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Silibinin, Synergistically Enhances Vinblastine-Mediated Apoptosis in Triple Negative Breast Cancer Cell Line: Involvement of Bcl2/Bax and Caspase-3 Pathway Silibinin, Synergistically Enhances Vinblastine-Mediated Apoptosis in Triple Negative Breaster Cancer Cell Line:Bcl2/Bax 和 Caspase-3 通路的参与
Pub Date : 2024-04-24 DOI: 10.18502/ijhoscr.v18i2.15375
H. Dariushnejad, Neda Roshanravan, Hunar Mustafa Wasman, Mostafa Cheraghi, Lale Pirzeh, V. Ghorbanzadeh
Background: Triple-negative breast cancer (TNBC) with a poor prognosis and survival is the most invasive subtype of breast cancer.  Usually, TNBC requires a chemotherapy regimen at all stages, but chemotherapy drugs have shown many side effects. We assumed that combination therapy of vinblastine and silibinin might reduce the vinblastine toxicity and dose of vinblastine. Materials and Methods: The MDA-MB-231 were cells subjected to MTT assay for IC50 determination and combination effects, which were measured based on Chou-Talalay's method. The type of cell death was determined by using a Flow-cytometric assay. Cell death pathway markers, including Bcl-2, Bax, and caspase-3 were analyzed by western blot and Real-Time PCR. Results: The treatment of MDA-MB-231 cells exhibited IC50 and synergism at the combination of 30 µM of silibinin and 4 µm of vinblastine in cell viability assay (CI=0.69). YO-PRO-1/PI double staining results showed a significant induction of apoptosis when MDA-MB-231 cells were treated with a silibinin and vinblastine combination (p<0.01). Protein levels of Bax and cleaved caspase-3 were significantly upregulated, and Bcl-2 downregulated significantly. Significant upregulation of Bax (2.96-fold) and caspase-3 (3.46-fold) while Bcl-2 was downregulated by 2-fold. Conclusion: Findings established a preclinical rationale for the combination of silibinin and vinblastine. This combination produces synergistic effects in MDA-MB-231 cells by altering pro- and anti-apoptotic genes, which may reduce the toxicity and side effects of vinblastine.
背景:三阴性乳腺癌(TNBC)预后差、生存率低,是乳腺癌中侵袭性最强的亚型。 通常,TNBC 在各个阶段都需要化疗,但化疗药物有很多副作用。我们认为,长春新碱和西利宾联合治疗可能会降低长春新碱的毒性,减少长春新碱的剂量。材料与方法用 MTT 法测定 MDA-MB-231 细胞的 IC50 值,并根据 Chou-Talalay 法测定联合疗法的效果。细胞死亡类型通过流式细胞仪测定。细胞死亡通路标记物,包括 Bcl-2、Bax 和 caspase-3 通过 Western 印迹和 Real-Time PCR 进行分析。结果在细胞活力测定中,30 µM 的西利宾和 4 µm 的长春新碱组合处理 MDA-MB-231 细胞的 IC50 和协同作用(CI=0.69)。YO-PRO-1/PI双重染色结果表明,当MDA-MB-231细胞接受西利宾和长春新碱的联合治疗时,可显著诱导细胞凋亡(p<0.01)。Bax 和裂解的 caspase-3 蛋白水平明显上调,Bcl-2 蛋白水平明显下调。Bax (2.96 倍)和 caspase-3 (3.46 倍)明显上调,而 Bcl-2 则下调了 2 倍。结论研究结果为西利宾和长春新碱的联合应用提供了临床前依据。这种联合疗法通过改变促凋亡基因和抗凋亡基因在 MDA-MB-231 细胞中产生协同效应,可降低长春新碱的毒性和副作用。
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引用次数: 0
A Case of Deep Venous Thrombosis in an HIV-Infected Patient despite Therapeutic Anticoagulation 一例艾滋病毒感染者在接受抗凝治疗后仍出现深静脉血栓的病例
Pub Date : 2024-04-24 DOI: 10.18502/ijhoscr.v18i2.15379
Wajeeha Aiman, Muhammad Ashar Ali, Navjot Grewal, Andreas A. Savopoulos, G. Guron
Patients with human immunodeficiency virus (HIV) infection have an increased likelihood of venous thromboembolism (VTE) owing to factors such as acquired protein C and S deficiency, antiphospholipid antibody syndrome, and heightened levels of pro-inflammatory cytokines. This case report highlights an exceptionally uncommon occurrence of deep venous thrombosis in an HIV-infected patient receiving a therapeutic dose of enoxaparin. This underscores the need for cautious consideration of the risk of VTE in HIV-infected individuals, even with preventive or therapeutic anticoagulant treatment. Further research is recommended to investigate HIV as a potential risk factor of prophylactic anticoagulation.
