Factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease.

OBJECTIVE: The aim of our study was to analyze the factors influencing the occurrence of hyperuricemia and poor cardiac and renal outcomes in chronic kidney disease (CKD). PATIENTS AND METHODS: One hundred and sixteen patients with CKD admitted to our hospital from January 2022 to September 2022 were picked as the subjects. Fasting venous blood of these subjects was collected to value the serum uric acid (SUA) levels on an automatic biochemical analyzer. Patients were then grouped as the CKD-only group (n=80) and hyperuricemia group (n=36), according to the SUA results, or the good prognosis group (n=88) and poor prognosis group (n=28), according to the presence of cardiovascular diseases. The changes in laboratory indexes and clinical data were analyzed and compared. Multivariate logistic regression analysis was used to analyze the risk factors for combined hyperuricemia and the risk factors for poor cardiac and renal outcomes in patients with CKD. The correlation between SUA level and cardiac and renal indexes was analyzed by Pearson analysis. RESULTS: Patients in the CKD hyperuricemia group had markedly higher content of systolic blood pressure (SBP), diastolic blood pressure (DBP), B-type natriuretic peptide (BNP), urinary retinol-binding protein (RBP), urinary N-acetyl-ß-D glucosidase (NAG), much higher proportion of heart failure episodes history, and much lower content of total cholesterol (TC), albumin (Alb), hemoglobin (Hb), urinary α1-microglobulin (α1-MG), and glomerular filtration rate (eGFR) than the CKD-only group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for combined hyperuricemia in CKD patients (p < 0.05). Besides, eGFR, albumin, and hemoglobin were independent protective factors for combined hyperuricemia in CKD patients (p < 0.05). Compared with the good prognosis group, the content of BNP, SBP, DBP, urinary RBP, urinary NAG, and SUA was much higher, the proportion of heart failure episodes history was obviously higher, and the levels of Alb, Hb, TC, eGFR, and urinary α1-MG were sharply lower in the poor prognosis group (p < 0.05). SUA, BNP, SBP, and history of heart failure episodes were independent risk factors for poor cardiac and renal outcomes (p < 0.05), and eGFR was an independent protective factor for poor cardiac and renal outcomes in patients with CKD (p < 0.05). The SUA level in CKD patients was positively correlated with BNP and SBP (r=0.463, 0.215, p < 0.05), but negatively correlated with eGFR (r=0.463, 0.215, p < 0.05). CONCLUSIONS: The serum SUA level was elevated with the aggravation of the CKD stage. High serum SUA level is a risk factor for the development of hyperuricemia and poor cardio-renal outcomes in CKD patients, suggesting that early monitoring of changes in SUA levels may help assess the risk of cardio-renal outcomes in CKD patients.

LncRNA HOTAIR participates in the development and progression of adrenocortical carcinoma via regulating cell cycle.

OBJECTIVE: To explore the role of HOTAIR in the pathogenesis of adrenocortical carcinoma (ACC) and its underlying mechanism. PATIENTS AND METHODS: Differentially expressed lncRNA (HOTAIR) in ACC was screened out from the GEO database. The survival analysis and ROC curve were performed according to HOTAIR expressions in ACC patients. The correlation between HOTAIR expression and clinical information of ACC patients was analyzed by chi-square test. The univariate and multivariate COX regression analysis was carried out to analyze the relationship between HOTAIR expression, disease-free survival (DFS) and overall survival (OS) of ACC patients. We then detected HOTAIR expression in 77 ACC tissues and 30 normal tissues by qRT-PCR (quantitative Real-time polymerase chain reaction). ACC cell lines were further screened out for the following in vitro experiments. After altering HOTAIR expression in ACC cells by plasmid transfection, proliferation and cell cycle were detected by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Finally, Western blot was utilized to detect expressions of cell cycle-related genes in ACC cells. RESULTS: HOTAIR was overexpressed in ACC tissues than that of normal tissues. HOTAIR expression was remarkably increased in ACC with T3 and T4 stage than that of T1 and T2 stage. Moreover, HOTAIR expression was remarkably increased in ACC with stage III and IV than that of stage I and II. HOTAIR was an independent prognostic factor for DFS and OS of ACC patients. For in vitro experiments, inhibited proliferation and arrested cell cycle were observed in H295R cells transfected with si-HOTAIR. Opposite results were obtained after SW-13 cells were transfected with HOTAIR overexpression plasmid. Furthermore, expressions of cell cycle-related genes, including Cyclin D1, p-Rb and p-GSK3ß were remarkably decreased after HOTAIR knockdown. CONCLUSIONS: We demonstrated for the first time that HOTAIR is overexpressed in ACC and is a prognostic risk factor in ACC patients. HOTAIR participates in the development and progression of ACC via shortening cell cycle and promoting proliferation of ACC cells.

Structural Conformation of Bovine Serum Albumin Layers at the Air-Water Interface Studied by Neutron Reflection.

The adsorption of bovine serum albumin (BSA) at the air-water interface has been studied by specular neutron reflection. The variation of the adsorbed amount and the total thickness of the BSA layer with respect to bulk BSA concentration was determined at pH 5, close to its isoelectric point (IP). While the surface excess showed a steady increase with bulk concentration the thickness of the protein layer was found to be close to the short axial length of 40 Å of the globular solution structure of BSA at concentrations below 0.1 g dm-3, suggesting that BSA molecules adsorb with their long axes parallel to the surface of water. At 1 g dm-3 the adsorbed layer can be modeled as an upper layer of 40 Å with a volume fraction of 0.4 and a sublayer of 30 Å underneath the top main layer with a volume fraction of 0.12. The results suggest that, although there is some structural deformation accompanying adsorption, there is no denaturation. The extent of immersion of the BSA in water was determined by performing the measurements in D2O and in a mixture of H2O and D2O whose contrast matches that of BSA. The signal is then only from the part of the layer out of water. At pH 5 this layer was about 10 +/- 5 Å at a bulk concentration of 5 x 10(-4) g dm-3 and decreased to 5 +/- 3 Å at 1 g dm-3. The fraction of the BSA layer immersed in water therefore varies from about 70 to over 90%. The effect of pH on the adsorption was examined at two BSA concentrations. While pH had little effect on the adsorption at a low BSA concentration of 5 x 10(-3) g dm-3, both surface excess and layer thickness showed pronounced peaks at pH 5 at the higher concentration of 1 g dm-3. The increased adsorption at pH 5 is attributed to the reduced lateral electrostatic repulsion around the IP. This adsorption pattern became less pronounced when the total ionic strength was increased from 0.02 to 1 M, indicating that the electrolyte screens the electrostatic repulsions within the adsorbed layer. Copyright 1999 Academic Press.

The Adsorption of Lysozyme at the Silica-Water Interface: A Neutron Reflection Study.

The adsorption of lysozyme (chicken egg white) from aqueous solution on to the hydrophilic silica surface and the variation of interfacial structure with solution conditions have been studied by neutron reflection. The accurate determination of the adsorbed layer thicknesses in combination with the dimension of the globular structure of lysozyme allows us to postulate the mean structural conformation of the lysozyme molecules within the adsorbed layer. It was found that the adsorption was completely reproducible with respect to lysozyme concentration, but it was irreversible. The effect of ionic strength on the adsorption of lysozyme was examined at pH 7 and at a bulk lysozyme concentration of 0.03 g dm-3. The adsorbed layer was not affected by changes in ionic strength when the total ionic strength was below 0.05 M, but above this concentration addition of NaCl gradually reduced the amount of lysozyme adsorbed. Complete removal of adsorbed lysozyme was achieved when the total ionic strength was above 0.5 M. The effect of solution pH on the amount of lysozyme adsorbed was characterized by varying the pH in cycles at fixed lysozyme concentrations. Adsorption was found to be completely reversible with respect to pH over a wide protein concentration range. The level of surface excess was dominated by the electrostatic repulsion between lysozyme molecules within the adsorbed layers, rather than the attraction between the surface and lysozyme. The lysozyme layer structure along the surface normal was characterized by varying the isotopic composition of the water. At pH 7 a monolayer 30 +/- 2 Å thick was formed when the lysozyme concentration was below 0.03 g dm-3, indicating that the lysozyme was adsorbed with its long axis parallel to the surface (sideways-on). At higher concentrations the thickness of the layer changed to 60 +/- 2 Å, suggesting the formation of a bilayer of lysozyme molecules in the sideways-on configuration. When the lysozyme concentration is above 1 g dm-3 the surface excess within the inner layer is sufficiently high that repulsion within the adsorbed layer becomes significant and the molecules start to tilt towards longways-on adsorption. At pH 4, the electrostatic repulsion between the adsorbed molecules is stronger than at pH 7, resulting in a lower surface excess and a tilting away from the sideways-on configuration at lower surface concentration. Copyright 1998 Academic Press.

