{"title":"Peptides with Diverse Functions from Scorpion Venom: A Great Opportunity for the Treatment of a Wide Variety of Diseases.","authors":"Narges Pashmforoosh, Masoumeh Baradaran","doi":"10.61186/ibj.3863","DOIUrl":"10.61186/ibj.3863","url":null,"abstract":"","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9791326","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}
Background: K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants; K-Ras4A and K-Ras4B, originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma.
Methods: Total RNA was extracted from breast tumors, and the NATs obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis.
Results: A statistically significant increase was found in the K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04).
Conclusion: Our findings revealed that expression levels of K-Ras4A and K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.
{"title":"K-Ras4A Plays a More Significant Role than K-Ras4B in Ductal Carcinoma of Breast.","authors":"Mohamad Mahdi Mortazavipour, Zeinab Mohamadalizadeh-Hanjani, Loabat Geranpayeh, Reza Mahdian, Shirin Shahbazi","doi":"10.61186/ibj.3857","DOIUrl":"10.61186/ibj.3857","url":null,"abstract":"<p><strong>Background: </strong>K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants; K-Ras4A and K-Ras4B, originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma.</p><p><strong>Methods: </strong>Total RNA was extracted from breast tumors, and the NATs obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis.</p><p><strong>Results: </strong>A statistically significant increase was found in the K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04).</p><p><strong>Conclusion: </strong>Our findings revealed that expression levels of K-Ras4A and K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733267","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}
Background: Dyskeratosis congenita (DC), an inherited and rare disease prevalent in males, is clinically manifested by reticulate hyperpigmentation, nail dystrophy, and leukoplakia. DC is associated with the increased risk of malignancy and other potentially lethal complications such as bone marrow failure, as well as lung and liver diseases. Mutations in 19 genes were found to be correlated with DC. Herein, we report a 12-year-old boy carrying a de novo mutation in TINF2 gene.
Methods: Whole exome sequencing (WES) was performed on DNA sample of the proband, and the variant was investigated in the family by Sanger sequencing. Population and bioinformatics analysis were performed.
Results: The NM_ 001099274.3(TINF2): c.844C>T (p.Arg282Cys) mutation was found by WES.
Conclusion: There was no history of the disease in the family, and the variant was classified as a de novo mutation.
背景:先天性角化不良症(DC)是一种遗传性罕见疾病,好发于男性,临床表现为网状色素沉着、甲营养不良和白斑病。先天性红斑狼疮与恶性肿瘤和其他潜在致命并发症(如骨髓衰竭)以及肺部和肝脏疾病的风险增加有关。研究发现,19 个基因的突变与 DC 相关。在此,我们报告了一名携带 TINF2 基因新突变的 12 岁男孩:方法:对病例的 DNA 样本进行了全外显子组测序(WES),并通过 Sanger 测序对家族中的变异基因进行了调查。结果:NM_ 00109927基因的变异在家族中进行了调查,并进行了群体分析和生物信息学分析:结果:通过 WES 发现了 NM_ 001099274.3(TINF2):c.844C>T (p.Arg282Cys) 突变:结论:该家族无病史,该变异被归类为新发变异。
{"title":"A de novo TINF2, R282C Mutation in a Case of Dyskeratosis Congenital Founded by Next-Generation Sequencing.","authors":"Motahareh Khakzad, Zahra Shahbazi, Majid Naderi, Morteza Karimipoor","doi":"10.61186/ibj.3783","DOIUrl":"10.61186/ibj.3783","url":null,"abstract":"<p><strong>Background: </strong>Dyskeratosis congenita (DC), an inherited and rare disease prevalent in males, is clinically manifested by reticulate hyperpigmentation, nail dystrophy, and leukoplakia. DC is associated with the increased risk of malignancy and other potentially lethal complications such as bone marrow failure, as well as lung and liver diseases. Mutations in 19 genes were found to be correlated with DC. Herein, we report a 12-year-old boy carrying a de novo mutation in TINF2 gene.</p><p><strong>Methods: </strong>Whole exome sequencing (WES) was performed on DNA sample of the proband, and the variant was investigated in the family by Sanger sequencing. Population and bioinformatics analysis were performed.</p><p><strong>Results: </strong>The NM_ 001099274.3(TINF2): c.844C>T (p.Arg282Cys) mutation was found by WES.</p><p><strong>Conclusion: </strong>There was no history of the disease in the family, and the variant was classified as a de novo mutation.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733263","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}
