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.
Natural antioxidants may help prevent oxidative stress-mediated aging. Astaxanthin (Asx) is a powerful antioxidant that has been used in various dietary supplements and cosmetics. Previously, we reported that combination of Asx with tocotrienol (T3) or capsaicin (Cap) exhibited synergistic antioxidative effects; however, the synergistic increase in activity was unremarkable. Herein, we employed curcumin (Cur) to more effectively enhance the antioxidant activity of Asx. The antioxidative activity of liposomes co-encapsulating Asx and Cur (Asx/Cur-lipo) showed effective synergism (activity increase of ~2). A shift in peak absorption suggested intermolecular interactions between Asx and Cur. Since synthetic Asx is a mixture of various stereoisomers, we examined the effect of Asx stereochemistry on the effective synergism by investigating liposomes prepared with 3R,3’R-form (Asx-R), and 3S,3’S-form (Asx-S). Antioxidative activities of Asx-R/Cur-lipo and Asx-S/Cur-lipo were evaluated. Only Asx-S/Cur-lipo exhibited a synergistic effect; however, the activity increase of Asx-S/Cur-lipo was lower than that of Asx/Cur-lipo. In conclusion, liposomes co-encapsulating a synthetic mixture of stereochemical isomers of Asx and Cur may be most potent in preventing oxidative stress-mediated aging.
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.
Although ginsenoside RK1 (RK1) possesses neuroprotective properties, it is unknown how it relates to vascular dementia (VD). The purpose of this work was to show that RK1 has a neuroprotective function in VD. First, the VD rat model was established by ligating the carotid artery with two-vessel occlusion (2-VO) surgery. RK1 was given daily for 30 days. A water maze test evaluated the learning and memory functions of the rats in each group. HE staining was used to assess the pathological damage of hippocampal tissue. The microglial marker Iba-1, proinflammatory factors [tumor necrosis factor alpha (TNF-α), Interleukin (IL)-1β, and IL-6], reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and peroxisome proliferator-activated receptor γ (PPARγ) in the hippocampal tissue were detected. The results show that RK1 reduced the escape latency of VD rats, increased the time VD rats stayed in the target quadrant and the number of times they crossed the platform, and alleviated the pathological damage of hippocampal tissue. In addition, RK1 also inhibited the activation of microglia and ROS production in the hippocampus of VD rats, reduced the content of proinflammatory factors and MDA, increased the content of antioxidant enzyme SOD, and activated PPARγ expression in hippocampal tissue. Overall, RK1 alleviates cognitive dysfunction and hippocampal tissue pathological damage in VD rats and inhibits hippocampal neuroinflammation and ROS production, which may be related to the activation of PPARγ in hippocampal tissue by RK1.
Diabetic cardiomyopathy (DCM), a life-threatening cardiovascular complication of diabetes, manifested as progressive cardiac dysfunction mediated through oxidative stress, inflammation, and apoptosis. Loganic acid (LA), a natural iridoid compound with anti-inflammatory and antioxidant properties, has demonstrated therapeutic potential in various inflammatory disorders, but its role in DCM remains unexplored. Here, we systematically investigated LA’s cardioprotective potential and its mechanisms. Utilizing a high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mouse model, LA (30 mg/kg, oral gavage) was administered for 8 weeks post-diabetes confirmation. Echocardiographic assay indicated that LA improved cardiac function. Histopathologic evaluation displayed that LA attenuated myocardial structural disorders, reduced collagen deposition, and suppressed cardiomyocyte apoptosis. Furthermore, LA treatment normalized redox imbalance (decreased MDA and increased GSH) and reduced inflammatory cytokine levels. In vitro, a diabetic cell model was established with AC16 cardiomyocytes exposed to high glucose (HG; 30 mM). The findings demonstrated that LA (25 or 50 μM) dose-dependently ameliorated HG-induced cardiomyocyte damage, oxidative stress, and inflammatory cytokine release. Mechanistically, LA treatment suppressed HG-induced activation of TLR4 signaling and phosphorylation of p38 MAPK. Collectively, these findings highlight LA as a novel therapeutic candidate in DCM, targeting the TLR4/p38 MAPK axis to attenuate diabetes-induced cardiac damage.
This study investigated the role of CA10 gene DNA methylation in bladder cancer progression, revealing that hypermethylation significantly reduces CA10 expression in tumor tissues compared to adjacent tissues. Utilizing TCGA data analysis with the ChAMP package for DMPs/DMRs, alongside qRT-PCR/semiquantitative RT-PCR for methylation and expression validation, researchers found that treatment with the demethylating agent 5-Aza-dC restored CA10 expression. Functional assays (flow cytometry, MTT, transwell) demonstrated that this restoration inhibited cancer cell proliferation, migration, and cell cycle progression. Furthermore, in vivo tumor xenograft models confirmed CA10’s tumor-suppressive role and the efficacy of epigenetic therapy in inhibiting tumor growth. The study identifies DNA methylation-driven silencing of CA10 as a key mechanism in bladder carcinogenesis and highlights its broader diagnostic potential across cancers.
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.
