Statement by the Korean Society of Occupational and Environmental Medicine on the proposed reform of working hours in South Korea.

The current 52-hour workweek in South Korea consists of 40 hours of regular work and 12 hours of overtime. Although the average working hours in South Korea is declining, it is still 199 hours longer than the Organisation for Economic Co-operation and Development average of 1,716 hours per year. In view to this, the South Korean government has now proposed to reform the workweek, mainly intending to increase the workweek to 69 hours when the workload is heavy. This reform, by increasing the labor intensity due to long working hours, goes against the global trend of reducing work hours for a safe and healthy working environment. Long working hours can lead to increased cerebrovascular and cardiovascular diseases, industrial accidents, mental health problems, and safety accidents due to lack of concentration. In conclusion, the Korean government's working hour reform plan can have a negative impact on workers' health, and therefore it should be thoroughly reviewed and modified.

Prognostic Implication of YY1 and CP2c Expression in Patients with Primary Breast Cancer.

Yin Yang 1 (YY1) is a transcription factor that regulates epigenetic pathways and protein modifications. CP2c is a transcription factor that functions as an oncogene to regulate cell proliferation. YY1 is known to interact with CP2c to suppress CP2c's transcriptional activity. This study aimed to investigate YY1 and CP2c expression in breast cancer and prognostic implications. In this study, YY1 and CP2c expression was evaluated using immunohistochemical staining, Western blot and RT-PCR assays. Of 491 patients with primary breast cancer, 138 patients showed YY1 overexpression. Luminal subtype and early stage were associated with overexpression (p < 0.001). After a median follow-up of 68 months, YY1 overexpression was found to be associated with a better prognosis (disease-free survival rates of 92.0% vs. 79.2%, p = 0.014). In Cox proportional hazards model, YY1 overexpression functioned as an independent prognostic factor after adjustment of hormone receptor/HER2 status and tumor size (hazard ratio of 0.50, 95% CI 0.26-0.98, p = 0.042). Quantitative analysis of YY1 and CP2c protein expression in tumors revealed a negative correlation between them. In conclusion, YY1 overexpression is a favorable prognostic biomarker in patients with breast cancer, and it has a negative correlation with CP2c at the protein level.

Over-expression of Long Non-coding RNA Urothelial Cancer-associated 1 as a Predictive Marker for Prostate Cancer.

BACKGROUND/AIM: To determine the expression of long non-coding RNA urothelial cancer-associated 1 (UCA1) by performing array-based quantitative polymerase chain reaction (PCR) and to identify the clinicopathological significance of UCA1 expression in prostate cancer using in situ hybridization (ISH) of surgically resected specimens. MATERIALS AND METHODS: Array-based quantitative PCR was performed using 10 pairs of fresh malignant (prostate cancer) and normal tissue samples to determine UCA1 expression. Single-color RNA ISH of surgically resected prostate cancer specimens was performed using 70 formalin-fixed, paraffin-embedded tissue specimens to examine the clinicopathological significance of UCA1. RESULTS: Prostate cancer tissues exhibited higher levels of UCA1 expression than paired benign tissues. Furthermore, a correlation between high UCA1 expression and unfavourable clinicopathological characteristics, including advanced pathologic T stage, extraprostatic extension, presence of Gleason pattern 5, and involvement of the resection margins was observed. Notably, increased UCA1 expression significantly correlated with high- or very-high-risk patients, as defined by the 2023 National Comprehensive Cancer Network guidelines. CONCLUSION: UCA1 could be used as a novel diagnostic and prognostic biomarker for establishing an effective treatment protocol for prostate cancer.

Integrating Tobacco Use Assessment and Treatment in the Oncology Setting: Quality Improvement Results from the Georgetown Lombardi Smoking Treatment and Recovery Program.

