Crossover of texture and morphology in (Ti1 − xAlx)1 − yYyN alloy films and the pathway of structure evolution

In our earlier published work, we have shown that there is a composition range of the (Ti 1 − x Al x ) 1 − y Y y N alloy films (0.72 b Ti/Al b 0.88) deposited at oblique vapour beam incidence and 500 °C (corresponding to zone T) in which mixed cubic TiN (c-TiN) and wurtzite AlN (w-AlN) structures were formed together with an unusual complex texture. The texture of c-TiN phase changed from 〈001〉 to b111N at a certain thickness forming a definite crossover. Moreover the c-TiNb111N and the w-AlN〈0001〉 crystals were epitaxially related with axes tilted to the direction of the vapour beam. Based on a comprehensive transmission electron microscopy (TEM) and diffraction (XRD and selected area electron diffraction (SAED)) structure and morphology analysis, we discovered the details of this exotic structure making it possible to construct the complex pathway of structure evolution including the formation of the w-AlN phase and the change of the dominating texture of c-TiN phase with thickness in dependence of the Ti/Al ratio and the deposition parameters. This pathway could be deduced from the fundamental phenomena of structure formation and may be generalised for multi-component thin film systems. A composition structure zone model has been also proposed for the (Ti 1 − x Al x ) 1 − y Y y N thin film system in the 0 b x b 1 composition range

Crossover of texture and morphology in (Ti 1 − x Al x ) 1 − y Y y N alloy films and the pathway of structure evolution

In our earlier published work, we have shown that there is a composition range of the (Ti 1 − x Al x ) 1 − y Y y N alloy films (0.72 b Ti/Al b 0.88) deposited at oblique vapour beam incidence and 500 °C (corresponding to zone T) in which mixed cubic TiN (c-TiN) and wurtzite AlN (w-AlN) structures were formed together with an unusual complex texture. The texture of c-TiN phase changed from 〈001〉 to b111N at a certain thickness forming a definite crossover. Moreover the c-TiNb111N and the w-AlN〈0001〉 crystals were epitaxially related with axes tilted to the direction of the vapour beam. Based on a comprehensive transmission electron microscopy (TEM) and diffraction (XRD and selected area electron diffraction (SAED)) structure and morphology analysis, we discovered the details of this exotic structure making it possible to construct the complex pathway of structure evolution including the formation of the w-AlN phase and the change of the dominating texture of c-TiN phase with thickness in dependence of the Ti/Al ratio and the deposition parameters. This pathway could be deduced from the fundamental phenomena of structure formation and may be generalised for multi-component thin film systems. A composition structure zone model has been also proposed for the (Ti 1 − x Al x ) 1 − y Y y N thin film system in the 0 b x b 1 composition range

Preliminary study of optimal extraction of biologically active compounds from sea buckthorn (Hippophae Rhamnoides L.) pomace

The processing of fruits results in high amounts of waste materials such as peels and seeds which is a critical subject in every industry. The aim of this study is to explore the best combination of drying and extraction method, to achieve the highest antioxidant content in sea buckthorn pomace (SBP), which appears as a by-product when making use of the berries. In the frame of our research the optimal drying conditions were previously tested, relying on the results vacuum drying was executed at 40 and 60 °C furthermore SBP was dried also by atmospheric dryer at 60 and 80°C. Drying curve was also determined. When extracting the antioxidant compounds, 20 and 40 % ethanol and acetone were used as solvents, applied in 1:30 proportion. Amount of total polyphenol content and antioxidant capacity (FRAP) were determined by spectrophotometry methods. Besides regarding amount of valuable components economical aspects must be considered for choosing the optimal drying technology. In case of vacuum drying duration was two times longer than in case of atmospheric technologies. The results show that the highest antioxidant capacity (4958.45 mg AAE/100g dm) was registered using 40% acetone extracted from the pomace, dried at 80°C. Further examination could reveal whether the extracted antioxidant content of the SBP, a by-product of fruit processing technologies, could be used natural food additives as bio-preservatives after appropriate clarification processes

