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BMC Ophthalmology Dec 2023Age-related macular degeneration (AMD) is a significant cause of severe vision loss. The main purpose of this study was to identify mass spectrometry proteomics-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Age-related macular degeneration (AMD) is a significant cause of severe vision loss. The main purpose of this study was to identify mass spectrometry proteomics-based potential biomarkers of AMD that contribute to understanding the mechanisms of disease and aiding in early diagnosis.
METHODS
This study retrieved studies that aim to detect differences relate to proteomics in AMD patients and healthy control groups by mass spectrometry (MS) proteomics approaches. The search process was accord with PRISMA guidelines (PROSPERO database: CRD42023388093). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes Pathway Analysis (KEGG) were performed on differentially expressed proteins (DEPs) in the included articles using the DAVID database. DEPs were included in a meta-analysis when their effect size could be computed in at least two research studies. The effect size of measured proteins was transformed to the log2-fold change. Protein‒protein interaction (PPI) analysis was conducted on proteins that were statistically significant in the meta-analysis using the String online database.
RESULTS
Eleven studies fulfilled the inclusion criteria, and 161 DEPs were identified. The GO analysis showed that AMD is significantly related to proteolysis, extracellular exosome and protein binding. In KEGG, the most significant pathway was the complement and coagulation cascades. Meta-analysis results suggested that eight proteins were statistically significant, and according to PPI results, the most significant four proteins were serotransferrin (TF), apolipoprotein A1 (APOA1), complement C3 (C3) and lipocalin-1 (LCN1).
CONCLUSIONS
Four possible biomarkers, TF, APOA1, C3 and LCN1, were found to be significant in the pathogenesis of AMD and need to be further validated. Further studies should be performed to evaluate diagnostic and therapeutic value of these proteins.
Topics: Humans; Proteomics; Macular Degeneration; Biomarkers; Proteins; Mass Spectrometry
PubMed: 38087257
DOI: 10.1186/s12886-023-03237-0 -
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 -
International Journal of Molecular... Mar 2024Bacteriophages associated with thermophiles are gaining increased attention due to their pivotal roles in various biogeochemical and ecological processes, as well as...
Bacteriophages associated with thermophiles are gaining increased attention due to their pivotal roles in various biogeochemical and ecological processes, as well as their applications in biotechnology and bionanotechnology. Although thermophages are not suitable for controlling bacterial infections in humans or animals, their individual components, such as enzymes and capsid proteins, can be employed in molecular biology and significantly contribute to the enhancement of human and animal health. Despite their significance, thermophages still remain underrepresented in the known prokaryotic virosphere, primarily due to limited in-depth investigations. However, due to their unique properties, thermophages are currently attracting increasing interest, as evidenced by several newly discovered phages belonging to this group. This review offers an updated compilation of thermophages characterized to date, focusing on species infecting the thermophilic bacilli. Moreover, it presents experimental findings, including novel proteomic data (39 proteins) concerning the model TP-84 bacteriophage, along with the first announcement of 6 recently discovered thermophages infecting : PK5.2, PK2.1, NIIg10.1, NIIg2.1, NIIg2.2, and NIIg2.3. This review serves as an update to our previous publication in 2021.
Topics: Bacillus; Bacteriophages; Proteomics
PubMed: 38542099
DOI: 10.3390/ijms25063125 -
Frontiers in Neurology 2023Spontaneous cervical artery dissection (sCeAD) is an important cause of stroke in young adults. The underlying pathophysiology remains unclear, without validated...
BACKGROUND
Spontaneous cervical artery dissection (sCeAD) is an important cause of stroke in young adults. The underlying pathophysiology remains unclear, without validated biomarkers to identify subjects at risk. Previous studies suggested the role of abnormalities in the connective component of the arterial wall.
PURPOSE
To assess dermal ultrastructural aberrations of connective tissue by skin biopsy and genetic variations in sCeAD patients.