As part of the NCI's Cancer Center Cessation (C3i) initiative, we initiated, expanded, and maintained an evidence-based tobacco treatment program at the Georgetown Lombardi Comprehensive Cancer Center. We present a quality improvement (QI) assessment of the implementation process and patient-level outcomes. At two hematology/oncology outpatient clinical sites, five oncology-based teams (clinical administrators, clinical staff, pharmacy, information technology, and tobacco treatment staff) developed implementation strategies for opt-out patient assessment and enrollment, centralized tobacco treatment, audit, feedback, and staff training. Among eligible patients (tobacco use in ≤30 days), we assessed demographic, clinical, and tobacco-related characteristics to examine predictors of enrollment (baseline completed), treatment engagement (≥one sessions completed), and self-reported 7-day abstinence (6 months post-enrollment). Across both sites, medical assistants screened 19,344 (82.4%) patients for tobacco use, which identified 1345 (7.0%) current tobacco users, in addition to 213 clinician referrals. Of the 687/1256 (54.7%) eligible patients reached, 301 (43.8%) enrolled, and 199 (29.0%) engaged in treatment, of whom 74.5% were African American and 68% were female. At the larger site, significant multivariate predictors of enrollment included African American race (vs. white/other) and clinician referral (vs. MA assessment). Treatment engagement was predicted by greater nicotine dependence, and abstinence (27.4%) was predicted by greater treatment engagement. In summary, the systematic utilization of multiple oncology-based teams and implementation strategies resulted in the development and maintenance of a high-quality, population-based approach to tobacco treatment. Importantly, these strategies addressed inequities in tobacco treatment, as the program reached and engaged a majority-African-American patient population. Finally, the opt-out patient assessment strategy has been implemented in multiple oncology settings at MedStar Health through the Commission on Cancer's Just Ask program.

Participation and Prognostic Impact of Cardiac Rehabilitation After Acute Coronary Syndrome: Big-Data Study of the Korean National Health Insurance Service.

BACKGROUND: To investigate the actual rate and quality of cardiac rehabilitation (CR) participation in South Korea and its short-term impact on clinical outcomes after acute coronary syndrome (ACS). METHODS: Data, including confirmed ACS diagnosis, socio-demographics, comorbidities, clinical outcomes, and CR claim codes, were collected from the Korean National Health Insurance Service claims database and compared between the CR and non-CR groups. RESULTS: Overall, 102,544 patients were included in the study, of which only 5.8% attended CR. Regarding testing, 83.6% of CR patients performed the cardiopulmonary exercise test, but follow-up testing was infrequently performed; in addition, 53.1% of them participated in an electrocardiogram monitoring exercise, but over half participated in only one session. After 1:1 propensity score matching, post-ACS cardiovascular events were significantly lower in the CR group than in the non-CR group. The cumulative 3-year hazard ratio for all-cause death was 0.612 (95% confidence interval [CI], 0.495-0.756), recurrent ACS was 0.92 (95% CI, 0.853-0.993), CR readmission was 0.817 (95% CI, 0.768-0.868), and major adverse cardiovascular events (MACE) was 0.827 (95% CI, 0.781-0.874) in the CR group. CR was associated with a significant dose-response effect on MACE, with a reduction in incidence from 0.854 to 0.711. CONCLUSION: The actual rate of CR participation in South Korea remains low, and participation quality was not outstanding despite National Health Insurance coverage. Nevertheless, the impact of CR on cardiovascular outcomes after ACS was significantly superior. Efforts to increase CR participation should be increased by establishing new CR facilities and strategies to resolve associated barriers.

Clarification of the Mechanism of Inhibiting the Maillard Reaction between Phosphatidylethanolamine and Sugars by Adding Fatty Acid Calcium Salts.

