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Recent studies suggested that gut microbiota was involved in the development of coronary artery disease. However, the changes of gut microbiota following acute myocardial infarction (AMI) remain unknown. In this study, a total of 66 male Wistar rats were randomly divided into control, AMI and SHAM groups. The controls (n = 6) were sacrificed after anesthesia. The AMI model was built by ligation of left anterior descending coronary artery. The rats of AMI and SHAM groups were sacrificed at 12 h, 1 d, 3 d, 7 d and 14 d post-operation respectively. Gut microbiota was analyzed by 16S rDNA high throughput sequencing. The gut barrier injuries were evaluated through histopathology, transmission electron microscope and immunohistochemical staining. The richness of gut microbiota was significantly higher in AMI group than SHAM group at 7 d after AMI (P

Contagious ecthyma is a highly contagious disease with worldwide distribution, which is caused by the Orf virus (ORFV) belonging to the Parapoxvirus. To study the alteration of host gene expression in response to ORFV infection at the transcriptional level, several young small-tailed Han sheep were inoculated with ORFV, and their oral mucosa tissue samples (T0, T3, T7 and T15) were collected on day 0, 3, 7 and 15 after ORFV infection respectively. RNA-seq transcriptome comparisons were performed, showing that 1928, 3219 and 2646 differentially expressed genes (DEGs) were identified among T3 vs. T0, T7 vs. T0, and T15 vs. T0 respectively. Gene Ontology (GO) analyses of the DEGs from these comparisons, revealed that ORFV might provoke vigorous immune response of the host cells during the early stage of infection. Moreover, GO and network analysis showed that positive and negative regulative mechanisms of apoptosis were integrated in the host cells through up or down-regulating the expression level of DEGs involved in apoptotic pathways, in order to reach a homeostasis of oral mucosa tissues during the exposure to ORFV infection. In conclusion, our study for the first time describes the direct effects of ORFV on the global host gene expression of its host using high-throughput RNA sequencing, which provides a resource for future characterizing the interaction mechanism between the mammalian host and ORFV.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

In wheat (Triticum aestivum L.), time from planting to spike emergence is influenced by genes controlling vernalization requirement and photoperiod response. Characterizing the available genetic diversity of known and novel alleles of VERNALIZATION1 (VRN1) and PHOTOPERIOD1 (PPD1) in winter wheat can inform approaches for breeding climate resilient cultivars. This study identified QTL for heading date (HD) associated with multiple VRN1 and PPD1 loci in a population developed from a cross between two early flowering winter wheat cultivars. When the population was grown in the greenhouse after partial vernalization treatment, major heading date QTLs co-located with the VRN-A1 and VRN-B1 loci. Copy number variation at the VRN-A1 locus influenced HD such that RIL having three copies required longer cold exposure to transition to flowering than RIL having two VRN-A1 copies. Sequencing vrn-B1 winter alleles of the parents revealed multiple polymorphisms in the first intron that were the basis of mapping a major HD QTL coinciding with VRN-B1. A 36 bp deletion in the first intron of VRN-B1 was associated with earlier HD after partial vernalization in lines having either two or three haploid copies of VRN-A1. The VRN1 loci interacted significantly and influenced time to heading in field experiments in Louisiana, Georgia and North Carolina. The PPD1 loci were significant determinants of heading date in the fully vernalized treatment in the greenhouse and in all field environments. Heading date QTL were associated with alleles having large deletions in the upstream regions of PPD-A1 and PPD-D1 and with copy number variants at the PPD-B1 locus. The PPD-D1 locus was determined to have the largest genetic effect, followed by PPD-A1 and PPD-B1. Our results demonstrate that VRN1 and PPD1 alleles of varying strength allow fine tuning of flowering time in diverse winter wheat growing environments.

In lung cancer, uPA, its receptor (uPAR), and the inhibitors PAI-1 and PAI-2 of the plasminogen activator family interact with MMP-2 and MMP-9 of the MMP family to promote cancer progression. However, it remains undetermined which of these markers plays the most important role and may be the most useful indicator to stratify the patients by risk.We determined the individual prognostic value of these 6 markers by analyzing a derivation cohort with 98 non-small cell lung cancer patients by immunohistochemical staining. The correlation between the IHC expression levels of these markers and disease prognosis was investigated, and an immunohistochemical panel for prognostic prediction was subsequently generated through prognostic model analysis. The value of the immunohistochemical panel was then verified by a validation cohort with 91 lung cancer patients.In derivation cohort, PAI-2 is the most powerful prognostic factor (HR = 2.30; P = 0.001), followed by MMP-9 (HR = 2.09; P = 0.019) according to multivariate analysis. When combining PAI-2 and MMP-9, the most unfavorable prognostic group (low PAI-2 and high MMP-9 IHC expression levels) showed a 6.40-fold increased risk of a poor prognosis compared to the most favorable prognostic group (high PAI-2 and low MMP-9 IHC expression levels). PAI-2 and MMP-9 IHC panel could more precisely identify high risk patients in both derivation and validation cohort.We revealed PAI-2 as the most powerful prognostic marker among PA and MMP protease family even after considering their close relationships with each other. By utilizing a combination of PAI-2 and MMP-9, more precise prognostic information than merely using pathological stage alone can be obtained for lung cancer patients.

