BACKGROUND: Frailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain. OBJECTIVE: We sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose. METHODS: The study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis ( n = 300), and a multicenter double-blind, randomized, placebo-controlled trial ( n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups. RESULTS: The intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways. CONCLUSIONS: The findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence. TRIAL REGISTRATION: ClinicalTrials.gov NCT03995342.

Objectives: The aim of this study was to explore the expression of Galectin-9 in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), evaluate its clinicopathological significance, and investigate whether Galecin-9 expression has prognostic value in HBV-associated HCC. Methods: Immunohistochemistry staining was performed to examine the expression of Galectin-9 in paraffin-embedded tissues from 140 cases of HBV-associated HCC specimens. The association between Gal-9 expression, clinicopathological features and prognosis was analyzed by Kaplan-Meier method, log-rank test and Cox regression analysis. Dual immunofluorescence (IF) staining was performed to identify the cell types that have positive Gal-9 expression. Results: Among the 140 cases of HBV-associated HCC, 39 (27.9%) cases showed high Gal-9 expression (score≥6), 21 (15%) cases showed moderate Gal-9 expression (6>score≥3), 33 (23.6%) cases showed weak Gal-9 expression (3>score>0), and 47 (33.6%) cases had no detectable Gal-9 expression (score=0). Positive Gal-9 expression (score>0) was associated with lymph node metastasis (P=0.029), Ki-67 proliferation index (P=0.009) and poor prognosis. Univariate and multivariate analyses showed that Gal-9 expression could be used as an independent prognostic marker for HBV-associated HCC. Dual IF staining indicated that Gal-9 was mainly expressed in CD68+CD163+ Kupffer cells (KCs) in HBV-associated HCC. Conclusions: Gal-9 was specifically expressed in certain HBV-associated HCC. Positive Gal-9 expression was significantly associated with poor prognosis, and Gal-9 could be used as a prognostic marker in HBV-associated HCC. Specific expression of Gal-9 on KCs indicated it may have immunosuppressive function in HBV-associated HCC.

Oligoasthenospermia (OAS) leads to male infertility, significantly impacting patients and their families. Previous studies have identified various mechanisms involved in OAS, including oxidative stress, apoptosis, and autophagy. Ferroptosis, a novel cell death form, is also linked to male infertility. Despite advancements, the involvement of ferroptosis in spermatogenesis and its potential role in causing OAS, as well as the identification of safe and effective natural drugs targeting this mechanism, remain unclear. This study aimed to investigate the potential role of ferroptosis in OAS and explore safe and effective inhibitors for treatment. Semen samples were collected from patients with OAS. Mouse models of OAS were induced using cyclophosphamide (CP) in vivo, and GC-2 cells were treated in vitro. The effects of salidroside (Sal) on mice and GC-2 cells were evaluated using various methods, including ATP, malondialdehyde, and glutathione peroxidase activity assays; transmission electron microscopy; immunohistochemistry; flow cytometry; lipid peroxidation (LPO) analysis; mitochondrial membrane potential (MMP) assessment; enzyme-linked immunosorbent assays; qRT-PCR; western blotting; RNA sequencing; and immunofluorescence. Human OAS sperm exhibits biochemical and morphological hallmarks of ferroptosis. Ferroptosis is crucial in CP-induced OAS in mice in vivo, and its inhibition can effectively improve OAS. Further search for safe and stable natural compounds found Sal improved the sperm quality by attenuating ferroptosis-mediated LPO in germ cells through increased GPX4 expression, thereby ameliorating OAS in vivo. Immunohistochemistry revealed that Sal increases GPX4 expression starting from primary spermatocytes, highlighting its action stage during spermatogenesis. In vitro, these results were verified using a mouse spermatocyte cell line, GC-2 cells. Mechanistically, RNA-Seq and bioinformatic analysis suggest that Sal likely promotes GPX4 expression by inhibiting the NF-κB pathway, thereby reducing ferroptosis. Ferroptosis plays an important role in OAS, and Sal could ameliorate OAS by attenuating ferroptosis via NF-κB pathway inhibition.