Liquid plasma promotes angiogenesis through upregulation of endothelial nitric oxide synthase-induced extracellular matrix metabolism: potential applications of liquid plasma for vascular injuries.

BACKGROUND: Applications of nonthermal plasma have expanded beyond the biomedical field to include antibacterial, anti-inflammatory, wound healing, and tissue regeneration. Plasma enhances epithelial cell repair; however, the potential damage to deep tissues and vascular structures remains under investigation. RESULT: This study assessed whether liquid plasma (LP) increased nitric oxide (NO) production in human umbilical vein endothelial cells by modulating endothelial NO synthase (eNOS) phosphorylation and potential signaling pathways. First, we developed a liquid plasma product and confirmed the angiogenic effect of LP using the Matrigel plug assay. We found that the NO content increased in plasma-treated water. NO in plasma-treated water promoted cell migration and angiogenesis in scratch and tube formation assays via vascular endothelial growth factor mRNA expression. In addition to endothelial cell proliferation and migration, LP influenced extracellular matrix metabolism and matrix metalloproteinase activity. These effects were abolished by treatment with NG-L-monomethyl arginine, a specific inhibitor of NO synthase. Furthermore, we investigated the signaling pathways mediating the phosphorylation and activation of eNOS in LP-treated cells and the role of LKB1-adenosine monophosphate-activated protein kinase in signaling. Downregulation of adenosine monophosphate-activated protein kinase by siRNA partially inhibited LP-induced eNOS phosphorylation, angiogenesis, and migration. CONCLUSION: The present study suggests that LP treatment may be a novel strategy for promoting angiogenesis in vascular damage. Video Abstract.

Association of Dietary Resistant Starch Intake with Obesity and Metabolic Syndrome in Korean Adults.

Research findings on the relationship between dietary resistant starch (RS) intake and metabolic diseases using population-based data are very scarce. This study examined the association of dietary RS intake with obesity and metabolic syndrome in Korean adults. A total of 12,491 adults (5292 men and 7199 women) were selected from the 2016-2018 Korea National Health and Nutrition Examination Survey data. The individual RS intake (g) was calculated by linking the 1-day 24 h recall data with the RS content database for common Korean foods. Obesity was defined as a BMI ≥ 25.0 kg/m2. Metabolic syndrome was defined as having three or more of the following: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated fasting blood glucose, and elevated blood pressure. Odds ratios (ORs) with 95% confidence intervals (CIs) for obesity and metabolic syndrome across quartiles (Qs) of RS intake were calculated using multiple logistic regression analysis. In men, the highest quartile of RS intake showed a significantly lower OR for metabolic syndrome compared to the lowest quartile after adjusting for covariates (OR = 0.71, 95% CI = 0.56-0.92, p-trend = 0.0057). Dietary RS intake in men was also inversely associated with obesity (Q4 vs. Q1: OR = 0.80, 95% CI = 0.67-0.97, p-trend = 0.0329) and elevated triglycerides (Q4 vs. Q1: OR = 0.80, 95% CI = 0.66-0.98, p-trend = 0.0314). In women, RS intake was not associated with metabolic syndrome. Our findings may serve as useful data for developing guidelines for RS intake and conducting further cohort and clinical studies to investigate the health effects of RS.

Anti-obesity effects of yuja (Citrus junos Sieb ex Tanaka) pomace extract fermented with lactic acid bacteria on the hepatocytes and epididymal fat tissue of rats.

This study investigated the anti-obesity effects of yuja pomace extract fermented with lactic acid bacteria in rats with high-fat diet-induced obesity over a period of eight weeks. Epididymal fat cell size was significantly smaller, by about 33%, in the treatment groups given yuja pomace extract fermented with lactic acid bacteria compared to the CON group. Electron microscopic observation of hepatocyte microstructure showed that the number of lipid droplets was lower in hepatocytes, the number of mitochondria was higher, along with distinct cristae, and the rough endoplasmic reticula were well developed with stacks of cisternae and ribosomes. Thus, it is believed that yuja pomace extract fermented with lactic acid bacteria, by influencing body weight and lipid accumulation, is effective in the prevention and treatment of obesity.

