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Effects of c-Kit Receptor, AKT, and NF-κB Inhibitors on Immune Evasion in Multiple Myeloma Cells. c-Kit受体、AKT和NF-κB抑制剂对多发性骨髓瘤细胞免疫逃避的影响
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18024
Abbas Ranjbar, Saeid Taghiloo, Parvin Nozari, Akbar Hedayatizadeh-Omran, Hossein Asgarian-Omran

Up-regulation of immune checkpoint ligands and secretion of soluble factors in the tumor microenvironment led to the survival of cancerous plasma cells in the bone marrow milieu. Therefore, we investigate the relationship between the inhibition of c-Kit receptor, AKT, and NF-κB signaling pathways and the regulation of immune escape mechanisms in multiple myeloma. The U266B1 cell line was treated with Masitinib as a c-Kit receptor inhibitor, Perifosine as AKT inhibitor, and Bortezomib as NF-κB inhibitor either in single or combined form. Apoptosis and cell viability were evaluated using flow cytometry and MTT assays, respectively. The relative expression of programmed death-ligand 1 (PD-L1), poliovirus receptor (PVR), and interleukin 6 (IL-6) were determined by real-time PCR. Also, the secretion of IL-6 was measured by ELISA. Our findings demonstrated decreased proliferation of U266B1 cells after co-treatment with Masitinib, Perifosine, and Bortezomib.  An increase in apoptosis was observed in the co-treatment of Masitinib and Perifosine. Furthermore, results elucidated that the expression of PD-L1 and IL-6 decreased after treatment with Masitinib, Perifosine, and Bortezomib in both single and co-treatments. Regarding PVR, combined treatment of U266B1 cells with Masitinib, Perifosine, and Bortezomib decreased the expression level of PVR. We showed that c-Kit receptor, AKT, and NF-κB pathway inhibitors not only serve as cytotoxic drugs but also inhibit the immune escape mechanisms of malignant plasma cells by disrupting signaling pathways.

肿瘤微环境中免疫检查点配体的上调和可溶性因子的分泌导致癌性浆细胞在骨髓环境中存活。因此,我们研究c-Kit受体、AKT和NF-κB信号通路的抑制与多发性骨髓瘤免疫逃逸机制的调节之间的关系。U266B1细胞系用Masitinib作为c-Kit受体抑制剂,Perifosine作为AKT抑制剂,Bortezomib作为NF-κB抑制剂单独或联合处理。细胞凋亡和细胞活力分别采用流式细胞术和MTT检测。实时荧光定量PCR检测程序性死亡配体1 (PD-L1)、脊髓灰质炎病毒受体(PVR)和白细胞介素6 (IL-6)的相对表达量。ELISA法检测IL-6的分泌。我们的研究结果表明,与马西替尼、泊替辛和硼替佐米共同治疗后,U266B1细胞的增殖降低。在马西替尼和蒲草碱联合治疗中观察到细胞凋亡的增加。此外,结果表明,在单独和联合使用马西替尼、泊替辛和硼替佐米治疗后,PD-L1和IL-6的表达均下降。在PVR方面,马西替尼、泊替辛和硼替佐米联合治疗U266B1细胞可降低PVR的表达水平。我们发现c-Kit受体、AKT和NF-κB通路抑制剂不仅可以作为细胞毒性药物,还可以通过破坏信号通路来抑制恶性浆细胞的免疫逃逸机制。
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引用次数: 0
Analyzing the Role of CircSnx5 in an Animal Model of Multiple Sclerosis. 分析CircSnx5在多发性硬化症动物模型中的作用。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18021
Leila Mohamed Khosroshahi, Mohammad Reza Zabihi, Behnia Akbari, Jamshid Hadjati, Farshid Noorbakhsh

