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In contrast to the well-recognized replicative and stress-induced premature senescence of normal somatic cells, mechanisms and clinical implications of senescence of cancer cells are still elusive and uncertain from patient-oriented perspective. Moreover, recent years provided multiple pieces of evidence that cancer cells may undergo senescence not only in response to chemotherapy or ionizing radiation (the so-called therapy-induced senescence) but also spontaneously, without any external insults. Since the molecular nature of the latter process is poorly recognized, the significance of spontaneously senescent cancer cells for tumor progression, therapy effectiveness, and patient survival is purely speculative. In this review, we summarize the most up-to-date research regarding therapy-induced and spontaneous senescence of cancer cells, by delineating the most important discoveries regarding the occurrence of these phenomena in vivo and in vitro. This review provides data collected from studies on various cancer cell models, and the narration is presented from the broader perspective of the most critical findings regarding the senescence of normal somatic cells.

Various types of tumors, particularly those originating from the ovary and gastrointestinal tract, display a strong predilection for the peritoneal cavity as the site of metastasis. The intraperitoneal spread of a malignancy is orchestrated by a reciprocal interplay between invading cancer cells and resident normal peritoneal cells. In this review, we address the current state-of-art regarding colonization of the peritoneal cavity by ovarian, colorectal, pancreatic, and gastric tumors. Particular attention is paid to the pro-tumoral role of various kinds of peritoneal cells, including mesothelial cells, fibroblasts, adipocytes, macrophages, the vascular endothelium, and hospicells. Anatomo-histological considerations on the pro-metastatic environment of the peritoneal cavity are presented in the broader context of organ-specific development of distal metastases in accordance with Paget’s “seed and soil” theory of tumorigenesis. The activity of normal peritoneal cells during pivotal elements of cancer progression, i.e., adhesion, migration, invasion, proliferation, EMT, and angiogenesis, is discussed from the perspective of well-defined general knowledge on a hospitable tumor microenvironment created by the cellular elements of reactive stroma, such as cancer-associated fibroblasts and macrophages. Finally, the paper addresses the unique features of the peritoneal cavity that predispose this body compartment to be a niche for cancer metastases, presents issues that are topics of an ongoing debate, and points to areas that still require further in-depth investigations.

One of the most neglected aspects of chemotherapy are changes, and possible consequences of these changes, that occur in normal somatic cells. In this review, we summarize effects of selected drugs used to treat ovarian cancer (platin derivatives—cisplatin and carboplatin; and taxanes—paclitaxel and docetaxel) on cellular metabolism, acquisition of reactive stroma features, cellular senescence, inflammatory reactions, apoptosis, autophagy, mitophagy, oxidative stress, DNA damage, and angiogenesis in various types of normal cells, including fibroblasts, epithelial cells, endothelial cells, and neurons. The activity of these drugs against the normal cells is presented from a broader perspective of their desirable anti-tumoral effects.

Recent studies have established a link between hypertension and an increased risk of cancer. The effects of antihypertensive treatment on cancer progression remain unclear. Objectives: Our study focused on whether serum from patients treated with antihypertensive drugs could decrease cancer-promoting properties of endothelial cells. We used cell lines, including endothelial cells (EAhy926) and various cancer cells, such as ovarian (SKOV-3), colorectal, pancreatic (PSN-1), breast (MCF-7), and lung cells. Serum was collected from hypertensive patients treated with amlodipine, nebivolol, and perindopril for 6 weeks, alongside samples from healthy individuals. Our findings indicate that the conditioned medium (CM) from EAhy926 cells exposed to hypertensive patient serum enhances cancer cell proliferation, migration, invasion, and adhesion. Notably, antihypertensive drugs, particularly nebivolol, were found to mitigate these effects significantly. Nebivolol-treated serum led to a reduction in cancer-promoting agents (like CXCL1, CXCL8, FGF5, tPA, TGF-β1, and VEGF) mRNA levels in cancer cells and increased expression of junctional proteins (E-cadherin, occludin, desmoglein) in endothelial cells. Additionally, these endothelial cells released fewer cancer-promoting proteins, including ANG1, CXCL1, CXCL12, EGF, TGF-β1, and VEGF. In summary, our study demonstrates that antihypertensive therapy, especially with nebivolol, potentially reverses hypertension-induced changes that exacerbate the cancer-promoting phenotype of endothelial cells. This suggests that beyond controlling blood pressure, antihypertensive treatments may also play a role in modulating cancer progression.

