Search

Objective: We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status.Design: Descriptive review conducted on English publications reporting breast-milk DHA and AA levels.Setting: We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included.Subjects: Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals.Results: Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, P<0·05). Data from the Asian region showed the highest DHA concentration but much lower AA concentration in breast milk compared with all other regions, independent of accessibility to marine foods. Comparison was made among Canada, Poland and Japan - three typical countries (each with sample size of more than 100 women) from different regions but all with high income and similar accessibility to fish/marine foods.Conclusions: The current review provides an update on worldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations. [ABSTRACT FROM AUTHOR]

The activation of stimulator of interferon genes (STING) signaling pathways plays an important role in the innate immune response. Although several STING agonists have been developed recently, the majority of clinical CDN STING agonists are administered by intratumoral (IT) injection. Therefore, there remains a need to develop diverse non-CDN small-molecule STING agonists with systemic administration. Herein, by using a scaffold hopping strategy, we designed a series of thieno [2,3-d]imidazole derivatives as novel STING agonists. Further structure-activity relationship study and optimization led to the discovery of compound 45 as a highly potent human STING agonist with an EC 50 value of 1.2 nM. Compound 45 was found to bind to multiple human STING isoforms and accordingly activated the downstream TBK1/IRF3 and NF-κB signaling pathways in the reporter cells bearing with different STING isoforms. The activation on STING signaling pathway was abolished in the STING knock-out cells, indicating that it is a specific STING agonist. Compound 45 significantly inhibited the tumor growth in allograft 4T1 and CT26 tumor models by systemic administration, and more significantly, 45 was able to induce tumor regression in CT26 tumor model without inducing weight loss, suggesting that compound 45 is a highly promising candidate worthy for further development. [Display omitted] • A series of thieno [2,3-d]imidazole derivatives were designed as STING agonists. • 45 was able to activate h-STING isoforms and m-STING. • 45 was identified as a highly potent h-STING agonist with an EC 50 value of 1.2 nM. • Intravenous or intratumoral administration of 45 could inhibit tumor growth dramatically, without inducing weight loss. [ABSTRACT FROM AUTHOR]