Chronic urticaria: unmet needs, emerging drugs, and new perspectives on personalised treatment

The Lancet, Journal Year: 2024, Volume and Issue: 404(10450), P. 393 - 404

Published: July 1, 2024

Language: Английский

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Chronic Spontaneous Urticaria

JAMA, Journal Year: 2024, Volume and Issue: 332(17), P. 1464 - 1464

Published: Sept. 26, 2024

Importance Chronic spontaneous urticaria affects approximately 1% of the general population worldwide, including 3 million people in US, impairs patients’ quality life, and is associated with multiple comorbidities. Observations patients any age but most common females aged 30 to 50 years. Diagnosis based on clinical presentation, ie, spontaneously recurring wheals, angioedema, or both. persists for more than 1 year (1 repeated episodes) may present comorbidities chronic inducible (>10%), autoimmune thyroiditis (approximately 20%), metabolic syndrome (6%-20%), anxiety (10%-31%) depression (7%-29%). Known endotypes (subtypes defined by distinct pathogenesis) are mediated mast cell–activating IgE and/or IgG autoantibodies (>50%). Approximately 40% have a Dermatology Life Quality Index 10, corresponding very large extremely negative effect life. Second-generation H antihistamines first-line treatment; partial complete response, as reduction symptoms greater 50%, observed patients. The 2022 international guideline recommends monoclonal anti-IgE antibody omalizumab second-line treatment antihistamine-refractory urticaria. However, at least 30% an insufficient response omalizumab, especially those IgG-mediated Cyclosporine, used off-label, can improve 54% 73% patients, nonresponse has adverse effects such kidney dysfunction hypertension. Conclusions Relevance inflammatory skin disease medical psychiatric impaired treatment, cyclosporine third-line

Language: Английский

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Functional fractions of Astragalus polysaccharides as a potential prebiotic to alleviate ulcerative colitis

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 271, P. 132580 - 132580

Published: May 23, 2024

Language: Английский

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Disease modification in chronic spontaneous urticaria

Allergy, Journal Year: 2024, Volume and Issue: 79(9), P. 2396 - 2413

Published: July 24, 2024

Chronic spontaneous urticaria (CSU) is a debilitating, inflammatory skin condition characterized by infiltrating immune cells. Available treatments are limited to improving the signs and symptoms. There an unmet need develop therapies that target disease-driving pathways upstream of mast cell activation inhibit or delay progression CSU associated comorbidities. Here, we aim define disease modification due treatment intervention criteria disease-modifying (DMTs) must meet in CSU. We have defined as favorable treatment-induced change underlying pathophysiology and, therefore, course, which clinically beneficial enduring. A DMT fulfil following criteria: (1) prevents delays CSU, (2) induces long-term, therapy-free clinical remission, sustained absence symptoms without for treatment, (3) affects mechanism demonstrated effect on signals and/or biomarker. DMTs should slow progression, achieve long-lasting mechanisms, reduce cell-activating IgE autoantibodies, cytokine profile polarization, normalize gut microbiome barrier. Treating at system level could provide valuable alternatives pharmacotherapy management. Specific yet be developed, but some show potential benefits, such inhibitors Bruton's Tyrosine Kinase, IL-4 IL-13. Future prevent symptoms, long-term benefits after discontinuing concomitant disorders.

Language: Английский

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Bioactive lipids in the skin barrier mediate its functionality in health and disease

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 260, P. 108681 - 108681

Published: June 17, 2024

Our skin protects us from external threats including ultraviolet radiation, pathogens and chemicals, prevents excessive trans-epidermal water loss. These varied activities are reliant on a vast array of lipids, many which unique to skin, that support physical, microbiological immunological barriers. The cutaneous physical barrier is dependent specific lipid matrix surrounds terminally-differentiated keratinocytes in the stratum corneum. Sebum- keratinocyte-derived lipids cover skin's surface regulate microbiota. Meanwhile, signal between resident infiltrating immune cells, driving inflammation its resolution response other threats. Lipids particular importance include ceramides, crucial for corneum formation therefore functionality, fatty acids, contribute acidic pH microbiota, as well matrix, bioactive metabolites these involved cell signalling, inflammation, numerous processes. diverse complex maintain homeostasis healthy implicated diseases, unrelated systemic conditions with manifestations, processes such ageing. also gut-skin axis, signalling two sites. Therefore, provide valuable resource exploration processes, local disease development progression, accessible biomarker discovery disease, an opportunity fully understand relationship host Investigation could diagnostic prognostic biomarkers, help identify new targets interventions. Development improvement existing vitro silico approaches explore lipidome, advances lipidomics technologies, will facilitate ongoing progress research.

