that ablation of induced non-clinical arrhythmia is safe and does not prolong the total procedure or fluoroscopy time.

Ceramides versus standard methods in prediction of subclinical atherosclerosis

2026-06-09 00:00:00

Ceramides are a heterogeneous group of bioactive membrane sphingolipids. Evidence suggests that specific ceramide species are potential biomarkers and mediators of cardiovascular disease. The aim of the study was to develop two prediction models for carotid intima-media thickness (CIMT) using readily available variables. One model included conventional biomarkers (total cholesterol, triglycerides, hypolipidemics) in addition to gender and age, while the other included blood concentrations of selected ceramides. Cer(d18:1/18:0) was inversely related to CIMT, while Cer(d18:1/24:1) was positively correlated. Given that the study is cross-sectional, the findings should be interpreted as associations and do not support any causal inference.

A new approach to prealbumin as a biomarker for fibromyalgia?

Elif Karabacak, Muhtesem E. Yayla, Gulsah Y. Ozturk, Bahadir Ozelbaykal — 2026-06-09 00:00:00

There are currently no laboratory markers available to diagnose Fibromyalgia (FM). The aim in this study was to investigate biochemical markers that would support the pathogenesis and diagnosis of FM. To the best of the knowledge of the authors, this is the first study to evaluate CRP/prealbumin and prealbumin values in patients with Fibromyalgia. The results suggest that the CRP, CRP/prealbumin, lymphocyte and platelet levels increase in the disease and the prealbumin level decreases, which may indicate the role of inflammation in the pathogenesis. It was concluded that the inflammatory markers identified in this study may be useful in facilitating early diagnosis and treatment of patients with FM. The study was presented to contribute to the literature on FM.

Nutritional status and muscle mass loss in patients with COPD, association with lung function, symptoms, comorbidities and long-term survival: data from the National Database Study

2026-06-09 00:00:00

Similar to other chronic diseases, nutritional status appears to be an important determinant in patients with COPD. In this study, a comprehensive assessment was made of nutritional status and its association with other clinical characteristics and survival in 343 patients from the National Database of COPD. Nutritional imbalances were common in patients with COPD. Less than one fifth of the patients in the cohort had normal nutritional parameters. Overweight and obesity predominated, while underweight and muscle wasting were associated with the highest mortality. Different nutritional categories were associated with different comorbidities. The causes of these differences remain unclear. Some studies suggest a possible influence of pro-inflammatory cytokines, which may differ in relation to nutritional categories. More research is needed to clarify this.

The burden of multimorbidity in patients with systemic lupus erythematosus - single-centre analysis

Marketa Dudkova, Martina Skacelova, Pavel Horak, Jakub Videman, Adela Skoumalova — 2026-06-09 00:00:00

The prevalence of multimorbidity, defined as the presence of at least two chronic diseases, is increasing in both the general population and among patients with rheumatic conditions. This study provides insight into the prevalence of multimorbidity in one of the most frequent systemic autoimmune disorders, systemic lupus erythematosus (SLE). This chronic inflammatory autoimmune disease is characterised by the involvement of multiple organs due to both the disorder itself and the frequent comorbidities that are associated with the underlying disease process. These factors have the potential to affect the quality of life, treatment options, healthcare utilisation and overall patient prognosis.

Uterine artery embolisation in symptomatic patients with placenta accreta spectrum disorders

David Brustman, Jan Raupach, Vendelin Chovanec, Pavel Ryska — 2026-06-09 00:00:00

This study explores the use of uterine artery embolization (UAE) in patients with postpartum hemorrhage caused by placenta accreta spectrum (PAS) disorders. The procedure was performed after conservative treatments failed, aiming to control bleeding and reduce the need for more invasive surgeries. UAE successfully improved symptoms in the majority of patients, with no major complications during or after the procedure. Follow-up showed no recurrence of bleeding. The results suggest that UAE is a safe and effective treatment option for managing PAS-related hemorrhage, offering a less invasive alternative to surgical interventions.