Prospective Associations between Dietary Patterns and Abdominal Obesity in Middle-Aged and Older Korean Adults.

This study aimed to identify major dietary patterns associated with abdominal obesity in middle-aged and older Korean adults. Data from the Korean Genome and Epidemiology Study were used. A total of 48,037 Korean adults aged ≥40 years without abdominal obesity at baseline were followed-up. Dietary assessment was conducted using a validated 106-item food-frequency questionnaire, and dietary patterns were identified using factor analysis. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥85 cm for women, according to the Korean Society for the Study of Obesity. Multivariable Cox proportional-hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the future risk of abdominal obesity for each dietary pattern after adjusting for potential covariates. After an average follow-up of 4.89 years, we reported 5878 cases (1932 men and 3946 women) of abdominal obesity. Based on factor analysis, three major dietary patterns were identified in both men and women: the "healthy", "coffee and sweets", and "multi-grain" patterns. In the fully adjusted model, the "healthy" pattern was inversely associated with the incidence of abdominal obesity (HR for fourth vs. first quartile: 0.86; 95% CI: 0.75-0.98; p for trend = 0.0358 for men; HR for fourth vs. first quartile: 0.90; 95% CI: 0.83-0.99; p for trend = 0.0188 for women), whereas the "coffee and sweets" pattern was positively associated with it (HR for fourth vs. first quartile: 1.23; 95% CI: 1.08-1.40; p for trend = 0.0495 for men; HR for fourth vs. first quartile: 1.14; 95% CI: 1.04-1.25; p for trend = 0.0096 for women). In contrast, the "multi-grain" pattern in men and women showed no significant association with the incidence of abdominal obesity. Diets rich in colorful vegetables, seaweeds, mushrooms, tubers, fruits, soy products, and fish and low in coffee, sweets, and oils/fats might be favorable for reducing the future risk of abdominal obesity, particularly in middle-aged and older Korean adults.

Critical Role of Regrowth Conditions in Post-Cryopreservation of In Vitro Plant Germplasm.

Cryopreservation is an effective option for the long-term conservation of plant genetic resources, including vegetatively propagated crops and ornamental plants, elite tree genotypes, threatened plant species with non-orthodox seeds or limited seed availability, as well as cell and root cultures useful for biotechnology. With increasing success, an arsenal of cryopreservation methods has been developed and applied to many species and material types. However, severe damage to plant material accumulating during the multi-step cryopreservation procedure often causes reduced survival and low regrowth, even when the optimized protocol is applied. The conditions at the recovery stage play a vital role in supporting material regrowth after cryopreservation and, when optimized, may shift the life-and-death balance toward a positive outcome. In this contribution, we provide an overview of the five main strategies available at the recovery stage to improve post-cryopreservation survival of in vitro plant materials and their further proliferation and development. In particular, we discuss the modification of the recovery medium composition (iron- and ammonium-free), exogenous additives to cope with oxidative stress and absorb toxic chemicals, and the modulation of medium osmotic potential. Special attention is paid to plant growth regulators used at various steps of the recovery process to induce the desired morphological response in cryopreserved tissues. Given studies on electron transport and energy provision in rewarmed materials, we discuss the effects of light-and-dark conditions and light quality. We hope that this summary provides a helpful guideline and a set of references for choosing the recovery conditions for plant species that have not been cryopreserved. We also propose that step-wise recovery may be most effective for materials sensitive to cryopreservation-induced osmotic and chemical stresses.

Identifying the Associations of Nightly Fasting Duration and Meal Timing with Type 2 Diabetes Mellitus Using Data from the 2016-2020 Korea National Health and Nutrition Survey.

