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Abstract Telomere dysfunction is a well-known molecular trigger of senescence and has been associated with various age-related diseases, including atherosclerosis. However, the mechanisms involved have not yet been elucidated, and the extent to which telomeres contribute to atherosclerosis is unknown. Therefore, we investigated the mechanism of metformin-induced telomere stabilization and the ability of metformin to inhibit vascular smooth muscle cell (VSMC) senescence caused by advanced atherosclerosis. The present study revealed that metformin inhibited the phenotypes of atherosclerosis and senescence in VSMCs. Metformin increased the phosphorylation of AMPK-dependent PGC-1α and thus increased telomerase activity and the protein level of TERT in OA-treated VSMCs. Mechanistically, the phosphorylation of AMPK and PGC-1α by metformin not only enhanced telomere function but also increased the protein level of TERT, whereas TERT knockdown accelerated the development of atherosclerosis and senescent phenotypes in OA-treated VSMCs regardless of metformin treatment. Furthermore, the in vivo results showed that metformin attenuated the formation of atherosclerotic plaque markers in the aortas of HFD-fed ApoE KO mice. Although metformin did not reduce plaque size, it inhibited the phosphorylation of the AMPK/PGC-1α/TERT signaling cascade, which is associated with the maintenance and progression of plaque formation, in HFD-fed ApoE KO mice. Accordingly, metformin inhibited atherosclerosis-associated phenotypes in vitro and in vivo. These observations show that the enhancement of telomere function by metformin is involved in specific signaling pathways during the progression of atherosclerosis. These findings suggest that telomere stabilization by metformin via the AMPK/p-PGC-1α pathway might provide a strategy for developing therapeutics against vascular diseases such as atherosclerosis.

Abstract Our recent studies have identified p21-activated kinase 4 (PAK4) as a key regulator of lipid catabolism in the liver and adipose tissue, but its role in glucose homeostasis in skeletal muscle remains to be explored. In this study, we find that PAK4 levels are highly upregulated in the skeletal muscles of diabetic humans and mice. Skeletal muscle-specific Pak4 ablation or administering the PAK4 inhibitor in diet-induced obese mice retains insulin sensitivity, accompanied by AMPK activation and GLUT4 upregulation. We demonstrate that PAK4 promotes insulin resistance by phosphorylating AMPKα2 at Ser491, thereby inhibiting AMPK activity. We additionally show that skeletal muscle-specific expression of a phospho-mimetic mutant AMPKα2S491D impairs glucose tolerance, while the phospho-inactive mutant AMPKα2S491A improves it. In summary, our findings suggest that targeting skeletal muscle PAK4 may offer a therapeutic avenue for type 2 diabetes.

Objectives: Despite the importance of choosing and using a valid assessment tool for fear of cancer recurrence (FCR) for early detection and interventions, the validity of the FCR inventory has yet to be thoroughly investigated in Korea. This study explored the psychometric properties of the Fear of Cancer Recurrence Inventory-Severity (FCRI-S) subscale and assessed its applicability to cancer survivors in Korea. Methods: The survey involved 93 Korean individuals who had survived cancer. The reliability of the FCRI-S subscale was assessed using Cronbach’s α and composite reliability (CR). Confirmatory factor analysis (CFA), along with tests for discriminant and convergent validity, was conducted to evaluate the construct validity of the FCRI-S subscale. Results: The FCRI-S subscale showed excellent internal consistency (Cronbach’s α=0.88; CR=0.89). CFA showed a good factor structure for the FCRI-S subscale, and the correlations of the FCRI-S subscale with FCR-related measures (r=0.69 to 0.80) and other psychosocial measures (r=-0.23 to 0.37) confirmed both the convergent and discriminant validity of the FCRI-S subscale. Conclusions: This study confirmed the robust psychometric characteristics of the FCRI-S subscale among cancer survivors in Korea. The use of the FCRI-S subscale would be helpful for health professionals to rapidly screen FCR levels in clinical settings.

Abstract Background Angelica Gigas (Purple parsnip) is an important medicinal plant that is cultivated and utilized in Korea, Japan, and China. It contains bioactive substances especially coumarins with anti-inflammatory, anti-platelet aggregation, anti-cancer, anti-diabetic, antimicrobial, anti-obesity, anti-oxidant, immunomodulatory, and neuroprotective properties. This medicinal crop can be genetically improved, and the metabolites can be obtained by embryonic stem cells. In this context, we established the protoplast-to-plant regeneration methodology in Angelica gigas. Results In the present investigation, we isolated the protoplast from the embryogenic callus by applying methods that we have developed earlier and established protoplast cultures using Murashige and Skoog (MS) liquid medium and by embedding the protoplast in thin alginate layer (TAL) methods. We supplemented the culture medium with growth regulators namely 2,4-dichlorophenoxyaceticacid (2,4-D, 0, 0.75, 1.5 mg L− 1), kinetin (KN, 0, 0.5, and 1.0 mg L− 1) and phytosulfokine (PSK, 0, 50, 100 nM) to induce protoplast division, microcolony formation, and embryogenic callus regeneration. We applied central composite design (CCD) and response surface methodology (RSM) for the optimization of 2,4-D, KN, and PSK levels during protoplast division, micro-callus formation, and induction of embryogenic callus stages. The results revealed that 0.04 mg L− 1 2,4-D + 0.5 mg L− 1 KN + 2 nM PSK, 0.5 mg L− 1 2,4-D + 0.9 mg L− 1 KN and 90 nM PSK, and 1.5 mg L− 1 2,4-D and 1 mg L− 1 KN were optimum for protoplast division, micro-callus formation and induction embryogenic callus. MS basal semi-solid medium without growth regulators was good for the development of embryos and plant regeneration. Conclusions This study demonstrated successful protoplast culture, protoplast division, micro-callus formation, induction embryogenic callus, somatic embryogenesis, and plant regeneration in A. gigas. The methodologies developed here are quite useful for the genetic improvement of this important medicinal plant.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires. Methods: We compared the QoL between severe and mild-to-moderate asthma and between severe asthma with and without biologics treatment. Data of mild-to-moderate were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea, and data of severe asthma were collected from the Precision Medicine Intervention in Severe Asthma. We included 183 patients with severe asthma treated with T2 biologics or conventional therapy between April 2020 and May 2021 and assessed QoL of them using the Questionnaire for Adult Korean Asthmatics (QLQAKA), Severe Asthma Questionnaire (SAQ), and EuroQoL-5Dimensions (EQ-5D) at baseline and 6 months. Results: The EQ-5D index (0.803) of severe asthma was lower than that of other chronic diseases representing a worse QoL. The scores for all questions of QLQAKA, except “cough,” were lower (less control) in the severe asthma group than in the mild-to-moderate asthma group at baseline and 6 months (P 0.05). Conclusion: QoL was worse in severe asthma than in mild-to-moderate asthma and other chronic diseases. T2 biologics equally improved QoL in patients with severe asthma.

