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Evaluation of Inflammatory Markers in Patients with Depressed Episodes in Major Depressive Disorder and Bipolar Disorder before and after Treatment. 重度抑郁症和双相情感障碍抑郁发作患者治疗前后炎症标志物的评价。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-04-30 DOI: 10.18502/ijaai.v22i2.12681
Laya Kafami, Sara Assadiasl, Sara Hashempour, Mohammad Hossein Niknam, Bahareh Mohebbi, Mohammad Amin Hashemnezhad, Bita Ansaripour, Arash Mirabzadeh, Banafsheh Mosharmovahed, Fateme Fazli, Mahshid Saleh, Nam I Mohammadian Khanssari, Ahmad Ali Noorbala

Depression is one of the current dilemmas in both developed and developing societies. Studies show that the severity of psychiatric symptoms is directly related to the degree of inflammation caused by cytokines secreted by the immune system. Hence, evaluating serum cytokine levels in patients with depression can help to understand the pathogenesis of the disease and make the best therapeutic decisions. The present study investigated the levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in patients with major depression or bipolar disorder during depressive episodes (BDDE) before and after a 6-month pharmaceutical intervention. Patients referring to 3 clinics were recruited for the study. The diagnosis of major depression or bipolar disorder in a depressive phase was made according to the Diagnostic and Statistical Manual of Mental Disorders -5(DSM-5) criteria. There was a significant difference in depression levels between the pre-intervention and 6-month follow-up in both groups. After 6 months, IL-1 and IL-6 levels in the bipolar disorder group had decreased while TNF-α levels had increased. There was also a significant difference between pre-intervention and follow-up levels of IL-1.  Serum levels of IL-1 and IL-6 decreased significantly in both groups after the 6-month follow-up, and symptom improvement was observed. TNF-α levels, on the other hand, decreased in the major depression group but increased in the bipolar disorder group. Considering that inflammation is a major outcome of depression, treatment strategies to reduce inflammation could be a practical approach to improving psychiatric symptoms.

抑郁症是当前发达社会和发展中社会共同面临的难题之一。研究表明,精神症状的严重程度与免疫系统分泌的细胞因子引起的炎症程度直接相关。因此,评估抑郁症患者的血清细胞因子水平可以帮助了解疾病的发病机制,并做出最佳的治疗决策。本研究调查了重度抑郁症或双相情感障碍患者在抑郁发作(BDDE)期间6个月药物干预前后的炎症因子、肿瘤坏死因子-α (TNF-α)、白细胞介素-1 (IL-1)和白细胞介素-6 (IL-6)水平。研究招募了3家诊所的患者。根据精神疾病诊断与统计手册-5(DSM-5)标准诊断抑郁症或抑郁期双相情感障碍。在干预前和6个月的随访中,两组的抑郁水平有显著差异。6个月后,双相情感障碍组IL-1和IL-6水平下降,TNF-α水平升高。干预前和随访期间IL-1水平也有显著差异。随访6个月后,两组患者血清IL-1、IL-6水平均显著下降,症状均有改善。另一方面,TNF-α水平在重度抑郁症组中下降,而在双相情感障碍组中升高。考虑到炎症是抑郁症的主要结果,减少炎症的治疗策略可能是改善精神症状的实用方法。
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引用次数: 0
The Alleviating Impacts of Quercetin on Inflammation and Oxidant-antioxidant Imbalance in Rats with Allergic Asthma. 槲皮素对过敏性哮喘大鼠炎症及氧化-抗氧化失衡的缓解作用。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-04-30 DOI: 10.18502/ijaai.v22i2.12675
Mohammad Amin Rajizadeh, Mohammad Abbas Bejeshk, Amir Hossein Doustimotlagh, Hamid Najafipour, Maryam Eftekhari, Merat Mahmoodi, Mahdokht Azizi, Fahimeh Rostamabadi, Hossein Pourghadamyari

