Scientific reports
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Recently, ex vivo three-dimensional organ culture systems have emerged to study the physiology and pathophysiology of human organs. These systems also have potential as a translational tool in tissue engineering; however, this potential is limited by our ability to longitudinally monitor the fate and action of cells used in regenerative therapies. Therefore, we investigated luciferase-mediated bioluminescence imaging (BLI) as a non-invasive technique to continuously monitor cellular behavior in ex vivo whole organ culture. ⋯ We conclude that BLI is a promising tool to monitor spatial and temporal cellular behavior in ex vivo organ culture. Hence, ex vivo organ culture systems allow pre-screening and pre-validation of novel therapeutic concepts prior to in vivo large animal experimentation. Thereby, organ culture systems can reduce animal use, and improve the speed of innovation by overcoming technological, ethical and financial challenges.
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Long noncoding RNAs (lncRNAs) play critical roles in cellular homeostasis. However, little is known about their effect in developing rat brains with hypoxic-ischemic brain damage (HIBD). To explore the expression and function of lncRNA in HIBD, we analyzed the expression profiles of lncRNAs in hypoxic-ischemic (HI) brains and sham control using microarray analysis. ⋯ Moreover, coding non-coding co-expression network analysis showed that the BC088414 lncRNA expression was correlated with apoptosis-related genes, including Casp6 and Adrb2. Silencing of lncRNA BC088414 in PC12 cells caused reduced mRNA level of Casp6 and Adrb2, decreased cell apoptosis and increased cell proliferation. These results suggested lncRNA might participate in the pathogenesis of HIBD via regulating coding genes.
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Mesenchymal stem cells (MSCs) have been shown to elicit cardio-protective effects in sepsis. However, the underlying mechanism remains obscure. While recent studies have indicated that miR-223 is highly enriched in MSC-derived exosomes, whether exosomal miR-223 contributes to MSC-mediated cardio-protection in sepsis is unknown. ⋯ Accordingly, these exosomal proteins were transferred to cardiomyocytes, leading to increased inflammation and cell death. By contrast, WT-exosomes encased higher levels of miR-223, which could be delivered to cardiomyocytes, resulting in down-regulation of Sema3A and Stat3. These data for the first time indicate that exosomal miR-223 plays an essential role for MSC-induced cardio-protection in sepsis.
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Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). ⋯ Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs.
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Ebola virus disease (EVD) has erupted many times in some zones since it was first found in 1976. The 2014 EVD outbreak in West Africa is the largest ever, which has caused a large number of deaths and the most serious country is Liberia during the outbreak period. Based on the data released by World Health Organization and the actual transmission situations, we investigate the impact of different transmission routes on the EVD outbreak in Liberia and estimate the basic reproduction number R0 = 2.012 in the absence of effective control measures. ⋯ Furthermore, we study the influence of control measures (isolation and safe burial measures) on EVD outbreak. It is found that if combined control measures are taken, the basic reproduction number will be less than one and thus EVD in Liberia may be well contained. The obtained results may provide new guidance to prevent and control the spread of disease.