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":null,"pages":null},"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":null,"pages":null},"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}
Systemic sclerosis (SSc) is a chronic autoimmune disease,featuring fibrosis in multiple organs. The serum from SSc patients contain inflammatory mediators, contributing to SSc pathogenesis and could be used to develop cell culture models. Here, we compared the fibrotic effects of serum samples from SSc patients with TGFβ1 on human dermal fibroblasts (HDFs). HDF cells were cultured in four different culture media supplementations; 10% SSc serum, 10% healthy human serum, 10% fetal bovine serum or 10% FBS supplemented with 10 ng/Ml human TGFβ. The collagen content in cell layers was measured by spectrophotometric Picro-Sirius red staining. The mRNA expression of α-SMA, COL I and III, TGFβ1, arginase and E-Cadherin genes were determined by real time RT-PCR. TGF-β1 levels in cell culture supernatants were measured using ELISA. Cell layer collagen content was significantly increased following TGF-β1 treatment, compared with FBS group and SSc serum treatment in comparison with healthy controls. Although not statistically significant, the mRNA expression of α-SMA, COLI and III, TGFβ1, and arginase increased upon TGF-β1 treatment in comparison with FBS group, and in SSc serum treatment group in comparison with healthy controls. E-Cadherin decreased following TGF-β1 treatment and SSc serum treatment in comparison with their counterparts. TGF-β1 levels increased in cell culture supernatants of HDF cells exposed to TGF-β1 and SSc serum. An in vitro model of SSc serum-induced fibrosis using human HDF cells was evaluated in comparison to the TGF-β1 fibrosis induced model and data suggested that it may be used in documenting the role of pro-fibrotic factors in serum or plasma from SSc patients.
{"title":"Comparison of a Suggested Model of Fibrosis in Human Dermal Fibroblasts by Serum from Systemic Sclerosis Patients with Transforming Growth Factor β Induced in vitro Model.","authors":"Elnaz Dadashzadeh, Marie Saghaeian Jazi, Nafiseh Abdolahi, Saeed Mohammadi, Mohsen Saeidi","doi":"10.22088/IJMCM.BUMS.11.1.31","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.1.31","url":null,"abstract":"<p><p>Systemic sclerosis (SSc) is a chronic autoimmune disease<b>,</b> <b>featuring fibrosis in multiple organs.</b> The serum from SSc patients contain inflammatory mediators, contributing to SSc pathogenesis and could be used to develop cell culture models. Here, we compared the fibrotic effects of serum samples from SSc patients with <i>TGFβ1</i> on human dermal fibroblasts (HDFs). HDF cells were cultured in four different culture media supplementations; 10% SSc serum, 10% healthy human serum, 10% fetal bovine serum or 10% FBS supplemented with 10 ng/Ml human TGFβ. The collagen content in cell layers was measured by spectrophotometric Picro-Sirius red staining. The mRNA expression of <i>α-SMA</i>, <i>COL I</i> and <i>III</i>, <i>TGFβ1</i>, arginase and E-Cadherin genes were determined by real time RT-PCR. TGF-β1 levels in cell culture supernatants were measured using ELISA. Cell layer collagen content was significantly increased following TGF-β1 treatment, compared with FBS group and SSc serum treatment in comparison with healthy controls. Although not statistically significant, the mRNA expression of α-SMA, <i>COLI</i> and <i>III</i>, <i>TGFβ1</i>, and arginase increased upon TGF-β1 treatment in comparison with FBS group, and in SSc serum treatment group in comparison with healthy controls. E-Cadherin decreased following TGF-β1 treatment and SSc serum treatment in comparison with their counterparts. TGF-β1 levels increased in cell culture supernatants of HDF cells exposed to TGF-β1 and SSc serum. An <i>in vitro</i> model of SSc serum-induced fibrosis using human HDF cells was evaluated in comparison to the TGF-β1 fibrosis induced model and data suggested that it may be used in documenting the role of pro-fibrotic factors in serum or plasma from SSc patients.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/72/95/ijmcm-11-31.PMC9653550.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695713","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: 2022-03-10DOI: 10.22088/IJMCM.BUMS.11.1.78
