Multi-Lineage Human Endometrial Organoids on Acellular Amniotic Membrane for Endometrium Regeneration.

Asherman's syndrome is an endometrial regeneration disorder resulting from injury to the endometrial basal layer, causing the formation of scar tissue in the uterus and cervix. This usually leads to uterine infertility, menstrual disorders, and placental abnormalities. While stem cell therapy has shown extensive progress in repairing the damaged endometrium and preventing intrauterine adhesion, issues of low engraftment rates, rapid senescence, and the risk of tumorigenesis remain to be resolved for efficient and effective application of this technology in endometrial repair. This study addressed these challenges by developing a co-culture system to generate multi-lineage endometrial organoids (MLEOs) comprising endometrial epithelium organoids (EEOs) and endometrial mesenchymal stem cells (eMSCs). The efficacy of these MLEOs was investigated by seeding them on a biocompatible scaffold, the human acellular amniotic membrane (HAAM), to create a biological graft patch, which was subsequently transplanted into an injury model of the endometrium in rats. The results indicated that the MLEOs on the HAAM patch facilitated endometrial angiogenesis, regeneration, and improved pregnancy outcomes. The MLEOs on the HAAM patch could serve as a promising strategy for treating endometrial injury and preventing Asherman's syndrome.

Angong Niuhuang Pill ameliorates cerebral ischemia/reperfusion injury in mice partly by restoring gut microbiota dysbiosis.

Angong Niuhuang Pill (ANP) is a famous traditional Chinese patent medicine and is used for treating ischemic or hemorrhagic stroke for centuries. However, the mechanism of action of ANP in stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of ANP in treating acute ischemic stroke from the perspective of the gut microbiota. A mouse model of acute ischemic stroke by middle cerebral artery occlusion (MCAO) was established, and 16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the sham, model, and ANP-treated MCAO mice. The results showed that ANP significantly ameliorated cerebral infarct volume, improved neurological deficits, and reduced histopathological injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, increased Nissl bodies, and decreased cell apoptosis. Moreover, ANP reversed gut microbiota dysbiosis by modulating the abundance of bacteria whose effects may mitigate MCAO damage, such as the phyla Bacteroidetes and Firmicutes, the families Lachnospiraceae and Prevotellaceae, and the genera Alloprevotella and Roseburia. Microbial metabolites related to inflammation and neuroprotection, such as prostaglandin I2 and uridine, were also regulated by ANP treatment. Uridine, guanosine, and inosine might be potential neuromodulators produced by the gut microbiota in the ANP-treated group. Spearman correlation analysis revealed that these metabolites were intimately related to certain genera, including Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter. Our results demonstrated that alleviating gut microbiota dysbiosis is one of the mechanisms by which ANP protects against ischemic stroke and suggest that targeting Alloprevotella, Lachnoclostridium, Enterorhabdus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter might be a potential anti-stroke therapy.

[Mechanism of Guanxinning against cerebral ischemia-reperfusion injury in mice based on transcriptomic analysis].

Guanxinning, a modern Chinese medicine preparation composed of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma, has the activities of activating blood circulation, resolving blood stasis, dredging vessels, and nourishing the heart. Clinical studies have demonstrated that Guanxinning has therapeutic effect on ischemic stroke, while the specific mechanism remains to be clarified. In this study, the potential mechanism of Guanxinning against cerebral ischemia-reperfusion injury in mice was explored and then verified in vitro. The mouse model of cerebral ischemia-reperfusion injury was established with middle cerebral artery embolization(MCAO) method. The pharmacological effects of Guanxinning on the model mice were investigated based on neurological function score, cerebral infarction area, pathological morphology, neuron injury, and apoptosis. The results showed that Guanxinning lowered neurological functional score, reduced cerebral infarction area, and ameliorated the histopathological morphology, neuronal damage, and apoptosis in the model mice. RNA samples were extracted from brain tissues and subjected to RNA sequencing(RNA-seq). The differentially expressed genes(DEGs) were screened with the thresholds of ■. GO function enrichment analysis and KEGG pathway enrichment analysis were performed for the 297 common DEGs, which indicated that Guanxinning may regulate the inflammatory response, oxidative stress response, energy metabolism, and apoptosis to treat cerebral ischemia-reperfusion injury in mice. Guanxinning exerted protective effect through inhibiting inflammation and reducing oxidative stress in hypoxia/reoxygenation injured SH-SY5 Y cells. Furthermore, Western blot indicated that Guanxinning down-regulated the protein levels of p-NF-κB p65 and p-p38 MAPK and up-regulated those of PPARγ and PGC-1α. The findings suggested that Guanxinning may inhibit inflammation and reduce oxidative stress by suppressing TNF signaling pathway and activating PPAR signaling pathway, thereby exerting the therapeutic effect on cerebral ischemia-reperfusion injury in mice. This study preliminarily reveals the mechanism of Guanxinning against cerebral ischemia-reperfusion injury and provides a basis for clinical application of Guanxinning.