Abstract Background Transmembrane 4 L six family member 5 (TM4SF5) translocates subcellularly and functions metabolically, although it is unclear how intracellular TM4SF5 translocation is linked to metabolic contexts. It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms. Methods Here, we explored the metabolic significance of TM4SF5 localization at mitochondria‐lysosome contact sites (MLCSs), using in vitro cells and in vivo animal systems, via approaches by immunofluorescence, proximity labelling based proteomics analysis, organelle reconstitution etc. Results Upon extracellular glucose repletion following depletion, TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506‐binding protein 8 (FKBP8) and lysosomal TM4SF5. Proximity labeling showed molecular clustering of phospho‐dynamic‐related protein I (DRP1) and certain mitophagy receptors at TM4SF5‐enriched MLCSs, leading to mitochondrial fission and autophagy. TM4SF5 bound NPC intracellular cholesterol transporter 1 (NPC1) and free cholesterol, and mediated export of lysosomal cholesterol to mitochondria, leading to impaired oxidative phosphorylation but intact tricarboxylic acid (TCA) cycle and β‐oxidation. In mouse models, hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria, both with positive relations to liver malignancy. Conclusions Our findings suggested that TM4SF5‐enriched MLCSs regulate glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming, presumably while hepatocellular carcinogenesis, recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial reprogramming to support biomolecule synthesis in addition to glycolytic energetics.

Abstract Subthreshold social anxiety (SSA) is a condition in which individuals experience social anxiety that does not reach the threshold required for a clinical diagnosis of a social anxiety disorder (SAD). Although SSA may not impair lives as severely as SAD, it can affect social functioning. However, only a few studies focused on structural neural correlates of SSA. We recruited 65 individuals with SSA and used the Leibowitz Social Anxiety Scale to assess their social and performance anxiety levels and other relevant measures of social anxiety. Voxel-wise whole-brain correlational analyses showed a positive association between the cortical thickness (CT) of the superior frontal gyrus (SFG) and social anxiety levels and a negative correlation between the CT of the fusiform gyrus (FG) and performance anxiety levels in individuals with SSA. Exploratory Pearson’s correlation analyses showed significant positive correlations between the CT of the SFG and Generalized Anxiety Disorder-7 total scores and negative associations between the CT of the FG and Beck Anxiety Inventory total scores. Our study provides insight into the neural basis of SSA, particularly performance anxiety, by highlighting the association between CT in specific brain regions and SSA characteristics.

Ginkgo biloba is an ancient plant that has survived up until the present day. Gingko biloba is a rich source of valuable secondary metabolites, particularly terpene trilactones (TTLs) such as ginkgolides and bilobalides, which are obtained from the leaves and seeds of the plant. TTLs have pharmacological properties, including anticancer, anti-dementia, antidepressant, antidiabetic, anti-inflammatory, anti-hypertensive, antiplatelet, immunomodulatory, and neuroprotective effects. However, ginkgo is a very-slow-growing tree that takes approximately 30 years to reach maturity. In addition, the accumulation of TTLs in these plants is affected by age, sex, and seasonal and geographical variations. Therefore, plant cell cultures have been established in ginkgo to produce TTLs. Extensive investigations have been conducted to optimize the culture media, growth regulators, nutrients, immobilization, elicitation, and precursor-feeding strategies for the production of TTLs in vitro. In addition, metabolic engineering and synthetic biology methods have been used for the heterologous production of TTLs. In this review, we present the research strategies applied to cell cultures for the production of TTLs.

Background: Drug-induced hypersensitivity such as anaphylaxis is an important cause of drug-related morbidity and mortality. Cefaclor is a leading cause of drug induced type I hypersensitivity in Korea, but little is yet known about genetic biomarkers to predict this hypersensitivity reaction. We aimed to evaluate the possible involvement of genes in cefaclor induced type I hypersensitivity. Methods: Whole exome sequencing (WES) and HLA genotyping were performed in 43 patients with cefaclor induced type I hypersensitivity. In addition, homology modeling was performed to identify the binding forms of cefaclor to HLA site. Results: Anaphylaxis was the most common phenotype of cefaclor hypersensitivity (90.69%). WES results show that rs62242177 and rs62242178 located in LIMD1 region were genome-wide significant at the 5 × 10−8 significance level. Cefaclor induced type I hypersensitivity was significantly associated with HLA-DRB1∗04:03 (OR 4.61 [95% CI 1.51–14.09], P

Abstract Mounting evidence suggests that probiotics are beneficial for treating Alzheimer’s disease (AD). However, the mechanisms by which specific probiotics modify AD pathophysiology are not clearly understood. In this study, we investigated whether Lactobacillus paracasei-derived extracellular vesicles (Lpc-EV) can directly act on neuronal cells to modify amyloid-beta (Aβ)-induced transcriptional changes and Aβ pathology in the brains of Tg-APP/PS1 mice. Lpc-EV treatment in HT22 neuronal cells counteracts Aβ-induced downregulation of Brain-derived neurotrophic factor (Bdnf), Neurotrophin 3 (Nt3), Nt4/5, and TrkB receptor, and reverses Aβ-induced altered expression of diverse nuclear factors, including the downregulation of Methyl-CpG binding protein 2 (Mecp2) and Sirtuin 1 (Sirt1). Systematic siRNA-mediated knockdown experiments indicate that the upregulation of Bdnf, Nt3, Nt4/5, and TrkB by Lpc-EV is mediated via multiple epigenetic factors whose activation converges on Mecp2 and Sirt1. In addition, Lpc-EV reverses Aβ-induced downregulation of the Aβ-degrading proteases Matrix metalloproteinase 2 (Mmp-2), Mmp-9, and Neprilysin (Nep), whose upregulation is also controlled by MeCP2 and Sirt1. Lpc-EV treatment restores the downregulated expression of Bdnf, Nt4/5, TrkB, Mmp-2, Mmp-9, and Nep; induces the upregulation of MeCP2 and Sirt1 in the hippocampus; alleviates Aβ accumulation and neuroinflammatory responses in the brain; and mitigates cognitive decline in Tg-APP/PS1 mice. These results suggest that Lpc-EV cargo contains a neuroactive component that upregulates the expression of neurotrophic factors and Aβ-degrading proteases (Mmp-2, Mmp-9, and Nep) through the upregulation of MeCP2 and Sirt1, and ameliorates Aβ pathology and cognitive deficits in Tg-APP/PS1 mice.

