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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 -
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 -
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 -
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 -
Briefings in Bioinformatics Jan 2022The emergence of single cell RNA sequencing has facilitated the studied of genomes, transcriptomes and proteomes. As available single-cell RNA-seq datasets are released...
The emergence of single cell RNA sequencing has facilitated the studied of genomes, transcriptomes and proteomes. As available single-cell RNA-seq datasets are released continuously, one of the major challenges facing traditional RNA analysis tools is the high-dimensional, high-sparsity, high-noise and large-scale characteristics of single-cell RNA-seq data. Deep learning technologies match the characteristics of single-cell RNA-seq data perfectly and offer unprecedented promise. Here, we give a systematic review for most popular single-cell RNA-seq analysis methods and tools based on deep learning models, involving the procedures of data preprocessing (quality control, normalization, data correction, dimensionality reduction and data visualization) and clustering task for downstream analysis. We further evaluate the deep model-based analysis methods of data correction and clustering quantitatively on 11 gold standard datasets. Moreover, we discuss the data preferences of these methods and their limitations, and give some suggestions and guidance for users to select appropriate methods and tools.
Topics: Cluster Analysis; Deep Learning; Gene Expression Profiling; Sequence Analysis, RNA; Single-Cell Analysis
PubMed: 34472590
DOI: 10.1093/bib/bbab345 -
Protein and Peptide Letters 2020Pancreatic neuroendocrine tumors (PanNETs) are rare tumors having usually an indolent behavior, but sometimes with unpredictable aggressiveness. PanNETs are more often...
Pancreatic neuroendocrine tumors (PanNETs) are rare tumors having usually an indolent behavior, but sometimes with unpredictable aggressiveness. PanNETs are more often non-functioning (NF), unable to produce functioning hormones, while 10-30% present as functioning (F) - PanNETs, such as insulinomas , gastrinomas , and other rare tumors. Diagnostic and prognostic markers, but also new therapeutic targets, are still lacking. Proteomics techniques represent therefore promising approaches for the future management of PanNETs. We conducted a systematic review to summarize the state of the art of proteomics in PanNETs. A total of 9 studies were included, focusing both on NF- and F-PanNETs. Indeed, proteomics is useful for the diagnosis, the prognosis and the detection of therapeutic targets. However, further studies are required. It is also warranted to standardize the analysis methods and the collection techniques, in order to validate proteins with a relevance in the personalized approach to PanNETs management.
Topics: Female; Humans; Male; Neoplasm Proteins; Pancreatic Neoplasms; Proteomics
PubMed: 31804164
DOI: 10.2174/0929866527666200504122116 -
European Urology Jun 2021Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal...
CONTEXT
Genomic stratification can impact prostate cancer (PC) care through diagnostic, prognostic, and predictive biomarkers that aid in clinical decision-making. The temporal and spatial genomic heterogeneity of PC together with the challenges of acquiring metastatic tissue biopsies hinder implementation of tissue-based molecular profiling in routine clinical practice. Blood-based liquid biopsies are an attractive, minimally invasive alternative.
OBJECTIVE
To review the clinical value of blood-based liquid biopsy assays in PC and identify potential applications to accelerate the development of precision medicine.
EVIDENCE ACQUISITION
A systematic review of PubMed/MEDLINE was performed to identify relevant literature on blood-based circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles (EVs) in PC.
EVIDENCE SYNTHESIS
Liquid biopsy has emerged as a practical tool to profile tumor dynamics over time, elucidating features that evolve (genome, epigenome, transcriptome, and proteome) with tumor progression. Liquid biopsy tests encompass analysis of DNA, RNA, and proteins that can be detected in CTCs, ctDNA, or EVs. Blood-based liquid biopsies have demonstrated promise in the context of localized tumors (diagnostic signatures, risk stratification, and disease monitoring) and advanced disease (response/resistance biomarkers and prognostic markers).
CONCLUSIONS
Liquid biopsies have value as a source of prognostic, predictive, and response biomarkers in PC. Most clinical applications have been developed in the advanced metastatic setting, where CTC and ctDNA yields are significantly higher. However, standardization of assays and analytical/clinical validation is necessary prior to clinical implementation.
