A total of 144 pigs ((Landrace×Yorkshire)×Duroc] with an average initial BW of 8.45±0.57 kg were used in a 5-wk growth trial. Pigs were randomly allocated to 4 treatments with 9 replications per pen in a randomized complex block design. Dietary treatments included: i) CON (basal diet), ii) ANT (CON+tylosin 1 g/kg), iii) H1 (CON+H. cordata 1 g/kg) and iv) T1 (CON+T. officinale 1 g/kg). In this study, pigs fed the ANT and T1 treatment had a higher (p<0.05) average daily gain (ADG) and gain:feed (G:F) ratio than those fed CON and H1 treatment. Dietary ANT and T1 treatment led to a higher energy digestibility than the CON group. No difference (p>0.05) was observed on the growth performance and apparent total tract digestibility with H1 supplementation compared with the CON treatment. The inclusion of ANT treatment led to a higher (p<0.05) lymphocyte concentration compared with the CON treatment. Dietary supplementation of herbs did not affect (p>0.05) the blood characteristics (white blood cell (WBC), red blood cell (RBC), IgG, lymphocyte). No difference was observed on (p<0.05) fecal microbial shedding (E. coli and lactobacillus) between ANT and CON groups. Treatments H1 and T1 reduced the fecal E. coli concentration compared with the CON treatment, whereas the fecal lactobacillus concentration was not affected by the herb supplementation (p>0.05). In conclusion, the inclusion of T. officinale (1 g/kg) increased growth performance, feed efficiency, energy digestibility similarly to the antibiotic treatment. Dietary supplementation of T. officinale and H. cordata (1 g/kg) reduced the fecal E. coli concentration in weaning pigs.

Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function. NRG2 KOs have higher extracellular dopamine levels in the dorsal striatum but lower levels in the mPFC; a pattern with similarities to dopamine dysbalance in schizophrenia. Like ErbB4 KO mice, NRG2 KOs performed abnormally in a battery of behavioral tasks relevant to psychiatric disorders. NRG2 KOs exhibit hyperactivity in a novelty-induced open field, deficits in prepulse inhibition, hypersensitivity to amphetamine, antisocial behaviors, reduced anxiety-like behavior in the elevated plus maze and deficits in the T-maze alteration reward test-a task dependent on hippocampal and mPFC function. Acute administration of clozapine rapidly increased extracellular dopamine levels in the mPFC and improved alternation T-maze performance. Similar to mice treated chronically with N-methyl-d-aspartate receptor (NMDAR) antagonists, we demonstrate that NMDAR synaptic currents in NRG2 KOs are augmented at hippocampal glutamatergic synapses and are more sensitive to ifenprodil, indicating an increased contribution of GluN2B-containing NMDARs. Our findings reveal a novel role for NRG2 in the modulation of behaviors with relevance to psychiatric disorders.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) drives cellular transformation. The objective of this study was to detect the potential effects of CIP2A in renal cell carcinomas (RCCs).

To compare the 2-h postprandial blood glucose (PPBG) excursion following a standard test meal in insulin-requiring patients with diabetes treated twice daily with human insulin mix 50 vs. insulin lispro mix 50 (LM50).