Background: Exposure to allergens or irritants in the workplace may affect asthma control and the quality of life (QoL) of patients with asthma. Objective: To examine the prevalence and characteristics of work-related asthma (WRA) in adult patients with severe asthma. Methods: We analyzed data from the Korean Severe Asthma Registry (KoSAR), which is a nationwide multicenter observational study on severe asthma in Korea. Severe asthma was defined according to the American Thoracic Society (ATS) and the European Respiratory Society (ERS) guidelines. WRA was identified on the basis of asthma symptom aggravation at the workplace, as indicated by responses to a structured questionnaire. We compared the demographic and clinical characteristics and QoL between adult patients with severe asthma and WRA and those without WRA. Results: Among 364 patients with severe asthma who were employed at the time of enrollment, 65 (17.9%) had WRA. There were no significant differences in age, sex, obesity, or smoking history between the WRA and non-WRA groups. However, individuals with WRA exhibited a higher prevalence of anxiety (7.7% vs 2.4%, P = 0.046) and depression (12.3% vs 3.7%, P = 0.010) than those without. The levels of asthma control, lung function, and frequency of asthma exacerbations were similar between the two groups, but patients with WRA reported lower QoL, as determined by the Quality of Life Questionnaire for Adult Korean Asthmatics (56.6 ± 14.6 vs. 63.5 ± 13.9, P

Abstract Pregnancy imposes a substantial metabolic burden on women, but little is known about whether or how multiple pregnancies increase the risk of maternal postpartum diabetes. In this study, we assessed the metabolic impact of multiple pregnancies in humans and in a rodent model. Mice that underwent multiple pregnancies had increased adiposity, but their glucose tolerance was initially improved compared to those of age-matched virgin mice. Later, however, insulin resistance developed over time, but insulin secretory function and compensatory pancreatic β cell proliferation were impaired in multiparous mice. The β cells of multiparous mice exhibited aging features, including telomere shortening and increased expression of Cdkn2a. Single-cell RNA-seq analysis revealed that the β cells of multiparous mice exhibited upregulation of stress-related pathways and downregulation of cellular respiration- and oxidative phosphorylation-related pathways. In humans, women who delivered more than three times were more obese, and their plasma glucose concentrations were elevated compared to women who had delivered three or fewer times, as assessed at 2 months postpartum. The disposition index, which is a measure of the insulin secretory function of β cells, decreased when women with higher parity gained body weight after delivery. Taken together, our findings indicate that multiple pregnancies induce cellular stress and aging features in β cells, which impair their proliferative capacity to compensate for insulin resistance.

Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) 10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (−117.50 ± 94.38 vs. −115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (−18.62 ± 24.68 vs. −14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (−3.40 ± 10.60 vs. −14.48 ± 24.01 %, P = 0.065), blood eosinophils (−36.47 ± 517.02 vs. −363.22 ± 1294.59, P = 0.013), and exacerbation frequency (−3.07 ± 4.42 vs. −3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Temporary immersion system (TIS) cultures are reported to be superior when compared to semi-solid (SS) and liquid (LQ) cultures for the in vitro plant regeneration of many plant species. In the present study, we used a TIS for plant regeneration of Gerbera jemesonii “Shy Pink” and compared the results with that of SS and LQ cultures. The number of shoots regenerated in the SS, LQ, and TIS cultures was 6.93, 3.13, and 3.03, respectively. The shoots regenerated with the SS and LQ cultures demonstrated 3.33 and 4.22% hyperhydricity, whereas the shoots regenerated with the TIS were healthy even though the number of shoots regenerated was less. The plantlets regenerated with the TIS demonstrated higher values for the number of roots, root length, biomass of the plantlets, leaf length/width, and area compared to the SS and LQ cultures. When the G. jemesonii “Shy Pink” plants were regenerated using the TIS, their levels of photosynthetic pigments were highest. The number of stomata on the abaxial surface of their leaves was 11.40, and the frequency of closed stomata was 59% for the plants regenerated with the TIS. The number of stomata was 21.4 and 14.5 for the plants regenerated with the SS and LQ cultures, respectively. Meanwhile, the frequency of closed stomata was 13% and 15% for the plants regenerated with SS and LQ cultures. Furthermore, G. jemesonii “Shy Pink” showed the highest survival of plants when regenerated in the TIS compared to SS and LQ cultures. The TIS was found to be the most suitable culture system for plant regeneration of G. jemesonii “Shy Pink” compared to SS and LQ cultures.

This study aimed to provide scientific data on the anti-Alzheimer’s disease (AD) effects of phenolic compounds from Drynariae Rhizoma (DR) extract using a multi-component approach. Screening of DR extracts, fractions, and the ten phenolic compounds isolated from DR against the key AD-related enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and monoamine oxidase-B (MAO-B) confirmed their significant inhibitory activities. The DR extract was confirmed to have BACE1-inhibitory activity, and the ethyl acetate and butanol fractions were found to inhibit all AD-related enzymes, including BACE1, AChE, BChE, and MAO-B. Among the isolated phenolic compounds, compounds (2) caffeic acid 4-O-β-D-glucopyranoside, (6) kaempferol 3-O-rhamnoside 7-O-glucoside, (7) kaempferol 3-o-b-d-glucopyranoside-7-o-a-L-arabinofuranoside, (8) neoeriocitrin, (9) naringin, and (10) hesperidin significantly suppressed AD-related enzymes. Notably, compounds 2 and 8 reduced soluble Amyloid Precursor Protein β (sAPPβ) and β-secretase expression by over 45% at a concentration of 1.0 μM. In the thioflavin T assay, compounds 6 and 7 decreased Aβ aggregation by approximately 40% and 80%, respectively, and degraded preformed Aβ aggregates. This study provides robust evidence regarding the potential of DR as a natural therapeutic agent for AD, highlighting specific compounds that may contribute to its efficacy.

Alzheimer’s disease (AD) is a progressive neurodegenerative condition characterized by memory and cognitive decline in older individuals. Beta-amyloid (Aβ), a significant component of senile plaques, is recognized as a primary contributor to AD pathology. Hence, substances that can inhibit Aβ production and/or accumulation are crucial for AD prevention and treatment. Agrimonia pilosa LEDEB. (A. pilosa) (Rosaceae), specifically its aerial parts, was identified in our previous screening study as a promising candidate with inhibitory effects on Aβ production. Therefore, in this study, A. pilosa extract was investigated for its anti-amyloidogenic effects, and its bioactive principles were isolated and identified. The ethanol extract of A. pilosa reduced the levels of sAPPβ and β-secretase by approximately 3% and 40%, respectively, compared to the DMSO-treated control group in APP-CHO cells (a cell line expressing amyloid precursor protein), which were similar to those in the positive control group. In addition, the ethanol extract of A. pilosa also hindered Aβ’s aggregation into fibrils and facilitated the disaggregation of Aβ aggregates, as confirmed by a Thioflavin T (Th T) assay. Subsequently, the active constituents were isolated using a bioassay-guided isolation method involving diverse column chromatography. Eleven compounds were identified—epi-catechin (1), catechin (2), (2S, 3S)-dihydrokaempferol 3-O-β-D-glucopyranoside (3), (-)-epiafzelechin 5-O-β-D-glucopyranoside (4), kaempferol 3-O-β-D-glucopyranoside (5), apigenin 7-O-β-D-glucopyranoside (6), dihydrokaempferol 7-O-β-D-glucopyranoside (7), quercetin 3-O-β-D-glucopyranoside (8), (2S, 3S)-taxifolin 3-O-β-D-glucopyranoside (9), luteolin 7-O-β-D-glucopyranoside (10), and apigenin 7-O-β-D-methylglucuronate (11)—identified through 1D and 2D NMR analysis and comparison with data from the literature. These compounds significantly decreased Aβ production by reducing β- and γ-secretase levels. Moreover, none of the compounds affected the expression levels of sAPPα or α-secretase. Further, compounds 1, 2, 4, 8, and 10 demonstrated a dose-dependent reduction in Aβ aggregation and promoted the disaggregation of pre-formed Aβ aggregates. Notably, compound 8 inhibited the aggregation of Aβ into fibrils by about 43% and facilitated the disassembly of Aβ aggregates by 41% compared to the control group containing only Aβ. These findings underscore the potential of A. pilosa extract and its constituents to mitigate a crucial pathological aspect of AD. Therefore, A. pilosa extract and its active constituents hold promise for development as therapeutics and preventatives of AD.

