Asthma Biologics Across the T2 Spectrum of Inflammation in Severe Asthma: Biomarkers and Mechanism of Action

Journal of Asthma and Allergy, Journal Year: 2025, Volume and Issue: Volume 18, P. 33 - 57

Published: Jan. 1, 2025

Airway inflammation, a hallmark feature of asthma, drives many canonical features the disease, including airflow limitation, mucus plugging, airway remodeling, and hyperresponsiveness. The T2 inflammatory paradigm is firmly established as dominant mechanism asthma pathogenesis, largely due to success inhaled corticosteroids biologic therapies targeting components pathway, IL-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP). However, up 30% patients may lack signatures meaningful inflammation (ie, low). In T2-low patients, be masked anti-inflammatory treatments or highly variable depending on exposure common triggers such allergens, respiratory infections, smoke pollution. epithelium epithelial cytokines (TSLP, IL-33) are increasingly recognized upstream drivers pathways modulators various effector cells, mast eosinophils, neutrophils, which impact pathological manifestations smooth muscle hypertrophy, hypercontractility, Approved biologics for severe target several distinct mechanisms action, leading differential effects spectrum biomarkers, treatment efficacy (reducing exacerbations, improving lung function, diminishing symptoms). approved anti-asthma primarily immune pathways, with little evidence suggesting benefit non-T2 asthma-associated mediators. Indeed, negative results challenge current assumptions about etiology raise doubts viability popular alternative T17. Novel data have emerged from use treat mediators furthered our understanding pathogenic that drive asthma. This review discusses contribute quantitatively outlines available summarizes challenges clinical trials address

Language: Английский

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Liposomal curcumin inhibits cigarette smoke induced senescence and inflammation in human bronchial epithelial cells

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 260, P. 155423 - 155423

Published: June 20, 2024

Curcumin, the principal curcuminoid of turmeric (Curcuma longa extract), is very well known for its multiple biological therapeutic activities, particularly anti-inflammatory and antioxidant potential. However, due to low water solubility, it exhibits poor bioavailability. In order overcome this problem, in current study, we have employed liposomal technology encapsulate curcumin with aim enhancing efficacy. The curcumin-loaded liposomes (PlexoZome®) were tested on a cigarette smoke extract-induced Chronic Obstructive Pulmonary Disease (COPD) vitro model using minimally immortalized human bronchial epithelial cells (BCiNS1.1). anti-senescence properties PlexoZome® explored. 5 µM demonstrated anti-senescent activity by decrease X-gal positive cells, reduction expression p16 p21 immunofluorescence staining. Moreover, also proteins related senescence (osteopontin, FGF basic uPAR) inflammation (GM-CSF, EGF ST2). Overall, results clearly demonstrate potential encapsulated managing CSE induced COPD, providing new direction respiratory clinics.

Language: Английский

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Evaluating the evidence for GM-CSF as a host-directed therapy in respiratory infections

Cytokine, Journal Year: 2025, Volume and Issue: 189, P. 156902 - 156902

Published: Feb. 24, 2025

Language: Английский

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Applications of mRNA Delivery in Cancer Immunotherapy

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 3339 - 3361

Published: March 1, 2025

Cancer treatment is continually advancing, with immunotherapy gaining prominence as a standard modality that has markedly improved the management of various malignancies. Despite these advancements, efficacy remains variable, certain cancers exhibiting limited response and patient outcomes differing considerably. Thus, enhancing effectiveness imperative. A promising avenue mRNA delivery, employing carriers such liposomes, peptide nanoparticles, inorganic exosomes to introduce cargos encoding tumor antigens, immune-stimulatory, or immune-modulatory molecules into immune microenvironment (TIME). This method aims activate system target eradicate cells. In this review, we characteristics limitations summarize application mechanisms currently prevalent in mRNA-based treatment. Additionally, given significant clinical checkpoint inhibitors (ICIs) chimeric antigen receptor (CAR)-based cell therapies solid tumors (including melanoma, non-small-cell lung cancer, head neck squamous carcinoma, triple-negative breast gastric cancer) leukemia, which have become first-line treatments, highlight discuss recent progress combining delivery ICIs, CAR-T, CAR-NK, CAR-macrophage therapies. combination enhances targeting capabilities ICIs CAR-cell-based therapies, while also mitigating long-term off-target toxicities associated conventional methods. Finally, analyze current systems, nuclease-induced instability, immunogenicity risks, complex carrier production, knowledge gaps concerning dosing safety. Addressing challenges crucial for unlocking potential cancer immunotherapy. Overall, exploring enriches our comprehension holds promise developing personalized effective strategies, potentially responses patients extending their survival time.

Language: Английский

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Pulmonary Alveolar Proteinosis and new therapeutic concepts

Klinische Pädiatrie, Journal Year: 2024, Volume and Issue: 236(02), P. 73 - 79

Published: Jan. 29, 2024

Abstract Pulmonary alveolar proteinosis (PAP) is an umbrella term used to refer a pulmonary syndrome which characterized by excessive accumulation of surfactant in the lungs affected individuals. In general, PAP rare lung disease affecting children and adults, although its prevalence incidence variable among different countries. Even though disease, it prime example on how modern medicine can lead new therapeutic concepts, changing ways techniques (genetic) diagnosis ultimately led into personalized treatments, all dedicated improve function impaired thus life expectancy quality patients. fact, technologies, such as sequencing gene therapy approaches, kind sources stem cells completely insights ontogeny immune macrophages have increased our understanding onset progression PAP, paved way for novel concepts beyond. As today, classical monocyte-derived are known important mediator sentinels within innate immunity. Furthermore, (known tissue resident (TRMs)) also be found various tissues, introducing e. g. broncho-alveolar space crucial cellular determinants other disorders. Given recent knowledge about factors impede their function, has development therapies, applied context with promising implications diseases play role. Thus, we here summarize latest forms introduce pre-clinical work currently conducted framework therapies adults who still suffer from this severe, potentially life-threatening disease.

