Παρασκευή 30 Ιουνίου 2017
A case of fatal idiosyncratic reaction to the designer drug 3,4-methylenedioxypyrovalerone (MDPV) and review of the literature
Abstract
The stimulant designer drug 3,4-methylenedioxypyrovalerone (MDPV) was first synthesized by Boehringer Ingelheim in 1969 and introduced on the black market in 2006. Only a small number of fatal intoxication cases have been reported in the literature, all with significant blood MDPV concentrations. In this report, we describe one fatality attributed to an idiosyncratic reaction to MDPV. The victim displayed agitation, violent behavior and delirium followed by cardiac arrest. Hyperthermia was observed at the hospital. The MDPV cardiac and femoral blood concentrations were 6 ng/mL. The presence of excited delirium syndrome and MDPV, a drug with a pharmacology similar to cocaine, leads to the conclusion that the victim suffered a fatal adverse reaction to MDPV. This is the first published case of idiosyncratic reaction to MDPV.
http://ift.tt/2sc0WUI
Sudden unexplained death in alcohol misuse (SUDAM) patients have different characteristics to those who died from sudden arrhythmic death syndrome (SADS)
Abstract
There is growing awareness of sudden unexplained death in alcohol misuse (SUDAM) in which there is no obvious cause of death, no evidence of acute alcohol toxicity or alcoholic ketoacidosis, and the heart is morphologically normal. This study describes the characteristics of a cohort with SUDAM from a tertiary cardiovascular referral center and compares the findings with those of individuals who died from sudden arrhythmic death syndrome (SADS). Cases in this retrospective cross-sectional study were identified from a database of referrals to our center spanning approximately 40 years. Cases with recorded heavy use of alcohol and non-alcohol users were selected, then limited to those with SUDAM or SADS aged 16 to 64 years. 62 cases of SUDAM and 41 cases of SADS were identified. The SUDAM group were older than the SADS group; mean age 35.8 years and 27.7 years respectively (P=0.0002). There was also a higher incidence of significant psychiatric illness in SUDAM (19.7%) than SADS (2.4%) cases. Post mortem liver examination was more likely to reveal heavy livers in SUDAM than SADS (2196.1g and 1572.4g respectively; P=0.0033) and more fatty liver change (24.2% and 2.4%). SUDAM tends to occur in individuals who are older and have heavier livers than those with SADS. Psychiatric illness is also more common. SADS, unlike SUDAM, is often associated with heritable channelopathies that may affect surviving family members. Therefore, differentiating between SUDAM and SADS identifies families likely to benefit from screening for these mutations, thus preventing further sudden arrhythmic deaths.
http://ift.tt/2tuJTRY
Blowfly puparia in a hermetic container: survival under decreasing oxygen conditions
Abstract
Despite widely accepted standards for sampling and preservation of insect evidence, unrepresentative samples or improperly preserved evidence are encountered frequently in forensic investigations. Here, we report the results of laboratory studies on the survival of Lucilia sericata and Calliphora vomitoria (Diptera: Calliphoridae) intra-puparial forms in hermetic containers, which were stimulated by a recent case. It is demonstrated that the survival of blowfly intra-puparial forms inside airtight containers is dependent on container volume, number of puparia inside, and their age. The survival in both species was found to increase with an increase in the volume of air per 1 mg of puparium per day of development in a hermetic container. Below 0.05 ml of air, no insect survived, and above 0.2 ml of air per 1 mg of puparium per day, survival reached its maximum. These results suggest that blowflies reveal a single, general pattern of survival under decreasing oxygen conditions and that this pattern is a product of number of developing insects, their age and the initial amount of available air. Implications for forensic entomology are discussed.
http://ift.tt/2tuBUnS
Immunohistochemical Analysis of Foxp3 + , CD4 + , CD8 + Cell Infiltrates and PD-L1 in Oral Squamous Cell Carcinoma
Abstract
The immunoexpression of the PD-L1 and the number of immune infiltrating cells have been shown to be a significant prognostic factors in various human cancers. Immunohistochemical method was used to examine the immunoexpression of PD-L1 and number of Foxp3+, CD4+, CD8+ cells in 78 cases of oral squamous cell carcinomas (OSCCs): with better prognosis - OSCCBP (n = 37), and with poorer prognosis - OSCCPP (n = 41), and 18 cases of normal mucosa as a control. The immunoexpression of PD-L1 and the mean number of Foxp3+ cells was significantly increased in OSCCPP group in comparison to OSCCBP and control groups. The mean number of CD4+ cells was significantly increased in OSCCPP group in comparison to OSCCBP and control groups. CD8+ cells were significantly more numerous in OSCCBP group in comparison to OSCCPP and control group. In both OSCCPP and OSCCBP groups there were positive significant correlations between number of Foxp3+ and CD4+ cells. We found positive correlations between the immunoexpression of PD-L1 and numbers of Foxp3+ cells, and negative correlation between the immunoexpression of PD-L1 and numbers of CD8+ cells in both OSCCPP and OSCCBP groups. We found also significant positive correlation between immunoexpression of PD-L1 and the number of CD4+ cells in OSCCPP group. In conclusion, our findings support the hypothesis of involvement of Tregs and PD-L1 in OSCC development and progression.
http://ift.tt/2u9pWO0
Precision oncology using a limited number of cells: optimization of whole genome amplification products for sequencing applications
Abstract
Background
Sequencing analysis of circulating tumor cells (CTCs) enables "liquid biopsy" to guide precision oncology strategies. However, this requires low-template whole genome amplification (WGA) that is prone to errors and biases from uneven amplifications. Currently, quality control (QC) methods for WGA products, as well as the number of CTCs needed for reliable downstream sequencing, remain poorly defined. We sought to define strategies for selecting and generating optimal WGA products from low-template input as it relates to their potential applications in precision oncology strategies.
Methods
Single pancreatic cancer cells (HPAF-II) were isolated using laser microdissection. WGA was performed using multiple displacement amplification (MDA), multiple annealing and looping based amplification (MALBAC) and PicoPLEX. Quality of amplified DNA products were assessed using a multiplex/RT-qPCR based method that evaluates for 8-cancer related genes and QC-scores were assigned. We utilized this scoring system to assess the impact of de novo modifications to the WGA protocol. WGA products were subjected to Sanger sequencing, array comparative genomic hybridization (aCGH) and next generation sequencing (NGS) to evaluate their performances in respective downstream analyses providing validation of the QC-score.
Results
Single-cell WGA products exhibited a significant sample-to-sample variability in amplified DNA quality as assessed by our 8-gene QC assay. Single-cell WGA products that passed the pre-analysis QC had lower amplification bias and improved aCGH/NGS performance metrics when compared to single-cell WGA products that failed the QC. Increasing the number of cellular input resulted in improved QC-scores overall, but a resultant WGA product that consistently passed the QC step required a starting cellular input of at least 20-cells. Our modified-WGA protocol effectively reduced this number, achieving reproducible high-quality WGA products from ≥5-cells as a starting template. A starting cellular input of 5 to 10-cells amplified using the modified-WGA achieved aCGH and NGS results that closely matched that of unamplified, batch genomic DNA.
Conclusion
The modified-WGA protocol coupled with the 8-gene QC serve as an effective strategy to enhance the quality of low-template WGA reactions. Furthermore, a threshold number of 5–10 cells are likely needed for a reliable WGA reaction and product with high fidelity to the original starting template.
http://ift.tt/2sbvDth
Solitary fibrous tumour of the pleura presenting as a giant intrathoracic mass
Solitary fibrous tumours (SFTs) are relatively rare neoplasms thought to originate from the submesothelial connective tissue. SFTs have been described in a variety of sites, including the pleura, orbit, lower respiratory tract, peritoneal cavity and heart. These neoplasms are usually benign, though locally aggressive, and metastatic behaviour has been observed in some cases. We describe a case of a 61-year-old man presenting with weight loss, poor appetite, malaise, worsening dyspnoea on exertion and lower extremity oedema, who was found to have a gigantic—21x21 cm—tumour occupying the entire right hemithorax causing compression and displacement of the mediastinum and liver. Transthoracic CT-guided biopsy revealed SFT of the pleura. The patient underwent preoperative angiography and embolisation of the tumour followed by successful surgical resection via thoracotomy.
http://ift.tt/2sbubr1
The role of neratinib in HER2-driven breast cancer
Future Oncology Ahead of Print.
http://ift.tt/2taWiIh
The Three Semiotic Lives of Domestic Cats: A Case Study on Animal Social Cognition
Abstract
The social cognition of domestic cats (Felis catus) is a scarcely studied topic due to the reputation of the animal as individualistic. Nevertheless, cats are capable of cognitively demanding cooperative activities such as a communal nest-moving. The cognitive abilities of free-ranging cats are evaluated against the background of the shared intentionality hypothesis, proposed by a research group of Michael Tomasello. Although their comparative studies are carried out on chimpanzees, they are valuable as a source of conceptual work linking empirical cognitive studies with the philosophical accounts of joint agency. We critically analyze theoretical cognitive concepts interpreting the triadic interactions of great apes and the collective hunting among chimpanzees. Contrary to the shared intentionality hypothesis, it is argued that cats have cognitive abilities to share attention, truly cooperate and constitute shared meanings. Finally, we introduce the concept of the natural interaction ritual by Randall Collins and outline its significance for our case study about cats as well as for a general biosemiotic theory of the development of symbols.
http://ift.tt/2taqVxu
Multicenter Phase I Dose Escalation Study of Hypofractionated Stereotactic Radiotherapy with Bevacizumab for Recurrent Glioblastoma and Anaplastic Astrocytoma
It has been reported previously that the combination of bevacizumab with hypofractionated stereotactic re-irradiation (HFSR) with 30Gy (6GyX5 fractions) was safe and efficacious in recurrent glioblastomas and high-grade gliomas (HGG). Because most recurrences are local, developing intensified HFSR dosing schedules remains of interest. We hypothesized that in combination with bevacizumab, HFSR doses could be further escalated, and designed a prospective phase I trial to establish the maximum tolerated dose (MTD) of a 3-fraction HFSR delivered concomitantly with standard doses of bevacizumab.
