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Upregulation of Neurotrophic Factors and Myelin Basic Protein in Schwann-like Cells by T3 Hormone Following Transdifferentiation of Human Adipose-derived Stem Cells. 人脂肪干细胞转分化后T3激素对雪旺样细胞中神经营养因子和髓鞘碱性蛋白的上调
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 Epub Date: 2022-10-03 DOI: 10.22088/IJMCM.BUMS.11.1.41
Giti Zarinfard, Maryam Aliakbari, Vajihe Asgari, Shahnaz Razavi

Peripheral nerve regeneration is a complicated phenomenon. Thyroid hormones are known as critical regulators in the nervous system development. The Schwann cells have the regenerative potency in the peripheral nervous system. In this study, the human adipose-derived stem cells were assessed in vitro, for transdifferentiation potency into Shwann-like cells (SLCs) as a candidate source for clinical cell therapy, under the treatment of triiodothyronine (T3) hormone, and compared with the untreated cells. The cell viability rate, myelination and neurotrophic factors expression of SLCs were evaluated two weeks post- induction by MTT assay, immunocytochemistry and real-time RT-PCR techniques, respectively. The obtained results revealed a significant decrease in SLCs viability, compared to the adipose-derived stem cells (P < 0.001). Immunocytochemistry technique was applied to detect SLCs markers, such as S100β, GFAP and myelin basic proteins (MBP) in the presence and absence of T3 treatment. The results indicated that administering T3 can significantly increase the differentiation and myelination potency of SLCs (P < 0.01). The findings of real-time RT-PCR technique indicated that the expression of Schwann cells markers, MBP, brain-derived neurotrophic factor and glial cell-derived neurotrophic factor were upregulated significantly with T3 hormone administration in comparison with the untreated cells (P < 0.05). The SLCs were able to express the neurotrophic factors and myelination related genes in the presence of T3 hormone. Furthermore, T3 administration improved myelination potency of adipose-derived stem cells, in vitro. Further in vivo experiments are necessary to confirm the advantages of using a combination of autologous SLCs and T3 hormone for peripheral nerve injury recovery.

周围神经再生是一个复杂的现象。甲状腺激素被认为是神经系统发育的关键调节因子。雪旺细胞在周围神经系统中具有再生能力。在本研究中,我们在体外评估了人脂肪干细胞在三碘甲状腺原氨酸(T3)激素的作用下转分化为shwan样细胞(SLCs)的能力,并将其作为临床细胞治疗的候选来源,并与未处理的细胞进行了比较。诱导2周后分别采用MTT法、免疫细胞化学法和实时RT-PCR技术检测SLCs的细胞存活率、髓鞘形成和神经营养因子的表达。所得结果显示,与脂肪来源的干细胞相比,SLCs的活力显著降低(P < 0.001)。应用免疫细胞化学技术检测T3处理前后SLCs标志物S100β、GFAP和髓鞘碱性蛋白(MBP)的表达。结果表明,给药T3能显著提高SLCs的分化和髓鞘形成能力(P < 0.01)。实时RT-PCR检测结果显示,与未给药的细胞相比,T3激素组雪旺细胞标志物、MBP、脑源性神经营养因子和胶质细胞源性神经营养因子的表达显著上调(P < 0.05)。在T3激素存在的情况下,SLCs能够表达神经营养因子和髓鞘形成相关基因。此外,在体外,给药T3可提高脂肪来源干细胞的髓鞘形成能力。需要进一步的体内实验来证实自体SLCs与T3激素联合应用在外周神经损伤恢复中的优势。
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引用次数: 2
Prevalence of Co-infection by Human Papillomavirus, Epstein- Barr Virus and Merkel Cell Polyomavirus in Iranian Oral Cavity Cancer and Pre-malignant Lesions. 伊朗口腔癌和恶性前病变中人类乳头瘤病毒、爱泼斯坦-巴氏病毒和梅克尔细胞多瘤病毒合并感染的流行率
IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 Epub Date: 2022-10-03 DOI: 10.22088/IJMCM.BUMS.11.1.64
Sagahr Saber Amoli, Ali Hasanzadeh, Farzin Sadeghi, Mohammad Chehrazi, Maryam Seyedmajidi, Arghavan Zebardast, Yousef Yahyapour

