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Radionuclide-based Diagnosis and Therapy of Prostate Cancer
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Sven-Erik Strand, Mohamed Altai, Joanna Strand, David Ulmert
Amino acids are essential to cell metabolism and growth. Several amino acid transporter systems are overexpressed in PCa. Anti-1-amino-3-[18F]Flurocyclobutane-1-carboxylic acid (18F-fluciclovine-FACBC) is a non-naturally occurring amino acid, and its transport is primarily mediated by sodium-dependent amino acid transporters. Because the amino acid transporters that are most involved in 18F-fluciclovine transport mediate influx and efflux of amino acids, washout of the radiotracer occurs over time. The specificity of 18F-fluciclovine for PCa relies on altered metabolic pathways overexpressed in PCa. Studies have shown a detection rate of 40 per cent for patients with biochemical recurrence and a PSA level of 0.79 ng/mL or less. Direct comparison between 18F-fluciclovine and 11C-choline PET/CT has demonstrated overall superior imaging performance for 18F-fluciclovine in biochemically recurrent PCa. A good overview of 18F-Fluciclovine is found in Parent and Schuster and colleagues [71].
Placental transport and metabolism
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
In vitro studies demonstrating alterations in amino acid transport have served as a prelude to a variety of in vivo investigations attempting to extend in vitro findings. While the numbers of patients in these studies is small, the results to date support the notion of the placenta as an arbiter of amino acid availability.
Dietary Influence on Muscle Protein Synthesis and Hypertrophy
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
James McKendry, Stuart M. Phillips
AAs are fundamental in driving increased MPS via mTORC1 activity, though, again, determining the mechanisms through which AAs drive increased rates of MPS has been somewhat elusive. Increased circulating concentrations of AAs following digestion and absorption of protein are transported into skeletal muscle. The L-type amino acid transporter 1 (LAT1) plays a vital role in transporting AAs, mainly the branched-chain amino acid (BCAA) leucine, into skeletal muscle (57). Once inside the muscle, AAs influence mTORC1 activity via conversion of the Rag GTPases (Rag A/B and Rag C/D) to a nucleotide-bound state and association with the Ragulator complex, which subsequently binds directly to Raptor and facilitates the recruitment of mTORC1 to the lysosomal surface, increasing mTORC1 kinase activity. Conversely, the absence of AAs results in mTORC1 dissociating from the lysosomal membrane, preventing the essential interactions with co-activators (69). AAs also augment mTORC1 activity via human vacuolar protein sorting 34 (VPS34) and a calcium (Ca2+)/calmodulin (CaM)–dependent interaction (51). Building on these important discoveries, mTORC1 has been shown to “sense” AAs through two distinct mechanisms: vacuolar H+–adenosine triphosphatase ATPase (v-ATPase) (117) and GATOR 1–, GATOR 2–, and Sestrin2-mediated regulation (11, 25), both of which act via Rag GTPases and the Ragulator complex. Leucyl-tRNA synthetase (LeuRS) has been proposed as another candidate contributing to the AA sensing mechanism (61), though much work is still required to fully elucidate the AA-mediated mTORC1 activity.
Optimizing levodopa therapy, when and how? Perspectives on the importance of delivery and the potential for an early combination approach
Published in Expert Review of Neurotherapeutics, 2023
Andrew Lees, Eduardo Tolosa, Fabrizio Stocchi, Joaquim J. Ferreira, Olivier Rascol, Angelo Antonini, Werner Poewe
As the natural precursor to dopamine, levodopa allows the synthesis and regulated release of dopamine, thus replacing the full range of tonic and phasic dopamine actions at pre- and post- synaptic receptors [39]. With continued neurodegeneration, the ability of the surviving nigrostriatal dopamine neurons (and other monoaminergic neurons) to synthesize and store dopamine diminishes, and it has been postulated that patients lose the ‘long-duration response’ to levodopa (LDR). Recent evidence argues that the LDR to levodopa is present from the first dose and may persist long-term [40] although motor fluctuations start to compromise the therapeutic response [41–43]. Additionally, pulsatile levodopa delivery can occur (or be exacerbated) as a direct consequence of impaired gastric emptying, large dietary neutral amino acids interfering with enteric absorption, as well as competition between amino acids and levodopa for the facilitative amino acid transporter (L1) to cross the blood brain barrier [44,45].
Tumour microbiota structure predicts hypopharyngeal carcinoma recurrence and metastasis
Published in Journal of Oral Microbiology, 2023
Xiaohui Yuan, Hui‑Ching Lau, Yujie Shen, Qiang Huang, Huiying Huang, Ming Zhang, Lei Tao, Chi-Yao Hsueh, Hongli Gong, Liang Zhou
To identify the extent to which HPV infection impacts tumour microbiota, LEfSe was used to evaluate differences between HPV-positive and HPV-negative groups. The HPV-positive tumours exhibited an enrichment of Porphyromondaceae, Micrococcaceae, Christensenellaceae, Corynebacteriaceae and Hungateiclostridiaceae at the family level, as well as Streptococcus, Collinsella, Barnesiella, Porphyromonas and Haemophilus at the genus level, indicating that HPV infection altered the tumour microbial communities (Figure 3A and 3B). Notably, we found a remarkable increase in Streptococcus abundance in the HPV-positive group. PICRUSTS analysis was used to predict the gene functions of the tumour microbiota and to reveal changes in microbial functional pathways across different groups. Transporter-, microbial metabolism- and transcription factor-related pathways were enriched in the microbiota of the HPV-positive group (Fig S1A). Transporter-related pathways included multiple sugar transport and polar amino acid transport. Microbial metabolism-related pathways included glycolysis/gluconeogenesis, pentose phosphate pathway purine metabolism and glycine, serine and threonine metabolism. These results suggest that HPV infection has an impact on microbial metabolism and the way microbiota interacts with hypopharyngeal environment, which may be the cause of the changes in microbiota.
Discovery of differentially expressed genes in the intestines of Pelteobagrus vachellii within a light/dark cycle
Published in Chronobiology International, 2020
Chuanjie Qin, Jiaxian Sun, Jun Wang, Yongwang Han, He Yang, Qingchao Shi, Yunyun Lv, Peng Hu
Moreover, a diurnal rhythmicity was noted for peptide absorption, for example, in nocturnal animals, the L-histidine absorption peak occurs during the dark phase(Furuya and Yugari 1974), which is coincident with higher expression levels of peptide transporter HPEPT1 (PEPT1) in the the dark compared with that in the light (Pan et al. 2002). In this study, b(0,+)-type amino acid transporter 1, sodium-coupled neutral amino acid transporter B, sodium-dependent neutral amino acid transporter 3, and excitatory amino acid transporter 1, all displayed upregulation at night, which contrasted with that of low affinity cationic amino acid transporter 2, a large neutral amino acids transporter. Excitatory amino acid transporter 1 is a sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate, L-aspartate, and D-aspartate (Arriza et al. 1994). The high-affinity transport of large neutral amino acids (e.g., phenylalanine, tyrosine, leucine, arginine, and tryptophan) is affected by sodium-independent, large neutral amino acids transporters. The peak time of mRNA expression was different for digestive enzymes and amino acid transporters within a light/dark cycle, which might suggest that the digestion and absorption of different amino acids was occurred at different times. Similarly, Senegalese sole (Solea senegalensis) showed their highest post-larval protein retention capacities when fed at nighttime (Marinho et al. 2014).