Journal of Clinical Biochemistry and Nutrition最新文献

Delta-tocotrienol (δ-T3) are beneficial for lipid metabolism. However, there are almost no reports on the specific numerical values of changes in blood tocotrienol levels when Japanese people consume tocotrienol. To observe the effect on blood δ-T3 and lipid concentrations after taking δ-T3, a crossover test was conducted with a control group, alpha-tocopherol (α-TP) group (264 ‍mg/day), and δ-T3 group (250 ‍mg/day). Participants took the target supplements for 14 days. This study revealed that plasma δ-T3 concentrations in healthy men and women increased significantly even with short-term intake (pre; 0.11 ± 0.03 to post; 0.40 ± 0.19 ‍μmol/L). The results of this study showed that α-TP and δ-T3 intake did not significantly affect any of the lipid profiles. However, the intake of δ-T3 tended to increase Low-density lipoprotein cholesterol (HDL-C) levels (pre: 59 ± 17 to post: 64 ± 20 ‍mg/dl). These results provide new evidence on changes in blood δ-T3 concentrations with δ-T3 intake in young people and suggest the potential of δ-T3 for the prevention of atherosclerosis.

In this study, we used single-cell sequencing, which can comprehensively detect the type and number of transcripts per cell, to efficiently stimulate peripheral blood mononuclear cells of type 1 diabetic patients with overlapping peptides of GAD, IA-2, and insulin antigens, and performed gene expression analysis by single-cell variable-diversity-joining sequencing and T-cell receptor repertoire analysis. Twenty male patients with type 1 diabetes mellitus participating in the KAMOGAWA-DM cohort were included. Four of them were randomly selected for BD Rhapsody system after reacting peripheral blood mononuclear cells with overlapping peptides of GAD, IA-2, and insulin antigen. Peripheral blood mononuclear cells were clustered into CD8⁺ T cells, CD4⁺ T cells, granulocytes, natural killer cells, dendritic cells, monocytes, and B cells based on Seurat analysis. In the insulin group, gene expression of inflammatory cytokines was elevated in cytotoxic CD8⁺ T cells and Th1 and Th17 cells, and gene expression related to exhaustion was elevated in regulatory T cells. In T cell receptors of various T cells, the T cell receptor β chain was monoclonally increased in the TRBV28/TRBJ2-7 pairs. This study provides insights into the pathogenesis of type 1 diabetes and provides potential targets for the treatment of type 1 diabetes.

There is a lack of evidence for compliance with and the acceptability of oral nutritional supplements (ONS) by post-acute care patients. Therefore, the present study examined compliance with fat-free ONS, which are easy to drink. Patients who started oral intake in the general ward after being transferred from the Emergency Department were offered three ONS including fat-free ONS: Isocal Clear, Maybalance Mini, and Medimil, three times a day for three days. On days 1 and 3, patients evaluated each ONS using a questionnaire. Thirty-five eligible patients participated in the present study, which began a median of 10 days after their admission. Median taste ratings for Isocal Clear, Maybalance, and Medimil on day 1 were 8, 7, and 3, respectively, while median ease-to-drink ratings were 8, 7, and 5, respectively. In contrast, median taste ratings on day 3 were 5, 0, and 0, respectively, while median ease-to-drink ratings were 7, 1, and 0, respectively. Intakes of the prescribed diet during the three days had a median value as low as 30-50%. In conclusion, good compliance with fat-free ONS by post-acute care patients may be achieved.

Uric acid, a water-soluble antioxidant ubiquitous in human bodily fluids at relatively high concentrations, reacts with a variety of reactive oxygen and nitrogen species. Ours and other previous studies identified allantoin, oxaluric acid, triuret, and 5-N-carboxyimino-6-aminopyrimidine-2,4(3H)-dione as specific metabolites reactive against free radicals, singlet oxygen, peroxynitrite, and hypochlorous anion, respectively. We analyzed human plasma spiked with these products using high-performance liquid chromatography-tandem mass spectrometry. We observed recoveries of 40-110% and coefficients of variance within 7%. Samples remained stable at -80°C for at least 4 weeks, indicating the analytical method is sound. Detection of these metabolites in biological samples enables the identification of each species generated in vivo. We observed changes in the products in human blood during pseudo-inflammation induced by treatment with lipopolysaccharide. Levels of allantoin, oxaluric acid, triuret, and 5-N-carboxyimino-6-aminopyrimidine-2,4(3H)-dione increased after addition of lipopolysaccharide. The formation of singlet oxygen was confirmed by increased formation of Trp-derived cis-hydroxide ([2S,3aR,8aR]-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid) (cis-WOH). We believe our method will aid development of strategies to treat oxidative stress-associated diseases.

Background: Cancer stem cells are essential for the development of tumors, their recurrence, metastasis, and resistance to treatment. Previous studies have shown that the silencing of EBF3 promotes the progression of malignant tumors, but its impact on the stem-like phenotype of tumor cells remains unexplored. Therefore, this work aims to investigate the influence of EBF3 on the stem-like phenotype of breast cancer (BC) cells and its underlying molecular mechanisms.

Methods: Bioinformatics analysis was utilized to predict EBF3 and miR-301b-3p expression and their binding sites in BC tissues. qRT-PCR was conducted to assess EBF3 and miR-301b-3p expression in BC cells. Cell viability was assessed using CCK-8 assay, while sphere-forming ability was assayed by sphere formation experiments. Western blot analysis was employed to assess the expression of stem cell-related markers and proteins associated with the glycolysis metabolic pathway. ECAR experiments and analysis of glycolysis metabolite production were performed to evaluate cellular glycolysis capacity. Dual-luciferase reporter assays and RIP were utilized to validate the binding relationship between EBF3 and miR-301b-3p.

