Journal of Clinical Biochemistry and Nutrition最新文献

The intestinal barrier represents the first line of host defense. Its dysfunction, defined as increased intestinal permeability, is widely recognized as an important factor in the clinical manifestation of various diseases. Consequently, maintenance of the intestinal barrier is necessary for human health. Caenorhabditis elegans has recently been used frequently as a model organism in studies of gut bacteria-host interactions and in screening for probiotics and prebiotics that promote gut health. Nevertheless, no quantitative method for evaluating the intestinal permeability of Caenorhabditis elegans has yet been established. This study assesses a newly developed evaluation method to assess the intestinal permeability of Caenorhabditis elegans quantitatively using liposomes encapsulating fluorescein isothiocyanate-dextran. The usefulness of this method was confirmed by measuring the intestinal permeability of Pseudomonas aeruginosa-infected or oxidative stress-induced worms. Furthermore, our method found that agaro-oligosaccharides, the hydrolysis products of agarose, have a beneficial function of preventing increased intestinal permeability. This approach can expand the utility of Caenorhabditis elegans for functional food discovery and drug candidate screening, with specific examination of their effects on gut function.

This study aimed to evaluate the physical stress associated with transarterial chemoembolization (TACE), a catheter-based treatment for hepatocellular carcinoma, by examining changes in serum opsonic activity (SOA). SOA was examined by measuring reactive oxygen species (ROS) produced by neutrophils using lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL). Sixty-four patients were enrolled, and SOA was measured at admission, the following day, and 3 days after TACE. The area under the curve (AUC) for LgCL did not change significantly from baseline to the day after TACE but increased significantly from the following day to 3 days post-TACE. In contrast, no changes were observed in the AUC of LmCL. Subgroup analyses revealed a significant increase in LgCL from day 1 to day 3 post-TACE among patients aged >75 years, males, body mass index (BMI) <25 ‍kg/m², those with a FIB-4 index of ≥2.67, cisplatin use, Hepatitis B virus/Hepatitis C virus-related liver disease, or a procedure time ≥120 ‍min. Multivariate analyses identified BMI <25 ‍kg/m² and cisplatin use as significant risk factors for increased LgCL. Although TACE is considered a minimally invasive procedure, low BMI and cisplatin use have been identified as notable sources of significant physical stresses.

Mitochondria which are the major intracellular reactive oxygen species (ROS) sources produce especially superoxide anion (O₂ ^•-) as a byproduct of energy production. It has been well known that O₂ ^•- is converted from oxygen (O₂) and is overproduced by excessive electron leakage from the mitochondrial electron transport chain (ETC), mainly complexes I and III. However we have previously reported that several point mutations (specifically G71E in C. elegans, I71E in Drosophila and V69E in mouse) in succinate dehydrogenase C subunit (SDHC) of complex II cause mitochondrial electron transport defect leading to O₂ ^•- overproduction from mitochondria. These mutations can cause endogenous oxidative stress resulting in tumorigenesis and apoptosis as well as premature death. Recently, we have also demonstrated that premature aging of hematopoietic stem cell with a mutation in SDHC is developed after the growth phase and normal development. Here, we review cellular damages by complex II electron transport defect-induced endogenous oxidative stress in premature aging models.

Aminothiols play an important role in the antioxidant defense system. Their serum profile may be a predictor of prognosis and cardiovascular events. This study followed-up 262 patients (202 men; age, 65 ± 13 years) who had been treated for cardiovascular disease. The patients were divided into two groups by the median total l-cysteine to total glutathione (tCySH/tGSH) ratio in serum at enrollment. There were 32 (11%) all-cause deaths, 20 (8%) cardiovascular deaths, and 32 (12%) major cardiovascular events in 5.5 ± 3.2 years. Twenty-nine (11%) patients were hospitalized for heart failure. The high tCySH/tGSH ratio group (≥80.70) had a higher incidence of all-cause death than the low tCySH/tGSH ratio group (<80.70; log-rank test, p = 0.025). Multivariate Cox regression analysis adjusted for age, sex, body mass index, current smoking, renal function, and log₁₀-transformed brain natriuretic peptide showed that the tCySH/tGSH ratio had predictive value for all-cause death, cardiovascular death, and heart failure. The adjusted hazard ratio for heart failure for the high versus low tCySH/tGSH ratio groups was 3.071 (95% confidence interval: 1.186-7.952; p = 0.021). The tCySH/tGSH ratio may be an useful biomarker to assess prognosis, cardiovascular events, and heart failure.

We developed an optical system that simultaneously monitors leukocytes producing the reactive oxygen species (ROS) superoxide and hypochlorite ions using only a few microliters of whole blood. Here, we report the first use of this system to measure circulating blood from a nonhuman primate. This observational pilot study involved rhesus monkeys recruited for a different purpose, brain positron emission tomography in the conscious state. The results indicated that (1) surgical inflammation influences the total ROS produced by leukocytes per unit of time; (2) blood analysis of a septic rhesus monkey exhibited a characteristic pattern of leukocyte ROS production; and (3) a strong positive correlation was observed between leukocyte ROS production and neutrophil counts at normal C-reactive protein (CRP) levels, which decreased under abnormal CRP levels. These findings suggest that the system can capture systemic inflammation in non-human primates and highlight the importance of monitoring leukocyte ROS production to understand inflammatory status. The difficulty of identifying subjective symptoms in veterinary medicine highlights the importance of technologies for easily and objectively monitor animals' physical conditions. Further analyses, including studies with larger animal populations and comparisons with conventional biomarkers, are needed to determine the specific inflammatory status reflected in leukocyte ROS production.