Purpose: Currently, there is no interventional approach to increase the intensity of Surya Namaskar a popular hatha yoga sequence used worldwide. Therefore, this study investigated how tempo-based high-intensity interval cardio yoga (HIICY) and traditional interval hatha yoga (TIHY) affects cardiometabolic fitness in active adults.Methods: Twenty physically active male and female individuals were randomly separated into HIICY (5 males, 5 females, 1.5 s tempo) and TIHY (5 males, 5 females, 3 s tempo) groups. The intervention included twelve exercise sessions for 4 weeks in both groups. Participants conducted a ramp test to determine their maximal oxygen uptake (V˙O2max), maximal velocity at V˙O2max (vV˙O2max), and maximal heart rate (HRmax). Afterward, they performed a 10-min high-intensity cardio yoga test (HICYT) to determine heart rate (HRpeak and HRmean), oxygen uptake (V˙O2peak and V˙O2mean), respiratory exchange ratio (RER), blood lactate concentrations (La−peak and ∆La−), fat and carbohydrate oxidations (FATox, CHOox), and energetic contributions (oxidative; WOxi, glycolytic; WGly, and phosphagen; WPCr, total energy demand; WTotal).Results:V˙O2max and vV˙O2max showed time and group × time interactions (p < 0.01, p < 0.0001, p < 0.001, respectively). V˙O2max after HIICY was significantly higher than in pre-testing and following TIHY (p < 0.001, p < 0.0001, respectively). V˙O2peak, V˙O2mean, RER, HRpeak, and HRmean during the 10-min HICYT showed significant time effects (p < 0.05). ∆La− indicated a group × time interaction (p < 0.05). Group x time interaction effects for FATox at the fourth and sixth minute were observed (p < 0.05, respectively). Absolute (kJ) and relative (%) WOxi, WGly, and WTotal showed time and group × time interaction effects (p < 0.05, p < 0.01, respectively). Furthermore, %WGly was reduced following HIICY (p < 0.05). Additionally, V˙O2max and vV˙O2max were highly correlated with WOxi in kJ (r = 0.91, 0.80, respectively). Moderate to high correlations were observed among CHOox, FATox, and absolute V˙O2max (r = 0.76, 0.62, respectively).Conclusion: A 4-week period of HIICY improved cardiometabolic fitness, oxidative capacity, and metabolic flexibility compared with TIHY, in physically active adults. Therefore, HIICY is suitable as HY-specific HIIT and time-efficient approach for relatively healthy individuals.

Background/Aims: There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. Methods: Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebo group (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. Results: Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological well-being (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. Conclusions: The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.

Abstract Sustainable cultivation and safe agricultural production are needed to ensure the safety of all living organisms and ecosystems. Most agricultural foods currently contain unacceptable levels of pesticide residues. In an attempt to ensure pest control and high crop yields, farmers spray a large number of pesticides in quantities that exceed the safety limits for agricultural crops. Pesticide residues are highly toxic to humans, causing severe and even deadly diseases. Traditional analytical strategies for laboratory pesticide detection are often limited because they are time‐consuming and require trained personnel, which makes them very costly. Hence, accurate, rapid, and on‐site analysis of pesticides is drawing increasing attention for food safety reasons. Therefore, on‐site or point‐of‐care (POC) detection of pesticide residues has become an approach of paramount importance. Recently, various portable detection technologies, such as colorimetric, fluorescence, electrochemical, surface plasmon resonance, chemiluminescence, phosphorescence, microfluidic, and surface‐enhanced Raman scattering techniques, have been designed for on‐site monitoring of pesticide residues in vegetables and fruits. These devices have demonstrated great power of detection in preclinical agricultural settings. This review highlights the emerging insights and novel advances in portable devices, POC technologies, and on‐site sensing approaches for the detection of pesticide residues in agricultural foods. However, greater rigor in the design of portable pesticide‐detection devices is essential. The increasing demand for rapid detection of hazardous pesticide components has prompted a timely opportunity to summarize recent developments and progress in portable devices and on‐site sensing strategies to evaluate food safety.

A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for treating type 2 diabetes mellitus, binds to the nucleophiles in vitro. Four DPP-4 inhibitors, including vildagliptin, were evaluated for comparison. Only saxagliptin and vildagliptin, which both contain a cyanopyrrolidine group, quickly reacted with L-cysteine to enzyme-independently produce thiazolinic acid metabolites. This saxagliptin–cysteine adduct was also found in saxagliptin-administered male Sprague–Dawley rats. In addition, this study newly identified cysteinyl glycine conjugates of saxagliptin and 5-hydroxysaxagliptin. The observed metabolic pathways were hydroxylation and conjugation with cysteine, glutathione, sulfate, and glucuronide. In summary, we determined four new thiazoline-containing thiol metabolites (cysteine and cysteinylglycine conjugates of saxagliptin and 5-hydroxysaxagliptin) in saxagliptin-administered male rats. Our results reveal that saxagliptin can covalently bind to the thiol groups of cysteine residues of endogenous proteins in vivo, indicating the potential for saxagliptin to cause drug-induced liver injury.

Anthocyanins are water-soluble pigments found in plants. They exist in various colors, including red, purple, and blue, and are utilized as natural colorants in the food and cosmetics industries. The pharmaceutical industry uses anthocyanins as therapeutic compounds because they have several medicinal qualities, including anti-obesity, anti-cancer, antidiabetic, neuroprotective, and cardioprotective effects. Anthocyanins are conventionally procured from colored fruits and vegetables and are utilized in the food, pharmaceutical, and cosmetic industries. However, the composition and concentration of anthocyanins from natural sources vary quantitively and qualitatively; therefore, plant cell and organ cultures have been explored for many decades to understand the production of these valuable compounds. A great deal of research has been carried out on plant cell cultures using varied methods, such as the selection of suitable cell lines, medium optimization, optimization culture conditions, precursor feeding, and elicitation for the production of anthocyanin pigments. In addition, metabolic engineering technologies have been applied for the hyperaccumulation of these compounds in varied plants, including tobacco and arabidopsis. In this review, we describe various strategies applied in plant cell and organ cultures for the production of anthocyanins.

Severe asthma constitutes a serious health burden with significant morbidity and socioeconomic costs. The development and introduction of new biologics targeting type 2 inflammation changed the paradigm for management of severe asthma and initiated a biological era. These changes impose a challenge to clinicians in managing difficult-to-treat and severe asthma. To understand the characteristics and heterogeneity of severe asthma and to develop a better strategy to manage it, the Korean Academy of Asthma, Allergy and Clinical Immunology, Working Group on Severe Asthma, has organized the Korean Severe Asthma Registry (KoSAR). In this review, we describe the challenges of severe asthma management regarding diagnosis, disease burden, heterogeneity, guidelines, and organization of severe asthma clinics. This review also examines the current global activities of national and regional registries and study groups. In addition, we present the KoSAR vision and organization and describe the findings of KoSAR in comparison with those of other countries.