Circular RNAs (circRNAs) are endogenous non-coding RNA molecules that form covalently closed molecular loops. By regulating gene expression, circRNAs are known to play crucial roles in the development and progression of various diseases, including autoimmune, neoplastic, and neurological disorders.   In this study, we examined the expression of circSnx5 in inflamed CNS tissue at different stages of experimental autoimmune encephalitis (EAE), an animal model for multiple sclerosis (MS), as well as in T cells that were activated and differentiated into different T helper phenotypes (Th1, Th17, Treg). EAE was induced and spinal cord tissues were isolated at different time points following disease induction. CD4+ T cells were isolated from mouse splenocytes and differentiated toward Th1, Th17, and Treg phenotypes, followed by the analysis of circSnx5 expression. Compared with control mice, enhanced expression of both circular and linear forms of Snx5 was detected in EAE lumbar spinal cords at the peak and post-peak phases of the disease. However, the ratio of the circular to linear forms (CLR) was decreased in EAE mice compared with controls. Expression of circSnx5 was highly correlated with the levels of inflammatory cytokines in the spinal cord tissue. Significant decreases were observed in circSnx5 expression levels following polyclonal activation of splenocytes. The expression of circSnx5 was also downregulated in differentiated T cells directed toward Th1, Th17, and Treg. Our findings suggest a potential role of circSnx5 in autoimmune neuroinflammation. The altered expression of circSnx5 during activation and differentiation may offer valuable insights into potential strategies for regulating inflammation in multiple sclerosis (MS).

环状RNA (circRNAs)是内源性非编码RNA分子,形成共价闭合的分子环。通过调节基因表达,circRNAs在各种疾病的发生和进展中发挥着至关重要的作用,包括自身免疫性疾病、肿瘤和神经系统疾病。在这项研究中,我们检测了circSnx5在实验性自身免疫性脑炎(EAE)(多发性硬化症(MS)的动物模型)不同阶段发炎的中枢神经系统组织中的表达,以及在被激活并分化为不同T辅助表型(Th1, Th17, Treg)的T细胞中的表达。诱导EAE,并在不同时间点分离脊髓组织。从小鼠脾细胞中分离CD4+ T细胞,分化为Th1、Th17和Treg表型,然后分析circSnx5的表达。与对照组小鼠相比,在疾病的高峰和峰后阶段,在EAE腰椎中检测到圆形和线性形式的Snx5表达增强。然而,与对照组相比,EAE小鼠的圆形形状与线性形状(CLR)的比例降低。circSnx5的表达与脊髓组织中炎症细胞因子的水平高度相关。脾细胞多克隆活化后,circSnx5表达水平显著降低。在分化的T细胞中,circSnx5的表达也下调至Th1、Th17和Treg。我们的发现提示circSnx5在自身免疫性神经炎症中的潜在作用。circSnx5在激活和分化过程中的表达改变可能为调节多发性硬化症(MS)炎症的潜在策略提供有价值的见解。
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引用次数: 0
Effectiveness of the Nasal Irrigation Effectiveness in Treating Allergic Rhinitis in Children 6 to 12 Years Old. 鼻冲洗法治疗6 ~ 12岁儿童变应性鼻炎的疗效观察。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18016
Bita Yadegari, Hamidreza Houshmand, Mir Reza Ghaemi

Nasal irrigation, a nonpharmacological intervention for alleviating nasal symptoms, has yet to gain widespread acceptance among caregivers due to procedural ambiguities and the absence of a standardized protocol. This study aimed to evaluate the efficacy of normal saline nasal irrigation in managing allergic rhinitis among children aged 6 to 12 years. This prospective, randomized, single-blind trial enrolled children aged 6 to 12 with allergic rhinitis. Patients were randomly assigned to receive either standard care (oral antihistamine and intranasal corticosteroid) or standard care plus nasal irrigation with saline solution. Symptom severity, assessed using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) at baseline, 1, and 3 months, included rhinorrhea, nasal congestion, sneezing, pruritus, ocular symptoms, and functional impairment. The intervention group demonstrated statistically significant improvements in several domains post-intervention. Specifically, a marked reduction in sneezing frequency and nasal cleansing requirements was observed. Moreover, this group reported significantly lower ocular symptoms, including irritation, itching, and watering, relative to the control group. Although overall PRQLQ scores did not differ significantly between groups, the intervention group exhibited lower scores at the 1- and 3-month follow-ups, indicative of enhanced quality of life. These findings suggest a potential beneficial effect of the intervention on participant well-being. The findings of this study indicate that nasal irrigation with 0.65% saline solution 4 times daily may serve as an effective adjunct treatment for children with allergic rhinitis. This regimen was associated with significant enhancements in both nasal symptom severity and quality of life.

