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Background: Inflammation markers in the blood may indicate a higher risk of unstable atherosclerosis. Selectins, a group of transmembrane glycoproteins, contribute to inflammation by helping certain blood cells bind to the endothelium., Methods: The study included 100 patients with stable early-onset coronary artery disease (CAD), 75 men (aged 50-54) and 25 women (aged 55-64). Tests performed included biochemical analysis, ultrasound, and Doppler imaging of arteries and peripheral vessels. A biochemical control group of 50 cases without CAD (74% men, average age 48 ± 3.20 years) was also studied., Results: Higher triglyceride levels were strongly linked to elevated plasma E-selectin levels. However, no significant relationship was found between plasma E-selectin levels and biochemical, clinical, radiographic, or echographic measures., Conclusion: Plasma E-selectin levels are not a reliable marker for detecting atherosclerotic plaques or related problems in individuals with stable, well-managed CAD. While E-selectin levels can be measured in clinical labs using immunoassays, they cannot replace standard cardiological and vascular imaging tests for diagnosing cardiac or vascular conditions.

Solid organ transplantation is a life-saving treatment for patients with end-stage organ failure, but it poses unique challenges due to metabolic and immunological changes in recipients. One significant complication is post-transplant diabetes mellitus (PTDM), which affects a variety of solid organ recipients. Leptin, a hormone produced by adipose tissue, regulates appetite and affects glucose metabolism. High leptin levels are associated with the development of PTDM, especially in kidney transplant recipients. Adiponectin, another adipokine, increases insulin sensitivity and has anti-diabetic properties. Low adiponectin levels are associated with insulin resistance and increase the risk of PTDM. As the incidence of PTDM increases due to the increased life expectancy among transplant patients, understanding the role of adipokines such as leptin and adiponectin becomes crucial for early detection and treatment. Additional studies on other adipokines may also provide valuable information on the pathogenesis of PTDM., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background : The pathogenesis of atherosclerosis is multifactorial and diverse. Pro-inflammatory cytokines are involved in these processes. It is suggested that inflammation may represent a novel and modifiable risk factor for cardiovascular disease. Therefore, this study aimed to gain insight into the relationship between plasma concentrations of TNF, VEGF, IL-6, and radiological parameters of atherosclerosis progression in patients with early-onset coronary artery disease (CAD). Methods: Seventy clinically stable patients were included in the study group. The age range for men was no more than 50 years, while for women, it was no more than 55 years. Fasting blood samples were obtained for plasma TNF, VEGF, and IL-6 protein measurements. Plasma cytokine concentrations were measured via ELISA. Doppler ultrasound of the carotid and peripheral arteries was performed in all patients. Results: After Bonferroni correction, there were no significant correlations between any cytokine and radiological parameters of atherosclerosis progression in our patients. Conclusions: The determination of plasma TNF, IL-6, and VEGF levels may not be a reliable marker for the vascular condition, and the measurement of these cytokines in plasma cannot replace the classical radiological examination of the vessels.

Introduction: Tumor necrosis factor (TNF), a pro-inflammatory cytokine, can be produced by cardiomyocytes, leading to metabolic disorders in the myocardium. The objective of this study was to assess the relationship between plasma levels of the TNF cytokine and the presence of known biochemical and clinical risk factors for cardiovascular disease, along with the parameters of cardiac morphology in patients diagnosed with coronary artery disease (CAD) at a young age. Materials and Methods: The study group included 75 men aged up to 50 years and 25 women aged up to 55 years. The plasma TNF concentration was measured by use of the ELISA assay. Echocardiography and electrocardiographic examinations were performed in all patients. Results: We observed positive correlations for TNF with the BMI ratio, weight, waist and hip circumference. We also found negative correlations for TNF with HDL levels and ApoA concentrations, and positive correlations with the ApoB/ApoA1 ratio, Apo B, IL6, LDL and TG concentrations. These results suggest an association between higher plasma TNF concentrations and components of metabolic syndrome, including dyslipidemia. TNF may be a potential risk factor for impaired diastolic function. Conclusions: While TNF may be useful for diagnosing certain risks in CAD patients, the TNF measurement cannot be used as a surrogate test for echocardiography.

Background: Kidneys play an essential role in the circulatory system, regulating blood pressure and intravascular volume. They are also set on maintaining an adequate filtration pressure in the glomerulus. During the CPB, a decrease in systemic blood pressure and hemoglobin concentration may lead to renal ischemia and subsequent acute kidney injury. Methods: One hundred nine adult patients were prospectively enrolled in this study. The intervention in this study was increasing the flow of the CPB pump to reach the target MAP of > 90 mmHg during the procedure. The control group had a standard pump flow of 2.4 L/min/m 2 . Results: Standard pump flow of 2.4 L/min/m 2 resulted in mean MAP < 90 mmHg during the CPB in most patients in the control group. Maintaining a higher MAP during CPB in this study population did not affect CSA-AKI incidence. However, it increased the intraoperative and postoperative diuresis and decreased renin release associated with CPB. Higher MAP during the CPB did not increase the incidence of cerebrovascular complications after the operation; patients in the highest MAP group had the lowest incidence of postoperative delirium, but the result did not obtain statistical significance. Conclusion: Maintaining MAP > 90 mmHg during the CPB positively impacts intraoperative and postoperative kidney function. It significantly reduces renal hypoperfusion during the procedure compared to MAP < 70 mmHg. MAP > 90 mmHg is safe for the central nervous system, and preliminary results suggest that it may have a beneficial impact on the incidence of postoperative delirium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Udzik, Pacholewicz, Biskupski, Safranow, Wojciechowska-Koszko, Kwiatkowski, Roszkowska, Rogulska, Dziedziejko, Marcinowska, Kwiatkowski and Kwiatkowska.)

Background: The COMT gene encodes the enzyme catechol-O-methyltransferase, which is a key modulator of dopaminergic and adrenergic neurotransmission. Hip osteoarthritis is accompanied by reduced mobility and some level of disability. In our study, we analyzed the association between some COMT gene polymorphisms and reduced mobility in patients after total hip replacement (THR)., Methods: The operative procedures were performed on 195 patients with symptomatic and radiologically advanced hip osteoarthritis. In the postoperative follow-up, we assessed hip function with the Harris Hip Score (HHS) and the degree of disability with the Oswestry Disability Index (ODI). These procedures were repeated three times at defined intervals (one week, six weeks, and six months) after the total hip replacement. Genomic DNA was extracted from peripheral blood. SNPs in the COMT genes rs4680:A>G , rs6269: A>G , rs4633: C>T , and rs4818: C>G were genotyped., Results: Our findings suggest an association between COMT gene variability and the level of disability measured by the Oswestry Disability Index (ODI) in patients after total hip replacement (THR)., Conclusions: A higher number of COMT G alleles (rs4818) is an independent factor in a significant reduction in disability degree at both one week and six months after total hip replacement (THR), regardless of age or gender.

