An Enterobacteriaceae bloom in aging animals is restrained by the gut microbiome.

The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of Caenorhabditis elegans to highlight trends shared among individuals, we employed 16s rRNA gene sequencing, CFU counts and fluorescent imaging, identifying an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormaechei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its potential for exacerbating infection susceptibility. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.

Identification of marker compounds in fermented Benincasa hispida and validation of the method for its analysis.

Fermentation is a process that improves health functionality by inducing the production and increase of bioactive compounds. In this study, to standardize the fermentation process for Benincasa hispida, marker compounds that are increased or produced during fermentation were identified based on UPLC-QTOF-MS/MS. Analysis method verification and content analysis were conducted using HPLC-PDA. The marker compounds produced or increased in content were identified as 2-furoic acid, 2,3-dihydroxybenzoic acid, and rubinaphthin A by comparing their retention times, UV and MS spectra, and molecular formulas with those reported in previous studies. In addition, the increase in the content of the marker compounds by fermentation was confirmed, and the analytical method was validated by measuring its specificity, linearity, limit of detection and quantitation, precision, and accuracy. These results suggest that the developed fermentation process, marker compound identification, and verified analysis method can be applied to develop potential functional food ingredients from fermented B. hispida.

An Enterobacteriaceae bloom in aging animals is restrained by the gut microbiome.

The gut microbiome plays important roles in host function and health. Core microbiomes have been described for different species, and imbalances in their composition, known as dysbiosis, are associated with pathology. Changes in the gut microbiome and dysbiosis are common in aging, possibly due to multi-tissue deterioration, which includes metabolic shifts, dysregulated immunity, and disrupted epithelial barriers. However, the characteristics of these changes, as reported in different studies, are varied and sometimes conflicting. Using clonal populations of C. elegans to highlight trends shared among individuals, and employing NextGen sequencing, CFU counts and fluorescent imaging to characterize age-dependent changes in worms raised in different microbial environments, we identified an Enterobacteriaceae bloom as a common denominator in aging animals. Experiments using Enterobacter hormachei, a representative commensal, suggested that the Enterobacteriaceae bloom was facilitated by a decline in Sma/BMP immune signaling in aging animals and demonstrated its detrimental potential for increasing susceptibility to infection. However, such detrimental effects were context-dependent, mitigated by competition with commensal communities, highlighting the latter as determinants of healthy versus unhealthy aging, depending on their ability to restrain opportunistic pathobionts.

Electrochemically Activatable Liquid Organic Hydrogen Carriers and Their Applications.

Hydrogen has been chosen as an environmentally benign energy source to replace fossil-fuel-based energy systems. Since hydrogen is difficult to store and transport in its gaseous phase, thermochemical liquid organic hydrogen carriers (LOHCs) have been developed as one of the alternative technologies. However, the high temperature and pressure requirements of thermochemical LOHC systems result in huge energy waste and impracticality. This Perspective proposes electrochemical (EC)-LOHCs capable of more efficient, safer, and lower temperature and pressure hydrogen storage/utilization. To enable this technology, several EC-LOHC candidates such as isopropanol, phenolic compounds, and organic acids are described, and the latest research trends and design concepts of related homo/hetero-based electrocatalysts are discussed. In addition, we propose efficient fuel-cell-based systems that implement electrochemical (de)hydrogenation of EC-LOHCs and present prospects for relevant technologies.

The Estimation of Genetic Parameters for Longevity According to Lactation Period Using a Multiple Trait Animal Model in Korean Holstein Cows.

Longevity is closely related to the survival rate of dairy cattle and refers to the period during which the cow has economic value, from first calving to culling. The purpose of this study was to analyze the culling patterns and survival rates of Korean Holstein cows and evaluate genetic characteristics related to parity and longevity of each lactation by using the test day milk yield collected in South Korea. The performance data of the dairy cattle were collected from 2004 to 2019 by the Nonghyup Dairy Cattle Improvement Center. The collected 1,702,304 records were used as pedigree data through the Korea Animal Improvement Association. The lactation period was divided into early-lactation (0-90 days: L1.1, L2.1, and L3.1), mid-lactation (91-299 days: L1.2, L2.2, and L3.2), and late-lactation (300 days-next parity: L1.3, L2.3, and L3.3). The heritability of longevity for the first, second, and third parity was 0.020, 0.028, and 0.039, respectively. In all parities, the heritability in late-lactation was higher than that in early- and mid-lactation. Most genetic correlations for survival in the first parity were higher than those in the second and third parities. The results of this study may serve as a basis for developing a more accurate model for evaluating longevity traits in South Korea.

SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma.

Treatment of solid cancers with chimeric antigen receptor (CAR) T cells is plagued by the lack of ideal target antigens that are both absolutely tumor specific and homogeneously expressed. We show that multi-antigen prime-and-kill recognition circuits provide flexibility and precision to overcome these challenges in the context of glioblastoma. A synNotch receptor that recognizes a specific priming antigen, such as the heterogeneous but tumor-specific glioblastoma neoantigen epidermal growth factor receptor splice variant III (EGFRvIII) or the central nervous system (CNS) tissue-specific antigen myelin oligodendrocyte glycoprotein (MOG), can be used to locally induce expression of a CAR. This enables thorough but controlled tumor cell killing by targeting antigens that are homogeneous but not absolutely tumor specific. Moreover, synNotch-regulated CAR expression averts tonic signaling and exhaustion, maintaining a higher fraction of the T cells in a naïve/stem cell memory state. In immunodeficient mice bearing intracerebral patient-derived xenografts (PDXs) with heterogeneous expression of EGFRvIII, a single intravenous infusion of EGFRvIII synNotch-CAR T cells demonstrated higher antitumor efficacy and T cell durability than conventional constitutively expressed CAR T cells, without off-tumor killing. T cells transduced with a synNotch-CAR circuit primed by the CNS-specific antigen MOG also exhibited precise and potent control of intracerebral PDX without evidence of priming outside of the brain. In summary, by using circuits that integrate recognition of multiple imperfect but complementary antigens, we improve the specificity, completeness, and persistence of T cells directed against glioblastoma, providing a general recognition strategy applicable to other solid tumors.

Exploring Barriers to and Facilitators of Physical Activity among Korean American Women.

Physical inactivity is prevalent among ethnic minority women including Korean American (KA) women. We explored the barriers to and facilitators of physical activity (PA) and strategies to promote continued engagement in a PA program with a component of an online community. We conducted a qualitative descriptive study of 37 KA middle-aged women who used to be physically inactive and participated in an exit interview following postintervention visit. Using a thematic analysis approach to analyze the data, we found the individual, interpersonal, and neighborhood/community-level barriers to and facilitators of PA; social influence and social support-related themes were evident. Participants expressed benefit and interest in lifestyle modification using social media. Such program that reduces the barriers and reinforces the facilitators may be able to help motivate KA women to increase their PA.

Enhancement of Immune Activities of Mixtures with Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii.

The objective of the present study was to develop a concoction of natural products that could dramatically improve immune function with minimal possible side effects. Sasa quelpaertensis Nakai and Ficus erecta var. sieboldii are plants that are native to Jeju Island, Korea and are known to be rich in physiologically active substances. We prepared a mixture of different proportions and extraction conditions using two natural plants and determined their optimum mixing ratio and extraction method by assessing immune function-related biomarkers in RAW264.7 macrophages. Optimal extract (HR02/04(8:2)-W) was selected from in vitro experiments and its immunity-enhancing efficacy was evaluated in mice. After oral administration of extract to BALB/c mice for 2 weeks, nitric oxide production in the peritoneal exudate cells, natural killer cell cytotoxicity, cytokine expression in splenocytes, and total cell number of immune tissues and phenotype analysis were evaluated. Our results demonstrated that HR02/04(8:2)-W significantly enhanced the immune system by increasing natural killer cell activity, cytokine expression, and total number of cells in immune tissues. In conclusion, our study validates the role of HR02/04(8:2)-W in enhancing immunity and its potential development as a functional food.

Comparative Analysis of the Nutritional Components and Antioxidant Activities of Different Brassica juncea Cultivars.

The purpose of this study was to compare the nutritional components and antioxidant activities of two different cultivars of Brassica juncea (Dolsan, Yeosu, Korea (BJD) and (Jeongseon, Gangwon, Korea (BJJ)). We investigated the proximate composition (moisture, crude ash, crude protein and crude lipid), antioxidant activities (2,2-Diphenyl-2-picrylhydrazil (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP)), total phenol content, total flavonoid content and sinigrin content by high-performance liquid chromatography analysis. Our results show that the proximate compositions of BJD and BJJ were not significantly different. However, both the DPPH radical scavenging and FRAP activities of the BJJ extracts were higher than those of the BJD extracts. The total phenol contents of the BJD and BJJ extracts were 6.56 and 9.80 mg gallic acid equivalent/g, respectively. The total flavonoids content of the BJD and BJJ extracts were 20.92 and 34.81 mg rutin equivalent/g, respectively, whereas the sinigrin contents, one of the major compounds in BJD and BJJ extracts, were 16.16 mg/g and 11.73 mg/g, respectively. In this study, we confirmed that, by comparing BJJ and BJD, the sinigrin content of BJD was higher than that of BJJ, but the antioxidant activity and phenol content of BJD were superior to that of BJJ.

