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Background Gut is a crucial organ for the host’s defense system due to its filtering action of the intestinal membrane from hazardous foreign substances. One strategy to strengthen the gut epithelial barrier function is to upregulate beneficial microflora populations and their metabolites. Sophorolipid (SPL), which is a glycolipid bio-surfactant, could increase beneficial microflora and decrease pathogenic bacteria in the gastrointestinal tract. Therefore, herein, we conducted an experiment with broiler chickens to investigate the fortifying effects of SPL on the host’s gut defense system by modulating the microbiota population. Methods A total of 540 1-day-old chicks (Ross 308) were used, and they were immediately allotted into three treatment groups (6 replications with 30 chicks/pen) according to their initial body weight. The dietary treatments consisted of CON (basal diet), BAM (10 mg/kg bambermycin), and SPL (10 mg/kg SPL). During the experiment, birds freely accessed feed and water, and body weight and feed intake were measured at the end of each phase. On d 35, birds (one bird/pen) were sacrificed to collect jejunum and cecum samples. Results Dietary SPL and BAM supplementation significantly accelerated birds’ growth and also significantly improved feed efficiency compared to CON. Intestinal microbial community was significantly separated by dietary SPL supplementation from that of CON, and dietary SPL supplementation significantly increased Lactobacillus spp. and Akkermansia muciniphila. Moreover, birds fed with dietary SPL also showed the highest concentration of cecal butyrate among all treatment groups. Gut morphological analysis showed that dietary SPL significantly increased villus height, ratio of villus height to crypt depth, goblet cell numbers, and the gene expression levels of claudin-1 and mucin 2. Additionally, dietary SPL significantly decreased the mRNA expression level of pro-inflammatory cytokine, interleukin-6, and increased that of anti-inflammatory cytokine, interleukin-10, compared to other treatments. Conclusions Dietary SPL increases the beneficial bacterial population and butyrate concentration, which leads to a strengthened gut barrier function. In addition, the intestinal inflammation was also downregulated by dietary SPL supplementation.

The public has gradually begun to regard inflammatory bowel disease (IBD) as a crucial health issue; however, its mode of action has not been fully elucidated. Sophorolipid (SPL), a glycolipid-type biosurfactant, could be used as a potential treatment in physical intestinal dystrophy. We conducted a 2 × 2 factorial experiment to investigate the protective effect of SPL in a dextran sulfate sodium (DSS)-induced colitis mouse model (first factor, presence of SPL in feed; second factor, presence of DSS in water). Forty C57BL/6 mice (8-week-old) were used, and they were allocated to treatments according to their initial body weight. After a 7 d adjustment period, the DSS treatment was initiated in specific groups. At day 14, DSS was withdrawn from mice, and half of the mice were randomly selected and euthanized to collect colon and colon content samples. Three days after the end of DSS treatment, the rest of the mice were euthanized to investigate the therapeutic effect of SPL. Dietary SPL improved the growth performance in 3 d after DSS treatment, and the histopathological score was lower in the DSS-treated SPL group than in the DSS-treated control group. Mucosal thickness and goblet cell numbers significantly increased in the SPL-supplemented groups compared to in the control group. Similarly, SPL supplementation upregulated the gene expression levels of mucin-2, interleukin-10, and transforming growth factor-β, and increased the concentration of short chain fatty acid compared to the control groups. In conclusion, dietary supplementation with SPL attenuated the pathological response against acute and chronic inflammation by the maintenance of the mucosal barrier and wound healing capacity.

Background In animals, weaning stress is the first and most critical stress. Weaning can negatively affect the growth performance of animals physically, psychologically, and pathologically. Our previous studies on the HT-29 cell line and early-weaned rats demonstrated that adequate sophorolipid (SPL) supplementation in feed could enhance the mucin-producing and wound healing capacities of the gut defense system by modulating gut microbiota. Methods We conducted an experiment with one hundred forty 21-day-old early weaned piglets (L x Y x D). They were allocated into 4 treatment and 7 replications (4 pigs per pen) according to their initial body weight. Body weight and feed intake were measured biweekly during experimental period. After 6 weeks, 28 pigs were randomly selected and sacrificed to collect plasma, jejunum, and cecal content samples. Results Dietary SPL supplementation at 5 and 10 mg/kg quadratically increased the average daily gain during the experimental period in the treatment groups when compared with the control group. The albumin levels of piglets fed with the SPL supplemented diet were downregulated to the normal range. Moreover, in feed, SPL supplementation at 5 and 10 mg/kg improved jejunal histological indices and gene expression levels related to mucin secretion and local inflammation markers. Consistent with these results, adequate SPL supplementation (5 and 10 mg/kg) increased the population of Prevotella, a beneficial bacterium, and its short-chain fatty acid production in the ceca of piglets. Conclusions The occurrence of diarrhea after weaning in piglets could be reduced by feeding a 10 ppm of SPL supplemented diet which improves the gut defense system by improving the microbial population and enhancing mucin layer integrity.