Post-transplant diabetes mellitus (PTDM) is a metabolic complication that often occurs after kidney transplantation. Factors that increase the risk of this complication are currently being researched, including polymorphisms in genes affecting carbohydrate-lipid metabolism. Leptin is a hormone that affects appetite and adipose tissue and plays an important role in regulating insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between leptin receptor gene polymorphisms and the development of post-transplant diabetes mellitus in patients treated with tacrolimus. The study was carried out in a group of 201 patients who underwent kidney transplantation. The follow-up period was 12 months. PTDM was diagnosed in 35 patients. Analysing the LEPR gene rs1137101 polymorphism, we observed in patients with PTDM an increased frequency of GG genotype carriers (GG vs AA, OR 3.36; 95 % CI 0.99-11.46; p = 0.04). There were no statistically significant differences in the distribution of the LEPR rs1137100 and LEPR rs1805094 polymorphisms between patients with and without PTDM. Multivariate regression analysis confirmed that female sex, advanced age, increased BMI and a higher number of LEPR rs1137101 G alleles were independent risk factors for PTDM development. The risk of PTDM development was almost 3.5 times greater in LEPR rs1137101 G allele carriers than in AA homozygotes (GG + AG vs AA; OR 3.48; 95 %CI (1.09-11.18), p = 0.035). The results suggest that patients after kidney transplantation with the LEPR gene rs1137101 G allele may have an increased risk of post-transplant diabetes development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Post-transplant diabetes mellitus (PTDM) is a common complication that occurs in kidney transplant patients, increasing the risk of infection, cardiovascular disease and loss of graft function. Currently, factors that increase the risk of this complication are being sought, among them polymorphisms in genes that regulate carbohydrate metabolism and influence pancreatic β-cell function. The aim of this study was to evaluate the association of selected polymorphisms of genes affecting carbohydrate metabolism, such as CDKAL1 rs10946398, GCK rs1799884, GCKR rs780094 and DGKB/TMEM195 rs2191349, with the development of post-transplant diabetes in kidney transplant patients. This study included 201 Caucasian patients after kidney transplantation treated with tacrolimus. An association was observed between the CDKAL1 rs10946398 gene polymorphism and PTDM. Among patients with PTDM, there was an increased prevalence of the CC genotype in the PTDM group compared to the group without PTDM. The chance of PTDM in those with the CC genotype was 2.60 times higher compared to those with the AC + AA genotypes (CC vs. AC + AA OR (95% CI): 2.60 (1.02-6.61), p = 0.040). Multivariate logistic regression analysis showed that advanced age and the CC genotype (rare homozygote) of CDKAL1 rs10946398 were risk factors for the development of PTDM at 1 year after transplantation. There was no statistically significant association between GCK rs1799884, GCKR rs780094 or DGKB/TMEM195 rs2191349 polymorphisms and the development of post-transplant diabetes mellitus in kidney transplant patients. The results of this study suggest that the CDKAL1 rs10946398 CC genotype is associated with the increased risk of PTDM development in patients after kidney graft transplantation treated with tacrolimus.

Renal transplantation is now the best treatment for end-stage renal failure. To avoid rejection and prolong graft function, organ recipients need immunosuppressive therapy. The immunosuppressive drugs used depends on many factors, including time since transplantation (induction or maintenance), aetiology of the disease, and/or condition of the graft. Immunosuppressive treatment needs to be personalised, and hospitals and clinics have differing protocols and preparations depending on experience. Renal transplant recipient maintenance treatment is mostly based on triple-drug therapy containing calcineurin inhibitors, corticosteroids, and antiproliferative drugs. In addition to the desired effect, the use of immunosuppressive drugs carries risks of certain side effects. Therefore, new immunosuppressive drugs and immunosuppressive protocols are being sought that exert fewer side effects, which could maximise efficacy and reduce toxicity and, in this way, reduce both morbidity and mortality, as well as increase opportunities to modify individual immunosuppression for renal recipients of all ages. The aim of the current review is to describe the classes of immunosuppressive drugs and their mode of action, which are divided by induction and maintenance treatment. An additional aspect of the current review is a description of immune system activity modulation by the drugs used in renal transplant recipients. Complications associated with the use of immunosuppressive drugs and other immunosuppressive treatment options used in kidney transplant recipients have also been described.

Behavioural and emotional disturbances (F92.8) are the most recognized disorders in a developmental psychiatry. As the problem is still alarmingly increasing, the searches for their etiopathogenesis and more effective preventing and therapy methods are required. The aim of the study was to assess the association between the quality of life, some psychopathological features, concentrations of selected immunoprotective (brain-derived neurotrophin, BDNF), and endocrine (cortisol, F) factors while adolescent disturbances. The study was performed in 123 inpatients of a psychiatric ward with F92.8 diagnosis, aged 13-18 years. The complete patients' interview, physical examination, and routine laboratory tests, including serum F and BDNF tests, were performed. All patients completed standardized questionnaires to estimate: the severity of psychopathological symptoms (SCL-90), the level of aggression (Buss-Perry). The changes in the plasma BDNF and F concentrations were shown in patients raised in foster homes and institutions. The significantly lower BDNF was observed in youth from foster and suicide-experienced families. The more severe psychopathological symptoms, especially aggression and hostility, were found in these ones, who abused alcohol, attempted suicide, had lower self-esteem and cognitive processes, and were lacking safety in dysfunctional families.

Acute kidney injury (AKI) can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules-peritubular capillary (PTC) network. Cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for ATP production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5-10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the endothelium, with an increase in its prothrombotic and pro-adhesive properties. This causes congestion in the microcirculation of the renal medulla. The next stage is the migration of pericytes with the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin-angiotensin-aldosterone system.

The intestinal microflora is extremely important, not only in the processes of absorption, digestion and biosynthesis of vitamins, but also in shaping the immune and cognitive functions of the human body. Several studies demonstrate a correlation between microbiota composition and such events as graft rejection, kidney interstitial fibrosis, urinary tract infections, and diarrhoea or graft tolerance. Some of those changes might be directly linked with pathologies such as colonization with pathogenic bacterial strains. Gut microbiota composition also plays an important role in metabolic complications and viral infections after transplantation. From the other side, gut microbiota might induce graft tolerance by promotion of T and B regulatory cells. Graft tolerance induction is still an extremely important issue regarding transplantology and might allow the reduction or even avoidance of immunosuppressive treatment. Although there is a rising evidence of the pivotal role of gut microbiota in aspects of kidney transplantation there is still a lack of knowledge on the direct mechanisms of microbiota action. Furthermore, some of those negative effects could be reversed by probiotics of faecal microbiota trapoinsplantation. While diabetes and hypertension as well as BKV and CMV viremia are common and important complications of transplantation, both worsening the graft function and causing systemic injuries, it opens up potential clinical treatment options. As has been also suggested in the current review, some bacterial subsets exhibit protective properties. However, currently, there is a lack of evidence on pro- and prebiotic supplementation in kidney transplant patients. In the current review, we describe the effect of the microbiota on the transplanted kidney in renal transplant recipients.

Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnant women leading to various complications. Consequently, factors predisposing its development are being sought. Previous studies have shown that the pathogenesis of GDM is similar to that of type 2 diabetes, and it is therefore thought that the two diseases may have a common genetic basis. The aim of this study was to examine the associations between thyroid adenoma-associated ( THADA ) rs7578597 T>C, succinate dehydrogenase complex assembly factor 4 ( SDHAF4 ) rs1048886 A>G, and microtubule-actin crosslinking factor 1 ( MACF1 ) rs2296172 A>G gene polymorphisms and the risk of GDM development as well as selected clinical parameters in women with GDM. We also examined the expression of these genes in the placenta of women with and without GDM in association with clinical parameters. This case-control study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. There were no statistically significant differences in the distribution of the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms between pregnant control women and women with GDM. The associations between clinical parameters such as body mass before pregnancy, body mass at birth, body mass increase during pregnancy, BMI before pregnancy, BMI at birth, BMI increase during pregnancy, glycated hemoglobin (HbA1c), daily insulin requirement, childbirth time, and newborn body mass and APGAR score, and the THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G genotypes were statistically non-significant. We only observed lower values of body mass before pregnancy and body mass at birth in women with the SDHAF4 rs1048886 AG genotype in comparison with AA genotype carriers. There was no statistically significant difference in the expression of THADA , SDHAF4 , and MACF1 genes in the placenta between women with GDM and healthy women. There were also no statistically significant correlations between THADA , SDHAF4 , and MACF1 gene expression in the placenta and clinical parameters. The results of our study suggest that THADA rs7578597 T>C, SDHAF4 rs1048886 A>G, and MACF1 rs2296172 A>G gene polymorphisms are not significant factors associated with GDM onset. In addition, SDHAF4 rs1048886 A>G may be associated with body mass before pregnancy and body mass at birth in pregnant women.