Human papillomavirus (HPV) is recognized as the most important risk factor in oral cavity cancer and pre-malignant lesions; however, the etiological association of concomitant infection with other oncogenic viruses as a co-factor has not been definitively proven. The present study aimed to determine the prevalence of co-infection with HPV, Epstein-Barr virus (EBV) and Merkel Cell PolyomaVirus (MCPyV) in oral cavity lesions in Iranian patients. One hundred and fourteen oral cavity samples, including 33 oral squamous cell carcinoma, 28 oral lichen planus, 16 oral epithelial dysplasia and 37 oral irritation fibromas were analyzed for the HPV, EBV and MCPyV infection by quantitative real-time PCR. According to histological features 32.5% and 28.9% of cases were oral irritation fibroma and oral squamous cell carcinoma, respectively. Infection with at least two viruses was detected in 21.1% of patients. In this group, co-infection with HPV/EBV was identified in 37.5% of cases, HPV/MCPyV in 29.2%, EBV/MCPyV in 12.5%, and HPV/EBV/MCPyV in 20.8%. There was no statistically significant difference between multiple infections and anatomical locations of cancer. The prevalence of triple viral infection (HPV/EBV/MCPyV) in well differentiated tumors was higher than EBV or MCPyV single infection. This study revealed that co-infection of HPV, EBV and MCPyV can be detected in both malignant and non-malignant oral cavity tissues, and co-infection with all three viruses in well differentiated tumors can be shown as a synergistic hypothesis of the pathogenic role of these viruses in oral malignant transformation.

人类乳头瘤病毒(HPV)被认为是口腔癌和恶性前病变的最重要风险因素;然而,与其他致癌病毒同时感染作为共同因素的病因学关联尚未得到明确证实。本研究旨在确定伊朗患者口腔病变中人类乳头瘤病毒(HPV)、爱泼斯坦-巴氏病毒(EBV)和梅克尔细胞多瘤病毒(MCPyV)的合并感染率。通过实时定量 PCR 分析了 114 份口腔样本,包括 33 份口腔鳞状细胞癌样本、28 份口腔扁平苔藓样本、16 份口腔上皮发育不良样本和 37 份口腔刺激性纤维瘤样本,以确定是否感染了 HPV、EBV 和 MCPyV。根据组织学特征,分别有 32.5% 和 28.9% 的病例为口腔刺激性纤维瘤和口腔鳞状细胞癌。21.1%的患者至少感染了两种病毒。其中,37.5%的病例同时感染了HPV/EBV,29.2%的病例同时感染了HPV/MCPyV,12.5%的病例同时感染了EBV/MCPyV,20.8%的病例同时感染了HPV/EBV/MCPyV。多重感染与癌症的解剖位置之间没有明显的统计学差异。在分化良好的肿瘤中,三重病毒感染(HPV/EBV/MCPyV)的发生率高于 EBV 或 MCPyV 单一感染。该研究表明,在恶性和非恶性口腔组织中均可检测到HPV、EBV和MCPyV的共感染,分化良好的肿瘤中三种病毒的共感染可作为这些病毒在口腔恶性转化中致病作用的协同假说。
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引用次数: 0
Increased Expression of Tight Junction Proteins and Blood-Brain Barrier Integrity in MCAO Rats Following Injection of miR-149-5p. 注射miR-149-5p后MCAO大鼠紧密连接蛋白和血脑屏障完整性的表达增加。
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.3.223
Meysam Forouzandeh, Hossein Mostafavi, Elham Ghasemloo, Parvin Mohammadi, Masoume Hosseini, Mehdi Eskandari

Cerebral ischemia is a common neurodegenerative disease in which damage to the blood-brain barrier (BBB) is the main consequence. In cerebral ischemia, the level of miR-149-5p and tight junction proteins are decreased, while the level of Calpine is increased, finally leading to increased BBB permeability. This study investigated the effect of miR-149-5p mimic on the expression of Calpain, Occludin, and ZO-1 and the consequences of cerebral ischemia. Cerebral ischemia model was performed via middle cerebral artery occlusion (MCAO) method on female Wistar rats. Four groups of Wistar rats were studied: Sham, cerebral ischemia without treatment, Scramble miR, and miR-149-5p mimic treatment. Then, neurological defects and BBB permeability (via Evans blue staining), cerebral edema (cerebrospinal fluid percentage), and ZO-1, Occludin, and Calapin expression (by quantitative real time- PCR) were investigated. qRT-PCR results showed miR-149-5p expression decreases after cerebral ischemia induction. In addition, Occludin and ZO-1 expression significantly increased in miR-149-5p group. In contrast, Calapin expression, BBB permeability, brain water content and neurological defects were significantly decreased. It seems that the increased level of miR-149-5p exerts its protective effect on cerebral ischemia due to increasing of tight junction proteins.

