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Possible Association of Three Polymorphisms in Cytokine TNF-a (238G/A, 308G/A, 1031T/C) with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis 细胞因子 TNF-a 的三种多态性(238G/A、308G/A、1031T/C)与多囊卵巢综合征可能存在关联:系统回顾与元分析
IF 0.9 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-10-31 DOI: 10.15419/bmrat.v10i10.839
Pemula Gowtham, Karthick Harini, Anbazhagan Thirumalai, P. Pallavi, K. Girigoswami, A. Girigoswami
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引用次数: 0
Combinatorial effects of metformin and glucose on the immune evasion of breast cancer 4T1 cells 二甲双胍和葡萄糖对乳腺癌 4T1 细胞免疫逃避的联合效应
IF 0.9 Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-10-30 DOI: 10.15419/bmrat.v10i10.835
Duy Khuong Pham, Hoai Nam Le, Anh Nhu Nguyen, Thao N. Huynh, Chau Nhat Truong, Van Phuc Pham
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引用次数: 0
Assessment of circulating miRNA-218, miRNA-222, and miRNA-146 as biomarkers of polycystic ovary syndrome in epileptic patients receiving valproic acid 评估循环miRNA-218、miRNA-222和miRNA-146作为接受丙戊酸治疗的癫痫患者多囊卵巢综合征的生物标志物
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-30 DOI: 10.15419/bmrat.v10i9.833
Mahya Rajabi, Seyed Mehdi Kalantar, Elham Mojodi, Mansour Salehi, Razieh Dehghani Firouzabadi, Seyed Masoud Etemadifar, Fateme Montazeri
Introduction: This study was designed to evaluate the relationship between taking sodium valproate (VPA) and the onset of polycystic ovarian syndrome (PCOS) in women with epilepsy (WWE) and analyze the biochemical factors and expression levels of three miRNAs as diagnostic or predictive biomarkers. These miRNAs target numerous genes and molecular pathways involved in hyperandrogenism, insulin resistance, and obesity in PCOS patients. Methods: The study was conducted on 120 WWE aged 18–35 years before and after monotherapy with VPA and 120 women with PCOS (WWP). After collecting the plasma samples of patients, the total RNA was extracted. Then, the miRNA-218, miRNA-222, and miRNA-146 expression levels were determined via qRT– PCR. Results: In this study, the relative expression levels of miRNA-146 and miRNA-218 showed a significant increase in the WWP and treated epileptic patients (P < 0.01). However, the expression level of miRNA-222 significantly (P0.05) reduced. Our finding showed a significant increase in the concentrations of anti-Müllerian hormone (AMH), free testosterone, and estradiol and an increased LH/FSH ratio after treatment compared with pre-treatment with VPA (P < 0.05). Conclusion: Significant changes were observed in the expression of the examined miRNAs after receiving VPA, especially miRNA-218. In addition, a significant correlation was found between PCOS and AMH, free testosterone, estradiol, and the LH/FSH ratio. Therefore, the miRNA-218 expression and these biochemical factors are valuable biomarkers for predicting PCOS symptoms. They are cost-effective for controlling side effect and timely medication adjustments in patients receiving VPA.