Lecithin is known to undergo heat induced deterioration by the Maillard reaction between 1 mol of any sugar, except 2-deoxy sugar, and 2 mol of phosphatidylethanolamine (PE). However, we have previously reported that adding fatty acid metal salts can inhibit heat deterioration of soybean lecithin (SL). To clarify the mechanism of inhibition, 1,2-di-O-stearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE), d-glucose, and calcium stearate or calcium decanoate were heated in octane. When DSPE and d-glucose with calcium stearate or calcium decanoate were heated in the octane, the heat deterioration of DSPE was significantly inhibited, and no increase in UV absorption at 350 nm was observed. From these reactant solutions, one compound having a phosphate group and no primary amine was isolated, and NMR spectra confirmed that two molar of stearic acid derived from DSPE were coordinated to the amino group and phosphate group of DSPE. Therefore, we concluded that adding fatty acid metal salts reduced the nucleophilic reactivity of the amino group of PE and inhibited the Maillard reaction with sugars because two molar of fatty acid derived from PE coordinated to the amino group and phosphate group of PE.

Hexane fraction of Prunus japonica thunb. Seed extract enhances boar sperm motility via CatSper ion channel.

Introduction: Mammalian sperm motility is facilitated by flagellar beating, which depends on active ion movement through ion channels and their regulation. Prunus japonica Thunb., also known as oriental bush cherry, is a widely used traditional medicinal plant. However, its significance in improving fertility and sperm quality has not been fully elucidated yet. One of our previous reports revealed that P. japonica seed extract (PJE) can improve human sperm motility through intracellular pH modulation. Aim of the study: The present study was designed to investigate the effects of PJE on boar spermatozoa and potential underlying mechanisms. Materials and methods: Sperm motility changes were examined using a computer-assisted sperm analysis (CASA) system under both capacitated and non-capacitated conditions. Intracellular calcium concentration was measured using either confocal microscopy or a fluorescent microplate reader with Fluo-4AM calcium fluorescent dye. Sperm capacitation-related proteins were analyzed using western blotting. Results: A significant increase in rapid motility, velocity, and linear displacement of sperm was observed in PJE-treated capacitated boar sperm, whereas the effect was insignificant in the non-capacitated counterparts. Intracellular calcium levels were significantly elevated upon PJE treatment (20-100 µg/L) in a concentration-dependent manner. The increase in intracellular calcium levels was inhibited when the sperm were treated with a CatSper (cation channel of sperm) channel inhibitor, 10 µM Mibefradil, indicating the involvement of the ion channel in the PJE modulatory mechanism. In addition, western blotting revealed an increased level of protein phosphorylation (p-tyrosine and p-PKA), which is a hallmark of sperm capacitation. Conclusions: PJE treatment resulted in a combination of increased motility, intracellular calcium concentration, and capacitation, thereby indicating its potential to ameliorate sperm motility parameters and induce capacitation of boar spermatozoa as a result of intracellular calcium elevation via the CatSper channel. Our observations further elaborate ion channel-related underlying mechanisms and show putative implications of the seed extract of traditionally used P. japonica Thunb. in ameliorating sperm quality.

Chemical constituents of the Ajuga multiflora bunge and their protective effects on dexamethasone-induced muscle atrophy in C2C12 myotubes.

Ajuga multiflora Bunge is a perennial ornamental herb and has been used for the treatment of fever in Korean folk medicine. In the course of searching for protective agents associated with the potential of A. multiflora against dexamethsone (DEX)-induced muscle atrophy, a new phytoecdysteroid, 29-hydroxyprecyasterone (1), together with four known compounds (2-5), were isolated from A. multiflora. The structures of the compounds were determined by spectroscopic analyses, including 1D-, 2D-NMR and HR-MS interpretation. To elucidate the effects of obtained compounds on DEX-induced muscle atrophy, the myotubes diameter, myosin heavy chain (MyHC) positive area, and fusion index were evaluated by immunofluorescence staining. Overall, each compound treatment effectively prevented the atrophic myotubes through an increase of MyHC-positive myotubes and the number of nuclei. Particularly, the measurement of myotube diameter showed that compounds 1 and 5 treatment significantly alleviated the myotube thickness.

Identifying the Relationship between the Korean Medicine and Western Medicine in Factors Affecting Medical Service Use.

