The development of Alzheimer's disease (AD) has been strongly linked to the apolipoprotein E (
APOE
) polymorphism. A number studies have reported that the
APOE
ε4 allele is a genetic risk factor for ...developing AD, whereas the
APOE
ε2 and
APOE
ε3 alleles are considered to be neutral or even protective; however, there are conflicting data about these relationships in certain ethnic populations. Several meta-analyses have been performed to reduce the heterogeneity of results from different studies and estimate the real association in specific ethnicities. The aim of this study was to investigate the association between the
APOE
polymorphism and AD in an Iranian population. Our results showed a higher incidence of AD among individuals carrying the
APOE
ε4 allele (OR = 4.81, 95% CI: 3.28–7.05), more notably in those with the
APOE
ε4/e4 genotype (OR = 7.47, 95% CI: 2.35–23.73), while carrying the
APOE
ε3 allele was demonstrated to have a protective effect (OR = 0.40, 95% CI: 0.30–0.54). The association between the
APOE
ε2 allele and AD was not statically significant. However, further studies focusing on other parameters such as age, sex and environmental conditions are needed to reveal the true association between the
APOE
polymorphism and AD.
Gastrointestinal (GI) cancer remains one of the common causes of morbidity and mortality. A high number of cases are diagnosed at an advanced stage, leading to a poor survival rate. This is primarily ...attributed to the lack of reliable diagnostic biomarkers and limited treatment options. Therefore, more sensitive, specific biomarkers and curative treatments are desirable. Functional proteomics as a research area in the proteomic field aims to elucidate the biological function of unknown proteins and unravel the cellular mechanisms at the molecular level. Phosphoproteomic and glycoproteomic studies have emerged as two efficient functional proteomics approaches used to identify diagnostic biomarkers, therapeutic targets, the molecular basis of disease and mechanisms underlying drug resistance in GI cancers. In this review, we present an overview on how functional proteomics may contribute to the understanding of GI cancers, namely colorectal, gastric, hepatocellular carcinoma and pancreatic cancers. Moreover, we have summarized recent methodological developments in phosphoproteomics and glycoproteomics for GI cancer studies.
The aim of this meta-analysis was to examine the association of ApoE polymorphism with the risk of developing PE.
A comprehensive search was carried out through PubMed, Scopus, and Embase. The ORs ...with corresponding 95% CIs were extracted. Fixed model was used for meta-analysis and in case of existing heterogeneity a random-effects model was applied.
Association of ApoE polymorphism with the risk of developing PE was not statistically significant (OR = 0.86, 95% CI: 0.67-1.11; OR = 0.92, 95%CI: 0.73-1.15, respectively for ε2 and ε4).
ApoE polymorphism might not be associated with the risk of PE.
The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this ...devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, post-translational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.
Altered mitochondrial function is tightly linked to lifespan regulation, but underlying mechanisms remain unclear. Here, we report the chronological and replicative lifespan variation across 167 ...yeast knock-out strains, each lacking a single nuclear-coded mitochondrial gene, including 144 genes with human homologs, many associated with diseases. We dissected the signatures of observed lifespan differences by analyzing profiles of each strain’s proteome, lipidome, and metabolome under fermentative and respiratory culture conditions, which correspond to the metabolic states of replicative and chronologically aging cells, respectively. Examination of the relationships among extended longevity phenotypes, protein, and metabolite levels revealed that although many of these nuclear-encoded mitochondrial genes carry out different functions, their inhibition attenuates a common mechanism that controls cytosolic ribosomal protein abundance, actin dynamics, and proteasome function to regulate lifespan. The principles of lifespan control learned through this work may be applicable to the regulation of lifespan in more complex organisms, since many aspects of mitochondrial function are highly conserved among eukaryotes.
Alzheimer's disease (AD) is one of the most complicated progressive neurodegenerative brain disorders, affecting millions of people around the world. Ageing remains one of the strongest risk factors ...associated with the disease and the increasing trend of the ageing population globally has significantly increased the pressure on healthcare systems worldwide. The pathogenesis of AD is being extensively investigated, yet several unknown key components remain. Therefore, we aimed to extract new knowledge from existing data. Ten gene expression datasets from different brain regions including the hippocampus, cerebellum, entorhinal, frontal and temporal cortices of 820 AD cases and 626 healthy controls were analyzed using the robust rank aggregation (RRA) method. Our results returned 1713 robust differentially expressed genes (DEGs) between five brain regions of AD cases and healthy controls. Subsequent analysis revealed pathways that were altered in each brain region, of which the GABAergic synapse pathway and the retrograde endocannabinoid signaling pathway were shared between all AD affected brain regions except the cerebellum, which is relatively less sensitive to the effects of AD. Furthermore, we obtained common robust DEGs between these two pathways and predicted three miRNAs as potential candidates targeting these genes; hsa-mir-17-5p, hsa-mir-106a-5p and hsa-mir-373-3p. Three transcription factors (TFs) were also identified as the potential upstream regulators of the robust DEGs; ELK-1, GATA1 and GATA2. Our results provide the foundation for further research investigating the role of these pathways in AD pathogenesis, and potential application of these miRNAs and TFs as therapeutic and diagnostic targets.
