Effect of Phosphatidylserine and Cholesterol on Membrane-mediated Fibril Formation by the N-terminal Amyloidogenic Fragment of Apolipoprotein A-I

Here, we examined the effects of phosphatidylserine (PS) and cholesterol on the fibril-forming properties of the N-terminal 1‒83 fragment of an amyloidogenic G26R variant of apoA-I bound to small unilamellar vesicles. A thioflavin T fluorescence assay together with microscopic observations showed that PS significantly retards the nucleation step in fibril formation by apoA-I 1‒83/G26R, whereas cholesterol slightly enhances fibril formation. Circular dichroism analyses demonstrated that PS facilitates a structural transition from random coil to α-helix in apoA-I 1‒83/G26R with great stabilization of the α-helical structure upon lipid binding. Isothermal titration calorimetry measurements revealed that PS induces a marked increase in capacity for binding of apoA-I 1‒83/G26R to the membrane surface, perhaps due to electrostatic interactions of positively charged amino acids in apoA-I with PS. Such effects of PS to enhance lipid interactions and inhibit fibril formation of apoA-I were also observed for the amyloidogenic region-containing apoA-I 8‒33/G26R peptide. Fluorescence measurements using environment-sensitive probes indicated that PS induces a more solvent-exposed, membrane-bound conformation in the amyloidogenic region of apoA-I without affecting membrane fluidity. Since cell membranes have highly heterogeneous lipid compositions, our findings may provide a molecular basis for the preferential deposition of apoA-I amyloid fibrils in tissues and organs

Modeling and simulation of spring steel damper based on parameter identification with a heuristic optimization approach

In seismic design of building frames, dampers are designed to absorb an earthquake’s energy. Conventional steel tension braces have disadvantages, such as pinching or deterioration of stiffness and strength under cyclic loading. A new type of elasto-plastic damper can potentially avoid such disadvantages at a relatively low cost. Main characteristics of the damper are twofold: i) hardening effect caused by geometric nonlinearity, and ii) asymmetric hysteretic restoring force in tensile and compressive loading conditions. The objective of the study is to present a constitutive model and identify the corresponding parameters. The process of parameter identification of the model is formulated as a non-smooth optimization problem and derivative-free optimization methods are suited for the problem. Through numerical examples, we investigate the seismic response reduction property of the damper. The results demonstrate the effectiveness of the optimization approach

Effects of Supplementation with Dried Neem Leaf Extract on Lipid Peroxidation and Antioxidant Enzyme mRNA Expression in the Pectoralis Major Muscle of Broiler Chickens

This study was conducted to evaluate the effects of dietary supplementation of dried neem (Azadirachta indica) leaf extract (DNE) on lipid peroxidation and the expression of genes encoding mRNAs in antioxidant enzymes in the pectoralis major muscle of chickens. A total of 24 male broiler chickens (ROSS308) were divided into three groups (n＝8) at 21 days of age. The control group of chickens was fed a basal diet, and the remaining two groups of chickens were fed a basal diet supplemented with DNE at a concentration of 0.5% or 2.0% until 35 days of age. Growth performance (body weight, weight gain, feed intake, and feed conversion ratio) and tissue weights did not differ among the three groups. The 2.0% DNE-supplemented diet decreased the muscle malondialdehyde content, a marker of lipid peroxidation, and drip loss compared to the control chickens. In addition, the expression of genes encoding mRNAs of antioxidant enzymes (i.e., Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, glutathione peroxidase 7, and catalase) were higher in the pectoralis major muscle of chickens fed the 2.0% DNE-supplemented diet than in the control chickens. Therefore, DNE supplementation increased the expression of genes encoding mRNAs in antioxidant enzymes and reduced lipid peroxidation and drip loss in the pectoralis major muscle of broiler chickens

Can Lemborexant for Insomnia Prevent Delirium in High-Risk Patients with Pancreato-Biliary Disease after Endoscopic Procedures under Deep Sedation?

Background and aim: Pancreato-biliary patients who undergo endoscopic procedures have high potential risk of delirium. Although benzodiazepine has traditionally been used to treat insomnia, this drug might increase delirium. Lemborexant may be useful for patients with insomnia, without worsening delirium, although there is no evidence for high-risk patients with pancreato-biliary disease. The aim of this pilot study was to evaluate the safety and efficacy of lemborexant for insomnia and the frequency of delirium after endoscopic procedures under deep sedation in patients with pancreato-biliary disease. Method: This retrospective study included consecutive patients who were administered lemborexant after endoscopic procedures for pancreato-biliary disease between September 2020 and June 2022. The primary outcome of this study was evaluation of the safety and efficacy of lemborexant for insomnia. Frequency of delirium was the secondary outcome. Result: In total, 64 patients who had the complication of insomnia after an endoscopic procedure were included in the study. Risk factors for delirium were advanced age (n = 36, 56.3%), dementia (n = 10, 15.6%), and regular alcohol use (n = 13, 20.3%), as well as the sedatives midazolam and pentazocine that were administered to all patients at the time of the endoscopic procedure. Successful asleep was achieved by 61/64 patients (95.3%). No fall event was observed during the night following the procedure in any patient. However, mild consciousness transformation was observed in one patient. Conclusions: In conclusion, lemborexant use may be effective and safe for use after endoscopic procedures in pancreato-biliary patients, without increasing the risk of delirium

Comparison of Endoscopic Hemostasis for Endoscopic Sphincterotomy Bleeding between a Novel Self-Assembling Peptide and Conventional Technique

Introduction: Recently, a novel self-assembling peptide hemostatic gel has become available in Japan. However, the safety and efficacy of this novel self-assembling peptide hemostatic gel remain unclear for bleeding after EST. The aim of this study was to evaluate the safety and efficacy of a novel self-assembling peptide hemostatic gel for bleeding after EST, and to perform a comparison to a conventional endoscopic hemostasis technique. Method: This retrospective study was carried out between January 2019 and October 2022. Patients who developed bleeding associated with EST were enrolled. The patients were divided into two groups based on the hemostasis technique used: a conventional hemostasis technique (Group A) or a novel self-assembling peptide hemostatic gel hemostasis technique (Group B). Result: A total of 62 patients (Group A, n = 36; Group B, n = 26) were included. Endoscopic hemostasis was initially obtained in 72.2% (26/32) of patients in Group A and in 88.4% (23/26) of patients in Group B, which was not significantly different (p = 0.1320). However, the procedure time was significantly shorter in Group B (mean, 9.38 min) compared with Group A (mean, 15.4 min) (p = 0.0103). There were no significant differences in the severity of bleeding between the two groups (p = 0.4530). Post-EST bleeding was observed in six patients (Group A, n = 4; Group B, n = 2). Adverse events were more frequently observed in Group A (n = 12) than in Group B (n = 1) (p = 0.0457). Conclusions: PuraStat application for EST bleeding might be safe and effective, and is comparable to the conventional endoscopic hemostasis technique, although further prospective randomized trials are needed