Asthma is an inflammatory disease of the airways. We assessed the anti-inflammatory and antioxidative impacts of quercetin, a plant derivative, on inflammatory and oxidative indices in lung tissue and serum of rats with asthma.Asth ma was induced by ovalbumin. Rats were divided into 4 groups: control, asthma+vehicle (Receieved normal saline), asthma+dexamethasone, and asthma+quercetin. After asthma induction, quercetin (50 mg/kg) and dexamethasone (2.5 mg/kg) were injected intraperitoneally once daily for 1 week. On day 50, lung histopathology indices; inflammatory factors; tissue gene expression, including GATA Binding Protein 3 (Gata-3), Tbx21 (T-bet), Transforming growth factor-β (TGF-β), Il10 (IL-10), Il1b (IL-1β), Il6 (IL-6), Acta2 (α-SMA), and Tnf (TNF-α); and oxidative stress indices (malondialdehyde [MDA], catalase [CAT], glutathione peroxidase [GPX], superoxide dismutase [SOD], and total antioxidant capacity [TAC]) in tissue and serum, were evaluated. The results showed that quercetin reduced Gata3, Tnf, Tgfb1, Il1b, and Acta2 gene expression and increased Tbx21 gene expression following asthma. Quercetin also improved oxidative stress by decreasing MDA levels and increasing TAC, CAT, SOD, and GPX levels in serum and lung tissue. Furthermore, quercetin decreased IL6 and TNFα levels and increased IL10 levels in lung tissue after asthma was treated with quercetin. Quercetin ameliorates oxidative stress and inflammation caused by asthma, especially at the tissue level. Therefore, quercetin can be considered a potent antiasthmatic agent.

哮喘是呼吸道的一种炎症性疾病。研究植物衍生物槲皮素对哮喘大鼠肺组织和血清炎症和氧化指标的抗炎和抗氧化作用。卵清蛋白诱导哮喘。将大鼠分为4组:对照组、哮喘+给药组(生理盐水)、哮喘+地塞米松组、哮喘+槲皮素组。哮喘诱导后,每日1次腹腔注射槲皮素(50 mg/kg)和地塞米松(2.5 mg/kg),连续1周。第50天,肺组织病理学指标;炎症因素;组织基因表达,包括GATA结合蛋白3 (GATA -3)、Tbx21 (T-bet)、转化生长因子-β (TGF-β)、IL-10 (IL-10)、il - 1b (IL-1β)、IL-6 (IL-6)、Acta2 (α-SMA)、Tnf (Tnf -α);测定组织和血清的氧化应激指标(丙二醛(MDA)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPX)、超氧化物歧化酶(SOD)和总抗氧化能力(TAC))。结果显示,槲皮素可降低哮喘患者Gata3、Tnf、Tgfb1、Il1b和Acta2基因表达,增加Tbx21基因表达。槲皮素还通过降低血清和肺组织中MDA水平和增加TAC、CAT、SOD和GPX水平来改善氧化应激。槲皮素治疗哮喘后肺组织中il - 6、tnf - α水平降低,il - 10水平升高。槲皮素可改善哮喘引起的氧化应激和炎症,特别是在组织水平上。因此,槲皮素可以被认为是一种有效的平喘剂。
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引用次数: 4
Food Protein-induced Enterocolitis Syndrome Due to Cuttlefish in a Child with Anaphylaxis to Crustaceans. 甲壳类动物过敏儿童中乌贼引起的食物蛋白诱导的肠结肠炎综合征。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-04-30 DOI: 10.18502/ijaai.v22i2.12682
Simona Barni, Marta Vazquez-Ortiz, Mattia Giovannini, Giulia Liccioli, Lucrezia Sarti, Giulia Lascialfari, Laura Pisano, Silvia Boscia, Francesca Mori

Shellfish is defined as any edible marine invertebrate and refers to crustaceans and mollusks. Crustaceans belong to the phylum Arthropods. Mollusks belong to the phylum Mollusca. This report illustrates a rare case of a 6-year-old girl with challenge-proven acute food protein-induced enterocolitis syndrome (FPIES) to cuttlefish (phylum Mollusca, class Cephalopoda), anaphylaxis to crustaceans (phylum Arthropoda), and tolerance to other mollusks, including clams and mussels (phylum Mollusca, class Bivalvia). The association of IgE-mediated food allergy and acute FPIES seen in this case is rare. To our knowledge, this is the first case of FPIES to cuttlefish reported in a child. This challenge highlights the need for further research into the allergens and mechanisms underpinning FPIES at a molecular level, enabling a better understanding of cross-reactivity patterns and the development of diagnostic and predictive tests to assist in clinical practice.