由于获得性蛋白 C 和 S 缺乏、抗磷脂抗体综合征以及促炎细胞因子水平升高等因素,人类免疫缺陷病毒(HIV)感染患者发生静脉血栓栓塞(VTE)的可能性增加。本病例报告强调了一名接受治疗剂量依诺肝素的 HIV 感染者发生深静脉血栓的异常罕见情况。这强调了即使接受了预防性或治疗性抗凝剂治疗,也需要谨慎考虑 HIV 感染者发生 VTE 的风险。建议开展进一步研究,将 HIV 作为预防性抗凝治疗的潜在风险因素进行调查。
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引用次数: 0
HHV-8 Linked to Kaposi's Sarcoma and Castleman's Disease in HIV-1-infected patient: Case Report and Review of the Literature HHV-8 与 HIV-1 感染者的卡波西肉瘤和 Castleman 病有关:病例报告与文献综述
Pub Date : 2024-04-24 DOI: 10.18502/ijhoscr.v18i2.15378
A. Zaghdoudi, Hajer Harrabi, Hanene Tiouiri Benaissa
Kaposi’s sarcoma (KS) and multicentric Castleman's disease (MCD) are both linked to human herpesvirus-8 (HHV-8) infection which most commonly affects people living with human immunodeficiency virus (HIV).  Herein, we describe the case of a 57-year-old patient who has been admitted for fever, night sweats, weight loss, and diffuse lymphadenopathy with abdominal pain. HIV status was confirmed by a positive Western blot test. His initial CD4 cell count was equal to 270 cells/µL. A histological study of a peripheral lymph node concluded that KS is associated with MCD. These two conditions found in the same patient highlight the malignant potential of HHV-8, particularly in the case of HIV-induced immunodeficiency.  
卡波西肉瘤(KS)和多中心卡斯特曼病(MCD)都与人类疱疹病毒-8(HHV-8)感染有关,而人类疱疹病毒-8感染最常见于人类免疫缺陷病毒(HIV)感染者。 在此,我们描述了一例因发热、盗汗、体重减轻、弥漫性淋巴结病伴有腹痛而入院的 57 岁患者。经 Western 印迹检测呈阳性,确诊为艾滋病病毒感染者。他最初的 CD4 细胞计数为 270 cells/µL。外周淋巴结的组织学检查结果表明,KS与MCD有关。在同一名患者身上发现的这两种病症凸显了 HHV-8 的恶性潜能,尤其是在艾滋病毒诱发免疫缺陷的情况下。
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引用次数: 0
Hemoglobin C Disorder in Anemic Patients Referred to the National Center for Thalassemia and Genetic Counseling in Damascus 大马士革国家地中海贫血症和遗传咨询中心转诊的贫血患者中的血红蛋白 C 紊乱症
Pub Date : 2024-04-24 DOI: 10.18502/ijhoscr.v18i2.15376
Aya Ahmad, Karam Fattoum, Wael Imam, Mhd Yasser Mukhalalaty, Musab Murad, Faizah Ali Al Quobaili
Background: Hemoglobinopathies are common inherited blood disorders in our Mediterranean area. The main structural hemoglobin variants are hemoglobin S and hemoglobin C, due to their prevalence. We conducted this retrospective study to investigate and characterize hemoglobin C patients referred to the National Center for Thalassemia and Genetic Counseling and the management of hemoglobin C disease in Damascus. Materials and Methods: The study included patients referred to the National Center for Thalassemia and Genetic Counseling in Damascus between 2000 and 2022 for hemoglobin C detection. Gender, age, geographical origin, hemoglobin electrophoresis profile, and blood transfusion were considered for hemoglobin C patient classification. Blood transfusion in five consecutive years and linear regression with hemoglobin S and C values were determined. Results: 30 (14 males and 16 females) out of 624 patients between 3 and 46 years old (mean ± SD: 17.3 ± 9.7 years) showed hemoglobin C disease. Only eight patients (one male and seven females) received blood transfusions, and the remaining patients (13 males and 9 females) did not receive any transfusion. Only one patient with 100% hemoglobin C was detected; 19 showed HbSC, and 10 had HbAC. There was a significant correlation between hemoglobin S and geographical origin (P-value=0). Conclusion: A Homozygote hemoglobin C patient has mild hemolytic anemia, whereas the hemoglobin C 100% patient has only a one-time blood transfusion (he was 17 years old) in our study. The inherited combination of hemoglobin C and S is less severe than hemoglobin S alone. There is a significant relationship between hemoglobin S and geographical origin (p-value=0).
