Investigation of cattle plasma proteome in response to pain and inflammation using next generation proteomics technique, SWATH-MS

Donor-derived, Cell-free DNA levels by Next Generation Targeted Sequencing are Elevated in Allograft Rejection after Lung Transplantation

ERJ Open Research ◽

10.1183/23120541.00462-2020 ◽

2020 ◽

pp. 00462-2020

Author(s):

KK Khush ◽

I De Vlaminick ◽

H Luikart ◽

DJ Ross ◽

M Nicolls

Keyword(s):

Lung Transplantation ◽

Predictive Value ◽

Tissue Injury ◽

Acute Cellular Rejection ◽

Targeted Sequencing ◽

Next Generation ◽

Cell Free Dna ◽

Chronic Lung Allograft Dysfunction ◽

Free Dna ◽

Cellular Rejection

Surveillance after lung transplantation (LT) is critical to the detection of acute cellular rejection (ACR) and prevention of Chronic Lung Allograft Dysfunction (CLAD). Therefore, we measured donor-derived cell-free DNA (dd-cfDNA) implementing a clinical-grade, next generation targeted sequencing assay in 107 plasma samples from 38 unique LT recipients with diagnostic cohorts classified as: (1) Biopsy-confirmed or treated acute cellular rejection (ACR), (2) antibody-mediated rejection (AMR), (3) Obstructive chronic lung allograft dysfunction (CLAD), (4) allograft infection (INFXN), and (5) Stable healthy allografts (STABLE). Our principal findings: (1) dd-cfDNA level was elevated in ACR (median 0.91%; IQR: 0.39–2.07%), CLAD (2.06%; IQR: 0.57–3.67%), and an aggregated cohort of rejection encompassing allograft injury (1.06%; IQR :0.38–2.51%), compared with the STABLE cohort (0.38%; IQR: 0.23–0.87%) (p=0.02). (2) dd-cfDNA level with AMR was elevated (1.34%; IQR: 0.34–2.40%) compared to STABLE although did not reach statistical significance (p=0.07) due to limitations in sample size. (3) No difference in dd-cfDNA for allograft INFXN (0.39%; IQR: 0.18–0.67%) versus STABLE, that may relate to differences in “tissue injury” with spectrum of bronchial colonisation versus invasive infection. (4) No difference for dd-cfDNA in unilateral versus bilateral LT. (5) “Optimal Threshold” for dd-cfDNA for aggregated rejection events representing allograft injury was determined as 0.85%, with Sensitivity=55.6%, Specificity=75.8%, Positive Predictive Value (PPV)=43.3%, and Negative Predictive Value (NPV)=83.6%. Measurement of plasma dd-cfDNA may be a clinically useful tool for the assessment of lung allograft health and surveillance for “tissue injury” with a spectrum of rejection.

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Next generation plasma proteome profiling to monitor health and disease

Nature Communications ◽

10.1038/s41467-021-22767-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Wen Zhong ◽

Fredrik Edfors ◽

Anders Gummesson ◽

Göran Bergström ◽

Linn Fagerberg ◽

...

Keyword(s):

Precision Medicine ◽

Plasma Proteome ◽

Next Generation ◽

Healthy Individuals ◽

Proteome Profiling ◽

Health And Disease ◽

Proteome Profile ◽

Early Diagnosis Of Diabetes ◽

Generation Sequencing

AbstractThe need for precision medicine approaches to monitor health and disease makes it important to develop sensitive and accurate assays for proteome profiles in blood. Here, we describe an approach for plasma profiling based on proximity extension assay combined with next generation sequencing. First, we analyze the variability of plasma profiles between and within healthy individuals in a longitudinal wellness study, including the influence of genetic variations on plasma levels. Second, we follow patients newly diagnosed with type 2 diabetes before and during therapeutic intervention using plasma proteome profiling. The studies show that healthy individuals have a unique and stable proteome profile and indicate that a panel of proteins could potentially be used for early diagnosis of diabetes, including stratification of patients with regards to response to metformin treatment. Although validation in larger cohorts is needed, the analysis demonstrates the usefulness of comprehensive plasma profiling for precision medicine efforts.

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Next generation plasma proteome profiling of COVID-19 patients with mild to moderate symptoms

EBioMedicine ◽

10.1016/j.ebiom.2021.103723 ◽

2021 ◽

Vol 74 ◽

pp. 103723

Author(s):

Wen Zhong ◽

Ozlem Altay ◽

Muhammad Arif ◽

Fredrik Edfors ◽

Levent Doganay ◽

...