Cross-correlations between plasma isoleucine (Ile), leucine (Leu), and valine (Val) concentrations are observed in healthy individuals (C group). A parallel shift in these correlations has been noted in patients with end-stage renal failure. To evaluate this shift, a novel b value metric is proposed to assess variations in individuals. Branched-chain amino acids (BCAAs) concentrations were analyzed in four groups: 69 healthy controls (C group), 97 patients with type 2 diabetes mellitus (T2DM), 63 patients with chronic kidney disease (CKD) not on hemodialysis (CKD), and 45 patients with CKD on hemodialysis (CKD-HD). The b value was calculated using the equation Y = aX + b, where coefficient a was derived from the regression line in the C, and each BCAA pair (X, Y) was substituted accordingly. The T2DM exhibited elevated BCAA levels; however, the b values for the (Ile, Leu) and (Ile, Val) pairs remained unchanged. The CKD and CKD-HD showed significant decreases in b values. In T2DM, increased BCAA levels followed the regression line observed in healthy individuals, whereas in CKD, decreased BCAA levels deviated from this pattern. The b value effectively detects changes in BCAA metabolism that are not captured by individual BCAA levels alone, serving as a novel indicator of altered BCAA metabolism and homeostasis.
Muscle-strengthening activities reduce the risk of various diseases and promote overall health. Physical activities targeting large muscle groups, such as weightlifting or resistance exercises, provide an additional health benefit. The present study investigated the relationship between strength training and health-related quality of life (HRQOL) through a cross-sectional study of 50 adults participating in large muscle group strengthening activities (LMG) and 50 adults who did not (NLMG). HRQOL was assessed using the SF-12v2 questionnaire, and sleep habits were assessed using the PSQI questionnaire. The LMG group had a significantly higher Role/Social component summary (RCS) score than the NLMG group (50.5 ± 7.2 vs 47.2 ± 8.3; respectively, p = 0.040). The physical component summary (PCS) and mental component summary (MCS) scores also tended to be higher in the LMG group than in the NLMG group (52.6 ± 8.4 vs 49.9 ± 10.2, respectively; p = 0.15 and 59.0 ± 7.9 vs 56.7 ± 6.0, respectively; p = 0.10). Linear regression analysis showed that a higher RCS score was significantly associated with LMG training, whereas higher PCS and MCS scores were associated with better sleep quality. These results suggest that strength training targeting large muscle groups may improve the social aspect of HRQOL, highlighting the potential benefits of incorporating such exercises into regular physical activity regimens.
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.
This study comprised two trials that evaluated the safety and anti-stress effects of rosemary extracts containing rosmarinic acid and diterpenes. Study I was a 4-week, single-arm, open-label safety trial involving 22 healthy adults who consumed high doses of the rosemary extract daily. No clinically relevant adverse events or abnormal laboratory findings were observed, thus confirming its safety. Study II was a randomized, double-blind, placebo-controlled, crossover trial with 40 participants that assessed psychological and physiological stress markers. After four weeks of rosemary extract intake, significant improvements were found in trait anxiety scores measured using the State-Trait Anxiety Inventory and heart rate variability, as indicated by a decreased low-frequency/high-frequency ratio. Additionally, a single dose administered before the mental workload test significantly reduced state anxiety scores. No significant differences were observed in salivary cortisol levels or visual analog scale scores between the groups. These results suggest that rosemary extract is safe for consumption and may effectively reduce chronic and acute stress in healthy individuals. These findings support the use of rosemary extract as a natural dietary supplement for stress management.
Probiotics are live microorganisms that confer a health benefit on the host. Nevertheless, there is few pertinent research on the impact of probiotics on the healthy individuals. Therefore, a placebo-controlled randomized trial was conducted to investigate the effects of Bifidobacterium animalis subsp. lactis BLa80 supplementation on the gut microbiota composition in healthy individuals. A total of 112 participants were assigned to two groups: a placebo group that received maltodextrin, and a BLa80 group that received a combination of maltodextrin and strain BLa80 at a dosage of 1 × 1010 colony-forming units per day. The study duration was 8 weeks and 16S rRNA sequencing was employed to analyze changes in gut microbiota. Furthermore, the study assessed the metabolic effects of BLa80 by monitoring alanine transaminase (ALT), aspartate aminotransferase (AST), and uric acid (UA). The BLa80 intervention demonstrated the ability to modulate the gut microbiota and significantly increase the proportion of Bifidobacterium spp. The BLa80 intervention markedly reduced metabolic pathways associated with Biofilm formation—Pseudomonas aeruginosa, cationic antimicrobial peptide (CAMP) resistance and other metabolic pathways associated with conditionally pathogenic bacteria and CAMP. No adverse effects were reported throughout the study. Additionally, the BLa80 intervention slowed the increase in uric acid levels compared to the placebo group. For the primary outcome, these results demonstrate that BLa80 is capable of transient enrichment in the human intestine. Additionally, BLa80 was effective in increasing the relative abundance of beneficial bacteria. In conclusion, the observed beneficial effects position BLa80 as a promising probiotic strain.