ALBERT

Description: Current evidence on the effects of coffee intake on cardiovascular diseases is not consistent, in part contributed by the genetic variability of the study subjects. While adenosine receptors (ADORAs) are involved in caffeine signaling, it remains unknown how genetic variations at the ADORA loci correlate the coffee intake with cardiovascular diseases. The present study examined the associations of coffee intake with dyslipidemia risk depending on genetic variants in the ADORA gene family. The study involved a population-based cohort of 4898 Korean subjects. Consumption of more than or equal to a cup of coffee per day was associated with lower dyslipidemia risk in females carrying the ADORA2B minor allele rs2779212 (OR: 0.645, 95% CI: 0.506–0.823), but not in those with the major allele. At the ADORA2A locus, male subjects with the minor allele of rs5760423 showed instead an increased risk of dyslipidemia when consuming more than or equal to a cup of coffee per day (OR: 1.352, 95% CI: 1.014–1.802). The effect of coffee intake on dyslipidemia risk differs depending on genetic variants at the ADORA loci in a sex-specific manner. Our study suggests that a dietary guideline for coffee intake in the prevention and management of dyslipidemia ought to consider ADORA-related biomarkers carefully.

Description: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer. Besides genetic and environmental factors, epigenetic alterations contribute to the tumorigenesis of NSCLC. Epigenetic changes are considered key drivers of cancer initiation and progression, and altered expression and activity of epigenetic modifiers reshape the epigenetic landscape in cancer cells. Euchromatic histone-lysine N-methyltransferase 2 (EHMT2) is a histone methyltransferase and catalyzes mono- and di-methylation at histone H3 lysine 9 (H3K9me1 and H3K9me2, respectively), leading to gene silencing. EHMT2 overexpression has been reported in various types of cancer, including ovarian cancer and neuroblastoma, in relation to cell proliferation and metastasis. However, its role in NSCLC is not fully understood. In this study, we showed that EHMT2 gene expression was higher in NSCLC than normal lung tissue based on publicly available data. Inhibition of EHMT2 by BIX01294 (BIX) reduced cell viability of NSCLC cell lines via induction of autophagy. Through RNA sequencing analysis, we found that EHMT2 inhibition significantly affected the cholesterol biosynthesis pathway. BIX treatment directly induced the expression of SREBF2, which is a master regulator of cholesterol biosynthesis, by lowering H3K9me1 and H3K9me2 at the promoter. Treatment of a cholesterol biosynthesis inhibitor, 25-hydroxycholesterol (25-HC), partially recovered BIX-induced cell death by attenuating autophagy. Our data demonstrated that EHMT2 inhibition effectively induced cell death in NSCLC cells through altering cholesterol metabolism-dependent autophagy.

Description: Ovarian cancer is the gynecological malignancy with the poorest prognosis, in part due to its high incidence of recurrence. Platinum agents are widely used as a first-line treatment against ovarian cancer. Recurrent tumors, however, frequently demonstrate acquired chemo-resistance to platinum agent toxicity. To improve chemo-sensitivity, combination chemotherapy regimens have been investigated. This study examined anti-tumor effects and molecular mechanisms of cytotoxicity of Oldenlandia diffusa (OD) extracts on ovarian cancer cells, in particular, cells resistant to cisplatin. Six ovarian cancer cells including A2780 and cisplatin-resistant A2780 (A2780cis) as representative cell models were used. OD was extracted with water (WOD) or 50% methanol (MOD). MOD significantly induced cell death in both cisplatin-sensitive cells and cisplatin-resistant cells. The combination treatment of MOD with cisplatin reduced viability in A2780cis cells more effectively than treatment with cisplatin alone. MOD in A2780cis cells resulted in downregulation of the epigenetic modulator KDM1B and the DNA repair gene DCLRE1B. Transcriptional suppression of KDM1B and DCLRE1B induced cisplatin sensitivity. Knockdown of KDM1B led to downregulation of DCLRE1B expression, suggesting that DCLRE1B was a KDM1B downstream target. Taken together, OD extract effectively promoted cell death in cisplatin-resistant ovarian cancer cells under cisplatin treatment through modulating KDM1B and DCLRE1B.

