Comparative effectiveness of single foods and food groups on body weight: a systematic review and network meta-analysis of 152 randomized controlled trials.

PURPOSE: This study aimed at quantifying and ranking the effects of different foods or food groups on weight loss. METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Embase to April 2021. We included randomized trials evaluating the comparative effects of two or more food groups, or compared a food group against a control group (usual diet, no intervention) for weight loss in adults. We conducted random-effects network meta-analysis with Bayesian framework to estimate mean difference [MD] and 95% credible interval [CrI] of the effect of food groups on weight loss. RESULTS: 152 RCTs with 9669 participants were eligible. Increased consumption of fish (MD - 0.85 kg, 95% CrI - 1.66, - 0.02; GRADE = low), whole grains (MD - 0.44 kg, 95% CrI - 0.88, 0.0; GRADE = very low), and nuts (MD - 0.37 kg, 95% CI - 0.72, - 0.01; GRADE = low) demonstrated trivial weight loss, well below minimal clinically important threshold (3.9 kg), when compared with the control group. Interventions with other food groups led to no weight loss when compared with either the control group or other food groups. The certainty of the evidence was rated low to very low with the point estimates for all comparisons less than 1 kg. None of the food groups showed an important reduction in body weight when restricted to studies conducted in participants with overweight or obesity. CONCLUSIONS: Interventions with a single food or food group resulted in no or trivial weight loss, especially in  individuals with overweight or obesity. Further trials on single foods or food groups for weight loss should be highly discouraged.

Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks.

Fingolimod (FTY720) is an oral drug approved by the Food and Drug Administration (FDA) for management of multiple sclerosis (MS) symptoms, which has also shown beneficial effects against Alzheimer's (AD) and Parkinson's (PD) diseases pathologies. Although an extensive effort has been made to identify mechanisms underpinning its therapeutic effects, much remains unknown. Here, we investigated Fingolimod induced proteome changes in the cerebellum (CB) and frontal cortex (FC) regions of the brain which are known to be severely affected in MS, using a tandem mass tag (TMT) isobaric labeling-based quantitative mass-spectrometric approach to investigate the mechanism of action of Fingolimod. This study identified 6749 and 6319 proteins in CB and FC, respectively, and returned 2609 and 3086 differentially expressed proteins in mouse CB and FC, respectively, between Fingolimod treated and control groups. Subsequent bioinformatics analyses indicated a metabolic reprogramming in both brain regions of the Fingolimod treated group, where oxidative phosphorylation was upregulated while glycolysis and pentose phosphate pathway were downregulated. In addition, modulation of neuroinflammation in the Fingolimod treated group was indicated by upregulation of retrograde endocannabinoid signaling and autophagy pathways, and downregulation of neuroinflammation related pathways including neutrophil degranulation and the IL-12 mediated signaling pathway. Our findings suggest that Fingolimod may exert its protective effects on the brain by inducing metabolic reprogramming and neuroinflammation pathway modulation.

Antibacterial activity of green gold and silver nanoparticles using ginger root extract.

Recent studies demonstrated that the speed of synthesis, biocompatibility, and antimicrobial activity of gold (Au) and silver (Ag) metals is enhanced when biosynthesized in nano-sized particles. In the present study, Au- and Ag-based nanoparticles (NPs) were synthesized via a biological process using aqueous Ginger root extract and characterized by various spectroscopic methods. The NPs have hexagonal and spherical shapes. The average particle size for Au and Ag NPs was 20 and 15 nm, respectively. The dynamic light scattering (DLS) technique has shown that the zeta potential values of synthesized NPs were 4.8 and - 7.11 mv, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of Ginger root extract revealed 25 compounds. The synthesized NPs showed significant activity against Staphylococcus aureus and Escherichia (E). coli in vitro, with IC50 and IC90 values for Au and Ag NPs, respectively, noted to be 7.5 and 7.3 µg/ml and 15 and 15.2 µg/ml for both bacterial strains. The protein leakage level was tremendous and morphological changes occurred in bacteria treated with biosynthesized NPs. These results suggest that the biosynthesized metallic NPs have the suitable potential for application as antibacterial agents with enhanced activities.

The association between maternal cadmium exposure and small for gestational age: a systematic review and meta-analysis.

Several observational studies have found an association between maternal Cadmium (Cd) exposure and Small for Gestational Age (SGA). However, these findings are inconsistent. We conducted this meta-analysis to evaluate the relationship between maternal cadmium exposure and SGA risk. A comprehensive search was performed through PubMed, Scopus, Embase, Web of Science, Cochrane Library and OpenGrey to retrieve all pertinent studies published before October 2020. A combined odds ratio (OR) and corresponding 95% confidence interval (CI) were employed to examine this correlation. As a result, nine eligible studies met the inclusion criteria and were included in a systematic review, of those six studies containing sample type of blood were included in meta-analysis, and present meta-analysis showed that maternal cadmium exposure increased the risk of SGA 1.31 times (OR = 1.31; 95% CI = 1.16-1.47 for highest versus lowest category of cadmium). This meta-analysis suggests that maternal Cd exposure may be a risk factor for SGA. However, large prospective studies from different ethnic populations with consideration of other influencing parameters are needed to confirm this finding.

