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Expression Analysis of Long Noncoding RNA-MALAT1 and Interleukin-6 in Inflammatory Bowel Disease Patients 长链非编码RNA-MALAT1和白细胞介素-6在炎症性肠病患者中的表达分析
4区 医学 Q4 ALLERGY Pub Date : 2023-11-07 DOI: 10.18502/ijaai.v22i5.13997
Mohsen Nemati Bajestan, Moein Piroozkhah, Vahid Chaleshi, Naser Elmi Ghiasi, Negar Jamshidi, Reza Mirfakhraie, Hedieh Balaii, Shabnam Shahrokh, Hamid Asadzadeh Aghdaei, Zahra Salehi, Ehsan Nazemalhosseini Mojarad
Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.
炎症性肠病(IBD)表现为胃肠道的慢性炎症。这项研究的重点是一种名为转移相关肺腺癌转录本1 (MALAT1)的长链非编码RNA (lncRNA)。MALAT1的失调与多种自身免疫性疾病有关,并调节促炎细胞因子。il - 6在包括IBD在内的免疫触发性疾病中的作用是另一个焦点。本研究仔细分析了IBD患者中MALAT1和IL6的表达,以揭示潜在的相互作用。 该研究涉及33名IBD患者(13名患有克罗恩病,20名患有溃疡性结肠炎)和20名健康对照者。实时定量聚合酶链反应测定MALAT1和IL6基因表达水平。利用LncRRIsearch和Cytoscape等工具构建了竞争性内源性RNA (ceRNA)调控网络。深入研究炎症性肠病数据库以了解il - 6在IBD中的作用。潜在靶向这些基因的药物也通过ddgidb被确定。结果显示,与健康对照组相比,IBD患者的MALAT1和IL6表达水平显著升高。MALAT1与IL6没有直接的线性相关,但IL6 可以作为MALAT1的目标。分析揭示了MALAT1和IL6之间的相互作用,由hsa-miR-202-3p、hsa-miR-1-3p和has-miR-9-5p调节。IL6在ibd相关炎症中的关键作用,可能与其他细胞因子相互作用,被强调。此外,还发现了治疗MALAT1的CILOBRADINE和治疗IL6的SILTUXIMAB等潜在药物。 本研究强调了MALAT1和IL6作为IBD患者诊断和治疗靶点的潜在价值。
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 The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb.
 Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6
 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified.
 This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.
","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"71 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135475687","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
Chronic Allergen Exposure Contributes to Steroid Resistance via Increased Phosphorylation of Glucocorticoid Receptors S226 and p38 MAPK in a Mouse Model of Asthma 在哮喘小鼠模型中,慢性过敏原暴露通过糖皮质激素受体S226和p38 MAPK磷酸化的增加有助于类固醇抵抗
4区 医学 Q4 ALLERGY Pub Date : 2023-11-07 DOI: 10.18502/ijaai.v22i5.13992
Yan Zhou, Limin Wang, Weizhong Jin, Chenhui Qiu, Hualiang Jin
Chronic allergen exposure can significantly induce p38 mitogen-activated protein kinase (MAPK) activation in asthma. p38 MAPK is involved in steroid resistance through phosphorylation of glucocorticoid receptors (GR) at S226. This study aims to investigate whether chronic allergen exposure can induce steroid resistance and whether it is associated with p38 MAPK activation in asthma. A mouse model of asthma was prepared by sensitizing and challenging mice with chronic ovalbumin (OVA) exposure. Key features of allergic asthma, encompassing bronchial hyperresponsiveness, pathology of lung tissues, cytokine profiles of inflammation in bronchoalveolar lavage fluid (BALF), and serum immunoglobulin (Ig)E concentration were evaluated. Furthermore, suppressive effects of corticosteroid on the splenocytes under stimulation of lipopolysaccharides, glucocorticoid receptor (GR) DNA binding ability of splenocytes, expression of GRα and phosphorylation of GR s226 in splenocytes, and p38 MAPK phosphorylation in splenocytes and lung tissues were determined. Chronic OVA exposure substantially induced airway hypersensitivity, leading to increased inflammatory infiltration in lung tissues. Additionally, it resulted in elevated levels of interleukin (IL)-4, IL-5, and IL-6 in BALF, as well as heightened levels of IgE in serum. Furthermore, OVA exposure substantially enhanced p38 MAPK phosphorylation in lung tissues. It also weakened the suppressive impacts of corticosteroids on splenocytes, impaired the GR DNA binding ability, and led to an enhanced phosphorylated state of GR S226 and p38 MAPK in splenocytes. Taken together, chronic allergen exposure contributes to steroid resistance in asthma, which is linked to an increased phosphorylated state of GR S226 and p38 MAPK.