Comparative study of the endometrial microenvironment's immunohistochemical profile in pre-tumour and tumour conditions: endometrial hyperplasia, endometrioid carcinoma, and serous carcinoma

Paata Jorjoliani, Zaza Bokhua, George Burkadze, Shota Kepuladze — 2026-05-06 09:45:10

Background. Endometrial carcinogenesis involves complex interactions between hormonal signaling and the local immune microenvironment. While atypical endometrial hyperplasia is a recognized precursor to carcinoma, the spatial and phenotypic evolution of immune and hormonal markers during progression remains incompletely characterized. Methods. A retrospective cohort of 150 endometrial specimens, including hyperplasia without atypia (n=40), hyperplasia with atypia (n=40), endometrioid carcinoma (n=40), and serous carcinoma (n=30), was analyzed using immunohistochemistry for CD3, CD4, CD8, FOXP3, CD68, CD163, estrogen receptor (ER), and progesterone receptor (PR). Digital whole-slide imaging and QuPath were applied to quantify immune cell densities in intratumoral and peritumoral compartments. Correlations between immune markers and hormonal receptors were evaluated, and a subgroup of 27 paired hyperplasia-carcinoma cases was analyzed separately. Results. CD3⁺ and CD8⁺ T-cell densities increased progressively from hyperplasia to carcinoma (P<0.001), with hyperplastic lesions demonstrating predominant peritumoral localization consistent with immune exclusion. FOXP3⁺ regulatory T cells were enriched in neoplastic lesions, particularly in ER/PR-positive tumors. CD8⁺ intratumoral and peritumoral densities showed significant inverse correlations with ER and PR expression (both r=-0.76, P<0.001), whereas FOXP3⁺ infiltration correlated positively with ER and PR (r=0.64, P<0.001). M2 CD163⁺ macrophages demonstrated an inverse association with ER (r=-0.49, P<0.01), while M1 CD68⁺/iNOS macrophages showed no statistically significant correlations. In the paired subgroup, higher peritumoral than intratumoral CD8⁺ densities persisted, indicating residual immune exclusion despite malignant transformation. Conclusions. Endometrial neoplastic progression is characterized by a transition from peritumoral immune exclusion in hyperplasia to increased intratumoral immune infiltration in carcinoma, although this shift is not universal. Hormone receptor-positive tumors exhibit enrichment of FOXP3⁺ regulatory T cells and CD163⁺ macrophages, suggesting hormone-linked immune suppression. These findings highlight combined immune-hormonal biomarkers as potential indicators of progression risk and support further investigation of integrated immunomodulatory and hormone-targeted therapeutic strategies.

Identification of abnormal expression profile of peripheral blood miRNA and its diagnostic value in grading the severity of COPD

Xiaoqing Zhang, Xiujuan Gong, Lianxia Zhang — 2026-05-04 14:56:47

Background. Chronic obstructive pulmonary disease (COPD) is now a major contributor to illness and death on a global scale. Traditional classifications based on pulmonary-function variables like the FEV1 (% predicted), lack sensitivity to early inflammatory changes and disease heterogeneity. In contrast, MiRNAs have emerged as promising biomarkers for respiratory conditions including COPD. The aim of this study was to examine the association between selected MiRNAs and COPD. Methods. A total of 200 COPD patients (GOLD I-IV, n=50 each) and 50 healthy controls were enrolled. Differentially expressed miRNAs were identified from the GEO database and validated by RT-qPCR. Univariate analysis and LASSO regression were used for feature selection. A logistic regression model incorporating selected variables was established for the forecast COPD severity. KEGG pathway enrichment of miR-518b target genes was performed using DAVID. Results. Five miRNAs (miR-216a, miR-518b, miR-106a, miR-1233, and miR-184) were substantially increased in COPD and correlated with disease severity (P<0.001). LASSO regression identified FEV1 (% predicted), DLCO (% predicted), CAT score, miR-518b, and age as key predictors. The combined model showed excellent classification performance (AUC=0.953; sensitivity=92.9%; specificity=81.3%). MiR-518b emerged as a strong independent risk factor (OR=18.91, P=0.003). Gene set enrichment of miR-518b targets pointed to involvement in both the Toll-like receptor and Hippo pathways, implicating its critical roles in inflammation and airway remodeling. Conclusions. MiR-518b is closely associated with COPD severity and may be useful in clinical practice. A model integrating miRNA expression and clinical parameters provides high predictive value for COPD classification and supports precision diagnosis.

