Adipose-derived stem cells therapy effectively attenuates PM2.5-induced lung injury

Abstract Background The adverse health effects of fine particulate matter (PM2.5) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM2.5-induced lung injury has not been investigated. Method C57BL/6 mice were exposed to PM2.5 every other day via intratracheal instillation for 4 weeks. After that, the mice received tail vein injections of ADSCs every 2 weeks. Results ADSC transplantation significantly attenuated systemic and pulmonary inflammation, cardiac dysfunction, fibrosis, and cell death in PM2.5-exposed mice. RNA-sequencing results and bioinformatic analysis suggested that the downregulated differentially expressed genes (DEGs) were mainly enriched in inflammatory and immune pathways. Moreover, ADSC transplantation attenuated PM2.5-induced cell apoptosis and pyroptosis in the lungs and hearts. Conclusion ADSCs protect against PM2.5-induced adverse health effects through attenuating pulmonary inflammation and cell death. Our findings suggest that ADSC transplantation may be a potential therapeutic approach for severe air pollution-associated diseases.

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Influence of DMT1 and iron status on inflammatory responses in the lung

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00343.2010 ◽

2011 ◽

Vol 300 (4) ◽

pp. L659-L665 ◽

Cited By ~ 22

Author(s):

Jonghan Kim ◽

Ramon M. Molina ◽

Thomas C. Donaghey ◽

Peter D. Buckett ◽

Joseph D. Brain ◽

...

Keyword(s):

Lung Injury ◽

Inflammatory Responses ◽

Iron Status ◽

Pulmonary Inflammation ◽

Intratracheal Instillation ◽

Cell Content ◽

Divalent Metal Transporter 1 ◽

Divalent Metal Transporter ◽

Metal Transporter

Divalent metal transporter 1 (DMT1) is the major iron transporter responsible for duodenal dietary iron absorption and is required for erythropoiesis. Recent studies suggest that loss of DMT1 activity could be involved in metal-related lung injury, but little is known about the effects of iron status and DMT1 function on pulmonary inflammation. To better define the role of DMT1 and iron status in pulmonary inflammatory responses, we performed bronchoalveolar lavage (BAL) following intratracheal instillation of lipopolysaccharide (LPS) to the Belgrade rat, an animal model deficient in DMT1 function. In the basal state, the BAL fluid of Belgrade rats had more macrophages and higher lactate dehydrogenase, myeloperoxidase, albumin, and hemoglobin levels compared with heterozygote control rats. Following LPS instillation, the macrophage fraction relative to total BAL cell content and levels of albumin and IgM were increased in Belgrade rats compared with controls. In contrast, heterozygote Belgrade rats made anemic by diet-induced iron deficiency exhibited attenuated inflammatory responses to LPS. These combined results show that pulmonary inflammation can be modified by both DMT1 and iron status. Loss of DMT1 alters pulmonary responses necessary for lung homeostasis in the basal state and enhances LPS-induced inflammation and therefore would contribute to progression of lung injury.

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HUMAN EXPOSURE TO MERCURY: A CRITICAL ASSESSMENT OF THE EVIDENCE OF ADVERSE HEALTH EFFECTS

Journal of Toxicology and Environmental Health Part A ◽

10.1080/009841096160817 ◽

1996 ◽

Vol 49 (3) ◽

pp. 221-270 ◽

Cited By ~ 62

Author(s):

Hope E. Ratcliffe, G. Marie Swanson, Law

Keyword(s):

Health Effects ◽

Human Exposure ◽

Critical Assessment ◽

Adverse Health Effects ◽

Adverse Health

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169. Evaluating and Designing Exhaust Systems to Avoid Fume Reentry and Adverse Health Effects

10.3320/1.2763004 ◽

1999 ◽

Author(s):

R. Petersen ◽

B. Cochran ◽

J. Carter

Keyword(s):

Health Effects ◽

Adverse Health Effects ◽

Adverse Health ◽

Exhaust Systems

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Study protocol for a randomised controlled trial examining the effect of blood and plasma donation on serum perfluoroalkyl and polyfluoroalkyl substance (PFAS) levels in firefighters