This study was conducted to evaluate the effects of 3 rearing systems (FL: flooring litter rearing, MC: multilayer cage rearing, PN: plastic net rearing) with or without supplemental narasin on growth performance, gastrointestine development and health of broilers. A total of 2,400 one-day-old Ross 308 mixed-sex broilers (1:1 ratio of males and females) were used in a completely randomized design utilizing a 3 × 2 factorial arrangement of treatments, with 12 replicates per treatment. Each replicate for FL, MC, and PN consisted of 34 birds per floor pen, 30 birds per cage, and 36 birds per net pen, respectively, ensuring the same stocking density (12 birds/m2) across the 3 systems. Results showed that lower ADG (average daily gain), ADFI (average daily feed intake), and FCR (feed conversation ratio) observed in the MC group than those of the other 2 systems from 1 to 36 d of age (P < 0.05). Narasin inclusion in the diets decreased ADFI and FCR significantly (P < 0.05). Multilayer cage and PN rearing systems reduced the relative weight of the gizzard significantly (P < 0.05). Compared with FL, MC reduced the relative weight of the duodenum, jejunum, and ileum (P < 0.05). The mRNA expression levels of the ileal IL-1β and IFN-γ in FL were higher than those in PN and MC (P < 0.05). Narasin decreased the ileal mRNA expression of TNF-α (P < 0.05). Different rearing systems changed the ileal microflora structure of broilers. The FL system increased the ileal microbial diversity of broilers and the relative abundance of Actinobacteria. Narasin combined with MC increased the relative abundance of Proteobacteria. In conclusion, birds reared in PN had a higher body weight. The MC birds had poorer intestinal development and health condition, higher abundance of Proteobacteria, but better FCR. The FL rearing appeared to be propitious for gastrointestinal development and health. Narasin inclusion in the diets improved FCR and changed the relative abundance Proteobacteria of broilers.

A new member of the mammalian period gene family, mPer3, was isolated and its expression pattern characterized in the mouse brain. Like mPer1, mPer2 and Drosophila period, mPer3 has a dimerization PAS domain and a cytoplasmic localization domain. mPer3 transcripts showed a clear circadian rhythm in the suprachiasmatic nucleus (SCN). Expression of mPer3 was not induced by exposure to light at any phase of the clock, distinguishing this gene from mPer1 and mPer2. Cycling expression of mPer3 was also found outside the SCN in the organum vasculosum lamina terminalis (OVLT), a potentially key region regulating rhythmic gonadotropin production and pyrogen-induced febrile phenomena. Thus, mPer3 may contribute to pacemaker functions both inside and outside the SCN.

High-grade serous ovarian cancer is an aggressive form of epithelial ovarian cancer (EOC), and accounts for the majority of deaths due to EOC. The critical cellular processes and underlying molecular mechanisms that define this malignancy remain poorly understood. Using a syngeneic murine model, we investigated the changes that accompanied the progression to increased aggressiveness induced by in vivo passage of mouse EOC cells. We found that enhanced anoikis resistance was a key cellular process associated with greater aggressiveness and tumorigenicity in vivo. Biochemical studies revealed that the enhanced anoikis resistance was associated with the activation of the Src/Akt/Erk signaling pathway. A higher rate of metabolism and autophagy were also associated with increased anoikis resistance. Blocking these pathways with specific inhibitors and/or genetic modifications significantly increased anoikis in vitro and inhibited tumor development in vivo. In addition, we demonstrated that similar signaling pathways were also involved in a human EOC cell line model. Collectively, our data suggest that anoikis resistance represents a critical and a distinguishing feature underlying the aggressiveness of ovarian cancer cells.

Prolonged exposure to nitrous oxide (N2O) results in development of acute tolerance to its antinociceptive effect. Cross-tolerance to N2O-induced antinociception is also observed in morphine-tolerant animals. Despite increasing evidence of tolerance development to N2O-induced antinociception, the details of the mechanisms that underlie this tolerance remain unknown. The present study was conducted to investigate the involvement of brain protein kinase C (PKC) isoform in these two types of tolerance to N2O-induced antinociception in mice. Prolonged exposure (41 min in total, including 30 min pre-exposure and 11 min of antinociceptive testing) to 70% N2O produced a reduction in N2O-induced antinociception, indicating development of acute tolerance. The prolonged exposure to 70% N2O caused an activation of PKCgamma isoform in the brain, but not the PKCepsilon isoform. Pretreatment with a PKCgamma-antisense oligonucleotide but not the corresponding mismatch oligonucleotide (i.c.v.) prevented the development of acute tolerance to N2O-induced antinociception. Chronic morphine treatment (10 mg/kg, s.c., b.i.d. for 5 days) resulted in development of tolerance to morphine-induced antinociception and cross-tolerance to N2O-induced antinociception. The development of tolerance to morphine and cross-tolerance to N2O were both inhibited by pretreatment with PKC inhibitor, chelerythrine (1 nmol, i.c.v.). Morphine-tolerant mice showed an activation of PKC within the brain, which was suppressed by pretreatment with chelerythrine (1 nmol, i.c.v.). Thus, activation of brain PKC, in particular, the PKCgamma isoform, appears to play an important role in the development of both acute tolerance and cross-tolerance to N2O-induced antinociception in mice.