慢性过敏原暴露可显著诱导哮喘患者p38丝裂原活化蛋白激酶(MAPK)的激活。p38 MAPK通过糖皮质激素受体(GR) S226位点的磷酸化参与类固醇抗性。本研究旨在探讨慢性过敏原暴露是否可诱导类固醇抵抗,以及是否与哮喘患者p38 MAPK激活有关。 通过致敏和激发慢性卵清蛋白暴露小鼠制备哮喘模型。我们评估了过敏性哮喘的主要特征,包括支气管高反应性、肺组织病理学、支气管肺泡灌洗液(BALF)炎症的细胞因子谱和血清免疫球蛋白(Ig)E浓度。进一步观察糖皮质激素对脂多糖刺激下脾细胞的抑制作用、脾细胞糖皮质激素受体(GR) DNA结合能力、脾细胞中GRα的表达和GR s226的磷酸化,以及脾细胞和肺组织中p38 MAPK的磷酸化。 长期暴露于OVA可显著诱导气道过敏,导致肺组织炎症浸润增加。此外,它导致BALF中白细胞介素(IL)-4、IL-5和IL-6水平升高,血清中IgE水平升高。此外,暴露于OVA可显著增强肺组织中p38 MAPK的磷酸化。它还削弱了皮质类固醇对脾细胞的抑制作用,损害了GR DNA的结合能力,导致脾细胞中GR S226和p38 MAPK的磷酸化状态增强。 综上所述,慢性过敏原暴露有助于哮喘中的类固醇抵抗,这与GR S226和p38 MAPK磷酸化状态的增加有关。
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 A mouse model of asthma was prepared by sensitizing and challenging mice with chronic ovalbumin (OVA) exposure. Key features of allergic asthma, encompassing bronchial hyperresponsiveness, pathology of lung tissues, cytokine profiles of inflammation in bronchoalveolar lavage fluid (BALF), and serum immunoglobulin (Ig)E concentration were evaluated. Furthermore, suppressive effects of corticosteroid on the splenocytes under stimulation of lipopolysaccharides, glucocorticoid receptor (GR) DNA binding ability of splenocytes, expression of GRα and phosphorylation of GR s226 in splenocytes, and p38 MAPK phosphorylation in splenocytes and lung tissues were determined.
 Chronic OVA exposure substantially induced airway hypersensitivity, leading to increased inflammatory infiltration in lung tissues. Additionally, it resulted in elevated levels of interleukin (IL)-4, IL-5, and IL-6 in BALF, as well as heightened levels of IgE in serum. Furthermore, OVA exposure substantially enhanced p38 MAPK phosphorylation in lung tissues. It also weakened the suppressive impacts of corticosteroids on splenocytes, impaired the GR DNA binding ability, and led to an enhanced phosphorylated state of GR S226 and p38 MAPK in splenocytes.
 Taken together, chronic allergen exposure contributes to steroid resistance in asthma, which is linked to an increased phosphorylated state of GR S226 and p38 MAPK.
