Mitochondria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways.

Metabolic diseases that include obesity and metabolic-associated fatty liver disease (MAFLD) are a rapidly growing worldwide public health problem. The pathogenesis of MAFLD includes abnormally increased lipogenesis, chronic inflammation, and mitochondrial dysfunction. Mounting evidence suggests that hydrogen sulfide (H2S) is an important player in the liver, regulating lipid metabolism and mitochondrial function. However, direct delivery of H2S to mitochondria has not been investigated as a therapeutic strategy in obesity-related metabolic disorders. Therefore, our aim was to comprehensively evaluate the influence of prolonged treatment with a mitochondria sulfide delivery molecule (AP39) on the development of fatty liver and obesity in a high fat diet (HFD) fed mice. Our results demonstrated that AP39 reduced hepatic steatosis in HFD-fed mice, which was corresponded with decreased triglyceride content. Furthermore, treatment with AP39 downregulated pathways related to biosynthesis of unsaturated fatty acids, lipoprotein assembly and PPAR signaling. It also led to a decrease in hepatic de novo lipogenesis by downregulating mTOR/SREBP-1/SCD1 pathway. Moreover, AP39 administration alleviated obesity in HFD-fed mice, which was reflected by reduced weight of mice and adipose tissue, decreased leptin levels in the plasma and upregulated expression of adipose triglyceride lipase in epididymal white adipose tissue (eWAT). Finally, AP39 reduced inflammation in the liver and eWAT measured as the expression of proinflammatory markers (Il1b, Il6, Tnf, Mcp1), which was due to downregulated mTOR/NF-κB pathway. Taken together, mitochondria-targeted sulfide delivery molecules could potentially provide a novel therapeutic approach to the treatment/prevention of obesity-related metabolic disorders.

Neutrophil Extracellular Trap Formation in Advanced Heart Failure Patients-Preliminary Report.

In end-stage heart failure, which is characterized by persistent or progressive ventricular dysfunction despite optimal medical therapy, a left ventricular assist device (LVAD) can be beneficial. Congestive heart failure provokes inflammatory and prothrombotic activation. The aim of this study was to evaluate the serum concentration of citrullinated histone 3 (CH3) representing neutrophil extracellular trap (NET) formation in patients referred for LVAD implantation. There were 10 patients with a median age of 61 (57-65) years enrolled in a prospective single-center analysis who underwent LVAD implantation. The CH3 plasma concentration was measured preoperatively and on the 1st and 7th postoperative days, followed by control measurements on the median (Q1-3) 88th (49-143) day. The preoperative CH3 concentration strongly correlated with brain natriuretic peptide (r = 0.879, p < 0.001). Significant differences in CH3 serum concentration were observed between pre- and postoperative measurements, including an increase on the first postoperative day (p < 0.001), as well as a decrease on the seventh day (p = 0.016) and in follow-up (p < 0.001). CH3 concentration, as a marker of NET formation, decreases after LVAD implantation.

Are Hair Scalp Trace Elements Correlated with Atherosclerosis Location in Coronary Artery Disease?

Coronary artery disease is among the leading current epidemiological challenges. The genetic, clinical, and lifestyle-related risk factors are well documented. The reason for specific epicardial artery locations remains unsolved. The coronary artery topography and blood flow characteristics may induce local inflammatory activation. The atherosclerotic plaque formation is believed to represent inflammatory response involving enzymatic processes co-factored by trace elements. The possible relation between trace elements and coronary artery disease location was the subject of the study. There were 175 patients (107 (61) men and 68 (39) females) in a median (Q1-3) age of 71 years (65-76) admitted for coronary angiography due to chronic coronary syndrome. The angiographic results focused on the percentage of lumen stenosis in certain arteries and were compared with the results for hair scalp trace elements. The correlation between left main coronary artery atherosclerotic plaques and nickel (Ni), zinc (Zn), and antimony (Sb) hair scalp concentration was noted. The analysis revealed a positive relation between left descending artery disease and chromium (Cr), sodium (Na), arsenic (As), and molybdenum (Mo) and a negative correlation with strontium (Sr). The atherosclerotic lesion in the circumflex artery revealed correlations in our analysis with sodium (Na), potassium (K), chromium (Cr), nickel (Ni), arsenic (As), and negative with strontium (Sr) (r) hair scalp concentrations. The negative correlations between right coronary artery disease and magnesium (Mg) and strontium (Sr) concentrations were noted. The possible explanation of different epicardial artery involvement and severity by atherosclerotic processes may lay in their topography and blood rheological characteristics that induce different inflammatory reactions co0factored by specific trace elements. The trace element concentration in the hair scalp may correlate with a particular coronary atherosclerotic involvement, including the severity of lumen reduction. This may indicate the missing link between the pathophysiological processes of atherosclerosis development and its location in coronary arteries.