Anti-Obesity Effect of Extract from Nelumbo Nucifera L., Morus Alba L., and Raphanus Sativus Mixture in 3T3-L1 Adipocytes and C57BL/6J Obese Mice.

The antioxidant and anti-adipogenic activities of a mixture of Nelumbo nucifera L., Morus alba L., and Raphanus sativus were investigated and their anti-obesity activities were established in vitro and in vivo. Among the 26 different mixtures of extraction solvent and mixture ratios, ethanol extract mixture no. 1 (EM01) showed the highest antioxidant (α,α-Diphenyl-ß-picrylhydrazyl, total phenolic contents) and anti-adipogenic (Oil-Red O staining) activities. EM01 inhibited lipid accumulation in 3T3-L1 adipocytes compared to quercetin-3-O-glucuronide. Furthermore, body, liver, and adipose tissue weights decreased in the high-fat diet (HFD)-EM01 group compared to in the high-fat diet control group (HFD-CTL). EM01 lowered blood glucose levels elevated by the HFD. Lipid profiles were improved following EM01 treatment. Serum adiponectin significantly increased, while leptin, insulin growth factor-1, non-esterified fatty acid, and glucose significantly decreased in the HFD-EM01 group. Adipogenesis and lipogenesis-related genes were suppressed, while fat oxidation-related genes increased following EM01 administration. Thus, EM01 may be a natural anti-obesity agent.

Antidiabetic effect of an extract of nutricultured Brassica napus containing vanadium from a Jeju water concentrate.

The purpose of this study was to determine the antidiabetic effect of an extract of nutricultured Brassica napus containing vanadium (BECV). The BECV was prepared following nutriculture of B. napus with a Jeju water vanadium concentrate for 7 day. The BECV was administered to db/db mice for 8 weeks at different dosages (0.028, 0.14, and 0.7 µg/kg; as vanadium concentration in BECV). After 8 weeks, the BECV results showed mouse blood glucose concentrations to significantly decrease, in a dose-dependent manner, compared with the results for control mice. In addition, the concentrations of triglyceride, total cholesterol, and glycated hemoglobin were significantly lower after 8 weeks of administration of 0.7 µg/kg BECV. Therefore, the BECV may have protective effects against type 2 diabetes.

TGFß/BMP immune signaling affects abundance and function of C. elegans gut commensals.

The gut microbiota contributes to host health and fitness, and imbalances in its composition are associated with pathology. However, what shapes microbiota composition is not clear, in particular the role of genetic factors. Previous work in Caenorhabditis elegans defined a characteristic worm gut microbiota significantly influenced by host genetics. The current work explores the role of central regulators of host immunity and stress resistance, employing qPCR and CFU counts to measure abundance of core microbiota taxa in mutants raised on synthetic communities of previously-isolated worm gut commensals. This revealed a bloom, specifically of Enterobacter species, in immune-compromised TGFß/BMP mutants. Imaging of fluorescently labeled Enterobacter showed that TGFß/BMP-exerted control operated primarily in the anterior gut and depended on multi-tissue contributions. Enterobacter commensals are common in the worm gut, contributing to infection resistance. However, disruption of TGFß/BMP signaling turned a normally beneficial Enterobacter commensal to pathogenic. These results demonstrate specificity in gene-microbe interactions underlying gut microbial homeostasis and highlight the pathogenic potential of their disruption.

Toxicological Evaluation of Brassica napus Extract Containing Vanadium, Nutricultured in Jeju Water.

This study evaluated the mutagenicity and acute toxicity of the juice extract of nutricultured Brassica napus containing vanadium (BECV). The BECV was prepared by nutriculture for 7 days in Jeju water containing vanadium. The mutagenic effects of BECV were investigated using the bacterial reverse mutation test, chromosome aberration test, and micronucleus test. Based on the results of the mutagenicity test, we propose that BECV is not a mutagenicity-inducing agent. In the acute oral toxicity study, male and female Sprague-Dawley rats were administered a single limiting dose of 0.014, 0.14, or 1.4 µg BECV/kg body weight; the rats were then observed for 7 days. No acute lethal effect was observed at the maximal dose of 1.4 µg BECV/kg body weight. In the subacute study, male and female rats were administered once daily, by oral gavage, a dose of 0.028, 0.14, and 0.7 µg/kg body weight of BECV for 28 days. No significant toxicity was observed not only hematological, biochemical, and pathological parameters but also the body and organ weights when compared to controls. The level of BECV with no observed adverse effects in male and female rats was 0.7 µg/kg body weight (concentration of vanadium in BECV) in the subacute toxicity study.