http://ift.tt/2tvJwGe
Mutagenesis and expression of methane monooxygenase to alter regioselectivity with aromatic substrates
Abstract
Soluble methane monooxygenase (sMMO) from methane-oxidising bacteria can oxygenate more than 100 hydrocarbons and is one of the most catalytically versatile biological oxidation catalysts. Expression of recombinant sMMO has to date not been achieved in Escherichia coli and so an alternative expression system must be used to manipulate it genetically. Here we report substantial improvements to the previously described system for mutagenesis of sMMO and expression of recombinant enzymes in a methanotroph (Methylosinus trichosporium OB3b) expression system. This system has been utilised to make a number of new mutants and to engineer sMMO to increase its catalytic precision with a specific substrate whilst increasing activity by up to six-fold. These results are the first 'proof-of-principle' experiments illustrating the feasibility of developing sMMO-derived catalysts for diverse applications.http://ift.tt/2uu5KFZ
Optimization of therapy against Pseudomonas aeruginosa with ceftazidime and meropenem using chemostats as model for infections
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that can cause life-threatening infections in patients admitted to intensive care units. Resistance rapidly develops against two drugs of choice, ceftazidime and meropenem. Several therapeutic protocols were compared for reduction in viable cells and limiting development of resistance. Chemostat cultures were exposed to antibiotic concentrations measured in the blood of patients at low (5th percentile), medium (50th percentile) or high (95th percentile) levels in several therapy protocols to simulate therapy. Cultures exposed to ceftazidime recovered after 1 day at low, 2 days at medium and 3 days at high concentrations and developed corresponding levels of resistance. Patterns were very similar for meropenem except that recovery was delayed. Fluctuating levels and intermittent treatment achieved similar reduction of cell numbers at lower resistance costs. Treatment alternating ceftazidime and meropenem reduced cell numbers more than monotherapy, while strongly limiting resistance. Combination therapy was even more effective in both respects. Therapeutic goals are best reached with least risk of resistance when ceftazidime and meropenem are used in combination or alternating, at the highest concentrations the patient can endure. Monotherapy should also apply the highest concentration that is safe for the shortest time that achieves treatment objectives.http://ift.tt/2tvKwu5
Effects of Different Substrates/Growth Media on Microbial Community of Saliva-derived biofilm
Abstract
The aims of this study were to investigate the effects of substrates (glass versus hydroxyapatite HA) and growth media (SHI medium versus a modified artificial saliva medium with cysteine) on the microbial community of saliva-derived biofilm in vitro. 16S rRNA gene sequencing technology was used to analyze the microbial community of saliva-derived biofilm cultured for 72 h anaerobically. The metagenomes of biofilms were predicted from the clusters of orthologous groups (COGs). No significant difference was found between the saliva-derived biofilms grown on HA and glass in ACE, Chao, Shannon and Simpson indices. The abundances of only a few bacteria on HA were significantly different from those on glass with a low relative abundance (< 0.5%). Compared with the biofilms developed in a modified artificial saliva medium with cysteine, biofilms in SHI medium were significantly higher (p< 0.05) in diversity. Linear discriminant analysis coupled with effect size measurement (LEfSe) showed some obligate anaerobic genera (Lactobacillus, Veillonella, Porphyromonas, and Leptotrichia) were more abundant in SHI medium biofilms. The biofilms grown in different media were also significantly different in predicted gene categories. In conclusion, the growth media, not the substrates, have significant effects on the microbial community of saliva-derived biofilm in vitro.http://ift.tt/2utywGT
Patterns and drivers of fungal community depth stratification in Sphagnum peat
Abstract
Peatlands store an immense pool of soil carbon vulnerable to microbial oxidation due to drought and intentional draining. We used amplicon sequencing and quantitative PCR to 1) examine how fungi are influenced by depth in the peat profile, water table and plant functional group at the onset of a multi-year mesocosm experiment, and 2) test if fungi are correlated with abiotic variables of peat and pore water. We hypothesized that each factor influenced fungi, but that depth would have the strongest effect early in the experiment. We found that: 1) communities were strongly depth stratified; fungi were four-times more abundant in the upper (10–20 cm) than the lower (30–40 cm) depth, and dominance shifted from ericoid mycorrhizal fungi to saprotrophs and endophytes with increasing depth; 2) the influence of plant functional group was depth-dependent, with Ericaceae structuring the community in the upper peat only; 3) water table had minor influences; and 4) communities strongly covaried with abiotic variables, including indices of peat and pore water carbon quality. Our results highlight the importance of vertical stratification to peatland fungi, and the depth-dependency of plant functional group effects, which must be considered when elucidating the role of fungi in peatland carbon dynamics.http://ift.tt/2tubpyT
Bacterial community composition and diversity in Kalakuli, an alpine glacial-fed lake in Muztagh Ata of the westernmost Tibetan Plateau
Abstract
It is widely accepted that bacterial community composition and diversity in remote alpine lakes are structured by environmental conditions such as nutrient status and temperature. However, the mechanisms that underlie and structure bacterial community composition and diversity in alpine lakes remain unclear. We used 16S rRNA gene-based Illumina MiSeq sequencing to investigate the complex ecological interactions between bacterial communities and nutrient status in Kalakuli Lake, an alpine glacial-fed lake in Muztagh Ata of the westernmost Tibetan Plateau. Our results indicated that the bacterial community was dominated by the Actinobacteria and Proteobacteria. The results of threshold estimates showed that there were apparent shifts in dominance from the Proteobacteria to Actinobacteria groups associated with increasing carbon to nitrogen (C:N) ratio, and the change points were 6.794 and 2.448, respectively. Using multiple statistical methods, we found that the abiotic factors of dissolved organic carbon and total nitrogen had substantial impacts on bacterial diversity, while bacterial community compositions were significantly correlated with both the biotic element of bacterial abundance, and the abiotic ones, temperature and pH. These findings demonstrated that the C:N ratio played a significant role in shifting dominant bacterial assemblages in the Kalakuli watershed and provided evidence of nutrients affecting bacterial community composition and diversity. We argue that this study could further shed light on how climate change-induced glacial retreat may impact bacterial communities in glacial-fed lakes under future global warming scenarios.http://ift.tt/2sbuEcF
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma [Research Articles]
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analysed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined four CCA clusters - Fluke-Positive CCAs (Clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations, conversely Fluke-Negative CCAs (Clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3'UTR deletion as a mechanism of FGFR2 upregulation. Integration of non-coding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores - mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.
http://ift.tt/2utKX5j
mTORC2 Regulates the Cystine-Glutamate Antiporter xCT [Research Watch]
mTORC2 controls glutamate and glutathione metabolism in cancer cells by phosphorylating xCT.
http://ift.tt/2tvLPcD
De Novo Methylation Halts PD-1 Blockade-Mediated T-cell Revitalization [Research Watch]
Heritable de novo methylation programs induce the terminal differentiation of exhausted T cells.
http://ift.tt/2utou8H
BAP1 and PTEN Stabilize IP3R3 to Promote Ca2+-Mediated Apoptosis [Research Watch]
BAP1 and PTEN prevent IP3R3 degradation, increasing Ca2+ flux and apoptosis to suppress tumor growth.
http://ift.tt/2tvI2fn
The RagD GTPase Regulates mTORC1 Activity to Promote Tumor Growth [Research Watch]
MiT/TFE transcription factors directly upregulate RagD, which activates mTORC1 to support tumor growth.
http://ift.tt/2utnMb9
Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element
The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (~5.2 Mb) is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb) in Drosophila ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4 Mb region of the D. ananassae F element, and a 1.7 Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons) are major contributors to this expansion (78.6%), while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%). Both D. melanogaster and D. ananassae F element genes exhibit distinct characteristics compared to D element genes (e.g., larger coding spans, larger introns, more coding exons, lower codon bias), but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F element genes can primarily be attributed to mutational biases instead of selection. The 5' ends of F element genes in both species are enriched in H3K4me2 while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.
http://ift.tt/2utzqTu
A High Density Linkage Map Reveals Sexual Dimorphism in Recombination Landscapes in Red Deer (Cervus elaphus)
High density linkage maps are an important tool to gain insight into the genetic architecture of traits of evolutionary and economic interest, and provide a resource to characterise variation in recombination landscapes. Here, we used information from the cattle genome and the 50K Cervine Illumina BeadChip to inform and refine a high density linkage map in a wild population of red deer (Cervus elaphus). We constructed a predicted linkage map of 38,038 SNPs and a skeleton map of 10,835 SNPs across 34 linkage groups. We identified several chromosomal rearrangements in the deer lineage relative to sheep and cattle, including six chromosome fissions, one fusion and two large inversions. Otherwise, our findings showed strong concordance with map orders in the cattle genome. The sex-averaged linkage map length was 2739.7cM and the genome-wide autosomal recombination rate was 1.04cM per Mb. The female autosomal map length was 1.21 longer than that of males (2767.4cM vs 2280.8cM, respectively). Sex differences in map length were driven by high female recombination rates in peri-centromeric regions, a pattern that is unusual relative to other mammal species. This effect was more pronounced in fission chromosomes that would have had to produce new centromeres. We propose two hypotheses to explain this effect: (1) that this mechanism may have evolved to counteract centromeric drive associated with meiotic asymmetry in oocyte production; and/or (2) that sequence and structural characteristics suppressing recombination in close proximity to the centromere may not have yet evolved at neo-centromeres. Our study provides insight into how recombination landscapes vary and evolve in mammals, and will provide a valuable resource for studies of evolution, genetic improvement and population management in red deer and related species.
