The classic ketogenic diet (KD) can be used successfully to treat medically refractory epilepsy. However, the KD reduces seizures in 50–70% of patients with medically refractory epilepsy, and its antiseizure effect is limited. In the current study, we developed a new modified KD containing leucine (Leu)-enriched essential amino acids. Compared with a normal KD, the Leu-enriched essential amino acid-supplemented KD did not change the levels of ketosis and glucose but enhanced the inhibition of bicuculline-induced seizure-like bursting in extracellular recordings of acute hippocampal slices from rats. The enhancement of antiseizure effects induced by the addition of Leu-enriched essential amino acids to the KD was almost completely suppressed by a selective antagonist of adenosine A1 receptors or a selective dose of pannexin channel blocker. The addition of Leu-enriched essential amino acids to a normal diet did not induce any antiseizure effects. These findings indicate that the enhancement of the antiseizure effects of the KD is mediated by the pannexin channel-adenosine A1 receptor pathway. We also analyzed amino acid profiles in the plasma and hippocampus. A normal KD altered the levels of many amino acids in both the plasma and hippocampus. The addition of Leu-enriched essential amino acids to a KD further increased and decreased the levels of several amino acids, such as threonine, histidine, and serine, suggesting that altered metabolism and utilization of amino acids may play a role in its antiseizure effects. A KD supplemented with Leu-enriched essential amino acids may be a new therapeutic option for patients with epilepsy, including medically refractory epilepsy.

Joint problems impair performance during exercise and daily activities and influence quality of life. The present study aimed to examine the effects of a combination of six non-essential amino acids (6AA) on joint conditions in an adult population. A total of 50 participants aged between 20 and 64 years with joint discomfort but no diagnosed joint disorder were randomly and blindly assigned to a control or 6AA group. The 6AA group took 12 g of the non-essential amino acid formulation orally (4 g three times a day) and the control group took equivalent doses of a placebo. Each group maintained the daily dose for 12 weeks. Primary outcome measures were evaluated with the visual analogue scale (VAS), the Japanese Knee Osteoarthritis Measure (JKOM), and the Japanese Orthopaedic Association score (JOA). These tests were taken before the experiment began at 4 weeks and 12 weeks after the intervention. The results of the VAS indicated that 6AA improved joint pain, discomfort, and stiffness both during a resting state and during normal activity. Participants’ scores on the JKOM and JOA also showed significant improvements in the group that had taken the 6AA supplement. These results demonstrate that 6AA improves symptoms of joint problems, such as pain, discomfort, stiffness, and difficulty in performing daily activities after 4 weeks of daily consumption.

No abstract

DNA methylation plays an important physiological function in cells, and environmental changes result in fluctuations in DNA methylation levels. Metal ions have become both environmental and health concerns, as they have the potential to disrupt the genomic DNA methylation status, even on specific sequences. In the current research, the methylation status of two typical repetitive DNA elements, i.e., long-interspersed nuclear element-1 (LINE-1) and alpha satellite (α-sat), was imaged and assessed using methylation-specific fluorescence in situ hybridization (MeFISH). This technique elucidated the effect of several metal ions on the methylation levels of repetitive DNA sequences. The upregulation and downregulation of the methylation levels of repetitive DNA elements by various metal ions were confirmed and depended on their concentration. This is the first example to investigate the effects of metal ions on DNA methylation in a sequence-specific manner.

Maintain a stable acid-base balance is essential for exercise performance. Pyruvate has obvious benefits to attenuate acidosis. However, the role of pyruvate on acid-base buffer during highintensity interval exercise (HIIE) remains unclear. PURPOSE: Assess the role of pyruvate on HIIE induced lactate acidosis from the perspective of energy metabolism. METHODS: In this double-blind, randomized, crossover trial, 14 male college football players (age: 20 ± 2 yrs; body fat: 13.11 ± 3.50%) were determined maximal aerobic power output using progressive ergometer cycle test. After one week of wash out period, they supplied sodium pyruvate or placebo (0.1g/kg/d) for 7 days. Sixty minutes after the last ingestion, resting oxygen consumption rate was collected. Then, subjects performed HIIE (4*1 min 110% VO2max, interval 1 min rest) to induce lactate acidosis. Venous and fingertip blood samples were collected for blood gas and lactate analysis. A portable Cortex Metamax 3B gas analysis system was used to measure oxygen consumption. Aerobic energy or ATP-PCr energy contribution: resting oxygen consumption was subtracted from the oxygen consumption obtained during each 110% VO2max or 1-min resting bout. Lactate difference before and after each 110% VO2max bout assumed to calculate glycolytic energy contribution. 1 mM of lactate corresponds to 3 ml of oxygen/kg of body mass. 1 L of oxygen corresponds to 20.92 kJ. RESULTS: Aerobic energy contribution of fourth 110% VO2max bout was significantly improved in pyruvate than placebo group (59.14 ± 7.07 kJ vs. 50.26 ± 10.72 kJ, p < 0.05). ATP-PCr and glycolytic energy contribution were not obviously changed. Blood pH (7.40 ± 0.03 vs. 7.37 ± 0.03, p < 0.01 ), HCO3 -(26.09 ± 0.82 vs. 24.86 ± 1.03, p < 0.01), BE (3.39 ± 0.86 vs. 2.06 ± 0.41, p < 0.01) before HIIE and Blood pH (7.20 ± 0.05 vs. 7.14 ± 0.08, p < 0.05 ), HCO3 -(14.56 ± 1.83 vs. 12.94 ± 2.25, p < 0.05) , BE (-12.79 ± 3.22 vs. -15.61 ± 4.39, p < 0.05) after HIIE in pyruvate group were significant higher than placebo group. CONCLUSIONS:The finding suggests that pyruvate supplementation can improve HIIE-induced lactate acidosis and aerobic energy contribution, which might indicate that pyruvate buffers HIIE-induced lactate acidosis by improving aerobic oxidation capacity.