As the internet has become popularized in recent years, cognitive behavioral therapy for insomnia (CBT-i) has shifted from a face-to-face approach to delivery via the internet (internet-based CBT-i, ICBT-i). Several studies have investigated the effects of ICBT-i on comorbid anxiety and depression; however, the results remain inconclusive. Thus, a meta-analysis was conducted to determine the effects of ICBT-i on anxiety and depression. Electronic databases, including PubMed, EMBASE, PsycINFO and the Cochrane Library (throughout May 28, 2015), were systematically searched for randomized controlled trials (RCTs) of ICBT-i. Data were extracted from the qualified studies and pooled together. The standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to assess the effects of ICBT-i on comorbid anxiety and depression. Nine records that included ten studies were ultimately qualified. The effect sizes (ESs) were -0.35 [-0.46, -0.25] for anxiety and -0.36 [-0.47, -0.26] for depression, which were stable using a between-group or within-group comparison and suggest positive effects of ICBT-i on both comorbid disorders. Although positive results were identified in this meta-analysis, additional high-quality studies with larger sample sizes are needed in the future.

This study was performed to investigate the correlation between CT perfusion with acetazolamide challenge and angiogenesis in C6 gliomas.Thirty-two male Sprague-Dawley rats were evaluated. The rats were divided randomly to four groups: eight rats with orthotopically implanted C6 gliomas at 10-days old (Group A), eight rats with gliomas at 14-days old (Group B), eight rats with gliomas at 18-days old (Group C), eight rats with orthotopically injected normal saline served as controls. CT perfusion was performed before and after administration of acetazolamide. Changes in perfusion parameters due to acetazolamide administration were calculated and analyzed.Elevated carbon dioxide partial pressure and decreased pH were found in all 32 rats post acetazolamide challenge (P

STUDY OBJECTIVES: Sleep disorders are a common symptom of Parkinson's disease (PD) and they significantly impair the sleep quality of the PD patients. However, there is no conclusive evidence to support the relation between PD and the prevalence of obstructive sleep apnea (OSA). The purpose of this meta-analysis review is to evaluate the association between PD and the prevalence of OSA. METHODS: A comprehensive literature search was conducted on PubMed and Embase through July 2013. Only studies that referred to PD and the prevalence of OSA and that met the selection criteria were included in the analysis. The odds ratios (ORs) were used to evaluate the relationship of PD and the prevalence of OSA by the fixed-effect model. RESULTS: Five eligible studies were analyzed in this study including 322 cases and 6,361 controls. The pooled-analysis showed the OR to be 0.60 (95% confidence interval (CI): 0.44 to 0.81, P = 0.001) and I(2) = 0.0% (χ(2) = 3.90, P = 0.420) in the fixed-effect model. CONCLUSIONS: Although we only included five small sample studies that indicated high homogeneity in the heterogeneity test, the results suggest that there is a significant negative association between PD and the prevalence of OSA; PD patients generally have a reduced prevalence of OSA. According to our analysis, these results are primarily due to the lower BMI of PD patients when compared with the general population controls.

