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Background Long-chain polyunsaturated fatty acids of the omega-6 and omega-3 families affect processes implicated in vascular and neural retinal disease pathogenesis. This study aimed to investigate the association between the dietary omega-6 to omega-3 fatty acid ratio and age-related macular degeneration (AMD). Methods We conducted a cross-sectional analysis using a nationwide representative sample of older adults (≥ 50 years), including 1,944 men and 2,592 women, from the Korea National Health and Nutrition Examination Survey (2017–2018). Omega-6 and omega-3 fatty acid intakes were collected through a 24-hour recall method and used to calculate the omega-6 to omega-3 fatty acid ratio. Associations between the ratio and AMD were determined using odds ratios (ORs) from multivariate logistic regressions. Results The prevalence of AMD was 19.8% and 17.7% in Korean men and women, respectively. In women, the multivariable-adjusted OR for incurring AMD was significantly higher in the 2nd (OR = 1.36; 95% CI = 1.02–1.81) and 3rd (OR = 1.36; 95% CI = 1.02–1.83) tertiles of the dietary omega-6 to omega-3 fatty acid ratio than in the 1st tertile (OR = 1, the reference OR) ( P  = 0.036 for this trend). However, this association was not observed in men. Conclusions These results suggest that high omega-6 to omega-3 fatty acid ratios may be associated with an increased prevalence of AMD among Korean women.

The aim of study was to investigate proliferation and differentiation capacities of Hanwoo myosatellite cells for the development of Hanwoo cell cultures. From P1 to P19, the number of live cells decreased and the cell size increased. It was confirmed that the PAX7 mRNA was higher in P3 than P6 and P9 ( p  < 0.05). The maximum differentiation score was measured from P1 to P12. The maximum differentiation score maintained high from P1 to P10. Immunostaining was performed for both P1 and P10 cells to investigate differentiation characteristics. And there were no significant differences in differentiation characteristics between P1 and P10 cells. MYOG mRNA was low, whereas C-FOS mRNA was high ( p  < 0.05) in the late passage. Myosin and Tom20 protein also showed low values in the late passage ( p  < 0.05). In conclusion, our results suggest that it is appropriate to use P1 to P10 for the production of cultured meat using Hanwoo muscle cells. If cell culture meat production is performed without differentiation, the passage range may increase further. These results provide basic essential data required for further development of Hanwoo cell cultures, which could provide a valuable source of protein for human populations in the future.

Cardiovascular diseases are the major cause of death globally and require ubiquitous monitoring due to their asymptomatic yet modifiable nature. Photoplethysmography is an effective optical sensing technique for non-invasive health monitoring. However, its reliance on the current relatively large and rigid inorganic semiconductor-based light-emitting diodes and silicon photodiodes hampers high-resolution integration thus restricts a sensing from single measurement point. So, it limits detectable biomarkers to monitor cardiovascular diseases in a ubiquitous manner. In order to facilitate, here we report a single smartphone type multi-functional cardiovascular health monitor based on the massive array of organic photodiodes integrated into the most user interactive display device. Therefore, we achieved: 1) multi-point concurrent photoplethysmography and high-resolution dynamic image sensing, and 2) user-interactive sensing within the large display area. These advancements enabled new functions, including high-accuracy screening for cardiovascular diseases, blood pressure monitoring from both fingers, monitoring of finger blood vessels and flow dynamics, and single-device-based biofeedback. Applied machine learning enhanced diagnostic accuracy, with pilot studies showing results comparable to medical-grade devices. As a result, we believe smartphones harnessing the sensor organic light-emitting diode display could evolve into mobile health monitors and digital therapeutics thus revolutionizing diagnostic and treatment. Cardiovascular diseases require precise and continuous monitoring, but current PPG technology is limited to single-point sensing. Here, the authors present a display with organic photodiodes that enables multi-point PPG, high-resolution imaging, and user-interactive sensing.

A pharmacological screen has identified the histone methyltransferase G9a as a target to reactivate imprinted genes in a mouse model of Prader–Willi Syndrome that improves growth and survival. Prader–Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11–q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In individuals with PWS, genes responsible for PWS on the maternal chromosome are present, but repressed epigenetically, which provides an opportunity for the use of epigenetic therapy to restore expression from the maternal copies of PWS-associated genes. Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642—two selective inhibitors of euchromatic histone lysine N -methyltransferase-2 (EHMT2, also known as G9a)—activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116 , in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N ( Snrpn ( S )) to ubiquitin protein ligase E3A ( Ube3a ( U )) (mouse model referred to hereafter as m + /p ΔS−U ). Both UNC0642 and UNC0638 caused a selective reduction of the dimethylation of histone H3 lysine 9 (H3K9me2) at PWS-IC, without changing DNA methylation, when analyzed by bisulfite genomic sequencing. This indicates that histone modification is essential for the imprinting of candidate genes underlying PWS. UNC0642 displayed therapeutic effects in the PWS mouse model by improving the survival and the growth of m + /p ΔS−U newborn pups. This study provides the first proof of principle for an epigenetics-based therapy for PWS.

