Journal of Clinical Biochemistry and Nutrition最新文献

Sepsis, a systemic inflammatory response often triggered by infection, can lead to multi-organ failure, with the intestine being one of the most vulnerable organs. The nuclear factor kappa-B (NF-κB) pathway plays a crucial role in immune responses, inflammation, and cell survival, making it central to sepsis-induced intestinal damage. Kakkalide (KA), a bioactive compound known for its anti-inflammatory, cardiovascular, neuroprotective, and anti-diabetic properties, has potential therapeutic effects. However, its impact on sepsis-induced intestinal injury remains unclear. In this study, murine sepsis models were used both in vivo and in vitro to evaluate the protective effects of KA on intestinal histopathology, apoptosis, and inflammation. Results showed that KA significantly reduced intestinal damage and apoptosis, as evidenced by hematoxylin-eosin and TUNEL staining. KA also improved intestinal barrier integrity, as indicated by reduced diamine oxidase activity, d-lactic acid content, and fluorescein isothiocyanate intensity, along with increased expression of zonula occludens-1. Furthermore, KA alleviates inflammation by reducing the levels of tumor necrosis factor-α, interleukin-1β, prostaglandin E2, inducible nitric oxide synthase, and cyclooxygenase-2. Immunofluorescence and Western blot analysis revealed that KA inhibited the sepsis-induced phosphorylation of inhibitor-kappaBα and RelA (P65) and prevented P65's translocation to the nucleus. These findings were confirmed in lipopolysaccharide-induced Caco-2 cells, suggesting that KA protected the intestinal barrier during sepsis by suppressing the NF-κB pathway.

Although coconut oil has attracted great attention as a functional food, enough supportive scientific evidence is lacking. In addition, the beneficial effects of coconut oil consumption on the prevention of metabolic disorders are controversial. Fetuin-A is a plasma glycoprotein secreted by hepatocytes and adipocytes. Circulating fetuin-A levels relate to insulin resistance due to macrophage-mediated adipose tissue inflammation. This study demonstrated that coconut oil feeding significantly downregulated the hepatic expression of fetuin-A and reduced its plasma level in KK mice-an obese diabetic model animal. The expression of monocyte chemoattractant protein-1, a potent inducer for macrophage infiltration, decreased in epididymal white adipose tissue in coconut oil-fed KK mice. The expression of CD68 and CD11c, markers of proinflammatory M1 macrophages, was significantly reduced by coconut oil feeding in epididymal white adipose tissue of KK mice. However, the mice did not exhibit improved insulin resistance. Our results may further support the potential of coconut oil as a dietary trigger that can reduce both circulating fetuin-A levels and infiltration of proinflammatory macrophages in visceral adipose tissue.

This case-control study of 124 early-pregnant women found that daily supplementation with 400 IU of vitamin D₃ significantly increased serum 1,25-(OH)D₃ levels and was associated with a lower incidence of threatened miscarriage. The study suggests that vitamin D₃ supplementation could reduce the risk of early miscarriage and improve pregnancy outcomes by modulating immune responses and hormonal stability.

Ergothioneine has antioxidant, anti-inflammatory, and cell-protective properties. Circadian rhythm disruption can lead to health issues, such as insomnia, mental illness, chronic diseases, and cancer. However, the impact of ergothioneine, as an antioxidant, on oxidative DNA damage and immune variations caused by circadian rhythm disruptions remains unclear. To investigate the effect of ergothioneine on oxidative DNA damage and immune responses caused by circadian rhythm disruption, 8-week-old mice were subjected to night time feeding and exercise restrictions for 14 days. Body weight, daytime running wheel activity, and anxiety-like behavior showed no significant differences between the night-restricted groups, regardless of ergothioneine administration. Serum interleukin-6 levels, 8-hydroxy-2'-deoxyguanosine levels in urine and nuclear DNA of the liver, testes, lungs, and pancreas were significantly reduced in the night-restricted group receiving ergothioneine compared with that of the group without ergothioneine, with no significant differences observed when compared to the control group. Ergothioneine can mitigate immune function changes and oxidative DNA damage induced by circadian rhythm disruption caused by abnormal dietary timing in mice. However, it did not alleviate obesity or mental state dysregulation. These findings have important implications for improving night-shift workers health and developing therapies for diseases associated with circadian rhythm disturbances.

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.

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.