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International Journal of Molecular... May 2024Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These... (Review)
Review
Numerous challenges remain within conventional cell-based therapy despite the growing trend of stem cells used to treat various life-debilitating diseases. These limitations include batch-to-batch heterogeneity, induced alloreactivity, cell survival and integration, poor scalability, and high cost of treatment, thus hindering successful translation from lab to bedside. However, recent pioneering technology has enabled the isolation and enrichment of small extracellular vesicles (EVs), canonically known as exosomes. EVs are described as a membrane-enclosed cargo of functional biomolecules not limited to lipids, nucleic acid, and proteins. Interestingly, studies have correlated the biological role of MSC-EVs to the paracrine activity of MSCs. This key evidence has led to rigorous studies on MSC-EVs as an acellular alternative. Using EVs as a therapy was proposed as a model leading to improvements through increased safety; enhanced bioavailability due to size and permeability; reduced heterogeneity by selective and quantifiable properties; and prolonged shelf-life via long-term freezing or lyophilization. Yet, the identity and potency of EVs are still relatively unknown due to various methods of preparation and to qualify the final product. This is reflected by the absence of regulatory strategies overseeing manufacturing, quality control, clinical implementation, and product registration. In this review, the authors review the various production processes and the proteomic profile of MSC-EVs.
Topics: Humans; Mesenchymal Stem Cells; Extracellular Vesicles; Proteomics; Umbilical Cord; Exosomes; Proteome
PubMed: 38791378
DOI: 10.3390/ijms25105340 -
Biomedicines Jan 2022Several biologic therapies that target inflammatory modulators are now used for treating patients with uncontrolled, severe asthma. Knowledge about how this type of... (Review)
Review
Several biologic therapies that target inflammatory modulators are now used for treating patients with uncontrolled, severe asthma. Knowledge about how this type of treatment modifies the molecular milieu is rapidly increasing. Thus, this systematic review aimed to compile the reported effects of therapeutic antibodies on the transcriptome or proteome of asthma patients. Studies of asthmatic patients under biological treatment describing transcriptomic or proteomic changes upon treatment were included. Preclinical or single gene/protein studies were not considered. PubMed and Scopus search was performed in August and September 2021. Following PRISMA guidelines and GRADE recommendations, we selected 12 studies on gene or protein expression changes in patients treated with the antibodies currently approved by EMA and the FDA. All studies were at low risk of bias as per the RoB2 tool. Different gene clusters have been identified to change upon omalizumab treatment, found a reduction in eosinophil-associated gene signatures after benralizumab treatment, and protein profiles were different in patients treated with mepolizumab and in those treated with benralizumab. The main potential biomarkers proposed by the selected studies are shown. These results may contribute to discovering biomarkers of response and selecting the best therapy for each patient.
PubMed: 35203504
DOI: 10.3390/biomedicines10020293 -
PloS One 2015Rotator cuff tendinopathy including tears is a cause of significant morbidity. The molecular pathogenesis of the disorder is largely unknown. This review aimed to... (Review)
Review
BACKGROUND
Rotator cuff tendinopathy including tears is a cause of significant morbidity. The molecular pathogenesis of the disorder is largely unknown. This review aimed to present an overview of the literature on gene expression and protein composition in human rotator cuff tendinopathy and other tendinopathies, and to evaluate perspectives of proteomics--the comprehensive study of protein composition--in tendon research.
MATERIALS AND METHODS
We conducted a systematic search of the literature published between 1 January 1990 and 18 December 2012 in PubMed, Embase, and Web of Science. We included studies on objectively quantified differential gene expression and/or protein composition in human rotator cuff tendinopathy and other tendinopathies as compared to control tissue.
RESULTS
We identified 2199 studies, of which 54 were included; 25 studies focussed on rotator cuff or biceps tendinopathy. Most of the included studies quantified prespecified mRNA molecules and proteins using polymerase chain reactions and immunoassays, respectively. There was a tendency towards an increase of collagen I (11 of 15 studies) and III (13 of 14), metalloproteinase (MMP)-1 (6 of 12), -9 (7 of 7), -13 (4 of 7), tissue inhibitor of metalloproteinase (TIMP)-1 (4 of 7), and vascular endothelial growth factor (4 of 7), and a decrease in MMP-3 (10 of 12). Fourteen proteomics studies of tendon tissues/cells failed inclusion, mostly because they were conducted in animals or in vitro.
