Novel insights into circular RNAs in clinical application of carcinomas

Circular RNAs (circRNAs), formed by nonsequential back-splicing of pre-messenger RNA (pre-mRNA) transcripts, have been widely concerned in recent years. With advances in high-throughput RNA sequencing (RNA-seq) technology, previous work has revealed that a large number of circRNAs, which are endogenous, abundant and stable in mammalian cells, may be involved in atherosclerotic vascular disease risk, neurological disorders, prion diseases and carcinomas. Remarkably, interaction between circRNAs and microRNA has already been observed to perform a significant role in a variety of cancers, including gastric cancer and colorectal cancer. Recent work has suggested that circRNAs may play critical roles in the initiation and development of cancers and could become potential new biomarkers for cancers. Herein, we review the current understanding of the roles of circRNAs in cancers and the potential implications of circRNAs in cancer-targeted therapy

CircRNA microarray profiling identifies a novel circulating biomarker for detection of gastric cancer

Abstract CircRNA expression profiles for gastric cancer (GC) were screened using plasma samples from 10 GC patients with different TNM stages and 5 healthy individuals as controls. Results showed lower expression of circ-KIAA1244 in GC tissues, plasmas, and cells compare to normal controls. Further clinical data analysis demonstrated that a decreased expression of circ-KIAA1244 in plasmas was negatively correlated with TNM stage and lymphatic metastasis, and a shorter overall survival time of GC patients. Moreover, we found that circ-KIAA1244 could be detected in GC plasma exosomes and showed no obvious significance compared to the expression level in the corresponding plasmas. This study revealed a GC-tissues-derived circ-KIAA1244 could serve a novel circulating biomarker for detection of GC

Collision-Free Path-Planning for Six-DOF Serial Harvesting Robot Based on Energy Optimal and Artificial Potential Field

Collision-free autonomous path planning under a dynamic and uncertainty vineyard environment is the most important issue which needs to be resolved firstly in the process of improving robotic harvesting manipulator intelligence. We present and apply energy optimal and artificial potential field to develop a path planning method for six degree of freedom (DOF) serial harvesting robot under dynamic uncertain environment. Firstly, the kinematical model of Six-DOF serial manipulator was constructed by using the Denavit-Hartenberg (D-H) method. The model of obstacles was defined by axis-aligned bounding box, and then the configuration space of harvesting robot was described by combining the obstacles and arm space of robot. Secondly, the harvesting sequence in path planning was computed by energy optimal method, and the anticollision path points were automatically generated based on the artificial potential field and sampling searching method. Finally, to verify and test the proposed path planning algorithm, a virtual test system based on virtual reality was developed. After obtaining the space coordinates of grape picking point and anticollision bounding volume, the path points were drew out by the proposed method. 10 times picking tests for grape anticollision path planning were implemented on the developed simulation system, and the success rate was up to 90%. The results showed that the proposed path planning method can be used to the harvesting robot

Gancao (Glycyrrhizae Radix) provides the main contribution to Shaoyao-Gancao decoction on enhancements of CYP3A4 and MDR1 expression via pregnane X receptor pathway in vitro

Abstract Background Chinese herbal formula Shaoyao Gancao decoction (SGD) is often used as an adjuvant with chemotherapeutic agents to treat cancer. Due to the herb-drug interactions, the alternations of drug metabolic enzyme and drug transporters induced by SGD deserve to be explored. We aimed to investigate the effect of SGD on the pregnane X receptor (PXR)-mediated transcriptional regulation of cytochrome P450 3A4 (CYP3A4) and drug transporter multidrug resistance protein 1 (MDR1) in vitro. Besides, we assessed the contribution of constituent herbs to SGD on the regulation of CYP3A4 and MDR1. Methods The dual luciferase reporter gene system containing the hPXR expression plasmid and the reporter gene plasmid of CYP3A4 or MDR1 was co-transfected to HepG2 and Caco2 cells. Luciferase activities were determined using a Dual-luciferase reporter assay kit. The gene expression of CYP3A4 and MDR1 in the hPXR-transfected LS174T cells were assessed by real-time qPCR. Finally, the contribution of constituent herbs from SGD was evaluated. Results SGD, Shaoyao and Gancao concentration-dependently increased promoter activities of CYP3A4 and MDR1 in vitro. Moreover, SGD, Shaoyao and Gancao up-regulated CYP3A4 and MDR1 mRNA in hPXR-transfected LS174T cells. As the herbal constituent of SGD, Gancao possesses significantly higher levels of metabolic enzyme and drug transporters compared with Shaoyao. Conclusion SGD tends to enhance CYP3A4 and MDR1 expression via PXR pathway, especially Gancao provides the main contribution. This study highlights a potential in vitro mechanism for SGD on the regulation of drug metabolic enzymes and drug transporters

