Prevention and management of lung cancer in China Hong, Qun‐Ying; Wu, Guo-Ming; Qian, Gui‐Sheng ...
Cancer,
September 1, 2015, 2015-Sep-01, 2015-09-00, 20150901, Letnik:
121, Številka:
S17
Journal Article
Energy metabolism is the foundation of survival for all organisms, and mitochondria are the most important energy‐supplying organelles in eukaryotic cells. However, the mitochondrial and ...energy/metabolism‐related properties of cancer stem cells (CSCs), the stem cell‐like subpopulation in tumor masses, remain unknown. In our study, we compared the masses of mitochondria and mitochondrial DNA (mtDNA), the mitochondrial membrane potential (Δψm), oxygen/glucose consumption, and the concentration of reactive oxygen species (ROS) and ATP between lung CSCs (LCSCs) and non‐LCSCs. In addition, the change in features during differentiation was examined. Some mitochondrial and energy metabolism‐related properties, such as perinuclear mitochondrial distribution, a lower quantity of mtDNA, higher Δψm, lower oxygen/glucose consumption, and lower intracellular concentrations of ROS and ATP, can be used as indicators of LCSCs.
Virus infection may induce excessive interferon (IFN) responses that can lead to host tissue injury or even death. β-arrestin 2 regulates multiple cellular events through the G protein-coupled ...receptor (GPCR) signaling pathways. Here we demonstrate that β-arrestin 2 also promotes virus-induced production of IFN-β and clearance of viruses in macrophages. β-arrestin 2 interacts with cyclic GMP-AMP synthase (cGAS) and increases the binding of dsDNA to cGAS to enhance cyclic GMP-AMP (cGAMP) production and the downstream stimulator of interferon genes (STING) and innate immune responses. Mechanistically, deacetylation of β-arrestin 2 at Lys171 facilitates the activation of the cGAS-STING signaling and the production of IFN-β. In vitro, viral infection induces the degradation of β-arrestin 2 to facilitate immune evasion, while a β-blocker, carvedilol, rescues β-arrestin 2 expression to maintain the antiviral immune response. Our results thus identify a viral immune-evasion pathway via the degradation of β-arrestin 2, and also hint that carvedilol, approved for treating heart failure, can potentially be repurposed as an antiviral drug candidate.
Osteoarthritis (OA) is the most common disease of arthritis, a chronic joint disease that is always correlated with massive destruction such as cartilage destruction, inflammation of the synovial ...membrane, and so on. This study aims to explore the role of long noncoding RNA (lncRNA) LOC101928134 in the synovial hyperplasia and cartilage destruction, more specifically, in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in an OA rat model. Microarray‐based gene expression analysis was conducted to screen out the lncRNA differentially expressed in OA and predict the target gene of the lncRNA with the involvement of the signaling pathway through Kyoto encyclopedia of genes and genomes (KEGG) analysis. A model of OA was established and treated with the small interfering RNA LOC101928134/inhibitor of JAK/STAT signaling pathway to investigate the relationship among LOC101928134, IFNA1, and the JAK/STAT signaling pathway in OA. The effect of LOC101928134 on the serum levels of IFNA1, interleukin‐1β, and tumor necrosis factor‐α, and the apoptosis of synovial and cartilage cells was evaluated. LOC101928134, which was found to be highly expressed in knee joint synovial tissues of OA rats, regulated the expression of IFNA1 gene and inhibited JAK/STAT signaling pathway. Downregulation of LOC101928134 resulted in reduced knee joint synovitis, relived inflammatory damage, and knee joint cartilage damage of OA rats. Besides, synovial cell apoptosis was enhanced upon LOC101928134 downregulation, while cartilage cell apoptosis of OA rats was suppressed. These results demonstrate that downregulation of LOC101928134 suppresses the synovial hyperplasia and cartilage destruction of OA rats via activation of JAK/STAT signaling pathway by upregulating IFNA1, providing a new candidate for the treatment of OA.
These results demonstrate that downregulation of LOC101928134 suppresses the synovial hyperplasia and cartilage destruction of osteoarthritis (OA) rats via activation of Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1, providing a new candidate for the treatment of OA.
As a common form of arthritis, osteoarthritis (OA) represents a degenerative disease, characterized by articular cartilage damage and synovium inflammation. Recently, the role of various microRNAs ...(miRs) and their specific expression in OA has been highlighted. Therefore, the aim of the current study was to elucidate the role by which miR-495 and chemokine ligand 4 (CCL4) influence the development and progression of OA. OA mice models were established, after which the CCL4 and collagen levels as well as cell apoptosis were determined in cartilage tissue of OA mice. The chondrocytes of the OA mice models were subsequently treated with a series of miR-495 mimic, inhibitor, and siRNA against CCL4. Afterwards, miR-495 expressions as well as the levels of CCL4, p50, p65, and IkBa and the extent of IkBa phosphorylation in addition to the luciferase activity of NF-kB were measured accordingly. Finally, cell apoptosis and cell cycle distribution were detected. miR-495 was highly expressed while NF-κB, CCL4, and collagen II were poorly expressed. Cell apoptosis was elevated in the cartilage tissue of the OA mice. CCL4 was a potential target gene of miR-495. Downregulation of miR-495 led to accelerated chondrocyte proliferation accompanied by diminished cell apoptosis among the OA mice. Taken together, the results of the current study demonstrated that inhibition of miR-495 suppressed chondrocyte apoptosis and promoted its proliferation through activation of the NF-κB signaling pathway by up-regulation of CCL4 in OA.
