Effects of dietary supplementation with a carvacrol-cinnamaldehyde-thymol blend on growth performance and intestinal health of nursery pigs.

BACKGROUND: Stress, herd transfer, and food changes experienced by nursery and fattening pigs can lead to reduced performance, reduced digestion and absorption, and impaired intestinal health. Given the role of essential oils in relieving stress and improving animal welfare, we hypothesized that essential oils may improve pig performance via promoting gut health and gut homeostasis laid by EOs supplementation during nursery continuously impacts performance in fattening pigs. RESULTS: A total of 100 piglets (Landrace × Large White; weighted 8.08 ± 0.34 kg, weaned at d 28) were randomly selected and divided into 2 treatments: (1) basal diet (Con); (2) basal diet supplement with 0.1% complex essential oils (CEO). The experiment period was 42 days. Then weaned piglets' growth performance and indications of intestinal health were assessed. Compared to the Con group, dietary supplemented CEO enhanced BW at 14 d (P < 0.05), and increased ADG during 1 ~ 14 d and 1 ~ 42 d (P < 0.05). Furthermore, CEO group had lower FCR during 1 ~ 42 d (P < 0.05). The CEO group also showed higher VH and VH:CD in duodenum and ileum (P < 0.05). Additionally, dietary CEO supplementation improved gut barrier function, as manifested by increased the mRNA expression of tight-junction protein and decreased serum DAO, ET and D-LA levels (P < 0.05). Finally, CEO supplementation alleviated gut inflammation, increased the activity of digestive enzymes. Importantly, piglets supplemented with CEOs during nursery also had better performance during fattening, suggesting that the establishment of intestinal health will also continuously affect subsequent digestion and absorption capacity. In short, dietary supplemented CEO improved performance and gut health via modulating increased intestine absorptive area, barrier integrity, digestive enzyme activity, and attenuating intestine inflammation. Meanwhile, essential oil supplementation during the nursery period also had a favorable effect on the performance of growing pigs. CONCLUSIONS: Therefore, the strategy of adding CEO to pig diets as a growth promoter and enhancing intestinal health is feasible.

Keratin 8 reduces colonic permeability and maintains gut microbiota homeostasis, protecting against colitis and colitis-associated tumorigenesis.

Keratin 8 (CK8) is the major component of the intermediate filaments of simple or single-layered epithelia. Gene targeting mice model suggest that CK8 is involved in colonic active ion transport, colorectal hyperplasia and inflammation. In the present study, we found that CK8 is downregulated in the colon during DSS-induced colitis and AOM/DSS-induced colitis-associated colorectal cancer (CAC) development. In human patients with colon cancer, CK8 is downregulated. Using CK8 heterozygous knockout mice (CK8+/-), we found that CK8+/- mice are highly susceptible to DSS-induced colitis and more prone to AOM/DSS-induced CAC than wild type (WT) mice. The colonic permeability is increased with DSS or AOM/DSS treatment, leading to alteration of gut microbiota in CK8+/- mice with CAC. Metagenomic analysis of fecal microbiota suggests Firmicutes and Proteobacteria are increased in CK8+/- mice with CAC, while Bacteroidetes and Verrucomicrobia are decreased. Antibiotic treatment decreases the incidence of colorectal cancer tumorigenesis and TLR4 inhibitor attenuates the susceptibility of CK8+/- mice to DSS-induced colitis. These data suggest CK8 protects mice from colitis and colitis-associated colorectal cancer by modulating colonic permeability and gut microbiota composition homeostasis.

Malaria from hyperendemicity to elimination in Hekou County on China-Vietnam border: an ecological study.

BACKGROUND: Malaria control and elimination are challenged by diversity and complexity of the determinants on the international border in the Great Mekong Sub-region. Hekou, a Chinese county on the China-Vietnam border, was used to document Chinese experiences and lessons for malaria control and elimination. METHODS: The design was an ecological study. Malaria burden before 1951 and procedures of 64 years (1952-2015) from malaria hyperendemicity to elimination are described. Single and bilinear regression analysis was utilized to analyse the relationship between the annual malaria incidence (AMI) and gross domestic product (GDP), urbanization rate, and banana planting area (BPA). RESULTS: There was a huge malaria burden before 1951. AMI was reduced from 358.62 per 1000 person-years in 1953 to 5.69 per 1000 person-years in 1960. A system of primary health services, comprising three levels of county township hospitals and village health stations maintained malaria control and surveillance activities in changing political and social-economic settings. However, potential under-reported of malaria and market-oriented healthcare led to a malaria epidemic in 1987. Strong political commitment reoriented malaria from a control to an elimination programme. High coverage of malaria intervention and population access to intervention was crucial for malaria control and elimination; meanwhile, AMI was closely associated with socio-economic development, correlation coefficients (R) -0.6845 (95% CI -0.7978, -0.6845) for national GDP, -0.7014 (-0.8093, -0.7014) for national urbanization rate and -0.5563 (-0.7147, -0.3437) for BPA. CONCLUSIONS: Multifactor, including political commitment, effective interventions, social and economic development and changing ecological environment, and the complicated interactions between these factors contribute to malaria elimination in Hekou County.

