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.

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 was to investigate the impact of exosomes-derived circ_0008039 on ferroptosis and stemness in colorectal cancer cells, as well as its associated molecular mechanisms. The cell colony formation ability was evaluated using the MTT assay and colony formation assay, respectively. Additionally, the sphere formation assay was employed to examine the cells’ ability to aggregate into spheres. The targeting relationship between circ_0008039, miR-302e, and SLC7A11 was verified through dual luciferase assay. Furthermore, RNA immunoprecipitation (RIP) analysis of circ_0008039 and miR-302e was conducted. Western blotting was utilized to detect the protein expression of exosome surface antigens (TSG101 and CD63), stem cell markers (CD133, Nanog, and SOX-2), as well as SLC7A11 in both exosomes and cell ‍lysates. The levels of glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), and Fe²⁺ were determined using corresponding kits. Circ_0008039 exhibited significant down­regulation in cancer tissues and cells. Furthermore, exosome-derived circ_0008039 played a crucial role in promoting cell viability, clone formation, and resistance to ferroptosis by inhibiting MDA, ROS, and Fe²⁺ levels. Additionally, circ_0008039 acted as a miR-302e sponge to regulate SLC7A11 expression. In ‍colorectal cancer (CRC) tissues, miR-302e was negatively correlated with SLC7A11 expression while circ_0008039 was negatively correlated with miR-302e expression. Mechanistic validation demonstrated that circ_0008039 regulated CRC cell proliferation, stemness maintenance and ferroptosis through the modulation of the miR-302e/SLC7A11 axis. The Circ_0008039/miR-302e/SLC7A11 axis plays a pivotal role in facilitating the proliferation and maintenance of stemness in CRC cells, while enhancing resistance to ferroptosis.

Despite adiponectin’s recognized anti-inflammatory properties, its ‍impact on cardiovascular homeostasis involves poorly defined mechanisms. We investigated the effect of adiponectin on chemokine-induced cell migration and their potential inter­molecular interactions. Our findings revealed that cell migration induced by recombinant PF4, MCP-1, or RANTES in HL-60 cells was ‍significantly inhibited by pre-treating cells with adiponectin. Surface plasmon resonance analysis and molecular docking analysis indicated that only PF4 binds to adiponectin with a higher affinity of adiponectin to the PF4 binding site respectively. These results suggest that adiponectin’s atheroprotective func­tions may be mediated by its ability to reduce PF4-induced monocyte migration through direct interaction.

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.

Glioblastoma (GBM) is a highly aggressive cancer that significantly impacts human health. Myeloid cells and bone marrow-derived macrophages (BMDMs) are major components of tumor micro­environ­ment; however, their roles in GBM tumorigenesis, progres­sion, and treatment response remain unclear due to considerable heterogeneity. Single-cell sequencing data for GBM were collected from the Gene Expression Omnibus (GEO) database to analyze the heterogeneity of GBM cell subpopulations. Trends in myeloid cell subpopulations were examined, identifying cancer-associated BMDMs and key genes that were specifically over­expressed in this subgroup. Validation was performed through experiments in vitro, including quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to measure mRNA expres­sions of chemokine (C-X-C motif) ligand 3 (CXCL3), vascular endothelial growth factor A (VEGF-A), and matrix metallo­peptidase 9 (MMP9); angiogenesis assays to observe endothelial cell tube formation; Cell Counting Kit-8 (CCK-8) assays to assess cell viability; colony formation assays for cell proliferation; Transwell assays to evaluate cell migration and invasion; and flow cytometry to measure apoptosis. Eight distinct cell types were identified in GBM, with a notable proportion of myeloid cells. Cancer-related BMDMs were characterized within the myeloid cell population, revealing specific overexpression of Glu-Leu-Arg (ELR) CXCL genes associated with angiogenesis and tumor develop­ment. Experiments in vitro confirmed that the ELR CXCL-related gene CXCL3 derived from BMDMs promoted angiogenesis and influenced GBM malignancy. The ELR CXCL + BMDM subgroup represented a critical cell type associated with the rapid growth of GBM, as the secreted CXCL3 enhanced angiogenesis and impacted GBM malignant progression.

Iron (Fe) is the most abundant metal ion in the body, but its excess accumulation causes Fe²⁺-dependent and lipid peroxidation-dependent cell death (ferroptosis) via the production of reactive oxygen species (ROS). It is thought that ferroptosis is related to ‍the progression of various kidney problems, including acute kidney injury and diabetic nephropathy. Mallotus japonicus (M. ‍japonicus), a deciduous shrub belonging to the Euphorbiaceae family, contains ellagitannins such as corilagin, geraniin, mallotinic acid, and mallotusinic acid, which have antioxidant properties. Here, we investigated whether M. japonicus leaf extract inhibits ferroptosis in human proximal tubular epithelial HK2 cells. M. japonicus extract suppressed HK2 cell death caused by erastin, a ‍ferroptosis inducer; this was accompanied by a reduction in intracellular Fe²⁺, ROS accumulation, and lipid peroxidation. Our findings suggested that the inhibitory effect of M. japonicus extract was due to the inhibition of transferrin receptor (CD71)-mediated Fe^3+/2+ uptake. Furthermore, we determined that mallotinic acid is a key compound that exhibits anti-ferroptosis effects. Overall, our results provide useful information for the use of M. japonicus extract in the treatment of kidney injuries.

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.

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.

To explore the interaction between Diabetic kidney disease (DKD) and serum selenium (Se) on mortality from all-cause. Information from the National Health and Nutrition Examination Surveys database (2011–2016) were retrospectively extracted for this cohort study. Associations of DKD and serum Se level with all-cause mortality were evaluated by weighted uni- and multi-variate COX regression analyses, with 95% confidence intervals (CIs) and hazard ratios (HRs). The interaction was measured by attributable proportion of interaction (APAB), relative excess risk due to interaction (RERI), synergy index (S) and 95% CIs. Among 793 adult patients, 98 died from all cause. DKD was linked to an increased all-cause mortality risk [HR = 3.69, 95% CI (1.75–7.81)], while elevated serum Se levels were linked to a decreased all-cause mortality risk [HR = 0.49, 95% CI (0.28–0.86)], after adjusting for co-variables including age, education level, physical activity (PA), CVD, WBC, neutrophil, HB, ALB, and Zn. Additionally, there was a potential antagonistic interaction between DKD and serum Se level on all-cause mortality, with the S value of 0.228. Se may ‍play a protective role in all-cause mortality related to DKD in ‍patients with DM, but this interaction effect needed further exploration.

In this study, we investigated the relationship between phase angle (PhA), measured using bioelectrical impedance analysis (BIA), and mild cognitive impairment (MCI). A cross-sectional analysis was conducted on 290 community residents (83.7% female, average age 74.9 years). Cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J), with MCI defined as a score of ≤25. Body composition, including PhA, was measured using BIA. Multiple regression analysis was used to examine the association between PhA and MCI presence, adjusting for potential confounders. MCI was found in 168 participants. The PhA (leg) was significantly lower in those with MCI than in those without (p = 0.013). A significant association between leg PhA and MCI was identified in the regression model (β = 0.103, p = 0.015), with an adjusted R² value of 0.50. These findings suggested that PhA may serve as an indicator of MCI. Longitudinal and inter­vention studies are needed to explore the potential of PhA in dementia prevention strategies. In addition, future research should focus on developing dementia prevention strategies that utilize PhA through longitudinal and interventional studies.

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.