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Alzheimer’s disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA-induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aβ42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of “SuperAgers”, humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aβ42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aβ42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration. Events that cause neurons to die in Alzheimer’s disease (AD) are poorly understood. Here, the authors provide evidence for a role of RNA interference in AD. Short RNAs causing neurotoxicity and DNA damage are seen in AD and aged brains, and are counteracted by nontoxic RNAs.

Extended CAG trinucleotide repeats (TNR) in the genes huntingtin ( HTT ) and androgen receptor ( AR ) are the cause of two progressive neurodegenerative disorders: Huntington’s disease (HD) and Spinal and Bulbar Muscular Atrophy (SBMA), respectively. Anyone who inherits the mutant gene in the complete penetrance range (>39 repeats for HD and 44 for SBMA) will develop the disease. An inverse correlation exists between the length of the CAG repeat and the severity and age of onset of the diseases. Growing evidence suggests that it is the length of uninterrupted CAG repeats in the mRNA rather than the length of poly glutamine (polyQ) in mutant (m) HTT protein that determines disease progression. One variant of m HTT (loss of inhibition; LOI) causes a 25 year earlier onset of HD when compared to a reference sequence, despite both coding for a protein that contains an identical number of glutamines. Short 21–22 nt CAG repeat (sCAGs)-containing RNAs can cause disease through RNA interference (RNAi). RNA hairpins (HPs) forming at the CAG TNRs are stabilized by adjacent CCG (in HD) or CUG repeats (in SBMA) making them better substrates for Dicer, the enzyme that processes CAG HPs into sCAGs. We now show that cells deficient in Dicer or unable to mediate RNAi are resistant to the toxicity of the HTT and AR derived HPs. Expression of a small HP that mimics the HD LOI variant is more stable and more toxic than a reference HP. We report that the LOI HP is processed by Dicer, loaded into the RISC more efficiently, and gives rise to a higher quantity of RISC-bound 22 nt sCAGs. Our data support the notion that RNAi contributes to the cell death seen in HD and SBMA and provide an explanation for the dramatically reduced onset of disease in HD patients that carry the LOI variant.

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration, but the specific events that cause cell death remain poorly understood. Death Induced by Survival gene Elimination (DISE) is a cell death mechanism mediated by short (s) RNAs acting through the RNA induced silencing complex (RISC). DISE is thus a form of RNA interference, in which G-rich 6mer seed sequences in the sRNAs (position 2-7) target hundreds of C-rich 6mer seed matches in genes essential for cell survival, resulting in the activation of cell death pathways. Here, using Argonaute precipitation and RNAseq (Ago-RP-Seq), we analyze RISC-bound sRNAs to quantify 6mer seed toxicity in several model systems. In mouse AD models and aging brain, in induced pluripotent stem cell-derived neurons from AD patients, and in cells exposed to Aβ42 oligomers, RISC-bound sRNAs show a shift to more toxic 6mer seeds compared to controls. In contrast, in brains of “SuperAgers”, humans over age 80 who have superior memory performance, RISC-bound sRNAs are shifted to more nontoxic 6mer seeds. Cells depleted of nontoxic sRNAs are sensitized to Aβ42-induced cell death, and reintroducing nontoxic RNAs is protective. Altogether, the correlation between DISE and Aβ42 toxicity suggests that increasing the levels of nontoxic miRNAs in the brain or blocking the activity of toxic RISC-bound sRNAs could ameliorate neurodegeneration.