http://ift.tt/2tvUj34
FlyExpress 7: An Integrated Discovery Platform To Study Co-expressed Genes Using In Situ Hybridization Images in Drosophila
Gene expression patterns assayed across development can offer key clues about a gene's function and regulatory role. Drosophila melanogaster is ideal for such investigations as multiple individual and high-throughput efforts have captured the spatiotemporal patterns of thousands of embryonic expressed genes in the form of in situ images. FlyExpress (www.flyexpress.net), a knowledgebase based on a massive and unique digital library of standardized images and a simple search engine to find co-expressed genes, was created to facilitate the analytical and visual mining of these patterns. Here, we introduce the next generation of FlyExpress resources to facilitate the integrative analysis of sequence data and spatiotemporal patterns of expression from images. FlyExpress 7 now includes over 100,000 standardized in situ images and implements a more efficient, user-defined search algorithm to identify co-expressed genes via Genomewide Expression Maps (GEMs). Shared motifs found in the upstream 5' regions of any pair of co-expressed genes can be visualized in an interactive dotplot. Additional webtools and linkouts to assist in the downstream validation of candidate motifs are also provided. Together, FlyExpress 7 represents our largest effort yet to accelerate discovery via the development and dispersal of new webtools that allow researchers to perform data-driven analyses of co-expression (image) and genomic (sequence) data.
http://ift.tt/2utMCbc
An RNA Recognition Motif-Containing Protein Functions in Meiotic Silencing by Unpaired DNA
Meiotic silencing by unpaired DNA (MSUD) is a biological process that searches pairs of homologous chromosomes (homologs) for segments of DNA that are unpaired. Genes found within unpaired segments are silenced for the duration of meiosis. In this report, we describe the identification and characterization of Neurospora crassa sad-7, a gene that encodes a protein with an RNA recognition motif. Orthologs of sad-7 are found in a wide range of ascomycete fungi. In N. crassa, sad-7 is required for a fully-efficient MSUD response to unpaired genes. Additionally, at least one parent must have a functional sad-7 allele for a cross to produce ascospores. Although sad-7-null crosses are barren, sad-7 strains grow at a wild-type rate and appear normal under vegetative growth conditions. With respect to expression, sad-7 is transcribed at baseline levels in early vegetative cultures, at slightly higher levels in mating-competent cultures, and at its highest level during mating. These findings suggest that SAD-7 is specific to mating-competent and sexual cultures. Although the role of SAD-7 in MSUD remains elusive, green fluorescent protein (GFP)-based tagging studies place SAD-7 within nuclei, perinuclear regions, and cytoplasmic foci of meiotic cells. This localization pattern is unique among known MSUD proteins and raises the possibility that SAD-7 coordinates nuclear, perinuclear, and cytoplasmic aspects of MSUD.
http://ift.tt/2tvxuwy
G9a - An Appealing Antineoplastic Target
Background: G9a is the primary enzyme for mono- and dimethylation at Lys 9 of histone H3 and forms predominantly the heteromeric complex as a G9a-GLP (G9a-like protein) that is a functional histone lysine methltransferase in vivo. Mounting evidence suggests that G9a catalyzes methylation of histone and nonhistone proteins, which plays a crucial role in diverse biological processes and human diseases. Methods: In this study, the current knowledge on biological functions of G9a and inhibitors were summarized. Results: we review the current knowledge on biological functions of G9a, with particular emphasis on regulating gene expression and cell processes, and involvement in human diseases. We outline a perspective on various classes of G9a inhibitors to date from both articles and patents with an emphasis on their discovery, activity and the current research status. Conclusion: We highlight the key knowledge on potential biological functions and various human diseases. We also reviewed the discovery and characterization of the reported G9a inhibitors. However, we also propose the challenges and future opportunities in study of G9a. This review could make a crucial contribution to the long journey to develop drug-like molecules targeting G9a.
http://ift.tt/2u8LsCu
Virus, Oncolytic Virus and Human Prostate Cancer
Background: Prostate cancer (PCa), a disease, is characterized by abnormal cell growth in the prostate - a gland in the male reproductive system. Although older age and a family history of the disease have been recognized as the risk factors of PCa, the cause of this cancer remains unclear. Currently, PCa is one of the leading causes of cancer death among men of all races. Method: In this review study, we first discuss the controversy of the contribution of virus infection to PCa, and subsequently summarize the development of oncolytic virotherapy for PCa in the past several years. Results: Mounting evidence suggests that infections with various viruses are causally linked to PCa pathogenesis. Published studies have provided strong evidence that at least two viruses (RXMV and HPV) contribute to prostate tumourigenicity and impact on the survival of patients with malignant PCa. Traditional therapies including chemotherapy and radiotherapy are unable to distinguish cancer cells from normal cells, which are a significant drawback and leads to toxicities for PCa patients undergoing treatment. So far, few other options are available for treating patients with advanced PCa. For PCa treatment, oncolytic virotherapy appears to be much more attractive, which uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cancer cell lysis through virus replication and expression of cytotoxic proteins. Conclusion: Virotherapy is being developed to be a novel therapy for cancers, which uses oncotropic and oncolytic viruses with their abilities to find and destroy malignant cells in the body. As oncolytic viruses are a relatively new class of anti-cancer immunotherapy agents, several important barriers still exist on the road to the use of oncolytic viruses for PCa therapy.
http://ift.tt/2u8t64v
Role of Oxidative Stress in Hepatitis C Virus Induced Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Hepatitis C virus (HCV) infection is the predominant cause of chronic liver diseases and HCC, particularly in Western countries. Multiple molecular mechanisms are involved in the development and progression of HCV-related HCC, of which oxidative stress plays a pivotal role. HCV infection induces overproduction of reactive oxygen species (ROS) and impairs the function of endogenous antioxidants. Excessive amount of ROS directly damages DNA, lipids and proteins. Meanwhile, ROS indirectly activates a series of signaling cascades, and modulates the activity of many transcription factors, resulting in altered expression of genes that control cell survival, proliferation, angiogenesis, invasion and metastasis. In this review, we aim to summarize the possible molecular mechanisms underlying the link between the oxidative stress and hepatocarcinogenesis in HCV-infected individuals, in order to facilitate discovery of possible approaches or interventional targets for HCV-related HCC.
http://ift.tt/2tzDiWV
Hepatitis B Virus (HBV) Infection and Hepatocellular Carcinoma- New Insights for an Old Topic
Background: Hepatocellular carcinoma (HCC) is the most deadly form of liver cancer. Chronic hepatitis and subsequent liver fibrosis and cirrhosis are the major causes of HCC. HBV infection results not only in HCC but also extra-hepatic cancers. However, the importance and approaches for HCC screening in HBV infected individuals, the risk factors of HCC, the possible mechanisms leading to HCC and the potential therapeutic approaches of HBV-related HCC have less been systematic reviewed. Methods: In this study, we reviewed the screening, risk, new biomarker, mechanism and therapeutic of HBV-related HCC. Results: Serum AFP should be used for the HCC screening in CHB patients. Higher HBV viral load is associated with increased risk of HCC. HBV genotype and genetic polymorphism contribute to the risk of HCC.Ku86, Ku86 antibody, miR-18a, miR-122 and miR-150 may be reliable markers of HBVrelated HCC. MicroRNAs and HBx play a key role in HBV-related HCC. Two types of drugs, conventional interferon (IFN), and nucleoside analogs (NAs), have recently become available for the treatment of CHB infection. However, treatment guidelines for these patients have not yet established. Conclusion: A comprehensive understanding of how HBV infection causes HCC is of great importance in developing more effective antiviral therapy and prevention of late stage consequences such as cirrhosis and HCC. Regular screening in HBV infected individuals is a practically useful approach in reducing the HCC incidence in these patients. More reliable markers for HCC early detection should be explored. Combining IFNs and NAs with other curative approaches have superior benefits in preventing HCC recurrence.
http://ift.tt/2tzsbx0
Epstein-Barr Virus-associated Gastric Cancer and Potential Mechanisms of Oncogenesis
Introduction: EBV-associated Gastric Cancer (EBVaGC) comprises about 9% of all cases of GC and constitutes a distinct clinicopathological and molecular entity. The pattern of viral expression in EBVaGC cannot be set to any of the previously EBV-associated malignancies. Several lines of evidence support that viral expression in EBVaGC is characterized by high transcription of the BamH1- A rightward transcript (BART), low-levels of EBNA-1 and lack of LMP1. The high transcription activity of the BamH1-A region is importantly directed to express BART miRNAs, supporting a critical role for these miRNAs during epithelial cell infection and carcinogenesis. Several studies have shown that promoter hypermethylation is also a prominent feature of EBVaGC. Based on the recent TCGA report, the specific fingerprint of genomic alterations in EBVaGC is marked by mutations in PIK3CA, ARID1A and BCOR genes, and amplification of 9p24.1 that harbors the genes for the JAK2, PD-L1 and PD-L2 proteins. The specific programs of viral gene expression, promoter methylation and genomic mutations found in EBVaGC target cell signaling pathways leading to increased proliferation, increased cell survival, immune evasion, augmented EMT and acquisition of stemness features. Less understood is the participation of EBV in chronic gastric inflammation, but some studies argue that EBV, similar to and together with Helicobacter pylori, is an early participant in the GC oncogenic process through promoting chronic inflammation and increased tissue damage. Conclusion: Here, we discuss the principal and distinctive carcinogenic routes promoted by EBV in the gastric epithelium.