Nightly fasting duration and meal timing are associated with metabolic disorders. This study aimed to investigate the relationships of nightly fasting duration and meal timing with type 2 diabetes mellitus (T2DM) using data from the 2016-2020 Korea National Health and Nutrition Survey. A total of 22,685 adults ≥ 19 years were included in this study. Nightly fasting duration was calculated by subtracting the interval between the day's first and last meal eating times from 24 h. The meal timing were analyzed using various parameters, including the times of the first and last eating episodes and the percentage of energy intake during the morning (05:00 to 9:00 a.m.), evening (06:00 to 09:00 p.m.), and night (after 09:00 p.m.). Men who fasted nightly for ≥ 12 h had lower odds of T2DM (odds ratio (OR): 0.86; 95% confidence interval (CI): 0.75-0.99) than those who fasted for < 12 h. Individuals who had their last meal after 09:00 p.m. had higher odds of T2DM (OR: 1.19, 95% CI: 1.03-1.38, men; OR: 1.19, 95% CI: 1.01-1.40, women). Additionally, the percentage of energy intake during the evening was associated with increased odds of T2DM (OR: 1.41, 95% CI: 1.08-1.84, men; OR: 1.32, 95% CI: 1.02-1.70, women). These findings emphasize the importance of nightly fasting duration and meal timing in modulating the risk of T2DM among Korean adults.

Liquid plasma as a treatment for cutaneous wound healing through regulation of redox metabolism.

The skin functions as the outermost protective barrier to the internal organs and major vessels; thus, delayed regeneration from acute injury could induce serious clinical complications. For rapid recovery of skin wounds, promoting re-epithelialization of the epidermis at the initial stage of injury is essential, wherein epithelial keratinocytes act as leading cells via migration. This study applied plasma technology, which has been known to enable wound healing in the medical field. Through in vitro and in vivo experiments, the study elucidated the effect and molecular mechanism of the liquid plasma (LP) manufactured by our microwave plasma system, which was found to improve the applicability of existing gas-type plasma on skin cell migration for re-epithelialization. LP treatment promoted the cytoskeletal transformation of keratinocytes and migration owing to changes in the expression of integrin-dependent focal adhesion molecules and matrix metalloproteinases (MMPs). This study also identified the role of increased levels of intracellular reactive oxygen species (ROS) as a driving force for cell migration activation, which was regulated by changes in NADPH oxidases and mitochondrial membrane potential. In an in vivo experiment using a murine dorsal full-thickness acute skin wound model, LP treatment helped improve the re-epithelialization rate, reaffirming the activation of the underlying intracellular ROS-dependent integrin-dependent signaling molecules. These findings indicate that LP could be a valuable wound management material that can improve the regeneration potential of the skin via the activation of migration-related molecular signaling within the epithelial cell itself with plasma-driven oxidative eustress.

What Is the Relationship between Antioxidant Efficacy, Functional Composition, and Genetic Characteristics in Comparing Soybean Resources by Year?

The aim of this study was to analyze the physiological activity of 48 soybean resources harvested in 2020 to identify the soybean resources' relationships with individual isoflavone compounds and their genetic properties. These data will subsequently be compared with the research results on soybeans harvested in 2019. Initially, with respect to the physiological activity (6 types) and substances (19 types), this study evaluated the differences between the cultivation year (two years), seed coat color (three colors), and the interaction of the year and seed coat color of soybeans through ANOVA. Among the physiological activities, there were differences in the estrogen, estrogen receptor alpha, and UCP-1 (uncoupling protein-1) activities depending on the cultivation year. Moreover, there were differences in NO (nitric oxide), revealing differences in the ABTS (2, 2'-azino-bis-3ethylbenzo-thiazoline-6-sulfonic acid) and DPPH (2, 2-diphenyl-2-picrylhydrazyl) radical scavenging activities due to the seed coat color and the interaction of the year and seed coat color. Soybeans harvested in 2020 exhibited increased ABTS, DPPH, and NO inhibitory activities and reduced estrogen, estrogen receptor alpha, and UCP-1 activities compared to those harvested in 2019. According to the ANOVA results, eight of the nineteen individual derivatives illustrated yearly differences, while three derivatives displayed differences due to the seed coat color. Secondly, according to the relationship between the efficacy, derivative substances, and genetic properties, it was determined that genistein 7-O-(2″-O-apiosyl)glucoside (F5) is the individual isoflavone derivative that affected the six types of physiological activity, on which the genome-wide association study (GWAS) showed no significant differences for genetic properties. These results were inconsistent with the 2019 data, where three types of individual compounds, including F5, were proposed as substances that correlated with efficacy and there was a high correlation with genetic properties. Therefore, this study selected B17, B23, B15, B24, and Y7 as excellent varieties that are stable and highly functional in the cultivation environment, producing only small annual differences. The results of this study will be utilized as basic data for predicting soybean varieties and their cultivation, which have high environmental stability under climate variation and properly retain the functional substances and efficacy.