Lifestyle modification is the first step in hypertension management. Our objective was to assess adherence to lifestyle recommendations by individuals who were aware of their hypertension and to identify characteristics associated with non-adherence. Using data from the Korea National Health and Nutrition Examination Survey conducted in 2010-2012, we compared the adherence to six lifestyle recommendations of hypertensive subjects aware of the status of their condition with that of those who were not aware, based on survey regression analysis. The characteristics associated with non-adherence were assessed by multiple logistic regression analysis. Of all hypertensive subjects, <20% adhered to a healthy diet and reduced salt intake and about 80% moderated alcohol consumption and did not smoke. Half of all subjects maintained normal body weight and engaged in physical activity. Most lifestyle features of aware hypertensive Koreans did not differ greatly from those of hypertensive individuals who were not aware. Reduction in salt intake was slightly more prevalent among those aware of their hypertensive status. Obesity was more prevalent among the aware hypertensive subjects, and the prevalence of obesity increased with the duration of hypertension. Male gender, younger age, residence in a rural area, low income, and the use of antihypertensive medication were associated with non-adherence to lifestyle recommendations by hypertensive individuals. Many hypertensive Koreans do not comply with lifestyle recommendations for the management of hypertension. The association between the use of antihypertensive medications and non-adherence suggested an over-reliance on medication rather than a commitment to a healthy lifestyle. Our study highlights that efforts encouraging healthy lifestyles, as the first step in hypertension management, need to be increased.

Background Trastuzumab is the only approved target agent for the first-line treatment of human epidermal growth factor receptor-2 (HER-2) positive gastric cancer; however, trastuzumab resistance is a major problem in clinical practice. To comprehend the mechanism of trastuzumab resistance, we focused on the Wnt/β-catenin signaling pathway and its influence on the phenotypes and behavior of trastuzumab-resistant gastric cancer cells. Methods Trastuzumab-resistant NCI-N87R cells were established in vitro from the human gastric cancer cell line NCI-N87 by dose-escalating repeated trastuzumab treatment. We investigated the phenotypes of NCI-N87R cells, including Wnt signaling pathway activity. Gastric cancer organoid cells were incubated with complete medium and Wnt3a-depletion medium, and their resistance to trastuzumab was compared. Results NCI-N87R exhibited stemness and epithelial-mesenchymal transition (EMT)-like phenotypes, along with decreased levels of the epithelial marker E-cadherin and increased levels of the mesenchymal markers Vimentin and Snail along with an increased Wnt signaling pathway activity. When gastric cancer cells were incubated in Wnt3a-conditioned medium. Wnt signaling pathway activity and resistance to trastuzumab increased. Gastric cancer patient-derived organoids incubated in Wnt3a-depletion medium were more susceptible to dose-dependent inhibition of cell viability by trastuzumab than those incubated in complete medium. Conclusions Trastuzumab-resistant gastric cancer cells exhibited EMT-like phenotype, and trastuzumab resistance was promoted by the Wnt/β-catenin signaling pathway. The Wnt/β-catenin pathway is a key signaling pathway for trastuzumab resistance in gastric cancer cells.

This study investigated the effects of the Albizia julibrissin Leaf extracts (AJLE) on adipocytes using 3T3-L1 cells. AJLE inhibited adipogenesis by reducing the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding proteins (C/EBPs) that regulate enzymes involved in fat synthesis and storage, and subsequently reduced intracellular lipid droplets, glycerol-3-phosphate dehydrogenase (GPDH), and triglyceride (TG). AJLE also increased the expression of brown adipocyte markers, such as uncoupling protein-1 (UCP-1), PR/SET domain 16 (PRDM16), and bone morphogenetic protein 7 (BMP7) by inducing the differentiation of brown adipocytes, as shown by a decrease in the lipid droplet sizes and increasing mitochondrial mass. AJLE increased the expression of transcription factor A, mitochondrial (TFAM), mitochondrial DNA (mtDNA) copy number, and UCP-1 protein expression, all of which are key factors in regulating mitochondrial biogenesis. AJLE-induced browning was shown to be regulated by the coordination of AMPK, p38, and SIRT1 signaling pathways. The ability of AJLE to inhibit adipogenesis and induce brown adipocyte differentiation may help treat obesity and related diseases.

Membrane-disrupting agents that selectively target virus versus host membranes could potentially inhibit a broad-spectrum of enveloped viruses, but currently such antivirals are lacking. Here, we develop a nanodisc incorporated with a decoy virus receptor that inhibits virus infection. Mechanistically, nanodiscs carrying the viral receptor sialic acid bind to influenza virions and are co-endocytosed into host cells. At low pH in the endosome, the nanodiscs rupture the viral envelope, trapping viral RNAs inside the endolysosome for enzymatic decomposition. In contrast, liposomes containing a decoy receptor show weak antiviral activity due to the lack of membrane disruption. The nanodiscs inhibit influenza virus infection and reduce morbidity and mortality in a mouse model. Our results suggest a new class of antivirals applicable to other enveloped viruses that cause irreversible physical damage specifically to virus envelope by viruses’ own fusion machine. In conclusion, the lipid nanostructure provides another dimension for antiviral activity of decoy molecules. Membrane-disrupting agents that selectively target virus versus host membranes could potentially be potent antivirals. Here the authors incorporate a decoy virus receptor into a nanodisc and show that it ruptures the viral membrane at low pH and traps viral RNAs in the endolysosome for degradation.

Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.