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引用次数: 0
PD-1/PD-L1 Interaction Regulates BCL2, KI67, BAX, and CASP3, Altering Proliferation, Survival, and Apoptosis in Acute Myeloid Leukemia PD-1/PD-L1相互作用调节BCL2、KI67、BAX和CASP3,改变急性髓性白血病的增殖、存活和凋亡
4区 医学 Q4 ALLERGY Pub Date : 2023-11-07 DOI: 10.18502/ijaai.v22i5.13998
Mojdeh Soltani, Mahshid Vosoughi, Mazdak Ganjalikhani-Hakemi, Hoorieh Shapoorian, Pezhman Beshkar, Nahid Eskandari, Behrooz Ghezelbash
Programmed death ligand‑1 (PD‑L1) is a pivotal inhibitory checkpoint ligand known to induce T-cell exhaustion via interaction with the programmed death‑1 (PD‑1) receptor. Beyond this, PD-L1’s intrinsic signaling pathways within cancer cells warrant further exploration. This study aims to elucidate the effect of PD-L1 stimulation on the proliferation, survival, and apoptosis of acute myeloid leukemia (AML) cell lines. Two human AML cell lines, HL-60 and THP-1 were cultured and treated with phorbol 12-myristate 13-acetate (PMA) to induce PD-L1overexpression. Post-treatment PD-L1 expression was confirmed via flow cytometry. Subsequently, cell surface PD-L1 was stimulated using a recombinant PD-1, 24 hours post-PMA treatment. The expression alterations in pivotal genes including BCL2, MKI67, BAX, and CASP3 were monitored using quantitative real-time polymerase chain reaction 24 and 48 hours post-treatment. Additionally, annexin-V through flow cytometry. Findings reveal that PD-L1 stimulation augments AML cell proliferation and survival by enhancing MKI67 and BCL2 expressions while concurrently inhibiting cell apoptosis due to decreased BAX and CASP3 expression following PD-L1 stimulation. Notably, stimulated cells expressed exhibited reduced annexin-V compared to control cells. This study underscores that PD-L1 stimulation fosters AML cell proliferation and survival while impeding cell apoptosis. The results hold potential implications for targeting PD-L1 in AML treatment strategies.
程序性死亡配体- 1 (PD - L1)是一种关键的抑制检查点配体,已知通过与程序性死亡- 1 (PD - 1)受体相互作用诱导t细胞衰竭。除此之外,PD-L1在癌细胞内的内在信号通路值得进一步探索。本研究旨在阐明PD-L1刺激对急性髓性白血病(AML)细胞系增殖、存活和凋亡的影响。培养2株人AML细胞株HL-60和THP-1,用PMA诱导pd - l1过表达。流式细胞术检测PD-L1表达。随后,在pma处理24小时后,用重组PD-1刺激细胞表面PD-L1。在治疗后24和48小时,采用实时定量聚合酶链反应监测关键基因BCL2、MKI67、BAX和CASP3的表达变化。此外,通过流式细胞术检测annexin-V。 研究结果表明,PD-L1刺激通过增强MKI67和BCL2的表达来增强AML细胞的增殖和存活,同时由于PD-L1刺激后BAX和CASP3的表达降低而抑制细胞凋亡。值得注意的是,与对照细胞相比,受刺激细胞表达的annexin-V减少。 这项研究强调,PD-L1刺激促进AML细胞增殖和存活,同时阻碍细胞凋亡。这些结果对靶向PD-L1的AML治疗策略具有潜在的意义。
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 Two human AML cell lines, HL-60 and THP-1 were cultured and treated with phorbol 12-myristate 13-acetate (PMA) to induce PD-L1overexpression. Post-treatment PD-L1 expression was confirmed via flow cytometry. Subsequently, cell surface PD-L1 was stimulated using a recombinant PD-1, 24 hours post-PMA treatment. The expression alterations in pivotal genes including BCL2, MKI67, BAX, and CASP3 were monitored using quantitative real-time polymerase chain reaction 24 and 48 hours post-treatment. Additionally, annexin-V through flow cytometry.
 Findings reveal that PD-L1 stimulation augments AML cell proliferation and survival by enhancing MKI67 and BCL2 expressions while concurrently inhibiting cell apoptosis due to decreased BAX and CASP3 expression following PD-L1 stimulation. Notably, stimulated cells expressed exhibited reduced annexin-V compared to control cells.
