scholarly journals Longitudinal stability of urinary extracellular vesicle protein patterns within and between individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leyla A. Erozenci ◽  
Sander R. Piersma ◽  
Thang V. Pham ◽  
Irene V. Bijnsdorp ◽  
Connie R. Jimenez

AbstractThe protein content of urinary extracellular vesicles (EVs) is considered to be an attractive non-invasive biomarker source. However, little is known about the consistency and variability of urinary EV proteins within and between individuals over a longer time-period. Here, we evaluated the stability of the urinary EV proteomes of 8 healthy individuals at 9 timepoints over 6 months using data-independent-acquisition mass spectrometry. The 1802 identified proteins had a high correlation amongst all samples, with 40% of the proteome detected in every sample and 90% detected in more than 1 individual at all timepoints. Unsupervised analysis of top 10% most variable proteins yielded person-specific profiles. The core EV-protein-interaction network of 516 proteins detected in all measured samples revealed sub-clusters involved in the biological processes of G-protein signaling, cytoskeletal transport, cellular energy metabolism and immunity. Furthermore, gender-specific expression patterns were detected in the urinary EV proteome. Our findings indicate that the urinary EV proteome is stable in longitudinal samples of healthy subjects over a prolonged time-period, further underscoring its potential for reliable non-invasive diagnostic/prognostic biomarkers.

2018 ◽  
Vol 50 (8) ◽  
pp. 590-604 ◽  
Author(s):  
Katherine J. Perschbacher ◽  
Guorui Deng ◽  
Rory A. Fisher ◽  
Katherine N. Gibson-Corley ◽  
Mark K. Santillan ◽  
...  

G protein-coupled receptor signaling mechanisms are implicated in many aspects of cardiovascular control, and dysfunction of such signaling mechanisms is commonly associated with disease states. Investigators have identified a large number of regulator of G protein signaling (RGS) proteins that variously contribute to the modulation of intracellular second-messenger signaling kinetics. These many RGS proteins each interact with a specific set of second-messenger cascades and receptor types and exhibit tissue-specific expression patterns. Increasing evidence supports the contribution of RGS proteins, or their loss, in the pathogenesis of cardiovascular dysfunctions. This review summarizes the current understanding of the functional contributions of RGS proteins, particularly within the B/R4 family, in cardiovascular disorders of pregnancy including gestational hypertension, uterine artery dysfunction, and preeclampsia.


Author(s):  
Meng Han ◽  
Bairen Pang ◽  
Cheng Zhou ◽  
Xin Li ◽  
Qi Wang ◽  
...  

Liquid biopsy of tumor-derived extracellular vesicles (EVs) has great potential as a biomarker source for prostate cancer (CaP) early diagnosis and predicting the stages of cancer. The contents of EVs play an important role in intercellular communication and have specific expression in blood and urine samples from CaP patients. Powered by high-throughput, next-generation sequencing and proteomic technologies, novel EV biomarkers are easily detected in a non-invasive manner in different stages of CaP patients. These identified potential biomarkers can be further validated with a large sample size, machine learning model, and other different methods to improve the sensitivity and specificity of CaP diagnosis. The EV-based liquid biopsy is a novel and less-invasive alternative to surgical biopsies which would enable clinicians to potentially discover a whole picture of tumor through a simple blood or urine sample. In summary, this approach holds promise for developing personalized medicine to guide treatment decisions precisely for CaP patients.


2020 ◽  
Author(s):  
Camila Espejo ◽  
Richard Wilson ◽  
Gregory M. Woods ◽  
Eduard Willms ◽  
Andrew F. Hill ◽  
...  

