Broccoli Cultivated with Deep Sea Water Mineral Fertilizer Enhances Anti-Cancer and Anti-Inflammatory Effects of AOM/DSS-Induced Colorectal Cancer in C57BL/6N Mice.

This study aimed to determine the alleviating effect of broccoli grown with deep sea water mineral (DSWM) fertilizer extracted from deep sea water on the development of colorectal cancer in C57BL/6N mice treated with AOM/DSS. Naturaldream Fertilizer Broccoli (NFB) cultured with deep sea water minerals (DSWM) showed a higher antioxidant effect and mineral content. In addition, orally administered NFB, showed a level of recovery in the colon and spleen tissues of mice compared with those in normal mice through hematoxylin and eosin (H&E) staining. Orally administered NFB showed the inhibition of the expression of inflammatory cytokine factors IL-1ß, IL-6, TNF, IFN-γ, and IL-12 while increasing the expression of IL-10. Furthermore, the expression of inflammatory cytokines and NF-κB in the liver tissue was inhibited, and that of inflammatory enzymes, such as COX-2 and iNOS, was reduced. In the colon tissue, the expression of p53 and p21 associated with cell cycle arrest increased, and that of Bcl-2 associated with apoptosis decreased. Additionally, the expression of Bax, Bad, Bim, Bak, caspase 9, and caspase 3 increased, indicating enhanced activation of apoptosis-related factors. These results demonstrate that oral administration of broccoli cultivated using DSWM significantly restores spleen and colon tissues and simultaneously inhibits the NF-κB pathway while significantly decreasing cytokine expression. Moreover, by inducing cell cycle arrest and activating cell apoptosis, they also suggest alleviating AOM/DSS-induced colon cancer symptoms in C57BL/6N mice.

Estrogen-Related Receptor γ Maintains Pancreatic Acinar Cell Function and Identity by Regulating Cellular Metabolism.

BACKGROUND & AIMS: Mitochondrial dysfunction disrupts the synthesis and secretion of digestive enzymes in pancreatic acinar cells and plays a primary role in the etiology of exocrine pancreas disorders. However, the transcriptional mechanisms that regulate mitochondrial function to support acinar cell physiology are poorly understood. Here, we aim to elucidate the function of estrogen-related receptor γ (ERRγ) in pancreatic acinar cell mitochondrial homeostasis and energy production. METHODS: Two models of ERRγ inhibition, GSK5182-treated wild-type mice and ERRγ conditional knock-out (cKO) mice, were established to investigate ERRγ function in the exocrine pancreas. To identify the functional role of ERRγ in pancreatic acinar cells, we performed histologic and transcriptome analysis with the pancreas isolated from ERRγ cKO mice. To determine the relevance of these findings for human disease, we analyzed transcriptome data from multiple independent human cohorts and conducted genetic association studies for ESRRG variants in 2 distinct human pancreatitis cohorts. RESULTS: Blocking ERRγ function in mice by genetic deletion or inverse agonist treatment results in striking pancreatitis-like phenotypes accompanied by inflammation, fibrosis, and cell death. Mechanistically, loss of ERRγ in primary acini abrogates messenger RNA expression and protein levels of mitochondrial oxidative phosphorylation complex genes, resulting in defective acinar cell energetics. Mitochondrial dysfunction due to ERRγ deletion further triggers autophagy dysfunction, endoplasmic reticulum stress, and production of reactive oxygen species, ultimately leading to cell death. Interestingly, ERRγ-deficient acinar cells that escape cell death acquire ductal cell characteristics, indicating a role for ERRγ in acinar-to-ductal metaplasia. Consistent with our findings in ERRγ cKO mice, ERRγ expression was significantly reduced in patients with chronic pancreatitis compared with normal subjects. Furthermore, candidate locus region genetic association studies revealed multiple single nucleotide variants for ERRγ that are associated with chronic pancreatitis. CONCLUSIONS: Collectively, our findings highlight an essential role for ERRγ in maintaining the transcriptional program that supports acinar cell mitochondrial function and organellar homeostasis and provide a novel molecular link between ERRγ and exocrine pancreas disorders.

Identification of New Non-BBB Permeable Tryptophan Hydroxylase Inhibitors for Treating Obesity and Fatty Liver Disease.

Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation.