Tacrolimus, in combination with mycophenolate mofetil and glucocorticoids, is the basis of immunosuppressive therapy after renal transplantation. Tacrolimus intrapatient variability (IPV) and the blood concentration normalized by the dose (concentration/dose ratio, C/D ratio) both have an effect on the function of the transplanted kidney. In this study, we examined whether the metabolism rate affected IPV, whether the C/D ratio value was stable in the long-term follow-up, and whether it could be used for IPV measurements. In addition, our study population was examined for the effect of the C/D ratio and IPV on long-term renal function. The C/D ratio and IPV were examined in 170 patients at appointments held at 3, 6, 12 and 24 months after RTx. The average time post renal transplantation was 70 months. Renal function defined as creatinine concentration at the last appointment was examined. Results: the mean C/D ratio in the study group was 1.63. A negative correlation between the C/D ratio and creatinine concentration at the end of the follow-up was observed. Between the C/D ratio < and ≥1.63 groups, significant differences in creatinine concentration at the last appointment were found. No relationship was identified between the mean C/D ratio and IPV. The C/D ratio values increased significantly over a longer post-transplant period (12, 24, 60 and 120 m). We did not find a correlation between the mean IPV and the creatinine concentration from the last appointment. Our study group was divided into terciles according to IPV, while no renal graft function differences were found at the same appointment. Conclusion: the C/D ratio is useful for assessing the effects of the metabolism rate of tacrolimus on the long-term renal graft function. The C/D ratio does not affect the IPV value. IPV calculated from variability of the C/D ratio does not influence transplanted kidney function. The C/D changes over time.

Genetic factors may predispose persons to decreased pain excitability. One of the interesting modulators affecting pain perception may be polymorphisms of the cannabinoid receptor type 1 ( CNR1 ) gene. In this study, we examined the association between three-nucleotide repeats (AAT) polymorphism located in the 3'UTR non-translational region of CNR1 and the patient's quality of life after total hip arthroplasty. Our study examined the degree of pain sensation, hip function, and the patient's performance at defined intervals after elective hip replacement due to degenerative changes. The study included 198 patients (128 women and 70 men). The average age was 67 years. PCR genotyping assay was used to identify the (AAT)n triplet repeat polymorphism in the CNR1 gene. The (AAT)n repeat number was determined by sequencing using a standard sequencing protocol. Our study found no statistically significant association between the degree of pain, hip function, and the change in the degree of disability and the (AAT)n polymorphism in the CNR1 gene, no statistically significant correlations between clinical symptoms, the patient's age, and the number of AAT repeats, no association between the length of the allele and the degree of pain, hip function, and the change in disability.

Type 2 diabetes is a disease that causes numerous complications disrupting the functioning of the entire body. Therefore, new treatments for the disease are being sought. Studies in recent years have shown that forkhead box O (FOXO) proteins may be a promising target for diabetes therapy. FOXO proteins are transcription factors involved in numerous physiological processes and in various pathological conditions, including cardiovascular diseases and diabetes. Their roles include regulating the cell cycle, DNA repair, influencing apoptosis, glucose metabolism, autophagy processes and ageing. FOXO1 is an important regulator of pancreatic beta-cell function affecting pancreatic beta cells under conditions of insulin resistance. FOXO1 also protects beta cells from damage resulting from oxidative stress associated with glucose and lipid overload. FOXO has been shown to affect a number of processes involved in the development of diabetes and its complications. FOXO regulates pancreatic β-cell function during metabolic stress and also plays an important role in regulating wound healing. Therefore, the pharmacological regulation of FOXO proteins is a promising approach to developing treatments for many diseases, including diabetes mellitus. In this review, we describe the role of FOXO proteins in the pathogenesis of diabetes and the role of the modulation of FOXO function in the therapy of this disease.

Compared to other addictive substances, patients with cannabis addiction are significantly outnumbered by those who report dependence on other, more addictive substances. Unfortunately, most cannabis addiction goes untreated, and among those who choose treatment, the requirements are much higher for adolescents and young adults., The Aim of the Study: To examine the relationship of cannabinoid dependency in the genetic context-the association between the rs1799732 polymorphism of the DRD2 gene and psychological traits and anxiety., Methods: The study group consisted of 515 male volunteers. Of these, 214 patients were diagnosed with cannabis addiction and 301 were non-addicted. Patients were diagnosed with NEO Five-Factor Personality Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI) questionnaires. The interactions between personality traits and polymorphisms in the DRD2 rs1799732 gene were investigated in a group of cannabis-addicted patients and non-addicted controls using the real-time PCR method., Results: Compared to the control group, the case group obtained significantly higher scores on the STAI State, STAI Trait, Neuroticism and Openness scales, as well as lower scores on the Extraversion, Agreeableness, and Conscientiousness scales. There was no statistically significant difference between addicts and the control group in the frequency of genotypes, but there was a statistically significant difference between addicts and the control group in the frequency of the DRD2 allele rs179973. The multivariate ANOVA analysis showed a statistically significant influence of the DRD2 rs1799732 genotype on the NEO-FFI agreeableness scale and a statistically significant effect of addiction to cannabinoids or its absence on the NEO-FFI agreeableness scale score., Conclusions: Studying homogeneous subgroups-as in our study-seems reasonable, particularly when combined with genetic determinants and psychological traits. In multigenic and multifactorial entities, such a strategy has a future.

Gestational diabetes mellitus (GDM) is carbohydrate intolerance in pregnant women leading to various complications. Currently, there is a search for factors predisposing to GDM. Among them are genetic polymorphisms of genes involved in insulin secretion as well as carbohydrate metabolism. Due to the similar pathogenesis of GDM to type 2 diabetes (T2DM), genetic polymorphisms associated with T2DM are considered. The aim of this study was to examine the associations between the COBLL1 rs7607980 T > C and IRS1 rs2943641 T > C gene polymorphisms and the risk of GDM as well as selected clinical parameters in women with GDM. Additionally, we examined the expression of these genes in the placenta of women with and without GDM in correlation with selected clinical parameters. This study included 328 pregnant women with normal glucose tolerance (NGT) and 251 pregnant women with GDM diagnosed on the basis of a 75 g oral glucose tolerance test (OGTT) at 24−28 weeks gestation. There were no statistically significant differences in the distribution of IRS1 rs2943641 gene polymorphisms between women with GDM and pregnant women with NGT. In the GDM group, we observed a decreased frequency of COBLL1 rs7607980 CC homozygous women (CC vs. TC+TT, p = 0.048); however, there was no statistically significant difference in the frequency of alleles between women with GDM and the control group. There were no statistically significant associations between COBLL1 rs7607980 gene polymorphism and clinical parameters in women with GDM. In GDM women with the IRS1 rs2943641 TT genotype, fasting glucose levels were significantly higher than in women with CC and TC genotypes. There was no statistically significant difference in the expression of COBLL1 and IRS1 genes in the placenta between women with GDM and healthy women. There were no statistically significant correlations between COBLL1 gene expression in the placenta and clinical parameters. The expression of IRS1 correlated significantly with an increase in BMI during pregnancy. The results of this study suggest that COBLL1 rs7607980 and IRS1 rs2943641 gene polymorphisms are not significant risk factors for GDM in our population. The IRS1 TT genotype may be associated with higher fasting glucose levels in women with GDM. Expression of the IRS1 gene in the placenta positively correlates with an increase in BMI during pregnancy in women with GDM.

Gestational diabetes mellitus (GDM) represents carbohydrate intolerance in pregnant women. The pathogenesis of GDM is very complex, but abnormalities in insulin production and secretion underlie the disease. Potassium channels play an important role in insulin production and secretion. The family of potassium channels includes (among others) the potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) and voltage-gated K+ channel ( KCNQ1 ). The aim of the study was to examine the distribution of the KCNJ11 rs5219 and KCNQ1 rs151290 and rs2237892 gene polymorphisms in women with GDM and pregnant women with normal carbohydrate tolerance, to verify whether these polymorphisms are risk factors for GDM. This study included 204 Caucasian pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT) from the West Pomeranian region of Poland. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks gestation. There were no statistically significant differences in distribution of the KCNJ11 rs5219 and KCNQ1 rs151290 and rs2237892 gene polymorphisms between women with GDM and pregnant women with normal carbohydrate tolerance. Moreover, there were no statistically significant associations between the studied genotypes and the selected clinical parameters in women with GDM. The results of our study suggest that the KCNJ11 rs5219 and KCNQ1 rs2237892 and rs151290 gene polymorphisms are not significant risk factors associated with the development of GDM in our population. There were also no differences in the expression of KCNJ11 and KCNQ1 genes in the placenta of women with GDM and normal carbohydrate tolerance. However, an association between KCNJ11 gene expression in placenta and APGAR score in newborns was found.