The immune system plays an important role in pregnancy. Chemokines recruit leukocytes at the maternal-fetal interface during early pregnancy. However, the role of the chemokine, C-C motif chemokine ligand 21 (CCL21), is less known. The aim of this study was to identify the expression of CCL21 and its receptor, CCR7, in the endometrium during estrous cycle and early pregnancy, and to investigate the functional effects of CCL21 on porcine trophectoderm (pTr) and porcine uterine luminal epithelial (pLE) cells. Our results indicated that CCL21 and CCR7 are increased in the glandular (GE) and luminal epithelium (LE) of the endometrium during early pregnancy, compared to estrous pigs. Recombinant CCL21 improved pTr and pLE cell proliferation through activation of the PI3K and MAPK pathways and suppression of tunicamycin-induced endoplasmic reticulum (ER) stress or LPS-induced inflammation. Collectively, these results provide novel insights into CCL21-mediated signaling mechanisms at the maternal-fetal interface during early pregnancy.

Early‐weaning syndrome is harmful to animals because an effect on growth in the early‐stage of life generally determines the overall growth rate. Sophorolipid (SPL), a surface‐active glycolipid compound, has been shown to exhibit antimicrobial activity and stimulate cell proliferation. Thus, in vitro and in vivo studies were conducted to evaluate the potential of SPL on the gut turnover after the wound. The in vitro experiment with HT‐29 cells showed the increased proliferation with increasing gene levels of collagenase‐1 and matrilysin‐1. Next, the 16‐day in vivo experiment was conducted with thirty rats (14‐day‐old), and the allocation was performed according to their body weight (BW) into three treatments: control diet (CON), 48 ppm of oxytetracycline‐supplemented diet (OTC) and 10 ppm of SPL‐supplemented diet (SPL). Dietary SPL accelerates the growth of rats in overall periods, and intestinal permeability was lower in SPL at day 16. Villus:crypt ratio and the goblet cell count were also higher in SPL than in CON at day 8. Caecal Streptococcus spp. were significantly reduced with dietary SPL and OTC at day 8 and 16, and total short‐chain fatty acid, acetate and butyrate levels were increased in the SPL at day 8. In conclusion, these data demonstrated that SPL could improve gut remodelling potential and modulate the gut environments, resulted in acceleration of post‐weaning growth. Therefore, SPL could have a potential as a feed additive aimed at promoting repair system after wound in animal's gut., Sophorolipid upregulated the wound healing process. Gut defence system was improved by dietary sophorolipid. Caecal populations of microflora and short‐chain fatty acid were modulated by oral sophorolipid intake.

Whey protein is a by-product of cheese and casein manufacturing processes. It contains highly bioactive molecules, such as epidermal growth factor, colony-stimulating factor, transforming growth factor-&alpha, and -&beta, insulin-like growth factor, and fibroblast growth factor. Effects of whey protein on immune responses after antigen (hemagglutinin peptide) injection were evaluated in rats. Experimental diets were formulated based on NIH-31M and supplemented with 1% amino acids mixture (CON) or 1% whey protein concentrate (WPC) to generate isocaloric and isonitrogenous diets. Rats were fed the experimental diets for two weeks and then exposed to antigen two times (Days 0 and 14). Blood was collected on Days 0, 7, 14, and 21 for hematological analysis. The WPC group showed decreased IgA and cytotoxic T cells before the antigen injection (Day 0) but increased IgG, IL-2, and IL-4 after antigen injection due to increased B cells and T cells. Helper T cells were increased at Days 14 and 21, but cytotoxic T cells were not affected by WPC. WPC may activate adaptive immunity (IgG) against antigen by modulating helper T cells. Bioactive molecules might contribute to the immune-enhancing effects of whey protein concentrate.

Gastrointestinal microbiota impact host's biological activities, including digestion of indigestible feed components, energy harvest, and immunity. In this study, fecal microbiota of high body weight (HW) and low body weight (LW) growing pigs at 103 days of age were compared. Principal coordinates analysis separated the HW and LW groups into two clusters, indicating their potential differences between microbial community composition. Although the abundances of two major phyla, Firmicutes and Bacteroidetes, did not significantly differ between the HW and LW groups, some genera showed significant differences. Among them, Peptococcus and Eubacterium exhibited strong positive correlations with body weight (BW) and average daily gain (ADG) (Rho > 0.40), whereas Treponema, Desulfovibrio, Parabacteroides, and Ruminococcaceae_unclassified exhibited strong negative correlations with BW and ADG (Rho < -0.40). Based on these results, the structure of intestinal microbiota may affect growth traits in pigs through host-microbe interactions. Further in-depth studies will provide insights into how best to reshape host-microbe interactions in pigs and other animals as well.