AbstractTasmanian devils are threatened with extinction by Devil Facial Tumor Disease (DFTD), which consists of two genetically independent transmissible cancers (DFT1 and DFT2). Both cancers typically cause death due to metastases. However, the mechanisms underpinning DFTD metastasis are not well understood. The nano-sized, membrane-enclosed extracellular vesicles (EVs) released by cancer cells have been implicated in metastasis, thus EVs may yield insights into DFTD metastasis. Here, we characterized EVs derived from cultured DFT1, DFT2, and devil fibroblast cells. The proteome of EVs was determined using data independent acquisition mass spectrometry and an in-house spectral library of >1,500 proteins. Relative to EVs from fibroblast cells, EVs from both DFT1 and DFT2 cell lines expressed higher levels of proteins associated with cell adhesion and focal adhesion functions. Furthermore, hallmark proteins of epithelial mesenchymal transition, which are associated with increased metastatic features in some cancers, were enriched in DFT2 EVs relative to DFT1 EVs, suggesting differential aggressiveness between the cancers and a target for novel differential diagnosis biomarkers. This first EV-based investigation of DFTD increases our understanding of the cancers’ EVs and their possible involvement in the metastatic process. As EVs are found in body fluids, these results offer potential for non-invasive biomarkers for DFTD.


ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Cheng Wang ◽  
Jun-Jun Wang ◽  
Chunni Zhang

Abstract Circulating microRNAs (miRNAs) are exceptionally stable molecule markers in extracellular environments for various diseases. Importantly, some circulating miRNAs that were encapsulated in extracellular microvesicles (MVs) have been identified as critical mediators of intercellular communication, and function as novel cell-cell crosstalk gene-regulators. Burgeoning evidence has demonstrated that several types of viruses, including the human cytomegalovirus (HCMV), can encode various miRNAs that play essential roles in disturbing the translation of either the eukaryotic host’s genes or virus own during multiple pathophysiological processes. Recently, HCMV-encoded miRNAs have also been uncovered in human circulation, moreover, some circulating HCMV-encoded miRNAs showed specific expression patterns in different diseases with no precise aetiology. In particular, dysregulated HCMV-encoded miRNAs can effectively regulate the host genes regulation, and were implicated in disease development. Given the clinical impact of circulating miRNAs and their abilities to profoundly modulate specific recipient cells, we postulate that characterization of altered HCMV-encoded miRNAs in host circulation may afford valuable insights into developing non-invasive diagnostic biomarkers and clarifying the potential pathophysiological mechanism for various complex diseases, even if the research on circulating HCMV miRNAs is just emerging. The focus of this review is on summarizing the updates on current developments and perspectives for diagnostic and discriminative usefulness of circulating HCMV-encoded miRNAs in various diseases, including essential hypertension, oral lichen planus disease, chronic hepatitis B and type 2 diabetes. We also review the physiological and pathophysiological effects of HCMV-encoded miRNAs on disease development and progression.


2021 ◽  
Vol 22 (2) ◽  
pp. 568
Author(s):  
Shiheng Lyu ◽  
Guixin Chen ◽  
Dongming Pan ◽  
Jianjun Chen ◽  
Wenqin She

14-3-3 proteins (14-3-3s) are among the most important phosphorylated molecules playing crucial roles in regulating plant development and defense responses to environmental constraints. No report thus far has documented the gene family of 14-3-3s in Citrus sinensis and their roles in response to stresses. In this study, nine 14-3-3 genes, designated as CitGF14s (CitGF14a through CitGF14i) were identified from the latest C. sinensis genome. Phylogenetic analysis classified them into ε-like and non-ε groups, which were supported by gene structure analysis. The nine CitGF14s were located on five chromosomes, and none had duplication. Publicly available RNA-Seq raw data and microarray databases were mined for 14-3-3 expression profiles in different organs of citrus and in response to biotic and abiotic stresses. RT-qPCR was used for further examining spatial expression patterns of CitGF14s in citrus and their temporal expressions in one-year-old C. sinensis “Xuegan” plants after being exposed to different biotic and abiotic stresses. The nine CitGF14s were expressed in eight different organs with some isoforms displayed tissue-specific expression patterns. Six of the CitGF14s positively responded to citrus canker infection (Xanthomonas axonopodis pv. citri). The CitGF14s showed expressional divergence after phytohormone application and abiotic stress treatments, suggesting that 14-3-3 proteins are ubiquitous regulators in C. sinensis. Using the yeast two-hybrid assay, CitGF14a, b, c, d, g, and h were found to interact with CitGF14i proteins to form a heterodimer, while CitGF14i interacted with itself to form a homodimer. Further analysis of CitGF14s co-expression and potential interactors established a 14-3-3s protein interaction network. The established network identified 14-3-3 genes and several candidate clients which may play an important role in developmental regulation and stress responses in this important fruit crop. This is the first study of 14-3-3s in citrus, and the established network may help further investigation of the roles of 14-3-3s in response to abiotic and biotic constraints.


