Search

The aim of this study was to investigate the distribution, tolerance, and anticancer and antiviral activity of Zn-based physiometacomposites (PMCs). Manganese, iron, nickel and cobalt-doped ZnO, ZnS or ZnSe were synthesized. Cell uptake, distribution into 3D culture and mice, and biochemical and chemotherapeutic activity were studied by fluorescence/bioluminescence, confocal microscopy, flow cytometry, viability, antitumor and virus titer assays. Luminescence and inductively coupled plasma mass spectrometry analysis showed that nanoparticle distribution was liver >spleen >kidney >lung >brain, without tissue or blood pathology. Photophysical characterization as ex vivo tissue probes and LL37 peptide, antisense oligomer or aptamer delivery targeting RAS/Ras binding domain (RBD) was investigated. Treatment at 25 μg/ml for 48 h showed ≥98–99% cell viability, 3D organoid uptake, 3-log inhibition of β-Galactosidase and porcine reproductive respiratory virus infection. Data support the preclinical development of PMCs for imaging and delivery targeting cancer and infectious disease.

Goblet cell hyperplasia is an important manifestation of cystic fibrosis (CF) disease in epithelial-lined organs. Explants of CF airway epithelium show normalization of goblet cell numbers; therefore, we hypothesized that small intestinal enteroids from Cftr knockout (KO) mice would not exhibit goblet cell hyperplasia. Toll-like receptors 2 and 4 (Tlr2 and Tlr4) were investigated as markers of inflammation and influence on goblet cell differentiation. Ex vivo studies found goblet cell hyperplasia in Cftr KO jejunum compared with wild-type (WT) mice. IL-13, SAM pointed domain-containing ETS transcription factor (Spdef), Tlr2, and Tlr4 protein expression were increased in Cftr KO intestine relative to WT. In contrast, WT and Cftr KO enteroids did not exhibit differences in basal or IL-13-stimulated goblet cell numbers, or differences in expression of Tlr2, Tlr4, and Spdef. Ileal goblet cell numbers in Cftr KO/Tlr4 KO and Cftr KO/Tlr2 KO mice were not different from Cftr KO mice, but enumeration was confounded by altered mucosal morphology. Treatment with Tlr4 agonist LPS did not affect goblet cell numbers in WT or Cftr KO enteroids, whereas the Tlr2 agonist Pam3Csk4 stimulated goblet cell hyperplasia in both genotypes. Pam3Csk4 stimulation of goblet cell numbers was associated with suppression of Notch1 and Neurog3 expression and upregulated determinants of goblet cell differentiation. We conclude that goblet cell hyperplasia and inflammation of the Cftr KO small intestine are not exhibited by enteroids, indicating that this manifestation of CF intestinal disease is not epithelial-automatous but secondary to the altered CF intestinal environment. NEW & NOTEWORTHY Studies of small intestinal organoids from cystic fibrosis (CF) mice show that goblet cell hyperplasia and increased Toll-like receptor 2/4 expression are not primary manifestations of the CF intestine. Intestinal goblet cell hyperplasia in the CF mice was not strongly altered by genetic ablation of Tlr2 and Tlr 4, but could be induced in both wild-type and CF intestinal organoids by a Tlr2-dependent suppression of Notch signaling.

Resveratrol is a polyphenol that is safe to administer to dogs and has immunomodulating properties. Canine in vitro work indicated that resveratrol spared polymorphonuclear cell (PMN) phagocytosis but reduced the robustness of PMN oxidative burst and resulted in a pro-inflammatory leukocyte cytokine profile. The objective of this study was to determine the short-term effect of resveratrol on the healthy canine innate immune system in vivo. The hypothesis was that resveratrol would spare phagocytosis, depress the vigor of PMN oxidative burst, and result in a proinflammatory stimulated leukocyte cytokine profile in vivo. In an open-label study, whole blood was collected from 12 healthy, adult client-owned dogs on day 0 and 3. Six dogs received resveratrol, 200 mg kg−1, orally once daily for three days and six dogs served as controls with no supplement administered. Phagocytosis, oxidative burst and pathogen associated molecular pathogen stimulated leukocyte production of tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 were measured. Results between days 0 and 3 were compared using two way repeated measures analysis of variance and Fisher least significant difference method. A P -value of