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This chapter overviews roles of DNA methylation in inflammatory cell biology with the focuses on lymphocytes and macrophages/monocytes in lung diseases, although the molecular mechanisms by which target genes are methylated and regulated in lung diseases remain unclear. Most of epigenetic studies on DNA methylation of target genes in lung diseases mainly demonstrated the correlation of DNA methylation of target genes with the levels of other corresponding factors, with the specificity of clinical phenomes, and with the severity of lung diseases. There is an urgent need to identify and validate the specificity and regulatory mechanisms of inflammatory cell epigenetics in depth. The epigenetic heterogeneity among different subsets of T cells and among promoters or non-promoters of target genes should be furthermore clarified in acute or chronic lung diseases and cancers. The hyper/hypo-methylation and modifications of chromosol and extrachromosomal DNA may result in alternations in proteins within inflammatory cells, which can be identified as disease-specific biomarkers and therapeutic targets.DNA methylations, including global methylation pattern and specific gene methylation, are associated with pathogenesis and progress of pulmonary fibrosis. This chapter illustrates alteration of DNA methylation in pulmonary fibrosis as a predictive or prognostic factor. Treatment with the DNA methylation inhibitors will be an emerging anti-fibrosis therapy, although we are still in the pre-clinical stage of using epigenetic markers as potential targets for biomarkers and therapeutic interventions.T cells recognize peptides bound to major histocompatibility complex (MHC) class I and class II molecules at the cell surface. This recognition is accomplished by the expression of T cell receptors (TCR) which are required to be diverse and adaptable in order to accommodate the various and vast number of antigens presented on the MHCs. Thus, determining TCR repertoires of effector T cells is necessary to understand the immunological process in responding to cancer progression, infection, and autoimmune development. Furthermore, understanding the TCR repertoires will provide a solid framework to predict and test the antigen which is more critical in autoimmunity. However, it has been a technical challenge to sequence the TCRs and provide a conceptual context in correlation to the vast number of TCR repertoires in the immunological system. The exploding field of single-cell sequencing has changed how the repertoires are being investigated and analyzed. In this review, we focus on the biology of TCRs, TCR signaling and its implication in autoimmunity. We discuss important methods in bulk sequencing of many cells. Lastly, we explore the most pertinent platforms in single-cell sequencing and its application in autoimmunity.Within the last decade, single-cell analysis has revolutionized our understanding of cellular processes and heterogeneity across all disciplines of life science. As the transcriptome, genome, or epigenome of individual cells can nowadays be analyzed at low cost and in high-throughput within a few days by modern techniques, tremendous improvements in disease diagnosis on the one hand and the investigation of disease-relevant mechanisms on the other were achieved so far. This relies on the parallel development of reliable cell capturing and single-cell sequencing approaches that have paved the way for comprehensive single-cell studies. Apart from single-cell isolation methods in high-throughput, a variety of methods with distinct specializations were developed, allowing for correlation of transcriptomics with cellular parameters like electrophysiology or morphology.For all single-cell-based approaches, accurate and reliable isolation with proper quality controls is prerequisite, whereby different options exist dependent on sample type and tissue properties. Careful consideration of an appropriate method is required to avoid incorrect or biased data that may lead to misinterpretations.In this chapter, we will provide a broad overview of the current state of the art in matters of single-cell isolation methods mostly applied for sequencing-based downstream analysis, and their respective advantages and drawbacks. Distinct technologies will be discussed in detail addressing key parameters like sample compatibility, viability, purity, throughput, and isolation efficiency.Clinical single-cell biomedicine has become a new emerging discipline, which integrates single-cell RNA and DNA sequencing, proteomics, and functions with clinical phenomes, therapeutic responses, and prognosis. It is of great value to discover disease-, phenome-, and therapy-specific diagnostic biomarkers and therapeutic targets on the basis of the principle of clinical single-cell biomedicine. This book reviews the roles of single-cell sequencing and methylation in diseases and explores disease-specific alterations of single-cell sequencing and methylation, especially focusing on potential applications of methodologies on human single-cell sequencing and methylation, on potential correlations between those changes with pulmonary diseases, and on potential roles of signaling pathways that cause heterogeneous cellular responses during treatment. This book also emphasizes the importance of methodologies in clinical practice and application, the potential of perspectives, challenges and solutions, and the significance of single-cell preparation standardization. Alterations of DNA and RNA methylation, demethylation in lung diseases, and a deep knowledge about the regulation and function of target gene methylation for diagnosing and treating diseases at the early stage are also provided. Importantly, this book aims to apply the measurement of single-cell sequencing and methylation for clinical diagnosis and