 This study underscores that PD-L1 stimulation fosters AML cell proliferation and survival while impeding cell apoptosis. The results hold potential implications for targeting PD-L1 in AML treatment strategies.","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"69 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135476707","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
The Effect of Oral Montelukast in Controlling Asthma Attacks in Children; A Randomized Double-blind Placebo Control Study 口服孟鲁司特对儿童哮喘发作的控制作用随机双盲安慰剂对照研究
4区 医学 Q4 ALLERGY Pub Date : 2023-11-07 DOI: 10.18502/ijaai.v22i5.13990
Mohsen Jafari, Masoomeh Sobhani, Kambiz Eftekhari, Armen Malekiantaghi, Mohammad Gharagozlou, Alireza Shafiei
Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The present study was conducted to investigate the clinical efficacy of oral Montelukast for asthma attacks in children. This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission. In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge. The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit.
口服孟鲁司特被推荐作为持续性哮喘的维持治疗,但其控制哮喘发作的有效性存在争议。本研究旨在探讨口服孟鲁司特治疗儿童哮喘发作的临床疗效。 本研究是一项双盲安慰剂对照临床试验,研究对象是在伊朗德黑兰Bahrami儿童医院急诊科住院一年的80名1-14岁哮喘患儿。患者随机分为病例组和对照组。除了标准的哮喘发作治疗外,病例组使用孟鲁司特,对照组使用安慰剂,疗程为一周。入院后1、4、8、24和48小时,以哮喘发作严重程度评分和室内空气氧饱和度百分比(SpO2)作为主要结局对患者进行评估。治疗前48小时,病例组与对照组哮喘发作严重程度评分和SpO2评分差异无统计学意义。在住院时间和入住重症监护病房的人数方面,两组之间没有显著差异。出院后无患者再次住院。 这项研究的结果表明,使用孟鲁司特与标准治疗哮喘发作的儿童没有额外的好处。
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 This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission.
 In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge.
 The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit.","PeriodicalId":14560,"journal":{"name":"Iranian journal of allergy, asthma, and immunology","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135476560","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
Role of Long Non-coding RNA HSD17B3-AS1 in Trauma for COVID-19. 长非编码RNA HSD17B3-AS1在新冠肺炎创伤中的作用。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2023-09-03 DOI: 10.18502/ijaai.v22i4.13607
Amir-Reza Javanmard, Hadi Esmaeili Gouvarchinghaleh, Ruhollah Dorostkar, Mahdi Tat

COVID-19, an acute respiratory syndrome caused by the SARS-CoV-2 virus, was first reported in late 2019 in Wuhan, China, and rapidly escalated into a global pandemic. The condition can lead to organ dysfunction and ultimately death through its onset of acute respiratory distress syndrome (ARDS). Disease severity has been linked to proinflammatory cytokines which activate the NF-κB and STAT transcription factors in infected cells. It has been proven that lncRNAs play a very important role in reducing or increasing inflammatory factors. This makes them potentially valuable in recognizing pathogenesis pathways and therapeutic targets in COVID-19. Nanocurcumin is known as an antioxidant, tumor suppressor and anti-inflammatory substance, and it can be effective to reduce inflammation caused by the disease of COVID-19. This study analyzed Sequence Read Archive data from COVID-19 patients with acute versus milder symptoms, identifying dysregulated genes and non-coding RNAs. To verify this correlation, the expression of the candidate gene was evaluated with quantitative polymerase chain reaction (qPCR) in mouse models, while immunoglobulin (Ig) G titer was measured using enzyme-linked immunosorbent assay (ELISA) in mouse serum samples. Here we introduced a novel lncRNA called HSD17B3-AS1, suggested as a therapeutic target in COVID-19 patients with acute symptoms. Furthermore, we revealed nanocurcumin is reducing the expression of HSD17B3-AS1 which leads to reduced inflammation in mice. These results suggest that HSD17B3-AS1 plays a significant regulatory role in managing COVID-19, and the downregulation of HSD17B3-AS1 by Nanocurcumin presents a promising treatment option for minimizing complications in COVID-19 patients.