Maryam Sadeghi-Zadeh, Farshad Homayouni Moghadam, Mohammad Hossein Nasr-Esfahani
Degeneration of dopaminergic (DA) neurons in the substantia nigra is known as the main cause of Parkinson's disease (PD). Preventing the loss of DA neurons alongside the cell-replacement therapy have brought tremendous hope for the treatment of PD. For this purpose, various studies have been done to findthe specificDA neuro-protective compounds or progressing DA-differentiation methods. Ferulic acid (FA) has strong neuro-protective effects, but at this point its role on protection and differentiation of DA neurons is not well-defined. Mouse neural stem cells (mNSCs) were treated with FA and expressions of TH(tyrosine hydroxylase)and NURR1 as the DA neuron specific markers were determined using real time qRT-PCR and immunostaining assays.Finally, efficacy of FA on DA differentiation was evaluated in comparison with other methods using fibroblast growth factor 8b (FGF8b) and sonic hedgehog (SHH). Treatment with FA could increase theThandNurr1gene expressions in mNSCs. Also, it enhancedβ-tubullin-IIIexpression and increased the neurite length in treated groups. Real time qRT-PCR and immunostaining assays showed that FA could increase DA differentiation in mNSCs effectively. Also, gene expression profile in some groups showed that FA can raise the differentiation rate of other neuronal subtypes such as cholinergic neurons. FA effectivelyinduces the DA differentiation in neural precursor cells by its ability to increase the expression of the NURR1 transcription factor, which is a known transcription factor for differentiation of midbrain DA neurons.
黑质多巴胺能(DA)神经元的退化被认为是帕金森病(PD)的主要原因。在细胞替代疗法的同时防止DA神经元的丢失,为帕金森病的治疗带来了巨大的希望。为此,人们进行了各种研究,以寻找特异性的DA神经保护化合物或发展DA分化方法。阿魏酸(FA)具有较强的神经保护作用,但其对DA神经元的保护和分化作用尚不明确。用FA处理小鼠神经干细胞(mNSCs),采用实时荧光定量pcr和免疫染色法检测TH(酪氨酸羟化酶)和NURR1作为DA神经元特异性标志物的表达。最后,与其他使用成纤维细胞生长因子8b (FGF8b)和sonic hedgehog (SHH)的方法相比,评估FA对DA分化的效果。FA处理可增加骨髓间充质干细胞Th和Nurr1基因的表达。治疗组β -微管蛋白- III表达增强,神经突长度增加。Real - time qRT-PCR和免疫染色结果显示,FA能有效促进骨髓间充质干细胞的DA分化。此外,在某些组的基因表达谱显示,FA可以提高其他神经元亚型如胆碱能神经元的分化率。FA通过增加NURR1转录因子的表达,有效诱导神经前体细胞DA分化,NURR1转录因子是已知的中脑DA神经元分化的转录因子。
{"title":"Ferulic Acid Induces NURR1 Expression and Promotes Dopaminergic Differentiation in Neural Precursor Cells.","authors":"Maryam Sadeghi-Zadeh, Farshad Homayouni Moghadam, Mohammad Hossein Nasr-Esfahani","doi":"10.22088/IJMCM.BUMS.11.1.78","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.1.78","url":null,"abstract":"<p><p><b>Degeneration of dopaminergic (DA) neurons in the substantia nigra is known as the main cause of Parkinson's disease (PD). Preventing the loss of DA neurons alongside the cell-replacement therapy have brought tremendous hope for the treatment of PD. For this purpose, various studies have been done to find</b> <b>the specific</b> <b>DA neuro-protective compounds or progressing DA-differentiation methods. Ferulic acid (FA) has strong neuro-protective effects, but at this point its role on protection and differentiation of DA neurons is not well-defined. Mouse neural stem cells (mNSCs) were treated with FA and expressions of TH</b> <b>(tyrosine hydroxylase)</b> <b>and NURR1 as the DA neuron specific markers were determined using real time qRT-PCR and immunostaining assays</b> <b><i>.</i> </b> <b>Finally, efficacy of FA on DA differentiation was evaluated in comparison with other methods using fibroblast growth factor 8b (FGF8b) and sonic hedgehog (SHH). Treatment with FA could increase the</b> <b><i>Th</i></b> <b>and</b> <b><i>Nurr1</i></b> <b>gene expressions in mNSCs. Also, it enhanced</b> <b><i>β</i></b> <b>-</b> <b><i>tubullin</i></b> <b>-</b> <b><i>III</i></b> <b>expression and increased the neurite length in treated groups. Real time qRT-PCR and immunostaining assays showed that FA could increase DA differentiation in mNSCs effectively. Also, gene expression profile in some groups showed that FA can raise the differentiation rate of other neuronal subtypes such as cholinergic neurons. FA effectively</b> <b>induces the DA differentiation in neural precursor cells by its ability to increase the expression of the NURR1 transcription factor, which is a known transcription factor for differentiation of midbrain DA neurons.</b></p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/71/0e/ijmcm-11-78.PMC9653552.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40695717","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}