ValiMP® is a mixture of phytochemical compounds containing manganese. An experiment was carried out to evaluate the effects of ValiMP® on growth performance, carcass characteristics, and pork quality in growing-finishing pigs. The trial was conducted in a 2x3 factorial design with two levels of CP (LP, 15% or HP, 16%), and three types of supplements (Control; 10 ppm ractopamine; or 0.25% ValiMP®). Dietary treatments were: LC (Low CP+control), LR (Low CP+ractopamine), LV (Low CP+ValiMP®), HC (High CP+control), HR (High CP+ractopamine), HV (High CP+ValiMP®). A total of 144 growing pigs at 50 kg initial body weight (BW) were allotted and fed one of the experimental diets for 70 days. But ractopamine in LR and HR treatments was supplemented during the last 35 days. BW and feed intake were measured weekly, and pork quality was determined in longissimus dorsi muscle. All values were statistically analyzed using ANOVA procedure of SAS 9.4 software and differences at P < 0.05 level were considered significantly different. Results showed dietary ractopamine or ValiMP® supplementation numerically promoted growth performance compared to control in HP treatments, although the extent was lesser in ValiMP® treatment. Ractopamine or ValiMP® also improved carcass composition in HP compared to LP. Lean percentage in HR was higher than in LR by 4.3%, and it was greater in HV than in LV by 5.9%, (P < 0.05). These changes occurred at the expense of fat percentage (P < 0.05). Among pork quality criteria, water-holding capacity determined by filter-paper fluid uptake method was significantly lower in HV than those in HC and HR (P < 0.05). Warner-Bratzler shear force, an indicative for meat tenderness, exhibited lower values in HV and HC than that in HR (P < 0.05). Overall, our results suggest ValiMP® improves growth performance and carcass composition with lesser extent to ractopamine, and pork quality more than ractopamine.

Western-style diets increase the risk for cardiovascular diseases. It is suggested that the risk could be prevented by lowering cholesterol concentrations in blood. In the present study, hypocholesterolemic effects of the probiotics isolated from kimchi (Lactobacillus curvatus KFP419, Leuconostoc paramesenteroides KJP421, and Leuconostoc mesenteroide subsp. mesenteroides KDK411) were investigated in hypercholesterolemia-induced rats. There was no difference in growth performance between the rats fed high cholesterol diet (HCD) and normal diet (ND). However, blood total cholesterol, low-density lipoprotein cholesterol, and hepatic cholesterol were elevated by the HCD compared to ND, and those concentrations were decreased by dietary supplementation of KFP419 and KDK411. It was concomitant with an increase in fecal excretion of neutral sterols (cholesterol, coprostanol, and coprostanone) in the rats fed HCD compared to ND and was even greater with KDK411 supplementation. These findings indicate that probiotics L. curvatus KFP419 and L. mesenteroide subsp. mesenteroides KDK411 isolated from kimchi ameliorate hypercholesterolemia in rats by assimilating and excreting cholesterol in feces.

The aim of this study is to investigate the dynamic gut microbial diversity in weaning swine after administering feed supplemented with probiotic bacteria that specifically inhibit the activity of quorum molecules. Initially, the universal quorum molecule autoinducer-2 (AI-2) bioassay results indicated that AI-2 activity was profoundly inhibited in enterohemorrhagic Escherichia coli (EHEC) O157:H7 in the presence of Lactobacillus acidophilus strain 30SC cell extract, although the growth of EHEC was not affected. Based on plate counting results, bacterial community analysis revealed a specific reduction in coliforms compared to the control, whereas the population of lactobacilli increased in weaning swine in in vivo trials. Supplementation with L. acidophilus strain 30SC did not affect the counts of other communities, such as total aerobes and yeast/mold. In addition, PCR-denaturing gradient gel electrophoresis analysis showed a significant difference in the 16S rRNA gene products after administering L. acidophilus strain 30SC. Selected bands were sequenced, and most of them were identified as uncultured bacterium clones or a Lactobacillus- and Bifidobacterium-specific community. Therefore, our results indicate that quorum-quenching probiotic bacteria can significantly modulate the gut microbiota of swine and these beneficial effects can contribute to the improvement of performance and health in the gastrointestinal tract of weaning pigs.

Probiotics have received attention as alternatives to antibiotics due to their relative biosafety. Despite the health-promoting effects of multispecies probiotic formulation (MPF) in weaning pigs were well-documented, the health-promoting potential of MPF in growing-finishing pigs remain limited. Therefore, we conducted a six-week experiment to investigate the beneficial effects of MPF supplementation (the formulations containing Lactobacillus plantarum CJLP243, L. fermentum LF21, L. salivarius E4101, Leuconostoc paramesenteroides KJP421, Bacillus subtilis CJMPB957 and B. licheniformis CJMPB283) on intestinal environments and hepatic lipid metabolism in growing-finishing pigs. The results showed that the growth performance of MPF group was improved compared to control group during the experimental period without affecting feed intake. The dietary MPF supplementation also significantly increased the jejunal mRNA expression levels of zonula occludens-1 (ZO-1) and decreased that of interleukin-12 (IL-12). Dietary MPF supplementation was found to not only reduce the hepatic triglyceride concentration but down-regulate hepatic mRNA expression levels of lipid metabolism-related markers, such as as sterol regulatory element-binding transcription factor 1c (SREBP-1c), CCAAT/enhancer binding protein α (CEBPα), acetyl coA carboxylase (ACC) and carnitine palmitoyl transferase 1β (CPT1β). Nonetheless, MPF supplementation also had the capability to modulate gut microbiota populations, including Clostridiaceae, Lachnospiraceae, and Turicibacter. Collectively, our results suggest that dietary MPF inclusion could be a promising approach to promote the growth performance and the overall health of growing-finishing pigs via modulation of gut microbiota.