Thrombospondin 1 Modulates Monocyte Properties to Suppress Intestinal Mucosal Inflammation.

Monocytes (Mos) play an important role in the pathogenesis of intestinal mucosal inflammation. This study aims to investigate the mechanism by which the intestinal epithelial cell-derived thrombospondin 1 (TSP1) modulates Mo properties and regulates intestinal inflammatory responses. In this study, the production of TSP1 by intestinal epithelial cells was evaluated by quantitative real-time PCR and Western blotting. The properties of Mos were analyzed by flow cytometry. A mouse model of colitis was created to assess the role of epithelium-derived TSP1 in the suppression of intestinal inflammation. The results demonstrated that mouse intestinal epithelial cells (IECs) expressed TSP1, which was markedly upregulated by butyrate or feeding with Clostridium butyricum. Coculture of the butyrate-primed IECs and Mos or exposure of Mos to TSP1 in the culture induced the expression of transforming growth factor (TGF)-ß in Mos. These TGF-ß+ Mos had tolerogenic properties that could promote generation of inducible regulatory T cells. Adoptive transfer with TSP1-primed Mos, or feeding C. butyricum could prevent experimental colitis in mice. In summary, C. butyricum induces intestinal epithelial cells to produce TSP1 and induces TGF-ß+ Mos, which further suppress experimental colitis in mice. The results implicate that the administration of C. butyricum or butyrate may have the potential to ameliorate chronic intestinal inflammation through inducing immunosuppressive Mos.

Effects of THAP11 on erythroid differentiation and megakaryocytic differentiation of K562 cells.

Hematopoiesis is a complex process regulated by sets of transcription factors in a stage-specific and context-dependent manner. THAP11 is a transcription factor involved in cell growth, ES cell pluripotency, and embryogenesis. Here we showed that THAP11 was down-regulated during erythroid differentiation but up-regulated during megakaryocytic differentiation of cord blood CD34+ cells. Overexpression of THAP11 in K562 cells inhibited the erythroid differentiation induced by hemin with decreased numbers of benzidine-positive cells and decreased mRNA levels of α-globin (HBA) and glycophorin A (GPA), and knockdown of THAP11 enhanced the erythroid differentiation. Conversely, THAP11 overexpression accelerated the megakaryocytic differentiation induced by phorbol myristate acetate (PMA) with increased percentage of CD41+ cells, increased numbers of 4N cells, and elevated CD61 mRNA levels, and THAP11 knockdown attenuated the megakaryocytic differentiation. The expression levels of transcription factors such as c-Myc, c-Myb, GATA-2, and Fli1 were changed by THAP11 overexpression. In this way, our results suggested that THAP11 reversibly regulated erythroid and megakaryocytic differentiation.

Expansion of the polyQ repeats in THAP11 forms intranuclear aggregation and causes cell G0/G1 arrest.

Polyglutamine diseases are a group of neurodegenerative disorders caused by expansion of a CAG repeat that encodes polyglutamine in each respective disease gene. The transcription factor THAP11, a member of THAP family, is involved in cell growth, ES cell pluripotency and embryogenesis. Previous studies suggest that THAP11 protein contains a 29-residue repeat polyglutamine motif and the number of polyglutamine ranges from 20 to 41 in Indian population. We have investigated the CAG numbers at the THAP11 locus in normal individuals and neurodegenerative disease patients of Chinese Han population and a 38Q expansion (THAP11(38Q)) was found in patients. Using fluorescence confocal-based cell imaging, THAP11(38Q) protein formed intranuclear inclusions easier than THAP11(29Q) in PC12 cells. Enhanced toxicity was investigated in THAP11(38Q)-expressing cells by growth inhibition and G0/G1 arrest. CREB-mediated transcription activity was inhibited by THAP11(38Q). The transcription factor, TBP, coactivator CBP, and chaperon protein, HSP70, could be recruited to THAP11(38Q). These results indicate that expansion of the polyglutamine in THAP11 forms intracellular aggregation and is toxic in PC12 cells, suggesting a putative role of THAP11 in polyglutamine disease.

