scholarly journals Changes in Serum MicroRNAs after Anti-IL-5 Biological Treatment of Severe Asthma

2021 ◽  
Vol 22 (7) ◽  
pp. 3558
Author(s):  
Manuel J. Rial ◽  
José A. Cañas ◽  
José M. Rodrigo-Muñoz ◽  
Marcela Valverde-Monge ◽  
Beatriz Sastre ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Airway Remodeling ◽  
Genetic Material ◽  
Membrane Vesicles ◽  
Early Response ◽  
Bioinformatic Analysis ◽  
Response To Treatment ◽  
Asthmatic Patients ◽  
Key Points ◽  
Severity Of The Disease

There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (p < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans (p < 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.

scholarly journals Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial

Blood ◽  
2018 ◽  
Vol 131 (13) ◽  
pp. 1456-1463 ◽  
Author(s):  
Anne-Ségolène Cottereau ◽  
Annibale Versari ◽  
Annika Loft ◽  
Olivier Casasnovas ◽  
Monica Bellei ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Risk Stratification ◽  
Hodgkin Lymphoma ◽  
Prognostic Value ◽  
Tumor Volume ◽  
Early Stage ◽  
Early Response ◽  
Metabolic Tumor Volume ◽  
Response To Treatment ◽  
Key Points

Key Points Baseline metabolic tumor volume is a strong prognostic factor in early-stage HL. Baseline metabolic tumor volume affects the early response to treatment and, combined with early PET, improves risk stratification.

scholarly journals The use of hyperpolarised 13C-MRI in clinical body imaging to probe cancer metabolism

2021 ◽  
Author(s):  
Ramona Woitek ◽  
Ferdia A. Gallagher
Keyword(s):  
Cancer Metabolism ◽  
Signal To Noise Ratio ◽  
Response Assessment ◽  
Early Response ◽  
Multiparametric Mri ◽  
Metabolic Reprogramming ◽  
Response To Treatment ◽  
Additional Information ◽  
Positron Emission ◽  
Breast And Prostate Cancer

AbstractMetabolic reprogramming is one of the hallmarks of cancer and includes the Warburg effect, which is exhibited by many tumours. This can be exploited by positron emission tomography (PET) as part of routine clinical cancer imaging. However, an emerging and alternative method to detect altered metabolism is carbon-13 magnetic resonance imaging (MRI) following injection of hyperpolarised [1-13C]pyruvate. The technique increases the signal-to-noise ratio for the detection of hyperpolarised 13C-labelled metabolites by several orders of magnitude and facilitates the dynamic, noninvasive imaging of the exchange of 13C-pyruvate to 13C-lactate over time. The method has produced promising preclinical results in the area of oncology and is currently being explored in human imaging studies. The first translational studies have demonstrated the safety and feasibility of the technique in patients with prostate, renal, breast and pancreatic cancer, as well as revealing a successful response to treatment in breast and prostate cancer patients at an earlier stage than multiparametric MRI. This review will focus on the strengths of the technique and its applications in the area of oncological body MRI including noninvasive characterisation of disease aggressiveness, mapping of tumour heterogeneity, and early response assessment. A comparison of hyperpolarised 13C-MRI with state-of-the-art multiparametric MRI is likely to reveal the unique additional information and applications offered by the technique.

scholarly journals Analysis of the Oxidative Burst and Its Relevant Signaling Pathways in Leptosphaeria maculans—Brassica napus Pathosystem

2021 ◽  
Vol 22 (9) ◽  
pp. 4812
Author(s):  
Cunchun Yang ◽  
W. G. Dilantha Fernando
Keyword(s):  
Cell Death ◽  
Signaling Pathways ◽  
Oxidative Burst ◽  
Defense Mechanisms ◽  
Leptosphaeria Maculans ◽  
Gene Interaction ◽  
Early Response ◽  
Marker Genes ◽  
Ros Accumulation ◽  
Microbe Interactions

An oxidative burst is an early response of plants to various biotic/abiotic stresses. In plant-microbe interactions, the plant body can induce oxidative burst to activate various defense mechanisms to combat phytopathogens. A localized oxidative burst is also one of the typical behaviors during hypersensitive response (HR) caused by gene-for-gene interaction. In this study, the occurrence of oxidative burst and its signaling pathways was studied from different levels of disease severity (i.e., susceptible, intermediate, and resistant) in the B. napus–L. maculans pathosystem. Canola cotyledons with distinct levels of resistance exhibited differential regulation of the genes involved in reactive oxygen species (ROS) accumulation and responses. Histochemical assays were carried out to understand the patterns of H2O2 accumulation and cell death. Intermediate and resistant genotypes exhibited earlier accumulation of H2O2 and emergence of cell death around the inoculation origins. The observations also suggested that the cotyledons with stronger resistance were able to form a protective region of intensive oxidative bursts between the areas with and without hyphal intrusions to block further fungal advancement to the uninfected regions. The qPCR analysis suggested that different onset patterns of some marker genes in ROS accumulation/programmed cell death (PCD) such as RBOHD, MPK3 were associated with distinct levels of resistance from B. napus cultivars against L. maculans. The observations and datasets from this article indicated the distinct differences in ROS-related cellular behaviors and signaling between compatible and incompatible interactions.

