Case-control study of apoE gene polymorphism in young CHD patients and controls in the Serbian population

Apolipoprotein E displays polymorphism with three common alleles, e2, e3, and e4. The aim of this research was to determine apoE gene polymorphism in a group of healthy patients and a group of patients with CHD, and to reveal the relation between anthropometric and biochemical parameters and the apoE genotype. In CHD group significantly higher values of blood pressure, waist circumference, BMI and fat %, triglycerides, insulin (HOMA IR) and CRP were found. A statistically significant higher presence of the e3e4 genotype and e4 allele was detected in the CHD group. Statistically significant differences between waist circumference, BMI, insulin and HOMA IR were found between subjects with e3e3 and e3e4 genotypes

A self-organized model for cell-differentiation based on variations of molecular decay rates

Systemic properties of living cells are the result of molecular dynamics governed by so-called genetic regulatory networks (GRN). These networks capture all possible features of cells and are responsible for the immense levels of adaptation characteristic to living systems. At any point in time only small subsets of these networks are active. Any active subset of the GRN leads to the expression of particular sets of molecules (expression modes). The subsets of active networks change over time, leading to the observed complex dynamics of expression patterns. Understanding of this dynamics becomes increasingly important in systems biology and medicine. While the importance of transcription rates and catalytic interactions has been widely recognized in modeling genetic regulatory systems, the understanding of the role of degradation of biochemical agents (mRNA, protein) in regulatory dynamics remains limited. Recent experimental data suggests that there exists a functional relation between mRNA and protein decay rates and expression modes. In this paper we propose a model for the dynamics of successions of sequences of active subnetworks of the GRN. The model is able to reproduce key characteristics of molecular dynamics, including homeostasis, multi-stability, periodic dynamics, alternating activity, differentiability, and self-organized critical dynamics. Moreover the model allows to naturally understand the mechanism behind the relation between decay rates and expression modes. The model explains recent experimental observations that decay-rates (or turnovers) vary between differentiated tissue-classes at a general systemic level and highlights the role of intracellular decay rate control mechanisms in cell differentiation.Comment: 16 pages, 5 figure

The Functional Renormalization Group and O(4) scaling

The critical behavior of the chiral quark-meson model is studied within the Functional Renormalization Group (FRG). We derive the flow equation for the scale dependent thermodynamic potential at finite temperature and density in the presence of a symmetry-breaking external field. Within this scheme, the critical scaling behavior of the order parameter, its transverse and longitudinal susceptibilities as well as the correlation lengths near the chiral phase transition are computed. We focus on the scaling properties of these observables at non-vanishing external field when approaching the critical point from the symmetric as well as from the broken phase. We confront our numerical results with the Widom-Griffiths form of the magnetic equation of state, obtained by a systematic epsilon-expansion of the scaling function. Our results for the critical exponents are consistent with those recently computed within Lattice Monte-Carlo studies of the O(4) spin system.Comment: 14 pages, 11 figure

Analysis of pollutant emissions of a lorry for different EURO standards and operating conditions

Environmental pollution is becoming an increasingly important problem that needs to be solved, and road vehicles contribution in that pollution is significant. In that sense, in this paper, a brief overview of models used to determine pollutant emissions is given, and then the environmental pollution of an actual lorry with a maximum permissible mass of up to 7.5 t is specifically considered. While determining pollutant emissions different Euro standards, average vehicle speeds, payload utilizations and longitudinal road slopes were taken into account. Emissions of carbon monoxide (CO), nitrogen oxides (NOx) and particulate matter (PM) were observed in detail in this paper

The LRP1 gene polymorphism is associated with increased risk of metabolic syndrome prevalence in the Serbian population