脑缺血是一种常见的神经退行性疾病,其主要后果是血脑屏障(BBB)受损。在脑缺血时,miR-149-5p和紧密连接蛋白水平降低,而Calpine水平升高,最终导致血脑屏障通透性增加。本研究探讨了miR-149-5p mimic对Calpain、Occludin和ZO-1表达的影响以及脑缺血的后果。采用大脑中动脉闭塞法(MCAO)建立雌性Wistar大鼠脑缺血模型。研究四组Wistar大鼠:假手术、脑缺血不治疗、Scramble miR和miR-149-5p模拟治疗。然后检测神经缺损和血脑屏障通透性(通过Evans蓝染色)、脑水肿(脑脊液百分比)以及ZO-1、Occludin和Calapin的表达(通过实时荧光定量PCR)。qRT-PCR结果显示,脑缺血诱导后miR-149-5p表达降低。此外,miR-149-5p组Occludin和ZO-1表达显著升高。相比之下,Calapin表达、血脑屏障通透性、脑含水量和神经缺损显著降低。似乎miR-149-5p水平的升高是通过紧密连接蛋白的增加来发挥其对脑缺血的保护作用。
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引用次数: 0
Novel Variant Identified in the Enhancer Region of Host Transcription Factor, BRN3A, is a Significant Risk Factor for HPV-Induced Uterine Cervix Cancer. 宿主转录因子增强子区的新变异BRN3A是hpv诱发宫颈癌的重要危险因素。
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.2.88
Anand Prakash, Biswa Pratim Das Purkayastha, Shikha Srivastava, Sunanda Chaturvedi, Akhtar Ali, Dau Dayal Aggarwal, Jagat Kumar Roy

Among the HPV-mediated cervical cancers, cellular factor BRN3A has gained considerable attention due to its role in promoting an anti-apoptotic cellular environment and in facilitating epitheliotropic transformations of the host. The majority of previous studies looked at BRN3A's molecular characteristics; however, the possibility of genetic variations in BRN3A's auto-regulatory region in relation to cervical cancer risk has been underestimated until now. In a retrospective study in the Eastern UP population, India, we detected genetic variations in the cis-regulatory proximal enhancer region located around 5.6 kb upstream of transcription start site of BRN3A. Our analysis of PCR and DNA sequencing confirmed this novel SNP (BRN3A g.60163379A>G) within the auto-regulatory region of BRN3A. As compared to control subjects, cancer cases exhibited a 1.32-fold higher allele frequency (χ2 = 6.315, p = 0.012). In homozygous (GG) but not in heterozygous conditions, odds ratio (OR) analysis suggests a significant association of cancer risk with the SNP (OR = 2.60, p ≤ 0.004). We further confirmed using the functional analysis that this SNP increased the luciferase gene activity in HPV-positive cervical cancer SiHa cells that were exposed to progesterone. As a result of the association of polymorphisms in a non-coding region of an oncogene with increased cancer risks, we are suggesting that this genetic variation in non-coding region can be used in prediction, diagnosis, or predicting the progression of the disease.

在hpv介导的宫颈癌中,细胞因子BRN3A因其在促进抗凋亡细胞环境和促进宿主上皮性转化中的作用而引起了相当大的关注。之前的大多数研究着眼于BRN3A的分子特征;然而,到目前为止,BRN3A自调节区域的遗传变异与宫颈癌风险相关的可能性一直被低估。在一项对印度东部UP人群的回顾性研究中,我们检测到了位于BRN3A转录起始位点上游约5.6 kb的顺式调控近端增强子区域的遗传变异。我们的PCR分析和DNA测序证实了这一新的SNP (BRN3A G . 60163379a >G)位于BRN3A的自调节区域。与对照组相比,癌症患者的等位基因频率高1.32倍(χ2 = 6.315, p = 0.012)。在纯合子(GG)而非杂合子条件下,优势比(OR)分析表明,癌症风险与SNP有显著关联(OR = 2.60, p≤0.004)。我们通过功能分析进一步证实,该SNP增加了暴露于黄体酮的hpv阳性宫颈癌SiHa细胞中荧光素酶基因的活性。由于癌基因非编码区多态性与癌症风险增加的关联,我们建议这种非编码区遗传变异可用于预测、诊断或预测疾病的进展。
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引用次数: 0
Nrf2 rs6721961 and Oxidative Stress in Preeclampsia: Association with the Risk of Preeclampsia and Early-Onset Preeclampsia. Nrf2 rs6721961和氧化应激在子痫前期:与子痫前期和早发性子痫前期的风险相关
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.2.127
Fatemeh Khadir, Zohreh Rahimi, Azita Ghanbarpour, Asad Vaisi-Raygani

