[Hepatopulmonary syndrome]. / Syndrome hépato-pulmonaire.

The hepatopulmonary syndrome (HPS) is one of the lung diseases associated with cirrhosis and portal hypertension. It should be discussed for any dyspnea in cirrhotic patients. HPS is a pulmonary vascular disease characterized by intrapulmonary vascular dilatations (IPVD). The pathogenesis is complex and seems to rely on communications between the portal and pulmonary circulations. The diagnosis is based on a triad of liver disease and portal hypertension, evidence of IPVDs, and impaired gas exchange (alveolar-arterial oxygen difference [A-aO2]≥15mmHg). HPS impairs prognosis (23% survival at 5years) and patients' quality of life. Liver transplantation (LT) allows regression of IPDVD in almost 100% of cases, normalization of gas exchange and improves survival with a 5-year post-LT survival between 76 and 87%. It is the only curative treatment, indicated in patients with severe HPS, defined by an arterial partial pressure of oxygen (PaO2) below 60mmHg. When LT is not indicated or feasible, long-term oxygen therapy may be proposed as a palliative treatment. A better understanding of the pathophysiological mechanisms is needed to improve the therapeutic possibilities in a near future.

Reconstruction and analysis of circRNA-miRNA-mRNA network in the pathology of lung cancer.

BACKGROUND: The presented study aimed to gain insights into the pathogenesis of lung cancer (LC) and provide novel bio-markers for LC by building a regulatory circular (circ) RNAmicro (mi) RNAmRNA network. MATERIALS AND METHODS: High-throughput sequencing data of circRNAs, miRNAs and mRNAs related to LC originated from GEO (Gene Expression Omnibus) database, and the differential expressions of circRNAs, miRNAs and mRNAs were screened with R language Limma. The circRNA-miRNA and miRNA-mRNA pairs were used to build the ceRNA network. The functions of differential expression circRNAs were elucidated by performing the functional enrichment analysis on GO and KEGG. Furthermore, the selected LC prognostic genes were verified by tissue chips and immunohistochemistry (IHC). RESULTS: On the whole, 20 downregulated circRNAs, 55 upregulated miRNAs and 243 downregulated mRNAs were identified in LC. Lastly, a circRNA-miRNA-mRNA ceRNA network was built, which was composed of 2 circRNAs, 2 miRNAs, and 2 mRNAs. As indicated from the analysis based on public databases and IHC, the differential genes (i.e., FXYD1 and SEMA5A) in this network acted as LC prognostic factors. As confirmed by performing IHC and survival analyses, FXYD1 and SEMA5A expressions in LC were downregulated, and their expressions displayed a relationship to the overall survival (OS) of LC cases. CONCLUSIONS: This study presents novel insights into the role of circRNAs in the development of LC via the ceRNA mechanism. The identified FXYD1 and SEMA5A gene could act as novel and vital LC prognostic indicators.

Use of cellular exosomes as a new carrier in breast cancer gene therapy.

BACKGROUND: Breast cancer is recognized as a major clinical challenge in gynecological diseases worldwide. Exosomes are small vesicles derived from multicellular bodies that are secreted by many cells into the extracellular environment and thus participate in intercellular communication through the transfer of genetic information such as encoded and non-encoded RNAs to target cells. Tumor-derived exosomes are thought to be a rich source of microRNAs (miRs) that can regulate the function of other cancer cells in the tumor microenvironment. However, the exact mechanisms by which tumor cell-derived exosomes affect their neighboring cells, as well as the bio-logical function of exosomal miRs in receptor cells, are not well understood. MATERIALS AND METHODS: In this study, after the overexpression of MiR-205 in breast cancer cells (MDA-MB-231 class), cell-derived exosomes were successfully isolated and characterized by electron microscopy and dynamic light scattering. RESULTS: The determination of MiR-205 expression levels in exosomes secreted from engineered cells confirmed the high expression of this miR in exosomes. It was also found that the treatment of tumor exosomes carrying this miR had an apoptotic induction effect and also had a significant effect on reducing the expression of Bcl-2 gene transcript in a time-dependent manner in breast cancer cells (P < 0.001). CONCLUSION: Overall, this study suggests that exosomal transfer of tumor suppressor miRs to cancer cells could be a suitable platform for nucleic acid transfer to these cells and be highly effective in cancer treatment.

Accuracy of the Compressed Sensing Accelerated 3D-FLAIR Sequence for the Detection of MS Plaques at 3T.

