Association of Three Genetic Loci with Molar Incisor Hypomineralization in Polish Children.

BACKGROUND: Molar incisor hypomineralization (MIH) is a qualitative, demarcated enamel defect of hypomineralization affecting one to four first permanent molars, often with incisor involvement. Its etiology is complex. However, evidence suggests the influence of genetic factors, potentially including the single nucleotide polymorphisms (SNPs) rs2889956, rs4811117 and rs13058467, which were previously linked to MIH in a genome-wide association study of German children. The aim was to replicate analyses of possible associations between the SNPs and molar incisor hypomineralization in Polish children. METHODS: The final study group consisted of 778 children aged 126-168 months old. Saliva samples were taken, and genomic DNA was extracted and genotyped using beadchip microarrays. RESULTS: Among the 778 subjects, there were 68 (8.7%) subjects with MIH and 710 (91.3%) subjects without MIH. There were no significant differences in distributions in age, sex, or the frequency of caries in permanent dentition between the MIH and non-MIH groups. The rs2889956, rs4811117, and rs13058467 genotype distributions in the studied group conformed to the expected Hardy-Weinberg equilibria, and there were no significant differences in the distributions of their alleles or genotypes between the MIH and non-MIH groups. CONCLUSION: Our replication study did not confirm highly significant associations between the single nucleotide polymorphisms rs2889956, rs4811117, and rs13058467 with molar incisor hypomineralization in Polish children.

rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population.

There is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m2: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10-5; beta: - 0.0458, 95% confidence interval (CI) - 0.0732 : - 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10-4; beta: - 0.0573, CI - 0.0947 : - 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.

The Impact of Different Types of Physical Effort on the Expression of Selected Chemokine and Interleukin Receptor Genes in Peripheral Blood Cells.

This study aimed to assess the post-effort transcriptional changes of selected genes encoding receptors for chemokines and interleukins in young, physically active men to better understand the immunomodulatory effect of physical activity. The participants, aged 16-21 years, performed physical exercise tasks of either a maximal multistage 20 m shuttle-run test (beep test) or a repeated speed ability test. The expression of selected genes encoding receptors for chemokines and interleukins in nucleated peripheral blood cells was determined using RT-qPCR. Aerobic endurance activity was a positive stimulant that induced increased expression of CCR1 and CCR2 genes following lactate recovery, while the maximum expression of CCR5 was found immediately post-effort. The increase in the expression of inflammation-related genes encoding chemokine receptors triggered by aerobic effort strengthens the theory that physical effort induces sterile inflammation. Different profiles of studied chemokine receptor gene expression induced by short-term anaerobic effort suggest that not all types of physical effort activate the same immunological pathways. A significant increase in IL17RA gene expression after the beep test confirmed the hypothesis that cells expressing this receptor, including Th17 lymphocyte subsets, can be involved in the creation of an immune response after endurance efforts.

Association of the rs3039851 Insertion/Deletion in the Gene PPP3R1, Which Encodes the Regulatory Calcineurin Subunit B Type 1, with Left Ventricular Mass in Polish Full-Term Newborns.

BACKGROUND: The five base-pair (bp) insertion/deletion (rs3039851) polymorphism in the PPP3R1 gene, which encodes calcineurin subunit B type 1, has been found to be associated with left ventricular hypertrophy (LVH) in hypertensive patients and in athletes. The aim of this study is to analyze the possible association between PPP3R1:rs3039851 polymorphism and left ventricular mass (LVM) in full-term healthy newborns. METHODS: The study group consisted of 162 consecutive, full-term, healthy newborns. Two-dimensional M-mode echocardiography was used to assess LVM. The PPP3R1:rs3039851 polymorphism was identified by PCR-RFLP in genomic DNA extracted from cord blood leukocytes. RESULTS: No significant differences were found between newborns homozygous for the reference allele (5I/5I, n = 135) and newborns carrying at least one 5D allele (n = 27) for LVM standardized for body mass, body length or body surface area (LVM/BM, LVM/BL or LVM/BSA, respectively). However, the frequency of PPP3R1:rs3039851 genotypes with a 5D allele (5I/5D + 5D/5D) among newborns with the largest LVM/BM or LVM/BSA (upper tertile) was statistically significantly higher compared with the prevalence in individuals with the lowest values of both indices (lower tertile). CONCLUSIONS: Our results suggest that the PPP3R1:rs3039851 polymorphism may contribute to subtle variation in left ventricular mass at birth.