Ahmad Taherpoor, Arastoo Vojdani, Seyed Mohamad Ali Hashemi, Arian Amali, Mohammad Reza Mardani, Majid Ghayour Mobarhan, Habibollah Esmaily, Mohammad Taghi Shakeri, Mansoureh Bakhshi, Mojtaba Meshkat, Amin Hooshyar Chechaklou, Samaneh Abolbashari, Aida Gholoobi, Zahra Meshkat
Background: Considering the high prevalence and clinical importance of herpes simplex virus (HSV) infection worldwide, we aimed to evaluate the seroprevalence of HSV-1 and HSV-2 in a population aged between 15 and 35 years in Mashhad, Iran.
Methods: This cross-sectional study was conducted on 916 cases composed of 288 (31.4%) men and 628 (68.6%) women. Using ELISA method, the presence of IgM and IgG antibodies against HSV-1 and HSV-2 was assessed.
Results: Among the population studied, 681 (74.3%) cases were positive for anti-HSV antibodies, while 235 (25.7%) cases were negative. Moreover, no IgMs were found and all positive subjects had IgG antibodies. Age (p < 0.001), occupation (p < 0.001), education (p = 0.006), smoking (p = 0.029), and BMI (p = 0.004) demonstrated a significant association with HSV-1 and HSV-2 infection.
Conclusion: Our study indicates a high seroprevalence of HSV infection; however, there was no cases positive for IgM antibodies, suggesting the high prevalence of latent infection.
{"title":"Seroprevalence of Herpes Simplex Viruses Types 1 and 2 in a Population, Age 15-35 Years, of Mashhad City.","authors":"Ahmad Taherpoor, Arastoo Vojdani, Seyed Mohamad Ali Hashemi, Arian Amali, Mohammad Reza Mardani, Majid Ghayour Mobarhan, Habibollah Esmaily, Mohammad Taghi Shakeri, Mansoureh Bakhshi, Mojtaba Meshkat, Amin Hooshyar Chechaklou, Samaneh Abolbashari, Aida Gholoobi, Zahra Meshkat","doi":"10.61186/ibj.3828","DOIUrl":"10.61186/ibj.3828","url":null,"abstract":"<p><strong>Background: </strong>Considering the high prevalence and clinical importance of herpes simplex virus (HSV) infection worldwide, we aimed to evaluate the seroprevalence of HSV-1 and HSV-2 in a population aged between 15 and 35 years in Mashhad, Iran.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on 916 cases composed of 288 (31.4%) men and 628 (68.6%) women. Using ELISA method, the presence of IgM and IgG antibodies against HSV-1 and HSV-2 was assessed.</p><p><strong>Results: </strong>Among the population studied, 681 (74.3%) cases were positive for anti-HSV antibodies, while 235 (25.7%) cases were negative. Moreover, no IgMs were found and all positive subjects had IgG antibodies. Age (p < 0.001), occupation (p < 0.001), education (p = 0.006), smoking (p = 0.029), and BMI (p = 0.004) demonstrated a significant association with HSV-1 and HSV-2 infection.</p><p><strong>Conclusion: </strong>Our study indicates a high seroprevalence of HSV infection; however, there was no cases positive for IgM antibodies, suggesting the high prevalence of latent infection.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733264","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}
Background: Different genotypes of Echinococcus granulosus sensu lato (s.l.) infect humans and ungulate animals, causing cystic echinococcosis. Simultaneous isoenzyme, as well as molecular characterizations of this parasite, has not yet been investigated in Iran. The present study aimed to evaluate the isoenzyme pattern of the E. granulosus sensu stricto (s.s.) and E. canadensis genotypes in Iran.