Background/aims: Chronic kidney disease CKD patients on intermittent hemodialysis IHD are exposed to SARS-CoV-2 infection and carry a risk of developing severe symptoms. The aim of this study was to evaluate the humoral and cellular immunity induced by two doses of mRNA vaccines, the Pfizer-BioNTech (Comirnaty) COVID-19 Vaccine and the Moderna (mRNA-1273) COVID-19 vaccine., Patients and Methods: The study included 281 patients from five dialysis centers in northern Poland. Within 2 weeks prior to the first dose of the vaccine, a blood sample was collected for an evaluation of SARS-CoV-2 antibodies. Thirty to forty-five days after the second dose of the vaccine, a blood sample was taken to evaluate humoral and cellular response., Results: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate. The strongest factors influencing the antibodies AB level after vaccination were a pre-vaccination history of SARS-CoV-2 infection, age, the neutrophil-to-lymphocyte ratio NLR, neutrophil absolute count, and the hemoglobin level. Cellular immunity was higher in patients with a pre-vaccination history of SARS-CoV-2 infection. Cellular immunity depended on the albumin level. Positive cellular response to vaccination was a positive factor reducing all-cause mortality, except for COVID-19 mortality (no such deaths were reported during our follow-up). Cellular immunity and humoral immunity were positively mutually dependent. High levels of albumin and hemoglobin, low neutrophil count, and a reduced NLR, translated into better response to vaccination., Conclusions: Patients with stage 5 CKD on IHD were characterized by a considerable SARS-CoV-2 vaccine-induced seroconversion rate and a good rate of cellular immunity. The factors that change with exacerbating inflammation and malnutrition (albumin, hemoglobin, neutrophil count, the NLR) affected the efficacy of the vaccination.

Gestational diabetes mellitus (GDM) is a common disorder that occurs in pregnant women, leading to many maternal and neonatal complications. The pathogenesis of GDM is complex and includes risk factors, such as: age, obesity, and family history of diabetes. Studies have shown that genetic factors also play a role in the pathogenesis of GDM. The present study investigated whether polymorphisms in the PPARG (rs1801282), TMEM163 (rs6723108 and rs998451), UBE2E2 (rs6780569), and WFS1 (rs4689388) genes are risk factors for the development of GDM and whether they affect selected clinical parameters in women with GDM. This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks gestation, according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. There were no statistically significant differences in the distribution of polymorphisms studied between women with GDM and pregnant women with normal carbohydrate tolerance, which suggests that these polymorphisms are not risk factors for GDM. We also examined the associations between studied gene polymorphisms and clinical parameters: fasting glucose, daily insulin requirement, body mass before pregnancy, body mass at birth, body mass increase during pregnancy, BMI before pregnancy, BMI at birth, BMI increase during pregnancy, new-born body mass, and APGAR score in women with GDM. We observed lower BMI values before pregnancy and at birth in women with PPARG rs17036160 TT genotype. The results of this study suggest that the PPARG (rs1801282), TMEM163 (rs6723108 and rs998451), UBE2E2 (rs6780569), and WFS1 (rs4689388) gene polymorphisms are not significant risk factors for GDM development in the Polish population and do not affect the clinical parameters in women with GDM; only rs1801282 of the PPARG gene may influence BMI values in women with GDM.

Coronary artery disease (CAD) is a syndrome resulting from myocardial ischaemia of heterogeneous pathomechanism. Environmental and genetic factors contribute to its development. Atherosclerotic plaques that significantly narrow the lumen of coronary arteries cause symptoms of myocardial ischaemia. Acute coronary incidents are most often associated with plaque rupture or erosion accompanied by local activation of the coagulation system with thrombus formation. Plaque formation and stability are influenced by endothelial function and vascular smooth muscle cell function. In this study, we investigated the association between polymorphisms in genes affecting endothelial and vascular smooth muscle cell (VSMC) function and the occurrence of unstable angina pectoris. The aim of this study was to evaluate the association between the PECAM1 (rs1867624), COL4A2 (rs4773144), PHACTR1 (rs9349379) and LMOD1 (rs2820315) gene polymorphisms and the risk of unstable angina. The study included 232 patients with unstable angina diagnosed on the basis of clinical symptoms and coronary angiography and 144 healthy subjects with no significant coronary lumen stenosis at coronary angiography. There were no statistically significant differences in the distribution of COL4A2 rs4773144 and PECAM1 rs1867624 gene polymorphisms between patients with unstable angina and control subjects. In patients with unstable angina, there was an increased frequency of PHACTR1 rs9349379 G allele carriers (GG and AG genotypes) (GG+AG vs. AA, OR 1.71; 95% CI 1.10-2.66, p = 0.017) and carriers of the LMOD1 rs2820315 T allele (TT and CT genotypes) (TT+CT vs. CC, OR 1.65; 95% CI 1.09-2.51, p = 0.019) compared to the control group. The association between these alleles and unstable angina was confirmed by multivariate logistic regression analysis, in which the number of G ( PHACTR1 rs9349379) and T ( LMOD1 rs2820315) alleles was an independent risk factor for unstable angina. The results suggest an association between PHACTR1 rs9349379 and LMOD1 rs2820315 polymorphisms and the risk of unstable angina.

Glucocorticoids, as multifunctional hormones, are widely used in the treatment of various diseases including nephrological disorders. They are known to affect immunological cells, effectively treating many autoimmune and inflammatory processes. Furthermore, there is a growing body of evidence demonstrating the potent role of glucocorticoids in non-immune cells such as podocytes. Moreover, novel data show additional pathways and processes affected by glucocorticoids, such as the Wnt pathway or autophagy. The endothelium is currently considered as a key organ in the regulation of numerous kidney functions such as glomerular filtration, vascular tone and the regulation of inflammation and coagulation. In this review, we analyse the literature concerning the effects of endothelial glucocorticoid receptor signalling on kidney function in health and disease, with special focus on hypertension, diabetic kidney disease, glomerulopathies and chronic kidney disease. Recent studies demonstrate the potential role of endothelial GR in the prevention of fibrosis of kidney tissue and cell metabolism through Wnt pathways, which could have a protective effect against disease progression. Another important aspect covered in this review is blood pressure regulation though GR and eNOS. We also briefly cover potential therapies that might affect the endothelial glucocorticoid receptor and its possible clinical implications, with special interest in selective or local GR stimulation and potential mitigation of GC treatment side effects.

The outburst of inflammatory response and hypercoagulability are among the factors contributing to increased mortality in severe COVID-19 cases. Pentoxifylline (PTX), a xanthine-derived drug registered for the treatment of vascular claudication, has been reported to display broad-spectrum anti-inflammatory and immunomodulatory properties via adenosine A2A receptor (A2AR)-related mechanisms, in parallel to its rheological actions. Prior studies have indicated the efficacy of PTX in the treatment of various pulmonary diseases, including the management of acute respiratory distress syndrome of infectious causes. Therefore, PTX has been proposed to have potential benefits in the treatment of SARS-CoV-2 symptoms, as well as its complications. The aim of this review is to discuss available knowledge regarding the role of PTX as a complementary therapeutic in SARS-CoV-2.

Aim: Leflunomide is a disease-modifying antirheumatic drug used in therapy for rheumatoid arthritis (RA). Previous studies indicated that oestrogens and androgens may affect the response to leflunomide in RA patients. The synthesis of androgens is regulated by cytochrome CYB5A. The aim of this study was to examine the association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA., Methods: The study included 111 women diagnosed with RA. Leflunomide was administered in monotherapy at a dose of 20 mg/day. All patients underwent a monthly evaluation for 12 months after the initiation of treatment with leflunomide., Results: After 12 months of therapy, the changes in individual disease activity parameters, such as: DAS28, ESR, CRP and VAS, were not statistically significantly different between rs1790834 genotypes in the Kruskal-Wallis test., Conclusions: The results of our study suggest lack of statistically significant association between the CYB5A gene rs1790834 polymorphism and the response to leflunomide in women with RA., (© 2021. The Author(s).)

