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Omalizumab in the treatment of Morbihan syndrome in an adolescent girl - case report and literature review. 奥马珠单抗治疗一名少女的莫尔比昂综合征--病例报告和文献综述。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.978
Zofia Mazurek-Durlak, Katarzyna Mularczyk, Przemko Kwinta, Grzegorz Lis, Ewa Cichocka-Jarosz

Morbihan syndrome (MS) is characterized by solid facial edema, usually related to rosacea or acne vulgaris. The facial edema deforms the patient's features, can impair peripheral vision, and affects quality of life. Its pathophysiology remains unclear. The disease usually has a slow and chronic course. MS most commonly affects middle-aged Caucasian men with rosacea and is rare in people below 20 years of age. MS is a diagnosis of exclusion. There is no standard treatment for MS, though systemic isotretinoin and antihistamines are mainly used. We present the case of an adolescent girl with MS nonresponding to 19 months of isotretinoin treatment with add-on antihistamines. Therapy with monthly administration of omalizumab (anti-IgE) for 6 months was an effective therapeutic option, improving the quality of life. Our case is the second description of omalizumab use in Morbihan syndrome, the first in an adolescent.

莫尔比昂综合征(Morbihan syndrome,MS)的特征是面部实性水肿,通常与酒渣鼻或寻常痤疮有关。面部水肿会使患者的五官变形,损害周边视力,影响生活质量。其病理生理学尚不清楚。该病的病程通常缓慢而慢性。多发性硬化症最常见于患有酒糟鼻的中年白种男性,20 岁以下的人很少发病。多发性硬化症是一种排除性诊断。目前还没有治疗多发性硬化症的标准方法,但主要使用全身性异维A酸和抗组胺药。我们介绍了一个患有多发性硬化症的少女病例,她在接受了 19 个月的异维A酸治疗后,对抗组胺药物无反应。每月使用奥马珠单抗(抗 IgE)治疗 6 个月是一种有效的治疗方案,可改善患者的生活质量。我们的病例是第二例使用奥马珠单抗治疗莫尔比昂综合征的病例,第一例是一名青少年。
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引用次数: 0
Real-life experience after 3 months with tezepelumab before marketing approval. 特珠单抗上市前使用 3 个月后的真实体验。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.1063
Victoria Villalobos Violán, Beatriz González Cano, Miguel Ángel Racionero Casero, Eloína González-Mancebo, Esther Mohedano Vicente, María Jesús Trujillo Trujillo, Mar Gandolfo-Cano

Background: Tezepelumab is a monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), implicated in asthma pathogenesis, and that has been approved for patients with severe uncontrolled asthma in Spain in October 2023. This study evaluates our experience with Tezepelumab for those patients who received the indicated drug off-label prior to its commercialization.

Methods: We conducted a real-life observational study on three patients from the Severe Asthma Unit of the Hospital Universitario de Fuenlabrada, Spain, who received Tezepelumab off-label before its official approval. We analyzed symptoms control based on ACT, exacerbations, reductions in the doses of oral corticosteroid, lung function, blood changes and safety at 3 months of treatment.

Results: Tezepelumab demonstrated efficacy in improving asthma control and a notable reduction in emergency department visits. OCS use decreased, with one patient halving their prednisone dose. Lung function, particularly FEV1 and FEV1/FVC parameters, improved, but no significant changes were observed in FeNO levels, blood eosinophil counts and total IgE. The treatment exhibited a favorable safety profile with no reported adverse effects during the study period.

Conclusions: In this preliminary real-world experience prior to the official approval of tezepelumab in Spain, this monoclonal antibody showed promising results and suggests its potential as a valuable alternative for the treatment of severe asthma.

背景介绍特珠单抗是一种靶向胸腺基质淋巴细胞生成素(TSLP)的单克隆抗体,与哮喘发病机制有关。本研究评估了在特珠单抗商业化之前在标签外接受该药治疗的患者使用特珠单抗的经验:我们对西班牙 Fuenlabrada 大学医院重症哮喘科的三名患者进行了实际观察研究,这些患者在特珠单抗正式获批之前在标签外接受了特珠单抗治疗。我们根据ACT、病情加重、口服皮质类固醇剂量的减少、肺功能、血液变化和治疗3个月后的安全性对症状控制情况进行了分析:结果:特非普鲁单抗对改善哮喘控制有显著疗效,并明显减少了急诊就诊次数。OCS用量减少,其中一名患者的泼尼松剂量减半。肺功能,尤其是FEV1和FEV1/FVC参数有所改善,但FeNO水平、血液嗜酸性粒细胞计数和总IgE没有明显变化。在研究期间,治疗的安全性良好,没有不良反应报告:在西班牙正式批准使用替塞单抗之前的这次初步实际体验中,这种单克隆抗体显示出了良好的效果,表明它有可能成为治疗严重哮喘的一种重要替代疗法。
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引用次数: 0
Are the presence of asthma and the COVID-19 infection associated with behavioral changes in Lebanese adolescents? 哮喘和 COVID-19 感染是否与黎巴嫩青少年的行为变化有关?
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.1054
Vanessa Azzi, Joya Maria Karam, Wendy D'Andrea, Diana Malaeb, Sami El Khatib, Fouad Sakr, Mariam Dabbous, Souheil Hallit, Michel Soufia

