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1.
Chemodynamic features of nanoparticles: Application to understanding the dynamic life cycle of SARS-CoV-2 in aerosols and aqueous biointerfacial zones.
Duval, JFL, van Leeuwen, HP, Norde, W, Town, RM
Advances in colloid and interface science. 2021;:102400
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Abstract
We review concepts involved in describing the chemodynamic features of nanoparticles and apply the framework to gain physicochemical insights into interactions between SARS-CoV-2 virions and airborne particulate matter (PM). Our analysis is highly pertinent given that the World Health Organisation acknowledges that SARS-CoV-2 may be transmitted by respiratory droplets, and the US Center for Disease Control and Prevention recognises that airborne transmission of SARS-CoV-2 can occur. In our theoretical treatment, the virion is assimilated to a core-shell nanoparticle, and contributions of various interaction energies to the virion-PM association (electrostatic, hydrophobic, London-van der Waals, etc.) are generically included. We review the limited available literature on the physicochemical features of the SARS-CoV-2 virion and identify knowledge gaps. Despite the lack of quantitative data, our conceptual framework qualitatively predicts that virion-PM entities are largely able to maintain equilibrium on the timescale of their diffusion towards the host cell surface. Comparison of the relevant mass transport coefficients reveals that virion biointernalization demand by alveolar host cells may be greater than the diffusive supply. Under such conditions both the free and PM-sorbed virions may contribute to the transmitted dose. This result points to the potential for PM to serve as a shuttle for delivery of virions to host cell targets. Thus, our critical review reveals that the chemodynamics of virion-PM interactions may play a crucial role in the transmission of COVID-19, and provides a sound basis for explaining reported correlations between episodes of air pollution and outbreaks of COVID-19.
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Resolving Human Lactation Heterogeneity Using Single Milk-Derived Cells, a Resource at the Ready.
Martin Carli, JF, Trahan, GD, Rudolph, MC
Journal of mammary gland biology and neoplasia. 2021;(1):3-8
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Abstract
Single cell RNA sequencing (scRNAseq) of human milk-derived cells (HMDCs) makes highly detailed analyses of the biology of human lactation possible. We explore this powerful application as an exciting tool to inspect the cellular composition of human milk. We point out some important challenges unique to this approach and highlight the importance of collaborations between biologists and well-trained bioinformaticians to utilize these data to their maximum potential. We extend this focus by discussing the first two such studies that describe HMDCs via scRNAseq and a variety of important questions in the field that warrant attention through further research. The stage is set to apply scRNAseq in human lactation biology, potentially leading to new insights regarding the molecular and cellular diversity of human secretory mammary epithelial cells.
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Intracellular Cl- Regulation of Ciliary Beating in Ciliated Human Nasal Epithelial Cells: Frequency and Distance of Ciliary Beating Observed by High-Speed Video Microscopy.
Yasuda, M, Inui, TA, Hirano, S, Asano, S, Okazaki, T, Inui, T, Marunaka, Y, Nakahari, T
International journal of molecular sciences. 2020;(11)
Abstract
Small inhaled particles, which are entrapped by the mucous layer that is maintained by mucous secretion via mucin exocytosis and fluid secretion, are removed from the nasal cavity by beating cilia. The functional activities of beating cilia are assessed by their frequency and the amplitude. Nasal ciliary beating is controlled by intracellular ions (Ca2+, H+ and Cl-), and is enhanced by a decreased concentration of intracellular Cl- ([Cl-]i) in ciliated human nasal epithelial cells (cHNECs) in primary culture, which increases the ciliary beat amplitude. A novel method to measure both ciliary beat frequency (CBF) and ciliary beat distance (CBD, an index of ciliary beat amplitude) in cHNECs has been developed using high-speed video microscopy, which revealed that a decrease in [Cl-]i increased CBD, but not CBF, and an increase in [Cl-]i decreased both CBD and CBF. Thus, [Cl-]i inhibits ciliary beating in cHNECs, suggesting that axonemal structures controlling CBD and CBF may have Cl- sensors and be regulated by [Cl-]i. These observations indicate that the activation of Cl- secretion stimulates ciliary beating (increased CBD) mediated via a decrease in [Cl-]i in cHNECs. Thus, [Cl-]i is critical for controlling ciliary beating in cHNECs. This review introduces the concept of Cl- regulation of ciliary beating in cHNECs.
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Antiepithelial-Mesenchymal Transition of Herbal Active Substance in Tumor Cells via Different Signaling.
