Mechanisms of carboplatin- and paclitaxel-dependent induction of premature senescence and pro-cancerogenic conversion of normal peritoneal mesothelium and fibroblasts.

Carboplatin (CPT) and paclitaxel (PCT) are the optimal non-surgical treatment of epithelial ovarian cancer (EOC). Although their growth-restricting influence on EOC cells is well known, their impact on normal peritoneal cells, including mesothelium (PMCs) and fibroblasts (PFBs), is poorly understood. Here, we investigated whether, and if so, by what mechanism, CPT and PCT induce senescence of omental PMCs and PFBs. In addition, we tested whether PMC and PFB exposure to the drugs promotes the development of a pro-cancerogenic phenotype. The results showed that CPT and PCT induce G2/M growth arrest-associated senescence of normal peritoneal cells and that the strongest induction occurs when the drugs act together. PMCs senesce telomere-independently with an elevated p16 level and via activation of AKT and STAT3. In PFBs, telomeres shorten along with an induction of p21 and p53, and their senescence proceeds via the activation of ERK1/2. Oxidative stress in CPT + PCT-treated PMCs and PFBs is extensive and contributes causatively to their premature senescence. Both PMCs and PFBs exposed to CPT + PCT fuel the proliferation, migration, and invasion of established (A2780, OVCAR-3, SKOV-3) and primary EOCs, and this activity is linked with an overproduction of multiple cytokines altering the cancer cell transcriptome and controlled by p38 MAPK, NF-κB, STAT3, Notch1, and JAK1. Collectively, our findings indicate that CPT and PCT lead to iatrogenic senescence of normal peritoneal cells, which paradoxically and opposing therapeutic needs alters their phenotype towards pro-cancerogenic. It cannot be excluded that these adverse outcomes of chemotherapy may contribute to EOC relapse in the case of incomplete tumor eradication and residual disease initiation. © 2023 The Pathological Society of Great Britain and Ireland.

An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of cancer survivors and their increased morbidity and mortality. Cellular and molecular determinants of these relations are far less understood, mainly because of several unsolved paths and contradicting findings in the literature. In this article, we provide a comprehensive view of the cellular and molecular etiology of cardiooncology. We pay particular attention to various intracellular processes that arise in cardiomyocytes, vascular endothelial cells, and smooth muscle cells treated in experimentally-controlled conditions in vitro and in vivo with ionizing radiation and drugs representing diverse modes of anti-cancer activity.

Nontraditional systems in aging research: an update.

Research on the evolutionary and mechanistic aspects of aging and longevity has a reductionist nature, as the majority of knowledge originates from experiments on a relatively small number of systems and species. Good examples are the studies on the cellular, molecular, and genetic attributes of aging (senescence) that are primarily based on a narrow group of somatic cells, especially fibroblasts. Research on aging and/or longevity at the organismal level is dominated, in turn, by experiments on Drosophila melanogaster, worms (Caenorhabditis elegans), yeast (Saccharomyces cerevisiae), and higher organisms such as mice and humans. Other systems of aging, though numerous, constitute the minority. In this review, we collected and discussed a plethora of up-to-date findings about studies of aging, longevity, and sometimes even immortality in several valuable but less frequently used systems, including bacteria (Caulobacter crescentus, Escherichia coli), invertebrates (Turritopsis dohrnii, Hydra sp., Arctica islandica), fishes (Nothobranchius sp., Greenland shark), reptiles (giant tortoise), mammals (blind mole rats, naked mole rats, bats, elephants, killer whale), and even 3D organoids, to prove that they offer biogerontologists as much as the more conventional tools. At the same time, the diversified knowledge gained owing to research on those species may help to reconsider aging from a broader perspective, which should translate into a better understanding of this tremendously complex and clearly system-specific phenomenon.

Diverse functional responses to high glucose by primary and permanent hybrid endothelial cells in vitro.