贝类被定义为任何可食用的海洋无脊椎动物,指甲壳类动物和软体动物。甲壳类动物属于节肢动物门。软体动物属于软体动物门。本报告报告了一例罕见的6岁女孩,她对乌贼(软体动物门,头足纲)、甲壳类动物(节肢动物门)和其他软体动物(包括蛤蜊和贻贝(软体动物门,双壳纲)有过敏反应,证实患有急性食物蛋白诱导的小肠结肠炎综合征(FPIES)。在这种情况下,ige介导的食物过敏和急性FPIES的关联是罕见的。据我们所知,这是第一例报道的儿童感染乌贼的病例。这一挑战突出表明,需要在分子水平上进一步研究构成fies的过敏原和机制,从而更好地理解交叉反应模式,并开发诊断和预测测试,以协助临床实践。
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引用次数: 0
Astragalus Polysaccharide Mediates Immunomodulatory Effects on Crosstalk between Human Peripheral Blood Mononuclear Cells and Ovarian Cancer Cell Line. 黄芪多糖介导人外周血单核细胞与卵巢癌细胞串扰的免疫调节作用。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-04-30 DOI: 10.18502/ijaai.v22i2.12678
Elham Shokati, Morteza Motallebnezhad, Elaheh Safari

Astragalus polysaccharide (APS) is a functional component of Astragalus membranaceus with antitumor and immunomodulatory properties. This study evaluated the effect of APS on the peripheral blood mononuclear cell (PBMC) proliferation, cytokine secretion, and regulatory T cell (Treg) induction in an in vitro coculture model of human PBMCs and A2780 human ovarian cancer cells. PBMC proliferation and Treg frequency were measured by flow cytometry. Cytokine levels were assessed by enzyme-linked immunosorbent assay. APS significantly enhanced the PBMC proliferation, reduced Treg frequency, decreased anti-inflammatory cytokines including interleukin [IL]-10, transforming growth factor beta (TGF-β), and vascular endothelial growth factor-A (VEGF-A), and increased the pro-inflammatory cytokine IL-6. These findings suggest that APS may be an effective immunomodulatory supplement for cancer therapy, particularly for ovarian cancer by enhancing antitumor immune responses.

黄芪多糖(Astragalus多糖,APS)是黄芪的一种功能性成分,具有抗肿瘤和免疫调节作用。本研究通过体外培养人外周血单核细胞(PBMC)和A2780人卵巢癌细胞模型,研究了黄芪多糖对外周血单核细胞(PBMC)增殖、细胞因子分泌和调节性T细胞(Treg)诱导的影响。流式细胞术检测PBMC增殖和Treg频率。采用酶联免疫吸附法测定细胞因子水平。黄芪多糖显著增强PBMC增殖,降低Treg频率,降低抗炎细胞因子包括白细胞介素[IL]-10、转化生长因子β (TGF-β)、血管内皮生长因子- a (VEGF-A),升高促炎细胞因子IL-6。这些发现表明,APS可能是一种有效的癌症治疗免疫调节补充剂,特别是通过增强抗肿瘤免疫反应来治疗卵巢癌。
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引用次数: 1
The Effects of Mesenchymal Stem Cells on the Gene Expression of TGF-beta and IFN-gamma in Patients with Rheumatoid Arthritis. 间充质干细胞对类风湿关节炎患者tgf - β和ifn - γ基因表达的影响
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-04-30 DOI: 10.18502/ijaai.v22i2.12679
Maryam Rahimi Khorashad, Mohsen Ghoryani, Arezoo Gowhari Shabgah, Zhaleh Shariati-Sarabi, Jalil Tavakkol Afshari, Mojgan Mohammadi