http://ift.tt/2u8IVIE
Molecular Approaches Target to Immunotherapy for HPV-Associated Cancers
Background: Infection with human papillomavirus (HPVs) causes many cancers, which account for about 10-20% of total human cancers. Two recently developed prophylactic vaccines against virus infection confer strong immunogenicity to provide long-term protection. The use of these vaccines has contributed to a substantial decrease in the rates of cervical cancer the second most common cancer of women worldwide. However, therapeutic vaccines that can eliminate preexisting HPV infections and treat an existing HPV-caused cancer have not been developed. Method: In this short review, we discuss development of immunotherapy for HPV-associated cancers and recent progresses in our understanding of the immunopathology of HPV infection. Results: Recent research advances have shown that molecular approaches target to immunotherapy for HPV infection-induced cancers to have the great potential and promise for developing immunotherapeutic vaccines. So far, the vast majority of the immunotherapeutic vaccines that are being tested are designed to target HPV viral genes and their proteins especially two E6 and E7 oncogenes. Conclusion: The developing immunotherapeutic vaccines aim to boost cell-mediated immunity. The boosted cell-mediated immunity strengthens the body's natural defenses to fight active infection and disease, thus to treat the existing cancers.
http://ift.tt/2tzvJzi
In Vitro Sensitivity Profiling of Neuroblastoma Cells Against A Comprehensive Small Molecule Kinase Inhibitor Library to Identify Agents for Future Therapeutic Studies
Background: Neuroblastoma (NB) constitutes about 8% of all childhood tumors, yet accounts for more than 15% of deaths, with an unacceptable overall survival rate. These rates are despite the current multimodal therapeutic approaches involving surgery, radiation, chemotherapy and myeloablation with hematopoietic stem cell rescue. Hence, efforts have intensified to identify new targets and novel therapeutic approaches to improve cure rates in these children. Numerous new agents for adult malignancies are developed and evaluated for cancer each year, providing an invaluable resource, with the added advantage of available pharmacologic and toxicity data for consideration. Methods: To identify potential therapeutic targets, we screened a small molecule library of 151 small kinase inhibitors against NB cell lines. Based on our initial screening data, we further examined the potential of Bcr-Abl targeting small molecule inhibitors to affect the growth and survival of NB cells. Results: There is diverse activity among the currently available Bcr-Abl inhibitors, possibly reflecting the molecular heterogeneity and off-target activity in each combination. In depth analyses of ponatinib, an oral multi-target kinase inhibitor and effective agent in the treatment of refractory Philadelphia chromosome (Ph) positive leukemia, show growth inhibition at sub-micromolar concentrations. In addition, we also identified the potential of this agent to interfere with insulin-like growth factor-1 receptor (IGF-1R) signaling pathways and Src activity, inhibit cell migration and induce apoptosis. Conclusion: Our findings provide initial data on ponatinib's potential to target key growth regulatory pathways and provide the rationale for further studies and evaluation in future early phase clinical trials for the treatment of refractory NB.
http://ift.tt/2u8P4En
Incidence of Hepatitis B Viral Reactivation After Kidney Transplantation With Low-dose Rituximab Administration.
http://ift.tt/2u8N6nG
Non-HLA Antibodies Impact on C4d staining, Stellate Cell Activation and Fibrosis in Liver Allografts.
http://ift.tt/2tzwOXR
Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus
Early diagnosis of diabetes mellitus can significantly improve therapeutic strategies and overall health span. Identifying biomarkers as a tool for determining the risk of developing diabetes as well as a monitoring strategy for progression of the disease state would be useful in predicting potential complications while simultaneously improving our ability to prevent and treat diabetes. Extracellular vesicles (EV) have recently emerged as prominent mediators of intercellular communication and as a potential source for the discovery of novel biomarkers. A deeper understanding of the cargo molecules present in EVs obtained from type 1 diabetes mellitus (T1D) patients may aid in the identification of novel diagnostic and prognostic biomarkers, and can potentially lead to the discovery of new therapeutic targets.
L'articolo Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus sembra essere il primo su European Review.
http://ift.tt/2sYY7t2
Mapping the Universe of RNA Tetraloop Folds
We report a map of RNA tetraloop conformations constructed by calculating pairwise distances among all experimentally determined four-nucleotide hairpin loops. Tetraloops with similar structures are clustered together and, as expected, the two largest clusters are the canonical GNRA and UNCG folds. We identify clusters corresponding to known tetraloop folds such as GGUG, RNYA, AGNN, and CUUG. These clusters are represented in a simple two-dimensional projection that recapitulates the relationship among the different folds.
http://ift.tt/2tuCaTp
ADAM, a hands-on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics
Summary
Aims
To design, construct and validate a pharmacokinetics simulator that offers students hands-on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens.
Methods
The Alberta Drug Administration Modeler (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes.
Results
The simulator effectively models one- and two-compartment drug behaviour in a mathematically-robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve-fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported.
Conclusions
The ADAM pharmacokinetics simulator is relatively inexpensive and straightforward to construct, and offers a realistic, hands-on PK learning opportunity for students that effectively complements didactic lectures.
http://ift.tt/2tavN5G
Effectiveness of ATP bioluminescence assay for presumptive identification of microorganisms in hospital water sources
Laboratory analysis of organisms in water include arduous methods, such as the multiple tube and membrane filter. The ATP bioluminescence system, proposes a new way of measuring cellular material in water by m...
http://ift.tt/2sbfP9W
An integrated study of human and animal infectious disease in the Lake Victoria crescent small-holder crop-livestock production system, Kenya
The neglected zoonotic diseases (NZD) are an understudied group that are a major cause of illness throughout the developing world. In general, little is known about the prevalence and burden of NZDs in affecte...
http://ift.tt/2ttzLsI
Recurrent Staphylococcal Scalded Skin Syndrome in an Extremely Low-Birth-Weight Neonate
AJP Rep 2017; 07: e134-e137
DOI: 10.1055/s-0037-1603971
Staphylococcal scalded skin syndrome (SSSS) in premature infants is a rare condition. We present SSSS in an extremely low-birth-weight (ELBW) infant with recurrent and confirmed bacterial sepsis. We present it to emphasize the importance for clinicians to not only recognize the clinical manifestations of SSSS, but also the need to closely monitor infants, especially very low-birth-weight (VLBW) and ELBW infants with SSSS for recurrence and bacterial sepsis. SSSS in preterm infants is a potentially lethal condition and early recognition and appropriate supportive care could be life-saving.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
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Orbital Subperiosteal Hematoma in the Newborn Causing Unilateral Proptosis: Ultrasound as First-Line Imaging Modality
AJP Rep 2017; 07: e138-e143
DOI: 10.1055/s-0037-1603953
Proptosis in the neonatal period is relatively infrequent and has diverse underlying etiologies. One of the more common causes appears to be orbital subperiosteal hematoma. Early detection, differentiation from other causes, and regular follow-up are essential as loss of vision can occur. We describe two cases of neonatal proptosis caused by orbital subperiosteal hematoma highlighting different diagnostic and management approaches, and provide a summary of previously reported cases. Spontaneous resolution occurs in most cases; however, emergent surgical evacuation is warranted in cases of optic nerve compression. This is the first report to provide orbital ultrasound images of uncomplicated neonatal orbital subperiosteal hematoma. Orbital ultrasound followed by magnetic resonance imaging (MRI) is a valid nonradiation approach for assessing neonatal proptosis due to subperiosteal orbital hematoma.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
http://ift.tt/2t9UvD0
Addendum: Massive Urinary Protein Excretion Associated with Greater Neonatal Risk in Preeclampsia
AJP Rep 2017; 07: e127-e127
DOI: 10.1055/s-0037-1604063
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | open access Full text
http://ift.tt/2tadWM3
Diabetes during Pregnancy: Influence of Body Mass Index on Composite Morbidity
AJP Rep 2017; 07: e128-e133
DOI: 10.1055/s-0037-1603913
Objective This study aims to compare composite maternal and neonatal morbidities (MM, NM) among pregnant women with diabetes mellitus whose body mass index (BMI) at delivery was < 30 (group 1), 30.0 to 39.9 (group 2), and ≥ 40 kg/m2 (group 3). We hypothesized that increased BMI class at delivery would be associated with worsening maternal and neonatal outcomes. Methods This is a retrospective cohort study. MM was defined as: chorioamnionitis, wound infection, eclampsia, diabetic ketoacidosis, hypoglycemia admission, third/fourth degree laceration, and/or death. NM was defined as umbilical arterial pH < 7.0, 5 minute Apgar < 4, respiratory distress syndrome, mechanical ventilation, neonatal sepsis, stillbirth, and/or death. Odds ratios were adjusted for possible confounders. Results MM was noted in 8, 13, and 24% of groups 1, 2, and 3, respectively, and significantly more common in group 2 versus 1 (adjusted odds ratio [aOR]: 1.66) and group 3 versus 1 (aOR: 3.06). NM was noted in 7, 8, and 15% of each BMI group, respectively, and differed significantly between group 3 vs. 2 (aOR: 1.77). Conclusions The increased rate of morbidities between the BMI groups is useful to inform diabetic women and highlights the need for further investigation of diabetes and obesity as comorbidities in pregnancy.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
http://ift.tt/2tacfOS
Mapping the Universe of RNA Tetraloop Folds
We report a map of RNA tetraloop conformations constructed by calculating pairwise distances among all experimentally determined four-nucleotide hairpin loops. Tetraloops with similar structures are clustered together and, as expected, the two largest clusters are the canonical GNRA and UNCG folds. We identify clusters corresponding to known tetraloop folds such as GGUG, RNYA, AGNN, and CUUG. These clusters are represented in a simple two-dimensional projection that recapitulates the relationship among the different folds.
http://ift.tt/2tuCaTp
In vitro characterization and in vivo toxicity, antioxidant and immunomodulatory effect of fermented foods; Xeniji™
Xeniji, produced by fermenting various types of foods with lactic acid bacteria and yeast, has been commonly consumed as functional food. However, nutrition value, bioactivities and safety of different ferment...
http://ift.tt/2ttmm3y
Prevalence, patterns, and perceived value of complementary and alternative medicine among cancer patients: a cross-sectional, descriptive study
Sophisticated conventional medicine (CM) has brought significant advances to cancer prevention, detection, and treatment. However, many cancer patients still turn to complementary and alternative medicine (CAM...