Background: Little evidence is available about psychological stressors in Lebanese asthmatic adolescents, where health-risk behaviors are a serious threat to public health. In addition, the COVID-19 epidemic has had a substantial influence on adolescents' mental health globally, especially in Lebanon, where the ongoing economic and political challenges have largely impacted their psychological well-being. This study aimed to explore the association of asthma and the COVID-19 infection with behaviors among Lebanese adolescents.

Methods: Data were collected in July 2023, using the snowball sampling technique. Inclusion criteria for participation in the study included being of a resident and citizen of Lebanon and aged 12-18 years. Behavioral problems were assessed using the Youth Self-Report (YSR) scale, which yields nine subscales (anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, aggressive behavior, and other problems) and a total score.

Results: Asthma was significantly associated with somatic complaints (Beta [β] = 2.98), attention problems (β = 0.01), and other behavioral problems (β = 0.68). Having contracted the COVID-19 infection, compared to healthy asymptomatic state (β = 1.55), was significantly associated with more anxious behaviors. In the case of stratifying the analysis in terms of gender, the results showed that the presence of asthma was significantly associated with more social behaviors (β = 3.31), thought problems (β = 2.91), attention problems (β = 0.02), other behavioral problems (β = 1.71), and total behavioral problems (β = 5.71) in males. In case stratifying the analysis as to school type, the presence of asthma was significantly associated with more somatic complaints (β = 2.77) in participants from private schools whereas it was significantly associated with more total behavioral problems (total YSR scores) (β = 5.05) in participants from public schools.

Conclusion: It is confirmed that asthma and psychiatric disorders are interconnected, so it would be of great importance to include screening through a psychological intervention in treating asthmatic adolescents by means of (1) recognizing factors affecting patients' mental health, and (2) regulating uncontrolled behaviors that can exacerbate symptoms in order to avoid the future morbidity.

背景:黎巴嫩哮喘青少年的健康风险行为严重威胁着公众健康,而有关黎巴嫩哮喘青少年心理压力的证据却很少。此外,COVID-19疫情对全球青少年的心理健康产生了重大影响,尤其是在黎巴嫩,持续的经济和政治挑战在很大程度上影响了他们的心理健康。本研究旨在探讨哮喘和 COVID-19 感染与黎巴嫩青少年行为的关联:数据收集于 2023 年 7 月,采用滚雪球抽样技术。参与研究的标准包括黎巴嫩居民和公民,年龄在 12-18 岁之间。行为问题采用青少年自我报告量表(YSR)进行评估,该量表有九个分量表(焦虑/抑郁、孤僻/抑郁、躯体不适、社交问题、思想问题、注意力问题、破坏规则行为、攻击行为和其他问题)和一个总分:哮喘与躯体不适(Beta [β] = 2.98)、注意力问题(β = 0.01)和其他行为问题(β = 0.68)明显相关。与健康无症状状态相比(β = 1.55),感染 COVID-19 与更多焦虑行为显著相关。如果按性别进行分层分析,结果显示,男性患哮喘与更多的社交行为(β = 3.31)、思想问题(β = 2.91)、注意力问题(β = 0.02)、其他行为问题(β = 1.71)和总行为问题(β = 5.71)明显相关。如果按学校类型进行分层分析,私立学校的受试者哮喘与更多的躯体不适(β = 2.77)显著相关,而公立学校的受试者哮喘与更多的总行为问题(YSR 总分)(β = 5.05)显著相关:研究证实,哮喘与精神疾病是相互关联的,因此,在治疗哮喘青少年时,通过心理干预进行筛查具有重要意义,其方法是:(1)识别影响患者心理健康的因素;(2)调节可能加重症状的失控行为,以避免未来的发病率。
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引用次数: 0
YBX-1 alleviates sepsis-stimulated lung epithelial cell injury. YBX-1 可减轻败血症刺激的肺上皮细胞损伤
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.1068
Xin Lu, Shouqian Dai, Pengfei Li, Yuqian Zhou, Feng Xu

Objective: To explore the role of Y-box binding protein 1 (YBX-1) in the lipopolysaccharide (LPS)-stimulated inflammation and oxidative stress of BEAS-2B cell line and clarify the underlying mechanism.