Suppressive Effect of the n-Hexane Extract of Litsea japonica Fruit Flesh on Monosodium-Iodoacetate-Induced Osteoarthritis in Rats.

We examined the antiosteoarthritic effect of the n-hexane extract of Litsea japonica fruit flesh (LJF-HE) in a rat model of monosodium-iodoacetate- (MIA-) induced osteoarthritis. LJF-HE significantly reduced the difference in weight-bearing capabilities of the hind paws between healthy and MIA-treated rats. Histological examination of the knee joints indicated that LJF-HE suppressed cartilage and bone destruction. Additionally, there were decreases in the expression of matrix metalloproteinase-2 and metalloproteinase-9 and cyclooxygenase-2 in the joints. The serum levels of deoxypyridinoline (DPD) and osteocalcin, which are markers of bone metabolism, also decreased. Furthermore, LJF-HE significantly suppressed infiltration of inflammatory cells into the synovium and inhibited the expression of proinflammatory cytokines such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1, and IL-6 in the joints and serum. The serum levels of leukotriene B4 and lipoxygenase were also significantly lowered by LJF-HE. Finally, LJF-HE inhibited the production of nitric oxide, prostaglandin E2, IL-6, and TNF-α in lipopolysaccharide-activated macrophages, which might be associated with inhibited phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Our data suggest that LJF-HE has an anti-inflammatory effect and may have potential as an antiosteoarthritic agent.

Anti-Photoaging Effect of Jeju Putgyul (Unripe Citrus) Extracts on Human Dermal Fibroblasts and Ultraviolet B-induced Hairless Mouse Skin.

Ultraviolet (UV) radiation stimulates the expression of matrix metalloproteinases (MMPs) and inflammatory cytokines. These signaling pathways participate in the degradation of the extracellular matrix and induce inflammatory responses that lead to photoaging. This study evaluated the antioxidant activity and the effect on MMPs and procollagen of putgyul extract in vitro. The anti-photoaging activity of putgyul extracts was estimated in vivo using hairless mice (HR-1). The putgyul extracts reduced MMP-1 production and increased the content of procollagen type I carboxy-terminal peptide in human dermal fibroblasts. Ultravilot-B (UVB)-induced expression of inflammatory cytokines and MMPs was detected in mice, and putgyul extracts suppressed the expression. These results suggest that putgyul extract inhibits photoaging by inhibiting the expression of MMPs that degrade collagen and inhibiting cytokines that induce inflammatory responses. The mouse model also demonstrated that oral administration of putgyul extracts decreased wrinkle depth, epidermal thickness, collagen degradation, and trans-epidermal water loss, and increased ß-glucosidase activity on UVB exposed skin. Putgyul extract protects against UVB-induced damage of skin and could be valuable in the prevention of photoaging.

Antioxidant and anti-ageing activities of citrus-based juice mixture.

The production of excessive reactive oxygen species by exposure to oxidative stress and solar radiation are primary factors in skin damage. We examined the effects of a citrus-based juice mixture and its bioactive compounds on antioxidant and anti-ageing activities in human dermal fibroblasts and hairless mice via the regulation of antioxidant enzymes and the mitogen-activated protein kinase pathway. The citrus-based juice mixture reduced H2O2-induced cell damage and intracellular reactive oxygen species production in human dermal fibroblasts. Citrus-based juice mixture pretreatment suppressed the activation of the H2O2-mediated mitogen-activated protein kinase pathway by activating the expression of activator protein 1 and matrix metalloproteinases. Moreover, it increased the expression levels of antioxidant enzymes such as glutathione reductase, catalase and manganese superoxide dismutase. In addition, oral administration of the citrus-based juice mixture decreased skin thickness and wrinkle formation and increased collagen content on an ultraviolet light B-exposed hairless mouse. These results indicate that the citrus-based juice mixture is a potentially healthy beverage for the prevention of oxidative stress-induced premature skin ageing.

Acute and subchronic (28 days) oral toxicity studies of Codonopsis lanceolata extract in Sprague-Dawley rats.