Lactobacillus plantarum YS2 (yak yogurt Lactobacillus) exhibited an activity to attenuate activated carbon-induced constipation in male Kunming mice.

The present study investigated the effects of Lactobacillus plantarum YS2 (LP-YS2) that was isolated from yak yogurt on activated carbon-induced constipation in Kunming (KM) mice. The KM mice were orally administered LP-YS2 and reference strain Lactobacillus delbrueckii ssp. bulgaricus. Administration of LP-YS2 [1.0 × 109 cfu/kg of body weight (BW)] promoted gastrointestinal peristalsis and reduced the first black stool defecation time (129 min), which clearly defines attenuation of the voiding difficulty in mice with constipation. The LP-YS2 treatment also increased the serum level of motilin (MTL; 178.2 pg/mL), gastrin (69.4 pg/mL), acetylcholine (Ach; 30.1 pg/mL), substance P (SP; 57.6 pg/mL), and vasoactive intestinal peptide (VIP; 53.2 pg/mL) and reduced the somatostatin (SS, 32.6 pg/mL) levels compared with the L. delbrueckii ssp. bulgaricus treatment (MTL, 139.7 pg/mL; gastrin, 43.1 pg/mL; Ach, 15.9 pg/mL; SP, 43.6 pg/mL; VIP, 32.3 pg/mL; SS, 55.1 pg/mL) and the control (MTL, 105.3 pg/mL; gastrin, 26.7 pg/mL; Ach, 9.7 pg/mL; SP, 30.2 pg/mL; VIP, 21.0 pg/mL; SS, 70.5 pg/mL). The LP-YS2 treatment significantly increased the colonic mRNA and protein expression of c-Kit (CD117, cluster of differentiation 117; 2.87 times mRNA expression of the control group), stem cell factor (30.40 times mRNA expression of the control group), and glial cell-derived neurotrophic factor (29.97 times mRNA expression of the control group) in mice with constipation. In addition, LP-YS2 reduced the expression of transient receptor potential vanilloid 1 (0.42 times mRNA expression of the control group) and nitric oxide synthase (0.49 times mRNA expression of the control group) in constipated mice. These results demonstrate that LP-YS2 was able to attenuate the activated carbon-induced constipation in KM mice.

Preventive effect of Lactobacillus plantarum KSFY02 isolated from naturally fermented yogurt from Xinjiang, China, on d-galactose-induced oxidative aging in mice.

Yogurt from Xinjiang, China, is a traditional and naturally fermented food, and abundant microorganisms are produced during its fermentation process. In this study, we carried out in vivo animal experiments to explore the effect of a newly isolated lactic acid bacterial strain, Lactobacillus plantarum KSFY02 (LP-KSFY02), on oxidative aging. We used d-galactose to induce oxidative aging in mice and analyzed the serum and tissues of those mice using molecular biology detection methods. The results showed that LP-KSFY02 could inhibit the decreases in the thymic, cerebral, cardiac, liver, spleen, and kidney indices of mice caused by oxidative aging. The LP-KSFY02 strain increased activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) and reduced levels of nitric oxide (NO) and malondialdehyde in the serum, liver, and spleen of the oxidative aging mice. Pathological observation demonstrated that LP-KSFY02 alleviated damage to the liver and spleen of oxidative aging mice. Quantitative PCR showed that LP-KSFY02 effectively upregulated mRNA expression of neuronal nitric oxide synthase (Nos1), endothelial nitric oxide synthase (Nos3), copper/zinc superoxide dismutase (Sod1), manganese superoxide dismutase (Sod2), catalase (Cat), heme oxygenase-1 (Hmox1), nuclear factor erythroid 2 related factor 2 (Nfe2l2), γ-glutamylcysteine synthetase (Gclm), and quinone oxidoreductase 1 (Nqo1) in mouse liver and spleen and downregulated expression of inducible nitric oxide synthase (Nos2). Western blot analysis revealed that LP-KSFY02 effectively upregulated protein expression of SOD1, SOD2, CAT, GSH1, and GSH2 in mouse liver and spleen tissues. Therefore, LP-KSFY02 can effectively prevent d-galactose-induced oxidative aging in mice. Its efficacy was superior to that of Lactobacillus delbrueckii ssp. bulgaricus (LDSB) and vitamin C, which are commonly used in the medical field as antioxidants. Thus, LP-KSFY02 is a high-quality strain with probiotic potential.