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder of women in reproductive age with significant effects on reproductive and metabolic functions. Many molecular players may be involved in PCOS pathology; however, miRNAs possess great ability in gene expression control in normal ovarian function and folliculogenesis. We appraised the relative expression of miR-146a, miR-222, miR-9, and miR-224 in serum and follicular fluid (FF) of PCOS patients compared to control subjects. PCOS (n = 35) and control (n = 30) subjects were recruited in the study during their enrolment in IVF cycles. Serum and FF of human subjects were collected and stored. Total RNA was isolated from samples and cDNA was synthesized using miRNA-specific stem-loop RT primers. Quantitative real-time PCR was used to evaluate the expression of miRNAs relative to U6 expression. The predictive value of miRNAs' expression for discrimination of PCOS patients from control subjects was evaluated by receiver-operating characteristic (ROC) curve analysis. miR-224 was not detected in serum and FF samples. Significantly, higher levels of miR-146a and miR-9 in serum of PCOS group were detected. In contrast, relative expression of miR-146a and miR-9 significantly decreased in FF. In PCOS group, relative expression of all detected miRNAs was elevated in serum in comparison to FF, whereas in control group no change was noticed. Combination of FF miRNAs showed improved predictive value with area under the ROC curve (AUC) of 0.84, 93.8% sensitivity, and 83.3% specificity. Contradicting alternations of miRNAs in serum and FF are indicative of different sources of miRNAs in body fluids. Presumptive target genes of studied miRNAs in signalling pathways may show the potential role of these miRNA in folliculogenesis.
{"title":"Evaluating the Differential Expression of miR-146a, miR-222, and miR-9 in Matched Serum and Follicular Fluid of Polycystic Ovary Syndrome Patients: Profiling and Predictive Value.","authors":"Zhale Ashrafnezhad, Mohammad Naji, Ashraf Aleyasin, Azim Hedayatpour, Forough Mahdavinezhad, Roghaye Gharaei, Maryam Qasemi, Fardin Amidi","doi":"10.22088/IJMCM.BUMS.11.4.320","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.4.320","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder of women in reproductive age with significant effects on reproductive and metabolic functions. Many molecular players may be involved in PCOS pathology; however, miRNAs possess great ability in gene expression control in normal ovarian function and folliculogenesis. We appraised the relative expression of miR-146a, miR-222, miR-9, and miR-224 in serum and follicular fluid (FF) of PCOS patients compared to control subjects. PCOS (n = 35) and control (n = 30) subjects were recruited in the study during their enrolment in IVF cycles. Serum and FF of human subjects were collected and stored. Total RNA was isolated from samples and cDNA was synthesized using miRNA-specific stem-loop RT primers. Quantitative real-time PCR was used to evaluate the expression of miRNAs relative to U6 expression. The predictive value of miRNAs' expression for discrimination of PCOS patients from control subjects was evaluated by receiver-operating characteristic (ROC) curve analysis. miR-224 was not detected in serum and FF samples. Significantly, higher levels of miR-146a and miR-9 in serum of PCOS group were detected. In contrast, relative expression of miR-146a and miR-9 significantly decreased in FF. In PCOS group, relative expression of all detected miRNAs was elevated in serum in comparison to FF, whereas in control group no change was noticed. Combination of FF miRNAs showed improved predictive value with area under the ROC curve (AUC) of 0.84, 93.8% sensitivity, and 83.3% specificity. Contradicting alternations of miRNAs in serum and FF are indicative of different sources of miRNAs in body fluids. Presumptive target genes of studied miRNAs in signalling pathways may show the potential role of these miRNA in folliculogenesis.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/66/01/ijmcm-11-320.PMC10506678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103020","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.11.4.285
Rana Hassan Abdul Majeed, Hanaa Ali Hussein, Mohd Azmuddin Abdullah
Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be explored. The main objective of this study was to examine the anticancer activity of Schiff base against Tongue Squamous Cell Carcinoma Fibroblasts (TSCCF) and normal human gingival fibroblasts (NHGF) and to propose its mechanism. A Novel Schiff base ligand was synthesized from the reaction of 5-C-2-4-NABA (5-chloro-2-((4-nitrobenzylidene) amino) benzoic acid). These Schiff bases possessed azomethine group (-HC=N-) and aromatic group (CH) as analyzed by Fourier transforms infrared (FTIR) spectroscopy and UV-Vis spectra. The in vitro cytotoxicity screening assay suggested promising activity against TSCCF with IC50 of 446.68 µg/mL, but insignificant activity against NHGF cells (IC50 of 977.24 µg/mL) after 72 h. The evidence of apoptotic induction was supported by DAPI staining of apoptotic nuclei with reduced cell numbers, suggesting that Schiff base could induce apoptotic bodies in cancer cells being observed. Based on the Schiff base structure, the anti-cancer mechanism may be attributed to the -HC=N- azomethine group. For the first time, our findings highlighted the anticancer activities of the new Schiff base against oral cancer cell lines.
{"title":"Preparation and Characterization of Novel Schiff Base Derived From 4-Nitro Benzaldehyde and Its Cytotoxic Activities.","authors":"Rana Hassan Abdul Majeed, Hanaa Ali Hussein, Mohd Azmuddin Abdullah","doi":"10.22088/IJMCM.BUMS.11.4.285","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.4.285","url":null,"abstract":"<p><p>Normal drugs exhibit activities against both normal and cancer cells. Furthermore, cancer cells may develop resistance to these drugs that alternative treatment must be explored. The main objective of this study was to examine the anticancer activity of Schiff base against Tongue Squamous Cell Carcinoma Fibroblasts (TSCCF) and normal human gingival fibroblasts (NHGF) and to propose its mechanism. A Novel Schiff base ligand was synthesized from the reaction of 5-C-2-4-NABA (5-chloro-2-((4-nitrobenzylidene) amino) benzoic acid). These Schiff bases possessed azomethine group (-HC=N-) and aromatic group (CH) as analyzed by Fourier transforms infrared (FTIR) spectroscopy and UV-Vis spectra. The <i>in vitro</i> cytotoxicity screening assay suggested promising activity against TSCCF with IC<sub>50</sub> of 446.68 µg/mL, but insignificant activity against NHGF cells (IC<sub>50</sub> of 977.24 µg/mL) after 72 h. The evidence of apoptotic induction was supported by DAPI staining of apoptotic nuclei with reduced cell numbers, suggesting that Schiff base could induce apoptotic bodies in cancer cells being observed. Based on the Schiff base structure, the anti-cancer mechanism may be attributed to the -HC=N- azomethine group. For the first time, our findings highlighted the anticancer activities of the new Schiff base against oral cancer cell lines.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/57/50/ijmcm-11-285.PMC10506673.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135827","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}
Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infecting mechanism depends on hosting angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as essential components and androgens as regulators for inducing the expression of these components. Therefore, hyperandrogenism-related disease such as polycystic ovary syndrome (PCOS) in insulin resistant women in reproductive-age is a high-risk factor for SARS-CoV-2 infection. Here, we describe the signaling pathways that might increase the susceptibility and severity of this new pandemic in PCOS women with insulin resistance (IR). Luteinizing hormone and insulin increase the risk of SARS-CoV-2 infection in these patients via the induction of steroidogenic enzymes expression through cAMP-response element binding protein and Forkhead box protein O1 (FOXO1), respectively. TMPRSS2 expression is activated through phosphorylation of FOXO1 in ovaries. In other words, SARS-CoV-2 infection is associated with temporary IR by affecting ACE2 and disturbing β-pancreatic function. Therefore, PCOS, IR, and SARS-CoV-2 infection are three corners of the triangle that have complicated relations, and their association might increase the risk of SARS-CoV-2 infection and severity.