Association between maternal cadmium exposure and preterm birth: a meta-analysis.

The association between Cadmium and the risk of preterm birth (PTB) has remained controversial. A number of studies found a positive correlation between maternal Cd exposure and PTB; however, there are conflicting reports about this correlation. Therefore, herein we performed this meta-analysis to examine the association between maternal Cd exposure and the risk of PTB.A systematic search was conducted through PubMed, Scopus, Embase and OpenGrey from inception to May 2020 to find all eligible studies. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to examine this correlation. A random-effects model was applied in this meta-analysis due to significant statistical heterogeneity among included studies.Overall, 10 eligible studies met the inclusion criteria and were included in our analysis, and results of the present meta-analysis indicated that maternal cadmium exposure is associated with the risk of PTB (OR = 1.32; 95% CI = 1.08-1.61).This meta-analysis suggests that maternal Cd exposure might be associated with the risk of PTB. Yet, large prospective studies from different ethnic populations which consider other influencing parameters are still required to confirm this finding.

Mitochondrial dysfunction in Alzheimer's disease - a proteomics perspective.

Mitochondrial dysfunction is involved in Alzheimer's disease (AD) pathogenesis. Mitochondria have their own genetic material; however, most of their proteins (∼99%) are synthesized as precursors on cytosolic ribosomes, and then imported into the mitochondria. Therefore, exploring proteome changes in these organelles can yield valuable information and shed light on the molecular mechanisms underlying mitochondrial dysfunction in AD. Here, we review AD-associated mitochondrial changes including the effects of amyloid beta and tau protein accumulation on the mitochondrial proteome. We also discuss the relationship of ApoE genetic polymorphism with mitochondrial changes, and present a meta-analysis of various differentially expressed proteins in the mitochondria in AD.Area covered: Proteomics studies and their contribution to our understanding of mitochondrial dysfunction in AD pathogenesis.Expert opinion: Proteomics has proven to be an efficient tool to uncover various aspects of this complex organelle, which will broaden our understanding of mitochondrial dysfunction in AD. Evidently, mitochondrial dysfunction is an early biochemical event that might play a central role in driving AD pathogenesis.

Recent Advances of Functional Proteomics in Gastrointestinal Cancers- a Path towards the Identification of Candidate Diagnostic, Prognostic, and Therapeutic Molecular Biomarkers.

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.

Application of Multiomics Approach to Investigate the Therapeutic Potentials of Stem Cell-derived Extracellular Vesicle Subpopulations for Alzheimer's Disease.

Alzheimer's disease (AD) presents a complex interplay of molecular alterations, yet understanding its pathogenesis remains a challenge. In this study, we delved into the intricate landscape of proteome and transcriptome changes in AD brains compared to healthy controls, examining 788 brain samples revealing common alterations at both protein and mRNA levels. Moreover, our analysis revealed distinct protein-level changes in aberrant energy metabolism pathways in AD brains that were not evident at the mRNA level. This suggests that the changes in protein expression could provide a deeper molecular representation of AD pathogenesis. Subsequently, using a comparative proteomic approach, we explored the therapeutic potential of mesenchymal stem cell-derived extracellular vehicles (EVs), isolated through various methods, in mitigating AD-associated changes at the protein level. Our analysis revealed a particular EV-subtype that can be utilized for compensating dysregulated mitochondrial proteostasis in the AD brain. By using network biology approaches, we further revealed the potential regulators of key therapeutic proteins. Overall, our study illuminates the significance of proteome alterations in AD pathogenesis and identifies the therapeutic promise of a specific EV subpopulation with reduced pro-inflammatory protein cargo and enriched proteins to target mitochondrial proteostasis.

Proteomics provides insights into the theranostic potential of extracellular vesicles.

Extracellular vesicles (EVs) encompass a diverse range of membranous structures derived from cells, including exosomes and microvesicles. These vesicles are present in biological fluids and play vital roles in various physiological and pathological processes. They facilitate intercellular communication by enabling the exchange of proteins, lipids, and genetic material between cells. Understanding the cellular processes that govern EV biology is essential for unraveling their physiological and pathological functions and their potential clinical applications. Despite significant advancements in EV research in recent years, there is still much to learn about these vesicles. The advent of improved mass spectrometry (MS)-based techniques has allowed for a deeper characterization of EV protein composition, providing valuable insights into their roles in different physiological and pathological conditions. In this chapter, we provide an overview of proteomics studies conducted to identify the protein contents of EVs, which contribute to their therapeutic and pathological features. We also provided evidence on the potential of EV proteome contents as biomarkers for early disease diagnosis, progression, and treatment response, as well as factors that influence their composition. Additionally, we discuss the available databases containing information on EV proteome contents, and finally, we highlight the need for further research to pave the way toward their utilization in clinical settings.