Most countries have banned the use of 4,4'-dichlorodiphenyltrichloroethane (DDT). However, owing to its extremely high lipophilic characteristics, DDT and its metabolite 4,4'-dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and in many types of food. The positive correlation between exposure to insecticides, including DDT and DDE, and weight gain, resulting in impaired energy metabolism in offspring following perinatal DDT and DDE exposure, was previously reported. Therefore the influence of DDT and DDE on myogenesis using C2C12 myoblasts was investigated in this study.; Results: DDT and DDE decreased myotube formation dose- and time-dependently. Among myogenic regulatory factors, DDT and DDE mainly decreased MyoD1 and Myf5 expression. DDT and DDE treatment also altered Myostatin expression, phosphorylation of protein kinase B, p70 ribosomal protein S6 kinase, forkhead box O protein 3 and mammalian target of rapamycin, resulting in attenuation of myotube formation.; Conclusion: These results may have significant implications for understanding the effects of developmental exposure of DDT and DDE on myogenesis and development of obesity and type 2 diabetes later in life. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.

Myogenesis occurs in both the prenatal and postnatal periods and the prenatal myogenesis is related to the postnatal myogenesis and the incidence of disease later in life. Glucocorticoids used as therapeutic agents for many diseases, but cause adverse effects on muscle homeostasis, including defects in fetal muscle development. The action of glucocorticoids on differentiated skeletal muscle was well studied, but their effects on myotube formation have not been well investigated. Dexamethasone (DEX) and cortisone (COR), two synthetic therapeutic glucocorticoids, suppress myotube formation in C2C12 cells. Both COR and DEX attenuated myotube formation through modulation of myogenic regulatory factors. In addition, they affected the IGF/PI3K/AKT/mTOR signaling pathway, resulting in increased proteolytic protein (atrogin-1 and MURF1) for muscle degradation and decreased ribosomal S6 phosphorylation. The current results conclude that COR and DEX inhibit myotube formation in C2C12 cells by modulating both the myogenic program via MRFs and protein metabolism via IGF/PI3K/AKT/mTOR signaling pathway. Glucocorticoids decrease myogenesis via AKT/mTOR signal pathway.

Etoxazole is an organofluorine insecticide widely used in agriculture. Exposure to insecticides is a serious environmental problem owing to their cytotoxic effects in humans and animals. Reproductive toxicity of various organofluorine insecticides have been shown in previous studies. However, few studies have evaluated the toxicity of etoxazole in mammals. We aimed to examine the toxic effects of etoxazole in porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. To estimate the effects of etoxazole, we conducted assays after treatment with multiple concentration of etoxazole (0, 2, 4, 6 and 9 μM) to pTr and pLE cells for 0–72 h. Etoxazole decreased the cell proliferation, viability, and migration of pTr and pLE cells. Further, etoxazole induced apoptosis via cell cycle arrest and disruption of mitochondrial membrane potential. We also found that pro-apoptotic proteins and endoplasmic reticulum (ER) stress-response proteins were activated in response to etoxazole. Finally, we observed that etoxazole altered the PI3K/AKT and MAPK signaling pathways and the mRNA expression of genes associated with implantation. Collectively, these results suggest that etoxazole disrupts normal cellular physiology and might cause early implantation failure.

The objective of this experiment was to investigate the effects of non-starch polysaccharide (NSP) and NSP-degrading enzyme complex (NEC) levels on growth performance and gut environment in growing pigs. NEC is known to improve the utilization of nutrient in feed. Beside of this increased digestibility, NEC is also known to promote gut health by increased villus height. Therefore, we conducted an experiment with diets included NSP-rich feed ingredients (wheat and barley) and NEC (Endo-Power(TM); α-1,6-galactosidase and β-galactomannanase). One hundred eight 8-week-old pigs were randomly allotted into a 2x3 factorial designed experiment with 6 replications. The high- (H-) or low-NSP contained (L-) diet supplemented with 3 dietary levels of NEC, 0% (CON), 0.1% (NEC-0.1), and 0.2% (NEC-0.2), was provided for four weeks. One pig from each pen was sacrificed to collect plasma, jejunum, ileal content and cecal content samples. The data was analyzed using ANOVA procedures of SAS 9.4. The means were compared by Duncan’s multi-range test at P

The present study was conducted to determine the effects of dietary ValiMP(®) (VMP) on growth performance and tissue characteristics in broilers. Previous studies have demonstrated that VMP, a mixture of phytogenic compounds with manganese, inhibited adipogenesis in 3T3-L1 preadipocytes, and promoted skeletal muscle hypertrophy in C2C12 myoblasts. However, its effects on growth, adipogenesis and myogenesis in broilers have yet been investigated. Therefore, a total of 240 1-day-old Ross 308 broilers were randomly assigned to one of the 4 treatments with 5 replications. Dietary treatments were 0% (CON), 0.125% (LV), 0.25% (MV), or 0.50% (HV) VMP supplemented to broiler diets, and the birds were fed the experimental diet for 35 days. At the end of the experiment, breast muscle, abdominal fat, and the liver were collected, and the statistical analyses were conducted by ANOVA procedure using SAS 9.3. Results showed that final body weight was increased in LV and MV treatments, with improved ADG in LV treatment compared to CON (p