scholarly journals Genetics and Epigenetics in Asthma

2021 ◽  
Vol 22 (5) ◽  
pp. 2412
Author(s):  
Polyxeni Ntontsi ◽  
Andreas Photiades ◽  
Eleftherios Zervas ◽  
Georgina Xanthou ◽  
Konstantinos Samitas
Keyword(s):  
Dna Methylation ◽  
Association Studies ◽  
Airway Remodeling ◽  
Methylation Pattern ◽  
Atopic Asthma ◽  
Genome Wide Association Studies ◽  
Childhood Onset ◽  
Gene Markers ◽  
Asthmatic Patients ◽  
Asthma Susceptibility

Asthma is one of the most common respiratory disease that affects both children and adults worldwide, with diverse phenotypes and underlying pathogenetic mechanisms poorly understood. As technology in genome sequencing progressed, scientific efforts were made to explain and predict asthma’s complexity and heterogeneity, and genome-wide association studies (GWAS) quickly became the preferred study method. Several gene markers and loci associated with asthma susceptibility, atopic and childhood-onset asthma were identified during the last few decades. Markers near the ORMDL3/GSDMB genes were associated with childhood-onset asthma, interleukin (IL)33 and IL1RL1 SNPs were associated with atopic asthma, and the Thymic Stromal Lymphopoietin (TSLP) gene was identified as protective against the risk to TH2-asthma. The latest efforts and advances in identifying and decoding asthma susceptibility are focused on epigenetics, heritable characteristics that affect gene expression without altering DNA sequence, with DNA methylation being the most described mechanism. Other less studied epigenetic mechanisms include histone modifications and alterations of miR expression. Recent findings suggest that the DNA methylation pattern is tissue and cell-specific. Several studies attempt to describe DNA methylation of different types of cells and tissues of asthmatic patients that regulate airway remodeling, phagocytosis, and other lung functions in asthma. In this review, we attempt to briefly present the latest advancements in the field of genetics and mainly epigenetics concerning asthma susceptibility.

scholarly journals Trasposon Mediated Horizontal Gene Transfer (T-HGT) of Circulating Tumor DNA Reshapes MM Clonal Architecture

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3065-3065
Author(s):  
Munevver Cinar ◽  
Steven Flygare ◽  
Marina Mosunjac ◽  
Ganji Nagaraju ◽  
Dongkyoo Park ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Drug Sensitivity ◽  
Genetic Material ◽  
Host Cells ◽  
Response To Treatment ◽  
Hierarchical Architecture ◽  
Tumor Evolution ◽  
Sequencing Analysis

Spatial genetic heterogeneity is a characteristic phenomenon that influences multiple myeloma's (MM) phenotype and drug sensitivity (Rasche L. et al and Bolli N et al.). Hence, the branch model of tumor evolution is not sufficient to explain the disorganized architecture observed in MM. In this study, we investigated whether MM ctDNA horizontal gene transfer (HGT) affect tumor genetic architecture and drug sensitivity, resembling what is seen in prokaryotes, and elucidated the mechanisms involved in the mobilization of genetic material from one cell to another. We identified that plasma from patients with MM transmits drug sensitivity or resistance to cells in culture. This transmission of drug sensitivity is mediated by ctDNA transfer of oncogenes to a host cell. Importantly, in vitro and in vivo demonstrated that ctDNA mainly targets cells resembling the cell of origin (tropism). Karyotype spreads and whole genome sequencing demonstrated that once patients ctDNA encounters host cells, it migrates into the nucleus where it ultimately integrates into the cell's genome. Integration to the genome was confirmed to be targeted to myeloma cells. Further sequencing analysis of multiple MM samples identified ctDNA tropism and integration is dependent on the 5' and 3' end presence of transposable elements (TE), particularly of the MIR and ALUsq family. These results were further validated by TE mediated delivery of GFP into MM cells in vitro and HSVTK in tumors of mouse xenografts. In conclusion, this data indicates for the first time that TE mediates MM ctDNA HGT into homologous tumor cells shaping the hierarchical architecture of tumor clones and affecting tumor response to treatment. Therapeutically, this unique quality of ctDNA can be exploited for targeted gene therapeutic approaches in MM and potentially other cancers. Disclosures Bernal-Mizrachi: Kodikas Therapeutic Solutions, Inc: Equity Ownership; TAKEDA: Research Funding; Winship Cancer Institute: Employment, Patents & Royalties.

scholarly journals MicroRNA Analysis of Human Stroke Brain Tissue Resected during Decompressive Craniectomy/Stroke-Ectomy Surgery

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1860
Author(s):  
Andrew P. Carlson ◽  
William McKay ◽  
Jeremy S. Edwards ◽  
Radha Swaminathan ◽  
Karen S. SantaCruz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Brain Tissue ◽  
Stroke Patient ◽  
Mirna Expression ◽  
Strong Association ◽  
Bioinformatic Analysis ◽  
Experimental Models ◽  
Aberrant Expression ◽  
Tissue Samples ◽  
Human Stroke