Keyword(s):

Plasma Proteome ◽

Next Generation ◽

Proteome Profiling

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The Proteomics Analysis of the Effects of Zhishi Rhubarb Soup on Ischemic Stroke

10.21203/rs.3.rs-583084/v1 ◽

2021 ◽

Author(s):

JING HUA ZHANG ◽

YUE JIA SHAO ◽

ZHEN HUI ◽

SULEI WANG ◽

CHI HUANG ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tissue Injury ◽

Protein Profile ◽

Artery Occlusion ◽

Liquid Chromatography Mass Spectrometry ◽

Brain Repair ◽

Chromatography Mass Spectrometry ◽

Heavy Burden ◽

Cerebral Artery Occlusion

Abstract Background: Stroke has always been a big threat around the world, but most severe in China with 2.5 million new stroke cases each year and 7.5 million stroke survivors, which also has laid a heavy burden on social and national healthcare system. The Zhishi Rhubarb Soup (ZRS) is a Traditional Chinese Medicine (TCM) that has been used clinically for many years in China. In order to explore the potential mechanism of ZRS as the pathogen of stroke. In this study, liquid chromatography mass spectrometry (LC-MS) was employed to uncover the mechanism underlying the effects of ZRS on stroke.Methods: In this study, the quantitative proteomics method LC-MS was used to analyze the proteomic differences of middle cerebral artery occlusion MCAO between normal and after ZSR treatment. Results: Further liquid chromatography mass spectrometry (LC-MS) analysis could observe a total of 3,5006 peptide were identified, 5160.0 proteins identified, of which 4094.0 can be quantified. Differentially expressed proteins with significance were extracted by data analysis and subject to Gene Ontology (GO) analysis showed the overviews of dysregulated proteins in the biological process (BP), cell component (CC), and molecular function (MF) categories. Proteins related to brain repair was found to change significantly, including BDNF, IL-10, IL-6, TGF-β，partly demonstrating the effects of ZRS on improving the tissue injury.Conclusion: ZRS was found to contribute to brain repair caused by ZRS treatment, and this could be partly mediated through the anti-inflammation effect by upregulating the vitamin transport. The results confirmed that ZRS presented a unique protein profile that indicated the adaptive mechanisms in acute stroke.

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Proteomic Analysis of Exosomes from Adipose-Derived Mesenchymal Stem Cells: A Novel Therapeutic Strategy for Tissue Injury

BioMed Research International ◽

10.1155/2020/6094562 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 4

Author(s):

Xin Xing ◽

Shuang Han ◽

Gu Cheng ◽

Yifeng Ni ◽

Zhi Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Proteomic Analysis ◽

Tissue Repair ◽

Tissue Injury ◽

Protein Profile ◽

Cell Communication ◽

Average Diameter ◽

Target Cells ◽

General Function

Exosomes are extracellular membranous nanovesicles that mediate local and systemic cell-to-cell communication by transporting functional molecules, such as proteins, into target cells, thereby affecting the behavior of receptor cells. Exosomes originating from adipose-derived mesenchymal stem cells (ADSCs) are considered a multipotent and abundant therapeutic tool for tissue injury. To investigate ADSC-secreted exosomes and their potential function in tissue repair, we isolated exosomes from the supernatants of ADSCs via ultracentrifugation, characterized them via transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. Then, we determined their protein profile via proteomic analysis. Results showed that extracellular vesicles, which have an average diameter of 116 nm, exhibit a cup-shaped morphology and express exosomal markers. A total of 1,185 protein groups were identified in the exosomes. Gene Ontology analysis indicated that exosomal proteins are mostly derived from cells mainly involved in protein binding. Protein annotation via the Cluster of Orthologous Groups system indicated that most proteins were involved in general function prediction, posttranslational modification, protein turnover, and chaperoning. Further, pathway analysis revealed that most of the proteins obtained participated in metabolic pathways, focal adhesion, regulation of the actin cytoskeleton, and microbial metabolism. Some tissue repair-related signaling pathways were also discovered. The identified molecules might serve as potential therapeutic targets for future studies.

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Fine Structural Changes in the Adenohypophyses of Rats Following Destruction of the Pituitary Stalk

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079917 ◽

1977 ◽

Vol 35 ◽

pp. 496-497

Author(s):

K. Kovacs ◽

E. Horvath ◽

J. M. Bilbao ◽

F. A. Laszlo ◽

I. Domokos

Keyword(s):

Structural Changes ◽

Tissue Injury ◽

Anterior Lobe ◽

Uranyl Acetate ◽

Male Rats ◽

Pituitary Stalk ◽

Sequence Of Events ◽

Pituitary Glands ◽

Electrolytic Lesions ◽

Ultrathin Sections

Electrolytic lesions of the pituitary stalk in rats interrupt adenohypophysial blood flow and result in massive infarction of the anterior lobe. In order to obtain a deeper insight into the morphogenesis of tissue injury and to reveal the sequence of events, a fine structural investigation was undertaken on adenohypophyses of rats at various intervals following destruction of the pituitary stalk.The pituitary stalk was destroyed electrolytically, with a Horsley-Clarke apparatus on 27 male rats of the R-Amsterdam strain, weighing 180-200 g. Thirty minutes, 1,2,4,6 and 24 hours after surgery the animals were perfused with a glutaraldehyde-formalin solution. The skulls were then opened and the pituitary glands removed. The anterior lobes were fixed in glutaraldehyde-formalin solution, postfixed in osmium tetroxide and embedded in Durcupan. Ultrathin sections were stained with uranyl acetate and lead citrate and investigated with a Philips 300 electron microscope.

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