严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)的感染机制依赖于宿主血管紧张素转换酶2 (ACE2)和跨膜蛋白酶丝氨酸2 (TMPRSS2)作为必需组分,雄激素作为诱导这些组分表达的调节因子。因此,育龄期胰岛素抵抗女性的多囊卵巢综合征(PCOS)等高雄激素相关疾病是SARS-CoV-2感染的高危因素。在这里,我们描述了可能增加多囊卵巢综合征(PCOS)妇女胰岛素抵抗(IR)的易感性和严重程度的信号通路。促黄体生成素和胰岛素分别通过cAMP-response element binding protein和Forkhead box protein O1 (FOXO1)诱导甾体原酶表达,从而增加了这些患者感染SARS-CoV-2的风险。TMPRSS2的表达是通过卵巢中fox01的磷酸化激活的。换句话说,SARS-CoV-2感染通过影响ACE2和干扰β-胰腺功能而与暂时性IR相关。因此,PCOS、IR和SARS-CoV-2感染是三角形的三个角,它们之间存在复杂的关系,它们之间的关联可能会增加SARS-CoV-2感染的风险和严重程度。
{"title":"A Review of Special Considerations on Insulin Resistance Induced Hyperandrogenemia in Women with Polycystic Ovary Syndrome: A Prominent COVID-19 Risk Factor.","authors":"Jamshid Roozbeh, Sahar Janfeshan, Afsoon Afshari, Aida Doostkam, Ramin Yaghobi","doi":"10.22088/IJMCM.BUMS.11.2.168","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.2.168","url":null,"abstract":"<p><p>Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infecting mechanism depends on hosting angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as essential components and androgens as regulators for inducing the expression of these components. Therefore, hyperandrogenism-related disease such as polycystic ovary syndrome (PCOS) in insulin resistant women in reproductive-age is a high-risk factor for SARS-CoV-2 infection. Here, we describe the signaling pathways that might increase the susceptibility and severity of this new pandemic in PCOS women with insulin resistance (IR). Luteinizing hormone and insulin increase the risk of SARS-CoV-2 infection in these patients via the induction of steroidogenic enzymes expression through cAMP-response element binding protein and Forkhead box protein O1 (FOXO1), respectively. TMPRSS2 expression is activated through phosphorylation of FOXO1 in ovaries. In other words, SARS-CoV-2 infection is associated with temporary IR by affecting ACE2 and disturbing β-pancreatic function. Therefore, PCOS, IR, and SARS-CoV-2 infection are three corners of the triangle that have complicated relations, and their association might increase the risk of SARS-CoV-2 infection and severity.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/91/80/ijmcm-11-168.PMC10116349.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388149","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.11.4.346
Amir Hossein Alipour, Seyed Mohammad Ali Hashemi, Afagh Moattari, Ali Farhadi, Jamal Sarvari
Epstein-Barr virus (EBV) represents one of the most important viral carcinogens. EBV nuclear antigen-1 (EBNA1) can induce the expression of different cellular and viral genes. In this study, we evaluated the EBNA1 effects on the expression patterns of human papillomavirus type 18 (HPV-18) E6 and E7 oncogenes and three cellular genes, including BIRC5, c-MYC, and STMN1, in a cervical adenocarcinoma cell line. HeLa cells were divided into three groups: one transfected with a plasmid containing the EBNA1 gene, one transfected with a control plasmid, and one without transfection. In all three groups, the expression levels of E6, E7, BIRC5, c-MYC, and STMN1 genes were checked using real-time PCR. Pathological staining was used to examine changes in cell morphology. Real-time PCR results showed that the expression level of HPV-18 E6 (P=0.02) and E7 (P=0.02) oncogenes significantly increased in HeLa cells transfected with the EBNA1 plasmid compared to cells transfected with control plasmid. Also, the presence of EBNA1 induced the expression of BIRC5 and c-MYC, which increased tenfold (P=0.03) and threefold (P=0.02), respectively. Regarding the STMN1 cellular gene, although the expression level in HeLa cells transfected with EBNA1 plasmid showed a twofold increase, this change was insignificant (P=0.11). Also, EBNA1 expression caused the creation of large HeLa cells with abundant cytoplasm and numerous nuclei. The EBV-EBNA1 could increase the expression levels of HPV-18 E6 and E7 viral oncogenes as well as c-MYC and BIRC5 cellular genes in the HeLa cell line. These findings indicate that the simultaneous infection of cervical cells with HPV-18 and EBV might accelerate the progression of cervical cancer.