Background: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first time, we investigated miRNA expression signatures in freshly removed human stroke brain tissue. Methods: Human brain samples were obtained during craniectomy and brain tissue resection in severe stroke patients with life-threatening brain swelling. The tissue samples were subjected to histopathological and immunofluorescence microscopy evaluation, next generation miRNA sequencing (NGS), and bioinformatic analysis. Results: miRNA NGS analysis detected 34 miRNAs with significantly aberrant expression in stroke tissue, as compared to non-stroke samples. Of these miRNAs, 19 were previously identified in stroke patient blood and CSF, while dysregulation of 15 miRNAs was newly detected in this study. miRNA direct target gene analysis and bioinformatics approach demonstrated a strong association of the identified miRNAs with stroke-related biological processes and signaling pathways. Conclusions: Dysregulated miRNAs detected in our study could be regarded as potential candidates for biomarkers and/or targets for therapeutic intervention. The results described herein further our understanding of the molecular basis of stroke and provide valuable information for the future functional studies in the experimental models of stroke.

scholarly journals Effect of Hypnosis on Pulmonary Function and Severity of the Disease in Asthmatic Patients: A Randomized Clinical Trial

2020 ◽  
Vol 1 (2) ◽  
pp. 95-101
Author(s):  
Z. Mohebbi ◽  
Sh. Najafi Doulatabad ◽  
M. Malekzadeh ◽  
S H Nabavizadeh ◽  
H. Marioryad ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pulmonary Function ◽  
Randomized Clinical Trial ◽  
Asthmatic Patients ◽  
Severity Of The Disease

scholarly journals Preliminary results using PET/MR in glioblastoma patients treated with regorafenib: an 18F-FET and DWI-ADC comparison

2021 ◽  
Author(s):  
Alessandro Spimpolo ◽  
Giuseppe Lombardi ◽  
Sara Berti ◽  
Cristina Campi ◽  
Maria Giulia Anglani ◽  
...  
Keyword(s):  
Early Response ◽  
Recurrent Glioblastoma ◽  
Response To Treatment ◽  
Fet Pet ◽  
Additional Information ◽  
Rano Criteria ◽  
Percentage Difference ◽  
Before And After ◽  
The Difference ◽  
Cancer Network

Abstract Introduction: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. DWI and 18F–FET PET are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in DWI/ADC- and 18F-FET PET-derived parameters in patients who underwent PET/MR at both baseline and soon after starting regorafenib. Method: We retrospectively selected 16 consecutive GBM patients who underwent 18F–FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze 4 SD patients who underwent a third PET/MR after another 4 cycles of regorafenib. 18F–FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and soon after treatment. A number of metrics were then derived and compared. Result: The average increases in FET and ADC pathological volumes were higher in PD than in SD patients, although in neither case did the difference reach significance. However, when the percentage difference in FET volumes was plotted against the corresponding percentage difference in ADC, a correlation was observed (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Conclusion: In recurrent glioblastoma patients treated with regorafenib, 18F-FET and ADC metrics, being obtained from completely different measures, could serve as semi-quantitative independent biomarkers of response to treatment. These promising parameters should be tested in a larger cohort of glioblastoma patients treated with regorafenib.

scholarly journals Assessment of quality of life in asthma patients in 5 to 18 years of children

2020 ◽  
Vol 7 (11) ◽  
pp. 2214
Author(s):  
Nikhil Jain ◽  
Karan Joshi
Keyword(s):  
Quality Of Life ◽  
Asthma Control ◽  
Persistent Asthma ◽  
Tertiary Hospital ◽  
P Value ◽  
Cross Sectional ◽  
Asthmatic Patients ◽  
Asthma Patients ◽  
Severity Of The Disease

Background: Asthma is a common cause of morbidity and mortality with prevalence of 300 million in world. The QOL of asthmatic patients cannot be determined only on the basis the severity of the disease, but requires a measurement of personal perception. This study was conducted with the aim to assess and compare the QOL using PedsQl scale in asthma patients between 5 to 18 years of age with different demographic and clinical variables.Methods: This was a cross-sectional observational study conducted at respiratory clinic in tertiary hospital, Rewa from October 2017 to June 2019. A total number of 150 asthmatic patients and their parents participated. Asthmatic patients (N=150) and their parents, presenting to asthma clinic of Gandhi Memorial Hospital, Rewa (after applying inclusion-exclusion criteria) were assessed for QOL using PedsQl scale 3.0. Statistical analysis was performed by SPSS version 20. Test of significance by student T-test and one way ANOVA.Results: The QOL is severely hampered by asthma with mean of 59 in intermittent asthma, 51 in mild, 44.74 in moderate and 40 in severe persistent asthma, significant p value of <0.05. Younger age, level of asthma control and severity were significantly related to QOL with p value of <0.05. Sex, socioeconomic status, were insignificantly related.Conclusions: QOL is impaired as the grading of asthma increases. Impairment of Quality of life are mostly associated with low level of asthma control, poly-therapy and frequent night attacks.

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