Új pathomechanizmusok és kezelési lehetőségek vizsgálata a vese ischémia/reperfúziós károsodásában és krónikus allograft nephropathiában = Investigation of new pathomechanisms and treatment possibilities of renal ischemia/reperfusion injury and chronic allograft nephropathy

Eredményeink az erythropoietin (EPO) védő szerepét igazolták egyoldali vese ischemia/reperfúziós (I/R) károsodásban. Ez a védő szerep elsősorban hímekben igazolható. Hátterében az EPO HSP72-mediálta hatása állhat, amellyel a Na+/K+ ATP-áz funkciójának megtartását segíti elő. Vizsgálataink során az EPO sejt-protektív hatásának hátterében egy új szignál molekulát is sikerült azonosítanunk, a szérum és glükokortikoid aktiválta kináz-1-t (SGK1). Ezek az eredmények az EPO által kifejtett sejtprotekció hátterében álló új pathomechanizmusokat írtak le. Eredményeink alapján az EPO, illetve a leírt útvonalakra ható egyéb szerek további vizsgálata és klinikai hasznosítása jöhet szóba. Másik vizsgálatunk során az I/R-s károsodás kivédésében szerepet játszó mechanizmusok során megfigyelhető nemi különbségeket írtuk le. Igazoltuk, hogy hímekben elsősorban a HIF 1α, míg nőstényekben a HSF útvonal tűnik fontosabbnak. Végül igazoltuk. hogy az SGK1 anti-apoptotikus és sejtvédő funkciójában is nemi különbségek mutathatók ki I/R-t követően. Ezekkel az eredményeinkkel magyarázhatóak az irodalomban korábban leírt és egymásnak ellentmondó közlések, amelyek a tesztoszteron SGK1 reguláló hatását mutatták be. | Our results suggest that EPO protects against severe, unilateral renal I/R injury, especially in male rats. This beneficial effect might be partly the result of EPO’s HSP72-mediated impact on Na+/K+ATPase-α1. Moreover, our data report a new signaling molecule to be involved in EPO cytoprotective actions, since we identified for the first time an important role of SGK1 in the renoprotective effect of EPO. These observations provide insights into a novel signaling mechanism by which EPO partly exerts its potent tissue protective actions. Given our results along with previous reports, the clinical use of EPO possibly leading to reduced cellular damage due to ischemic events should be considered. Our study has revealed a gender-dependent protective mechanism during renal I/R injury. In males mostly the HIF 1α, while in females the HSF is the dominant transcriptional pathway. The EPO treatment results in disappearance of the characteristic signal pathway activation in both genders. The explanation for that could be either a direct negative feedback effect on the transcription factors or an indirect renal protective effect of EPO by which these transcriptional factors do not need to be activated. We could also demonstrate that the anti-apoptotic SGK1 shows a gender-specific expression pattern after renal I/R with higher levels in male rats. These results confirm previous contradictory reports showing that SGK1 might be up-regulated and activated by testosterone

Chronic kidney disease may evoke anxiety by altering CRH expression in the amygdala and tryptophan metabolism in rats