Overlapped optics induced perfect coherent effects.

For traditional coherent effects, two separated identical point sources can be interfered with each other only when the optical path difference is integer number of wavelengths, leading to alternate dark and bright fringes for different optical path difference. For hundreds of years, such a perfect coherent condition seems insurmountable. However, in this paper, based on transformation optics, two separated in-phase identical point sources can induce perfect interference with each other without satisfying the traditional coherent condition. This shifting illusion media is realized by inductor-capacitor transmission line network. Theoretical analysis, numerical simulations and experimental results are performed to confirm such a kind of perfect coherent effect and it is found that the total radiation power of multiple elements system can be greatly enhanced. Our investigation may be applicable to National Ignition Facility (NIF), Inertial Confined Fusion (ICF) of China, LED lighting technology, terahertz communication, and so on.

Polydatin attenuated food allergy via store-operated calcium channels in mast cell.

AIM: To investigate the effect of polydatin (PD), a resveratrol glucoside, on mast cell degranulation and anti-allergic activity. METHODS: After the rats were orally sensitized with ovalbumin (OVA) for 48 d and underwent PD treatment for 4 d, all the rats were stimulated by 100 mg/mL OVA for 24 h and then sacrificed for the following experiments. The small intestines from all the groups were prepared for morphology examination by hematoxylin and eosin staining. We also used a smooth muscle organ bath to evaluate the motility of the small intestines. The OVA-specific immunoglobulin E (IgE) production and interleukin-4 (IL-4) levels in serum or supernatant of intestinal mucosa homogenates were analyzed by enzyme-linked immunosorbent assay (ELISA). Using toluidine blue stain, the activation and degranulation of isolated rat peritoneal mast cells (RPMCs) were analyzed. Release of histamine from RPMCs was measured by ELISA, and regulation of PD on intracellular Ca(2+) mobilization was investigated by probing intracellular Ca(2+) with fluo-4 fluorescent dye, with the signal recorded and analyzed. RESULTS: We found that intragastric treatment with PD significantly reduced loss of mucosal barrier integrity in the small intestine. However, OVA-sensitization caused significant hyperactivity in the small intestine of allergic rats, which was attenuated by PD administration by 42% (1.26 ± 0.13 g vs OVA 2.18 ± 0.21 g, P < 0.01). PD therapy also inhibited IgE production (3.95 ± 0.53 ng/mL vs OVA 4.53 ± 0.52 ng/mL, P < 0.05) by suppressing the secretion of Th2-type cytokine, IL-4, by 34% (38.58 ± 4.41 pg/mL vs OVA 58.15 ± 6.24 pg/mL, P < 0.01). The ratio of degranulated mast cells, as indicated by vehicles (at least five) around the cells, dramatically increased in the OVA group by 5.5 fold (63.50% ± 15.51% vs phosphate-buffered saline 11.15% ± 8.26%, P < 0.001) and fell by 65% after PD treatment (21.95% ± 4.37% vs OVA 63.50% ± 15.51%, P < 0.001). PD mediated attenuation of mast cell degranulation was further confirmed by decreased histamine levels in both serum (5.98 ± 0.17 vs OVA 6.67 ± 0.12, P < 0.05) and intestinal mucosa homogenates (5.83 ± 0.91 vs OVA 7.35 ± 0.97, P < 0.05). Furthermore, we demonstrated that administration with PD significantly decreased mast cell degranulation due to reduced Ca(2+) influx through store-operated calcium channels (SOCs) (2.35 ± 0.39 vs OVA 3.51 ± 0.38, P < 0.01). CONCLUSION: Taken together, our data indicate that PD stabilizes mast cells by suppressing intracellular Ca(2+) mobilization, mainly through inhibiting Ca(2+) entry via SOCs, thus exerting a protective role against OVA-sensitized food allergy.

