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One of the most common chronic liver disorders, affecting mainly people in Western countries, is nonalcoholic fatty liver disease (NAFLD). Unfortunately, its pathophysiological mechanism is not fully understood, and no dedicated treatment is available. Simple steatosis can lead to nonalcoholic steatohepatitis and even to fibrosis, cancer, and cirrhosis of the liver. NAFLD very often occurs in parallel with type 2 diabetes mellitus and in obese people. Furthermore, it is much more likely to develop in patients with metabolic syndrome (MS), whose criteria include abdominal obesity, elevated blood triacylglycerol level, reduced high-density lipoprotein cholesterol level, increased blood pressure, and high fasting glucose. An important phenomenon in MS is also insulin resistance (IR), which is very common in NAFLD. Liver IR and NAFLD development are linked through an interaction between the accumulation of free fatty acids, hepatic inflammation, and increased oxidative stress. The liver is particularly exposed to elevated levels of reactive oxygen species due to a large number of mitochondria in hepatocytes. In these organelles, the main DNA repair pathway is base excision repair (BER). The present article will illustrate how impairment of BER may be related to the development of NAFLD.

Urolithiasis is the third most common urological disease after urinary tract infections and prostate diseases, and it is characterised by an occurrence rate of about 15%, which continues to rise. The increase in the incidence of kidney stones observed in recent decades, is most likely caused by modifications in dietary habits (high content of protein, sodium and sugar diet) and lifestyle (reduced physical activity) in all industrialised countries. Moreover, men are more likely than women to be diagnosed with kidney stones. A growing body of evidence suggests that inflammation, oxidant–antioxidant imbalance, angiogenesis, purine metabolism and urea cycle disorders may play a crucial role in nephrolithiasis development. Patients with urolithiasis were characterised by an increased level of reactive oxygen species (ROS), the products of lipid peroxidation, proinflammatory cytokines as well as proangiogenic factors, compared to controls. Furthermore, it has been shown that deficiency and disorders of enzymes involved in purine metabolism and the urea cycle might be causes of deposit formation. ROS generation suggests that the course of kidney stones might be additionally potentiated by inflammation, purine metabolism and the urea cycle. On the other hand, ROS overproduction may induce activation of angiogenesis, and thus, allows deposit aggregation.

Urolithiasis is one of the most common urological diseases worldwide with an unclear aetiology. However, a growing body of evidence suggests the potential role of molecular disturbances of the inflammation as well as oxidative and nitrative stresses, in the pathogenesis of urolithiasis. Therefore, we aimed to detect the potential association between six selected single-nucleotide polymorphisms (SNPs) and the development of nephrolithiasis. Moreover, we verified the association of urolithiasis development and mRNA expression of IL-6 , IL-8 , SOD2 , and NOS2 in peripheral blood mononuclear cells (PBMCs). Total genomic DNA and mRNA were isolated from the peripheral blood of 112 patients with urolithiasis and 114 healthy subjects. Using Taq-Man® probes, we genotyped the following SNPs: rs1800797 and rs2069845 in IL-6 , rs2227307 in IL-8 , rs4880 in SOD2 , rs2297518 and rs2779249 in NOS2 . In turn, the evaluation of mRNA expression was performed using real-time PCR and 2 -ΔCt methods. We found that the C/T genotype of the c.47 T>C– SOD2 SNP increased the frequency of urolithiasis occurrence whereas the T/T homozygote of the same polymorphism decreased the risk of urolithiasis development in the Polish population. Moreover, our study confirmed that patients with urolithiasis were characterised by decreased IL-6 , IL-8 , and SOD2 mRNA expression levels compared to the controls. In conclusion, our results suggest that polymorphic variants and changes in mRNA expression of IL-6 , IL8 , SOD2 , and NOS2 may be involved in the pathophysiology of urolithiasis.

Bladder cancer (BC) is a severe health problem of the genitourinary system and is characterised by a high risk of recurrence. According to the recent GLOBOCAN report, bladder cancer accounts for 3% of diagnosed cancers in the world, taking 10th place on the list of the most common cancers. Despite numerous studies, the full mechanism of BC development remains unknown. Nevertheless, precious results suggest a crucial role of oxidative stress in the development of BC. Therefore, this study explores whether the c. 47 C > T (rs4880)— SOD2 , (c. 1823 C > T (rs2297518) and g.-1026 C > A (rs2779249)— NOS2(iNOS) polymorphisms are associated with BC occurrence and whether the bladder carcinogenesis induces changes in SOD2 and NOS2 expression and methylation status in peripheral blood mononuclear cells (PBMCs). In this aim, the TaqMan SNP genotyping assay, TaqMan Gene Expression Assay, and methylation‐sensitive high‐resolution melting techniques were used to genotype profiling and evaluate the expression of the genes and the methylation status of their promoters, respectively. Our findings confirm that heterozygote of the g.-1026 C > A SNP was associated with a decreased risk of BC. Moreover, we detected that BC development influenced the expression level and methylation status of the promoter region of investigated genes in PBMCs. Concluding, our results confirmed that oxidative stress, especially NOS2 polymorphisms and changes in the expression and methylation of the promoters of SOD2 and NOS2 are involved in the cancer transformation initiation of the cell urinary bladder.