新冠肺炎是一种由SARS-CoV-2病毒引起的急性呼吸综合征,于2019年末在中国武汉首次报告,并迅速升级为全球大流行。这种情况可导致器官功能障碍,并最终因急性呼吸窘迫综合征(ARDS)发作而死亡。疾病的严重程度与促炎细胞因子有关,这些细胞因子激活受感染细胞中的NF-κB和STAT转录因子。已经证明lncRNA在减少或增加炎症因子方面发挥着非常重要的作用。这使得它们在识别新冠肺炎的发病途径和治疗靶点方面具有潜在的价值。纳米姜黄素是一种抗氧化、抑瘤和抗炎物质,可有效减少新冠肺炎引起的炎症。这项研究分析了新冠肺炎急性和轻度症状患者的序列读取档案数据,确定了失调基因和非编码RNA。为了验证这种相关性,在小鼠模型中用定量聚合酶链式反应(qPCR)评估候选基因的表达,而在小鼠血清样本中用酶联免疫吸附试验(ELISA)测量免疫球蛋白(Ig)G滴度。在这里,我们介绍了一种新的lncRNA,称为HSD17B3-AS1,被建议作为新冠肺炎急性症状患者的治疗靶点。此外,我们发现纳米姜黄素降低了HSD17B3-AS1的表达,从而减少了小鼠的炎症。这些结果表明,HSD17B3-AS1在管理新冠肺炎中发挥着重要的调节作用,纳米姜黄素对HSD17B3-AS1的下调为新冠肺炎患者减少并发症提供了一种有前景的治疗选择。
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引用次数: 0
The Radiological Manifestations of Phagocytic Primary Immunodeficiencies in Children. 儿童吞噬细胞原发性免疫缺陷的放射学表现。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-09-03 DOI: 10.18502/ijaai.v22i4.13612
Mitra Khalili, Zahra Chavoshzadeh, Sepideh Darougar, Mahboubeh Mansouri, Narges Eslami, Delara Babaie, Mehrnaz Mesdaghi, Abdollah Karimi, Shahnaz Armin, Alireza Fahimzad, Roxana Mansour Ghanaei, Sedigheh Rafiee Tabatabaie, Fatemeh Akrami

Primary immunodeficiencies are a diverse group of rare genetic disorders, among which phagocytic dysfunction impairs neutrophil function in a wide range of inherited disorders. Due to the heterogeneity of the disorders a multidisciplinary approach is often required for early diagnosis and initiation of appropriate treatments. The aim of this study was to evaluate the imaging findings in children admitted with phagocytic primary immunodeficiencies. Thirty-five children who fulfilled the inclusion criteria for phagocytic dysfunction were enrolled in this study. The patients were under close observation and monitoring from January 2011 until data locking in December 2017. The diagnosis of phagocytic immunodeficiency was confirmed by the patient's clinical course, presentation features, and laboratory data.  Among the 35 patients studied, the most frequent condition was chronic granulomatous disease (CGD) (23 patients), followed by different types of neutropenia (8 patients) and Job's syndrome (4 patients). Mediastinal and hilar lymphadenopathies and consolidation were the most frequent presentations. There was a significant relationship between mediastinal/hilar lymphadenopathies and fungal infections. A meaningful relationship was also found between pulmonary nodules without halo signs in patients with concomitant tuberculosis and fungal infections. A significant correlation was found between CGD, pulmonary fibrotic changes, and mediastinal lymphadenopathies. The most frequent radiological manifestations in children included mediastinal and hilar consolidations. Physicians' awareness of the radiological and clinical manifestations of these inherited diseases may be helpful in the early diagnosis and timely initiation of specific prophylaxis measures to prevent infections and also to initiate hematopoietic stem cell transplantation as the curative management modality.