Language: Английский

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Chlorinated Anthracenes Induced Pulmonary Immunotoxicity in 3D Coculture Spheroids Simulating the Lung Microenvironment

Environmental Science & Technology, Journal Year: 2024, Volume and Issue: 58(27), P. 11923 - 11934

Published: June 25, 2024

Chlorinated anthracenes (Cl-Ants), persistent organic pollutants, are widely detected in the environment, posing potential lung toxicity risks due to frequent respiratory exposure. However, direct evidence and a comprehensive understanding of their mechanisms lacking. Building on our prior findings Cl-Ants' immunotoxic risks, this study developed three-dimensional coculture spheroid model mimicking lung's immune microenvironment. The objective is explore pulmonary immunotoxicity comprehend its mechanisms, taking into account heightened reactivity exposure Cl-Ants. results demonstrated that Cl-Ants led reduced size, increased macrophage migration outward, lowered cell viability, elevated 8-OHdG levels, disturbed anti-infection balance, altered cytokine production. Specifically, chlorine substituent number correlates with extent disruption indicators caused by Cl-Ants, stronger effects observed dichlorinated Ant compared those monochlorinated Ant. Furthermore, we identified critical regulatory genes associated viability (ALDOC ALDOA), bacterial response (TLR5 MAP2K6), GM-CSF production (CEBPB). Overall, offers initial vitro low-dose Cl-PAHs' immunotoxicity, advancing structure-related improving external assessment methods for environmental which holds significance future monitoring evaluation.

Language: Английский

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Real-world outdoor air exposure effects in a model of the human airway epithelium – A comparison of healthy and asthmatic individuals using a mobile laboratory setting

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 289, P. 117495 - 117495

Published: Dec. 7, 2024

Language: Английский

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Histological Features of Delayed Foreign Body Granuloma With Epithelioid Histiocyte Aggregation and Eosinophilic Reaction due to Hyaluronic Acid Injection

Case Reports in Dentistry, Journal Year: 2024, Volume and Issue: 2024(1)

Published: Jan. 1, 2024

Background: Dermal fillers such as hyaluronic acid (HA) have been widely used in recent years a less surgically invasive cosmetic treatment. Although delayed foreign body granuloma may occur rare adverse reaction after the procedure, detailed histological reports are still limited. When occurring on buccal mucosa of oral cavity, histopathology resemble some lesions minor salivary gland origin due to material properties HA. Here we report associated with HA showing eosinophilic infiltration mucosa, characteristic and immunohistological features. Case Presentation: A 61‐year‐old woman presented swelling burning sensation right mucosa. On initial examination, 25 × 20‐mm mass was palpated anterior margin masseter muscle. Examination biopsy specimen revealed multiple pseudoduct‐like structures containing mucoid substance within mucosal lamina propria. The positively stained Alcian blue (AB) surrounded by CD68‐positive epithelioid cells multinucleated giant cells. Many histiocytes had infiltrated into surrounding area, numerous infiltrates were also evident. After review patient’s history, diagnosis injection made. Conclusion: We reported case histiocytic following It suggested that marked around macrophages not only an allergic reaction, but part increased macrophage aggregation.

Language: Английский

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Immune Resilience to SARS-CoV-2 Infection by Shifting Risk Within Normal and Disease Populations

Published: July 5, 2023

ABSTRACT: The idea of a Common Mucosal Immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential modulate the impact vaccination-induced against infection airway, has been poorly understood. consequent failure current SARS-CoV-2 vaccination satisfy expectations with respect prevention infection, viral transmission, duration pattern clinical protection, led public health medical decisions now under review. This review summarises knowledge CMS in man, including powerful role it plays lessons what can not be achieved by systemic for airway infection. both disease optimising delivery using selected isolates from respiratory microbiome, demonstrated through randomised controlled trials (RCT’s) subjects chronic disease, otherwise healthy individuals risk factors, whom resilience introduced.

Language: Английский

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The Common Mucosal System Fifty Years on: From Cell Traffic in the Rabbit to Immune Resilience to SARS-CoV-2 Infection by Shifting Risk within Normal and Disease Populations

Vaccines, Journal Year: 2023, Volume and Issue: 11(7), P. 1251 - 1251

Published: July 17, 2023

The idea of a common mucosal immune system (CMS) is 50 years old. Its relevance to protection at sites and its potential modulate the impact vaccination-induced against infection airway has been poorly understood. consequent failure current SARS-CoV-2 vaccination satisfy expectations with respect prevention infection, viral transmission, duration protection, pattern clinical led public health medical decisions now under review. This review summarises knowledge CMS in man, including powerful role it plays lessons what can cannot be achieved by systemic for infection. both disease optimising delivery using selected isolates from respiratory microbiome demonstrated through randomised controlled trials (RCTs) subjects chronic disease, otherwise healthy individuals risk factors, whom resilience introduced. dedicated two giants immunology: Professors John Bienenstock Allan Cripps. Their recent deaths are keenly felt their colleagues students.

Language: Английский

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