{"title":"Epstein-Barr Virus Nuclear Antigen 1 Increases the Expression of Viral Oncogenes and Cellular Genes in the HeLa Cell Line.","authors":"Amir Hossein Alipour, Seyed Mohammad Ali Hashemi, Afagh Moattari, Ali Farhadi, Jamal Sarvari","doi":"10.22088/IJMCM.BUMS.11.4.346","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.4.346","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) represents one of the most important viral carcinogens. EBV nuclear antigen-1 (EBNA1) can induce the expression of different cellular and viral genes. In this study, we evaluated the EBNA1 effects on the expression patterns of human papillomavirus type 18 (HPV-18) <i>E6</i> and <i>E7</i> oncogenes and three cellular genes, including <i>BIRC5</i>, <i>c-MYC</i>, and <i>STMN1</i>, in a cervical adenocarcinoma cell line. HeLa cells were divided into three groups: one transfected with a plasmid containing the <i>EBNA1</i> gene, one transfected with a control plasmid, and one without transfection. In all three groups, the expression levels of <i>E6, E7, BIRC5, c-MYC,</i> and <i>STMN1</i> genes were checked using real-time PCR. Pathological staining was used to examine changes in cell morphology. Real-time PCR results showed that the expression level of HPV-18 <i>E6</i> (P=0.02) and <i>E7</i> (P=0.02) oncogenes significantly increased in HeLa cells transfected with the EBNA1 plasmid compared to cells transfected with control plasmid. Also, the presence of EBNA1 induced the expression of <i>BIRC5</i> and <i>c-MYC,</i> which increased tenfold (P=0.03) and threefold (P=0.02), respectively. Regarding the <i>STMN1</i> cellular gene, although the expression level in HeLa cells transfected with EBNA1 plasmid showed a twofold increase, this change was insignificant (P=0.11). Also, EBNA1 expression caused the creation of large HeLa cells with abundant cytoplasm and numerous nuclei. The EBV-EBNA1 could increase the expression levels of HPV-18 <i>E6</i> and <i>E7</i> viral oncogenes as well as <i>c-MYC</i> and <i>BIRC5</i> cellular genes in the HeLa cell line. These findings indicate that the simultaneous infection of cervical cells with HPV-18 and EBV might accelerate the progression of cervical cancer.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/ce/85/ijmcm-11-346.PMC10506676.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41141190","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.11.3.244
Fazlollah Shokri, Hossein Mozdarani, Mir Davood Omrani
Current cancer therapies include chemotherapy, radiation therapy, immunotherapy, and surgery. Despite these treatment methods, a major point in cancer treatment is early detection. RNAs (mRNA, miRNAs, and LncRNA) can be used as markers to improve cancer diagnosis and treatment. This research examined how radiotherapy affected CCL5, miR-214, and MALAT-1 gene expression in the immune pathway in peripheral blood samples from radiation therapy-treated breast cancer patients. Before and after radiotherapy, peripheral blood was collected from 15 patients in four steps. Blood samples were collected in an outpatient facility from 20 healthy female volunteers with no history of malignant or inflammatory conditions. RNA was extracted from the blood samples and cDNA was synthesized. CCL5, miR-214, and MALAT-1 gene expression were determined by real-time polymerase chain reaction (RT-PCR). CCL5 protein levels in the serum were determined in 80 samples (60 BC and 20 healthy controls) using Quantikine Enzyme-Linked Immunosorbent Assay (ELISA) kits (R&D Systems). The data were then statistically evaluated. There was a significant difference between CCL5 levels in tumoral and adjacent normal blood samples (p < 0.05). The results also show that the level of gene expression and serum concentration of CCL5 protein in different phases of radiotherapy is significantly different. On the other hand, the