METHOD
We searched the PubMed and Scopus databases until August 2023 with PRISMA guidelines. Original articles assessing skin biopsy in sCeAD patients were included. Two reviewers independently conducted the screening.
FINDINGS
We included 16 studies compromising 459 patients. Thirteen studies assessed ultrastructural changes and found aberrations of collagen and elastic fibers, described as irregular contours and calibers of collagen fibrils, composite flower-like fibrils, fragmented moth-eaten elastin, and microcalcifications, cumulatively in 50.5% of patients. Seven studies showed no causative mutations in collagen type I, III, V, or elastin genes. One study showed linkage between connective tissue alterations and mutation on chromosomes 15q2 and 10q26 using genome-wide linkage analysis, while another study found significant copy number variant enrichments in genes involved in extracellular matrix (COL5A2/COL3A1/SNTA1) and collagen fibril organizations (COL5A2/COL3A1). Finally, differential expression of extracellular proteins was linked to connective tissue disorder in patients with recurrent sCeAD using a quantitative proteomics approach.
CONCLUSION
Current literature supports the hypothesis that an underlying, subclinical connective tissue disorder, likely genetically determined, may predispose to arterial wall weakness and sCeAD. Further studies with larger sample sizes and robust methodology are needed to better define the role of connective tissue in sCeAD pathogenesis.
PubMed: 37885478
DOI: 10.3389/fneur.2023.1241084 -
Diagnostics (Basel, Switzerland) Jun 2024This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic... (Review)
Review
OBJECTIVE
This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars.
MATERIALS AND METHODS
A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods.
RESULTS
Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy.
CONCLUSIONS
The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery.
PubMed: 38928661
DOI: 10.3390/diagnostics14121246 -
Journal of Clinical Laboratory Analysis Apr 2024Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids,... (Review)
Review
BACKGROUND
Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids, particularly dried capillary blood spots, are an accessible, easy-to-use technology that have seen increased utility in basic science research over the past decade. However, their use is yet to reach the kidney patient population clinically or in large-scale discovery science initiatives. The aim of this study was to systematically evaluate the existing literature surrounding the use of dried biofluids in kidney research.
METHODS
A systematic literature review was conducted using three search engines and a predefined search term strategy. Results were summarised according to the collection method, type of biofluid, application to kidney disease, cost, sample stability and patient acceptability.
RESULTS
In total, 404 studies were identified and 67 were eligible. In total, 34,739 patients were recruited to these studies with a skew towards male participants (> 73%). The majority of samples were blood, which was used either for monitoring anti-rejection immunosuppressive drug concentrations or for kidney function. Dried biofluids offered significant cost savings to the patient and healthcare service. The majority of patients preferred home microsampling when compared to conventional monitoring.
CONCLUSION
There is an unmet need in bringing dried microsampling technology to advance kidney disease despite its advantages. This technology provides an opportunity to upscale patient recruitment and longitudinal sampling, enhance vein preservation and overcome participation bias in research.
Topics: Humans; Dried Blood Spot Testing; Kidney Diseases
PubMed: 38525922
DOI: 10.1002/jcla.25032 -
BMC Medicine Jan 2024Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk...
BACKGROUND
Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality.
METHODS
We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool.
RESULTS
Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies.
CONCLUSIONS
In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting.