Molecular analysis and comparison of CD34+ and CD133+ very small embryonic-like stem cells purified from umbilical cord blood.

Very small embryonic like stem cells (VSELs) are a dormant population of stem cells that, as proposed, are deposited during embryogenesis in various tissues, including bone marrow (BM). These cells are released under steady state conditions from their tissue locations and circulate at a low level in peripheral blood (PB). Their number increases in response to stressors as well as tissue/organ damage. This increase is evident during neonatal delivery, as delivery stress prompts enrichment of umbilical cord blood (UCB) with VSELs. These cells could be purified from BM, PB, and UCB by multiparameter sorting as a population of very small CXCR4+ Lin- CD45- cells that express the CD34 or CD133 antigen. In this report, we evaluated a number of CD34+ Lin- CD45- and CD133+ Lin- CD45- UCB-derived VSELs. We also performed initial molecular characterization of both cell populations for expression of selected pluripotency markers and compared these cells at the proteomic level. We noticed that CD133+ Lin- CD45- population is more rare and express, at a higher level, mRNA for pluripotency markers Oct-4 and Nanog as well as the stromal-derived factor-1 (SDF-1) CXCR4 receptor that regulates trafficking of these cells, however both cells population did not significantly differ in the expression of proteins assigned to main biological processes.

Metabolomic Analysis of Respiratory Epithelial Lining Fluid in Patients with Chronic Obstructive Pulmonary Disease-A Systematic Review.

Chronic obstructive pulmonary disease (COPD), as the third leading cause of death among adults, is a significant public health problem around the world. However, about 75% of smokers do not develop the disease despite the severe smoking burden. COPD is a heterogeneous disease, and several phenotypes, with differences in their clinical picture and response to treatment, have been distinguished. Metabolomic studies provide information on metabolic pathways, and therefore are a promising tool for understanding disease etiopathogenesis and the development of effective causal treatment. The aim of this systematic review was to analyze the metabolome of the respiratory epithelial lining fluid of patients with COPD, compared to healthy volunteers, refractory smokers, and subjects with other lung diseases. We included observational human studies. Sphingolipids, phosphatidylethanolamines, and sphingomyelins distinguished COPD from non-smokers; volatile organic compounds, lipids, and amino acids distinguished COPD from smokers without the disease. Five volatile organic compounds were correlated with eosinophilia and four were associated with a phenotype with frequent exacerbations. Fatty acids and ornithine metabolism were correlated with the severity of COPD. Metabolomics, by searching for biomarkers and distinguishing metabolic pathways, can allow us to understand the pathophysiology of COPD and the development of its phenotypes.

Empirical investigations into Kruskal-Wallis power studies utilizing Bernstein fits, simulations and medical study datasets.

Bernstein fits implemented into R allow another route for Kruskal-Wallis power-study tool development. Monte-Carlo Kruskal-Wallis power studies were compared with measured power, a Monte-Carlo ANOVA equivalent and with an analytical method, with or without normalization, using four simulated runs, each with 60-100 populations (each population with N = 30,000 from a set of Pearson-type ranges): random selection gave 6300 samples analyzed for predictive power. Three medical-study datasets (Dialysis/systolic blood pressure; Diabetes/sleep-hours; Marital-status/high-density-lipoprotein cholesterol) were also analyzed. In three from four simulated runs (run_one, run_one_relaxed, and run_three) with Pearson types pooled, Monte-Carlo Kruskal-Wallis gave predicted sample sizes significantly slightly lower than measured but more accurate than with ANOVA methods; the latter gave high sample-size predictions. Populations (run_one_relaxed) with ANOVA assumptions invalid gave Kruskal-Wallis predictions similar to those measured. In two from three medical studies, Kruskal-Wallis predictions (Dialysis: similar predictions; Marital: higher than measured) were more accurate than ANOVA (both higher than measured) but in one (Diabetes) the reverse was found (Kruskal-Wallis: lower; Monte-Carlo ANOVA: similar to measured). These preliminary studies appear to show that Monte-Carlo Kruskal-Wallis power studies, based on Bernstein fits, might perform better than ANOVA equivalents in many settings (and provide reasonable results when ANOVA cannot be used); and both Monte-Carlo methods appeared to be considerably more accurate than the analytical version analyzed.