The association between C-reactive protein/albumin ratio and coronary collateral circulation in patients with chronic coronary syndromes and chronic total occlusion

2026-04-16 09:37:01

Background. The C-reactive protein-to-albumin ratio (CAR) has recently gained attention as a novel biomarker reflecting both systemic inflammation and nutritional status. Since inflammation plays a critical role in the formation of the coronary collateral circulation (CCC), this study aimed to investigate the association between CAR and the extent of CCC in patients with chronic coronary syndromes (CCS) and chronic total occlusion (CTO). Methods. A total of 123 consecutive patients with CCS and angiographically documented CTO were included. CCC was assessed using the Rentrop classification and patients were divided into two groups: poor CCC (grades 0-1) and good CCC (grades 2-3). Laboratory data including C-reactive protein (CRP), albumin, lipid parameters, renal and liver function tests, glucose, and complete blood count were recorded. CAR was calculated by dividing CRP (mg/L) by albumin (g/dL), and neutrophil-to-lymphocyte ratio (NLR) was also evaluated. Results. Patients with poor CCC had significantly higher CRP, CAR, and NLR levels (P<0.05 for all). In multivariate logistic regression, both CAR (OR=1.200, 95% CI: 1.102-1.394, P<0.001) and NLR were independently associated with poor CCC. ROC analysis showed that CAR had better predictive value (AUC=0.79) than CRP (AUC=0.75, P=0.02) and NLR (AUC=0.67, P=0.03). A CAR cutoff of 2.36 yielded 67% sensitivity and 68% specificity. Conclusion. Elevated CAR is independently associated with impaired CCC in patients with CCS and CTO. CAR may serve as a simple and superior marker over traditional inflammatory indices in assessing collateral vessel development.

20-year experience with laparoscopic adrenalectomy at a high-volume center

2026-03-10 09:11:33

Objective. To evaluate transperitoneal laparoscopic adrenalectomies performed at the University Hospital, Olomouc over a period of 20 years. Introduction. Thanks to the increased availability of imaging, the detection of adrenal disease is increasing. Laparoscopic adrenalectomy is now regarded as the gold standard for the treatment of adrenal disease due to its safety and efficacy despite the increasing popularity of robotic-assisted surgery. Methods. Over a period of 20 years, from 2002 to 2021, we retrospectively evaluated a cohort of 405 patients who had undergone laparoscopic adrenalectomy. The indication criteria for laparoscopic adrenalectomy were hormonally active symptomatic tumours (pheochromocytoma, Conn's syndrome, Cushing's syndrome, etc.), symptomatic cysts or myelolipomas, carcinomas, metastatic disabling or incidentalomas, growing at a rate >1 cm or more per year. Data collected focused on sex, age, medical classification, imaging, operative time, side dominance, hormonal activity, complications associated with surgery, length of hospital stay, and histopathologic verification. No patient who had undergone laparoscopic adrenalectomy was excluded from the cohort. Patients in our cohort were not operated by a single surgeon. Results. Women accounted for 52.1% (211) and men 47.9% (194). The mean age was 55.6 years, BMI 28.7, and median ASA score was 2. Preoperative imaging included abdominal CT in 352 (86.9%) patients, abdominal MRI with contrast agent in 8 (2.0%), and PET/CT in 45 (11.1%) patients. More frequent findings were on the right side in 223 (54.39%) patients. Hormonal activity was found in 271 patients (67 %). Hormone overproduction from the right adrenal gland was found in 120 (44.3%) patients, and from the left in 151 (55.7%). Adenoma was the most frequent histological finding, followed by hyperplasia. Conversion to open surgery was due to bleeding in 2 patients. There was no perioperative or postoperative mortality. According to the Clavien-Dindo classification, minor complications (Grade I) occurred in 375 patients (92.6%). Grade II complications were reported in 17 patients (4.2%). Grade III complications were identified in 13 patients (3.2%) due to operative field bleeding; in three cases (0.7%), surgical revision of the adrenalectomy bed was required. Conclusion. Laparoscopic adrenalectomy is a safe surgical method for the management of adrenal disease and our retrospective follow-up confirmed that it remains the gold standard.