Comparison of Antioxidative Effects of Insect Tea and Its Raw Tea (Kuding Tea) Polyphenols in Kunming Mice.

Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge precipitation. The present study was designed to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by gavage. After determination in serum, liver and spleen, ITP-treated mice showed higher superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) activities and lower nitric oxide (NO), malonaldehyde (MDA) activities than VC-treated mice, KTP-treated mice and untreated oxidation mice (control group). By H&E section observation, the mice induced by d-galactose-induced oxidation showed more changes than normal mice, and oxidative damage appeared in liver and spleen tissues; ITP, VC and KTP improved oxidative damage of liver and spleen tissues, and the effects of ITP were better than VC and KTP. Using quantitative polymerase chain reaction (qPCR) and western blot experiments, it was observed that ITP could increase the mRNA and protein expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese superoxide dismutase (Mn-SOD), cupro/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor erythroid 2 related factor 2 (Nrf2), gamma glutamylcysteine synthetase (γ-GCS), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and reduce inducible nitric oxide synthase (iNOS) expression in liver and spleen tissues compared to the control group. These effects were stronger than for VC and KTP. Both ITP and KTP had good antioxidative effects, and after the transformation of insects, the effects of ITP were better than that of KTP and even better than VC. Thus, ITP can be used as an antioxidant and anti-ageing functional food.

Lactobacillus casei Strain Shirota Enhances the In Vitro Antiproliferative Effect of Geniposide in Human Oral Squamous Carcinoma HSC-3 Cells.

This study investigated the enhanced antiproliferative effect of Lactobacillus casei strain Shirota (LcS) on geniposide actions in human oral squamous carcinoma HSC-3 cells. An MTT assay, flow cytometry, qPCR assay, western blot and HPLC were used for this study. The concentration of 1.0 × 106 CFU/mL of LcS had no effect on the HOK normal oral epithelial cells and HSC-3 cancer cells. The 25 and 50 µg/mL geniposide concentrations also had no impact on HOK normal oral epithelial cells, but they had remarkable inhibitory effects on the growth of HSC-3 cancer cells, which are enhanced in the presence of LcS. By the flow cytometry assay, the LcS-geniposide-H (1.0 × 106 CFU/mL LcS and 50 µg/mL geniposide)-treated HSC-3 cancer cells had the largest number of cells undergoing apoptosis compared to cells treated with other combinationsand obviously more than cells treated with only geniposide-H (50 µg/mL geniposide). Geniposide-H could increase the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, p53, p21, IκB-α, Fas, FasL, TIMP-1, and TIMP-2 as well as decrease those of Bcl-2, Bcl-xL, HIAP-1, HIAP-2, NF-κB, COX-2, iNOS, MMP-2, and MMP-9 compared to other groups of cells, and LcS further enhanced these changes, with results that are greater than for the cells treated with only a high concentration of geniposide. The results of this study show thatLcS enhanced the antiproliferative effect of geniposide in HSC-3 cancer cells.

Protective effects of Lactobacillus rhamnosus GG against dyslipidemia in high-fat diet-induced obese mice.

Recent reports suggest that gut microbiota can be a major determinant of dyslipidemia and non-alcoholic fatty liver disease (NAFLD) and its modulation by treating probiotics is a valid strategy to exert a protective effect. In this study, high-fat diet (HFD)-fed mice were orally administrated with Lactobacillus rhamnosus GG (LGG) for 13 weeks. Significant reductions in the weights of the liver, mesenteric and subcutaneous adipose tissues were observed in LGG-treated HFD-fed mice compared to LGG-non-treated controls. The serum levels of triglyceride and cholesterol were also significantly reduced in LGG-treated mice. Gut microbial composition analysis showed that shifts in the diversity of dominant gut bacteria were caused by HFD and restored by LGG treatment. A remarkable decrease of hepatic fat content was also observed in LGG-treated mice, accompanied by downregulated expressions of lipogenic and pro-inflammatory genes in the liver. LGG-treated mice had lower expression levels of genes involved in cholesterol synthesis, but conversely, higher expression levels of cholesterol efflux-related genes compared to LGG-non-treated controls. The cholesterol-lowering effect of LGG was also found to be mediated by suppression of FXR and FGF15 signaling, resulting in the upregulation of hepatic CYP7A1. Our findings confirm a therapeutic potential of probiotics for ameliorating dyslipidemia and NAFLD.