Methods: A total of 32 (8 humans and 24 animals) cystic echinococcosis cysts were isolated from Shiraz, Tehran, Ilam, and Birjand from May 2018 to December 2020. The DNAs were extracted and their genotypes were determined by molecular methods. Enzymes were extracted from the cysts and subjected to polyacrylamide gel electrophoresis. The activities of glucose-6-phosphate sehydrogenase (G6PD), malate dehydrogenase (MDH), malic enzyme (ME), nucleoside hydrolyse 1 (NH1), and isocitrate dehydrogenase (ICD) were examined in the cyst samples using isoenzyme method and compared it with the genotyping findings.
Results: DNA sequence analysis of the samples showed that the specimens contained 75% E. granulosus s.s. (G1) and 25% E. canadensis (G6) genotypes. The isoenzyme pattern of ICD in both genotypes produced a six-band pattern with different relative factors. The G6PD also produced two bands with different relative migrations in both genotypes. The MDH and NH1 systems revealed a two-band pattern, while only one band was generated in the ME enzyme in the E. granulosus s.s. genotype. In the E. canadensis, the MDH and NH1 enzymes showed one band, and the ME enzyme represented a two-band pattern.
Conclusion: Our findings suggest that E. granulosus s.s. and E. canadensis genotypes have entirely different isoenzyme patterns for NH1, G6PD, MDH, and ME.
背景:不同基因型的颗粒棘球蚴感染人类和蹄类动物,导致囊性棘球蚴病。伊朗尚未对这种寄生虫的同工酶和分子特征进行过调查。本研究旨在评估伊朗严格意义上的粒细胞棘球蚴病(E. granulosus sensu stricto,s.s.)和卡那氏棘球蚴病(E. canadensis)基因型的同工酶模式:2018年5月至2020年12月,从设拉子、德黑兰、伊拉姆和比尔詹德共分离出32个(8个人和24只动物)囊状棘球蚴病囊肿。提取了 DNA,并通过分子方法确定了其基因型。从包囊中提取酶并进行聚丙烯酰胺凝胶电泳。采用同工酶法检测囊肿样本中葡萄糖-6-磷酸脱氢酶(G6PD)、苹果酸脱氢酶(MDH)、苹果酸酶(ME)、核苷水解酶 1(NH1)和异柠檬酸脱氢酶(ICD)的活性,并与基因分型结果进行比较:结果:样本的DNA序列分析表明,样本中含有75%的E. granulosus s.s.(G1)和25%的E. canadensis(G6)基因型。这两种基因型的 ICD 同工酶模式产生了六条带,相对因子各不相同。两种基因型的 G6PD 也产生了两条相对迁移率不同的条带。MDH 和 NH1 系统显示出两条带的模式,而在 E. granulosus s.s. 基因型中 ME 酶只产生一条带。在 E. canadensis 基因型中,MDH 和 NH1 酶显示一个条带,而 ME 酶显示两个条带:我们的研究结果表明,E. granulosus s.s.和 E. canadensis 基因型的 NH1、G6PD、MDH 和 ME 同工酶模式完全不同。
{"title":"Comparison of Isoenzyme Pattern of Echinococcus granulosus sensu stricto (G1-G3) and E. canadensis (G6/G7) Protoscoleces","authors":"Majid Dousti, Seyed Mahmoud Sadjjadi, Rahmat Solgi, Arghavan Vafafar, Yosef Sharifi, Amirhossein Radfar, Gholam Reza Hatam","doi":"10.61186/ibj.3815","DOIUrl":"10.61186/ibj.3815","url":null,"abstract":"<p><strong>Background: </strong>Different genotypes of Echinococcus granulosus sensu lato (s.l.) infect humans and ungulate animals, causing cystic echinococcosis. Simultaneous isoenzyme, as well as molecular characterizations of this parasite, has not yet been investigated in Iran. The present study aimed to evaluate the isoenzyme pattern of the E. granulosus sensu stricto (s.s.) and E. canadensis genotypes in Iran.