背景:血红蛋白病是地中海地区常见的遗传性血液疾病。由于血红蛋白 S 和血红蛋白 C 的发病率较高,因此主要的结构性血红蛋白变异体是血红蛋白 S 和血红蛋白 C。我们进行了这项回顾性研究,以调查和描述转诊至国家地中海贫血和遗传咨询中心的血红蛋白 C 患者以及大马士革血红蛋白 C 疾病的管理情况。材料和方法:研究对象包括 2000 年至 2022 年期间因检测出 C 型血红蛋白而转诊至大马士革国家地中海贫血和遗传咨询中心的患者。在对 C 型血红蛋白患者进行分类时,考虑了性别、年龄、地域、血红蛋白电泳图谱和输血情况。确定了连续五年的输血量以及与血红蛋白 S 和 C 值的线性回归。结果在 624 名 3 至 46 岁的患者中,有 30 人(男性 14 人,女性 16 人)患有血红蛋白 C 疾病(平均 ± SD:17.3 ± 9.7 岁)。只有 8 名患者(1 名男性和 7 名女性)接受了输血,其余患者(13 名男性和 9 名女性)未接受任何输血。只有一名患者的血红蛋白 C 含量为 100%;19 名患者的血红蛋白 C 含量为 HbSC,10 名患者的血红蛋白 C 含量为 HbAC。血红蛋白 S 与地理来源有明显的相关性(P 值=0)。结论在我们的研究中,同型血红蛋白 C 患者有轻度溶血性贫血,而血红蛋白 C 100%患者仅输血一次(17 岁)。血红蛋白 C 和血红蛋白 S 的遗传组合比单独的血红蛋白 S 严重程度要轻。血红蛋白 S 与地理来源之间有明显的关系(P 值=0)。
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引用次数: 0
Risk of Sarcopenia Identified by Sarc-Calf, Nutritional Status and Hand Grip Strength in Patients with Hematological Cancer 通过血液肿瘤患者的 Sarc-Calf、营养状况和手部握力识别肌少症风险
Pub Date : 2024-04-21 DOI: 10.18502/ijhoscr.v18i2.15370
Lorraine Pires Avancini, Laís Freitas da Costa, Mariana de Souza Vieira, Vanusa Felício de Souza, Rayne de Almeida Marques, Jose Luiz Marques Rocha, G. Petarli, V. Guandalini
Background: Hematological cancer patients are prone to the development of sarcopenia and impaired nutritional and functional status. SARC-CalF is a screening tool for the risk of sarcopenia that has shown good results in this population. This study aimed to identify the risk of sarcopenia by SARC-CalF and to verify its association with nutritional status and Hand Grip Strength (HGS) in patients with hematological cancer. Materials and Methods: Adult patients, of both sexes, with hematological cancer, and in outpatient care participated in the study. We measured the Hand Grip Strength of the Dominant Hand (HGSD) and the Adductor Pollicis Muscle Thickness of the Dominant Hand (APMTD). Moreover, we applied the Patient-Generated Subjective Global Assessment (PG-SGA) and SARC-CalF. Data were analyzed with SPSS® software, 22.0, with a significance level of 5.0%. Results: Fifty-one patients aged an average of 60.4 ± 15.1 years were evaluated. Of those, 58.8% were elderly, 51% female, and 80.4% declared themselves non-white. The predominant diagnosis was Mature B Lymphoid Cell Neoplasia (37.7%), and 60.8% of the patients had a diagnosis time of ≤ 3 years. PG-SGA revealed that 35.3% of the patients were malnourished; APMTD and HGSD revealed that 60.8% and 25.5% had reduced muscle strength, respectively. SARC-CalF exposed that 39.2% of the patients were at risk for sarcopenia. Significant associations were found between SARC-CalF and diagnosis time ≤ 3 years (p = 0.039), PG-SGA (p = 0.020), APMTD (p = 0.039) and HGSD (p = 0.002). After binary logistic regression adjusted for age and sex, the reduced HGSD remained associated with the risk of sarcopenia. Conclusion: SARC-CalF identified a risk of sarcopenia in 39.2% of patients. The reduced HGSD was associated with the risk of sarcopenia.