The therapeutic and immunomodulatory potential of mesenchymal stem cells (MSCs) in rheumatoid arthritis (RA) has attracted considerable scientific attention in recent decades. This study aimed to evaluate the expression of genes encoding interleukin (IL)4 and IL10, as well as interferon-gamma (IFNG) and transforming growth factor beta (TGFB1) in refractory RA patients following intravenous injection of autologous bone marrow-derived MSCs (BM-MSCs). This study was registered in Iranian Registry of Clinical Trials (IRCT) (2015102824760N1) and ClinicalTrials.gov (identifier: NCT03333681). Blood samples were taken from 13 patients before and 1 and 6 months after the MSC injection to evaluate the clinical manifestations, paraclinical factors, and expression of IL4, IL10, IFNG, and TGFB1 genes employing the SYBR Green real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique. There was a significant increase in the expression of TGFB1 at 1 and 6 months after the MSC injection compared to that in the baseline, while the expression of IL4 and IL10 did not change significantly. On the other hand, the expression of IFNG increased significantly after 1 month but decreased significantly at 6 months compared to 1 month after the intervention. Nevertheless, it showed no significant decrease compared to the baseline. A significant decrease was observed for the expression of IFNG 6 months after the injection compared to that after 1 month, which was in concordance with the rise in the expression of the TGFB1 gene. A significant change in the gene expression of TGFB1 and IFNG in our study was consistent with the amelioration of clinical manifestations, suggesting a mechanism of action for MSCs in the treatment of RA.