</p><p><strong>Methods: </strong>A total of 32 (8 humans and 24 animals) cystic echinococcosis cysts were isolated from Shiraz, Tehran, Ilam, and Birjand from May 2018 to December 2020. The DNAs were extracted and their genotypes were determined by molecular methods. Enzymes were extracted from the cysts and subjected to polyacrylamide gel electrophoresis. The activities of glucose-6-phosphate sehydrogenase (G6PD), malate dehydrogenase (MDH), malic enzyme (ME), nucleoside hydrolyse 1 (NH1), and isocitrate dehydrogenase (ICD) were examined in the cyst samples using isoenzyme method and compared it with the genotyping findings.</p><p><strong>Results: </strong>DNA sequence analysis of the samples showed that the specimens contained 75% E. granulosus s.s. (G1) and 25% E. canadensis (G6) genotypes. The isoenzyme pattern of ICD in both genotypes produced a six-band pattern with different relative factors. The G6PD also produced two bands with different relative migrations in both genotypes. The MDH and NH1 systems revealed a two-band pattern, while only one band was generated in the ME enzyme in the E. granulosus s.s. genotype. In the E. canadensis, the MDH and NH1 enzymes showed one band, and the ME enzyme represented a two-band pattern.</p><p><strong>Conclusion: </strong>Our findings suggest that E. granulosus s.s. and E. canadensis genotypes have entirely different isoenzyme patterns for NH1, G6PD, MDH, and ME.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10349272","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}
{"title":"In Commemoration of Dr. Mahdokht Pourmansour, an Outstanding Specialist in the Production of the B.C.G. Vaccine in Iran.","authors":"Fatemeh Bardestani, Ehsan Mostafavi","doi":"10.52547/ibj.3903","DOIUrl":"https://doi.org/10.52547/ibj.3903","url":null,"abstract":"","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10314760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9846773","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}
Mahboobeh Jafari, Fatemeh Karami, Aria Setoodeh, Ali Rahmanifar, Hamideh Bagherian, Mohammad Reza Alaei, Farzaneh Rohani, Sirous Zeinali
Background: Methylmalonic aciduria is a rare inherited metabolic disorder with autosomal recessive inheritance pattern. There are still MMA patients without known mutations in the responsible genes. This study aimed to identify mutations in Iranian MMA families using autozygosity mapping and NGS.
Methods: Multiplex PCR was performed on DNAs isolated from 12 unrelated MMA patients and their family members using 19 STR markers flanking MUT, MMAA, and MMAB genes, followed by Sanger sequencing. WES was carried out in the patients with no mutation.
Results: Haplotype analysis and Sanger sequencing revealed two novel, mutations, A252Vf*5 and G87R, within the MMAA and MUT genes, respectively. Three patients showed no mutations in either autozygosity mapping or NGS analysis.
Conclusion: High-frequency mutations within exons 2 and 3 of MUT gene and exon 7 of MMAB gene are consistent with the global expected frequency of genetic variations among MMA patients.
