Ultra-High-Throughput Clinical Proteomics Reveals Classifiers of COVID-19 Infection

Cell Systems, Journal Year: 2020, Volume and Issue: 11(1), P. 11 - 24.e4

Published: June 2, 2020

The COVID-19 pandemic is an unprecedented global challenge, and point-of-care diagnostic classifiers are urgently required. Here, we present a platform for ultra-high-throughput serum plasma proteomics that builds on ISO13485 standardization to facilitate simple implementation in regulated clinical laboratories. Our low-cost workflow handles up 180 samples per day, enables high precision quantification, reduces batch effects large-scale longitudinal studies. We use our collected from cohort of early hospitalized cases the SARS-CoV-2 identify 27 potential biomarkers differentially expressed depending WHO severity grade COVID-19. They include complement factors, coagulation system, inflammation modulators, pro-inflammatory factors upstream downstream interleukin 6. All protocols software implementing approach freely available. In total, this work supports development routine proteomic assays aid decision making generate hypotheses about therapeutic targets.

Language: Английский

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Apolipoproteins in vascular biology and atherosclerotic disease

Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 19(3), P. 168 - 179

Published: Oct. 8, 2021

Language: Английский

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COVID-19 and Alzheimer’s disease: how one crisis worsens the other

Translational Neurodegeneration, Journal Year: 2021, Volume and Issue: 10(1)

Published: April 30, 2021

Abstract Alzheimer’s disease (AD) has emerged as a key comorbidity of coronavirus 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The morbidity and mortality COVID-19 are elevated in AD due to multiple pathological changes patients such the excessive expression viral receptor angiotensin converting enzyme 2 pro-inflammatory molecules, various complications including diabetes, lifestyle alterations AD, drug-drug interactions. Meanwhile, also been reported cause neurologic symptoms cognitive impairment that may ultimately result probably through invasion SARS-CoV-2 into central nervous system, COVID-19-induced inflammation, long-term hospitalization delirium, post-COVID-19 syndrome. In addition, crisis worsens behavioral uninfected poses new challenges for prevention. this review, we first introduce pathogenesis AD. Next, provide comprehensive discussion on aggravating effects underlying mechanisms from molecular social levels. We highlight influence function, propose possible routes brain potential impairment. Last, summarize negative impacts pandemic dementia

Language: Английский

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Discovery of target genes and pathways at GWAS loci by pooled single-cell CRISPR screens

Science, Journal Year: 2023, Volume and Issue: 380(6646)

Published: May 4, 2023

Most variants associated with complex traits and diseases identified by genome-wide association studies (GWAS) map to noncoding regions of the genome unknown effects. Using ancestrally diverse, biobank-scale GWAS data, massively parallel CRISPR screens, single-cell transcriptomic proteomic sequencing, we discovered 124

Language: Английский

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Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024

Journal of clinical lipidology, Journal Year: 2024, Volume and Issue: 18(3), P. e320 - e350

Published: April 24, 2024

BACKGROUNDThis joint expert review by the Obesity Medicine Association (OMA) and National Lipid (NLA) provides clinicians an overview of pathophysiologic clinical considerations regarding obesity, dyslipidemia, cardiovascular disease (CVD) risk.METHODSThis is based upon scientific evidence, perspectives authors, peer OMA NLA leadership.RESULTSAmong individuals with adipose tissue may store over 50% total body free cholesterol. Triglycerides represent up to 99% lipid species in tissue. The potential for expansion accounts greatest weight variance among most individuals, percent fat ranging from less than 5% 60%. While population studies suggest a modest increase blood low-density lipoprotein cholesterol (LDL-C) levels excess adiposity, adiposopathic dyslipidemia pattern often described adiposity includes elevated triglycerides, reduced high density (HDL-C), increased non-HDL-C, apolipoprotein B, LDL particle concentration, small, dense particles.CONCLUSIONSObesity increases CVD risk, at least partially due promotion adiposopathic, atherogenic profile. also worsens other cardiometabolic risk factors. Among patients interventions that reduce improve outcomes are generally associated improved levels. Given improvement LDL-C reduction overweight or early treat both (LDL-C and/or non-HDL-C) priorities reducing CVD. This risk. leadership. particles.

Language: Английский

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Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024

Obesity Pillars, Journal Year: 2024, Volume and Issue: 10, P. 100108 - 100108

Published: March 12, 2024

This joint expert review by the Obesity Medicine Association (OMA) and National Lipid (NLA) provides clinicians an overview of pathophysiologic clinical considerations regarding obesity, dyslipidemia, cardiovascular disease (CVD) risk. is based upon scientific evidence, perspectives authors, peer OMA NLA leadership. Among individuals with adipose tissue may store over 50% total body free cholesterol. Triglycerides represent up to 99% lipid species in tissue. The potential for expansion accounts greatest weight variance among most individuals, percent fat ranging from less than 5% 60%. While population studies suggest a modest increase blood low-density lipoprotein cholesterol (LDL-C) levels excess adiposity, adiposopathic dyslipidemia pattern often described adiposity includes elevated triglycerides, reduced high density (HDL-C), increased non-HDL-C, apolipoprotein B, LDL particle concentration, small, dense particles. increases CVD risk, at least partially due promotion adiposopathic, atherogenic profile. also worsens other cardiometabolic risk factors. patients interventions that reduce improve outcomes are generally associated improved levels. Given improvement LDL-C reduction overweight or early treat both (LDL-C and/or non-HDL-C) priorities reducing CVD.

Language: Английский

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The Importance of Lipoprotein Lipase Regulation in Atherosclerosis

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 782 - 782

Published: July 6, 2021

Lipoprotein lipase (LPL) plays a major role in the lipid homeostasis mainly by mediating intravascular lipolysis of triglyceride rich lipoproteins. Impaired LPL activity leads to accumulation chylomicrons and very low-density lipoproteins (VLDL) plasma, resulting hypertriglyceridemia. While lipoprotein cholesterol (LDL-C) is recognized as primary risk factor for atherosclerosis, hypertriglyceridemia has been shown be an independent cardiovascular disease (CVD) residual atherosclerosis development. In this review, we focus on machinery discuss potential triglycerides, remnant particles, mediators onset progression atherosclerotic (ASCVD). This review details number important factors involved maturation transportation capillaries, where triglycerides are hydrolyzed, generating Moreover, other also reported impact clearance from plasma promote retention capillaries. Apolipoproteins (Apo) angiopoietin-like proteins (ANGPTLs) play crucial regulating recent insights into regulation may elucidate new pharmacological means address challenge

Language: Английский

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Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis

Pharmacological Research, Journal Year: 2022, Volume and Issue: 183, P. 106376 - 106376

Published: July 30, 2022

Language: Английский

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Role of apolipoprotein C1 in lipoprotein metabolism, atherosclerosis and diabetes: a systematic review

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Dec. 5, 2022

Abstract Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 involved in triglyceride-rich lipoproteins by inhibiting binding very low density (VLDL) VLDL-receptor (VLDL-R), lipoprotein receptor (LDL-R) and LDL related protein (LRP), reducing activity lipase (LPL) stimulating VLDL production, all these effects leading increase plasma triglycerides. takes also part high (HDL) Cholesterol Ester Transfer Protein (CETP). The functionality apoC1 on CETP impaired diabetes that might account, at least part, for increased observed patients with diabetes. Its different possible modulation inflammation makes net impact cardiometabolic risk difficult figure out be considered as pro-atherogenic or anti-atherogenic depending overall metabolic context. Making link between total levels cardio-metabolic diseases due exchangeability this biological depend essentially its association HDL. humans entirely elucidated further studies are needed determine precise lipid pleiotropic vascular wall biology. In review, we will present data structure distribution among lipoproteins, HDL discuss links apoC1, atherosclerosis

Language: Английский

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Supervised discovery of interpretable gene programs from single-cell data

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(7), P. 1084 - 1095

Published: Sept. 21, 2023

Factor analysis decomposes single-cell gene expression data into a minimal set of programs that correspond to processes executed by cells in sample. However, matrix factorization methods are prone technical artifacts and poor factor interpretability. We address these concerns with Spectra, an algorithm combines user-provided the detection novel together best explain covariation. Spectra incorporates existing sets cell-type labels as prior biological information, explicitly models cell type represents input gene-gene knowledge graph using penalty function guide toward graph. show outperforms approaches challenging tumor immune contexts, it finds factors change under checkpoint therapy, disentangles highly correlated features CD8

Language: Английский

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