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Impact of Berberine on the Expression of Apollon Gene in Chronic Lymphocytic Leukemia 小檗碱对慢性淋巴细胞白血病Apollon基因表达的影响
Pub Date : 2021-05-31 DOI: 10.5812/tms.115983
Niloofar Ghanizade, Maral Hemati, Habib Jaafarinejad, Mehrnoosh Pashaei, P. Kokhaei
Background: The incidence of B-chronic lymphocytic leukemia (B-CLL) resulting from the clonal accumulation of apoptosis-resistant malignant B lymphocytes is growing in the adult population of Iran. Inhibitors of apoptosis proteins (IAPs) are considered as factors that can delay the onset of CLL cell apoptosis. Berberine is an isoquinoline alkaloid isolated from Cotridis rhizoma that exhibits anti-tumor activities through various mechanisms. Objectives: In this study, we investigated the impact of berberine on the level of Apollon expression in peripheral blood mononuclear cells (PBMCs) of 12 cases newly diagnosed with CLL and 6 healthy donors. Methods: At first, the level of Apollon expression was assessed in PBMCs of CLL patients compared to the healthy donors. Peripheral blood mononuclear cells were cultured in RPMI-1640 medium with 5% fetal bovine serum (FBS) and 1% penicillin/streptomycin for 48 hours, and the effect of berberine (25 µM) on the level of Apollon expression in CLL patients was assessed and compared to that of healthy donors. Results: We found that the expression level of Apollon was not significantly different between CLL patients and healthy donors (P = 0.640). Moreover, berberine induced no significant differences in Apollon expression as compared to the untreated (control) group (P = 0.545 and P = 0.267 in CLL patients and healthy donors, respectively). Conclusions: Overall, our results suggest that berberine has no direct effect on the expression of Apollon gene in CLL patients, and pro-apoptotic impacts of berberine may be exerted through other mechanisms.
背景:在伊朗成年人群中,由抗凋亡恶性B淋巴细胞克隆积累引起的B-慢性淋巴细胞白血病(B- cll)发病率正在上升。凋亡蛋白抑制剂(IAPs)被认为是可以延缓CLL细胞凋亡发生的因素。小檗碱是一种从黄芪中分离得到的异喹啉类生物碱,通过多种机制表现出抗肿瘤活性。目的:研究黄连素对12例新诊断的CLL患者和6例健康供者外周血单核细胞(PBMCs)中Apollon表达水平的影响。方法:首先比较CLL患者外周血单核细胞中Apollon的表达水平,并与健康供者进行比较。将外周血单个核细胞在含有5%胎牛血清(FBS)和1%青霉素/链霉素的rpm -1640培养基中培养48小时,评估小檗碱(25µM)对CLL患者Apollon表达水平的影响,并与健康供者进行比较。结果:我们发现CLL患者与健康供者之间Apollon表达水平无显著差异(P = 0.640)。此外,与未治疗组(对照组)相比,黄连素诱导的Apollon表达无显著差异(CLL患者和健康供者分别P = 0.545和P = 0.267)。结论:综上所述,小檗碱对CLL患者Apollon基因表达无直接影响,其促凋亡作用可能通过其他机制发挥作用。
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引用次数: 0
Distribution of DD Genotype of Angiotensin-Converting Enzyme Gene and Its Correlation with Diabetic Retinopathy 血管紧张素转换酶基因DD型的分布及其与糖尿病视网膜病变的相关性
Pub Date : 2021-05-31 DOI: 10.5812/tms.115489
Hamid Ali-Bahar, Maysam Mard-Soltani, Yousef Paridar, Zahra Nasirbaghban, Z. Hashemi, Alireza Zakeri, S. Khalili
Background: One of the major microvascular complications of diabetes mellitus (DM) is diabetic retinopathy (DR). Studies have shown that angiotensin-converting enzyme (ACE) gene polymorphisms are correlated with DR progression. Accordingly, the elucidation of the association between ACE gene polymorphism and the risk of DR development seems to be highly crucial. Methods: In this study, 195 individuals with type 2 diabetes mellitus (T2DM) were classified as the case group with retinopathy (99 people) and control group without retinopathy (96 people). Screening for DR was performed by ophthalmologists using clinical examination and fluorescein angiography. Different ACE genotypes (II, ID, and DD) were identified by the collection of blood samples, extraction of DNA, and PCR amplification using specific primers. Results: The frequency distribution of genotypes was significantly different between the case and control groups (P = 0.009). Interestingly, possessing a DD genotype made diabetic patients approximately 2.5 folds (95% CI = 1.271 - 4.840, P = 0.007) and 3.25 folds (95% CI = 1.312 - 8.051, P = 0.01) more susceptible to DR when compared to having DI and II genotypes, respectively. Moreover, having a D allele made diabetic individuals nearly 1.75 folds (95% CI = 1.167 - 2.623, P = 0.007) more susceptible to DR than possessing an I allele. Conclusions: Our results potentiate the hypothesis that the DD genotype and D allele of the ACE gene might play a role in the pathogenesis of DR.