背景:血液肿瘤患者容易出现肌肉疏松症,营养和功能状况也会受损。SARC-CalF 是一种筛查肌肉疏松症风险的工具,在这一人群中显示出良好的效果。本研究旨在通过 SARC-CalF 确定血液肿瘤患者的肌肉疏松症风险,并验证其与营养状况和手握力(HGS)之间的关联。材料与方法:参与研究的患者均为门诊患者,男女不限。我们测量了支配手的握力(HGSD)和支配手的内收肌厚度(APMTD)。此外,我们还采用了患者自发主观全面评估(PG-SGA)和 SARC-CalF。数据采用 SPSS® 软件 22.0 进行分析,显著性水平为 5.0%。结果接受评估的 51 名患者平均年龄为(60.4 ± 15.1)岁。其中 58.8%为老年人,51%为女性,80.4%自称非白人。主要诊断为成熟 B 淋巴细胞瘤(37.7%),60.8%的患者确诊时间不超过 3 年。PG-SGA显示35.3%的患者营养不良;APMTD和HGSD分别显示60.8%和25.5%的患者肌力下降。SARC-CalF 显示 39.2% 的患者有肌少症风险。研究发现,SARC-CalF 与诊断时间≤ 3 年(p = 0.039)、PG-SGA(p = 0.020)、APMTD(p = 0.039)和 HGSD(p = 0.002)之间存在显著关联。在对年龄和性别进行二元逻辑回归调整后,HGSD 的降低仍与肌肉疏松症的风险相关。结论SARC-CalF 确定了 39.2% 的患者存在肌少症风险。HGSD的降低与肌少症的风险有关。
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引用次数: 0
Serum Interleukin 6 (IL -6) as Prognostic Marker in Egyptian CLL patients 血清白细胞介素 6 (IL -6) 作为埃及 CLL 患者的预后指标
Pub Date : 2024-04-21 DOI: 10.18502/ijhoscr.v18i2.15369
E. A. Hassan, E. Abdelhady, H. Abdelsamee, Mohamed Tarif Hamza sallam, M. El-Razzaz
Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Currently, several biomarkers are being used as CLL prognosticators, including elevated protein levels, elevated RNA levels, gene mutations, and epigenetic changes. Materials and Methods: This study is a prospective study conducted on 55 patients newly diagnosed with CLL, serum IL-6 level was measured initially and after a 6-month treatment course. Correlation with the course of the disease and the known CLL prognostic parameters was done initially and after 6 months. Results: The initial serum IL-6 level in the patient group (pre-treatment) ranges from 36-91 pg/mL (median 57), and in the patient group (post-treatment) ranges from 1-32 pg/mL (median 2). Serum IL-6 level was positively correlated with WBC count, β2 microglobulin, LDH, ESR, B symptoms, Uric Acid, BM Aspirate (% of lymphocytes), and Binet and Rai staging systems. Conclusion: Serum IL-6 is a useful poor prognostic marker in newly diagnosed CLL patients; its prognostic value goes with the other known prognostic markers such as the BM lymphocyte count, ESR, and LDH.
