NF-κB is constitutively activated in psoriatic epidermis. However, how activated NF-κB promotes keratinocyte hyperproliferation in psoriasis is largely unknown. Here we report that the NF-κB activation triggered by inflammatory cytokines induces the transcription of microRNA (miRNA) miR-31, one of the most dynamic miRNAs identified in the skin of psoriatic patients and mouse models. The genetic deficiency of miR-31 in keratinocytes inhibits their hyperproliferation, decreases acanthosis and reduces the disease severity in psoriasis mouse models. Furthermore, protein phosphatase 6 (ppp6c), a negative regulator that restricts the G1 to S phase progression, is diminished in human psoriatic epidermis and is directly targeted by miR-31. The inhibition of ppp6c is functionally important for miR-31-mediated biological effects. Moreover, NF-κB activation inhibits ppp6c expression directly through the induction of miR-31, and enhances keratinocyte proliferation. Thus, our data identify NF-κB-induced miR-31 and its target, ppp6c, as critical factors for the hyperproliferation of epidermis in psoriasis.

HUC-MSCs seem to be an optimal choice for stem cell-based therapy. However, before the cells translate from basic to clinical research, some problems still remain to be solved: i) building regulatory guidelines as well as an efficient and safe manufacturing procedure; ii) establishing donor's genetic testing and long-term closely monitoring system; iii) conducting further clinical trials to determine the optimum and standard dosage, time, route, frequency and many other technical issues of HUC-MSCs transplantation.

The Y-box binding protein-1 (YB-1) is a transcription/ translation factor that is highly expressed in primary breast tumors where it is consistently associated with poor survival. It induces human epidermal growth factor receptor (her-2) along with its dimerization partner egfr by directly binding to their promoters. In addition to promoting growth by inducing receptor tyrosine kinases, YB-1 also protects cells against apoptosis through mechanisms that have not been fully revealed. Given this, we addressed whether YB-1 might be an eventual therapeutic target for breast cancer by inhibiting it with small interfering RNAs in vitro and in vivo. Inhibiting YB-1 suppressed the growth of six of seven breast cancer cell lines that had amplified her-2 or were triple negative. Importantly, targeting YB-1 induced apoptosis in BT474-m1 and Au565 breast cancer cells known to have her-2 amplifications. The potential role of signal transducers and activators of transcription 3 (STAT3) was pursued to address the underlying mechanism for YB-1-mediated survival. Inhibition of YB-1 decreased P-STAT3 S727 but not P-STAT3 Y705 or total STAT3. This was accompanied by decreased P-ERK1/2 T202/Y204

Germination is considered to be an effective process for improving the nutritional quality and functionality of cereals. In this study, changes of nutritional ingredients, antinutritional components, chemical composition, and antioxidant activities of buckwheat seeds over 72 h of germination were investigated, and the reasons for these changes are discussed. With the prolonged germination time, the contents of crude protein, reducing sugar, total phenolics, total flavonoids, and condensed tannins increased significantly, while the levels of crude fat, phytic acid, and the activity of trypsin inhibitor decreased. Phenolic compounds, such as rutin, vitexin, isovitexin, orientin, isoorientin, chlorogenic acid, trans-3-hydroxycinnamic acid, and p-hydroxybenzoic acid increased significantly during the germination process, which may be due to the activation of phenylalanine ammonialyase. The improvement of flavonoids led to significant enhancement of the antioxidant activities of germinated buckwheat. Germinated buckwheat had better nutritional value and antioxidant activities than ungerminated buckwheat, and it represented an excellent natural source of flavonoids and phenolic compounds, especially rutin and C-glycosylflavones. Therefore, germinated buckwheat could be used as a promising functional food for health promotion.

Peripherally derived regulatory T (pTreg) cell generation requires T-cell receptor (TCR) signalling and the cytokines TGF-β1 and IL-2. Here we show that TCR signalling induces the microRNA miR-31, which negatively regulates pTreg-cell generation. miR-31 conditional deletion results in enhanced induction of pTreg cells, and decreased severity of experimental autoimmune encephalomyelitis (EAE). Unexpectedly, we identify Gprc5a as a direct target of miR-31. Gprc5a is known as retinoic acid-inducible protein 3, and its deficiency leads to impaired pTreg-cell induction and increased EAE severity. By generating miR-31 and Gprc5a double knockout mice, we show that miR-31 promotes the development of EAE through inhibiting Gprc5a. Thus, our data identify miR-31 and its target Gprc5a as critical regulators for pTreg-cell generation, suggesting a previously unrecognized epigenetic mechanism for dysfunctional Treg cells in autoimmune diseases.

Many annotated long noncoding RNAs (lncRNAs) harbor predicted short open reading frames (sORFs), but the coding capacities of these sORFs and the functions of the resulting micropeptides remain elusive. Here, we report that human lncRNA MIR155HG encodes a 17–amino acid micropeptide, which we termed miPEP155 (P155). MIR155HG is highly expressed by inflamed antigen-presenting cells, leading to the discovery that P155 interacts with the adenosine 5′-triphosphate binding domain of heat shock cognate protein 70 (HSC70), a chaperone required for antigen trafficking and presentation in dendritic cells (DCs). P155 modulates major histocompatibility complex class II–mediated antigen presentation and T cell priming by disrupting the HSC70-HSP90 machinery. Exogenously injected P155 improves two classical mouse models of DC-driven auto inflammation. Collectively, we demonstrate the endogenous existence of a micropeptide encoded by a transcript annotated as “non-protein coding” and characterize a micropeptide as a regulator of antigen presentation and a suppressor of inflammatory diseases.

Parastagonospora nodorum is a necrotrophic fungal pathogen that causes Septoria nodorum blotch (SNB) (formerly Stagonospora nodorum blotch) on wheat. P. nodorum produces necrotrophic effectors (NE) that are recognized by dominant host sensitivity gene products resulting in disease development. The NE-host interaction is critical to inducing NE-triggered susceptibility (NETS). To date, seven NE-host sensitivity gene interactions, following an inverse gene-for-gene model, have been identified in the P. nodorum-wheat pathosystem. Here, we used a wheat mapping population that segregated for sensitivity to two previously characterized interactions (SnTox1-Snn1 and SnTox3-Snn3-B1) to identify and characterize a new interaction involving the NE designated SnTox6 and the host sensitivity gene designated Snn6. SnTox6 is a small secreted protein that induces necrosis on wheat lines harboring Snn6. Sensitivity to SnTox6, conferred by Snn6, was light-dependent and was shown to underlie a major disease susceptibility quantitative trait locus (QTL). No other QTL were identified, even though the P. nodorum isolate used in this study harbored both the SnTox1 and SnTox3 genes. Reverse transcription-polymerase chain reaction showed that the expression of SnTox1 was not detectable, whereas SnTox3 was expressed and, yet, did not play a significant role in disease development. This work expands our knowledge of the wheat-P. nodorum interaction and further establishes this system as a model for necrotrophic specialist pathosystems.

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