A disease similarity approach identifies short-lived Niemann-Pick type C disease mice with accelerated brain aging as a novel mouse model for Alzheimer's disease and aging research.

Since its first description in 1906 by Dr. Alois Alzheimer, Alzheimer's disease (AD) has been the most common type of dementia. Initially thought to be caused by age-associated accumulation of plaques, in recent years, research has increasingly associated AD with lysosomal storage and metabolic disorders, and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions. However, the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined. Here, we applied a disease similarity approach to identify unknown molecular targets of AD by using transcriptomic data from congenital diseases known to increase AD risk, namely Down Syndrome, Niemann Pick Disease Type C (NPC), and Mucopolysaccharidoses I. We uncovered common pathways, hub genes, and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of AD pathology, many of which have never been associated with AD. We then investigated common molecular alterations in brain samples from an NPC disease mouse model by juxtaposing them with brain samples of both human and mouse models of AD. Detailed phenotypic and molecular analyses revealed that the NPC mut mouse model can serve as a potential short-lived in vivo model for AD research and for understanding molecular factors affecting brain aging. This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on AD research while highlighting shortcomings and lack of correlation in diverse in vitro models. Considering the lack of an AD mouse model that recapitulates the physiological hallmarks of brain aging, the characterization of a short-lived NPC mouse model will further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of AD from a perspective of accelerated brain aging.

Proteomic profiling of mesenchymal stem cell-derived extracellular vesicles: Impact of isolation methods on protein cargo.

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.

Amyloid-beta and tau protein beyond Alzheimer's disease.

ABSTRACT: 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.

Common molecular signatures between coronavirus infection and Alzheimer's disease reveal targets for drug development.

Cognitive decline has been reported as a common consequence of COVID-19, and studies have suggested a link between COVID-19 infection and Alzheimer's disease (AD). However, the molecular mechanisms underlying this association remain unclear. To shed light on this link, we conducted an integrated genomic analysis using a novel Robust Rank Aggregation method to identify common transcriptional signatures of the frontal cortex, a critical area for cognitive function, between individuals with AD and COVID-19. We then performed various analyses, including the KEGG pathway, GO ontology, protein-protein interaction, hub gene, gene-miRNA, and gene-transcription factor interaction analyses to identify molecular components of biological pathways that are associated with AD in the brain also show similar changes in severe COVID-19. Our findings revealed the molecular mechanisms underpinning the association between COVID-19 infection and AD development and identified several genes, miRNAs, and TFs that may be targeted for therapeutic purposes. However, further research is needed to investigate the diagnostic and therapeutic applications of these findings.

Common Molecular Signatures Between Coronavirus Infection and Alzheimer's Disease Reveal Targets for Drug Development.

BACKGROUND: Cognitive decline is a common consequence of COVID-19, and studies suggest a link between COVID-19 and Alzheimer's disease (AD). However, the molecular mechanisms underlying this association remain unclear. OBJECTIVE: To understand the potential molecular mechanisms underlying the association between COVID-19 and AD development, and identify the potential genetic targets for pharmaceutical approaches to reduce the risk or delay the development of COVID-19-related neurological pathologies. METHODS: We analyzed transcriptome datasets of 638 brain samples using a novel Robust Rank Aggregation method, followed by functional enrichment, protein-protein, hub genes, gene-miRNA, and gene-transcription factor (TF) interaction analyses to identify molecular markers altered in AD and COVID-19 infected brains. RESULTS: Our analyses of frontal cortex from COVID-19 and AD patients identified commonly altered genes, miRNAs and TFs. Functional enrichment and hub gene analysis of these molecular changes revealed commonly altered pathways, including downregulation of the cyclic adenosine monophosphate (cAMP) signaling and taurine and hypotaurine metabolism, alongside upregulation of neuroinflammatory pathways. Furthermore, gene-miRNA and gene-TF network analyses provided potential up- and downstream regulators of identified pathways. CONCLUSION: We found that downregulation of cAMP signaling pathway, taurine metabolisms, and upregulation of neuroinflammatory related pathways are commonly altered in AD and COVID-19 pathogenesis, and may make COVID-19 patients more susceptible to cognitive decline and AD. We also identified genetic targets, regulating these pathways that can be targeted pharmaceutically to reduce the risk or delay the development of COVID-19-related neurological pathologies and AD.