Cui, X, Lin, Q, Huang, P, Liang, Y
Oxidative medicine and cellular longevity. 2020;:9253745
Abstract
Epithelial-mesenchymal transition (EMT) is a biological process through which epithelial cells differentiate into mesenchymal cells. EMT plays an important role in embryonic development and wound healing; however, EMT also contributes to some pathological processes, such as tumor metastasis and fibrosis. EMT mechanisms, including gene mutation and transcription factor regulation, are complicated and not yet well understood. In this review, we introduce some herbal active substances that exert antitumor activity through inhibiting EMT that is induced by hypoxia, high blood glucose level, lipopolysaccharide, or other factors.
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Regulation of mucin 1 expression and its relationship with oral diseases.
Kashyap, B, Kullaa, AM
Archives of oral biology. 2020;:104791
Abstract
OBJECTIVE The aim of this study is to describe the polymorphic mucin 1 (MUC1), and to provide an overview of the known complex and multiple functions of MUC1 in normal oral mucosa and oral mucosal lesions in compromised situations as well as exploring the challenges associated with the heterogeneous nature of MUC1. We will review the current knowledge and provide insights into the future management possibilities of using MUC1 as a therapeutic agent. METHODS A literature search of the electronic databases included MEDLINE (1966 -December 2019) and hand searches of cross-references were undertaken using terms related to mucins, MUC1. RESULTS MUC1 is a large transmembrane glycoprotein expressed on the apical surface of most of epithelial cell surfaces. Not only is it involved in lubrication, cell surface hydration, and protection against degrading enzymes, MUC1 also promotes abnormal cellular signalling, angiogenesis, anti-adhesion and tumorigenesis. Aberrant glycosylation, overexpression, loss of apical constraint are characteristics of the transformation of a normal cell to a cancerous cell. This review summarizes studies of MUC1 expression and function with a special emphasis on oral epithelial cells in normal and abnormal conditions. In addition, current knowledge of MUC1 and unexplored areas of MUC1 are presented. CONCLUSION MUC1 is an archetypical transmembrane protein, the presence of MUC1 in ectopic regions may lead to dysregulation of certain enzymes and activation of various pathways, favouring the development of inflammatory responses and tumour formation. This review examines the potential of MUC1 in the development of future therapeutics.
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Mycotoxins: Biotransformation and Bioavailability Assessment Using Caco-2 Cell Monolayer.
Tran, VN, Viktorová, J, Ruml, T
Toxins. 2020;(10)
Abstract
The determination of mycotoxins content in food is not sufficient for the prediction of their potential in vivo cytotoxicity because it does not reflect their bioavailability and mutual interactions within complex matrices, which may significantly alter the toxic effects. Moreover, many mycotoxins undergo biotransformation and metabolization during the intestinal absorption process. Biotransformation is predominantly the conversion of mycotoxins meditated by cytochrome P450 and other enzymes. This should transform the toxins to nontoxic metabolites but it may possibly result in unexpectedly high toxicity. Therefore, the verification of biotransformation and bioavailability provides valuable information to correctly interpret occurrence data and biomonitoring results. Among all of the methods available, the in vitro models using monolayer formed by epithelial cells from the human colon (Caco-2 cell) have been extensively used for evaluating the permeability, bioavailability, intestinal transport, and metabolism of toxic and biologically active compounds. Here, the strengths and limitations of both in vivo and in vitro techniques used to determine bioavailability are reviewed, along with current detailed data about biotransformation of mycotoxins. Furthermore, the molecular mechanism of mycotoxin effects is also discussed regarding the disorder of intestinal barrier integrity induced by mycotoxins.
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Mucosal-Associated Invariant T Cells in Tumors of Epithelial Origin.
Zumwalde, NA, Gumperz, JE
Advances in experimental medicine and biology. 2020;:63-77
Abstract
Mucosal-associated invariant T (MAIT) cells are innate T lymphocytes that circulate in blood and also reside in mucosal tissues. Blood MAIT cells are typically highly Th1-polarized, while those in mucosal tissues include both Th1- and Th17-polarized subsets. MAIT cells mount cytokine and cytolytic responses as a result of T cell receptor (TCR)-mediated recognition of microbially derived metabolites of riboflavin (vitamin B2) presented by the MR1 antigen-presenting molecule. Additionally, MAIT cells can be activated by inflammatory cytokines produced by antigen-presenting cells (APCs) that have been exposed to pathogen-associated molecular patterns (PAMPs). Since the antigenic metabolites of riboflavin recognized by MAIT cells are produced by many microorganisms, including pathogens as well as non-pathogenic colonists, the inflammatory state of the tissue may be a key feature that determines the nature of MAIT cell responses. Under normal conditions where inflammatory cytokines are not produced, MAIT cell responses to microbial metabolites may simply serve to help maintain a healthy balance between epithelial cells and microbial colonists. In contrast, in situations where inflammatory cytokines are produced (e.g., pathogenic infection or damage to epithelial tissue), MAIT cell responses may be more potently pro-inflammatory. Since chronic inflammation and microbial drivers are associated with tumorigenesis and also trigger MAIT cell responses, the nexus of MAIT cells, local microbiomes, and epithelial cells may play an important role in epithelial carcinogenesis. This chapter reviews current information about MAIT cells and epithelial tumors, where the balance of evidence suggests that enrichment of Th17-polarized MAIT cells at tumor sites associates with poor patient prognosis. Studying the role of MAIT cells and their interactions with resident microbes offers a novel view of the biology of epithelial tumor progression and may ultimately lead to new approaches to target MAIT cells clinically.