The determination of genetic background in metabolic syndrome (MetS) represents one of the necessary steps to prevent the disorder, thus reducing the cost of medical treatments and helping to design targeted therapy. The study explores the association between individual alleles of the LRP1 gene and the diagnosis of MetS to find correlation between the low-density lipoprotein receptor-related (LRP1) gene polymorphism and each individual anthropometric and biochemical parameter. The study included 93 males and females, aged from 19 to 65, divided into two groups. The genotype of each person was determined from the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) profile. Results indicated the association of the T allele form of exon 3 LRP1 gene with development and progression of MetS that further pointed out its negative impact on tested anthropometric and biochemical parameters. The presence of the T allele in patients multiplies the chance of occurrence of deviations from the reference values of body mass index (BMI), (4.24-fold) and low-density lipoprotein (LDL) (20.26-fold) compared to C allele carriers. The results showed that T allele presence multiplies the chance (4.76 fold) for the occurrence of MetS in comparison to C allele carriers. Correlation found that the T allele of the LRP1 gene with MetS determinants is not negligible, therefore, the T allele may be considered as a risk factor for MetS development

The role of thrombin in the proliferation of vascular smooth muscle cells (VSMCs) and atherosclerosis

Glatke mišićne ćelije krvnih sudova (VSMCs) su od vitalnog značaja, kako za strukturu tako i za funkcionisanje i dinamiku krvnih sudova. Proliferacija i abnormalna akumulacija VSMCs su među ključnim događajima u nastanku raznih vaskularnih oboljenja, uključujući aterosklerozu i hipertenziju. Kardiovaskularne bolesti su vodeći uzrok smrtnosti ljudske populacije u čijoj osnovi u najvećoj meri dominira ateroskleroza kao patološka komponenta. Ateroskleroza jedan je od glavnih uzroka infarkta miokarda, moždanog udara i perifernih vaskularnih bolesti, koji čine približno polovinu svih smrtnih slučajeva u razvijenim zemljama. Ona uključuje orkestrirane procese endotelijalne disfunkcije, inflamacije, proliferacije VSMCs i reorganizaciju ekstracelularnog matriksa. Dediferencijacija i proliferacija VSMCs predstavljaju ključne događaje u nastanku aterosklerotskih lezija, postangioplastične restenoze i odbacivanja kalema pri bajpasu krvnih sudova. Trombin je moćni modulator mnogih procesa kao što su regulisanje tonusa i propustljivosti krvnog suda, migracije i proliferacije VSMCs, privlačenja monocita u aterosklerotske lezije i raznih proinflamatornih markera, a sve ovo, takođe, doprinosi progresiji kardiovaskularnih oboljenja.Vascular smooth muscle cells (VSMCs) are vital to the structure, functioning and dynamics of blood vessels. Proliferation and abnormal accumulation of VSMCs are among the key events in the development of various vascular diseases including atherosclerosis and hypertension. Cardiovascular diseases are the leading cause of mortality in human population which is based largely dominated by atherosclerosis as a pathological component. Atherosclerosis is a major cause of myocardial infarction, stroke and peripheral vascular disease, which constitute approximately half of all deaths in developed countries. It involves orchestrated processes of endothelial dysfunction, inflammation, proliferation of VSMCs and extracellular matrix reorganization. Dedifferentiation and proliferation of VSMCs is a key event in the development of atherosclerotic lesions, postangioplastic restenosis and rejection of the bypass graft vessels. Thrombin is a potent modulator of many processes such as regulation of muscle tone and permeability of the blood vessel, migration and proliferation of VSMCs, attracting monocytes into atherosclerotic lesions and a variety of inflammatory markers, and all this also contributes to the progression of cardiovascular disease

PCSK9 and Hypercholesterolemia: Therapeutic Approach

Despite the intensive research and progress in modern pharmacotherapy, hypercholesterolemia and related cardiovascular complications remain one of the leading causes of mortality and disability in the modern world. A significant contribution to the treatment of hypercholesterolemia was made by the discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9). This enzyme is responsible for the degradation of the low-density lipoprotein (LDL) receptor (LDLR) found at the surface of the plasma membrane in the liver and directly associated with serum LDL level. Limitations in standard therapy used in the treatment of lipid disorders have led to the development of new drugs, such as an inhibitor of PCSK9. Over the past years, the greatest achievement in discovering the PCSK9 inhibitor was made by designing monoclonal antibodies that disable PCSK9 to bind LDLR and RNA interference to reduce PCSK9 production, but one of the main disadvantages is costeffectiveness. In this review, we will summarize the most recent findings of basic and clinical studies which focus on PCSK9 function, regulation and therapeutic target for the treatment of hypercholesterolemia and associated cardiovascular diseases

