Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes.
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SUBMITTER: Yuan Y
PROVIDER: S-EPMC7039706 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionAging is characterized by the progressive loss of physiological capacity. Changes in gene expression can alter activity in defined age-related molecular pathways leading to cellular aging and increased aging disease susceptibility. The aim of the current study was to evaluate whether hyperbaric oxygen therapy (HBOT) affects gene expression in normal, non-pathological, aging adults.MethodsThirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th HBOT session, and 1-2 weeks following the last session. Differential gene expression analysis was performed.ResultsFollowing 60 sessions of HBOT, 1342 genes and 570 genes were differently up- and downregulated (1912 total), respectively (p < 0.01 FDR), compared to baseline. Out of which, five genes were downregulated with a >1.5-fold change: ABCA13 (FC = -2.28), DNAJ6 (FC = -2.16), HBG2 (FC = -1.56), PDXDC1 (FC = -1.53), RANBP17 (FC = -1.75). Two weeks post-HBOT, ABCA13 expression was significantly downregulated with a >1.5fold change (FC = -1.54, p = 0.008). In conclusion, for the first time in humans, the study provides direct evidence of HBOT is associated with transcriptome changes in whole-blood samples. Our results demonstrate significant changes in gene expression of normal aging population.
| S-EPMC8660606 | biostudies-literature
Project description:BackgroundDeconvolution analyses have been widely used to track compositional alterations of cell types in gene expression data. Although a large number of novel methods have been developed, due to a lack of understanding of the effects of modeling assumptions and tuning parameters, it is challenging for researchers to select an optimal deconvolution method suitable for the targeted biological conditions.ResultsTo systematically reveal the pitfalls and challenges of deconvolution analyses, we investigate the impact of several technical and biological factors including simulation model, quantification unit, component number, weight matrix, and unknown content by constructing three benchmarking frameworks. These frameworks cover comparative analysis of 11 popular deconvolution methods under 1766 conditions.ConclusionsWe provide new insights to researchers for future application, standardization, and development of deconvolution tools on RNA-seq data.
| S-EPMC8042713 | biostudies-literature
Project description:Thousands of RNA-binding proteins orchestrate RNA processing and altered protein-RNA interactions frequently lead to disease. Here, we present experimental and computational analysis pipelines of fractionated eCLIP-seq (freCLIP-seq), a modification of enhanced UV-crosslinking and RNA immunoprecipitation followed by sequencing. FreCLIP-seq allows transcriptome-wide analysis of protein-RNA interactions at single-nucleotide level and provides an additional level of resolution by isolating binding signals of individual RNA-binding proteins within a multicomponent complex. Binding occupancy can be inferred from read counts and crosslinking events. For complete details on the use and execution of this protocol, please refer to Biancon et al. (2022).
| S-EPMC9676202 | biostudies-literature
Project description:The present study explores for the first time the effect of hyperbaric oxygen (HBO) on gingival mesenchymal stem cells’ (G-MSCs) gene expression profile, intracellular pathways activation, pluripotency and differentiation potential under an experimental inflammatory setup. G-MSCs were isolated from five healthy individuals (n=5) and characterized. Single (24h) or double (72h) HBO stimulation (100%O2, 3bar, 90min) was performed under experimental in-flammatory [IL-1β(1ng/ml)/TNF-α(10ng/ml)/IFN-γ(100ng/ml)] and non-inflammatory mi-cro-environment. Next Generation Sequencing and KEGG pathway enrichment analysis, G-MSCs’ pluripotency gene expression, Wnt-/β-catenin pathway activation, proliferation, colo-ny-formation and differentiation were investigated. G-MSCs demonstrated all mesenchymal stem/progenitor cells’ characteristics. The benefi-cial effect of a single HBO stimulation was evident, with anti-inflammatory effects and induction of differentiation (TLL1, ID3, BHLHE40), proliferation/cell survival (BMF, ID3, TXNIP, PDK4, ABL2), migration (ABL2) and osteogenic differentiation (p<0.05). A second HBO stimulation at 72h had a detrimental effect, significantly increasing the inflammation-induced cellular stress and ROS accumulation through HMOX1, BHLHE40 and ARL4C amplification and pathway en-richment (p<0.05). Results outline a positive short-term single HBO anti-inflammatory, regenerative and dif-ferentiation stimulatory effect on G-MSCs. A second (72h) stimulation is yet detrimental on the same properties. The current results could open new perspectives in the clinical application of short-termed HBO induction in G-MSCs-mediated periodontal reparative/regenerative mecha-nisms.