Extracellular vesicles as reconfigurable therapeutics for eye diseases: Promises and hurdles.

A large number of people worldwide suffer from visual impairment. However, most available therapies rely on impeding the development of a particular eye disorder. Therefore, there is an increasing demand for effective alternative treatments, specifically regenerative therapies. Extracellular vesicles, including exosomes, ectosomes, or microvesicles, are released by cells and play a potential role in regeneration. Following an introduction to EV biogenesis and isolation methods, this integrative review provides an overview of our current knowledge about EVs as a communication paradigm in the eye. Then, we focused on the therapeutic applications of EVs derived from conditioned medium, biological fluid, or tissue and highlighted some recent developments in strategies to boost the innate therapeutic potential of EVs by loading various kinds of drugs or being engineered at the level of producing cells or EVs. Challenges faced in the development of safe and effective translation of EV-based therapy into clinical settings for eye diseases are also discussed to pave the road toward reaching feasible regenerative therapies required for eye-related complications.

Proteome-Wide Profiling Using Sample Multiplexing of a Human Cell Line Treated with Cannabidiol (CBD) and Tetrahydrocannabinol (THC).

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.

Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan.

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.

Oxidative Stress Induced Dysfunction of Protein Synthesis in 661W Mice Photoreceptor Cells.

Photoreceptor cells are highly susceptible to oxidative-stress-induced damage due to their high metabolic rate. Oxidative stress plays a key role in driving pathological events in several different ocular diseases, which lead to retinal degeneration and ultimately blindness. A growing number of studies have been performed to understand downstream events caused by ROS induced oxidative stress in photoreceptor cells; however, the underlying mechanisms of ROS toxicity are not fully understood. To shed light on ROS induced downstream pathological events, we employed a tandem mass tag (TMT) labelling-based quantitative mass-spectrometric approach to determine proteome changes in 661W photoreceptor cells following oxidative stress induction via the application of different concentrations of H2O2 at different time points. Overall, 5920 proteins were identified and quantified, and 450 differentially expressed proteins (DEPs) were identified, which were altered in a dose and time dependent manner in all treatment groups compared to the control group. These proteins were involved in several biological pathways, including spliceosome and ribosome response, activated glutathione metabolism, decreased ECM-receptor interaction, oxidative phosphorylation, abnormally regulated lysosome, apoptosis, and ribosome biogenesis. Our results highlighted ECM receptor interaction, oxidative phosphorylation and spliceosome pathways as the major targets of oxidative stress that might mediate vascular dysfunction and cellular senescence.

Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.

Alzheimer's disease (AD) is the most common form of dementia that remains incurable and has become a major medical, social, and economic challenge worldwide. AD is characterized by pathological hallmarks of senile plaques (SP) and neurofibrillary tangles (NFTs) that damage the brain up to twenty years before a clinical diagnosis is made. Interestingly these pathological features have also been observed in retinal neurodegenerative diseases including age related macular degeneration (ARMD), glaucoma and diabetic retinopathy (DR). An association of AD with these diseases has been suggested in epidemiological studies and several common pathological events and risk factors have been identified between these diseases. The E4 allele of Apolipoprotein E (APOE) is a well-established genetic risk factor for late onset AD. The ApoE ε4 allele is also associated with retinal neurodegenerative diseases however in contrast to AD, it is considered protective in AMD, likewise ApoE E2 allele, which is a protective factor for AD, has been implicated as a risk factor for AMD and glaucoma. This review summarizes the evidence on the effects of ApoE in retinal neurodegenerative diseases and discusses the overlapping molecular pathways in AD. The involvement of ApoE in regulating amyloid beta (Aß) and tau pathology, inflammation, vascular integrity, glucose metabolism and vascular endothelial growth factor (VEGF) signaling is also discussed.

Association of maternal blood lead concentration with the risk of small for gestational age: A dose-response meta-analysis.

In spite of growing evidence for the negative effect of lead, knowledge about the dose-response relationship of maternal blood lead level (BLL) and the risk of small for gestational age (SGA) is limited. We performed this meta-analysis to evaluate the dose-response relation between maternal BLL and the risk of SGA. A systematic search through Embase and PubMed was performed. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated. The nonlinear and linear relationships between maternal BLL and the risk of SGA were also investigated. Results from 51,065 patients showed a significant association between maternal BLL and risk of SGA in highest versus lowest analysis (OR: 1.54; 95% CI: 1.12-2.10, p = 0.007). While there was no association in linear dose-response (OR: 1.02; 95% CI: 1.00-1.04, p = 0.021) meta-analysis, a direct relationship was observed in the nonlinear model (nonlinearity p < 0.001). Results of this dose-response meta-analysis showed that maternal BLL higher than ∼ 0.3 µg/dL is directly associated with the risk of SGA.