treatment and to understand clinical values of those parameters and to headline and foresee the potential values of the application of single-cell sequencing in non-cancer diseases.There are many kinds of microorganisms in the gastrointestinal tract of mammals, some of which are closely related to the host. Rumen microorganisms are essential for normal physiological activities of their host by decomposing plant crude lignin and providing essential nutrients. The composition and diversity of this microbial population are influenced by the host, environment, and diet. #link# Despite its importance, little is known about the effects of factors such as altitude variation on rumen microbial population abundance and diversity in different ruminants. Here, we described the changes in overall rumen bacteria in four groups of cattle, including the Zhongdian yellow cattle and Zhongdian yaks, grazing at high altitudes (3600 m); the Jiangcheng yellow cattle and Jiangcheng buffalo were kept at an altitude of 1100 m. We found that there was a significant difference in rumen bacterial abundance of the Zhongdian yellow cattle and Zhongdian yaks at high altitude and there was obvious homogeneity in rumen bacterial abundance and diversity in the Jiangcheng yellow cattle and Jiangcheng buffalo at low altitude. Therefore, our research concluded that under the same dietary environment, there were differences in the abundance and diversity of certain bacteria in the rumen of different breeds of cattle, indicating that host genetic factors and intestinal microorganisms related to altitudinal variation had a greater influence on rumen bacterial abundance in the cattle.PF-06410293 (Amsparity™/Abrilada™) is a biosimilar of the anti-tumor necrosis factor (TNF)-α antibody adalimumab. It is approved for use in all indications for which adalimumab is approved, including inflammatory joint diseases (e.g. link2 rheumatoid arthritis), uveitis, psoriasis and Crohn's disease. PF-06410293 has similar physicochemical and pharmacodynamic properties to those of EU- and US-sourced reference adalimumab, and the pharmacokinetic similarity of the agents is supported. PF-06410293 demonstrated therapeutic equivalence to EU-sourced reference adalimumab in patients with rheumatoid arthritis, and was generally well tolerated in this population. The tolerability, efficacy, safety and immunogenicity profiles of PF-06410293 were similar to those of EU-sourced reference adalimumab, and switching from reference adalimumab to PF-06410293 appeared to have no impact on safety or efficacy. The role of adalimumab in the management of immune-mediated inflammatory diseases is well established and PF-06410293 provides an effective biosimilar alternative for patients requiring adalimumab therapy.
Oropharyngeal dysphagia is an emerging age-related disorder that affects 23% of inpatients leading to malnutrition, dehydration, or aspiration pneumonia. Anticholinergic drugs can cause reduced peristalsis and dry mouth, both related to dysphagia.
To determine the association between anticholinergic burden and oropharyngeal dysphagia in older inpatients.
Retrospective descriptive observational study. link3 There are 239 patients. Dysphagia diagnosis based on routine volume-viscosity swallow test. Characteristics age, functional loss (instrumental and basic activities), frailty (Frail-VIG-Index), geriatric syndromes, polypharmacy, and anticholinergic-cognitive-burden scale at admission.
25.5% of elderly patients diagnosed with dysphagia are more dependent and frailer than non-dysphagic patients. 83.6% scored ≥ 3 points on the ACB Scale [odds ratio 4.46 (2.13-9.33)], which is statistically associated with dysphagia (p < 0.001).
Patients with an ACB of ≥ 3 points at admission are more than four times as likely to develop oropharyngeal dysphagia. Evaluating anticholinergic burden routinely should be considered and, whenever possible, reduce it.
Patients with an ACB of ≥ 3 points at admission are more than four times as likely to develop oropharyngeal dysphagia. Evaluating anticholinergic burden routinely should be considered and, whenever possible, reduce it.
To determine the potential effectiveness of a novel 10-week manualised Practical Body Image therapy (PBI) with mirror exposure (ME), when used as an adjuvant to an intensive treatment package (TAU) in adolescent inpatients with Anorexia Nervosa (AN). To evaluate the effectiveness of ME in an adolescent population.
Using a randomised control design, 40 girls aged 11-17years with AN were assigned to PBI with TAU (n = 20) and TAU alone (n = 20). Both groups completed self-report measures of body image at week 1 and week 10 of the study to measure the potential effectiveness of PBI. The PBI group completed measures at week 7 to evaluate the ME component.
31 participants completed the study; 16 TAU, 15 PBI. PBI participants had greater improvement in all outcomes than TAU participants. Medium effect sizes were seen for self-reported weight concern, body image avoidance in terms of clothing and body image anxiety. ME produced effect sizes in self-reported body image avoidance in terms of clothing and grooming that were greater than 0.40, n = 14.
The findings demonstrate that PBI supports an intensive inpatient treatment package and addresses elements of negative body image. PBI was beneficial for addressing body image dissatisfaction with improvements in weight concerns, body image avoidance and physical appearance trait anxiety following the ME component. The magnitude of the effect sizes is comparable to previous studies. Tolinapant clinical trial indicated the intervention was acceptable to users. PBI is a promising new adjuvant treatment for AN.
Level Irandomized controlled trial.
Level I randomized controlled trial.
Read More: https://www.selleckchem.com/products/astx660.html
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