2023-10-05 | GSE244404 | GEO
Project description:RNA-seq, a next-generation sequencing based method for transcriptome analysis, is rapidly emerging as the method of choice for comprehensive transcript abundance estimation. The accuracy of RNA-seq can be highly impacted by the purity of samples. A prominent, outstanding problem in RNA-seq is how to estimate transcript abundances in heterogeneous tissues, where a sample is composed of more than one cell type and the inhomogeneity can substantially confound the transcript abundance estimation of each individual cell type. Although experimental methods have been proposed to dissect multiple distinct cell types, computationally "deconvoluting" heterogeneous tissues provides an attractive alternative, since it keeps the tissue sample as well as the subsequent molecular content yield intact.Here we propose a probabilistic model-based approach, Transcript Estimation from Mixed Tissue samples (TEMT), to estimate the transcript abundances of each cell type of interest from RNA-seq data of heterogeneous tissue samples. TEMT incorporates positional and sequence-specific biases, and its online EM algorithm only requires a runtime proportional to the data size and a small constant memory. We test the proposed method on both simulation data and recently released ENCODE data, and show that TEMT significantly outperforms current state-of-the-art methods that do not take tissue heterogeneity into account. Currently, TEMT only resolves the tissue heterogeneity resulting from two cell types, but it can be extended to handle tissue heterogeneity resulting from multi cell types. TEMT is written in python, and is freely available at https://github.com/uci-cbcl/TEMT.The probabilistic model-based approach proposed here provides a new method for analyzing RNA-seq data from heterogeneous tissue samples. By applying the method to both simulation data and ENCODE data, we show that explicitly accounting for tissue heterogeneity can significantly improve the accuracy of transcript abundance estimation.
| S-EPMC3622628 | biostudies-literature
Project description:Implantation is currently the best option for tooth replacement in periodontitis. Some major contraindications for the immediate implant are acute periodontitis and active infection. We present the case of a 51-year-old female patient with the highest grade and stage periodontitis treated with advanced platelet-rich fibrin-enriched zirconia implants and with hyperbaric oxygen therapy (HBOT). In particular, HBOT before and after implantation promoted bone regeneration and implant integration, also providing an antiseptic effect. After six months, the implants were well established and fully healed from periodontal disease within 14 months. Further research could confirm a new indication for HBOT in treating periodontitis and dental implantation.
| S-EPMC7825644 | biostudies-literature
Project description:Carbon Monoxide (CO) intoxication is still a leading cause of mortality and morbidity in many countries. Due to the problematic detection in the environment and subtle symptoms, CO intoxication usually goes unrecognized, and both normobaric and hyperbaric oxygen (HBO) treatments are frequently administered with delay. Current knowledge is mainly focused on acute intoxication, while Delayed Neurological Sequelae (DNS) are neglected, especially their treatment. This work details the cases of two patients presenting a few weeks after CO intoxication with severe neurological impairment and a characteristic diffused demyelination at the brain magnetic resonance imaging, posing the diagnosis of DNS. After prolonged treatment with hyperbaric oxygen, combined with intravenous corticosteroids and rehabilitation, the clinical and radiological features of DNS disappeared, and the patients' neurological status returned to normal. Such rare cases should reinforce a thorough clinical follow-up for CO intoxication victims and promote high-quality studies.
