One fundamental issue in public health is the safety of food products derived from plants and animals. A recent study raised a concern that microRNAs, which widely exist in everyday foods, may alter consumers’ functions. However, some studies have strongly questioned the likelihood of dietary uptake of functional microRNAs in mammals. Here we use a microRNA gene knockout animal model to show that miR-144/451 null mice can orally uptake miR-451 from a daily chow diet, and ingestion of wild type blood, that contains abundant miR-451, also enhances the level of miR-451 in the circulating blood of knockout mice. Moreover, reducing miR-451 level in miR-144/451 knockout blood by consuming food lacking miR-451 reduces the anti-oxidant capacity of miR-144/451 null red blood cells by targeting the 14-3-3ζ/Foxo3 pathway, while increasing miR-451 level via gavage-feeding of wild type blood increases the anti-oxidant capacity of miR-144/451 null red blood cells. We conclude that 1) some miRNAs in food can pass through the gastrointestinal tract into the blood to affect consumers’ function and 2) microRNA knockout animals such as miR-144/451 null mice can acquire the deleted genetic information from daily foods, which might alter the results and conclusions from the studies using such animals.

Purpose This study aims to identify intellectual structures, emerging trends and future research opportunities via a bibliometric analysis of senior tourism research from 1998 until 2017. Design/methodology/approach A detailed search of 700 core articles and 7,221 citations collated from Web-of-Science and Scopus was implemented and analyzed through CiteSpace. Findings The results reveal a slow increase in the amount of research, with six main areas of research. The most cited articles are mainly older. The USA has a solid leadership in publications, followed by Australia and China. The network of journals and institutions show a core peripheral structure where Tourism Management and University of Queensland are ranked first. The identification of structural holes, critical articles and the development of new emerging tendencies highlights the priorities in the senior tourism domain, pointing to new opportunities for research. Originality/value The originality of this paper consists in a temporal and dynamic analysis of the past two decades, using CiteSpace for a co-citation and co-occurrence network analysis.

The monolayered intrarenal urothelium covers the renal papilla and ureteropelvic junction (UPJ). In response to increased renal pressure during obstruction or ischemic injuries, intrarenal urothelial cells begin to proliferate and form a multilayered urothelium. Little is known regarding the mechanism and pathophysiological role of urothelium hyperplasia during renal obstruction. In this study, we investigated the expression of interleukin (IL)-33, an IL-1 family cytokine, in kidneys with unilateral ureteral obstruction (UUO)-induced obstructive injury. IL-33 levels in hydronephrotic urine and serum were upregulated 2 days after UUO. The number of ST2-expressing immune cells was increased in the UUO kidney. We found that IL-33 was upregulated in vimentin-positive cells in the cortical and medullar layers and the UPJ stroma. Moreover, IL-33 expression was predominantly induced in multilayered keratin 5-positive urothelial cells in the UPJ. IL-33 was not detected in terminally differentiated superficial umbrella cells expressing uroplakin 3a. In vivo, we confirmed that deficiency of IL33 or its receptor ST2 attenuated UUO-induced hyperplasia of the UPJ urothelium. Deficiency of IL33 attenuated the expression of UUO-induced type 2 inflammatory cytokines and upregulated uroplakins and urothelial differentiation signaling in UPJ tissues. Our results collectively suggest that the IL-33/ST2 axis mediates the activation of innate immune responses and contributes to urothelial hyperplasia by regulating urothelial differentiation in obstructive kidney injury.

Human mesenchymal stem cells (MSCs) modified by targeting DNA hypermethylation of genes in the Salvador/Warts/Hippo pathway were induced to differentiate into neuronal cells in vitro. The differentiated cells secreted a significant level of brain-derived neurotrophy factor (BDNF) and the expression of BDNF receptor tyrosine receptor kinase B (TrkB) correlated well with the secretion of BDNF. In the differentiating cells, CREB was active after the binding of growth factors to induce phosphorylation of ERK in the MAPK/ERK pathway. Downstream of phosphorylated CREB led to the functional maturation of differentiated cells and secretion of BDNF, which contributed to the sustained expression of pERK and pCREB. In summary, both PI3K/Akt and MAPK/ERK signaling pathways play important roles in the neuronal differentiation of MSCs. The main function of the PI3K/Akt pathway is to maintain cell survival during neural differentiation; whereas the role of the MAPK/ERK pathway is probably to promote the maturation of differentiated MSCs. Further, cellular levels of protein kinase C epsilon type (PKC-ε) and kinesin heavy chain (KIF5B) increased with time of induction, whereas the level of NME/NM23 nucleoside diphosphate kinase 1 (Nm23-H1) decreased during the time course of differentiation. The correlation between PKC-ε and TrkB suggested that there is cross-talk between PKC-ε and the PI3K/Akt signaling pathway.

Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown. In this study, we generated a DPP10 antibody to label DPP10 protein in adult rat brain by immunohistochemistry. Absent from glia, DPP10 proteins appear mainly in the cell bodies of DPP10(+) neurons, not only at the plasma membrane but also in the cytoplasm. At least 6.4% of inhibitory interneurons in the hippocampus coexpressed Kv4.3, KChIP1, and DPP10, with the highest density in the CA1 strata alveus/oriens/pyramidale and the dentate hilus. Colocalization of Kv4.3/KChIP1/DPP10 was also detected in at least 6.9% of inhibitory interneurons scattered throughout the neocortex. Both hippocampal and neocortical Kv4.3/KChIP1/DPP10(+) inhibitory interneurons expressed parvalbumin or somatostatin, but not calbindin or calretinin. Furthermore, we found colocalization of Kv4.2/Kv4.3/KChIP3/DPP10 in neocortical layer 5 pyramidal neurons and olfactory bulb mitral cells. Together, although DPP10 is also expressed in some brain neurons lacking Kv4 (such as parvalbumin- and somatostatin-positive Golgi cells in the cerebellum), colocalization of DPP10 with Kv4 and KChIP at the plasma membrane of ISA -expressing neuron somata supports the existence of Kv4/KChIP/DPPL ternary complex in vivo.