Milk is known as a safe food and contains easily absorbable minerals and proteins, including whey protein, which has demonstrated antiosteoporotic effects on ovariectomized rats. This study evaluated the antiosteoporotic effect of whey protein concentrate hydrolysate (WPCH) digested with fungal protease and whey protein concentrate (WPC). Two experiments were conducted to determine (1) efficacy of WPCH and WPC and (2) dose-dependent impact of WPCH in ovariectomized rats (10 weeks old). In Experiment I, ovariectomized rats (n=45) were allotted into three dietary treatments of 10 g/kg diet of WPC, 10 g/kg diet of WPCH, and a control diet. In Experiment II, ovariectomized rats (n=60) were fed four different diets (0, 10, 20, and 40 g/kg of WPCH). In both experiments, sham-operated rats (n=15) were also fed a control diet containing the same amount of amino acids and minerals as dietary treatments. After 6 weeks, dietary WPCH prevented loss of bone, physical properties, mineral density, and mineral content, and improved breaking strength of femurs, with similar effect to WPC. The bone resorption enzyme activity (tartrate resistance acid phosphatase) in tibia epiphysis decreased in response to WPCH supplementation, while bone formation enzyme activity (alkaline phosphatase) was unaffected by ovariectomy and dietary treatment. Bone properties and strength increased as the dietary WPCH level increased (10 and 20 g/kg), but there was no difference between the 20 and 40 g/kg treatment. WPCH and WPC supplementation ameliorated bone loss induced by ovariectomy in rats.

Butylated hydroxytoluene (BHT) is a synthetic phenolic antioxidant that has been used as an additive for fat- or oil-containing foods. The exposure index value increases with extended usage of the chemical. Further, estimated total amount of BHT could exceed standard regulation, considering dietary intake or another exposure. Although BHT may induce side effects in reproductive systems, adequate research had not yet been performed to confirm them. In this study, we investigated the effects of BHT on mouse Leydig cells (TM3), which are components of testis. Our results indicated that BHT suppressed cellular proliferation and induced cell cycle arrest in TM3 cells. Moreover, BHT hampered cytosolic and mitochondrial calcium homeostasis in TM3 cells. Furthermore, BHT treatment led to endoplasmic reticulum (ER) stress and DNA fragmentation, simultaneously stimulating intrinsic apoptosis signal transduction. To elucidate the mode of action of BHT on Leydig cells, we performed western blot analysis and confirmed the activation of the PI3K/AKT and MAPK pathways. Collectively, our results demonstrated that BHT has toxic effects on mouse Leydig cells via induction of calcium dysregulation and ER-mitochondria dysfunction.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is a major dietary flavonol found in diverse fruits and vegetables such as onions, cauliflower, apple skin, lettuce and chili peppers. In recent studies, quercetin is reported as a functional compound and shows a wide range of biological effects such as antioxidant, anti-inflammatory and antiangiogenic properties in obesity, diabetes, cardiovascular diseases and various cancers. However, to date, the therapeutic effect of quercetin on the progression of endometriosis, which is a common gynecological disease in reproductive-aged women and brings chronic pelvic pain and infertility, has not been examined in depth. Results of this study demonstrated that quercetin inhibited the proliferation and induced the cell cycle arrest in VK2/E6E7 and End1/E6E7 cells. Furthermore, it induced cell apoptosis with DNA fragmentation, loss of mitochondrial membrane potential and reactive oxygen species production. The effects accompanied down-regulation of ERK1/2, P38 MAPK and AKT signaling molecules. Additionally, the administration of quercetin indicated antiproliferative and anti-inflammatory effects on endometriosis autoimplanted mouse models. The mRNA expression of Ccnd1 significantly decreased in response to quercetin intraperitoneal injection when compared to that in vehicle-treated mice. The knockdown of CCND1 mRNA attenuated the proliferation with sub-G0/G1 cell cycle arrest and increased the apoptosis of VK2/E6E7 and End1/E6E7 cells. Furthermore, the treatment of quercetin induced miR-503-5p, miR-1283, miR-3714 and miR-6867-5p related to CCND1 in both cell lines and also stimulated miR-503-5p and miR-546 expression in the mouse model. Hence, quercetin may potentially act as a natural therapeutic to reduce and treat human endometriosis.

Oct4-Sox2-Nanog transcriptional networks are critical for the maintenance of embryonic stem (ES) cell self-renewal and induction of pluripotency. However, in transcription factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), Nanog is initially dispensable and Oct4 remains the sole factor that could not be substituted/omitted. Here, we show that mouse fibroblasts could be reprogrammed into iPSCs by Nanog and Bmi1, which replaces Sox2, Klf4, and c-Myc, in the absence of Oct4. Furthermore, we show that in the presence of shh agonists (oxysterol and purmophamine), which replaces the function of Bmi1, a single transcription factor, Nanog is sufficient to reprogram mouse fibroblasts into iPSCs. Nanog-induced iPSCs resemble mESCs in terms of morphology, global gene expression profiles, epigenetic status and pluripotency both in vitro and in vivo. These findings support that Nanog can replace the Oct4 for the somatic cell reprogramming and underlie the mechanisms of Nanog in reprogramming process.

