Lipidome profiling with Raman microspectroscopy identifies macrophage response to surface topographies of implant materials

Biomaterial characteristics such as surface topographies have been shown to modulate macrophage phenotypes. The standard methodologies to measure macrophage response to biomaterials are marker-based and invasive. Raman microspectroscopy (RM) is a marker-independent, noninvasive technology that allows the analysis of living cells without the need for staining or processing. In the present study, we analyzed human monocyte-derived macrophages (MDMs) using RM, revealing that macrophage activation by lipopolysaccharides (LPS), interferons (IFN), or cytokines can be identified by lipid composition, which significantly differs in M0 (resting), M1 (IFN-γ/LPS), M2a (IL-4/IL-13), and M2c (IL-10) MDMs. To identify the impact of a biomaterial on MDM phenotype and polarization, we cultured macrophages on titanium disks with varying surface topographies and analyzed the adherent MDMs with RM. We detected surface topography–induced changes in MDM biochemistry and lipid composition that were not shown by less sensitive standard methods such as cytokine expression or surface antigen analysis. Our data suggest that RM may enable a more precise classification of macrophage activation and biomaterial–macrophage interaction.

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NOTCH4 Exhibits Anti-Inflammatory Activity in Activated Macrophages by Interfering With Interferon-γ and TLR4 Signaling

Frontiers in Immunology ◽

10.3389/fimmu.2021.734966 ◽

2021 ◽

Vol 12 ◽

Author(s):

Susana López-López ◽

María José Romero de Ávila ◽

Natalia Carolina Hernández de León ◽

Francisco Ruiz-Marcos ◽

Victoriano Baladrón ◽

...

Keyword(s):

Notch Signaling ◽

Macrophage Activation ◽

Transcriptional Activity ◽

Target Genes ◽

Regulatory Element ◽

Interferon Γ ◽

Negative Regulator ◽

Signal Pathways ◽

Macrophage Response ◽

Ifn Γ

NOTCH4 is a member of the NOTCH family of receptors whose expression is intensively induced in macrophages after their activation by Toll-like receptors (TLR) and/or interferon-γ (IFN-γ). In this work, we show that this receptor acts as a negative regulator of macrophage activation by diminishing the expression of proinflammatory cytokines, such as IL-6 and IL-12, and costimulatory proteins, such as CD80 and CD86. We have observed that NOTCH4 inhibits IFN-γ signaling by interfering with STAT1-dependent transcription. Our results show that NOTCH4 reprograms the macrophage response to IFN-γ by favoring STAT3 versus STAT1 phosphorylation without affecting their expression levels. This lower activation of STAT1 results in diminished transcriptional activity and expression of STAT1-dependent genes, including IRF1, SOCS1 and CXCL10. In macrophages, NOTCH4 inhibits the canonical NOTCH signaling pathway induced by LPS; however, it can reverse the inhibition exerted by IFN-γ on NOTCH signaling, favoring the expression of NOTCH-target genes, such as Hes1. Indeed, HES1 seems to mediate, at least in part, the enhancement of STAT3 activation by NOTCH4. NOTCH4 also affects TLR signaling by interfering with NF-κB transcriptional activity. This effect could be mediated by the diminished activation of STAT1. These results provide new insights into the mechanisms by which NOTCH, TLR and IFN-γ signal pathways are integrated to modulate macrophage-specific effector functions and reveal NOTCH4 acting as a new regulatory element in the control of macrophage activation that could be used as a target for the treatment of pathologies caused by an excess of inflammation.

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The Impact of Membrane Lipid Composition on Macrophage Activation in the Immune Defense against Rhodococcus equi and Pseudomonas aeruginosa

International Journal of Molecular Sciences ◽

10.3390/ijms12117510 ◽

2011 ◽

Vol 12 (11) ◽

pp. 7510-7528 ◽

Cited By ~ 18

Author(s):

Axel Schoeniger ◽

Stephanie Adolph ◽

Herbert Fuhrmann ◽

Julia Schumann

Keyword(s):

Pseudomonas Aeruginosa ◽

Lipid Composition ◽

Macrophage Activation ◽

Rhodococcus Equi ◽

Membrane Lipid ◽

Immune Defense ◽

Membrane Lipid Composition ◽

The Impact

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The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder

10.21203/rs.3.rs-1038190/v1 ◽

2021 ◽

Author(s):

Cuihong Zhou ◽

Fen Xue ◽

Qingqing Shi ◽

Shanshan Xue ◽

Tian Zhang ◽

...

Keyword(s):

Early Intervention ◽

Lipid Composition ◽

Stress Disorder ◽

Neuroprotective Effect ◽

Post Traumatic Stress ◽

Therapeutic Mechanism ◽

Specific Regulation ◽

Induced Changes ◽

The Impact ◽

The Brain

Abstract The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of posttraumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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Effect of Glycosaminoglycans on Thrombin- and Atroxin-Induced Fibrin Assembly and Structure

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647117 ◽

1989 ◽

Vol 62 (04) ◽

pp. 1057-1061 ◽

Cited By ~ 7

Author(s):

Marcus E Carr ◽

Patrick L Powers

Keyword(s):