Methods: LPS-stimulated BEAS-2B cells were used as a cell model of sepsis-stimulated acute lung injury (ALI). Immunoblot and quantitative polymerase chain reaction assays were used to detect the expression of YBX-1 in LPS-stimulated BEAS-2B cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, TdT-mediated dUTP nick end labeling, and immunoblot assays were conducted to determine the effects of YBX-1 on cell survival. JC-1 staining and adenosine triphosphate production were used to detect the effects of YBX-1 on mitochondrial function. Immunostaining and enzyme-linked immunosorbent serologic assay were performed to examine the effects of YBX-1 on the inflammation and oxidative stress of cells. Immunoblot assay was conducted to confirm the mechanism.

Results: YBX-1 was lowly expressed in LPS-stimulated BEAS-2B cells and enhanced the survival of LPS-stimulated lung epithelial cells. In addition, YBX-1 improved mitochondrial function of LPS-stimulated BEAS-2B cells. YBX-1 inhibited the inflammation and oxidative stress of LPS-stimulated BEAS-2B cells. Mechanically, YBX-1 inhibited mitogen-activated protein kinase (MAPK) axis, thereby alleviating sepsis-stimulated ALI.

Conclusion: YBX-1 alleviated inflammation and oxidative stress of LPS-stimulated BEAS-2B cells via MAPK axis.

目的探讨Y-盒结合蛋白1(YBX-1)在脂多糖(LPS)刺激的BEAS-2B细胞系炎症和氧化应激中的作用,并阐明其潜在机制:方法:以LPS刺激的BEAS-2B细胞作为脓毒症刺激的急性肺损伤(ALI)细胞模型。免疫印迹和定量聚合酶链反应检测 YBX-1 在 LPS 刺激的 BEAS-2B 细胞中的表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-溴化四氮唑、TdT 介导的 dUTP 缺口标记和免疫印迹检测来确定 YBX-1 对细胞存活的影响。JC-1 染色和三磷酸腺苷生成被用来检测 YBX-1 对线粒体功能的影响。免疫染色法和酶联免疫吸附血清法检测了 YBX-1 对细胞炎症和氧化应激的影响。免疫印迹分析证实了这一机制:结果:YBX-1在LPS刺激的BEAS-2B细胞中低表达,并能提高LPS刺激的肺上皮细胞的存活率。此外,YBX-1 还能改善 LPS 刺激的 BEAS-2B 细胞的线粒体功能。YBX-1 可抑制 LPS 刺激的 BEAS-2B 细胞的炎症和氧化应激。从机制上讲,YBX-1 可抑制丝裂原活化蛋白激酶(MAPK)轴,从而缓解败血症刺激的 ALI:结论:YBX-1 可通过 MAPK 轴减轻 LPS 刺激的 BEAS-2B 细胞的炎症和氧化应激反应。
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引用次数: 0
Cold-induced anaphylaxis triggered by drinking cold water. 饮用冷水引发的冷诱发过敏性休克。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.1041
Abdulaziz S Alrafiaah, Elena Netchiporouk, Moshe Ben-Shoshan

Cold urticaria is an inducible urticaria in which hives and angioedema appear after exposure to cold. The symptoms of cold urticaria often are limited to hives/angioedema. However, in up to 20% of cases, cold exposure may trigger anaphylaxis. We report the case of an 11-year-old boy previously diagnosed with chronic spontaneous urticaria who developed facial swelling, itchy hives, difficulty in breathing, vomiting and abdominal pain within 5 minutes of drinking cold water. He received a standard dose of non-sedating second-generation antihistamines at home. He was observed in the emergency room for 2 hours and discharged with an epinephrin autoinjector. During the subsequent outpatient clinic visit, an ice cube test was performed which confirmed the new diagnosis of comorbid cold-induced chronic urticaria. On further questioning, the parents reported occurrence of hives following swimming in the swimming pool. Cold-induced urticaria should be suspected in cases of anaphylaxis associated with cold exposure. Patients with chronic forms of urticaria who present with new anaphylaxis should be assessed for a potential concomitant cold-induced form.