{"title":"Identification of Novel Mutations in the MMAA and MUT Genes among Methylmalonic Aciduria Families.","authors":"Mahboobeh Jafari, Fatemeh Karami, Aria Setoodeh, Ali Rahmanifar, Hamideh Bagherian, Mohammad Reza Alaei, Farzaneh Rohani, Sirous Zeinali","doi":"10.61186/ibj.3782","DOIUrl":"10.61186/ibj.3782","url":null,"abstract":"<p><strong>Background: </strong>Methylmalonic aciduria is a rare inherited metabolic disorder with autosomal recessive inheritance pattern. There are still MMA patients without known mutations in the responsible genes. This study aimed to identify mutations in Iranian MMA families using autozygosity mapping and NGS.</p><p><strong>Methods: </strong>Multiplex PCR was performed on DNAs isolated from 12 unrelated MMA patients and their family members using 19 STR markers flanking MUT, MMAA, and MMAB genes, followed by Sanger sequencing. WES was carried out in the patients with no mutation.</p><p><strong>Results: </strong>Haplotype analysis and Sanger sequencing revealed two novel, mutations, A252Vf*5 and G87R, within the MMAA and MUT genes, respectively. Three patients showed no mutations in either autozygosity mapping or NGS analysis.</p><p><strong>Conclusion: </strong>High-frequency mutations within exons 2 and 3 of MUT gene and exon 7 of MMAB gene are consistent with the global expected frequency of genetic variations among MMA patients.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10826912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074087","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}
Mehdi Alikhani, Maryam Esmaeili, Mohammad Tashakoripour, Mohammad Ali Mohagheghi, Mahmoud Eshagh Hosseini, Eliette Touati, Massoud Vosough, Marjan Mohammadi
Background: The role of inflammatory cytokines, such as tumor necrosis-α (TNF-α) and IL-8, in gastric carcinogenesis has been investigated, but their impact remains to be further elucidated.
Methods: In this study, we measured the serum concentrations of these cytokines and H. pylori serostatus in dyspeptic patients, presenting with normal mucosa (NM = 53), chronic gastritis (CG = 94), and gastric cancer (GC = 82), by ELISA.
Results: Moderate levels of TNF-α were detected in the NM group (19.9 ± 19.5 pg/ml), which were nearly doubled in patients with CG (35.7 ± 28.0 pg/ml) and drastically declined in GC patients (1.8 ± 5.9 pg/ml). The serum levels of IL-8, however, were not statistically different amongst these three groups.
Conclusion: TNF-α serum concentration seemed to undergo up- and downregulation, when moving from NM to CG and from CG to GC, respectively. If confirmed in a prospective study, this cytokine can behave as a serum indicator of gastric inflammation and malignant transformation.
{"title":"Alteration in Serum Levels of Tumor Necrosis Factor Alpha is associated with Histopathologic Progression of Gastric Cancer","authors":"Mehdi Alikhani, Maryam Esmaeili, Mohammad Tashakoripour, Mohammad Ali Mohagheghi, Mahmoud Eshagh Hosseini, Eliette Touati, Massoud Vosough, Marjan Mohammadi","doi":"10.52547/ibj.3847","DOIUrl":"https://doi.org/10.52547/ibj.3847","url":null,"abstract":"<p><strong>Background: </strong>The role of inflammatory cytokines, such as tumor necrosis-α (TNF-α) and IL-8, in gastric carcinogenesis has been investigated, but their impact remains to be further elucidated.</p><p><strong>Methods: </strong>In this study, we measured the serum concentrations of these cytokines and H. pylori serostatus in dyspeptic patients, presenting with normal mucosa (NM = 53), chronic gastritis (CG = 94), and gastric cancer (GC = 82), by ELISA.</p><p><strong>Results: </strong>Moderate levels of TNF-α were detected in the NM group (19.9 ± 19.5 pg/ml), which were nearly doubled in patients with CG (35.7 ± 28.0 pg/ml) and drastically declined in GC patients (1.8 ± 5.9 pg/ml). The serum levels of IL-8, however, were not statistically different amongst these three groups.</p><p><strong>Conclusion: </strong>TNF-α serum concentration seemed to undergo up- and downregulation, when moving from NM to CG and from CG to GC, respectively. If confirmed in a prospective study, this cytokine can behave as a serum indicator of gastric inflammation and malignant transformation.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10871148","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}
Seyed Mohammad Ali Hashemi, Abdolvahab Moradi, Seyed Younes Hosseini, Hadi Razavi Nikoo, Taravat Bamdad, Zahra Faghih, Jamal Sarvari, Alijan Tabarraei
Background: The p53 mutation is uncommon in Epstein–Barr virus-linked gastric carcinoma, but its suppression occurs through mechanisms such as ubiquitin specific peptidase 7 (USP7) inhibitions via Epstein–Barr virus nuclear antigen-1 (EBNA1) activity. This study aimed to evaluate the effect of EBNA1 on p53-inhibiting gene expression and the impact of USP7 inhibition on p53 suppression.