Self-renewal, differentiation, and tumorigenicity characterize cancer stem cells (CSCs), which are rare and maintained by specific cell fate regulators. CSCs are isolated from glioblastoma multiforme (GBM) and may be responsible for the lethality of incurable brain tumors. Brain CSCs may arise from the transformation of undifferentiated, nestin-positive neural stem or progenitor cells and GFAP-expressing astrocytes. Here, we report a role of Nanog in the genesis of cancer stem-like cells. Using primary murine p53-knockout astrocytes (p53−/− astrocytes), we provide evidence that enforced Nanog expression can increase the cellular growth rate and transform phenotypes in vitro and in vivo. In addition, Nanog drives p53−/− astrocytes toward a dedifferentiated, CSC-like phenotype with characteristic neural stem cell/progenitor marker expression, neurosphere formation, self-renewal activity, and tumor development. These findings suggest that Nanog promotes dedifferentiation of p53-deficient mouse astrocytes into cancer stem-like cells by changing the cell fate and transforming cell properties.

In the current study, the probiotic potential of approximately 350 strains of lactic acid bacteria isolated from Korean infant feces and Kimchi was investigated. Common probiotic properties of the bacterial strains, such as acid tolerance, bile tolerance and adhesion to human intestinal epithelial cells (HT-29 cells), were examined. Some strains were found to have immune modulatory and antimicrobial properties. Antagonistic activity against a panel of pathogenic bacteria was found to be strain dependent. To evaluate the immune modulatory activity of the strains, lymphocyte interferon (IFN)-γ secretion was determined in conjunction with cell proliferation. Some strains of Lactobacillus gasseri, L. fermentum and L. plantarum exhibited increased IFN-γ levels and lymphocyte proliferation. To evaluate the effects of these immune modulating lactobacilli on host life span, Caenorhabditis elegans was used as an in vivo model. Nematodes that were supplied heat-killed lactobacilli as a food source exhibited obvious differences in life span compared with those fed Escherichia coli OP50. The mean life span (determined as mean percent survival) of worms fed L. plantarum CJLP133 and L. fermentum LA12 was 13.89% and 13.69% greater, respectively, than that of control nematodes after 21 days (P=0.036 and 0.043, respectively). In addition, some of safety profiles, including hemolytic type, gelatin hydration and degradation of urea, were found to be positive. These newly identified lactobacilli hold promise for use as probiotic agents, feed additives and/or in food applications.

Somatic cells can be reprogrammed into induced pluripotent stem (iPS) cells by the transcription factors Oct4, Sox2, and Klf4 in combination with c-Myc. Recently, Sox2 plus Oct4 was shown to reprogram fibroblasts and Oct4 alone was able to reprogram mouse and human neural stem cells (NSCs) into iPS cells. Here, we report that Bmi1 leads to the transdifferentiation of mouse fibroblasts into NSC-like cells, and, in combination with Oct4, can replace Sox2, Klf4 and c-Myc during the reprogramming of fibroblasts into iPS cells. Furthermore, activation of sonic hedgehog signaling (by Shh, purmorphamine, or oxysterol) compensates for the effects of Bmi1, and, in combination with Oct4, reprograms mouse embryonic and adult fibroblasts into iPS cells. One- and two-factor iPS cells are similar to mouse embryonic stem cells in their global gene expression profile, epigenetic status, and in vitro and in vivo differentiation into all three germ layers, as well as teratoma formation and germline transmission in vivo. These data support that converting fibroblasts with Bmi1 or activation of the sonic hedgehog pathway to an intermediate cell type that expresses Sox2, Klf4, and N-Myc allows iPS generation via the addition of Oct4.

MicroRNAs (miRNAs) are an abundant class of small regulatory RNAs that regulate the stability and translation of cognate mRNAs. Although an increasing number of porcine miRNAs has recently been identified, the full repertoire of miRNAs in pig remains to be elucidated. To identify porcine miRNAs potentially involved in myogenesis and adipogenesis, we constructed small RNA cDNA libraries from skeletal muscle and adipose tissue and identified 89 distinct miRNAs that are conserved in pig, of which 15 were new. Expression analysis of all newly identified and selected known porcine miRNAs revealed that some miRNAs were enriched in a tissue-specific manner, whereas others were expressed ubiquitously in the porcine tissues examined. Our results expand the number of known porcine miRNAs and provide useful information for further investigating the biological functions of miRNAs associated with growth and development of skeletal muscle or adipose tissue in pig.

The effects of a Lactobacillus casei 393 fermented milk product (FMP) on bone metabolism were examined. FMP (>0.1 mg mL −1 ) supplementation significantly increased osteoblastic MC3T3-E1 cells proliferation whereas skim milk powder supplementation did not show any positive effect up to 1 mg mL −1 . The FMP (1%) supplemented ovariectomised rats had increased bone weight, bone mineral density, and bone breaking force compared with control ovariectomised rat. In addition, the activity of tartrate resistant acid phosphatase, a biomarker of osteoclasts, was significantly reduced in the FMP group. Based on the results, the L. casei 393 FMP had a preventative effect on bone loss in ovariectomised rats.