原发性免疫缺陷是一组罕见的遗传性疾病,其中吞噬功能障碍损害了多种遗传性疾病中的中性粒细胞功能。由于疾病的异质性,通常需要多学科的方法来进行早期诊断和开始适当的治疗。本研究的目的是评估因吞噬细胞原发性免疫缺陷而入院的儿童的影像学表现。35名符合吞噬功能障碍纳入标准的儿童被纳入本研究。从2011年1月到2017年12月数据锁定,患者一直处于密切观察和监测之下。吞噬细胞免疫缺陷的诊断通过患者的临床病程、表现特征和实验室数据得到证实。在研究的35名患者中,最常见的情况是慢性肉芽肿性疾病(CGD)(23名患者),其次是不同类型的中性粒细胞减少症(8名患者)和乔布斯综合征(4名患者)。纵隔和肺门淋巴结病和巩固是最常见的表现。纵隔/肺门淋巴结病与真菌感染之间存在显著关系。在伴有结核病和真菌感染的患者中,没有晕染迹象的肺结节之间也发现了有意义的关系。CGD、肺纤维化改变和纵隔淋巴结病之间存在显著相关性。儿童最常见的放射学表现包括纵隔和肺门实变。医生对这些遗传性疾病的放射学和临床表现的认识可能有助于早期诊断和及时采取具体的预防措施来预防感染,也有助于启动造血干细胞移植作为治疗管理模式。
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引用次数: 0
Case of Polyethylene Glycol Allergy Confirmed with Basophil Activation Test and Oral Challenge Successfully Immunized with SARS-CoV-2 Vaccine. 经嗜碱性粒细胞激活试验和口服激发试验证实的聚乙二醇过敏病例成功接种严重急性呼吸系统综合征冠状病毒2型疫苗。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-09-03 DOI: 10.18502/ijaai.v22i4.13615
Maria Pasali, Styliani Taka, Caterina Chliva, Alexandros Katoulis, Michael Makris

Polyethylene glycols (PEG) or macrogols are polymers of ethylene oxide widely used in drugs either as active substances or, more commonly, as excipients. We report a Caucasian 32-year-old woman with referred anaphylaxis almost instantly after oral intake of a macrogol-containing laxative. Despite an anaphylactic reaction, the patient showed negative results for both the skin test and specific IgE to monomer, while the basophil activation test and oral challenge were positive. The patient was later successfully vaccinated with a polysorbate 80-containing SARS-CoV-2 vaccine following an additional work-up. As a result, the inactive form of PEG cannot be fully diagnosed, and it is considered a "hidden" allergen. Allergens like polysorbates need special consideration due to their possible cross-reactivity by their specific derivatives.

聚乙二醇(PEG)或聚乙二醇是环氧乙烷的聚合物,广泛用作药物中的活性物质或更常见的赋形剂。我们报告了一名32岁的高加索女性,在口服含有聚乙二醇的泻药后几乎立即出现过敏反应。尽管有过敏反应,但患者的皮肤测试和单体特异性IgE均呈阴性,而嗜碱性粒细胞活化测试和口服激发均呈阳性。经过额外的检查,该患者后来成功接种了含有聚山梨醇酯80的严重急性呼吸系统综合征冠状病毒2型疫苗。因此,PEG的非活性形式无法完全诊断,它被认为是一种“隐藏”的过敏原。过敏原,如聚山梨醇酯,由于其特定衍生物可能具有交叉反应性,需要特别考虑。
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引用次数: 1
Tumor Necrosis Factor-α (-308G>A) Gene Polymorphism and Its Association with Asthma and Atopy Status. 肿瘤坏死因子-α(-308G>A)基因多态性及其与哮喘和精神状态的关系。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-09-03 DOI: 10.18502/ijaai.v22i4.13606
Anahita Razaghian, Nima Parvaneh, Ali Akbar Amirzargar, Mohammad Gharagozlou

Asthma is one of the most prevalent chronic lung diseases that afflict genetically predisposed individuals. Certain cytokine gene polymorphisms have been associated with asthma. Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine that can modulate nonspecific inflammation to influence asthma. This study aimed to define the relationship between the TNF gene polymorphism at position -308 and asthma susceptibility, as well as atopic and non-atopic asthma. Using polymerase chain reaction with sequence-specific primers, we investigated genotype frequencies and alleles of a polymorphic gene coding for TNF-α in 86 pediatric patients with asthma and 470 healthy controls of the same race. Seventy-four patients underwent a skin prick test. The homozygous AA variant (-308, rs1800629) was the most common genotype among patients, accounting for 63.3% of all cases. In contrast, homozygous GG (-308) was significantly less prevalent in the patient group compared to the control group. TNF A (-308) allele frequency was 85.5% among asthma patients and 16.6% among healthy controls. The genotype and allele frequencies of TNF (-308 A>G, rs1800629) did not differ between atopic and non-atopic asthma. In conclusion, TNF (-308) AA and AG genotypes are associated with asthma susceptibility in Iranian children, although there was no significant difference in polymorphism between atopic and non-atopic asthma and no difference in asthma severity groups.

