Background/Objectives: Neurodegeneration associated with diabetes and metabolic dysfunction involves interconnected processes, including advanced glycation end product (AGE)-related signaling, RAGE/NOX4-dependent oxidative stress, dysregulated endoplasmic reticulum (ER) stress, and mitochondrial apoptosis. Phycocyanobilin (PCB), a tetrapyrrolic chromophore of C-phycocyanin, has been proposed to exert pleiotropic cytoprotective effects; however, its actions within glycation-associated neuronal stress pathways remain incompletely defined. Methods: Differentiated SH-SY5Y neurons were exposed to AGEs (300 μg/mL) for a 24 h period to examine whether PCB modulates neuronal injury along the RAGE-NOX4-oxidative-stress-ER-stress-mitochondrial axis. The selective RAGE antagonist TTP488 (100 μmol/L) was included as a pharmacological reference. Neuronal viability, neurite integrity, intracellular and mitochondrial reactive oxygen species, ER stress signaling, and apoptotic markers were assessed using complementary biochemical, molecular, and functional assays. Results: PCB pretreatment (10-50 μmol/L) significantly improved neuronal viability, preserved neurite structure, and reduced oxidative stress under the AGE challenge. These effects were accompanied by attenuation of AGEs-induced upregulation of RAGE and NOX4 expression, suppression of PERK-eIF2α-ATF4-CHOP signaling, restoration of mitochondrial apoptotic balance, inhibition of caspase activation, and reduced DNA fragmentation. The overall protective profile of PCB was comparable to that observed with TTP488 at the level of downstream pathway modulation. Conclusions: These findings suggest that PCB mitigates glycation-associated neuronal injury through coordinated regulation of oxidative, ER stress, and mitochondrial apoptotic pathways linked to RAGE/NOX4 signaling, supporting further investigation of PCB as a functional food-derived bioactive in metabolic stress-related neurodegeneration.
Optimizing training intensity and volume is crucial for adolescent swimmers, as excessive high-intensity exercise may cause fatigue, overtraining, and hinder recovery. Research has shown that training load affects immune function and sleep. This study examined how progressively increasing training intensity impacts salivary immunity, sleep quality, perceived fatigue, and performance in adolescent swimmers. Eighteen male swimmers participated in a three-week protocol with daily 100-min sessions at 70%, 80%, and 90% of maximum heart rate, respectively. Saliva and questionnaire data were collected twice weekly to assess cortisol, testosterone, α-amylase, immunoglobulin A, lactoferrin, and perceived exertion. Sleep was measured using actigraphy. Performance was evaluated weekly through 200-m freestyle and 25-m lap counts within 16 min. Results showed a significant weekly increase in maximum heart rate (p < 0.001). Muscle soreness and perceived exertion were significantly higher after training at 80% and 90% intensities (p < 0.05) compared to rest days. Sleep quality and most salivary immune markers did not significantly change over time. However, the testosterone/cortisol ratio decreased after 5 days at 80% intensity (p < 0.01). Performance significantly improved at 80% and 90% intensities compared to 70%. In conclusion, a progressively incremental training program enhanced athletic performance without negatively affecting sleep or immune markers. These findings support controlled intensity increases for improving performance while maintaining physiological balance in adolescent swimmers.
Athletic training and menstruation both contribute to iron depletion and anemia in female athletes. We hypothesized that oral iron supplementation during the menstrual period would increase the hemoglobin (Hb) level and reduce fatigue in female athletes. Twenty-two female athletes were randomly assigned to either the control (CON) or experimental (EXP) groups. Participants in the EXP group received one capsule of ferrous bisglycinate chelate (equivalent to 20 mg of elemental iron) daily during their menstrual periods in the second, third, and fourth menstrual cycles (M2-M4), whereas those in the CON group took a placebo. Blood samples from each subject were collected after each menstrual period, and Hb, hematocrit, and blood cell counts were analyzed. The results indicated that iron supplementation significantly increased the levels of Hb, hematocrit, and red blood cell (RBC) count from the first menstrual bleeding period (M1) to the fifth menstrual bleeding period (M5). The immune-related cell populations and rating of perceived exertion fatigue indicators showed no significant differences from M1 to M5. In conclusion, daily supplementation with ferrous bisglycinate chelate during the menstrual period significantly increased Hb levels, hematocrit levels, and RBC counts in female athletes.
Background:Intracerebral haemorrhage (ICH) is a leading cause of mortality and morbidity worldwide. Identifying early prognostic biomarkers is crucial to optimise clinical management of critically ill patients with ICH. The haemoglobin-to-red cell distribution width ratio (HRR) has recently emerged as a potential predictor in various critical illnesses, but its role in ICH remains unclear. This study aimed to evaluate associations between HRR and mortality in patients with ICH. Methods:This retrospective cohort study included the data of adults (≥18 years) extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (version 1). HRR was calculated from the first available haemoglobin and RDW measurements within one day of each other. Patients were categorised into HRR quartiles. The primary outcomes were 28-day and 1-year all-cause mortality. Associations were assessed using Cox proportional hazards models. Results:The data of 1915 patients (mean age 67.5 years) were analysed retrospectively. After adjusting for possible confounders, compared with the lowest HRR quartile (Q1), patients in Q3 and Q4 had significantly lower 28-day mortality (Q3: adjusted hazard ratio (aHR) = 0.72; 95% CI = 0.54, 0.97; Q4: aHR = 0.67; 95% CI = 0.49, 0.90). Similarly, higher HRR quartiles were associated with reduced 1-year mortality risk (Q3: aHR = 0.64; 95% CI = 0.49, 0.84; Q4: aHR = 0.56; 95% CI = 0.42, 0.75). Conclusions:Lower HRR at admission is independently associated with higher short-term and long-term mortality in ICU patients with ICH. HRR may serve as a candidate prognostic biomarker for early risk stratification in this high-risk population. Further prospective studies are warranted to confirm these findings.
Direct-acting antivirals (DAAs) cure most chronic hepatitis C virus (HCV) infections, yet whether the gut microbiota returns toward a healthy state after viral clearance remains uncertain. We systematically reviewed DAA-era adult HCV studies using sequencing-based fecal microbiota assessment (PROSPERO CRD420261374682). Longitudinal alpha-diversity change was pooled by REML random-effects meta-analysis with Hartung–Knapp adjustment, and compositional/functional findings were synthesized narratively. Seven studies met qualitative criteria and five longitudinal reports were extractable. Because participant overlap between two Thai reports could not be excluded, the primary conservative non-overlap analysis of four reports (180 paired observations) gave Hedges’ g = 0.13 (95% CI −0.53 to 0.80; I2 ≈ 89%); the five-report sensitivity estimate was directionally positive but imprecise (g = 0.35, 95% CI −0.38 to 1.07). Recovery concentrated in richness (Chao1), whereas evenness-weighted diversity (Shannon, Hill) barely moved; beneficial taxa such as Faecalibacterium and Blautia increased after SVR. These findings are consistent with uneven, richness-led microbial recovery, but the overall certainty of the pooled evidence is very low (GRADE); functional and clinical recovery remain insufficiently characterized and undemonstrated.
