L-citrulline enriched fermented milk with Lactobacillus helveticus attenuates dextran sulfate sodium (DSS) induced colitis in mice.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory gastrointestinal diseases that causes worldwide suffering. L. helveticus is a probiotic that can enhance intestinal barrier function via alleviation of excessive inflammatory response. Citrulline, a functional amino acid, has been reported to stimulate muscle synthesis and to function with a prebiotic-like action with certain Lactobacillus strains. The aim of this study was to investigate the potential synergistic effect of combining L. helveticus and citrulline on protection against damage induced by dextran sulfate sodium (DSS) in a mouse model. 6-week-old male C57BL/6J mice were fed with DSS water and randomly divided for administering with different milk treatments: 1) plain milk (control or DSS control), 2) 1% (w/v) citrulline enriched milk (Cit_milk), 3) milk fermented with L. helveticus (LHFM) and 4) DSS+milk fermented with L. helveticus with 1% (w/v) citrulline (Cit_LHFM). The treatment effects on the survival and macroscopic and microscopic signs were examined. All treatments presented different degrees of protective effects on attenuating the damages induced by DSS. All treatments reduced the body weight loss, disease activity index (DAI), histological scores, pro-inflammatory cytokine expression (IL-6, TNF-α and IFN-γ) and production (IL-4) (all P <0.05) and the tight junction (TJ) protein (zonula occluden-1 (ZO-1) expression. LHFM and Cit_LHFM improved survival rate (both at P<0.05). Particularly, Cit_LHFM showed greater effects on protecting the damages induced by DSS, especially in ameliorating colonic permeability, TJ protein (ZO-1, occludin and claudin-1) expression and distribution as well as in reducing IL-4 and IL-17 expression (all P <0.05). Our findings suggested that the combination of and citrulline had significant synergistic effect on protecting against injury from DSS-induced colitis. Therefore, citrulline enriched L. helveticus fermented milk is suggested to be a potential therapy for treating IBD.

Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers.

The underlying basis for cancer immune evasion is important for effective immunotherapy and prognosis in breast cancers. Human leucocyte antigens (HLA)-I comprising three classical antigens (HLA-A, -B and -C) is mandatory for anti-tumor immunity. Its loss occurred frequently in many cancers resulting in effective immune evasion. Most studies examined HLA-I as a whole. Alterations in specific locus could have different clinical ramifications. Hence, we evaluated the expression of the three HLA-I loci in a large cohort of breast cancers. Low expression of HLA-A, -B and -C were found in 71.1%, 66.3%, and 60.2% of the cases. Low and high expression in all loci was found in 48.3% and 17.9% of the cases respectively. The remaining showed high expression in one or two loci. Cases with all HLA high expression (all HLA high) was frequent in the ER-HER2- (27.4%) and ER-HER2+ (23.1%) cases and was associated with characteristic pathologic features related to these tumor (higher grade, necrosis, high tumor infiltrating lymphocyte (TIL), pT stage, low hormonal receptor, high basal marker expression) (p ≤ 0.019). Interestingly, in HER2+ cancers, only cases with all HLA high and high TIL showed significantly better survival. In node positive cancers, concordant high HLA expression in primary tumors and nodal metastases was favorable prognostically (DFS: HR = 0.741, p < 0.001; BCSS: HR = 0.699, p = 0.003). The data suggested an important clinical value of a combined analysis on the co-expression HLA-I status in both primary and metastatic tumors. This could be a potential additional key component to be incorporated into TIL evaluation for improved prognostication.