Chondroitin Sulfate ◽

Fiber Diameter ◽

Lag Phase ◽

Low Molecular Weight ◽

Fibrin Gels ◽

Fiber Size ◽

Induced Changes ◽

The Impact ◽

Fiber Radius ◽

Turbidity Increase

SummaryThis study was performed to quantitate the impact of several glycosaminoglycans (GAG) on fibrin assembly and structure. Gel formation was monitored as the increase in optical density at 633 nm subsequent to thrombin (2 NIH u/ml) or atroxin (0.10 mg/ml) addition to solutions of buffered fibrinogen (1 mg/ml) or plasma. Gel absorbance was measured as a function of wavelength (400 to 800 nm) and gel fiber diameter and mass/length ratio (μ) were calculated. Chondroitin sulfate A (CSA)shortened the lag phase, enhanced the maximal rate of turbidity increase, and increased the final gel turbidity of fibrin gels formed by thrombin or atroxin. CSA (16 mg/ml) increased fiber μ from 1.3 to 3.1 × 1013 dalton/cm and fiber radius from 6.0 to 8.6 × 10-6 cm in thrombin-induced gels. μ increased from 0.7 to 2.7 × 1013 dalton/cm and fiber radius from 4 to 7.8 × 10-6 cm for atroxin-induced gels. Above 16 mg/ml, CSA caused fibrinogen precipitation in purified solutions but not in plasma. CSA inhibited thrombin-induced plasma clotting of plasma but effects in atroxin-mediated plasma gels paralleled those seen in purified solutions. Chondroitin sulfate B (CSB)-induced changes in fibrin were similar but slightly less dramatic than those seen with CSA. μ increased from 0.9 to 2.0 × 1013 dalton/cm for thrombin-induced fibrin gels and from 0.8 to 2.3 × 1013 dalton/cm for atroxininduced gels. Low molecular weight heparin (Mr = 5100) slowed fibrin assembly and reduced fiber size by 50% in thrombininduced gels. Changes in μ of atroxin-induced gels were much less pronounced (<20%). This study documents pronounced GAGinduced changes in fibrin structure which vary with GAG species and may mediate significant physiologic functions.

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The impact of the new WHO classification of tumours of the thyroid gland on the frequency of particular thyroid tumours diagnoses - the single institution experience

10.26226/morressier.5b4709846f4cb30010951b1c ◽

2018 ◽

Author(s):

Dariusz Lange ◽

Agata Stanek-Widera

Keyword(s):

Thyroid Gland ◽

Who Classification ◽

Single Institution ◽

The Impact

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ON THE CLASSIFICATION OF DIGITAL TECHNOLOGIES IN CIVIL PROCESS

10.34076/2219-6838-2019-3-27-35 ◽

2019 ◽

pp. 27-35

Author(s):

Alexandr Neznamov

Keyword(s):

Information Processing ◽

Scientific Community ◽

Digital Technologies ◽

Significant Feature ◽

Legal Proceedings ◽

Civil Process ◽

Civil Proceedings ◽

Processing Information ◽

The Impact

Digital technologies are no longer the future but are the present of civil proceedings. That is why any research in this direction seems to be relevant. At the same time, some of the fundamental problems remain unattended by the scientific community. One of these problems is the problem of classification of digital technologies in civil proceedings. On the basis of instrumental and genetic approaches to the understanding of digital technologies, it is concluded that their most significant feature is the ability to mediate the interaction of participants in legal proceedings with information; their differentiating feature is the function performed by a particular technology in the interaction with information. On this basis, it is proposed to distinguish the following groups of digital technologies in civil proceedings: a) technologies of recording, storing and displaying (reproducing) information, b) technologies of transferring information, c) technologies of processing information. A brief description is given to each of the groups. Presented classification could serve as a basis for a more systematic discussion of the impact of digital technologies on the essence of civil proceedings. Particularly, it is pointed out that issues of recording, storing, reproducing and transferring information are traditionally more «technological» for civil process, while issues of information processing are more conceptual.

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Influence of internal and external risks on sustainability of financial system of Аltai krai

Voprosy regionalnoj ekonomiki ◽

10.21499/2078-4023-2018--4-133-136 ◽

2018 ◽

Vol 35 (4) ◽

pp. 133-136

Author(s):

R. N. Ibragimov

Keyword(s):

Sustainable Development ◽

Financial Stability ◽

Management Strategy ◽

Financial System ◽

Risk Management Strategy ◽

The Sustainable Development ◽

The Stability ◽

The Impact

The article examines the impact of internal and external risks on the stability of the financial system of the Altai Territory. Classification of internal and external risks of decline, affecting the sustainable development of the financial system, is presented. A risk management strategy is proposed that will allow monitoring of risks, thereby these measures will help reduce the loss of financial stability and ensure the long-term development of the economy of the region.

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Fish diversity

10.1093/oso/9780198785552.003.0001 ◽

2017 ◽

Author(s):

Derek Burton ◽

Margaret Burton

Keyword(s):

Life Style ◽

Fish Diversity ◽

Additional Species ◽

The Impact ◽

Current Species

Fish diversity is considered in terms of variety of their morphological, taxonomic, habitat and population attributes. Fish, with over 30, 000 current species, represent the largest group of vertebrates. The complexity of classification of a group of this size and antiquity, together with recognition of additional species, demands continuous ongoing revision. The impact of the recent fundamental changes in fish classification in 2016 is discussed. Life in water involves adaptations to widely different habitats which can result in physiological morphological and life-style variations which are reviewed.

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