Various types of human endothelial cells, including human umbilical vein endothelial cells (HUVECs) and the established hybrid EAhy926 cells, are used in experimental research. Here, we compared the biological properties of HUVECs and EAhy926 cells under normal (5 mM) and high glucose (30 mM; HG) conditions. The results showed that HG induced cellular senescence and a stronger DNA damage response in HUVECs than in EAhy926 cells. The magnitude of oxidative stress elicited in HUVECs by HG was also greater than that elicited in their established counterparts. Both endothelial cell types promoted the progression of breast (MCF7), ovarian (OVCAR-3), and lung (A549) cancer cells; however, the effects elicited by HG-treated HUVECs on adhesion (MCF7, OVCAR-3), proliferation (OVCAR-3), and migration (OVCAR-3) were more pronounced. Finally, HG stimulated the production of a higher number of proangiogenic agents in HUVECs than in EAhy926 cells. Collectively, our study shows that the functional properties of primary and established endothelial cells exposed to HG differ substantially, which seems to result from the higher sensitivity of the former to this stressor. The interchangeability of both types of endothelial cells in biomedical research should be considered with great care to avoid losing some biological effects due to the choice of cells with higher stress tolerance.

Proteomic Profiling of Leukocytes Reveals Dysregulation of Adhesion and Integrin Proteins in Chronic Kidney Disease-Related Atherosclerosis.

A progressive loss of functional nephrons defines chronic kidney disease (CKD). Complications related to cardiovascular disease (CVD) are the principal causes of mortality in CKD; however, the acceleration of CVD in CKD remains unresolved. Our study used a complementary proteomic approach to assess mild and advanced CKD patients with different atherosclerosis stages and two groups of patients with different classical CVD progression but without renal dysfunction. We utilized a label-free approach based on LC-MS/MS and functional bioinformatic analyses to profile CKD and CVD leukocyte proteins. We revealed dysregulation of proteins involved in different phases of leukocytes' diapedesis process that is very pronounced in CKD's advanced stage. We also showed an upregulation of apoptosis-related proteins in CKD as compared to CVD. The differential abundance of selected proteins was validated by multiple reaction monitoring, ELISA, Western blotting, and at the mRNA level by ddPCR. An increased rate of apoptosis was then functionally confirmed on the cellular level. Hence, we suggest that the disturbances in leukocyte extravasation proteins may alter cell integrity and trigger cell death, as demonstrated by flow cytometry and microscopy analyses. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD018596.

The impact of acetylsalicylic acid dosed at bedtime on circadian rhythms of blood pressure in the high-risk group of cardiovascular patients-a randomized, controlled trial.

PURPOSE: Time 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. METHODS: All 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. RESULTS: There 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. CONCLUSIONS: The 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.

Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells.

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.

Primary high-grade serous ovarian cancer cells are sensitive to senescence induced by carboplatin and paclitaxel in vitro.

BACKGROUND: Various types of normal and cancer cells undergo senescence in response to carboplatin and paclitaxel, which are considered the gold standard treatments in ovarian cancer management. Surprisingly, the effect of these drugs on ovarian cancer cell senescence remained unknown. METHODS: The experiments were conducted on primary high-grade serous ovarian cancer cells. Molecular markers of senescence were evaluated using cytochemistry and immunofluorescence. Cell cycle distribution was analyzed using flow cytometry. Expression of cyclins and signaling pathways was tested using western blot. Telomere length and telomerase activity were measured using qPCR, and the colocalization of telomeres with DNA damage foci using immuno-FISH. Oxidative stress-related parameters were quantified using appropriate fluorescence probes. Production of cancerogenic agents was analyzed using qPCR and ELISA. RESULTS: Carboplatin applied with paclitaxel induces senescence of ovarian cancer cells in vitro. This activity was reflected by permanent G2/M growth arrest, a high fraction of cells expressing senescence biomarkers (SA-ß-Gal and γ-H2A.X), upregulated expression of p16, p21, and p53 cell cycle inhibitors, and decreased expression of cyclin B1. Neither telomere length nor telomerase activity changed in the senescent cells, and the majority of DNA damage was localized outside telomeres. Moreover, drug-treated cancer cells exhibited increased production of STAT3 protein, overproduced superoxide and peroxides, and increased mitochondrial mass. They were also characterized by upregulated ANG1, CCL11, IL-6, PDGF-D, TIMP-3, TSP-1, and TGF-ß1 at the mRNA and/or protein level. CONCLUSIONS: Our findings imply that conventional chemotherapy may elicit senescence in ovarian cancer cells, which may translate to the development of a cancer-promoting phenotype, despite the inability of these cells to divide.