背景:慢性淋巴细胞白血病(CLL慢性淋巴细胞白血病(CLL)是成人中最常见的白血病。目前,有几种生物标志物被用作 CLL 的预后指标,包括蛋白质水平升高、RNA 水平升高、基因突变和表观遗传学变化。材料和方法:本研究是一项前瞻性研究,对 55 例新诊断为 CLL 的患者进行了血清 IL-6 水平测定,测定的对象包括最初和 6 个月疗程后的患者。最初和 6 个月后的血清 IL-6 水平与病程和已知的 CLL 预后参数之间存在相关性。结果显示患者组(治疗前)的初始血清IL-6水平为36-91皮克/毫升(中位数为57),患者组(治疗后)的初始血清IL-6水平为1-32皮克/毫升(中位数为2)。血清 IL-6 水平与白细胞计数、β2 微球蛋白、LDH、血沉、B 症状、尿酸、骨髓穿刺液(淋巴细胞百分比)以及 Binet 和 Rai 分期系统呈正相关。结论血清IL-6是新诊断的CLL患者预后不良的有用标记物;其预后价值与其他已知的预后标记物(如BM淋巴细胞计数、血沉和LDH)相同。
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引用次数: 0
Influence of Different Glucose Concentrations on the Expression of miR-29c-3p microRNA in Mesenchymal Stem Cells 不同葡萄糖浓度对间质干细胞中 miR-29c-3p microRNA 表达的影响
Pub Date : 2024-04-21 DOI: 10.18502/ijhoscr.v18i2.15367
Somayeh Mansournejad, M. Mehrabi, Reza Yari, Mahshid Saleh
Background: miR-29c-3p manages a set of genes involved in regenerative medicine, and It seems that hyperglycemia in diabetic patients influences the power of stem cells to tissue regeneration the difficulties of diabetes by affecting the expression miR-29c-3p in mesenchymal stem cells. The study aims to analyze the effect of various glucose concentrations on the miR-29c-3p expression in mesenchymal stem cells. Materials and Methods: After receiving donated mesenchymal stem cells from Tarbiat Modares University, these cells were cultivated in a DMEM culture medium, including three different concentrations of glucose 250, 140, and 100 mg/dl. RNA was extracted from these cells after 72 hours, the Real-Time PCR technique assessed the expression of miR-29c-3p, and the results were analyzed by REST software. Results: miR-29c-3p expression in cells at concentrations of 140 and 250 mg/dL compared to typical situations (100 mg/dl) was significantly decreased (P˂0.05), which declined at a concentration of 250 mg/dl was more. Conclusion: Reduced miR-29c-3p expression in mesenchymal stem cells in chronic and mild diabetic situations demonstrated that diabetes might be one of the significant reasons for mesenchymal stem cells' reduced ability to repair tissue damage.
背景:miR-29c-3p管理着一组参与再生医学的基因,而糖尿病患者的高血糖似乎通过影响间充质干细胞中miR-29c-3p的表达来影响干细胞组织再生的能力,从而解决糖尿病带来的困难。本研究旨在分析不同浓度的葡萄糖对间充质干细胞中 miR-29c-3p 表达的影响。材料与方法:接受塔尔比亚特莫达尔斯大学捐赠的间充质干细胞后,这些细胞在DMEM培养基中培养,其中包括三种不同浓度的葡萄糖250、140和100 mg/dl。72 小时后从这些细胞中提取 RNA,用 Real-Time PCR 技术评估 miR-29c-3p 的表达,并用 REST 软件分析结果。结果:与典型情况(100 mg/dl)相比,浓度为 140 mg/dL 和 250 mg/dL 的细胞中 miR-29c-3p 的表达明显下降(P˂0.05),浓度为 250 mg/dl 时下降幅度更大。结论慢性和轻度糖尿病患者间充质干细胞中的miR-29c-3p表达减少,表明糖尿病可能是间充质干细胞修复组织损伤能力下降的重要原因之一。
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引用次数: 0
Assessment of Torque Teno Virus (TTV) Frequency in Healthy Blood Donors in the Central Region of Iran, Yazd 伊朗中部亚兹德地区健康献血者体内托克特诺病毒 (TTV) 感染频率评估
Pub Date : 2024-04-21 DOI: 10.18502/ijhoscr.v18i2.15366
Zahra Naderipour, Farzane Behnezhad, J. Charostad, M. Nakhaie, Nadieh Baniasadi, Y. Ghelmani, Fateme Akhavan Tafti, Azam Dehghani, Akram Astani
Background: Torque teno virus (TTV) is a globally prevalent virus in humans, yet comprehensive knowledge about its prevalence, predominant transmission routes, and pathogenesis remains limited. This study aimed to assess the frequency of TTV infection among healthy blood donors in Yazd, Iran. Materials and Methods: A total of 236 healthy blood donors, devoid of HIV/HBV/HCV infection markers, participated in the study from 2015 to 2016. Nested Polymerase Chain Reaction (PCR) utilizing a set of oligo primers for the 5΄- UTR region was employed to detect TTV DNA in serum samples. Results: The TTV genome was identified in 161 out of 236 (61.2%) healthy blood donors. The mean age for men and women was 43 and 57 years, respectively. Of the participants, 156 were male, and 107 were female. Donor age exhibited a significant association with virus presence (P=0.007); however, gender did not show a statistically significant association with the frequency of TTV infection in healthy blood donors (P=0.3). Conclusion: The study revealed a notably high frequency of the Torque teno virus in Yazd province, aligning with similar findings globally. Further investigations are warranted to elucidate the clinical implications of the virus in the healthy population.