CONCLUSIONS
Based on methods, which only allowed simultaneous quantification of a limited number of prespecified mRNA molecules or proteins, several proteins appeared to be differentially expressed/represented in rotator cuff tendinopathy and other tendinopathies. No proteomics studies fulfilled our inclusion criteria, although proteomics technologies may be a way to identify protein profiles (including non-prespecified proteins) that characterise specific tendon disorders or stages of tendinopathy. Thus, our results suggested an untapped potential for proteomics in tendon research.
Topics: Gene Expression; Humans; Proteins; Proteomics; Publication Bias; Rotator Cuff; Shoulder Impingement Syndrome
PubMed: 25879758
DOI: 10.1371/journal.pone.0119974 -
Human Reproduction Update 2014'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies.... (Review)
Review
BACKGROUND
'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.
METHODS
Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.
RESULTS
The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.
CONCLUSION
A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.
Topics: Embryo Implantation; Endometrium; Female; Genomics; Guidelines as Topic; High-Throughput Nucleotide Sequencing; Humans; Metabolomics; Systems Biology
PubMed: 24082038
DOI: 10.1093/humupd/dmt048 -
Frontiers in Plant Science 2020Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static...
Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static protein synthesis machines that are not subject to extensive regulation but only read mRNA and produce polypeptides accordingly. New and increasing evidence across various model organisms demonstrated the heterogeneous nature of ribosomes. This heterogeneity can constitute specialized ribosomes that regulate mRNA translation and control protein synthesis. A prominent example of ribosome heterogeneity is seen in the model plant, , which, due to genome duplications, has multiple paralogs of each ribosomal protein (RP) gene. We support the notion of plant evolution directing high RP paralog divergence toward functional heterogeneity, underpinned in part by a vast resource of ribosome mutants that suggest specialization extends beyond the pleiotropic effects of single structural RPs or RP paralogs. Thus, Arabidopsis is a highly suitable model to study this phenomenon. Arabidopsis enables reverse genetics approaches that could provide evidence of ribosome specialization. In this review, we critically assess evidence of plant ribosome specialization and highlight steps along ribosome biogenesis in which heterogeneity may arise, filling the knowledge gaps in plant science by providing advanced insights from the human or yeast fields. We propose a data analysis pipeline that infers the heterogeneity of ribosome complexes and deviations from canonical structural compositions linked to stress events. This analysis pipeline can be extrapolated and enhanced by combination with other high-throughput methodologies, such as proteomics. Technologies, such as kinetic mass spectrometry and ribosome profiling, will be necessary to resolve the temporal and spatial aspects of translational regulation while the functional features of ribosomal subpopulations will become clear with the combination of reverse genetics and systems biology approaches.
PubMed: 32670337
DOI: 10.3389/fpls.2020.00948 -
The Cochrane Database of Systematic... Dec 2015About 10% of reproductive-aged women suffer from endometriosis which is a costly chronic disease that causes pelvic pain and subfertility. Laparoscopy is the 'gold... (Review)
Review
BACKGROUND
About 10% of reproductive-aged women suffer from endometriosis which is a costly chronic disease that causes pelvic pain and subfertility. Laparoscopy is the 'gold standard' diagnostic test for endometriosis, but it is expensive and carries surgical risks. Currently, there are no simple non-invasive or minimally-invasive tests available in clinical practice that accurately diagnoses endometriosis.
OBJECTIVES
1. To provide summary estimates of the diagnostic accuracy of urinary biomarkers for the diagnosis of pelvic endometriosis compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.Urinary biomarkers were evaluated as replacement tests for surgical diagnosis and as triage tests to inform decisions to undertake surgery for endometriosis.
