Non-alcoholic steatohepatitis (NASH) is associated with significant morbidity and mortality due to liver cirrhosis, liver failure, and hepatocellular carcinoma, and represents a leading indication ...for liver transplantation in the United States (U.S.). A growing spectrum of novel therapies are currently in clinical development and target several mechanisms of action which address hepatic steatosis, steatohepatitis, and hepatic fibrosis. Cenicriviroc (Allergan, Dublin, Ireland) is a novel oral antagonist of CC-motif chemokine receptors 2 and 5 (CCR2/5) which have demonstrated expression on circulating monocytes and Kupffer cells. Preclinical models have confirmed that CCR2/5 antagonism may block fat accumulation and Kupffer cell activation and disrupt monocyte/macrophage recruitment and hepatic stellate cell activation responsible for fibrogenesis. Herein we review results from the phase 2b CENTAUR trial and study designs for the phase 2b TANDEM and phase 3 AURORA trials and discuss the potential role of cenicriviroc in future pharmacotherapy for NASH fibrosis. Keywords: cenicriviroc, fatty liver, non-alcoholic steatohepatitis, liver fibrosis, antifibrotic therapy, clinical trials
Background/purpose: Ultraviolet (UV) irradiation affects the function and complexion of the skin by inducing changes in physical properties through formation of erythema, proliferation of epithelial ...cells, DNA damage, activation or inactivation of various enzymes and proteins, and free radical formation. In this study, the authors intended to observe the overall course of changes in barrier function and reflectance of the skin induced by photodamage, and healing reaction in the course of time, and alteration of the skin complexion.
Methods: The subjects were chosen from 15 healthy Korean men 20–35 in age, that fall into the category of Fitzpatrick's skin types II, III, and IV without history of recent exposure to sunlight, photosensitivity, or having taken any drugs that induce phototoxicity or photoallergic reactions. The subjects were artificially exposed to suberythemogenic dose 0.5 minimal erythemal dose (MED), 0.75 MED, 1 MED and high dose (2.5 MED) by solar simulator, and changes in skin barrier function and skin reflectance were assessed with a Tewameter, a Corneometer, and a Colorimeter for 4 weeks.
Results: Transepidermal water loss (TEWL) increased abruptly at Day 1 of single solar UV (SSUV) exposure, and slowly returned to the original level from Day 2/Day 3. In the case of exposure with 0.75 MED, it returned to the original level at Day 4 of exposure, and at Days 7 and 28 in the cases of 1 MED and 2.5 MED exposure, respectively. Water‐holding capacity sharply declined at Day 1 of exposure, hitting the lowest point at Day 2, and then slowly recovered starting on Day 3. In the case of exposure with 0.75 MED and 1 MED, it returned to the original level at Days 7 and 28 in the case of 2.5 MED exposure. The a* values abruptly increased and reached the peak at Day 1 and slowly returned to the original level at Day 2, while the b* values slowly increased at Day 3, peaking at Day 7 and slowly returning to the original level thereafter. The L* values abruptly declined at Day 1, maintaining plateau through Day 7 and slowly returning to the baseline level thereafter. The individual typology angle (ITA°) were compatible with L* values change. The erythema index increased abruptly at Day 1 of SSUV exposure, peaking at Day 2 and slowly returned to the original level starting at Day 3. Melanin index slowly started to increase on Day 3 of SSUV exposure, peaking at Day 7 and gradually returned to the original level thereafter. However, L*, a*, b*, erythema index, and melanin index did not return to the original level during the 28‐day course of this study.
Conclusion: This study shows that in the skin of Korean subjects, changes in skin barrier function and delayed melanization do occur even in exposure to a suberythemogenic dose of SSUV. Also, given the fact that restoration of barrier function occurs as the process of melanization begins, melanization is considered to be a useful predictive indicator of the restoration of the skin barrier function after sunburn.
The effective dose under ordinary clinical computed tomography (CT) protocols using three kinds of 64-channel and a 40-channel CT ranged from 0.6 to 15.5 mSv in early 2010s. And the organ dose ranged ...from 1.6 to 130.4 mGy: orbital and brain doses for brain stroke CT were the highest. For the comparison of the effective dose between late 1990s and early 2010s, multidetector CT (MDCT) for high-resolution lung CT was 2.4 times higher than that of single-detector CT (SDCT) and the ratio was the highest. However, the effective dose at MDCT was 20 % lower than that of SDCT in chest CT due to applying dose-saving techniques. In organ dose comparisons, high-resolution lung CT at MDCT was 3.5-4.5 times higher than that of SDCT, and showed 1.1-1.5 times higher than that of SDCT in the head and chest CT. For the abdomen CT, the primary organ dose at MDCT was ∼30 % lower than that of SDCT.
Peroxiredoxin (PRX) is a crucial antioxidant protein that protects against endogenously produced peroxides in prokaryotes to eukaryotes. To date, 6 different isoforms have been identified in mammals. ...In this study, we describe the first members of the PRX protein family to be characterized in Chicken. Through bioinformatics analysis, we observed that at least 4 different classes of PRX protein have been evolutionarily conserved in chickens. Furthermore, in vitro functional assays of the candidate chicken PRX proteins demonstrated that they had levels of antioxidant activity similar to those of the mammalian enzymes. The expression patterns of the PRX transcript in several chicken tissues were not tissue specific, suggesting that they might play an essential role as a housekeeping gene in all tissues to protect against oxidative damage. In conclusion, the sequences of the putative members of this functional gene family in chickens could be effectively retrieved in silico through bioinformatics analysis, and the functionality of their gene products evaluated by in vitro comparative assay.