Background: There has been a concerning increase in the prevalence and socioeconomic burden of asthma in Korea. Korea's National Health Insurance System (NHIS) covers insurance payment and claims management for all Koreans. Using National Health Insurance Sharing Service (NHISS) claims data. This study aimed to investigate patterns of healthcare utilization and direct cost in patients with asthma over a 10-year period. Methods: In this retrospective population-based study, we examined NHISS claims records between July 2005 and June 2016 and investigated healthcare utilization among patients with asthma based on age group and severity of disease (non-severe asthma [NSA] and severe asthma [SA]). Results: From 2006 to 2015, the total number of patients with asthma in Korea steadily increased from 743 968 to 2 286 309, with a corresponding increase in prevalence from 1.62% to 4.74%. The proportion of patients with SA decreased from 3.16% in 2006 to 1.56% in 2015; the proportion was consistently higher in men than in women. In addition, patients with SA had a higher cost per outpatient visit than patients with NSA, and the number of outpatient visits per year increased. The inhaled corticosteroid (ICS) prescription rate among patients with asthma decreased from 22.9% in 2006 to 15.7% in 2015. Furthermore, for a period of 10 years, more than 40% of patients with SA have been prescribed short-acting β-2 agonists (SABAs). Conclusions: Although patients with SA comprised a small proportion of patients with asthma, they incurred greater medical costs per person. The pharmaceutical prescription pattern indicated a lack of ICS-based prescriptions and frequent SABA prescriptions.

Purpose: This study aimed at comparing previous calculating formulas of maximal lactate accumulation rate (νLa.max) and a modified formula of pure νLa.max (PνLa.max) during a 15-s all-out sprint cycling test (ASCT) to analyze their relationships.Methods: Thirty male national-level track cyclists participated in this study (n = 30) and performed a 15-s ASCT. The anaerobic power output (Wpeak and Wmean), oxygen uptake, and blood lactate concentrations (La−) were measured. These parameters were used for different calculations of νLa.max and three energy contributions (phosphagen, WPCr; glycolytic, WGly; and oxidative, WOxi). The PνLa.max calculation considered delta La−, time until Wpeak (tPCr−peak), and the time contributed by the oxidative system (tOxi). Other νLa.max levels without tOxi were calculated using decreasing time by 3.5% from Wpeak (tPCr −3.5%) and tPCr−peak.Results: The absolute and relative WPCr were higher than WGly and WOxi (p < 0.0001, respectively), and the absolute and relative WGly were significantly higher than WOxi (p < 0.0001, respectively); νLa.max (tPCr −3.5%) was significantly higher than PνLa.max and νLa.max (tPCr−peak), while νLa.max (tPCr−peak) was lower than PνLa.max (p < 0.0001, respectively). PνLa.max and νLa.max (tPCr−peak) were highly correlated (r = 0.99; R2 = 0.98). This correlation was higher than the relationship between PνLa.max and νLa.max (tPCr −3.5%) (r = 0.87; R2 = 0.77). νLa.max (tPCr−peak), PνLa.max, and νLa.max (tPCr −3.5%) were found to correlate with absolute Wmean and WGly.Conclusion: PνLa.max as a modified calculation of νLa.max provides more detailed insights into the inter-individual differences in energy and glycolytic metabolism than νLa.max (tPCr−peak) and νLa.max (tPCr −3.5%). Because WOxi and WPCr can differ remarkably between athletes, implementing their values in PνLa.max can establish more optimized individual profiling for elite track cyclists.

Beta-amyloid (Aβ) proteins, major contributors to Alzheimer’s disease (AD), are overproduced and accumulate as oligomers and fibrils. These protein accumulations lead to significant changes in neuronal structure and function, ultimately resulting in the neuronal cell death observed in AD. Consequently, substances that can inhibit Aβ production and/or accumulation are of great interest for AD prevention and treatment. In the course of an ongoing search for natural products, the roots of Davallia mariesii T. Moore ex Baker were selected as a promising candidate with anti-amyloidogenic effects. The ethanol extract of D. mariesii roots, along with its active constituents, not only markedly reduced Aβ production by decreasing β-secretase expression in APP–CHO cells (Chinese hamster ovary cells which stably express amyloid precursor proteins), but also exhibited the ability to diminish Aβ aggregation while enhancing the disaggregation of Aβ aggregates, as determined through the Thioflavin T (Th T) assay. Furthermore, in an in vivo study, the extract of D. mariesii roots showed potential (a tendency) for mitigating scopolamine-induced memory impairment, as evidenced by results from the Morris water maze test and the passive avoidance test, which correlated with reduced Aβ deposition. Additionally, the levels of acetylcholine were significantly elevated, and acetylcholinesterase levels significantly decreased in the brains of mice (whole brains). The treatment with the extract of D. mariesii roots also led to upregulated brain-derived neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p-CREB) in the hippocampal region. These findings suggest that the extract of D. mariesii roots, along with its active constituents, may offer neuroprotective effects against AD. Consequently, there is potential for the development of the extract of D. mariesii roots and its active constituents as effective therapeutic or preventative agents for AD.

Abstract Background Fear of cancer recurrence (FCR) has been addressed as a cause of emotional distress among breast cancer survivors (BCSs). This study aimed to systematically review the evidence on randomized controlled trials (RCTs) of cognitive behavioral therapy (CBT) designed to reduce FCR among BCSs. Methods A systematic review of published original research articles meeting the inclusion criteria was conducted. Five electronic databases, including the Cochrane Library, CINAHL, PubMed, PsycINFO, and Web of Science, were independently searched to identify relevant articles. The Consolidated Standards of Reporting Trials (CONSORT) 2010 checklist was used to evaluate the quality of the eligible studies. Results Through a database search and a manual review process, seventeen quantitative studies with an RCT study design were included in the current systematic review. The interventions varied greatly in length and intensity, but the study designs and methodologies were similar. RCTs with face-to-face interventions of at least 1 month seemed to be more effective in reducing FCR outcomes and complying with than the CONSORT 2010 criteria than those with a brief online or telephone format of interventions; nevertheless, most RCT interventions appeared to be effective. Conclusions These findings highlight the importance of conducting well-designed CBT interventions to reduce FCR in BCSs with diverse populations at multiple sites, thereby improving the quality of research in this area.

