Regulation of Carcinogenesis by Sensory Neurons and Neuromediators

Cancers, Journal Year: 2022, Volume and Issue: 14(9), P. 2333 - 2333

Published: May 9, 2022

Interactions between the immune system and nervous are crucial in maintaining homeostasis, disturbances of these neuro-immune interactions may participate carcinogenesis metastasis. Nerve endings have been identified within solid tumors humans experimental animals. Although involvement efferent sympathetic parasympathetic innervation has extensively investigated, role afferent sensory neurons neuropeptides tumor development, growth, progression is recently appreciated. Similarly, current findings point to significant Schwann cells as part interactions. Hence, this review, we mainly focus on local systemic effects nerve activity well Specific denervation vagal fibers, or vagotomy, animal models, reported markedly increase lung metastases breast carcinoma pancreatic gastric with formation liver demonstrating protective fibers against cancer. Clinical studies revealed that patients ulcers who undergone a vagotomy greater risk stomach, colorectal, biliary tract, cancers. Protective also documented by epidemiological high predicts longer survival rates colon, non-small cell lung, prostate, However, several inhibition neuronal reduces development tumors, including gastric, pancreatic, head neck, cervical, ovarian, skin These contradictory likely be due post-nerve injury-induced activation level aggressiveness model used, heterogeneity fibers. As inflammatory response increase, apparent might mostly alterations response. more insights into inductive permissive mechanisms, such systemic, cellular neuro-immunological mechanisms metastasis formation, needed understand growth spread.

Language: Английский

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A Systematic Review of Keratinocyte Secretions: A Regenerative Perspective

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7934 - 7934

Published: July 19, 2022

Cell regenerative therapy is a modern solution for difficult-to-heal wounds. Keratinocytes, the most common cell type in skin, are difficult to obtain without creation of another wound. Stem differentiation towards keratinocytes challenging process, and it reproduce chemically defined media. Nevertheless, co-culture with stem cells usually achieves efficient differentiation. This systematic review aims identify secretions normal human reported literature correlate them process. An online search revealed 338 references, which 100 met selection criteria. A total 80 different keratinocyte were reported, can be grouped mainly into cytokines, growth factors, antimicrobial peptides. The growth-factor group mostly affects keratinocytes, especially epidermal factor members transforming family. reflected nature involved studies, as focused on interaction inflammation. highlights secretory function well need intense investigation characterize these evaluate their capacities.

Language: Английский

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Chronic Nodular Prurigo: An Update on the Pathogenesis and Treatment

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(20), P. 12390 - 12390

Published: Oct. 16, 2022

Chronic nodular prurigo (CNPG) is a recalcitrant chronic itchy disorder that affects the quality of life. It can be triggered by multiple etiologies, such as atopic dermatitis, diabetes, and renal diseases. The mechanisms CNPG are complicated involved interaction cutaneous, immune, nervous systems. Diverse immune cells, including eosinophils, neutrophils, T macrophages, mast cells infiltrated lesional skin CNPG, which initiated inflammatory cytokines pruritogens release. In addition, between activated peripheral sensory nerve fibers neurotransmitters caused neuroinflammation in intractable itch. This itch-scratch vicious cycle results disease exacerbation. difficult to treat with traditional therapies. Recently, great advances have been made pathophysiology both inflammation pruritus transmission CNPG. this review, we summarize updated novel therapies for

Language: Английский

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Kaempferol therapy improved MC903 induced-atopic dermatitis in a mouse by suppressing TSLP, oxidative stress, and type 2 inflammation

Journal of Dermatological Science, Journal Year: 2023, Volume and Issue: 111(3), P. 93 - 100

Published: June 28, 2023

Language: Английский

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Neurotrophins: Neuroimmune Interactions in Human Atopic Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6105 - 6105

Published: March 24, 2023

Allergic diseases are accompanied by a variety of symptoms such as pruritus, coughing, sneezing, and watery eyes, which can result in severe physiological even psychological impairments. The exact mechanisms these conditions not yet completely understood. However, recent studies demonstrated high relevance neurotrophins allergic inflammation, they induce cytokine release, mediate interaction between immune cells neurons, exhibit different expression levels health disease. In this review, we aim to give an overview the current state knowledge concerning role atopic disorders dermatitis, asthma, rhinitis.

Language: Английский

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Epigenetic control of inflammation in Atopic Dermatitis

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 154, P. 199 - 207

Published: April 27, 2023

Atopic dermatitis (AD), also known as atopic eczema, is a common but complex chronic, itchy skin condition with underlying inflammation of the skin. This ailment prevalent worldwide and affects people all ages, particularly children below five years age. The itching resulting rashes in AD patients are often result inflammatory signals, thus necessitating closer look at inflammation-regulating mechanisms for putative relief, care therapy. Several chemical- well genetically-induced animal models have established importance targeting pro-inflammatory microenvironment. Epigenetic gaining attention towards better understanding onset progression inflammation. physiological processes implications pathophysiology AD, such as, barrier dysfunction either due to reduced filaggrin / human β‐defensins or altered microbiome, reprograming Fc receptors overexpression high affinity IgE receptors, elevated eosinophil numbers IL-22 production by CD4 + T cells epigenetic that include differential promoter methylation and/or regulation non-coding RNAs. Reversing these changes has been verified reduce burden through secretion cytokines IL-6, IL-4, IL-13, IL-17, etc, benefit against experimental models. A thorough remodeling potential opening avenues novel diagnostic, prognostic therapeutic options.

