Immunotherapy for NAFLD and NAFLD-related hepatocellular carcinoma

The progression of non-alcoholic fatty liver disease (NAFLD), the most common liver disease, leads to non-alcoholic steatohepatitis and hepatocellular carcinoma. Despite the increasing incidence and prevalence of NAFLD, its therapeutic and preventive strategies to lower the disease burden is limited. In recent years, immunotherapy, including anti-programmed cell death 1/programmed cell death 1 ligand 1 treatment, has emerged as a potential approach to reach satisfactory modulation for the progression of NAFLD and treatment of NAFLD-related hepatocellular carcinoma. However, the effectiveness of immunotherapy against NAFLD and NAFLD-related hepatocellular carcinoma is in the early phase and it is yet not advanced. In addition, conflicting results are being reported regarding the prognosis of patients with NAFLD-related hepatocellular carcinoma and high expression of programmed cell death 1/programmed cell death 1 ligand 1. Herein, this review will discuss and elucidate the attempts and underlying mechanisms of immunotherapy against NAFLD and NAFLD-related hepatocellular carcinoma

Islands stretch test for measuring the interfacial fracture energy between a hard film and a soft substrate

We present a technique for measuring the interfacial fracture energy, $\Gamma_i$, between a hard thin film and a soft substrate. A periodic array of hard thin islands is fabricated on a soft substrate, which is then subjected to uniaxial tension under an optical microscope. When the applied strain reaches a critical value, delamination between the islands and the substrate starts from the edge of the islands. As the strain is increased, the interfacial cracks grow in a stable fashion. At a given applied strain, the width of the delaminated region is a unique function of the interfacial fracture energy. We have calculated the energy release rate driving the delamination as a function of delamination width, island size, island thickness, and applied strain. For a given materials system, this relationship allows determination of the interfacial fracture energy from a measurement of the delamination width. The technique is demonstrated by measuring the interfacial fracture energy of plasma-enhanced chemical vapor deposition SiNx islands on a polyimide substrate. We anticipate that this technique will find application in the flexible electronics industry where hard islands on soft substrates are a common architecture to protect active devices from fracture.Engineering and Applied Science

Downregulation of protein kinase CK2 activity induces age-related biomarkers in C. elegans

Studies show that a decrease in protein kinase CK2 (CK2) activity is associated with cellular senescence. However, the role of CK2 in organism aging is still poorly understood. Here, we investigated whether protein kinase CK2 (CK2) modulated longevity in Caenorhabditis elegans. CK2 activity decreased with advancing age in the worms. Knockdown of kin-10 (the ortholog of CK2 beta) led to a short lifespan phenotype and induced age-related biomarkers, including retardation of locomotion, decreased pharyngeal pumping rate, increased lipofuscin accumulation, and reduced resistance to heat and oxidative stress. The long lifespan of age-1 and akt-1 mutants was significantly suppressed by kin-10 RNAi, suggesting that CK2 acts downstream of AGE-1 and AKT-1. Kin-10 knockdown did not further shorten the short lifespan of daf-16 mutant worms but either decreased or increased the transcriptional activity of DAF-16 depending on the promoters of the target genes, indicating that CK2 is an upstream regulator of DAF-16 in C. elegans. Kin-10 knockdown increased production of reactive oxygen species (ROS) in the worms. Finally, the ROS scavenger N-acetyl-L-cysteine significantly counteracts the lifespan shortening and lipofuscin accumulation induced by kin-10 knockdown. Therefore, the present results suggest that age-dependent CK2 downregulation reduces longevity by associating with both ROS generation and the AGE-1-AKT-1-DAF-16 pathway in C. elegans. © Copyright 2017 Elsevier B.V., All rights reserved.1111sci

The discovery and characterization of tungsten insertase in tungsten cofactor biosynthesis

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Inorganic Islands on a Highly Stretchable Polyimide Substrate

For a flexible electronic device integrating inorganic materials on a polymer substrate, the polymer can deform substantially, but the inorganic materials usually fracture at small strains. This paper describes an approach to make such a device highly stretchable. A polyimide substrate is first coated with a thin layer of an elastomer, on top of which SiNx islands are fabricated. When the substrate is stretched to a large strain, the SiNx islands remain intact. Calculations confirm that the elastomer reduces the strain in the SiNx islands by orders of magnitude.Engineering and Applied Science

Pediatric application of cuffed endotracheal tube: a secondary publication translated into Korean

A young child’s larynx was formerly believed to be narrowest at the cricoid level, circular in section, and funnel shaped. This supported the routine use of uncuffed endotracheal tubes in young children despite the benefits of cuffed tubes, such as lower risk for air leakage and aspiration. In the late 1990s, evidence supporting the pediatric use of cuffed tubes emerged largely from anesthesiology studies, while some technical flaws of the tubes remained a concern. Since the 2000s, imaging-based studies have clarified laryngeal anatomy, revealing that it is narrowest at the glottis, elliptical in section, and cylindrical in shape. The update was contemporaneous with technical advances in the design, size, and material of cuffed tubes. The American Heart Association currently recommends the pediatric use of cuffed tubes. In this review, we present the rationale for using cuffed tubes in young children based on our updated knowledge of pediatric anatomy and technical advances

Effects of Berberine and Hwangryunhaedok-Tang on Oral Bioavailability and Pharmacokinetics of Ciprofloxacin in Rats

Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat bacterial infection and inflammatory diseases in eastern Asia. The combination of berberine-containing herbal medicines and ciprofloxacin can be an excellent antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the pretreatment effect of berberine and HR, vehicle, berberine (25 and 50 mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20 mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were coadministered by single oral gavage. Pharmacokinetic data were estimated by noncompartmental model. Compared with ciprofloxacin alone (control group), coadministration of berberine (50 mg/kg) and ciprofloxacin significantly decreased Cmax of ciprofloxacin (P<0.05). In addition, the pretreatment of berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreased Cmax and AUC0→∞, compared with control group (P<0.05). The oral bioavailability of ciprofloxacin was reduced by cotreatment of berberine and pretreatment of berberine and HR. Our results suggest that the expression of P-glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR

Characteristics of thyroid nodules in infant with congenital hypothyroidism

PurposeThis study aimed to assess the characteristics of thyroid nodules among infants diagnosed with congenital hypothyroidism.MethodsA retrospective study of 660 infants (374 males, 286 females) diagnosed with congenital hypothyroidism was carried out at the Pediatric Endocrine Clinic in Soonchunhyang University Hospital, Korea, between May 2003 and February 2013. The average age at diagnosis was 1.16±1.68 months.ResultsOf the 28 patients (4.2%) with thyroid nodules, 17 (2.6%) had cystic thyroid nodules and 11 (1.6%) had solid thyroid nodules. There were no significant differences in gender or age between congenital hypothyroidism patients who hadthyroid nodules and those who did not. All nodules were asymptomatic. The average age at diagnosis of congenital hypothyroidism with nodules was 1.42±1.39 months. All detected nodules measured less than 1 cm in diameter. Twenty-two of the 28 infants (78.6%) had only one nodule, while multiple nodules were found in 6 infants (21.4%). Of the 28 infants diagnosed with nodules, 16 underwent thyroid ultrasonography during follow-up and 8 of them (50%) showed no signs of nodules at thyroid ultrasonography.ConclusionThe prevalence of thyroid nodules in infants with congenital hypothyroidism was 4.2%. Most thyroid nodules were small in size and benign, disappearing during follow-up observation. We therefore conclude that thyroid nodules in infants with congenital hypothyroidism can simply be observed and do not require direct treatment