Effect of Polyphenols and Zinc Co-Supplementation on the Development of Neoplasms in Rats with Breast Cancer.

The aim of the study was to evaluate the effect of selected polyphenolic compounds: epicatechin, apigenin, and naringenin, administered separately or in combination with zinc (Zn), on the growth and development of the neoplastic process induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rats. The impact of supplementation with the above-mentioned compounds on the content of modified derivatives: 1-methyladenosine, N6-methyl-2'-deoxyadenosine, O-methylguanosine, 7-methylguanine, 3-methyladenine, 1-methylguanine, 2-amino-6,8-dihydroxypurine, and 8-hydroxy-2'-deoxyguanosine in the urine of rats with mammary cancer was also assessed. Female Sprague-Dawley rats divided into 7 groups were used in the study: animals without supplementation and animals supplemented with apigenin, epicatechin, and naringenin separately or in combination with zinc. To induce mammary cancer, rats were treated with DMBA. Modified derivatives were determined by a validated high-performance liquid chromatography coupled to mass spectrometry method. Based on the obtained results, it can be said that supplementation of the animals with naringenin inhibits the development and progression of the neoplastic process in rats treated with 7,12-dimethylbenzanthracene. Neoplastic tumors were found in only 2 of 8 rats (incidence: 25%) and were considered to be at most grade 1 malignancy. The first palpable tumors in the group of animals receiving naringenin appeared two-three weeks later when compared to other groups. The combination of zinc with flavonoids (apigenin, epicatechin, and naringenin) seems to stimulate the process of carcinogenesis. The level of N6-methyl-2'-deoxyadenosine and 3-methyladenine in the urine of rats was statistically significantly higher in the groups supplemented with apigenin, epicatechin, and naringenin administered in combination with Zn than in the groups receiving only polyphenolic compounds. In conclusion, supplementation of rats with selected flavonoids administered separately or in combination with Zn has an impact on the development of neoplasms and the level of modified nucleosides in the urine of rats with breast cancer. Our results raise the question of whether simultaneous diet supplementation with more than one anti-cancer agent may reduce/stimulate the risk of carcinogenesis.

The Nox2-ROS-Nlrp3 Inflammasome Signaling Stimulates in the Hematopoietic Stem/Progenitor Cells Lipogenesis to Facilitate Membrane Lipid Raft Formation.

Proliferation, metabolism, and migration of hematopoietic stem/progenitor cells (HSPCs) are coordinated by receptors expressed on outer cell membranes that are integrated into microdomains, known as membrane lipid rafts (MLRs). These structures float freely in the cell membrane bilayer and are enriched in cholesterol and sphingolipids for their functional integrity. Receptors, if expressed in MLRs, have prolonged occupancy on the cell surface and enhanced signaling power. Based on this, we have become interested in the regulation of synthesis of MLRs components in HSPCs. To address this, we tested the effect of selected factors that promote proliferation or migration and their potential involvement in the synthesis of MLRs components in HSPCs. Based on our previous research showing that HSPCs from Nox2-KO and Nlrp3-KO mice display a profound defect in MLRs formation, we focused on the role of Nox2-ROS-Nlrp3 inflammasome in regulating lipogenesis in HSPCs. We found that while at steady state conditions, Nox2-derived ROS is required for a proper expression of enzymes regulating lipogenesis, during inflammation, this effect is augmented by Nlrp3 inflammasome. Thus, our data sheds new light on the regulation of lipogenesis in HSPCs and the involvement of the Nox2-ROS-Nlrp3 inflammasome axis that differently regulates lipogenesis at steady state conditions and in response to inflammation, modulating MLRs-mediated responsiveness of these cells to external stimuli.

Anticancer activity and metabolic alteration in colon and prostate cancer cells by novel moxifloxacin conjugates with fatty acids.