Acute myocardial infarction (MI) is the most severe clinical manifestation of ischemic heart disease. Despite this, the mechanisms that disrupt mitochondrial homeostasis and contribute to cardiomyocyte loss during MI are poorly understood, emphasizing the urgent need for new therapeutic interventions. Poricoic acid A (PAA), the principal active component of pachymaria, possesses a range of pharmacological effects. However, the specific role and mechanisms by which PAA addresses mitochondrial dysfunction in MI remain unclear. This study aims to elucidate the impact of PAA on MI and uncover its potential regulatory mechanisms. We developed MI cell models using mouse primary cardiomyocytes incubated in a Forma Steri-Cult chamber containing 1% oxygen, 94% nitrogen, and 5% carbon dioxide. Our results demonstrate that PAA significantly improves cardiomyocyte injury in hypoxia-induced mouse primary cardiomyocytes. Furthermore, PAA activates the AMP-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1-alpha/Sirtuin 3 (AMPK/PGC-1α/SIRT3) signaling pathway in hypoxia-induced mouse primary cardiomyocytes. PAA enhances the oxidative stress response in hypoxia-induced mouse primary cardiomyocytes by activating SIRT3. Additionally, it improves mitochondrial dysfunction in these cardiomyocytes and reduces apoptosis by activating SIRT3. In summary, PAA inhibits mitochondrial dysfunction associated with MI by activating SIRT3, indicating its promise as a therapeutic agent for MI.

Deficiency of pyridoxal 5'-phosphate (PLP) causes neurological abnormalities. The decline in blood PLP concentration has been associated with the onset of dementia, but no studies have been conducted on Japanese. This study aimed to determine the relationship between serum PLP concentration and Alzheimer's disease (AD) in older Japanese individuals. A total of 266 participants, 84 healthy participants, 87 participants with mild cognitive impairment (MCI), and 95 patients with AD were randomly selected from those who visited the National Center for Geriatrics and Gerontology for Longevity Sciences. Serum PLP concentration was significantly lower in the AD compared to the NC. Participants were divided into quartiles (Q1-Q4). The relationship between quartiles of serum PLP concentration and cognitive function was analyzed using logistic regression analyses adjusted with covariate factors (sex, age, number of applicable frailty evaluations, APOE4, educational level, albumin, homocysteine, vitamin B₁, B₁₂, and folate). The odds ratios (ORs) for MCI or AD were significantly lower for Q3 and Q4 compared to Q1, and the ORs (95% CI) for Q3 and Q4 were 0.40 (0.16-0.98) and 0.37 (0.13-0.99), respectively. Lower serum PLP concentration is independently related to the incidence of MCI or AD. Further research is needed to clarify the causal relationship.

Lung adenocarcinoma (LUAD) is one of the primary culprits of cancer-related deaths. Current treatment modalities for LUAD have certain limitations, necessitating innovating effective LUAD treatment strategies. Prostaglandin E synthase (PTGES) and TF activating protein 2C (TFAP2C) in the process of drug resistance in LUAD are less studied and need further in-depth research. This study aimed to investigate the specific molecular mechanisms of PTGES and TFAP2C in gefitinib resistance in LUAD. The results indicated that PTGES and TFAP2C were considerably overexpressed in LUAD tissues and cells. Chromatin immunoprecipitation and dual luciferase assay validated that TFAP2C targeted the PTGES promoter region. In addition, gene set enrichment analysis results demonstrated the notable enrichment of PTGES in the NOTCH3 signaling pathway. Overexpression of PTGES remarkably enhanced the viability of PC-9/GR (gefitinib-resistant) cells and their response to gefitinib resistance, which was reversed by the addition of a NOTCH3 inhibitor. Furthermore, overexpressing PTGES upon the TFAP2C silence restored the great inhibition effect conferred by TFAP2C silence in PC-9/GR cells on cell viability and cell response to gefitinib resistance. This study confirmed that TFAP2C can transcriptionally activate PTGES through the NOTCH3 signaling pathway to enhance the response of LUAD cells to gefitinib resistance, proffering a new approach for the treatment of gefitinib resistance in LUAD cells.

To investigate the possible effects of Kurarinone on the ferroptosis and EMT of high glucose (HG)-stimulated HK2 cells, and uncover the mechanism. HK2 cells were treated with glucose to construct a DN cell model. CCK-8 and FCM assays exhibited the effects on growth as well as apoptosis of HK2 cells. DCF staining as well as Immunoblot assays exhibited the effects on ferroptosis. JC-1 staining exhibited the effects on mitochondrial function. Immunoblot assays showed the effects on the EMT process of HK2 cells. Immunoblot assays confirmed the mechanism. Kurarinone inhibited the apoptosis of HG-stimulated HK2 cells. It also blocked the ferroptosis of HG-stimulated HK2 cells. Further data showed that Kurarinone suppressed the mitochondrial damage in HG-stimulated HK2 cells, and restrained EMT process. Mechanically, Kurarinone activated the Nrf-2 pathway in HG-stimulated HK2 cells. Kurarinone activates the Nrf-2 pathway and alleviates HG-stimulated ferroptosis and EMT in HK2 cells.

[This corrects the article DOI: 10.3164/jcbn.24-178.].