Results: EBF3 was downregulated in BC tissues and cells, and overexpression of EBF3 repressed the glycolysis capacity of BC cells, thereby suppressing stem-like phenotype. Furthermore, miR-301b-3p was identified as a direct target of EBF3, and its expression was increased in BC. Cell experiments revealed that miR-301b-3p suppressed EBF3 expression, thereby promoting the glycolysis capacity and stem-like phenotype of BC cells.

Conclusion: miR-301b-3p enhanced glycolysis and promoted the stem-like phenotype of BC cells by targeting EBF3. These findings can offer new therapeutic approaches for BC.

3-(4-Hydroxy-3-methoxyphenyl) propionic acid is an in vivo metabolite of 4-hydroxy-3-methoxycinnamic acid which is abundantly found in coffee bean, rice bran, fruits, and vegetables. Previous studies reported that polyphenols and their metabolites exhibit positive effects on muscle health. Thus, the effect of 3-(4-hydroxy-3-methoxyphenyl) propionic acid on muscle atrophy induced by dexamethasone was investigated using mouse C2C12 skeletal myotubes. Dexamethasone treatment (10 ‍μM) reduced the diameter and myosin heavy chain protein expression in C2C12 myotubes; it also increased muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/Atrogin-1 and muscle ring finger protein-1, along with their upstream regulator Krüppel-like factor 15. Dexamethasone dephosphorylated FoxO3a transcription factor and increased total FoxO3a expression. Interestingly, 10 ‍μM 3-(4-hydroxy-3-methoxyphenyl) propionic acid treatment significantly attenuated dexamethasone-induced reduction in myotube thickness and muscle protein degradation and suppressed muscle atrophy-associated ubiquitin ligases. 3-(4-Hydroxy-3-methoxyphenyl) propionic acid also prevented dexamethasone-induced Krüppel-like factor 15 and FoxO3a expression. In conclusion, these results suggest that in vivo metabolite of polyphenols per se could be the real origin of the anti-muscular atrophy activity, as 3-(4-hydroxy-3-methoxyphenyl) propionic acid ameliorated glucocorticoid-induced muscle atrophy by suppressing Atrogin-1 and MuRF-1.

Frequent or long-term circadian disorders can lead to a range of health problems, including chronic insomnia, depression, chronic diseases, and cancer. It has also been shown that altering the feeding time of mice from night to day can result in circadian disorder. Recent studies have revealed complex interactions between circadian rhythm and oxidative stress. However, little is known about the impact of circadian rhythm disorders caused by time-restricted feeding on mental state, immune function, and oxidative DNA damage. In this study, we investigated the effects of circadian rhythm disruption by controlling the timing of feeding and exercise on oxidative DNA damage and immune responses in 8-week-old mice for 14 days. Body weight, daytime running wheel activity, serum interleukin-6 levels, urinary 8-hydroxy-2'-deoxyguanosine levels, and nuclear DNA (liver, lung, testes, and pancreas) were significantly increased in the night-restricted group compared with the control group. Additionally, the mice in the night-restricted group exhibited anxiety-like behavior. These results indicated that the circadian rhythm disruption due to abnormal dietary timing can lead to obesity, mental state dysregulation, immune function changes and oxidative DNA damage in mice. This oxidative DNA damage may contribute to the initiation and increased risk of cancer.

Choline is an essential nutrient for normal brain function, but its bioavailability is not as high as choline esters. Among choline esters, lysophosphatidylcholine (LPC) has unexplored potential as a choline source and cognitive enhancer in humans. This placebo-controlled, double-blinded study, involving healthy participants aged 40-74 years, aimed to assess the effects of an 8-week intake of lysolecithin containing 480 ‍mg LPC on cognitive function and plasma levels of choline and LPC. Twenty-three participants were assigned to both the placebo and lysolecithin groups, and memory was assessed as the primary outcome. Additionally, subjective mental function was assessed. Plasma levels of derivatives of reactive oxygen metabolites were also evaluated for a safety assessment. No significant between-group differences were observed in the memory or mental function score, but a post-hoc analysis yielded significant within-group increases from baseline in subjective mental acuity and calmness in the lysolecithin group. Lysolecithin intake slightly increased plasma choline and LPC18:2 concentrations over 8 weeks, but plasma levels of saturated and total LPC concentrations, associated with inflammation, and derivatives of reactive oxygen metabolites remained unchanged. No adverse events were attributed to lysolecithin supplementation. This study demonstrated lysolecithin's good tolerability and potential as a new choline supplement.

In sedentary modern society, disuse osteoporosis is a health issue. Here, we investigate whether prune extract prevents disuse osteoporosis in rats. After feeding a control diet or 10% (wt/wt) prune extract-containing diet for 14 ‍days, we performed sham operation in the left leg and sciatic denervation in the right leg to induce disuse osteoporosis in rats. The rats were fed the same diet prior to surgery for 7 days. The rats fed a control diet before sham operation on both legs were set as the control group, and those with sciatic denervation in the right leg fed a control diet or prune extract containing diet were set as the denervation with control diet and denervation with prune extract diet groups, respectively. Femoral bone volume/tissue volume, trabecular number, and trabecular thickness were reduced in the right leg of denervation with control diet group; however, this reduction was not observed in the denervation with prune extract diet group. Similar results were obtained for mRNA levels of osteoblast-related genes, such as osteocalcin. Overall, prune extract inhibited bone loss by preventing the decrease in osteoblast-related gene expression in disuse osteoporosis, thus showing to improve the bone metabolism and quality of life.