Abstract Background Although mounting evidence indicates that insulin resistance (IR) co‐occurs with mitochondrial dysfunction in skeletal muscle, there is no clear causal link between mitochondrial dysfunction and IR pathogenesis. In this study, the exact role of mitochondria in IR development was determined. Methods Six‐week‐old C57BL/6 mice were fed a high‐fat diet for 2 weeks to induce acute IR or for 24 weeks to induce chronic IR (n = 8 per group). To characterize mitochondrial function, we measured citrate synthase activity, ATP content, mitochondrial DNA (mtDNA) content, and oxygen consumption rate in gastrocnemius and liver tissues. We intraperitoneally administered mitochondrial division inhibitor 1 (mdivi‐1) to mice with acute IR and measured mitochondrial adaptive responses such as mitophagy, mitochondrial unfolded protein response (UPRmt), and oxidative stress (n = 6 per group). Results Acute IR occurred coincidently with impaired mitochondrial function, including reduced citrate synthase activity (−37.8%, P

Light-emitting diodes (LEDs) are currently being used as a light source for in vitro regeneration or the growth of plants in a controlled environment. However, it is crucial to define the target system’s sensitivity to light quality before LEDs may be employed as the exclusive source of light. The objective of the present work was to investigate the influence of red (R), blue (B), white (W), and a combination of red plus blue (1:1) and red, blue, and green (1:1:1) LEDs on Gerbera jamesonii cv. ‘Shy Pink’ during in vitro regeneration. It was observed that LED lighting had a substantial impact on the process of shoot regeneration, shoot growth, and rooting of the shoots. When compared to other light treatments, red plus blue (1:1) LED had the greatest impact on the regeneration of shoots, growth of shoots, and root regeneration from shoot and root growth. Length of shoots, height of plantlets, and petiole length were affected by a red LED, and leaf length, width, and area were affected by a blue LED. The content of photosynthetic pigments (Chl a, Chl b, total chlorophyll, and carotenoids) was higher with acclimatized plants upon transplantation, which were regenerated under blue LEDs. In acclimatized plants, photosynthetic efficiency was calculated. Higher internal CO2 concentrations (Ci), photosynthetic rates (Pn), stomatal conductance (Gs), and transpiration rates (Tr) were seen in plants that were grown under red plus blue (1:1) LED. However, the plants that were grown under white LEDs had higher chlorophyll fluorescence (Fv/Fm). Collectively, the current results suggest that red and blue LED is suitable for in vitro regeneration of Gerbera jamesonii cv. ‘Shy Pink’ plants compared to red, blue, and white LEDs.

Osteoporosis, one of the most common bone diseases, results from an imbalance between bone formation and resorption. Osteoblasts are primarily involved in bone formation, whereas osteoclasts are involved in bone resorption. Therefore, any substances that can increase osteoblastic differentiation would be beneficial for the prevention or treatment of osteoporosis. In this study, peanut sprouts, a germinated product of peanuts, significantly enhanced osteoblastic differentiation of pre-osteoblastic MC3T3-E1 cells, as determined by the alkaline phosphatase (ALP) assay. The ethyl acetate fraction of peanut sprout extract was subjected to diverse column chromatographies using silica gel, ODS, and Sephadex LH-20 as stationary phases, and three nucleobases, namely, adenine, uracil, and thymine, and three phenolic acids, including caffeic acid, coumaric acid, and ferulic acid, were isolated as active constituents. In particular, adenine at 4 μg/mL and caffeic acid at 1 μg/mL increased ALP activity by 40 and 30%, respectively, compared with the osteoblastic differentiation medium-treated group, and these two compounds were set as marker compounds. Furthermore, extraction of peanut sprouts grown for 14–17 days with 60% ethanol was the best condition to obtain a high quantity of extract for peanut sprouts by analyzing the contents of marker compounds through HPLC. Together, these results suggest that peanut sprouts and their isolated compounds significantly enhance osteoblastic differentiation. Therefore, peanut sprouts have the potential to be developed as functional foods against osteoporosis.

Abstract Wild ginseng (Panax ginseng) adventitious root cultures were prepared by elicitation using methyl jasmonate and investigated further to find new secondary metabolites. Chromatographic fractionation of wild ginseng adventitious root cultures led to the isolation of eleven compounds. The chemical structures of isolated compounds were identified as four known flavanone derivatives (1–4), one new curcubinoyl derivative, jasmogin A (5) and six new curcubinoyl-flavanone conjugates, jasmoflagins A-F (6–11) by extensive spectroscopic analysis. Newly isolated curcubinoyl derivatives showed inhibitory activity against lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages. Therefore, our present study suggested that elicitor stimulated plant cell cultures might contribute to the production of new metabolites.

Myostatin (MSTN) is a well-reported negative regulator of muscle growth and a member of the transforming growth factor (TGF) family. MSTN has important functions in skeletal muscle (SM), and its crucial involvement in several disorders has made it an important therapeutic target. Several strategies based on the use of natural compounds to inhibitory peptides are being used to inhibit the activity of MSTN. This review delivers an overview of the current state of knowledge about SM and myogenesis with particular emphasis on the structural characteristics and regulatory functions of MSTN during myogenesis and its involvements in various muscle related disorders. In addition, we review the diverse approaches used to inhibit the activity of MSTN, especially in silico approaches to the screening of natural compounds and the design of novel short peptides derived from proteins that typically interact with MSTN.

The global obesity epidemic and the growing elderly population largely contribute to the increasing incidence of type 2 diabetes. Insulin resistance acts as a critical link between the present obesity pandemic and type 2 diabetes. Naturally occurring reactive oxygen species (ROS) regulate intracellular signaling and are kept in balance by the antioxidant system. However, the imbalance between ROS production and antioxidant capacity causes ROS accumulation and induces oxidative stress. Oxidative stress interrupts insulin-mediated intracellular signaling pathways, as supported by studies involving genetic modification of antioxidant enzymes in experimental rodents. In addition, a close association between oxidative stress and insulin resistance has been reported in numerous human studies. However, the controversial results with the use of antioxidants in type 2 diabetes raise the question of whether oxidative stress plays a critical role in insulin resistance. In this review article, we discuss the relevance of oxidative stress to insulin resistance based on genetically modified animal models and human trials.

Legume medicinal plants Astragalus membranaceus are widely used in the world and have very important economic value, ecological value, medicinal value, and ornamental value. The bioengineering technology of medicinal plants is used in the protection of endangered species, the rapid propagation of important resources, detoxification, and the improvement of degraded germplasm. Using bioengineering technology can effectively increase the content of secondary metabolites in A. membranaceus and improve the probability of solving the problem of medicinal plant resource shortage. In this review, we focused on biotechnological research into A. membranaceus, such as the latest advances in tissue culture, including callus, adventitious roots, hairy roots, suspension cells, etc., the metabolic regulation of chemical compounds in A. membranaceus, and the research progress on the synthetic biology of astragalosides, including the biosynthesis pathway of astragalosides, microbial transformation of astragalosides, and metabolic engineering of astragalosides. The review also looks forward to the new development trend of medicinal plant biotechnology, hoping to provide a broader development prospect for the in-depth study of medicinal plants.

At present, most precious compounds are still obtained by plant cultivation such as ginsenosides, glycyrrhizic acid, and paclitaxel, which cannot be easily obtained by artificial synthesis. Plant tissue culture technology is the most commonly used biotechnology tool, which can be used for a variety of studies such as the production of natural compounds, functional gene research, plant micropropagation, plant breeding, and crop improvement. Tissue culture material is a basic and important part of this issue. The formation of different plant tissues and natural products is affected by growth conditions and endogenous substances. The accumulation of secondary metabolites are affected by plant tissue type, culture method, and environmental stress. Multi-domain technologies are developing rapidly, and they have made outstanding contributions to the application of plant tissue culture. The modes of action have their own characteristics, covering the whole process of plant tissue from the induction, culture, and production of natural secondary metabolites. This paper reviews the induction mechanism of different plant tissues and the application of multi-domain technologies such as artificial intelligence, biosensors, bioreactors, multi-omics monitoring, and nanomaterials in plant tissue culture and the production of secondary metabolites. This will help to improve the tissue culture technology of medicinal plants and increase the availability and the yield of natural metabolites.