SEARCH METHODS
The searches were not restricted to particular study design, language or publication dates. We searched the following databases to 20 April - 31 July 2015: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP and ClinicalTrials.gov (trial register). MEDION, DARE, and PubMed were also searched to identify reviews and guidelines as reference sources of potentially relevant studies. Recently published papers not yet indexed in the major databases were also sought. The search strategy incorporated words in the title, abstract, text words across the record and the medical subject headings (MeSH) and was modified for each database.
SELECTION CRITERIA
Published peer-reviewed, randomised controlled or cross-sectional studies of any size were considered, which included prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more urinary biomarkers with surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS
Two authors independently collected and performed a quality assessment of the data from each study. For each diagnostic test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. If two or more tests were evaluated in the same cohort, each was considered as a separate data set. The bivariate model was used to obtain pooled estimates of sensitivity and specificity whenever sufficient data sets were available. The predetermined criteria for a clinically useful urine test to replace diagnostic surgery was one with a sensitivity of 94% and a specificity of 79% to detect endometriosis. The criteria for triage tests were set at sensitivity of equal or greater than 95% and specificity of equal or greater than 50%, which in case of negative result rules out the diagnosis (SnOUT test) or sensitivity of equal or greater than 50% with specificity of equal or greater than 95%, which in case of positive result rules the diagnosis in (SpIN test).
MAIN RESULTS
We included eight studies involving 646 participants, most of which were of poor methodological quality. The urinary biomarkers were evaluated either in a specific phase of menstrual cycle or irrespective of the cycle phase. Five studies evaluated the diagnostic performance of four urinary biomarkers for endometriosis, including three biomarkers distinguishing women with and without endometriosis (enolase 1 (NNE); vitamin D binding protein (VDBP); and urinary peptide profiling); and one biomarker (cytokeratin 19 (CK 19)) showing no significant difference between the two groups. All of these biomarkers were assessed in small individual studies and could not be statistically evaluated in a meaningful way. None of the biomarkers met the criteria for a replacement test or a triage test. Three studies evaluated three biomarkers that did not differentiate women with endometriosis from disease-free controls.
AUTHORS' CONCLUSIONS
There was insufficient evidence to recommend any urinary biomarker for use as a replacement or triage test in clinical practice for the diagnosis of endometriosis. Several urinary biomarkers may have diagnostic potential, but require further evaluation before being introduced into routine clinical practice. Laparoscopy remains the gold standard for the diagnosis of endometriosis, and diagnosis of endometriosis using urinary biomarkers should only be undertaken in a research setting.
Topics: Biomarkers; Diagnosis, Differential; Endometriosis; Female; Humans; Keratin-19; Peptide Fragments; Peptides; Phosphopyruvate Hydratase; Proteomics; Vitamin D-Binding Protein
PubMed: 26695425
DOI: 10.1002/14651858.CD012019 -
Biomolecules Jan 2024Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be... (Review)
Review
Ocular graft-versus-host disease (oGVHD) affects ~50% of post-stem cell transplant patients and is the only form of GVHD diagnosed without a biopsy. As it must be distinguished from other dry eye diseases, there is a need to identify oGVHD biomarkers to improve diagnosis and treatment. We conducted a systematic review of 19 scholarly articles published from 2018 to 2023 including articles focused on adult patients diagnosed with oGVHD following allogeneic hematopoietic stem cell transplant and used biomarkers as the outcome measure. Articles that were not original investigations or were not published in English were excluded. These clinical investigations explored different molecular oGVHD biomarkers and were identified on 3 October 2023 from the Scopus, PubMed, and Embase databases by using search terms including ocular graft-versus-host disease, biomarkers, cytokines, proteomics, genomics, immune response, imaging techniques, and dry-eye-related key terms. The Newcastle-Ottawa scale for case-control studies was used to assess bias. From the 19 articles included, cytokine, proteomic, lipid, and leukocyte profiles were studied in tear film, as well as ocular surface microbiota and fluorescein staining. Our findings suggest that cytokine profiling is the most studied oGVHD biomarker. Additionally, variations correlating these biomarkers with disease state may lead to a more targeted diagnosis and therapeutic approach. Limitations include language bias, publication bias, and sampling bias, as well as a lack of appropriate controls for included studies.
