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Allergen-specific immunotherapy (AIT) has shown beneficial effects against atopic dermatitis (AD); however, the mechanisms and parameters underlying the efficacy of AIT remain unclear. Here, we report that the community structure and function of the oral and gut microbiota are changed in patients with AD undergoing AIT. Transplantation of fecal microbiota from patients who respond well to AIT improves AD-like dermatitis in mice. The abundance of Brevundimonas vesicularis in the gut of AD patients has been found to be positively correlated with disease severity and is decreased following AIT. Furthermore, we find that B. vesicularis from the oral cavity might ectopically colonize the gut of AD patients. In AD model mice, meanwhile, B. vesicularis promotes the skewing of the Treg/Th17 balance toward Th17 polarization and attenuates the efficacy of ovalbumin-specific immunotherapy. Our findings provide potential strategies for the optimization of AIT for AD via the modulation of the gut microbiota.
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Dermatitis Atópica , Humanos , Ratones , Animales , Dermatitis Atópica/terapia , Desensibilización Inmunológica , Alérgenos , IntestinosRESUMEN
Background: The real-world experience of dupilumab in Chinese is limited, and the initial loading dose has not yet been deeply explored in patients aged <6 years. Objective: To explore the efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis and investigate the effect of higher loading dose for disease control in patients aged <6 years. Methods: A total of 155 patients were divided into three groups according to age: <6 years, 6-11 years, and >11 years. Among patients aged <6 years, 37 patients received a high loading dose of 300 mg for body weight <15kg or 600 mg for body weight ≥15kg, and another 37 patients received a standard loading dose of 200 mg for body weight <15kg or 300 mg for body weight ≥15kg. Multiple physicians and patient-reported outcome measures were evaluated at baseline and 2, 4, 6, 8, 12, and 16 weeks after dupilumab treatment. Results: The proportion of patients showing an improvement of ≥75% in the Eczema Area and Severity Index was 68.0% (17/25), 76.9% (10/13), and 62.5% (25/40) in the aged <6, 6-11, and >11 years groups, respectively, at week 16. After increasing the loading dose, 69.6% (16/23) of patients aged <6 years achieved 4-point improvement in Pruritus Numerical Rating Scale at week 2, compared with 23.5% (8/34) of patients receiving standard loading dose (P < 0.001). Obesity (odds ratio=0.12, 95% confidence interval: 0.02-0.70) was predictive of a poor response to dupilumab treatment, while female (odds ratio=3.94, 95% confidence interval: 1.26-12.31) predicted good response at week 16. The change of serum C-C motif ligand 17(CCL17/TARC) could reflect the response to dupilumab (r = 0.53, P = 0.002 in EASI) among patients aged <18 years. No major adverse events were reported during the treatment. Conclusions: Dupilumab was effective and well-tolerated in Chinese patients with atopic dermatitis. The increased loading dose helped achieve rapid pruritus control in patients aged <6 years.
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Anticuerpos Monoclonales Humanizados , Dermatitis Atópica , Anticuerpos Monoclonales Humanizados/administración & dosificación , Dermatitis Atópica/terapia , Humanos , Masculino , Femenino , Niño , Estudios Retrospectivos , Resultado del Tratamiento , Relación Dosis-Respuesta a DrogaRESUMEN
Background: Omalizumab is an effective treatment for chronic spontaneous urticaria (CSU) patients aged ≥12 years, but its efficacy in patients aged <12 years has not been fully documented. We evaluated the therapeutic efficacy and safety of omalizumab in Chinese CSU population across all age groups. Objectives: To assess the efficacy and safety of omalizumab treatment against CSU in China. Methods: This study was a retrospective and observational study, and the clinical data of CSU patients treated with omalizumab from October 2018 to August 2021 were collected and analyzed. Results: We enrolled 235 patients in this study, and 54.0% (n = 127/235) of patients were female. All patients received at least three injections of omalizumab treatment, and the mean treatment duration was 3.4 ± 1.0 months. At the end of week-12, 98.7% (n = 232/235) of patients responded to omalizumab, among which 91.1% (n = 214/235) achieved a complete response (CR). An excellent response to omalizumab treatment was observed across all ages. All patients aged <12 years (n = 26) achieved a CR at the end of week-12, and clinical improvement was maintained until treatment cessation. Eighty-seven patients received 3-9-month follow-up after the end of treatment, with a mean duration of 5.7 ± 2.0 months, and 17.2% (n = 15/87) patients experienced recurrence after discontinuing treatment. No factors associated with therapeutic response and recurrence to omalizumab treatment were found in this study. Conclusion: Omalizumab is a safe and efficacious therapy for CSU patients, including those aged <12 years. We recommend addition of omalizumab to the treatment regimen in CSU patients under 12 years of age. Trial registration number: This study was registered in Chinese Clinical Trial Registry (www.chictr.org.cn, Registration number: ChiCTR2200056599).
