Journal of Clinical Biochemistry and Nutrition最新文献

Consuming a diet high in antioxidants can help lower the risk of stroke. Although the association between the comprehensive dietary antioxidant index (CDAI) and stroke has not been extensively researched, it is a useful tool for evaluating the antioxidant capacity of the diet. To look at any possible processes that may be at play in the association between stroke risk and CDAI. The National Health and Nutrition Examination Survey (NHANES) database, which collected data on stroke patients between 2003 and 2018, was utilized. The study involved three independent variables: CDAI, stroke, serum albumin, and gamma-glutamyltransferase (GGT) as mediating factors. The association between CDAI and stroke was examined using logistic regression models, and the non-linear relationship between the two was investigated using restricted cubic splines (RCS). Furthermore, the possible mediating function of serum albumin and GGT in the connection between CDAI and stroke was examined by the use of mediation analysis. Spearman correlation coefficients were used to evaluate the relationship between the stroke risk and the CDAI component parts. 31,313 non-stroke participants and 1,215 stroke patients were included in this research. The data revealed a negative connection between CDAI and stroke (OR: 0.96, 95% CI: 0.93-0.99, p<0.01) after controlling for all confounding factors. A 38% reduction in the risk of stroke was linked to the highest quartile level of CDAI (OR: 0.62, 95% CI: 0.48-0.80, p<0.001). A non-linear negative connection (P-non-linear = 0.0346) between CDAI and stroke was revealed using RCS analysis. Significant mediation effects on the link between CDAI and stroke are attributed to serum albumin (10.98%; p<0.001) and GGT (0.33%; p<0.024), respectively. The Spearman correlation coefficient results showed that vitamin A (r = 0.76) and vitamin E (r = 0.75) in CDAI were most strongly correlated with stroke, while carotenoids reduce the risk of stroke by mediating serum albumin (Proportion of mediation = 25.16%). There was a negative correlation found between CDAI and stroke risk. It could be advantageous to consume more vitamin A and E to help avoid cardiovascular illnesses.

Cancer remains a leading cause of global morbidity and mortality, necessitating continuous innovations in diagnosis and therapy. Redox biology, the balance between reactive oxygen species production and antioxidant defenses, plays a central role in tumor initiation, progression, and therapeutic response. Elevated reactive oxygen species levels drive DNA damage, genomic instability, and tumor-promoting signaling, whereas adaptive antioxidant responses promote survival, therapeutic resistance, and recurrence. Chemotherapy and radiotherapy partly exert their cytotoxic effects through reactive oxygen species generation. However, tumors with enhanced redox-buffering capacity often evade reactive oxygen species-mediated killing. Ferroptosis, iron-dependent cell death driven by lipid peroxidation, is a key redox-linked pathway that synergizes with radiotherapy, offering new radiosensitization strategies. Redox imaging is a non-invasive approach to map oxidative and reductive dynamics in tumors. This review outlines the unique strengths of advancements, including optical imaging with redox-sensitive probes, positron emission tomography tracers targeting glutamine metabolism or system X_c ^-, magnetic resonance imaging with nitroxide-based probes and dynamic nuclear polarization, and electron paramagnetic resonance imaging. Together, these developments underscore the potential of redox imaging as a research and clinical tool. By enabling functional tumor characterization, patient stratification, and treatment monitoring, redox-based imaging provides a framework for precision oncology and development of redox-modulating therapies.

Gastric cardia adenocarcinoma (GCA), an aggressive gastric cancer with rising incidence and poor prognosis, often requires chemotherapy and surgery. This study aimed to explore the regulatory mechanism of ZNF649 on 5-FU sensitivity in GCA. ZNF649 expression in GCA was analyzed using The Cancer Genome Atlas (TCGA) database. The relationship between ZNF649 expression and methylation level was analyzed using MethylMix and MethPrimer. GCA data was used to predict ZNF649-related signaling pathways via gene set enrichment analysis (GSEA). qPCR, western blot, and immunohistochemistry were used to detect ZNF649 expression at mRNA and protein levels. MSP was used to detect ZNF649 methylation in clinical samples. Cell viability and apoptosis were assessed by CCK8 and flow cytometry. ZNF649 was downregulated in GCA tissues and cells, negatively correlating with DNA methylation in its promoter. Overexpressing ZNF649 increased GCA cell sensitivity to 5-FU, lowering IC50 values and enhancing apoptosis. ZNF649 negatively regulated the Hedgehog pathway. Knocking down ZNF649 activated Hedgehog signaling, reducing 5-FU sensitivity. DNA methylation silences ZNF649, activating the Hedgehog pathway and weakening GCA cell sensitivity to 5-FU. Targeting ZNF649 and the Hedgehog pathway may overcome 5-FU resistance in GCA patients.