Methods: MKN-45 cells were transfected with the EBNA1 plasmid. A stable EBNA1 expression cell line was developed through selection based on hygromycin B resistance. Murine double minute (MDM)4, MDM2, sirtuin (SIRT)3, histone deacetylase (HDAC)1, proteasome 26S subunit, Non-ATPase (PSMD)10, USP7, and p53 expression were checked using real-time PCR. Also, cells containing EBNA1 or control plasmid were treated with GNE-6776, and the expression of the interested genes and cell survival were assessed.
Results: MDM4, MDM2, and PSMD10 were significantly upregulated in the MKN-45 cell line following EBNA1 transfection. Morphological changes were observed in the cells harboring EBNA1 after 20 days. In the control cells, USP7 inhibition significantly upregulated the HDAC1, PSMD10, MDM4, and MDM2 genes after 24 h, but downregulated these genes after four days. In the EBNA1-harboring cells, MDM2, MDM4, and PSMD10 genes were significantly upregulated after 24 h, and this effect was sustained for all genes except for MDM4, even after four days. Furthermore, USP7 inhibition induced apoptosis in both cell groups.
Conclusion: EBNA1 enhances the expression of p53-inhibiting genes. Two events—p53 protein overexpression and apoptosis activation—followed the suppression of the USP7 protein and provided evidence for its possible function. The significance of the EBNA1-USP7 interaction in p53 suppression warrants additional investigation and possibly reconsideration.
{"title":"A New Insight Into p53-Inhibiting Genes in Epstein–Barr Virus-Associated Gastric Adenocarcinoma","authors":"Seyed Mohammad Ali Hashemi, Abdolvahab Moradi, Seyed Younes Hosseini, Hadi Razavi Nikoo, Taravat Bamdad, Zahra Faghih, Jamal Sarvari, Alijan Tabarraei","doi":"10.52547/ibj.3784","DOIUrl":"https://doi.org/10.52547/ibj.3784","url":null,"abstract":"<p><strong>Background: </strong>The p53 mutation is uncommon in Epstein–Barr virus-linked gastric carcinoma, but its suppression occurs through mechanisms such as ubiquitin specific peptidase 7 (USP7) inhibitions via Epstein–Barr virus nuclear antigen-1 (EBNA1) activity. This study aimed to evaluate the effect of EBNA1 on p53-inhibiting gene expression and the impact of USP7 inhibition on p53 suppression.</p><p><strong>Methods: </strong>MKN-45 cells were transfected with the EBNA1 plasmid. A stable EBNA1 expression cell line was developed through selection based on hygromycin B resistance. Murine double minute (MDM)4, MDM2, sirtuin (SIRT)3, histone deacetylase (HDAC)1, proteasome 26S subunit, Non-ATPase (PSMD)10, USP7, and p53 expression were checked using real-time PCR. Also, cells containing EBNA1 or control plasmid were treated with GNE-6776, and the expression of the interested genes and cell survival were assessed.</p><p><strong>Results: </strong>MDM4, MDM2, and PSMD10 were significantly upregulated in the MKN-45 cell line following EBNA1 transfection. Morphological changes were observed in the cells harboring EBNA1 after 20 days. In the control cells, USP7 inhibition significantly upregulated the HDAC1, PSMD10, MDM4, and MDM2 genes after 24 h, but downregulated these genes after four days. In the EBNA1-harboring cells, MDM2, MDM4, and PSMD10 genes were significantly upregulated after 24 h, and this effect was sustained for all genes except for MDM4, even after four days. Furthermore, USP7 inhibition induced apoptosis in both cell groups.</p><p><strong>Conclusion: </strong>EBNA1 enhances the expression of p53-inhibiting genes. Two events—p53 protein overexpression and apoptosis activation—followed the suppression of the USP7 protein and provided evidence for its possible function. The significance of the EBNA1-USP7 interaction in p53 suppression warrants additional investigation and possibly reconsideration.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10816101","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}
Timofei A Pankratov, Andrey V Gannesen, Yuri A Nikolaev
Background: Lysozyme is a part of human and animal noncellular immunity. The regulation of its activity by hormones is poorly studied. The aim of this study was to test the in vitro activity of lysozyme in the presence of catecholamines, natriuretic hormones, and estradiol (E2).