| S-EPMC9104642 | biostudies-literature
Project description:IntroductionAspirin is a common antipyretic, analgesic, and anti-inflammatory drug, which has been reported to extend life in animal models and application in the treatment of aging-related diseases. However, it remains unclear about the effects of aspirin on bone marrow-derived mesenchymal stromal cells (BM-MSCs). Here, we aimed to analyze the influence of aspirin on senescence and young BM-MSCs.MethodsBM-MSCs were serially passaged to construct a replicative senescence model. SA-β-gal staining, PCR, western blot, and RNA-sequencing were performed on BM-MSCs with or without aspirin treatment, to examine aspirin's impact on bone marrow-derived mesenchymal stem cells.ResultsSA-β-gal staining, PCR, and western blot revealed that aspirin could alleviate the cellular expression of senescence-related indicators of BM-MSCs, including a decrease of SA-β-gal-positive cells and staining intensity, and downregulation of p16, p21, and p53 expression after aspirin treatment. RNA-sequencing results shown in the biological processes related to aging, aspirin could influence cellular immune response and lipid metabolism.ConclusionThe efficacy of aspirin for retarding senescence of BM-MSCs was demonstrated. Our study indicated that the mechanisms of this delay might involve influencing immune response and lipid metabolism.
| S-EPMC8793730 | biostudies-literature
Project description:Objective:To determine the concentration of thiobarbituric acid reactive substances (TBARS) in erythrocytes and blood plasma, and the activities of selected antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in erythrocytes in patients receiving hyperbaric oxygen (HBO) treatment due to difficult-to-heal "skin wounds". Material and Methods. Indices of oxidative stress were assessed in venous blood taken from 23 patients three times: immediately before HBO procedure, approx. 5 minutes after leaving the hyperbaric chamber, and after 25 HBO procedures. Moreover, selected blood counts were measured in the collected material two times: prior to treatment and after 25 HBO procedures. Results:A statistically significant positive correlation between the CAT activity and the TBARS concentration in the erythrocytes of patients was found before treatment in the hyperbaric chamber (r = 0.394; P ? 0.05). No statistically significant changes in the TBARS concentration in erythrocytes and blood plasma were observed both after the first HBO procedure and after 25 procedures. No statistically significant changes in the activities of CAT, SOD, and GPx were noted. Platelet count decreased by 18.7% (P ? 0.05) after 25 HBO procedures. Granulocyte count decreased by approx. 21% (P ? 0.05), and granulocyte percentage by 11.8% (P ? 0.01). In turn, the percentage of lymphocytes and monocytes increased after the treatment by 16.6% (P < 0.05) and 16.4% (P < 0.05), respectively. Conclusions:Exposure to HBO due to difficult-to-heal skin wounds does not significantly affect the levels of oxidative stress in the peripheral blood of patients and, from the point of view of oxidation-reduction processes, appears to be a safe therapeutic method for the treatment of chronic wounds.
| S-EPMC7415099 | biostudies-literature
Project description:BACKGROUND:Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning. OBJECTIVES:To examine randomised trials of the efficacy of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning. SEARCH STRATEGY:We searched the following electronic databases; Cochrane Injuries Group Specialised Register (searched June 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2), MEDLINE (Ovid SP) 1950 to June 2010, EMBASE (Ovid SP) 1980 to June 2010, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to June 2010, ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to June 2010. SELECTION CRITERIA:All randomised controlled trials of HBO compared to NBO, involving non-pregnant adults who are acutely poisoned with carbon monoxide (regardless of severity). DATA COLLECTION AND ANALYSIS:Two authors independently extracted from each trial information on: the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up. MAIN RESULTS:Seven randomised controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials involving 1361 participants, two found a beneficial effect of HBO for the reduction of neurologic sequelae at one month, while four others did not. One of these is an incomplete publication (an abstract of an interim analysis). Although pooled random effects meta-analysis does not suggest a significant benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by a high risk of bias introduced during the analysis including an apparent change in the primary outcome. Both were also stopped early 'for benefit', which is likely to have inflated the observed effect. In contrast three negative trials had low power to detect a benefit of HBO due to exclusion of severely poisoned patients in two and very poor follow-up in the other. One trial that was said to be finished around eight years ago has not reported the final analysis in any forum. AUTHORS' CONCLUSIONS:Existing randomised trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomised controlled trial.
| S-EPMC7066484 | biostudies-literature