Language: Английский

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Increased intestinal permeability and lipopolysaccharide contribute to swainsonine-induced systemic inflammation

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 284, P. 116912 - 116912

Published: Aug. 23, 2024

Long-term consumption of swainsonine could be poisonous to livestock, including facilitating apoptosis by impairing lysosomal function and inhibiting autophagic degradation, leading liver inflammation even death in livestock. However, the mechanism induced systemic inflammatory responses remained unclear, especially effects on intestinal permeability, lipopolysaccharide (LPS) level oxidative stress response were unknown. In this study, increased permeability as evidenced significant down-regulation colonic goblet cells, Akkermansia muciniphila tight junction protein Occludin, Claudin 1 ZO-1, up-regulation mRNA expression indicator tyrosine phosphatase receptor type H (Ptprh) ileum mice. Simultaneously, elevated LPS biosynthetic genes microbiota facilitated more bacterial endotoxin enter blood. High concentration free-form high levels proinflammatory cytokines response, thereby causing inflammation. These findings provided a new perspective swainsonine-induced inflammation, suggesting that may potential trigger factors.

Language: Английский

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Gut microbial alteration in chronic spontaneous urticaria unresponsive to second generation antihistamines and its correlation with disease characteristics‐ a cross‐sectional case‐control study

Clinical and Translational Allergy, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Gut microbial involvement has been speculated in chronic spontaneous urticaria (CSU). The aim of the study was to compare gut microbiome composition and diversity CSU patients uncontrolled with second-generation antihistamines (sgAHs) healthy individuals, as well explore any association between disease characteristics. A cross-sectional case-control including 20 unresponsive standard doses sgAHs, 15 age-and-sex matched controls conducted. Clinico-demographic profile, laboratory investigations stool analysis were conducted all participants. 16S RNA gene sequencing DNA isolation performed for samples, followed by bioinformatic analysis. (mean age 39.5 ± 9.3, M:F 1:4) 35 13, 1:2) statistically comparable. median (IQR) duration 42 months (7-81). Concomitant angioedema concomitant symptomatic dermographism present 30% 20% patients, respectively. At inclusion, 60% receiving add-on omalizumab, while remaining 40% on up-dosed sgAHs. Stool revealed increased higher richness compared individuals. showed reduced load short-chain fatty acid (SCFA) producing microbiota opportunistic pathogens. Firmicutes/Bacteroides (F/B) ratio patients. Among Bacteroides Firmicutes count associated activity poor control; however, there no link type therapy. dysbiosis is seen linked control.

Language: Английский

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Lsm2 is critical to club cell proliferation and its inhibition aggravates COPD progression

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 28, 2025

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition, with its severity inversely related to the levels of Club cell 10 kDa secretory protein (CC10). The gene Lsm2, involved in RNA metabolism and proliferation, has an unclear role COPD development. An vitro model was developed by stimulating 16HBE cells cigarette smoke extract (CSE). To establish vivo model, mice defective Lsm2 expression lung or club were exposed for 3 months. Multiplexed immunohistochemistry (mIHC) employed identify specific where predominant. sequencing single-nucleus conducted investigate pathogenesis COPD. In this study, we found that increases expression, knocking down significantly reduces viability vitro. mIHC showed primarily expressed cells. Knockout either lungs specifically cells, exacerbated injury inflammation caused exposure vivo. Single-nucleus analysis revealed cell-specific knockout leads reduction population, particularly those expressing Chia1+/Crb1+. This decrease subsequently number ciliated epithelial Knocking out results significant numbers, which increased vulnerability accelerating progression Our findings highlight critical proliferation inhibition aggravates progression.

Language: Английский

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Effects of Feeding Reduced Protein Diets on Milk Quality, Nitrogen Balance and Rumen Microbiota in Lactating Goats

Animals, Journal Year: 2025, Volume and Issue: 15(6), P. 769 - 769

Published: March 7, 2025

Lowering dietary protein content is one of the effective ways to reduce nitrogen (N) emissions and conserve feed resources. However, it unclear how reducing levels affects milk quality efficiency N utilization in lactating goats. It therefore difficult determine exactly much reduction optimal. The objective this study was evaluate effects low-protein diets on quality, balance rumen microbiota A total 50 goats were enrolled a completely randomized design maintained either diet with 15.82% level as control group (CON) or reduced 13.85% (R2 group), 11.86% (R4 9.84% (R6 group) 7.85% (R8 respectively. results showed that dry matter intake, yield, fecal urinary excretion decreased linearly levels. Specifically, yield by R8 (p < 0.05). Furthermore, contents protein, fat lactose 0.05), but R2 R4 have no influence > R6 only at 4th week. Fecal decreasing affected relative abundance including Christensenellaceae_R-7_group, NK4A214_group UCG-005 In conclusion, lowering altering during lactation. This phenomenon most pronounced when 8 percentage points. Nevertheless, should not be more than 6 points ensure normal performance goat

Language: Английский

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Synergistic regulation of colon microflora and metabolic environment by resistant starch and sodium lactate in hyperlipidemic rats

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 141933 - 141933

Published: March 1, 2025

Language: Английский

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