前言:本研究旨在评估服用丙戊酸钠(VPA)与癫痫女性(WWE)多囊卵巢综合征(PCOS)发病的关系,并分析作为诊断或预测生物标志物的三种mirna的生化因素和表达水平。这些mirna靶向多囊卵巢综合征患者中涉及高雄激素、胰岛素抵抗和肥胖的许多基因和分子途径。方法:对120例18-35岁的WWE和120例PCOS (WWP)患者进行VPA单药治疗前后的研究。采集患者血浆样本后,提取总RNA。然后,通过qRT - PCR检测miRNA-218、miRNA-222和miRNA-146的表达水平。结果:在本研究中,miRNA-146和miRNA-218的相对表达水平在WWP和治疗癫痫患者中显著升高(P <0.01)。而miRNA-222的表达水平明显降低(P0.05)。我们的研究结果显示,与VPA治疗前相比,治疗后抗勒管激素(AMH)、游离睾酮和雌二醇浓度显著增加,LH/FSH比值升高(P <0.05)。结论:接受VPA治疗后,各组mirna的表达均发生显著变化,其中以miRNA-218表达变化最为明显。此外,PCOS与AMH、游离睾酮、雌二醇和LH/FSH比值有显著相关。因此,miRNA-218的表达和这些生化因子是预测PCOS症状的有价值的生物标志物。它们在控制VPA患者的副作用和及时调整药物方面具有成本效益。
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引用次数: 0
Epstein–Barr virus-encoded RNA expression and its relationship with the clinicopathological parameters of Vietnamese patients with nasopharyngeal carcinoma 越南鼻咽癌患者Epstein-Barr病毒编码RNA表达及其与临床病理参数的关系
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-30 DOI: 10.15419/bmrat.v10i9.830
Tran Ngoc Dung, Pham Van Thinh, Nguyen Mai Hanh, Nguyen Thuy Linh, Pham Van Thi, Dang Thai Tra, Truong Dinh Tien, Le Tai The, Nguyen Manh Hung, Dang Thanh Chung
Introduction: Nasopharyngeal carcinoma (NPC) is a common malignancy in Viet Nam, and its pathogenesis is closely associated with Epstein–Barr virus (EBV) infection. However, the relationship between EBV infection and clinicopathological characteristics related to NPC prognosis in Vietnamese patients remains poorly understood. This study aimed to investigate the association between EBV infection and various clinical parameters in Vietnamese patients with NPC. Methods: We collected clinical data from 31 patients with histologically confirmed NPC and evaluated their samples for EBV-encoded RNA (EBER) expression using the chromosomal in situ hybridization (CISH) technique. We examined the relationship between EBER expression and several clinical parameters, including age, sex, lymph node metastasis, tissue invasion and metastasis, clinical stage, and histological NPC type. Results: The patients' ages ranged from 19 to 74 years, with 80.64% aged >40 years and 87.1% male. In addition, 80.65% had lymph node metastasis, and 38.71% had tissue invasion and distant metastasis. Most patients (67.74%) were diagnosed at a late stage (III or IV), with the most common histological type being type III (48.39%), followed by type I (29.03%) and II (22.58%). EBER expression was observed in 48.39% of the patients and was significantly associated with younger age (<40, p = 0.0362) and undifferentiated carcinoma (type III, p = 0.0007). However, EBER expression was not significantly associated with sex, lymph node metastasis, tissue invasion and metastasis, or clinical stage. Conclusions: Our study suggests that EBV infection may contribute to NPC pathogenesis. It also shows significant associations between EBV infection and younger age and undifferentiated carcinoma type. The CISH technique could help screen asymptomatic high-risk individuals, managing and predicting the NPC prognosis. The small sample size and single-center design limit the generalizability of our findings.
鼻咽癌(NPC)是越南常见的恶性肿瘤,其发病机制与eb病毒(EBV)感染密切相关。然而,越南患者EBV感染与鼻咽癌预后相关的临床病理特征之间的关系尚不清楚。本研究旨在探讨越南鼻咽癌患者EBV感染与各种临床参数的关系。方法:收集31例经组织学证实的鼻咽癌患者的临床资料,采用染色体原位杂交(CISH)技术检测其样本中ebv编码RNA (EBER)的表达。我们研究了EBER表达与几个临床参数的关系,包括年龄、性别、淋巴结转移、组织侵袭和转移、临床分期和组织学鼻咽癌类型。结果:患者年龄19 ~ 74岁,40岁占80.64%,男性占87.1%。80.65%有淋巴结转移,38.71%有组织浸润及远处转移。大多数患者(67.74%)诊断为晚期(III或IV期),最常见的组织学类型为III型(48.39%),其次是I型(29.03%)和II型(22.58%)。48.39%的患者有EBER表达,且与年龄较小(<40, p = 0.0362)和未分化癌(III型,p = 0.0007)显著相关。然而,EBER的表达与性别、淋巴结转移、组织浸润转移及临床分期无显著相关性。结论:本研究提示EBV感染可能与鼻咽癌发病有关。它还显示EBV感染与年轻和未分化癌类型之间存在显著关联。CISH技术可以帮助筛查无症状的高危人群,管理和预测鼻咽癌预后。小样本量和单中心设计限制了我们研究结果的普遍性。
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引用次数: 0
Early Alzheimer’s disease diagnosis using an XG-Boost model applied to MRI images 应用MRI图像的XG-Boost模型诊断早期阿尔茨海默病
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-30 DOI: 10.15419/bmrat.v10i9.832
Khoi Nguyen, My Nguyen, Khiet Dang, Bao Pham, Vy Huynh, Toi Vo, Lua Ngo, Huong Ha