BMJ Open ◽

10.1136/bmjopen-2020-044833 ◽

2021 ◽

Vol 11 (5) ◽

pp. e044833

Author(s):

Gabriel Silver ◽

Yordanka Krastev ◽

Miriam K Forbes ◽

Brenton Hamdorf ◽

Barry Lewis ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Health Effects ◽

Whole Blood ◽

Sulfonic Acid ◽

Controlled Trial ◽

Adverse Health Effects ◽

Plasma Donation ◽

Adverse Health ◽

Study Results ◽

Randomised Controlled

IntroductionPerfluoroalkyl and polyfluoroalkyl substances (PFAS) are a diverse group of compounds that have been used in hundreds of industrial applications and consumer products including aqueous film-forming foam (AFFF) for many years. Multiple national and international health and environmental agencies have accepted that PFAS exposures are associated with numerous adverse health effects. Australian firefighters have been shown to have elevated levels of PFAS in their blood, specifically perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), due to the historical use of AFFF. While PFAS concentrations decline over time once the source of exposure has been removed, their potential adverse health effects are such that it would be prudent to develop an intervention to lower levels at a faster rate than occurs via natural elimination rates.Methods and analysisThis is a randomised controlled trial of current and former Australian firefighters in the Metropolitan Fire Brigade/Fire Rescue Victoria, and contractors, with previous occupational exposure to PFAS and baseline elevated PFOS levels. The study is investigating whether whole blood donation every 12 weeks or plasma donation every 6 weeks will significantly reduce PFAS levels, compared with a control group. We have used covariate-adaptive randomisation to balance participants’ sex and blood PFAS levels between the three groups and would consider a 25% reduction in serum PFOS and PFHxS levels to be potentially clinically significant after 12 months of whole blood or plasma donation. A secondary analysis of health biomarkers is being made of changes between screening and week 52 in all three groups.Ethics and disseminationThis trial has been approved by Macquarie University Human Research Ethics Committee (reference number: 3855), final protocol V.2 dated 12 June 2019. Study results will be disseminated via peer-reviewed publications and presentations at conferences.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000204145).

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Adverse Health Effects of Frailty: Systematic Review and Meta‐Analysis of Middle‐Aged and Older Adults With Implications for Evidence‐Based Practice

Worldviews on Evidence-Based Nursing ◽

10.1111/wvn.12508 ◽

2021 ◽

Author(s):

Wen Chu ◽

Shu‐Fang Chang ◽

Hsu‐Yu Ho

Keyword(s):

Systematic Review ◽

Older Adults ◽

Health Effects ◽

Evidence Based Practice ◽

Meta Analysis ◽

Evidence Based ◽

Middle Aged ◽

Adverse Health Effects ◽

Adverse Health

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Disrupting the Flow of Perception-Action through Design

Adaptive Behavior ◽

10.1177/1059712321989099 ◽

2021 ◽

pp. 105971232198909

Author(s):

Harry Heft

Keyword(s):

Cultural History ◽

Health Effects ◽

Sense Of Place ◽

Attentional Focus ◽

Good Design ◽

Adverse Health Effects ◽

Adverse Health ◽

Directed Action ◽

Perception Action

It is usually a mark of good design when technologies and tools that mediate goal-directed action are such that the user’s attentional focus is maintained on the intended ends of action rather than on the technologies and tools themselves. When the mediators become the focus, the continuity of goal-directed action is disrupted, and the flow of action can be re-directed. What then is the purpose of the projects designed by the RAAAF studio, as described by Rietveld, which seem to be intended to do both? Disruption of the continuity of goal-directed perception-action may prompt reflection about the circumstances at work, and in so doing provoke a transformation in habitual patterns of action and of thought. The project “The End of Sitting” is intended to remediate the adverse health effects of standard chair-dominated offices through an unconventional office landscape that prompts intermittent postural readjustments, boosting the levels of activity common in such settings. The project “Bunker 599” demonstrates that seemingly unremarkable features of the landscape can sometimes conceal aspects of culture’s history, and that design can function to draw attention to a hidden and even vanishing history. Design can enrich an individual’s sense of place in a stream of cultural history.