近几十年来,间充质干细胞(MSCs)在类风湿关节炎(RA)中的治疗和免疫调节潜力引起了相当大的科学关注。本研究旨在评估难治性RA患者静脉注射自体骨髓源性间充质干细胞(BM-MSCs)后编码白细胞介素(IL)4和IL10以及干扰素- γ (IFNG)和转化生长因子β (TGFB1)基因的表达。本研究已在伊朗临床试验登记处(IRCT) (2015102824760N1)和ClinicalTrials.gov(标识符:NCT03333681)注册。采用SYBR Green实时逆转录酶聚合酶链式反应(RT-PCR)技术,对13例患者在注射MSC前、注射后1、6个月的血样进行临床表现、临床旁因素及il - 4、il - 10、IFNG、TGFB1基因的表达进行评估。在注射MSC后1个月和6个月,TGFB1的表达与基线相比显著增加,而IL4和IL10的表达没有明显变化。另一方面,与干预后1个月相比,干预后1个月IFNG的表达明显增加,干预后6个月IFNG的表达明显下降。然而,与基线相比,它没有显示出明显的下降。与注射后1个月相比,注射后6个月IFNG的表达明显下降,这与TGFB1基因表达升高是一致的。在我们的研究中,TGFB1和IFNG基因表达的显著变化与临床表现的改善是一致的,提示MSCs在治疗RA中的作用机制。
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引用次数: 2
The Effectiveness of Probiotics in Treating Food and Cow's Milk Allergies among Pediatric Age Group: A Meta-analysis of Randomized Controlled Trials. 益生菌治疗儿童食品和牛奶过敏的有效性:一项随机对照试验的meta分析。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-04-30 DOI: 10.18502/ijaai.v22i2.12674
Hua Feng, Yongning Wu
The global prevalence of allergies is on the rise. Food allergies are of special concern among children under 5 years of age, leading to morbidity and mortality. Though the standard management is avoidance, probiotics are being used widely to prevent and treat food allergies. We aimed to determine the effect of probiotics as a therapeutic option for controlling food and cow's milk allergy among children under 5 years of age. A systematic search of electronic medical literature databases was conducted. We included all eligible randomized controlled trials available from inception until May 2021. The primary outcome of interest was the relief of allergic symptoms, while the secondary outcome was the induction of tolerance. Two investigators undertook the literature search, screening, data extraction, and quality appraisal independently. Data analysis and synthesis were performed using STATA 14 software. Subgroup analysis was performed for the duration of use and follow-up, and the age category of children included in the outcome were done. Twenty trials involving 4043 pediatric patients with food allergies were included in the review. Subgroup analysis also revealed that probiotics were effective in treating food allergies across the various subgroups included in the model. Around 15 trials reported our primary outcome, relief of symptoms, as a binary variable, which was pooled to obtain a risk ratio of 0.86 (95% confidence interval [CI], 0.77-0.95), with very low heterogeneity (I2 7.7%). Six trials were included for the secondary outcome of interest, which gave an imprecise pooled estimate of 1.29 (95% CI, 0.98-1.70) with significant heterogeneity (I2 7). Thus, we conclude that probiotics can serve as a vital therapeutic option in tackling food allergies among children less than 5 years of age. Further larger studies exploring the effectiveness of individual strains and their safety pattern are essential.
全球过敏的患病率正在上升。食物过敏在5岁以下儿童中引起特别关注,导致发病率和死亡率。虽然标准的管理是避免,但益生菌正在广泛用于预防和治疗食物过敏。我们的目的是确定益生菌作为控制5岁以下儿童食物和牛奶过敏的治疗选择的效果。系统检索电子医学文献数据库。我们纳入了从开始到2021年5月所有符合条件的随机对照试验。主要结局是过敏症状的缓解,而次要结局是诱导耐受性。两位研究者独立进行文献检索、筛选、数据提取和质量评价。采用STATA 14软件进行数据分析和综合。对使用时间和随访进行亚组分析,并对纳入结果的儿童进行年龄分类。20项涉及4043名儿童食物过敏患者的试验被纳入综述。亚组分析还显示,益生菌在治疗模型中各个亚组的食物过敏方面都很有效。大约15项试验报告了我们的主要结局,症状缓解,作为一个二元变量,合并得到的风险比为0.86(95%可信区间[CI], 0.77-0.95),异质性非常低(I2 7.7%)。6项试验纳入了次要结局,其不精确的汇总估计为1.29 (95% CI, 0.98-1.70),具有显著的异质性(i27)。因此,我们得出结论,益生菌可以作为治疗5岁以下儿童食物过敏的重要治疗选择。进一步研究单个菌株的有效性及其安全模式是必要的。
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引用次数: 0
Investigating the Safety and Efficacy of the Synthetic Drug Herbix on Immune Responses Involved in the Treatment of a Mouse Model of Herpes Simplex Virus. 研究合成药物Herbix治疗小鼠单纯疱疹病毒模型免疫反应的安全性和有效性。
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-02-20 DOI: 10.18502/ijaai.v22i1.12008
Mohammad Ali Khodadoust, Gholam Reza Keramatian, Najmeh Kaffash Farkhad, Jalil Tavakol-Afshari

Herpes simplex virus-1 (HSV-1) infections can cause significant harm to individuals, including blindness, congenital defects, genital herpes, and even cancer, with no definitive cure .so, finding new treatment strategies is crucial. In this study, 25 male BALB/c mice were used to conduct a mouse model of herpes by subcutaneously injecting an HSV-1 suspension (100 µL of 1×  PFU/mL). The mice were divided into 5 groups with groups 1 to 3 designated as intervention groups, and groups 4 and 5 serving as positive and negative control groups, respectively. After 2 days of virus inoculation, the mice were treated with different concentrations of Herbix (100, 200, and 300 mg/mL) via subcutaneous injection. Mice Blood samples (0.5 to 1 mL) were taken from the mice before and after the experiments, and after three-week follow-up period, the mice were sacrificed and the spleens were removed for lymphocyte analysis. we found that administration of Herbix at a dose of 300 mg/mL showed the greatest efficacy, characterized by a delay in skin lesion formation, an increment in survival rate and lymphocyte proliferation, upregulation of the gene expression of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α), and an increase in the polarization of cytotoxic and helper T lymphocytes compared to the control group. These results suggest that Herbix at a dose of 300 mg/mL is effective in treating murine herpes and stimulating immune responses, making it a potential candidate for further investigation as an antiherpetic drug.