Visceral fat level correction of the left ventricular hypertrophy electrocardiographic criteria.

BACKGROUND: Left ventricular hypertrophy (LVH) is a well-known risk factor for cardiovascular events. Even though there are many electrocardiographic (ECG) criteria for LVH, they still provide poor performance, especially among obese patients. The aim of this study was to examine whether adding visceral fat to ECG LVH criteria improves accuracy in the diagnosis. METHODS: One thousand seven hundred twenty two patients were included in the study. All patients underwent a complete physical examination, office blood pressure measurement, analysis of body composition, 12-lead ECG, and M-mode two-dimensional echocardiography. Four standard ECG criteria for LVH were analyzed, including Cornell voltage criteria, Cornell duration criteria, Sokolow-Lyon voltage criteria, and Sokolow-Lyon product criteria. Adjustments of ECG LVH criteria were performed using visceral fat level (VFATL) and BMI. Transthoracic echocardiography was used as a reference method to compare the quality of ECG LVH criteria. RESULTS: Multivariate logistic regression models were created and revealed a significant increase of area under curve (AUC) after VFATL and BMI addition to ECG LVH criteria. Improvement of sensitivity at 90% specificity was observed in all created models. The odds ratio (OR) of the analyzed ECG criteria increased after adding VFATL and BMI to the models. Furthermore, ROC curves analysis exposed better characteristics in detecting LVH of VFATL-adjusted criteria than BMI-adjusted and unadjusted criteria. CONCLUSIONS: Adjusting ECG indexes to BMI or VFATL improves the sensitivity of LVH detection. VFATL-corrected indexes are more sufficiently than BMI-corrected. After advancements in indexes, both lean and morbidly obese individuals outcomes show a greater prevalence of correct LVH diagnosis.

Malignant Ascites Promote Adhesion of Ovarian Cancer Cells to Peritoneal Mesothelium and Fibroblasts.

Although malignant ascites (MAs) are known to contribute to various aspects of ovarian cancer progression, knowledge regarding their role in the adhesion of cancer cells to normal peritoneal cells is incomplete. Here, we compared the effect of MAs and benign ascites (BAs) on the adhesion of A2780 and OVCAR-3 cancer cells to omentum-derived peritoneal mesothelial cells (PMCs) and peritoneal fibroblasts (PFBs). The results showed that MAs stimulated the adhesion of A2780 and OVCAR-3 cells to PMCs and PFBs more efficiently than did BAs, and the strongest binding occurred when both cancer and normal cells were exposed to the fluid. Intervention studies showed that MAs-driven adhesion of A2780 cells to PMCs/PFBs depends on the presence of TGF-ß1 and HGF, whereas binding of OVCAR-3 cells was mediated by TGF-ß1, GRO-1, and IGF-1. Moreover, MAs upregulated α5ß1 integrin expression on PFBs but not on PMCs or cancer cells, vimentin expression in all cells tested, and ICAM-1 only in cancer cells. When integrin-linked kinase was neutralized in PMCs or PFBs, cancer cell adhesion to PMCs and PFBs decreased. Collectively, our report shows that MAs may contribute to the early stages of ovarian cancer metastasis by modulating the proadhesive interplay between normal and cancer cells.

Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells.

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.

May Measurement Month 2018: an analysis of blood pressure screening campaign results from Poland.

