NHN (South Korea)

Skin aging causes reduced hydration, elasticity, and increased wrinkles. Recent safety and compliance concerns over oral collagen supplements have increased interest in plant-based alternatives like Hibiscus sabdariffa with antioxidant and anti-aging properties. However, clinical evidence regarding its efficacy remains limited. We aimed to evaluate the effects of this plant-based collagen alternative (VC-H1, Hibiscus Enzyme Extract) supplement on skin hydration, transepidermal water loss (TEWL), desquamation, elasticity, and wrinkle reduction in photoaged individuals. A randomized, double-blind, placebo-controlled clinical trial was conducted with 98 participants (aged 35–60 years) presenting with dry skin and periorbital wrinkles. Participants randomly received 1.5 g/day of VC-H1 or placebo for 12 weeks. Skin hydration, TEWL, deep moisture, keratin index, elasticity, and wrinkle parameters were assessed at baseline, 6 weeks, and 12 weeks. VC-H1 supplementation significantly increased skin hydration, reduced the TEWL and keratin index, and improved deep moisture content for those receiving it compared with the controls. Wrinkle depth significantly decreased, and skin elasticity also improved. Those in the VC-H1 group showed greater overall improvement than those in the control group. Oral VC-H1 supplementation significantly improved skin hydration, elasticity, and wrinkle reduction, suggesting its potential as a plant-based alternative to traditional collagen supplements for skin rejuvenation.

Abstract BackgroundDonepezil is a selective oral acetylcholinesterase inhibitor to treat Alzheimer’s disease (AD). Most patients with AD need help with taking oral donepezil for forgetfulness etc. Therefore, long acting injectables (LAIs) can improve patient’s compliance and quality of life. Because of narrow therapeutic window of donepezil, precisely size controlled microsphere technology is needed for drug release control. We have developed IVL3003 as a novel sustained release monodisperse subcutaneous (SC) LAI of donepezil for one month using IVL‐DrugFluidics® technology. The purpose of this study is to evaluate the physicochemical characteristics of IVL3003 and investigate the inter‐species pharmacokinetic profile differences in beagle and monkey models.MethodVarious one month formulations of donepezil microspheres were prepared by IVL‐DrugFluidics®. Characterization of IVL3003 was performed by scanning electron microscopy (SEM), and the size distribution was measured by laser particle size analyzer (PSA). The amount of donepezil and encapsulation efficiency (EE, %) was determined by HPLC. Size distributions were expressed as span value and CV(%). Non‐clinical models were used to optimize formulations and to evaluate their pharmacokinetic properties. IVL3003 was administered to male beagle dogs (n = 3/group, 11 months old, body weight 9∼11 kg) and male cynomolgus monkeys (n = 3/group, 30∼50 months old, body weight 2.6∼3.3 kg). Plasma concentrations were monitored for one month.ResultsThe SEM images of the microspheres appeared spherical and smooth. Donepezil was well encapsulated and homogeneously. The EE(%) of microspheres was 97.5% and the residual solvent was 232.2 ppm. The span value was 0.25 and CV(%) was 10.01%. The plasma concentrations of donepezil were maintained for 28 days without any initial burst and had small individual variation. There was no big difference between species in plasma concentration and showed a similar PK profile in both.ConclusionsAs we postulated, narrow distribution of the particles was led to improvement of controlled‐release characteristics. These results proved the excellence of IVL‐DrugFluidics® as an ideal microsphere fabrication method in manufacturing uniform and monodispersed microspheres. Long‐acting injectable, IVL3003 is expected to increase the compliance and the safety in the treatment of Alzheimer’s patients. We have filed Ph I for IVL3003 recently as the 1st donepezil containing LAI.

Alcoholic liver disease (ALD) is damage to the liver and mainly caused by binge alcohol. ALD have decreased junctional protein expression and modulated intestinal permeability. We investigated whether plant-releasing exosome-like nanovesicles can prevent liver damage and leaky gut from binge alcohol. In this study, we characterized the exosome-like nanovesicles from pomegranate juice and confirmed the round shape of a lipid bilayer. After 14 days of pomegranate-derived exosome-like nanovesicle (PNVs) pretreatment, binge alcohol (6 g/kg/dose) was administered to mice three times orally every 12 h. Exposure to binge alcohol increased levels of oxidative and nitric oxide stress marker proteins such as CYP2E1, 3-Nitrotyrosine, and inducible nitric oxide synthase in both liver and gut damage. Also, binge alcohol significantly elevated the plasma endotoxemia, inflammatory fatty liver, and leaky gut. However, PNVs reduced the oxidative stress and apoptosis marker proteins and prevented the leaky gut and endotoxemia. Markedly, PNV treatment significantly prevented a decrease in the amount of intestinal junctional proteins and an increase in leaky gut in mice exposed to alcohol. These results showed that PNVs can prevent leaky gut and liver damage caused by binge alcohol and suggest that it may be useful hepatoprotective or intestinal protective agents for the first time.