Data on regional differences in the current prevalence of hypertension in Poland remain limited. This study aimed to assess the prevalence, awareness, treatment, and control of hypertension among Polish adults in 2013-2014 (WOBASZ II study) and to compare these parameters with data from 2003-2005 (WOBASZ study). The study was conducted in two independent, representative samples. The WOBASZ II study included 3,406 women and 2,757 men, while the WOBASZ study examined 7,783 women and 6,972 men. The greatest increase in hypertension prevalence over 10 years was observed among men from Świętokrzyskie Voivodeship (39.7% vs. 51.8%) and women from Łódzkie Voivodeship (32.7% vs. 44%). Increases in hypertension awareness were noted in men from Wielkopolskie Voivodeship (50.8% vs. 59.5%) and women from Świętokrzyskie Voivodeship (65.7% vs. 77%). Treatment rates rose in men from Warmińsko-Mazurskie Voivodeship (16.8% vs. 40.3%) and women from Opolskie Voivodeship (24.7% vs. 44.4%). Improvements in hypertension control were seen in men from Wielkopolskie Voivodeship (3.5% vs. 13.3%) and women from Lubuskie Voivodeship (5.6% vs. 27.4%). Pronounced differences were observed in the prevalence, awareness, treatment, and control of arterial hypertension among voivodeships, highlighting the necessity of region-specific public health interventions and resource allocation to effectively manage hypertension. Additionally, changes observed over the decade from 2003/04-2013/14 highlight evolving epidemiological trends and demonstrate the impact of such interventions on hypertension management.

PurposeTime of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients.MethodsAll patients (n = 114) had been diagnosed with coronary heart disease and arterial hypertension prior to the enrolment and had been treated with 75 mg per day of ASA in the morning. The patients were randomly assigned to one of the two study groups receiving 75 mg of ASA per day in a single antiplatelet therapy for 3 months in the morning (n = 58) or in the evening (n = 56). The control group (n = 61) consisted of patients with arterial hypertension but without coronary heart disease, not receiving ASA. In all the patients, during each visit, clinical blood pressure (BP) and ambulatory blood pressure measurements (ABPM) were performed.ResultsThere was a significant reduction in 24-h BP and blood pressure at night in the ASA group evening group compared with the ASA morning group and the control group.ConclusionsThe present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA.

Background/Objectives: Uric acid can act as a prooxidant or an antioxidant; therefore, its effects on human umbilical vein endothelial cells (HUVECs) were investigated to better understand its role in promoting cellular senescence and vascular dysfunction. Methods: HUVECs were exposed to different concentrations of exogenous uric acid levels typically found in patients with cardiovascular conditions (5 mg/dL, 7.5 mg/dL, and 10 mg/dL) to assess cell viability, proliferation, and senescence markers including SA-β-Gal activity, γ-H2A.X and 53BP1 expression, as well as mitochondrial dysfunction parameters such as reactive oxygen species (ROS) production, mitochondrial mass, and mitochondrial membrane potential (ΔΨm). Additionally, the secretion of factors related to the senescence-associated secretory phenotype (SASP) was quantified. Results: Uric acid concentrations of 7.5 mg/dL and above significantly reduced HUVEC viability, enhanced proliferation, and increased markers of cellular senescence, including SA-β-Gal activity and γ-H2A.X/53BP1 expression. Higher uric acid levels also led to increased ROS production, increased mitochondrial mass, and reduced membrane potential. Uric acid also dose-dependently increased IL-6, IL-8, HGF, GRO-1, and TGF-β1 levels. Conclusions: High uric acid concentrations (≥7.5 mg/dL) promote HUVEC senescence, possibly due to ROS-induced DNA damage. In addition, uric acid triggers the production of pro-inflammatory cytokines and growth factors.