This study was conducted using data from the Korea Medical Panel Survey (KMPS) carried out in 2015. Importantly, the purpose of this study was to investigate the relationship between Korean medicine (KM) and Western medicine (WM) in medical service use. The general characteristics and the frequency of utilization of medical services were analyzed for 18,130 participants. Chi-square analysis was used to examine the factors that affected medical service use. Additionally, logistic regression analysis was conducted to examine the odds ratio (OR) between the KM Use with WM Use and KM&WM Use with disease group. The proportion of respondents who used KM&WM was the highest among those over 65 years of age and it was found to be statistically significant (p < 0.001). The OR for using KM and WM was 3.236 and it was also statistically significant (p < 0.001). Further, the ORs of KM&WM Use for all seven disease groups were greater than 1 and were statistically significant (p < 0.001) except for respiratory disease. The significant ORs of KM&WM Use were 10.342 (musculoskeletal), 2.073 (exogenous causes), 1.988 (nervous), 1.677 (digestive), 1.541 (circulatory) and 1.386 (skin). The findings in this study were attributed to a combination of social aspects such as the increasing incidence of chronic diseases among the elderly population, policy aspects such as the collaborative pilot project to promote collaborative treatment (CT), economic aspects, such as a lower total cost for CT and scientific aspects such as evidence supporting the efficacy of CT.

Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice.

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2',7'-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.

Persimmon Water Extract Suppresses Hepatic Lipotoxicity by Regulating Lipid Metabolites.

This study was performed to investigate the effects of persimmon (Diospyros kaki) on high-fat diet (HFD)-induced hepatic lipotoxicity. The compounds of persimmon water extract (PWE) were identified as gallic acid, glucogallin, 1-O-Galloyl-(2-O-acetyl)-glu, and trihydroxy-octadecadienoic acid. The PWE was ingested by C57BL/6 mice with an HFD for 8 weeks. The PWE improved glucose tolerance and suppressed weight gain by inhibiting increases in the weight of liver and adipose tissues. The results of serum biomarker analysis showed that PWE suppressed biomarkers such as liver injury and dyslipidemia. In ex vivo tests, reduction of oxidative stress and improvement of mitochondrial dysfunction were confirmed in the liver of PWE groups. In a molecular study, it was confirmed that PWE decreased lipid accumulation, insulin resistance, inflammation, and apoptosis in the liver. Finally, in a metabolite analysis of liver tissue using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), it was confirmed that PWE has an effect on lipid metabolism. In particular, PWE reduced phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs). Notably, it is presumed that the reduction of lysoPCs and PCs in the PWE group is related to the improvement of liver dysfunction due to lipotoxicity.

In vitro assessment of Prunus japonica seed extract on human spermatozoa hypermotility and intracellular alkalization.

Prunus japonica var. nakaii is used in traditional Korean medicine to treat various conditions; however, it has not been investigated for treating male infertility. In this study, we investigated the in vitro effects of the ethanolic extract of P. japonica seeds on human sperm motility and identified its mechanism of action. Eleven male volunteers were selected, and the effects of the extract on human spermatozoa were assessed through a computer-assisted semen analysis. The P. japonica seed extract increased the percentage of total and progressive motility of spermatozoa. To understand the mechanism of action, we monitored intracellular alkalization using flow cytometry and obtained electrophysiological recordings of human voltage-gated proton channels hHv1 that were overexpressed in HEK-293 cells. The extract shifted the activation curves in a concentration-dependent manner. Two major constituents of the extract, linoleic acid and oleic acid, exhibited proton channel activity. Our in vitro experiments suggested that P. japonica seed extract could be potentially used to rescue sperm motility in idiopathic infertility patients via pharmacological modulation of the proton channels during capacitation. Therefore, our results indicate the therapeutic potential of P. japonica seed extract for treating male infertility.

Effects of Perilla frutescens var. acuta in amyloid ß toxicity and Alzheimer's disease-like pathology in 5XFAD mice.