http://ift.tt/2satdvc
High-frequency oscillations: The state of clinical research
Summary
Modern electroencephalographic (EEG) technology contributed to the appreciation that the EEG signal outside the classical Berger frequency band contains important information. In epilepsy, research of the past decade focused particularly on interictal high-frequency oscillations (HFOs) > 80 Hz. The first large application of HFOs was in the context of epilepsy surgery. This is now followed by other applications such as assessment of epilepsy severity and monitoring of antiepileptic therapy. This article reviews the evidence on the clinical use of HFOs in epilepsy with an emphasis on the latest developments. It highlights the growing literature on the association between HFOs and postsurgical seizure outcome. A recent meta-analysis confirmed a higher resection ratio for HFOs in seizure-free versus non–seizure-free patients. Residual HFOs in the postoperative electrocorticogram were shown to predict epilepsy surgery outcome better than preoperative HFO rates. The review further discusses the different attempts to separate physiological from epileptic HFOs, as this might increase the specificity of HFOs. As an example, analysis of sleep microstructure demonstrated a different coupling between HFOs inside and outside the epileptogenic zone. Moreover, there is increasing evidence that HFOs are useful to measure disease activity and assess treatment response using noninvasive EEG and magnetoencephalography. This approach is particularly promising in children, because they show high scalp HFO rates. HFO rates in West syndrome decrease after adrenocorticotropic hormone treatment. Presence of HFOs at the time of rolandic spikes correlates with seizure frequency. The time-consuming visual assessment of HFOs, which prevented their clinical application in the past, is now overcome by validated computer-assisted algorithms. HFO research has considerably advanced over the past decade, and use of noninvasive methods will make HFOs accessible to large numbers of patients. Prospective multicenter trials are awaited to gather information over long recording periods in large patient samples.
http://ift.tt/2t9nqqX
Cancer Cell-Autonomous Parainflammation Mimics Immune Cell Infiltration
Parainflammation is a unique variant of inflammation, characterized by epithelial-autonomous activation of inflammatory response. Parainflammation has been shown to strongly promote mouse gut tumorigenesis upon p53 loss. In a recent study, we explored the prevalence of parainflammation in human cancer and determined its relationship to certain molecular and clinical parameters affecting treatment and prognosis. Parainflammation can be identified from a 40-gene signature and is found in both carcinoma cell lines and a variety of primary tumors, independently of tumor microenvironment. Here, we discuss the implications of our findings in analyses of tumor microenvironment, suggesting that as tumor cell gene expression may often mimic immune and inflammatory infiltration, caution should be applied when interpreting tumor expression data. We also address the connection between parainflammation and prevalence of p53 mutations in specific types of tumors, and cancer prevention by regular usage of NSAIDs. We suggest that parainflammation may serve as a novel biomarker for screening patients who may particularly benefit from NSAID treatment. Cancer Res; 77(14); 1–5. ©2017 AACR.
http://ift.tt/2tyF9ef
RNA Editing in Pathogenesis of Cancer
Several adenosine or cytidine deaminase enzymes deaminate transcript sequences in a cell type or environment-dependent manner by a programmed process called RNA editing. RNA editing enzymes catalyze A>I or C>U transcript alterations and have the potential to change protein coding sequences. In this brief review, we highlight some recent work that shows aberrant patterns of RNA editing in cancer. Transcriptome sequencing studies reveal increased or decreased global RNA editing levels depending on the tumor type. Altered RNA editing in cancer cells may provide a selective advantage for tumor growth and resistance to apoptosis. RNA editing may promote cancer by dynamically recoding oncogenic genes, regulating oncogenic gene expression by noncoding RNA and miRNA editing, or by transcriptome scale changes in RNA editing levels that may affect innate immune signaling. Although RNA editing markedly increases complexity of the cancer cell transcriptomes, cancer-specific recoding RNA editing events have yet to be discovered. Epitranscriptomic changes by RNA editing in cancer represent a novel mechanism contributing to sequence diversity independently of DNA mutations. Therefore, RNA editing studies should complement genome sequence data to understand the full impact of nucleic acid sequence alterations in cancer. Cancer Res; 77(14); 1–7. ©2017 AACR.
http://ift.tt/2u7srQJ
AXL-Driven EMT State as a Targetable Conduit in Cancer
The receptor tyrosine kinase (RTK) AXL has been intrinsically linked to epithelial–mesenchymal transition (EMT) and promoting cell survival, anoikis resistance, invasion, and metastasis in several cancers. AXL signaling has been shown to directly affect the mesenchymal state and confer it with aggressive phenotype and drug resistance. Recently, the EMT gradient has also been shown to rewire the kinase signaling nodes that facilitate AXL–RTK cross-talk, protracted signaling, converging on ERK, and PI3K axes. The molecular mechanisms underplaying the regulation between the kinome and EMT require further elucidation to define targetable conduits. Therapeutically, as AXL inhibition has shown EMT reversal and resensitization to other tyrosine kinase inhibitors, mitotic inhibitors, and platinum-based therapy, there is a need to stratify patients based on AXL dependence. This review elucidates the role of AXL in EMT-mediated oncogenesis and highlights the reciprocal control between AXL signaling and the EMT state. In addition, we review the potential in inhibiting AXL for the development of different therapeutic strategies and inhibitors. Cancer Res; 77(14); 1–8. ©2017 AACR.
http://ift.tt/2tyn5ky
LSD1 inhibitor T-3775440 inhibits SCLC cell proliferation by disrupting LDS1 interactions with SNAG domain proteins INSM1 and GFI1B
T-3775440 is an irreversible inhibitor of the chromatin demethylase LSD1, which exerts anti-proliferative effects by disrupting the interaction between LSD1 and GFI1B, a SNAG domain transcription factor, inducing leukemia cell transdifferentiation. Here we describe the anti-cancer effects and mechanism of action of T-3775440 in small cell lung cancer (SCLC). T-3775440 inhibited proliferation of SCLC cells in vitro and retarded SCLC tumor growth in vivo. T-3775440 disrupted the interaction between LSD1 and the transcriptional repressor INSM1, thereby inhibiting expression of neuroendocrine-associated genes such as ASCL1. INSM1 silencing phenocopied the effects of T-3775440 on gene expression and cell proliferation, consistent with the likelihood T-3775440 mediated its effects in SCLC by inhibiting INSM1. T-3775440 also inhibited proliferation of an SCLC cell line that overexpressed GFI1B, rather than INSM1, by disrupting the interaction between LSD1 and GFI1B. Taken together, our results argue that LSD1 plays an important role in neuroendocrine-associated transcription and cell proliferation of SCLC via interactions with the SNAG domain proteins INSM1 and GFI1B. Targeting these critical interactions with LSD1 inhibitors offers a novel rational strategy to therapeutically manage SCLC.
http://ift.tt/2u7TEmj
Discrimination and Characterization of Heterocellular Populations Using Quantitative Imaging Techniques
http://ift.tt/2t9Ki9C
Low-complexity DOA estimation from short data snapshots for ULA systems using the annihilating filter technique
This paper addresses the problem of DOA estimation using uniform linear array (ULA) antenna configurations. We propose a new low-cost method of multiple DOA estimation from very short data snapshots. The new e...
http://ift.tt/2sZP23f
Dendritic cell-based immunotherapy: a basic review and recent advances.
| Related Articles |
Dendritic cell-based immunotherapy: a basic review and recent advances.
Immunol Res. 2017 Jun 28;:
Authors: Constantino J, Gomes C, Falcão A, Neves BM, Cruz MT
Abstract
Dendritic cells (DCs) are considered a very promising arm to activate the immune system in immunotherapeutic strategies against cancer. DCs are the most powerful antigen-presenting cells (APCs), being highly efficient at generating robust immune responses. They are also considered the center of the immune system, since they provide a crucial link between both innate and adaptive immune responses. Thus, DC-based cancer immunotherapy aims to take advantage of these unique characteristics of DCs to better fight cancer. During the last decade, they have been the subject of numerous studies intending to develop immunotherapeutic strategies against cancer through vaccination. For this purpose, it is essential to gain a better insight into DC immunobiology, regulation of innate and adaptive immune systems, and tumor microenvironment, as well as applying the latest advances in science in order to boost their enormous anti-tumor immunotherapeutic potential. In this review, we will hold focus on DC immunobiology (from their origin, location, and special properties and distinct subsets to the innate and adaptive immunity), on the new concept of cancer immunoediting, and on the knowledge given by clinical trials using DC vaccines. Finally, future perspectives for this emerging field are highlighted.
PMID: 28660480 [PubMed - as supplied by publisher]
http://ift.tt/2svmNWF
A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8(+) T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.
| Related Articles |
A Poly(Lactic-co-Glycolic) Acid Nanovaccine Based on Chimeric Peptides from Different Leishmania infantum Proteins Induces Dendritic Cells Maturation and Promotes Peptide-Specific IFNγ-Producing CD8(+) T Cells Essential for the Protection against Experimental Visceral Leishmaniasis.