Vitamin D modulates the basal secretion of inflammatory cytokines in breast cancer cells: An in-vitro study

Lina Elsalem, Lina Aldarayseh, Nosayba Al-Azzam, Haneen A. Basheer — 2026-01-23 14:04:25

Background. Proinflammatory cytokines are a pivotal factor in cancer initiation and progression. The paracrine and autocrine secretions of such inflammatory cytokines are reported in different cancer types. Recently, C-C motif ligand (CCL) 5 (CCL5), CCL22, granulocyte-colony stimulating factor (G-CSF), and interleukin-1 receptor antagonist (IL-1 RA) have been detected in basal secretions of breast cancer (BC) cells and linked to BC pathogenesis. While Vitamin D has been found to have anti-inflammatory effects, its modulation on cytokine expression is rarely studied in relation to cancer. Aims. In this study, we evaluated whether vitamin D could modulate cytokine basal levels in BC. Materials and Methods. This in vitro study was conducted on BC cell lines, MCF-7 and MDA-MB-231. Cells were treated with vitamin D (10 and 100 nM), and cytokine levels were measured using the Enzyme-Linked Immunosorbent Assay (ELISA). Results. There was a significant reduction in CCL5 total levels in MCF-7 cells at both concentrations (P≤0.01) and in MDA-MB-231 at 100 nM (P≤0.05). Both concentrations reduced CCL22 levels significantly in MCF-7 (P≤0.05) and MDA-MB-231 (P≤0.01). Regarding G-CSF, a significant reduction was found in MCF-7 at both concentrations (P≤0.05) and at 100 nM in MDA-MB-231 (P≤0.01). In comparison, IL-1 RA levels were significantly elevated in MCF-7 (100 nM (P≤0.01)) and MDA-MB-231 (10 nM (P≤0.05) and 100 nM (P≤0.01)). Conclusion. Vitamin D down-regulated the pro-inflammatory and up-regulated the anti-inflammatory cytokines. This indicates that vitamin D can modulate the expression of inflammatory mediators, particularly in a cancer setting. The results support the potential use of vitamin D as an anti-cancer agent with anti-inflammatory properties.

Mini review on the laboratory diagnosis of amyloidosis: An overview of methods, applications, and trends in analytical approaches

2026-01-06 12:24:22

Amyloidosis represents a clinically and molecularly heterogeneous group of serious, potentially life-threatening disorders characterized by the extracellular deposition of insoluble amyloid fibrils derived from misfolded precursor proteins. These deposits disrupt tissue architecture and function, often affecting vital organs such as the heart and kidneys. Accurate diagnosis and subtyping of amyloidosis are essential for effective clinical management and personalized therapeutic interventions. This review provides an integrated overview of modern approaches to the laboratory diagnosis of amyloidosis, divided into three main areas: (1) histological and immunological methods (including Congo red staining, immunohistochemistry, immunofluorescence, and immunoelectron microscopy) for the initial detection and characterization of amyloid deposition, (2) electrophoretic techniques (capillary electrophoresis, isoelectric focusing, immunofixation electrophoresis) used primarily for the analysis of amyloid-associated proteins in serum and urine, and (3) mass spectrometry-based proteomic analyses that have significantly improved subtype specificity and clinical decision-making. By emphasizing the complementary roles of these techniques, the review aims to support timely, accurate, and subtype-specific diagnosis, ultimately improving clinical outcomes and treatment strategies for patients affected by amyloidosis.

A case-control study of promoter and 5'UTR VEGF polymorphisms in diabetic retinopathy

2025-12-18 10:47:21

Aims. Angiogenesis is activated in the retina of diabetic patients with retinopathy complications. Vascular endothelial growth factor (VEGF) plays an essential role as a mediator of the retinal induced neovascularization. VEGF levels are increased significantly in the vitreous and aqueous ocular fluids in the patients with proliferative diabetic retinopathy. The aim of this study is to investigate whether VEGF promoter/5'UTR polymorphisms are associated with diabetic retinopathy (DR) development and/or severity. Methods. In this case-control study, Type 2 diabetic patients with or without DR, and normal controls were recruited. DR was classified based on the presence or absence of proliferative changes. The genotyping was analysed by polymerase chain reaction followed by restriction fragment length polymorphism. Results. A total of 259 subjects (172 with diabetes+DR, 87 healthy controls; male:female, 125:134) were recruited. The average age was 59.5+9.6 years, diabetes duration was 8.5+4.5 years, body mass index was 30.6+6.0 kg/m2, and HbA1c was 7.37+1.2% (57 mmol/mol). Significant differences in the distribution of genotypes in T(-1,498)C, G(-1,190)A and G(-1,154)A polymorphism in diabetic patients versus controls, and DR patients versus DM without DR patients were shown. No association between DR severity and polymorphisms was detected. Non-significant differences in allele frequency were found. The haplotypes TGAGC, TGACT and CAGCT were significantly increased in DM patients, whereas CGGCC was the most common haplotype in DR patients. Conclusions. Multiple VEGF polymorphisms and CGGCC haplotype are significantly correlated with a higher DR risk in Type 2 diabetic patients.