哮喘是最常见的慢性肺部疾病之一,折磨着遗传易感性个体。某些细胞因子基因多态性与哮喘有关。肿瘤坏死因子α(TNF-α)是一种强效的炎症细胞因子,可调节非特异性炎症影响哮喘。本研究旨在明确308位TNF基因多态性与哮喘易感性以及特应性和非特应性哮喘之间的关系。使用序列特异性引物聚合酶链式反应,我们研究了86名哮喘儿童患者和470名同种族健康对照中编码TNF-α的多态性基因的基因型频率和等位基因。74名患者接受了皮肤点刺试验。纯合AA变异体(-308,rs1800629)是患者中最常见的基因型,占所有病例的63.3%。相反,与对照组相比,患者组中纯合GG(-308)的发病率明显较低。哮喘患者中TNF-A(-308)等位基因频率为85.5%,健康对照组为16.6%。TNF的基因型和等位基因频率(-308A>G,rs1800629)在特应性和非特应性哮喘之间没有差异。总之,TNF(-308)AA和AG基因型与伊朗儿童的哮喘易感性有关,尽管特应性和非特应性哮喘之间的多态性没有显著差异,哮喘严重程度组也没有差异。
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引用次数: 0
Impaired CD4+ Cytotoxic T Lymphocyte Activity in Polyomavirus BK Infected Kidney Transplant Recipients. 多瘤病毒BK感染的肾移植受者CD4+细胞毒性T淋巴细胞活性受损。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-09-03 DOI: 10.18502/ijaai.v22i4.13610
Nasrin Noshadi, Ramin Yaghoubi, Afsoon Afshari, Mohsen Forouzanfar, Saeede Soleimanian

The reactivation of polyomavirus BK (BKPyV) contributes to increased morbidity and mortality rates of transplant patients, especially kidney transplant recipients (KTRs). CD4+ T cells are important immune cells active during BKPyV infection in KTRs. This research tried to examine the phenotype of CD4+ T cells in the stage of BKPyV activation in KTRs.The re cipients were separated into 2 groups of BKPyV-active and nonactive KTRs (10 patients in each group) and were compared with 10 healthy control subjects. The viral load was evaluated by Taq-man quantitative real-time PCR. The frequency of different CD4+ T cell subsets was determined by analyzing markers such as CD45RO, CCR7, CD27, CD107a, perforin, and granzyme B using flow cytometry. The gene expression levels of transcription factors, including TBX21, GATA3, STAT3, and STAT6, contributing to CD4+ T cell activation, were also assessed. A significantly higher proportion in CCR7+CD27+CD45RO-CD4+ T cell (naive Tcell) subsets was detected in BKPyV-active KTRs compared to nonactive ones. A significant increase was detected in the frequency of CD107a+, perforin+, and granzyme B+ CD4+ T cells in the BKPyV-active group compared to the nonactive group. In CD4+ T cells of KTRs, the mRNA expression of TBX21  and GATA3 was significantly increased in KTRs without BKPyV reactivation compared to BKPyV-active ones. This investigation focused on the CD4+ T cell as an immunodominant T cell type with potential cytotoxicity. Based on these results, BKPyV may have a direct influence on the repertoire of CD4+ T cell subsets. Particularly, cytotoxic CD4+ T cells need further investigation to be considered as a therapeutic approach for BKPyV infection.