Preeclampsia as a multifactor hypertensive disorder of pregnancy is associated with enhanced placental oxidative stress. The Keap1-Nrf2 pathway protects cells against oxidative stress. We examined the possible association between the Nrf2 variants in relation to oxidative stress parameters with the risk of preeclampsia. We studied 150 preeclampsia women and 150 women with a normal pregnancy to find the frequency of Nrf2 rs6721961 genotypes using the PCR-RFLP method. Also, an association between the Nrf2 genotypes with the levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) was analyzed. Significantly lower TAC and higher MDA levels were found in preeclampsia patients compared to controls (P<0.0001). For the first time, we report an association between the Nrf2 rs6721961 polymorphism and preeclampsia risk. The present study indicated that the GT genotype and the T allele of the Nrf2 rs6721961 increased the risk of preeclampsia by 2.81 and 2.39 times, respectively. Also, the Nrf2 TT genotype was associated with a 3.9-fold increased risk of early-onset preeclampsia. We detected a positive association between the levels of body mass index, MDA, and the Nrf2 polymorphism with the risk of preeclampsia and a negative correlation between the level of TAC with the preeclampsia risk. Also, an association between the rs6721961 TT genotype with higher serum MDA levels was found. Our study suggests oxidative stress is involved in the pathogenesis of preeclampsia and the Nrf2 rs6721961 polymorphism through alteration in the levels of oxidative stress parameters might increase the risk of preeclampsia and early-onset preeclampsia.

先兆子痫作为一种多因素妊娠高血压疾病与胎盘氧化应激增强有关。Keap1-Nrf2通路保护细胞免受氧化应激。我们研究了Nrf2变异与氧化应激参数与子痫前期风险之间的可能关联。我们研究了150例子痫前期妇女和150例正常妊娠妇女,采用PCR-RFLP方法寻找Nrf2 rs6721961基因型的频率。此外,还分析了Nrf2基因型与丙二醛(MDA)水平和总抗氧化能力(TAC)之间的关系。与对照组相比,子痫前期患者的TAC显著降低,MDA水平显著升高(PNrf2 rs6721961多态性与子痫前期风险相关)。本研究表明,Nrf2 rs6721961的GT基因型和T等位基因分别使子痫前期风险增加2.81倍和2.39倍。此外,Nrf2 TT基因型与早发性子痫前期风险增加3.9倍相关。我们发现体重指数、MDA和Nrf2多态性水平与子痫前期风险呈正相关,而TAC水平与子痫前期风险呈负相关。此外,rs6721961 TT基因型与较高的血清MDA水平之间存在关联。我们的研究提示氧化应激参与了子痫前期的发病机制,Nrf2 rs6721961多态性通过改变氧化应激参数的水平可能增加子痫前期和早发性子痫前期的风险。
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引用次数: 1
hsa-miR-508-5p as a New Potential Player in Intervertebral Disc Degeneration. hsa-miR-508-5p作为椎间盘退变的新潜在参与者。
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.2.137
Akram Gholipour, Mahshid Malakootian, Maziar Oveisee