A comparison of ARMS and direct sequencing for EGFR mutation analysis and tyrosine kinase inhibitors treatment prediction in body fluid samples of non-small-cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is strongly associated with the therapeutic effect of tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer (NSCLC). Nevertheless, tumor tissue that needed for mutation analysis is frequently unavailable. Body fluid was considered to be a feasible substitute for the analysis, but arising problems in clinical practice such as relatively lower mutation rate and poor clinical correlation are not yet fully resolved. METHOD: In this study, 50 patients (32 pleural fluids and 18 plasmas) with TKIs therapy experience and with direct sequencing results were selected from 220 patients for further analysis. The EGFR mutation status was re-evaluated by Amplification Refractory Mutation System (ARMS), and the clinical outcomes of TKIs were analyzed retrospectively. RESULTS: As compared with direct sequencing, 16 positive and 23 negative patients were confirmed by ARMS, and the other 11 former negative patients (6 pleural fluids and 5 plasmas) were redefined as positive, with a fairly well clinical outcome (7 PR, 3 SD, and 1 PD). The objective response rate (ORR) of positive patients was significant, 81.3% (direct sequencing) and 72.7% (ARMS) for pleural fluids, and 80% (ARMS) for plasma. Notably, even reclassified by ARMS, the ORR for negative patients was still relatively high, 60% for pleural fluids and 46.2% for plasma. CONCLUSIONS: When using body fluids for EGFR mutation analysis, positive result is consistently a good indicator for TKIs therapy, and the predictive effect was no less than that of tumor tissue, no matter what method was employed. However, even reclassified by ARMS, the correlation between negative results and clinical outcome of TKIs was still unsatisfied. The results indicated that false negative mutation still existed, which may be settled by using method with sensitivity to single DNA molecule or by optimizing the extraction procedure with RNA or CTC to ensure adequate amount of tumor-derived nucleic acid for the test.

[Erlotinib in the treatment of advanced non-small-cell lung cancer (NSCLC)].

OBJECTIVE: Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement of survival in non-small-cell lung cancer (NSCLC) after the failure of front-line chemotherapy. The aim of this study was to evaluate the antitumor efficacy and toxicity of Erlotinib in the treatment of advanced NSCLC patients. METHODS: A total of 104 patients with advanced NSCLC admitted in our department during December 2006 to November 2008 were enrolled in this study. Eligible patients received oral Erlotinib 150 mg/d until disease progression or intolerable toxicity. Best clinical response was determined using RECIST criteria, the adverse events were evaluated according to the NCI criteria. RESULTS: The total effective rate was 27.9% (29/104) and the clinical benefit was 76.0% (79/104). The median progression-free survival was 5.1 months (95%CI 4.0 - 8.0). The median survival time was 13.1 months (95%CI 10.0 - 15.7). The 1-year survival rate was 61.5%. Significant survival benefit from erlobinib therapy was observed for patients with good personal status (HR 0.56, P = 0.006), adenocarcinoma (HR 0.43, P = 0.004) and skin rash (HR 0.46, P = 0.005). But patients with smoking (HR 2.75, P < 0.001) and liver metastasis (HR 2.91, P = 0.002) add the risk of death. The adverse events were mild (grade < or = 2), most common toxicities were skin rash in 73.1% (76/104) and diarrhea in 41.3% (43/104). Only 6.7% (7/104) patients got adverse events of grade > or = 3. CONCLUSION: Erlotinib is an effective and well-tolerated treatment option for advanced NSCLC and could offer an alternative for patients after the failure of first-line chemotherapy, unsuitable for or not wishing to receive chemotherapy.

[Establishment of nonmyeloablative allogeneic stem cell transplantation model in H-2 haploidentical mice and its related study].

To explore the feasibility of nonmyeloablative conditioning regimens, hematopoietic reconstitution, chimera level and the occurrence of GVHD after nonmyeloablative allogeneic stem cell transplantation in H-2 haploidentical mice, CB6F1 mice were used as the recipient and were divided into 3 groups, mice were pretreated five days before transplantation. Group A was pretreated with myeloablative conditioning regimens (TBI with 10.5 Gy), group B was pretreated by TBI (2 Gy) + Ara-C + Cy and group C-TBI (2 Gy) + Ara-C + CY + Flu, respectively. For all recipient mice, the prevention of GVHD was not given, and 2 x 10(7) bone marrow cells mixed 1 x 10(7) spleen cells from C57BL/6 mice were injected through tail vein on day 0, and then hematopoietic recovery, engraftment and GVHD of recipients were observed. The results of chimera detection after transplantation showed that the engraftment of group A remained full donor chimerism, and engraftments of group B and group C were associated with mixed chimerism or full donor chimerism, but the chimerism of group B remained below 80% and tended to decrease after 50 days whereas chimerism of group C was above 80% (chimerism close to or being full donor type) and preserved even after 50 days. GVHD occurred in all the recipient mice due to that prevention was not given, wherein the occurrence and death rate of GVHD in group A was obviously higher than that of group B and group C (P <0.01), but there was no statistical difference between group B and group C. In conclusion, the nonmyeloablative conditioning regimens mainly based on fludarabine can form stable and lasting engraftment in the body of recipients. The mixed chimerism established in recipients induce tolerance of transplantation and decrease or avoid the occurrence of GVHD.