Multi-Omics-Based Autophagy-Related Untypical Subtypes in Patients with Cerebral Amyloid Pathology.

Recent multi-omics analyses paved the way for a comprehensive understanding of pathological processes. However, only few studies have explored Alzheimer's disease (AD) despite the possibility of biological subtypes within these patients. For this study, unsupervised classification of four datasets (genetics, miRNA transcriptomics, proteomics, and blood-based biomarkers) using Multi-Omics Factor Analysis+ (MOFA+), along with systems-biological approaches following various downstream analyses are performed. New subgroups within 170 patients with cerebral amyloid pathology (Aß+) are revealed and the features of them are identified based on the top-rated targets constructing multi-omics factors of both whole (M-TPAD) and immune-focused models (M-IPAD). The authors explored the characteristics of subtypes and possible key-drivers for AD pathogenesis. Further in-depth studies showed that these subtypes are associated with longitudinal brain changes and autophagy pathways are main contributors. The significance of autophagy or clustering tendency is validated in peripheral blood mononuclear cells (PBMCs; n = 120 including 30 Aß- and 90 Aß+), induced pluripotent stem cell-derived human brain organoids/microglia (n = 12 including 5 Aß-, 5 Aß+, and CRISPR-Cas9 apolipoprotein isogenic lines), and human brain transcriptome (n = 78). Collectively, this study provides a strategy for precision medicine therapy and drug development for AD using integrative multi-omics analysis and network modelling.

A Correlation Study on In Vitro Physiological Activities of Soybean Cultivars, 19 Individual Isoflavone Derivatives, and Genetic Characteristics.

The functionality of soybeans is an important factor in the selection and utilization of excellent soybean cultivars, and isoflavones are representative functional substances in soybeans, which exhibit effects on antioxidants, estrogen activity, and cancer, and prevent cardiovascular diseases. This study analyzed ABTS, DPPH, estrogen, ER (ER) alpha, UCP-1, and NO inhibition activities in 48 types of soybean cultivars, as well as the relationship with 19 isolated types of individual isoflavone derivatives. Statistical analysis was conducted to find individual isoflavone derivatives affecting physiological activities, revealing the high correlation of three types of derivatives: genistein 7-O-(6″-O-acetyl)glucoside (6″-O-acetylgenistin), genistein 7-O-(2″-O-apiosyl)glucoside, and glycitein. Based on these results, 15 types of soybean cultivars were selected (one control type, seven yellow types, six black types, and one green type), which have both high physiological activities and a high content of individual isoflavone derivatives. In addition, these high correlations were further verified through a genome-wide association study (GWAS) to determine the association between activities, substances, and genetic characteristics. This study comprehensively describes the relationship between the specific physiological activities of soybean resources, individual isoflavone derivative substances, and SNPs, which will be utilized for in-depth research, such as selection of excellent soybean resources with specific physiological activities.

Optimization of a Cryopreservation Method for the Endangered Korean Species Pogostemon yatabeanus Using a Systematic Approach: The Key Role of Ammonium and Growth Regulators.