Long-Term Survival after Coronary Artery Surgical Revascularization-Does Ambient Temperature Matter?

Background and Objectives: The progression of global warming results in an increased exposure to extreme heat, leading to exaggeration of preexisting diseases and premature deaths. The aim of the study was to present possible risk factors for all-cause long-term mortality in patients who underwent surgical revascularization, including an assessment of the influence of ambient temperature exposure. Materials and Methods: Retrospective analysis included 153 (123 (80%) males and 30 (20%) females) patients who underwent off-pump revascularization and were followed for a median time of 2533 (1035-3250) days. The demographical, clinical data and ambient temperature exposure were taken into analysis for prediction of all-cause mortality. Individual exposure was calculated based on the place of habitation. Results: In the multivariate logistic regression model with backward stepwise elimination method, risk factors such as dyslipidaemia (p = 0.001), kidney disease (p = 0.005), age (p = 0.006), and body mass index (p = 0.007) were found to be significant for late mortality prediction. In addition to traditional factors, environmental characteristics, including tropical nights (p = 0.043), were revealed to be significant. Conclusions: High night-time ambient temperatures known as tropical nights may be regarded as additional long-term mortality risk factor after surgical revascularization.

Long-Term Nitrogen Dioxide Exposure as a Possible 5-Year Mortality Risk Factor in Diabetic Patients Treated Using Off-Pump Surgical Revascularization-A Retrospective Analysis.

Background: There is mounting evidence that diabetic-related cardiac metabolism abnormalities with oxidative stress and inflammatory mechanism activation align with the functional impairments that result in atherosclerotic lesion formation. Among the possible non-traditional coronary lesion risk factors, environmental exposure may be significant, especially in diabetic patients. Methods: A total of 140 diabetic patients (115 (82%) males and 25 (18%) females) with a mean age of 65 (60-71) underwent surgical revascularization due to multivessel coronary disease. The possible all-cause mortality risk factors, including demographical and clinical factors followed by chronic air pollution exposure, were identified. Results: All patients were operated on using the off-pump technique and followed for 5.6 (5-6.1) years. The multivariable model for 5-year mortality prediction presented the nitrogen dioxide chronic exposure (HR: 3.99, 95% CI: 1.16-13.71, p = 0.028) and completeness of revascularization (HR: 0.19, 95% CI: 0.04-0.86, p = 0.031) as significant all-cause mortality risk factors. Conclusions: Ambient air pollutants such as an excessive chronic nitrogen dioxide concentration (>15 µg/m3) may increase 5-year all-cause mortality in diabetic patients following surgical revascularization.

Quantification of Aortic Valve Fibrotic and Calcific Tissue from CTA: Prospective Comparison with Histology.

Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm3 [95% LoA: -0.27 cm3, 0.19 cm3] and 0.02 cm3 [95% LoA: -0.14 cm3, 0.19 cm3], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Assessment of COVID-19 risk factors of early and long-term mortality with prediction models of clinical and laboratory variables.

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.

Demographical and Clinical Factors Predictive for Aortic Dilatation. When should we be Concerned about the Size?

Background: Thoracic aortic aneurysms are often an accidental finding and result from a degenerative process. Medical therapy includes pharmacological control of arterial hypertension and smoking cessation, that slows the growth of aneurysms. An association between the dilatation of the ascending and abdominal aorta has been already reported. The aim of the study was to identify possible demographic and clinical factors that may implicate further imaging diagnostics in patients with ascending aorta dilatation. Methods: There were 181 (93 (53%) males and 88 (47%) females) patients with a median age of 54 (41-62) years who underwent cardiac magnetic resonance due to non-vascular diseases, were enrolled into retrospective analysis. Results: Multivariable analysis revealed ascending aorta dilatation (odds ratios (OR) = 7.45, 95% confidence interval (CI): 1.98-28.0, p = 0.003) and co-existence of coronary artery disease (OR = 8.68, 95% CI: 2.15-35.1, p = 0.002) as significant predictors for thoracic descending aorta dilatation. In patients with abdominal aorta dilatation, the multivariable analysis showed a predictive value of ascending aortic dilatation (OR = 14.8, 95% CI: 2.36-92.8, p = 0.004) and age (OR = 1.04, 95% CI: 1.00-1.08, p = 0.027). In addition, cut-off values were established for age groups determining the risk of thoracic aorta dilatation over 49 years and abdominal aorta dilatation over 54 years. Conclusions: The results of our analysis showed predictive factors, including ascending aorta dilatation and co-existence of coronary artery disease, particularly over 49 years of age for thoracic, while ascending aorta dilatation and age, particularly over 54 years, for abdominal aorta dilatation. These features may be considered to increase clinical vigilance in patients with aortic diameter abnormalities.