鼻腔冲洗是一种用于缓解鼻部症状的非药物干预措施,但由于程序不明确和缺乏标准化方案,尚未得到护理人员的广泛接受。本研究旨在评估生理盐水鼻腔冲洗治疗过敏性鼻炎对 6 至 12 岁儿童的疗效。这项前瞻性、随机、单盲试验招募了 6 至 12 岁的过敏性鼻炎患儿。患者被随机分配接受标准治疗(口服抗组胺药和鼻内皮质类固醇)或标准治疗加生理盐水鼻腔冲洗。在基线、1个月和3个月时,使用小儿鼻结膜炎生活质量问卷(PRQLQ)评估症状严重程度,包括鼻出血、鼻塞、打喷嚏、瘙痒、眼部症状和功能障碍。干预后,干预组在多个方面都有了统计学意义上的显著改善。具体而言,打喷嚏的频率和鼻腔清洁的需求明显减少。此外,与对照组相比,干预组的眼部症状(包括刺激、瘙痒和流泪)明显减少。虽然各组的 PRQLQ 总分没有明显差异,但干预组在 1 个月和 3 个月的随访中得分较低,表明生活质量有所提高。这些研究结果表明,干预可能会对参与者的幸福感产生有益的影响。本研究结果表明,用 0.65% 生理盐水冲洗鼻腔,每天 4 次,可作为过敏性鼻炎患儿的有效辅助治疗方法。这种疗法可显著改善鼻部症状的严重程度和生活质量。
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引用次数: 0
Establishing an HLA-Typed Plateletpheresis Donor Registry at the Iranian Blood Transfusion Organization. 在伊朗输血组织建立hla型血小板献血者登记。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18020
Fatemeh Sabaghi, Minoo Shahidi, Majid Safa, Mohammad Faranoush, Mostafa Jamali, Ebadollah Salekmoghadam, Fatemeh Mohamadali, Shahin Sharifi, Saeed Mohammadi, Reza Golestani

Administering human leukocyte antigen (HLA)-compatible platelets is a tactic for treating patients with poor responses to random platelet injections. HLA-matched platelet provision requires many donors with HLA-typed and organized information. This study, the first of its kind in Iran, aimed to develop a registry system of HLA-typed platelet donors to facilitate the provision of compatible platelets to patients, leveraging the diversity of HLA alleles across Iran's various provinces. This study involved the HLA-typing of 1850 plateletpheresis donors, who were also registered as unrelated stem cell donors, across all blood centers in Iran from 2015 to 2022. HLA-A and HLA-B genotyping was conducted at a low-resolution using polymerase chain reaction-sequence specific primers (PCR-SSP) and real-time PCR. Statistical analysis was performed to determine allelic genotypes and donor profiles. The majority of the donors were male (99.7%), with a mean age of 36 years. The high donor rate in Tehran indicates a larger pool of potential HLA-platelet donors due to a denser population and more donation facilities. The donors were recruited for HLA-compatible plateletpheresis. The frequency of HLA-AB alleles among donors was relatively consistent with those documented by Iranians. Our findings can be utilized to create a foundational HLA database. A registry system for HLA-typed platelet donors is crucial due to high HLA polymorphism and ethnic diversity. This system facilitates the rapid identification of compatible donors based on HLA typing. Additional inquiries are needed to expand the plateletpheresis registry and make a request-supply mechanism between the Iranian Blood Transfusion Organization and hospitals.