Introduction: Early Alzheimer's disease (AD) diagnosis is critical to improving the success of new treatments in clinical trials, especially at the early mild cognitive impairment (EMCI) stage. This study aimed to tackle this problem by developing an accurate classification model for early AD detection at the EMCI stage based on magnetic resonance imaging (MRI). Methods: This study developed the proposed classification model through a machine-learning pipeline with three main steps. First, features were extracted from MRI images using FreeSurfer. Second, the extracted features were filtered using principal component analysis (PCA), backward elimination (BE), and extreme gradient (XG)-Boost importance (XGBI), the efficiency of which was evaluated. Finally, the selected features were combined with cognitive scores (Mini Mental State Examination [MMSE] and Clinical Dementia Rating [CDR]) to create an XG-Boost three-class classifier: AD vs. EMCI vs. cognitively normal (CN). Results: The MMSE and CDR had the highest importance weights, followed by the thickness of the left superior temporal sulcus and banks of the superior temporal lobe. Without feature selection, the model had the lowest accuracy of 69.0%. After feature selection and the addition of cognitive scores, the accuracy of the PCA, BE, and XGBI approaches improved to 74.0%, 90.9%, and 91.5%, respectively. The BE with tuning parameters model was chosen as the final model since it had the highest accuracy of 92.0%. The area under the receiver operating characteristic curve for the CN, AD, and EMCI classes were 0.98, 0.94, and 0.88, respectively. Conclusion: Our proposed model shows promise in early AD diagnosis and can be fine-tuned in the future through testing on a multi-dataset.
在临床试验中,早期阿尔茨海默病(AD)的诊断对于提高新疗法的成功率至关重要,尤其是在早期轻度认知障碍(EMCI)阶段。本研究旨在通过建立基于磁共振成像(MRI)的EMCI阶段早期AD检测的准确分类模型来解决这一问题。方法:本研究通过三个主要步骤的机器学习管道开发了所提出的分类模型。首先,使用FreeSurfer从MRI图像中提取特征。其次,使用主成分分析(PCA)、反向消除(BE)和极端梯度(XG)-Boost重要性(XGBI)对提取的特征进行过滤,并对其效率进行评估。最后,将选择的特征与认知评分(迷你精神状态检查[MMSE]和临床痴呆评分[CDR])相结合,创建XG-Boost三级分类器:AD、EMCI和认知正常(CN)。结果:MMSE和CDR的重要性权重最高,其次是左侧颞上沟厚度和颞上叶壁厚度。在没有特征选择的情况下,模型的准确率最低,为69.0%。经过特征选择和认知分数的加入,PCA、BE和XGBI方法的准确率分别提高到74.0%、90.9%和91.5%。选择带参数调优的BE模型作为最终模型,其准确率最高,达到92.0%。CN类、AD类和EMCI类的受试者工作特征曲线下面积分别为0.98、0.94和0.88。结论:我们提出的模型在早期AD诊断中显示出希望,并且可以在未来通过多数据集的测试进行微调。
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引用次数: 0
Efficacy of trocar site, intraperitoneal, and laparoscopically guided posterior transversus abdominis muscle bupivacaine injection for reducing pain after laparoscopic hysterectomy surgery: A double-blind randomized clinical trial 套管针部位、腹腔和腹腔镜引导下后腹横肌注射布比卡因减轻腹腔镜子宫切除术后疼痛的疗效:一项双盲随机临床试验
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-30 DOI: 10.15419/bmrat.v10i9.831
Masoomeh Nataj Majd, Zahra Asgari, Narjes Marjani, Parand Gheshlaghi, Mahroo Rezaeinejad, Mina Fatehnejad
Background: Few studies have investigated the pain-reducing effects of bupivacaine after laparoscopic hysterectomy. Therefore, this study compared the efficacy of three methods of bupivacaine injection—subcutaneous injection into the trocar site, intraperitoneal injection, and posterior transversus abdominis muscle block under laparoscopic guidance—for reducing pain after laparoscopic hysterectomy; the efficacy of each method was also compared with that of placebo. Methods: This double-blind randomized clinical trial study included 95 patients with good general health who underwent elective laparoscopic hysterectomy for benign disease in 2021. The patients were allocated into three intervention groups (subcutaneous injection of 10 cc bupivacaine 0.25%, heavy under trocar sites; 10 cc bupivacaine 0.25%, heavy injection into the transversus abdominis plane block; and 10 cc bupivacaine 0.25%, heavy intraperitoneal injection) and a control group. Abdominal and shoulder pain 2–4, 8, 12, and 24 h after the surgery were compared between groups. Results: The four groups were homogenous in age, weight, height, body mass index, surgery duration, surgery type, and family history of cancer (P > 0.05). The mean abdominal and shoulder pain score significantly decreased from the first time point (hours 2–4) to 8, 12, and 24 hours after surgery in the trocar site, intraperitoneal, and control groups (P < 0.001). However, we did not observe a significant decrease in abdominal and shoulder pain in the transversus abdominis plane block group (P > 0.05). Conclusion: The present study indicates that bupivacaine administration methods of transversus abdominis plane block and trocar site injection are effective and safe for reducing pain following laparoscopic hysterectomy.
