A multiplex inhalation platform to model in situ like aerosol delivery in a breathing lung-on-chip

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 6, 2023

Prolonged exposure to environmental respirable toxicants can lead the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) fibrosis. The limited number FDA-approved inhaled drugs for these serious lung conditions has led a shift from in vivo towards use alternative vitro human-relevant models better predict toxicity particles preclinical research. While there are several inhalation upper airways, fragile dynamic nature alveolar microenvironment reproducible distal lung. Here, we present mechanistic approach using new generation systems, Cloud α AX12. This novel tool consists cloud-based chamber (VITROCELL) that integrates breathing AX Lung-on-chip system (AlveoliX). ultrathin porous membrane AX12 plate was used create complex multicellular model enables key physiological culture conditions: air-liquid interface (ALI) three-dimensional cyclic stretch (CS). Human-relevant cellular were established a) alveolar-capillary primary cell-derived immortalized epithelial cells ( iAECs), macrophages (THP-1) endothelial (HLMVEC) cells, b) upper-airways Calu3 cells. Primary human hAEpCs) validate results obtained cell lines. To mimic relevant aerosol exposures with AX12, three different using: titanium dioxide (TiO2) zinc oxide nanoparticles polyhexamethylene guanidine toxic chemical c) an anti-inflammatory corticosteroid, fluticasone propionate (FL). Our suggest important synergistic effect on air-blood barrier sensitivity, cytotoxicity inflammation, when combined. best our knowledge, this is first time been described lung-on-chip technology. thus represents state-of-the-art pre-clinical study risks, drug safety efficacy.

Language: Английский

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Single-Cell RNA Sequencing in Ovarian Cancer: Current Progress and Future Prospects

Progress in Biophysics and Molecular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Prognostic value of CD163+ macrophages in solid tumor malignancies: A scoping review

Immunology Letters, Journal Year: 2025, Volume and Issue: unknown, P. 106970 - 106970

Published: Jan. 1, 2025

Tumor-associated macrophages (TAMs) play crucial roles in development and progression of malignant diseases. Notably, CD163

Language: Английский

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Nanocarriers and macrophage interaction: from a potential hurdle to an alternative therapeutic strategy

Beilstein Journal of Nanotechnology, Journal Year: 2025, Volume and Issue: 16, P. 97 - 118

Published: Jan. 31, 2025

In the coming decades, development of nanocarriers (NCs) for targeted drug delivery will mark a significant advance in field pharmacology. NCs can improve solubility, ensure precise distribution, and enable passage across biological barriers. Despite these potential advantages, interaction with many matrices, particularly existing macrophages, must be considered. this review, we explore dual role macrophages NC delivery, highlighting their physiological functions, challenges posed by mononuclear phagocyte system, innovative strategies to exploit macrophage interactions therapeutic advantage. Recent advancements treating liver lung diseases, focusing on polarization RNA-based therapies, have highlighted developments macrophage-NC interaction. Furthermore, delve into intriguing nanomedicine neurology traumatology, associated interaction, exciting possibilities it holds future.

Language: Английский

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Hallmarks of Aging in Macrophages: Consequences to Skin Inflammaging

Cells, Journal Year: 2021, Volume and Issue: 10(6), P. 1323 - 1323

Published: May 26, 2021

The skin is our largest organ and the outermost protective barrier. Its aging reflects both intrinsic extrinsic processes resulting from constant insults it exposed to. Aging in accompanied by specific epigenetic modifications, accumulation of senescent cells, reduced cellular proliferation/tissue renewal, altered extracellular matrix, a proinflammatory environment favoring undesirable conditions, including disease onset. Macrophages (Mφ) are most abundant immune cell type comprise group heterogeneous plastic cells that key for homeostasis host defense. However, they have also been implicated orchestrating chronic inflammation during aging. Since Mφ related to innate adaptive immunity, possible age-modified promote immunity exacerbation exhaustion, emergence pathologies, such as cancer. In this review, we will highlight recent findings pertaining effects hallmarks over Mφ, supporting recognition types driving force inflammaging age-related diseases. We present research targeting potential therapeutic interventions inflammatory disorders

Language: Английский

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Monocytes and macrophages in ANCA-associated vasculitis

Autoimmunity Reviews, Journal Year: 2021, Volume and Issue: 20(10), P. 102911 - 102911

