SUMMARY The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here we report that during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendodermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a “seesaw model,” in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.

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The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit.

This paper presents a comprehensive review of the impacts of natural polysaccharides on gut microbiota and immune responses as well as their interactions.

In this study, three polysaccharides including water-soluble polysaccharide (WSP), dilute alkali-soluble polysaccharide (DASP) and concentrated alkali-soluble polysaccharide (CASP) were extracted from purple sweet potatoes and then administered to normal and cyclophosphamide (CTX) treated mice by gavage. The results showed that WSP and CASP could restore the spleen index and immune cytokine (IL-2 and IL-6) levels in CTX treated mice, while DASP could enhance the levels of TNF-α, IL-2 and IL-6. As compared to the normal control group, WSP and CASP treatment groups exhibited increased levels of Bacteroidetes, Lachnospiraceae and Oscillospira, but decreased levels of Firmicutes, Alcaligenaceae and Sutterella in normal mice. When compared with a model control group, all the three polysaccharide treatment groups showed relatively higher abundances of Bacteroidetes, Ruminococcaceae, Lachnospiraceae, Ruminococcus and Oscillospira but lower levels of Firmicutes, Proteobacteria, Alcaligenaceae and Sutterella in CTX treated mice. Moreover, all the polysaccharides could enhance the production of acetic acid, propionic acid and butyric acid in normal mice, while WSP could upregulate the production of these short chain fatty acids in CTX treated mice.

Nuage is an electron-dense cytoplasmic structure in germ cells that contains ribonucleoproteins and participates in piRNA biosynthesis. Despite the observation that clustered mitochondria are associated with a specific type of nuage called intermitochondrial cement (pi-body), the importance of mitochondrial functions in nuage formation and spermatogenesis is yet to be determined. We show that a germ cell-specific protein GASZ contains a functional mitochondrial targeting signal and is largely localized at mitochondria both endogenously in germ cells and in somatic cells when ectopically expressed. In addition, GASZ interacts with itself at the outer membrane of mitochondria and promotes mitofusion in a mitofusin/MFN-dependent manner. In mice, deletion of the mitochondrial targeting signal reveals that mitochondrial localization of GASZ is essential for nuage formation, mitochondrial clustering, transposon repression, and spermatogenesis. MFN1 deficiency also leads to defects in mitochondrial activity and male infertility. Our data thus reveal a requirement for GASZ and MFNmediated mitofusion during spermatogenesis.

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