There are reports of ocular tropism due to respiratory viruses such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Various studies have shown ocular manifestation in coronavirus ...disease-2019 (COVID-19) patients. We aimed to identify ophthalmic manifestations in COVID-19 patients and establish an association between ocular symptoms and SARS-CoV-2 infection.
A systematic search of Medline, Scopus, Web of Science, Embase, and Cochrane Library was conducted for publications from December 2019 to April 2021. The search included MeSH terms such as SARS-CoV-2 and ocular manifestations. The pooled prevalence estimate (PPE) with 95% confidence interval (CI) was calculated using binomial distribution and random effects. The meta-regression method was used to examine factors affecting heterogeneity between studies.
Of the 412 retrieved articles, 23 studies with a total of 3,650 COVID-19 patients were analyzed. The PPE for any ocular manifestations was 23.77% (95% CI: 15.73-31.81). The most prevalent symptom was dry eyes with a PPE of 13.66% (95% CI: 5.01-25.51). The PPE with 95% CI for conjunctival hyperemia, conjunctival congestion/conjunctivitis, and ocular pain was 13.41% (4.65-25.51), 9.14% (6.13-12.15), and 10.34% (4.90-15.78), respectively. Only two studies reported ocular discomfort and diplopia. The results of meta-regression analysis showed that age and sample size had no significant effect on the prevalence of any ocular manifestations. There was no significant publication bias in our meta-analysis.
There is a high prevalence of ocular manifestations in COVID-19 patients. The most common symptoms are dry eyes, conjunctival hyperemia, conjunctival congestion/conjunctivitis, ocular pain, irritation/itching/burning sensation, and foreign body sensation.
Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are secreted by cells and play a critical role in cell‐to‐cell communication. Despite the promising reports regarding ...their diagnostic and therapeutic potential, the utilization of EVs in the clinical setting is limited due to insufficient information about their cargo and a lack of standardization in isolation and analysis methods. Considering protein cargos in EVs as key contributors to their therapeutic potency, we conducted a tandem mass tag (TMT) quantitative proteomics analysis of three subpopulations of mesenchymal stem cell (MSC)‐derived EVs obtained through three different isolation techniques: ultracentrifugation (UC), high‐speed centrifugation (HS), and ultracentrifugation on sucrose cushion (SU). Subsequently, we checked EV marker expression, size distribution, and morphological characterization, followed by bioinformatic analysis. The bioinformatic analysis of the proteome results revealed that these subpopulations exhibit distinct molecular and functional characteristics. The choice of isolation method impacts the proteome of isolated EVs by isolating different subpopulations of EVs. Specifically, EVs isolated through the high‐speed centrifugation (HS) method exhibited a higher abundance of ribosomal and mitochondrial proteins. Functional apoptosis assays comparing isolated mitochondria with EVs isolated through different methods revealed that HS‐EVs, but not other EVs, induced early apoptosis in cancer cells. On the other hand, EVs isolated using the sucrose cushion (SU) and ultracentrifugation (UC) methods demonstrated a higher abundance of proteins primarily involved in the immune response, cell‐cell interactions and extracellular matrix interactions. Our analyses unveil notable disparities in proteins and associated biological functions among EV subpopulations, underscoring the importance of meticulously selecting isolation methods and resultant EV subpopulations based on the intended application.
Cannabis (
), popularly known as marijuana, is the most commonly used psychoactive substance and is considered illicit in most countries worldwide. However, a growing body of research has provided ...evidence of the therapeutic properties of chemical components of cannabis known as cannabinoids against several diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease, schizophrenia and glaucoma; these have prompted changes in medicinal cannabis legislation. The relaxation of legal restrictions and increased socio-cultural acceptance has led to its increase in both medicinal and recreational usage. Several biochemically active components of cannabis have a range of effects on the biological system. There is an urgent need for more research to better understand the molecular and biochemical effects of cannabis at a cellular level, to understand fully its implications as a pharmaceutical drug. Proteomics technology is an efficient tool to rigorously elucidate the mechanistic effects of cannabis on the human body in a cell and tissue-specific manner, drawing conclusions associated with its toxicity as well as therapeutic benefits, safety and efficacy profiles. This review provides a comprehensive overview of both in vitro and in vivo proteomic studies involving the cellular and molecular effects of cannabis and cannabis-derived compounds.
Cannabis has been used historically for both medicinal and recreational purposes, with the most notable cannabinoids being cannabidiol (CBD) and tetrahydrocannabinol (THC). Although their therapeutic ...effects have been well studied and their recreational use is highly debated, the underlying mechanisms of their biological effects remain poorly defined. In this study, we use isobaric tag-based sample multiplexed proteome profiling to investigate protein abundance differences in the human neuroblastoma SH-SY5Y cell line treated with CBD and THC. We identified significantly regulated proteins by each treatment and performed a pathway classification and associated protein–protein interaction analysis. Our findings suggest that these treatments may lead to mitochondrial dysfunction and induce endoplasmic reticulum stress. These data can potentially be interrogated further to investigate the potential role of CBD and THC in various biological and disease contexts, providing a foundation for future studies.
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