The present study aimed to investigate the role of microRNA (miR)-219-5p in spinal cord injury (SCI) and to examine the underlying molecular mechanism. SCI rat and cell models were conducted in the current study, while reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of miR-219-5p in the SCI mice and neurons. Bioinformatics analysis was applied to predict the target genes of miR-219-5p, and dual-luciferase reporter assay was performed to verify the prediction. In addition, MTT assay and flow cytometry were conducted to determine the cell viability and cell apoptosis of the neurons, respectively. Western blot analysis was also performed to detect the expression of associated proteins. The study results demonstrated that miR-219-5p was highly expressed in SCI mice and neurons, and directly targets liver receptor homolog-1 (LRH-1). The neuron viability was significantly reduced by SCI, however, it was recovered upon transfection with an miR-219-5p inhibitor. Neuron apoptosis was notably induced by SCI and inhibited by miR-219-5p inhibition. The LRH-1/Wnt/β-catenin signaling pathway was also inhibited by SCI, while it was significantly enhanced by the miR-219-5p inhibitor. Furthermore, LRH-1 overexpression eliminated the effects of the miR-219-5p inhibitor on SCI. In conclusion, these data indicated that the miR-219-5p inhibitor served a protective role in SCI via regulating the LRH-1/Wnt/β-catenin signaling pathway.
Abstract A new pollination mechanism is reported of an orchid species, Bulbophyllum penicillium, based on a field observation in Southeast Yunnan of China. This species has a sensitive lip, and there is a distance of 2–3 mm between it and column apex. Once the lip is touched by a landing insect, it will move up and down or swing left and right continuously, just like a moving caterpillar. By suck a lip movement, the pollinator, a very small fruit fly (Drosophila sp.) ca. 1 mm in height, will be pressed toward the column apex where anther and stigma are located, and then cross-pollination takes place. This unique mode of pollination, depending on the movement of lip rather than insect itself, has never been found before in either Orchidaceae or other families of angiosperms.
Zhong-Jian Liu, Lai-Qiang Huang, Yi-Bo Luo, Hong-Hwa Chen and Yves Van de Peer report the first genome sequence of a crassulacean acid metabolism (CAM) plant, the orchid Phalaenopsis equestris. They identify genes encoding CAM pathway enzymes and find that gene duplication was likely a key process in the evolution of CAM photosynthesis. Orchidaceae, renowned for its spectacular flowers and other reproductive and ecological adaptations, is one of the most diverse plant families. Here we present the genome sequence of the tropical epiphytic orchid Phalaenopsis equestris, a frequently used parent species for orchid breeding. P. equestris is the first plant with crassulacean acid metabolism (CAM) for which the genome has been sequenced. Our assembled genome contains 29,431 predicted protein-coding genes. We find that contigs likely to be underassembled, owing to heterozygosity, are enriched for genes that might be involved in self-incompatibility pathways. We find evidence for an orchid-specific paleopolyploidy event that preceded the radiation of most orchid clades, and our results suggest that gene duplication might have contributed to the evolution of CAM photosynthesis in P. equestris. Finally, we find expanded and diversified families of MADS-box C/D-class, B-class AP3 and AGL6-class genes, which might contribute to the highly specialized morphology of orchid flowers.
Ultrasound targeted microbubble destruction (UTMD) was introduced as a promising method to improve anti-tumor therapeutic efficacy, while minimizing side effects to healthy tissues. Nevertheless, the acoustical phenomenon behind the UTMD as well as the exact mechanisms of autophagy action involved in the increased anti-cancer response are still not fully understood. Therefore, we examined the drug resistance-reversing effects of low-intensity focused ultrasound with microbubble (LIFU+MB) in paclitaxel (PTX)-resistant ovarian cancer cells. Cell viability was evaluated using CCK8 (Cell Counting Kit-8), apoptosis was detected by flow cytometry, quantitative real-time PCR and Western blot were used to detect the expressions of mRNA and protein, and autophagy was observed by transmission electron microscopy (TEM). We revealed that the level of autophagy was increased (p < 0.05) in PTX-resistant ovarian cancer cells. Treatment of LIFU+MB combined with PTX can notably inhibit proliferation as well as increase apoptosis (p < 0.01) in drug-resistant cells. We proposed that LIFU+MB might affect the sensitivity of ovarian cancer cells to PTX by modulating autophagy. To verify the hypothesis, we analyzed the autophagy level of drug-resistant cells after the treatment of LIFU+MB and found that autophagy was significantly inhibited. Altogether, our findings demonstrated that LIFU+MB could reverse PTX resistance in ovarian cancer via inhibiting autophagy, which provides a novel strategy to improve chemosensitivity in ovarian cancer.