Intervertebral disc degeneration (IDD) is widely known as the principal cause of low back pain, diminishing patients' quality of life and imposing a huge economic burden on healthcare systems worldwide. However, the underlying mechanisms of IDD remain to be determined. This study aimed to scrutinize data sets via bioinformatics to identify microRNAs (miRNAs)/genes and pathways associated with IDD. The array profiling of patients with IDD and individuals without IDD was acquired from the Gene Expression Omnibus (GEO) database (viz., GSE19943, GSE63492, and GSE34095). The expression profiles of miRNAs and genes with differential patterns were analyzed using GEO2R. The target genes of the chosen miRNA were then examined, and in silico functional analyses were performed on the signaling pathways and biological processes of the differentially expressed genes. Three human miRNAs were up and downregulated in IDD patients in the examined data sets. Among them, hsa-miR-508-5p had a significant differential expression in the IDD group, and SEC11A, IPO5, FN1, and MRPS10, as the targets of hsa-miR-508-5p, were upregulated in the IDD group. Furthermore, extracellular matrix-receptor interactions, focal adhesion, and actin cytoskeleton regulation were important pathways involved in IDD. Our analysis identified hsa-miR-508-5p as a novel miRNA involved in IDD pathogenies. Our findings not only further confirmed the significant role of miRNAs in IDD pathogenesis but also extended the spectrum of the miRNAs and genes involved in IDD. Though, still, further experimental investigations are needed to confirm our findings.

椎间盘退变(IDD)被广泛认为是腰痛的主要原因,降低了患者的生活质量,给世界各地的医疗保健系统带来了巨大的经济负担。然而,IDD的潜在机制仍有待确定。本研究旨在通过生物信息学检查数据集,以鉴定与IDD相关的microRNAs (miRNAs)/基因和途径。从Gene Expression Omnibus (GEO)数据库(即GSE19943、GSE63492和GSE34095)中获得IDD患者和非IDD个体的阵列图谱。利用GEO2R分析mirna和差异模式基因的表达谱。然后对所选miRNA的靶基因进行检测,并对差异表达基因的信号通路和生物学过程进行硅功能分析。在检查的数据集中,IDD患者中有三种人类mirna上调和下调。其中,hsa-miR-508-5p在IDD组中表达差异显著,作为hsa-miR-508-5p靶点的SEC11A、IPO5、FN1、MRPS10在IDD组中表达上调。此外,细胞外基质-受体相互作用、局灶黏附和肌动蛋白细胞骨架调节是IDD的重要途径。我们的分析发现hsa-miR-508-5p是一种参与IDD发病的新型miRNA。我们的发现不仅进一步证实了mirna在IDD发病机制中的重要作用,而且扩展了与IDD相关的mirna和基因的谱。不过,还需要进一步的实验研究来证实我们的发现。
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引用次数: 2
Sesamin Acts as Anti-leukemic Compound Interacting with Novel Phosphoprotein Targets and Inducing Apoptosis in Leukemic Cells. 芝麻素作为抗白血病化合物与新的磷酸化蛋白靶点相互作用并诱导白血病细胞凋亡。
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 Epub Date: 2022-10-04 DOI: 10.22088/IJMCM.BUMS.11.1.1
Pattharin Wannapruk, Kamolchanok Deesrisak, Sittiruk Roytrakul, Dalina Tanyong

Leukemia is one of the high-incidence cancers that is characterized by an abnormal production of immature white blood cells. Subject to many reports on the side effects of conventional chemotherapy, herbs and natural compounds have been studied as an alternative medicine. In this study, sesamin, a lignan in sesame seed with pharmaceutical functions including anti-cancer, was chosen and treated with MOLT-4 and NB4 leukemic cell lines in various concentrations for 24 and 48 hours. The effect of sesamin on cell inhibition and expression levels of apoptotic genes in leukemic cell lines were investigated by MTT assay and real-time PCR, respectively. Moreover, apoptotic proteins were studied by mass spectrometry and bioinformatics tools to investigate the relation between sesamin and targeted proteins. Results showed that sesamin increased cell inhibition in both cell lines in dose- and time-dependent manner. Levels of caspase-3, -7, -8, and -9 gene expressions significantly increased, while BCL-2 decreased drastically in sesamin-treated cells. From bioinformatics study, PARP4, IPPK and caspase family proteins were found to be involved in sesamin that induced apoptosis in leukemic cells. Besides, doxorubicin, a chemotherapeutic drug, also shared the same protein targets as sesamin in apoptosis pathway. Sesamin demonstrates its potential to enhance cell inhibition and promotes cell apoptosis in both MOLT-4 and NB4 leukemic cell lines. This study will benefit the development of sesamin as an effective anti-leukemia drug in the future.

