Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease

All capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and damage to the ESL coupled to proteinuria is seen for example in diabetic kidney disease (DKD). We used the principles of ion exchange chromatography in vivo to elute the highly negatively charged components of the ESL with a 1 M NaCl solution in rats. Ultrastructural morphology and renal function were analyzed and 17 PGs and hyaluronan were identified in the ESL. The high salt solution reduced the glomerular ESL thickness, led to albuminuria and reduced GFR. To assess the relevance of ESL in renal disease the expression of PGs in glomeruli from DKD patients in a next generation sequencing cohort was investigated. We found that seven of the homologues of the PGs identified in the ESL from rats were differently regulated in patients with DKD compared to healthy subjects. The results show that proteoglycans and glycosaminoglycans are essential components of the ESL, maintaining the permselective properties of the glomerular barrier and thus preventing proteinuria.publishedVersio

Approaches to Analysis of Interstate Cooperation

At the present day cultural diplomacy plays a rather important role in the development of international relations and world politics. This concept is receiving increasing attention from various countries, international and non-governmental organizations and other actors. This trend exists due to a number of reasons, such as the desire of states to create a positive image of their country, the expansion of international cooperation, changes in the global and domestic political situation, the protection of national interests, the prevention of conflicts between states, etc. Cultural diplomacy, beyond historical precedents, consists of a relatively new practice of a country’s foreign policy, which has traditionally focused on trade and security and defense issues. It is true that in European countries there are institutions of cultural foreign relations since the beginning of the century, but in the last decade the issues, related to the projection of the international image of countries, have become more important

Serum levels of galactose-deficient IgA are elevated in patients with IgA nephropathy but do not correlate to disease activity or progression

Abstract Introduction IgA nephropathy (IgAN) is the most common glomerulonephritis globally. Because of the heterogeneity of the disease prognostic biomarkers are highly needed. Aim To investigate associations between galactose-deficient IgA1 (Gd-IgA1) concentrations in plasma and urine and disease activity and progression in patients with IgAN. Methods Serum and urine samples were collected at the time of kidney biopsy (baseline) in patients with IgAN (n = 40) and analysed for Gd-IgA1. Patients with chronic kidney disease (CKD) without IgAN (n = 21) and healthy controls (n = 19) were examined as controls. In 19 patients with IgAN, analyses of Gd-IgA1 were repeated after a median follow up time of approximately 10 years. Results Serum Gd-IgA1 and Gd-IgA1:IgA were significantly elevated at the time of kidney biopsy in patients with IgAN compared to patients with non-IgAN CKD and healthy controls (p < 0.001). Urinary Gd-IgA1:creatinine was significantly elevated in patients with IgAN compared to patients with non-IgAN CKD. Neither serum Gd-IgA1, nor serum Gd-IgA1:IgA, correlated significantly to estimated GFR, urine albumin:creatinine (UACR), or blood pressure, at baseline. Serum Gd-IgA1 and Gd-IgA1:IgA at time of biopsy did not correlate significantly to annual changes in eGFR or UACR during follow up. In patients with IgAN, serum Gd-IgA1 decreased significantly over time during approximately 10 years of follow up (Δ-20 ± 85%, p = 0.027). Urinary Gd-IgA1:creatinine showed a strong positive correlation to UACR in patients with IgAN and likely reflected unspecific glomerular barrier injury. Conclusion Although serum Gd-IgA1 and the Gd-IgA1:IgA ratio were significantly elevated in patients with IgAN at the time of kidney biopsy they were not related to disease activity or progression in this patient cohort

Synthesis and Characterization of Inorganic-Organic Derivatives of Layered Perovskite-like Niobate HSr₂Nb₃O₁₀ with <i>n</i>-Amines and <i>n</i>-Alcohols

A protonated and hydrated Dion-Jacobson-phase HSr2Nb3O10∙yH2O was used to prepare two series of inorganic–organic derivatives containing non-covalently intercalated n-alkylamines and covalently grafted n-alkoxy groups of different lengths, as they are promising hybrid materials for photocatalytic applications. Preparation of the derivatives was carried out both under the conditions of standard laboratory synthesis and by solvothermal methods. For all the hybrid compounds synthesized structure, quantitative composition, a type of bonding between inorganic and organic parts as well as light absorption range were discussed using powder XRD, Raman, IR and NMR spectroscopy, TG, elemental CHN analysis, and DRS. It was shown that the inorganic–organic samples obtained contain approximately one interlayer organic molecule or group per proton of the initial niobate, as well as some amount of intercalated water. In addition, the thermal stability of the hybrid compounds strongly depends on the nature of the organic component anchoring to the niobate matrix. Although non-covalent amine derivatives are stable only at low temperatures, covalent alkoxy ones can withstand heat up to 250 °C without perceptible decomposition. The fundamental absorption edge of both the initial niobate and the products of its organic modification lies in the near-ultraviolet region (370–385 nm)

Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease

All capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and damage to the ESL coupled to proteinuria is seen for example in diabetic kidney disease (DKD). We used the principles of ion exchange chromatography in vivo to elute the highly negatively charged components of the ESL with a 1 M NaCl solution in rats. Ultrastructural morphology and renal function were analyzed and 17 PGs and hyaluronan were identified in the ESL. The high salt solution reduced the glomerular ESL thickness, led to albuminuria and reduced GFR. To assess the relevance of ESL in renal disease the expression of PGs in glomeruli from DKD patients in a next generation sequencing cohort was investigated. We found that seven of the homologues of the PGs identified in the ESL from rats were differently regulated in patients with DKD compared to healthy subjects. The results show that proteoglycans and glycosaminoglycans are essential components of the ESL, maintaining the permselective properties of the glomerular barrier and thus preventing proteinuria

Influence of oxygen vacancies on magnetic and transport properties of thin Zn1-xCoxOy films

The features of the structural, transport and magnetic properties of thin Zn1-xCoxOy films (x=0-0.45), fabricated on С-sapphire substrates by the pulsed laser deposition method are studied. It is found that the transport and ferromagnetic properties of the wurtzite Zn1-xCoxOy films nonmonotonously depend on Co concentration at room temperature. For the Zn0.87Co0.13Oy film, the strongest ferromagnetic signal is observed that is caused by formation of the greatest number of metallic Co clusters. A further increase of doping impurity concentration in the films leads to the oxidation of metallic Co and formation of the paramagnetic Co3O4 phase, in consequence of which the ferromagnetic signal subsides

Interval Hypoxic Training in Rehabilitation Program for Adolescents with Overweight / Obesity and Comorbid Arterial Hypertension: Open-Label Randomized Study

Background. Searching for new strategies for the rehabilitation of adolescents with obesity and comorbid arterial hypertension (AHT) before significant pathological changes development in the cardiovascular system remains the urgent challenge. Objective. The aim of the study was to examine the effect of interval hypoxic training (IHT) on blood pressure (BP) levels in adolescents with overweight / obesity and comorbid AHT. Methods. Adolescents aged 14-17 years with body mass index SDS ≥ 1 and grade I AHT (mean level of systolic and/or diastolic BP ≥ 95th percentile for population of corresponding age, sex and height) have been randomized to the group «aerobic training» (treadmill walking) and “aerobic training + IHT” (usage of hypoxicator in intermittent operation cycles). All patients were on subcaloric diet (10% reduction in caloric intake for given age). Primary outcome measure was the difference between groups on systolic/diastolic BP levels according to 24-hour BP monitoring after completion of training program (10 classes each). The effects of IHT on body composition (bioelectrical impedance analysis), heart rate variability and psychoemotional state (Spielberger scale, assessment of health, activity and mood) were further estimated. Results. 43 patients were assigned to the index group, and 42 — to the control group. 67 patients have completed the research program. 5 patients (12%) from the IHT group and 13 patients (31%; p = 0.029) from the control group prematurely discontinued participation in the trial due to poor exercise tolerance. The groups were comparable in baseline systolic and diastolic BP. Decrease in BP occurred in both groups after 10 workouts. There were no differences in decrease value: mean difference for SBP was 2.4 mm Hg (95% CI -6.6 ... 1.8), for DBP — 0.2 mm Hg (-3.6 ... 4.0). However, the incidence of reaching the targeted SBP (&lt; 95th percentile for the corresponding age and sex) after completion of the treatment was recorded in 66% patients in the experimental group and in 42% patients in the control group (p = 0,047). Positive dynamics in several indicators of heart rate variability and psychoemotional state were mentioned in the IHT group. Conclusion. The IHT implementation in the complex of rehabilitation program for adolescents with overweight / obesity and AHT has no additional positive effect on BP levels. However, the incidence of reaching the targeted SBP (&lt; 95th percentile for the corresponding age and sex) after completion of the treatment was recorded in 66% patients in the experimental group and in 42% patients in the control group (p = 0,054)

Influence of oxygen vacancies on magnetic and transport properties of thin Zn

The features of the structural, transport and magnetic properties of thin Zn1-xCoxOy films (x=0-0.45), fabricated on С-sapphire substrates by the pulsed laser deposition method are studied. It is found that the transport and ferromagnetic properties of the wurtzite Zn1-xCoxOy films nonmonotonously depend on Co concentration at room temperature. For the Zn0.87Co0.13Oy film, the strongest ferromagnetic signal is observed that is caused by formation of the greatest number of metallic Co clusters. A further increase of doping impurity concentration in the films leads to the oxidation of metallic Co and formation of the paramagnetic Co3O4 phase, in consequence of which the ferromagnetic signal subsides

Orellanine specifically targets renal clear cell carcinoma

Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells. Orellanine would thus target both primary and metastatic ccRCC in vitro and in vivo. We found that orellanine induces dose-dependent cell death in proximal tubular cells and in all ccRCC cells tested, both primary and cell lines, with no toxicity detected in control cells. The toxic action of orellanine involve decreased protein synthesis, disrupted cell metabolism and induction of apoptosis. In nude rats carrying human ccRCC xenografts, brief orellanine treatment eliminated more than 90% of viable tumor mass compared to control rats. This identifies orellanine as a potential treatment concept for ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC