Effects of Elobixibat on Constipation and Lipid Metabolism in Patients With Moderate to End-Stage Chronic Kidney Disease

Objective:The aim of this study was to investigate the effects of elobixibat on constipation and lipid metabolism; and determine the factors associated with the effect of elobixibat on constipation in patients with moderate to end-stage chronic kidney disease (CKD).Methods:Stool frequency and serum lipid parameters were retrospectively analyzed before and after 4 weeks of elobixibat administration in 42 patients (CKD stage G3, 6; stage G4, 9; stage G5, 9; stage G5D, 18). Relationships between the change in stool frequency after initiation of elobixibat and various clinical parameters were analyzed by using linear regression analysis.Results:Elobixibat increased stool frequency from 0.5 ± 0.4 per day to 1.1 ± 0.6 per day (p < 0.001) regardless of whether patients were undergoing dialysis, on concomitant laxatives, or were administered elobixibat before or after breakfast. Elobixibat reduced low-density lipoprotein cholesterol concentration (from 90.9 ± 37.2 mg/dL to 77.5 ± 34.8 mg/dL, p < 0.05) and increased high-density lipoprotein cholesterol concentration (from 44.9 ± 14.3 mg/dL to 57.0 ± 25.8 mg/dL, p < 0.05), but did not change triglyceride concentration. Adverse effects were observed in two patients (nausea and diarrhea). Only phosphate concentration was correlated with the change in stool frequency after initiation of elobixibat (standard coefficient = 0.321, p = 0.043).Conclusions:Elobixibat improved constipation and lipid metabolism in patients with moderate to end-stage CKD, without serious adverse events.

Loss-of-function mutation in Pcsk1 increases serum APOA1 level and LCAT activity in mice

Background The convertase subtilisin/kexin family 1 gene (PCSK1) has been associated in various human genetics studies with a wide spectrum of metabolic phenotypes, including early-onset obesity, hyperphagia, diabetes insipidus, and others. Despite the evident influence of PCSK1 on obesity and the known functions of other PCSKs in lipid metabolism, the role of PCSK1 specifically in lipid and cholesterol metabolism remains unclear. This study evaluated the effect of loss of PCSK1 function on high-density lipoprotein (HDL) metabolism in mice. Results HDL cholesterol, apolipoprotein A1 (APOA1) levels in serum and liver, and the activities of two enzymes (lecithin-cholesterol acyltransferase, LCAT and phospholipid transfer protein, PLTP) were evaluated in 8-week-old mice with a non-synonymous single nucleotide mutation leading to an amino acid substitution in PCSK1, which results in a loss of protein’s function. Mutant mice had similar serum HDL cholesterol concentration but increased levels of serum total and mature APOA1, and LCAT activity in comparison to controls. Conclusions This study presents the first evaluation of the role of PCSK1 in HDL metabolism using a loss-of-function mutant mouse model. Further investigations will be needed to determine the underlying molecular mechanism.

pixOL: pixel-wise dipole-spread function engineering for simultaneously measuring the 3D orientation and 3D localization of dipole-like emitters

Interactions between biomolecules are characterized by both where they occur and how they are organized, e.g., the alignment of lipid molecules to form a membrane. However, spatial and angular information are mixed within the image of a fluorescent molecule-the microscopy's dipole spread function (DSF). We demonstrate the pixOL algorithm for simultaneously optimizing all pixels within a phase mask to produce an engineered Green's tensor-the dipole extension of point-spread function engineering. The pixOL DSF achieves optimal precision for measuring simultaneously the 3D orientation and 3D location of a single molecule, i.e., 1.14 degree orientation, 0.24 sr wobble angle, 8.17 nm lateral localization, and 12.21 nm axial localization precisions over an 800-nm depth range using 2500 detected photons. The pixOL microscope accurately and precisely resolves the 3D positions and 3D orientations of Nile red within a spherical supported lipid bilayer, resolving both membrane defects and differences in cholesterol concentration, in 6 dimensions.

Serum Sodium Concentration and Increased Risk for Primary Epiretinal Membrane

Aims: To examine the prevalence of primary epiretinal membranes (ERMs) and associated systemic factors.Methods: The cross-sectional, community-based Tongren Health Care Study enrolled participants who received regular health examinations in the Beijing Tongren Hospital from 2017 to 2019. Using fundus photographs, retinal specialists assessed the presence of ERMs and their systemic associations.Results: Primary ERMs were detected in 841/22820 individuals, with a prevalence of 3.7% [95% confidence intervals (CI): 3.4–3.9%] in the total study population (mean age: 44.5 ± 13.8 years) and 6.5% (95% CI: 6.1–7.0%) in individuals aged 40+ years. In multivariable analysis, a higher ERMs prevalence was associated with older age [odds ratio (OR): 1.10; P < 0.001], higher serum cholesterol concentration (OR: 1.14; P = 0.003) and higher serum sodium concentration (SSC) (OR: 1.12; P < 0.001). In women, a higher SSC, even within the normal range, was associated with an increased risk of ERMs (OR: 1.19; P < 0.001). Female participants with an SSC of 144–145mmol/L as compared with those with an SSC of 135–137 mmol/L had a 5-fold increased odds of having ERMs (All women: OR: 5.33; P < 0.001; Women aged 40+years: OR: 4.63; P < 0.001).Conclusion: Besides older age and higher serum cholesterol concentration, a higher SSC, even if within the normal range, was independently associated with a higher ERM prevalence in women.

Herbal Plants as Feed Additives in Broiler Chicken Diets

This study evaluated the effect of some herbal plants as natural feed additives on broiler production parameters, carcass parts, and breast meat quality. A total of 150 broiler chicks, Cobb 500 hybrid, were allocated to five treatments with 30 broilers /group, for 42 days. The experimental treatments were: Control (C); a diet containing 5% alfalfa meal (A); a diet containing 5% alfalfa meal and 1% basil (AB); a diet containing 5% alfalfa and 1% thyme (AT) and a diet containing 5% alfalfa and 1% sage (AS). Bodyweight was significantly (P<0.05) affected in AS group compared with C and A groups. Feed conversion ratio was significantly higher only in A and AB groups. Experimental groups had significantly greater (P<0.05) gizzard weight. The total polyphenols content and the antioxidant capacity were significantly (P<0.05) higher in AB, AT, and AS groups versus the C group. The cholesterol concentration was significantly (P<0.05) decreased in AB, AT, and AS meat samples compared with C and A samples. Instrumental colour measurements indicated significant alterations (P<0.05) among the groups regarding the values of L*, a*, b*, H°, C*, and ΔE*. The texture analysis showed that hardness, gumminess, and chewiness were significantly (P<0.05) higher in AB, AT, and AS groups than in C and A groups.

FORMULATION AND CARACTERIZATION OF QUERCETIN NIOSOME WITH CONCENTRATION VARIATIONS OF SPAN 20 SURFACTANT

Quercetin has low solubility, absorption and bioavailability which limits its practical use as a drug or supplement. Therefore, it is important to formulate a quercetin niosome system with various concentrations of span 20 as a surfactant. This investigation aimed to formulate and analyse a quercetin niosome preparation with span 20 variations to provide optimal quercetin solubility. Niosomes were prepared using various concentrations of span 20. In the present study, the quercetin niosome used the reverse phase evaporation (RPE) method. Quercetin niosome is characterised by its organoleptic properties, pH value, particle morphology comprising the particle shape and size, and encapsulation efficiency. Organoleptic observations of the quercetin niosome included a yellow colour, distinctive quercetin odour and thick consistency for all formulas. The pH remained within the physiological pH range of skin. Quercetin niosome morphology was close to spherical while the niosome particle size results were 2.13 µm (F1), 2.99 µm (F2) and 3.31 µm (F3). The quercetin niosome encapsulation efficiency results were 81.86 ± 0.47% (F1), 84.02 ± 0.26% (F2) and 88.24 ± 0.10% (F3). Quercetin niosome were successfully prepared using multiple span 20 concentrations below the cholesterol concentration characterised by the measurement results of organoleptic, pH, particle morphology and encapsulation efficiency.

Analysis of Serum Biochemical Indexes, Egg Quality, and Liver Transcriptome in Laying Hens Fed Diets Supplemented with Gynostemma pentaphyllum Powder

Gynostemma pentaphyllum (GP), known as “southern ginseng”, can reduce the blood pressure and blood lipid levels. In this study, 300 layer chicks of one day old were divided randomly into three groups (control group (base diet), high addition group (base diet with 1% GP), and low addition group (base diet with 0.5% GP)). After 29 weeks, the growth performance, egg quality, and serum index were determined. Additionally, liver mRNA was identified using RNA-seq to investigate the molecular mechanisms. The results indicated that the serum total cholesterol and triglycerides decreased significantly in the GP addition group. The addition of GP increased the egg weight, Haugh unit and redness (a*) of the egg yolk color, and reduced the yolk cholesterol concentration. Moreover, 95 differentially expressed genes (DEGs) were screened between the control and GP addition group. GO and the KEGG analysis showed that the PPAR pathway was significantly enriched. Five fatty acid metabolism-related genes (FABP3, CYP7A1, ANKRD22, SCD1, and PCK1) were validated by qRT-PCR analysis, which confirmed the tendency of the expression. These DEGs in the PPAR pathway may be the key factors of GP affecting fatty acid metabolism. These results may provide a theoretical basis for further research and new insights into GP as a feed additive.

Single virus assay reveals membrane determinants and mechanistic features of Sendai virus binding

Sendai virus (SeV, formally murine respirovirus) is a membrane-enveloped, negative sense RNA virus in the Paramyxoviridae family, and is closely related to human parainfluenza viruses. SeV has long been utilized as a model paramyxovirus and has recently gained attention as a viral vector candidate for both laboratory and clinical applications. To infect host cells, SeV must first bind to sialic-acid glycolipid or glycoprotein receptors on the host cell surface via its hemagglutinin-neuraminidase (HN) protein. Receptor binding induces a conformational change in HN, which allosterically triggers the viral fusion (F) protein to catalyze membrane fusion. While it is known that SeV binds to α2,3-linked sialic acid receptors, and there has been some study into the chemical requirements of those receptors, key mechanistic features of SeV binding remain unknown, in part because traditional approaches often convolve binding and fusion. Here, we develop and employ a fluorescence microscopy-based assay to observe SeV binding to supported lipid bilayers (SLBs) at the single particle level, which easily disentangles binding from fusion. Using this assay, we investigate mechanistic questions of SeV binding. We identify chemical structural features of ganglioside receptors that influence viral binding and demonstrate that binding is cooperative with respect to receptor density. We measure the characteristic decay time of unbinding and provide evidence supporting a "rolling" mechanism of viral mobility following receptor binding. We also study the dependence of binding on target cholesterol concentration. Interestingly, we find that while SeV binding shows striking parallels in cooperative binding with a prior report of Influenza A virus, it does not demonstrate a similar sensitivity to cholesterol concentration and receptor nano-cluster formation.

The protective effect of the aqueous extract of parsley (Petroselinum sativum ) seeds on experimentally – induced oxidative stress in rats

In this study, the potential protective effect of aqueous extract of parsley (Petroselinum sativum) seeds against hydrogen peroxide (H2O2) – induced oxidative stress in male rats was assessed. Three groups of male albino rats were randomly divided (n=7) and were handled for twenty-eight days as follows: rats in group I served as control; animals in group || were provided with drinking water containing 0.5% H2O2 and those in group III received orally 8 mg/100 gm B.W. of aqueous extract of parsley seeds plus 0.5% H2O2 in drinking water. After four weeks experimental period, a significant increase in lipid peroxidation products (MDA), and decrease in glutathione (GSH) concentrations were observed in plasma, kidney, liver and heart tissues of H2O2 treated animals as compared with the control group. These biomarkers (GSH and MDA) are interrelated and indicate the occurrence of oxidative stress. Plasma total cholesterol (TC) concentration was significantly increased in H2O2 treated rats. By administration of aqueous extract of parsley along with H2O2, plasma and tissue GSH levels were significantly increased while the elevation in MDA level was diminished in plasma and different tissues examined. A decrease in plasma cholesterol concentration was recorded in H2O2 and parsley treated group as compared with the control one and H2O2 treated groups. These results indicate that aqueous extract of parsley have hypocholesterolemic and antioxidant effect.