Effects of Glycated Whey Protein Concentrate on Pro-inflammatory Cytokine Expression and Phagocytic Activity in RAW264.7 Macrophages.

The aim of this study was to determine the stimulatory effects of Maillard reaction, a non-enzymatic browning reaction on the expression of pro-inflammatory cytokines and phagocytic activity induced by whey protein concentrate (WPC). Glycated WPC (G-WPC) was prepared by a reaction between WPC and the lactose it contained. The fluorescence intensity of G-WPC dramatically increased after one day, and high molecular weight complexes formed via the Maillard reaction were also observed in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles. G-WPC demonstrated immunomodulatory effects, including stimulation of increased nitric oxide production and cytokine expressions (i.e., tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6), compared to WPC. Furthermore, the phagocytic activity of RAW264.7 cells was significantly increased upon treatment with G-WPC, compared to WPC. Therefore, we suggest that G-WPC can be utilized as an improved dietary source for providing immune modulating activity.

Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice.

Although recent studies have reported that Lactobacillus rhamnosus GG (LGG), the most extensively studied probiotic strain, exerts an anti-hyperglycemic effect on several rodent models, the underlying mechanism remains unclear. In this study, twenty male C57BL/KsJ-db/db (db/db) mice were divided into 2 groups, LGG-treated and control group, which received a daily dose of LGG (1 × 10(8) CFU per mouse) and PBS orally for 4 weeks, respectively. We observed that glucose tolerance was significantly improved in LGG-treated db/db mice. Insulin-stimulated Akt phosphorylation and GLUT4 translocation were higher in skeletal muscle of LGG-treated mice relative to their controls. It was also observed that LGG treatment caused significant reductions in endoplasmic reticulum (ER) stress in skeletal muscle and M1-like macrophage activation in white adipose tissues. Our results indicate that the anti-diabetic effect of LGG in db/db mice is associated with alleviated ER stress and suppressed macrophage activation, resulting in enhanced insulin sensitivity. These findings suggest a therapeutic potential of probiotics for prevention and treatment of type 2 diabetes.

Doenjang prepared with mixed starter cultures attenuates azoxymethane and dextran sulfate sodium-induced colitis-associated colon carcinogenesis in mice.

BACKGROUNDS: Doenjang is traditional Korean fermented soybean paste and widely known for its various health benefits including anticancer effect. In this study, we manufactured doenjang with the grain-type meju using probiotic mixed starter cultures of Aspegillus oryzae, Bacillus subtilis-SKm, and Lactococcus lactis-GAm to improve the qualities and beneficial properties of doenjang. MATERIALS AND METHODS: The inhibitory effects of the doenjang prepared with the grain-type meju using mixed starter cultures were investigated in azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced colon carcinogenesis mice model. AOM and DSS colon carcinogenesis was induced in female C57BL/6 mice, and doenjang was orally administered for 4 weeks. Body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically evaluated. The serum levels of proinflammatory cytokines as well as the expression of inflammation- and apoptosis-related genes in colonic tissue were also analyzed. RESULTS: Administration of the doenjang using probiotic mixed starter cultures ameliorated the symptoms of colon cancer, and reduced the incidence of neoplasia, and reduced the levels of serum proinflammatory cytokines such as interleukin-6, and tumor necrosis factor-α and inducible nitric oxide synthase and cycloooxygenase-2 expression levels in colonic tissue. In addition, it increased Bax and reduced Bcl-2 expression levels and increased p21 and p53 expression in the colonic tissues. CONCLUSION: These findings indicate that the doenjang attenuated colon carcinogenesis induced by AOM and DSS by ameliorating the symptoms of colon cancer, reducing the occurrence of neoplasia, regulating proinflammatory cytokine levels, and controlling the expressions of inflammation- and apoptosis-related genes in the colonic tissue.

Supplementation of Heat-Treated Lactiplantibacillus plantarum nF1 Changes the Production of Short-Chain Fatty Acids in Healthy Infants.

Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

Effect of Heat-Treated Lactiplantibacillus plantarum nF1 on the Immune System Including Natural Killer Cell Activity: A Randomized, Placebo-Controlled, Double-Blind Study.

