D-mannose Dimer Introduced Human Recombinant Interleukin-1α, NEO IL-1α, Exhibits Altered Tissue Distribution in Mice

Abstract

Previous studies have demonstrated that the carbohydrate-introduced recombinant human IL-l alpha exhibited impairment in both biologic activities in all the experiments in vitro and receptor binding capacity compared with intact IL-l alpha. However, the glycosylated IL-l alpha exhibited selective activities in vivo. In this study, we compared the tissue distribution of IL-l alpha and IL-l alpha coupled with D-Mana (l-6)Man [Man2 alpha) (l-6)IL-l alpha] in mice. Mice were injected by intravenous and intraperitoneal routes with 2.0 mu g radiolabeled IL-l alpha. At 1 and 2 h after IP injection, the level of Man2 alpha) (l-6)IL-l alpha decreased twofold compared with that of IL-l alpha in kidney. In contrast, at 1 hour after administration, Man2 alpha) (l-6)IL-l alpha exhibited higher levels than IL-l alpha in blood, heart, and liver. No significant difference was observed in brain at each time point. IV injection demonstrated that Man2 alpha)(l-6)IL-l alpha decreased to approximately one-half the level of rhIL-l alpha in kidney. In contrast, Man(2 alpha) (l-6)IL-l alpha increased twofold over that of IL-l alpha in liver at 1 h after dosing. These findings are consistent with the result of IP injection. There was no significant difference between IL-l alpha and glycosylated IL-l alpha at 4 h after IV administration. These differences in tissue distribution may contribute to the selective activities of glycosylated IL-l alpha in vivo. The results also suggest that by coupling with mannose dimer, it is possible to develop neocytokines prone to liver distribution.

High-Throughput RNA Sequencing Reveals NDUFC2-AS lncRNA Promotes Adipogenic Differentiation in Chinese Buffalo (Bubalus bubalis L.)

“…A total of 21,693 mRNAs were obtained, 2008 of which were identified as DE mRNAs in both groups (1021 up- and 987 downregulated) (Table S4). Well-known adipogenesis markers, such as the peroxisome proliferator-activated receptor gamma (PPARG) [25], lipoprotein lipase (LPL) [26], and thyroid hormone responsive protein (THRSP) [27] were consistently upregulated in the adult group, which is to be expected given the animals development of adipose tissue at this age. For lncRNAs prediction, a total of 9494 lncRNAs were obtained (Table S5), including 6512 intergenic lncRNAs (69%), 625 intronic lncRNAs (7%), 584 antisense lncRNAs (6%), 114 bidirectional lncRNAs (1%), and 1659 unclassified lncRNAs (17%) (Figure 1b).…”

N-acetylneuraminic acid coupled human recombinant TNFα exhibits enhanced anti-tumor activity against Meth-A fibrosarcoma and reduced toxicity

“…Man 2 (1-6)-IL-1 exhibited comparable activities to nonglycosylated IL-1 in the down-regulation of the serum level of glucose and the recovery of peripheral white blood cells from myelosuppression in 5-Xuorouracil-treated mice, irrespective of the decrease of all other activities in vivo [13]. In addition, the tissue distribution of Man 2 (1-6)-IL-1 in mice diVered from that of nonglycosylated IL-1 [14]. D-Gal-conjugated IL-1 exhibited a decrease in all the activities in vivo with a similar magnitude [16].…”

“…In the previous studies, we have synthesized neoglyco human IL-1 by conjugating human recombinant IL-1 a variety of carbohudrates, including D-Man (1-6)Man [Man 2 (1)(2)(3)(4)(5)(6)], Gal or N-acetylneuraminic acid (NeuAc), a major constituent of sialic acid [12][13][14][15][16][17][18][19]. Although these carbohydrate-conjugated IL-1 variants exhibited reduced activities in vitro, the activities in vivo were diVerent depending on the type of carbohydrates [12,15,18].…”

Selection and validation of suitable reference genes in adipose tissue of Jianzhou Da'er Goat (Capra hircus)

“…The ACTB was the most frequently used reference gene in human adipose tissue, while the HSP90 and ALAS1 were found to be the most stable reference genes in adipose tissue of the native Iranian goat (Capra hircus), and the UXT, EIF3K, and RPLP0 were suggested to be the most stable reference genes in bovine (Bovine) subcutaneous and alpine caprine (Capra hircus) omental adipose tissue (Gabrielsson et al 2005;Bonnet et al 2013;Najafpanah et al 2013). Additionally, four lipid metabolism-related genes, including the fatty acid synthase (FASN), hormone-sensitive lipase (HSL), lipoprotein lipase (LPL), and phosphotyrosine interaction domain containing 1 (PID1), were selected as the target genes and their main functions were listed in Table 1 (Wakil 1989;Goldberg 1996;Schweiger et al 2006;Yin et al 2019).…”

“…In the present paper, we selected six housekeeping genes involved in different biological processes as candidate reference genes, including the ACTB, ALAS1, EIF3K, HSP90, RPLP0, and UXT. Also, the FASN, HSL, LPL, and PID1, which were found to play crucial roles in lipid metabolism processes, were considered as the target genes (Wakil 1989;Goldberg 1996;Schweiger et al 2006;Yin et al 2019). Subsequently, the expression levels of selected genes were detected by the RT-qPCR technique in abdominal and dorsal adipose of Jianzhou da'er goat, respectively.…”