Front Immunol. 2017;8:684
Authors: Athanasiou E, Agallou M, Tastsoglou S, Kammona O, Hatzigeorgiou A, Kiparissides C, Karagouni E
Abstract
Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4(+) TH1 and CD8(+) T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L. infantum proteins (cysteine peptidase A, histone H1, and kinetoplastid membrane protein 11), in order to be encapsulated in poly(lactic-co-glycolic) acid nanoparticles with or without the adjuvant monophosphoryl lipid A (MPLA) or surface modification with an octapeptide targeting the tumor necrosis factor receptor II. We aimed to construct differentially functionalized peptide-based nanovaccine candidates and investigate their capacity to stimulate the immunomodulatory properties of dendritic cells (DCs), which are critical regulators of adaptive immunity generated upon vaccination. According to our results, DCs stimulation with the peptide-based nanovaccine candidates with MPLA incorporation or surface modification induced an enhanced maturation profile with prominent IL-12 production, promoting allogeneic T cell proliferation and intracellular production of IFNγ by CD4(+) and CD8(+) T cell subsets. In addition, DCs stimulated with the peptide-based nanovaccine candidate with MPLA incorporation exhibited a robust transcriptional activation, characterized by upregulated genes indicative of vaccine-driven DCs differentiation toward type 1 phenotype. Immunization of HLA A2.1 transgenic mice with this peptide-based nanovaccine candidate induced peptide-specific IFNγ-producing CD8(+) T cells and conferred significant protection against L. infantum infection. Concluding, our findings supported that encapsulation of more than one chimeric multi-epitope peptides from different immunogenic L. infantum proteins in a proper biocompatible delivery system with the right adjuvant is considered as an improved promising approach for the development of a vaccine against VL.
PMID: 28659922 [PubMed - in process]
http://ift.tt/2suZKvb
Prospective study of the innate cellular immune response in low vaccine responder children.
| Related Articles |
Prospective study of the innate cellular immune response in low vaccine responder children.
Innate Immun. 2017 Jan;23(1):89-96
Authors: Surendran N, Nicolosi T, Kaur R, Morris M, Pichichero M
Abstract
We recently reported our findings from a longitudinal, prospective study where we identified 10% infants who were low vaccine responders (LVR) at age 9-12 mo following routine primary series vaccine schedule. We found multiple cellular deficiencies in LVR children, including low number of memory B cells, reduced polyclonal stimulation of naïve/memory T cell response and suboptimal APC response. These children outgrew their poor vaccine response by the time they received booster doses of vaccine. Studies in human infant innate immunity are rare because of the unique challenges in specimen collection. As innate immunity instructs adaptive immunity, we hypothesized that the primary immune defect lies with innate immunity and in this study we sought to determine the ontogeny of innate immune response in LVR children between 6 and 36 mo of age. Interestingly, suboptimal APC response observed in LVR children at 6-9 mo of age characterized by significantly ( P < 0.05) low basal MHC II expression, low R848 induced IRF7 fold change, as well as low IFN-α, IL-12p70 and IL-1β levels, came to parity with normal vaccine responders by 12-15 mo of age, suggesting that the observed immune deficiency in LVR children may be the result of delayed maturation of immune system.
PMID: 27864558 [PubMed - indexed for MEDLINE]
http://ift.tt/2svmNpD
Expansion and Adipogenesis Induction of Adipocyte Progenitors from Perivascular Adipose Tissue Isolated by Magnetic Activated Cell Sorting
http://ift.tt/2sv4UqT
A clinical study on the effects of recombinant human colony stimulating factor on the expression of Bcl-2 in serum of patients with basal ganglia hemorrhage and its clinical significance
OBJECTIVE: We investigated the effects of the colony-stimulating factor (CSF-1) on Bcl-2 expression in serums of patients with basal ganglia hemorrhage and subsequently, its clinical significance.
PATIENTS AND METHODS: The expression levels of Bcl-2 in serums of patients with basal ganglia hemorrhage were analyzed, and the effects of the CSF-1 on Bcl-2 expression were observed. Samples of peripheral blood were taken from 120 patients with basal ganglia hemorrhage admitted to the Neurology Department and 120 healthy people undergoing a physical examination at Xiangyang Central Hospital between May 2013 to December 2014. The detection of Bcl-2 levels in serums of patients was performed using the ELISA method, and patients were divided into two groups, the colony-stimulating factor (CSF-1) group and the control group. The CSF-1 group was treated with recombinant human granulocyte colony-stimulating factor after routine treatment, while the control group was treated only with routine treatment. The two groups of patients were followed up for observation of treatment effects.
RESULTS: Before treatment, serum Bcl-2 levels in both the CSF-1 and control group showed no significant differences; however, their levels were significantly higher than those of the healthy cohort (p<0.05). After treatment, serum Bcl-2 levels of the CSF-1 group were significantly higher than those of the control group (p<0.05). However, compared to the healthy control group, the levels remained significantly higher and the differences were statistically significant (p<0.05). When compared to the recovering conditions of patients in the CSF-1 group and the control group, we found that the average hospitalization time and occurrences of complications in the CSF-1 group were significantly less than those in the control group (p<0.05).
CONCLUSIONS: CSF-1 is clinically effective in improving the serum Bcl-2 levels after a basal ganglia hemorrhage, and it can be used as adjuvant therapy in the treatment of basal ganglia hemorrhage.
L'articolo A clinical study on the effects of recombinant human colony stimulating factor on the expression of Bcl-2 in serum of patients with basal ganglia hemorrhage and its clinical significance sembra essere il primo su European Review.
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Study on the expression and mechanism of inflammatory factors in the brain of rats with cerebral vasospasm
OBJECTIVE: We investigated the significance of IL-1 and ICAM-1 in rat's subarachnoid hemorrhage (SAH) cerebral vasospasm (CVS) model.
MATERIALS AND METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly divided into the SAH group and the Sham group. Cisterna magna auto blood injection was used to prepare the CVS models. We studied and compared changes in the basilar arteries diameters before and after SAH. We measured the cerebrovascular inner diameter before and after SAH modeling using the ultrasound. ELISA method was used to measure the expression of IL-1 and ICAM-1 in peripheral blood. The expression of MAPK and P38 in the brain was tested using Western blot. Brain cells apoptosis was studied using TUNEL method.
RESULTS: Cerebrovascular inner diameter reduced significantly in the SAH group as compared to the control group. The expression of IL-1 and ICAM-1 increased significantly after 48 hours. Compared to the Sham group, p-38 and p-MAPK expression levels in the SAH group increased significantly after 48 hours. Results showed that 48 hours after the operation, the level of apoptosis was significantly higher in the SAH group.
IL-1 and ICAM-1 expression levels were associated with a P38-MAPK signal pathway in the brain. p38 and MAPK activation were closely related to apoptosis in the cortex.
CONCLUSIONS: We suggest that the cerebral basilar vasospasm was occurred in rats 48 hours after ASH onset, with an increase in IL-1 and ICAM-1 expression and brain cells apoptosis.
L'articolo Study on the expression and mechanism of inflammatory factors in the brain of rats with cerebral vasospasm sembra essere il primo su European Review.
http://ift.tt/2usnEsN
Current directions in research and treatment of fear of cancer recurrence.
Purpose of review: An expert meeting in Ottawa in 2015 galvanized efforts to answer key questions relevant to the understanding and management of fear of cancer recurrence (FCR). The aim of this review is to summarize key developments. Recent findings: A consensus on the definition of FCR has helped to further research in this area. There have been a number of theories put forward to account for the development of FCR, all of which share key components. Importantly, a number of important trials have been published that confirm both brief and more intensive interventions can successfully treat FCR. Summary: The consensus definition of FCR is an important development, as is the development of treatments for FCR. There are now evidence-based options for the management of patients with clinical levels of FCR. Future research priorities include determining the optimal cut-off points for identifying clinically significant FCR, testing the major tenets of the recent theoretical formulations of FCR; and determining the relative efficacy and cost-effectiveness of different treatment approaches for managing FCR. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2tt7Gld
http://ift.tt/2tt7Gld
Long-Term Outcomes in a Population-based Cohort with Respiratory Nontuberculous Mycobacteria Isolation
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1120-1128, July 2017.
http://ift.tt/2u7yWD5
Transbronchial Lung Cryobiopsy and Video-assisted Thoracoscopic Lung Biopsy in the Diagnosis of Diffuse Parenchymal Lung Disease. A Meta-analysis of Diagnostic Test Accuracy
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1197-1211, July 2017.
http://ift.tt/2ty2jBA
Mortality after Respiratory Isolation of Nontuberculous Mycobacteria. A Comparison of Patients Who Did and Did Not Meet Disease Criteria
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1112-1119, July 2017.
http://ift.tt/2u7PElR
Fetal Growth and Childhood Lung Function in the Swedish Twin Study on Prediction and Prevention of Asthma
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1147-1153, July 2017.
http://ift.tt/2tytTyP
Oxygen Delivery during Severe Anemia When Blood Transfusion Is Refused on Religious Grounds
http://ift.tt/2u7cwSz
Environmental Mycobacterial Latency: A Role in Human Disease?
http://ift.tt/2u7PAm7
Respiratory Pattern and Tidal Volumes Differ for Pressure Support and Volume-assured Pressure Support in Amyotrophic Lateral Sclerosis
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1139-1146, July 2017.
http://ift.tt/2u7kafX
Accuracy of Nasal Nitric Oxide Measurement as a Diagnostic Test for Primary Ciliary Dyskinesia. A Systematic Review and Meta-analysis
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1184-1196, July 2017.
http://ift.tt/2tyidMf
Effect of 4-Aminopyridine on Genioglossus Muscle Activity during Sleep in Healthy Adults
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1177-1183, July 2017.
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Apparent Sporadic Lymphangioleiomyomatosis in a Man as a Result of Extreme Mosaicism for a TSC2 Mutation
http://ift.tt/2tytRXJ
Advancing a Common Understanding and Approach to Dyspnea Management. Consensus Proposal for the Chronic Breathlessness Syndrome
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Care of the Critically Ill Burn Patient. An Overview from the Perspective of Optimizing Palliative Care
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1094-1102, July 2017.
http://ift.tt/2tykVRR
The Experience of Patients with Alcohol Misuse after Surviving a Critical Illness. A Qualitative Study
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1154-1161, July 2017.