Sageretia thea is used in the preparation of herbal medicine in China and Korea; this plant is rich in various bioactive compounds, including phenolics and flavonoids. The objective of the current study was to enhance the production of phenolic compounds in plant cell suspension cultures of Sageretia thea. Optimum callus was induced from cotyledon explants on MS medium containing 2,4-dichlorophenoxyacetic acid (2,4-D; 0.5 mg L−1), naphthalene acetic acid (NAA, 0.5 mg L−1), kinetin (KN; 0.1 mg L−1) and sucrose (30 g L−1). Browning of callus was successfully avoided by using 200 mg L−1 ascorbic acid in the callus cultures. The elicitor effect of methyl jasmonate (MeJA), salicylic acid (SA), and sodium nitroprusside (SNP) was studied in cell suspension cultures, and the addition of 200 µM MeJA was found suitable for elicitation of phenolic accumulation in the cultured cells. Phenolic and flavonoid content and antioxidant activity were determined using 2,2 Diphenyl 1 picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethybenzothiazoline-6-sulphonic acid (ABTS), ferric reducing antioxidant power (FRAP) assays and results showed that cell cultures possessed highest phenolic and flavonoid content as well as highest DPPH, ABTS, and FRAP activities. Cell suspension cultures were established using 5 L capacity balloon-type bubble bioreactors using 2 L of MS medium 30 g L−1 sucrose and 0.5 mg L−1 2,4-D, 0.5 mg L−1 NAA, and 0.1 mg L−1 KN. The optimum yield of 230.81 g of fresh biomass and 16.48 g of dry biomass was evident after four weeks of cultures. High-pressure liquid chromatography (HPLC) analysis showed the cell biomass produced in bioreactors possessed higher concentrations of catechin hydrate, chlorogenic acid, naringenin, and other phenolic compounds.

Purpose The purpose of this study is to examine the location, rate, cause, and types of injuries according to the injured area by age and sports in female athletes. Methods The subject of the study was 426 female athletes who were registered as combat sports(Judo, Taekwondo, Fencing) athletes at the Korean Sports & Olympic Committee. We collected the data via online questionnaires, and conducted a frequency analysis using R statistics program. Results As a result, 51.4% of athletes experienced injuries in the past year, and the highest injury rate was shown in Taekwondo-University(0.43) during competition and Taekwondo-Professional(5.55) during training. The cause of injuries during competition was mainly due to 'as a result of me or the opponent's hittings, skills, or fouls' among internal factors, and 'recurrent injuries' among external factors. Among internal factors during training except for torso area and professional athletes, most of the injuries were also caused by ‘as a result of me or the opponent's hittings, skills, or fouls’ and ‘recurrent injuries’ among external factors. The frequency of injury was the highest in the lower extremity area across all age groups. The most frequently injured area, in the case of Judo, is skin-bleeding in the head, skin-bruise, muscle-inflammation, bone-fracture, spondylopathy(disc, stenosis, etc.) in the torso, muscle-inflammation in the upper extremity, ligament-sprain, rupture in the lower extremity. Taekwondo athletes had skin-bruise in the head, upper and lower extremities, and muscle-inflammation in the torso area, as the frequent injury cases, and Fencing athletes had all skin-bruise regardless of injuries. Conclusions The results of this study will be used to take measures for preventing injuries or to change training programs.

Purpose The purpose of this study is to identify the negative effects of long-term exercise (training and competition) suspension of male elite athletes due to compulsory military service on athletic performance, and to provide a basis for enhancing the importance of providing support systems and social conditions for maintaining athletic performance. Methods In this study, 17,418 male athletes aged 18 to 21 who were registered as athletes for the Korean Sports & Olympic Committee from 2003 to 2005 were enrolled. The athlete registration data includes information about the athlete's gender, age, sport and affiliation. According to the continuity of registration and belonging information, the compulsory military service type was classified into a manipulator. According to the form of Compulsory military service performed by male elite athletes, the return rate was confirmed and the career (year) was calculated. Results As a result of the survey, 12.49% of the athletes who served as general soldiers returned to the athletes after compulsory military service, showing a relatively low return rate compared to 78.91% of the Korea Armed Forces Athletic Corps, 76.55% of the National Police Agency's sports team, and 71.43% of the social service. Also, Athletes who served as general soldiers had a career of 2.46 years (± 1.94), while the Korea Armed Forces Athletic Corps was 10.21 years (± 3.58), the National Police Agency's sports team was 9.45 years (± 3.26), and the social service was 5.86 years (± 4.06), The exemption was 11.08 years (± 2.27), and the compulsory military service exception was 9.79 years (± 5.55). Conclusions Male elite athletes' decrease in athletic performance after compulsory military service is a natural result, as confirmed through the results of this study, and it is necessary to seek a support system between compulsory military service to maintain athletic performance.

Abstract Miraculin, derived from the miracle fruit (Synsepalum dulcificum), is a taste-regulating protein that interacts with human sweet-taste receptors and transforms sourness into sweet taste. Since miracle fruit is cultivated in West Africa, mass production of miraculin is limited by regional and seasonal constraints. Here, we investigated mass production of recombinant miraculin in carrot (Daucus carota L.) callus cultures using an air-lift bioreactor. To increase miraculin expression, the oxidative stress-inducible SWPA2 promoter was used to drive the expression of miraculin gene under various stress treatments. An 8 h treatment of hydrogen peroxide (H2O2) and salt (NaCl) increased the expression of miraculin gene by fivefold compared with the untreated control. On the other hand, abscisic acid, salicylic acid, and methyl jasmonate treatments showed no significant impact on miraculin gene expression compared with the control. This shows that since H2O2 and NaCl treatments induce oxidative stress, they activate the SWPA2 promoter and consequently up-regulate miraculin gene expression. Thus, the results of this study provide a foundation for industrial-scale production of recombinant miraculin protein using transgenic carrot cells as a heterologous host.

The purpose of this comparison of case reports is to introduce the results of the application of new devices for the management of growing Class III malocclusions in children. Two 8-year-old boys had a chief complaint of anterior crossbite. Anterior crossbite correction using a tandem traction bow appliance (TTBA) or a Carriere Motion 3D Class III appliance with a Transforce appliance was planned. By comparing cephalometric radiographs before and after treatment, changes in skeletal growth and incisor inclination to the Frankfort horizontal (FH) plane could be measured. Both devices increased SNA and ANB angles, N –| Pg-A, U1 to SN, and U1 to FH. Both appliances improved facial features and resolution of anterior crossbite. The TTBA and Carriere Motion 3D Class III appliance had similar effects when applied as early treatment for growing mesio-occlusions and anterior crossbite in two boys. However, long-term outcome assessments and well-designed comparative studies are still required.

