Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is the major complication of liver surgery and liver transplantation, that may increase the postoperative morbidity, mortality, tumor progression, and metastasis. The underlying mechanisms have been extensively investigated in recent years. Among these, oxidative stress, inflammatory responses, immunoreactions, and cell death are the most studied. Non-coding RNAs (ncRNAs) are defined as the RNAs that do not encode proteins, but can regulate gene expressions. In recent years, ncRNAs have emerged as research hotspots for various diseases. During the progression of HIRI, ncRNAs are differentially expressed, while these dysregulations of ncRNAs, in turn, have been verified to be related to the above pathological processes involved in HIRI. ncRNAs mainly contain microRNAs, long ncRNAs, and circular RNAs, some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity, and as therapeutic targets to attenuate HIRI. Here, we briefly summarize the common pathophysiology of HIRI, describe the current knowledge of ncRNAs involved in HIRI in animal and human studies, and discuss the potential of ncRNA-targeted therapeutic strategies. Given the scarcity of clinical trials, there is still a long way to go from pre-clinical to clinical application, and further studies are needed to uncover their potential as therapeutic targets.

The role of miRNA-144-3p/Oprk1/KOR in nicotine dependence and nicotine withdrawal in male rats.

INTRODUCTION: The kappa-opioid receptor (KOR) has been implicated in mediating the behavioral and biochemical effects associated with nicotine reward and withdrawal; however, its underlying mechanisms remain to be further explored. METHODS: Adult male Sprague-Dawley rats were used to establish a nicotine dependence and withdrawal model by injecting nicotine (3 mg/kg/day, s.c.) or vehicle for 14 days, followed by the termination of nicotine for 7 days. Body weight gain, pain behaviors, and withdrawal scores were assessed in succession. MicroRNA (miRNA) sequencing was performed, and quantitative real-time PCR was used to detect the expression of candidate miRNAs and Oprk1. Western blotting was performed to examine KOR protein expression of KOR. Luciferase assay was conducted to validate the relationship of certain miRNAs/Oprk1. RESULTS: The behavioral results showed that nicotine dependence and withdrawal induced behavioral changes. Biochemical analyses demonstrated that miR-144-3p expression decreased and Oprk1/KOR expression increased in the prefrontal cortex, nucleus accumben, and hippocampus. Further investigation suggested that miR-144-3p exerted an inhibitory effect on Oprk1 expression in PC12 cells. CONCLUSIONS: This study revealed that miR-144-3p/Oprk1/KOR might be a potential pathway underlying the adverse effects induced by nicotine dependence and withdrawal, and might provide a novel therapeutic target for smoking cessation. IMPLICATIONS: This study demonstrates an impact of nicotine dependence and nicotine withdrawal on behavioral outcomes and the expressions of miR-144-3p/Oprk1/KOR in male rats. These findings have important translational implications given the continued use of nicotine and the difficulty in smoking cessation worldwide, which can be applied to alleviated the adverse effects induced by nicotine dependence and withdrawal, thus assist smokers to quit smoking.

The application of optical technology in the diagnosis and therapy of oxidative stress-mediated hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury (HIRI) is defined as liver tissue damage and cell death caused by reperfusion during liver transplantation or hepatectomy. Oxidative stress is one of the important mechanisms of HIRI. Studies have shown that the incidence of HIRI is very high, however, the number of patients who can get timely and efficient treatment is small. The reason is not hard to explain that invasive ways of detection and lack of timely of diagnostic methods. Hence, a new detection method is urgently needed in clinic application. Reactive oxygen species (ROS), which are markers of oxidative stress in the liver, could be detected by optical imaging and offer timely and effective non-invasive diagnosis and monitoring. Optical imaging could become the most potential tool of diagnosis of HIRI in the future. In addition, optical technology can also be used in disease treatment. It found that optical therapy has the function of anti-oxidative stress. Consequently, it has possibility to treat HIRI caused by oxidative stress. In this review, we mainly summarized the application and prospect of optical techniques in oxidative stress-induced by HIRI.

Conversion of Dioscorea zingiberensis saponins to prosapogenin A by enzymatic hydrolysis.

Prosapogenin A is a secondary saponin in Dioscorea zingiberensis, and it showed remarkable pharmacological effects. Due to very low content and lack of well-developed biotransformation, its preparation was not efficient and clean. This study aims to establish an eco-friendly strategy for preparation of Prosapogenin A from plant material. Physical separation was employed to recycle starch and cellulose, and then D101 resin and polyamide packed-bed column was incorporated for purification of total steroidal saponins (TSS). After these pretreatments, purity of TSS was largely increased to 83.2% with recovery at 87.6%, which was subjected to enzymatic hydrolysis. Optimized reaction system was constructed in 0.20 M HAc-NaAc buffer (pH4.2) containing cellulase/TSS (3:1, w/w), and the hydrolysis was performed at 53 °C for 6 h. Consequently, TSS was almost completely hydrolyzed to Prosapogenin A, while the highest yield reached 5.62%. The newly proposed approach is promising for efficient preparation of Prosapogenin A in industrial applications.

