Two experiments were conducted to determine the efficiency of utilizing SID Lys and Thr for whole-body protein retention (kSIDLys and kSIDThr) in pregnant gilts. In Exp. 1, 45 gilts (158.0 ± 8.0 kg at day 39.4 ± 1 of gestation) in 2 groups were used in a 3-period nitrogen (N)-balance study. Gilts were assigned to 1 of 4 diets set to provide 60, 70, 80, and 90% of predicted daily SID Lys requirement for protein retention (NRC, 2012) in each of early (day 41 to 52, 10.44 g/d), mid- (day 68 to 79, 9.60 g/d), and late gestation (day 96 to 107, 16.04 g/d). Diets contained 3,300 kcal ME/kg and 11.6% CP; given at a rate of 2.13 kg/d in early and mid-gestation and at 2.53 kg/d during late gestation. The 12-d balance period (7-d adaptation; 5-d urine and fecal collection) was based on total urine collection using urinary catheters and determination of fecal N digestibility using indigestible marker. The SID Lys required for whole-body protein retention was estimated using the NRC (2012) model and the predicted Lys content of each gestation pool. Lysine efficiency at each diet Lys level was calculated as the ratio of daily Lys retention and SID Lys intake. The linear and quadratic response in whole-body N and Lys retention and Lys efficiency for each balance period was determined. The kSIDLys was determined from the slope generated by regressing whole-body Lys retention vs. SID Lys intake, with y-intercept set to 0. In Exp. 2, 45 gilts (165.7 ± 13.6 kg at day 39.1 ± 2 of gestation) were assigned to 1 of 4 diets set to provide 60, 70, 80, and 90% of the predicted daily SID Thr requirement for protein retention in each of early (6.46 g/d), mid- (6.05 g/d), and late gestation (9.75 g/d). Animal management, N-balance procedure, data collection and calculation, and statistical analyses were patterned from Exp. 1. In early and mid-gestation, whole-body N retention, as well as Lys and Thr retention, was not affected by the dietary SID Lys and Thr. In late gestation, there was a linear increase (P < 0.001) in whole-body N, Lys and Thr retention. The kSIDLys and kSIDThr in late gestation were determined to be 0.54. The lack of response in whole-body protein retention in early and mid-gestation may in partly reflect excess Lys and Thr intake. Lysine and Thr efficiency calculated at the lowest dietary Lys and Thr was 0.49 and 0.32 in early gestation and 0.61 and 0.52 in mid-gestation, respectively. Based on the available evidence, kSIDLys and kSIDThr do not appear to be constant throughout gestation.
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http://dx.doi.org/10.1093/jas/skz169 | DOI Listing |
Mol Ther
January 2025
Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai, China, 200241. Electronic address:
CAR T-cell therapy has achieved remarkable clinical success in treating hematological malignancies. However, its clinical efficacy in solid tumors is less satisfactory, partially due to poor in vivo expansion and limited persistence of CAR-T cells. Here, we demonstrated that the overexpression of glucocorticoid-induced tumor necrosis factor receptor-related protein ligand (GITRL) enhances the anti-tumor activity of CAR-T cells.
View Article and Find Full Text PDFRheumatology (Oxford)
January 2025
Nephrology Center and Department of Rheumatology, Toranomon Hospital, Tokyo, Japan.
Objectives: To evaluate the efficacy and safety of first-line targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD).
Methods: This retrospective cohort study included 216 patients with RA prescribed their first tsDMARDs at two hospitals between 2013 and 2022. Dose reduction and contraindication guidelines for tsDMARDs according to kidney function were followed.
Pharmaceutics
January 2025
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Acute liver injury (ALI) is a prevalent and potentially lethal condition globally, where pharmacotherapy plays a vital role. However, challenges such as rapid drug excretion and insufficient concentration at hepatic lesions often impede the treatment's effectiveness. We successfully prepared glycyrrhizinate monoammonium cysteine (GMC)-loaded lipid nanoparticles (LNPs) using high-pressure homogenization.
View Article and Find Full Text PDFMolecules
January 2025
Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
In recent years, the near-infrared (NIR) fluorescence theranostic system has garnered increasing attention for its advantages in the simultaneous diagnosis- and imaging-guided delivery of therapeutic drugs. However, challenges such as strong background fluorescence signals and rapid metabolism have hindered the achievement of sufficient contrast between tumors and surrounding tissues, limiting the system's applicability. This study aims to integrate the pegylation strategy with a tumor microenvironment-responsive approach.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Rare Diseases, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland.
Circular RNAs (circRNAs) are a class of unique transcripts characterized by a covalently closed loop structure, which differentiates them from conventional linear RNAs. The formation of circRNAs occurs co-transcriptionally and post-transcriptionally through a distinct type of splicing known as back-splicing, which involves the formation of a head-to-tail splice junction between a 5' splice donor and an upstream 3' splice acceptor. This process, along with exon skipping, intron retention, cryptic splice site utilization, and lariat-driven intron processing, results in the generation of three main types of circRNAs (exonic, intronic, and exonic-intronic) and their isoforms.
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