名古屋学芸大学

OBJECTIVE:Although nutritional and exercise interventions in mixed populations of non-dialysis and dialysis chronic kidney disease patients can improve muscle health, no study has specifically targeted dialysis patients or assessed their dietary intake. This systematic review and me-ta-analysis examined whether combined interventions improve physical performance, nutritional status, dietary intake, and quality of life (QOL) in adults receiving dialysis. METHODS:Following the PRISMA 2020 statement (PROSPERO CRD42024543470, registered on May 16, 2024), PubMed, Ichushi Web, and Web of Science were searched to September 30, 2024 for randomized, cluster-randomized, or crossover trials comparing combined nutrition plus exercise with sole either alone or with no intervention in adults (≥18 years) on hemodialysis or peritoneal dialysis. Favorable outcomes included physical performance, skeletal muscle mass, body mass index, energy and protein intake, QOL, and mortality, whereas the unfavorable outcome was gastrointestinal symptoms. Random-effects meta-analyses calculated mean differences (MDs) with 95% confidence intervals (CIs). RESULTS:Eight trials with 231 hemodialysis patients were eligible; seven contributed to quantitative synthesis. Nutritional interventions involved mainly oral supplements, and exercise (resistance, aerobic, or neuromuscular electrical stimulation) was performed two to three times/week for 3-12 months. Combined therapy significantly improved the 6MWT distance (MD 45.17 m, 95% CI 12.60-77.75), gait speed (MD 0.09 m/s, 95% CI 0.02 to 0.17), and TUG time (MD -1.44 s, 95% CI -2.63 to -0.25). No significant differences were observed in the Sit-to-Stand test, lean body mass, BMI, intake, or QOL. CONCLUSIONS:Compared with nutritional intervention alone, combined nutrition and exercise intervention was associated with improved physical performance outcomes in hemodialysis patients but showed no clear benefit for dietary intake, body composition, or QOL. The certainty of evidence was very low for all outcomes.

Agaro-oligosaccharides (AOSs) are agar-derived oligosaccharides composed of D-galactose and 3,6-anhydro-L-galactose. This study investigated the effects of dietary AOS on colonic mucin-related markers and their relationships with the cecal microbiota and short-chain fatty acids (SCFAs) in normal mice. Female BALB/c mice received a control diet or a diet with 5% cellulose replaced by AOS for 28 days (six mice in two cages per group). Colonic mucin-related markers, cecal microbiota, and SCFAs were assessed alongside in vitro experiments using Akkermansia muciniphila and HT-29 cells. AOS increased colonic Alcian blue–periodic acid–Schiff-positive area, fecal mucin content, and colonic Muc2 and Spdef mRNA expression. 16S rRNA sequencing revealed higher Akkermansia abundance, while species-specific qPCR indicated a higher A. muciniphila-to-total bacterial 16S rRNA gene copy ratio. Cecal acetate, propionate, and butyrate concentrations decreased; estimated total amounts decreased for acetate and butyrate but not significantly for propionate. In vitro, AOS increased A. muciniphila culture OD660 at 0.2–0.5% but decreased it at 1.0% and increased HT-29 MUC2 mRNA expression after 2 h. Despite limited cage-level replication and untested barrier function and microbial causality, these findings associate dietary AOS substitution with increased colonic mucin-related markers and a short-term MUC2 mRNA response in HT-29 cells.

The gut microbiota forms a complex ecosystem through metabolic interdependence (cross-feeding). However, conventional fecal metabolomics typically quantifies only total metabolite pools, making it difficult to distinguish extracellular-enriched metabolite pools from predominantly cell-associated ones, and thus limiting reconstruction of in situ metabolic networks. Here, we quantified fecal metabolites in paired fractions from the same specimen: an undisrupted fraction representing the extracellular pool and a strongly bead-beaten fraction representing the total pool; the intracellular pool was defined as the difference between total and extracellular measurements. Stool samples from 63 healthy individuals were analyzed for short-chain fatty acids, polyamines, and water-soluble vitamins, and the results were integrated with shotgun metagenomic profiles of species composition and functional genes. Vitamins exhibited two distinct behaviors. Adenosylcobalamin (a vitamin B12 coenzyme) was detectable only after disruption, and together with thiamine (B1) and niacin (B3) was classified as an intracellular-retained type (Type 1). In contrast, biotin (B7) and pantothenate (B5) showed higher extracellular proportions (Type 2). Integrative analyses further indicated that Type 1 thiamine was negatively associated with Blautia, consistent with intensive microbial utilization, whereas Type 2 biotin was strongly positively associated with Alistipes, suggesting links to ecological niches shaped by luminal pH and fermentation modes (carbohydrate vs protein fermentation). Fraction-resolved quantification provides a practical operational framework to differentiate extracellular from cell-associated metabolite pools, helping reconcile metagenomic potential with metabolomic reality and enabling deeper inference of cross-feeding structure in the gut ecosystem.

Huntingtin-associated protein 1 (HAP1) is a neurocytoplasmic protein implicated in intracellular trafficking, vesicular transport, and neuroprotection. Although HAP1 is abundantly expressed in hypothalamic regions involved in neuroendocrine regulation, its distribution and cellular specificity within the hypothalamic–pituitary axis remain poorly understood. Therefore, the present study aimed to characterize the expression pattern and cellular localization of HAP1 in neuroendocrine and neurosecretory systems of the adult mouse hypothalamic–pituitary axis. Adult male C57BL/6 J mice were analyzed using Western blotting, single-label immunoperoxidase histochemistry, and double-label immunofluorescence immunohistochemistry combined with hormone-specific markers. HAP1 immunoreactivity was detected throughout the pituitary gland, showing moderate scattered labeling in the anterior lobe, diffuse expression in the intermediate lobe, and intense accumulation in the posterior lobe. In the anterior and intermediate pituitary, HAP1 was highly expressed in thyrotrophs, corticotrophs, and melanotrophs, whereas gonadotrophs exhibited relatively low expression. In contrast, somatotrophs and lactotrophs lacked detectable HAP1 immunoreactivity. In the posterior pituitary, HAP1 was absent from S100β-positive pituicytes but strongly co-localized with oxytocin (OXT)- and arginine vasopressin (AVP)-containing neurosecretory structures, putative herring bodies. In the hypothalamus, HAP1 was prominently expressed in magnocellular neurons of the paraventricular and supraoptic nuclei and extensively co-localized with OXT- and AVP-producing neurons. Collectively, these findings demonstrate a highly cell-type-specific and compartmentalized distribution of HAP1 across the hypothalamic–pituitary axis. The continuous localization of HAP1 from hypothalamic neuronal somata to neurosecretory terminals provides an anatomical basis for investigating potential roles in vesicular trafficking, neuropeptide transport, and neurosecretory regulation, as well as its possible contribution to selective cellular resilience within neuroendocrine systems.