Li Lin,Ye Jiahao,Zhao Zhenyu,Hu Siyuan,Liang Hao,Ouyang Ji,Hu Zhixi
Heart failure (HF) is a chronic condition that progressively worsens and continues to be a major financial burden and public health concern. The “gut-heart” axis provides an innovative perspective and therapeutic strategy for preventing and treating heart failure. Shenfu injection (SFI) is a Traditional Chinese Medicine-based treatment demonstrating potential as a therapeutic strategy for heart failure. However, the precise therapeutic mechanisms of SFI in heart failure are not completely characterized. In this study, HF models were established utilizing subcutaneous multipoint injection of isoproterenol (ISO) at a dosage of 5 mg kg−1·d−1 for 7 days. Serum levels of inflammatory biomarkers were quantified using protein microarrays. Rat feces were analyzed using untargeted metabolomics research and 16S rRNA sequencing. The link between gut microbiota and metabolites was examined using a MetOrigin and Spearman correlation analysis. Our results show that Shenfu injection effectively enhances cardiac function in rats with ISO-induced heart failure by potentially modulating pro-/anti-inflammatory imbalance and reducing serum and urine Trimethylamine-N-oxide (TMAO) levels. Moreover, SFI significantly increases the abundance of Bacteroidota at the phylum level, thereby improving disrupted gut microbiota composition. Additionally, SFI supplementation enriches specific genera known for their capacity to produce short-chain fatty acids. SFI was found to be associated with three key metabolic pathways, as revealed by fecal metabonomics analysis, including the pentose phosphate pathway, pyrimidine metabolism, and purine metabolism. Metabolite tracing analysis revealed that Taurine and hypotaurine metabolism was found to be specific to the microbial community. The biosynthesis of Pyrimidine metabolism, Purine metabolism, beta-alanine metabolism, Naphthalene degradation, Pantothenate, and CoA biosynthesis were identified as co-metabolic pathways between microbes and host. The Spearman correlation analysis was also significantly correlated to differentially expressed metabolites regulated by SFI and the gut microbiota. These results suggest that SFI improves ISO-induced heart failure by modulating co-metabolism and regulating the TMAO-inflammation axis.
Rili Hao,Xinyu Song,Feng Li,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li
Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl 2 (1.5 mg/kg/day body weight). For the CdCl 2 -treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl 2 -initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.
Individualized biological hydroxyapatite (BHA) scaffolds are essential for repairing critical craniomaxillofacial bone defects. Additive manufacturing relies on synthetic hydroxyapatite and biomimetic structures, making the resulting scaffolds inferior to natural bone. A subtractive manufacturing solution is proposed to cut natural bone blocks and then sinter them into BHA scaffolds. However, BHA scaffolds with fragile mechanical performance, fail to maintain scaffold integrity, due to microcracks generated by loss of organics from extracellular matrix (ECM). To preserve natural structure and enhance mechanical properties, ECM-gelatin hydrogel (ECM-Gel) is utilized as a micron-level coating to smooth surface microcracks like a facial mask. ECM-Gel shows potential in regulating blood clot fibrin network which may induce a favorable macrophage-mediated bone regeneration. Therefore, a gelatin hydrogel-masked BHA (G-BHA) scaffold system is developed using crosslinker genipin (2 and 8 mM). ECM-Gel formed a “hybrid layer”, smoothing the micron-level microcracks and enhancing mechanical properties of BHA; it activated platelets to lock blood clot with dense fibrin network, inducing M2 macrophage via a potential endocytosis-macroautophagy-inflammation axis for bone regeneration. In vivo experiments confirmed G-BHA scaffolds promoted ectopic and in situ bone regeneration. Therefore, ECM-gel-masking demonstrates great potential in developing individualized bioauthentic bone scaffolds with favorable blood clot and macrophage-mediated bone regeneration.
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