Journal of Clinical Biochemistry and Nutrition最新文献

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopamine (DA) neurons and presence of Lewy bodies, with prion-like propagation of α-synuclein (α-syn) also attracting attention recently. However, the specific causes for PD-related pathogenesis, including cell vulnerability and α-syn propagation, occurring only in selective neurons remain unclear. Therefore, we aimed to investigate the interactions between DA and α-syn protein to clarify its effects on α-syn degradation, secretion, and toxicity. We generated PC12 cells expressing human α-syn and M127A mutant in a tetracycline-inducible manner. In these cells, intracellular α-syn levels were controlled via autophagic/lysosomal degradation and secretion to extracellular space. Notably, M127A mutation decreased the intracellular degradation and secretion of α-syn. Using the generated cells, we investigated the association between cell viability and oxidized methionine [Met(O)] in α-syn. We also investigated the effects of Met(O) on α-syn toxicity and stability upon DA induction. Wildtype α-syn overexpression decreased the cell viability, and inhibition of methionine sulfoxide reductase, a methionine sulfoxide-reducing enzyme, further amplified this effect, suggesting that α-syn cytotoxicity is associated with methionine oxidation. Notably, vulnerabilities of M127A mutant cells were lower than those of wildtype α-syn-expressing cells. Overall, our results suggest M127 as the major target for oxidative modification by DA and that this modification is associated with both cell vulnerability and α-syn intracellular stability and secretion in PD pathogenesis.

Liver impairment can alter the metabolic capacity of the organ significantly, potentially affecting the efficacy and safety of Helicobacter pylori (H. pylori) eradication regimens. Although this issue is highly significant, no standardized guidelines currently exist for H. pylori eradication therapy in patients with liver dysfunction. To bridge this gap, we systematically reviewed studies on the efficacy and safety of H. pylori eradication therapy in individuals with liver impairment. The systematic review included a search of PubMed, the Igaku Chuo Zasshi, and the Cochrane Library database to identify eligible randomized controlled trials (RCTs) and/or non-randomized controlled trials (NRCTs). Three RCTs and five NRCTs were included. Research on the effectiveness of H. pylori eradication treatment in patients with and without liver disease has produced inconsistent findings, with a study reporting higher eradication rates in the liver disease group, and others finding no significant difference, leaving no definitive consensus. Two studies reported eradication rates <70% in patients with HCV infection, whereas other studies demonstrated eradication rates >80% in groups with liver impairment. Furthermore, even in cases of advanced liver impairment such as non-alcoholic steatohepatitis (NASH) or liver cirrhosis, eradication rates did not decline, and adverse events were either minimal or comparable with those observed in groups without liver impairment. H. pylori eradication therapy is applicable and safe for patients with liver disease; however, treatment indications should be determined carefully by considering reduced hepatic metabolic capacity and specific indications for eradication, while remaining vigilant for potential adverse effects.

Autonomic dysfunction is involved in functional dyspepsia (FD) however, the details have not been elucidated. The aim is to clarify the relationship among autonomic nervous system (ANS) activity, life events, and abdominal symptoms by real-time recordings. This is a prospective multicenter study including 9 patients with FD and 23 healthy controls (HC). The ANS activity was recorded for 24 ‍h using a T-shirt-type wearable device. Life events and abdominal symptoms were simultaneously recorded with ANS activity by smartphone application software. We defined low-frequency/high-frequency (LF/HF) and HF as activity indicators of the sympathetic and parasympathetic nerves, respectively. The number of abnormal LF/HF and HF in patients with FD was significantly higher than that in HC. The number of abnormal LF/HF and HF signals was significantly positively correlated with dyspeptic symptoms. The number of abnormal LF/HF signals was significantly negatively correlated with quality of life (QOL). During the symptomatic period, the HF levels were elevated in the HC group. In contrast, HF significantly decreased in patients with FD, which may imply parasympathetic nervous system dysfunction. In conclusion, patients with FD have abnormal ANS activity, which is associated with symptoms and lower QOL, and they exhibit parasympathetic nervous system dysfunction during symptomatic period.

This study investigates the nutritional applicability of balanced therapeutic diets for elderly individuals (aged 65 and above) with dysphagia, using the International Dysphagia Diet Standardization Initiative (IDDSI) and the 2022 Chinese Dietary Guidelines as dual frameworks. Ingredient data were collected from "Meishichina", a Chinese culinary database, and processed into dishes complying with IDDSI levels 1-7. Nutritional values were calculated using West China Hospital Nutrition Software, and statistical analyses, including ANOVA and Spearman correlation, were conducted to compare nutrients across IDDSI levels. Results showed significant variation in protein, fat, and carbohydrate content among food categories and IDDSI levels (p≤0.05), with meats and eggs contributing mainly to protein and fat, while fruits and grains contributed carbohydrates. Spearman analysis revealed positive correlations between IDDSI levels and energy, protein, and fat intake (p≤0.05). Only IDDSI level 7 met the elderly-specific target of 1,000 ‍kcal and 60 ‍g protein per meal. To address the nutritional gaps in other levels, supplementation with "Yi Quan Su" enteral nutrition powder was calculated based on the deficits. These findings highlight the nutritional limitations of texture-modified diets at lower IDDSI levels and emphasize the importance of targeted supplementation to meet the needs of older adults with dysphagia.

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.

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 R ² 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.

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.

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.

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.