Aims: Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnant women. In the GDM pathogenesis, the low-grade inflammation plays a significant role. Various inflammatory mediators are considered to be risk factors leading to GDM development including cytokines. Studies suggest that some cytokines such as: IL-1β and IL-10 play an important role in GDM pathogenesis. The aim of the study was to examine the associations between IL-1β rs16944, and IL-10 rs1800872 gene polymorphisms and GDM., Methods: This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test administered at 24-28 weeks' gestation. Among the pregnant women with GDM, 152 (75%) were treated with diet control alone throughout the pregnancy, whereas the remaining 52 (25%) were treated with diet control and insulin until delivery., Results: There were no statistically significant differences in the distribution of IL-1β rs16944 and IL-10 rs1800872 between GDM and healthy women. However among women treated with insulin, we observed the increased frequency of IL-1β rs16944 AA genotype carriers. Additionally, we observed increased daily insulin requirement in women with IL-1β rs16944 AA genotype. Moreover, women with IL-10 rs1800872 AA genotype had higher body mass and BMI before pregnancy as well as higher body mass and BMI increase during pregnancy., Conclusions: The results of our study suggest the association between IL-1β rs16944 AA genotype and increased frequency of the need of insulin treatment as well as increased daily insulin requirement.

The imbalanced network of adipokines may contribute to the development of systemic low-grade inflammation, metabolic diseases and coronary artery disease (CAD). In the last decade, three classic adipokines-adiponectin, leptin and resistin-have been of particular interest in studies of patients with CAD due to their numerous properties in relation to the cardiovascular system. This has directed our attention to the association of adipokines with cardiac structure and function and the development of heart failure (HF), a common end effect of CAD. Thus, the purpose of this study was to analyse the associations of plasma concentrations of adiponectin, leptin and resistin with parameters assessed in the echocardiographic examinations of CAD patients. The presented study enrolled 167 Caucasian patients (133 male; 34 female) with CAD. Anthropometric, echocardiographic and basic biochemical measurements, together with plasma concentrations of adiponectin, leptin and resistin assays, were performed in each patient. Adiponectin concentrations were negatively associated with left ventricular ejection fraction (LVEF) and shortening fraction (LVSF), and positively associated with mitral valve E/A ratio (E/A), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter LVESD, and left atrium diameter (LAD). Resistin concentrations were negatively associated with E/A. Leptin concentrations, although correlated with HF severity assessed by the New York Heart Association (NYHA) Functional Classification, were not independently associated with the echocardiographic parameters of cardiac structure or function. In conclusion, adiponectin and resistin, but not leptin, are associated with the echocardiographic parameters of cardiac remodelling and dysfunction. These associations suggest that adiponectin and resistin might be involved in mechanisms of cardiac remodelling or compensative response. We also suggest the possible benefits of adiponectin and resistin level measurements in the monitoring of patients with CAD.

Gestational diabetes mellitus (GDM) is carbohydrate intolerance that occurs during pregnancy. This disease may lead to various maternal and neonatal complications; therefore, early diagnosis is very important. Because of the similarity in pathogenesis of type 2 diabetes and GDM, the genetic variants associated with type 2 diabetes are commonly investigated in GDM. The aim of the present study was to examine the associations between the polymorphisms in the ADCY5 (rs11708067, rs2877716), CAPN10 (rs2975760, rs3792267), and JAZF1 (rs864745) genes and GDM as well as to determine the expression of these genes in the placenta. This study included 272 pregnant women with GDM and 348 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks gestation, according to International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. There were no statistically significant differences in the distribution of the ADCY5 gene (rs11708067, rs2877716) and CAPN10 gene (rs2975760, rs3792267) polymorphisms between pregnant women with normal carbohydrate tolerance and pregnant women with GDM. We have shown a lower frequency of JAZF1 gene rs864745 C allele carriers among women with GDM CC + CT vs. TT (OR = 0.60, 95% CI = 0.41-0.87, p = 0.006), and C vs. T (OR = 0.75, 95% CI = 0.60-0.95, p = 0.014). In addition, ADCY5 and JAZF1 gene expression was statistically significantly increased in the placentas of women with GDM compared with that of healthy women. The expression of the CAPN10 gene did not differ significantly between women with and without GDM. Our results indicate increased expression of JAZF1 and ADCY5 genes in the placentas of women with GDM as well as a protective effect of the C allele of the JAZF1 rs864745 gene polymorphism on the development of GDM in pregnant women.

Background/aims: Renalase is an enzyme with monoamine oxidase activity that metabolizes catecholamines; therefore, it has a significant influence on arterial blood pressure regulation and the development of cardiovascular diseases. Renalase is mainly produced in the kidneys. Nephrectomy and hemodialysis (HD) may alter the production and metabolism of renalase. The aim of this study was to examine the effect of bilateral nephrectomy on renalase levels in the serum and erythrocytes of hemodialysis patients., Methods: This study included 27 hemodialysis patients post-bilateral nephrectomy, 46 hemodialysis patients without nephrectomy but with chronic kidney disease and anuria and 30 healthy subjects with normal kidney function. Renalase levels in the serum and erythrocytes were measured using an ELISA kit., Results: Serum concentrations of renalase were significantly higher in post-bilateral nephrectomy patients when compared with those of control subjects (101.1 ± 65.5 vs. 19.6 ± 5.0; p < 0.01). Additionally, renalase concentrations, calculated per gram of hemoglobin, were significantly higher in patients after bilateral nephrectomy in comparison with those of healthy subjects (994.9 ± 345.5 vs. 697.6 ± 273.4, p = 0.015). There were no statistically significant differences in plasma concentrations of noradrenaline or adrenaline. In contrast, the concentration of dopamine was significantly lower in post-nephrectomy patients when compared with those of healthy subjects (116.8 ± 147.7 vs. 440.9 ± 343.2, p < 0.01)., Conclusions: Increased serum levels of renalase in post-bilateral nephrectomy hemodialysis patients are likely related to production in extra-renal organs as a result of changes in the cardiovascular system and hypertension.

Acute kidney injury (AKI) is a global health challenge of vast proportions, as approx. 13.3% of people worldwide are affected annually. The pathophysiology of AKI is very complex, but its main causes are sepsis, ischemia, and nephrotoxicity. Nephrotoxicity is mainly associated with the use of drugs. Drug-induced AKI accounts for 19-26% of all hospitalized cases. Drug-induced nephrotoxicity develops according to one of the three mechanisms: (1) proximal tubular injury and acute tubular necrosis (ATN) (a dose-dependent mechanism), where the cause is related to apical contact with drugs or their metabolites, the transport of drugs and their metabolites from the apical surface, and the secretion of drugs from the basolateral surface into the tubular lumen; (2) tubular obstruction by crystals or casts containing drugs and their metabolites (a dose-dependent mechanism); (3) interstitial nephritis induced by drugs and their metabolites (a dose-independent mechanism). In this article, the mechanisms of the individual types of injury will be described. Specific groups of drugs will be linked to specific injuries. Additionally, the risk factors for the development of AKI and the methods for preventing and/or treating the condition will be discussed.