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The complex physical and chemical reactions between the large number of low-energy (0-30 eV) electrons (LEEs) released by high energy radiation interacting with genetic material can lead to the formation of various DNA lesions such as crosslinks, single strand breaks, base modifications, and cleavage, as well as double strand breaks and other cluster damages. When crosslinks and cluster damages cannot be repaired by the cell, they can cause genetic loss of information, mutations, apoptosis, and promote genomic instability. Through the efforts of many research groups in the past two decades, the study of the interaction between LEEs and DNA under different experimental conditions has unveiled some of the main mechanisms responsible for these damages. In the present review, we focus on experimental investigations in the condensed phase that range from fundamental DNA constituents to oligonucleotides, synthetic duplex DNA, and bacterial (i.e., plasmid) DNA. These targets were irradiated either with LEEs from a monoenergetic-electron or photoelectron source, as sub-monolayer, monolayer, or multilayer films and within clusters or water solutions. Each type of experiment is briefly described, and the observed DNA damages are reported, along with the proposed mechanisms. Defining the role of LEEs within the sequence of events leading to radiobiological lesions contributes to our understanding of the action of radiation on living organisms, over a wide range of initial radiation energies. Applications of the interaction of LEEs with DNA to radiotherapy are briefly summarized.
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Daño del ADN , ADN/química , ADN/efectos de la radiación , Electrones/efectos adversos , Animales , HumanosRESUMEN
Radiobiological damage is principally triggered by an initial cation and a secondary electron (SE). We address the fundamental questions: What lesions are first produced in DNA by this cation or nonionizing SE? What are their relative contributions to isolated and potentially lethal cluster lesions? Five monolayer films of dry plasmid DNA deposited on graphite or tantalum substrates are bombarded by 0.1-100 eV electrons in a vacuum. From measurements of the current transmitted through the films, 3.5 and 4.5 cations per incident 60 and 100 eV electrons, respectively, are estimated to be produced and stabilized within DNA. Damage analysis at 6, 10, 20, 30, 60, and 100 eV indicates that essentially all lesions, but preferentially cluster damages, are produced by non-ionizing or weakly ionizing electrons of energies below 12 eV. Most of these lesions are induced within femtosecond times, via transient anions and electron transfer within DNA, with little contributions from the numerous cations.
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Daño del ADN , Electrones , Radiobiología , Cinética , Plásmidos/genéticaRESUMEN
The stainless steel mesh (SSM) has received growing consideration as an electrocatalyst for efficient hydrogen and oxygen evolution reactions. Recently, the application of SSM as an oxygen evolution reaction (OER) electrocatalyst has been more promising, while its hydrogen evolution reaction (HER) catalytic activity is very low, which definitely affects its overall water splitting activity. Herein, a simple chemical bath deposition (CBD) method followed by phosphorization is employed to significantly boost the overall water splitting performance of SSM. The CBD method could allow the voids between the SSM fibers to be filled with Ni and P. Electrocatalytic studies show that the CBD-treated and phosphorized stainless steel (denoted SSM-Ni-P) exhibits an HER overpotential of 149 mV, while the phosphorization-free CBD-treated SSM (denoted as SSM-Ni) delivers an OER overpotential of 223 mV, both at a current density of 10 mA cm-2. An asymmetric alkaline electrolyzer assembled based on the SSM-Ni-P cathode (HER) and SSM-Ni anode (OER) achieved an onset and 10 mA cm-2 current densities at an overall potential of 1.62 V, granting more prospects for the application of inexpensive and highly active electrocatalysts for electrocatalytic water splitting reactions.
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The mechanisms of action of low-energy electrons (LEEs) generated in large quantities by ionizing radiation constitute an essential element of our understanding of early events in radiolysis and radiobiology. We present the 2-20 eV electron energy dependence of the yields of base damage (BD), BD-related cross-links (CLs), and non-double-strand break (NDSB) clustered damage induced in DNA. These new yield functions are generated by the impact of LEEs on plasmid DNA films. The damage is analyzed by gel electrophoresis with and without enzyme treatment. Maxima at 5 and 10 eV in BDs and BD-related CLs yield functions, and two others, at 6 and 10 eV, in those of NDSB clustered damage are ascribed to core-excited transient anions that decay into bond-breaking channels. The mechanism causing all types of DNA damages can be attributed to the capture of a single electron by a base followed by multiple different electron transfer pathways.
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Daño del ADN , ADN/efectos de la radiación , Aniones/química , Muerte Celular/efectos de la radiación , ADN/química , Electrones , Purinas/química , Pirimidinas/químicaRESUMEN
Previous studies have shown independently that the skin and gut microbiota are closely associated with atopic dermatitis (AD); however, the microbiota across different habitats of AD patients as an integrated community has not been characterized. In the present study, we comparatively analyzed the structure and function of the microbial communities in the skin, oral cavity, and gut of 172 AD patients and 120 healthy controls through 16S ribosomal RNA gene amplicon sequencing. The skin and oral cavity, but not the gut, of AD patients demonstrated differential reduction in the microbial diversity, and these were distinctly correlated with disease severity. Different degrees of shifts in the community structure were found among different habitats, and the lineage distance between the skin and oral microbiota of AD patients was closer than that observed in the controls. The different habitats of AD patients exhibited site-specific alterations at the genus level, and many oral-specific microbes of AD showed opposing directions of enrichment in the skin and oral cavity. Most interestingly, an inverse association in the functional pathways was found between the skin and oral microbiota of AD patients. Additionally, the alterations of the microbiota in different body sites of AD patients were differentially affected by age.
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Bacterias/aislamiento & purificación , Dermatitis Atópica/microbiología , Microbiota/inmunología , Mucosa Bucal/microbiología , Piel/microbiología , Adolescente , Adulto , Factores de Edad , Bacterias/genética , Bacterias/inmunología , Estudios de Casos y Controles , Niño , Preescolar , ADN Bacteriano/aislamiento & purificación , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Femenino , Humanos , Lactante , Mucosa Intestinal/microbiología , Masculino , Microbiota/genética , Persona de Mediana Edad , Filogenia , ARN Ribosómico 16S/genética , Índice de Severidad de la Enfermedad , Piel/patología , Adulto JovenRESUMEN
From the whole plants of Aster sampsonii, ten compounds were isolated, and were characterized as (4alphaR, 4'alphaR, 5S, 5'S, 9alphaR, 9'alphaR)-4, 4', 4alpha, 4'alpha, 5, 5', 6, 6', 7, 7', 8, 8'-dodecahydro-3, 3', 4alpha, 4'alpha, 5, 5'-hexamethyl-2H, 2'H-9alpha, 9' alpha-binaphtho[2, 3-b]furan-2, 2'-dione(1), furanoligularenone(2), (4alphaR, 5S, 8alphaR)-4alpha, 5, 6, 7, 8, 8alpha-hexahydro-8alpha-hydroxy-3, 4alpha, 5-trimethylnaphtho[2, 3-b]furan-2(4H)-one(3), (4alphaR, 5S, 8alphaS)4alpha, 5, 6, 7, 8, 8alpha-hexahydro-8alpha-hydroxy-3, 4alpha, 5-trimethylnaphtho[2, 3-b]furan-2(4H)-one(4), methyl-1'-hydroxy-2', 6'-dimethoxy-4'-oxocyclohexanacetate(5), 1'-hydroxy-2'-methoxy-4'-oxocyclohexanacetate methyl(6), loliolide (7), jacaranone (8), beta-sitosterol(9), friedeline (10). The structures of all compounds were elucidated on the basis spectroscopic data, including IR, EI-MS, HR-ESI-MS, and 1D and 2D NMR data. The bioassays showed weak sterilization activities for compound 3. Compounds 1-8 were obtained from A. sampsonii for the first time.