Several similarities between shear-stress-induced mechanically damaged erythrocytes and physiologically aged erythrocytes have been reported, including mechanical fragility, increased aggregability, altered membrane charge, and loss of membrane lipid. Additionally, we found that mechanically circulated blood using a centrifugal blood pump showed an increase in erythrocyte membrane oxidation. This raised the question of how much oxidation can be induced under shear stress and how it relates to cellular aging. Therefore, we investigated membrane oxidation in density-isolated erythrocytes (young and old) exposed to shear conditions. Human stored blood was exposed to shear stresses of 5, 10, 30, 60, and 90 ‍Pa for exposure times of 0, 5, 10, and 15 ‍min. The sheared blood was then layered onto a centrifuge tube preloaded with two Percoll density solutions (1.10 and 1.12 ‍g/ml). After centrifugation, erythrocytes from the two density layers were collected and designated as young and old erythrocytes, which were used as the study samples. Across all shear conditions, old erythrocytes showed higher lipid peroxide fluorescence per unit area compared with young erythrocytes. However, the rate of increase in oxidation before and after shear exposure was greater in young erythrocytes. These findings suggest that there may be a limit to the extent of membrane oxidation.

Photodynamic therapy is a cancer treatment that is minimally invasive and combines photosensitizers with laser irradiation. Among the photosensitizers used in photodynamic therapy, porphyrin compounds have been widely applied because they specifically accumulate in cancer cells, and this approach has already been introduced into clinical practice. However, the detailed mechanism of porphyrin accumulation in cancer cells has not yet been clarified. The authors focused on the structural similarity between heme and porphyrin and demonstrated that the heme carrier protein 1 (HCP1) functions as an importer not only for heme but also for porphyrins. In addition, the expression of HCP1 was found to be regulated by reactive oxygen species (ROS) generated in mitochondria. Certain adjuvant treatments-such as hyperthermia, radiation, and chemical compounds including anticancer drugs-induced mitochondrial ROS production and increased the accumulation of porphyrin compounds through the upregulation of HCP1, thereby enhancing the effectiveness of cancer therapy by laser irradiation. Furthermore, ROS derived from mitochondria were also implicated in the excretion mechanism of porphyrins. Since mitochondria are a major source of ROS through respiratory metabolism, their accurate regulation is essential for optimizing cancer therapy using photodynamic therapy.

Near-infrared photothermal cancer therapy has attracted increasing attention due to its non-invasiveness, high selectivity, and spatiotemporally controllable local treatment. A novel near-infrared photothermal agent was developed, consisting of a plasma membrane-adhesive indocyanine green conjugated with a polycation bearing quaternary ammonium salt groups, called adhesive indocyanine green, for locally administered near-infrared photothermal cancer therapy. In this study, the photothermal effects of adhesive indocyanine green on the plasma membrane were investigated using a rat gastric mucosal cancer cell line. Upon light irradiation, adhesive indocyanine green exhibited a photothermal effect without generating singlet oxygen. Due to electrostatic interaction, adhesive indocyanine green adhered to negatively charged polysaccharides on the plasma membrane of rat gastric mucosal cancer cells. When the cells were irradiated with near-infrared light at 808 ‍nm at 108 ‍J/cm², levels of intracellular reactive oxygen species significantly increased despite the absence of a detectable temperature rise in the cell culture medium. These results indicate the generation of intracellular reactive oxygen species by the photothermal effects of plasma membrane-adhesive near-infrared photothermal agents.

Myocardial ischemia-reperfusion (I/R) injury remains a devastating clinical problem, contributing substantially to morbidity and mortality worldwide. In the present study, we investigated the potential role of Micheliolide (MCL) in attenuating cardiac I/R injury. H9c2 cardiomyocytes were pretreated with MCL for 24 ‍h and then subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cellular injury was evaluated by measuring cell viability and lactate dehydrogenase (LDH) release, while cell death was assessed using propidium iodide (PI) staining. Oxidative stress was determined by assessing superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione peroxidase (GSH-Px) activity, while the expression levels of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and pyroptosis-related proteins were examined by Western blotting. The results demonstrated that MCL significantly alleviated OGD/R-induced damage in H9c2 cells. Moreover, MCL inhibited OGD/R-induced oxidative stress and pyroptosis while enhancing AMPK pathway activation. Importantly, the protective effect of MCL was attenuated in the presence of the AMPK inhibitor Compound C, indicating that activation of the AMPK signaling pathway is required for MCL-mediated cytoprotection.