背景:很少有研究调查布比卡因在腹腔镜子宫切除术后的镇痛效果。因此,本研究比较了三种布比卡因注射方式(套管针部位皮下注射、腹腔注射、腹腔镜引导下腹后横肌阻滞)对腹腔镜子宫切除术后疼痛的缓解效果;并将各方法的疗效与安慰剂进行比较。方法:这项双盲随机临床试验研究纳入了95例一般健康状况良好的患者,这些患者于2021年因良性疾病接受了选择性腹腔镜子宫切除术。患者被分为三个干预组(皮下注射0.25%布比卡因10 cc,套管针下重;0.25%布比卡因10 cc,重注于腹横面阻滞;布比卡因0.25%,重腹腔注射10 cc)和对照组。比较两组术后2 ~ 4、8、12、24 h的腰肩疼痛情况。结果:四组患者在年龄、体重、身高、体质指数、手术时间、手术类型、癌症家族史等方面均具有同一性(P >0.05)。套管针部位组、腹腔内组和对照组的平均腹部和肩部疼痛评分从第一个时间点(2-4小时)到术后8、12和24小时均显著降低(P <0.001)。然而,我们没有观察到腹横平面阻滞组腹部和肩部疼痛的显著减少(P >0.05)。结论:经腹平面阻滞加套管针部位注射布比卡因给药方法可有效、安全地减轻腹腔镜子宫切除术后疼痛。
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引用次数: 0
Tridax procumbens leaf antioxidants and hormonal activity ameliorate variable stress-induced erectile and reproductive impairments in Wistar rats 原藜叶抗氧化剂和激素活性改善Wistar大鼠可变应激诱导的勃起和生殖障碍
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-30 DOI: 10.15419/bmrat.v10i9.834
Salami Shakiru Ademola, Amasiatu Chioma Irenemarie, Allen Michael Olabode, Salahdeen Hussein Mofomosara, Murtala Babatunde Adekunle
Introduction: The role of Tridax procumbens leaf extract in erectile dysfunction (ED) of chronic variable stress (CVS) etiology is unknown. This study investigates the potential of the ethanol fraction of Tridax procumbens leaf (EETP) in modulation of CVS-induced ED. Methods: Twenty-five male Wistar rats were divided into five groups of five rats each. Groups 1 & 2 (without stress) were treated with normal saline (vehicle) and 100 mg/kg of EETP, respectively. Groups 3–5 were treated as stress groups, with Group 3 co-treated with 100 mg/kg of EETP, and group 4 co-treated with vitamin C (7 mg/kg). Treatments were administered by oral gavage once daily for seven weeks. Oxidative biomarkers, cortisol, testosterone, and sperm parameters were determined, as well as the contractile mechanism of the corpus cavernosa to cumulative doses of calcium chloride, potassium chloride, acetylcholine, and sodium nitroprusside. Furthermore, the contractile mechanism was also determined after incubation in acetovanillone, nicorandil, methyl blue, and glibenclamide. Results: Serum cortisol was significantly reduced, while testosterone was significantly increased in the EETP supplemented groups when compared to the CVS-only exposed group. Furthermore, malonaldehyde activity was decreased while superoxide dismutase concentration was increased in the EETP- and vitamin C-supplemented groups when compared to the CVS-only exposed group. Contraction (%) responses to calcium chloride and potassium chloride were also significantly reduced in the CVS-only exposed group when compared to the EETP-supplemented groups. The relaxation responses (%) to acetylcholine and SNP were significantly increased in the CVS group supplemented with EETP and vitamin C when compared to the CVS-only exposed group. The incubation of the cavernosa tissues in acetovanillone and nicorandil resulted in increased relaxation (%) in the CVS-only group, while incubation in glibenclamide caused increased relaxation in the EETP-supplemented groups compared to CVSonly exposed group. Sperm motility (%) was significantly reduced while abnormal spermatozoa was increased in the CVS-only exposed group when compared to the groups supplemented with EETP and Vitamin C. Conclusion: Variable stress-induced dysfunctions in erectile mechanism were attenuated through supplementation with EETP.