寒冷性荨麻疹是一种诱发性荨麻疹,患者在暴露于寒冷环境后会出现荨麻疹和血管性水肿。寒冷性荨麻疹的症状通常仅限于荨麻疹/血管性水肿。然而,在多达 20% 的病例中,接触寒冷可能会引发过敏性休克。我们报告了一例 11 岁男孩的病例,他之前被诊断为慢性自发性荨麻疹,在饮用冷水后 5 分钟内出现面部肿胀、荨麻疹瘙痒、呼吸困难、呕吐和腹痛。他在家服用了标准剂量的非镇静剂第二代抗组胺药。他在急诊室观察了 2 个小时,出院时使用了肾上腺素自动注射器。在随后的门诊就诊中,医生对他进行了冰块试验,结果确诊为合并寒冷诱发的慢性荨麻疹。经进一步询问,家长称在游泳池游泳后出现了荨麻疹。在与寒冷接触相关的过敏性休克病例中,应怀疑是寒冷诱发的荨麻疹。慢性荨麻疹患者如果出现新的过敏性休克,应评估是否可能同时患有寒冷诱发的荨麻疹。
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引用次数: 0
Primary, secondary and tertiary prevention of food allergy: current practices and future directions. 食物过敏的一级、二级和三级预防:当前做法和未来方向。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.1023
Caoimhe Cronin, Noah Salzberg, Yuxin Woon, Juan Trujillo Wurttele

The incidence of food allergies has risen around the globe, and experts have been exploring methods of preventing such allergies in young children to ease the burden of disease and reduce the morbidity and mortality caused by anaphylaxis to food allergens. Such preventative measures can be categorised as primary, secondary and tertiary prevention, which are discussed in detail in this review. Primary prevention is defined as the prevention of becoming sensitised towards specific allergens. The evidence suggests that avoiding common allergenic foods during pregnancy and breastfeeding is not protective against food allergies, and guidelines recommend weaning from 4 to 6 months of age, with recent studies supporting the early introduction of peanuts at 4 months to prevent peanut allergy. Secondary prevention targets patients who are already sensitised and aims to halt the progression of sensitisation, with evidence for high rates of success and safety in trials of early introduction to milk and peanuts using oral immunotherapy in sensitised infants. Tertiary allergy prevention focuses on reducing the risk of a patient having anaphylaxis, with oral immunotherapy being the most common method of promoting tolerance in allergic children. Several studies have demonstrated successful reintroduction for milk, egg and peanut; however, no such guidelines are recommended for other foods. Finally, dietary advancement therapy in the form of milk and egg ladders has been employed as a method of primary, secondary and tertiary prevention of allergies, particularly in Ireland, the UK and Canada.

食物过敏的发病率在全球范围内不断上升,专家们一直在探索预防幼儿食物过敏的方法,以减轻疾病负担,降低因食物过敏原引起的过敏性休克所导致的发病率和死亡率。这些预防措施可分为一级预防、二级预防和三级预防,本综述将对此进行详细讨论。一级预防是指防止对特定过敏原过敏。有证据表明,在孕期和母乳喂养期间避免食用常见的致敏食物并不能预防食物过敏,指南建议在婴儿 4 到 6 个月大时断奶,最近的研究支持在婴儿 4 个月大时尽早添加花生以预防花生过敏。二级预防针对的是已经过敏的患者,目的是阻止过敏的发展,有证据表明,在过敏婴儿中使用口服免疫疗法及早添加牛奶和花生的试验成功率高且安全。过敏三级预防的重点是降低患者发生过敏性休克的风险,口服免疫疗法是促进过敏儿童耐受性的最常用方法。有几项研究表明,重新引入牛奶、鸡蛋和花生的做法是成功的;但对于其他食物,目前还没有推荐此类指南。最后,以牛奶和鸡蛋阶梯为形式的饮食促进疗法已被用作过敏症的一级、二级和三级预防方法,尤其是在爱尔兰、英国和加拿大。
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引用次数: 0
Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants. 直接口腔刺激试验的安全性:对婴儿轻度β-内酰胺过敏进行脱标签试验。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.887
Francisca Cunha, Inês Cunha, Eva Gomes

Background: Around 10% of people report a drug allergy and avoid some medications because of fear of allergic reactions. However, only after a proper diagnostic workup can some of these reactions be confirmed as allergic or nonallergic hypersensitivities. Beta-lactams (BLs) are the most common medication suspected of being involved in drug hypersensivity reactions (DHRs) in children. Recently, direct oral provocation tests (DPT) with BLs gained popularity within pediatric populations as a tool for delabeling children with suspected BL allergies. This study aimed to evaluate the safety of direct provocation tests in infants with mild cutaneous non-immediate reactions to BLs.