Altered Long Noncoding RNA and Messenger RNA Expression in Experimental Intracerebral Hemorrhage - a Preliminary Study

Background/Aims: Functional recovery in the chronic phase is a difficult problem in intracerebral hemorrhage (ICH) treatment. Long noncoding RNAs (lncRNAs) are demonstrated to be involved in central nervous system (CNS) disorders. However, the roles of lncRNAs in post-ICH injury and repair are poorly understood, especially those that may be attributed to long-term neurological deficit. The present study depicted the lncRNA and messenger RNA (mRNA) profile by microarray at late stage after an experimental ICH. Methods: LncRNA and mRNA microarray was used to first identify differentially expressed genes. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine bio-functions and signaling pathways, with which differentially expressed genes are most closely related. Quantitative real-time polymerase chain reaction (PCR) was used to validate the results of microarray. Finally, the lncRNA-mRNA co-expression network was constructed to find the interaction of genes. Results: A total of 625 differentially expressed lncRNAs and 826 expressed mRNAs were identified. Altered genes were enriched in mitochon-drial matrix, G-protein coupled receptor signaling pathway, and olfactory transduction, which may be associated with ICH-induced pathophysiologic changes in the long term. A co-expression network profile based on 5 validated differentially expressed lncRNAs and 205 interacted mRNAs was composed of 210 nodes and 298 connections. Conclusion: Mitochondrial matrix, reduced G-protein coupled receptor activity, and impaired olfactory transduction may be involved in the sequelae following ICH. Further, these dysregulated lncRNAs and mRNAs may be the promising therapeutic targets to overcome obstacles in functional recovery following ICH

Advances of circular RNAs in thyroid cancer: An overview

Circular RNA (circRNA) is a general term for a type of single-stranded RNAs, they are primarily generated via exon back-splice process in precursor mRNAs (pre-mRNAs). circRNAs refer to an emerging type of endogeneity-correlated closed molecules of RNA in a covalent manner. They mainly function as microRNA sponges, protein brackets, and regulatory element in transcription and splicing process. Recently, it has also starting been noticed that they serve as extraordinary models involved in polypeptides producing process. Although circRNAs have been extensively studied, their function in thyroid carcinoma is still lacking. Thus, we present the latest advances in circRNA research and summarize their fundamental rules of regulating process as well as the mechanism. More importantly, We mainly review the role and mechanism of circRNA in thyroid cancer, which provides an emerging perspective and theoretically supports the treatment of thyroid cancer

ICU-free days as a more sensitive primary outcome for clinical trials in critically ill pediatric patients.