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Posterior Tracheal Laceration Treated with a Stent
http://ift.tt/2ty2exM
Reply: Response to Risks and Cough-Aggravating Factors in Prolonged Cough
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1232-1233, July 2017.
http://ift.tt/2tyuOzd
Summary for Clinicians: Lymphangioleiomyomatosis Diagnosis and Management Clinical Practice Guideline
http://ift.tt/2u7cqub
A 55-Year-Old Man with a Trachea Undressed
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Molecular Profiling of Malignant Pleural Effusion in Metastatic Non–Small-Cell Lung Carcinoma. The Effect of Preanalytical Factors
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1169-1176, July 2017.
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Reply: Careful Planning Reduces Cryobiopsy Complications
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1230-1230, July 2017.
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Careful Planning Reduces Cryobiopsy Complications
Annals of the American Thoracic Society, Volume 14, Issue 7, Page 1229-1229, July 2017.
http://ift.tt/2t9GtS4
Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects
http://ift.tt/2sZTqPN
Extensive Lymph Node Surgery Does Not Increase Survival in Melanoma
A conservative approach to lymph node removal surgery may be best for people with melanoma that has spread from the skin to one or a small number of nearby lymph nodes, new results from a large international clinical trial suggest.
http://ift.tt/2urRVYr
Effect of PM2.5 mediated oxidative stress on the innate immune cellular response of Der p1 treated human bronchial epithelial cells
OBJECTIVE: To investigate the effect of stimulation of Human Bronchial Epithelial Cells (HBEC) by Der p1 and PM2.5 on the expression of innate immune cell factors to find new therapeutic targets for treatment of bronchial asthma.
MATERIALS AND METHODS: The Der p1 antigen exposure model in the HEBC line, 16HBE-14o, was established in vitro. PM2.5 at a concentration of 50 µM/cm2, was added to these cells for 0.5 h, 1 h, 2 h and 3 h. Cells were treated with the following reagents for the indicated times: 300 ng/mL Der p1 for 21 h, 50 µM/cm2 PM2.5 for 3 h, 10 mM Nac for 3 h and PM2.5 contamination for 3 h. The experiment was divided into five groups: control (group A), Der p1 exposure group (group B), PM2.5 treated group (group C), PM2.5+Der p1 exposure group (group D), Nac+PM2.5+Der p1 exposure group (group E). ELISA method was adopted to test the expression levels of malondialdehyde, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP), and Real-time RT-PCT was used to measure IL-25, IL-33 and TSLP mRNA.
RESULTS: The protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group D were significantly higher than those in the other groups, while the protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group E were significantly lower than those in group D (p<0.05).
CONCLUSIONS: PM2.5 can enhance the Der p1 antigen-induced HBEC innate immune response through the expression of IL-25, IL-33 and TSLP, which may exacerbate the occurrence rate of bronchial asthma.
L'articolo Effect of PM2.5 mediated oxidative stress on the innate immune cellular response of Der p1 treated human bronchial epithelial cells sembra essere il primo su European Review.
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The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole
Abstract
Background
Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors. Our aim was to evaluate the efficacy of tamoxifen (T) and letrozole (L) in HGOC in clinical practice and investigate factors influencing clinical outcome.
Methods
A retrospective review of patients with relapsed HGOC treated with either tamoxifen or letrozole at the Royal Marsden Hospital between 2007 and 2012 was performed. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included CA125 response, clinical benefit rate (CBR) and duration of response. Platinum-sensitivity and ER-status were evaluated as predictors of treatment response.
Results
97 patients were included (43 T, 54 L); median age 63 years (20–92); 91% high-grade serous; median number of lines of prior chemotherapy 3 (1–8); 60% platinum-resistant, 40% platinum-sensitive; 52% ER + ve, 1% ER-ve, 47% unknown. 14 patients (6 T, 8 L) achieved a partial response, with ORR (RECIST) of 14% (T) and 15% (L). The CBR for ≥3 months was 65% (22/43) for tamoxifen and 56% (22/54) for letrozole. There was no significant difference in ORR (p = 0.99) or CBR (p = 0.14) between tamoxifen and letrozole. 22 patients (23%) had a CA-125 response with hormonal therapy (10 T – 23% and 12 L – 22%). ORR did not differ by platinum sensitivity (p = 0.42); or ER-status (positive vs unknown, p = 0.12). Responders to letrozole had longer durations of response than responders to tamoxifen (26 vs 11.5 months, p = 0.03), but equivalent disease stability duration (9.6 vs 7.2 months respectively, p = 0.11).
Conclusions
Within the constraints of a retrospective study, we identified that patients treated with letrozole had a significantly longer duration of response than those treated with tamoxifen. Treatment with either tamoxifen or letrozole is a rational treatment option for patients with ER + ve HGOC, with equivalent ORR, CBR and disease stability.
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Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion
Abstract
Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.
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Microguided Endodontics: a method to achieve minimally invasive access cavity preparation and root canal location in mandibular incisors using a novel computer-guided technique
Abstract
Aim
To present a novel miniaturized and minimally invasive treatment approach for root canal localization in mandibular incisors with pulp canal calcification and apical periodontitis.
Summary
A 51-year-old male patient presented with pain from his mandibular incisors. The patient had a history of severe dental trauma over 30 years ago. Both mandibular central incisors (teeth 31, 41) were tender to percussion and had a yellowish discoloration. They did not respond to thermal and electrical sensitivity tests. Two periapical radiographs from different projections revealed severe pulp canal calcifications and signs of periapical periodontitis. To facilitate the "Microguided Endodontics" technique, a CBCT and an intraoral surface scan were aligned using special software. This allowed the virtual planning of optimal access cavities up to the apical third of the root. In this technique, a 3D-printed template guides a customized drill to the orifice of the root canal. After negotiation of the root canals, conventional root canal treatment was performed. This case report demonstrates that minimally invasive and apically extended access cavities are feasible in mandibular incisors with this technique.
This article is protected by copyright. All rights reserved.
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Comparison of transvaginal surgery and methotrexate/mifepristone-combined transcervical resection in the treatment of cesarean scar pregnancy
OBJECTIVE: To explore the safety and efficiency of transvaginal surgical treatment of cesarean scar pregnancy (CSP).
PATIENTS AND METHODS: A retrospective analysis of 54 CSP patients that received treatment in our hospital from October 2011 to September 2015 was performed, dividing two groups: Group A (n=34) received transvaginal cesarean scar pregnancy focus clearance surgery while Group B (n=20) received transcervical resection following methotrexate/mifepristone-combined treatment. The basic clinical findings were collected and analyzed, along with the curative effects between the two groups.
RESULTS: Differences in age (30.91 ± 4.59 years vs. 31.91 ± 5.53 years) for gravidity (2.97 ± 1.24 times vs. 2.75 ± 1.48 times), cesarean section (1.24 ± 0.43 vs. 1.20 ± 0.41), time interval from last cesarean section (56.53 ± 32.93 months vs. 58.70 ± 39.44 months), menelipsis (51.35 ± 10.90 days vs. 57.85 ± 16.62 days), pre-operative serum-hCG (27953.65 ± 37517.10 mIU/L vs. 17368.24 ± 35094.14 mIU/L), operation time (43.34 ± 12.38 min vs 40.07 ± 16.88 min), menstruation recovery time (1.23 ± 0.53 months vs. 1.55 ± 0.76 months) were not statistically significant (p > 0.05). The differences in the intraoperative blood loss (43.34 ± 12.38 ml vs. 40.07 ± 16.88 ml), average hospital stay (7.61 ± 2.47 days vs. 12.42 ± 3.64 days), time for β-hCG to return to normal (18.50 ± 8.19 mIU/L vs. 29.00 ± 12.96 mIU/L) between the two groups were statistically significant (p < 0.05). Group A was significantly lower than Group B.
CONCLUSIONS: Transvaginal surgery is an effective and relatively safe treatment option for CSP patients.
L'articolo Comparison of transvaginal surgery and methotrexate/mifepristone-combined transcervical resection in the treatment of cesarean scar pregnancy sembra essere il primo su European Review.
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Analysis of differential expression of miR-223 in platelets of elderly CHD patients before and after the autologous stem cell transplantation
OBJECTIVE: The aim of this study was to investigate the differential expression of miR-223 in the platelets of elderly patients with coronary heart disease (CHD) before and after autologous stem cell transplantation.
PATIENTS AND METHODS: In this study, 26 elderly CHD patients were enrolled for treatment from February 2014 to August 2015. Elbow venous blood was collected before and after autologous stem cell transplantation, respectively. Phosphorylation levels of vasodilator stimulated phosphoprotein (VASP) of platelets were assayed before and after the treatment through the flow cytometer. The VASP and Ago-2 protein expression were detected by using ELISA and Western blot, respectively.
RESULTS: The differential expression of miR-223, VASP and Ago-2 in CHD patients before and after treatment were detected using qRT-PCR. The platelet aggregation rate in the blood of patients was measured before and after the treatment by a platelet aggregation test. Compared to the levels before the treatment, the results of flow cytometry revealed that the phosphorylation levels of VASP in platelet of CHD patients who received the autologous stem cell transplantation was significantly increased (p<0.05). Also, ELISA and Western blot results showed that the protein expression of Ago-2 in elderly patients that received the treatment was significantly increased at (2.36±0.17) µg/L. However, there was no statistically significant difference in the comparison of VASP protein expression before and after treatment (p<0.05). The results of qRT-PCR showed that the expressions of Ago-2 and miR-223 in elderly CHD patients were significantly increased after autologous stem cell transplantation compared to those before the treatment with statistically significant differences (p<0.05). However, there were no statistically significant differences identified in the comparison of the mRNA expression of the VASP gene before and after the treatment (p>0.05).
CONCLUSIONS: Therefore, the miR-223 expression of platelets was significantly decreased after elderly CHD patients received autologous stem cell transplantation. Moreover, it leads to a decrease in protein expression and phosphorylation levels of VASP in order to reduce the occurrence of platelet aggregation.