前言:原藜叶提取物在慢性可变应激(CVS)病因性勃起功能障碍(ED)中的作用尚不清楚。方法:将25只雄性Wistar大鼠分为5组,每组5只。第1组&2只(无应激)分别用生理盐水(对照)和100 mg/kg EETP处理。3 ~ 5组作为应激组,其中3组共给予100 mg/kg EETP, 4组共给予维生素C (7 mg/kg)。治疗方法为每日灌胃1次,连续7周。测定氧化生物标志物、皮质醇、睾酮和精子参数,以及海绵体对氯化钙、氯化钾、乙酰胆碱和硝普钠累积剂量的收缩机制。此外,在乙酰香草酮、尼可地尔、甲基蓝和格列本脲中孵育后,也确定了收缩机制。结果:与cvs暴露组相比,EETP补充组血清皮质醇显著降低,而睾酮显著升高。此外,与仅暴露cvs组相比,补充EETP和维生素c组丙二醛活性降低,超氧化物歧化酶浓度升高。与eetp补充组相比,cvs暴露组对氯化钙和氯化钾的收缩反应(%)也显著降低。与仅暴露CVS组相比,添加EETP和维生素C的CVS组对乙酰胆碱和SNP的松弛反应(%)显著增加。海绵体组织在乙酰香草酮和尼可地尔中孵育后,cvs组的松弛度增加(%),而在格列本脲中孵育后,eetp补充组的松弛度比仅暴露于cvs组增加。与补充EETP和维生素c组相比,仅暴露于cvs组的精子活动力(%)显著降低,而异常精子数量增加。结论:补充EETP可减轻应激引起的勃起机制的可变功能障碍。
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引用次数: 0
Endocrine-disrupting pesticides and SARS-CoV-2 infection: Role of ACE2, TMPRSS2 and CD147 内分泌干扰农药与SARS-CoV-2感染:ACE2、TMPRSS2和CD147的作用
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-09-30 DOI: 10.15419/bmrat.v10i9.829
Swati Dixit, Haseeb Ahsan, Fahim Halim Khan
COVID-19 is a global pandemic caused by severe acute respiratory syndrome (SARS) coronavirus- 2 (SARS-CoV-2). The three main receptors used by SARS-CoV-2 to bind and gain entry into human cells are ACE, TMPRSS2, and CD147. These molecular factors have crucial roles in human metabolism and homeostasis, but the upregulation of these factors causes severe diseases such as myocarditis, prostate cancer, and other endocrine-related cancers. Studies have found that once humans come into contact with SARS-CoV-2, the chances of being affected by such disorders increase; indeed, infection with the virus is associated with increased morbidity and mortality from heart attacks and pulmonary inflammation. Notably, exposure to some pesticides, such as chlorpyrifos, cypermethrin, and imidacloprid, which are identified as potential endocrine disruptors, causes such disorders by interfering with hormonal signaling pathways, such as the insulinglucagon pathway and the thyroid pathway. This review focuses on the potential role of pesticides in exacerbating the comorbidities linked with SARS-CoV-2 and their effect on the molecular factors associated with SARS-CoV-2. Understanding the potential therapeutic implications of this link between SARS-CoV-2 severity and pesticides requires further clinical trials and investigations.
