Background The function of diverse ruminal microbes is tightly linked to rumen development and host physiology. The system of ruminal microbes is an excellent model to clarify the fundamental ecological relationships among complex nutrient–microbiome–host interactions. Here, neonatal lambs are introduced to different dietary regimes to investigate the influences of early-life crosstalk between nutrients and microbiome on rumen development. Results We find starchy corn-soybean starter-fed lambs exhibit the thickest ruminal epithelia and fiber-rich alfalfa hay-fed lambs have the thickest rumen muscle. Metabolome and metagenome data reveal that indole-3-carboxaldehyde (3-IAld) and prostaglandin D2 (PGD2) are the top characteristic ruminal metabolites associated with ruminal epithelial and muscular development, which depend on the enhanced ruminal microbial synthesis potential of 3-IAld and PGD2. Moreover, microbial culture experiment first demonstrates that Bifidobacterium pseudolongum is able to convert tryptophan into 3-IAld and Candida albicans is a key producer for PGD2. Transcriptome sequencing of the ruminal epithelia and smooth muscle shows that ruminal epithelial and muscular development is accompanied by Wnt and Ca 2+ signaling pathway activation. Primary cell cultures further confirm that 3-IAld promotes ruminal epithelial cell proliferation depending on AhR-wnt/β-catenin signaling pathway and PGD2 accelerates ruminal smooth muscle cell proliferation via Ca 2+ signaling pathway. Furthermore, we find that 3-IAld and PGD2 infusion promote ruminal epithelial and musculature development in lambs. Conclusions This study demonstrates that early-life ruminal microbiome-derived 3-IAld and PGD2 are effective promoters of rumen development, which enhances our understanding of nutrient–microbiome–host interactions in early life.
Chuxi Zhang,Shuang Jia,Jinlong Huang,Haichuan Peng,Jiao Zhang,Lubing Liu,Wei Zhang,Hongbo Xin,Xiaolei Wang
In this study, we aimed to achieve an efficient repair of damaged skeletal muscles using polyvinyl alcohol (PVA) soluble microneedle patches (MNP) loaded with carbonized wormwood and prostaglandin E2 (inflammatory factors). The introduction of carbonized wormwood imparted the MNP with near-infrared light heating characteristics that improved the efficiency of prostaglandin E2 delivery while also promoting circulation in the damaged muscle area. Our experimental results showed that, compared with the classical moxibustion treatment, the system could more quickly restore muscle strength and the cross-sectional area of muscle bundle fibers in a mouse model of muscular injury. In addition, it could also successfully induce the proliferation and differentiation of muscle stem cells to effectively repair injured muscle tissues. Above all, this light-controlled photothermal MN (microneedle) drug-delivery system avoided the common problems of traditional moxibustion such as large levels of smoke, slow efficacy and risk of scalding. Collectively, we put forward a safe, accurate and efficient approach for skeletal muscle damage treatment using carbonized wormwood.
Xiao-Wei Gu,Zi-Cong Chen,Zhen-Shan Yang,Yan Yang,Ya-Ping Yan,Yue-Fang Liu,Ji-Min Pan,Ren-Wei Su,Zeng-Ming Yang
Embryo implantation involves a sterile inflammatory reaction that is required for the invasion of the blastocyst into the decidua. Adenosine triphosphate (ATP) released from stressed or injured cells acts as an important signaling molecule to regulate many key physiological events, including sterile inflammation. We found that the amount of ATP in the uterine luminal fluid of mice increased during the peri-implantation period, and this depended on the presence of an embryo. We further showed that the release of ATP from receptive epithelial cells was likely stimulated by lactate released from the blastocyst through connexin hemichannels. The ATP receptor P2y2 was present on uterine epithelial cells during the preimplantation period and increased in the stromal cells during the time at which decidualization began. Pharmacological inhibition of P2y2 compromised decidualization and implantation. ATP-P2y2 signaling stimulated the phosphorylation of Stat3 in uterine luminal epithelial cells and the expression of early growth response 1 ( Egr1 ) and prostaglandin-endoperoxide synthase 2 ( Ptgs2, also known as Cox-2 ), all of which are required for decidualization and/or implantation, in stromal cells. Short exposure to high concentrations of ATP promoted decidualization of primary stromal cells, but longer exposures or lower ATP concentrations did not. The expression of genes encoding ATP-degrading ectonucleotidases increased in the decidua during the peri-implantation period, suggesting that they may limit the duration of the ATP signal. Together, our results indicate that the blastocyst-induced release of ATP from uterine epithelial cells during the peri-implantation period may be important for the initiation of stromal cell decidualization.
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