单纯疱疹病毒-1 (HSV-1)感染会对个体造成重大伤害,包括失明、先天性缺陷、生殖器疱疹,甚至癌症,而且没有明确的治愈方法。因此,寻找新的治疗策略至关重要。本研究采用25只雄性BALB/c小鼠皮下注射HSV-1混悬液(100µL, 1× PFU/mL),建立小鼠疱疹模型。将小鼠分为5组,1 ~ 3组为干预组,4、5组分别为阳性对照组和阴性对照组。病毒接种2 d后,小鼠皮下注射不同浓度的Herbix(100、200、300 mg/mL)。实验前后取小鼠血液0.5 ~ 1ml,随访3周后处死,取脾进行淋巴细胞分析。我们发现,与对照组相比,剂量为300 mg/mL的Herbix显示出最大的疗效,其特点是延迟皮肤病变形成,增加存活率和淋巴细胞增殖,上调干扰素α (IFN-α)和肿瘤坏死因子α (TNF-α)的基因表达,增加细胞毒性和辅助T淋巴细胞的极化。这些结果表明,300 mg/mL剂量的Herbix可有效治疗小鼠疱疹并刺激免疫反应,使其成为进一步研究的潜在候选抗疱疹药物。
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引用次数: 0
New Presentation of CD27 Deficiency; Coronary Ectasia and COVID-19. CD27缺乏的新表现冠状动脉扩张与COVID-19
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-02-20 DOI: 10.18502/ijaai.v22i1.12013
Zahra Golchehre, Samin Sharafian, Nader Momtazmanesh, Zahra Chavoshzadeh, Abdollah Karimi, Hassan Abolhassani, Maryam Kazemi Aghdam, Koroush Vahidshahi, Seyedehatefeh Hashemimoghaddam, Farid Kosari, Zahra Khafafpour, Bibi Shahin Shamsian, Mohammad Keramatipour

CD27 is a costimulatory receptor involved in the maturation of the innate and adaptive immunity. CD27, through interaction with CD70, plays a role in the control of Epstein-Barr virus (EBV) infection. CD27 deficiency leads to an immune dysregulation disease characterized by EBV susceptibility. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might put patients with primary immunodeficiency at risk for adverse outcomes. Chromogenic in situ hybridization (CISH) study was performed to detect EBV in the lymphoma tissue. Genetic analysis of the patient was done with Whole Exome Sequencing and detected variant was confirmed with PCR-Sanger sequencing. Here we report a 20-month-old boy with CD27 deficiency who developed lymphoma and coronary artery ectasia and had been infected with SARS-CoV-2. Clinical and laboratory findings were incompatible with atypical Kawasaki syndrome or multisystem inflammatory syndrome in children (MIS-C). As CD27 deficiency is a rare immune defect, publishing clinical data about the identified patient(s) can shed light on our knowledge about the related phenotype and the spectrum of clinical manifestations associated with CD27 deficiency. Thus, our findings expanded the spectrum of manifestations beyond EBV infection, highlighting this unusual cardiac sequela that could be related to EBV infection, lymphoma, or an underlying disease.