Colonoscopists occasionally encounter mixed lesions with overlapping histological features. The frequency and combinations of such mixed colorectal polyps remain poorly understood. We comprehensively analyzed the frequencies and combinations of histologically mixed premalignant colorectal polyps. This study had a retrospective, single-center, cross-sectional design. Patients who underwent colonoscopy at the Toyoshima Endoscopy Clinic between March 2022 and July 2023 were eligible. We excised lesions diagnosed as conventional adenomas or clinically significant serrated polyps. Among these polyps, we focused on mixed lesions and analyzed their frequency and combinations. Among 9,682 resected colorectal lesions, 61 (0.63%) were classified as mixed lesions. The most common combination was microvesicular hyperplastic polyp (MVHP) + goblet cell-rich hyperplastic polyp (GCHP) (41.0%), followed by sessile serrated lesion (SSL) + traditional serrated adenoma (TSA) (21.3%), MVHP + conventional adenoma (9.8%), and TSA + conventional adenoma (9.8%). The mixed rates for MVHPs, GCHPs, SSLs, TSAs, and conventional adenomas were 2.3%, 3.7%, 2.9%, 53.5%, and 0.28%, respectively. Mixed MVHP + GCHP lesions were significantly larger than pure GCHPs (5.3 ‍mm vs 4.0 ‍mm, p<0.01). The frequencies and combinations of mixed premalignant colorectal lesions found in this study may reflect the histogenesis of neoplasia and genetic mutations.

Recommended levels of dietary carotenoids remain uncertain, although their health benefits have gained renewed interest. One reason is that humans have a unique bioavailability of carotenoids compared to other mammals, which is not well understood. This position paper suggests that humans' bioavailability of dietary carotenoids reflects the mammalian nocturnal bottleneck-a period when the ancestors of modern mammals became nocturnal during the Mesozoic era to avoid predatory dinosaurs. The roles of carotenoids are closely linked to evolutionary processes involving light and vision. Vertebrates developed advanced color vision by using specific xanthophylls in their photoreceptor cells. In contrast, mammals' color vision declined due to their nocturnal lifestyle. Primates later returned to daytime activity and accumulated two xanthophylls, lutein and zeaxanthin, from their diet, in the macular lutea of the eyes, to protect color vision. Additionally, humans uniquely store β-carotene and lycopene in exposed skin. Throughout primate evolution, humans' ability to accumulate dietary carotenoids shifted from xanthophylls toward less polar carotenoids, including β-carotene and lycopene, unlike the high selectivity of xanthophylls observed in birds. Overall, carotenoid deposition in human tissues is not highly specialized, likely due to remnants of the mammalian nocturnal bottleneck. We should consider this when evaluating recommended carotenoid intake.

The rising incidence of chronic metabolic diseases places a significant economic burden on healthcare systems. Although the efficacy of lifestyle interventions has been reported, clinical nutrition typically emphasizes total energy and macronutrient intake without consensus on ideal dietary patterns. The Dietary Inflammatory Index (DII) assesses the inflammatory potential of diets and has been linked to diseases like cardiovascular disease, cancer, and type 2 diabetes. However, DII use in clinical practice is limited by its complexity. In this study, we developed a method to calculate DII scores using a clinically available food frequency questionnaire (FFQ). Thirty healthy volunteers provided 3-day dietary records (DR) and completed the FFQ. Dietitians calculated the intake of 29 nutrients from the DR. A created table of nutrient content per FFQ item enabled nutrient intake and DII score calculation from the FFQ. Statistical analysis showed significant correlations between 27 of 29 nutrient intakes and DII scores from the DR and FFQ. Regression equations were developed to predict actual nutrient intakes from the FFQ. The estimated DII (eDII) calculated using the equations correlated strongly with the DR-derived DII (r = 0.716, p<0.0001). With low bias and variance, our method supports individualized and inflammation-targeted dietary interventions.