Heat-treated Lactiplantibacillus plantarum nF1 (HT-nF1) increases immune cell activation and the production of various immunomodulators (e.g., interleukin (IL)-12) as well as immunoglobulin (Ig) G, which plays an important role in humoral immunity, and IgA, which activates mucosal immunity. To determine the effect of HT-nF1 intake on improving immune function, a randomized, double-blind, placebo-controlled study was conducted on 100 subjects with normal white blood cell counts. The HT-nF1 group was administered capsules containing 5 × 1011 cells of HT-nF1 once a day for 8 weeks. After 8 weeks of HT-nF1 intake, significant changes in IL-12 were observed in the HT-nF1 group (p = 0.045). In particular, the change in natural killer (NK) cell activity significantly increased in subjects with low secretory (s) IgA (≤49.61 µg/mL) and low NK activity (E:T = 10:1) (≤3.59%). These results suggest that HT-nF1 has no safety issues and improves the innate immune function by regulating T helper (Th)1-related immune factors. Therefore, we confirmed that HT-nF1 not only has a positive effect on regulating the body's immunity, but it is also a safe material for the human body, which confirms its potential as a functional health food ingredient.

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Lactobacillus rhamnosus GG improves insulin sensitivity and reduces adiposity in high-fat diet-fed mice through enhancement of adiponectin production.

Recently, a probiotic Lactobacillus rhamnosus GG (LGG) has shown several beneficial effects, including improved insulin sensitivity. To clarify the mechanism underlying the insulin-sensitizing effect of LGG, mice were orally administrated with LGG for 13 weeks, and their body weight, insulin sensitivity, and expression of genes related to glucose and lipid metabolism were examined. LGG-treated mice showed attenuated weight gain and enhanced insulin sensitivity in high fat diet group, while no change was observed in normal diet-fed group. The expression of fatty acid oxidative genes in the liver was increased and gluconeogenic genes were decreased. GLUT4 mRNA expression in skeletal muscle and adiponectin production in adipose tissue were significantly increased. This was corroborated with the increased activation of AMPK in skeletal muscle and adipose tissue. Taken together, these results indicate that LGG treatment improves insulin sensitivity and reduces lipid accumulation by stimulating adiponectin secretion and consequent activation of AMPK.

The probiotic Lactobacillus rhamnosus BFE5264 and Lactobacillus plantarum NR74 promote cholesterol efflux and suppress inflammation in THP-1 cells.

BACKGROUND: The balance between the rate of cholesterol uptake/accumulation and the rate of cholesterol efflux is reflected in the amount of lipid accumulation in macrophages. Based upon the fact that liver X receptors (LXRs) play a role in cholesterol efflux, we studied the effects of probiotics on cholesterol efflux and anti-inflammatory action in macrophages. We confirmed changes in LXR expression by treatment of LXR-transfected CHO-K1 cells with lactic acid bacteria (LAB), and co-cultured THP-1 cells with LAB to investigate changes in cholesterol efflux and inflammation. RESULTS: The experiment with CHO-K1 cells showed upregulation of LXR-ß by LAB. Treatment of THP-1 cells with LAB promoted LXR expression in THP-1, which eventually led to significant upregulation of ABCA1 and ABCG1 expression. The treatment with live LAB also significantly promoted cholesterol efflux. LAB suppressed expression of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, which resulted from activation of LXR. CONCLUSION: Our study shows that Lactobacillus rhamnosus BFE5264 and Lactobacillus plantarum NR74 activated LXR and induced cholesterol efflux by promoting expression of ABCA1 and ABCG1. Both strains also suppressed proinflammatory cytokines including IL-1ß and TNF-α. This study could account for the observation that LAB may block foam cell formation by cholesterol efflux and immune modulation.

Anticancer Effects of Washed-Dehydrated Solar Salt Doenjang on Colon Cancer-Induced C57BL/6 Mice.