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The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis.
Tomaipitinca, L, Mandatori, S, Mancinelli, R, Giulitti, F, Petrungaro, S, Moresi, V, Facchiano, A, Ziparo, E, Gaudio, E, Giampietri, C
Nutrients. 2019;(4)
Abstract
: Autophagy plays a role in several physiological and pathological processes as it controls the turnover rate of cellular components and influences cellular homeostasis. The liver plays a central role in controlling organisms' metabolism, regulating glucose storage, plasma proteins and bile synthesis and the removal of toxic substances. Liver functions are particularly sensitive to autophagy modulation. In this review we summarize studies investigating how autophagy influences the hepatic metabolism, focusing on fat accumulation and lipids turnover. We also describe how autophagy affects bile production and the scavenger function within the complex homeostasis of the liver. We underline the role of hepatic autophagy in counteracting the metabolic syndrome and the associated cardiovascular risk. Finally, we highlight recent reports demonstrating how the autophagy occurring within the liver may affect skeletal muscle homeostasis as well as different extrahepatic solid tumors, such as melanoma.
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New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress.
Georgescu, SR, Mitran, CI, Mitran, MI, Caruntu, C, Sarbu, MI, Matei, C, Nicolae, I, Tocut, SM, Popa, MI, Tampa, M
Journal of immunology research. 2018;:5315816
Abstract
Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for epithelial cells. To this date, over 150 genotypes are known and are classified into two major groups, low-risk and high-risk strains, depending on the ability of the virus to induce malignant transformation. The host's immunity plays a central role in the course of the infection; therefore, it may not be clinically manifest or may produce various benign or malignant lesions. The pathogenic mechanisms are complex and incompletely elucidated. Recent research suggests the role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV infection and the associated carcinogenic processes. Chronic inflammation induces OS, which in turn promotes the perpetuation of the inflammatory process resulting in the release of numerous molecules which cause cell damage. Reactive oxygen species exert a harmful effect on proteins, lipids, and nucleic acids. Viral oncogenes E5, E6, and E7 are involved in the development of chronic inflammation through various mechanisms. In addition, HPV may interfere with redox homeostasis of host cells, inducing OS which may be involved in the persistence of the infection and play a certain role in viral integration and promotion of carcinogenesis. Knowledge regarding the interplay between chronic inflammation and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has important consequences on the development of new therapeutic strategies.
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Airway Epithelial Differentiation and Mucociliary Clearance.
Whitsett, JA
Annals of the American Thoracic Society. 2018;(Suppl 3):S143-S148
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Abstract
The lung is continuously exposed to particles, toxicants, and microbial pathogens that are cleared by a complex mechanical, innate, and acquired immune system. Mucociliary clearance, mediated by the actions of diverse conducting airway and submucosal gland epithelial cells, plays a critical role in a multilayered defense system by secreting fluids, electrolytes, antimicrobial and antiinflammatory proteins, and mucus onto airway surfaces. The mucociliary escalator removes particles and pathogens by the mechanical actions of cilia and cough. Abnormalities in mucociliary clearance, whether related to impaired fluid secretion, ciliary dysfunction, lack of cough, or the disruption of epithelial cells lining the respiratory tract, contribute to the pathogenesis of common chronic pulmonary disorders. Although mucus and other airway epithelial secretions play a critical role in protecting the lung during acute injury, impaired mucus clearance after chronic mucus hyperproduction causes airway obstruction and infection, which contribute to morbidity in common pulmonary disorders, including chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, cystic fibrosis, bronchiectasis, and primary ciliary dyskinesia. In this summary, the molecular and cellular mechanisms mediating airway mucociliary clearance, as well as the role of goblet cell metaplasia and mucus hyperproduction, in the pathogenesis of chronic respiratory diseases are considered.