Methods: Hormones were incubated with lysozyme, and the activity of lysozome was further determined using a test culture of Micrococcus luteus in the early exponential growth stage. The activity of lysozyme was assessed based on the rate of change in the OD of the test culture. Molecular docking was performed using SwissDock server http://www.swissdock.ch/docking), and molecular structures were further analyzed and visualized in the UCSF Chimera 1.15rc software.
Results: According to the results, epinephrine and norepinephrine increased lysozyme activity up to 180% compared to the hormone-free enzyme. Changing the pH of the medium from 6.3 to 5.5, increased the lysozyme activity in the presence of E2 up to 150-200 %. The results also showed that exposure to hormones could modify lysozyme ctivity, and this effect depends on the temperature and pH value. The molecular docking revealed a decrease in the activation energy of the active site of enzyme during the interaction of catecholamines with the amino acid residues, asp52 and glu35 of the active site.
Conclusion: Our findings demonstrate an additional mechanism for the involvement of lysozyme in humoral regulation of nonspecific immunity with respect to human pathogenic microflora and bacterial skin commensals by direct modulation of its activity using human hormones.
{"title":"Regulation of Lysozyme Activity by Human Hormones","authors":"Timofei A Pankratov, Andrey V Gannesen, Yuri A Nikolaev","doi":"10.52547/ibj.3614","DOIUrl":"https://doi.org/10.52547/ibj.3614","url":null,"abstract":"<p><strong>Background: </strong>Lysozyme is a part of human and animal noncellular immunity. The regulation of its activity by hormones is poorly studied. The aim of this study was to test the in vitro activity of lysozyme in the presence of catecholamines, natriuretic hormones, and estradiol (E2).</p><p><strong>Methods: </strong>Hormones were incubated with lysozyme, and the activity of lysozome was further determined using a test culture of Micrococcus luteus in the early exponential growth stage. The activity of lysozyme was assessed based on the rate of change in the OD of the test culture. Molecular docking was performed using SwissDock server http://www.swissdock.ch/docking), and molecular structures were further analyzed and visualized in the UCSF Chimera 1.15rc software.</p><p><strong>Results: </strong>According to the results, epinephrine and norepinephrine increased lysozyme activity up to 180% compared to the hormone-free enzyme. Changing the pH of the medium from 6.3 to 5.5, increased the lysozyme activity in the presence of E2 up to 150-200 %. The results also showed that exposure to hormones could modify lysozyme ctivity, and this effect depends on the temperature and pH value. The molecular docking revealed a decrease in the activation energy of the active site of enzyme during the interaction of catecholamines with the amino acid residues, asp52 and glu35 of the active site.</p><p><strong>Conclusion: </strong>Our findings demonstrate an additional mechanism for the involvement of lysozyme in humoral regulation of nonspecific immunity with respect to human pathogenic microflora and bacterial skin commensals by direct modulation of its activity using human hormones.</p>","PeriodicalId":14500,"journal":{"name":"Iranian Biomedical Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9971709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10816100","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}