Reverse cholesterol transport (RCT) is pivotal in the return of excess cholesterol from peripheral tissues to the liver for excretion in bile and eventually feces. RCT from macrophages is a critical ...anti-atherogenicity mechanism of HDL. As the cholesterol absorption inhibitor ezetimibe promoted RCT in mice, which lack cholesterol ester transfer protein (CETP), we investigated its effects in hamsters, which have CETP.
A high-cholesterol diet (HC) increased cholesterol levels throughout lipoprotein fractions and ezetimibe markedly reduced VLDL/LDL cholesterol levels under both normal chow (NC) and HC. However, ezetimibe did not affect and reduced HDL-cholesterol levels under NC and HC, respectively. Intraperitoneal injection of 3H-cholesterol pre-labeled macrophages in an in vivo RCT assay increased tracer accumulation in the liver but reduced it in bile under HC, and these changes were completely cancelled by ezetimibe. Under both NC and HC, ezetimibe reduced tracer levels in the liver but increased them in feces, indicating promotion of RCT in vivo. We performed a RCT assay using hamsters subjected to bile duct ligation (BDL) to clarify whether a transintestinal cholesterol efflux (TICE) pathway contributes to ezetimibe's enhancement of RCT. BDL markedly inhibited macrophage-derived 3H-cholesterol excretion to feces and cancelled ezetimibe's stimulatory effect on RCT, suggesting that biliary cholesterol excretion is a major contributor in RCT promotion by ezetimibe but the contribution of the TICE pathway is minimal.
In conclusions, ezetimibe exerts an additive anti-atherogenic property by enhancing RCT in hamsters. Our findings suggest that this property is independent of the TICE pathway.
•Reverse cholesterol transport is a pivotal anti-atherogenicity mechanism of HDL.•Previous studies showed that exetimibe promoted RCT in CETP-lacking mice.•In this study, we showed that ezetimibe promoted RCT in CETP-expressing hamsters.•RCT promoted by ezetimibe was independent of a transintestinal cholesterol efflux.•Therefore, ezetimibe promotes RCT independent of CETP.
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GEOZS, IJS, KILJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We confirmed the safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel in a small number of patients with cis-platinum-intolerant core high-risk head and neck cancer.
To assess ...treatment efficacy, we planned a phase 2 study of postoperative bio-chemoradiotherapy for patients with cis-platinum-intolerant core high-risk head and neck cancer and will compare the results to those of previously collected radiotherapy data.
Patients who underwent definitive surgery for oral cavity, laryngeal, oropharyngeal, or hypopharyngeal advanced cancer, whose postoperative pathological results indicated core high risk for recurrence (eg, positive margin in the primary site or extranodal extension) and who were cis-platinum-intolerant, will undergo postoperative bio-chemoradiotherapy. The primary end point is 2-year disease-free survival.
The expected 2-year disease-free survival is set at 55%, and the calculated sample size is 35 patients, according to a statistical analysis based on previous reports.
This treatment method is expected to improve the survival rate of patients with severe head and neck cancer.
UMIN Clinical Trials Registry UMIN000031835; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000036355 (Archived by WebCite at http://www.webcitation.org/71fejVjMr).
The aim of this study is to clarify effectiveness of hochuekkito and ninjin’yoeito for various symptoms after clipping of unruptured cerebral aneurysms. Patients who were treated with hochuekkito ...and/or ninjin’yoeito after clipping of unruptured cerebral aneurysms from August 2020 to June 2021 were included in this study. Effect for acute and chronic symptoms were retrospectively investigated. The results indicated that hochuekkito and ninjin’yoeito improve post–operative symptoms such as headache and fatigue.
A two‐dimensional individual‐based fish movement model coupled with fish bioenergetics was developed to simulate the observed migration and growth of Japanese sardine (Sardinops melanostictus) in the ...western North Pacific. In the model, derived from the observed ocean–environmental data as the driving force, fish movement was adapted as a kinesis behavior. The model successfully simulated the observed transport patterns during the egg and larval stages and the northward migrations during the juvenile stage in 2005, 2006 and 2007. The model results showed that both temperature during the larval stage in the Kuroshio Extension and the prey availability during the early juvenile stage in the Kuroshio–Oyashio transitional area are important factors for growth of Japanese sardine. In autumn, the observed juvenile sardine were mainly distributed in the subarctic water region off the Kuril Islands, which is an area (158–165°E, 43–47°N) with a high chlorophyll‐a (Chl‐a) concentration. The model reproduced the fish distribution, which has a high density in this region. The high Chl‐a concentration area in autumn may contribute to increasing the survival rate of Japanese sardine by cascading up the food chain, from the high primary production, and is an important habitat for recruitment success of Japanese sardine.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
We recently reported that plasma albumin redox state, which correlates with albumin synthesis rate, could be associated with the quality of dietary protein. Aiming to elucidate the association ...between them, plasma albumin redox state was investigated in rats fed various kinds of AIN-93G-based low protein diets. Plasma albumin redox state was shifted to a more oxidized state in rats fed 3% casein (CN) diet than those fed 3% whey protein or 3% wheat gluten diet, while supplementing 3% CN diet with cystine reversed it to a more reduced state, indicating that cystine would complement the shortage of cysteine in CN, thereby increasing albumin synthesis rate. Supplementation with glutathione, a cysteine-containing antioxidative tripeptide, normalized hepatic glutathione redox state modulated by ingestion of 3% CN diet, but it only reversed the oxidized shift of plasma albumin redox state to an extent similar to cystine alone or the constituting amino acid mixture of glutathione (i.e., glutamic acid, cystine, and glycine), indicating that glutathione would primarily serve as a source of cysteine rather than exert its antioxidative activity. Plasma albumin would thus be influenced by amino acid balance in dietary proteins, and it could be useful as a biomarker that contributes to prevention of protein under-nutriton, caused by not only insufficient protein intake but also ingestion of poor-quality protein.