Methods: The authors retrospectively analyzed the data of 151 infants between 2015 and 2022, referred for evaluating a suspected allergy to BLs that occurred before age 24 months.

Results: The mean age of the children, including 55% male kids, at the suspected reaction was 15.9 months and the mean age at the time of the DPT was 39.6 months. In most cases, antibiotics were prescribed to treat common upper respiratory infections, such as acute otitis (54.3%) and acute tonsillitis (27.2%). Amoxicillin was considered the culprit drug in 62.9% of the cases, and the combination of amoxicillin-clavulanic acid in the case of 33.8% of children. The most frequent associated cutaneous clinical manifestations were maculopapular exanthema in 74.8% and delayed urticaria/angioedema in 25.2%. Of the 151 infants evaluated, parents of 149 infants agreed for a direct DPT, and only three had a positive test (2%). Symptoms resulting from the DPT were mild and easily treatable.

Conclusions: A direct DPT without prior tests is a safe and effective procedure to delabel BL allergy, even in infants. The authors wish to emphasize the importance of properly validating BL allergy suspicions by promoting appropriate diagnostic procedures in infants as, in most cases, DHRs can be excluded and there is no need for further therapeutic restrictions.

背景:约有 10% 的人报告对药物过敏,并因害怕过敏反应而避免服用某些药物。然而,只有经过适当的诊断检查后,其中一些反应才能被确认为过敏性或非过敏性过敏反应。β-内酰胺类药物(BLs)是被怀疑与儿童药物过敏反应(DHRs)有关的最常见药物。最近,β-内酰胺类药物直接口服激发试验(DPT)在儿科人群中逐渐流行起来,成为对怀疑对β-内酰胺类药物过敏的儿童进行脱敏的一种工具。本研究旨在评估直接激发试验对BL轻度皮肤非即刻反应婴儿的安全性:作者回顾性分析了 2015 年至 2022 年间 151 名婴儿的数据,这些婴儿在 24 个月之前因评估疑似对 BLs 过敏而转诊:疑似过敏反应发生时,患儿的平均年龄为 15.9 个月,其中 55% 为男性,接受白喉、破伤风和百日咳治疗时的平均年龄为 39.6 个月。在大多数病例中,抗生素被用于治疗常见的上呼吸道感染,如急性中耳炎(54.3%)和急性扁桃体炎(27.2%)。在 62.9% 的病例中,阿莫西林被认为是罪魁祸首,而在 33.8% 的病例中,阿莫西林-克拉维酸联合用药被认为是罪魁祸首。最常见的相关皮肤临床表现是74.8%的患儿出现斑丘疹性红斑,25.2%的患儿出现迟发性荨麻疹/血管性水肿。在接受评估的 151 名婴儿中,149 名婴儿的父母同意直接进行白喉、百日咳和破伤风三联疫苗检测,只有 3 名婴儿的检测结果呈阳性(2%)。白喉、百日咳、破伤风三联疫苗引起的症状轻微,易于治疗:结论:无需事先检测的直接 DPT 是一种安全有效的 BL 过敏脱敏方法,即使对婴儿也是如此。作者希望强调,通过在婴儿中推广适当的诊断程序来正确验证对 BL 过敏的怀疑非常重要,因为在大多数情况下,DHR 可以被排除,也没有必要进一步限制治疗。
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引用次数: 0
RNF135 promotes cell proliferation and autophagy in lung adenocarcinoma by promoting the phosphorylation of ULK1. RNF135 通过促进 ULK1 的磷酸化来促进肺腺癌的细胞增殖和自噬。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-03-01 eCollection Date: 2024-01-01 DOI: 10.15586/aei.v52i2.1048
Lichun Zhuang, Guanhui Shi, Yuejun Sun

Objective: To detect the expression of RING finger protein 135 (RNF135) in lung adenocarcinoma tissues and explore its role in the progression of lung adenocarcinoma.

Methods: Bioinformation analysis, quantitative polymerase chain reaction, and immunoblotting technique discovered the expression of RNF135 in lung adenocarcinoma tissues. Cell counting kit-8 and colony formation, immunostaining, and immunoblot assays examined the effects of RNF135 on cell growth and autophagy. Co-immunoprecipitation (Co-IP), immunostaining, and immuoblotting were conducted to confirm the mechanism.