Language: Английский

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Navigating the evolving landscape of atopic dermatitis: Challenges and future opportunities: The 4th Davos declaration

Allergy, Journal Year: 2024, Volume and Issue: 79(10), P. 2605 - 2624

Published: Aug. 4, 2024

Abstract The 4th Davos Declaration was developed during the Global Allergy Forum in which aimed to elevate care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. forum addressed high prevalence AD, a strategic focus on advancing research, treatment, management meet evolving challenges field. This multidisciplinary brought together top leaders from clinical practice, policy, patient advocacy discuss critical aspects including neuroimmunology, environmental factors, comorbidities, breakthroughs prevention, diagnosis, treatment. discussions were geared towards fostering collaborative approach integrate these advancements into practical, patient‐centric care. underlined mounting burden attributing it significant lifestyle changes. It acknowledged progress understanding AD developing targeted therapies but recognized gap translating innovations practice. Emphasis placed need for enhanced awareness, education, stakeholder engagement address this effectively consider factors comprehensive disease strategy. marks milestone journey improve people AD. By promoting holistic that combines application, sets roadmap stakeholders collaborate outcomes reflecting commitment adapt respond dynamic changing world.

Language: Английский

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Pathogenesis of Inflammation in Skin Disease: From Molecular Mechanisms to Pathology

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10152 - 10152

Published: Sept. 21, 2024

Many skin diseases begin with inflammatory changes on a molecular level. To develop more thorough understanding of pathology and to identify new targets for therapeutic advancements, mechanisms inflammation in the context disease should be studied. Current research efforts better understand have focused examining role processes at several stages response such as dysregulation innate immunity sensors, disruption both transcriptional post-transcriptional regulation, crosstalk between immune neuronal (neuro-immune crosstalk). This review seeks summarize recent developments our highlight opportunities advancements. With focus publications within past 5 years (2019–2024), databases PubMed EBSCOhost were used search peer-reviewed papers regarding disease. Several themes interest determined through extensive included based their relative representation current potential. psoriasis, atopic dermatitis, hidradenitis suppurativa, scleroderma described paper demonstrate widespread influence

Language: Английский

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Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 152(4), P. 916 - 926

Published: July 13, 2023

Pruritus is the most common and burdensome symptom of atopic dermatitis (AD). Pruritus-targeted treatments in AD are lacking, particularly for patients with milder skin disease.We sought to evaluate impact selective κ-opioid receptor agonist difelikefalin (DFK) on pruritus intensity pruritus- immune-related biomarkers subjects moderate severe AD-related pruritus.A phase 2 clinical trial investigated efficacy safety oral DFK 0.25, 0.5, 1.0 mg pruritus. A biomarker substudy evaluated effects expression pruritus, TH2-associated genes, barrier-related genes.In (N = 401), all doses reduced itch versus placebo; however, results were not statistically significant at week 12. In a subgroup mild inflammation (itch-dominant phenotype), 12 placebo. substudy, downregulated key pruritus-related genes (eg, IL-31 TRPV1) phenotype CCL17). Gene set variation analysis confirmed that DFK, but placebo, TH2 pathways. improved barrier integrity markers upregulated claudins lipid metabolism-associated SEC14L6, ELOVL3, CYP1A2, AKR1D1).DFK treatment those an "itch-dominant" phenotype, had genes. promising therapy pruritus; further studies warranted.

Language: Английский

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Atopic dermatitis – Perspectives and unmet medical needs

JDDG Journal der Deutschen Dermatologischen Gesellschaft, Journal Year: 2023, Volume and Issue: 21(4), P. 349 - 353

Published: March 24, 2023

Summary Atopic dermatitis (AD) is a chronic inflammatory skin disease for which many new insights have been gained in recent years through better understanding of pathophysiology, concomitant diseases and therapeutics particular. In this review, practice‐relevant results from current research are presented. Many studies performed on the diagnosis AD different subtypes, yet no diagnostic biomarker or clinical predictor treatment response has established. For topical treatment, some agents such as Janus kinase (JAK) inhibitors advanced stages trials already approved countries, will be available Europe certain eczema subtypes foreseeable future. Current systemic therapies include two antibodies inhibition interleukin (IL)‐4/13 signaling cascades three oral JAK with somewhat efficacy safety profiles. Among antibody development, promising targets blockade IL‐31, neurokinin‐1 receptor sensory neurons, OX40/OX40L axis cutaneous dendritic cell T lymphocyte interaction. Primary prevention modulation sequential progression well effects by early therapeutic intervention important questions future AD.

Language: Английский

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