► We inserted multiple platelet factor 4-driven human FVIII genes into a HAC vector. ► We generated an integration-free hemophilia mouse-derived iPS cells. ► We confirmed the iPS cell-mediated FVIII ...expression in megakaryocytes/platelets.
Human artificial chromosome (HAC) has several advantages as a gene therapy vector, including stable episomal maintenance and the ability to carry large gene inserts. Induced pluripotent stem (iPS) cells also have a great potential for gene therapy, which can be generated from an individual’s own tissues and contribute to any tissues when reintroduced. A Sendai virus (SeV) vector with reprogramming factors is a powerful tool for generating iPS cells because of the high infection efficiency without the risk of integration into host chromosomes. In this study, we developed an iPS cell-mediated and integration-free coagulation factor VIII (FVIII) expression system using non-integrating SeV- and HAC-vectors. Multiple human FVIII genes, which were under the control of the megakaryocyte-specific platelet factor-4 (PF4) promoter for development of a treatment for hemophilia A, were inserted into a HAC vector (PF4-FVIII-HAC). The PF4-FVIII-HAC was introduced into SeV vector-mediated iPS cells derived from a mouse model of hemophilia A. After in vitro differentiation of iPS cells with the PF4-FVIII-HAC into megakaryocytes/platelets, the PF4-FVIII-HAC resulted in expression of FVIII. This study has developed the iPS cell-mediated PF4-driven FVIII expression system using two non-integrating vectors; therefore, this system may be a promising tool for safer gene- and cell-therapy of hemophilia A.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
TAGS trial revealed the efficacy and safety of trifluridine/tipiracil(Lonsurf®)treatment in patients with metastatic gastric cancer following gastrectomy. Here, we successfully treated 38 months ...survival case after recurrences following radical gastrectomy for advanced adenocarcinoma of esophago-gastric junction using historical recommended chemotherapy regimens and trifluridine/tipiracil as a fifth-line chemotherapy. Trifluridine/tipiracil therapy contributed to effective and safety treatment even in late-line chemotherapy for recurrent gastric cancer.
Quantitative 1H-NMR (1H-qNMR) is useful for determining the absolute purity of organic molecules; however, it is sometimes difficult to identify the target signal(s) for quantitation because of their ...overlap and complexity. Therefore, we focused on the 31P nucleus because of the simplicity of its signals and previously reported 31P-qNMR in D2O. Here we report 31P-qNMR of an organophosphorus compound, sofosbuvir (SOF), which is soluble in organic solvents. Phosphonoacetic acid (PAA) and 1,4-BTMSB-d4 were used as reference standards for 31P-qNMR and 1H-qNMR, respectively, in methanol-d4. The purity of SOF determined by 31P-qNMR was 100.63 ± 0.95%, whereas that determined by 1H-qNMR was 99.07 ± 0.50%. The average half bandwidths of the 31P signal of PAA and SOF were 3.38 ± 2.39 Hz and 2.22 ± 0.19 Hz, respectively, suggesting that the T2 relaxation time of the PAA signal was shorter than that of SOF and varied among test laboratories. This difference most likely arose from the instability in the chemical shift due to the deuterium exchange of the acidic protons of PAA, which decreased the integrated intensity of the PAA signal. Next, an aprotic solvent, DMSO-d6, was used as the dissolving solvent with PAA and DSS-d6 as reference standards for 31P-qNMR and 1H-qNMR, respectively. SOF purities determined by 31P-qNMR and 1H-qNMR were 99.10 ± 0.30% and 99.44 ± 0.29%, respectively. SOF purities determined by 31P-qNMR agreed with the established 1H-qNMR values, suggesting that an aprotic solvent is preferable for 31P-qNMR because it is unnecessary to consider the effect of deuterium exchange.
Trigeminal neuralgia is a nerve disorder that causes unilateral severe facial pain. The clinical features of trigeminal neuralgia are agonizing, paroxysmal, anticipated in one or more divisions of ...the trigeminal nerve, with repetitive bursts of a few seconds, exacerbated by cutaneous stimuli. Microvascular decompression is proven effective, resulting in a positive outcome. Here, we report two cases of trigeminal neuralgia associated with the vertebral artery, who underwent endoscopic microvascular decompression. This case report aims to show the benefit of computational fluid dynamics evaluation of the neurovascular contact and its effect on change in wall shear stress magnitude of the offending vertebral artery after surgical management with microvascular decompression.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The self-expandable metallic stent (SEMS) is an excellent non-invasive tool for emergent bowel obstruction. This study was designed to evaluate the clinical usefulness of the SEMS for avoiding ...perioperative complications.
We analyzed a total of 47 consecutive patients who had a bowel obstruction due to colorectal cancer at initial diagnosis between 2012 and 2017 from hospital records.
Perioperative complications occurred in 30% (14/47) of patients. Univariate and multivariate logistic regression analyses identified an age of more than 75 years p=0.037, OR=6.84 (95% CI=1.11-41.6) and the absence of an SEMS treatment p=0.028, OR=18.5 (95% CI=1.36-250.0) as independent risk factors for perioperative complications. Pneumonia (12.7% (6/47)) was the most common complication. There were no pneumonia patients (0% (0/15)) who were treated with the SEMS. In contrast to patients with the non-SEMS treatment, 18.7% (6/32) of all patients and 35.7% (5/14) of elderly patients had pneumonia.
The SEMS is a safe and effective treatment for avoiding perioperative complications, particularly pneumonia, and may be a crucial strategy in elderly patients with acute obstruction due to colorectal cancer.
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