COVID-19是由严重急性呼吸综合征(SARS)冠状病毒-2 (SARS- cov -2)引起的全球大流行疾病。SARS-CoV-2结合并进入人类细胞的三种主要受体是ACE、TMPRSS2和CD147。这些分子因子在人体代谢和体内平衡中起着至关重要的作用,但这些因子的上调会导致严重的疾病,如心肌炎、前列腺癌和其他内分泌相关的癌症。研究发现,一旦人类接触到SARS-CoV-2,感染此类疾病的几率就会增加;事实上,感染这种病毒与心脏病发作和肺部炎症的发病率和死亡率增加有关。值得注意的是,接触一些农药,如毒死蜱、氯氰菊酯和吡虫啉,这些被认为是潜在的内分泌干扰物,通过干扰激素信号通路,如胰岛素-胰高血糖素通路和甲状腺通路,导致这些疾病。本文综述了农药在加剧SARS-CoV-2相关合并症中的潜在作用及其对SARS-CoV-2相关分子因子的影响。了解SARS-CoV-2严重程度与农药之间这种联系的潜在治疗意义,需要进一步的临床试验和调查。
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引用次数: 0
Plasmablastic transformation of multiple myeloma post-autologous hematopoietic stem cell transplant 自体造血干细胞移植后多发性骨髓瘤的质母转化
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-08-31 DOI: 10.15419/bmrat.v10i8.820
Nurul Asyikin Nizam Akbar, Mohd Nazri Hassan, Salfarina Iberahim, Nur Ilyia Syazwani Saidin, Wardah Roslan, Nur Ain Izzati Abd Halim, Abu Dzarr Abdullah, Hany Hakimi Wan Hanafi, Nur Diyana Mohd Shukri, Sumaiyah Adzahar
The present case report describes the uncommon and adverse plasmablastic transformation of multiple myeloma (MM) following autologous hematopoietic stem cell transplantation. To the best of our knowledge, this is the first case of plasmablastic myeloma (PBM) after an autologous hematopoietic transplant to be reported in Malaysia. A 41-year-old man initially diagnosed with MM IgG kappa reported lower back pain symptoms for a year, along with other associated symptoms. After receiving several lines of chemotherapy, the patient displayed a partial response (PR), and an autologous stem cell transplant (ASCT) was subsequently performed. Two months after the transplant, the patient showed signs of anemia, with a hemoglobin level of 8.0 g/dL. A peripheral blood film revealed the presence of a leucoerythroblastic blood film with normocytic normochromic red blood cells and rouleaux formation but no apparent plasma cells. The main infiltrating cells in the bone marrow aspirate (BMA) and trephine biopsy were plasmablasts with kappa light chain restriction. An increase in serum kappa free light chain (FLC), serum lambda FLC, and a low albumin/globulin (A/G) ratio were observed. In addition, serum protein electrophoresis showed an IgG kappa paraprotein band in the gamma region. Post-ASCT, the disease transformed into PBM, which conferred a poor prognosis on thepatient despite his post-transplant status. This case report highlights the diagnostic challenges of plasmablastic transformation in MM. Diagnosing PBM is thus crucial for the prompt and proper management of affected patients. Another consideration in the present case is whether the transplant procedure itself or the immunopathogenesis that took place after the ASCT resulted in the subsequent transformation into PBM.
本病例报告描述了自体造血干细胞移植后多发性骨髓瘤(MM)的罕见和不良的浆母细胞转化。据我们所知,这是马来西亚首例自体造血移植后发生浆母细胞骨髓瘤(PBM)的病例。一名最初诊断为MM IgG kappa的41岁男性报告腰痛症状一年,并伴有其他相关症状。在接受了几线化疗后,患者显示出部分缓解(PR),随后进行了自体干细胞移植(ASCT)。移植两个月后,患者出现贫血症状,血红蛋白水平为8.0 g/dL。外周血膜显示有一层白细胞母细胞血膜,其中有正红细胞和rouleaux形成,但未见浆细胞。骨髓抽吸(BMA)和环钻活检的浸润细胞主要为kappa轻链限制的质母细胞。血清游离轻链(FLC)、lambda FLC升高,白蛋白/球蛋白(a /G)比降低。此外,血清蛋白电泳在γ区显示IgG κ pa副蛋白条带。asct后,该疾病转变为PBM,尽管患者移植后状态良好,但预后较差。本病例报告强调了MM中质母细胞转化的诊断挑战。因此,诊断PBM对于受影响患者的及时和适当管理至关重要。本病例的另一个考虑因素是移植手术本身或ASCT后发生的免疫发病机制是否导致随后转化为PBM。
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引用次数: 0
Comparison of cancer stem cell enrichment between spheroids derived from single-cell and multicellular aggregate cultures 单细胞和多细胞聚集培养的球状肿瘤干细胞富集的比较
Q4 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2023-08-31 DOI: 10.15419/bmrat.v10i8.823