管理人类白细胞抗原(HLA)兼容的血小板是治疗对随机血小板注射反应不良的患者的一种策略。提供hla匹配的血小板需要许多具有hla类型和组织信息的供体。该研究是伊朗首个此类研究,旨在开发HLA型血小板供体的注册系统,以促进向患者提供兼容的血小板,利用伊朗各省HLA等位基因的多样性。该研究涉及2015年至2022年伊朗所有血液中心的1850名血小板献血者的hla分型,这些献血者也被登记为无关干细胞献血者。采用聚合酶链反应-序列特异性引物(PCR- ssp)和实时PCR在低分辨率下进行HLA-A和HLA-B基因分型。统计分析确定等位基因型和供体谱。献血者以男性居多(99.7%),平均年龄36岁。德黑兰的高供体率表明,由于人口密集和更多的捐赠设施,潜在的hla -血小板供体池更大。招募供者进行hla相容血小板采血。供体中HLA-AB等位基因的频率与伊朗人记录的频率相对一致。我们的发现可以用来创建一个基础的HLA数据库。HLA型血小板供体的登记系统是至关重要的,因为HLA高多态性和种族多样性。该系统有助于基于HLA分型快速识别相容供体。需要进行更多的调查,以扩大采血小板登记,并在伊朗输血组织和医院之间建立请求-供应机制。
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引用次数: 0
Evaluation of Heterologous Prime-boost Vaccine Strategy Using Full-length Cytomegalovirus Glycoprotein B to Trigger BALB/c Mice Immunity. 利用全长巨细胞病毒糖蛋白B触发BALB/c小鼠免疫的异源免疫强化疫苗策略的评价
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18023
Somayeh Azadfar, Ahad Yamchi, Ahmad Majd, Alijan Tabarraei

Human cytomegalovirus glycoprotein B (gB) emerges as a viable candidate for eliciting neutralizing antibodies. This research specifically focused on exploring the immune reaction prompted by the nonglycosylated variant of the gB, with a comprehensive assessment of humoral immunity in mice. The gB coding sequence was optimized and expressed in pET-15b. Additionally, pcDNA3.1(+) vectors were also used for cloning the same gB sequence as the DNA vaccine. The gB was purified using a Ni-NTA chromatographic column. SDS-PAGE and Western blotting were used to confirm protein expression and purification. Using the prime-boost strategy, 8 different BALB/c mice were injected with DNA vaccine plus gB heterologous vaccine at 3 intervals. We evaluated the interferon (IFN-γ), interleukin (IL-4), immunoglobulin (Ig) G1, IgG2a, and IgG2b using enzyme-linked immunosorbent assay.  It was shown that the mice administered with DNA vaccine plus gB had higher IFN- γ and IL-4 levels compared to controls. On the other hand, the mice that received 3 doses of gB showed the highest levels of IgG1 and IgG2a. However, IgG2b was at its highest in mice administrated with DNA vaccine plus gB. The total IgG was higher in mice that received gB than in other interventions. According to the findings, the DNA vaccine enhanced total IgG in immunized mice more effectively than the gB. This could be attributed to conformational changes owing to a lack of glycan moiety. Furthermore, combining nonglycosylated gB with DNA as a heterologous vaccine strategy enhances innate immunity by increasing the IFN- γ levels.