This study researched the mineral composition of Korean washed-dehydrated solar salt (WDS) without bittern. It also evaluated the anticancer effects of doenjang (WDSD) prepared using WDS on azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer in C57BL/6 mice. The mineral composition of WDS showed lower Mg (11.71 ± 1.89 g/kg) and S (9.77 ± 2.88 g/kg) contents, and it was confirmed that mice in the WDSD group (AOM/DSS+WDSD) displayed significantly lower weight loss, colon length reduction, and tumor formation compared with the control (Con) group. In addition, pathologically, it was confirmed that the extent of epithelial cell damage and inflammation in the colon tissue of the WDSD group was restored to a state similar to that of the Nor group. Besides, WDSD regulated the protein expression of apoptosis (Bcl-2-associated X protein [Bax], B cell lymphoma-2 [Bcl-2], B cell lymphoma-extra large [Bcl-xL], and caspase 9, caspase 3), and p53, p21, and proinflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α), thereby inducing the apoptosis and cell cycle arrest of cancer cells and suppressing inflammation. In addition, the intestinal microbiota of the mice treated with WDSD were more diverse, with an abundance of Bifidobacterium, a lactic acid bacterium beneficial to colon health, was also a greater presence of Faecalibaculum, which showed antitumor effects. These results indicate that solar salts and their different processing methods affect their functional health-promoting properties. In addition, the inhibitory effect on colon cancer was further enhanced when doenjang was prepared with WDS with low Mg and S content.

Catechin with Lactic Acid Bacteria Starters Enhances the Antiobesity Effect of Kimchi.

The antiobesity effects of kimchi with catechin and lactic acid bacteria as starters were studied in C57BL/6 mice with high-fat diet (HFD)-induced obesity. We prepared four types of kimchi: commercial kimchi, standard kimchi, green tea functional kimchi, and catechin functional kimchi (CFK). Body weight and weight of adipose tissue were significantly lower in the kimchi-treated groups than in the HFD and Salt (HFD +1.5% NaCl) groups. In addition, in the CFK group, the serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol were significantly lower and those of high-density lipoprotein cholesterol were markedly higher than the corresponding levels in the HFD and Salt groups. Moreover, CFK reduced fat cells and crown-like structures in the liver and epididymal fat tissues. The protein expression of adipo/lipogenesis-related genes in the liver and epididymal fat tissues was significantly lower (1.90-7.48-fold) in the CFK group than in the HFD and Salt groups, concurrent with upregulation of lipolysis-related genes (1.71-3.38-fold) and downregulation of inflammation-related genes (3.17-5.06-fold) in epididymal fat tissues. In addition, CFK modulated the gut microbiomes of obese mice by increasing the abundance of Bacteroidetes (7.61%), while in contrast, Firmicutes (82.21%) decreased. In addition, the presence of the Erysipelotrichaceae (8.37%) family in the CFK group decreased, while the number of beneficial bacteria of the families, Akkermansiaceae (6.74%), Lachnospiraceae (14.95%), and Lactobacillaceae (38.41%), increased. Thus, CFK exhibited an antiobesity effect through its modulation of lipid metabolism and the microbiome.

Effects of Pear Extracts on Microbiome and Immunocytokines to Alleviate Air Pollution-Related Respiratory Hypersensitivity.

Pears are ancient functional foods for modern times. Particularly, Korean pears (Pyrus pyrifolia cv.) have been used as folk medicine for respiratory diseases and have strong potential for the treatment of hazardous aerosol-related diseases. Thus, the effects of pear ethanol extracts on air pollution-related respiratory hypersensitivity were studied by toxicokinetics, pro-inflammatory cytokines, and microbiomics in preclinical and randomized double-blind clinical studies. The mild-asthma subjects, who lived in the same city, Seoul, Korea, were separated into the placebo and the treatment (pear extracts, as brix 55; arbutin 5.01 mg and chlorogenic acid 0.18 mg/3 mL per day) groups for 4 weeks (n = 20). As results, there were positive associations between urinary 2-naphthol (NT) or 1-hydroxypyrene (OHP), exposure biomarkers for polyaromatic hydrocarbons in PM2.5, and pro-inflammatory cytokines, interleukin (IL)-4 or IgE, respectively, in the human subjects. The pear extracts somewhat reduced 2-NT and 1-OHP levels. The proportions of fiber-degrading bacteria that stimulate growth of beneficial microflora for immune defense, that is, Bifidobacterium and Eubacterium, were significantly higher in the pear consuming group than in the placebo group. Moreover, pro-inflammatory cytokines, including IgE, IL-4, IL-5, and IL-13, were significantly suppressed by the pear extracts in the preclinical tests of the ovalbumin-induced asthma mice. Thus, we suggest that air pollution-related respiratory hypersensitivity can be alleviated by Korean pear extracts by modulation of microbiome and immunocytokines.

Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice.

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis.