Basic Life Science Research Articles

Retractions in academic publishing: insights from highly ranked global universities

Purpose The study aims to profile the scientific retractions in the top five global universities and provide descriptive statistics on specific subjects. Design/methodology/approach The data for reasons behind retractions is manually extracted from the Retraction Watch Database. The top five global universities according to the Times Higher Education global ranking of 2024 are selected for this study. Findings The study found that Stanford University emerged with the highest number of retractions in the assessment across institutions in the field of basic life sciences and health sciences. Notably, the predominant reasons for these retractions were identified, with “unreliable results” being the most prevalent, accounting for 53 retractions. Following closely was the category of “errors in results and/or conclusions”, contributing to 51 retractions. MIT has the longest time between publication and retraction of any subject group, with an average of 1,701 days. Research limitations/implications This study has some limitations, as it only analysed the retractions of the top five global universities. Originality/value The study provides a comprehensive analysis of retractions in academic publishing, focusing on reasons, time gaps, article types and accessibility categories across prestigious universities. The paper underscores the critical role of retractions in maintaining the integrity of scientific literature, emphasizing the importance of transparent correction and responsible peer review to ensure the reliability and trustworthiness of published research. Results show that common reasons for retractions include duplication, fake peer review and plagiarism, underlining the need for ethical research standards.

Label-free morphological profiling and isolation of immune cell subsets using VisionSort, a novel, AI-based flow cytometry platform.

Abstract Identification, characterization, and minimally invasive isolation of specific populations of human immune cells are critical for understanding and treating disease. Here we present data on label-free identification of three immune cell subsets by morphological profiling using VisionSort; a label-free, artificial intelligence (AI)-driven cellular analysis and sorting platform. By capturing single-cell digital phenotypes, we characterized mouse T-cells and generated ‘ground truth’ functional profiles for activated and non-activated T cells. A set of machine-learning derived classifiers was generated to identify these phenotypic classes in unlabeled T-cell subsets. The classifier showed an area under the curve (AUC) performance for differentiating between phenotypically defined T cell populations of 0.917. In addition, by using unsupervised machine learning, we were able to resolve activated and non-activated T cell populations label free, using morphological data alone. Using a similar approach, we show label-free differentiation/classification of B cells from plasma cells with an AUC score of 0.941 and M1 and M2 polarized macrophages with an AUC score of 0.878 +/- 0.002 (n=6). Here we report results on the use of a novel, label-free cytometry platform to characterize and isolate human immune cell subsets using morphological profiling and AI with applications for investigators in basic life sciences and drug developers in small molecule, antibody, and cell therapy R&D.

Label-free morphometric characterization of T cells for cell and gene therapy research and development.

Abstract Identification, characterization, and minimally invasive isolation of T cells is critical for developing cellular therapies. Here we used VisionSort, an artificial intelligence (AI)-driven cellular analysis and sorting platform, to characterize and isolate human T cell subsets with therapeutically relevant phenotypes, label-free. By capturing single-cell digital phenotypes, we characterized human T-cells and generated ‘ground truth’ functional profiles for 1) glycolysis level, 2) exhaustion state 3) activation or resting profiles and 4) viability. A set of machine-learning derived classifiers was generated to identify these phenotypic classes label-free. The classifiers showed area under the curve (AUC) performance ranges for detecting specific, phenotypically defined T-cell populations between 0.923 and 0.995. Using a combination of supervised and unsupervised machine learning approaches, we also show identification of follicular helper T (Tfh) cells from other CD4+ T cells based on morphology alone. When we analyzed the morphological profiles of T cell subsets by unsupervised machine learning using uniform maniform projection and approximation (UMAP), we found that both gamma delta (γδ) T cells were distinct from alpha beta (αβ) T cells and CD8+ T cells were distinct from CD4+ T cells. Here we report on the use of AI-based cytometry to characterize and isolate phenotypically defined T cell subsets label-free, with applications in basic life science and cell therapy R&D.

Recombinant production of antibody antigen-binding fragments with an N-terminal human growth hormone tag in mammalian cells

Antigen-binding fragments (Fabs) of antibodies are both key biopharmaceuticals and valuable tools for basic life science. To streamline the production of diverse Fabs by capitalizing on standard and highly optimized protein production protocols, we here explore a method to prepare recombinant Fabs as secreted fusion proteins with an N-terminal human growth hormone domain and an octa-histidine tag. These tagged Fabs can be purified with standard immobilized metal chelate affinity chromatography. We first demonstrated Fab overproduction using the rat monoclonal antibody NZ-1. Optimization of linker residues enabled the complete removal of the tags by TEV protease, leaving only two additional residues at the N-terminus of the heavy chain. We purified NZ-1 Fab at ∼4 μg/mL of culture supernatant and further confirmed that the NZ-1 Fab from the fusion protein maintained its native fold and binding affinity for target cell-surface antigens. We also showed that several other Fabs of mouse IgG1s, the major subclass in mice, could be produced with the same procedure. Our preparation method can provide greater flexibility in functional and structural modifications of target Fabs because specialized purification techniques are not necessary.

Pandemic-Era Digital Education: Insights from an Undergraduate Medical Programme.

The undergraduate medical programme at Newcastle University (NU) includes a fundamental 'Essentials of Medical Practice' (EOMP) phase comprising the first 2 years of study. This period is designed to support entrants in their transition from further education into the advanced study and practice of clinical medicine. The anatomical sciences of gross anatomy, histology and embryology, and life sciences including physiology, pharmacology and genetics are key disciplines taught within the integrated case-based EOMP curriculum. Learners apply basic science knowledge to clinical scenarios during training in practical examination, communication and reasoning skills. Within the modern pedagogic landscape, the development and introduction of technology-enhanced learning strategies have enhanced the provision of remote learning resources in pre-clinical education. However, the emergence of COVID-19 has resulted in widespread technological challenges for educators and learners, and has raised pedagogic, logistical and ethical concerns. Nonetheless, the pandemic has produced favourable conditions for the creation of valuable digital visualisation strategies for learning and teaching, and for developing and modernising universal approaches to remote education. Here, we describe our technology-enhanced adaptations to COVID-19 across the domains of teaching, learning and academic support for pre-clinical learners studying basic life sciences and clinical skills. Moreover, we outline research-informed digital visualisation solutions to pandemic-era challenges and reflect upon experiences gained within our own educational context. In doing so, we provide insights into the impacts and successes of our interventions. While providing a record of unprecedented contemporary circumstances, we also aim to utilise our observations and experiences of COVID-19 pedagogy when developing ongoing strategies for delivering curricula and futureproofing educational practice.

Inclusion of Social and Structural Determinants of Health to Advance Understanding of their Influence on the Biology of Chronic Disease.

Social Determinants of Health (SDOH) consider social, political, and economic factors that contribute to health disparities in patients and populations. The most common health-related SDOH exposures are food and housing insecurity, financial instability, transportation needs, low levels of education, and psychosocial stress. These domains describe risks that can impact health outcomes more than health care. Epidemiologic and translational research demonstrates that SDOH factors represent exposures that predict harm and impact the health of individuals. International and national guidelines urge health professionals to address SDOH in clinical practice and public health. The further implementation of these recommendations into basic and translational research, however, is lagging. Herein, we consider a precision health framework to describe how SDOH contributes to the exposome and exacerbates physiologic pathways that lead to chronic disease. SDOH factors are associated with various forms of stressors that impact physiological processes through epigenetic, inflammatory, and redox regulation. Many SDOH exposures may add to or potentiate the pathologic effects of additional environmental exposures. This overview aims to inform basic life science and translational researchers about SDOH exposures that can confound associations between classic biomedical determinants of disease and health outcomes. To advance the study of toxicology through either qualitative or quantitative assessment of exposures to chemical and biological substances, a more complete environmental evaluation should include SDOH exposures. We discuss common approaches to measure SDOH factors at individual and population levels and review the associations between SDOH risk factors and physiologic mechanisms that influence chronic disease. We provide clinical and policy-based motivation to encourage researchers to consider the impact of SDOH exposures on study results and data interpretation. With valid measures of SDOH factors incorporated into study design and analyses, future toxicological research may contribute to an evidence base that can better inform prevention and treatment options, to improve equitable clinical care and population health. © 2022 Wiley Periodicals LLC.

Applications and challenges of rhodopsin-based optogenetics in biomedicine.

Optogenetics is an emerging bioengineering technology that has been rapidly developed in recent years by cross-integrating optics, genetic engineering, electrophysiology, software control, and other disciplines. Since the first demonstration of the millisecond neuromodulation ability of the channelrhodopsin-2 (ChR2), the application of optogenetic technology in basic life science research has been rapidly progressed, especially in neurobiology, which has driven the development of the discipline. As the optogenetic tool protein, microbial rhodopsins have been continuously explored, modified, and optimized, with many variants becoming available, with structural characteristics and functions that are highly diversified. Their applicability has been broadened, encouraging more researchers and clinicians to utilize optogenetics technology in research. In this review, we summarize the species and variant types of the most important class of tool proteins in optogenetic techniques, the microbial rhodopsins, and review the current applications of optogenetics based on rhodopsin qualitative light in biology and other fields. We also review the challenges facing this technology, to ultimately provide an in-depth technical reference to support the application of optogenetics in translational and clinical research.

Sustained Rise in Retractions in the Life Sciences Literature during the Pandemic Years 2020 and 2021

The COVID-19 pandemic has been devastating to all human endeavors, and scientific research has not been spared. We queried how the retraction of publications might have been affected during the pandemic years 2020–2021. Searches performed with Retraction Watch Database (RWD) revealed that the total number of retractions (as proxied by retraction-related notices) rose steadily from 2013 into the pandemic years 2020–2021. Interestingly, while retractions in the physical and social sciences tapered during 2020–2021, those of the basic life sciences and health sciences showed robust increases in 2020, with the former maintaining a steep rise in 2021. This rise in retractions belied a tapering of total relevant publications in the same year and is confirmed with a complementary search strategy in Scopus. The retraction rate in the medical sciences, particularly those relating to infectious disease, is clearly affected by the anomalous high retraction rate of COVID-19-related papers. However, the sustained increase in the retraction rate of the basic life sciences papers, could be due, at least partly, to retraction spikes in several journals. The rise in retractions in the life and medical sciences could be attributed to heightened post-publication peer review of papers in online platforms such as PubPeer, where numerous problematic papers have been revealed.

Building Indian Biomedical Leadership to Bridge the Gap Between Science, Primary Health Care and Public Health.

The Indian biomedical landscape has been characterized by the existence of somewhat polarized institutional structures and professional growth. While some scientific and public health challenges have been met with existing structures, there is still a large unmet scientific and public health need. Broadly, the physical separation of science, engineering, medical campuses and industry has led to silos of excellence and accomplishment with huge gaps in innovation and implementation. The lack of inter-disciplinary educational options has further reinforced the cultural underpinning of “guilds” that have found it difficult to collaborate. Strikingly, with almost a comparable number of institutions that train doctors in the allopathic or traditional disciplines such as Ayurveda, Unani etc., an “integrative medicine” framework has not emerged, apart from an over reliance on specialization at the expense of primary care. This paper is written by two physician-scientists, the first is located in a basic life science research center. The second, a practicing family physician, from the institutional anchor of a life sciences research institution. In this, we trace our experiences, primarily from a principal investigator’s perspective, describing the scientific projects and try to explore the lessons learnt along the way. We will first describe the research in the lab’s core area of human cervical cancer progression and our more recent effort with Dengue genomics and vaccine design. We then describe the lab's engagement with medical campuses and other agencies as well as review our various meetings and interactions so far with our colleagues from Africa to grasp what might be the “generalizable lessons” for the future. The Indian council of medical research initiated a program with Africa in health sciences. Building upon those interactions, we have taken some incremental steps in that direction and described our efforts.

Metal-free Lewis pairs catalysed synthesis of fluorescently labelled polyester-based amphiphilic polymers for biological imaging

In recent years, the use of fluorescent amphiphilic polymers as the bioimaging agents has achieved significant progress, and promoted the development of the early stage cancer diagnosis and treatment. In this study, a serials of novel nitrobenzoxadiazole (NBD) fluorophore-functionalized polyester-based amphiphilic polymers were designed and synthesized via a two-step process: a hydrophobic polyester backbone was synthesized first by ring-opening alternating copolymerization (ROAC) of phthalic anhydride (PA) and allyl glycidyl ether (AGE) monomers using NBD-OH fluorophore as the initiator and metal-free Lewis pairs as the catalyst; then hydrophilic modified by three different hydrophilic pendants, PEG-SH, mercaptoacetic acid and mono-6-thio-β-cyclodextrin, through thiol-ene click reaction. Notably, directly using fluorophore as the initiator to initiate the ROAC of cyclic anhydrides and epoxides has never been reported. The influence of the feed ratio, type of Lewis pair and reaction temperature upon the polymerization performance were presented and the quantitative introduction of NBD and three kinds of hydrophilic pendants were described in detail as well. Due to the amphiphilic properties, these polymers could facilely self-assemble into fluorescent polymeric nanoparticles, which were characterized by a series of characterization techniques including surface tensiometer, dynamic light scattering (DLS), transmission electronic microscopy (TEM), and fluorescence spectroscopy. These fluorescent polymeric nanoparticles with diameters of tens or hundreds of nanometers showed good particle stability and good fluorescence performance in aqueous solution. The biocompatibility of these fluorescent polymeric nanoparticles was also excellent. In fact, the biological imaging of A549 cells could be realized successfully in the presence of the fluorescent polymeric nanoparticles. This work provides a new strategy and may inspire new approaches to the design and preparation of the biocompatible fluorescent amphiphilic polymers which could be used as the potential biological imaging agents in basic life science research and clinical applications.

Multifunctional Cellular Targeting, Molecular Delivery, and Imaging by Integrated Mesoporous-Silica with Optical Nanocrescent Antenna: MONA.

Multifunctional nanoprobes have attracted significant attention in a wide range of disciplines such as nanomedicine, precision medicine, and cancer diagnosis and treatment. However, integrating multifunctional ability in a nanoscale structure to precisely target, image, and deliver with cellular spatial/temporal resolution is still challenging in cellulo applications. This is because the development of such high-precision resolution needs to be carried out without labeling, photobleaching, and structurally segregating live cells. In this study, we present an integrated nanostructure of a mesoporous-silica nanosphere with an optical nanocrescent antenna (MONA) for multifunctional cellular targeting, drug delivery, and molecular imaging with spatiotemporal resolution. MONA comprises a systematically constructed Au nanocrescent (AuNC) antenna as a nanosensor and optical switch on a mesoporous-silica nanosphere as a cargo to molecular delivery. MONA made of antiepithelial cell adhesion molecules (anti-EpCAM)-conjugated AuNC facilitates the specific targeting of breast cancer cells, resulting in a highly focused photothermal gradient that functions as a molecular emitter. This light-driven molecular, doxorubicin (DOX) delivery function allows rapid apoptosis of breast cancer cells. Since MONA permits the tracking of quantum biological electron-transfer processes, in addition to its role as an on-demand optical switch, it enables the monitoring of the dynamic behavior of cellular cytochrome c pivoting cell apoptosis in response to the DOX delivery. Owing to the integrated functions of molecular actuation and direct sensing at the precisely targeted spot afforded by MONA, we anticipate that this multifunctional optical nanoantenna structure will have an impact in the fields of nanomedicine, cancer theranostics, and basic life sciences.

Reproducibility and research integrity: the role of scientists and institutions

Reproducibility and research integrity are essential tenets of every scientific study and discovery. They serve as proof that an established and documented work can be verified, repeated, and reproduced. New knowledge in the biomedical science is built on the shoulders of established and proven principles. Thus, scientists must be able to trust and build on the knowledge of their colleagues. Scientific innovation and research discoveries especially in the field of medicine has contributed to improving the lives of patients and increasing life expectancies. However, the growing concerns of failure to comply with good scientific principles has resulted in issues with research integrity and reproducibility. Poor reproducibility and integrity, therefore, may lead to ineffective interventions and applications. Here we comment on research reproducibility in basic medical and life sciences with regards to issues arising and outline the role of stakeholders such as research institutions and their employees in addressing this crisis.

Modularize and Unite: Toward Creating a Functional Artificial Cell

An artificial cell is a simplified model of a living system, bringing breakthroughs into both basic life science and applied research. The bottom-up strategy instructs the construction of an artificial cell from nonliving materials, which could be complicated and interdisciplinary considering the inherent complexity of living cells. Although significant progress has been achieved in the past 2 decades, the area is still facing some problems, such as poor compatibility with complex bio-systems, instability, and low standardization of the construction method. In this review, we propose creating artificial cells through the integration of different functional modules. Furthermore, we divide the function requirements of an artificial cell into four essential parts (metabolism, energy supplement, proliferation, and communication) and discuss the present researches. Then we propose that the compartment and the reestablishment of the communication system would be essential for the reasonable integration of functional modules. Although enormous challenges remain, the modular construction would facilitate the simplification and standardization of an artificial cell toward a natural living system. This function-based strategy would also broaden the application of artificial cells and represent the steps of imitating and surpassing nature.

Nanomaterials Upscaling Cell Production and Advancing Exosome-Based Stem Cell Therapies

The COVID-19 pandemic underlined that by investing in both basic and clinical life science research and if there are enough volunteers, it is feasible to have -validated by Phase III clinical trials- vaccines in less than a year. Regarding the treatment options for the people who were infected by COVID-19, we know that it was the large clinical trials - like SOLIDARITY (WHO) and RECOVERY (UK)- that gave the most valid results, and that although hundreds of drugs were repurposed, sadly, most proved to be unsuccessful. Repurposing drugs and compassionate use, were the only options for the first half of 2020. The same applied to the convalescent plasma (CP) approach; however, apart from CP, other cell derived therapeutics were deployed, such as synthetic monoclonal antibodies, which were also tested and given provisional licences by health authorities. Unfortunately, synthetic antibody production comes with problems related to low and slow yield that were not overcome, while SARS-CoV-2 viral mutations may possibly render them less effective. One approach that works and is currently assessed in several clinical trials, is mesenchymal stromal cell (MSCs) and extracellular vesicle (EV) administration for therapy. Interdisciplinarity may prove key here. Easy to produce nanomaterials and biomaterials should be further investigated to increase bioproduction of MSCs, both at the level of therapeutics, as the base substrate for EV production and to upscale synthetic antibody production for therapy.

Assessment of Clinical Awareness of Cardiopulmonary Resuscitation Among Dental Undergraduate Students in the Vidarbha Region

Background: Cardiopulmonary resuscitation (CPR) is an important link in the chain of survival during the early minutes of cardiac arrest. Prompt identification and immediate help increase the chances of survival for victims. As dental students start working on patients from their 3rd year of professional life, important life-threatening situations and lifesaving skills should be known to them. Aims and Objectives: The aim of the present study was to assess the awareness of CPR among dental students from 3rd and final year. Materials and Methods: In this study, students of 3rd year and final year of dental colleges of the Vidarbha region were included to access the basic knowledge regarding basic life science skills while performing CPR through a questionnaire that consisted of 20 questions. The questionnaire was circulated among students in Google forms and responses were noted. After excluding the incomplete response, the results were then analyzed. Results: The results were expressed in appropriate graphs and tables. It was observed that the participants included were lacking about complete knowledge of CPR. Among 206 students who responded, a large number of them (around 94%) had not heard of basic life support (BLS)/CPR. Rescue breathing in infants was not known to around 85% of students, chest compression and ventilation ratio in a child was known by only about 11% of students, and the first response in suspected foreign body obstruction was not known to about 90% of the students. The overall result was not favorable and the students had low confidence in performing BLS/CPR. Conclusion: The result of the current study indicates a strong need for emphasis on both theoretical and practical training in CPR for undergraduate dental students. This might prove beneficial to save more lives while avoiding medicolegal complications which may occur in the dental clinic also, thus benefiting both the patient and the dental practitioners as well.

Phenotypic screening system using three-dimensional (3D) culture models for natural product screening.

Recent progress in three-dimensional (3D) cell culture systems has attracted much attention in the fields of basic life science and drug development. Newly established methods include 3D co-culture, spheroid culture, and organoid culture; these methods enable more human tissue-like culture and have largely replaced traditional two-dimensional (2D) monolayer culture. By combining 3D culture methods with high-content imaging analysis, it is possible to obtain diverse and convincing data even during initial screening (which requires rapid and easy operating procedures). Until recently, 3D culture methods were considered expensive, time-consuming, complex, and unstable. However, by exploiting the self-assembling nature of cells and adding several technical improvements, we have developed several phenotypic screenings aimed at discovering anticancer compounds.

GdClean: removal of Gadolinium contamination in mass cytometry data.

Mass cytometry (Cytometry by Time-Of-Flight, CyTOF) is a single-cell technology that is able to quantify multiplex biomarker expressions and is commonly used in basic life science and translational research. However, the widely used Gadolinium (Gd)-based contrast agents (GBCAs) in magnetic resonance imaging (MRI) scanning in clinical practice can lead to signal contamination on the Gd channels in the CyTOF analysis. This Gd contamination greatly affects the characterization of the real signal from Gd-isotope-conjugated antibodies, severely impairing the CyTOF data quality and ruining downstream single-cell data interpretation. We first in-depth characterized the signals of Gd isotopes from a control sample that was not stained with Gd-labeled antibodies but was contaminated by Gd isotopes from GBCAs, and revealed the collinear intensity relationship across Gd contamination signals. We also found that the intensity ratios of detected Gd contamination signals to the reference Gd signal were highly correlated with the natural abundance ratios of corresponding Gd isotopes. We then developed a computational method named by GdClean to remove the Gd contamination signal at the single-cell level in the CyTOF data. We further demonstrated that the GdClean effectively cleaned up the Gd contamination signal while preserving the real Gd-labeled antibodies signal in Gd channels. All of these shed lights on the promising applications of the GdClean method in preprocessing CyTOF datasets for revealing the true single-cell information. The R package GdClean is available on GitHub at https://github.com/JunweiLiu0208/GdClean. Supplementary data are available at Bioinformatics online.

Anti-inflammatory Compounds from the Hydrolysate of Indian Marine Green Mussel (Perna viridis L)

Natural products offer a great hope in identifying bioactive compounds and their development into drugs to treat several diseases including inflammatory problems. Ocean has been considered as a rich source of such compounds with novel structures and important biological activities. Traditional medicine is widespread and natural compounds represent a large source of naturally occurring secondary metabolites that might lead to novel drugs. The ocean also offers the potential for producing metabolites, which may be different from the terrestrial organisms. Due to the complex nature and dynamic system in the ocean, the marine organisms have developed unique metabolic and physiologic capabilies that ensure their survival in extreme variations of pressure, salinity and temperature. Marine organisms, including mussel, have produced a variety of chemically interesting and biologically significant secondary metabolites. Some are expected to serve as lead compounds for drug development or pharmacological tools for basic life science studies. Marine animals can survive in an inimical environment surrounded by various pathogenic organisms, including human pathogens. They are also potential sources for bioactive compounds as observed in edible bivalves, such as Meretrix casta (Chemnitz), Polymesoda (Geloina) Polymesoda erosa (Solander), Perna viridis (Linnaeus), Crassostrea gryphoides (Schlothim), and Villorita cyprinoides (Grey). Recent studies conducted have shown that green mussels are an inexpensive source of protein for human consumption and possess some important complex potential bioactive compounds useful as medicines. Isolation of bioactive compounds like anti-inflammatory from marine sources has been receiving special attention among natural bioactive compounds because of their economic significance effectiveness and the increasing incidents of drug resistance lead to difficulties in the pharmacological field. The present study reviewed the anti-inflammatory compounds from the hydrolysate prepared from green mussel which will be identified and characterized for commercial use.

Using proteomic and transcriptomic data to assess activation of intracellular molecular pathways.

Analysis of molecular pathway activation is the recent instrument that helps to quantize activities of various intracellular signaling, structural, DNA synthesis and repair, and biochemical processes. This may have a deep impact in fundamental research, bioindustry, and medicine. Unlike gene ontology analyses and numerous qualitative methods that can establish whether a pathway is affected in principle, the quantitative approach has the advantage of exactly measuring the extent of a pathway up/downregulation. This results in emergence of a new generation of molecular biomarkers-pathway activation levels, which reflect concentration changes of all measurable pathway components. The input data can be the high-throughput proteomic or transcriptomic profiles, and the output numbers take both positive and negative values and positively reflect overall pathway activation. Due to their nature, the pathway activation levels are more robust biomarkers compared to the individual gene products/protein levels. Here, we review the current knowledge of the quantitative gene expression interrogation methods and their applications for the molecular pathway quantization. We consider enclosed bioinformatic algorithms and their applications for solving real-world problems. Besides a plethora of applications in basic life sciences, the quantitative pathway analysis can improve molecular design and clinical investigations in pharmaceutical industry, can help finding new active biotechnological components and can significantly contribute to the progressive evolution of personalized medicine. In addition to the theoretical principles and concepts, we also propose publicly available software for the use of large-scale protein/RNA expression data to assess the human pathway activation levels.

A Multi-Omics Analysis of PON1 Lactonase Activity in Relation to Human Health and Disease.

Paraoxonase 1 (PON1) enzyme has antioxidative properties and is present in mammalian blood and several other body fluids. In blood, PON1 is usually integrated into the high-density lipoprotein (HDL) cholesterol. PON1 is a highly versatile enzyme displaying diverse functions such as arylesterase, lactonase, and paraoxonase, among others. PON1 activities are usually investigated with artificial substrates, for example, dihydrocoumarin and thiobutyl butyrolactone for lactonase activity. The PON1 enzyme activities measured with different substrates tend to be falsely assumed as being equivalent in the literature, although there are poor or weak correlations among the PON1 enzyme activities with different substrates. In addition, and despite our knowledge of the factors influencing PON1 paraoxonase and arylesterase activities, there is little knowledge of PON1 lactonase activity variations and attendant mechanisms. This is important considering further that the lactonase activity is the native activity of PON1. We report here a multi-omics analysis of PON1 lactonase activity. The influence of genetic variations, particularly of single nucleotide polymorphisms and epigenetic, proteomic, and lipidomic variations on PON1 lactonase activity are reviewed. In addition, the influence of various environmental, clinical, and demographic variables on PON1 lactonase activity is discussed. Finally, we examine the associations between PON1 lactonase activity and health states and common complex diseases such as atherosclerosis, dementias, obesity, and diabetes. To the best of our knowledge, this is the first multi-omics analysis of PON1 lactonase activity with an eye to future applications in basic life sciences and translational medicine and the nuances of critically interpreting PON1 function with lactones as substrates.