LF-A and LF-A/X showed enhanced toxicity as compared to LF-HMA in macrophage cytotoxicity assays (Fig. 2A, Table 1).
All individual values are expressed as a fold change compared to LF diet at the 2 week time point.
The destabilizing residue Phe clearly had a large impact on toxin activity, as the EC50 was increased ∼6-fold compared to LF with the most stabilizing residue, Met (Table 1).
In each case, we used twice the amount of PA compared to LF or EF.
Data collected over several years in our laboratory indicated that purified LF-HMA, either made in our laboratory or purchased from List Laboratories, was less toxic in macrophage toxicity assays when compared to LF purified from the B. anthracis Sterne strain.
MiR-182 showed marked over-expression, as detected already after 3 months of treatment, whereas miR-125a-5p miR-125a-5p miR-125a-5ped in HF compared to LF tissues.
LDLR-/ mice on both high fat diets (HFSC or HFC) developed extensive hepatic steatosis, compared to LF-fed lean controls after 16 as well as 20 weeks of feeding (Additional file 5: Figure S3).
The overall respiratory quotient (RQ) of LF-fed AOiGHD was significantly elevated compared to LF-fed controls (Fig. 5A B, middle panels; note right shift in the percent relative cumulative frequency distribution [PRCF] of RQs, 50th percentile LF-controls RQ 0.829 vs. LF-AOiGHD RQ 0.893, p<0.001) and this difference was more pronounced during the absorptive state (night-time feeding).
The improvement following HF-NMES was significantly higher compared to LF-NMES (p = 0.005).
In this particular case, HPMCAS-HF containing HME provided the highest bioavailability and also had better physical stability as compared to extrudates using HPMCAS-LF and copovidone.
In agreement, cells of the intestinal villi of mice fed the Fe-Lf diet contained high levels of Lf, as compared to mice fed the control diet.