The role of DNA methylation in the regulation of HLA expression

Adam Strnad, Martin Petrek — 2025-12-04 08:32:32

DNA methylation plays a critical role in the regulation of gene expression in the human leukocyte antigen (HLA) system which is a key component of immune function. This article reviews the molecular mechanisms by which DNA methylation influences HLA gene regulation, highlighting its impact on their antigen presentation and immune tolerance functions. We describe how methylation patterns vary in HLA class I and II genes, affecting their expression in a tissue- and allele-specific manner. In addition, we examine the interplay of DNA methylation in shaping immune responses. A focus is on the role of methylation in immune-mediated, namely autoimmune diseases, where aberrant epigenetic modifications at HLA loci contribute to disease susceptibility and progression. We also explore how single nucleotide polymorphisms (SNPs) within CpG sites can alter methylation patterns and gene expression, providing insights into genetic-epigenetic interactions. These findings may contribute to the development of new diagnostic and therapeutic strategies for immune-mediated diseases.

Effects of intravesical cocktail instillation on outcomes and serum pain factors of patients with bladder pain syndrome

Yunpeng Jia, Yuanning Zhang, Bo Wang, Junjia Shi — 2025-11-11 15:09:11

Aims. We aimed to assess the effects of intravesical cocktail instillation on the outcomes and serum pain factors of patients with bladder pain syndrome (BPS). Methods. The clinical data of 86 female BPS patients hospitalized between March 2017 and March 2024 were collected for retrospective analysis. All patients were treated with oral medication (amitriptyline) + local intravesical instillation of drugs, and then assigned to a control group (sodium hyaluronate intravesical instillation) and a research group [intravesical instillation of dimethyl sulfoxide (DMSO) + chondroitin sulfate (CS) + low-molecular-weight heparin (LMWH) cocktail]. Results. The research group (n=43) had lower urination frequency in 24 h, Pelvic Pain and Urgency/Frequency Patient Symptom Scale score, and O'Leary-Sant interstitial cystitis symptom index and interstitial cystitis problem index, as well as larger single urination volume than those of the control group (n=43) after 3 and 6 months of treatment (P<0.05). In the serum, the levels of substance P (SP), 5-hydroxytryptamine (5-HT), prostaglandin E₂ (PGE₂), neuropeptide Y (NPY), β-endorphin (β-EP), and dopamine (DA) declined in the two groups after 1 month of treatment in comparison to the pre-treatment levels. The levels of SP, 5-HT, PGE₂, and NPY were lower, while the levels of β-EP and DA were higher in the research group than those in the control group (P<0.05). Conclusion. The intravesical instillation of DMSO + CS + LMWH cocktail is superior in long-term outcomes. It is more conducive to improving the levels of serum pain factors, with a good safety profile and without increasing adverse reactions.

Efficacy and safety of bifidobacterium triple viable capsules combined with entecavir in the treatment of Hepatitis B cirrhosis

