Markers of T Cell Senescence in Humans Xu, Weili; Larbi, Anis
International journal of molecular sciences,
08/2017, Letnik:
18, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to ...infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as "immunosenescence" can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers.
Bipolar disorder is a mood disorder that negatively influences millions of lives in the world. This field deserves more attention, research, and investment, especially in developing countries like ...China. This article aims to explore the broader knowledge scope of bipolar disorder and is divided into 5 sections and 3 main parts. The first part introduced its various types, diagnostics procedures and methods, common symptoms, causes and risk factors, and social influences on different levels, etc. The second part introduced various treatment strategies, including commonly used ones and recently developed ones, emphasizing the research of viability and functionality of cognitive behavior therapy(CBT)’s application in treating the disorder in modern society. In the third part, the article introduced several bipolar treatment treatment phenomena in China and suggested several ways in terms of how they can be ameliorated from multiple perspectives, including treatment and diagnosis, hospital improvement, research area, and societal efforts.
The molecular characterization of immune subsets is important for designing effective strategies to understand and treat diseases. We characterized 29 immune cell types within the peripheral blood ...mononuclear cell (PBMC) fraction of healthy donors using RNA-seq (RNA sequencing) and flow cytometry. Our dataset was used, first, to identify sets of genes that are specific, are co-expressed, and have housekeeping roles across the 29 cell types. Then, we examined differences in mRNA heterogeneity and mRNA abundance revealing cell type specificity. Last, we performed absolute deconvolution on a suitable set of immune cell types using transcriptomics signatures normalized by mRNA abundance. Absolute deconvolution is ready to use for PBMC transcriptomic data using our Shiny app (https://github.com/giannimonaco/ABIS). We benchmarked different deconvolution and normalization methods and validated the resources in independent cohorts. Our work has research, clinical, and diagnostic value by making it possible to effectively associate observations in bulk transcriptomics data to specific immune subsets.
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•Characterization of 29 human immune cell type by RNA-seq and flow cytometry•Modules of specific, co-expressed, and housekeeping genes are defined•The mRNA heterogeneity and abundance are cell type specific•The proposed normalization approach enables absolute deconvolution
Monaco et al. generate an RNA-seq dataset on 29 immune cell types and identify modules of cell type-specific, co-expressed, and housekeeping genes. The mRNA heterogeneity and abundance of the different cell types were examined. Absolute deconvolution of PBMCs was obtained by taking into account mRNA abundance when normalizing the signature matrix.
In nature, cells self-assemble into spatially coded tissular configurations to execute higher-order biological functions as a collective. This mechanism has stimulated the recent trend in synthetic ...biology to construct tissue-like assemblies from protocell entities, with the aim to understand the evolution mechanism of multicellular mechanisms, create smart materials or devices, and engineer tissue-like biomedical implant. However, the formation of spatially coded and communicating micro-architectures from large quantity of protocell entities, especially for lipid vesicle-based systems that mostly resemble cells, is still challenging. Herein, we magnetically assemble giant unilamellar vesicles (GUVs) or cells into various microstructures with spatially coded configurations and spatialized cascade biochemical reactions using a stainless steel mesh. GUVs in these tissue-like aggregates exhibit uncustomary osmotic stability that cannot be achieved by individual GUVs suspensions. This work provides a versatile and cost-effective strategy to form robust tissue-mimics and indicates a possible superiority of protocell colonies to individual protocells.
Pharmaceutical wastewater treatment plants (PWWTPs), which receive wastewater containing extremely high levels of antibiotics, are regarded as potential hot spots for antibiotic-resistance ...development in the environment. Six sampling campaigns in six PWWTPs in Southeastern China were carried out to assess the prevalence and fate of antibiotic resistance genes (ARGs). Different genes were monitored in different PWWTPs (PWWTP A: lincosamides; PWWTP B: aminoglycosides and macrolides; PWWTP C: quinolones; PWWTP D: macrolides and quinolones; PWWTP E: cephalosporins; and PWWTP F: quinolones and macrolides) using real-time quantitative polymerase chain reactions (PCRs), according to the antibiotic type produced. The levels of typical ARG subtypes in the final effluents ranged from (1.03±0.91)×101 to (6.78±0.21)×107copies/mL. The absolute abundance of ARGs in effluents accounted for 0%–577% of influents to the six PWWTPs with a median value of 6%. Most of the ARGs are transported to the dewatered sludge, with concentrations from (1.38±0.21)×105 to (6.84±0.43)×1010copies/g dry weight (dw). In different treatment units (before/after biological units), a clear trend of proliferation or attenuation was not observed for the ARGs, aside from a strong attenuation in moving bed bio-film reactor (MBBR) in PWWTP C. Through correlation analyses, this study demonstrated that the bacterial abundance and antibiotic concentrations within the PWWTPs influenced the fate of the associated ARGs, and this was possibly related primarily to the intrinsic resistance mechanisms of corresponding ARGs. Macrolide ARGs, which tend to locate in plasmids and transposons, positively correlate weakly with total macrolide antibiotic concentrations but positively correlate strongly with 16S rRNA concentrations. Furthermore, ARG concentrations in the wastewater from fermentation were significantly higher than in the wastewater from chemical synthesis and preparation. This is the first comprehensive study on the behavior of antibiotic resistance genes under extremely high-level antibiotic selection pressures in pharmaceutical wastewater treatment plants (PWWTPs) in Southeastern China.