Left main coronary artery disease treated with beating heart surgery: 10-year single center results.

Introduction: Left main (LM) coronary disease is believed to represent a complex, advanced, and potentially life-threatening atherosclerotic syndrome that can be treated by either percutaneous or surgical interventions. Despite its satisfactory results, the declined number of off-pump coronary artery bypass grafting (OPCAB) is observed. Aim: To compare 10-year survival and point out possible mortality risk factors in patients referred for left main and multivessel OPCAB surgery followed by transit time bypass measurements. Material and methods: There were 159 patients (128 (81%) men and 31 (19%) women) in a median age of 66 (60-70) years enrolled in retrospective analysis who were referred to surgical intervention due to left main (51, 32%) and multivessel (108, 68%) disease. The regression analysis for long-term mortality risk and the Kaplan-Meyer survival curve were analyzed. Results: Multivariable analysis pointed female sex (HR = 1.08, 95% CI: 1.03-1.14, p = 0.001) and diabetes mellitus (HR = 6.33, 95% CI: 1.86-21.52, p = 0.003) as possible risk factors for 10-year mortality risk. There was no significant difference in Kaplan-Meyer 10-year mortality comparison between left main and multivessel disease patients treated by off-pump surgical revascularization (HR = 0.93, 95% CI: 0.40-2.13, p = 0.86). Conclusions: Off-pump surgery in the left main disease, compared to multivessel disease, represents a safe surgical technique with satisfactory long-term results. The female sex and diabetes mellitus were found as possible risk factors for 10-year mortality risk in multivariable analysis.

Coronary artery culprit lesions progression and ambient temperature exposure - personalised analysis.

Introduction: Global warming is claimed to be an important cardiovascular disease risk factor. The air pollution and ambient temperatures are believed to have a significant influence on increased morbidity and premature deaths. Aim: To point out possible causative factors for coronary angiography progression in patients presenting with chronic coronary syndrome. Material and methods: There were 66 patients (41 [62%] men and 25 [38%] women) with a median age of 71.5 (62-76) years, who underwent repeated coronary angiographies due to chronic coronary syndrome within a median time interval of 145 (96-296) days. In 18 (27%) patients coronary artery lesion progression was observed despite optimal pharmacotherapy. The demographical, clinical, and personalised epidemiological factors including air pollution particles and ambient temperature exposure were taken into account in the analysis. Results: In the multivariate logistic regression model with backward stepwise elimination method, tropical nights (p = 0.047) and mean daily temperatures (p = 0.043) were revealed as predictors of coronary lesion progression > 30%. The analysis of seasonal temperature changes showed significant differences related to minimal winter temperatures between both groups (p = 0.018). Conclusions: Coronary artery lesion progression can be related to either high values of daily temperatures or to low ambient temperature. The dichotomous characteristics of temperature exposure to atherosclerosis progression suggest a detrimental role of environmental extremities on human health.

Recovery of Metals from the "Black Mass" of Waste Portable Li-Ion Batteries with Choline Chloride-Based Deep Eutectic Solvents and Bi-Functional Ionic Liquids by Solvent Extraction.