Hypertension remains the most important cardiovascular risk factor in Poland. May Measurement Month is a global initiative organized by the International Society of Hypertension aimed at raising awareness of hypertension and the need for blood pressure (BP) screening and demonstrating the potential of the opportunistic BP measurements. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in 146 sites in May 2018. Blood pressure was measured in 6450 subjects (mean age: 41 ± 15 years; 59% females). After multiple imputation, the age and sex standardized systolic and diastolic BP was 126.7/78.4 mmHg in the whole analysed group, 132.8/81.3 mmHg in subjects taking antihypertensive drugs, and 125.7/78.0 mmHg in those not taking any antihypertensive drugs. After multiple imputation, the proportions of subjects with high BP (systolic ≥140 mmHg or diastolic ≥90 mmHg or on treatment for raised BP) were 22.2% in the whole analysed group, 39.2% in subjects taking antihypertensive drugs, and 18.6% those not taking any antihypertensive drugs. Overall, hypertension was present in 32.8% of participants, among them 38.7% were not aware of the disease, 53.1% were taking antihypertensive drugs, and 32.3% had BP controlled to target (<140/90 mmHg). Blood pressure was increasing with increasing body mass index and alcohol intake. Smokers and project participants with diabetes had increased average BP. In conclusion, this project provides additional evidence for a considerable potential for further reduction of cardiovascular risk through improvement in detection and treatment of hypertension in Poland.

High incidence and clinical characteristics of fibromuscular dysplasia in patients with spontaneous cervical artery dissection: The ARCADIA-POL study.

The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.

The peritoneal "soil" for a cancerous "seed": a comprehensive review of the pathogenesis of intraperitoneal cancer metastases.

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.

Prevalence of smoking and clinical characteristics in fibromuscular dysplasia. The ARCADIA-POL study.

PURPOSE: Smoking was identified as a potential factor contributing to fibromuscular dysplasia (FMD). To evaluate the prevalence of smoking and clinical characteristics in FMD subjects. MATERIAL AND METHODS: We analysed 190 patients with confirmed FMD in at least one vascular bed. The rate of smokers in FMD patients was compared to that in two control groups selected from a nationwide survey. RESULTS: The rate of smokers in FMD patients was 42.6%. There were no differences in frequency of smokers between FMD patients and: a group of 994 matched control subjects from general population and a group of matched hypertensive subjects. There were no differences in the characteristics of FMD (including rates of multisite FMD and significant renal artery stenosis) and its complications (including rates of dissections and aneurysms) between smokers and non-smokers. Smokers as compared with non-smokers were characterized by higher left ventricle mass index. CONCLUSIONS: There is no difference in the rate of smokers between FMD patients and subjects from the general population. Moreover, we did not find any association between smoking and clinical characteristics of FMD patients nor its extent and vascular complications. Our results do not support the hypothesis that smoking is involved in the pathophysiology of FMD.

Do we know more about hypertension in Poland after the May Measurement Month 2017?-Europe.

Elevated blood pressure (BP) is a worldwide burden, leading to over 10 million deaths yearly. May Measurement Month (MMM) is a global initiative organized by the International Society of Hypertension aimed at raising awareness of hypertension and the need for BP screening. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the globally approved MMM17 Study Protocol. In Poland 5834 (98.9%, Caucasian) individuals were screened. After multiple imputation, 2601 (35.3%) had hypertension. Of individuals not receiving anti-hypertensive medication, 976 (20.6%) were hypertensive. Of individuals receiving anti-hypertensive medication, 532 (49.1%) had uncontrolled BP. In the crude screened group, 81.4% declared to not receive any anti-hypertensive treatment, while the remaining 18.6% were on such medications. In overweight and obese patients both systolic and diastolic BP were significantly higher than in normal weight and underweight subjects. In addition, BP measured on Sundays was significantly lower than on Mondays. MMM17 was one of the largest recent BP screening campaigns in Poland. We found that over 1/3 of participants were hypertensive. Almost half of the treated subjects had uncontrolled BP. These results suggest that opportunistic screening can identify substantial numbers with raised BP.

The Epithelial-Mesenchymal Transition Initiated by Malignant Ascites Underlies the Transmesothelial Invasion of Ovarian Cancer Cells.

The role of the epithelial-mesenchymal transition (EMT) in ovarian cancer cell progression is unquestioned. In this report, we describe that malignant ascites, fluid that accumulates in the peritoneal cavity in a large group of patients with ovarian cancer, stimulate EMT in two representative ovarian cancer cell lines (A2780, SKOV-3). In addition, we identify the ascites-derived mediators of EMT and signaling pathways initiated in the cancer cells that underlie this phenomenon. Finally, we demonstrate that EMT induced in the cancer cells in response to the malignant ascites contributes to their increased transmesothelial invasion. Altogether, our study provides new insight into the mechanistic aspects of the malignant ascites-dependent exacerbation of the intraperitoneal progression of ovarian cancer.

