The effect on mouse immune systems of cow's colostrum produced 6 to 7 days after parturition

Five-week-old male mice were divided into 2 groups in which they were orally given sterile saline solution (control solution) or cow's colostrum powder prepared from milk produced 6 to 7 days after parturition in sterile saline solution (colostrum solution). The mice were given the solution once a day for 5 weeks. The level of intestinal total IgG was significantly lower in the mice given the colostrum solution than in the mice given the control solution, and the intestinal IgA and serum IgG levels tended to be lower in the mice given the colostrum solution. The numbers of spleen CD11b(+), CD19(+), and IFN-gamma(+)CD4(+) cells were also significantly lower in mice given the colostrum solution. DNA microarray analysis of mRNAs extracted from Peyer's patch cells showed that the gene expression of proteins relating to T cell activation of acquired immune responses or Fc epsilon-mediated mast cell activation was obviously lower in the mice given the colostrum solution than in the mice given the control solution, whereas that of proteins relating to T regulatory cells or intestinal innate immune system was noticeably higher in mice given the colostrum solution. These results suggest that the oral ingestion of cow's colostrum suppresses the acquired immune system and type I allergic reactions, and enhances the innate immune system.ArticleMILCHWISSENSCHAFT-MILK SCIENCE INTERNATIONAL. 65(1):11-15 (2010)journal articl

Protective role of ALDH2 against acetaldehyde-derived DNA damage in oesophageal squamous epithelium.

Acetaldehyde is an ethanol-derived definite carcinogen that causes oesophageal squamous cell carcinoma (ESCC). Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that eliminates acetaldehyde, and impairment of ALDH2 increases the risk of ESCC. ALDH2 is produced in various tissues including the liver, heart, and kidney, but the generation and functional roles of ALDH2 in the oesophagus remain elusive. Here, we report that ethanol drinking increased ALDH2 production in the oesophagus of wild-type mice. Notably, levels of acetaldehyde-derived DNA damage represented by N(2)-ethylidene-2'-deoxyguanosine were higher in the oesophagus of Aldh2-knockout mice than in wild-type mice upon ethanol consumption. In vitro experiments revealed that acetaldehyde induced ALDH2 production in both mouse and human oesophageal keratinocytes. Furthermore, the N(2)-ethylidene-2'-deoxyguanosine levels increased in both Aldh2-knockout mouse keratinocytes and ALDH2-knockdown human keratinocytes treated with acetaldehyde. Conversely, forced production of ALDH2 sharply diminished the N(2)-ethylidene-2'-deoxyguanosine levels. Our findings provide new insight into the preventive role of oesophageal ALDH2 against acetaldehyde-derived DNA damage

Preclinical Validation of Talaporfin Sodium-Mediated Photodynamic Therapy for Esophageal Squamous Cell Carcinoma

<div><p>Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.</p></div