Cryopreservation provides a secure long-term conservation option for rare and endangered plant species with non-orthodox or limitedly available seeds. Wide application of cryopreservation to biobank wild flora is hampered by the need to re-optimize nearly all protocol steps for every new species. We applied a systematic approach to simplify optimization of a multi-stage droplet-vitrification method for the endangered wetland Korean species, Pogostemon yatabeanus. This approach consisted of a standard procedure pre-selected based on material type and size, which was complemented with 11 additional treatments to reveal the most impactful conditions. Effect of ammonium nitrate at various protocol steps was also tested. The highest shoot tip survival (92%) and plant regeneration (90%) after cryopreservation were achieved using preculture with 10% sucrose followed by 40 min osmoprotection and 60 min treatment with vitrification solution A3-80% (33.3% glycerol + 13.3% dimethyl sulfoxide + 13.3% ethylene glycol + 20.1% sucrose) on ice. A three-step regrowth procedure starting with ammonium-free medium with 1 mg/L GA3 and 1 mg/L BA followed by ammonium-containing medium with and without growth regulators was essential for the development of healthy plants from cryopreserved shoot tips. This approach enables fast optimization of the cryopreservation procedure for new osmotic stress-sensitive plant species.

The clinical use of blood-test factors for Alzheimer's disease: improving the prediction of cerebral amyloid deposition by the QPLEXTM Alz plus assay kit.

Alzheimer's disease (AD) is the leading cause of dementia, and many studies have focused on finding effective blood biomarkers for the accurate diagnosis of this disease. Predicting cerebral amyloid deposition is considered the key for AD diagnosis because a cerebral amyloid deposition is the hallmark of AD pathogenesis. Previously, blood biomarkers were discovered to predict cerebral amyloid deposition, and further efforts have been made to increase their sensitivity and specificity. In this study, we analyzed blood-test factors (BTFs) that can be commonly measured in medical health check-ups from 149 participants with cognitively normal, 87 patients with mild cognitive impairment, and 64 patients with clinically diagnosed AD dementia with brain amyloid imaging data available. We demonstrated that four factors among regular health check-up blood tests, cortisol, triglyceride/high-density lipoprotein cholesterol ratio, alanine aminotransferase, and free triiodothyronine, showed either a significant difference by or correlation with cerebral amyloid deposition. Furthermore, we made a prediction model for Pittsburgh compound B-positron emission tomography positivity, using BTFs and the previously discovered blood biomarkers, the QPLEXTM Alz plus assay kit biomarker panel, and the area under the curve was significantly increased up to 0.845% with 69.4% sensitivity and 90.6% specificity. These results show that BTFs could be used as co-biomarkers and that a highly advanced prediction model for amyloid plaque deposition could be achieved by the combinational use of diverse biomarkers.

Plexin-A4 mediates amyloid-ß-induced tau pathology in Alzheimer's disease animal model.

Amyloid-ß (Aß) and tau are major pathological hallmarks of Alzheimer's disease (AD). Several studies have revealed that Aß accelerates pathological tau transition and spreading during the disease progression, and that reducing tau can mitigate pathological features of AD. However, molecular links between Aß and tau pathologies remain elusive. Here, we suggest a novel role for the plexin-A4 as an Aß receptor that induces aggregated tau pathology. Plexin-A4, previously known as proteins involved in regulating axon guidance and synaptic plasticity, can bound to Aß with co-receptor, neuropilin-2. Genetic downregulation of plexin-A4 in neurons was sufficient to prevent Aß-induced activation of CDK5 and reduce tau hyperphosphorylation and aggregation, even in the presence of Aß. In an AD mouse model that manifests both Aß and tau pathologies, genetic downregulation of plexin-A4 in the hippocampus reduced tau pathology and ameliorated spatial memory impairment. Collectively, these results indicate that the plexin-A4 is capable of mediating Aß-induced tau pathology in AD pathogenesis.