There is no prognostic model that is reliable and practical for patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). This study aimed to establish and ...validate a Surgery-Specific Cancer of the Liver Italian Program (SSCLIP) scoring system for those patients.
668 eligible patients who underwent CLR for HCC from five separate tertiary hospitals were selected. The SSCLIP was constructed from a training cohort by adding independent predictors that were identified by Cox proportional hazards regression analyses to the original Cancer of the Liver Italian Program (CLIP). The prognostic performance of the SSCLIP at 12 and 36-months was compared with data from existing models. The patient survival distributions at different risk levels of the SSCLIP were also assessed.
Four independent predictors were added to construct the SSCLIP, including age (HR = 1.075, 95%CI: 1.019-1.135, P = 0.009), albumin (HR = 0.804, 95%CI: 0.681-0.950, P = 0.011), prothrombin time activity (HR = 0.856, 95%CI: 0.751-0.975, P = 0.020) and microvascular invasion (HR = 19.852, 95%CI: 2.203-178.917, P = 0.008). In both training and validation cohorts, 12-month and 36-month prognostic performance of the SSCLIP were significantly better than those of the original CLIP, model of end-stage liver disease-based CLIP, Okuda and Child-Turcotte-Pugh score (all P < 0.05). The stratification of risk levels of the SSCLIP showed an enhanced ability to differentiate patients with different outcomes.
A novel SSCLIP to predict survival of HCC patients who received CLR based on objective parameters may provide a refined, useful prognosis algorithm.
Poststroke depression (PSD) is the most frequent and important neuropsychiatric problem afflicting these patients. Anemia is common in many of these individuals presenting with acute stroke. This ...study determined whether there is a relationship between anemia on hospital admission and PSD. Two hundred eighty-four acute stroke patients were included in the study. Among them, there were 88 PSD patients, whereas another 196 were non-PSD patients. Clinical depression symptoms were diagnosed according to DSM-4 (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria and a HAMD-17 (the 17-item Hamilton Depression Scale) score ≥8 at 1 month after stroke. In the PSD patients, 27.3% of them presented with anemia, whereas only 12.8% of the non-PSD patients had this condition. There was a negative correlation between hemoglobin level and HAMD-17 score in all patients. A binary logistic regression analysis revealed that anemia was independently associated with PSD after adjustment for sex, National Institutes of Health Stroke Scale scores, mRS (modified Rankin Scale) scores, BI (Barthel Index) scores, RBC (red blood cell), and hematocrit. In conclusion, anemia at admission is associated with PSD seen in these patients 1 month later. Therefore, anemia is a possible predictor of PSD.
The purpose of this paper is to propose a methodology for the strength optimization of mechanical clinched joint. To this end, a mathematical optimization model which introduces ductile damage ...constraint to prevent the onset of fracture during the clinch joining of thin metal sheets is proposed. Meanwhile, Bezier curve is used to describe the outline shape of the clinching die, which can be used to search a lot of potential shapes by changing the location of the control point. In addition, a new solving method based on the direct communication between FE-analysis and genetic algorithm (GA) is proposed. The results indicate that the shape of the die groove can be replaced by arc curve to simplify the structure of the clinching tools for general applications. If the requirement of the joint strength is not very high or the ductility of the sheet is good, the clearance between the lower sheet and the die groove is not necessarily equal to zero, but if the requirement is very high or the ductility is poor, the zero clearance is very necessary.
Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This ...study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients.
This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots.
The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742-0.806) and 0.820 (95% CI: 0.762-0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT.
The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.
The rapid discovery of novel viruses using next generation sequencing (NGS) technologies including DNA-Seq and RNA-Seq, has greatly expanded our understanding of viral diversity in recent years. The ...timely identification of novel viruses using NGS technologies is also important for us to control emerging infectious diseases caused by novel viruses. In this study, we identified a novel duck coronavirus (CoV), distinct with chicken infectious bronchitis virus (IBV), using RNA-Seq. The novel duck-specific CoV was a potential novel species within the genus Gammacoronavirus, as indicated by sequences of three regions in the viral 1b gene. We also performed a survey of CoVs in domestic fowls in China using reverse-transcription polymerase chain reaction (RT-PCR), targeting the viral nucleocapsid (N) gene. A total of 102 CoV positives were identified through the survey. Phylogenetic analysis of the viral N sequences suggested that CoVs in domestic fowls have diverged into several region-specific or host-specific clades or subclades in the world, and IBVs can infect ducks, geese and pigeons, although they mainly circulate in chickens. Moreover, this study provided novel data supporting the notion that some host-specific CoVs other than IBVs circulate in ducks, geese and pigeons, and indicated that the novel duck-specific CoV identified through RNA-Seq in this study is genetically closer to some CoVs circulating in wild water fowls. Taken together, this study shed new insight into the diversity, distribution, evolution and control of avian CoVs.
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