人巨细胞病毒糖蛋白B (gB)作为诱导中和抗体的可行候选物出现。本研究专门探讨了gB非糖基化变体引发的免疫反应,并对小鼠的体液免疫进行了综合评估。对gB编码序列进行优化,并在pET-15b中进行表达。此外,pcDNA3.1(+)载体也用于克隆与DNA疫苗相同的gB序列。采用Ni-NTA色谱柱纯化gB。SDS-PAGE和Western blotting检测了蛋白的表达和纯化。采用“先补后补”的方法,对8只不同的BALB/c小鼠按3个间隔注射DNA疫苗加gB异源疫苗。我们使用酶联免疫吸附法评估干扰素(IFN-γ)、白细胞介素(IL-4)、免疫球蛋白(Ig) G1、IgG2a和IgG2b。结果表明,与对照组相比,DNA疫苗加gB小鼠具有更高的IFN- γ和IL-4水平。另一方面,接受三剂量gB的小鼠显示出最高水平的IgG1和IgG2a。而IgG2b在DNA疫苗加gB组小鼠中最高。注射gB的小鼠总IgG高于其他干预组。结果表明,DNA疫苗比gB疫苗更有效地提高了免疫小鼠的总IgG。这可能是由于缺乏聚糖部分而引起的构象变化。此外,将非糖基化的gB与DNA结合作为异源疫苗策略通过增加IFN- γ水平来增强先天免疫。
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引用次数: 0
Investigating the Relationship between FGF2 Gene Expression and Airway Remodeling in Severe Asthma. 重度哮喘患者FGF2基因表达与气道重塑关系的研究。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18015
Mahsa Manafi Varkiani, Majid Mirsadraee, Mohammadreza Khakzad, Soheila Moadikhah, Simin Moadikhah, Amirhossein Hashemiattar

Severe asthma causes chronic airway inflammation and structural changes in the bronchial wall. Fibroblast growth factor 2 (FGF2) plays an inflammatory role in specific pathways in airway remodeling in asthma. Assessing the relationship between sputum pattern, bronchial thickness by high-resolution computed tomography (HRCT) scan, and FGF2 expression level can evaluate the role of FGF2 in asthma remodeling. The study aimed to investigate the correlation between airway wall thickness and FGF2 gene expression in 100 participants with severe asthma. The method involved measuring airway wall thickness using HRCT and analyzing FGF2 gene expression through real-time reverse transcriptase polymerase chain reaction. The participants were divided into 2 groups based on bronchodilator responsiveness and classified into different asthma phenotypes based on sputum cell count. The baseline data did not show a significant difference between the groups. The study found significant differences in airway variables between different asthma subgroups. FGF2 expression was associated with various characteristics of asthma, including body mass index, forced expiratory volume in 1 second (FEV1), and airway wall thickness. The receiver operating characteristic curve analysis showed that a fold change higher than 2.42 in FGF2 expression indicated asthma. Based on our research, FGF2 may play a critical role in airway thickness regardless of inflammation. We found increased FGF2 levels with disease severity and wall thickness in atopic severe persistent asthma patients with FEV1 below 60%. Further research is needed to understand FGF2's role across broader FEV1 ranges and other phenotypes.

严重哮喘引起慢性气道炎症和支气管壁结构改变。成纤维细胞生长因子2 (FGF2)在哮喘气道重塑的特定途径中发挥炎症作用。通过高分辨率计算机断层扫描(HRCT)评估痰样、支气管厚度与FGF2表达水平的关系,可以评估FGF2在哮喘重塑中的作用。本研究旨在探讨100例重度哮喘患者气道壁厚度与FGF2基因表达的相关性。方法包括使用HRCT测量气道壁厚度,通过实时逆转录酶聚合酶链反应分析FGF2基因表达。根据支气管扩张剂反应性分为两组,根据痰细胞计数分为不同的哮喘表型。基线数据没有显示两组之间的显著差异。研究发现不同哮喘亚组之间气道变量存在显著差异。FGF2的表达与哮喘的各种特征相关,包括体重指数、1秒用力呼气量(FEV1)和气道壁厚度。受试者工作特征曲线分析显示,FGF2表达变化大于2.42倍即为哮喘。根据我们的研究,无论炎症如何,FGF2可能在气道厚度中起关键作用。我们发现,在FEV1低于60%的特应性重度持续性哮喘患者中,FGF2水平随疾病严重程度和壁厚的增加而增加。需要进一步的研究来了解FGF2在更广泛的FEV1范围和其他表型中的作用。
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引用次数: 0
Neutrophil Markers as Predictors of COVID-19 Severity at Hospital Admission: A Cross-sectional Study. 中性粒细胞标志物作为入院时COVID-19严重程度的预测指标:一项横断面研究
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18017
Maedeh Vahabi, Abdolrahman Rostamian, Ensie Sadat Mirsharif, Keyvan Latifi, Sara Iranparast, Tooba Ghazanfari