Published: July 20, 2021

Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) are characterized by inflammation of small-to-medium-sized blood vessels and the presence autoantibodies against proteases sited in neutrophils monocytes. Increasing evidence indicates a substantial role monocytes macrophages pathogenesis AAV. Activated contribute to necroinflammation peripheral vasculitic lesions as well central mechanisms autoimmunity. The intermediate monocyte subset (CD14++CD16+) is increased show elevated expression CD14, Toll-like receptor 2/4, MHCII integrins, likely reflecting activation extravasation. Monocytes differentiate locally predominantly into alternatively activated (M2) macrophages, which known for cell-clearance phagocytosis, but may ultimately lead fibrosis. Phagocytotic function can be impaired surface on apoptotic causes release inflammatory cytokines immunogenic contents, presumably resulting vicious circle neutrophil, T B cell consequent ANCA production. Considering their crucial initiating fibrogenesis, represent logic first-line target new treatment options

Language: Английский

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Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis

Brain, Journal Year: 2021, Volume and Issue: 144(9), P. 2709 - 2721

Published: April 10, 2021

Limbic encephalitis with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leucocyte antigen CSF proteomic profiles. Patients anti-AK5 limbic were mostly male (20/26, 76.9%) a median age 66 years (range 48-94). The predominant symptom was severe episodic amnesia in all frequently associated depression (17/25, 68.0%). Weight loss, asthenia anorexia also highly characteristic, being present 11/25 (44.0%) patients. Although epilepsy always lacking at disease onset, seizures developed later subset patients (4/25, 16.0%). All presented abnormalities, such as pleocytosis (18/25, 72.0%), oligoclonal bands 72.0%) increased Tau (11/14, 78.6%). Temporal lobe hyperintensities almost onset (23/26, 88.5%), evolving nearly invariably towards atrophy subsequent MRIs (17/19, 89.5%). This finding line poor response immunotherapy, only 5/25 (20.0%) responding. IgG1 the subclass, most detected one highest titres nine CSF-serum paired samples. A temporal biopsy from our showed massive lymphocytic infiltrates dominated by both CD4+ CT8+ T cells, intense granzyme B expression abundant macrophages/microglia. Human (HLA) analysis 11 striking association HLA-B*08:01 [7/11, 63.6%; odds ratio (OR) = 13.4, 95% confidence interval (CI): 3.8-47.4], C*07:01 (8/11, 72.7%; OR 11.0, CI: 2.9-42.5), DRB1*03:01 14.4, 3.7-55.7), DQB1*02:01 13.5, 3.5-52.0) DQA1*05:01 3.7-55.7) alleles, which formed extended haplotype B8-C7-DR3-DQ2 6/11 (54.5%) (OR 16.5, 4.8-57.1). Finally, compared profile five that 40 control subjects other more common non-paraneoplastic (five leucine-rich glioma inactivated 1 contactin-associated protein-like 2), well paraneoplastic neurological syndromes Yo Ma2). These comparisons revealed 31 seven significantly upregulated proteins encephalitis, respectively mapping apoptosis pathways innate/adaptive immune responses. findings suggest manifestations result distinct cell-mediated pathogenesis, major cytotoxicity-induced leading prompt aggressive neuronal likely explaining prognosis immunotherapy.

Language: Английский

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Recent advances in strategies to target the behavior of macrophages in wound healing

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115199 - 115199

Published: July 28, 2023

Chronic wounds and scar formation are widespread due to limited suitable remedies. The macrophage is a crucial regulator in wound healing, controlling the onset termination of inflammation regulating other processes related healing. current breakthroughs developing new medications drug delivery methods have enabled accurate targeting macrophages oncology rheumatic disease therapies through clinical trials. These successes cleared way utilize drugs various disorders. This review thus summarizes involvement normal pathologic It further details targets available for intervention therapeutic strategies behavior tissue repair regeneration.

Language: Английский

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Tumor-associated macrophages: Potential therapeutic targets and diagnostic markers in cancer

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154739 - 154739

Published: Aug. 4, 2023

Language: Английский

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Looking to the Future of the Role of Macrophages and Extracellular Vesicles in Neuroinflammation in ALS

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11251 - 11251

Published: July 8, 2023

Neuroinflammation is a common pathological feature of amyotrophic lateral sclerosis (ALS). Although scientific evidence to date does not allow defining neuroinflammation as an ALS trigger, its role in exacerbating motor neuron (MNs) degeneration and disease progression attracting research interest. Activated CNS (Central Nervous System) glial cells, proinflammatory peripheral infiltrated T lymphocytes monocytes/macrophages, well the immunoreactive molecules they release, represent active players for immune dysregulation enhancing neuroinflammation. The crosstalk between cells significantly correlates with survival patients since modification macrophages can downregulate inflammation at periphery along nerves CNS. As putative vehicles misfolded protein inflammatory mediators extracellular vesicles (EVs) have also drawn particular attention field ALS. Both release EVs, which are able modulate behavior neighboring recipient cells; unfortunately, mechanisms involved EVs-mediated communication remain unclear. This review aims synthesize current literature regarding EV-mediated cell-to-cell brain under ALS, point view on responding understand biological process exploit it management.

Language: Английский

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