背景:糖尿病视网膜病变(DR)是糖尿病(DM)的主要微血管并发症之一。研究表明,血管紧张素转换酶(ACE)基因多态性与DR进展相关。因此,阐明ACE基因多态性与DR发生风险之间的关系似乎非常重要。方法:将195例2型糖尿病(T2DM)患者分为有视网膜病变的病例组(99人)和无视网膜病变的对照组(96人)。眼科医生通过临床检查和荧光素血管造影筛查DR。不同的ACE基因型(II型、ID型和DD型)通过采集血样、提取DNA和使用特定引物进行PCR扩增进行鉴定。结果:病例组与对照组基因型频率分布差异有统计学意义(P = 0.009)。有趣的是,与DI和II基因型相比,拥有DD基因型的糖尿病患者患DR的可能性分别增加了约2.5倍(95% CI = 1.271 - 4.840, P = 0.007)和3.25倍(95% CI = 1.312 - 8.051, P = 0.01)。此外,拥有D等位基因的糖尿病人比拥有I等位基因的糖尿病人患DR的几率高1.75倍(95% CI = 1.167 - 2.623, P = 0.007)。结论:我们的研究结果支持了ACE基因DD基因型和D等位基因可能在DR发病机制中起作用的假设。
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引用次数: 0
Alteration in Lactate Production and Decrease in MTT Dye Reduction in Serum-starved Human Peripheral Blood Mononuclear Cells (PBMCs) 血清饥饿人外周血单个核细胞乳酸生成的改变和MTT染料减少的减少
Pub Date : 2021-02-28 DOI: 10.5812/tms.115363
M. Mehri, F. Saeedi, Roghaye Porbagher, Amrollah Mastafazadeh
Background: Immunometabolism targeting therapy of auto-inflammatory diseases is an emerging strategy compared to immune system global suppression. However, our knowledge in this field needs promotion. Objectives: We examined the effects of serum starvation stress on metabolic activity in human peripheral blood mononuclear cells (PBMCs). Methods: Fresh immune cells were isolated from four healthy adult volunteers and cultivated with or without fetal bovine serum (FBS) at various time points under standard conditions. Glucose and intra- and extracellular lactate levels were assessed using routine techniques, and 3-(4, 5 -dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction assay was used to determine mitochondrial function. Results: Spindle shape macrophage-like cells, which appeared early, were replaced at 96 h by large round monocytes/macrophage-like cells, with more frequency in the non-starved group. Interestingly, serum starvation dictated a status, especially in monocyte/macrophage-like cells, that led to prolong decrement in mitochondrial dehydrogenase-mediated reduction of MTT. This difference was confirmed with the MTT assay quantitatively (P < 0.05). Moreover, the intra- and extracellular lactate concentrations were lower in starved cells than in non-starved controls (P < 0.05), and glucose levels were higher in 72 h starved cell culture supernatants than in non-starved control cells (P < 0.05). Conclusions: This study showed that under serum starvation-induced metabolic stress, lactate production is altered in immune cells, and total oxidative mitochondrial activity is reduced in macrophage-like cells. These findings open a new window to target immune cell metabolism for the treatment of autoinflammatory and autoimmune diseases.