A logical network-based drug-screening platform for Alzheimer's disease representing pathological features of human brain organoids.

Developing effective drugs for Alzheimer's disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood-brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs.

Metabolic Profiling of Primary Metabolites and Galantamine Biosynthesis in Wounded Lycoris radiata Callus.

Plants are continuously exposed to abiotic and biotic factors that lead to wounding stress. Different plants exhibit diverse defense mechanisms through which various important metabolites are synthesized. Humans can exploit these mechanisms to improve the efficacy of existing drugs and to develop new ones. Most previous studies have focused on the effects of wounding stress on the different plant parts, such as leaves, stems, and roots. To date, however, no study has investigated the accumulation of primary and galantamine content following the exposure of a callus to wounding stress. Therefore, in the present study, we exposed Lycoris radiata calli to wounding stress and assessed the expression levels of several genes involved in metabolic pathways at various time points (0, 3, 6, 12, 24, 48, 72, and 96 h of exposure). Furthermore, we quantify the primary and galantamine content using gas chromatography-time-of-flight mass spectrometry and the high-performance liquid chromatography qRT-PCR analysis of eight galantamine pathway genes (LrPAL-2, LrPAL-3, LrC4H-2, LrC3H, LrTYDC2, LrN4OMT, LrNNR, and LrCYP96T) revealed that seven genes, except LrN4OMT, were significantly expressed following exposure to wounding stress. Galantamine contents of calli after 3, 6, 12, 24, 48, 72, and 96 h of exposure were respectively 2.5, 2.5, 3.5, 3.5, 5.0, 5.0, and 8.5 times higher than that after 0 h of exposure. Furthermore, a total of 48 hydrophilic metabolites were detected in the 0 h exposed callus and 96 h exposed callus using GC-TOFMS. In particular, a strong positive correlation between galantamine and initial precursors, such as phenylalanine and tyrosine, was observed.

Aroma Characteristics of Raw and Cooked Tenebrio molitor Larvae (Mealworms).

This study compared aroma compositions and sensory aroma attributes of raw and cooked Tenebrio molitor larvae (mealworms). Main sensory aroma attributes of raw mealworms were strong wet-soil-like, and less-intense oily, shrimp-like and sweet-corn-like. Quantitatively, the major aroma components of raw mealworms were hydrocarbons and aldehydes. As cooking proceeded, sweet-corn-like, roasted, and fried-oil-like sensory attributes were increasingly perceived with steaming, roasting, and frying, respectively. Some pyrazines, pyrrolidines, and carbonyls increased or appeared in roasted and fried mealworms. Partial least squares regression also showed differences in raw and cooked mealworms based on aroma components and their sensory attributes. Unlike raw mealworms, steamed mealworms had a relatively strong sweet-corn-like aroma attribute, which was related to 2,4,6-trimethyl-heptane, 2,4-dimethyl-dodecane, and 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one. In comparison, roasted and fried mealworms exhibited roasted, shrimp-like, and fried-oil-like aroma attributes, which were associated with intermediates of the Maillard reaction and lipid oxidation, such as pyrazines, alcohols, and aldehydes. This result during thermal reactions was very similar to those of meat and/or seafood. The use of mealworms as a savory-type flavor enhancer can be expected.

Protective Effects of N-Acetylcysteine against Radiation-Induced Oral Mucositis In Vitro and In Vivo.