expression level of the miR-214 gene was significantly decreased in patients compared to the control group, but this decrease was not significant for the MALAT-1 gene (p< 0.05). Also, after each stage of radiotherapy, the expression level of these two genes showed a decrease, but in the fourth week after radiotherapy, this decrease was significant (p< 0.05). Radiotherapy is associated with a decrease in the expression of miR-214 and MALAT-1, as a result, an increase in the expression of CCL5. An increase in the concentration of CCL5 protein is accompanied by an increase in the level of monocytes, which ultimately causes the infiltration of macrophages and can ultimately cause cancer recurrence. It is suggested that these genes can probably be used as diagnostic and therapeutic radiotherapy markers in breast cancer.
{"title":"Evaluation of the Effect of Radiotherapy on CCL5/miR-214 -3p/MALAT1 Genes Expression in Blood Samples of Breast Cancer Patients.","authors":"Fazlollah Shokri, Hossein Mozdarani, Mir Davood Omrani","doi":"10.22088/IJMCM.BUMS.11.3.244","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.3.244","url":null,"abstract":"<p><p>Current cancer therapies include chemotherapy, radiation therapy, immunotherapy, and surgery. Despite these treatment methods, a major point in cancer treatment is early detection. RNAs (mRNA, miRNAs, and LncRNA) can be used as markers to improve cancer diagnosis and treatment. This research examined how radiotherapy affected <i>CCL5, miR-214, and MALAT-1</i> gene expression in the immune pathway in peripheral blood samples from radiation therapy-treated breast cancer patients. Before and after radiotherapy, peripheral blood was collected from 15 patients in four steps. Blood samples were collected in an outpatient facility from 20 healthy female volunteers with no history of malignant or inflammatory conditions. RNA was extracted from the blood samples and cDNA was synthesized. <i>CCL5, miR-214</i>, and <i>MALAT-1</i> gene expression were determined by real-time polymerase chain reaction (RT-PCR). <i>CCL5</i> protein levels in the serum were determined in 80 samples (60 BC and 20 healthy controls) using Quantikine Enzyme-Linked Immunosorbent Assay (ELISA) kits (R&D Systems). The data were then statistically evaluated. There was a significant difference between <i>CCL5</i> levels in tumoral and adjacent normal blood samples (p < 0.05). The results also show that the level of gene expression and serum concentration of <i>CCL5</i> protein in different phases of radiotherapy is significantly different. On the other hand, the expression level of the <i>miR-214</i> gene was significantly decreased in patients compared to the control group, but this decrease was not significant for the <i>MALAT-1</i> gene (p< 0.05). Also, after each stage of radiotherapy, the expression level of these two genes showed a decrease, but in the fourth week after radiotherapy, this decrease was significant (p< 0.05). Radiotherapy is associated with a decrease in the expression of <i>miR-214</i> and <i>MALAT-1</i>, as a result, an increase in the expression of <i>CCL5</i>. An increase in the concentration of <i>CCL5</i> protein is accompanied by an increase in the level of monocytes, which ultimately causes the infiltration of macrophages and can ultimately cause cancer recurrence. It is suggested that these genes can probably be used as diagnostic and therapeutic radiotherapy markers in breast cancer.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/c4/58/ijmcm-11-244.PMC10440003.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10425850","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.11.4.334
Parviz Basiri, Saeid Afshar, Razieh Amini, Ali Reza Soltanian, Massoud Saidijam, Ali Mahdavinezhad