SummaryBackgroundTegoprazan is a novel, fast‐ and long‐acting potassium‐competitive acid blocker that suppresses gastric acid secretion, which could benefit patients with non‐erosive reflux disease (NERD), a type of gastroesophageal reflux disease.AimTo evaluate the efficacy and safety profiles of tegoprazan compared with those of a placebo in Korean patients with NERD.MethodsIn this phase 3, double‐blind, placebo‐controlled, multicentre study, 324 Korean patients with NERD were randomised into three treatment groups: tegoprazan 50 mg, tegoprazan 100 mg and placebo. These drugs were provided once daily for 4 weeks. The primary endpoint was the proportion of patients with complete resolution of major symptoms (both heartburn and regurgitation) for the last 7 days of the 4‐week treatment period. Other outcomes related to efficacy, safety and tolerability were also evaluated.ResultsAmong all, 42.5% (45/106), 48.5% (48/99) and 24.2% (24/99) of patients showed complete resolution of major symptoms at week 4 after receiving tegoprazan 50 mg, tegoprazan 100 mg, and placebo, respectively. Both doses of tegoprazan showed superior efficacy than the placebo (P = 0.0058 and P = 0.0004, respectively). The complete resolution rates of heartburn and proportions of heartburn‐free days (as other efficacy outcomes) were significantly higher in both tegoprazan groups than in the placebo group (P < 0.05 for all). No significant difference in the incidence of treatment‐emergent adverse events were noted.ConclusionsTegoprazan 50 and 100 mg showed superior therapeutic efficacy compared with the placebo, as well as a favourable safety profile in patients with NERD.Registration number: ClinicalTrials.gov identifier NCT02556021.

In this paper, we propose an efficient approach that computes the dynamic time warping (DTW) distance in time-series similarity search. The DTW distance is known to offer the high accuracy in similarity search, but it has difficulty in supporting the large database due to its high computational complexity. Recently, FastDTW and FTW have been proposed for efficient computation of DTW distances, but they have still performance limitations. In this paper, we propose a hybrid approach, called HybridFTW, which combines the advantages of both FastDTW and FTW. First, HybridFTW takes the advantage of FastDTW that provides fast computation through the limitation of allowable ranges. We call these allowable ranges dynamic (warping) bands, which reduce the computation spaces on the fly, and we reanalyze previous FastDTW and FTW in the viewpoint of static and dynamic bands. Second, HybridFTW also takes the advantage of FTW that exploits the early abandon effect by using the segment-based tight lower bound. To maximize the synergy of combining two methods, we obtain the dynamic band of FastDTW during the process of computing the lower bound in FTW. Using HybridFTW, we next propose range search and k-NN search algorithms and prove their correctness through formal theorems. Experimental results on real and synthetic data sets show that HybridFTW improves the search performance by up to 38 times over FastDTW and by up to 12 times over FTW.

In this paper, we propose an immersive panorama TV service system. The proposed system provides real-time panorama videos and/or images for smart displays such as smart TVs, smart phones, and tablet PCs. Panorama videos and/or images are collected at sports events by panorama cameras. Collected contents are sent to servers, and then provide to smart devices with sports live videos. Users can select their view among panorama cameras, and can choose their view angle and zooming factor inside selected panorama camera. The proposed system provides immersive and realistic views of sports live events on users television.

Almost all small area estimations are obtained by minimizing the mean squared error. Recently relative error prediction methods have been developed and adapted to small area estimation. Usually the estimators obtained by using relative error prediction is called a shrinkage estimator. Especially when data set consists of large range values, the shrinkage estimator is known as having good statistical properties and an easy interpretation. In this paper we study the shrinkage estimators based on logistic regression type estimators for small area estimation. Some simulation studies are performed and the Economically Active Population Survey data of 2005 is used for comparison.