背景:与免疫系统整体抑制相比,免疫代谢靶向治疗自身炎症性疾病是一种新兴的治疗策略。然而,我们在这方面的知识还需要提高。目的:研究血清饥饿应激对人外周血单核细胞(PBMCs)代谢活性的影响。方法:从4名健康成人志愿者中分离新鲜免疫细胞,在标准条件下,在不同时间点加胎牛血清或不加胎牛血清培养。葡萄糖和细胞内及细胞外乳酸水平采用常规技术评估,3-(4,5 -二甲基噻唑-2-基)- 2,5 -二苯基溴化四唑(MTT)还原法测定线粒体功能。结果:早期出现的梭形巨噬细胞样细胞在96 h被较大的圆形单核细胞/巨噬细胞样细胞所取代,非饥饿组出现频率更高。有趣的是,血清饥饿决定了一种状态,特别是单核细胞/巨噬细胞样细胞,导致线粒体脱氢酶介导的MTT减少延长。MTT法定量证实了这一差异(P < 0.05)。此外,饥饿细胞的细胞内和细胞外乳酸浓度低于非饥饿对照组(P < 0.05),饥饿72 h细胞培养上清液的葡萄糖水平高于非饥饿对照组(P < 0.05)。结论:本研究表明,在血清饥饿诱导的代谢应激下,免疫细胞乳酸生成改变,巨噬细胞样细胞线粒体总氧化活性降低。这些发现为靶向免疫细胞代谢治疗自身炎症和自身免疫性疾病打开了一扇新的窗口。
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引用次数: 0
Adverse Events and Side Effects of Chimeric Antigen Receptor (CAR) T Cell Therapy in Patients with Hematologic Malignancies 嵌合抗原受体(CAR) T细胞治疗血液恶性肿瘤患者的不良事件和副作用
Pub Date : 2021-02-28 DOI: 10.5812/tms.116301
Pooria Safarzadeh Kozani, Shima Shabani
: Chimeric antigen receptor (CAR) T cell therapy is rapidly being established as a new cancer treatment modality especially for the treatment of hematologic malignancies. Alongside being capable of inducing durable responses in such malignancies, CAR T cell therapy has always been accompanied by exclusive toxicities such as cytokine release syndrome (CRS), that can range from mild to life-threatening. These toxicities require intensive monitoring and fast and executive management procedures to reduce the level of damages or the rate of mortality in CAR T cell therapy recipients. In this review, we tend to introduced some of the most common CAR T cell therapy-related toxicities and their clinical demonstrations. Furthermore, we also introduce some of the management procedures commonly considered in this regard.
嵌合抗原受体(CAR) T细胞疗法正迅速成为一种新的癌症治疗方式,特别是在血液系统恶性肿瘤的治疗中。除了能够在这些恶性肿瘤中诱导持久的反应外,CAR - T细胞疗法一直伴随着排他毒性,如细胞因子释放综合征(CRS),其范围从轻微到危及生命。这些毒性需要密切监测和快速执行的管理程序,以降低CAR - T细胞治疗受者的损害水平或死亡率。在这篇综述中,我们倾向于介绍一些最常见的CAR - T细胞治疗相关的毒性及其临床表现。此外,我们还介绍了在这方面通常考虑的一些管理程序。
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引用次数: 5
Alzheimer’s Disease and its Risk Factors: A Case-control Study 阿尔茨海默病及其危险因素:一项病例对照研究
Pub Date : 2021-02-28 DOI: 10.5812/tms.113857
M. Dolatshahi, S. Mahmoudi, Mansour Torabi nia, Vahid Kheirandish
Objectives: The etiology of Alzheimer’s disease is supposed to involve environmental exposure and genetic vulnerability. The present study aimed to assess the association between Alzheimer’s disease and its risk factors. Methods: We conducted a case-control study of 95 Alzheimer’s disease patients and 98 matched controls. All participants (case and control groups) were examined by mini-mental state examination. This information was collected by a risk factor questionnaire from January to June 2019. Data were analyzed using logistic regression analysis via SPSS-22 software. Results: The findings revealed the effect of risk factors' odds ratios on the occurrence of Alzheimer’s disease by logistic regression analysis. Sex (female), chronic disease, loneliness or being single, and family history showed positive associations with AD, whereas daily physical exercise, religious beliefs, high level of social communication, and male sex had negative associations with AD development (P < 0.05). Conclusions: The study highlighted the difficulty of etiology and recommended that the effective interventions for social support of older people, psychological condition, chronic disease, and lifestyle may be promising preventive policies.
目的:阿尔茨海默病的病因被认为与环境暴露和遗传易感性有关。本研究旨在评估阿尔茨海默病及其危险因素之间的关系。方法:对95例阿尔茨海默病患者和98例匹配的对照组进行病例对照研究。所有参与者(病例组和对照组)均采用简易精神状态检查。这些信息是通过2019年1月至6月的风险因素问卷收集的。数据采用SPSS-22软件进行logistic回归分析。结果:通过logistic回归分析,揭示了危险因素的比值比对阿尔茨海默病发生的影响。性别(女性)、慢性病、孤独或单身、家族史与AD呈正相关,日常体育锻炼、宗教信仰、高社交水平、男性与AD呈负相关(P < 0.05)。结论:该研究强调了病因的困难,并建议对老年人的社会支持、心理状况、慢性疾病和生活方式进行有效的干预可能是有希望的预防政策。
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引用次数: 0
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