Topics: Adult; Humans; Proteomics; Biomarkers; Biopsy; Cytokines; Graft vs Host Disease
PubMed: 38254702
DOI: 10.3390/biom14010102 -
Expert Review of Proteomics Aug 2021Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee...
INTRODUCTION
Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to the finding of this 'OA biomarker' is mass spectrometry (MS), which offers the possibility to analyze different molecules in tissues or fluids. Several proteomic, lipidomic, metabolomic and other - omic approaches aim to identify these molecular profiles; however, variation in methods and techniques complicate the finding of promising candidate biomarkers.
AREAS COVERED
In this systematic review, we aim to provide an overview of molecules in knee OA patients. Possible biomarkers in several tissue types of OA and non-OA patients, as well as current limitations and possible future suggestions will be discussed.
EXPERT OPINION
According to this review, we do not believe one specific biomarker will function as predictive molecule for OA. Likely, a group of molecules will give insight in OA development and possible therapeutic targets. For clinical implementation of MS-analysis in clinical decision-making, standardized procedures, large cohort studies and sharing protocols and data is necessary.
Topics: Adipose Tissue; Biomarkers; Humans; Knee Joint; Mass Spectrometry; Osteoarthritis, Knee; Proteomics
PubMed: 34228576
DOI: 10.1080/14789450.2021.1952868 -
Journal of Nanobiotechnology Apr 2023One-third of the world's population has anemia, contributing to higher morbidity and death and impaired neurological development. Conventional anemia treatment raises... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One-third of the world's population has anemia, contributing to higher morbidity and death and impaired neurological development. Conventional anemia treatment raises concerns about iron bioavailability and gastrointestinal (GI) adverse effects. This research aims to establish how iron oxide nanoparticles (IONPs) interact with probiotic cells and how they affect iron absorption, bioavailability, and microbiota variation.
METHODS
Pointing to the study of the literature and developing a review and critical synthesis, a robust search methodology was utilized by the authors. The literature search was performed in the PubMed, Scopus, and Web of Science databases. Information was collected between January 2017 and June 2022 using the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) protocols for systematic reviews and meta-analyses. We identified 122 compatible research articles.
RESULTS
The research profile of the selected scientific articles revealed the efficacy of IONPs treatment carried by probiotics versus conventional treatment. Therefore, the authors employed content assessment on four topics to synthesize previous studies. The key subjects of the reviewed reports are the characteristics of the IONPs synthesis method, the evaluation of cell absorption and cytotoxicity of IONPs, and the transport of IONPs with probiotics in treating anemia.
CONCLUSIONS
To ensure a sufficient iron level in the enterocyte, probiotics with the capacity to attach to the gut wall transport IONPs into the enterocyte, where the maghemite nanoparticles are released.
Topics: Humans; Anemia; Iron; Magnetic Iron Oxide Nanoparticles; Probiotics
PubMed: 37038224
DOI: 10.1186/s12951-023-01880-9 -
Food Science & Nutrition Jan 2021This systematic review aimed at investigating longitudinal changes in human milk bioactive protein concentrations in Chinese population. Both English and Chinese... (Review)
Review
This systematic review aimed at investigating longitudinal changes in human milk bioactive protein concentrations in Chinese population. Both English and Chinese databases were searched. The data were pooled into six defined lactation stages. Weighted means of protein concentrations in each stage and the statistical significance of means of different lactation stages were calculated. The data of 11 bioactive proteins were retrieved. Concentrations of sIgA, IgM, and IgG decreased sharply during the first 14 days of lactation. The levels of α-lactalbumin, lactoferrin, and β-casein also decreased throughout lactation. Conversely, lysozyme levels increased over lactation. The changing patterns of the serum albumin, osteopontin, and bile salt-stimulated lipase (BSSL) were not conclusive. This study represents the most comprehensive summary of bioactive proteins in Chinese human milk. In the future, mass spectrometry-based analysis of human milk proteomics may be used to investigate the longitudinal changes of many more bioactive proteins.
PubMed: 33473267
DOI: 10.1002/fsn3.2061