Codonopsis lanceolata is a perennial plant that has been used as a food and in traditional medicine for the treatment of cough, bronchitis, and inflammation in East Asia including Korea, Japan, and China. However, information regarding its toxicity is limited. Therefore, we performed a safety evaluation of aqueous C. lanceolata root extract (CLE) in Sprague-Dawley rats. Assessment of acute toxicity revealed that CLE did not influence mortality, clinical appearance, body weight gain, or necropsy findings at a dose of 5000 mg/kg body weight. In the subchronic oral toxicity, data revealed that several significant alteration in food consumption, water consumption, protein excretion, WBCs levels, TGs, BUN levels, and the absolute and relative weights in the liver, spleen and lungs. However, these changes were transient and were not considered treatment related because they showed no apparent dose dependent. These results suggest that CLE (1250, 2500, and 5000 mg/kg body weight/day) administered orally does not cause acute or subchronic toxicity to male or female rats. The 50% lethal dose (LD50) of CLE was determined to be greater than 5000 mg/kg.

Codonopsis lanceolata extract prevents diet-induced obesity in C57BL/6 mice.

Codonopsis lanceolata extract (CLE) has been used in traditional medicine in the Asian-Pacific region for the treatment of bronchitis, cough, and inflammation. However, it is still unclear whether obesity in mice can be altered by diet supplementation with CLE. To investigate whether CLE could have preventative effects on high fat diet (HFD)-induced obesity, male C57BL/6 mice were placed on either a normal chow diet, 60% HFD, or a HFD supplemented with CLE (60, 180, and 360 mg/kg/day) for 12 weeks. CLE decreased body weight and subcutaneous and visceral fat weights in HFD-induced obese mice. CLE group mice showed lower fat accumulation and a smaller adipocyte area in the adipose tissue compared with the HFD group mice. CLE group mice exhibited lower serum levels of triglycerides, total cholesterol, low density lipoprotein (LDL), glucose, and insulin compared with the HFD group mice. In addition, CLE decreased liver weight and lowered the increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in HFD-induced obese mice. These results indicate that CLE can inhibit the development of diet-induced obesity and hyperlipidemia in C57BL/6 mice.

Assessment and comparison of the antioxidant activities and nitrite scavenging activity of commonly consumed beverages in Korea.

In this study, the antioxidant potential of commercial beverages against a variety of radicals was determined using various antioxidant activity analytical methods. The physicochemical properties (pH value and °Brix), total phenolic content and antioxidant activities were assessed. Our results showed that the pH value and sugar content (°Brix) of commonly consumed beverages ranged from 2.4 to 3.9 and from 3.8 to 18.5, respectively. The DPPH radical scavenging activity and nitrite scavenging ability were highest in No. 45 vitamin beverage (87.5% and 86.0%, respectively). However, no clear correlation appeared between the total phenolic content and the DPPH radical scavenging activity (R=0.2565). The total phenolic content and oxygen radical absorbance capacity (ORAC) values were highest in No. 55 pomegranate beverage (183.3 mg GAE/100 mL and 1824.4 µM TE/mL, respectively). In particular, a high correlation was shown between the total phenolic content and the ORAC value (R=0.7954). Based on the results of various antioxidant activity methods, the greatest preventative antioxidant capacity of consumed beverages in Korea was found in No. 55 pomegranate. These results will enable further research on the daily phenolic compound intake as well as on the development of healthy beverages.

Antioxidant activity and anti-adipogenic effects of wild herbs mainly cultivated in Korea.

Wild herbs, which are edible plants that grow in mountainous areas, have diverse biological effects such as anti-obesity and anti-cancer activities. The aim of this study was to evaluate the total phenolic and flavonoid contents as well as the antioxidant activity of methanol extracts of Aster scaber, Ligularia fischeri, Kalopanax pictus, Codonopsis lanceolata, and Cirsium setidens and to assess their effects on lipid accumulation and reactive oxygen species (ROS) production during adipogenesis of 3T3-L1 cells. The results revealed that among the five studied wild herb extracts, Ligularia fischeri showed the highest total phenolic contents (215.8 ± 14.2 mg GAE/g) and Aster scaber showed the highest total flavonoid content (103.9 ± 3.4 mg RE/g). Furthermore, Aster scaber and Ligularia fischeri extracts showed higher antioxidant activity than the other wild herbs. Regarding anti-adipogenic activity, the Cirsium setidens extract significantly inhibited lipid accumulation (~80%) and ROS production (~50%) during adipogenesis of 3T3-L1 cells compared with control cells. These results suggest that wild herbs could be used for the development of functional foods as well as health promoting and pharmaceutical agents.