Although accumulation of amyloid ß (Aß) plaque is a major hallmark of Alzheimer's disease (AD), various pathologies have been suggested therapeutic targets. Therefore, therapies-targeting multiple pathologies would be required for effective managements of AD. Accordingly, natural products, which has multiple active ingredients, have been receiving a lot of attention. In this study, we tested whether standardized ethanol extract of leaves of Perilla frutescens var. acuta (L.) Britt. (Lamiaceae) (ELPF) could modulate various pathologies in AD using 5XFAD mice. ELPF blocked Aß aggregation and disassembled pre-formed Aß aggregates. ELPF blocked Aß aggregates-induced LTP impairment and ELPF-disassembled Aß aggregates failed to impair hippocampal LTP. Systemic administration of ELPF blocked Aß aggregates-induced memory impairment in a passive avoidance test. ELPF-disassembled Aß aggregates failed to impair passive avoidance memory. Prolonged administration of ELPF ameliorated memory impairments in 5XFAD mice. In the hippocampus of 5XFAD mice, ELPF administration significantly reduced Aß deposits and neuroinflammation. These results demonstrate that ELPF could be a promising therapeutic candidate for AD.

Blood Salvage and Autotransfusion With Single Leukoreduction Does Not Increase the Risk of Tumor Recurrence After Liver Transplantation for Advanced Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). BACKGROUND: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. METHODS: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74 of 129 without autotransfusion were matched with 74 of 220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. RESULTS: Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/ 38.3%/39.7% for nonautotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the 2 groups in overall recurrence [hazard ratio (HR) = 0.72 (0.43-1.21)], intrahepatic recurrence [HR = 0.70 (0.35-1.40)], and extrahepatic recurrence [HR = 0.82 (0.46-1.47)]. Also, there were no significant differences in overall death [HR = 0.57 (0.29-1.12)], HCC-related death [HR = 0.59 (0.29-1.20)], and HCC-unrelated death [HR = 0.48 (0.09-2.65)]. CONCLUSIONS: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models.

Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.

Application of Linear Gradient Solvent System in Centrifugal Partition Chromatography Facilitating Bioassay-Guided Fractionation of Yongdamsagan-Tang, Traditional Oriental Decoction.

As important pharmaceutical resources, traditional herbal medicines retain continuous attention. To do that, isolation and identification of bioactive molecules from traditional herbal decoction are important. However, conventional fractionation through octadecyl silica column faces irreversible sample adsorption that causes a bias in bioactivity assessment. However, liquid-liquid chromatographic system suffers tedious K value calculation as well as insufficient capacity in separation power when crude extract composed of widely ranging polarities. Here, we developed a comprehensive linear gradient solvent system for centrifugal partition chromatography (CPC) to aid bioassay-guided isolation. The lower aqueous phase of the n-hexane-acetonitrile-water (10:2:8, v/v) was used as the stationary, whereas its upper organic phase followed by the upper phase of ethyl acetate-acetonitrile-water and water-saturated n-butanol-acetonitrile-water in the same ratio were eluted in a linear gradient mode, thereby increasing polarity in the mobile phase. The HPLC profiling of CPC fraction showed that proposed gradient CPC was suitable to separate metabolites from Yongdamsagan-Tang, a traditional medicinal decoction made of ten herbal plants. Exhibiting a high recovery yield of 98.3%, antioxidant response element (ARE) luciferase-inducing assay in HepG2 cells indicated that the fractions composed of baicalein and wogonin, the marker natural products of Scutellaria baicalensis, were to be the most effective molecules from Yongdamsagan-Tang. The presented results demonstrated that bioassay-guided separation that assisted with a linear gradient CPC is an incomparable alternative to HPLC and biphasic CPC in terms of higher yield rate and redundant K value calculation, respectively, which led to an unbiased/time-saving separation and identification of bioactive molecules from the complex crude extract of natural products.

Bioassay-Guided Isolation of Two Eudesmane Sesquiterpenes from Lindera strychnifolia Using Centrifugal Partition Chromatography.