Lithium-ion portable batteries (LiPBs) contain valuable elements such as cobalt (Co), nickel (Ni), copper (Cu), lithium (Li) and manganese (Mn), which can be recovered through solid-liquid extraction using choline chloride-based Deep Eutectic Solvents (DESs) and bi-functional ionic liquids (ILs). This study was carried out to investigate the extraction of metals from solid powder, black mass (BM), obtained from LiPBs, with various solvents used: six choline chloride-based DESs in combination with organic acids: lactic acid (1:2, DES 1), malonic acid (1:1, DES 2), succinic acid (1:1, DES 3), glutaric acid (1:1, DES 4) and citric acid (1:1, DES 5 and 2:1, DES 6). Various additives, such as didecyldimethylammonium chloride (DDACl) surfactant, hydrogen peroxide (H2O2), trichloroisocyanuric acid (TCCA), sodium dichloroisocyanurate (NaDCC), pentapotassium bis(peroxymonosulphate) bis(sulphate) (PHM), (glycine + H2O2) or (glutaric acid + H2O2) were used. The best efficiency of metal extraction was obtained with the mixture of {DES 2 + 15 g of glycine + H2O2} in two-stage extraction at pH = 3, T = 333 K, 2 h. In order to obtain better extraction efficiency towards Co, Ni, Li and Mn (100%) and for Cu (75%), the addition of glycine was used. The obtained extraction results using choline chloride-based DESs were compared with those obtained with three bi-functional ILs: didecyldimethylammonium bis(2,4,4-trimethylpentyl) phosphinate, [N10,10,1,1][Cyanex272], didecyldimethylammonium bis(2-ethylhexyl) phosphate, [N10,10,1,1][D2EHPA], and trihexyltetradecylphosphonium bis(2,4,4-trimethylpentyl) phosphinate, [P6,6,6,14][Cyanex272]/toluene. The results of the extraction of all metal ions with these bi-functional ILs were only at the level of 35-50 wt%. The content of metal ions in aqueous and stripped organic solutions was determined by ICP-OES. In this work, we propose an alternative and highly efficient concept for the extraction of valuable metals from BM of LiPBs using DESs and ILs at low temperatures instead of acid leaching at high temperatures.

The Protective Effect of the Crosstalk between Zinc Hair Concentration and Lymphocyte Count-Preliminary Report.

BACKGROUND: An imbalance between pro- and anti-inflammatory mechanisms is indicated in the pathophysiology of atherosclerotic plaque. The coronary artery and carotid disease, despite sharing similar risk factors, are developed separately. The aim of this study was to analyze possible mechanisms between trace element hair-scalp concentrations and whole blood counts that favor atherosclerotic plaque progression in certain locations. METHODS: There were 65 (36 (55%) males and 29 (45%) females) patients with a median age of 68 (61-73) years enrolled in a prospective, preliminary, multicenter analysis. The study group was composed of 13 patients with stable coronary artery disease (CAD group) referred for surgical revascularization due to multivessel coronary disease, 34 patients with carotid artery disease (carotid group) admitted for vascular procedure, and 18 patients in a control group (control group). RESULTS: There was a significant difference between the CAD and carotid groups regarding lymphocyte (p = 0.004) counts. The biochemical comparison between the coronary and carotid groups revealed significant differences regarding chromium (Cr) (p = 0.002), copper (Cu) (p < 0.001), and zinc (Zn) (p < 0.001) concentrations. Spearman Rank Order Correlations between lymphocyte counts and trace elements in the analyzed groups were performed, revealing a strong correlation with zinc (R = 0.733, p < 0.001) in the control group (non-CAD, non-carotid). CONCLUSION: Significant differences in hair-scalp concentrations related to atherosclerosis location were observed in our analysis. The interplay between zinc concentration and lymphocyte count may play a pivotal role in cardiovascular disease development.

Extracellular Vesicles to Predict Outcomes After Transcatheter Aortic Valve Implantation - a Prospective, Multicenter Cohort Study.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at intermediate and high surgical risk. Circulating extracellular vesicles (EVs) are nanoparticles involved in cardiovascular diseases. We aimed to (i) determine the effect of TAVI on plasma concentrations of five EV subtypes and (ii) evaluate the predictive value of EVs for post-TAVI outcomes. METHODS: Blood samples were collected 1 day before TAVI and at hospital discharge. Concentrations of EVs were evaluated using flow cytometry. RESULTS: Concentration of leukocytes EVs decreased after TAVI, compared to the measurement before (p = 0.008). Among 123 patients discharged from the hospital, 19.5% experienced MACCE during the median of 10.3 months. Increased pre-TAVI concentration of phosphatidylserine-exposing EVs was an independent predictor of MACCE in multivariable analysis (OR 5.313, 95% CI 1.164-24.258, p = 0.031). CONCLUSIONS: Patients with increased pre-TAVI concentration of procoagulant, PS-exposing EVs have over fivefold higher odds of adverse outcomes.