The Denaturation of Lysozyme Layers Adsorbed at the Hydrophobic Solid/Liquid Surface Studied by Neutron Reflection.

We have studied the adsorption of lysozyme layers at a hydrophobic silicon water interface using specular neutron reflection. The hydrophobic surface was obtained by self-assembly of a densely packed monolayer of octadecyltrichlorosilane (OTS) onto the natural silica layer on the smooth surface of a (111) silicon block. The effect of pH on the adsorbed lysozyme layer was examined at a constant lysozyme concentration of 0.03 g dm-3 and at a constant ionic strength of 0.02 M. Reflectivity profiles at different pH show that adsorption is irreversible with respect to pH, the composition and structure of the final layer being dependent on the route by which the pH was achieved. The adsorbed protein layer was found to divide into approximately two regions, a densely packed thin layer next to the OTS surface and a diffuse thicker layer extending into the bulk solution. None of the dimensions of this structure corresponds to those of the globular protein in solution, suggesting that, unlike its adsorption at the hydrophilic silica/water interface, lysozyme is denatured at the OTS/water surface. The irreversible adsorption is explained by the combined interaction of the hydrophobic attraction of the hydrophobic fragments in lysozyme to the OTS surface and electrostatic repulsion within the adsorbed layer. The hydrophobic surface induces the exposure of hydrophobic fragments from the lysozyme assembly. The thickness of the dense layer suggests that the denatured protein adsorbs in the form of peptide chains with the hydrophobic amino acid side chains attached to the OTS surface with the hydrophilic side chains extending into the bulk solution. Since lysozyme is more stable at pH 7 than at pH 4, the difference in initial adsorption is dominated by the greater relative stability of lysozyme to denaturation at the higher pH. A change of pH from 7 to 4 reduces the stability of the protein to unfolding and results in more adsorption than when the pH is changed in the opposite direction. Solution pH also affects the net charges within the hydrophilic tail region and the structural distribution of the tail region was found to vary with pH. Copyright 1998 Academic Press.

Microemulsions with Didodecyldimethylammonium Bromide Studied by Neutron Contrast Variation

The structure of water-in-oil microemulsion droplets, stabilized by didodecyldimethylammonium bromide (DDAB), has been investigated by small-angle neutron scattering (SANS). Detailed information about the curved surfactant film has been obtained by selectively deuterating the water, DDAB, and cyclohexane components. For each surfactant h -DDAB and d -DDAB and concentration, three sets of complementary neutron contrast data were analyzed together in terms of a Schultz distribution of core-shell particles. The modeling was consistent with a simple liquid-like surfactant layer, of density 0.80 g cm-3 , with no evidence for any solvent penetration. This film thickness was found to be 11-12 A, about 70% of an all-trans C12 chain length. At the water interface the area per head was 56-61 A2 , while for the alkyl chains at the outer surface it was 90-125 A2 (15-30% lower than that for a truncated cone molecular configuration). The cyclohexane-water interfacial tensions gammao/w , measured by surface light scattering, were used along with the droplet polydispersities to find that the rigidity of the DDAB film, 2K + K ; is close to 1.0k B T . This means that rather than acting as an effective parameter in the SANS analysis, the polydispersity is a natural consequence of the film rigidity. These results show that the film bending energy model accounts well for the behavior of such DDAB microemulsions.

The Influence of Sorbitol on the Adsorption of Surfactants at the Air-Liquid Interface

Neutron reflection and surface tension have been used to study the adsorption of the nonionic surfactant monododecyl hexaethylene glycol (C12E6) and the mixed nonionic-anionic surfactants n-dodecyl triethylene glycol (C12E3) and Sodium dodecyl sulfate (SDS) at the air-liquid interface. Water and a sorbitol (d-glucitol, CH2OH(HCOH)4CH2OH)/water mixture were selected as the solvents. The addition of 300 g/liter of sorbitol to an aqueous solution of C12E6 reduces the critical micellar concentration, cmc, from approximately 7 x 10(-5) to approximately 3 x 10(-5) M, and increases the surface pressure at the cmc; the effect on the C12E3/SDS mixture is less. Despite these changes, the pattern of adsorption at the air-liquid interface is essentially unaltered by the addition of sorbitol, and the surface tension and neutron reflectivity data are in good agreement. The consequences of the sorbitol addition are however seen directly in the structure of the C12E6 monolayer. The ethylene oxide (EO) chain is more extended than in water, and more displaced from the solvent, consistent with dehydration of the ethylene oxide group.