Results: RNF135 was highly expressed in lung adenocarcinoma. In addition, RNF135 promoted lung adenocarcinoma cell growth. Further, data confirmed that RNF135 promoted autophagy in lung adenocarcinoma cells. Mechanically, RNF135 directly interacted with Unc-51-like autophagy activating kinase 1 (ULK1) to promote its phosphorylation level.

Conclusion: RNF135 promoted cell growth and autophagy in lung adenocarcinoma by promoting the phosphorylation of ULK1.

目的检测RING指蛋白135(RNF135)在肺腺癌组织中的表达,并探讨其在肺腺癌进展中的作用:生物信息分析、定量聚合酶链反应和免疫印迹技术发现了RNF135在肺腺癌组织中的表达。细胞计数试剂盒-8和集落形成、免疫染色和免疫印迹检测了RNF135对细胞生长和自噬的影响。为了证实其作用机制,还进行了共免疫沉淀(Co-IP)、免疫染色和免疫印迹分析:结果:RNF135在肺腺癌中高表达。此外,RNF135 还能促进肺腺癌细胞的生长。此外,数据证实 RNF135 促进了肺腺癌细胞的自噬。在机制上,RNF135直接与Unc-51样自噬激活激酶1(ULK1)相互作用,促进其磷酸化水平:结论:RNF135通过促进ULK1的磷酸化来促进肺腺癌细胞的生长和自噬。
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引用次数: 0
Polyphyllin II inhibits NLPR3 inflammasome activation and inflammatory response of Mycobacterium tuberculosis-infected human bronchial epithelial cells. 多粘菌素 II 可抑制 NLPR3 炎症小体的激活和受结核分枝杆菌感染的人支气管上皮细胞的炎症反应。
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-01-01 DOI: 10.15586/aei.v52i1.998
Guodong Cheng, Gengzhi Ye, Ying Ma, Yuqing Wang

Background: The bronchial infection by Mycobacterium tuberculosis (Mtb) is increasing in prevalence and severity worldwide. Despite appropriate tuberculosis treatment, most patients still develop bronchial stenosis, which often leads to disability. Polyphyllin II (PP2) is a steroidal saponin extracted from Rhizoma Paridis. In this study, we aimed to explore the effect of PP2 on the advancement of Mtb-induced bronchial infection.

Method: The effects of PP2 on cell viability were measured by using MTT and lactate dehydrogenase (LDH) kit. The mRNA and protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 were elucidated by RT-qPCR and ELISA, respectively. The expression of NLR family pyrin domain containing 3 (NLRP3) related inflammasome (NLRP3, IL-1β, and cleaved-caspase-1) and the activated degree of protein kinase B (AKT)/nuclear factor-kappa B (NF-kB; p-AKT and p-NF-κB) were detected by Western blotting.

Results: PP2 at 0, 1, 5, and 10 μM had little cytotoxicity on 16HBE cells. PP2 inhibited Mtb-induced cell proliferation and decreased LDH levels. We further found that PP2 could suppress Mtb-induced inflammatory responses and activation of NLPR3 inflammasome. Additionally, the role of PP2 in Mtb is associated with the AKT/NF-kB signaling pathway.

Conclusion: PP2 inhibited Mtb infection in bronchial epithelial cells, by inhibiting Mtb-induced inflammatory reactions and activation of NLPR3 inflammasome. These effects may be exerted by suppressing the AKT/NF-kB pathway, which will provide a prospective treatment.