Mechanisms associated with the enhanced contractile response to endothelin-1 in hyperinsulinaemic diabetes have been examined using the rat aorta. Functions for angiotensin II, endothelin-1 receptor expression and extracellular signal-regulated kinase (ERK) have been investigated.

A total of 96 growing pigs ((Landrace×Yorkshire)×Duroc; BW = 26.58±1.41 kg) were used in a 6-wk feeding trail to evaluate the effects of fermented chlorella (FC) supplementation on growth performance, nutrient digestibility, blood characteristics, fecal microbial and fecal noxious gas content in growing pigs. Pigs were randomly allotted into 1 of 4 dietary treatments with 6 replicate pens (2 barrows and 2 gilts) per treatment. Dietary treatments were: i) negative control (NC), basal diet (without antibiotics); ii) positive control (PC), NC+0.05% tylosin; iii) (fermented chlorella 01) FC01, NC+0.1% FC, and iv) fermented chlorella 02 (FC02), NC+0.2% FC. In this study, feeding pigs PC or FC01 diets led to a higher average daily gain (ADG) and dry matter (DM) digestibility than those fed NC diet (p<0.05), whereas the inclusion of FC02 diet did not affect the ADG and DM compared with the NC group. No difference (p>0.05) was observed on the body weight, average daily feed intake (ADFI), gain:feed (G:F) ratio, the apparent total tract digestibility of N and energy throughout the experiment. The inclusion of PC or FC did not affect the blood characteristics (p>0.05). Moreover, dietary FC treatment led to a higher (p<0.05) lactobacillus concentration and lower E. coli concentration than the NC treatment, whereas the antibiotic supplementation only decreased the E. coli concentration. Pigs fed FC or PC diet had reduced (p<0.05) fecal NH3 and H2S content compared with those fed NC diet. In conclusion, our results indicated that the inclusion of FC01 treatment could improve the growth performance, nutrient digestibility, fecal microbial shedding (lower E. coli and higher lactobacillus), and decrease the fecal noxious gas emission in growing pigs when compared with the group fed the basal diet. In conclusion, dietary FC could be considered as a good source of supplementation in growing pigs because of its growth promoting effect.

A 5-wk trial with 96 ((Landrace× Yorkshire)×Duroc) pigs (BW = 26.56±0.42 kg) was conducted to investigate the effect of eugenol and cinnamaldehyde as feed additive in growing pigs. Pigs were assigned to 1 of 3 treatments in a randomized complete block design according to their sex and BW. Each treatment contained 8 replications with 4 pigs (2 gilts and 2 barrows) per pen. Treatments included: control (basal diet; CON); (basal diet+1,000 mg eugenol/kg; ET); (basal diet+1,000 mg cinnamaldehyde/kg; CT). Administration of eugenol and cinnamaldehyde did not did not affect (p>0.05) the growth performance and apparent total tract digestibility. Dietary CT and ET led to a higher (p<0.05) lymphocyte concentration compared with CON. The inclusion of CT and ET decreased (p<0.05) the fecal E. coli concentration (p>0.05). Pigs fed the diets supplemented with eugenol and cinnamaldehyde had reduced (p<0.05) NH3 and H2S concentration throughout the experiment. In conclusion, results obtained in the present study indicated that supplementation of eugenol and cinamaldehyde had no effect on growth performance of pigs but exhibited lymphocyte-enhancing activity and decreased the fecal E. coli concentration and fecal noxious gas content (NH3 and H2S).

Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.