Heart failure with reduced ejection fraction (HFrEF) is increasingly recognized as a systemic metabolic disorder. The aim of this study was to characterize amino acid-related metabolic differences between heart failure with moderately reduced ejection fraction (HFmrEF) (LVEF 40–49%) and HFrEF (LVEF < 40%) and to derive a biologically interpretable composite metabolomic index capable of discriminating between these two stages of systolic dysfunction. We conducted a cross-sectional metabolomic analysis of 42 patients stratified by left ventricular ejection fraction (LVEF < 40% vs. 40–49%). The reference group comprised patients with mildly reduced ejection fraction (LVEF 40–49%), without inclusion of individuals with preserved or normal cardiac function. Targeted amino acid profiling was performed using liquid chromatography-tandem mass spectrometry (LC–MS/MS). Metabolites were standardized and analyzed individually and in combination. A composite index (Heart Failure Amino Acid-Derived Systolic Index: HASI-40), integrating markers of proteolysis and metabolic resilience, was derived to distinguish patients with HFrEF from those with HFmrEF. Discrimination was assessed using receiver operator curve (ROC) analysis with internal validation and multivariable adjustment. Patients with LVEF < 40% exhibited a coordinated metabolic phenotype characterized by reduced methionine, sarcosine, serine, and taurine. While individual metabolites did not retain significance after multiple-testing correction, the composite HASI-40 index remained strongly associated with HFrEF (OR 5.56, 95% CI: 1.70–18.14; p = 0.004), although the wide confidence interval indicates limited precision due to sample size. The index demonstrated good discrimination with an area under the curve (AUC) of 0.862, which improved when combined with age (AUC 0.932). The index represents a standardized composite measure and does not define a diagnostic cutoff for individual patients. These findings suggest that HFmrEF and HFrEF exhibit partially distinct metabolic phenotypes despite overlapping clinical characteristics. These findings suggest that HASI-40 captures metabolic differences between patients with HFmrEF (LVEF 40–49%) and those with HFrEF (LVEF < 40%), reflecting progression toward more advanced systolic dysfunction. However, due to the absence of a control group with preserved ejection fraction, small sample size, and lack of external validation, the index should be considered exploratory and hypothesis-generating rather than clinically applicable.

The pro-coagulative characteristics of HF patients are postulated, though no specific therapeutic targets have been proposed. A total of 88 patients (17 female, 19%) with a median age of 68 years (range, 63 − 74) and a de novo congestive HF diagnosis were enrolled in the prospective study. Co-morbidities, laboratory tests, and imaging results (echocardiography, coronary angiography) were compared to the concentration of peripheral blood citrullinated histone 3 (CitH_3), a marker of neutrophil extracellular trap (NET) formation, on admission. The analyzed population was divided into two groups based on LVEF performance: HFmrEF (42 patients, 47%) and HFrEF (46 patients, 53%), with a median (Q1–Q3) age of 68 (62–74) vs. 69 (63–74) years ( p  = 0.789), respectively. The significant difference in CitH_3 serum concentration between the heart failure with preserved ejection fraction (HFrmEF) group (395 pg/ml [201–482]) and the heart failure with reduced ejection fraction (HFrEF) group (1941 pg/ml [405–3376]) was noted ( p  = 0.019). A negative correlation was noted between LVEF and citH_3 in the analyzed group ( r = -0.444, p  = 0.005), and with serum NT-pro-BNP ( r  =  -0.435, p  < 0.001). No correlation between citH_3 and NT-pro-BNP was found ( r  = 0.305, p  = 0.939). Patients with heart failure and a decreased left ventricular ejection fraction can be characterized by increased neutrophil extracellular trap formation. The negative correlation between left ventricular characteristics and CitH_3 concentration suggested an increased pro-thrombotic state in HF patients. NETs could be considered a potential therapeutic target in HF patients to improve clinical outcomes. Further studies are required to confirm these findings.