The positive and pro-economic trend in the management of cancer treatment is the search for the antineoplastic potential of known, widely used and safe drugs with a different clinical purpose. A good candidate seems to be moxifloxacin with broad-spectrum antibacterial activity, which as the member of the fourth generation fluoroquinolone is known to affect not only bacterial but also eukaryotic DNA topoisomerases, however at high concentration. Due to the fact that the modification of parent drug with lipid component can improve anticancer potential by increasing of bioavailability, selectivity, and cytotoxic efficiency, we evaluated the mechanisms of cytotoxic activity of novel moxifloxacin conjugates with fatty acids and verified metabolic profile in SW480, SW620 and PC3 cell lines. Our study revealed that cytotoxic potential of moxifloxacin conjugates was stronger than free moxifloxacin, moreover, they remained non-toxic to normal HaCaT cells. PC3 were more sensitive to MXF conjugates than colon cancer cells. The most promising cytotoxic activity exhibited conjugate 4m and 16m with oleic and stearic acid reducing viability of PC3 and SW620 cells. Tested conjugates activated caspases 3/7 and induced late-apoptosis, mainly in PC3 and SW620 cells. However, the most pronounced inhibition of NF-κB activation and IL-6 secretion was observed in SW480. Metabolomic analysis indicated influence of the moxifloxacin conjugates on intensity of lipid derivatives with the most successful metabolite profile in PC3. Our findings suggested the cytotoxic potential of moxifloxacin conjugates, especially with oleic and stearic acid can be beneficial in oncological therapy, including their possible anti-inflammatory and known antibacterial effect.

Proteomic Analysis of Murine Bone Marrow Very Small Embryonic-like Stem Cells at Steady-State Conditions and after In Vivo Stimulation by Nicotinamide and Follicle-Stimulating Factor Reflects their Germ-Lineage Origin and Multi Germ Layer Differentiation Potential.

Very small embryonic-like stem cells (VSELs) are a dormant population of development early stem cells deposited in adult tissues that as demonstrated contribute to tissue/organ repair and regeneration. We postulated developmental relationship of these cells to migrating primordial germ cells (PGCs) and explained the quiescent state of these cells by the erasure of differently methylated regions (DMRs) at some of the paternally imprinted genes involved in embryogenesis. Recently, we reported that VSELs began to proliferate and expand in vivo in murine bone marrow (BM) after exposure to nicotinamide (NAM) and selected pituitary and gonadal sex hormones. In the current report, we performed proteomic analysis of VSELs purified from murine bone marrow (BM) after repeated injections of NAM + Follicle-Stimulating Hormone (FSH) that in our previous studies turned out to be an effective combination to expand these cells. By employing the Gene Ontology (GO) resources, we have performed a combination of standard GO annotations (GO-CAM) to produce a network between BM steady-state conditions VSELs (SSC-VSELS) and FSH + NAM expanded VSELs (FSH + NAM VSELs). We have identified several GO biological processes regulating development, organogenesis, gene expression, signal transduction, Wnt signaling, insulin signaling, cytoskeleton organization, cell adhesion, inhibiting apoptosis, responses to extra- and intracellular stimuli, protein transport and stabilization, protein phosphorylation and ubiquitination, DNA repair, immune response, and regulation of circadian rhythm. We report that VSELs express a unique panel of proteins that only partially overlapped with the proteome of BM - derived hematopoietic stem cells (HSCs) and hematopoietic mononuclear cells (MNCs) and respond to FSH + NAM stimulation by expressing proteins involved in the development of all three germ layers. Thus, our current data supports further germ-lineage origin and multi germ layer differentiation potential of these cells.

Toll-like receptor polymorphisms (TLR2 and TLR4) association with the risk of infectious complications in cardiac surgery patients.

BACKGROUND: Postoperative infection is a common healthcare-associated problem, and unfortunately, a serious complication in cardiac surgery patients. Toll-like receptors (TLRs) are crucial in activating non-specific immunity mechanisms and integrating elements of the immune system, due to interactions between specific and non-specific responses. OBJECTIVES: In this study, the association of TLR2 or TLR4 with the risk of postoperative infections in cardiac surgery patients undergoing a coronary artery bypass grafting (CABG) procedures was investigated. MATERIAL AND METHODS: Our research was carried out on a cohort of 299 consecutive adult patients with ischemic heart disease (IHD) who underwent a planned CABG procedure. These patients were monitored for the presence of a postoperative infection over a 30-day observation period. All patients were investigated for 2 TLR2 gene mutations - R753Q (rs5743708) and T16934A (rs4696482), and 2 polymorphisms of the TLR4 gene - D299G (rs4986790) and T399I (rs4986791). The final stage of the study was an evaluation of the hypothetical association between TLR2 and TLR4 gene variances and postoperative infections in patients undergoing CAGB procedures. RESULTS: The prevalence of infections in the final cohort was 15.3% (46/299). The most common infections were surgical site infections, which were diagnosed in 21 patients (45.6%), bloodstream infections in 15 patients (32.6%) and pneumonia in 10 patients (21.8%). Logistic regression demonstrated that the presence of the AG+GG of D299G (rs4986790) and CT+TT of T399I (rs4986791) variants was related to a higher incidence of infection in patients undergoing CAGB procedures. CONCLUSIONS: To our knowledge, this is the first study of its kind to demonstrate that TLR2 and TLR4 mutations affect the risk of post-CABG infections. Being a carrier of the AG+GG of D299G (rs4986790) or CT+TT of T399I (rs4986791), TLR4 variants constitute a postoperative risk factor for infection in patients undergoing CAGB procedures.

