Cleavage-embryo genes and transposable elements are regulated by histone variant H2A.X.

During mammalian preimplantation development, stimulation of zygotic genome activation (ZGA) and transposable elements (TEs) shapes totipotency profiling. A rare mouse embryonic stem cells (mESCs) subpopulation is capable of transiently entering a state resembling 2-cell stage embryos, with subtypes of TEs expressed and ZGA genes transiently activated. In this study, we found that deletion of H2A.X in mESCs led to a significant upregulation of ZGA genes and misregulated TEs. ChIP-seq analysis indicated a direct association of H2A.X at the Dux locus for silencing the Dux gene and its downstream ZGA genes in mESCs. We also demonstrated that histone variant H2A.X is highly enriched in human cleavage embryos when ZGA genes and TEs are active. Therefore, we propose that H2A.X plays an important role in regulating ZGA genes and TEs to establish totipotency.

Gut Microbiota May Not Be Fully Restored in Recovered COVID-19 Patients After 3-Month Recovery.

Coronavirus disease 2019 (COVID-19) has infected over 124 million people worldwide. In addition to the development of therapeutics and vaccines, the evaluation of the sequelae in recovered patients is also important. Recent studies have indicated that COVID-19 has the ability to infect intestinal tissues and to trigger alterations of the gut microbiota. However, whether these changes in gut microbiota persist into the recovery stage remains largely unknown. Here, we recruited seven healthy Chinese men and seven recovered COVID-19 male patients with an average of 3-months after discharge and analyzed their fecal samples by 16S rRNA sequencing analysis to identify the differences in gut microbiota. Our results suggested that the gut microbiota differed in male recovered patients compared with healthy controls, in which a significant difference in Chao index, Simpson index, and ß-diversity was observed. And the relative abundance of several bacterial species differed clearly between two groups, characterized by enrichment of opportunistic pathogens and insufficiency of some anti-inflammatory bacteria in producing short chain fatty acids. The above findings provide preliminary clues supporting that the imbalanced gut microbiota may not be fully restored in recovered patients, highlighting the importance of continuous monitoring of gut health in people who have recovered from COVID-19.

Itraconazole Induces Regression of Infantile Hemangioma via Downregulation of the Platelet-Derived Growth Factor-D/PI3K/Akt/mTOR Pathway.

Infantile hemangioma is the most common benign vascular tumor of infancy. We have previously reported that itraconazole, a common antifungal agent, can clinically improve or cure infantile hemangioma; however, the underlying molecular mechanisms are still unclear. Here, we show that itraconazole treatment significantly inhibits proliferation and promotes apoptosis of the endothelial cells of mouse hemangioma cell line and infantile primary hemangioma endothelial cell. Itraconazole also remarkably reduced angiogenesis of hemangioma endothelial cell in vitro. We further performed transcriptome profiling via mRNA microarrays in hemangioma endothelial cell upon itraconazole treatment, and identified cytokine-cytokine receptor interaction as the top significantly enriched pathway. Importantly, itraconazole significantly reduced platelet-derived growth factor-D level, resulting in suppression of platelet-derived growth factor-ß activation and inhibition of its downstream effectors, such as PI3K, Akt, 4E-BP1, and p70S6K, which are important for cellular growth and survival of infantile hemangioma. In conclusion, our results suggest that platelet-derived growth factor-D is a target of itraconazole in infantile hemangioma.

Efficacy and safety of itraconazole use in infants.

BACKGROUND: Itraconazole has been used to treat fungal infections, in particular invasive fungal infections in infants or neonates in many countries. DATA SOURCES: Literature search was conducted through Ovid EMBASE, PubMed, ISI Web of Science, CNKI and Google scholarship using the following key words: "pediatric" or "infant" or "neonate" and "fungal infection" in combination with "itraconazole". Based on the literature and our clinical experience, we outline the administration of itraconazole in infants in order to develop evidence-based pharmacotherapy. RESULTS: Of 45 articles on the use of itraconazole in infancy, 13 are related to superficial fungal infections including tinea capitis, sporotrichosis, mucosal fungal infections and opportunistic infections. The other 32 articles are related to systemic fungal infections including candidiasis, aspergillosis, histoplasmosis, zygomycosis, trichosporonosis and opportunistic infections as caused by Myceliophthora thermophila. CONCLUSION: Itraconazole is safe and effective at a dose of 5 mg/kg per day in a short duration of therapy for superficial fungal infections and 10 mg/kg per day for systemic fungal infections in infants. With a good compliance, it is cost-effective in treating infantile fungal infections. The profiles of adverse events induced by itraconazole in infants are similar to those in adults and children.