PATIENT SUMMARY
Traces of tumors can be isolated from blood samples from patients with prostate cancer either as whole cells or as DNA fragments. These traces provide information on tumor features. These minimally invasive tests can guide diagnosis and treatment selection.
Topics: Biomarkers, Tumor; Circulating Tumor DNA; Clinical Decision-Making; Humans; Liquid Biopsy; Male; Neoplastic Cells, Circulating; Prostatic Neoplasms
PubMed: 33422353
DOI: 10.1016/j.eururo.2020.12.037 -
European Urology Aug 2020While upper tract urothelial carcinoma (UTUC) share histological appearance with bladder cancer (BC), the former has differences in etiology and clinical phenotype...
CONTEXT
While upper tract urothelial carcinoma (UTUC) share histological appearance with bladder cancer (BC), the former has differences in etiology and clinical phenotype consistent with characteristic molecular alterations.
OBJECTIVE
To systematically evaluate current genomic sequencing and proteomic data examining molecular alterations in UTUC.
EVIDENCE ACQUISITION
A systematic review using PubMed, Scopus, and Web of Science was performed in December 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement.
EVIDENCE SYNTHESIS
A total of 46 publications were selected for inclusion in this report, including 13 studies assessing genome-wide alterations, 18 studies assessing gene expression or microRNA expression profiles, three studies assessing proteomics, one study assessing genome-wide DNA methylation, and 14 studies evaluating distinct pathway alteration patterns. Differences between sporadic and hereditary UTUC, and between UTUC and BC, as well as molecular profiles associated with exposure to aristolochic acid are highlighted. Molecular pathways relevant to UTUC biology, such as alterations in FGFR3, TP53, or microsatellite instability, are discussed. Our findings are limited by tumor and patient heterogeneity and different platforms used in the studies.
CONCLUSIONS
Molecular events in UTUC and BC can be shared or distinct. Consequently, molecular subtypes differ according to location. Further work is needed to define the epigenomic and proteomic features of UTUC, and understand the mechanisms by which they shape the clinical behavior of UTUC.
PATIENT SUMMARY
We report the current data on the molecular alterations specific to upper tract urothelial carcinoma (UTUC), resulting from novel genomic and proteomic technologies. Although UTUC biology is comparable with that of bladder cancer, the rates and UTUC-enriched alterations support its uniqueness and the need for precision medicine strategies for this rare tumor type.
Topics: Carcinoma, Transitional Cell; High-Throughput Nucleotide Sequencing; Humans; Kidney Neoplasms; Molecular Diagnostic Techniques; Ureteral Neoplasms
PubMed: 32571725
DOI: 10.1016/j.eururo.2020.05.039 -
Diagnostics (Basel, Switzerland) Apr 2024: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children... (Review)
Review
: To evaluate the clinical usefulness of demographic data, fetal imaging findings and urinary analytes were used for predicting poor postnatal renal function in children with congenital megacystis. : A systematic review was conducted in MEDLINE's electronic database from inception to December 2023 using various combinations of keywords such as "luto" [All Fields] OR "lower urinary tract obstruction" [All Fields] OR "urethral valves" [All Fields] OR "megacystis" [All Fields] OR "urethral atresia" [All Fields] OR "megalourethra" [All Fields] AND "prenatal ultrasound" [All Fields] OR "maternal ultrasound" [All Fields] OR "ob-stetric ultrasound" [All Fields] OR "anhydramnios" [All Fields] OR "oligohydramnios" [All Fields] OR "renal echogenicity" [All Fields] OR "biomarkers" [All Fields] OR "fetal urine" [All Fields] OR "amniotic fluid" [All Fields] OR "beta2 microglobulin" [All Fields] OR "osmolarity" [All Fields] OR "proteome" [All Fields] AND "outcomes" [All Fields] OR "prognosis" [All Fields] OR "staging" [All Fields] OR "prognostic factors" [All Fields] OR "predictors" [All Fields] OR "renal function" [All Fields] OR "kidney function" [All Fields] OR "renal failure" [All Fields]. Two reviewers independently selected the articles in which the accuracy of prenatal imaging findings and fetal urinary analytes were evaluated to predict postnatal renal function. : Out of the 727 articles analyzed, 20 met the selection criteria, including 1049 fetuses. Regarding fetal imaging findings, the predictive value of the amniotic fluid was investigated by 15 articles, the renal appearance by 11, bladder findings by 4, and ureteral dilatation by 2. The