Topics: Humans; Heart Failure; Proteomics; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 38273315
DOI: 10.1186/s12916-024-03249-7 -
Brain Sciences May 2024The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This... (Review)
Review
The role of the extracellular matrix (ECM) in Parkinson's disease (PD) is not well understood, even though it is critical for neuronal structure and signaling. This systematic review identified the top deregulated ECM-related pathways in studies that used gene set enrichment analyses (GSEA) to document transcriptomic, proteomic, or genomic alterations in PD. PubMed and Google scholar were searched for transcriptomics, proteomics, or genomics studies that employed GSEA on data from PD tissues or cells and reported ECM-related pathways among the top-10 most enriched versus controls. Twenty-seven studies were included, two of which used multiple omics analyses. Transcriptomics and proteomics studies were conducted on a variety of tissue and cell types. Of the 17 transcriptomics studies (16 data sets), 13 identified one or more adhesion pathways in the top-10 deregulated gene sets or pathways, primarily related to cell adhesion and focal adhesion. Among the 8 proteomics studies, 5 identified altered overarching ECM gene sets or pathways among the top 10. Among the 4 genomics studies, 3 identified focal adhesion pathways among the top 10. The findings summarized here suggest that ECM organization/structure and cell adhesion (particularly focal adhesion) are altered in PD and should be the focus of future studies.
PubMed: 38928523
DOI: 10.3390/brainsci14060522 -
European Journal of Ophthalmology Sep 2023This review focuses on utility of artificial intelligence (AI) in analysis of biofluid markers in glaucoma. We detail the accuracy and validity of AI in the exploration...
PURPOSE
This review focuses on utility of artificial intelligence (AI) in analysis of biofluid markers in glaucoma. We detail the accuracy and validity of AI in the exploration of biomarkers to provide insight into glaucoma pathogenesis.
METHODS
A comprehensive search was conducted across five electronic databases including Embase, Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science. Studies pertaining to biofluid marker analysis using AI or bioinformatics in glaucoma were included. Identified studies were critically appraised and assessed for risk of bias using the Joanna Briggs Institute Critical Appraisal tools.
RESULTS
A total of 10,258 studies were screened and 39 studies met the inclusion criteria, including 23 cross-sectional studies (59%), nine prospective cohort studies (23%), six retrospective cohort studies (15%), and one case-control study (3%). Primary open angle glaucoma (POAG) was the most commonly studied subtype (55% of included studies). Twenty-four studies examined disease characteristics, 10 explored treatment decisions, and 5 provided diagnostic clarification. While studies examined at entire metabolomic or proteomic profiles to determine changes in POAG, there was heterogeneity in the data with over 175 unique, differentially expressed biomarkers reported. Discriminant analysis and artificial neural network predictive models displayed strong differentiating ability between glaucoma patients and controls, although these tools were untested in a clinical context.
CONCLUSION
The use of AI models could inform glaucoma diagnosis with high sensitivity and specificity. While insight into differentially expressed biomarkers is valuable in pathogenic exploration, no clear pathogenic mechanism in glaucoma has emerged.
Topics: Humans; Artificial Intelligence; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Glaucoma; Glaucoma, Open-Angle; Prospective Studies; Proteomics; Retrospective Studies
PubMed: 36426575
DOI: 10.1177/11206721221140948 -
Frontiers in Plant Science 2023The timing of seedling emergence is a major agricultural and ecological fitness trait, and seed germination is controlled by a complex molecular network including...
The timing of seedling emergence is a major agricultural and ecological fitness trait, and seed germination is controlled by a complex molecular network including phytohormone signalling. One such phytohormone, abscisic acid (ABA), controls a large array of stress and developmental processes, and researchers have long known it plays a crucial role in repressing germination. Although the main molecular components of the ABA signalling pathway have now been identified, the molecular mechanisms through which ABA elicits specific responses in distinct organs is still enigmatic. To address the fundamental characteristics of ABA signalling during germination, we performed a meta-analysis focusing on the Arabidopsis dry seed proteome as a reflexion basis. We combined cutting-edge proteome studies, comparative functional analyses, and protein interaction information with genetic and physiological data to redefine the singular composition and operation of the ABA core signalosome from the onset of seed imbibition. In addition, we performed a literature survey to integrate peripheral regulators present in seeds that directly regulate core component function. Although this may only be the tip of the iceberg, this extended model of ABA signalling in seeds already depicts a highly flexible system able to integrate a multitude of information to fine-tune the progression of germination.
PubMed: 37476171
DOI: 10.3389/fpls.2023.1192652