Home Blood Pressure Measurement and Self-Interpretation of Blood Pressure Readings During Pregnancy: Hy-Result e-Health Prospective Study.

Introduction: Hy-Result is a rule management system designed to help patients to be compliant with the home blood pressure measurement (HBPM) monitoring schedule and to understand their BP readings. The aim of the Hy-Result e-Health prospective study is to evaluate the practice and experience of women using the Hy-Result coaching app for self-interpretation of BP readings during and after pregnancy. Methods: Participants were asked to: i) measure their BP at home; ii) use the Hy-Result app and send their PDF report to the researcher; iii) answer anonymously to 3 online independent questionnaires (Q). Results: A total of 107 women accepted to measure their BP and use the app. Among them 82 (77%) performed HBPM and used successfully the system and 72 (88%) shared to the investigator their PDF report by email. Of these, 95% declared the software was "easy" or "very easy" to use; 93% believe the software helps them to monitor their BP more effectively (74% agree, 18% somewhat agree); 94% that the color code classification was "clear"; 76 (93%) affirmed that the app helped them when consulting their physician for their BP evaluation. Majority (87%) perceived the software to be reliable. Furthermore, 71 (87%) said they trust the system and 51 (62%) declared that performing HBPM and self-interpret their readings was "reassuring" whereas 6 (7%) felt that it was "a concern". Conclusion: This study shows that the majority (88%) of pregnant women performed HBPM and successfully used the Hy-Result software for self-interpretation of the BP readings. The use of the validated Hy-Result system by pregnant women may thus be recommended in common practice by healthcare professionals and patient associations.

Effect of Edaravone on MicroRNA Expression in Exosomes after Hepatic Ischemia-reperfusion Injury.

BACKGROUND AND OBJECTIVE: Hepatic ischemia-reperfusion injury (HIRI) results in serious complications after liver resection and transplantation. Edaravone (ED) has a protective effect on IRI. This study was designed to evaluate whether ED could protect the liver of rats from HIRI injury and explored its exosomal miRNA-related mechanism. METHODS: The sham group, hepatic ischemia/reperfusion (IR group), and hepatic ischemia/reperfusion + edaravone (ED group) models were established. We determined the protective effect of ED by measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD); enzyme-linked immunosorbent assay for tumor necrosis factor- α (TNF-α) and interleukin-1ß (IL-1ß); hematoxylin-eosin staining and immunohistochemistry for histopathological changes. Exosomal miRNAs were subjected to second-generation sequencing to identify their differential expression. The results were analyzed using bioinformatics methods and validated using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: HIRI rats showed higher levels of ALT, AST, oxidative stress, and inflammatory markers; ED attenuated these effects. The sequencing results showed 6 upregulated and 13 downregulated miRNAs in the IR vs. sham groups, 10 upregulated and 10 downregulated miRNAs in the ED vs. IR groups. PC-3p-190-42101 was screened as an overlapping differentially expressed miRNA, and RT-qPCR validation showed that its expression in HIRI rats was significantly decreased; ED prevented this downregulation. Moreover, the expression of PC-3P-190-42101 was significantly correlated with the level of inflammatory factors. CONCLUSION: These findings indicate that ED can regulate the level of inflammatory factors by affecting the expression of miRNA PC-3p-190-42101 in plasma exosomes to protect the liver from IRI.

Substantial nitrogen oxides emission reduction from China due to COVID-19 and its impact on surface ozone and aerosol pollution.

A top-down approach was employed to estimate the influence of lockdown measures implemented during the COVID-19 pandemic on NOx emissions and subsequent influence on surface PM2.5 and ozone in China. The nation-wide NOx emission reduction of 53.4% due to the lockdown in 2020 quarter one in China may represent the current upper limit of China's NOx emission control. During the Chinese New Year Holiday (P2), NOx emission intensity in China declined by 44.7% compared to the preceding 3 weeks (P1). NOx emission intensity increased by 20.3% during the 4 weeks after P2 (P3), despite the unchanged NO2 column. It recovered to 2019 level at the end of March (P4). The East China (22°N - 42°N, 102°E - 122°E) received greater influence from COVID-19. Overall NOx emission from East China for 2020 first quarter is 40.5% lower than 2019, and in P4 it is still 22.9% below the same period in 2019. The 40.5% decrease of NOx emission in 2020 first quarter in East China lead to 36.5% increase of surface O3 and 12.5% decrease of surface PM2.5. The elevated O3 promotes the secondary aerosol formation through heterogeneous pathways. We recommend that the complicated interaction between PM2.5 and O3 should be considered in the emission control strategy making process in the future.

Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs.