Functional Polymorphism in the ADRB3 Gene, Encoding the Beta-3 Adrenergic Receptor, and Response to Intra-Detrusor Injection of Botulinum Toxin-A in Women with Overactive Bladder.

BACKGROUND: There are reports suggesting an association between the rs4994 polymorphism in the ADRB3 gene encoding the beta-3 adrenergic receptor and OAB risk in females. The injection of botulinum toxin-A into the bladder wall is recommended as a possible treatment for OAB patients in whom first-line therapies have failed. The aim of our study was to analyze the possible association between the ADRB3:rs4994 polymorphism and the patient-perceived response to a single intra-detrusor injection of botulinum toxin-A in Polish women with overactive bladder. METHODS: The study group consisted of 115 consecutive female patients with OAB. The response to botulinum toxin-A was evaluated at three months after injection, as absolute or relative reductions in OAB symptoms or in scores from questionnaires ICIQ-OAB (parts A and B) and ICIQ-LUTS-QoL (parts A and B). ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs. RESULTS: There were no statistically significant differences between ADRB3:rs4994 [T];[T] homozygotes and [T];[C]+[C];[C] subjects for absolute or relative reductions in symptoms or in scores from all four questionnaire parts at three months after the injection of botulinum toxin-A. CONCLUSIONS: Our results do not support the hypothesis that ADRB3:rs4994 polymorphism is associated with the response to the intra-detrusor injection of botulinum toxin-A in Polish females with overactive bladder.

Association studies between chromosomal regions 1q21.3, 5q21.3, 14q21.2 and 17q21.31 and numbers of children in Poland.

Number of children is an important human trait and studies have indicated associations with single-nucleotide polymorphisms (SNPs). Aim: to give further evidence for four associations using a large sample of Polish subjects. Data from the POPULOUS genetic database was provided from anonymous, healthy, unrelated, Polish volunteers of both sexes (N = 5760). SNPs (n = 173) studied: (a) 69 from the chromosome 17 H1/H2 inversion; (b) six from 1q21.3, 5q21.3 and 14q21.2; and (c) 98 random negative controls. Zero-inflated negative-binomial regression (z.i.) was performed (0-3 numbers of children per individual (NCI) set as non-events; adjustors: year of birth, sex). Significance level p = 0.05 with Bonferroni correction. Statistically-significant differences (with data from both sexes combined) were obtained from highly-linked inversion SNPs: representative rs12373123 gave means: homozygotes TT: 2.31 NCI (n = 1418); heterozygotes CT: 2.35 NCI (n = 554); homozygotes CC: 2.44 NCI (n = 43) (genotype p = 0.01; TTvs.CC p = 0.004; CTvs.CC p = 0.009). (Male data alone gave similar results.) Recessive modeling indicated that H2-homozygotes had 0.118 more children than H1-homozygotes + heterozygotes (z.i.-count estimates ± standard errors: CT, - 0.508 ± 0.194; TT, - 0.557 ± 0.191). The non-over-dispersed count model detected no interactions: of importance there was no significant interaction with age. No positive results were obtained from negative-control SNPs or (b). Conclusions: association between the H1/H2 inversion and numbers of children (previously reported in Iceland) has been confirmed, albeit using a different statistical model. One limitation is the small amount of data, despite initially ~ 6000 subjects. Causal studies require further investigation.

Contributing Factors to Sensorimotor Adaptability in Reactive Agility Performance in Youth Athletes.