BACKGROUND AND PURPOSE: The use of 3D FLAIR improves the detection of brain lesions in MS patients, but requires long acquisition times. Compressed sensing reduces acquisition time by using the sparsity of MR images to randomly undersample the k-space. Our aim was to compare the image quality and diagnostic performance of 3D-FLAIR with and without compressed sensing for the detection of multiple sclerosis lesions at 3T. MATERIALS AND METHODS: Twenty-three patients with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds, 27%; compressed sensing factor of 1.3). Two blinded readers independently evaluated both conventional and compressed sensing FLAIR for image quality (SNR and contrast-to-noise ratio) and the number of MS lesions visible in the periventricular, intra-juxtacortical, infratentorial, and optic nerve regions. The volume of white matter lesions was measured with automatic postprocessing segmentation software for each FLAIR sequence. RESULTS: Image quality and the number of MS lesions detected by the readers were similar between the 2 FLAIR acquisitions (P = .74 and P = .094, respectively). Almost perfect agreement was found between both FLAIR acquisitions for total MS lesion count (Lin concordance correlation coefficient = 0.99). Agreement between conventional and compressed sensing FLAIR was almost perfect for periventricular and infratentorial lesions and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing with the segmentation software did not reveal a significant difference between conventional and compressed sensing FLAIR in total MS lesion volume (P = .63) or the number of MS lesions (P = .15). CONCLUSIONS: With a compressed sensing factor of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the detection of MS plaques at 3T.

Regulatory effects of the novel synthesized Indole-3-carbaldehyde on expression of cell cycle genes: A study on Cyclin D and P21 expression by acute promylocytic leukemia cell line (NB4)

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Novel seminal fluid proteins in the seed beetle Callosobruchus maculatus identified by a proteomic and transcriptomic approach.

The seed beetle Callosobruchus maculatus is a significant agricultural pest and increasingly studied model of sexual conflict. Males possess genital spines that increase the transfer of seminal fluid proteins (SFPs) into the female body. As SFPs alter female behaviour and physiology, they are likely to modulate reproduction and sexual conflict in this species. Here, we identified SFPs using proteomics combined with a de novo transcriptome. A prior 2D-sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis identified male accessory gland protein spots that were probably transferred to the female at mating. Proteomic analysis of these spots identified 98 proteins, a majority of which were also present within ejaculates collected from females. Standard annotation workflows revealed common functional groups for SFPs, including proteases and metabolic proteins. Transcriptomic analysis found 84 transcripts differentially expressed between the sexes. Notably, genes encoding 15 proteins were highly expressed in male abdomens and only negligibly expressed within females. Most of these sequences corresponded to 'unknown' proteins (nine of 15) and may represent rapidly evolving SFPs novel to seed beetles. Our combined analyses highlight 44 proteins for which there is strong evidence that they are SFPs. These results can inform further investigation, to better understand the molecular mechanisms of sexual conflict in seed beetles.

Functional features of EVI1 and EVI1Δ324 isoforms of MECOM gene in genome-wide transcription regulation and oncogenicity.

The MDS1 and ecotropic viral integration site 1 (EVI1) complex locus (MECOM) gene encodes several transcription factor variants including MDS1-EVI1, EVI1 and EVI1Δ324. Although MDS1-EVI1 has been associated with tumor-suppressing activity, EVI1 is a known oncogene in various cancers, whose expression is associated with poor patient survival. Although EVI1Δ324 is co-transcribed with EVI1, its activity in cancer cells is not fully understood. Previous reports described that unlike EVI1, EVI1Δ324 protein cannot transform fibroblasts because of its disrupted N-terminal zinc finger (ZNF) domain. To better understand EVI1Δ324 biology and function, we obtained genome-wide binding occupancies and expression data in ovarian cancer cells. We characterized its DNA-binding sites, binding motif and target genes. Comparative analyses with previous study show that EVI1 and EVI1Δ324 share similar transcriptional activities linked to their common C-terminus ZNF domain. They bind to an E-twenty-six family (ETS)-like motif, target to a large extent the same genes and cooperate with AP1 transcription factor. EVI1Δ324-occupied genes were 70.7% similar to EVI1-bound genes. More strikingly, EVI1 and EVI1Δ324 differentially expressed genes were 99.87% identical, indicating comparable transcriptional regulatory functions. Consistently with gene ontologies linked to these target genes, EVI1Δ324 expression in HeLa cells could enhance anchorage-independent growth, such as EVI1, showing that EVI1Δ324 expression also lead to pro-oncogenic effects. The main specific feature of EVI1 variant is its N-terminus ZNF domain that binds DNA through GATA-like motif. We found that most GATA-like EVI1 chromatin immunoprecipitation sequencing peaks are far from genes and are not involved in transcriptional regulation. These genomic regions were enriched in simple sequence repeats and displayed high meiotic recombination rates. Overall, our genomics analyses uncovered common and specific features of two major MECOM isoforms. Their influence on transcription and downstream cell proliferation was comparable. However, EVI1-specific GATA-like binding sites, from its N-terminus ZNF domain, associated with high recombination rates, suggesting possible additional oncogenic potential for EVI1 in modulating genomic stability.