MicroRNAs (miRNAs) have emerged as essential gene expression regulators associated with human diseases such as colorectal cancer (CRC). The purpose of this study was to evaluate the expression of miR-330-3p and its target gene BMI1 in tissue samples of patients with CRC, polyp, and healthy adjacent tissue samples and their association with clinicopathological and demographic factors such as age, tumor stage, grade, and lymph node invasion of the tumor. Following the extraction of total RNA from approximately 50 mg of colon and rectum tissue of 82 patients with CRC, 13 polypoid lesions, and 26 marginal healthy tissues using RiboEx reagent, cDNA synthesis was performed, and then quantitative real-time PCR was used to detect the expression levels of miR-330-3p and BMI1. Alterations in the gene expression were assessed using the 2(-∆∆ CT) method. The expression of miR-330-3p in all of the CRC samples was significantly lower than in adjacent healthy tissues and polyp (P<0.001). BMI1 was up-regulated in 97.9% of CRC tissue compared to healthy adjacent tissues and polyps (P<0.001). A negative reverse correlation between the miR-330-3p and BMI1 gene was observed in the CRC samples (r= -0.882, P<0.001). Down-regulation of miR-330-3p and BMI1 overexpression strongly correlates with higher tumor stage and lymph node invasion. The AUC for miR-330-3p and BMI1expression was 0.982 (sensitivity, 98.5%; specificity, 78.8%), and 0.971 (sensitivity, 97.6%; specificity, 84.6%) (P<0.001), respectively. Our results indicated that miR-330-3p and BMI1 expression probably could be considered potential diagnostic or prognostic biomarkers for CRC patient.
{"title":"Evaluation of miR-330-3p and BMI1 Expression in Colorectal Cancer Patients, Healthy Adjacent Tissues, and Polypoid Adenomatous Lesions.","authors":"Parviz Basiri, Saeid Afshar, Razieh Amini, Ali Reza Soltanian, Massoud Saidijam, Ali Mahdavinezhad","doi":"10.22088/IJMCM.BUMS.11.4.334","DOIUrl":"https://doi.org/10.22088/IJMCM.BUMS.11.4.334","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) have emerged as essential gene expression regulators associated with human diseases such as colorectal cancer (CRC). The purpose of this study was to evaluate the expression of miR-330-3p and its target gene BMI1 in tissue samples of patients with CRC, polyp, and healthy adjacent tissue samples and their association with clinicopathological and demographic factors such as age<b>, </b>tumor stage, grade, and lymph node invasion of the tumor. Following the extraction of total RNA from approximately 50 mg of colon and rectum tissue of 82 patients with CRC, 13 polypoid lesions, and 26 marginal healthy tissues using RiboEx reagent, cDNA synthesis was performed, and then quantitative real-time PCR was used to detect the expression levels of miR-330-3p and BMI1. Alterations in the gene expression were assessed using the 2<sup>(-∆∆ CT)</sup> method. The expression of miR-330-3p in all of the CRC samples was significantly lower than in adjacent healthy tissues and polyp (P<0.001). BMI1 was up-regulated in 97.9% of CRC tissue compared to healthy adjacent tissues and polyps (P<0.001). A negative reverse correlation between the miR-330-3p and BMI1 gene was observed in the CRC samples (r= -0.882, P<0.001). Down-regulation of miR-330-3p and BMI1 overexpression strongly correlates with higher tumor stage and lymph node invasion. The AUC for miR-330-3p and BMI1expression was 0.982 (sensitivity, 98.5%; specificity, 78.8%), and 0.971 (sensitivity, 97.6%; specificity, 84.6%) (P<0.001), respectively. Our results indicated that miR-330-3p and BMI1 expression probably could be considered potential diagnostic or prognostic biomarkers for CRC patient.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"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/3b/b9/ijmcm-11-334.PMC10506674.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41109379","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}