Morphine tolerance developed after repeated or continuous morphine treatment is a global health concern hindering the control of chronic pain. In our previous research, we have reported that the expression of lncRNAs and microRNAs have been greatly modified in the spinal cord of morphine tolerated rats, and the modulating role of miR-873a-5p, miR-219-5p and miR-365 have already been confirmed. However, whether circular RNAs, another essential kind of non-coding RNA, are involved in the pathogenesis of morphine tolerance is still beyond our knowledge. In this study, we conducted microarray analysis for circRNA profile and found a large number of circRNAs changed greatly in the spinal cord by morphine treatment. Among them, we selected nine circRNAs for validation, and seven circRNAs are confirmed. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) analysis were used for functional annotation. Besides, we confirmed the modified expression of seven circRNAs after validation by real-time PCR, selected 3 most prominently modulated ones among them and predicted their downstream miRNA-mRNA network and analyzed their putative function via circRNA-miRNA-mRNA pathway. Finally, we enrolled the differentially expressed mRNAs derived from the identical spinal cord, these validated circRNAs and their putative miRNA targets for ceRNA analysis and screened a promising circRNA-miRNA-mRNA pathway in the development of morphine tolerance. This study, for the first time, provided valuable information on circRNA profile and gave clues for further study on the circRNA mechanism of morphine tolerance.

Identification of lncRNA expression profiles and ceRNA analysis in the spinal cord of morphine-tolerant rats.

Morphine tolerance is a challenging clinical problem that limits the use of morphine in pain treatment, but the mechanisms of morphine tolerance remain unclear. Recent research indicates that long noncoding RNAs (lncRNAs) might be a novel and promising target in the pathogeneses of diseases. Therefore, we hypothesized that lncRNAs might play a role in the development of morphine tolerance. Male Sprague-Dawley rats were intrathecally injected with 10 µg morphine twice daily for 7 consecutive days. The animals were then sacrificed for lncRNA microarray tests, and the results were validated by RT-qPCR. Next, functional predictions for the differentially expressed mRNAs (DEmRNAs) were made with the Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), and predictions for the differentially expressed lncRNAs (DElncRNAs) were made based on competitive endogenous RNA (ceRNA) analyses. The rats successfully developed morphine tolerance. LncRNA microarray analysis revealed that, according to the criteria of a log2 (fold change) > 1.5 and a P-value < 0.05, 136 lncRNAs and 278 mRNAs were differentially expressed in the morphine tolerance group (MT) compared with the normal saline group (NS). The functions of the DEmRNAs likely involve in the processes of the ion channel transport, pain transmission and immune response. The ceRNA analysis indicated that several possible interacting networks existed, including (MRAK150340, MRAK161211)/miR-219b/Tollip.Further annotations of the potential target mRNAs of the miRNAs according to the gene database suggested that the possible functions of these mRNAs primarily involved the regulation of ubiquitylation, G protein-linked receptors, and Toll-like receptors, which play roles in the development of morphine tolerance. Our findings revealed the profiles of differentially expressed lncRNAs in morphine tolerance conditions, and among these lncRNAs, some DElncRNAs might be new therapeutic targets for morphine tolerance.

A randomized comparison of the prone ventilation endotracheal tube versus the traditional endotracheal tube in adult patients undergoing prone position surgery.

Endotracheal tube displacement or dislocation is a severe complication that can occur in patients who require prone position ventilation. We hypothesized the prone position tube (PPT) would reduce the incidence of displacement of an endotracheal tube in an adult prone operation compared to a traditional tube (TT). A total of 80 adult patients undergoing neurosurgery or spine surgery were recruited. Sixty patients with prone position ventilation were randomly divided into the traditional routine endotracheal tube group (Group TT, n = 30) and the prone position ventilation endotracheal tube group (Group PPT, n = 30). The primary outcome measures were the incidence of the endotracheal tube displacement during surgery, and the secondary outcomes were symptoms of sore throat, dysphagia and dysphonia during follow-up in the post-anesthesia care unit (PACU). The incidence of tube displacement was significantly lower in the PPT group (0 [0%] of 30 patients) compared to the TT group (22 [73.3%] of 30 patients; odds ratio [OR] 0.73, 95% CI 0.591-0.910; P = 0.005). There was no statistical difference in sore throat, dysphagia and vocal function between the two groups (P > 0.05) during follow-up. Compared to the traditional tube, the improved prone positon tube reduced the incidence of displacement of the endotracheal tube. This study was registered with ClinicalTrials.gov on April 29, 2015 (No. NCT02449356).

miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats.

Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morphine tolerance by targeting CaMKIIγ. We found that the expression of miR-219-5p was decreased significantly after chronic morphine treatment. Overexpression of miR-219-5p by lentivirus injection prevents the development of morphine tolerance. CaMKIIγ, the target gene of miR-219-5p was downregulated by overexpression of miR-219-5p both in vivo and in vitro. Furthermore, we found that lentiviral-mediated miR-219-5p decreased the expression of NMDA receptor subunit 1 (NR1), leading to attenuation of morphine tolerance. Overall, the data demonstrate that miR-219-5p plays a crucial role in alleviating morphine tolerance by inhibiting the CaMKII/NMDA receptor pathway. Overexpression of miR-219-5p may be a potential strategy to ameliorate morphine tolerance.