COVID-19 is capable of undermining self-tolerance in a host's immune system and triggering autoimmunity by hyper-activating the innate and adaptive immune systems, which has not investigated in Iranian society until now. In the innate immune system neutrophils are the predominant immune cells that protect the human body against invaders. Here, we sought to explore 2 important variables related to neutrophil: DNA complexes with myeloperoxidase (MPO-DNA) as a reliable indicator of neutrophil extracellular traps (NETs) by MPO-DNA complex evaluation using a sandwich ELISA and the underlying role of IL-8 in (NETs) formation during COVID-19 infection. According to our results, in 103 COVID-19 patients, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in ICU patients (14.62±11.81) compared to non-ICU patients (3.16±3.33). Elevated IL-8 levels were observed in COVID-19 patients, particularly in ICU patients. MPO-DNA levels, indicating NETosis, were significantly higher in COVID-19 patients and strongly correlated with neutrophil counts (r=0.472). Thus, our studies suggest that neutrophils count, IL-8, and MPO-DNA can be used as powerful biomarkers in diagnosing COVID-19 severity. patients with severe COVID-19 infection are prone to heart disease because most of them develop excessive NET formation. Additionally, In COVID-19 patients, a higher MPO-DNA level may increase the risk of developing heart disease too.

COVID-19能够破坏宿主免疫系统的自我耐受性,并通过过度激活先天和适应性免疫系统触发自身免疫,迄今为止尚未在伊朗社会进行调查。在先天免疫系统中,中性粒细胞是保护人体免受入侵者侵害的主要免疫细胞。在这里,我们试图探索与中性粒细胞相关的两个重要变量:通过夹心ELISA法对MPO-DNA复合物进行评估,将MPO-DNA复合物作为中性粒细胞胞外陷阱(NETs)的可靠指标,以及IL-8在COVID-19感染期间(NETs)形成中的潜在作用。结果显示,103例COVID-19患者中,ICU患者中性粒细胞与淋巴细胞比值(NLR)(14.62±11.81)明显高于非ICU患者(3.16±3.33)。IL-8水平在COVID-19患者中升高,特别是在ICU患者中。表明NETosis的MPO-DNA水平在COVID-19患者中显著升高,且与中性粒细胞计数密切相关(r=0.472)。因此,我们的研究表明,中性粒细胞计数、IL-8和MPO-DNA可以作为诊断COVID-19严重程度的有力生物标志物。严重感染COVID-19的患者容易发生心脏病,因为他们中的大多数人会形成过多的NET。此外,在COVID-19患者中,较高的MPO-DNA水平也可能增加患心脏病的风险。
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引用次数: 0
Ellagic Acid Ameliorates Ovarian Cancer via Modification of Pyroptosis and Inflammation. 鞣花酸通过改变卵巢焦亡和炎症改善卵巢癌。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18025
Yan Sun, Xin Hu, Ying Wang

Ovarian cancer is 1 of the most serious female malignancies worldwide. Despite intensive efforts to overcome ovarian cancer, there remain limited treatment options for this disease. Ellagic acid (EA), a well-known phytochemical with anti-inflammatory properties, is suggested as a therapeutical strategy as it can inhibit the growth of certain cancer cells. However, its effect on human ovarian carcinoma cells has not yet been fully elucidated. The present study aimed to explore the effect of EA on ovarian carcinoma and further expound the underlying mechanisms of EA-induced ovarian cancer cell death. Human ovarian carcinoma cell lines, A2780 and OVCAR3, were treated with EA (0, 10, 20, 50, and 100 μM) and assessed for viability, cell cycle (cyclin D1 and cyclin E), pyroptosis (gasdermin D [GSDMD] and gasdermin E [GSDME]), autophagy (microtubule-associated protein 1A/1B-light chain 3 [MAP1LC3] and autophagy protein 5 [ATG5]), and inflammation (interleukin [IL]-1b and IL-6) via 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA). The findings showed that EA could significantly inhibit cell viability, decrease cyclin D1 and E levels, downregulate GSDMD and GSDME, and suppress the levels of inflammatory markers, including IL-1b and IL-6. However, the protein levels of autophagic markers including LC3 and ATG5 remained mostly unchanged. The findings suggest that EA could suppress ovarian cancer cell viability and proliferation by arresting both cell lines at the G1 phase of the cell cycle through modification of cell death mediated by inflammatory-caused pyroptosis.