The association between infection burden in Iranian patients with acute myocardial infarction and unstable angina.

AIM: to evaluate the association of ischemic heart disease (IHD) with the number of pathogens (infection burden) among individuals with infection. METHODS: a total of 120 patients with IHD as the acute myocardial infarction (AMI; n=60) or unstable angina (UA; n=60) group and 60 healthy subjects with sex- and age-matched as control group were enrolled in this study. Serum samples of all participants were tested for the presence of antibodies to Helicobacter pylori (H. pylori), cytomegalovirus (CMV), type-1 herpes simplex virus (HSV-1) and type- 2 HSV (HSV-2) by using ELISA. RESULTS: Regarding the association of the infection burden with IHD, the prevalence ratios and 95% confidence intervals (CI) were 3.18 (CI: 1.50-6.72; P<0.001) for 3 seropositivities and 3.83 (CI: 0.84-17.43; P<0.05) for 4 seropositivities. The rate of subjects with high infection burden (3 seropositivities) was significantly higher in IHD group as compared to control group (53.4% vs 21.6%; P<0.01). Moreover, the mean number of seropositivities was also significantly higher in patients with IHD in comparison to control group (2.47 vs 1.68; P<0.01). The seroprevalence of anti-H. pylori antibodies in AMI and UA groups was significantly higher compared to control group (P<0.0001). The seroprevalence of anti-CMV antibodies in AMI and UA group was also significantly higher than those observed in control group (P<0.01). Moreover, the seroprevalence of anti-HSV-1 antibodies was significantly higher in AMI and UA groups in comparison to control group (P<0.001). The seroprevalence of anti-HSV-2 antibodies was similarly expressed in patients and healthy control group. CONCLUSION: the infection burden was significantly higher in patients with IHD, which represent that the parameter should also be considered as an independent risk factor for development of IHD. The seroprevalence of H. pylori, CMV and HSV-1 were also higher in patients with IHD.

Polymorphisms within exon 9 but not intron 8 of the vitamin D receptor are associated with the nephropathic complication of type-2 diabetes.

The impact of several environmental and genetic factors on diabetes and its complications is well documented but there is an urgent need to understand more about genetic risk factors associated with this disease. The present study was aimed at examining the two single nucleotide polymorphisms (SNP) in intron 8 and exon 9 of the vitamin D receptor (VDR) gene in nephropathic and non-nephropathic type-2 diabetic patients. In this clinical study, peripheral blood samples were obtained from 100 type-2 diabetic patients, 100 nephropathic type-2 diabetic patients and 100 healthy controls. DNA was extracted and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to examine two SNP polymorphisms within the VDR gene. Our results showed a significant difference in the Taq-1 evaluated genotypes of exon 9 in the VDR gene of diabetic individuals with (P=0.012) and without (P ≤ 0.001) nephropathy. Analysis of the Taq-1 evaluated alleles of nephropathic (P=0.917) and non-nephropathic (P=1.000) did not show a significant difference. We also evaluated the intron 8 Apa-1 alleles in patients with (P=0.480) and without nephropathy (P=0.543) and determined there were no differences between these groups. Our results also showed that the frequency of Apa-1 genotypes did not differ in nephropathic (P=0.224) and non-nephropathic (P=0.236) diabetic patients. Based on our results, it can be concluded that VDR and its functional polymorphism in exon 9 may play an important role in pathogenesis of type-2 diabetes and more investigations are required to clarify their role in nephropathy.

Serotoninergic mechanisms and sleep.

Serotoninergic neurons play a critical role in the sleep mechanism. This is supported by a lot of converging experiments and has provided the basis for a great deal of research. A critical analysis is first developed, supported by more recent data which are not in complete agreement with the theory that raphe nuclei are actively implied in slow wave sleep. On the other hand, numerous experimental evidences were collected during the sixties on the EEG synchronizing influence of the lower brain stem and preoptic area. Recent data showed that serotonin could also play here a crucial role in the induction of sleep. Nevertheless, at the moment, it is difficult to make a critical examination of the interaction and regulation of these putative 5-HT-related areas of the brain, but we can postulate that the occurrence of true physiological sleep-waking continuum necessitates their successive or conjoint activation.

[Hypnotic effect of serotonin administered in the vago-aortic afferent pathway]. / Effet hypnogène de la sérotonine par mise en jeu de la voie vago-aortique afférente.

A minute amount of serotonin injected in the nodose ganglion circulation area develops abrupt myosis and general electrocortical synchronization activity in "encéphale isolé" Cat preparation. This hypnogenic effect of serotonin can still be reproduced after transection of vago-aortic nerves caudally to the nodose ganglia. The same injections become ineffective after rostral transection of the same pathway. These results suggest that serotonin may trigger some signs of sleep through peripheric nervous elements in which are probably localized in the nodose ganglia.