背景:托克天奴病毒(TTV)是一种全球流行的人类病毒,但人们对其流行率、主要传播途径和发病机制的全面了解仍然有限。本研究旨在评估伊朗亚兹德健康献血者感染 TTV 的频率。材料和方法:共有 236 名健康献血者参与了 2015 年至 2016 年期间的研究,这些献血者均无 HIV/HBV/HCV 感染标记物。利用一套针对 5΄- UTR 区域的寡聚引物进行巢式聚合酶链反应(PCR),检测血清样本中的 TTV DNA。结果:在 236 名健康献血者中,有 161 人(61.2%)检测到了 TTV 基因组。男性和女性的平均年龄分别为 43 岁和 57 岁。其中男性 156 人,女性 107 人。献血者的年龄与病毒的存在有明显的关联(P=0.007);然而,性别与健康献血者感染 TTV 的频率在统计学上没有明显的关联(P=0.3)。结论研究显示,亚兹德省的托克-特诺病毒感染频率明显较高,这与全球的类似研究结果一致。有必要进行进一步调查,以阐明该病毒在健康人群中的临床影响。
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引用次数: 0
Potential Diagnostic Value of Abnormal Pyroptosis Genes Expression in Myelodysplastic Syndromes (MDS): A Primary Observational Cohort Study 骨髓增生异常综合征 (MDS) 中热休克基因异常表达的潜在诊断价值:一项原发性观察队列研究
Pub Date : 2024-04-21 DOI: 10.18502/ijhoscr.v18i2.15371
Mohammad Soltani, Mohammad Jafar Sharifi, Parvin Khalilian, Mehran Sharifi, Pardis Nematollahi, Hooriyeh Shapourian, M. Hakemi
Background: Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. Materials and Methods: In the present study, we evaluated the expression of genes that form the inflammasome (NLRP3, ASC, and CASP1) in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with p value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. Results:  We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with a p-value of 0.001 and 1.86 with p=0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with p=0.0001 for Caspase-1 and an AUC of 0.665 with p=0.0139 for ASC to MDS discrimination. Conclusion: Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.  