Rongquan Liu, Yun Ji, Jie Zhang — 2025-10-02 08:14:21

Background. Liver cirrhosis caused by hepatitis B is a critical progression of chronic hepatitis B. It is often accompanied by intestinal dysbiosis and impaired intestinal mucosal barrier function, which further exacerbate hepatic inflammation and fibrosis. Therefore, exploring effective combined therapeutic approaches to improve patient outcomes is of significant importance. Objective. This study compares the efficacy and safety of entecavir combined with bifidobacterium triple viable capsules versus entecavir alone in treating Hepatitis B cirrhosis. Methods. This retrospective case-control study enrolled 110 patients with Hepatitis B cirrhosis diagnosed and treated from January 2021 to January 2024. The control group received entecavir alone, while the observation group received entecavir combined with bifidobacterium triple viable capsules Efficacy was assessed at 24 weeks and 48 weeks post-treatment. Comparisons were made between the two groups regarding changes in intestinal flora count, intestinal mucosal barrier function, liver function, HBV-DNA negativity rate, liver fibrosis indices, liver stiffness measurement (LSM), inflammatory factor indices, and treatment safety. Results. At 24 weeks and 48 weeks post-treatment, the observation group exhibited significant modulation of the intestinal microecology, with a notable decrease in the count of pathogenic bacteria (Candida albicans, Enterobacteriaceae, Enterococcus) in feces compared to pre-treatment and the control group (all P<0.05), and a significant increase in the count of probiotics (Lactobacillus, Bifidobacterium) (all P<0.05). Meanwhile, the observation group showed more significant improvement in intestinal mucosal barrier function, with lower levels of endotoxin, D-lactic acid, and diamine oxidase compared to the control group (all P<0.05). Regarding liver-related indices, the observation group demonstrated significantly greater improvement in liver function (ALT, AST, TBIL, ALB), liver fibrosis markers (HA, PC-III, IV-C, LN), and LSM compared to the control group (all P<0.05), with more pronounced improvement at 48 weeks than at 24 weeks (P<0.05). Notably, the observation group exhibited a higher HBV-DNA negativity rate at 48 weeks (90.91% vs 76.36%, P=0.039) and superior regulation of inflammatory factors (decreased TNF-α, IL-6, IL-8, and increased IL-10) (all P<0.05). The final clinical efficacy assessment revealed a significantly higher total effective rate in the observation group compared to the control group (83.64% vs 65.45%, P=0.029). Adverse event rates were comparable between the observation and control groups (7.27% vs. 10.91%, P=0.507), supporting the safety of the intervention. Conclusion. The treatment regimen of bifidobacterium triple viable capsules combined with entecavir is significantly superior to entecavir alone in improving intestinal flora, repairing the intestinal mucosal barrier, promoting liver function recovery, and alleviating liver fibrosis in patients with Hepatitis B cirrhosis. It also demonstrates more pronounced long-term efficacy, a higher HBV-DNA negativity rate, superior overall clinical efficacy, and good safety.

Validity of the AMS questionnaire for screening hypogonadism in men with type 2 diabetes: A cross-sectional study

2025-10-01 10:56:46

Background. Hypogonadism is common among men with type 2 diabetes mellitus (T2DM), but diagnosis can be confounded by overlapping symptoms from diabetic complications. The Aging Males' Symptoms (AMS) questionnaire is widely used for screening, yet its validity in this specific population remains unclear. Objective. To evaluate the relationship between AMS scores and serum testosterone levels in men with T2DM, assess diagnostic accuracy at various AMS cut-offs, and examine the influence of diabetic comorbidities on AMS scores. Methods. We conducted a cross-sectional study in 158 men with T2DM. Participants completed the AMS questionnaire and underwent morning testosterone measurement. Comorbidities such as neuropathy, nephropathy, and obstructive sleep apnea were assessed. AMS diagnostic performance was evaluated using different cut-off values (≥27, 30, 35, 40). Results. AMS total score showed a modest inverse correlation with testosterone (ρ = -0.16, P=0.047), primarily driven by the physical subscale. Neuropathy and nephropathy were associated with higher sexual subscale scores. An AMS ≥27 cut-off had high sensitivity (91%) but poor specificity (21%) for testosterone <12 nmol/L. Conclusion. AMS scores correlate weakly with testosterone levels in men with T2DM. Diabetic complications can elevate AMS scores independently, suggesting the need for caution and possibly higher cut-offs when using AMS for hypogonadism screening in this population.

Comparing the efficiency of two prophylactic approaches in patients at risk of developing Intraoperative Floppy Iris Syndrome

2025-09-19 11:39:19

Background and Aims. Intraoperative Floppy Iris Syndrome (IFIS) is a condition that can lead to a number of complications during cataract surgery that threaten final vision of patients using alpha1-adrenergic receptor antagonists (α1-ARAs). There are two recommended pharmacological approaches to preventing IFIS development: intraoperative intracameral epinephrine and application of atropine drops twice a day for one week before surgery. The primary aim of this study was to identify the incidence and grade of IFIS using these two prophylactic approaches in patients at risk of IFIS development and to determine which approach is more effective for mild and severe IFIS. The second aim was to evaluate complication rates between the two. Methods. The study consisted of 164 eyes of 164 men using α1-ARAs. 83 eyes were treated with atropine sulphate 1% drops (Group 1) while 81 eyes received an injection of epinephrine to the anterior chamber during cataract surgery (Group 2). Results. Even though the incidence of IFIS was lower in the epinephrine group this was not statistically significant at the 5% level (P=0.269). Apropos severity, there was a statistically significantly higher incidence of moderate and severe forms of IFIS in Group 2 (P<0.0001). There was no significant difference between groups in the development of surgical complications (P=0.165). Conclusions. The instillation of epinephrine was more effective in preventing the overall incidence of IFIS. Nevertheless, the occurrence of IFIS in its moderate and severe forms was statistically significantly higher in this group. Trial registration. The study protocol was retrospectively registered in the Clinical Trial registry clinicaltrials.gov under ID number NCT06266962