SKA3 Expression as a Prognostic Factor for Patients with Pancreatic Adenocarcinoma.

The spindle and kinetochore-associated complex subunit 3 (SKA3) is a protein essential for proper chromosome segregation during mitosis and thus responsible for maintaining genome stability. Although its involvement in the pathogenesis of various cancer types has been reported, the potential clinicopathological significance of SKA3 in pancreatic ductal adenocarcinoma (PDAC) has not been fully elucidated. Therefore, this study aimed to assess clinicopathological associations and prognostic value of SKA3 in PDAC. For this purpose, in-house immunohistochemical analysis on tissue macroarrays (TMAs), as well as a bioinformatic examination using publicly available RNA-Seq dataset, were performed. It was demonstrated that SKA3 expression at both mRNA and protein levels was significantly elevated in PDAC compared to control tissues. Upregulated mRNA expression constituted an independent unfavorable prognostic factor for the overall survival of PDAC patients, whereas altered SKA3 protein levels were associated with significantly better clinical outcomes. The last observation was particularly clear in the early-stage tumors. These findings render SKA3 a promising prognostic biomarker for patients with pancreatic ductal adenocarcinoma. However, further studies are needed to confirm this conclusion.

Overexpression of cyclin F/CCNF as an independent prognostic factor for poor survival in clear cell renal cell carcinoma.

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.

Ubiquitin B, Ubiquitin C, and ß-Catenin as Promising Diagnostic and Prognostic Tools in Prostate Cancer.

Prostate cancer (PC) is a major global public health concern, imposing a significant burden on men and ranking as the second most prevalent malignancy. This study delves into the intricate world of ubiquitination processes and expression regulation, with a specific focus on understanding the roles of ubiquitin B (UBB), ubiquitin C (UBC), and ß-Catenin in PC development. We thoroughly analyze the expression profiles of UBB, UBC, and ß-Catenin, investigating their interactions and associations with clinical and histopathological data. These findings offer valuable insights into their potential as robust prognostic markers and their significance for patient survival. Our research uncovers the upregulation of UBB and UBC expression in PC tissues, and an even more pronounced expression in lymph node metastases, highlighting their pivotal roles in PC progression. Moreover, we identify a compelling correlation between high UBB and UBC levels and diminished overall survival in PC patients, emphasizing their clinical relevance. Additionally, we observe a significant reduction in membranous ß-Catenin expression in PC tissues. Importantly, abnormal ß-Catenin expression is strongly associated with shorter survival in PC patients and serves as a significant, independent prognostic factor for patient outcomes. Kaplan-Meier survival analysis indicates that patients with tumors characterized by simultaneous UBB and aberrant ß-Catenin expression exhibit the poorest overall survival. These collective insights underline the clinical importance of evaluating UBB, UBC, and ß-Catenin as combined prognostic markers in PC.

The Interplay between Dyslipidemia and Neighboring Developments in Coronary Artery Disease Progression: A Personalized Approach.

(1) Background: Estimates suggest that up to 10% of global annual cardiovascular deaths could be related to environmental factors. Not only air pollution components, but also noise exposure and climate changes, are highlighted as nontraditional causes of cardiovascular morbidity. The aim of this study was to identify possible urbanization risk factors for the progression of coronary artery disease in a group of patients with chronic coronary syndrome. (2) Method: There were 77 patients (50 (65%) males and 27 (35%) females) with a median age of 70 (60-74) years who underwent repetitive angiography due to chronic coronary syndrome between 2018 and 2022. The Gensini score was calculated for assessment of coronary artery disease advancement. Environmental factors including neighboring developments were taken into account in this analysis, including housing, commercial, and industrial developments within 300, 500, and 700 m distances (buffer) from the place of habitation. (3) Results: The multivariable analysis results for prediction of Gensini score progression in relation to 700 m buffer urbanization pointed out the significance of hyperlipidemia (OR: 4.24, 95% CI 1.34-13.39, p = 0.014), initial Gensini score (OR: 1.02, 95% CI 1.00-1.05, p = 0.112), and neighborhood housing (OR: 0.03, 95% CI 0.01-0.49, p = 0.025). (4) Conclusions: Hyperlipidemia and housing neighborhood can be regarded as possible factors for coronary disease progression in patients with chronic coronary syndrome with the use of optimal medical therapy.