背景:骨髓增生异常综合征(MDS骨髓增生异常综合征(MDS)由无效造血和骨髓细胞学发育不良以及体细胞基因突变和染色体异常决定。越来越多的证据表明,NLRP3 炎症小体激活和细胞凋亡在 MDS 的发病机制中起着关键作用。虽然 MDS 可通过多种形态学和细胞遗传学检测进行诊断,但这些检测在实际应用中大多存在局限性或问题。材料与方法:在本研究中,我们评估了 MDS 患者骨髓标本中组成炎性体的基因(NLRP3、ASC 和 CASP1)的表达情况,并将其结果与其他白血病的结果进行了比较,以评估其对 MDS 的诊断价值。这项观察性队列研究的主要样本来自骨髓增生异常综合征患者(27 例)和非骨髓增生异常综合征血液癌症患者(45 例)的抽吸样本。在提取 RNA 和合成 c.DNA 后,采用实时 PCR 方法(SYBER Green 检测法)测定候选转录本和看家转录本。使用 Kruskal-Wallis 对相对基因表达量进行比较,P 值小于 0.05 的差异被认为具有显著性。用隐性操作曲线(ROC)分析所有标记物的鉴别能力、临界值和曲线下面积(AUC)。结果 我们发现,与非 MDS 血液恶性肿瘤相比,Caspase-1 和 ASC 基因在 MDS 标本中的表达水平更高。Caspase-1和ASC的相对平均表达量分别为10.22和1.86,P值分别为0.001和0.019。ROC曲线分析显示,Caspase-1的AUC为0.739,p=0.0001;ASC的AUC为0.665,p=0.0139。结论我们的研究结果表明,Caspase-1和ASC基因表达水平可作为诊断MDS的潜在生物标志物。建议进行大样本量的前瞻性研究。
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引用次数: 0
Antileukemia Activity of Human Natural Killer Cell-Derived Nanomagic Bullets against Acute Myeloid Leukemia (AML) 人类自然杀伤细胞衍生的纳米魔法子弹对急性髓性白血病(AML)的抗白血病活性
Pub Date : 2024-04-21 DOI: 10.18502/ijhoscr.v18i2.15368
Zahra Kashani Khatib, Asma Maleki, A. Pourfatollah, A. Hamidieh, Shirin Ferdowsi
Background: Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro. Materials and Methods: The MACS method was performed for the separation of NK cells from the buffy coats of healthy donors, and an EXOCIBE kit was used for the isolation of NK-Exo. After treating the KG-1 cell line with different doses of NK-Exo, MTT assay, and annexin V-PE were done to evaluate cell proliferation and apoptosis, respectively, and for confirmation of involved proteins, Real-Time PCR and western blotting were performed. Results: Anti-tumor activity of NK-Exo and LAK-Exo was dose- and time-dependent. Their highest activities were observed following 48 hours of incubation with 50 µg/ml exosome (p<0.0001). However, this cytotoxic activity was also seen over a short period of time with low concentrations of NK-Exo (p<0.05) and LAK-Exo (p<0.001).The cytotoxic effect of LAK-Exo on target cells was significantly higher than NK-EXO. The induction of apoptosis by different pathways was time-point dependent. Total apoptosis was 34.56% and 51.6% after 48 hours of tumor cell coculture with 50µg/ml NK-Exo and LAK-Exo, respectively. Significant expression of CASPASE3, P38, and CYTOCHROME C genes was observed in the cells treated with 50 µg/ml NK-Exo and LAK-Exo. Conclusion: Our study confirmed the antileukemia activity of NK-Exo against AML tumor cells in vitro. Therefore, NK-Exo can be considered as a promising and effective treatment for leukemia therapy.
背景:癌症是医学界严重的健康问题之一,在治疗方面,人们采用了严厉的治疗方法。然而,癌症患者的预后仍然很差。应用 NK 细胞衍生的外泌体(NK-Exo)是癌症免疫疗法的一种新方法。这种纳米颗粒的尺寸范围为 30-120 纳米,是一种小型的母细胞模型。本研究在体外研究了NK-Exo和LAK-Exo(活化的NK细胞衍生外泌体)对急性髓性白血病(AML)的抗肿瘤活性。材料与方法:采用MACS方法从健康供体的水包衣中分离NK细胞,并使用EXOCIBE试剂盒分离NK-Exo。用不同剂量的 NK-Exo 处理 KG-1 细胞系后,分别用 MTT 检测和附件素 V-PE 评估细胞增殖和凋亡情况,并用 Real-Time PCR 和 Western 印迹法确认相关蛋白。结果NK-Exo和LAK-Exo的抗肿瘤活性呈剂量和时间依赖性。与 50 µg/ml 外泌体培养 48 小时后,它们的活性最高(p<0.0001)。然而,低浓度的NK-Exo(p<0.05)和LAK-Exo(p<0.001)也能在短时间内显示出这种细胞毒性活性。不同途径诱导细胞凋亡与时间点有关。肿瘤细胞与50µg/ml NK-Exo和LAK-Exo共培养48小时后,凋亡率分别为34.56%和51.6%。在使用 50 µg/ml NK-Exo 和 LAK-Exo 处理的细胞中观察到 CASPASE3、P38 和 CYTOCHROME C 基因的显著表达。结论我们的研究证实了 NK-Exo 在体外对 AML 肿瘤细胞的抗白血病活性。因此,NK-Exo 可被视为一种治疗白血病的有效方法。
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International journal of hematology-oncology and stem cell research
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