Chronic kidney disease (CKD) is associated with anxiety; however, its exact mechanism is not well understood. Therefore, the aim of the present study was to assess the effect of moderate CKD on anxiety in rats. 5/6 nephrectomy was performed in male Wistar rats. 7 weeks after, anxiety-like behavior was assessed by elevated plus maze (EPM), open field (OF), and marble burying (MB) tests. At weeks 8 and 9, urinalysis was performed, and blood and amygdala samples were collected, respectively. In the amygdala, the gene expression of Avp and the gene and protein expression of Crh , Crhr1 , and Crhr2 were analyzed. Furthermore, the plasma concentration of corticosterone, uremic toxins, and tryptophan metabolites was measured by UHPLC-MS/MS. Laboratory tests confirmed the development of CKD. In the CKD group, the closed arm time increased; the central time and the total number of entries decreased in the EPM. There was a reduction in rearing, central distance and time in the OF, and fewer interactions with marbles were detected during MB. CKD evoked an upregulation of gene expression of Crh , Crhr1 , and Crhr2 , but not Avp , in the amygdala. However, there was no alteration in protein expression. In the CKD group, plasma concentrations of p-cresyl-sulfate, indoxyl-sulfate, kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid, 5-hydroxyindoleacetic acid, picolinic acid, and quinolinic acid increased. However, the levels of tryptophan, tryptamine, 5-hydroxytryptophan, serotonin, and tyrosine decreased. In conclusion, moderate CKD evoked anxiety-like behavior that might be mediated by the accumulation of uremic toxins and metabolites of the kynurenine pathway, but the contribution of the amygdalar CRH system to the development of anxiety seems to be negligible at this stage

The Role of a Key Amino Acid Position in Species-Specific Proteinaceous dUTPase Inhibition

Protein inhibitors of key DNA repair enzymes play an important role in deciphering physiological pathways responsible for genome integrity, and may also be exploited in biomedical research. The staphylococcal repressor StlSaPIbov1 protein was described to be an efficient inhibitor of dUTPase homologues showing a certain degree of species-specificity. In order to provide insight into the inhibition mechanism, in the present study we investigated the interaction of StlSaPIbov1 and Escherichia coli dUTPase. Although we observed a strong interaction of these proteins, unexpectedly the E. coli dUTPase was not inhibited. Seeking a structural explanation for this phenomenon, we identified a key amino acid position where specific mutations sensitized E. coli dUTPase to StlSaPIbov1 inhibition. We solved the three-dimensional (3D) crystal structure of such a mutant in complex with the substrate analogue dUPNPP and surprisingly found that the C-terminal arm of the enzyme, containing the P-loop-like motif was ordered in the structure. This segment was never localized before in any other E. coli dUTPase crystal structures. The 3D structure in agreement with solution phase experiments suggested that ordering of the flexible C-terminal segment upon substrate binding is a major factor in defining the sensitivity of E. coli dUTPase for StlSaPIbov1 inhibition

Role of the kisspeptin-KISS1R axis in the pathogenesis of chronic kidney disease and uremic cardiomyopathy

The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory ( Il6, Tnf ), fibrosis ( Col1 ), and apoptosis markers ( Bax/Bcl2 ) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle

The kisspeptin-1 receptor antagonist peptide-234 aggravates uremic cardiomyopathy in a rat model

Uremic cardiomyopathy is characterized by diastolic dysfunction, left ventricular hypertrophy (LVH), and fibrosis. Dysregulation of the kisspeptin receptor (KISS1R)-mediated pathways are associated with the development of fibrosis in cancerous diseases. Here, we investigated the effects of the KISS1R antagonist peptide-234 (P234) on the development of uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (i) Sham, (ii) chronic kidney disease (CKD) induced by 5/6 nephrectomy, (iii) CKD treated with a lower dose of P234 ( ip. 13 µg/day), (iv) CKD treated with a higher dose of P234 ( ip. 26 µg/day). Treatments were administered daily from week 3 for 10 days. At week 13, the P234 administration did not influence the creatinine clearance and urinary protein excretion. However, the higher dose of P234 led to reduced anterior and posterior wall thicknesses, more severe interstitial fibrosis, and overexpression of genes associated with left ventricular remodeling ( Ctgf, Tgfb, Col3a1, Mmp9 ), stretch ( Nppa ), and apoptosis ( Bax, Bcl2, Casp7 ) compared to the CKD group. In contrast, no significant differences were found in the expressions of apoptosis-associated proteins between the groups. Our results suggest that the higher dose of P234 hastens the development and pathophysiology of uremic cardiomyopathy by activating the fibrotic TGF-β-mediated pathways