CD27是一种参与先天免疫和适应性免疫成熟的共刺激受体。CD27通过与CD70的相互作用,在eb病毒(EBV)感染的控制中发挥作用。CD27缺乏导致以EBV易感性为特征的免疫失调疾病。严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)可能使原发性免疫缺陷患者面临不良后果的风险。采用显色原位杂交(CISH)技术检测EBV在淋巴瘤组织中的表达。用全外显子组测序对患者进行遗传分析,用PCR-Sanger测序证实检测到的变异。在这里,我们报告了一个患有CD27缺乏症的20个月大的男孩,他患有淋巴瘤和冠状动脉扩张,并感染了SARS-CoV-2。临床和实验室结果与儿童不典型川崎综合征或多系统炎症综合征(misc)不相符。由于CD27缺乏症是一种罕见的免疫缺陷,发表有关已确定患者的临床数据可以阐明我们对与CD27缺乏症相关的表型和临床表现谱的了解。因此,我们的研究结果扩大了EBV感染以外的表现范围,强调了这种不寻常的心脏后遗症可能与EBV感染、淋巴瘤或潜在疾病有关。
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引用次数: 1
Immunosuppressive Effects of Two Probiotics, Lactobacillus paracasei DSM 13434 and Lactobacillus plantarum DSM 15312, on CD4+ T Cells of Multiple Sclerosis Patients. 副干酪乳杆菌DSM 13434和植物乳杆菌DSM 15312对多发性硬化症患者CD4+ T细胞的免疫抑制作用
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-02-20 DOI: 10.18502/ijaai.v22i1.12004
Khadijeh Chakamian, Behrouz Robat-Jazi, Abdorreza Naser Moghadasi, Fatemeh Mansouri, Masoumeh Nodehi, Elahe Motevaseli, Maryam Izad, Saeed Yekaninejad, Mahdieh Shirzad, Kiana Bidad, Mona Oraei, Bita Ansaripour, Ali Akbar Saboor-Yaraghi

T cells play an important role in the development and progression of multiple sclerosis (MS), an autoimmune disease of the central nervous system. In the present study, the immunomodulatory impacts of two Lactobacillus strains, L paracasei DSM 13434 and L plantarum DSM 15312, on the frequency and cytokine production of CD4+ T cells in MS patients were explored. Thirty MS patients were enrolled in this study. The CD4+ T cells were isolated, cultured, and exposed to the media containing cell-free supernatants of L plantarum (group1), L paracasei (group 2), the mixture group of cell-free supernatants of both probiotics (group 3), and vehicle (control) group (group 4). The frequencies of T helper (Th) 1, Th17, Th2, and T regulatory type 1 (Tr1) cells and mean fluorescent intensity (MFI) of the associated cytokines were assessed using flow cytometry. The levels of interleukin 17 (IL-17), transforming growth factor β (TGF-β), and interferon-gamma (IFN-γ) cytokines in supernatants of all groups were measured by enzyme-linked immunosorbent assay. The percentage of Th1 cells and the MFI of IFN-γ in Th1 cells (CD4+ IFN-γ+) in all three probiotic treatment groups were significantly decreased compared to the control group. However, no significant changes were observed in the proportion and MFI of Th2, Th17, and Tr1 cells. A significant decrease was observed in IL-17 secretion in the supernatant of cultured CD4+ T cells in all three treatment groups in comparison with control. The levels of TGF-β and IFN-γ were not significantly different among any of the study groups.  Collectively, cell-free supernatants of the lactobacilli showed an in vitro anti-inflammatory effect. However, further studies are needed to prove the real effects of probiotics on MS.

T细胞在多发性硬化症(MS)的发生和发展中发挥重要作用,多发性硬化症是一种中枢神经系统的自身免疫性疾病。本研究探讨了副干酪乳杆菌(L paracasei DSM 13434)和植物乳杆菌(L plantarum DSM 15312)两株乳杆菌对MS患者CD4+ T细胞频率和细胞因子产生的免疫调节作用。30例多发性硬化症患者参加了这项研究。将CD4+ T细胞分离、培养并暴露于含有L plantarum(1组)、L paracasei(2组)、两种益生菌的无细胞上清混合组(3组)和载体(对照)组(4组)的培养基中。使用流式细胞术评估T辅助(Th) 1、Th17、Th2和T调节性1型(Tr1)细胞的频率和相关细胞因子的平均荧光强度(MFI)。采用酶联免疫吸附法检测各组上清液中白细胞介素17 (IL-17)、转化生长因子β (TGF-β)、干扰素γ (IFN-γ)细胞因子水平。与对照组相比,3个益生菌处理组的Th1细胞百分比和Th1细胞中IFN-γ的MFI (CD4+ IFN-γ+)均显著降低。然而,Th2、Th17和Tr1细胞的比例和MFI未见明显变化。与对照组相比,3个治疗组培养的CD4+ T细胞上清液中IL-17的分泌均显著减少。TGF-β和IFN-γ水平在各研究组之间无显著差异。总的来说,乳酸菌的无细胞上清液显示出体外抗炎作用。然而,益生菌对多发性硬化症的真正作用还需要进一步的研究来证明。
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引用次数: 0
MicroRNA-122 Is More Effective than Rapamycin in Inhibition of Epithelial-mesenchymal Transition and mTOR Signaling Pathway in Triple Negative Breast Cancer. MicroRNA-122 在抑制三阴性乳腺癌上皮-间质转化和 mTOR 信号通路方面比雷帕霉素更有效
IF 1.5 4区 医学 Q4 ALLERGY Pub Date : 2023-02-20 DOI: 10.18502/ijaai.v22i1.12006
Majdedin Ghalavand, Ruhollah Dorostkar, Hojat Borna, Samira Mohammadi-Yeganeh, Seyed Mahmood Hashemi