2013 ◽  
Author(s):  
AL Bookout ◽  
Y Jeong ◽  
M Downes ◽  
RT Yu ◽  
RM Evans ◽  
...  

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 437
Author(s):  
Ting Gong ◽  
Weiyong Wang ◽  
Houqiang Xu ◽  
Yi Yang ◽  
Xiang Chen ◽  
...  

Testicular expression of taste receptor type 1 subunit 3 (T1R3), a sweet/umami taste receptor, has been implicated in spermatogenesis and steroidogenesis in mice. We explored the role of testicular T1R3 in porcine postnatal development using the Congjiang Xiang pig, a rare Chinese miniature pig breed. Based on testicular weights, morphology, and testosterone levels, four key developmental stages were identified in the pig at postnatal days 15–180 (prepuberty: 30 day; early puberty: 60 day; late puberty: 90 day; sexual maturity: 120 day). During development, testicular T1R3 exhibited stage-dependent and cell-specific expression patterns. In particular, T1R3 levels increased significantly from prepuberty to puberty (p < 0.05), and expression remained high until sexual maturity (p < 0.05), similar to results for phospholipase Cβ2 (PLCβ2). The strong expressions of T1R3/PLCβ2 were observed at the cytoplasm of elongating/elongated spermatids and Leydig cells. In the eight-stage cycle of the seminiferous epithelium in pigs, T1R3/PLCβ2 levels were higher in the spermatogenic epithelium at stages II–VI than at the other stages, and the strong expressions were detected in elongating/elongated spermatids and residual bodies. The message RNA (mRNA) levels of taste receptor type 1 subunit 1 (T1R1) in the testis showed a similar trend to levels of T1R3. These data indicate a possible role of T1R3 in the regulation of spermatid differentiation and Leydig cell function.


Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1465
Author(s):  
Ramon de Koning ◽  
Raphaël Kiekens ◽  
Mary Esther Muyoka Toili ◽  
Geert Angenon

Raffinose family oligosaccharides (RFO) play an important role in plants but are also considered to be antinutritional factors. A profound understanding of the galactinol and RFO biosynthetic gene families and the expression patterns of the individual genes is a prerequisite for the sustainable reduction of the RFO content in the seeds, without compromising normal plant development and functioning. In this paper, an overview of the annotation and genetic structure of all galactinol- and RFO biosynthesis genes is given for soybean and common bean. In common bean, three galactinol synthase genes, two raffinose synthase genes and one stachyose synthase gene were identified for the first time. To discover the expression patterns of these genes in different tissues, two expression atlases have been created through re-analysis of publicly available RNA-seq data. De novo expression analysis through an RNA-seq study during seed development of three varieties of common bean gave more insight into the expression patterns of these genes during the seed development. The results of the expression analysis suggest that different classes of galactinol- and RFO synthase genes have tissue-specific expression patterns in soybean and common bean. With the obtained knowledge, important galactinol- and RFO synthase genes that specifically play a key role in the accumulation of RFOs in the seeds are identified. These candidate genes may play a pivotal role in reducing the RFO content in the seeds of important legumes which could improve the nutritional quality of these beans and would solve the discomforts associated with their consumption.


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