Description: In this paper, we propose AR Pointer, a new augmented reality (AR) interface that allows users to manipulate three-dimensional (3D) virtual objects in AR environment. AR Pointer uses a built-in 6-degrees of freedom (DoF) inertial measurement unit (IMU) sensor in an off-the-shelf mobile device to cast a virtual ray that is used to accurately select objects. It is also implemented using simple touch gestures commonly used in smartphones for 3D object manipulation, so users can easily manipulate 3D virtual objects using the AR Pointer, without a long training period. To demonstrate the usefulness of AR Pointer, we introduce two use-cases, constructing an AR furniture layout and AR education. Then, we conducted two experiments, performance tests and usability tests, to represent the excellence of the designed interaction methods using AR Pointer. We found that AR Pointer is more efficient than other interfaces, achieving 39.4% faster task completion time in the object manipulation. In addition, the participants gave an average of 8.61 points (13.4%) on the AR Pointer in the usability test conducted through the system usability scale (SUS) questionnaires and 8.51 points (15.1%) on the AR Pointer in the fatigue test conducted through the NASA task load index (NASA-TLX) questionnaire. Previous AR applications have been implemented in a passive AR environment where users simply check and pop up the AR objects those are prepared in advance. However, if AR Pointer is used for AR object manipulation, it is possible to provide an immersive AR environment for the user who want/wish to actively interact with the AR objects.

Description: Developing innovative and pervasive smart technologies that provide medical support and improve the welfare of the elderly has become increasingly important as populations age. Elderly people frequently experience incidents of discomfort in their daily lives, including the deterioration of cognitive and memory abilities. To provide auxiliary functions and ensure the safety of the elderly in daily living situations, we propose a projection-based augmented reality (PAR) system equipped with a deep-learning module. In this study, we propose three-dimensional space reconstruction of a pervasive PAR space for the elderly. In addition, we propose the application of a deep-learning module to lay the foundation for contextual awareness. Performance experiments were conducted for grafting the deep-learning framework (pose estimation, face recognition, and object detection) onto the PAR technology through the proposed hardware for verification of execution possibility, real-time execution, and applicability. The precision of the face pose is particularly high by pose estimation; it is used to determine an abnormal user state. For face recognition results of whole class, the average detection rate (DR) was 74.84% and the precision was 78.72%. However, for face occlusions, the average DR was 46.83%. It was confirmed that the face recognition can be performed properly if the face occlusion situation is not frequent. By object detection experiment results, the DR increased as the distance from the system decreased for a small object. For a large object, the miss rate increased when the distance between the object and the system decreased. Scenarios for supporting the elderly, who experience degradation in movement and cognitive functions, were designed and realized, constructed using the proposed platform. In addition, several user interfaces (UI) were implemented according to the scenarios regardless of distance between users and the proposed system. In this study, we developed a bidirectional PAR system that provides the relevant information by understanding the user environment and action intentions instead of a unidirectional PAR system for simple information provision. We present a discussion of the possibility of care systems for the elderly through the fusion of PAR and deep-learning frameworks.

Description: Isoquinoline alkaloids-enriched herbal plants have been used as traditional folk medicine for their anti-inflammatory, antimicrobial, and analgesic effects. They induce cell cycle arrest, apoptosis, and autophagy, leading to cell death. While the molecular mechanisms of these effects are not fully understood, it has been suggested that binding to nucleic acids or proteins, enzyme inhibition, and epigenetic modulation by isoquinoline alkaloids may play a role in the effects. This review discusses recent evidence on the molecular mechanisms by which the isoquinoline alkaloids can be a therapeutic target of cancer treatment.