Association between tea and coffee consumption and prevalence of metabolic syndrome in Poland - results from the WOBASZ II study (2013-2014).

The study aimed to assess a relationship between tea and coffee consumption and metabolic syndrome (MetS). Cross-sectional study of a random sample of total Polish population was done (The WOBASZ II Study), and the present analysis included 5146 participants at age 20 years and above. Tea and coffee consumption was assessed by 24-h recall method. MetS was defined according to IDF/NHLBI/AHA criteria. After adjustment for covariates, coffee consumption was related to blood pressure and HDL cholesterol, and moderate drinkers had 17% lower odds of MetS compared with non-drinkers (OR = 0.83, 95%CI = 0.72-0.97). Tea consumption was related to some components but not to MetS in general. Inverse association between coffee consumption and MetS may reflect the content of the antioxidants that offer cardiovascular protection. However, weak relation of tea with components of MetS points toward the potential importance of composition of polyphenols and the types of tea consumed.

Cardiovascular disease (CVD) risk factors in Kraków and in the whole Poland adult population. Results from the WOBASZ study and Polish arm of the HAPIEE project.

In Kraków, the second largest town in Poland, cardiovascular disease (CVD) mortality rate is lower than in most top largest towns in Poland and lower than the rate for total Polish population. AIM: The aim of the present analysis was to compare socioeconomic status (SES), prevalence of CVD risk factors and SCORE assessment of risk in Krakow with residents of other big towns in Poland and with general Polish population. MATERIALAND METHODS: We used data from the two large, population studies which used comparable methods for risk factors assessment: 1) Polish part of the HAPIEE Project in which 10 615 residents of Krakow at age between 45-69 years were examined, and (2) The WOBASZ Study which contributed with a sub-sample 6 888 of residents of Poland at corresponding age group. WOBASZ sample included 992 residents of big towns other than Krakow. Age-standardized proportions of persons with CVD risk factors were compared between Krakow and the other big towns in Poland and between Krakow and the whole Poland using χ2 test. RESULTS: The striking observation was that in Krakow proportions of participants with university education were substantially higher than average for the other big towns and the whole Poland. Also, the proportion of occupationally active men and women was the highest in Krakow. In both sexes, prevalence of smoking, hypercholesterolemia and hypertension in Krakow was similar to the other big towns but the prevalence of hypercholesterolemia and hypertension (in men only) was lower than average for Poland. The distribution by SCORE risk categories were similar in all three samples studied. In general, the distribution by BMI categories was less favourable but the prevalence of central obesity was lower among residents of Kraków than among residents of the other big towns and citizens of the whole Poland. Prevalence of diabetes was higher in Krakow than in the other samples studied. The differences between population of Krakow and population of other parts of Poland in the exposure to the main risk factors were found diverse and not big enough to be followed by differences in the distribution by the categories of SCORE risk assessment. The study suggested the importance of obesity and diabetes which are not used for the SCORE risk assessment and especially the importance of psychosocial and economic factors which may influence CVD risk and contribute more to the explanation of the regional differences in CVD mortality.

Alterations of receptors and insulin-like growth factor binding proteins in senescent cells.

The knowledge about cellular senescence expands dynamically, providing more and more conclusive evidence of its triggers, mechanisms, and consequences. Senescence-associated secretory phenotype (SASP), one of the most important functional traits of senescent cells, is responsible for a large extent of their context-dependent activity. Both SASP's components and signaling pathways are well-defined. A literature review shows, however, that a relatively underinvestigated aspect of senescent cell autocrine and paracrine activity is the change in the production of proteins responsible for the reception and transmission of SASP signals, i.e., receptors and binding proteins. For this reason, we present in this article the current state of knowledge regarding senescence-associated changes in cellular receptors and insulin-like growth factor binding proteins. We also discuss the role of these alterations in senescence induction and maintenance, pro-cancerogenic effects of senescent cells, and aging-related structural and functional malfunctions.