Serum vitamin D levels in patients with lung metastases

2025-09-03 10:47:48

Background and Aim. Vitamin D deficiency is linked to increased cancer risk and death but the effect of vitamin D substitution on the prognosis of patients with malignant disease is debatable. We aimed to investigate the value of serum vitamin D3 levels in patients with a history of malignancy and confirmed lung metastases. Materials and Method. Serum Vitamin D2 (25-hydroxyergokalciferol) and D3 (25‑hydroxycholekalciferol) levels were measured in 38 patients (28 with and 10 without lung metastases) using high performance liquid chromatography (HPLC). Serum Vitamin D2 + D3 levels of patients with lung metastases were analysed with respect to season, number of metastases, number of malignancies in the history, value according to the ASA (The American Society of Anaesthesiologists) physical status classification, and compared to patients with a history of malignancy without confirmed lung metastasis. Results. Overall, mean serum vitamin D3 levels were significantly higher in summer (summer vs. winter; 85.06 nmol/L vs. 61.01 nmol/L; P=0.013). There was no significant difference in vitamin D3 levels in summer or winter between patients with or without lung metastases. There was also no significant difference in vitamin D3 levels in the summer months between patients with a history of one malignancy versus those with two or more. In winter however, patients with a history of one malignancy had significantly higher vitamin D3 levels (mean, 75.25 nmol/L) than those with two or more malignancies (mean 44.6 nmol/L) (P=0.027). The differences between vitamin D3 levels in patients with ASA 2 and 3 were not statistically significant. Conclusion. Vitamin D supplementation may be advisable for patients with a history of multiple malignancies, particularly during the winter months. However, confirmation in a clinical trial with a larger patient cohort is warranted before firm recommendations can be made.

Minimal residual disease and prognostic significance of circulating tumour cells in early-stage colorectal cancer

2025-08-20 09:42:09

Aim. The recurrence rate of colorectal cancer remains high even after radical surgery. Existing criteria for administering adjuvant treatment lack sufficient precision, often leading to undertreatment or overtreatment. This study investigates circulating tumour cells (CTCs) as a potential prognostic biomarker to improve the accuracy of patient selection. Methods. Forty-six colorectal cancer patients without distant metastases who underwent radical surgery were enrolled in this prospective study conducted at Tomas Bata Hospital in Zlín. The study protocol was approved by the hospital's Ethics Committee. Circulating tumour cells (CTCs) were measured in peripheral blood samples collected preoperatively, on the second postoperative day, and one month after surgery. CTCs were detected and characterized using semiautomated microscopy. Comprehensive clinicopathological data were recorded as part of standardized perioperative care. The prognostic significance of CTCs was evaluated based on the time to recurrence (TTR) parameter. Results and Conclusion. Growing evidence from circulating tumour cell (CTC) research supports their potential role as a valuable biomarker in cancer management. In this study involving stage I-III colorectal cancer patients, a recurrence rate of 20% was observed among individuals with detectable CTCs, whereas no recurrence occurred in patients with a sustained absence of CTCs. Despite this apparent difference, the time to recurrence (TTR) did not differ significantly between the groups (log-rank test, P=0.175). Although the result was not statistically significant, the observed trend suggests a possible prognostic value of CTCs that merits investigation in a larger cohort. Furthermore, neither individual time-point measurements nor dynamic changes in CTC levels demonstrated a significant correlation with TTR.