The diagnostics of anaerobic glycolytic metabolism which play a subordinate role in elite rowing and parameters such as maximum lactate accumulation rate (νLa.max) have thus far not been associated with ergometer rowing performance. The aim of the study was to quantify the glycolytic energy metabolism (WGly) during a 2000 m ergometer rowing time trial (RTT) and νLa.max during a 10 s maximum ergometer rowing sprint test (RST) and to unravel associations between those variables and RTT performance. Combined post-exercise lactate measurements and oxygen uptake after RST and RTT were used to determine νLa.max and glycolytic energy contribution (WGly) in seven male and three female German U 23 national rowers (N = 10, 19.8 ± 0.9 years, 183.2 ± 7.0 cm height, 79.9 ± 13.3 kg body mass, 16.4 ± 5.1 % body fat). WGly during RTT ranged from 7 to 15.5% and νLa.max between 0.25 and 0.66 mmol∙L−1∙s−1. νLa.max correlated with WGly (p < 0.05, r = 0.74) and the mechanical power output (W) for the first 300 m (300first) during RTT (p < 0.05, r = 0.67). νLa.max further correlated with ∆300first−last (W) for the first and last 300 m (300last) during RTT (p < 0.01, r = 0.87) and also within the subgroup of male rowers. νLa.max displays a wide spectrum of individual differences in rowers. Due to this and its correlation to specific phases of RTT, it contributes to an individual energetic performance profile in rowing. Future studies must undermine the role of νLa.max for exercise performance and whether it serves as a marker that can be specifically targeted for a training-induced increase or decrease.

TXNIP is a critical regulator of glucose homeostasis, fatty acid synthesis, and cholesterol accumulation in the liver, and it has been reported that metabolic diseases, such as obesity, atherosclerosis, hyperlipidemia, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD), are associated with endoplasmic reticulum (ER) stress. Because CHIP, an E3 ligase, was known to be involved in regulating tissue injury and inflammation in liver, its role in regulating ER stress-induced NAFLD was investigated in two experimental NAFLD models, a tunicamycin (TM)-induced and other diet-induced NAFLD mice models. In the TM-induced NAFLD model, intraperitoneal injection of TM induced liver steatosis in both CHIP+/+ and CHIP+/− mice, but it was severely exacerbated in CHIP+/− mice compared to CHIP+/+ mice. Key regulators of ER stress and de novo lipogenesis were also enhanced in the livers of TM-inoculated CHIP+/− mice. Furthermore, in the diet-induced NAFLD models, CHIP+/− mice developed severely impaired glucose tolerance, insulin resistance and hepatic steatosis compared to CHIP+/+ mice. Interestingly, CHIP promoted ubiquitin-dependent degradation of TXNIP in vitro, and inhibition of TXNIP was further found to alleviate the inflammation and ER stress responses increased by CHIP inhibition. In addition, the expression of TXNIP was increased in mice deficient in CHIP in the TM- and diet-induced models. These findings suggest that CHIP modulates ER stress and inflammatory responses by inhibiting TXNIP, and that CHIP protects against TM- or HF–HS diet-induced NAFLD and serves as a potential therapeutic means for treating liver diseases.

Alzheimer’s disease (AD) is a serious neurodegenerative brain disease that interferes with daily life. The accumulation of beta-amyloid (Aβ), along with oxidative stress-inducing neurocellular apoptosis, has been considered one of the causes of AD. Thus, the purpose of this study is to find natural products that can reduce Aβ accumulation. The ethanol extract of Metasequoia glyptostroboides Hu & Cheng fruits (Cupressaceae) significantly reduced the aggregation of Aβ into oligomers and fibrils determined by Thioflavin T (ThT) assay. The solvent-partitioned ethyl acetate layer was further separated based on the bioassay-guided isolation method combined with the ThT assay. As a result, five compounds were isolated and elucidated as taxoquinone (1), sugiol (2), suginal (3), sandaracopimarinol (4), and sandaracopimaradien-19-ol (5) by comparing NMR data with references. All the compounds significantly reduced the aggregation of Aβ and enhanced the disaggregation of pre-formed Aβ aggregates in a dose-dependent manner. Furthermore, the inhibition of Aβ aggregation by the compounds protected PC12 cells from Aβ aggregate-induced toxicity. Among the five compounds, sandaracopimarinol (4) and sandaracopimaradien-19-ol (5) were the most effective. These results suggest that M. glyptostroboides and isolated five compounds have a potential for further study to be developed as anti-AD agents.

Obtusifolin, a major anthraquinone component present in the seeds of Cassia tora, exhibits several biological activities, including the amelioration of memory impairment, prevention of breast cancer metastasis, and reduction of cartilage damage in osteoarthritis. We aimed to evaluate the inhibitory effects of obtusifolin and its analogs on CYP1A enzymes, which are responsible for activating procarcinogens, and investigate its inhibitory mechanism and chemopreventive effects. P450-selective substrates were incubated with human liver microsomes (HLMs) or recombinant CYP1A1 and CYP1A2 in the presence of obtusifolin and its four analogs. After incubation, the samples were analyzed using liquid chromatography-tandem mass spectrometry. Molecular docking simulations were performed using the crystal structure of CYP1A2 to identify the critical interactions between anthraquinones and human CYP1A2. Obtusifolin potently and selectively inhibited CYP1A2-mediated phenacetin O-deethylation (POD) with a Ki value of 0.031 µM in a competitive inhibitory manner in HLMs, whereas it exhibited negligible inhibitory effect against other P450s (IC50 > 28.6 µM). Obtusifolin also inhibited CYP1A1- and CYP1A2-mediated POD and ethoxyresorufin O-deethylation with IC50 values of

Background: Beta-lactams (BLs) are commonly used antibiotics and leading causative agents of drug-induced anaphylaxis. Few studies on the culprit drugs and risk factors of BL-induced anaphylaxis are available. Our goal was to evaluate the culprit drugs and compare the risk factors in patients with BL-induced anaphylaxis to matched tolerant controls in a hospital setting. Methods: We retrospectively enrolled all patients who developed anaphylaxis from intravenous BL during hospitalization from 9 Korean hospitals. We compared clinical parameters between patients with BL-induced anaphylaxis and 4-fold BL-tolerant controls matched by age, sex, BL use, and the purpose of BL administration. Results: Seventy-four cases of BL-induced anaphylaxis and 296 BL-tolerant controls were enrolled. Cephalosporin accounted for 77% of total BL-induced anaphylaxis, and the top derivatives were ceftriaxone (23.0%), cefazedone (10.8%), and cefbuperazone (9.5%). Among penicillin derivatives, piperacillin (16.2%) was the most common, followed by ampicillin (2.7%). History of drug allergy (odds ratio [OR], 19.91; 95% confidence interval [CI] 5.33–74.44), previous exposure to the causative BL (OR, 7.71; 95% CI, 1.62–36.76), and concurrent administration of angiotensin-converting enzyme inhibitors (ACEIs) (OR, 5.97; 95% CI, 1.28–27.91) were independent risk factors associated with BL-induced anaphylaxis. Food allergy (OR, 13.93; 95% CI 1.31–148.9) and previous exposure to BL (OR, 6.59; 95% CI, 1.30–33.31) were identified as risk factors for cephalosporin-induced anaphylaxis. Conclusions: To prevent BL-induced anaphylaxis, attention should be paid to histories of drug or food allergy, previous exposure to BLs, and ACEI use. The risk factors and clinical outcomes might vary according to the BL classes.