Exposure of mice to the anesthetic gas nitrous oxide (N(2)O) produces a marked antinociceptive effect. Protein kinase C is a key regulatory enzyme that may be targeted by general anesthetics. However, a relationship between N(2)O-induced antinociception and protein kinase C has yet to be established. The present study was conducted to identify whether protein kinase C might influence N(2)O-induced antinociception in mice. Regular exposure (11 min) to N(2)O produced concentration-dependent antinociception in mice, as determined using the abdominal constriction test. N(2)O-induced antinociception was attenuated by i.c.v. pretreatment with phorbol 12,13-dibutyrate, a protein kinase C activator. This phorbol 12,13-dibutyrate antagonism of N(2)O-induced antinociception was reversed by i.c.v. pretreatment with calphostin C, a protein kinase C inhibitor. Long-term exposure (41 min in total, including 30 min prior to, and 11 min of analgesic testing) to 70% N(2)O produced reduced analgesic effects, compared with regular exposure to 70% N(2)O, thus indicating acute tolerance to N(2)O-induced antinociception. However, mice pretreated with calphostin C, chelerythrine, which is another protein kinase C inhibitor, and phorbol 12,13-dibutyrate, did not develop acute tolerance. Regarding activation of protein kinase C, regular exposure to 70% N(2)O did not increase protein kinase C within the membrane fraction of brain tissue, as determined by immunoblot analysis, but long-term exposure to 70% N(2)O did. The i.c.v. pretreatment with calphostin C and phorbol 12,13-dibutyrate prevented the increase in protein kinase C observed with long-term exposure to 70% N(2)O. These results suggest that brain protein kinase C negatively regulates the antinociceptive effect of N(2)O, and that activation of brain protein kinase C is related to the development of acute tolerance to N(2)O-induced antinociception in mice.

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug that reportedly reduces the risk of Alzheimer's disease (AD) development. The anti-inflammatory effect of ibuprofen occurred via inhibition of cyclooxygenases and anti-amyloidogenesis through modulation of γ-secretase. Presenilin 1 and 2 conditional double-knockout (cDKO) mice exhibited age-dependent memory impairment and forebrain degeneration without elevation of amyloid β deposition. Therefore, cDKO mice can be an ideal animal model on which to independently test the effects of ibuprofen anti-inflammatory properties on the prevention of AD. Three- and six-month-old cDKO mice were fed diet containing 375 ppm ibuprofen for six months. After multiple, well-validated behavioral tests, treatment with ibuprofen improved cognition-related behavioral performance, and drug efficacy was correlated with the timing of administration. Ibuprofen was more effective on six-month-old than on three-month-old cDKO mice. Biochemical analysis demonstrated that the effects of ibuprofen on glial fibrillary acidic protein and CD68 expression levels were uneven in different brain regions of cDKO mice and that age also influenced such effects. Tau hyperphosphorylation and the cleavage of caspase-3 decreased after ibuprofen treatment, and this effect was more significant in the older than the younger group of mice, which was consistent with the results of behavioral tests.

Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRASG12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older). KRASG12D overexpression in these cells activated transforming growth factor-β signaling and expression of CDKN2B, which, along with CDKN2A, led to cellular senescence and protected cells from KRAS-mediated transformation via inhibition of retinoblastoma phosphorylation. These results show a critical role of CDKN2B inactivation in pancreatic carcinogenesis, and provide a useful adult animal model by genetic engineering via lentiviral delivery.

This experiment was conducted to investigate the effects of different corn particle sizes on growth performance, gastrointestinal development, carcass processing yields and intestinal microbiota of caged broilers. One-day-old Ross 308 broilers were randomly divided into 8 treatments with 10 replicates per treatment and 30 birds per replicate pen. The experiment lasted 37 d. Feed and water were provided ad libitum. The results showed as follows: birds fed diets with the FG corn between d 1 and 13 and CG corn between d14 to 37 had increased body weight, daily gain, and feed intake (P < 0.05). Birds fed diets with CG corn between d 24 to 37 had a heavier relative weight of gizzard at d 38 (P < 0.05). Birds fed diets with FG corn from d 1 to 13 and the CG corn from d 14 to 37 had a higher carcass yield and a relative thigh weight at d 38 (P < 0.05). The intestinal microbiota was significantly affected by different corn particle sizes. The relative abundance of Lactobacillaceae was significantly decreased, whereas that of Peptostreptococcaceae was increased (P < 0.05) in birds fed with the CG corn between d1 to 37. The relative abundance of Acinetobacter was significantly increased in birds fed the FG corn between d1 to 37 (P < 0.05). In conclusion, the use of FG corn in the starter phase and CG corn in the grower and finisher phases was beneficial to growth performance, gastrointestinal development and intestinal microbial structure of broilers reared in cages.