Potential of silymarin and its polyphenols to affect Nrf2 signalling pathway in human skin cells

2025-07-25 08:33:25

Introduction. Human skin is constantly exposed to various agents causing oxidative stress. In response, skin cells can activate transcriptional nuclear factor erythroid 2-related factor 2 (Nrf2), which influences the expression of several protective genes. However, accumulating evidence suggests severe adverse effects of chronic Nrf2 activation. Phytochemicals are popular for supporting skin health. Some are potent Nrf2 inducers and their long-term use may be hazardous. Silymarin (SM), an extract from Silybum marianum fruits, and its major flavonolignan silybin (SB) are used in cosmetic formulations for their protective and regenerative activities. However, knowledge about their potential to modulate Nrf2-driven pathway in skin cells or tissue is lacking. Methods. Here we evaluated effects of SM, SB, silychristin (SC), silydianin (SD), isosilybin (ISB) and 2,3-dehydrosilybin (DHSB) and taxifolin (TA) on Nrf2 nuclear translocation, the level of Nrf2-control proteins (Keap1 and Bach1) and selected Nrf2-driven genes (NAD(P)H:quinone oxidoreductase 1 and heme oxygenase 1) in human primary fibroblasts and keratinocytes. Results. SM and its components significantly stimulated Nrf2 nuclear translocation; SM and SB were most potent on both cell types. The effect of SM and compounds was more pronounced in fibroblasts than on keratinocytes. Regardless, effects of SM and studied compounds on the Nrf2 regulating and Nrf2-controled proteins were non-significant. Conclusion. SM and its components do not have a significant effect on the studied proteins, and seem to be safe with respect to possible negative effects associated with the Nrf2 signalling pathway activation during dermal application. However, we cannot give a definitive answer on their effect after repeated long-term application to the whole skin. Further experiments on human skin ex vivo or clinical studies on volunteers are necessary.

The relationship of the systemic immune inflammation index to severity in chronic spontaneous urticaria

2025-05-07 11:30:02

Background and aims. Chronic spontaneous urticaria (CSU) is a skin condition causing red, raised, itchy and sometimes painful hives which lasts longer than six weeks. While the cause is unclear, the Urticaria Activity Score-7 (UAS-7), can help to determine the severity of the disease while the Systemic Immune Inflammation Index (SII) defined as neutrophils × platelets/lymphocytes, is a recent marker that shows the inflammatory and immune status and can be easily calculated from routine blood tests using neutrophil, lymphocyte, and platelet counts. We aimed to determine whether the SII correlates with UAS-7 in CSU patients. Methods. We conducted this study on 245 patients with CSU. The UAS-7 score was obtained from all patients. Four groups were generated according to the UAS-7 score as ≤6, 7-15, 16-27, and 28-42. The correlation between the UAS-7 score and SII was evaluated. Results. There was a statistically significant difference between the groups in terms of white blood cell count, neutrophil count, platelet count, Neutrophil-lymphocyte ratio (NLR), Platelet- lymphocyte ratio (PLR), and SII (P<0.05). A positive correlation was found between SII, NLR and PLR, and UAS-7 score. The strongest correlation was between SII and UAS-7, with P<0.001, r=0.642. Conclusion. SII, which is easy to calculate, practical, and objective can be used for predicting the severity of the urticaria and for guiding the follow-up and treatment of these patients.

Serum drug levels and medication adherence in heart failure: A comparative cohort analysis

2025-03-11 14:45:53

Objective. To determine changes in medication adherence in two cohorts of heart failure patients differing by year of data collection and using a direct method of adherence detection - serum drug level testing. Methods. We added a second cohort of patients to a prospective monocentric registry of chronic heart failure patients (LEVEL-CHF registry). The two cohorts share the same inclusion criteria but differ by the year of enrolment (2018 and 2020). Stable patients with heart failure with reduced ejection fraction were enrolled in a specialized university hospital center. Results. We included 402 records of 366 individual patients, 274 in 2018 and 128 in 2020. 36 patients were enrolled in both cohorts. Of the total 81% of patients were fully adherent, and 19% were non-adherent to a varying degree. Between 2018 and 2020 there was a statistically significant increase in BMI (P=0.047) and fasting glycemia (P=0.009). Patients in the 2020 cohort were less adherent than those in the 2018 cohort (P<0.01). Patients in the two cohorts had similarly severe heart failure and did not substantially differ in NYHA class. There were no statistically significant differences between adherent and non-adherent patients after adjusting for multiple comparisons. Conclusions. In this comparison, most patients were fully adherent to all their medication and very few were non-adherent to multiple medications. We found no clinically relevant differences between adherent and non-adherent patients. Serum drug level testing is an effective method of adherence testing in clinical practice.