Obesity, insulin resistance and cardiovascular disease

Gojaznost se definiše kao prekomerno prisustvo masnog tkiva u organizmu koje može dovesti do mnogih zdravstvenih komplikacija koje pogoršavaju kvalitet života i skraćuju životni vek. Gojaznost je rezultat fizioloških odgovora organizma u situaciji kada je kalorijski unos veći od stvarnih energetskih potreba organizma u dužem vremenskom periodu, bez adekvatnog utroška energije. Prema podacima Svetske zdravstvene organizacije (WHO) gojaznost zauzima peto mesto u paleti vodećih uzroka smrti na globalnom nivou i može se definisati kao hroničan poremećaj metabolizma koji je udružen sa kardiovaskularnim oboljenjima (CVD) kao i sa povećanom stopom morbiditeta i mortaliteta. Danas je prihvaćeno mišljenje da je gojaznost usko povezana sa razvojem rezistencije na insulin (IR). Metaboličke i hormonske promene, koje su posledica pre svega visceralne gojaznosti karakteristične za metabolički sindrom, dovode vremenom do pojave IR u adipoznom tkivu, jetri i mišićnom tkivu. Pretpostavlja se da IR koja se javlja usled gojaznosti predstavlja prvi korak u razvoju CVD. Delimično, IR povećava rizik za nastanak nekih CVD zbog hipertenzije i dislipidemije, kao i promena u adipocitokinima, koje vode inflamaciji krvnih sudova. Osim toga, gojaznost nepovoljno utiče kako na hemodinamiku, tako i na strukturu i funkciju kardiovaskularnog sistema (CVS). Kardiovaskularne komplikacije koje su povezane sa gojaznošću doprinose visokoj stopi morbiditeta i mortaliteta. Usled porasta broja gojaznih osoba, kao i prisustva IR i CVD kod ovih osoba, izučavanje masnog tkiva i njegovog uticaja na razvoj različitih patofizioloških stanja kao što su IR i CVD predstavljaju veoma važno polje biomedicinskih istraživanja, rezultati kojih bi zasigurno omogućili nove terapeutske pristupe u lečenju ovih poremećaja. Takođe, u cilju sprečavanja razvoja gojaznosti, a samim tim i oboljenja koja nastaju kao posledica ovog poremećaja, veoma veliki značaj imaju prevencija i edukacija o mogućim aspektima koje prekomerna akumulacija masnog tkiva može imati na normalno funkcionisanje organizma.Obesity is defined as abnormal or excessive fat tissue accumulation that may impair health and well-being and also increases death risk. Obesity occurs as a result of physiological responses of the organism in situations when the caloric intake is greater than energy expenditure/ consumption over an extended period of time, resulting in energy conservation. According to the World Health Organization (WHO) overweight and obesity are the fifth of the leading risk factors for global deaths and they could be defined as a chronic metabolic disorder associated with cardiovascular diseases (CVD) and increased risk of morbidity and mortality. Today, it is accepted that obesity is closely related to insulin resistance (IR). Metabolic and hormonal changes occurring first of all with increased visceral obesity which is a characteristic of metabolic syndrome, lead to IR development in adipose, liver and muscle tissue. It is assumed that IR, which occurs due to obesity, represents the first step in CVD development. Partly, IR increases the risk for CVD development due to the presence of multiple risk factors as hypertension and dyslipidemia, and changes in adipocytokines lead to blood vessel inflammation. Besides that, obesity adversely affects hemodynamic, structure and function of cardiovascular system (CVS). Cardiovascular complications associated with obesity greatly contribute to increased risk of morbidity and mortality. Due to the rising number of obese patients and also presence of IR and CVD in these patients, the study of adipose tissue and its effects on the development of various pathophysiological states as IR and CVD represents a very important area of biomedical research which would lead to new therapeutic approaches in these conditions. Also, in order to prevent obesity development and associated disorders, prevention and education are of great importance