A silicon carbide (SiC) powder compact was prepared with submicrometer β‐SiC, yttrium nitrate as a sintering additive, and polysiloxane‐phenol resin as precursors for nanosized SiC. By hot‐pressing, ...fully dense SiC ceramics with good electrical conductivity, as high as 3 × 104 (Ω·m)−1 at room temperature, were obtained. The ceramics could be machined to complex shapes by electrodischarge machining.
Abstract
Purpose
Patients with diabetes mellitus have an elevated risk of atrial fibrillation (AF). However, whether insulin resistance may elevate risk of AF incidence in non-diabetic is ...inconsistent. The aim of our study was to verify the association between insulin resistance and incidence of AF in non-diabetics.
Methods
We evaluated population-based cohorts embedded in the Korean Genome Epidemiology Study. Insulin resistance was expressed as Homeostasis Model Assessment for Insulin resistance (HOMA-IR). Baseline data including HOMA-IR and electrocardiography (ECG) were obtained at 2001. Subsequent biennial ECG was performed for identification of AF until 2016.
Results
Among the 8220 participants (46.8% male; median age 49 years), 25 participants had AF (0.3%) at baseline and 101 participants developed AF (1.2%) during follow up of 12 years. In multivariate Cox regression analysis, high HOMA-IR (≥1.4) was significantly associated with incident AF compared with low HOMA-IR (<1.40) (adjusted hazard ratio HR 1.9, 95% confidence interval CI 1.3–3.0). In subgroup analysis, these association was consistent regardless of obesity (BMI<25; adjust HR 1.8, 95% CI 1.1–3.0, BMI≥25; adjust HR 2.3, 95% CI 1.3–4.0)
Subgroup analysis
Conclusion
Based on prospective cohort study, insulin resistance (HOMA-IR) was associated with AF independently of obesity in non-diabetics.
The Delta-Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism essential for cell fate specification. Mind bomb 1 (Mib1) has been identified as a ubiquitin ligase ...that promotes the endocytosis of Delta. We now report that mice lacking Mib1 die prior to embryonic day 11.5, with pan-Notch defects in somitogenesis, neurogenesis, vasculogenesis and cardiogenesis. The Mib1 â/â embryos exhibit reduced expression of Notch target genes Hes5 , Hey1 , Hey2 and Heyl , with the loss of N1icd generation. Interestingly, in the Mib1 â/â mutants, Dll1 accumulated in the plasma membrane, while it was localized in the cytoplasm near the nucleus in the wild types, indicating that Mib1 is essential for the endocytosis of Notch ligand. In accordance with the pan-Notch defects in Mib1 â/â embryos, Mib1 interacts with and regulates all of the Notch ligands, jagged 1 and jagged 2, as well as Dll1, Dll3 and Dll4. Our results show that Mib1 is an essential regulator, but not a potentiator, for generating functional Notch ligands to activate Notch signaling.
Microalgal hydrogen (H2) production via photo-fermentative process is an environmentally friendly alternative to the fossil fuel-based energy. Palm kernel expeller (PKE), a low-cost biomass had ...presented a significant advantage as organic nutrients' source in this study to fuel the photo-fermentative process. However, the increase of PKE concentrations beyond a threshold of 15.0 g/L had led to the decrease in H2 production. As this metabolic photo-fermentative process was driven by light illumination, it was essential to investigate the impact exerted by various light intensities on microalgal H2 productions. Accordingly, the oxygen (O2) concentration evolutions stemming from increasing photosynthetic dissolved oxygen (DO) concentrations within the culture mediums were evaluated and remodelled with the Andrew's substrate inhibition model. The absolute inhibition of photo-fermentation was predicted at 29.6 g/L of PKE with 0.006 g/L. day of photosynthetic oxygenation rate under a specific light intensity ranging from 100 to 500 μmol/m2s. On the other hand, at the optimum 5–15 g/L of PKE, the maximum H2 production rate could be attained at about 46 mL-H2/g-biomass.day with 200 μmol/m2s of light intensity. Further increasing of light intensities had also increased the photosynthetic activities, leading to the increased DO accumulations that favoured the culture photorespirations over photo-fermentative H2 productions. The sustainability of producing microalgal H2 was finally verified from the recycled study using a similar PKE organic nutrients' source to continuously generate H2 that had steadily maintained after the second cycle onwards with merely 4% of a gradual decrease until fourth cycle.
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•Photo-fermentative H2 production from microalgae subsisting palm kernel expeller.•Remodelled microalgal H2 kinetics from substrate concentration and light intensity.•High photosynthesis to drive microalgae for producing photo-fermentative H2.•Spent palm kernel expeller could sustain high iterative microalgal H2 productions.
Persistent left superior vena cava is a rare but well-recognised condition. We describe a case of persistent left superior vena cava draining directly into the left atrium, with a fixed anatomical ...right-to-left shunt and paradoxical embolic events causing recurrent brain abscess. Surgical ligation was curative.
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