CD127 (the alpha chain of the IL-7 receptor) is an 80 kDa type I membrane glycoprotein that mediates the signal for the differentiation, maturation, and survival of lymphocyte development. In this study, the full-length cDNA of pig Cd127 was cloned and sequenced. Pig CD127 cDNA contains an open reading frame (1,380 bp) encoding 459 amino acids. Phylogenetic analysis revealed that pig CD127 is most homologous to that of cow (Bos taurus) with 87% amino acid identity and less homologous to that of chicken (Gallus gallus) with 36% amino acid identity among those of species. Structurally, pig CD127 has well-conserved cytoplasmic tail that transmits a signal and little diversity of extracellular domain, compared with those of other mammalian species. Expression analysis indicates that the mRNA transcript of pig CD127 is mainly detected in lymphoid tissues, but still detected in nonlymphoid tissues. Future studies will be focused on determining a more defined expression pattern of pig CD127 and the role of CD127 during the lymphocyte development in pigs.

CD82, which was originally referred to as KAI1 (kangai 1), is a member of the tetraspanin protein family, which contains four transmembrane domains. CD82 is implicated in a variety of biological processes, including apoptosis, cell adhesion, and cell migration. In this study, the full-length cDNA of pig CD82 was cloned and sequenced. Pig Cd82 cDNA contains an open reading frame (801 bp) encoding 266 amino acids. Sequence alignment results indicated that pig CD82 cDNA evidenced 85.45%, 85.63%, 77.03%, and 77.78% identity with human, cattle, rat, and mouse, respectively. In the expression study, the constitutive expression of swine Cd82 mRNA was detected in a variety of tissues, including lymphoid tissues as well as nonlymphoid tissues. Future studies will be focused on the functional role of CD82 during the course of pig infectious diseases or tumor development.

This study characterizes the factors responsible for the cholesterol reduction by Lactobacillus acidophilus ATCC 43121. In addition, two-dimensional gel electrophoresis (2-DE) and protein profiling was also used to study the response of ATCC 43121 at the proteome level in the presence of cholesterol. The results show that the cell-free supernatant (CFS) produced by ATCC 43121 in the presence of bile salts could also reduce the cholesterol in the broth, whereas all previous reports have suggested a mechanism by live cells. The active fraction was partially purified by 60% ammonium sulfate precipitation, and subsequent Sephacryl S-100 column chromatography. The molecular weight of the component with cholesterol-reducing activity was estimated to be approximately 12 kDa by SDS-PAGE. These results suggest that the novel protein isolated from CFS may be an important factor in the mechanism for cholesterol reduction by ATCC 43121. In addition, the proteins expressed by ATCC 43121 in the presence of cholesterol micelles were detected by 2-DE, five protein spots with at least a 2.5-fold increase in amounts being identified. The responsible proteins may be involved in the stress-response, translation, and metabolic processes. These results may suggest a new possibility for the mechanism underlying cholesterol reduction by lactic acid bacteria (LAB), differing from the conclusions of previous reports.

Recently, Bmi1 was shown to control the proliferation and self-renewal of neural stem cells (NSCs). In this study, we demonstrated the induction of NSC-like cells (NSCLCs) from mouse astrocytes by Bmi1 under NSC culture conditions. These NSCLCs exhibited the morphology and growth properties of NSCs, and expressed NSC marker genes, including nestin, CD133, and Sox2. In vitro differentiation of NSCLCs resulted in differentiated cell populations containing astrocytes, neurons, and oligodendrocytes. Following treatment with histone deacetylase inhibitors (trichostatin A and valproic acid), the potential of NSCLCs for proliferation, dedifferentiation, and self-renewal was significantly inhibited. Our data indicate that multipotent NSCLCs can be generated directly from astrocytes by the addition of Bmi1.

This study was performed to examine an efficient way to use oil by-product which is obtained during the purification process of conjugated linoleic acid (CLA) from safflower oil. The CLA by-product (CBP) was fed to the laying hens to accumulate CLA in the egg yolk. Egg yolk samples from 3 different dietary groups were analyzed: control; CBP, 2%; and CLA-80 (which contained 80% free form of CLA), 2%. Fatty acids from the yolk were analyzed by gas chromatography, and the parameters of egg quality were determined. During the feeding trial, there was little alteration in the egg quality and egg production of the tested groups. The CLA contents in the test group with CBP, which contain CLA as glyceride form, significantly increased in the first week of feeding and had the highest level among the tested groups throughout the feeding trials, whereas the CLA group showed an increase in CLA contents from the third week. Moreover, the contents of total CLA isomers in CLA-80 and CBP oils were decreased by 12.92 and 0.51% after heat treatment in 48 h, and the contents of linoleic acid (LA) isomer in LA-80 (which contained 80% free form of LA) and LA by-product (LBP) oils were decreased by 19.63 and 5.78%, respectively. It was confirmed that a major form of fats in CBP was mainly esterified forms, whereas the fats in CLA-80 and LA-80 were composed of free fatty acids. There was no significant difference in the egg quality and production among the tested groups. It is meaningful that the oil by-product could be utilized as a source for functional foods of animal origin without influencing egg quality and production.