多瘤病毒BK(BKPyV)的再激活导致移植患者,尤其是肾移植受者(KTRs)的发病率和死亡率增加。CD4+T细胞是KTRs中BKPyV感染期间活跃的重要免疫细胞。本研究试图检测KTRs中BKPyV激活阶段CD4+T细胞的表型。将受试者分为BKPyV活性和非活性KTRs 2组(每组10名患者),并与10名健康对照受试者进行比较。病毒载量通过Taq-man定量实时PCR进行评估。通过使用流式细胞术分析标记物如CD45RO、CCR7、CD27、CD107a、穿孔素和颗粒酶B来确定不同CD4+T细胞亚群的频率。还评估了有助于CD4+T细胞活化的转录因子的基因表达水平,包括TBX21、GATA3、STAT3和STAT6。在BKPyV活性KTR中检测到CCR7+CD27+CD45RO-CD4+T细胞(幼稚T细胞)亚群的比例显著高于非活性KTR。与非活性组相比,BKPyV活性组中CD107a+、穿孔素+和颗粒酶B+CD4+T细胞的频率显著增加。在KTRs的CD4+T细胞中,与BKPyV活性KTRs相比,没有BKPyV再激活的KTRs中TBX21和GATA3的mRNA表达显著增加。本研究的重点是CD4+T细胞作为一种具有潜在细胞毒性的免疫显性T细胞类型。基于这些结果,BKPyV可能对CD4+T细胞亚群有直接影响。特别是,细胞毒性CD4+T细胞需要进一步研究才能被认为是BKPyV感染的治疗方法。
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引用次数: 0
Teucrium polium Extract Alleviates Pathological Features of Asthma via lL-12 and IFN-γ Modulation in Murine OVA-induced Allergic Asthma. 在小鼠OVA诱导的变态反应性哮喘中,土茯苓提取物通过IL-12和IFN-γ调节减轻哮喘的病理特征。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-09-03 DOI: 10.18502/ijaai.v22i4.13605
Shole Daneshvar-Ghahfarokhi, Vahid Mohammadi-Shahrokhi, Amir Rahnama, Reza Nosratabadi

Asthma is a chronic disorder characterized by airway overreaction and remodeling, eosinophilia, and neutrophilic inflammation, accompanied by thickening of the airways and breathlessness. Teucrium polium (TP) is a plant with anti-inflammatory properties and is considered for the treatment of allergic disorders. In this study, we examined the effects of TP extract on ovalbumin (OVA)-induced asthma. Thirty female mice (5-6 weeks old) were divided into 5 groups of 6 each, including a control group and 4 groups treated with OVA, OVA + TP extract (50 mg/kg), OVA + TP extract (150 mg/kg), OVA + TP extract (300 mg/kg). Twenty-four hours after the last treatment, lung, serum, and spleen samples were collected and used for the evaluation of leukocyte infiltration, serum cytokine Interferon-gamma (IFN-γ) levels, and the expression of the Interleukin-12A (IL12A) gene, respectively. Hematoxylin-eosin staining was used to evaluate pathological changes in the lung tissue sections. Treatment with TP extract reduced inflammatory cells such as eosinophils and neutrophils in the airways. Furthermore, it increased serum levels of IFN-γ and IL-12A at a dose of 50, 150, and 300 mg/kg compared to the OVA group. This study showed that the administration of TP extract could improve pathological features, such as airway inflammation, and reduce systemic inflammation.

哮喘是一种慢性疾病,其特征是气道过度反应和重塑、嗜酸性粒细胞增多和中性粒细胞炎症,并伴有气道增厚和呼吸困难。磷藻(TP)是一种具有抗炎特性的植物,被认为可以治疗过敏性疾病。在本研究中,我们检测了TP提取物对卵清蛋白(OVA)诱导的哮喘的影响。将30只雌性小鼠(5-6周龄)分为5组,每组6只,包括对照组和4组,用OVA、OVA+TP提取物(50mg/kg)、OVA+-TP提取物(150mg/kg)和OVA+TP提取液(300mg/kg)处理。最后一次治疗24小时后,收集肺、血清和脾脏样本,分别用于评估白细胞浸润、血清细胞因子干扰素-γ(IFN-γ)水平和白细胞介素-12A(IL12A)基因的表达。苏木精-伊红染色用于评估肺组织切片的病理变化。TP提取物治疗减少了气道中的炎症细胞,如嗜酸性粒细胞和中性粒细胞。此外,与OVA组相比,在50、150和300mg/kg的剂量下,它提高了血清IFN-γ和IL-12A的水平。本研究表明,TP提取物的给药可以改善气道炎症等病理特征,减少全身炎症。
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引用次数: 0
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Iranian journal of allergy, asthma, and immunology
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