Azurin is a copper-containing redox protein naturally produced by Pseudomonas aeruginosa, which has shown promising activity against human cancer cells by inducing apoptosis. The present study describes the design of a recombinant vector, pT7-MAT-Tag-2-Azu, for azurin production in E. coli cells. The cytotoxic effects of purified azurin were tested on three breast cancer cell lines (MCF-7, MDA-MB-231, and HCC38) and a normal breast epithelial cell line (MCF10A) using the MTT assay. The results showed cytotoxicity against cancer cell lines with minimal effects on normal cells. Further analysis showed that azurin induced apoptosis through mitochondrial pathways, as evidenced by increased expression of apoptosis-related genes (Bax, TP53, Apaf-1, caspase-3, -8, -9) and their corresponding proteins, elevated levels of reactive oxygen species (ROS), and DNA damage, mitochondrial membrane potential (MMP), or brine shrimp lethality assay. Furthermore, in silico molecular docking, simulations predicted a stable, electrostatically driven interaction between azurin and the p53 protein, providing a structural basis for its mechanism of action. These findings suggest that recombinant azurin may serve as a potential therapeutic agent for breast cancer after further multifaceted research.

RationaleN−3 polyunsaturated fatty acids (n−3 PUFA) influence multiple biochemical mechanisms postulated in the pathogenesis of schizophrenia that may influence BDNF synthesis.ObjectivesA randomized placebo-controlled study was designed to compare the efficacy of a 26-week intervention composed of either 2.2 g/day of n−3 PUFA or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. The secondary outcome measure of the study was to describe the association between n−3 PUFA clinical effect and changes in peripheral BDNF levels.MethodsSeventy-one patients aged 16–35 were enrolled in the study and randomly assigned to the following study arms: 36 to the EPA + DHA group and 35 to the placebo group. Plasma BDNF levels were assessed three times, at baseline and at weeks 8 and 26 of the intervention. BDNF levels were determined in plasma samples using Quantikine Human BDNF ELISA kit. Plasma BDNF level changes were further correlated with changes in the severity of symptoms in different clinical domains.ResultsA significantly greater increase in plasma BDNF levels was observed in the intervention compared to the placebo group (Cohen’s d = 1.54). Changes of BDNF levels inversely correlated with change in depressive symptoms assessed using the Calgary Depression Rating Scale in Schizophrenia (Pearson’s r = − 0.195; p = 0.018).ConclusionsThe efficacy of a six-month intervention with n−3 PUFA observed in first-episode schizophrenia may be related to an increase in BDNF levels, which may be triggered by the activation of intracellular signaling pathways including transcription factors such as cAMP-reactive element binding protein.

Breast cancer is associated with high mortality and morbidity rates. As about 20–30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from L. plantarum and L. rhamnosus cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine–hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics’ potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.

How we deal with stress and certain traits of our personality can be influenced not only by psycho-social factors, but also by biological factors, including genetics. Research studies suggest that the long allele of the DRD4 gene (DRD4-7R) is associated with novelty seeking and risk taking—features potentially important for healthcare workers. The aim of this study was to assess the DRD4-7R polymorphism and its impact on propensity for risk taking and ways of coping with stress in medical professionals This preliminary study involved 82 volunteers from among active healthcare professionals, including 33 medical doctors (MDs). All participants were asked to fill out psychological questionnaires for assessment of their stress-coping strategies (Mini-COPE) and risk-taking propensity (IVE). A swab of the inside of the cheek was taken from the study participants to determine the polymorphism within the gene for the dopamine D4 receptor gene (DRD4). In our study, medical doctors (MDs) tend to have the DRD4-7R allele more often than other medical professionals. Our study also indicates that DRD4-R7 allele carriers are significantly less likely to use stimulants and other substances to help themselves with stress coping and less likely to expect emotional support. The DRD4 gene polymorphism may be important for the development of specific personality traits and ways of coping with stress. However, further research with larger numbers of participants is needed.

An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools. This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model. The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling. A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, the mean number of correct responses was 9.0 (95% CI 8.9-9.1). Health service users performed worse than social networking users by 2.3 points (95% CI 2.1-2.5) in an analysis adjusted for potential confounders. Internet users had fewer true beliefs about DS if they presented higher trust in their advertising (adjusted β=-.37; 95% CI -.39 to -.34), used DS (adjusted β=-.14; 95% CI -.17 to -.12), experienced their positive effect (adjusted β=-.16; 95% CI -.18 to -.13), were older or younger than 35 years (adjusted β=-.14; 95% CI -.17 to -.12), expressed interest in the topic of DS (adjusted β=-.10; 95% CI -.13 to -.08), reported getting information about the products from friends (adjusted β=-.13; 95% CI -.15 to -.11), and believed that medicines are harmful (adjusted β=-.12; 95% CI -.15 to -.10). The proposed 5-predictor model could explain 31.2% of the variance in knowledge about DS. The model appeared resistant to overfitting and was able to forecast most of the observed associations. Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.

p53 constitutes an extremely versatile molecule, primarily involved in sensing the variety of cellular stresses. Functional p53 utilizes a plethora of mechanisms to protect cell from deleterious repercussions of genotoxic insults, where senescence deserves special attention. While the impressive amount of p53 roles has been perceived solely by the prism of antioncogenic effect, its presence seems to be vastly connected with metabolic abnormalities underlain by cellular aging, obesity, and inflammation. p53 has been found to regulate multiple biochemical processes such as glycolysis, oxidative phosphorylation, lipolysis, lipogenesis, β-oxidation, gluconeogenesis, and glycogen synthesis. Notably, p53-mediated metabolic effects are totally up to results of insulin action. Accumulating amount of data identifies p53 to be a factor activated upon hyperglycemia or excessive calorie intake, thus contributing to low-grade chronic inflammation and systemic insulin resistance. Prominent signs of its actions have been observed in muscles, liver, pancreas, and adipose tissue being associated with attenuation of insulin signalling. p53 is of crucial importance for the regulation of white and brown adipogenesis simultaneously being a repressor for preadipocyte differentiation. This review provides a profound insight into p53-dependent metabolic actions directed towards promotion of insulin resistance as well as presenting experimental data regarding obesity-induced p53-mediated metabolic abnormalities.