This experiment was conducted to evaluate effects of various periods of rye silage feeding on the growth performance, blood characteristics, and carcass quality of finishing pigs. A total of sixteen [()] pigs (90.26 kg in average initial body weight) were tested in individual cages for a 30 day period. Dietary treatments included 1) CON (basal diet), 2) S10 (basal diet for 20 days and 3% rye silage for 10 days) 3) S20 (basal diet for 10 days and 3% rye silage for 20 days) and 4) S30 (3% rye silage for 30 days). There were no significant differences in the ADG and gain/feed ratio among the treatments(p>0.05), however the ADFI was higher in pigs fed the CON diet than with pigs fed diets with rye silage (p

White soyflakes (SFs) were heat-treated by steam pressure cooking for four conditions to compared laboratory analytical values with in vivo qualities of soybean meal. The heat-treatment conditions consisted of no heat-treatment (SF-1), 5 min at 95 °C (SF-2), 5 min at 110 °C (SF-3), 15 min at 110 °C (SF-4), and 60 min at 110 °C (SF-5) under 1.07 kg/cm 2 pressure. The pepsin digestibility (PD), urease activity index (UAI), protein solubility in 0.2% KOH solution (KOH), and protein dispersibility index (PDI) were measured. Twenty pigs (14.1 ± 0.92 kg) were used to determine the energy and nitrogen digestibility. Experimental diets were formulated to contain 217 g/kg CP and 14.1 ME MJ/kg. Two growth trials were also conducted with 60 pigs per trial. The diets contained 191 g/kg CP and 14.2 ME MJ/kg. The nitrogen and energy digestibility were highest in SF-4 (P in vivo quality due to their small decrease (95–93%) during heat treatment. The abrupt drop of UAI was sensitive to detect under heat treatment (SF-1 and SF-2); however, the constant value (nearly zero) in adequate and over heat treatments (SF-3, SF-4, and SF-5) revealed their useless in adequate and over heat treatments ( r = −0.40). The KOH was sensitively changed from 96 to 84% after low heat treatment (SF-0 and SF-1), and also decreased from 76 to 41% after extreme heat treatment (SF-4 and SF-5). They exhibited linear negative correlation through heat treatments ( r = −0.97). The PDI dropped steeply (65–22%) after low heat treatment (SF1 to SF-3), and gradually decreased with further heat treatments ( r = −0.68). The analytical value of PDI to under heat treatment was much more correlation with in vivo quality than did UAI. These results suggested that the combination of the KOH and PDI is more effective at predicting the in vivo quality from the laboratory analytical value than the combination of the UAI and KOH.

Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.

4,4'-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4'-dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 adipocytes. Treatment of DDT or DDE resulted in increased lipid accumulation accompanied by increased expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome-proliferator activated receptor-γ (PPARγ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase, and leptin. Moreover, treatment of DDT or DDE increased protein levels of C/EBPα, PPARγ, AMP-activated protein kinase-α (AMPKα), and ACC, while significant decrease of phosphorylated forms of AMPKα and ACC were observed. These finding suggest that increased lipid accumulation caused by DDT and DDE may mediate AMPKα pathway in 3T3-L1 adipocytes.

Weaning is a stressful condition for mammals and negatively affects growth performance by dystrophy of intestinal villi and crypts. Dietary plasma protein (PP) has shown the increased growth perfor...

An experiment was conducted to examine the effects of different types of vitamin D3 on skeletal muscle development using growing rats. Three-week-old rats were fed a vitamin D3-deficient diet for 4 weeks and vitamin D3-replete diets for the next 4 weeks as each of vitamin D3 (vit D3, 1,000 IU/kg diet), 25-hydroxyvitamin D3 (25-OH D3, 400 IU/kg diet), and 1α-hydroxyvitamin D3 (1α-OH D3, 4 IU/kg diet) was supplemented. Negative control group was fed a vitamin D3-deficient diet, and positive control group was fed a vitamin D3-supplemented diet (1,000 IU/kg diet) for the whole experimental period, 8 weeks. In results, body weight, feed intake, and body composition (lean and fat) were not affected by vitamin D3 dose and type. Quantitative gene expression of skeletal muscle differentiation markers (MyoD, Myogenin, Mrf4, Myf5, and Myostatin) also showed no difference. However, skeletal muscle fiber type distribution (myofibrillar ATPase staining) was changed in bicep femoris (BF) of the rats fed different types ...

Somatic cells can be reprogrammed to generate induced pluripotent stem cells (iPSCs) by overexpression of four transcription factors, Oct4, Klf4, Sox2, and c-Myc. However, exogenous expression of pluripotency factors raised concerns for clinical applications. Here, we show that iPS-like cells (iPSLCs) were generated from mouse somatic cells in two steps with small molecule compounds. In the first step, stable intermediate cells were generated from mouse astrocytes by Bmi1. These cells called induced epiblast stem cell (EpiSC)-like cells (iEpiSCLCs) are similar to EpiSCs in terms of expression of specific markers, epigenetic state, and ability to differentiate into three germ layers. In the second step, treatment with MEK/ERK and GSK3 pathway inhibitors in the presence of leukemia inhibitory factor resulted in conversion of iEpiSCLCs into iPSLCs that were similar to mESCs, suggesting that Bmi1 is sufficient to reprogram astrocytes to partially reprogrammed pluripotency. Next, Bmi1 function was replaced with Shh activators (oxysterol and purmorphamine), which demonstrating that combinations of small molecules can compensate for reprogramming factors and are sufficient to directly reprogram mouse somatic cells into iPSLCs. The chemically induced pluripotent stem cell-like cells (ciPSLCs) showed similar gene expression profiles, epigenetic status, and differentiation potentials to mESCs.