卵巢癌是世界上最严重的女性恶性肿瘤之一。尽管努力克服卵巢癌,但这种疾病的治疗选择仍然有限。鞣花酸(EA)是一种众所周知的具有抗炎特性的植物化学物质,它可以抑制某些癌细胞的生长,因此被认为是一种治疗策略。然而,其对人卵巢癌细胞的作用尚未完全阐明。本研究旨在探讨EA对卵巢癌的作用,并进一步阐明EA诱导卵巢癌细胞死亡的潜在机制。用EA(0、10、20、50和100 μM)处理人卵巢癌细胞株A2780和OVCAR3,通过3-(4,5-二甲基噻唑-2-基)-2,5二苯基溴化四氮唑(MTT)、实时聚合酶链反应(RT-PCR)检测细胞活性、细胞周期(cyclin D1和cyclin E)、凋亡(gasdermin D [GSDMD]和gasdermin E [GSDME])、自噬(微管相关蛋白1A/ 1b -轻链3 [MAP1LC3]和自噬蛋白5 [ATG5])和炎症(白细胞介素[IL]-1b和IL-6)。酶联免疫吸附试验(ELISA)。结果显示,EA可显著抑制细胞活力,降低cyclin D1和E水平,下调GSDMD和GSDME水平,抑制炎症标志物IL-1b和IL-6水平。然而,自噬标志物LC3和ATG5的蛋白水平基本保持不变。研究结果表明,EA可以通过改变炎症引起的细胞凋亡介导的细胞死亡,在细胞周期的G1期抑制两种细胞系的细胞活力和增殖。
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引用次数: 0
Rare Allergic Reaction to Local Anesthesia: A Case Report. 局部麻醉罕见过敏反应1例报告。
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18027
Rakhi Issrani, Raha Ahmed Shamikh Almufarrij, Rital Jamal Salamh Alwaqid, Mohammed Saad Alqarni, Namdeo Prabhu, Muhammad Nadeem Baig

One of the most commonly used local anesthetic (LA) agents in dentistry is lidocaine. Hypersensitivity reactions to lidocaine have been reported. In such cases, it is crucial to record a detailed clinical history and perform allergy testing to select a suitable alternative LA agent. This report presents the experience of observing a case of lidocaine allergy, supported by a review of the literature on the condition. A rare case of delayed hypersensitivity reaction to lidocaine is reported, where the patient exhibited swelling and erythema of the upper labial mucosa. Intradermal testing confirmed an allergic reaction to lidocaine. The patient was successfully treated with an alternative LA agent, allowing for the completion of dental procedures without complications. This highlights the importance of careful diagnostic measures to manage such rare but significant allergic reactions effectively. This case highlights the importance of recording a proper clinical history and performing allergy testing before the administration of LA to prevent severe allergic reactions. Additionally, patients identified as allergic to LA agents should be thoroughly counseled, informed about their condition, and provided with a clear explanation of all available treatment options.