PURPOSE: Radiation-induced oral mucositis limits delivery of high-dose radiation to targeted cancers. Therefore, it is necessary to develop a treatment strategy to alleviate radiation-induced oral mucositis during radiation therapy. We previously reported that inhibiting reactive oxygen species (ROS) generation suppresses autophagy. Irradiation induces autophagy, suggesting that antioxidant treatment may be used to inhibit radiation-induced oral mucositis. MATERIALS AND METHODS: We determined whether treatment with N-acetyl cysteine (NAC) could attenuate radiation-induced buccal mucosa damage in vitro and in vivo. The protective effects of NAC against oral mucositis were confirmed by transmission electron microscopy and immunocytochemistry. mRNA and protein levels of DNA damage and autophagy-related genes were measured by quantitative real-time polymerase chain reaction and western blot analysis, respectively. RESULTS: Rats manifesting radiation-induced oral mucositis showed decreased oral intake, loss of body weight, and low survival rate. NAC intake slightly increased oral intake, body weight, and the survival rate without statistical significance. However, histopathologic characteristics were markedly restored in NAC-treated irradiated rats. LC3B staining of rat buccal mucosa revealed that NAC treatment significantly decreased the number of radiation-induced autophagic cells. Further, NAC inhibited radiation-induced ROS generation and autophagy signaling. In vitro, NAC treatment significantly reduced the expression of NRF2, LC3B, p62, and Beclin-1 in keratinocytes compared with that after radiation treatment. CONCLUSION: NAC treatment significantly inhibited radiation-induced autophagy in keratinocytes and rat buccal mucosa and may be a potentially safe and effective option for the prevention of radiation-induced buccal mucosa damage.

Agrimonia pilosa Ledeb. Ameliorates Hyperglycemia and Hepatic Steatosis in Ovariectomized Rats Fed a High-Fat Diet.

Estrogen deficiency is associated with obesity, dyslipidemia, and increased insulin resistance in postmenopausal women. An efficient therapeutic agent prevents or improves postmenopausal conditions induced by estrogen deficiency. Here, we investigated the effects of aqueous Agrimonia pilosa Ledeb. extract on glucose and lipid metabolism in ovariectomized rats fed a high-fat diet (HFD). Female Sprague-Dawley rats were sham-operated or ovariectomized, and 3 weeks later were assigned to the following groups: sham-operated + HFD (S); ovariectomized + HFD (OVX); and ovariectomized + HFD with 0.5% A. pilosa aqueous extract (OVX + 0.5A) groups. Ovariectomy significantly increased body weight and dietary intake relative to the S group. However, A. pilosa treatment did not significantly affect weight gain or dietary intake. Blood triacylglycerol, total cholesterol, and low-density lipoprotein cholesterol levels tended to decrease in the A. pilosa-supplemented group. Blood glucose levels were significantly lower in the OVX + 0.5A group than those in the OVX group. Blood adiponectin and insulin concentrations increased significantly after A. pilosa treatment in the ovariectomized group. A. pilosa supplementation tended to decrease liver weights and prevented lipid accumulation. These effects correlated with reduced hepatic expression of lipogenesis-related genes (fatty acid synthase, acetyl-coenzyme A carboxylase alpha, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase). Therefore, A. pilosa may improve metabolic disorders in ovariectomized rats.

Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination.

Non-thermal plasma (NTP) has been studied as a novel therapeutic tool for cancer that does not damage healthy cells. In this study, we show that NTP-treated solutions (NTS) can induce death in various leukemia cells through mechanistic target of rapamycin (mTOR) ubiquitination. Previously, we manufactured and demonstrated the efficacy of NTS in solid cancers. NTS did not exhibit any deleterious side effects, such as acute death or weight loss in nude mice. In the present study, NTS induced cell death in myeloid leukemia cells, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We found that mTOR was downregulated in NTS-treated cells via the ubiquitin-proteasome system (UPS). We also identified 'really interesting new gene' finger protein 126 (RNF126) as a novel binding protein for mTOR through protein arrays and determined the role of E3 ligase in NTS-induced mTOR ubiquitination. NTS-derived reactive oxygen species (ROS) affected RNF126 expression and lysosomal dysfunction. These findings suggest that NTS has potential antileukemic effects through RNF126-mediated mTOR ubiquitination with no deleterious side effects. Thus, NTS may represent a new therapeutic method for chemotherapy-resistant leukemia.

Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model.

OBJECTIVE: Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive. DESIGN: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis. RESULTS: Composition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid ß plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice. CONCLUSION: These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.