BACKGROUND:Integrated ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is widely performed in hilar and mediastinal lymph node (HMLN) staging of non-small cell lung cancer (NSCLC). However, the diagnostic efficiency of PET/CT remains controversial. This retrospective study is to evaluate the accuracy of PET/CT and the characteristics of false negatives and false positives to improve specificity and sensitivity. METHODS:219 NSCLC patients with systematic lymph node dissection or sampling underwent preoperative PET/CT scan. Nodal uptake with a maximum standardized uptake value (SUV(max)) >2.5 was interpreted as PET/CT positive. The results of PET/CT were compared with the histopathological findings. The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficiency of PET/CT. Univariate and multivariate analysis were conducted to detect risk factors of false negatives and false positives. RESULTS:The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT in detecting HMLN metastases were 74.2% (49/66), 73.2% (112/153), 54.4% (49/90), 86.8% (112/129), and 73.5% (161/219). The ROC curve had an area under curve (AUC) of 0.791 (95% CI 0.723-0.860). The incidence of false negative HMLN metastases was 13.2% (17 of 129 patients). Factors that are significantly associated with false negatives are: concurrent lung disease or diabetes (p4.0 (p=0.009). Postoperatively, 45.5% (41/90) patients were confirmed as false positive cases. The univariate analysis indicated age > 65 years old (p=0.009), well differentiation (p=0.002), and SUV(max) of primary tumor ≦4.0 (p=0.007) as risk factors for false positive uptake. CONCLUSION:The SUV(max) of HMLN is a predictor of malignancy. Lymph node staging using PET/CT is far from equal to pathological staging account of some risk factors. This study may provide some aids to pre-therapy evaluation and decision-making.

Non-destructive measurement of acceleration-induced displacement fields within a closed object is a fundamental challenge. Inferences of how the brain deforms following skull impact have thus relied largely on indirect estimates and course-resolution cadaver studies. We developed a magnetic resonance technique to quantitatively identify the modes of displacement of an accelerating soft object relative to an object enclosing it, and applied it to study acceleration-induced brain deformation in human volunteers. We show that, contrary to the prevailing hypotheses of the field, the dominant mode of interaction between the brain and skull in mild head acceleration is one of sliding arrested by meninges.

3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), an effective free radical scavenger, provides neuroprotection in stroke models and patients. In this study, we investigated its neuroprotective effects in a chronic rotenone rat model for Parkinson's disease. Here we showed that a five-week treatment with edaravone abolished rotenone's activity to induce catalepsy, damage mitochondria and degenerate dopamine neurons in the midbrain of rotenone-treated rats. This abolishment was attributable at least partly to edaravone's inhibition of rotenone-induced reactive oxygen species production or apoptotic promoter Bax expression and its up-regulation of the vesicular monoamine transporter 2 (VMAT2) expression. Collectively, edaravone may provide novel clinical therapeutics for PD.

Leucine-rich repeat flightless-I-interacting protein 2 (LRRFIP2) is a myeloid differentiation factor 88-interacting protein with a positive regulatory function in toll-like receptor signaling. In this study, seven LRRFIP2 protein variants (LvLRRFIP2A-G) were identified in Litopenaeus vannamei. All the seven LvLRRFIP2 protein variants encode proteins with a DUF2051 domain. LvLRRFIP2s were upregulated in hemocytes after challenged with lipopolysaccharide, poly I:C, CpG-ODN2006, Vibrio parahaemolyticus, Staphylococcus aureus, and white spot syndrome virus (WSSV). Dual-luciferase reporter assays in Drosophila Schneider 2 cells revealed that LvLRRFIP2 activates the promoters of Drosophila and shrimp AMP genes. The knockdown of LvLRRFIP2 by RNA interference resulted in higher cumulative mortality of L. vannamei upon V. parahaemolyticus but not S. aureus and WSSV infections. The expression of L. vannamei AMP genes were reduced by dsLvLRRFIP2 interference. These results indicate that LvLRRFIP2 has an important function in antibacterials via the regulation of AMP gene expression. [ABSTRACT FROM AUTHOR]

Leucine-rich repeat flightless-I-interacting protein 2 (LRRFIP2) is a myeloid differentiation factor 88-interacting protein with a positive regulatory function in toll-like receptor signaling. In this study, seven LRRFIP2 protein variants (LvLRRFIP2A-G) were identified in Litopenaeus vannamei. All the seven LvLRRFIP2 protein variants encode proteins with a DUF2051 domain. LvLRRFIP2s were upregulated in hemocytes after challenged with lipopolysaccharide, poly I:C, CpG-ODN2006, Vibrio parahaemolyticus, Staphylococcus aureus, and white spot syndrome virus (WSSV). Dual-luciferase reporter assays in Drosophila Schneider 2 cells revealed that LvLRRFIP2 activates the promoters of Drosophila and shrimp AMP genes. The knockdown of LvLRRFIP2 by RNA interference resulted in higher cumulative mortality of L. vannamei upon V. parahaemolyticus but not S. aureus and WSSV infections. The expression of L. vannamei AMP genes were reduced by dsLvLRRFIP2 interference. These results indicate that LvLRRFIP2 has an important function in antibacterials via the regulation of AMP gene expression. [ABSTRACT FROM AUTHOR]