Background: VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells. Several studies suggest that VAV1 signaling plays significant roles in allograft rejection. The aim of this study was to examine the association between VAV1 gene polymorphisms and renal allograft function., Methods: The study included 270 patients after allograft renal transplantation. We examined the associations between VAV1 gene polymorphisms and complications after transplantation, such as delayed graft function, acute rejection, and chronic allograft dysfunction., Results: There were no statistically significant associations between VAV1 genotypes and delayed graft function and chronic allograft dysfunction. Among patients with acute allograft rejection, we observed decreased frequencies of VAV1 rs2546133 TT and CT genotypes (P = .03) and T allele (P = .02), as well as VAV1 rs2617822 GG and AG genotypes (P = .05) and G allele (P = 0.04). In the multivariate regression analysis, the higher number of VAV1 rs2546133 T alleles showed a protective effect against the acute rejection in kidney allograft recipients., Conclusions: The results of our study suggest that polymorphisms in the VAV1 gene are associated with kidney allograft rejection., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is an inflammatory disease leading to kidney insufficiency and uremia. Renalase is a novel flavoprotein with enzymatic activities. Previous studies have shown that chronic kidney disease may influence renalase serum levels. Renalase metabolises catecholamines and therefore may be involved in the pathogenesis of hypertension and other diseases of the circulatory system. In this study, we examined renalase levels in serum, erythrocytes and urine from haemodialysis CKD patients. The study enrolled 77 haemodialysis CKD patients and 30 healthy subjects with normal kidney function as the control group. Renalase serum and urine concentrations in CKD patients were significantly increased when compared with control subjects (185.5 ± 64.3 vs. 19.6 ± 5.0 ng/mL; p < 0.00001 and 207.1 ± 60.5 vs. 141.6 ± 41.3 ng/mL; p = 0.00040, respectively). In contrast, renalase levels in erythrocytes were significantly lower in CKD patients when compared with control subjects (176.5 ± 60.9 vs. 233.2 ± 83.1 ng/mL; p = 0.00096). Plasma levels of dopamine, adrenaline and noradrenaline were also significantly lower in CKD patients when compared with controls. Conclusions: Increased serum and urine concentrations of renalase in haemodialysis CKD patients are likely related to compensatory production in extrarenal organs as a result of changes in the cardiovascular system and hypertension. The decreased plasma concentrations of catecholamines may be due to their increased degradation by plasma renalase. Decreased renalase levels in erythrocytes may be probably due to lower renalase synthesis by the kidneys in CKD. The results indicate the presence of renalase in erythrocytes.

Overweight and obesity are among the most widespread health problems worldwide. The primary cause of obesity is an inability to control overeating. Therefore, today, obesity needs to be treated more as an eating disorder, i.e., a mental disorder, and thus, it should be approached as such. Taking the above together, this study aimed to assess the impact of supportive psychotherapy on reducing body weight in young overweight and obese women who attempted slimming therapy and, additionally, the possibility of maintaining the weight-loss effect in the long term. Sixty young women aged 20-30 were randomized into three groups that differed in therapeutic management. With the help of an individually selected diet plan, the highest effectiveness in weight loss was demonstrated in people whose weight reduction was supported by goal-oriented psychotherapy. In this group, a sustained effect of slimming and even further weight loss were observed six months following the discontinuation of the therapy. In conclusion, traditional slimming therapies using an individual diet plan and a dietitian's care are effective; however, supportive psychotherapeutic work provides more beneficial results and maintains the change from a long-term perspective.

Favipiravir (FPV) is a novel antiviral drug acting as a competitive inhibitor of RNA-dependent RNA polymerase (RdRp), preventing viral transcription and replication. FPV was approved in Japan in 2014 for therapy of influenza unresponsive to standard antiviral therapies. FPV was also used in the therapy of Ebola virus disease (EVD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we discuss the mechanisms of action, pharmacokinetic parameters, toxicity, and adverse effects of FPV, as well as clinical studies evaluating the use of FPV in the therapy of influenza virus (IV) infection, EVD, and SARS-CoV-2 infection, along with its effectiveness in treating other human RNA infections.

Adiponectin is the adipokine associated with insulin sensitization, reducing liver gluconeogenesis, and increasing fatty acid oxidation and glucose uptake. Adiponectin is present in the kidneys, mainly in the arterial endothelium and smooth muscle cells, as well as in the capillary endothelium, and might be considered as a marker of many negative factors in chronic kidney disease. The last few years have brought a rising body of evidence that adiponectin is a multipotential protein with anti-inflammatory, metabolic, anti-atherogenic, and reactive oxygen species (ROS) protective actions. Similarly, adiponectin has shown many positive and direct actions in kidney diseases, and among many kidney cells. Data from large cross-sectional and cohort studies showed a positive correlation between serum adiponectin and mortality in chronic kidney disease. This suggests a complex interaction between local adiponectin action, comorbidities, and uremic milieu. In this review we discuss the role of adiponectin in chronic kidney disease.

Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels. They participate in intercellular communication or communication between the intracellular and extracellular environments. Connexins affect cell homeostasis, growth and differentiation by enabling the exchange of metabolites or by interfering with various signalling pathways. Alterations in the functionality and the expression of connexins have been linked to the occurrence of many diseases. Connexins have been already linked to cancers, cardiac and brain disorders, chronic lung and kidney conditions and wound healing processes. Connexins have been shown either to suppress cancer tumour growth or to increase tumorigenicity by promoting cancer cell growth, migration and invasiveness. A better understanding of the complexity of cancer biology related to connexins and intercellular communication could result in the design of novel therapeutic strategies. The modulation of connexin expression may be an effective therapeutic approach in some types of cancers. Therefore, one important challenge is the search for mechanisms and new drugs, selectively modulating the expression of various connexin isoforms. We performed a systematic literature search up to February 2020 in the electronic databases PubMed and EMBASE. Our search terms were as follows: connexins, hemichannels, cancer and cancer treatment. This review aims to provide information about the role of connexins and gap junctions in cancer, as well as to discuss possible therapeutic options that are currently being studied.

Introduction: Coronary artery disease (CAD) is a significant public health problem because it is one of the major causes of death worldwide. Several studies have investigated the associations between CAD and polymorphisms in genes connected with platelet aggregation and the risk of venous thromboembolism., Aim: In this study, we examined the associations between polymorphisms in GP6 (rs1671152), PEAR1A (rs12566888), MRVI1 (rs7940646), PIK3CG (rs342286), JMJD1C (rs10761741), SHH (rs2363910), and CAD in the form of unstable angina as well as selected clinical and biochemical parameters. The study enrolled 246 patients with diagnosed unstable angina and 189 healthy controls., Results: There were no significant differences in the distribution of the studied polymorphisms between the patients with unstable angina and the controls. In patients with the GP6 rs1671152 GG genotype, we observed increased BMI values and an increased frequency of type 2 diabetes diagnosis., Conclusions: The results of this study suggest a lack of association between GP6 (rs1671152), PEAR1A (rs12566888), MRVI1 (rs7940646), PIK3CG (rs342286), JMJD1C (rs10761741), SHH (rs2363910), and unstable angina. The results indicate an association between GP6 (rs1671152) and type 2 diabetes., Competing Interests: The authors declare no conflict of interest.

Endocan, previously referred to as an endothelial-cell-specific molecule-1 (ESM-1) is a member of a proteoglycan family that is secreted by vascular endothelial cells of different organs, mainly lungs and kidneys. It is assumed to participate in endothelial activation and the triggering of inflammatory reactions, especially in microvasculatures. Thanks to its solubility in human fluids, i.e., urine and blood plasma, its stability and its low concentrations in physiological conditions, endocan has been proposed as an easily available, non-invasive biomarker for identifying and predicting the course of many diseases. Recently, endocan has been studied in relation to kidney diseases. In general, endocan levels have been linked to worse clinical outcomes of renal dysfunction; however, results are conflicting and require further evaluation. In this review, authors summarize available knowledge regarding the role of endocan in pathogenesis and progression of selected kidney diseases.