利多卡因是牙科最常用的局部麻醉(LA)药物之一。对利多卡因的过敏反应已有报道。在这种情况下,记录详细的临床病史并进行过敏试验以选择合适的替代LA剂是至关重要的。本报告提出的经验观察利多卡因过敏的情况下,通过回顾文献的条件支持。报告一例罕见的延迟性利多卡因超敏反应,患者表现为上唇黏膜肿胀和红斑。皮内检查证实对利多卡因过敏。患者成功地用一种替代的LA剂治疗,允许完成牙科手术,没有并发症。这突出了仔细诊断措施的重要性,以有效地管理这种罕见但显著的过敏反应。本病例强调了在给药前记录正确的临床病史和进行过敏测试的重要性,以防止严重的过敏反应。此外,对LA药物过敏的患者应该得到充分的咨询,告知他们的病情,并向他们提供所有可用治疗方案的明确解释。
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引用次数: 0
Upregulation of MicroRNA-144 Suppresses Nrf2 Antioxidant Signaling Pathway in Patients with Severe COVID-19. MicroRNA-144在重症COVID-19患者中抑制Nrf2抗氧化信号通路的表达
IF 1.2 4区 医学 Q4 ALLERGY Pub Date : 2025-02-13 DOI: 10.18502/ijaai.v24i1.18018
Mahdieh Nasirzadeh, Mahdi Pouramir, Shiva Gholizadeh-Ghaleh Aziz, Shahriar Alipour

MicroRNAs (miRs) play a pivotal role in the pathogenesis of viral infections. It has been proven that the Nrf2 (NFE2 like bZIP transcription factor 2) antioxidant signaling pathway is inhibited in COVID-19 patients. Two microRNAs (MIR144 and MIR153-1) have been identified as important Nrf2 regulators. The aim of this study was to analyze the MIR144 and MIR153-1 expression in COVID-19 patients and investigate their association with the Nrf2 signaling pathway. The study had 82 participants with both mild and severe COVID-19 manifestations and 25 healthy as a control group. Ficoll density-gradient centrifugation was used to separate peripheral blood mononuclear cells from ethylenediaminetetraacetic acid blood tubes. MIR144, MIR153-1, and NFE2L2 expressions were studied using real-time polymerase chain reaction. We employed the commercially available enzyme-linked immunosorbent assay to measure plasma Nrf2 protein concentration and the activity of antioxidant enzymes, superoxide dismutase, and catalase. Compared to the control group, MIR144 expression was significantly increased in the severe group, while NFE2L2 expression decreased. There was no significant difference in the MIR153-1 expression rate between COVID-19 patients and controls. Nrf2 protein and antioxidant enzyme activity significantly decreased in the severe group. A negative correlation between MIR144 expression and Nrf2 protein concentration was observed. Taken together, the current study's findings showed that MIR144 upregulation probably interferes with the Nrf2 antioxidant signaling pathway in COVID-19 patients.

MicroRNAs (miRs)在病毒感染的发病机制中起着关键作用。已证实Nrf2 (NFE2 like bZIP转录因子2)抗氧化信号通路在COVID-19患者中受到抑制。两个microrna (MIR144和MIR153-1)已被确定为重要的Nrf2调节因子。本研究的目的是分析MIR144和MIR153-1在COVID-19患者中的表达,并探讨它们与Nrf2信号通路的关系。该研究有82名患有轻度和重度COVID-19症状的参与者和25名健康参与者作为对照组。采用Ficoll密度梯度离心分离法从乙二胺四乙酸血管中分离外周血单个核细胞。实时聚合酶链反应检测MIR144、MIR153-1和NFE2L2的表达。我们采用市售酶联免疫吸附法测定血浆Nrf2蛋白浓度和抗氧化酶、超氧化物歧化酶和过氧化氢酶的活性。与对照组相比,重度组MIR144表达显著升高,NFE2L2表达降低。MIR153-1表达率在新冠肺炎患者与对照组之间无显著差异。重度组Nrf2蛋白和抗氧化酶活性显著降低。MIR144的表达与Nrf2蛋白浓度呈负相关。综上所述,目前的研究结果表明,MIR144的上调可能会干扰COVID-19患者的Nrf2抗氧化信号通路。
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引用次数: 0
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Iranian journal of allergy, asthma, and immunology
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