A total of 144 ((Duroc×Yorkshire)×Landrace)) pigs with an average initial BW of 28.85±0.63 kg were used in this 6-wk growth trial. Pigs were randomly allotted to 1 of 4 treatments in a completely random block design. Each dietary treatment consisted of 9 replicate pens, with 4 pigs per replicate. Dietary treatments included: i) NC (basal diet), ii) PC (NC+apramycin 0.5 g/kg), iii) BPT1 (NC+bacteriophage 0.25 g/kg) and iv) BPT2 (NC+bacteriophage 0.5 g/kg). The inclusion of antibiotics and bacteriophages did not affect the (p>0.05) ADG, ADFI and G:F compared with the basal diet. Dietary antibiotics and bacteriophages supplementation led to a higher (p<0.05) DM digestibility than the NC treatment. Pigs fed the bacteriophage supplemented diet increased (p<0.05) the N digestibility compared with those fed NC treatment. Supplementation of antibiotics led to a higher (p<0.05) energy digestibility than the NC treatment. No difference (p>0.05) was observed in the RBC, WBC, lymphocyte concentration and fecal moisture among treatments. Pigs fed PC and BPT2 treatments reduced (p<0.05) the E. coli concentration compared with those fed NC treatment. The inclusion of BPT2 treatment led to a higher (p<0.05) lactobacillus concentration compared with NC and PC treatment. Dietary antibiotic and bacteriophage supplementation reduced (p<0.05) the Salmonella concentration compared with NC treatment. In conclusion, our study suggested that bacteriophage at the level of 0.5 g/kg could be used as an antibiotics alternative for growing pigs.

Vernalization genes determine winter/spring growth habit in temperate cereals and play important roles in plant development and environmental adaptation. In wheat (Triticum L. sp.), it was previously shown that allelic variation in the vernalization gene VRN1 was due to deletions or insertions either in the promoter or in the first intron. Here, we report a novel Vrn-B1 allele that has a retrotransposon in its promoter conferring spring growth habit. The VRN-B1 gene was mapped in a doubled haploid population that segregated for winter-spring growth habit but was derived from two spring tetraploid wheat genotypes, the durum wheat (T. turgidum subsp. durum) variety 'Lebsock' and T. turgidum subsp. carthlicum accession PI 94749. Genetic analysis revealed that Lebsock carried the dominant Vrn-A1 and recessive vrn-B1 alleles, whereas PI 94749 had the recessive vrn-A1 and dominant Vrn-B1 alleles. The Vrn-A1 allele in Lebsock was the same as the Vrn-A1c allele previously reported in hexaploid wheat. No differences existed between the vrn-B1 and Vrn-B1 alleles, except that a 5463-bp insertion was detected in the 5'-UTR region of the Vrn-B1 allele. This insertion was a novel retrotransposon (designated as retrotrans_VRN), which was flanked by a 5-bp target site duplication and contained primer binding site and polypurine tract motifs, a 325-bp long terminal repeat, and an open reading frame encoding 1231 amino acids. The insertion of retrotrans_VRN resulted in expression of Vrn-B1 without vernalization. Retrotrans_VRN is prevalent among T. turgidum subsp. carthlicum accessions, less prevalent among T. turgidum subsp. dicoccum accessions, and rarely found in other tetraploid wheat subspecies.

Several studies have reported that HLA-DRB1 may be correlated with pemphigus vulgaris (PV), but most have been based on small samples and the results remain inconsistent and unclear.

The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.