Sensorimotor adaptability facilitates adjusting behaviour for changing environmental stimuli to maintain appropriate goal-directed motor performance. Its effectiveness is associated with perceptual-cognitive modulation. As the factors affecting it are still not completely known, the aim of our study was therefore to analyse the association between selected variables (demographic, training, anthropometric, genetic) and sensorimotor adaptation in reactive agility tasks in youth team-sport athletes. The study group consisted of 85 youth athletes (aged 12.61 ± 0.98 years). Based on an initial evaluation, participants were divided into faster and slower agility groups. The resultant differences between change of direction speed tests and reactive agility tests provided the REAC-INDEX as a dependent variable. The independent variables were as follows: gender, calendar age, body mass, height, BMI, maturity offset, training status and the BDNF rs6265 polymorphism. Multiple linear regression showed that the maturity offset (ß = 0.269; p = 0.012) and calendar age (ß = -0.411; p < 0.001) significantly contributed to the REAC-INDEX of all participants (R2 = 0.13). In the slower group, the c.196G BDNF allele had a significant influence (ß = -0.140; p = 0.044) on the REAC-INDEX. The best predictive model comprised female gender (ß = 0.799; p < 0.001), maturity offset (ß = -0.586; p < 0.001) and training experience (ß = -0.225; p = 0.009), contributing to 49% of RA variance. Sensorimotor adaptability is mainly dependent on gender and age, and can be improved through systematic sports training. The BDNF rs6265 polymorphism may be considered a contributing factor to SA variability in the initial stages of training, although polymorphism-related differences blurred as the effect of participation in sports training increased.

Association of Polymorphism within the Putative miRNA Target Site in the 3'UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder.

The study aims at looking into associations between the polymorphism rs6276 that occurs in the putative miRNA target site in the 3'UTR region of the DRD2 gene in patients with substance use disorder (SUD) comorbid with a maniacal syndrome (SUD MANIA). In our study, we did not state any essential difference in DRD2 rs6276 genotype frequencies in the studied samples of SUD MANIA, SUD, and control subjects. A significant result was found for the SUD MANIA group vs. SUD vs. controls on the Neuroticism Scale of NEO FFI test, and DRD2 rs6276 (p = 0.0320) accounted for 1.7% of the variance. The G/G homozygous variants were linked with lower results on the neuroticism scale in the SUD MANIA group because G/G alleles may serve a protective role in the expression of neuroticism in patients with SUD MANIA. So far, there have been no data in the literature on the relationship between the miRSNP rs6276 region in the DRD2 gene and neuroticism (personal traits) in patients with a diagnosis of substance use disorder comorbid with the affective, maniacal type disturbances related to SUD. This is the first report on this topic.

The Genetic Variants in the Renin-Angiotensin System and the Risk of Heart Failure in Polish Patients.

(1) Background: Heart failure (HF) is a complex disease and one of the major causes of morbidity and mortality in the world. The renin-angiotensin system (RAS) may contribute to the pathogenesis of HF. (2) Aim: To investigate the association of RAS key genetic variants, rs5051 (A-6G) in the gene encoding angiotensinogen (AGT), rs4646994 (I/D) in the gene for angiotensin I converting enzyme (ACE), and rs5186 (A1166C) in the gene encoding type 1 receptor for angiotensin II (AGTR1), with the HF risk in the cohort of Polish patients. (3) Methods: The study group consisted of 415 patients that were diagnosed with HF, while the control group comprised of 152 healthy individuals. Genomic DNA were extracted from blood and genotyping was carried out using either PCR or PCR-RFLP for ACE or AGT and AGTR1 variants, respectively. (4) Results: No association has been found between the I/D ACE and heart failure. The HF risk was significantly higher for AG AGT heterozygotes (overdominance: AG versus AA + GG) and for carriers of the G AGT allele in codominant and dominant modes of inheritance. However, the risk of HF was significantly lower in the carriers of at least one C AGTR1 allele (AC or CC genotypes) or in AC AGTR1 heterozygotes (overdominant mode). There was a significant relationship for AGT and HF patients in NYHA Class I-II for whom the risk was higher for the carriers of the G allele, and for the AG heterozygotes. There was also a significant interaction between heterozygote advantage of AGT and BMI increasing the risk for HF. (5) Conclusion: Our results suggest that the A(-6)G AGT polymorphism may be associated with HF in the Polish population and the HF risk seems to be modulated by the A1166C AGTR1 polymorphism.

