Effectiveness of strategic environmental assessment in Poland

The paper presents the results of an evaluation of the effectiveness of SEA obtained as a result of a survey with the participation of stakeholders. In Poland, several hundred SEAs are conducted annually at the local and regional levels and several at the national level. Although the survey demonstrated that SEA is evaluated as effective or quite effective, the respondents pointed to several irregularities in the non-procedural dimension of effectiveness. The main ones in terms of substantive effectiveness are that SEA is rarely used to help develop plans/programmes and procedures are highly politicised. Moreover, low effectiveness in terms of variant assessment and cumulative impacts and nearly non-existent monitoring of the actual effects of implementing plans/programmes influence substantive effectiveness significantly. The respondents pointed to the problem resulting from the fact that plan-makers are unwilling to take into account the SEA recommended changes. They also emphasised that there are certain attempts to put pressure on SEA consultants to make the conclusions less stringent. Respondents indicate that in Poland the costs associated with conducting SEA often outweigh the profits. The research shows that the society is properly informed about SEA, but public involvement is still low.     

Clearance of FGF‐23 during continuous renal replacement therapy

FGF‐23 is a 32 kDa protein that is a key regulator of phosphorus and vitamin D metabolism. Emerging evidence also demonstrates that FGF‐23 increases within 24 hours of acute kidney injury (AKI) and may be associated with adverse clinical outcomes. We conducted this study to evaluate FGF23 clearance during continuous veno‐venous hemofiltration (CVVH) in critically ill patients with AKI. We demonstrate that plasma clearance of FGF‐23 during CVVH is ～11 mL/min and the mean sieving coefficient is 0.27 ± 0.1. Future studies will need to clarify FGF‐23's role in adverse outcomes among AKI patients, and whether therapies aimed at reducing FGF‐23 levels may be beneficial.     

Combining 1,3-Ditriazolylbenzene and Quinoline to Discover a New G-Quadruplex-Interactive Small Molecule Active against Cancer Stem-Like Cells

Quadruplex nucleic acids are promising targets for cancer therapy. In this study we used a fragment-based approach to create new flexible G-quadruplex (G4) DNA-interactive small molecules with good calculated oral drug-like properties, based on quinoline and triazole heterocycles. G4 melting temperature and polymerase chain reaction (PCR)-stop assays showed that two of these compounds are selective G4 ligands, as they were able to induce and stabilize G4s in a dose- and DNA sequence-dependent manner. Molecular docking studies have suggested plausible quadruplex binding to both the G-quartet and groove, with the quinoline module playing the major role. Compounds were screened for cytotoxicity against four cancer cell lines, where 4,4′-(4,4′-(1,3-phenylene)bis(1H-1,2,3-triazole-4,1-diyl))bis(1-methylquinolin-1-ium) ( 1 d ) showed the greater activity. Importantly, dose–response curves show that 1 d is cytotoxic in the human colon cancer HT-29 cell line enriched in cancer stem-like cells, a subpopulation of cells implicated in chemoresistance. Overall, this study identified a new small molecule as a promising lead for the development of drugs targeting G4 in cancer stem cells.     

Beneficial Changes in Rat Vascular Endocannabinoid System in Primary Hypertension and under Treatment with Chronic Inhibition of Fatty Acid Amide Hydrolase by URB597

Our study aimed to examine the effects of hypertension and the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on vascular function and the endocannabinoid system in spontaneously hypertensive rats (SHR). Functional studies were performed on small mesenteric G3 arteries (sMA) and aortas isolated from SHR and normotensive Wistar Kyoto rats (WKY) treated with URB597 (1 mg/kg; twice daily for 14 days). In the aortas and sMA of SHR, endocannabinoid levels and cannabinoid CB₁ receptor (CB₁R) expression were elevated. The CB₁R antagonist AM251 diminished the methanandamide-evoked relaxation only in the sMA of SHR and enhanced the vasoconstriction induced by phenylephrine and the thromboxane analog U46619 in sMA in SHR and WKY. In the sMA of SHR, URB597 elevated anandamide levels, improved the endothelium-dependent vasorelaxation to acetylcholine, and in the presence of AM251 reduced the vasoconstriction to phenylephrine and enhanced the vasodilatation to methanandamide, and tended to reduce hypertrophy. In the aortas, URB597 elevated endocannabinoid levels improved the endothelium-dependent vasorelaxation to acetylcholine and decreased CB₁R expression. Our study showed that hypertension and chronic administration of URB597 caused local, resistance artery-specific beneficial alterations in the vascular endocannabinoid system, which may bring further advantages for therapeutic application of pharmacological inhibition of FAAH.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Interleukins 6 and 15 Levels Are Higher in Subcutaneous Adipose Tissue,but Obesity Is Associated with Their Increased Content in Visceral Fat Depots

Excess adiposity is associated with chronic inflammation, which takes part in the development of obesity-related complications. The aim of this study was to establish whether subcutaneous (SAT) or visceral (VAT) adipose tissue plays a major role in synthesis of pro-inflammatory cytokines. Concentrations of interleukins (IL): 1β, 6, 8 and 15 were measured at the protein level by an ELISA-based method and on the mRNA level by real-time PCR in VAT and SAT samples obtained from 49 obese (BMI > 40 kg/m²) and 16 normal-weight (BMI 20–24.9 kg/m²) controls. IL-6 and IL-15 protein concentrations were higher in SAT than in VAT for both obese (p = 0.003 and p < 0.0001, respectively) and control individuals (p = 0.004 and p = 0.001, respectively), while for IL-1β this was observed only in obese subjects (p = 0.047). What characterized obese individuals was the higher expression of IL-6 and IL-15 at the protein level in VAT compared to normal-weight controls (p = 0.047 and p = 0.016, respectively). Additionally, obese individuals with metabolic syndrome had higher IL-1β levels in VAT than did obese individuals without this syndrome (p = 0.003). In conclusion, concentrations of some pro-inflammatory cytokines were higher in SAT than in VAT, but it was the increased pro-inflammatory activity of VAT that was associated with obesity and metabolic syndrome.