L'articolo Analysis of differential expression of miR-223 in platelets of elderly CHD patients before and after the autologous stem cell transplantation sembra essere il primo su European Review.
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Lung Interstitial Macrophages: Establishing Identity and Uncovering Heterogeneity
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 1, Page 7-9, July 2017.
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Three Unique Interstitial Macrophages in the Murine Lung at Steady State
American Journal of Respiratory Cell and Molecular Biology, Volume 57, Issue 1, Page 66-76, July 2017.
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Analysis on application timing of IABP in emergency PCI treatment of patients with combined acute myocardial infarction and cardiac shock
OBJECTIVE: To study the application timing and effect of intra-aortic balloon pump (IABP) in the emergency PCI treatment of patients with combined acute myocardial infarction (AMI) and cardiogenic shock (CS).
PATIENTS AND METHODS: 84 cases of patients with combined AMI and CS under PCI in emergency treatment were randomly divided into the control group (n=42) and observational group (n=42). The control group underwent IABP again, after the invalidation of internal medicine drug treatment, while the observational group underwent IABP before the operation. We compared the effects of treatment.
RESULTS: After the intervention, the averages of arterial pressure and urine volume were increased in both groups than before (p <0.05). The average of heart rate was decreased, and the improvement in the observational group was more significant (p <0.05). However, the mortality rate in the observational group during the perioperative period was decreased than the control group as well as, the success rate of off-respirator was significant (p <0.05). The comparison of IABP complication occurrence rate as well as the survival rate after 1-year follow-up between both groups was not significantly different. Additionally, whereas the NYHA grouping in two groups was gradually improved, the difference was not statistically significant between both groups. However, in the observational group, the LVEF after one-month follow-up was significantly higher than in the control group (p <0.05), but not when comparing 1-year. VEDd at each time point in two groups were also similar.
CONCLUSIONS: The early IABP can improve hemodynamics of patients with combined AMI and CS under emergency PCI. It can reduce perioperative mortality rate, improve the success rate of off-respirator, but cannot increase IABP complication incidence rate while having little influence on the long-term survival rate and cardiac function indicator.
L'articolo Analysis on application timing of IABP in emergency PCI treatment of patients with combined acute myocardial infarction and cardiac shock sembra essere il primo su European Review.
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Effects of epoxyeicosatrienoic acids (EETs) on retinal macular degeneration in rat models
OBJECTIVE: Here we use a rat model to investigate the effects of epoxyeicosatrienoic acids (EETs) on retinal macular degeneration along with pathological and physiological mechanisms of the disease.
MATERIALS AND METHODS: Six choroidal neovascularization (CNV) rats were created with a 532 nm laser and received intravitreal injections of EETs in both eyes. On day 1, 3, 7 and 14 after photocoagulation, the thickness and area of CNV were measured with HE staining and choroidal flat mounts. COX-2 and VEGF levels in CNV were detected by immunohistochemistry method. Protein and mRNA expression were studied by Western blotting and RT-PCR.
RESULTS: 14 days after photocoagulation, CNV thickness and area were significantly reduced (p<0.01) in the treatment group compared with the control group. COX-2 and VEGF had high expression in vascular endothelial cells and stromal cells of CNV. Peak expression of COX-2 and VEGF was significantly higher (p<0.01) in the treatment group than in the control group. 7 days after photocoagulation, VEGF protein and mRNA expression were significantly lower (p<0.05) in the treatment group than in the control group, whereas COX-2 mRNA showed no significant difference (p>0.05). FFA found that CNV fluorescein leakage area was significantly reduced (p<0.05) in the treatment group than in the control group. 14 days after photocoagulation, neovascularization area was significantly smaller (p<0.05) in the treatment group than in the control group. Vitreous EETs levels in the treatment group were significantly higher than in the control group. Compared with the control group, the celecoxib treatment group had significantly increased vitreous EETs (p<0.05).
CONCLUSIONS: Intravitreal injection of celecoxib could suppress the thickness and area of laser-induced macular degeneration CNV. It also improved the vitreous EETs levels in CNV model rats. COX-2 expression was upregulated in the early generation of laser-induced CNV, which may play an important role in regulating expression of VEGF.
L'articolo Effects of epoxyeicosatrienoic acids (EETs) on retinal macular degeneration in rat models sembra essere il primo su European Review.
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Sensitive and selective LC-MS/MS assay for quantitation of flutrimazole in human plasma
OBJECTIVE: A highly sensitive liquid chromatography-tandem mass spectrometry method was developed and validated for the determination of flutrimazole in human plasma. This study was to investigate the application of sensitive and selective LC-MS/MS method for quantitation of flutrimazole in human plasma.
MATERIALS AND METHODS: The analysis and internal standard were extracted with ether and hexane (v:v, 1:1) followed by a rapid isocratic elution with a 0.1% formic acid/methanol (v:v, 20:80) on a C18 column (50 mm × 2.1 mm I.D.) and subsequent analysis by mass spectrometry in the multi-reaction-monitoring mode. The precursor to production transitions of m/z 279.0 → 183.1 and m/z 441.0 → 295.1 were used to measure the analyte and the internal standard.
RESULTS: The assay was linear over the concentration range of 0.996-99.6 ng•mL-1 for flutrimazole in human plasma. The lower limit of quantification was 0.996 ng•mL-1 and the extraction recovery was larger than 78.83% for flutrimazole. The inter- and intra-day precision of the method at three concentrations was less than 9.26%.
CONCLUSIONS: The LC-MS/MS method was firstly applied to quantitation of flutrimazole in human plasma.
L'articolo Sensitive and selective LC-MS/MS assay for quantitation of flutrimazole in human plasma sembra essere il primo su European Review.
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Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus
Early diagnosis of diabetes mellitus can significantly improve therapeutic strategies and overall health span. Identifying biomarkers as a tool for determining the risk of developing diabetes as well as a monitoring strategy for progression of the disease state would be useful in predicting potential complications while simultaneously improving our ability to prevent and treat diabetes. Extracellular vesicles (EV) have recently emerged as prominent mediators of intercellular communication and as a potential source for the discovery of novel biomarkers. A deeper understanding of the cargo molecules present in EVs obtained from type 1 diabetes mellitus (T1D) patients may aid in the identification of novel diagnostic and prognostic biomarkers, and can potentially lead to the discovery of new therapeutic targets.
L'articolo Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus sembra essere il primo su European Review.
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Assessments of M-mode color echocardiography on fetal right ventricular diastolic function with umbilical cord around neck
OBJECTIVE: To investigate the fetal right ventricular diastolic function under the condition of umbilical cord around neck (UCAN), and analyze the changes of the right ventricular propagation velocity (Vp), then discuss the clinical value of the color M-mode echocardiography in the evaluation of fetal ventricular diastolic function quantitatively.
PATIENTS AND METHODS: All patients enrolled were with singleton pregnancy from Cangzhou Central Hospital from December 2013 to December 2015 as the experimental group. The control group consisted of normal fetuses without UCAN and the experimental group consisted of the fetuses with UCAN. Besides, this paper analyzed values of Tei index of the left and right ventricle as well as Vp of the right ventricle diastole using color M-mode echocardiography.
RESULTS: The Vp values of the experimental group were significantly lower than those of the control group (p < 0.05); the Tei index of the right ventricle of the experimental group was significantly higher than that of the control group (p < 0.05); the Tei indexes of the left and right ventricles of the experimental group had no statistical difference (p > 0.05). The heart function and the right ventricular diastolic function were reduced in fetuses with UCAN; however, the effect of the left and the right ventricular diastolic function had no significant changes in fetuses with UCAN.
CONCLUSIONS: It had great significance to select the appropriate index of cardiac function for estimating the right ventricular diastolic function and the whole heart function of UCAN, and it is of huge practical application value in clinical practice.
L'articolo Assessments of M-mode color echocardiography on fetal right ventricular diastolic function with umbilical cord around neck sembra essere il primo su European Review.
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Fas/FasL induces myocardial cell apoptosis in myocardial ischemia-reperfusion rat model
OBJECTIVE: Myocardium ischemia reperfusion is easy to induce myocardial injury. Fas/FasL is an important signaling pathway mediating cell apoptosis. This study aims to analyze the cell apoptosis and Fas/FasL expression in myocardial cell ischemia reperfusion rat model.
MATERIALS AND METHODS: Coronary artery ligation method was used to establish myocardial ischemia reperfusion model. Rats were grouped according to different ischemia and reperfusion time: Group A, myocardial ischemia for 30 min and reperfusion for 24 h; Group B, myocardial ischemia for 30 min and reperfusion for 48 h; Group C, myocardial ischemia for 1 h and reperfusion for 24 h. Myocardial injury indicators were tested. Myocardial cell apoptosis was detected by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Fas and FasL mRNA and protein expressions were evaluated by Real-time PCR (RT-PCR) and Western blot.
RESULTS: Creatine kinase (CK), lactic dehydrogenase (LDH), and malondialdehyde (MDA) significantly elevated, while superoxide dismutase (SOD) obviously declined in the experimental group compared with control and blank group (p<0.05). CK, LDH, and MDA gradually upregulated, whereas SOD was reduced in experimental groups following the time extension of ischemia and reperfusion (p<0.05). Apoptosis cell number was markedly higher in the experimental group compared with control and blank group (p<0.05). Apoptosis cell number gradually increased in the experimental groups following ischemia and reperfusion time extension (p<0.05). Fas/FasL mRNA and protein markedly upregulated in the experimental group compared with control and blank group (p<0.05). Fas/FasL mRNA and protein expressions enhanced in experimental groups following the time extension of ischemia and reperfusion (p<0.05).
CONCLUSIONS: Fas/FasL induces myocardial cell apoptosis in the process of myocardium ischemia reperfusion in rat model.
L'articolo Fas/FasL induces myocardial cell apoptosis in myocardial ischemia-reperfusion rat model sembra essere il primo su European Review.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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