Omar Nafiis Hairuddin, Badrul Hisham Yahaya, Mohamad Johari Ibahim, Abhi Verakumarasivam, Chan Soon Choy, Musalmah Mazlan, Nurhidayah Ab. Rahim, Syarifah Masyitah Habib Dzulkarnain, Siti Farizan Mansor
Introduction: Cancer stem cells (CSCs) represent a distinct group of cells within cancerous tissue that possess the ability to initiate tumorigenesis and exhibit potency, self-renewal, and drug resistance. The study of CSCs often encounters challenges in obtaining these cells of interest or generating a sufficient quantity for downstream analysis. Nevertheless, it is feasible to enrich CSCs in vitro by subjecting them to conditions that stimulate their CSC properties, such as prolonged exposure to drugs or radiation, or by promoting their self-renewal capability through spheroid culture. Spheroids are a specific type of cell culture that organizes cells into a three-dimensional structure, closely mimicking the in vivo environment. These spheroids consist of a heterogeneous cell population, including CSCs or tumor-propagating cells responsible for tumor growth and maintenance. In our study, we cultured spheroids derived from single cells as well as multicellular aggregates to enrich CSCs based on their self-renewal capability and the structural organization provided by the three-dimensional context. Methods: Comparing the spheroid cultures with the parental adherent monolayer cells, we observed higher expression of CSC markers, pluripotent genes, and adipogenic differentiation in both multicellular spheroids (MCS) and single cell-derived spheroids (SCDS) of the two tested cell lines. Results: The spheroids exhibited progressive growth in size throughout the culture period. When comparing the two methods, SCDS demonstrated greater expression of surface markers and all three pluripotent genes associated with CSCs. Furthermore, when assessing drug resistance potential and the expression of the ABCG2 drug efflux gene, only 5637 SCDS displayed increased resistance to cisplatin and upregulation of ABCG2. Conclusion: In conclusion, both the MCS and SCDS methods effectively enriched the population of bladder CSCs in the 5637 and HT-1376 bladder cancer cell lines. However, the SCDS method demonstrated a higher upregulation of CSC markers and pluripotent gene expression compared to MCS. It is worth noting that spheroid culture and CSC enrichment are not mutually exclusive and can coexist with increased chemotherapy resistance and upregulation of ABCG2 drug efflux gene expression. Moreover, the drug efflux capability may vary depending on the specific cell line and clonal lineage. These strategies can serve as valuable models for CSC enrichment, the study of cancer cell behavior, disease modeling, and personalized chemotherapy investigations.
简介:癌症干细胞(CSCs)是癌组织中一组独特的细胞,具有启动肿瘤发生的能力,并表现出效力、自我更新和耐药性。CSCs的研究在获得这些感兴趣的细胞或产生足够数量的下游分析方面经常遇到挑战。然而,体外富集CSC是可行的,方法是将其置于刺激其CSC特性的条件下,如长时间暴露于药物或辐射中,或通过球体培养促进其自我更新能力。球状体是一种特殊类型的细胞培养,它将细胞组织成三维结构,密切模仿体内环境。这些球体由异质细胞群组成,包括csc或负责肿瘤生长和维持的肿瘤增殖细胞。在我们的研究中,我们培养了来自单细胞和多细胞聚集体的球体,以丰富CSCs的自我更新能力和三维环境提供的结构组织。方法:将球体培养物与亲本贴壁单层细胞进行比较,观察到两种被试细胞系在多细胞球体(MCS)和单细胞衍生球体(SCDS)中CSC标记物、多能基因和脂肪分化的表达均较高。结果:在整个培养过程中,球体呈渐进式增长。当比较两种方法时,SCDS显示出更多的表面标记和与CSCs相关的所有三种多能性基因的表达。此外,在评估耐药潜力和ABCG2药物外排基因表达时,只有5637 SCDS对顺铂的耐药增加和ABCG2上调。结论:MCS和SCDS方法均能有效富集5637和HT-1376膀胱癌细胞系膀胱CSCs。然而,与MCS相比,SCDS方法显示出更高的CSC标记和多能基因表达上调。值得注意的是,球体培养和CSC富集并不相互排斥,可以与化疗耐药增加和ABCG2药物外排基因表达上调共存。此外,药物外排能力可能取决于特定的细胞系和克隆谱系。这些策略可以作为CSC富集、癌细胞行为研究、疾病建模和个性化化疗研究的有价值模型。
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Biomedical Research and Therapy
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