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•The ARGs would proliferate or attenuate in different treatment units of pharmaceutical wastewater treatment plants (PWWTPs).•A big part of the ARGs may be transported to the dewatered sludge.•The bacterial abundance and antibiotic concentration within the PWWTPs influenced the fate of the associated ARG together.•The intrinsic resistance mechanisms of corresponding ARGs play a key role in their fate.•ARGs concentration in the wastewater from fermentation was significantly higher than chemical synthesis and preparation.
The impact of cardiovascular risk burden on cognitive trajectories and brain structure changes remains unclear.
This study aimed to examine whether cardiovascular risk burden assessed by the ...Framingham General Cardiovascular Risk Score (FGCRS) is associated with cognitive decline and structural brain differences.
Within the Rush Memory and Aging Project, 1,588 dementia-free participants (mean age: 79.5 years) were followed for up to 21 years. FGCRS was assessed at baseline and categorized into tertiles (lowest, middle, and highest). Episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with a battery of 19 tests, from which composite scores were derived. A subsample (n = 378) of participants underwent magnetic resonance imaging. Structural total and regional brain volumes were estimated. Data were analyzed using linear mixed-effects models and linear regression models.
In all participants, FGCRS ranged from 4 to 28 (mean score: 15.6 ± 3.7). Compared with the lowest tertile of FGCRS, the highest tertile was associated with faster decline in global cognition (β = −0.019; 95% confidence interval CI: −0.035 to −0.003), episodic memory (β = −0.023; 95% CI: −0.041 to −0.004), working memory (β = −0.021; 95% CI: −0.035 to −0.007), and perceptual speed (β = −0.027; 95% CI: −0.042 to −0.011) over the follow-up. In magnetic resonance imaging data analyses, higher FGCRS was related to smaller volumes of the hippocampus (β = −0.021; 95% CI: −0.042 to −0.000), gray matter (β = −1.569; 95% CI: −2.757 to −0.382), and total brain (β = −1.588; 95% CI: −2.832 to −0.344), and greater volume of white matter hyperintensities (β = 0.035; 95% CI: 0.001 to 0.069).
Higher cardiovascular risk burden may predict decline in episodic memory, working memory, and perceptual speed and is associated with neurodegeneration and vascular lesions in the brain.
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SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms ...underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.
OBJECTIVES
To identify sex‐specific associations between risk factors and injurious falls over the short (<4 years) and long (4–10 years) term.
DESIGN
Longitudinal cohort study between 2001 and 2011.
...SETTING
Swedish National Study on Aging and Care, Kungsholmen, Sweden.
PARTICIPANTS
Community‐dwelling adults aged 60 and older (N = 3,112).
MEASUREMENTS
An injurious fall was defined as a fall that required inpatient or outpatient care. Information was collected on participant and exposure characteristics using structured interviews, clinical examinations, and physical function tests at baseline.
RESULTS
The multivariate model showed that, in the short term, living alone (hazard ratio (HR)=1.83, 95% confidence interval (CI)=1.13–2.96), dependency in instrumental activities of daily living (IADLs) (HR=2.59, 95% CI=1.73–3.87), and previous falls (HR=1.71, 95% CI=1.08–2.72) were independently associated with injurious falls in women. Low systolic blood pressure (HR=1.96, 95% CI=1.04–3.71), impaired chair stands (HR=3.00, 95% CI=1.52–5.93), and previous falls (HR=2.81, 95% CI=1.32–5.97) were associated with injurious falls in men. Long‐term risk factors were underweight (HR=2.03, 95% CI=1.40–2.95), cognitive impairment (HR=1.49, 95% CI=1.08–2.06), fall‐risk increasing drugs (HR=1.67, 95% CI=1.27–2.20 for ≥2 drugs), and IADL dependency (HR=1.58, 95% CI=1.32–5.97) for women and smoking (HR=1.71, 95% CI=1.03–2.84), heart disease (HR=2.20, 95% CI=1.5–3.24), impaired balance (HR=1.68, 95% CI=1.08–2.62), and a previous fall (HR=3.61, 95% CI=1.98–6.61) for men.
CONCLUSION
Men and women have different fall risk profiles, and these differences should be considered when developing preventive strategies. Some risk factors were more strongly predictive of injurious falls over shorter than longer periods and vice versa, suggesting that it may be possible to identify older men and women at short‐ and long‐term risk of injurious falls. J Am Geriatr Soc 67:246–253, 2019.
In the present study, a novel angiotensin I-converting enzyme (ACE)-inhibitory peptide, P-2a2, was purified to homogeneity from walnut protein hydrolysate by ultrafiltration, consecutive column ...chromatography, and high-performance liquid chromatography. The purified peptide was characterized by matrix-assisted laser desorption ionization time-of-flight mass spectrophotometry and a liquid-phase peptide sequencer. The molecular mass of P-2a2 was tested to be 1033.42 D. Its amino acid sequence was determined to be Trp-Pro-Glu-Arg-Pro-Pro-Gln-Ile-Pro. The potent ACE-inhibitory peptide is an enneapeptide and shows a high ACE-inhibitory activity, with an IC50 value of 25.67 μg/mL.
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