Insulin resistance (IR) is characterised by increased gluconeogenesis in the liver and the resistance of peripheral receptors to insulin. Several factors, including IR, type 2 diabetes, new-onset diabetes after transplant (NODAT) and secondary parathyroidism, are related to chronic kidney disease (CKD). These factors are associated with higher mortality due to the increased risk of cardiovascular complications. Many factors have been identified as potential markers of IR in CKD. These factors include fibroblast growth factors (FGFs), a subfamily of endocrine polypeptides. In this study, we examined the association of FGF19, FGF21 and FGF23 with selected parameters related to carbohydrate metabolism and insulin resistance in non diabetic patients with predialysis CKD and in non diabetic patients after renal transplantation. The study included 108 non diabetic subjects: 40 patients with predialysis CKD, 45 patients with CKD who had undergone renal transplantation, and 23 healthy subjects (control group). In patients who had undergone renal transplantation, concentrations of FGF23 were increased compared to the control group and patients with predialysis CKD. The highest and lowest FGF19 concentrations were observed in CKD patients and in patients who had undergone kidney transplantation, respectively. This difference was statistically significant. Leptin concentrations were higher in CKD patients compared to the control group and patients who had undergone kidney transplantation. There were no statistically significant differences in adiponectin concentrations, lean body mass or fat tissue mass between the studied groups. HOMA-IR and insulin levels were significantly increased in CKD patients and in patients who had undergone renal transplantation in comparison to the control group. The results of the study suggest the involvement of FGF in carbohydrate metabolism and insulin resistance in patients with predialysis CKD, as well as a correlation with kidney function., Competing Interests: The authors report no conflicts of interest in this work.

Background: Vascular endothelial growth factor-A (VEGF-A) is a protein that plays a role in the formation and function of blood vessels, promotes increased vascular permeability or migration of monocytes through endothelial layers. We have tested the hypothesis that plasma levels of VEGF-A may be associated with biochemical and radiological parameters as a marker of cardiovascular risk in Caucasian patients with early-onset CAD., Methods: The study group included 100 patients: 75 men not older than 50 years and 25 women not older than 55 years at the moment of CAD diagnosis. The control group (patients without CAD) comprised 50 healthy cases. ELISA test was used to measure plasma concentrations of VEGF. Doppler ultrasound of carotid and peripheral arteries was carried out in each patient. Serum glucose, complete lipid profile, ApoA1, ApoB, Lp(a) and blood count were measured in each case., Results: Only very weak correlations of plasma VEGF levels with biochemical cardiovascular risk factors in the CAD subjects have been demonstrated. In the study group, VEGF concentration was significantly positively correlated with the same blood parameters as white blood cells, platelets, plateletcrit, apolipoprotein B, total and LDL cholesterol fraction. The plaque of common carotid arteries and bifurcation was present in 39% of CAD patients, however, there was no significant association between VEGF plasma concentration and any measured parameters in Doppler ultrasound of carotid and peripheral arteries., Conclusions: The circulating VEGF is only marginally associated with an increased risk for atherosclerosis.

Allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein that is encoded by the AIF1 gene. The main functions of AIF-1 are the activation of macrophages and enhancing the production of pro-inflammatory cytokines. To date, three different AIF-1 isoforms have been identified. In this study, we examined the expression of AIF-1 isoforms on the level of mRNA, and we compared the percentage of AIF-1-positive white blood cells (WBCs) in blood and AIF-1/CD68 cells in the synovial membranes in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). We examined 15 patients with RA and 15 patients with OA who had previously undergone knee arthroplasty. Peripheral blood and synovial membranes (SMs) were collected from these patients during knee arthroplasty. We identified three AIF-1 mRNA expression variants in peripheral mononuclear cells (PBMCs) and SMs from patients in both groups. Spearman's rank correlation coefficient tests showed strong, positive, and significant correlations between the three AIF-1 mRNA expression variants in PBMCs and/or SMs in patients with RA and OA. There were no statistically significant correlations for any of the AIF-1 mRNA expression variants between PBMCs and SMs in patients with RA and OA. We observed a statistically significant increased percentage of AIF-1-positive cells in patients with RA in comparison to patients with OA. The percentage of AIF-1-positive cells in the blood of patients with RA and OA was 1.35 ± 0.81% and 0.71 ± 0.25% ( p < 0.01), respectively, whereas the percentage of AIF-1/CD68-positive WBC cells in the SMs was 24.05 ± 7.17% and 4.78 ± 1.52% ( p < 0.001), respectively. In conclusion, three AIF-1 mRNA expression variants occurred in PBMCs and SM cells in patients with RA and OA. The AIF-1 mRNA expression levels of the variants correlated with each other in PBMCs and SM cells, but there were no statistically significant correlations for AIF-1 mRNA expression variants between PBMCs and SM cells in patients with RA and OA. Both in the blood and SMs, we observed an increased percentage of AIF-1-positive cells in patients with RA in comparison to patients with OA. The above results suggested that AIF-1 was the cytokine involved in the pathogenesis of RA. The precise knowledge of the role of AIF-1 in RA pathogenesis and the development of inflammatory response requires further investigations.

A new approach to improve the effectiveness of acute myeloid leukemia (AML) treatment is to use the properties of purinergic signaling molecules secreted into the bone marrow milieu in response to leukemic cell growth. Therefore, our study aimed to evaluate the effects of extracellular adenine nucleotides and adenosine on the growth and death parameters in the leukemic THP-1 cell line. Cells were exposed to ATP, ADP, AMP, adenosine and nonhydrolyzable analogues of ATP and ADP (ATPγS and ADPβS) in a 1-1000 μM broad concentration range. The basal mRNA expression of the P1 and P2 receptors was evaluated by real-time PCR. Changes in the processes of cell growth and death were assessed by flow cytometry analysis of proliferation, cell cycle and apoptosis. Chemotaxis toward stromal cell-derived factor-1 (SDF-1) was performed using the modified Boyden chamber assay, and chemokine receptor type 4 (CXCR4) surface expression was quantified by flow cytometry. We indicated several antileukemic actions. High micromolar concentrations (100-1000 μM) of extracellular adenine nucleotides and adenosine inhibit the growth of cells by arresting the cell cycle and/or inducing apoptosis. ATP is characterized by the highest potency and widest range of effects, and is responsible for the cell cycle arrest and the apoptosis induction. Compared to ATP, the effect of ADP is slightly weaker. Adenosine mostly has a cytotoxic effect, with the induction of apoptosis. The last studied nucleotide, AMP, demonstrated only a weak cytotoxic effect without affecting the cell cycle. In addition, cell migration towards SDF-1 was inhibited by low micromolar concentrations (10 μM). One of the reasons for this action of ATPγS and adenosine was a reduction in CXCR4 surface expression, but this only partially explains the mechanism of antimigratory action. In summary, extracellular adenine nucleotides and adenosine inhibit THP-1 cell growth, cause death of cells and modulate the functioning of the SDF-1/CXCR4 axis. Thus, they negatively affect the processes that are responsible for the progression of AML and the difficulties in AML treatment.

Introduction: Rheumatoid arthritis (RA) is an important public health problem because this disease often causes disability. RA is a chronic, destructive autoimmune disease that leads to joint destruction and the development of extraarticular manifestations. VAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells and affects T cell development, proliferation and activation. The VAV1 gene contains 27 exons and is located on chromosome 19. In this study, we examined the association between VAV1 rs2546133 and rs2617822 polymorphisms and RA., Methods: We examined 422 patients with RA and 338 healthy subjects as the control group., Results: Among RA patients, there was a statistically significant increase in the frequency of VAV1 rs2546133 polymorphism in T allele carriers (TT + CT versus CC, odds ratio: 1.69, 95% confidence interval 1.05-2.73, p = 0.035). There was no statistically significant difference in the distribution of the rs2617822 genotypes and alleles between RA patients and the control group. Additionally, patients who carried the VAV1 rs2546133 T and rs2617822 G allele presented an increased frequency of extraarticular manifestations: vasculitis, amyloidosis and Sjogren syndrome., Conclusions: The results suggest an association between VAV1 gene rs2617822 polymorphism and RA., Competing Interests: The authors declare no conflict of interest.