postnatal renal function showed a statistically significant relationship with the occurrence of oligo- or anhydramnion in four studies, with an abnormal echogenic/cystic renal cortical appearance in three studies. Single articles proved the statistical prognostic value of the amniotic fluid index, the renal parenchymal area, the apparent diffusion coefficient (ADC) measured on fetal diffusion-weighted MRI, and the lower urinary tract obstruction (LUTO) stage (based on bladder volume at referral and gestational age at the appearance of oligo- or anhydramnios). Regarding the predictive value of fetal urinary analytes, sodium and β2-microglobulin were the two most common urinary analytes investigated (n = 10 articles), followed by calcium (n = 6), chloride (n = 5), urinary osmolarity (n = 4), and total protein (n = 3). Phosphorus, glucose, creatinine, and urea were analyzed by two articles, and ammonium, potassium, N-Acetyl-l3-D-glucosaminidase, and microalbumin were investigated by one article. The majority of the studies (n = 8) failed to prove the prognostic value of fetal urinary analytes. However, two studies showed that a favorable urinary biochemistry profile (made up of sodium < 100 mg/dL; calcium < 8 mg/dL; osmolality < 200 mOsm/L; β2-microglobulin < 4 mg/L; total protein < 20 mg/dL) could predict good postnatal renal outcomes with statistical significance and urinary levels of β2-microglobulin were significantly higher in fetuses that developed an impaired renal function in childhood (10.9 ± 5.0 mg/L vs. 1.3 ± 0.2 mg/L, -value < 0.05). : Several demographic data, fetal imaging parameters, and urinary analytes have been shown to play a role in reliably triaging fetuses with megacystis for the risk of adverse postnatal renal outcomes. We believe that this systematic review can help clinicians for counseling parents on the prognoses of their infants and identifying the selected cases eligible for antenatal intervention.
PubMed: 38611669
DOI: 10.3390/diagnostics14070756 -
Journal of Periodontal Research Jun 2024The current study aimed to: (1) systematically review the published literature regarding the proteomics analyses of saliva and gingival crevicular fluid (GCF) in healthy... (Review)
Review
AIM
The current study aimed to: (1) systematically review the published literature regarding the proteomics analyses of saliva and gingival crevicular fluid (GCF) in healthy humans and gingivitis and/or periodontitis patients; and (2) to identify the differentially expressed proteins (DEPs) based on the systematic review, and comprehensively conduct meta-analyses and bioinformatics analyses.
METHODS
An online search of Web of Science, Scopus, and PubMed was performed without any restriction on the year and language of publication. After the identification of the DEPs reported by the included human primary studies, gene ontology (GO), the Kyoto encyclopedia of genes and genomes pathway (KEGG), protein-protein interaction (PPI), and meta-analyses were conducted. The risk of bias among the included studies was evaluated using the modified Newcastle-Ottawa quality assessment scale.
RESULTS
The review identified significant differences in protein expression between healthy individuals and those with gingivitis and periodontitis. In GCF, 247 proteins were upregulated and 128 downregulated in periodontal diseases. Saliva analysis revealed 79 upregulated and 70 downregulated proteins. There were distinct protein profiles between gingivitis and periodontitis, with 159 and 31 unique upregulated proteins in GCF, respectively. Meta-analyses confirmed significant upregulation of various proteins in periodontitis, including ALB and MMP9, while CSTB and GSTP1 were downregulated. AMY1A and SERPINA1 were upregulated in periodontitis saliva. HBD was upregulated in gingivitis GCF, while DEFA3 was downregulated. PPI analysis revealed complex networks of interactions among DEPs. GO and KEGG pathway analyses provided insights into biological processes and pathways associated with periodontal diseases.
CONCLUSION
The ongoing MS-based proteomics studies emphasize the need for a highly sensitive and specific diagnostic tool for periodontal diseases. Clinician acceptance of the eventual diagnostic method relies on its ability to provide superior or complementary information to current clinical assessment procedures. Future research should prioritize the multiplex measurement of multiple biomarkers simultaneously to enhance diagnostic accuracy and large study cohorts are necessary to ensure the validity and reliability of research findings.
PubMed: 38873831
DOI: 10.1111/jre.13313