The fundamental mechanism responsible for the aggressiveness of metastatic cancers such as triple-negative breast cancer (TNBC) is the epithelial-mesenchymal transition (EMT). In cancer microenvironments, the Phosphoinositide 3-kinases (PI3K)-Akt- mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in regulating the EMT mechanism. The current study focuses on the impacts of rapamycin, a newly retargeted chemotherapeutic agent against mTOR, and MicroRNA (miR)-122 on the aggressive behavior of TNBC.  The half-maximal inhibitory concentration (IC50) of rapamycin on 4T1 cells was determined using an MTT assay. Also, miR-122 was transiently transfected into 4T1 cells to study its effect on the pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression level of central mTOR and EMT-related cascade genes. Moreover, cell mobility and migration were evaluated using scratch and migration assays, respectively. Both rapamycin and miR-122 significantly decreased the expression levels of PI3K, AKT, and mTOR, as well as ZeB1 and Snail genes. However, no significant change was observed in Twist gene expression. Furthermore, scratch and migration assays revealed that the migration of 4T1 cells was markedly reduced, especially following miR-122 induction. Our experimental findings and gene enrichment studies indicated that miR-122 mainly operates on multiple metabolic pathways, as well as EMT and mTOR, while rapamycin has restricted targets in cancer cells.  Consequently, miR-122 can be considered a potential cancer microRNA therapy option, which can be validated in the future in animal studies to demonstrate its efficacy in cancer control.

导致三阴性乳腺癌(TNBC)等转移性癌症具有侵袭性的基本机制是上皮-间质转化(EMT)。在癌症微环境中,磷脂酰肌醇3-激酶(PI3K)-Akt-哺乳动物雷帕霉素靶标(mTOR)信号通路在调控EMT机制中发挥着关键作用。本研究的重点是雷帕霉素(一种新的针对mTOR的再靶向化疗药物)和MicroRNA(miR)-122对TNBC侵袭行为的影响。 雷帕霉素对4T1细胞的半数最大抑制浓度(IC50)是通过MTT试验测定的。此外,miR-122还被瞬时转染到4T1细胞中,以研究其对通路的影响。实时定量聚合酶链反应(qRT-PCR)评估了 mTOR 和 EMT 相关级联基因的表达水平。此外,还使用划痕和迁移试验分别评估了细胞的移动性和迁移性。雷帕霉素和 miR-122 都能显著降低 PI3K、AKT 和 mTOR 以及 ZeB1 和 Snail 基因的表达水平。然而,Twist 基因的表达没有明显变化。此外,划痕和迁移试验显示,4T1 细胞的迁移明显减少,尤其是在 miR-122 诱导后。我们的实验结果和基因富集研究表明,miR-122 主要作用于多种代谢途径、EMT 和 mTOR,而雷帕霉素在癌细胞中的作用靶点有限。 因此,miR-122 可被视为一种潜在的癌症 microRNA 治疗方案,未来可在动物实验中验证其对癌症控制的疗效。
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Iranian journal of allergy, asthma, and immunology
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