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Neurobiology of Disease Jun 2024Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has... (Meta-Analysis)
Meta-Analysis Review
Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3Â 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.
Topics: Humans; Diabetes Mellitus, Type 2; Alzheimer Disease; Animals; Epigenesis, Genetic
PubMed: 38643861
DOI: 10.1016/j.nbd.2024.106485 -
Biomolecules Jan 2024Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of... (Review)
Review
Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.
Topics: Humans; Biomarkers; Proteolysis; Physicians; Zinc; Matrix Metalloproteinases
PubMed: 38254696
DOI: 10.3390/biom14010096 -
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 -
The Iowa Orthopaedic Journal 2024Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined....
BACKGROUND
Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined. Recent data suggests that the collagen-degrading menstrual hormone relaxin may cyclically impact female ACL tissue quality. This review aims to identify any correlation between menstrual relaxin peaks and rates of female ACL injury.
METHODS
A systematic review was performed, utilizing the MEDLINE, EMBASE, and CINAHL databases. Included studies had to directly address relaxin/female ACL interactions. The primary outcome variable was relaxin proteolysis of the ACL, at cellular, tissue, joint, and whole-organism levels. The secondary outcome variable was any discussed method of moderating relaxin levels, and the clinical results if available.
RESULTS
AllThe numerous relaxin receptors on female ACLs upregulate local collagenolysis and suppress local collagen production. Peak serum relaxin concentrations (SRC) occur during menstrual cycle days 21-24; a time phase associated with greater risk of ACL injury. Oral contraceptives (OCPs) reduce SRC, with a potential ACLprotective effect.
CONCLUSION
A reasonable correlative and plausible causative relationship exists between peak relaxin levels and increased risk of ACL injury in females, and further investigation is warranted. .
Topics: Humans; Relaxin; Female; Anterior Cruciate Ligament Injuries; Menstrual Cycle; Athletic Injuries; Athletes
PubMed: 38919370
DOI: No ID Found