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.
{"title":"Upregulation of Neurotrophic Factors and Myelin Basic Protein in Schwann-like Cells by T3 Hormone Following Transdifferentiation of Human Adipose-derived Stem Cells.","authors":"Giti Zarinfard, Maryam Aliakbari, Vajihe Asgari, Shahnaz Razavi","doi":"10.22088/IJMCM.BUMS.11.1.41","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.1.41","url":null,"abstract":"<p><p>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 <i>in vitro</i>, 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, <i>in vitro</i>. Further <i>in vivo</i> experiments are necessary to confirm the advantages of using a combination of autologous SLCs and T3 hormone for peripheral nerve injury recovery.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 1","pages":"41-54"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/64/ijmcm-11-41.PMC9653553.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-10-03DOI: 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.
{"title":"Prevalence of Co-infection by Human Papillomavirus, Epstein- Barr Virus and Merkel Cell Polyomavirus in Iranian Oral Cavity Cancer and Pre-malignant Lesions.","authors":"Sagahr Saber Amoli, Ali Hasanzadeh, Farzin Sadeghi, Mohammad Chehrazi, Maryam Seyedmajidi, Arghavan Zebardast, Yousef Yahyapour","doi":"10.22088/IJMCM.BUMS.11.1.64","DOIUrl":"10.22088/IJMCM.BUMS.11.1.64","url":null,"abstract":"<p><p>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. <b>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.</b> This study revealed that co-infection of HPV, EBV and MCPyV can be detected in both malignant and non-malignant oral cavity tissues, and <b>co-infection with all three viruses in well differentiated tumors</b> can be shown as a synergistic hypothesis of the pathogenic role of these viruses in oral malignant transformation.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 1","pages":"64-77"},"PeriodicalIF":1.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/43/ijmcm-11-64.PMC9653548.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Increased Expression of Tight Junction Proteins and Blood-Brain Barrier Integrity in MCAO Rats Following Injection of miR-149-5p.","authors":"Meysam Forouzandeh, Hossein Mostafavi, Elham Ghasemloo, Parvin Mohammadi, Masoume Hosseini, Mehdi Eskandari","doi":"10.22088/IJMCM.BUMS.11.3.223","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.3.223","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 3","pages":"223-235"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/77/77/ijmcm-11-223.PMC10440002.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10406762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 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。
{"title":"Novel Variant Identified in the Enhancer Region of Host Transcription Factor, BRN3A, is a Significant Risk Factor for HPV-Induced Uterine Cervix Cancer.","authors":"Anand Prakash, Biswa Pratim Das Purkayastha, Shikha Srivastava, Sunanda Chaturvedi, Akhtar Ali, Dau Dayal Aggarwal, Jagat Kumar Roy","doi":"10.22088/IJMCM.BUMS.11.2.88","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.2.88","url":null,"abstract":"<p><p>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 <i>BRN3A</i>. Our analysis of PCR and DNA sequencing confirmed this novel SNP (<i>BRN3A</i> g.60163379A>G) within the auto-regulatory region of <i>BRN3A</i>. As compared to control subjects, cancer cases exhibited a 1.32-fold higher allele frequency (χ2 = 6.315, <i>p</i> = 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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 2","pages":"88-103"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/68/ijmcm-11-088.PMC10116355.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Nrf2 rs6721961 and Oxidative Stress in Preeclampsia: Association with the Risk of Preeclampsia and Early-Onset Preeclampsia.","authors":"Fatemeh Khadir, Zohreh Rahimi, Azita Ghanbarpour, Asad Vaisi-Raygani","doi":"10.22088/IJMCM.BUMS.11.2.127","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.2.127","url":null,"abstract":"<p><p>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 <i>Nrf2</i> 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 <i>Nrf2</i> rs6721961 genotypes using the PCR-RFLP method. Also, an association between the <i>Nrf2</i> 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 <i>Nrf2</i> rs6721961 polymorphism and preeclampsia risk. The present study indicated that the GT genotype and the T allele of the <i>Nrf2</i> rs6721961 increased the risk of preeclampsia by 2.81 and 2.39 times, respectively. Also, the <i>Nrf2</i> 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 <i>Nrf2</i> 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 <i>Nrf2</i> rs6721961 polymorphism through alteration in the levels of oxidative stress parameters might increase the risk of preeclampsia and early-onset preeclampsia.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 2","pages":"127-136"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/28/ijmcm-11-127.PMC10116352.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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。
{"title":"hsa-miR-508-5p as a New Potential Player in Intervertebral Disc Degeneration.","authors":"Akram Gholipour, Mahshid Malakootian, Maziar Oveisee","doi":"10.22088/IJMCM.BUMS.11.2.137","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.2.137","url":null,"abstract":"<p><p>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 <i>SEC11A</i>, <i>IPO5</i>, <i>FN1</i>, and <i>MRPS10</i>, 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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 2","pages":"137-149"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/46/67/ijmcm-11-137.PMC10116350.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Sesamin Acts as Anti-leukemic Compound Interacting with Novel Phosphoprotein Targets and Inducing Apoptosis in Leukemic Cells.","authors":"Pattharin Wannapruk, Kamolchanok Deesrisak, Sittiruk Roytrakul, Dalina Tanyong","doi":"10.22088/IJMCM.BUMS.11.1.1","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.1.1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/0e/ijmcm-11-1.PMC9653549.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Exploring VEGF-Linked Pathways: Investigating Multiple miRNAs for Their Therapeutic Potential in Angiogenesis Targets and as Biomarkers in Recurrent Glioblastoma Multiforme.","authors":"Morteza Hadizadeh, Ramin Soltani, Taimour Langaee, Marziye Shadpirouz, Sorayya Ghasemi","doi":"10.22088/IJMCM.BUMS.11.4.306","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.4.306","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 4","pages":"306-319"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/af/ijmcm-11-306.PMC10506677.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41119811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 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.
{"title":"FN14 mRNA Expression Correlates with an Increased Number of Veins during Angiogenesis in the Process of Liver Fibrosis.","authors":"Elena I Lebedeva, Andrei S Babenka, Pelin Hastemir, Anatoliy T Shchastniy, Dmitry A Zinovkin, Md Zahidul Islam Pranjol","doi":"10.22088/IJMCM.BUMS.11.4.274","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.4.274","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 4","pages":"274-284"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/50/ijmcm-11-274.PMC10506679.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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。
{"title":"Vitexin Induces Apoptosis in MCF-7 Breast Cancer Cells through the Regulation of Specific miRNAs Expression.","authors":"Reza Najafipour, Abdol Mabood Momeni, Yousef Mirmazloomi, Sahar Moghbelinejad","doi":"10.22088/IJMCM.BUMS.11.3.197","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.3.197","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":"11 3","pages":"197-206"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/34/eb/ijmcm-11-197.PMC10440000.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10041376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}