H5N6 avian influenza virus (AIV) has caused sporadic, recurring outbreaks in China and Southeast Asia since 2013, with 19 human infections and 13 deaths. Seventeen of these infections occurred since December 2015, indicating a recent rise in the frequency of H5N6 cases. To assess the relative threat of H5N6 virus to humans, we summarized and compared clinical data from patients infected with H5N6 (n = 19) against data from 2 subtypes of major public health concern, H5N1 (n = 53) and H7N9 (n = 160). To assess immune responses indicative of prognosis, we compared concentrations of serum cytokines/chemokines in patients infected with H5N6, H5N1, H7N9, and 2009 pandemic H1N1 and characterized specific immune responses from 1 surviving and 2 nonsurviving H5N6 patients. H5N6 patients were found to have higher incidences of lymphopenia and elevated alanine aminotransferase and lactate dehydrogenase levels compared with H5N1 and H7N9 patients. Hypercytokinemia was detected at substantially higher frequencies from H5N6 patients compared to those infected with other AIV subtypes. Evaluation of adaptive immunity showed that both humoral and cellular responses could be detected in the H5N6-infected survivor, but cellular responses were absent in the nonsurvivors. In addition, the surviving patient had lower concentrations of both pro- and anti-inflammatory cytokines/chemokines compared to the nonsurvivors. Our results support that H5N6 virus could potentially be a major public health threat, and suggest it is possible that the earlier acquisition of cellular immunity and lower concentrations of cytokines/chemokines contributed to survival in our patient. Analysis of more patient samples will be needed to draw concrete conclusions.
Pholidota imbricata belongs to tribe Coelogninae in Orchidaceae distributed in Sichuan, Xizang, and Yunnan. Here, we report the first complete chloroplast (cp) genome and the cp genome features of P. imbricata. The complete cp genome sequence of P. imbricata is 159,292 bp in length and presented a typical quadripartite structure including one large single-copy region (LSC, 87,515 bp), one small single-copy region (SSC, 20,999 bp), and two inverted repeat regions (IRs, 25,389 bp each). The cp genome encoded 141 genes, of which 108 were unique genes (80 protein-coding genes, 24 tRNAs, and 4 rRNAs). The phylogenetic relationships show that P. imbricata is sister to the species of the genus Pleione in tribe Coelogninae.
Abstract The emergence of drug resistance in avian influenza virus (AIV) is a serious concern for public health. Neuraminidase (NA) isolated from a fatal case of avian-origin H10N8 influenza virus infection was found to carry a drug-resistant mutation, NA-Arg292Lys (291 in N8 numbering). In order to understand the full potential of H10N8 drug resistance, the virus was first passaged in the presence of the most commonly used neuraminidase inhibitors (NAIs), oseltamivir and zanamivir. As expected, the Arg292Lys substitution was detected after oseltamivir treatment, however a novel Val116Asp substitution (114 in N8 numbering) was selected by zanamivir treatment. Next generation sequencing (NGS) confirmed that the mutations arose early (after passages 1-3) and became dominant in the presence of the NAI inhibitors. Extensive crystallographic studies revealed that N8-Arg292Lys resistance results mainly from loss of interactions with the inhibitor carboxylate, while rotation of Glu276 was not impaired as observed in the N9-Arg292Lys, a group 2 NA structure. In the case of Val116Asp, the binding mode between oseltamivir and zanamivir is different. Asp151 forms stabilized hydrogen bond to guanidine group of zanamivir, which may compensate the resistance caused by Val116Asp. By contrast, the amino group of oseltamivir is too short to maintain this hydrogen bond, which result in resistant. Moreover, the oseltamivir-zanamivir hybrid inhibitor MS-257 displays higher effectiveness to Val116Asp than oseltamivir, which support this notion. Author Summary Aside from vaccination, NAIs are currently the only alternative for the clinical treatment and prophylaxis of influenza. Understanding the mechanisms of resistance is critical to guide in drug development. In this study, two drug-resistant NA substitutions, Val116Asp and Arg292Lys, were discovered from oseltamivir and zanamivir treatment of H10N8 virus. Crystal structural analyses revealed two distinct mechanisms of these two resistant mutations and provide the explanation for the difference in susceptibility of different NAIs. Zanamivir and laninamivir were more effective against the resistant variants than oseltamivir, and Arg292Lys results in more serious oseltamivir resistance in N9 than N8 subtype. This study is well-correlated to influenza pandemic/epidemic pre-warning, as the discovery of inhibitor resistant viruses will help for new drug preparedness.
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