In this study, a centrifugal partition chromatography (CPC) separation was applied to identify antioxidant-responsive element (ARE) induction molecules from the crude extract of Lindera strychnifolia roots. CPC was operated with a two-phase solvent system composed of n-hexane-methanol-water (10:8.5:1.5, v/v/v) in dual mode (descending to ascending), which provided a high recovery rate (>95.5%) with high resolution. Then, ARE induction activity of obtained CPC fractions was examined in ARE-transfected HepG2 cells according to the weight ratios of the obtained fractions. The fraction exhibiting ARE-inducing activity was further purified by preparative HPLC that led to isolation of two eudesmane type sesquiterpenes as active compounds. The chemical structures were elucidated as linderolide U (1) and a new sesquiterpene named as linderolide V (2) by spectroscopic data. Further bioactivity test demonstrated that compounds 1 and 2 enhanced ARE activity by 22.4-fold and 7.6-fold, respectively, at 100 µM concentration while 5 µM of sulforaphane induced ARE activity 24.8-fold compared to the control.

Immature Persimmon Suppresses Amyloid Beta (Aß) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice.

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aß)1-42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aß1-42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aß1-42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3ß, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS2).

Genome-Wide Differential Methylation Profiles from Two Terpene-Rich Medicinal Plant Extracts Administered in Osteoarthritis Rats.

Extracts from the plants Phlomis umbrosa and Dipsacus asperoides-which are widely used in Korean and Chinese traditional medicine to treat osteoarthritis and other bone diseases-were used to treat experimental osteoarthritis (OA) rats. Genome-wide differential methylation regions (DMRs) of these medicinal-plant-treated rats were profiled as therapeutic evidence associated with traditional medicine, and they need to be investigated further using detailed molecular research to extrapolate traditional practices to modern medicine. In total, 49 protein-encoding genes whose expression is differentially regulated during disease progression and recovery have been discovered via systematic bioinformatic analysis and have been approved/proposed as druggable targets for various bone diseases by the US food and drug administration. Genes encoding proteins involved in the PI3K/AKT pathway were found to be enriched, likely as this pathway plays a crucial role during OA progression as well as during the recovery process after treatment with the aforementioned plant extracts. The four sub-networks of PI3K/AKT were highly regulated by these plant extracts. Overall, 29 genes were seen in level 2 (51-75%) DMRs and were correlated highly with OA pathogenesis. Here, we propose that these genes could serve as targets to study OA; moreover, the iridoid and triterpenoid phytochemicals obtained from these two plants may serve as potential therapeutic agents.

Epigenetic mechanisms involved in the neuroprotective effect of scorpion extract in a Parkinson's disease murine model based on multi-omics approach.

OBJECTIVE: To investigate whether scorpion extract elicits a neuroprotective effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice models, and the genes associated with the therapeutic effects using RNA sequencing (seq) analysis. METHODS: This study investigated the changes in interaction between messenger ribonucleic acid (mRNA) expression and deoxyribonucleic acid (DNA) methylation related to the protective effects of scorpion extracts, in the substantia nigra (SN) region of a MPTP-induced Parkinson's disease (PD) model. RESULTS: In this model, scorpion extracts attenuated the motor impairment as demonstrated by the rotarod and open field tests. Scorpion extracts consistently attenuated the decrease of tyrosine hydroxylase (TH) positive neural cells in the SN and striatum of mice. We profiled genome- wide DNA methylation using Methyl-Seq and measured the transcriptome using RNA-Seq in murine SN in the following groups: vehicle-treated MPTP-induced PD mice and scorpion extract- treated MPTP-induced PD mice. In total, 13 479 differentially expressed genes were identified in association with the anti-PD effect of the scorpion extract, mainly in the promoter and coding regions. Among them, 47 were negatively correlated down- regulated genes. Nineteen genes out of 47 down- regulated genes were negatively correlated with the expression of the other 28 genes. Among these genes, SGSM1 was related to dopaminergic neu- rons including dopamine transporters, TH, dihy- droxyphenylalanine decarboxylase, and dopamine D2 receptor. CONCLUSION: This study provides insights into the anti-parkinsonian effects of scorpion extract and reveals the epigenetic targets in its therapeutic mechanism.