The pulsed electric field (PEF) is a non-thermal food processing technology that induces electroporation of the cell membrane thus improving mass transfer through the cell membrane. In this study, the drying and rehydration kinetics, microstructure, and carotenoid content of carrot (Daucus carota) pretreated by PEF during convective drying at 50 °C were investigated. The PEF treatment was conducted with different field strengths (1.0–2.5 kV/cm) using a fixed pulse width of 20 µs and at a pulse frequency of 50 Hz. The PEF 2.5 kV/cm showed the shortest drying time, taking 180 min, whereas the control required 330 min for the same moisture ratio, indicating a 45% reduction in drying time. The rehydration ability also increased as the strengths of PEF increased. PEF 2.5 kV/cm resulted in 27.58% increase in moisture content compared to the control after rehydration (1 h). Three mathematical models were applied to the drying and rehydration data; the Page and Peleg models were selected as the most appropriate models to describe the drying and rehydration kinetics, respectively. The cutting force of the sample was decreased as the strength of PEF increased, and a more homogeneous cellular structure was observed in the PEF pretreatment group. The reduction in drying time by PEF was beneficial to the carotenoid content, and PEF 2.5 kV/cm showed the highest preservation content of carotenoid. Overall, these results suggested that the pretreatment of PEF and the drying and rehydration rate influence the quality of products, functional components, and cellular structure.

Objective: The purpose of this study is both to estimate the efficacy and the safety of Yukgunja-tang (YGJT) and to establish evidence for the use of herbal medicines in the management of patients with cancer-related anorexia. Methods: We enrolled 40 patients with cancer-related anorexia. The enrolled participants were randomly allocated to 2 groups: the control group (n = 20), which received nutrition counseling, and the treatment group (n = 20), which received nutrition counseling and was administered YGJT at twice a day for 4 weeks (a total of 56 times @ 3.0 g each time). The primary outcome of this study was the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were the FAACT score with the ACS score excluded, the score on the Visual Analog Scale (VAS) for appetite, and the results on laboratory tests regarding appetite, such as leptin, tumor necrosis factors (TNF-α), interleukin-6 (IL-6), and ghrelin. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (complete blood cell count, chemistry, urine test), and adverse events, were documented on the case report form (CRF) at every visit. Result: The difference in the primary outcome, that is, the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), between the control and the treatment groups was statistically significant (P = .023) as was the difference in the FAACT scores with the ACS score excluded, a secondary outcome, between the 2 groups; however, no statistically significant differences were noted in the scores on the VAS or the levels of leptin, TNF-α, IL-6, and ghrelin. In addition, no significant differences in the numbers and the types of adverse events or in the results on the laboratory tests between the control and the treatment groups were recorded. Conclusion: These results obtained in this research confirmed the efficacy and the safety of using YGJT as a herb-medicine treatment option for patients with cancer-related anorexia.

This study applied pulsed electric fields (PEFs) to accelerate the withering and drying processes during cold-brewed black tea production. PEF pretreatment was administered at 1.0, 1.5, and 2.0 kV/cm electric field strengths, combined with varying withering times from 8 to 12 hr. During the 12-hour withering process, the redness value (a*) and total color change (∆E) of PEF-treated leaves significantly increased (p < 0.05). Furthermore, the homogenous redness of tea leaves during fermentation depended on the PEF strength applied. In addition, PEF pretreatment remarkably reduced the drying time, up to a 50% reduction at a 2.0 kV/cm field strength. Additionally, the 2.0 kV/cm PEF-pretreated black tea exhibited a notable 42% increase in theaflavin (TF) content and a 54% increase in thearubigin (TR) content. Sensory evaluation scores were highest for black tea that received PEF pretreatment at 2.0 kV/cm. These findings highlight the significant potential of PEFs in enhancing the efficiency of withering and drying processes while positively impacting the physicochemical and sensory properties of cold-brewed black tea.

This study aimed to investigate the effects of jet-milling on the lutein extraction contents of spinach powder (SP), as well as the effects of pulsed electric field (PEF), as a non-thermal pasteurization technology, on the preservation of spinach juice (SJ) lutein contents. SP particles were divided into SP-coarse (Dv50 = 315.2 μm), SP-fine (Dv50 = 125.20 μm), and SP-superfine (Dv50 = 5.59 μm) fractions, and SP-superfine was added to SJ due to its having the highest contents of lutein extract. PEFs and thermal treatment were applied to evaluate the effects of preserving the lutein content of PEF during storage (25 days). The juice was then designated as untreated (no pasteurization), PEF-1,2 (SJ treated with PEF 20 kV/cm 110 kJ/L, 150 kJ/L), or Thermal-1,2 (SJ treated with 90 °C, 10 min and 121 °C, 15 min). The sizes and surface shapes of the superfine SP particles were more homogeneous and smoother than those of the other samples. SJ made with SP-superfine and treated with PEF had the highest lutein content and antioxidant activities among the group during storage. A complex of jet-milling and PEF could have great potential as a method to improve the lutein contents of lutein-enriched juice in the food industry.