Capillary Blood Recovery Variables in Young Swimmers: An Observational Case Study.

Sport diagnostics is still in pursuit of the optimal combination of biochemical and hematological markers to assess training loads and the effectiveness of recovery. The biochemical and hematological markers selected for a panel should be specific to the sport and training program. Therefore, the aim of this study was to evaluate the usefulness of selected biochemical and hematological variables in professional long-distance and sprint swimming. Twenty-seven participants aged 15-18 years took part in the study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activities and creatinine (Cr), C-reactive protein (CRP), ferritin, total bilirubin (TB), direct bilirubin (DB) and iron concentrations were measured for 10 weeks and compared with the traditional sport diagnostic markers of creatine kinase (CK) activity and urea (U) concentration. Additionally, capillary blood morphology was analyzed. An effective panel should consist of measurements of CK and AST activities and urea, TB, DB and ferritin concentrations. These markers provide a good overview of athletes' post-training effort changes, can help assess the effectiveness of their recovery regardless of sex or competitive distance and are affordable. Moreover, changes in ferritin concentration can indicate inflammation status and, when combined with iron concentration and blood morphology, can help to avoid iron deficiencies, anemia and adverse inflammatory states in swimmers.

Dietary Inclusion of Dried Chicory Root Affects Cecal Mucosa Proteome of Nursery Pigs.

Prebiotics are known to have many beneficial effects on intestinal health by modulating the gut microbiota composition, thereby affecting epithelial cell proliferation and metabolism. This study had two aims: (1) to identify the protein constituents in the cecal mucosa of 50-day-old healthy (PIC × Penarlan P76) barrows, and (2) to assess the effects of 4% inclusion of dried chicory root in a cereal-based diet on the cecal mucosa proteome changes. Pigs (eight per group) were randomly allotted to the groups and were fed a control diet from the tenth day of life (C) or a diet supplemented with 4% of died chicory root (CR), for 40 days. At the age of 50 days, animals were sacrificed and cecal tissue samples were collected. It was found that feeding a CR diet significantly decreased the expression of 16 cecal mucosa proteins. Among them, fifteen proteins were down-regulated, while only one (KRT20) was shown to be up-regulated when compared to the C group. Dietary supplementation with CR caused down-expression of metabolism-associated proteins including enzymes involved in the process of glycolysis (G6PD, TPI1, ALDH9A1, CKMT1 and AKR1A1) as well as those engaged in transcriptional and translational activity (PRPF19, EEF1G) and several structural proteins (ACTR3, KRT77, CAP1 and actin). From our findings, it is possible to conclude that dietary chicory root at 4% had beneficial effects on the gut health of pigs as indicated by a changed abundance of certain cecal proteins such as KRT20, SERPINB1, HSP27, ANAXA2 and ANAXA4.

Angiotensin 1-7 Stimulates Proliferation of Lung Bronchoalveolar Progenitors-Implications for SARS-CoV-2 Infection.

SARS-CoV-2 infection leads to severe lung damage due to pneumonia and, in more severe cases, leads to acute respiratory distress syndrome, or ARDS. This affects the viability of bronchoalveolar cells. An important role in the pathogenesis of these complications is the hyperactivation of the renin-angiotensin-aldosterone (RAA) pathway and induction of cytokine storm that occurs in an Nlrp3 inflammasome-dependent manner. To shed more light on the susceptibility of lung tissue to SARS-CoV-2 infection, we evaluated murine bronchioalveolar stem cells (BASC), alveolar type II cells (AT2), and 3D-derived organoids expression of mRNA encoding genes involved in virus entry into cells, components of RAA, and genes that comprise elements of the Nlrp3 inflammasome pathway. We noticed that all these genes are expressed by lung alveolar stem cells and organoids-derived from these cells. Interestingly, all these cells express a high level of ACE2 that, on the one hand, serves as an entry receptor for SARS-CoV-2 and, on the other, converts angiotensin II into its physiological antagonist, angiotensin 1-7 (Ang 1-7), which has been reported to have a protective role in lung damage. To shed more light on the role of Ang 1-7 on lung tissue, we exposed lung-derived BASC and AT2 cells to this mediator of RAA and noticed that it increases the proliferation of these cells. Based on this, Ang 1-7 could be employed to alleviate the damage to lung alveolar stem/progenitor cells during SARS-CoV-2 infection.