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Gene engineered mesenchymal stem cells: greater transgene expression and efficacy with minicircle vs. plasmid DNA vectors in a mouse model of acute lung injury

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02245-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Maria Florian ◽

Jia-Pey Wang ◽

Yupu Deng ◽

Luciana Souza-Moreira ◽

Duncan J. Stewart ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Acute Lung Injury ◽

Lung Injury ◽

Transgene Expression ◽

Vascular Inflammation ◽

Pulmonary Inflammation ◽

Necrosis Factor Alpha ◽

Monocyte Chemoattractant Protein 1 ◽

Therapeutic Benefits

Abstract Background Acute lung injury (ALI) and in its severe form, acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance the potency of mesenchymal stem cells (MSCs) to develop more effective treatments. Genetic modification of MSCs has been demonstrated to significantly improve the therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear. Given the acute nature of ARDS, transient transfection is desirable to avoid off-target effects of long-term transgene expression, as well as the potential adverse consequences of genomic integration. Methods Here, we explored whether a minicircle DNA (MC) vector containing human angiopoietin 1 (MC-ANGPT1) can provide a more effective platform for gene-enhanced MSC therapy of ALI/ARDS. Results At 24 h after transfection, nuclear-targeted electroporation using an MC-ANGPT1 vector resulted in a 3.7-fold greater increase in human ANGPT1 protein in MSC conditioned media compared to the use of a plasmid ANGPT1 (pANGPT1) vector (2048 ± 567 pg/mL vs. 552.1 ± 33.5 pg/mL). In the lipopolysaccharide (LPS)-induced ALI model, administration of pANGPT1 transfected MSCs significantly reduced bronchoalveolar lavage (BAL) neutrophil counts by 57%, while MC-ANGPT1 transfected MSCs reduced it by 71% (p < 0.001) by Holm-Sidak’s multiple comparison test. Moreover, compared to pANGPT1, the MC-ANGPT1 transfected MSCs significantly reduced pulmonary inflammation, as observed in decreased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). pANGPT1-transfected MSCs significantly reduced BAL albumin levels by 71%, while MC-ANGPT1-transfected MSCs reduced it by 85%. Conclusions Overall, using a minicircle vector, we demonstrated an efficient and sustained expression of the ANGPT1 transgene in MSCs and enhanced the therapeutic effect on the ALI model compared to plasmid. These results support the potential benefits of MC-ANGPT1 gene enhancement of MSC therapy to treat ARDS.

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Impact of Carcinogenic Chromium on the Cellular Response to Proteotoxic Stress

International Journal of Molecular Sciences ◽

10.3390/ijms20194901 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4901 ◽

Cited By ~ 6

Author(s):

Leonardo M. R. Ferreira ◽

Teresa Cunha-Oliveira ◽

Margarida C. Sobral ◽

Patrícia L. Abreu ◽

Maria Carmen Alpoim ◽

...

Keyword(s):

Stress Response ◽

Health Effects ◽

Cellular Response ◽

Molecular Mechanisms ◽

Critical Role ◽

Chemical Properties ◽

Adverse Health Effects ◽

Proteotoxic Stress ◽

Adverse Health ◽

The Impact

Worldwide, several million workers are employed in the various chromium (Cr) industries. These workers may suffer from a variety of adverse health effects produced by dusts, mists and fumes containing Cr in the hexavalent oxidation state, Cr(VI). Of major importance, occupational exposure to Cr(VI) compounds has been firmly associated with the development of lung cancer. Counterintuitively, Cr(VI) is mostly unreactive towards most biomolecules, including nucleic acids. However, its intracellular reduction produces several species that react extensively with biomolecules. The diversity and chemical versatility of these species add great complexity to the study of the molecular mechanisms underlying Cr(VI) toxicity and carcinogenicity. As a consequence, these mechanisms are still poorly understood, in spite of intensive research efforts. Here, we discuss the impact of Cr(VI) on the stress response—an intricate cellular system against proteotoxic stress which is increasingly viewed as playing a critical role in carcinogenesis. This discussion is preceded by information regarding applications, chemical properties and adverse health effects of Cr(VI). A summary of our current understanding of cancer initiation, promotion and progression is also provided, followed by a brief description of the stress response and its links to cancer and by an overview of potential molecular mechanisms of Cr(VI) carcinogenicity.

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