Acute coronary syndrome occurs when the heart muscle does not receive adequate oxygen and nutrients in a timely manner. Acute coronary syndromes are primarily due to atherosclerosis of the coronary arteries, i.e., coronary heart disease. Nitric oxide (NO) is synthesised from L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme, nitric oxide synthase (NOS), which mediates endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) is predominantly expressed in endothelial cells. Three NOS isoforms have been detected in different tissue: (1) neuronal NOS (nNOS) (NOS1), (2) eNOS (NOS2), and (3) inducible NOS (iNOS) (NOS3). These isoforms are encoded by three different genes. NOS3 is located on chromosome 7q35-36 and contains 26 exons. Previous studies have suggested that NOS3 polymorphisms may be associated with acute coronary syndromes. Therefore, the aim of the study was to examine the associations between NOS3 rs1799983 (894G/T)andrs2070744 (-786T/C) polymorphisms and unstable angina. This study included 246 patients with unstable angina, as confirmed by coronary angiography. We also included 189 healthy controls who were also assessed by this technique. There were no significant differences in genotype distributions of NOS3 rs1799983and rs2070744 polymorphisms in patients with unstable angina and healthy controls in both univariate and multivariate analyses. In patients with the NOS3 rs1799983 TT genotype, we observed a higher BMI (TT vs. GT + GG, p = 0.068), and in patients with the NOS3 rs2070744 TT genotype, we observed a higher waist circumference (TT vs. TC + CC, p = 0.023; TT vs. CC, p = 0.0053). These data suggest a lack of association between the NOS3 rs1799983andrs2070744 polymorphisms and unstable angina in our patient population. However, these polymorphisms may be associated with some obesity parameters, rs1799983 in females and rs2070744 in males., (© 2020 S. Karger AG, Basel.)

Background and Objectives : Chronic kidney disease (CKD) is an important public health problem associated with, e.g., progressive renal insufficiency, bone mineral disorders, and increased inflammatory marker levels. The objective of this study was to compare selected biochemical parameters and to evaluate potential correlations between selected anthropometric parameters and levels of sclerostin and interleukin 6 (IL-6) in blood plasma. Materials and Methods : The study group consisted of 34 patients aged 59.8 ± 9.8 years, receiving hemodialysis therapy. The control group consisted of 31 individuals aged 55.4 ± 9.37 years, presenting with GFR (glomerular filtration rate) of more than 60 mL/min/1.73 m 2 . Selected anthropometric and biochemical parameters were assessed at baseline, as well as 3 and 6 months into the study. Statistical analyses were performed using the Statistica 2014 software package (StatSoft, Inc.Tulsa, OK, USA). Analyses included descriptive statistics, intergroup comparisons using the Mann-Whitney U-test or the Kruskal-Wallis test, and Spearman's correlation analysis. The significance level was set at p ≤ 0.005. Results : At all measurement time points, i.e., at baseline, at month 3, and at month 6, the IL-6 levels in the study group were significantly higher than those in the control group. No correlations were observed in the study group between SCL or IL-6 levels and anthropometric parameters such as body weight, body mass index (BMI), or waist circumference. Conclusions : Patients receiving hemodialysis replacement therapy present with significantly higher levels of IL-6 in their blood. Anthropometric parameters (body weight, BMI, and waist circumference) have no impact on sclerostin and IL-6 levels in patients undergoing hemodialysis therapy. The results obtained are satisfactory, and the research will be continued.

Introduction: Renalase is a novel flavin adenine dinucleotide-dependent amine oxidase with catecholamine-degrading activity. The kidneys are the main source of this enzyme., Objectives: In this study, we examined the concentrations of renalase in the serum, urine, and erythrocytes of patients with chronic kidney disease (CKD)., Patients and Methods: We enrolled 155 white patients with CKD and 30 healthy controls. Renalase concentrations were measured using an enzyme‑linked immunosorbent assay., Results: Serum renalase levels were higher in patients with CKD than in controls: median (Q1-Q3), 103 ng/ml (55.6-166 ng/ml) vs 17.7 ng/ml (16.3-21.8 ng/ml); P <0.001. Renalase levels in erythrocytes were lower in patients with CKD than in controls (median [Q1-Q3], 122 ng/ml [67.2-189 ng/ml] vs 254 ng/ml [166-293 ng/ml]; P <0.001). Urinary renalase levels did not differ between patients with CKD and controls (median [Q1-Q3], 147 ng/ml [102-193 ng/ml] vs 144 ng/ml [116-170 ng/ml]; P = 0.78). Urinary and erythrocyte renalase concentrations were negatively correlated with estimated glomerular filtration rate (eGFR). A multivariate general linear model analysis adjusted for age, sex, and eGFR of CKD patients showed that higher plasma dopamine and total protein concentrations were independent predictors of higher serum renalase levels (β = 0.32, P <0.001 and β = 0.25, P <0.001, respectively)., Conclusions: Our results indicate that serum renalase concentrations are elevated in patients with CKD, whereas renalase concentrations in urine and erythrocytes are correlated with impaired kidney function.

Background: Over the last two decades, many studies have investigated the association between interleukin 6 (IL-6) and pathogenesis and progression of coronary artery disease (CAD). Patients with CAD manifested at a young age are a particularly interesting group. They differ from older patients, not only in terms of the severity of coronary artery atherosclerosis, but also risk factor profiles, short- and long-term prognosis after myocardial infarction (MI). The role of IL-6 in younger patients with CAD is less well-known. Therefore, our study aimed to analyze the relationship between IL-6 level and other inflammations, atherosclerosis, and cardiac function parameters in early onset CAD patients., Methods: The study covered 100 patients with early onset CAD and a group of 50 healthy participants. Plasma levels of IL-6 and basic biochemical parameters, anthropometric, echocardiographic, and arteries Doppler ultrasound measurements were performed., Results: We did not observe a significant difference in IL-6 concentration in plasma between patients with early onset CAD and a control group, but IL-6 level was negatively correlated with echocardiographic measurements of ascending aorta diameter, left ventricular shortening fraction, and right ventricular end-diastolic diameter in our patients., Conclusions: In patients with early onset CAD, plasma IL-6 level is associated with other inflammation parameters and with cardiac function, potentially contributing to right ventricular remodeling and left ventricular systolic dysfunction. This suggests possible prognostic benefits of long-time observation of IL-6 level after the acute coronary syndrome.

Glomerulonephritis (GN) represents a collection of kidney diseases characterized by inflammation within the renal glomeruli and small blood vessels. The lesions that occur in other nephron structures mainly result from the harmful effects of proteinuria. In recent years, an emphasis has been placed on gaining a better insight into the pathogenesis and pathophysiology of GN in order to facilitate diagnoses and provide efficient and targeted treatments of the disease. Owing to the advanced molecular and genetic diagnostic techniques available today, researchers have been able to elucidate that most cases of GN are determined by genetic risk factors and are associated with the abnormal functioning of the immune system (the immunologically mediated forms of GN). MicroRNAs (miRNAs) are a group of single-stranded, non-coding molecules, approximately 20 nucleotides in length, that act as regulatory factors in the post-transcriptional processes capable of regulating the expression of multiple genes. In this paper we present the available research aiming to determine effects of miRNAs on the development and progression of GN and discuss the potential role of miRNAs as new diagnostic markers and therapeutic targets.

Gestational diabetes mellitus (GDM) is a carbohydrate intolerance that occurs in women during pregnancy. The aims of this study were to develop a model to predict the risk of GDM development using common clinical parameters and selected genetic polymorphisms and to analyse the performance of the model using receiver operator characteristic (ROC) curves. ROC analysis was used to examine whether the evaluation of genetic polymorphisms may enhance the accuracy of GDM prediction in comparison to using common clinical risk factors only. This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75 g oral glucose tolerance test at 24-28 weeks gestation. The difference between the AUC of ROC curves for the model 1 including only age and BMI and the model 2 also including 8 genetic polymorphisms was highly significant (p=0.0001) in favour of model 2 (0.090±0.023). Moreover, the additional use of 8 genetic polymorphisms may increase both the sensitivity and specificity of GDM prediction by 10%. The results of this study indicate that the use of 8 genetic polymorphisms associated with carbohydrate and lipid metabolism and type 2 diabetes [ PTGS2 ( COX2 ) rs6681231, FADS1 rs174550, HNF1B rs4430796, ADIPOQ rs266729, IL18 rs187238, CCL2 rs1024611, HHEX rs5015480 and CDKN2A/2B rs10811661] together with clinical risk factors (BMI and age) may significantly improve the prediction of GDM., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)