白血病是一种高发病率的癌症,其特征是不成熟白细胞的异常产生。由于许多关于常规化疗副作用的报道,草药和天然化合物已被研究作为替代药物。本研究选取芝麻籽中具有抗癌药理作用的木脂素芝麻素,以不同浓度的MOLT-4和NB4白血病细胞株处理24和48小时。采用MTT法和real-time PCR法分别研究芝麻素对白血病细胞系细胞抑制和凋亡基因表达水平的影响。此外,通过质谱和生物信息学工具研究凋亡蛋白,探讨芝麻素与靶蛋白的关系。结果表明,芝麻素对两种细胞系的抑制作用均呈剂量依赖性和时间依赖性。在芝麻素处理的细胞中,caspase-3、-7、-8和-9基因表达水平显著升高,而BCL-2基因表达水平急剧下降。生物信息学研究发现,芝麻素诱导白血病细胞凋亡与PARP4、IPPK和caspase家族蛋白有关。此外,化疗药物阿霉素与芝麻素在凋亡通路中也有相同的蛋白靶点。芝麻素在MOLT-4和NB4白血病细胞系中显示出增强细胞抑制和促进细胞凋亡的潜力。本研究将有助于芝麻素作为一种有效的抗白血病药物的开发。
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引用次数: 0
Exploring VEGF-Linked Pathways: Investigating Multiple miRNAs for Their Therapeutic Potential in Angiogenesis Targets and as Biomarkers in Recurrent Glioblastoma Multiforme. 探索VEGF相关通路:研究多种miRNA在血管生成靶点中的治疗潜力以及作为复发性多型胶质母细胞瘤的生物标志物。
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.4.306
Morteza Hadizadeh, Ramin Soltani, Taimour Langaee, Marziye Shadpirouz, Sorayya Ghasemi

Alternative pathways frequently operate as the origins of resistance to drugs that block the vascular endothelial growth factor (VEGF) pathway. To find possible therapeutic targets and indicators, this study explored the VEGF pathway and how miRNAs control it in recurrent glioblastoma multiforme (rGBM). Differentially expressed miRNAs (DEmiRNAs) were identified by using GBM GSE profiles (GSE32466). To find pathways containing DEmiRNAs, VEGF pathway genes, and their related genes, DIANA-miRPath v3.0 and the ToppGene database were utilized. miRNAs linked to VEGF signaling pathway genes, interactional genes, and DEmiRNAs were discovered by extracting common pathways. The ability of these miRNAs to distinguish rGBM patients from those with primary GBM was assessed using ROC analysis. The study revealed that in rGBM, 30 miRNAs were significantly up-regulated and 49 miRNAs were considerably down-regulated. Among them, the VEGF pathway was connected to 22 up-regulated miRNAs and 29 down-regulated miRNAs. The MAPK pathway shared the most genes with the VEGF pathway, accounting for 1,014 of the interacting genes, which were discovered to have interactions with VEGF signaling pathway genes. Furthermore, 14 miRNAs were identified as having a great deal of potential as molecular biomarkers and therapeutic targets for rGBM. The results indicate that the VEGF pathway in rGBM is regulated by a number of interrelated pathways. The discovered miRNAs hold promise as rGBM biomarkers and therapeutic targets, offering possibilities for novel therapy strategies and aiding rGBM diagnosis and prognosis.

替代途径通常是阻断血管内皮生长因子(VEGF)途径的药物耐药性的来源。为了寻找可能的治疗靶点和指标,本研究探讨了复发性多形性胶质母细胞瘤(rGBM)中VEGF通路以及miRNA如何控制它。通过使用GBM GSE图谱(GSE32466)鉴定差异表达的miRNA(DEmiRNA)。为了找到包含DEmiRNA、VEGF通路基因及其相关基因的通路,利用DIANA-miRPathv3.0和ToppGene数据库。通过提取常见途径发现了与VEGF信号通路基因、相互作用基因和DEmiRNA相关的miRNA。使用ROC分析评估这些miRNA区分rGBM患者和原发性GBM患者的能力。研究表明,在rGBM中,30个miRNA显著上调,49个miRNA明显下调。其中,VEGF通路与22个上调的miRNA和29个下调的miRNA相连。MAPK通路与VEGF通路共享最多的基因,占1014个相互作用基因,这些基因被发现与VEGF信号通路基因有相互作用。此外,14种miRNA被鉴定为具有作为rGBM的分子生物标志物和治疗靶点的巨大潜力。结果表明,rGBM中的VEGF通路受到许多相关通路的调节。所发现的miRNA有望成为rGBM的生物标志物和治疗靶点,为新的治疗策略提供可能性,并帮助rGBM诊断和预后。
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引用次数: 0
FN14 mRNA Expression Correlates with an Increased Number of Veins during Angiogenesis in the Process of Liver Fibrosis. 肝纤维化过程中血管生成过程中FN14mRNA表达与静脉数量增加相关。
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.4.274
Elena I Lebedeva, Andrei S Babenka, Pelin Hastemir, Anatoliy T Shchastniy, Dmitry A Zinovkin, Md Zahidul Islam Pranjol