Human noroviruses are major causes of nonbacterial gastroenteritis and are transmitted by both food and water, as well as person-to-person. Asymptomatic norovirus infection of food handlers may play a role in transmission. The outbreak of norovirus infections was recognized in the PyeongChang Winter Olympics, starting with security staff on 3 February 2018. The Ministry of Food and Drug Safety in the Republic of Korea conducted norovirus surveillance from asymptomatic food handlers of food-catering facilities related to the Olympics to prevent the spread of noroviruses. Rectal swab samples (707) from food handlers were collected and examined for noroviruses by using real-time reverse transcription PCR and conventional reverse transcription PCR. Five of 707 samples were identified as noroviruses. Genotypes of the norovirus-positive samples were determined with sequencing analysis. Identified genotypes of norovirus in asymptomatic food handlers included GI.3, GII.4, and GII.17. The GII.17 strain was prevalent among the genotypes, accounting for three of five detections. Food handlers with noroviruses detected in rectal swabs were excluded from cooking, and all food handled by infected food handlers was discarded. Surveillance of norovirus infection for food handlers contributed to preventing norovirus spread.

This study aimed to investigate and optimize the quality and sensory properties of baked products with lutein-enriched marigold flower powder (MP). Lutein-enriched marigold flowers produced via hydroponic methods using LED lights were used as a functional material in sponge cakes to increase lutein content. MP particles were divided into coarse (Dv50 = 315 μm), fine (Dv50 = 119 μm), and superfine MP (Dv50 = 10 μm) fractions and added to the sponge cake after being designated to control (sponge cake prepared without MP), coarse MPS (sponge cake prepared with coarse MP), fine MPS (sponge cake prepared with fine MP), and superfine MPS (sponge cake prepared with superfine MP) groups. The sizes and surface properties of superfine MP particles were more homogeneous and smoother than the other samples. As the particle size decreased, the specific volume increased, whereas baking loss, hardness, and chewiness of the sponge cake decreased. Superfine MP and superfine MPS had the highest lutein content. The flavor of marigold and the overall acceptability of sponge cake with superfine MP were 7.90 ± 0.97 and 7.55 ± 0.76, which represents the highest values among the samples. The results of this study have shown that jet milling can contribute to improvements in texture, lutein content, and sensory qualities for baked products with MP.

Viscum album var. coloratum (Kom.) Ohwi is a traditional herbal medicine used in East Asia to treat hypertension, skeletal muscle disorders, and cancer. The inhibitory effects of Viscum album (VA) extract on chemokines and its therapeutic potential in erlotinib-induced skin rash were investigated in this study. ELISA was used to measure the levels of chemokines, MCP-1 and RANTES, which are thought to be mediators of erlotinib-induced skin rash in RAW264.7 cells. Western blot analysis was used to look into the activation of signaling pathways like AKT, MAPK, and EGF. In order to investigate the active compounds in VA extract, solvent fractionation and preparative HPLC were performed sequentially. VA extract significantly reduced the production of TNF-α, MCP-1, and RANTES but not IL-1. Furthermore, macrophage transmigration was inhibited without causing cell toxicity. VA extract had no effect on the phosphorylation of EGF receptors stimulated by EGF or suppressed by erlotinib in both A549, a non-small cell lung cancer cells, and Hacat, a human skin keratinocyte. The isolated viscumneoside III and viscumneoside V from VA extract significantly suppressed the expression of MCP-1, according to activity guided fractionation with organic solvent fractionation and preparative HPLC. These findings suggest that VA extract and its active compounds, viscumneoside III and viscumneoside V, regulate MCP-1 production and may have the potential to suppress erlotinib-induced skin toxicity by modulating macrophage activity without neutralizing anti-cancer efficacy.