Journal of Clinical Biochemistry and Nutrition最新文献

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.

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.

Zinc is an essential element and important for inflammatory bowel disease patients. Herein, we aimed to elucidate the correlation between serum zinc concentration and various parameters, especially the disease activity index and endoscopic scores, in these patients. We measured serum zinc concentrations in 37 patients with Crohn's disease and 64 with ulcerative colitis and retrospectively analyzed patient characteristics, blood test values, disease activity, and endoscopic scores. Hypozincemia (<80 ‍μg/dl) was observed in 45.9% and 29.7% of patients with Crohn's disease and ulcerative colitis, respectively. Serum zinc concentration showed a weak negative correlation with Crohn's Disease Activity Index and C-reactive protein levels in Crohn's disease patients, and a weak negative correlation with white blood cell count in ulcerative colitis patients. The zinc concentrations in ulcerative colitis patients were significantly lower in Mayo endoscopic sub-score grade 2 than in grades 0 and 1. The simple endoscopic score for Crohn's disease moderately correlated with zinc concentration. In addition, serum zinc concentration showed a moderate correlation with serum albumin and Onodera's prognostic nutritional index in both Crohn's disease and ulcerative colitis patients. Serum zinc concentration clearly correlated with inflammatory bowel disease activity, endoscopy scores, and immunonutritional parameters, suggesting the importance of monitoring zinc levels.

Previous studies have suggested a relationship between the urinary 8-hydroxydeoxyguanosine level and hypertension, but an association between the urinary 8-hydroxydeoxyguanosine level and systolic blood pressure has not been reported. The aim of this cross-sectional study was to examine the association between the 8-hydroxydeoxyguanosine level, a marker of DNA oxidative damage, and arteriosclerosis-related factors in healthy, urban residents aged ≥50 years who participated in annual health promotion activities in Mitaka City, Tokyo from 2008 to 2018. Arteriosclerosis-related factors were used as independent variables and the urinary 8-hydroxydeoxyguanosine creatinine concentration-corrected level (urinary 8-hydroxydeoxyguanosine/creatinine) as the dependent variable in multiple logistic regression. Two hundred and forty-eight participants were divided into two groups using a cutoff point of 6.2/6.3 ‍ng/mg creatinine, which corresponds to the urinary 8-hydroxydeoxyguanosine/creatinine levels in approximately 80% of the participants. A high urinary 8-hydroxydeoxyguanosine/creatinine level was significantly associated with a body mass index ≥25, obesity, and systolic blood pressure ≥140. Our findings suggest that in healthy individuals aged ≥50 years, arteriosclerosis-related factors such as inappropriate weight management and poor systolic blood pressure control may be associated with the urinary 8-hydroxydeoxyguanosine level.

Dietary fiber-rich diets are gaining popularity as an alternative therapy for skin health. Plant-based prebiotic partially hydrolyzed guar gum (PHGG) dietary fiber promotes gastrointestinal health, which is imperative for skin health through the gut microbiome. In this randomized, double-blind, and placebo-controlled study, the purpose was to assess the therapeutic effects of PHGG on skin hydration, trans-epidermal water loss (TEWL), and skin viscoelastic properties during the winter season. Healthy male and female subjects (n = 70; 9 male and 61 female; mean age: 45.5 ± 8.1 years) were recruited. They received either the 5 ‍g PHGG dietary fiber (n = 35) or a 5 ‍g placebo (n = 35) for twelve weeks. Skin moisture, TEWL, skin elasticity and skin color parameters, and related features were assessed at baseline, after 6 and 12 weeks, and questionnaires to evaluate the study outcomes. The results confirmed the improvement in skin conditions throughout the winter season by restoring skin hydration, reducing TEWL, and improving skin elasticity parameters. After 6 weeks of PHGG intake, there was a substantial decrease in TEWL and improvement in viscoelasticity metrics when compared to placebo. Subject satisfaction with efficacy reflected these encouraging findings, and PHGG was well tolerated, with no adverse events occurring during the study period.

Helicobacter pylori (H. pylori) infection promotes the migration of polymorphonuclear leukocytes from the gastric mucosal microcirculation through chemokine induction, leading to the excessive production of ROS. Like eukaryotes, H. pylori possesses superoxide dismutase and catalase, and is resistant to ROS from host polymorphonuclear leukocytes. Oxidants such as monochloramine produced by ROS cause chronic inflammation in the gastric mucosa. H. pylori-derived virulence factor m1-type VacA induces intracellular ROS accumulation and autophagy, which degrades the H. pylori-derived oncoprotein, CagA. In CD44v9-positive gastric cancer stem-like cells, reduced-type glutathione levels increase within the cell because of the cystine transporter on the cell surface, wherein oxidative stress-induced autophagy no longer occurs. As a result, the oncoprotein CagA accumulates in the cells, thus becoming tumorigenic.

Type 1 diabetes mellitus (T1DM) may be associated with other autoimmune diseases. Celiac disease (CD), another autoimmune disorder that mainly affects the small intestine, is caused by intolerance to gluten ingestion. CD has a higher prevalence in patients with T1DM than in the general population. However, the prevalence of CD in patients with T1DM in Japan is unknown. This study investigated the prevalence of CD in Japanese patients with T1DM. We included 115 patients with T1DM treated at Hyogo Brain and Heart Center from December 2020 to April 2021. A questionnaire survey about dietary habits and abdominal symptoms was administered, and serum anti-tissue transglutaminase (TTG) antibody titers were determined for all participants. A CD (CD-seropositive) diagnosis was based on TTG levels >10 U/ml. Fifty-eight patients (50.4%) had some abdominal symptoms (such as constipation, diarrhea, and abdominal pain). The average TTG-IgA antibody titer was 0.75 ± 0.49 U/ml and negative (<10 U/ml) in all patients. In conclusion, the prevalence of CD among patients with T1DM at our hospital was 0%. Thus, the prevalence of CD in Japan is low compared to that in other countries, even among patients with T1DM, who are considered to have high comorbidity rates.

Liposome lipid peroxidation induced by cold atmospheric pressure plasma jet (CAPPJ) irradiation was investigated. The formation of thiobarbituric acid reactive substances (TBARS), an indicator of lipid peroxidation final products, as a function of irradiation was observed. Lipid radicals, peroxidation reaction intermediates generated by CAPPJ irradiation, were confirmed by increased NBD-pen fluorescence intensity. Additionally, lipid peroxidation products, liposomal phosphatidylcholine (PC) isomers, were analyzed by LC-MS/MS. Products specific to singlet oxygen (¹O₂) oxidation, 16:0/10-hydroperoxy-8E,12Z-octadecanoic acid (10-8E,12Z-HpODE) PC and 16:0/12-9E,13E-HpODE PC, were not detected, but radical oxidation specific products 16:0/13-9E,11E-HpODE PC and 16:0/9-10E,12E-HpODE PC were. This suggests that during CAPPJ irradiation, radicals, rather than ¹O₂, are the primary reactive species of lipid peroxidation. This is also supported by the β-carotene quenching of ¹O₂ not suppressing TBARS and lipid radical generation. Also, neither TBARS formation nor lipid radical generation were suppressed by SOD, indicating that the superoxide radical (O₂ ^•-) is not responsible for the lipid peroxidation reaction. As the CAPPJ irradiation of water produces large quantities of hydroxyl radical (^•OH) and ^•OH scavengers decreased the amount of TBARS produced by CAPPJ irradiation, it is highly plausible that ^•OH is the primary species involved in CAPPJ-induced liposome lipid peroxidation.