In this study, we hypothesize that angiogenesis of special hepatic vessels such as sinusoid capillaries or veins is closely associated with increasing production of connective tissue in fibrogenesis. Thirty-six male Wistar rats were induced with hepatitis and cirrhosis of the liver using thioacetamide. The number of sinusoidal capillaries, veins, arteries and the area of connective tissue were counted and determined. Immunohistochemical study was performed on paraffin sections using monoclonal mouse anti-CD31. mRNA expression was determined using qPCR. We found a statistically significant reduction in the number of sinusoidal capillaries (p<0.0001) and an increase in the number of interlobular veins (p<0.0001) in the fibrosis and cirrhosis groups compared to the control group. There are no differences in the number of interlobular arteries (p=0.282) in the three groups. In our analysis, we found that the expression (mRNA) of Fn14 correlated with the number of veins in liver fibrosis (r=0.44, p=0.008). Our data shows that modulation of veins angiogenesis during fibrosis in chronic liver diseases may play an important role in increasing pathological changes of the liver.

在这项研究中,我们假设特殊肝血管(如血窦毛细血管或静脉)的血管生成与纤维化过程中结缔组织生成的增加密切相关。用硫代乙酰胺诱导36只雄性Wistar大鼠发生肝炎和肝硬化。对正弦毛细血管、静脉、动脉的数量和结缔组织的面积进行计数和测定。使用单克隆小鼠抗CD31对石蜡切片进行免疫组织化学研究。使用qPCR测定mRNA表达。我们发现正弦毛细血管的数量在统计学上显著减少(p
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引用次数: 0
Vitexin Induces Apoptosis in MCF-7 Breast Cancer Cells through the Regulation of Specific miRNAs Expression. 牡荆素通过调控特异性miRNAs表达诱导MCF-7乳腺癌细胞凋亡
Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2022-01-01 DOI: 10.22088/IJMCM.BUMS.11.3.197
Reza Najafipour, Abdol Mabood Momeni, Yousef Mirmazloomi, Sahar Moghbelinejad

In this research, we investigated microRNAs (miRNAs) expression profile in MCF-7 breast cancer cell line which treated with 150 µM vitexin. Profiling of miRNAs expression was performed using TaqMan MiRNA Array. Apoptosis was analyzed by flow cytometry and the expression of some genes involved in "anti-proliferative" signaling pathways were evaluated by western blotting and real time PCR methods. Twenty microRNAs were differentially expressed in vitexin treated cells compared to the control. Among them, let-7- b, c were up regulated while miRNA-17-5p was down regulated with highest score. Also, we detected the expression changes of mentioned miRNAs target genes as well as genes involved in caspase apoptosis pathways. Our results provide the first evidence that vitexin can effect miRNA expression in MCF-7 cells. Also based on our finding, vitexin can be an attractive miRNA mediated chemo preventive and therapeutic agent in breast cancer.

在本研究中,我们研究了150µM牡荆素处理MCF-7乳腺癌细胞株中microRNAs (miRNAs)的表达谱。使用TaqMan MiRNA Array进行MiRNA表达谱分析。流式细胞术检测细胞凋亡,western blotting和real - time PCR检测“抗增殖”信号通路相关基因的表达。与对照组相比,20个microrna在牡荆素处理的细胞中差异表达。其中let-7- b、c上调,miRNA-17-5p下调得分最高。同时,我们检测了上述mirna靶基因以及caspase凋亡通路相关基因的表达变化。我们的研究结果首次证明牡荆素可以影响MCF-7细胞中miRNA的表达。此外,我们的研究结果表明,牡荆素可能是一种有吸引力的miRNA介导的乳腺癌化疗预防和治疗药物。
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引用次数: 0
期刊
International Journal of Molecular and Cellular Medicine
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