BACKGROUND: Our objective was to assess the association between intensive care unit (ICU)-free days and patient outcomes in pediatric prehospital care and to evaluate whether ICU-free days is a more sensitive outcome measure for emergency medical services research in this population. METHODS: This study used data from a previous pediatric prehospital trial. The original study enrolled patients ≤12 years of age and compared bag-valve-mask-ventilation (BVM) versus endotracheal intubation (ETI) during prehospital resuscitation. For the current study, we defined ICU-free days as 30 minus the number of days in the ICU (range, 0-30 days) and assigned 0 ICU-free days for death within 30 days. We compared ICU-free days between the original study treatment groups (BVM vs ETI) and with the original trial outcomes of survival to hospital discharge and Pediatric Cerebral Performance Category (PCPC). RESULTS: Median ICU-free days for the BVM group (n = 404) versus ETI group (n = 416) was not statistically different: 0 ICU-free days (interquartile range, 0-10) versus 0 (0-0), P = 0.219. Median ICU-free days were greater for BVM group in 3 subgroups: foreign body aspiration 30 (0-30) versus 0 (0-21), P = 0.028; child maltreatment 0 (0-14.2) versus 0 (0-0), P = 0.004; and respiratory arrest 25 (1-29) versus 7.5 (0-27.7), P = 0.015. In the original trial, neither survival nor PCPC demonstrated differences in all 3 subgroups-survival was greater with BVM for child maltreatment and respiratory arrest and favorable PCPC was greater with BVM for foreign body aspiration. Overall, in the current study, patients with more ICU-free days also had greater survival to hospital discharge and more favorable PCPC scores. CONCLUSIONS: This initial study of the association between ICU-free days and patient outcomes during prehospital pediatric resuscitation appears to support the use of ICU-free days as a clinical endpoint in this population. ICU-free days may be more sensitive than either mortality or PCPC alone while capturing aspects of both measures

Exploring Pharmacological Mechanisms of Xuefu Zhuyu Decoction in the Treatment of Traumatic Brain Injury via a Network Pharmacology Approach

Objectives. Xuefu Zhuyu decoction (XFZYD), a traditional Chinese medicine (TCM) formula, has been demonstrated to be effective for the treatment of traumatic brain injury (TBI). However, the underlying pharmacological mechanisms remain unclear. This study aims to explore the potential action mechanisms of XFZYD in the treatment of TBI and to elucidate the combination principle of this herbal formula. Methods. A network pharmacology approach including ADME (absorption, distribution, metabolism, and excretion) evaluation, target prediction, known therapeutic targets collection, network construction, and molecule docking was used in this study. Results. A total of 119 bioactive ingredients from XFZYD were predicted to act on 47 TBI associated specific proteins which intervened in several crucial pathological processes including apoptosis, inflammation, antioxidant, and axon genesis. Almost each of the bioactive ingredients targeted more than one protein. The molecular docking simulation showed that 91 pairs of chemical components and candidate targets had strong binding efficiencies. The “Jun”, “Chen”, and “Zuo-Shi” herbs from XFZYD triggered their specific targets regulation, respectively. Conclusion. Our work successfully illuminates the “multicompounds, multitargets” therapeutic action of XFZYD in the treatment of TBI by network pharmacology with molecule docking method. The present work may provide valuable evidence for further clinical application of XFZYD as therapeutic strategy for TBI treatment

Plasma Metabolomics Analysis Based on GC-MS in Infertile Males with Kidney-Yang Deficiency Syndrome

Introduction. Chinese medicine syndrome diagnosis is the key requisite in the treatment of male infertility with traditional Chinese medicine (TCM). Kidney-Yang deficiency syndrome (KYDS) is the critical Chinese medicine syndrome of male infertility. To explore the modernized mechanisms of KYDS in male infertility, this study aims to investigate the metabolomics of males with KYDS. Methods. The gas chromatography-mass spectrometry method was applied to analyze the plasma samples of 67 infertile males with KYDS compared with 55 age-matched healthy controls. The chemometric methods including principal component and partial least squares-discriminate analyses were employed to identify the potential biochemical patterns. With the help of the variable importance for the projection and receiver operating characteristic curve analyses, the potential biomarkers were extracted to define the clinical utility. Simultaneously the high-quality KEGG metabolic pathways database was used to identify the related metabolic pathways. Results. The metabolomics profiles of infertile males with KYDS including 10 potential biomarkers and six metabolic pathways were identified. They precisely distinguished infertile males with KYDS from healthy controls. Conclusions. These potential biomarkers and pathways suggest the substantial basis of infertile males with KYDS. The metabolomics profiles highlight the modernized mechanisms of infertile males with KYDS