背景:在全球范围内,支气管结核分枝杆菌(Mtb)感染的发病率和严重程度都在不断上升。尽管对结核病进行了适当的治疗,但大多数患者仍会出现支气管狭窄,这往往会导致残疾。多粘菌素 II(PP2)是从黄连中提取的一种甾体皂甙。本研究旨在探讨 PP2 对 Mtb 诱导的支气管感染进展的影响:方法:使用 MTT 和乳酸脱氢酶(LDH)试剂盒测定 PP2 对细胞活力的影响。采用 RT-qPCR 和 ELISA 方法分别检测肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β 和 IL-8 的 mRNA 和蛋白水平。免疫印迹法检测了NLR家族含吡咯啉结构域3(NLRP3)相关炎性体(NLRP3、IL-1β和裂解-caspase-1)的表达和蛋白激酶B(AKT)/核因子-kappa B(NF-kB;p-AKT和p-NF-κB)的活化程度:0、1、5 和 10 μM 的 PP2 对 16HBE 细胞几乎没有细胞毒性。PP2 可抑制 Mtb 诱导的细胞增殖并降低 LDH 水平。我们还发现 PP2 能抑制 Mtb 诱导的炎症反应和 NLPR3 炎性体的激活。此外,PP2在Mtb中的作用与AKT/NF-kB信号通路有关:结论:PP2通过抑制Mtb诱导的炎症反应和NLPR3炎性体的活化,抑制支气管上皮细胞的Mtb感染。这些作用可能是通过抑制 AKT/NF-kB 通路产生的,这将为治疗提供一个前景。
{"title":"Polyphyllin II inhibits NLPR3 inflammasome activation and inflammatory response of <i>Mycobacterium tuberculosis</i>-infected human bronchial epithelial cells.","authors":"Guodong Cheng, Gengzhi Ye, Ying Ma, Yuqing Wang","doi":"10.15586/aei.v52i1.998","DOIUrl":"10.15586/aei.v52i1.998","url":null,"abstract":"<p><strong>Background: </strong>The bronchial infection by <i>Mycobacterium tuberculosis (Mtb)</i> is increasing in prevalence and severity worldwide. Despite appropriate tuberculosis treatment, most patients still develop bronchial stenosis, which often leads to disability. Polyphyllin II (PP2) is a steroidal saponin extracted from Rhizoma Paridis. In this study, we aimed to explore the effect of PP2 on the advancement of <i>Mtb</i>-induced bronchial infection.</p><p><strong>Method: </strong>The effects of PP2 on cell viability were measured by using MTT and lactate dehydrogenase (LDH) kit. The mRNA and protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-8 were elucidated by RT-qPCR and ELISA, respectively. The expression of NLR family pyrin domain containing 3 (NLRP3) related inflammasome (NLRP3, IL-1β, and cleaved-caspase-1) and the activated degree of protein kinase B (AKT)/nuclear factor-kappa B (NF-kB; p-AKT and p-NF-κB) were detected by Western blotting.</p><p><strong>Results: </strong>PP2 at 0, 1, 5, and 10 μM had little cytotoxicity on 16HBE cells. PP2 inhibited <i>Mtb</i>-induced cell proliferation and decreased LDH levels. We further found that PP2 could suppress <i>Mtb</i>-induced inflammatory responses and activation of NLPR3 inflammasome. Additionally, the role of PP2 in <i>Mtb</i> is associated with the AKT/NF-kB signaling pathway.</p><p><strong>Conclusion: </strong>PP2 inhibited <i>Mtb</i> infection in bronchial epithelial cells, by inhibiting <i>Mtb</i>-induced inflammatory reactions and activation of NLPR3 inflammasome. These effects may be exerted by suppressing the AKT/NF-kB pathway, which will provide a prospective treatment.</p>","PeriodicalId":7536,"journal":{"name":"Allergologia et immunopathologia","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity. 特应性皮炎儿童和青少年的抗氧化防御能力:与疾病严重程度的关系
IF 1.8 4区 医学 Q3 Medicine Pub Date : 2024-01-01 DOI: 10.15586/aei.v52i1.933
Roseani da Silva Andrade, Fabíola Isabel Suano de Souza, Carolina Sanchez Aranda, Marcia Carvalho Mallozi, Ariel Cordeiro Ferreira, Talita Lemos Neves Barreto, Fernando Luiz Affonso Fonseca, Roseli Oselka Saccardo Sarni, Dirceu Solé

Background: Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, in early childhood. Chronic skin inflammation is associated with overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production of free radicals and antioxidant defense, results in tissue inflammation due to the upregulation of genes that encode inflammatory cytokines. This condition plays an important role in the pathogenesis of AD.

Objective: To compare the antioxidant defense in children and adolescents with AD with that of healthy individuals and to verify the association of antioxidant defense with disease severity and nutritional status.

Methods: Cross-sectional study that evaluated 48 children and adolescents with AD and 25 controls for nutritional assessment (body mass index z score [BMIZ] and height for age z score [HAZ]) and levels of vitamins A, C, E, and D, zinc (Zn), copper (Cu), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), high-sensitivity C-reactive protein (CRP) and interleukin 33 (IL-33).

Results: There was no significant difference in the comparison between AD and control groups for serum levels of vitamins (A, D, C, and E), copper, and antioxidant enzymes. Serum zinc levels were higher in the AD group (β = 24.20; 95% CI 13.95-34.91; P < 0.001) even after adjusting the BMIZ, HAZ, gender, IL-33, and CRP. Children and adolescents with moderate or severe AD compared to mild AD (SCORAD - 36.7±17.4 vs 11.8 ± 3.9; P < 0.001) had lower values of the vitamin E/total lipid ratio (3.68 [0.29;12.63] vs 5.92 [3.27;17.37]; P = 0.013).

Conclusion: Children and adolescents with AD had higher concentrations OF elevated levels of zinc compared to controls, a fact not observed for other biomarkers of antioxidant defense. AD in moderate or severe forms presented lower concentrations of vitamin E, a potent antioxidant fat soluble.

背景:特应性皮炎(AD)是一种复发性慢性皮肤炎症性疾病,一般在儿童早期发病。慢性皮肤炎症与过量产生活性氧(ROS)(如超氧化物和过氧化氢)有关。氧化应激是自由基的产生与抗氧化防御之间的失衡,由于编码炎症细胞因子的基因上调,导致组织炎症。这种情况在注意力缺失症的发病机制中起着重要作用:比较患有 AD 的儿童和青少年与健康人的抗氧化防御能力,并验证抗氧化防御能力与疾病严重程度和营养状况的关系:横断面研究:对48名患有AD的儿童和青少年以及25名对照组进行营养评估(体重指数z评分[BMIZ]和年龄身高z评分[HAZ]),并评估维生素A、C、E和D、锌(Zn)、铜(Cu)、抗氧化酶(超氧化物歧化酶[SOD]、过氧化氢酶[CAT]、谷胱甘肽过氧化物酶[GPx])、高敏C反应蛋白(CRP)和白细胞介素33(IL-33)的水平。结果AD组和对照组的血清维生素(A、D、C和E)、铜和抗氧化酶水平比较无明显差异。即使调整了BMIZ、HAZ、性别、IL-33和CRP,AD组的血清锌水平也更高(β = 24.20; 95% CI 13.95-34.91; P < 0.001)。与轻度AD(SCORAD - 36.7±17.4 vs 11.8±3.9;P <0.001)相比,中度或重度AD儿童和青少年的维生素E/总脂质比值较低(3.68 [0.29;12.63] vs 5.92 [3.27;17.37];P = 0.013):结论:与对照组相比,患有注意力缺失症的儿童和青少年体内锌的浓度更高,而在其他抗氧化防御生物标志物中却没有发现这一现象。中度或重度AD患者的维生素E浓度较低,而维生素E是一种有效的脂溶性抗氧化剂。
{"title":"Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity.","authors":"Roseani da Silva Andrade, Fabíola Isabel Suano de Souza, Carolina Sanchez Aranda, Marcia Carvalho Mallozi, Ariel Cordeiro Ferreira, Talita Lemos Neves Barreto, Fernando Luiz Affonso Fonseca, Roseli Oselka Saccardo Sarni, Dirceu Solé","doi":"10.15586/aei.v52i1.933","DOIUrl":"10.15586/aei.v52i1.933","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, in early childhood. Chronic skin inflammation is associated with overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production of free radicals and antioxidant defense, results in tissue inflammation due to the upregulation of genes that encode inflammatory cytokines. This condition plays an important role in the pathogenesis of AD.</p><p><strong>Objective: </strong>To compare the antioxidant defense in children and adolescents with AD with that of healthy individuals and to verify the association of antioxidant defense with disease severity and nutritional status.</p><p><strong>Methods: </strong>Cross-sectional study that evaluated 48 children and adolescents with AD and 25 controls for nutritional assessment (body mass index z score [BMIZ] and height for age z score [HAZ]) and levels of vitamins A, C, E, and D, zinc (Zn), copper (Cu), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), high-sensitivity C-reactive protein (CRP) and interleukin 33 (IL-33).</p><p><strong>Results: </strong>There was no significant difference in the comparison between AD and control groups for serum levels of vitamins (A, D, C, and E), copper, and antioxidant enzymes. Serum zinc levels were higher in the AD group (β = 24.20; 95% CI 13.95-34.91; P < 0.001) even after adjusting the BMIZ, HAZ, gender, IL-33, and CRP. Children and adolescents with moderate or severe AD compared to mild AD (SCORAD - 36.7±17.4 vs 11.8 ± 3.9; P < 0.001) had lower values of the vitamin E/total lipid ratio (3.68 [0.29;12.63] vs 5.92 [3.27;17.37]; P = 0.013).</p><p><strong>Conclusion: </strong>Children and adolescents with AD had higher concentrations OF elevated levels of zinc compared to controls, a fact not observed for other biomarkers of antioxidant defense. AD in moderate or severe forms presented lower concentrations of vitamin E, a potent antioxidant fat soluble.</p>","PeriodicalId":7536,"journal":{"name":"Allergologia et immunopathologia","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139376982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Allergologia et immunopathologia
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